Pakistan journal of pharmaceutical sciencesYunpeng Hu, Chen Li, Yiyao Cui
BACKGROUND: Breast cancer (BC) remains a significant global health threat with complex pathogenesis often linked to chemotherapy resistance and inflammatory microenvironments. Histidine triad nucleotide-binding protein 2 (HINT2) is a mitochondrial protein involved in metabolism and immunity, but its specific role in BC and potential as a therapeutic target require further elucidation. OBJECTIVES: This study aimed to identify novel therapeutic targets for BC and evaluate the anti-tumor efficacy and molecular mechanisms of Albiflorin (Al), a natural monoterpene glycoside. METHODS: Proteomic profiling was performed on BC xenografts in nude mice to identify differentially expressed proteins. In-vivo and in-vitro models (MDA-MB-231 cells) were established to assess the effects of Al (20 mg/kg or 20 µM) on tumor growth, apoptosis and cytokine production. Molecular docking and co-immunoprecipitation (Co-IP) were used to investigate the interactions among HINT2, NLRP3 and Al. RESULTS: HINT2 was significantly upregulated in BC tissues and identified as a primary pro-tumorigenic factor. Co-IP confirmed an endogenous interaction between HINT2 and NLRP3. Al exhibited strong binding affinity to HINT2 (-7.36 kcal/mol) and significantly suppressed tumor volume and weight. Furthermore, Al treatment downregulated the HINT2/NLRP3 axis, reduced inflammatory cytokines (IL-1β, IL-6, TNF-α) and promoted apoptosis by modulating Caspase-3, Bax and Bcl-2 levels. CONCLUSION: Albiflorin suppresses BC progression by inhibiting the HINT2/NLRP3 signaling pathway, suggesting HINT2 is a viable biomarker and Al a promising therapeutic agent for BC treatment.
Journal of foot and ankle researchLevi Kadiri, Anthony Maher, Andy Bridgen
BACKGROUND: Diabetic foot osteomyelitis (DFO) is a serious complication of diabetic foot ulcers and is associated with increased risk of amputation, morbidity, and mortality. Bone biopsy remains the most definitive diagnostic modality, yet controversy persists over its diagnostic utility This study reviews the diagnostic concordance of histopathology and microbiology in bone biopsy specimens from patients with DFO and examines the clinical implications of the findings. METHODS: A systematic review was conducted using PubMed, Medline, CINHAL, Cochrane Library, and Google Scholar. Studies included adult patients with DFO in whom bone biopsy specimens underwent both histopathological and microbiological analysis. Five core studies met the eligibility criteria. Data on study design, setting, population, diagnostic methods, concordance rates, and outcomes were extracted and synthesized utilising a quantitative narrative synthesis. RESULTS: Across the five studies (n = 308 patients), histopathology and microbiology showed modest concordance, with mean rates of concordant positive results of 43.4% and common discordant findings. Histopathology demonstrated higher specificity, while microbiology had higher sensitivity, ranging from 70% to 83.9% but greater susceptibility to contamination. Positive histopathology was more strongly associated with the need for revision surgery or extended antibiotic therapy. DISCUSSION: Histopathology appears to offer superior diagnostic specificity, whereas microbiology provides valuable information for antimicrobial management. Frequent discordance underscores the importance of interpreting results in a clinical context. Further robust, prospective studies are needed to clarify the optimal diagnostic approach and standardise definitions.
Pakistan journal of pharmaceutical sciencesTong Wei, Xuezhen Li, Zhitao Guo
BACKGROUND: Postoperative chemotherapy for breast cancer often leads to intestinal dysbiosis and immune suppression. Traditional Chinese medicine shows potential in regulating gut microbiota and enhancing immune function, offering a promising adjunctive therapeutic strategy. OBJECTIVES: To explore the effects of a traditional Chinese medicine compound on the recovery of intestinal bifidobacteria and CD4+ T-cell activation in breast cancer patients undergoing postoperative chemotherapy. METHODS: Female patients with newly diagnosed breast cancer were randomly assigned to a control group (triamcinolone tablets) and an observation group (control treatment plus kidney-tonifying and compound traditional Chinese medicine soup). Intestinal flora and immune indices were measured and analyzed using SPSS 22.0. RESULTS: After chemotherapy, the observation group showed significant increases in bifidobacteria to 9.01±1.49 lg (CFU/g) and in CD4+ T-cell counts to 969/μL. The expression levels of peripheral blood CD4+ T cells and the differences in S2, nm23 and Her-2 indices were significant between the groups, with the observation group showing greater CD4+ T cell activation. The incidence of adverse reactions was significantly lower in the observation group (P-values: 0.002, 0.006 and 0.030). The observation group also demonstrated better control of gastrointestinal conditions and disease progression (P<0.001). CONCLUSION: The traditional Chinese medicine compound effectively maintained intestinal flora balance, promoted beneficial bacterial growth, reduced adverse reactions and offered better therapeutic prospects for breast cancer patients.
Pakistan journal of pharmaceutical sciencesSana Hassan, Sadia Jafar Rana, Saman Zafar, Tahir Ali Chohan, Qalander Khan, Khizar Abbas, Muhammad Sohail Arshad
BACKGROUND: Chemotherapy-induced alopecia negatively impacts the mental health of cancer patients. Topical minoxidil, a widely recommended drug for hair regrowth, causes scalp irritation and contact dermatitis. Oral minoxidil causes multiple cardiovascular and neurological side effects. Cetirizine hydrochloride, an antihistamine with a better safety profile than minoxidil, may stimulate hair follicle activity by modulating prostaglandin levels. OBJECTIVES: The present study aimed to develop a cetirizine hydrochloride-loaded emulgel and evaluate its potential, in combination with microneedling, for the treatment of chemotherapy-induced alopecia. METHODS: Different emulgel formulations comprising cetirizine HCl, liquid paraffin, carbopol 940, propylene glycol, oleic acid, Tween 20, Span 20 and propylparaben were optimized using central composite design and response surface methodology. Physicochemical evaluation of the prepared emulgel included physical examination, determination of pH, viscosity, spreadability, drug content and stability. Interactions and compatibility among formulation constituents were assessed using In-silico analysis and Fourier transform infrared spectroscopy. In-vitro drug release, ex-vivo permeation and in-vivo hair growth studies were carried out to evaluate the performance efficiency of emulgel. RESULTS: The prepared emulgels exhibited acceptable physicochemical properties and remained stable for 3 months. Constituents were found to be compatible with each other. The optimized formulation F4 released >95% drug at pH 5.5 within 360 minutes. During an ex-vivo study, ~94% of the drug permeated across rat skin within 6 hours following application of emulgel on the microneedle-pretreated skin. In cyclophosphamide-induced alopecia in rats, application of emulgel to microneedle-pierced skin for 15 days promoted hair growth. CONCLUSION: The prepared cetirizine HCl-loaded emulgel and microneedle combination may be a promising approach to treating chemotherapy-induced alopecia.
Pakistan journal of pharmaceutical sciencesOrcun Can
BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.
Uveal melanoma (UM) is driven by activating GNAQ/GNA11 mutations, predominantly at the hotspot Q209 residue. However, the functional impact of distinct GNAQ Q209 substitutions on downstream signaling and malignant progression remains unclear. Using immune-competent, multistep UM mouse models combining eye-restricted mutant GNAQ with BAP1 loss and MYC activation, we directly compared GNAQQ209L and GNAQQ209R in an otherwise matched genetic context. Tumors arising from either allele shared similar histology and cell-state composition. However, GNAQQ209L tumors progressed faster and were associated with reduced survival. In contrast, GNAQQ209R tumor-derived cell lines exhibited greater ex vivo fitness (proliferation, clonogenicity, and migration), whereas GNAQQ209L-derived lines were relatively fragile in 2D culture. At the molecular level, GNAQQ209R tumors preferentially engaged the FAK-YAP axis in primary lesions and derived cell lines. Together, these results support an allele-dependent, context-specific trade-off in which higher output GNAQQ209L favors rapid in vivo expansion, while GNAQQ209R promotes adaptability, potentially via FAK-YAP signaling, nominating allele-stratified therapeutic opportunities.
