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176 papers

Oestrogen receptor phosphorylation profiles and in silico PAM50 subtyping reflect sexual dimorphism in breast cancer.

Chatterji S et al. · Jul 1, 2026

Breast cancer (BC) is most prevalent in females but also accounts for <1% of male cancer cases and 0.2% of male cancer-related deaths. Distribution of histological subtypes, receptor status, and age of diagnosis varies based on sex, and a growing body of evidence supports sex-specific molecular differences in BC. However, this is limited by the smaller number of male cases available for study compared to the thousands of cases of female BC. We combined publicly available male BC gene expression datasets for 195 patients from 4 studies and split randomly into discovery and validation sets. Clustering and gene expression analysis were performed. Two stable clusters were identified initially, confirmed in the validation set. Cluster C1 was enriched for genes associated with MAPK signalling and arylesterase activity. Cluster C2 showed enrichment of genes associated with proliferation, invasion, and metastasis, along with enrichment of gene ontology and pathway terms related to ECM regulation, particularly collagen-containing ECM. Of note, when stratified by ERα and PR status, no enrichment was observed with the predicted PAM50 classification. ERα and MAPK signalling were enriched in both clusters, albeit through different gene sets. Since these pathways were enriched, we investigated the signalling regulation of ERα based on immunohistochemical expression of phosphorylated ERα (S104, S118, S167, S294) and their prognostic roles. This analysis also revealed distinctions from female BC, showing a lack of prognostic outcome for any of these biomarkers. We show that male BC does not align with female BC in the same way that intrinsic subtypes of female BC are not identical. As BC heterogeneity is well recognised, we propose that male BC should be considered as a potentially unique clinical subtype of BC.

Medicine

Sustained Hypoxia-Inducible Factor 1-Alpha Accumulation Disrupts the Articular Niche to Promote Osteoarthritis Pathogenesis.

Gong W et al. · Jul 1, 2026

The precise role of hypoxia-inducible factor-1α (HIF-1α) in osteoarthritis (OA) pathogenesis remains controversial, often debated between a protective compensatory factor and a disease mediator. Here, we demonstrate that sustained, uncoupled HIF-1α accumulation functions as a potent, compartment-specific pathogenic driver of joint destruction. Using genetically engineered mouse models, we reveal that chondrocyte-specific HIF-1α overexpression (Acan CreERT2 ; Hif1αdPA fl/fl ) triggers spontaneous OA and exacerbates destabilization of the medial meniscus (DMM)-induced post-traumatic joint degeneration. Mechanistically, continuous HIF-1α activation drives pathological angiogenesis that physically dismantles the avascular, hypoxic cartilage niche, forcing a profound metabolic dysregulation that culminates in catastrophic matrix degradation. Conversely, sustained HIF-1α activation within the synovial and superficial cartilage compartments (Prg4- GFPCreERT2; Hif1αdPA fl/fl ) drives a slowly progressive, late-onset spontaneous OA through chronic inflammatory accumulation that actively suppresses Col2a1 expression. Furthermore, this robust inflammatory priming establishes a highly vulnerable microenvironment, whereby DMM surgery significantly accelerates the progression of trauma-induced joint collapse. Finally, transient whole-joint HIF-1α induction via an intra-articular injection of lipid nanoparticles (LNP-mRNA) closely recapitulates these detrimental effects. Collectively, our study reconciles existing controversies by establishing sustained HIF-1α accumulation as a spatiotemporally dynamic, broad disease amplifier across the articular ecosystem, highlighting its targeted inhibition as a promising therapeutic strategy for OA.

Medicine

Feasibility of a field-based submaximal stair ascent test for estimating aerobic capacity and lower-limb strength in middle-aged and older adults.

