Category: Statistics

J Cell Biol. 2026 May 4;225(5):e202505190. doi: 10.1083/jcb.202505190. Epub 2026 Mar 12.

ABSTRACT

Tetraspanins are integral membrane proteins that play a crucial role in organizing and regulating cellular signaling by serving as scaffolds that compartmentalize receptors and other signaling molecules within membrane microdomains. Here, we report how the tetraspanin CD82 modulates the molecular organization and signaling of the EGF receptor (EGFR), a key molecule involved in cellular proliferation, differentiation, and survival. Combining multicolor super-resolution microscopy with advanced image reconstruction and analysis techniques, we demonstrate that CD82 selectively associates with EGFR, promotes receptor oligomerization, and acts as a regulator of ligand-independent receptor phosphorylation in a palmitoylation-dependent manner. Additionally, CD82 promotes a more compact molecular organization of EGFR, which correlates with altered endocytosis and downstream signaling outcomes. These findings underscore the importance of tetraspanins in the spatial and functional regulation of cell surface receptors, with implications for controlling aberrant signaling in disease and positions CD82 as a potential target for developing therapeutic strategies aimed at modulating EGFR signaling by influencing receptor organization.

PMID:41817402 | DOI:10.1083/jcb.202505190

Immunotherapy. 2026 Mar 12:1-17. doi: 10.1080/1750743X.2026.2643128. Online ahead of print.

ABSTRACT

INTRODUCTION: Muscle-invasive urothelial carcinoma (MIUC) represents one-quarter of cancers and carries morbidity and mortality. Although cisplatin neoadjuvant chemotherapy plus radical cystectomy improves survival, patients may be ineligible due to renal dysfunction or comorbidities. Immune checkpoint inhibitors (ICIs), established in metastatic disease, are emerging as neoadjuvant options.

METHODS: A systematic search of PubMed, Embase, and the Cochrane Library identified clinical trials evaluating ICIs in MIUC. Meta-analysis was conducted using a random-effects model. Statistical analyses were performed in R software (version 4.4.1), with p < 0.05 considered significant.

RESULTS: Eleven studies comprising 573 patients (82.02% male) were included. The pooled pathologic complete response (pCR) rate was 35% (95% CI: 31%-39%). Overall survival (OS), recurrence-free survival (RFS), and event-free survival (EFS) at 2 years were 85% (95% CI: 77%-90%), 78% (95% CI: 72%-83%), and 73% (95% CI: 66%-79%), respectively. Additionally, the incidence of grade ≥3 cardiovascular, hematological, and immune-related adverse events (AEs) was 3% (95% CI: 2%-6%), 16% (95% CI: 11%-23%), and 5% (95% CI: 3%-8%), respectively.

CONCLUSIONS: Neoadjuvant ICIs demonstrate favorable efficacy and acceptable safety in MIUC, particularly among cisplatin-ineligible patients. Randomized trials are needed to confirm long-term oncological outcomes and establish their role in curative treatment.

PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42025640278.

PMID:41816870 | DOI:10.1080/1750743X.2026.2643128

J Med Screen. 2026 Mar 12:9691413261430309. doi: 10.1177/09691413261430309. Online ahead of print.

ABSTRACT

ObjectiveEvidence is scarce about whether colorectal cancer screening can affect the quality of life of participants, particularly in terms of novel screening strategies in Eastern populations.MethodsFrom 2018 to 2021, the TARGET-C trial randomly allocated 19,373 participants to one of three screening strategies: (A) one-time colonoscopy; (B) annual faecal immunochemical test with positives referred for colonoscopy; and (C) annual risk-adapted screening with low-risk participants referred for faecal immunochemical test and high-risk participants referred for colonoscopy. Two rounds of follow-up after baseline screening were conducted over the 3-year period. Based on the TARGET-C, a EuroQol five-dimensional questionnaire-based quality of life survey was administrated to the participants, and utility scores and related changes were used as the main outcomes.ResultsTaking by-strategy utility scores for participants before being screened at baseline as the comparators (n = 2921), the changes in utility scores after baseline screening were -0.008 (P < 0.050) for strategy A, 0.006 (P < 0.050) for strategy B and 0.000 (P > 0.050) for strategy C, and the overall difference in quality of life changes among the three strategies was significant (P < 0.001). Taking the same comparators as above, the changes in utility scores for participants in the second round of follow-up (n = 9201) were 0.011 (P < 0.050), 0.011 (P < 0.050) and 0.005 (P < 0.050), respectively, and the overall difference was neither clinically meaningful nor statistically significant (P = 0.113).ConclusionsNone of the three colorectal cancer screening strategies had a major effect on the participants’ quality of life over the 3 years. Within one round of screening, incorporating risk-adapted screening and/or faecal immunochemical test might offset the quality of life impact from colonoscopy screening.