Radiology. Imaging cancerLars J Grimm, Victoria Wells, Jay A Baker, Sujata V Ghate, Meghana Konanur, Connie Kim, Eun L Langman, Derek L Nguyen, Sora C Yoon, Marc D Ryser
BACKGROUND: Conventional treatments for common and plantar warts often have limited efficacy and high recurrence rates. 5-Aminolevulinic acid photodynamic therapy (5-ALA-PDT) has attracted increasing attention as an alternative therapeutic option for these lesions. This study investigated the potential of 5-ALA-PDT as an alternative treatment option for patients with refractory common and plantar warts. OBJECTIVE: To explore the clinical efficacy of 5-ALA-PDT and recombinant human interferon alpha 2b (rhIFN-α2b) spray combination therapy against common and plantar warts. METHODS: We enrolled 104 patients with common or plantar warts and randomly assigned them to the intervention (5-ALA-PDT combined with rhIFN-α2b spray; n = 51) or control (cryotherapy; n = 53) group to compare treatment efficacy, recurrence rate, and adverse events. RESULTS: After three consecutive treatment cycles, the 4-week complete recovery and total effective rates were 90.20% and 96.08% in the intervention group, versus 62.26% (p = 0.002) and 77.36% (p = 0.013) in the control group. Recurrence rates were significantly lower in the intervention group at 8 weeks (2.17% vs. 24.24%), 12 weeks (4.35% vs. 33.33%), and 6 months (4.35% vs. 39.39%; all p < 0.05). All adverse events were mild to moderate and localized. CONCLUSION: 5-ALA-PDT combined with rhIFN-α2b spray exhibited superior clinical efficacy in treating common and plantar warts, significantly improving treatment efficacy, reducing medium-term recurrence, and demonstrating good safety and tolerability.
Nursing in critical careBruna Cristina Velozo, Aglecia Moda Vitoriano Budri, Larissa Cassiano Bernardo, Meire Cristina Novelli E Castro, Gabriela Dos Santos Cruz, Geovana Rodrigues Go…
BACKGROUND: The lack of consensus on the best pressure injury (PI) risk assessment tools demonstrates the need for further comparative research to identify the most effective options for intensive care unit (ICU) populations. AIM: This study compared the predictive validity and reliability of five PI risk assessment tools in adult ICU patients. STUDY DESIGN: A prospective cohort study was conducted with patients aged ≥ 18 years, admitted to the ICUs for at least 24 h and without pre-existing PI. Five tools (Braden Scale, CALCULATE, Cubbin & Jackson, EVARUCI and Sunderland) were used daily to assess PI risk until either a PI developed or the participant was discharged, died or completed 21 days in the ICUs. The main outcome measures included area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, relative risk and reliability. RESULTS: Of the 150 participants, 40 (26.7%) developed PIs. None of the five tools demonstrated good predictive accuracy. AUC values ranged from 0.605 to 0.692 across the five tools, with none exceeding the predefined threshold of 0.70. Participants classified as high risk by Sunderland, Cubbin & Jackson and EVARUCI had a 3.0, 2.5 and 2.1 times higher risk, respectively, of developing a PI. Cubbin & Jackson was the only tool to achieve acceptable reliability values in Cronbach's alpha, intraclass correlation coefficient (ICC) and Cohen's weighted kappa. CONCLUSIONS: High-risk classification using the Sunderland, Cubbin & Jackson and EVARUCI scales was more strongly associated with subsequent PI development than classification using the other tools. Reliability findings varied across parameters, with Cubbin & Jackson being the only tool to meet acceptable thresholds across all assessed reliability measures. RELEVANCE TO CLINICAL PRACTICE: PI assessment in ICU patients should integrate validated tools with clinical judgement to address patient-specific and device-related risk factors.
Reviews in medical virologyIrene G Manders, Eline L van Tuinen, Martijn Weisfelt, Marco Goeijenbier, Jayant S Kalpoe, Steven F L van Lelyveld, Eric C M van Gorp, Ken Ho Hua
Varicella zoster virus (VZV) and herpes simplex virus (HSV) are major causes of viral meningitis and encephalitis. Standard intermittent intravenous acyclovir requires hospitalisation, reducing patient comfort and prolonging admissions. Continuous infusion may maintain therapeutic plasma and cerebrospinal fluid (CSF) concentrations while enabling treatment through Outpatient Parenteral Antimicrobial Therapy (OPAT). Objectives to evaluate the feasibility, pharmacokinetic target attainment, and cost reduction of continuous intravenous acyclovir for HSV and VZV neurological infections in an OPAT setting. We conducted a case series of eight patients with HSV or VZV neurological infections who received continuous intravenous acyclovir through our OPAT programme after initial hospital-based therapy. Steady-state plasma concentrations were measured to assess pharmacokinetic target attainment. Costs were calculated based on daily costs of discontinued inpatient care and OPAT. Existing literature on continuous intravenous acyclovir and acyclovir in OPAT was reviewed. No persistent complications associated with continuous intravenous acyclovir administration were observed. All patients completed treatment with good clinical responses; one had persistent ptosis, and another developed postherpetic neuralgia. Acyclovir plasma concentrations remained above the therapeutic threshold in all seven measured cases, suggesting adequate CSF exposure. Hospital admissions were shortened, with no readmissions. The acyclovir OPAT programme led to cost savings of 3486 EUR per patient. Despite this small case series, continuous intravenous acyclovir appears to be feasible for treating HSV and VZV neurological infections in an OPAT setting, with potential benefits in patient comfort, healthcare costs, and hospital resource utilization. Larger studies are warranted to assess safety and efficacy.
Drug development researchLamia W Mohamed, Ahmed A Saadeldin, Ayman B Farag
Vascular endothelial growth factor receptor-2 (VEGFR-2) is a vital mediator of angiogenesis. Therefore, VEGFR-2 inhibition is considered a promising therapeutic target to combat cancer. In the present study, a series of 22 imidazo[4,5-b]pyridine-acrylonitrile-based derivatives was designed and synthesized. All compounds were evaluated for their VEGFR-2 inhibitory activity. Seven of the tested compounds showed high inhibitory activity against VEGFR-2 with IC50 (0.029-0.087 µM) compared to reference drug sorafenib IC50 = 0.091 µM. Four of these derivatives were selected for in vitro cytotoxic activity against breast cancer (MCF-7) and hepatocellular (HepG2) carcinoma cell lines, showing IC50 (0.073-0.196 µM) and (0.20-0.21 µM), respectively, relative to sorafenib IC50 0.16 and 0.19 µM, respectively. Compound 2f exhibiting a superior VEGFR-2 inhibition (IC50 = 0.029 µM compared to sorafenib IC50 = 0.091 µM) and cytotoxicity against MCF-7 and HepG2 (IC50 = 0.073 µM and IC50 = 0.09 µM, respectively), was subjected to cell cycle analysis, apoptosis assay, and molecular modeling studies, which strongly supported the results. It caused cell cycle arrest at G2/M phase by 13.67% and a promising apoptosis induction. 2f exhibited a promising binding score and pose inside the VEGFR-2 active sites. It also showed a good safety profile with a moderate selectivity index. Based on the prediction of physicochemical and pharmacokinetic properties for 2f, it showed excellent prediction results to be orally bioavailable.
Eruptive disseminated Spitz nevus (EDSN) is an exceptionally rare condition characterized by widespread Spitz-spectrum melanocytic lesions. We report a 21-year-old woman with an estimated 50,000-60,000 lesions involving the entire cutaneous surface, predominantly the trunk and proximal extremities. Lesions began at age 17 with hundreds of lesions and increased dramatically over subsequent years. Initial HRAS sequencing and ROS1 FISH were negative; broader molecular profiling was performed at re-presentation. Seven representative lesions from distinct sites were sampled: five Spitz nevi and two atypical Spitz tumors, without melanoma. Strong, diffuse ALK expression was detected in three lesions, while RNA sequencing identified an identical TPM3 exon 8::ALK exon 20 fusion in two of seven lesions from anatomically separate sites. Although compatible with shared clonality, this finding does not establish a common clonal origin because TPM3::ALK is a recurrent Spitz driver and transcript-level concordance does not prove an identical genomic breakpoint. A constitutional NF1 p.S1249F variant was classified as a variant of uncertain significance and was also present in two clinically unaffected brothers, arguing against an independently sufficient pathogenic role. TPM3::ALK remains the only demonstrated oncogenic driver. To our knowledge, this represents the first longitudinal molecular follow-up of EDSN, with findings compatible with either clonal dissemination or recurrent independent acquisition of the same driver.
