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The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.

Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with ≥ 99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.

Humans

A Meta-analysis of the intervention effects of ball sports on children with autism Spectrum disorder.

PURPOSE: To evaluate the overall efficacy of ball sports interventions for children with autism spectrum disorder (ASD) and to explore potential moderators that may influence intervention outcomes. METHODS: Randomized controlled trials were retrieved from nine databases (e.g., CNKI, PubMed) from 2000 to April 2025. Meta-analysis was conducted using RevMan 5.4 and Stata 18.0, with subgroup analyses by age, duration, frequency, session length, and ball sport type. RESULTS: A total of 14 randomized controlled trials involving 406 children were ultimately included. Meta-analysis results indicated that ball sports had a significant overall intervention effect on children with ASD (SMD&#xa0;=&#xa0;-1.12, 95% CI: -1.56, -0.68, P&#xa0;<&#xa0;0.05), with significant improvements observed in social skills (SMD&#xa0;=&#xa0;-0.55), verbal communication (SMD&#xa0;=&#xa0;-0.85), and behavioral problems (SMD&#xa0;=&#xa0;-1.10). Subgroup analysis indicated that interventions involving mini-basketball or other ball sports with simple rules-conducted over a 12-week period, 3-5 times per week, for 30-60&#xa0;min per session-yielded better outcomes, with children aged 3-6&#xa0;years showing more consistent benefits. CONCLUSION: Ball-based interventions effectively alleviate core ASD symptoms. Structured moderate-intensity programs are recommended as adjunct therapies. Future studies should standardize protocols and examine long-term benefits.

Humans

Artificial intelligence (AI) uses in stereotactic radiosurgery (SRS): diagnosis with brain metastasis (BM) - A systematic review.

BACKGROUND: Brain metastases (BM) are the most common intracranial tumors in adults, and stereotactic radiosurgery (SRS) has become a mainstay of management. However, several diagnostic challenges persist in the SRS pathway, particularly the differentiation of radiation necrosis (RN) from true tumor progression, which conventional MRI and even advanced imaging techniques often cannot reliably resolve. Recent advances in artificial intelligence (AI) offer the potential to address these diagnostic limitations. This systematic review synthesizes current literature on AI applications for MRI-based diagnostic decision support in BM patients undergoing SRS, with a focus on radiomics and deep learning tools for distinguishing RN from progression, classifying molecular and histologic subtypes, and predicting treatment response. METHODS: A systematic review was performed in accordance with PRISMA guidelines. PubMed, Web of Science, and Scopus were searched using a targeted query combining terms related to AI, brain metastasis, diagnosis or imaging, and SRS. After screening 483 records and applying strict inclusion and exclusion criteria, 18 studies published between 2015 and 2025 were included. Data were extracted on study design, cohort characteristics, imaging modality, AI methodology, validation strategy, and reported diagnostic performance. RESULTS: Among the 18 included studies, AI models demonstrated strong performance across diagnostic tasks in the BM-SRS pathway. The differentiation of RN from true tumor progression was the most extensively studied application, addressed by 14 of 18 studies, with reported AUCs ranging from 0.71 to 0.94. Support vector machines, random-forest ensembles, convolutional neural networks, and transformer-based multimodal architectures were widely used. The literature evolved from single-sequence radiomic classifiers in 2018 to multimodal deep learning frameworks fusing imaging with clinical and genomic data in 2025. Contrast-enhanced T1-weighted MRI was the dominant imaging input, and texture-based radiomic features (GLCM, GLSZM, GLDM, and wavelet-derived features) were the most consistently predictive. The highest-performing models reached AUCs of 0.85-0.91 through multimodal integration of imaging with clinical and genomic features, and consistently outperformed expert neuroradiologist read on matched cases. Remaining studies addressed longitudinal segmentation-based detection of local failure and adverse radiation effects, BRAF mutation status in melanoma BM, early Gamma Knife treatment response, and primary tumor histology classification, with more variable performance. CONCLUSION: AI models, particularly those integrating MRI-derived radiomic features with clinical and genomic data, show high accuracy in supporting diagnostic decisions for BM patients treated with SRS. The post-SRS differentiation of radiation necrosis from true tumor progression has reached the greatest level of maturity and is closest to clinical translation, with potential to reduce unnecessary biopsies, personalize surveillance intervals, and rationalize treatment-pathway decisions. Other diagnostic applications, including molecular subtyping and primary tumor histology classification, remain exploratory and require further multicenter validation. Integration of AI tools into multidisciplinary tumor-board workflows, combined with prospective validation and standardized reporting, will be essential to realize the full clinical benefits of AI in SRS for brain metastases.