PMID:41816867 | DOI:10.1177/09691413261430309

J Med Screen. 2026 Mar 12:9691413261429395. doi: 10.1177/09691413261429395. Online ahead of print.

ABSTRACT

BackgroundPhysically Disabled women face multiple barriers to cervical screening, contributing to lower uptake and increased health inequalities. Human papillomavirus self-sampling has been shown to increase screening participation in under-screened populations, but little is known about its acceptability for Disabled women.MethodsA cross-sectional online survey was conducted with 1493 UK-based participants who identified as having a physical disability, impairment, condition, or difference that makes cervical screening difficult or impossible. Participants completed questions on the acceptability of human papillomavirus self-sampling, attitudes and beliefs relating to self-sampling, and future screening preferences. Descriptive statistics and multinomial logistic regression were used to analyse responses.ResultsMost participants reported that they would be able to carry out self-sampling themselves (63.3%) and would be willing for a healthcare professional to use a self-sampling kit on their behalf (59.1%). Many (70.5%) had concerns about not performing the test correctly. Around half (53.0%) would prefer self-sampling at home if offered a screening choice. Women who had never attended screening, or who had delayed/missed appointments, were significantly more likely to prefer self-sampling (odds ratios 13.11 and 5.25, respectively) than women who had always attended. Approximately a fifth of participants (18.7%) would prefer a non-speculum clinician-taken test.ConclusionHuman papillomavirus self-sampling was acceptable to many physically Disabled women and preferred over conventional screening, particularly among those who had delayed/missed screening or never attended. Implementation should include tailored accessible instructions to support human papillomavirus self-sampling, disability-informed clinical support, and consideration of non-speculum clinician-taken samples to ensure equitable access and reduce inequalities in cervical screening.

PMID:41816861 | DOI:10.1177/09691413261429395

Scand J Public Health. 2026 Mar 12:14034948261424666. doi: 10.1177/14034948261424666. Online ahead of print.

ABSTRACT

AIMS: Overdose deaths have been increasing in parts of Europe, including Norway, where opioid analgesics have been the leading cause since 2016. This study quantifies the risk of overdose death following exposure to dispensed opioid analgesics, stratified by sex and age, and examines associated causes of death.

METHODS: Nationwide data from 2010 to 2018 on overdose deaths were obtained from the Norwegian Cause of Death Registry and linked with the Norwegian Prescription Database to identify prior opioid analgesic dispensations. Aggregated prescription data and population figures from Statistics Norway were also used.

RESULTS: From 2010 to 2018, 42% of individuals who died from an overdose had been dispensed opioid analgesics in the previous year. Among those dispensed strong opioid analgesics, the overdose death rate was low but exceeded the population death rate among men aged 20-49 and women aged 20-39 years. The rate was higher in men and remained stable over time. Opioids other than heroin or methadone were listed as the cause of death in 62% of cases with prior dispensed opioid analgesics, compared with 24% among those without.

CONCLUSIONS: The risk of overdose deaths following exposure to strong opioid analgesics was low but higher than population death rates for men under 50 and women under 40 years. Preventive strategies based on risk markers such as sex, age and opioid analgesic strengths, combined with other known risk markers, can help guide safer prescription of opioid analgesics and reduce overdose death.

PMID:41816855 | DOI:10.1177/14034948261424666

Cleft Palate Craniofac J. 2026 Mar 12:10556656261429897. doi: 10.1177/10556656261429897. Online ahead of print.