Nursing in critical careRajini Peter, K N Ashwini, P Dhivya, Aljo Joy, E Selmar Mellisha
BACKGROUND: Pressure injuries (PIs) remain a persistent challenge in intensive care units (ICUs), causing pain, extended hospital stays and increased costs. Data from India are limited. AIM: To determine the incidence and risk factors for pressure injuries among adult ICU patients in a tertiary care public hospital. STUDY DESIGN: A prospective cohort study was conducted from August to October 2024 in the adult ICUs of a public hospital in central India. All eligible patients were enrolled via total enumeration. Demographic and clinical variables, Braden and APACHE-II scores, and nursing hours per patient-day were collected. New PIs were staged per international guidelines by two nurse-researchers. Data were analysed using descriptive statistics and univariable logistic regression. RESULTS: Of 324 patients, 50 (15.4%; 95% CI: 11.7-19.8) developed 87 new PIs, with an incidence density of 39.1 per 1000 patient-days (95% CI: 31.32-48.23). Most lesions were stage I/II, primarily sacrococcygeal, with a median onset of 4 days. Among the 16 variables examined using univariable analyses, early fever (OR 7.33, 95% CI 3.38-15.88), exclusive non-oral feeding (OR 5.73, 95% CI 2.75-11.95), needing repositioning assistance (OR 4.56, 95% CI 2.06-10.09), medical ICU (OR 3.73, 95% CI 1.87-7.46), vasoactive drug-use (OR 2.31, 95% CI 1.21-4.44), moderate-to-obese body build (OR 2.84, 95% CI 1.23-6.57) and longer ICU stay (OR 1.23/day, 95% CI 1.15-1.31) had the strongest associations with PI. CONCLUSIONS: PIs affect approximately one-in-six ICU patients, with several factors associated with higher odds. Multi-centre studies are needed to examine generalisability and validate ICU-specific risk assessment tools. RELEVANCE TO CLINICAL PRACTICE: High-risk profiles requiring prioritised preventive measures, as early assessment, nutritional optimisation and mobility support include those with prolonged stays, fever, non-oral feeding, medical ICU admission, vasoactive drug-use and non-thin build.
British journal of health psychologyCaroline F Z Stuhlmann, Rachel Sommer, Tracey A Revenson
OBJECTIVES: Living with a stigmatizing skin disease may hinder normative development during emerging adulthood. The present study aimed to examine indirect effects of internalized stigma in the relationship between social stigma and psychosocial adjustment among young adults with visible chronic skin diseases. Indicators of psychosocial adjustment spanned several domains: mental health (depression, anxiety, quality of life), physical health (somatic symptoms), intimacy and health behaviour (physical activity). DESIGN: This cross-sectional study recruited young adult patients with chronic skin disease from an outpatient dermatology clinic. Data were obtained through self-report, electronic medical records and a physical exam. METHODS: Young adults (N = 195, Mage = 28.06 years; 49% female) with psoriasis (55%), atopic dermatitis (23%) or hidradenitis suppurativa (22%) self-reported sociodemographic information and measures for social stigma (PSQ), internalized stigma (WBIS-adapted) and psychosocial adjustment (PHQ-9, GAD-7, DLQI, SSS-8, DIS, days of physical activity per week). Bootstrapped mediation analyses tested indirect effects of internalized stigma on the relationship of social stigma and each psychosocial adjustment outcome, controlling for covariates. RESULTS: Indirect effects of internalized stigma on the relationship of social stigma with each outcome were significant (p's < .01, R2 = .10 to .64). CONCLUSIONS: Findings indicated that stigma has implications for many areas of functioning and well-being, highlighting how emerging adulthood contextualizes the experience of living with the stigma of visible skin disease. Internalized stigma was a major driving force, serving as a potential target for clinical and psychoeducational interventions to improve the well-being of young adults with chronic visible skin disease.
Veterinary ophthalmologySamantha J Dacanay-DeFebo, Gillian C Shaw, Kimberley Sebastian, Mika Tamura, Anne Gemensky-Metzler, Georgina M Newbold
OBJECTIVE: To describe the clinical presentation, management, and histopathologic findings in dogs with cutaneous periocular histiocytic disease. PROCEDURES: Retrospective review of 14 dogs (18 eyes) with cutaneous periocular histiocytic disease from January 2015 to January 2025. Follow-up data were obtained for 9 dogs (12 eyes). Variables evaluated included age, sex, breed, lesion location, characteristics and duration, histopathologic diagnosis, additional histopathologic staining or further testing performed, treatment, presence of other ocular/periocular disease, and recurrence of the mass after surgery. RESULTS: The most prevalent lesion location was the lower eyelid followed by the lateral canthus. All of the lesions were interpreted as histiocyte-rich lesions with no identifiable underlying cause. Successful treatment for the 9 dogs (12 eyes) with follow-up was achieved by surgical excision alone in 2 dogs (2 eyes) and surgical excision with medical management in 7 dogs (10 eyes). Medical management included oral corticosteroids and/or other oral immunosuppressive drugs, subconjunctival corticosteroids, and topical immunomodulatory therapies. Of the nine dogs with follow up, only three dogs experienced lesion recurrence. Following medical management, none of the lesions had recurred in dogs with follow up at the final recheck exam. CONCLUSION: Histiocytic lesions can affect the periocular tissues and should be included in differential diagnoses for mass lesions around the eyes. Recurrence is uncommon after surgical excision and lesions appear to respond to various immunomodulatory treatments.
Pigment cell & melanoma researchZuo Baiyi, Liu Guanying, Huang Xin, Wei Tianqi, Zhou Zhaokang, Xu Beilei, Luo Lingling, Li Chengrang
Vitiligo is an acquired depigmentation disorder characterized by the loss of epidermal melanocytes and can markedly impair patients' quality of life. Because of its dual effects on immunosuppression and repigmentation, UVB phototherapy has become a first-line treatment for vitiligo. It is particularly valuable in inducing repigmentation of skin lesions. Since epidermal melanocytes are markedly reduced or even absent in vitiligo lesions, migration of melanocyte stem cells (McSCs) from the hair follicle bulge to the interfollicular epidermis is considered a critical step in UVB-induced repigmentation, as it enables the replenishment of epidermal melanocytes. Therefore, this review summarizes the molecular mechanisms by which UVB induces McSC migration. Current evidence suggests that UVB primarily regulates McSC migration, proliferation, and differentiation indirectly by remodeling the McSC niche. In this process, keratinocytes, inflammatory cells, and other niche-associated cells release multiple paracrine mediators, including SCF, EDN1, bFGF, PGE2, and WNT. These factors coordinately regulate the physiological activities of McSCs. In addition, we propose that changes in the expression of melanocyte surface receptors may be an important limiting factor governing the migratory response of McSCs. This review also discusses the molecular markers of McSCs and the physiological changes that accompany their migration. Based on current evidence, we further hypothesize that some melanocytes migrating to the epidermis may retain the ability to dedifferentiate and return to the hair follicle. This process may represent an important mechanism by which UVB-induced McSC migration does not deplete the McSC reservoir.