Humans

Electrospun Nanofiber Dressings for Diabetic Wounds: From Single-Layer to Intelligent Composite Systems.

Diabetic chronic wounds have become a major challenge for clinical treatment due to their complex pathological microenvironment, including persistent inflammatory response, angiogenesis disorder, excessive oxidative stress, and susceptible infection. Traditional dressings as a passive barrier have difficulty meeting the above multiple treatment needs. Electrospinning technology, with its ability to mimic the fibrous network structure of the natural extracellular matrix (ECM), offers a high specific surface area, controllable porosity, and excellent drug-loading capacity, making it an ideal platform for developing a new generation of multifunctional wound dressings. This article provides a systematic review of the research progress on electrospun nanofiber dressings in the treatment of diabetic wounds, focusing on the design evolution from basic single-layer structures to advanced complex structures and elucidating the mechanisms of action and quantifiable effects of each structural type in addressing specific pathological challenges. We also compared the current status of clinical translation for electrospun dressings with that of other advanced wound care platforms and proposed a standardized preclinical evaluation framework. A large number of research data show that these advanced designs can effectively improve the quality of healing. Finally, this paper points out the challenges faced by this field, such as scalable fabrication, in vivo reliability of smart systems, and long-term biosafety, and provides theoretical basis and technical reference for the design of efficient and intelligent electrostatic spinning diabetic wound dressings.

Nanofibers

Intentions to use different modalities of long-acting HIV PrEP among men who have sex with men and transgender and gender diverse persons in the Netherlands.

Insight into intentions to use long-acting HIV pre-exposure prophylaxis (PrEP) is essential for successful implementation. We assessed intention to use three hypothetical long-acting PrEP modalities (oral, intramuscular and subdermal) among HIV-negative men who have sex with men (MSM) and transgender and gender diverse persons in Amsterdam, recruited through the Amsterdam Cohort Studies (ACS-participants) and social media (survey-participants). Intention was measured per modality using a 7-point Likert scale. We modeled the probability of high intention to use long-acting PrEP using relative risk regression. Of 1258 participants [1231 (97.9%) MSM; 557 ACS and 701 survey; median age 40 years (IQR 32-50)], 76% had ever used oral short-acting PrEP. Intention to use was highest for monthly oral long-acting PrEP [ACS: median 4.5 (IQR 2-6), 38% high intention; survey: median 7 (IQR 6-7), 81% high intention], followed by 2-monthly intramuscular PrEP [ACS: median 3 (IQR 2-5), 19% high intention; survey: median 5 (IQR 3-7), 47% high intention], and implants [ACS: median 2 (IQR 1-4), 9% high intention; survey: median 4 (IQR 2-7), 37% high intention]. PrEP-experienced participants had higher intention to use oral long-acting PrEP and injectables than PrEP-na&#xef;ve participants. Offering multiple PrEP modalities may improve the acceptability of HIV prevention strategies and increase PrEP uptake and retention in PrEP care.

Humans

Sutimlimab for cold agglutinin disease: an updated perspective from approval to real-world clinical treatment.