Hyvärinen M et al. · Jul 1, 2026

Background Assessing functional capacity is a key aspect of exercise testing and offers important insights into health in adult populations. However, accurate assessment often requires laboratory-based maximal tests. This pilot study investigated whether a field-based self-paced submaximal stair ascent test could feasibly assess aerobic capacity and lower-limb strength in middle-aged and older adults. Methods Twenty-eight participants (20 women, 8 men) aged 40 to 70 years completed maximal treadmill and isometric leg press tests to assess maximal oxygen consumption (VO 2 max) and lower-limb strength, respectively. Participants also performed two separate self-paced stair ascents of four and six flights. Ascent time, mean vertical power, as well as rate of perceived exertion, absolute heart rate, and relative heart rate following the test were recorded. Results Ascent time and mean vertical power were associated with VO 2 max and lower-limb strength, with standardized regression coefficients ranging from -0.61 to -0.27 and from 0.41 to 0.73, respectively. However, these associations were attenuated and no longer statistically significant after controlling for age and sex. Predictive models based on the two best-performing stair ascent predictors selected by LASSO regression showed weak-to-moderate ability to predict VO 2 max (R 2 = 0.21-0.52) with cross-validated model performance significantly different from zero. In contrast, the models did not significantly predict lower-limb strength. Conclusions These preliminary findings suggest that a brief self-paced stair ascent test may offer a feasible field-based approach for estimating aerobic capacity in middle-aged and older adults. However, its predictive accuracy appears limited and should be further examined in larger samples.

Medicine

Integrating Individual Placement Support in Early Psychosis Programs: A Necessary Step to Foster Return to Employment in First Episode Psychosis Patients.

Renda M et al. · Jul 1, 2026

Introduction Return to studies or employment, a major element of recovery after a first episode of psychosis (FEP), is out of reach of a significant proportion of patients. Specific programs such as Individual Placement Support (IPS) have been proposed to overcome this hurdle. While some early intervention programs include IPS, others must rely on IPS programs that are open to a wider range of patients. The aim of this paper was to explore the accessibility of IPS for FEP patients treated in such a context. Methods One hundred and eighty nine patients of an ongoing FEP cohort study who were treated at our program in the period where the IPS program was available and for whom sufficient data was available were included in the study. We assessed reasons for non-referral to RESSORT and compared baseline and outcome characteristics of patients who did or did not enter the program. Results A small minority of patients had access to RESSORT. Patients who entered RESSORT had better premorbid functioning and a higher degree of insight at baseline than the ones who did not enter the program. Patients who entered RESSORT had a significantly higher rate of return to premorbid PAS score, without significant difference on other dimensions of functioning. Conclusions When IPS programs are not embedded in early intervention programs, FEP patients have limited chances to access them. Integrating supported employment skills within the role of case managers may be a solution in programs where resources are lacking to develop an IPS program specifically dedicated to FEP patients.

Medicine

A Prospective Evaluation of Glucagon Stimulation Test Safety in Adults With Chronic Moderate-to-Severe Traumatic Brain Injury.

Snyder C et al. · Jul 1, 2026

Introduction Growth hormone deficiency (GHD) is a common and clinically significant consequence of moderate-to-severe traumatic brain injury (msTBI). The glucagon stimulation test (GST) is widely used to assess growth hormone deficiency; however, the safety of GST has not been systematically evaluated in adults with chronic msTBI. Methods This prospective study enrolled 138 adults aged 18-65 years with chronic msTBI (≥ 1-year post-injury) from a single academic Brain Injury Center neuroendocrine registry. All participants underwent standardized GST with systematic symptom assessment at baseline and serial intervals over 240 min. Adverse events and symptoms were graded by severity using predefined clinical criteria, and participants were analysed by GHD status and by presence of any adverse event. Results GST was well tolerated, with no serious adverse events, test terminations, or prolonged sequelae. The most common adverse effect was nausea (30.4%), with vomiting in 9.4% of participants; antiemetics were required in 16.7% of cases. Female sex was significantly associated with nausea (p Conclusions In adults with chronic msTBI, the glucagon stimulation test demonstrates a favourable safety profile with transient, non-severe adverse effects and no serious neurological or metabolic complications. These findings support GST as a safe and practical method for evaluating growth hormone deficiency in this population.