Annals of medicineAtheer G Almutairi, Leena I Aloraini, Abeer G Almutairi, Houriah Nukaly, Saleha Khan, Asem Shadid, Azzam Alkhalifah
BACKGROUND AND OBJECTIVES: Lichen planus (LP) is a chronic, lymphocytic, inflammatory skin disorder that can affect the skin, hair follicles, nails, and mucous membranes. It has limited treatment options. The pathogenesis of LP includes inflammation driven by interferons and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Thus, Janus kinase inhibitors (JAKi) have been proposed as a viable therapeutic approach for LP. JAKi have recently been approved to treat some lymphocytic skin disorders such as alopecia areata and atopic dermatitis. The purpose of the systematic review was to assess the effects of JAKi on LP. MATERIALS AND METHODS: We searched PubMed, Scopus, and Google Scholar and included all studies published between January 2015 and May 2024 that assess the clinical effects of JAKi on lichen planus, including cutaneous and mucosal/adnexal variants. The risk of bias in included studies was assessed using Joanna Briggs Institute (JBI) tools, classifying bias as low, moderate and high concerns. RESULTS: A total of 57 full-text publications were evaluated, of which 34 papers were excluded because they did not match the criteria. Therefore, this systematic review included 23 papers, seven of them were case series and the remaining 16 were case reports. There were 13 papers on tofacitinib, six on baricitinib, and two papers each on ruxolitinib and upadacitinib. CONCLUSION: Several case series and case reports have shown beneficial effects of JAK inhibitors to treat LP. Few patients had minor adverse events.
The Journal of dermatological treatmentYanchen Liu, Haoran Hu, Linfeng Li
OBJECTIVES: Randomized evidence for systemic targeted therapies in prurigo nodularis (PN) has expanded, but cross-trial differences limit valid comparison. We mapped randomized evidence and assessed comparative effects using exact Week-16 ≥ 4-point itch numerical rating scale response (NRS4). METHODS: MEDLINE, Embase, CENTRAL, and Web of Science were searched through 14 August 2026. Studies with extractable randomized arm-level Week-16 NRS4 data were synthesized using a fixed-effect contrast-based network meta-analysis. Risk of bias was assessed with RoB 2 and confidence with CINeMA. RESULTS: Twenty-four randomized studies were represented by 117 reports, but only seven cohorts (1,435 participants; 19 arms; 10 active nodes) contributed to the aligned network. Dupilumab (OR 4.04, 95% CI 2.42-6.75; low confidence) and global phase III nemolizumab (OR 5.81, 95% CI 3.81-8.86; low confidence) were effective versus placebo. The indirect nemolizumab-versus-dupilumab comparison was imprecise (OR 1.44, 95% CI 0.74-2.79; low confidence). CONCLUSIONS: Indirect evidence did not establish superiority of either biologic. The randomized evidence bases substantially exceeded the quantitatively comparable network, reflecting incomplete results availability and cross-trial differences. REGISTRATION: PROSPERO CRD420261401106.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupJohannes Crezee, C Paola Tello Valverde, M Willemijn Kolff, H J G Desirée van den Bongard, Ben J Slotman, Akke Bakker, H Petra Kok
BACKGROUND: Thermoradiotherapy at 40-43 °C is an effective treatment for locoregional recurrent (LRR) breast cancer patients. During hyperthermia temperature monitoring is often limited to skin temperatures, but their predictive value for achieving locoregional tumor control (LRC) remains unclear for tumor depths ≥1cm. This study compared predictive value of skin versus invasive intratarget temperatures. METHODS: We reported earlier the thermal dose-effect relationship in 112 patients with LRR breast cancer treated in 2010-2017 with postoperative re-irradiation (8 × 4 Gy/23 × 2 Gy) and 4-5 weekly hyperthermia sessions with 434 MHz microwave applicators. Bolus cooling enabled semi-superficial target depths (1-4 cm), thermocouple thermometry monitored both skin and intratarget temperatures. The present study analyzes relationships between LRC and average skin and intratarget median temperature T50 and best session with highest median thermal dose CEM43T50 (cumulative equivalent minutes at 43 °C). Pearson correlation coefficient analysis evaluated correlation between intratarget and skin temperature parameters. RESULTS: Average median skin and invasive temperatures were T50 = 40.6 °C (Interquartile Range IQR 40.3-40.8) and T50 = 40.7 °C (IQR 40.0-41.3), respectively, without association between skin and intratarget temperatures. Median CEM43T50 for skin and intratarget were 2.8 (IQR 2.0-4.3) and 7.2 min (IQR 3.4-15.9) in the best hyperthermia session, respectively. Twenty-four patients developed infield recurrences; median time-to-recurrence was 3.4 years (IQR 2.7-4.6 years). Univariate and multivariate analysis showed significant association of intratarget temperature parameters with LRC (p = 0.015; p = 0.021, respectively), but not for skin temperature parameters and LRC (p = 0.131; p = 0.215, respectively). CONCLUSION: Temperature monitoring using both skin and invasive intratarget measurements is key for ensuring good quality superficial hyperthermia delivery for tumor depths ≥1cm.
International journal of molecular medicineRuyan Jie, Ying Tang, Tingting Wu, Chenfan Zhang, Man Song, Xiaotong Zhao, Mingwei Chen
Diabetic foot ulcer (DFU) is a severe complication of diabetes, characterized by chronic, difficult‑to‑heal foot wounds. It has been hypothesized that miR‑222‑3p may influence wound healing via the regulation of angiogenesis. To elucidate the underlying mechanism, experimental investigations were conducted in vitro using human dermal microvascular endothelial cells (HMEC‑1) and in vivo in a mouse model of streptozotocin‑induced diabetes. Methylglyoxal (MGO), a glycolytic intermediate, is known to contribute to diabetic vascular complications. The results demonstrated that MGO‑treated HMEC‑1 cells exhibited an increased expression of miR‑222‑3p and impaired microvascular endothelial cell function. The overexpression of miR‑222‑3p in MGO‑treated HMEC‑1 cells further suppressed cell proliferation, migration and tube formation, while it enhanced apoptosis. Moreover, the upregulation of miR‑222‑3p reduced the expression of apelin (APLN), and dual‑luciferase reporter assays confirmed APLN as a direct downstream target of miR‑222‑3p. The silencing of APLN markedly impaired HMEC‑1 cell function. Notably, both the exogenous supplementation with Apelin‑13 and the overexpression of APLN significantly reversed endothelial dysfunction caused by the upregulation of miR‑222‑3p. In vivo, in both normal and diabetic mice, the elevated expression of miR‑222‑3p in skin wounds reduced APLN levels in the peri‑wound tissue and impaired wound healing. However, the overexpression of APLN or the inhibition of miR‑222‑3p with an antagomiR reversed this impairment. Collectively, these results suggest that miR‑222‑3p impairs microvascular endothelial cell function by targeting APLN, thereby contributing to delayed wound healing in diabetic skin.
NMR in biomedicineIrene Garcia-Bocanegra, Jesus David Urbano-Gamez, Antonio Perez-Cardona, Laura Barrios, Maria Isabel Somoza-Ramírez, Luis Vicioso, Elena Pardo-Susacasa, Gema D…
Advances in molecular characterization have significantly redefined our understanding of breast tumor heterogeneity, enabling improved diagnostics and the development of tailored therapeutic strategies. In particular, integrative omics approaches offer a broader scope for exploring the molecular and biochemical complexity of breast cancer. Notably, metabolomics through high-resolution magic angle spinning (HR-MAS) NMR spectroscopy enables nondestructive metabolic profiling of intact tissue samples, preserving the native biochemical context and offering unique potential for refining breast cancer subtyping and gaining deeper insight into disease biology. However, the reproducibility and comparability of HR-MAS-based metabolomics across studies are still limited by methodological variations, underscoring the need for standardized and reliable protocols to manage the complexity of breast cancer tissue spectra. In this study, LCModel analysis in combination with the Electronic REference To access In vivo Concentrations (ERETIC2) method as a quantitative reference was implemented for absolute metabolite quantification of breast cancer samples, providing a robust metabolic profiling approach. Generalized linear models were applied to evaluate the associations between quantified metabolites and tumor immunohistochemical classification, and transcriptomic correlation analysis was used to explore gene expression profiles underlying the observed metabolic alterations. A total of 27 metabolites were quantified from breast tumor samples spanning the Luminal A, Luminal B (human epidermal growth factor receptor 2-negative, HER2-), Luminal B (HER2+), and triple-negative breast cancer (TNBC) subtypes. Strong positive associations were observed between phosphocholine (PCho), betaine (Bet), total choline (tCho), and total creatine (tCr) and immunohistochemical subtype, whereas alanine, glucose, and myo-inositol showed negative associations. Notably, Luminal B (HER2-) tumors exhibited the highest PCho levels, linked to upregulated expression of choline kinase alpha (CHKA) and other enzymes of the Kennedy pathway. In contrast, Luminal B (HER2+) tumors exhibited elevated levels of alanine (Ala), glucose (Glc), and myo-inositol (Ins), indicating distinct metabolic reprogramming within the luminal subgroups. Additionally, this study highlights the potential role of betaine (Bet) in interconnecting metabolic and epigenetic pathways in breast cancer, as its concentrations were found to vary across subtypes and correlate with genes involved in fatty acid metabolism, DNA methylation, and estrogen signaling. Robust HR-MAS NMR profiling captured subtype-dependent metabolic signatures, and integrative analysis with transcriptomics identified gene expression differences associated with these signatures, thereby advancing the understanding of breast cancer heterogeneity.