INTRODUCTION: Sutimlimab, a classical complement pathway (CP) inhibitor, was approved in 2022 in the US, EU, and Japan for the treatment of cold agglutinin disease (CAD), a rare form of autoimmune hemolytic anemia (AIHA) characterized by CP&#x2011;mediated extravascular hemolysis and circulatory symptoms related to IgM&#x2011;mediated red blood cell (RBC) agglutination. This review reexamines the clinical trial data and compares those findings with published real&#x2011;world experience (RWE), providing clinicians with efficacy and safety data that extend beyond the clinical trial experience in this rare AIHA. AREAS COVERED: The first-in-human trials, the two seminal clinical trials (CARDINAL and CADENZA), and the published post&#x2011;marketing RWE are presented. Literature searches for CAD and sutimlimab were conducted in PubMed and in abstracts from ASH and EHA from 2016 to present. All articles and abstracts regarding sutimlimab and CAD were included. EXPERT OPINION: Long-term data from clinical trials and published RWE support the safety and efficacy of sutimlimab. Targeting the CP as primary therapy for CAD offers a unique, targeted management strategy that minimizes exposure to immunosuppressive regimens. The rapid onset of sutimlimab's activity provides a potentially lifesaving treatment option in situations where immediate control of hemolysis is critical. Opportunities remain to increase our understanding of the role of complement inhibition combined with immunosuppressive therapy in CAD. The impact of complement inhibition on morbidity and mortality in CAD remains to be determined.

Humans

Does Timing Matter? Age of First Mobile Phone Acquisition and Psychological Outcomes in Middle and Late Adolescence.

The age at which adolescents acquire their first smartphone has decreased markedly in recent years; however, evidence on its long-term effects on psychosocial adjustment remains limited. This study investigated whether age at first mobile phone acquisition is associated with psychosocial functioning in middle and late adolescence, including social integration and competence, emotion regulation difficulties, disordered eating behaviors and problematic social media use (PSMU). The sample comprised 1179 adolescents aged 15-17 years (53.8% female). Linear regression and generalized additive mixed models were used to examine both linear and nonlinear associations, adjusting for age, gender and school clustering. Earlier smartphone acquisition was linearly but weakly associated with greater emotion regulation difficulties, disordered eating and PSMU, even after adjustment for covariates. In contrast, associations with social integration and competence were nonlinear: acquiring a first smartphone between ages 6 and 10 or after age 13 was associated with lower social integration in adolescence, whereas acquisition between ages 11 and 13 was linked to higher social functioning. These findings suggest that the developmental timing of first smartphone access shows a modest association with subsequent psychosocial functioning during middle and late adolescence. Focusing on the timing of access, alongside other demographic and contextual factors, may contribute to a better understanding of digital influences on adolescent well-being.

Humans

Discrepancies in CPAK classification between CT and long-leg radiography: a systematic review and meta-analysis.

OBJECTIVE: To determine whether substantial differences in coronal plane alignment of the knee phenotype distribution, as well as systematic angular measurement discrepancies, exist between CT and long-leg radiography. MATERIALS AND METHODS: From February 2021 to April 2025, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies comparing CT- and long-leg radiography-derived coronal plane alignment classifications of the knee in patients with osteoarthritis. The primary outcome was distribution of coronal plane alignment phenotypes. Secondary outcomes included differences in medial proximal tibial angle, lateral distal femoral angle, arithmetic hip-knee-ankle angle, and joint line obliquity. RESULTS: Four studies (1,134 knees) were included. Compared with long-leg radiography-derived classification, CT-derived classification increased type I phenotypes (risk difference: 0.10; 95% confidence interval: 0.01-0.20; P&#x2009;=&#x2009;0.040) and decreased type III (risk difference: -0.04; 95% confidence interval: -0.07 to -0.01; P&#x2009;=&#x2009;0.020) and type V phenotypes (risk difference: -0.04; 95% confidence interval: -0.07 to -0.01; P&#x2009;=&#x2009;0.004). CT yielded significantly lower medial proximal tibial angle (weighted mean difference:&#x2009;-&#x2009;1.18&#xb0;; P&#x2009;<&#x2009;0.001), arithmetic hip-knee-ankle angle (weighted mean difference:&#x2009;-&#x2009;0.95&#xb0;; P&#x2009;<&#x2009;0.001), and joint line obliquity (weighted mean difference:&#x2009;-&#x2009;1.40&#xb0;; P&#x2009;<&#x2009;0.001) than long-leg radiography. Heterogeneity was high for type I phenotype (I2&#x2009;=&#x2009;81%), lateral distal femoral angle (I2&#x2009;=&#x2009;70%), and joint line obliquity (I2&#x2009;=&#x2009;69%). CONCLUSION: Discrepancies between CT-based software-generated and long-leg radiography-derived measurements substantially affect coronal plane alignment classification and angular parameters. Surgeons should consider these modality-specific variations and employ compensatory verification strategies to ensure optimal alignment.