Medicine

Pregnancy and kidney transplantation: optimized clinical and obstetric management to reduce maternal and perinatal complications.

Santos ACM et al. · Jul 1, 2026

Objective Review the literature to provide guidance on the appropriate clinical and obstetric management of pregnant women with kidney transplants to reduce maternal and perinatal complications. Methods The PubMed and SciELO databases, which evaluated pregnancy and kidney transplantation, were searched, focusing on clinical and obstetric management. Other variables of interest were preconception counseling, fertility, the safety of immunosuppressants, maternal complications, perinatal complications, graft worsening during pregnancy, and postpartum guidance. Results A total of 354 articles were identified, of which 76 were included in the analysis. Studies suggest that attempts to conceive should begin at least one year after kidney transplantation in the absence of graft rejection, with stable renal function (creatinine Conclusion Pregnancy in kidney transplant recipients is challenging due to maternal and perinatal risks. However, the present review demonstrates that clinical and obstetric management by an experienced multidisciplinary team contributes to better maternal and perinatal outcomes in pregnancies among kidney transplant recipients.

Medicine

Association between inflammatory markers and mortality in hemodialysis patients.

Cindoglu C et al. · Jul 1, 2026

Introduction This study aimed to evaluate the association between mortality and biomarkers reflecting inflammatory and nutritional status in hemodialysis (HD) patients, including the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), hemoglobin, albumin, lymphocyte and platelet (HALP) score, and prognostic nutritional index (PNI). Methods This retrospective cohort study included 135 patients on routine HD. Baseline sociodemographic data, complete blood count, and biochemical parameters were recorded. Patients were followed for one year and classified as survivors or non-survivors. Predictors of mortality were analyzed using logistic regression (Enter method), with multicollinearity assessed by the variance inflation factor (VIF) and tolerance statistics. Results The mean age of the patients included in the study was 55.2 ± 16.6 years, and 47.4% were male. In univariate analyses, age, albumin, calcium, CRP, white blood cell count, neutrophil count, hematocrit, hemoglobin, SII, NLR, CAR, and PNI were found to be significantly associated with survival (all p Conclusion Our study demonstrated that easily accessible and low-cost parameters, particularly CAR and PNI, are clinically valuable in predicting survival. The identification of hemoglobin levels as an independent predictor further supports the prognostic significance of hematological parameters. This study may serve as a basis for future research on the prognostic use of these biomarkers, emphasizing the need for large-scale and prospective studies.

Medicine

Liver Transplantation for HBV-Related Disease in France: NUC Type Before LT Is Associated With Patient Survival.

Bienvenue I et al. · Jul 1, 2026

Background & aims Liver transplantation (LT) is indicated for liver complications related to hepatitis B virus (HBV) infection: acute liver failure (ALF), decompensated cirrhosis or hepatocellular carcinoma (HCC). The present study aimed to describe and evaluate patient survival after LT for HBV-related disease in France and identify the factors influencing survival. Methods The present retrospective cohort study based on medical record information included all adult patients transplanted with positive HBsAg (+/- coinfection with Hepatitis D virus (HDV)) between January 1, 2005 and December 31, 2023 in all French LT centres. Results The study population consisted of 1083 patients, the majority of whom were men (81.5%) with a median [IQR] age at LT listing of 52.8 [42.5-59.8] years. Indications for LT were HBV-related HCC (47.2%), HBV-related cirrhosis (28.5%), HDV-related cirrhosis (11.2%), HBV-related ALF (10.5%), HDV-related HCC (1.4%) and other (0.7%). Median [IQR] post-LT follow-up was 6.0 [2.2-11.1] years. Patient survival at 1, 5, 10 and 15 years after LT was 91.6%, 80.1%, 71.8% and 63.6% respectively. Multivariate analysis showed that independent significant prognostic factors were age at LT (HR: 1.030; 95CI: 1.019-1.042; p Conclusions Survival after LT for HBV-related liver disease is good. NUC type prior to LT seems to be associated with patient survival.