Pharmacology research & perspectivesNtemena Yikon'a, Ngosa Mumba, Sarah Pedretti, Helen Hoenck, Jonathan Peter, Owen Ngalamika
Angiotensin-converting enzyme inhibitors (ACEIs) are widely prescribed but are associated with adverse drug reactions (ADR), including angioedema, which is typically reported in 0.1%-0.7%. Data from sub-Saharan Africa are limited. This study aimed to estimate the incidence and risk factors of enalapril-associated ADRs in a Zambian cohort, with particular focus on angioedema. We conducted an ambispective cohort study of 400 adults initiating enalapril at two tertiary hospitals in Lusaka, Zambia. Enalapril was the only ACEI available to the participants, and the primary outcome was the occurrence of enalapril-associated ADRs requiring treatment discontinuation or modification. Kaplan-Meier methods were used to estimate event-free survival, and Cox proportional hazards regression was used to identify factors associated with ADR occurrence. Angioedema occurred in 19/400 participants (4.8%). Overall, 22% (88/400) of participants experienced at least one ADR impacting treatment. The most frequent ADRs were cough (10.3%) and dizziness (5.0%). In multivariable analysis, male sex was independently associated with a lower risk of ADR (adjusted hazard ratio [aHR] 0.59, 95% CI 0.37-0.93). No significant associations were identified for the high rate of angioedema. The incidence of enalapril-associated angioedema in this cohort was substantially higher than that reported in global as well as African American populations. These findings have clinical relevance for prescribing and monitoring ACEIs in sub-Saharan African populations. Further studies are needed to confirm this signal and explore underlying mechanisms.
Japan journal of nursing science : JJNSHideaki Aoyagi, Yasumi Matsubara, Akiko Okada, Akiko Hayashi, Makiko Seto, Yuichiro Iida
AIM: Developing effective nursing support for cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer requires understanding nurses' knowledge and nursing practices regarding CTRCD. This study elucidated these aspects among Certified Nurse Specialists (CNSs) and Certified Nurses (CNs) in Japan. METHODS: A web-based survey was administered to 1490 nurses, including CNSs in cancer nursing and CNs in cancer chemotherapy, breast cancer, and heart failure. The survey assessed participants' characteristics, knowledge of CTRCD, nursing practices, consultation experiences, and interprofessional collaboration. We calculated descriptive statistics and conducted group comparisons between oncology nurses specializing in cancer nursing and cardiology nurses specializing in heart failure nursing. RESULTS: We obtained 261 responses, including 214 (82.0%) from oncology nurses and 47 (18.0%) from cardiology nurses. These two groups exhibited significant differences in their knowledge of CTRCD definitions, risk factors, and related agents (p < 0.01). Among oncology nurses, 88 (56.8%) provided patient education on CTRCD risk and 94 (63.9%) monitored CTRCD symptoms; thus, practice implementation remained around half. A higher proportion of cardiology nurses reported having received questions or consultations regarding CTRCD from patients or staff (p < 0.05). Only 27 participants (10.3%) reported access to onco-cardiology educational opportunities at their respective institutions. CONCLUSION: Differences in knowledge and practices regarding CTRCD were identified between oncology and cardiology nurses. Improving nursing practices, particularly patient education and symptom observation, is essential for early CTRCD detection and treatment. Furthermore, systematic educational programs and structured collaborative frameworks, including interprofessional collaboration, are needed at both the institutional and national levels.
International wound journalSerge Ynesta, Marion Mourgues, Chloé Geri, Martin Inizan, Denis Barritault, Frédéric Sedel, Jean-Charles Kerihuel, Luc Téot
ReGenerating Tissue Agents (RGTA, trade name CACIPLIQ20) contain a structural analogue of heparan sulfates (HSs) that promotes tissue regeneration in hard-to-heal chronic wounds resistant to the best standard of care for 6 months or longer. The MATHCOW study aimed to evaluate the real-life performance and safety of RGTA administered in addition to optimal treatment in diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), and leg ulcers with an ischemic component (arterial ulcers). The primary outcome measure was the rate of ulcer closure within the first 20 weeks of treatment. A total of 191 patients were recruited; 173 signed informed consent and constituted the intention-to-treat (ITT) analysis set. The per-protocol (PP) population included 114 patients. The primary endpoint was 50 wound closures at 20 weeks in the ITT analysis (28.9%) and 46 wound closures in the PP analysis (40.4%). Closure rates varied according to ulcer type: 43.7% for VLUs, 46.2% for DFUs, and 14.6% for arterial ulcers. Other endpoints also improved, including clinician global impression, pain, and ulcer area. Adverse events were recorded in 4% of cases. This open-label study confirms the performance and tolerability of RGTA in a population of patients with particularly hard-to-heal chronic ulcers.
International journal of dermatologyTim J Zeuner, Titus J Brinker
A growing number of artificial intelligence (AI) systems for melanoma diagnosis now match dermatologist-level performance. Early detection is a driving factor, yet it is rarely validated beyond aggregate diagnostic accuracy. More targeted studies are necessary so these claims become verifiable and the promise of early detection can actually be delivered to patient care.
Physiotherapy research international : the journal for researchers and clinicians in physical therapyKim Michéle Feder, Lonny Stokholm, Hans Bjarke Rahr, Kim Gordon Ingwersen, Marianne Djernes Lautrup
BACKGROUND: Breast cancer survival has improved substantially, yet many women continue to experience late effects that may require physiotherapy. Shoulder impairment, lymphedema, and fatigue are among the most common physiotherapy-relevant late effects following primary breast cancer treatment. Understanding how guideline treatments for breast cancer influence these impairments is essential for the early identification of high-risk patients and the development of targeted rehabilitation strategies. PURPOSE: To investigate the association between Danish guideline treatments for breast cancer and the risk of three physiotherapy-relevant self-reported late effect dimensions 3-7 years postoperatively. METHODS: National cohort study of 5729 women who underwent surgical treatment for primary breast cancer between 2015 and 2019. Participants completed a questionnaire 3-7 years postoperatively addressing shoulder impairment, lymphedema, and fatigue. Treatment codes were extracted from the Danish National Patient Registry and categorized according to Danish guideline regimens for surgery and radiotherapy. Logistic regression analyses, adjusted for relevant confounders, were performed to estimate associations, and absolute risks were calculated. RESULTS: Compared with breast-conserving surgery (BCS) and sentinel lymph node biopsy (SLNB) with radiotherapy, treatment combinations involving mastectomy or axillary lymph node dissection (ALND) with radiotherapy were associated with approximately threefold higher odds of self-reported late effects. The highest risk was observed after mastectomy and SLNB with radiotherapy (ORadj 3.10, 95% CI 2.48-3.88), followed by mastectomy with ALND and radiotherapy (ORadj 2.90, 95% CI 2.02-4.15) and BCS with ALND and radiotherapy (ORadj 2.76, 95% CI 2.25-3.39). Shoulder impairment was consistently the most frequent self-reported late effect across all treatment types. DISCUSSION: Guideline treatments involving mastectomy, and/or ALND in combination with radiotherapy substantially increased the risk of self-reported late effects, particularly shoulder impairment. These findings highlight the need for early targeted physiotherapy interventions and improved detection strategies to mitigate late effects in breast cancer survivors.