Humans

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

OBJECTIVES: To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures. MATERIALS AND METHODS: Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5&#x2009;&#xb1;&#x2009;7.7 years; 17 men); 30 completed the MRI extension at 1.5&#x2009;T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs). RESULTS: PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p&#x2009;<&#x2009;0.05). PWV decreased after multiple doses (-0.87&#x2009;m/s, 95% CI: -1.26 to -0.48&#x2009;m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (&#x3c1;&#x2009;=&#x2009;0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and &#xb9;&#xb2;&#x2079;Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. CONCLUSION: PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. KEY POINTS: Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized &#xb9;&#xb2;&#x2079;Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Humans

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans

Feasibility of Prone Positioning in Patients With Obesity and Acute Respiratory Distress Syndrome.

BACKGROUND: Prone positioning in patients with obesity remains uncommon because of concerns about feasibility, safety, and efficacy. OBJECTIVE: To evaluate the feasibility, safety, and clinical outcomes of manual prone positioning in patients with acute respiratory distress syndrome (ARDS) across different classes of obesity. METHODS: This was a retrospective cohort study involving patients with ARDS who underwent manual prone positioning across 15 hospitals between April 2014 and July 2024. Patients were stratified into 5 groups based on body mass index. Standardized prone positioning protocols were followed across institutions. RESULTS: A total of 1448 patients with ARDS underwent prone positioning. Across all obesity categories, prone positioning was associated with shorter intensive care unit and hospital stays, improved oxygenation, and better clinical outcomes. Notably, patients with class III obesity showed the greatest increase in gas exchange efficiency, with a 37% improvement in ratio of Pao2 to fraction of inspired oxygen, compared with 28% in patients with normal weight (P < .05). Complication rates were low across all groups. CONCLUSIONS: Prone positioning is feasible and safe in patients with ARDS across all obesity classes. Patients with class III obesity showed the greatest improvements in oxygenation. Future prospective studies should further explore the long-term impact of prone positioning in patients with class III obesity to refine clinical guidelines and optimize care.

Humans

Differences in Radiological Risk Perceptions Following Online and In-Person Workshops.

Nuclear energy is widely regarded as a critical part of the pathway toward a secure, low-carbon electricity grid, yet long-term management of used nuclear fuel remains a persistent challenge. Although technically viable options for interim and consolidated storage exist, public concern and community opposition - rooted in historical distrust and risk perception - continue to complicate siting decisions. In response, recent federal efforts have emphasized collaboration-based approaches and community engagement, though empirical evidence on the effectiveness of different engagement strategies remains limited. This study examines how the structure and delivery of community engagement influence changes in public attitudes toward hosting interim used nuclear fuel storage facilities. Using survey data from 13 educational workshops around the United States, we evaluate: (1) the inclusion of trust-building content prior to technical content, and (2) engagement format, comparing online and in-person workshops. Analyses focus on participant changes in perceptions of safety, risk, and support for hosting, using the Wilcoxon rank-sum test and other non-parametric hypothesis tests on surveys conducted before and after workshops. Results indicate that workshop participation is associated with some measurable attitude changes, with significant (p < 0.05) differences in response variability for some questions across workshop formats. In particular, when comparing nuclear energy to other clean energy sources, in-person workshop participants are substantially more likely to gain a more favorable opinion of nuclear energy than online participants. These findings contribute empirical evidence on how trust-building and delivery mode shape outcomes in public engagement on complex and contested energy policy issues such as storage of used nuclear fuel.

nuclear fuel cycle

Empathic Accuracy and Behavioral Empathy After a Moderate Dose of Beer.