Medicine

Antibiotics in Veterinary Ophthalmology: Resistance, Stewardship, and Emerging Antibiotic-Sparing Strategies.

Sebbag L et al. · Jul 1, 2026

Antimicrobial resistance (AMR) is a growing challenge in veterinary ophthalmology, particularly in cases of bacterial keratitis, where progressive stromal infection can threaten vision and globe integrity within hours to days. This review synthesizes current evidence on pathogen distribution, antimicrobial susceptibility profiles, multidrug resistance (MDR) prevalence, and determinants of nonsusceptibility in veterinary patients, highlighting the emerging role of antibiotic-sparing alternatives. Across contemporary studies, Staphylococcus pseudintermedius, β-hemolytic streptococci, and Pseudomonas aeruginosa are consistently among the most frequently isolated pathogens. The highest MDR burdens are reported in referral populations and among methicillin-resistant staphylococci worldwide. Feline data remain comparatively limited but show regional variability in resistance patterns, while equine studies reveal temporal shifts in isolate distribution and a rising prevalence of methicillin-resistant organisms in tertiary settings. Recent topical antimicrobial exposure is the most consistently identified predictor of reduced culture positivity and elevated resistance rates in subsequent ocular isolates, highlighting the importance of early microbiologic sampling and judicious antibiotic use. Interpreting antimicrobial susceptibility testing (AST) in ophthalmology remains challenging because clinical breakpoints are generally derived from systemic dosing regimens, despite substantially higher, albeit transient, drug concentrations being achieved at the ocular surface following topical administration. Moreover, the ocular surface microenvironment, including tear proteins, inflammation, biofilm formation, and concurrent serum therapy, may substantially influence antimicrobial activity and therapeutic response. The review concludes with practical ophthalmology-specific stewardship recommendations, a One Health perspective on resistant ocular pathogens, and a forward-looking discussion of antibiotic-sparing adjuncts within a broader multimodal strategy to preserve antimicrobial effectiveness.

Medicine

Sarcopenia Predicts Mortality and Hepatic Encephalopathy After TIPS in Older Adults With Cirrhosis and Improves Prognostic Scores.

Saltini D et al. · Jul 1, 2026

Background and aims The role of transjugular intrahepatic portosystemic shunt (TIPS) in older adults remains controversial because of limited risk-stratification tools. We aimed to assess whether sarcopenia and myosteatosis are independently associated with post-TIPS mortality and overt hepatic encephalopathy (OHE) in patients aged ≥ 70 years, and whether adding sarcopenia to established prognostic scores improves discrimination for post-TIPS mortality. Methods This multicenter retrospective study included 115 consecutive patients with cirrhosis aged ≥ 70 years undergoing TIPS for refractory ascites or secondary prophylaxis of variceal bleeding. Sarcopenia and myosteatosis were assessed by computed tomography at L3. Post-TIPS mortality and time to first OHE episode were analysed using Kaplan-Meier and Cox regression. Sarcopenia was integrated into established prognostic scores, and predictive performance was evaluated using time-dependent ROC analyses. Results Sarcopenia and myosteatosis were present in 60% and 80% of patients, respectively. During follow-up, 49% died and 45% developed OHE. Sarcopenia was independently associated with both mortality and OHE, whereas myosteatosis and adipose-tissue indices were not. Incorporating sarcopenia improved the discriminative performance of all scores, with MELD 3.0-sarcopenia showing the highest accuracy (AUC 0.845). Predicted survival probabilities clearly separated patients across MELD 3.0 categories according to sarcopenia status. For OHE, sarcopenia increased the risk while underdilated TIPS was protective, defining four distinct risk profiles. Conclusions Sarcopenia is highly prevalent and independently predicts both mortality and OHE after TIPS in older adults. Its integration into prognostic tools enhances risk stratification and supports individualised decision-making in this vulnerable population.

Medicine