Rhode Island medical journal (2013)Jonathan London, John Patresan, Alexander Belkin, Radowan Elnair
Sweet syndrome (acute febrile neutrophilic dermatosis) is characterized by fever, leukocytosis, and tender erythematous skin lesions with neutrophilic infiltrate. Although associated with granulocyte colony-stimulating factor (G-CSF) use, its occurrence with pegfilgrastim-the pegylated form-is rare, with fewer than five reported cases. Sweet syndrome has also been rarely linked to FLT3 inhibitors such as quizartinib. We report a 71-year-old male with acute myeloid leukemia who developed bullous Sweet syndrome following concurrent exposure to pegfilgrastim and quizartinib.
Radiographics : a review publication of the Radiological Society of North America, IncSoudabeh Fazeli, James E Stepenosky, Saba Naamo, David J Hall, Rebecca Rakow-Penner, Haydee Ojeda-Fournier
Screening and diagnostic evaluation for breast cancer is increasingly common during pregnancy and lactation due to delayed childbearing and identification of elevated hereditary and familial risk during reproductive years, with patients often undergoing risk assessment beginning at 25 years of age. Although mammography is safe for pregnant and lactating patients, its sensitivity may be reduced because hormonal changes increase parenchymal density and can obscure malignant lesions. US is widely used because it does not involve exposure to ionizing radiation and serves as the primary modality for evaluating symptomatic patients. However, its role in routine screening remains uncertain because evidence regarding screening performance and outcomes in pregnant and lactating populations is limited. MRI is contraindicated during pregnancy but may be performed during lactation for screening of patients at high risk for or with newly diagnosed breast cancer, despite its pronounced background parenchymal enhancement. Timely evaluation of breast symptoms and imaging abnormalities is critical given the rising incidence of pregnancy-associated breast cancer and the potential for delayed diagnosis. Therefore, radiologists must balance diagnostic performance with maternal and fetal safety when selecting imaging modalities. The authors review the current American College of Radiology Appropriateness Criteria and the guidelines of other professional organizations; summarize the epidemiology of pregnancy-associated breast cancer and the physiologic breast changes that affect imaging interpretation; and highlight modality-specific limitations, safety considerations, and contraindications. Strategies for identifying patients at high risk for breast cancer who require continued screening and for effectively communicating imaging risks, benefits, and expectations to patients and referring clinicians are also discussed.
Pharmacology research & perspectivesLouis-Edmond Barbaro, Nouha Ben Othman, Delphine Viard, Fanny Rocher, Elliot Ewig, Raja Mroue, Claire Amigues, Alexandre O Gérard
Tocilizumab is an interleukin-6 (IL-6) receptor antagonist indicated for various rheumatologic conditions. While hepatotoxicity is a recognized adverse effect, it predominantly manifests as hepatocellular injury. We report a rare case of drug-induced liver injury (DILI) presenting with a cholestatic pattern and cholangitis features in a 75-year-old patient treated for giant cell arteritis. Following the third tocilizumab infusion, the patient developed jaundice and abdominal pain. Laboratory investigations revealed a cholestatic pattern of liver injury (ALT/ALP (R) ratio ≤ 2) with marked cholestasis. Imaging findings raised suspicion for cholangitis. After ruling out infectious, autoimmune, and metabolic aetiologies, a liver biopsy confirmed neutrophilic cholangitis and marked intrahepatic and sinusoidal cholestasis. Drug discontinuation, along with ursodeoxycholic acid treatment, led to clinical and biochemical resolution. This case is notable as tocilizumab-induced liver injury rarely presents with cholangitic features. The pathophysiology may involve the disruption of IL-6 signaling, which plays a pivotal role in maintaining biliary epithelial integrity. Clinicians should be vigilant for this atypical cholestatic presentation to ensure prompt drug withdrawal.
Pakistan journal of pharmaceutical sciencesShuhui Dai, Xuanhe Zhang, Zhen Qiao, Liudan Li, Litong Ye
BACKGROUND: Chemotherapy-induced neutropenia (CIN) is a common dose-limiting toxicity in patients with solid tumors, often leading to infections, treatment delays, or dose reductions. However, studies on the dynamic patterns of CIN across multiple chemotherapy cycles and their prediction remain limited. OBJECTIVES: To longitudinally observe CIN evolution across two consecutive cycles, develop a predictive model for severe CIN in cycle 2 (T2) based on cycle 1 (T1) characteristics, and classify patients by early recovery capacity to form a personalized bundle care strategy. METHODS: This single-center retrospective cohort study using electronic medical record (EMR) data enrolled 138 patients with solid tumors (89.1% breast cancer) who received ≥2 chemotherapy cycles between January 1, 2015, and January 31, 2025, at Zhuhai Maternal and Child Health Care Hospital, China. Neutrophil kinetic parameters were collected for T1 and T2. A multivariable logistic regression model predicted grade 3-4 CIN in T2 using T1 variables, with internal bootstrap validation. K-means clustering based on T1 recovery patterns identified patient subgroups. RESULTS: Severe CIN incidence decreased from 88.0% in T1 to 42.7% in T2 (p<0.001); neutrophil nadir rebounded from 0.40 × 109/L (IQR: 0.10-0.70) in cycle 1 to 1.05 × 109/L (IQR: 0.50-1.80) in cycle 2 (p<0.001). The prediction model (age, T1 nadir, T1 days to nadir, T1 recovery duration) achieved a test AUC of 0.677 and an accuracy of 78.6%. Out of the 138 total patients, 120 with complete recovery data were utilized for clustering analysis, identifying three groups: rapid (n=21), similar (n=79) and slow (n=20). The slow-recovery group exhibited significantly higher rates of febrile neutropenia (25.0% vs. 10.1% and 4.8%, p=0.043) and chemotherapy delays (35.0% vs. 15.2% and 9.5%, p=0.021). CONCLUSION: CIN severity generally improves from first to second cycle, but with substantial inter-individual heterogeneity. A T1-based prediction model combined with recovery stratification can identify high-risk patients for personalized CIN management. Further validation in diverse populations is warranted.
Journal of applied clinical medical physicsJun Yang, Longman Long, Guang Li, Jian Zeng, Caixiao Peng, Jingting Yan
BACKGROUND: Breast Imaging Reporting and Data System (BI-RADS) 4a nodules represent a diagnostic dilemma, with a malignancy rate ranging from 2% to 10%. The majority of these nodules prove benign after biopsy, leading to unnecessary invasive procedures, patient anxiety, and healthcare costs. Current clinical practice lacks a reliable, noninvasive tool to accurately distinguish benign from malignant BI-RADS 4a lesions. Emerging evidence suggests that integrating multiparametric ultrasound data with clinical factors through artificial intelligence may improve diagnostic precision, but a validated multimodal model specifically for this ambiguous category is lacking. PURPOSE: To develop and validate a multimodal artificial intelligence model that integrates ultrasound radiomics, hemodynamic features, and clinical data for the accurate differentiation of benign and malignant BI-RADS 4a breast nodules, with the ultimate goal of supporting clinical decisionmaking and safely reducing unnecessary biopsies. METHODS: This prospective, multicenter study enrolled 350 pathologically confirmed BI-RADS 4a nodules from 331 patients in one tertiary hospital and two secondary hospitals. Clinical data, grayscale ultrasound images, and hemodynamic parameters were collected for each nodule. Radiomics features were extracted from the ultrasound images. A multimodal fusion model was constructed using the Light Gradient Boosting Machine (LightGBM) algorithm following feature selection via Least Absolute Shrinkage and Selection Operator (LASSO) regression. The model was developed and hyperparameter-tuned on a training set (n = 260) using nested cross-validation and was evaluated on a temporally independent test set (n = 90). Model interpretability was enhanced using SHapley Additive exPlanations (SHAP). RESULTS: On the independent test set, the multimodal LightGBM model demonstrated excellent diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI: 0.91-0.99), with a sensitivity of 100% (95% CI: 81.5%-100%) and a specificity of 86.1% (95% CI: 75.8%-93.1%). Its performance was significantly superior to baseline classifiers including Logistic Regression, Support Vector Machine, and Random Forest (all p < 0.05). SHAP analysis identified wavelet-transformed texture features, the presence of a penetrating vessel, and BRCA mutation status as the top predictors of malignancy. Applying this model could have potentially avoided 32.4% (24/74) of unnecessary biopsies on benign nodules while maintaining perfect sensitivity. CONCLUSION: A multimodal AI model based on LightGBM can accurately differentiate benign and malignant BI-RADS 4a breast nodules. It shows significant potential as a clinical decision-support tool to reduce unnecessary biopsies without compromising sensitivity, enabling more precise management for this challenging patient population.