ABSTRACT

ObjectiveTo evaluate long-term effects of presurgical nasoalveolar molding (PNAM) on occlusal relationships and craniofacial development in children with unilateral cleft lip and palate (UCLP) using the 5-year-olds’ index and cone-beam computed tomography (CBCT).DesignRetrospective cohort study.SettingTertiary-level Class A specialized stomatological hospital.ParticipantsSixty-four patients with complete UCLP.InterventionsThirty patients underwent PNAM treatment, and 34 patients did not.Main Outcome MeasureCBCT scans were used to assess dental occlusion via the 5-year-old index and to measure craniofacial variables. Intergroup differences were analyzed using the Mann-Whitney U test and the chi-square test, while the correlation between occlusion and craniofacial variables was examined using the Pearson correlation coefficient. A P value of less than .05 was considered statistically significant.ResultsA comparison of 5-year-olds’ index scores in the two groups showed median scores of 3.0 (PNAM group) and 3.5 (non-PNAM group), respectively, with no significant difference found. For prognosis, no significant difference in orthognathic surgery need was found, but the PNAM group had a higher nonsurgery rate (60%) versus 50% in the non-PNAM group. In craniofacial development, the PNAM group had significantly longer maxillary length; favorable prognosis group showed smaller SNB angles, shorter mandibular body, larger ANB angles, and longer maxillary length. Correlation analysis showed 5-year-olds’ index positively correlated with SNB/mandibular body length, and negatively with ANB/maxillary length.ConclusionsEarly childhood evaluations showed that treatment with/without PNAM in the neonatal period was not a major factor influencing occlusal relationships or craniofacial development in patients with UCLP. Furthermore, correlation between 5-year-olds’ index and skeletal morphology in children with UCLP has been confirmed.

PMID:41816816 | DOI:10.1177/10556656261429897

J Cereb Blood Flow Metab. 2026 Mar 12:271678X261415784. doi: 10.1177/0271678X261415784. Online ahead of print.

ABSTRACT

We investigated dynamic changes in nicotinamide adenine dinucleotide (NAD⁺) metabolism in the human occipital lobe using ultra-high field ³¹P functional magnetic resonance spectroscopy (fMRS) at 7 T. Twenty-five healthy volunteers (mean age 24 ± 4 years, 10 females) performed a visual task alternating between fixation and flashing checkerboard stimuli. ³¹P MRS spectra were acquired from a visual cortex voxel functionally localized by prior functional magnetic resonance imaging (fMRI). Linear mixed-effects modeling revealed a significant reduction in NAD⁺ concentrations during the first stimulation block, while no significant change was observed during the second block. No significant changes were observed for other high-energy phosphate metabolites (ATP, phosphocreatine, and inorganic phosphate), indicating specificity in the NAD⁺ response. Exploratory analyses, dividing the blocks in two halves, suggested further reductions in NAD⁺ and tNAD in the second halves of both stimulation blocks, though these trends were not statistically significant. Our findings demonstrate the feasibility of using fMRS at 7 T to detect stimulus-induced dynamics in cerebral NAD⁺ metabolism in vivo, providing insights into the interplay between glycolysis and oxidative phosphorylation during neural activation.

PMID:41816808 | DOI:10.1177/0271678X261415784

Pan Afr Med J. 2025 Dec 8;52:147. doi: 10.11604/pamj.2025.52.147.43262. eCollection 2025.

ABSTRACT

INTRODUCTION: the COVID-19 pandemic had a devastating impact on society, with healthcare workers (HCWs) on the frontline bearing the brunt. As such, HCWs directly involved in the diagnosis, treatment, and care of patients with COVID-19 were at risk of developing psychological distress and other mental health symptoms. The overall aim of this study was to assess mental health symptoms among HCWs treating patients exposed to COVID-19 in Gauteng, South Africa. This research was critically important to determine the physiological burden on HCWs in response to the pandemic, so that mental health responses to the pandemic by HCWs, and psychosocial support structures in place for HCWs in South Africa can be considered.

METHODS: a cross-sectional study was conducted among frontline HCWs in the Inner City and Johannesburg South region (region F) of Gauteng, South Africa. Data was collected through both an online and an in-person approach. All participants completed a questionnaire enquiring about their socio-demographic characteristics and mental health symptoms. The presence and severity of symptoms of depression, anxiety, and insomnia of HCWs exposed to COVID-19 were assessed using the patient health questionnaire-9 (PHQ-9), the generalised anxiety disorder-7 (GAD-7), and the insomnia severity index-7 (ISI-7). Data analysis was performed using SPSS version 26.0 statistical software.