Health promotion journal of Australia : official journal of Australian Association of Health Promotion ProfessionalsFarwa Rizvi, Victoria White, Patricia M Livingston, Kylee Bellingham, Sue-Anne McLachlan, Jennifer Philip
BACKGROUND: Participation in breast cancer screening among culturally diverse women in Australia remains below national targets. Healthcare providers, particularly general practitioners (GPs), play a pivotal role in bridging communication and knowledge gaps and in advocacy, especially for under-screened South Asian (Pakistani and Indian) women. OBJECTIVE: To explore communication and health education strategies used by healthcare providers to encourage breast cancer screening among culturally diverse South Asian women living in Victoria. METHODS: A qualitative study involving semi-structured interviews with 15 GPs and non-primary healthcare providers in Victoria, Australia. Participants were recruited using purposive and snowball sampling methods, drawing from primary care, specialist networks and peer-to-peer referrals. Reflexive thematic analysis was applied to identify communication strategies and system-level insights. RESULTS: Three major themes were identified: (1) encouraging health engagement; (2) communication strategies; (3) cultural sensitivity of healthcare providers. Trust-building strategies were important in encouraging health engagement and reducing resistance to screening and misconceptions. Participants reported low levels of health literacy, including limited awareness of BreastScreen Victoria's free service. While interpreters aided communication, they also posed challenges in maintaining efficient consultations. Healthcare providers promoted patient-centred, visual resources to support screening discussions. Cultural sensitivity was emphasised through the use of culturally competent tools and healthcare providers' ongoing cultural training. Existing screening informational resources were considered insufficient to address the cultural preferences of screening South Asian women. CONCLUSIONS: Strengthening breast cancer screening for culturally diverse women relies on building trust through culturally competent healthcare providers who can support their patients' engagement with screening through empowering communication, tailored tools and shared decision-making. SO WHAT: Healthcare providers are key enablers of breast cancer screening participation among South Asian women. Investing in culturally competent communication, tailored resources and workforce training could substantially improve screening engagement among South Asian women who remain under-screened despite access to free screening services.
The aim of this research was to synthesise evaluative research on support surfaces in pressure ulcer care in nursing homes, by examining how studies address effectiveness, efficiency, user satisfaction and context of use. Following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines, six databases were used. Studies assessing support surfaces in nursing homes were included. Data extraction covered studies' characteristics, support surfaces evaluated and methodologies employed. Among the 68 included studies, 40 focused primarily on support surface evaluation, mainly assessing effectiveness or efficiency (n = 31, 78%) rather than context of use (n = 5, 12%) or user satisfaction (n = 4, 10%). Residents' perspectives were captured in 42.5% (n = 17) of studies and quality of life in 25% (n = 10), with one qualitative study identified. Mattresses predominated among the 188 support surfaces evaluated (47%, n = 88). Studies were concentrated among seven research teams (49%, n = 33), and industry funding was the most common source overall (37%, n = 25). Current research prioritises effectiveness and efficiency assessment over holistic usability assessment. The limited incorporation of residents' and professionals' experiences and quality of life outcomes reveals a gap between biomedical approaches and person-centred perspectives. Future research should place residents' and professionals' experiences at the centre of support surface evaluation to generate clinically relevant and ethically grounded evidence.
The Lancet. OncologyGuang-Yi Sun, Si-Ye Chen, Yu Tang, Hui Fang, Yong-Wen Song, Yue-Ping Liu, Jing Jin, Ning Li, Ning-Ning Lu, Yuan Tang, Shu-Nan Qi, Bo Chen, Hao Jing, Yi-Rui Zha…
BACKGROUND: Hypofractionated radiotherapy is an established alternative to conventional fractionation for breast cancer, but long-term evidence after mastectomy with regional nodal irradiation is scarce. We aimed to assess the long-term efficacy and adverse event profile of hypofractionated versus conventional fractionated postmastectomy radiotherapy in high-risk breast cancer. METHODS: This randomised, non-inferiority, open-label, phase 3 trial was done at a national cancer centre in China. Eligible patients were women aged 18-75 years with high-risk breast cancer who had undergone modified radical mastectomy and axillary dissection with a Karnofsky performance score 60% or higher. Participants were randomly assigned (1:1) to conventional fractionated radiotherapy (50 Gy in 25 fractions over 5 weeks) or hypofractionated radiotherapy (43·5 Gy in 15 fractions over 3 weeks) to the chest wall and supraclavicular region, using a computer-generated sequence with concealed allocation and no masking. The primary endpoint was 5-year cumulative incidence of locoregional recurrence, analysed in the modified intention-to-treat population (including all eligible patients who underwent randomisation, but excluding those who were considered ineligible or withdrew consent after randomisation) and a 5% margin was used to establish non-inferiority. In this prespecified long-term analysis, outcomes at 10 years were analysed without additional confirmatory non-inferiority testing. Safety was analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT00793962, and is closed to enrolment. FINDINGS: Between June 12, 2008, and June 16, 2016, 2157 patients were assessed for eligibility. 1337 were excluded and 820 patients were enrolled and randomly assigned (414 to conventional fractionated radiotherapy and 406 to hypofractionated radiotherapy). Five patients were excluded in each group and 810 were included in the analyses (409 to conventional fractionated radiotherapy and 401 to hypofractionated radiotherapy). Median follow-up was 11·5 years (IQR 9·6-13·8). Median patient age was 49 years (range 24-74), and 761 (94%) patients had stage III disease. All patients were female, and data on race and ethnicity were not collected. At 10 years, cumulative locoregional recurrence was 10·3% (95% CI 7·3-13·3) with conventional fractionated radiotherapy and 12·0% (8·8-15·2) with hypofractionated radiotherapy (hazard ratio 1·19, 95% CI 0·79-1·82). The most common grade 3 adverse events at 10 years were ischaemic heart disease (five [1%] of 409 patients in the conventional fractionated radiotherapy group vs five [1%] of 401 patients in the hypofractionated radiotherapy group), lymphoedema (four [1%] vs three [<1%]), shoulder dysfunction (two [<1%] vs one [<1%]), and skin adverse events (none vs one [<1%]). No grade 4-5 events, brachial plexopathy, serious adverse events, or treatment-related deaths occurred. INTERPRETATION: Hypofractionated postmastectomy radiotherapy provided durable locoregional control with no increase in severe late adverse events compared with conventional fractionation, supporting its use as a more time-efficient option than conventional fractionated radiotherapy. FUNDING: Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, National High Level Hospital Clinical Research Funding, Cooperation Fund of CHCAMS, and CAMS Innovation Fund for Medical Sciences.
Japan journal of nursing science : JJNSSarina Enami, Yui Shimoyama, Hiroshige Matsumoto, Chikako Honda, Akari Maeda-Suzuki, Mari Ikeda, Kyoko Yoshioka-Maeda
AIM: This study aimed to investigate these aspects in female community-dwelling cancer survivors. METHODS: This secondary analysis of a community-based cancer survey was conducted in Tokyo, Japan. Emotional well-being (EWB) and functional well-being (FWB) were measured using two subdomains of the Functional Assessment of Cancer Therapy-General. The sample comprised 163 survivors of breast and gynecological cancers. We used descriptive statistics and multivariate regression analyses to explore the association between the challenges and EWB and FWB. RESULTS: All participants were women, of whom 118 and 45 were breast and gynecological cancer survivors, respectively. The most frequent challenges experienced but not addressed (referred to as "unaddressed challenges") were "anxieties about progression and prognosis", followed by "balancing hobbies and treatments", and "depressed mood". Although initial analyses suggested that the presence of challenges related to "depressed mood" and "balancing hobbies and treatments" was associated with lower EWB, these associations did not maintain statistical significance after adjusting for multiple testing. Conversely, excluding challenges related to "fertility preservation," all unaddressed challenges related to diagnosis and medical treatment and finances remained robustly associated with lower scores in EWB and FWB. Among unaddressed challenges related to balancing daily life and treatment, "balancing housework and treatment" and "balancing hobbies and treatments" remained associated with lower scores in EWB and FWB. CONCLUSIONS: Female community-dwelling survivors of breast and gynecological cancers face various unaddressed challenges that diminish EWB and FWB. Early identification and targeted public health interventions are required to address survivors' daily life challenges and improve well-being.