RESULTS: a total of 234 out of 260 contacted individuals completed the survey. The majority of the participants were female (n=190, 81.2%), aged between 36 and 45 years (n=79, 33.8%), were unmarried (n=105,44.9%), and had a tertiary education (n=217, 92.7%). The majority of the participants worked in the public sector (151, 64.5%), while the minority (n=83, 35.5%) worked in the private sector. A considerable proportion of HCWs reported symptoms of depression (n=102, 43.6%), anxiety (n=105, 44.9%), and insomnia (n=70, 29.9%). It was found that there were no significant differences in symptoms of depression (X²=4.8, p>0.05), anxiety (X²=0.8, p>0.05), and insomnia (X²=2.1, p>0.05) between public and private sector HCWs. The results further showed that 49.1% of the participants indicated that psychological services did exist in their place of work, and 50.9% said they did not exist. Perceptions that psychological services existed were more common among HCWs in private healthcare facilities (66.3%) than among HCWs in public healthcare facilities (39.7%). Psychosocial support systems such as mental health counselling, support groups, psychological services, and employee assistance programmes were identified as some of the key services requested by HCWs.

CONCLUSION: the prevalence of depression, anxiety, and insomnia was shown in HCWs in Gauteng, South Africa, and there were differences in perceptions of the psychosocial support systems that exist in the region between private and public sector HCWs. The results indicate that a considerable proportion of HCWs have depression, anxiety, or insomnia, with only half indicating the presence of workplace psycho-social support structures. Psycho-social support structures for HCWs need to be strengthened and made more visible.

PMID:41816780 | PMC:PMC12973459 | DOI:10.11604/pamj.2025.52.147.43262

J Vasc Bras. 2026 Feb 6;24:e20240149. doi: 10.1590/1677-5449.202401492. eCollection 2025.

ABSTRACT

BACKGROUND: Injuries to the retrohepatic vena cava are associated with high mortality rates and vascular control must be obtained prior to exposure. Various treatment techniques have been described, including triple hepatic vascular exclusion, atriocaval shunt, and endovascular and hybrid strategies.

OBJECTIVES: To determine which of these is associated with the lowest mortality rate.

METHODS: A systematic literature review was conducted, guided by the Cochrane Handbook and PRISMA guidelines. The PUBMED, LILACS, Embase, Web of science, and Scopus databases were searched and Ryyan software was employed to manage the studies identified.

RESULTS: Sixteen studies were selected, reporting 96 cases, in 49 of which the patients were treated with triple hepatic exclusion, in 38 with an atriocaval shunt, and in 9 with endovascular or hybrid techniques, with the third of these groups being statistically less frequent (p < 0.0001). The mortality rate was 53.8%, with no statistically significant differences between any of the techniques studied (p = 0.9085).

CONCLUSIONS: Injuries to the retrohepatic vena cava had similar mortality rates regardless of the technique employed for treatment.

PMID:41816770 | PMC:PMC12974593 | DOI:10.1590/1677-5449.202401492

Turk J Med Sci. 2025 Dec 28;56(1):351-363. doi: 10.55730/1300-0144.6169. eCollection 2026.

ABSTRACT

BACKGROUND/AIM: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder with high treatment costs and significant psychosocial burden. In 2021, Türkiye launched a national premarital SMA carrier screening program integrated with in vitro fertilization (IVF) with preimplantation genetic testing (PGT) services for couples identified as carriers. This study aimed to compare the costs associated with the carrier screening and prevention program versus a no-screening (treatment-only) scenario.

MATERIALS AND METHODS: A cost comparison model was developed using data from the Turkish Statistical Institute, the Ministry of Health, and the Social Security Institution. The annual costs of SMA treatment (with nusinersen and risdiplam) and the costs associated with carrier screening, genetic counseling, and IVF with PGT were compared. Projections estimated 115 new SMA cases annually based on national birth rates and carrier frequencies.

RESULTS: The total annual cost of the premarital carrier screening and prevention program was estimated at TRY 112,801,201.6 (EUR 2,418,550.6). In contrast, the treatment of 115 new cases of SMA with nusinersen would cost TRY 1,091,623,700 in the first year alone, reaching a cumulative cost of TRY 2,183,247,377 over three years. The three-year cumulative cost for risdiplam treatment was calculated as TRY 1,196,414,795. The cost of preventing the birth of one SMA-affected child through the screening program was estimated as TRY 854,554.6, whereas treatment costs per child reached as high as TRY 18,984,759.6 with nusinersen.

CONCLUSION: The SMA premarital carrier screening and prevention program in Türkiye significantly reduces healthcare expenditures and disease burden. Primary prevention through carrier screening is associated with lower overall costs than long-term treatment, offering both economic and social advantages for public health policy.

PMID:41816748 | PMC:PMC12974293 | DOI:10.55730/1300-0144.6169