Experimental dermatologyYulu Wang, Kevin M Truong-Balderas, Yi Gao, Claudia Lasalle, Sabrina Schundler, Bethany E Perez White, Kyle T Amber, Adrian P Mansini
Autophagy is increasingly recognised as a regulator of epithelial stress adaptation in the skin, but its role in inflammatory dermatoses remains difficult to interpret because autophagy intersects with barrier biology, keratinocyte differentiation, immune signalling, intracellular trafficking and lysosomal degradation. Keratinocytes are immune-competent epithelial cells that integrate cytokine exposure, oxidative stress, microbial sensing and tissue injury into inflammatory output. In this review, we synthesize evidence on keratinocyte autophagy as a disease-dependent regulator of epidermal homeostasis and cutaneous inflammation. We summarize core autophagy machinery, selective autophagy programs relevant to epidermal differentiation and the interpretive value of autophagic flux and lysosomal competence. We then discuss how autophagy influences keratinocyte differentiation, organelle clearance, lipid handling, barrier support, inflammatory restraint and stress adaptation. Disease-specific evidence is reviewed in psoriasis, AP1S3-associated pustular autoinflammation, atopic dermatitis and vitiligo. Across these settings, keratinocyte autophagy cannot be classified as uniformly protective or pathogenic; its effects depend on inflammatory context, trafficking state, cell-type-specific outputs and the ability of lysosomes to complete degradation. We also consider lessons from other barrier epithelia, therapeutic implications and common methodological limitations. A keratinocyte-centered, flux-aware interpretation provides a framework for organizing disease-specific autophagy biology and for designing more rigorous mechanistic studies in inflammatory dermatoses.
BACKGROUND: Merkel Cell Carcinoma (MCC) is a rare, aggressive neuroendocrine and epithelial skin cancer. Somatostatin analogues, such as lanreotide, have shown efficacy in managing other neuroendocrine tumors. Retrospective studies suggest that lanreotide may induce partial response or disease stabilization in patients with advanced MCC. To test this hypothesis, we conducted a Phase II, non-randomized, open trial investigating lanreotide in MCC patients with advanced disease (ClinicalTrials.gov identifier: NCT02351128). METHODS: Patients with Stage IIIB-IV MCC received lanreotide monotherapy (120 mg every 28 days) at any line of systemic therapy, until disease progression or unacceptable toxicity. The primary endpoint was disease control rate (DCR) (defined as the proportion of patients with complete response, partial response, and stable disease) at 3 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), somatostatin receptor (SSTR) tumor expression, and treatment safety. RESULTS: Between April, 2015, and November, 2016, 35 patients received lanreotide, with 12 evaluable at 3 months. The DCR at 3 months was 33.3% (4) among evaluable patients (all with stable disease) and 11.4% for the full cohort. Statistical analyses showed no significant difference from the expected 20% response rate (p = 0.205 for intention-to-treat; p = 0.939 for per-protocol). Kaplan-Meier analysis revealed median OS and PFS of 3.1 months (95% CI, 2-5.5) and 3.5 months (95% CI, 2.3-5.5), respectively. SSTR tumor expression did not correlate with treatment response. CONCLUSION: Although limited by its implementation before the era of immunotherapy, this non-randomized study shows the limited effectiveness of lanreotide as monotherapy in treating patients with advanced MCC. TRIAL REGISTRATION: Identifier: NCT02351128.
International wound journalMaegan Spiteri, Louise Savine, Peter R Worsley, Spyros Masouros
This study aimed to evaluate the physiological effectiveness of lateral pressure application in maintaining baseline transcutaneous oxygen (TcPO2) and carbon dioxide (TcPCO2) tensions in the buttocks during sitting, compared with a conventional static foam cushion. Secondary aims were to determine whether body mass index (BMI) influenced the physiological response when lateral pressure was applied and to investigate the relationship between transcutaneous oximetry and underbody interface pressure. A prospective, controlled, repeated-measures laboratory study was conducted with 30 healthy adults. Participants underwent two 20-min sitting conditions: sitting on static foam alone and sitting on static foam with lateral pressure applied by a prototype device. Transcutaneous gas tensions were measured at the right ischial tuberosity using an oximeter and normalised to unloaded standing baselines. Tissue responses were categorised according to the Chai and Bader tissue-response criteria, where changes in gas tensions of < 25% are Category 1, least risk, and changes of > 25% are Category 3, highest risk. Underbody interface pressures were recorded using a pressure-mapping array. Statistical comparisons between conditions were performed using paired parametric or non-parametric tests as appropriate. Mean and peak underbody interface pressures were significantly reduced (p < 0.0001) when lateral pressure was applied. Lateral pressure significantly reduced the mean change in TcPCO2 compared to static foam alone (11.9% ± 25.6% and 47.8% ± 72.9%, respectively, p < 0.0001) and reduced the change in TcPO2 to -29.5% ± 23.5% compared to -50.4% ± 34.8% with static foam alone (p < 0.0001). Eleven participants exhibited a Category 3 ischaemic response on static foam, compared with only two when lateral pressure was applied. Twenty-nine of 30 participants moved to a more favourable or unchanged tissue-response category when lateral pressure was applied. No correlation was found between interface pressure and changes in gas tensions. No significant differences were observed between BMI groups. Application of lateral pressure during sitting maintained tissue perfusion at the ischial tuberosity more effectively than static foam alone. These findings support the physiological rationale for applying lateral pressure as a novel strategy for pressure-ulcer prevention in seated patients.
MicrobiologyOpenXiaolei Zhu, Wen Zhang, Tinghong Ye, Heng Zhang, Jufang Tan, Yi Sun
Basal cell carcinoma (BCC) is the most common malignant skin tumor. Skin-resident lipophilic Malassezia yeasts are associated with various cutaneous disorders, while their correlative patterns and potential biological effects in BCC tissues remain insufficiently defined. We used RT-qPCR screening of archived FFPE BCC specimens and metagenomic sequencing of three paired fresh tumor and peritumoral tissues to characterize tissue-associated Malassezia colonization. M. globosa was the most abundant species in FFPE samples and was also detectable in fresh tissues. In vitro functional assays (CCK-8, EdU) in HaCaT keratinocytes and A-431 epidermoid carcinoma cells showed that 12 h stimulation with optimal concentrations of M. globosa (1.2 × 107 CFU/mL) and M. yamatoensis (1.6 × 107 CFU/mL) significantly promoted epithelial cell proliferation. Transcriptome sequencing and subsequent RT-qPCR validation further showed that both strains significantly upregulate pro-inflammatory genes (IL-1β, IL-6, TNF-α) and oxidative stress-related genes (SOD1, SOD2) in these cell lines. Collectively, our findings describe a correlative association between Malassezia colonization and BCC lesions and offer preliminary in vitro mechanistic clues.
Clinics in plastic surgeryPierre-Olivier Grenier, Marilyn G Liang
Capillary malformation (CM), or port wine birthmark, is a congenital low-flow vascular malformation of dilated capillaries and postcapillary venules. It often affects the face and may darken, thicken, or develop nodules over time. Most CMs are isolated but can be associated with syndromes such as Sturge-Weber, characterized by a facial CM, leptomeningeal vascular malformation, and ocular findings such as glaucoma. CMs also occur in other syndromes, emphasizing the need for thorough clinical evaluation. Management is multidisciplinary, with pulsed-dye laser as the gold standard treatment; excision may be required for tissue overgrowth.