OBJECTIVES: Empathic accuracy (EA) represents a person's ability to correctly infer the emotions of another person. One past study in men found lower EA for positive emotions after a moderate dose of hard liquor compared to after placebo, particularly among non-hazardous drinkers. The present study aimed to replicate this finding, using a moderate dose of beer and a mixed design. Moreover, we added a novel measure of behavioral empathy. METHODS: Participants (62% men) completed the Alcohol Use Disorders Identification Test, Empathy Quotient, and Revised Drinking Motives Questionnaire. Before and after drinking either beer (6.6% alcohol, n&#xa0;=&#xa0;28) or its 0.0% equivalent (placebo, n&#xa0;=&#xa0;38), they watched videoclips of targets talking about emotional autobiographical events and rated how targets felt while talking. Behavioral empathy was assessed by presenting participants with painful scenarios and asking whether they would help the people in pain. RESULTS: The previous finding of lower EA for positive emotions after alcohol was not replicated. Nonetheless, after alcohol non-hazardous drinkers were less willing to help people in pain. Trait affective empathy (i.e., a person's long-term disposition to experience emotional responses congruent to another's feelings) and the drinking to cope motive did not significantly moderate the findings. CONCLUSIONS: Although alcohol may alter empathy, its effects are not consistent and may depend on the dose and type of alcohol consumed. The moderating roles of trait empathy and trait aggressivity deserves further study.

Humans

Marine air promotes structural compaction and coating growth of soot aerosols after long-range transport from East Asia.

Soot aerosol, a key global warming contributor, undergoes morphological and chemical transformations during atmospheric transport, particularly in humidified marine environments. This study investigates morphology, mixing state, and aging mechanisms of soot particles collected in the Bohai Sea and Yellow Sea. Transmission electron microscopy analyses reveal that coated soot particles dominate the marine atmosphere, accounting for over 98 % of soot-containing particles, with a mean mixing state index (&#x3c7;) of 0.83. The fractal dimension (Df) of soot particles is 1.84 &#xb1; 0.05 in the Northern Yellow Sea, 1.90 &#xb1; 0.08 in the Bohai Sea, and 1.96 &#xb1; 0.07 in the Southern Yellow Sea, indicating structural compaction during long-range transport. Correspondingly, the average Dp/Dcore ratios (particle to core size ratio) are 5.3 in the Bohai Sea, 4.2 in the Northern Yellow Sea, and 3.9 in the Southern Yellow Sea. Notably, those ratios are higher in marine environments compared to those observed during continental regional transport from northern to southern China (3.54), suggesting enhanced coating growth in humid marine air. The results highlight the important role of marine atmospheres in accelerating soot aging, which in turn leads to significantly stronger light absorption compared to soot in continental air. Our results highlight the necessity of incorporating compact morphologies, uniform mixing states, and thick coatings into optical models for accurate radiative forcing simulations.

Aerosols

Insights into the regulation of the HOTAIR proximal promoter.

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

Humans

The Incidence of Suicide Following Metabolic and Bariatric Surgery: A Prognosis Systematic Review and Meta-Analysis of Longitudinal Studies.

BACKGROUND: Metabolic and bariatric surgery (MBS) effectively manages severe obesity but may lead to psychological complications such as completed suicides and suicide attempts. This review aimed to analyze suicide and self-harm incidence post-MBS. METHODS: We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library databases on August 16, 2022, for longitudinal studies with incidence data on suicide following MBS. We performed a single proportion meta-analysis on the incidence of outcomes and assessed the certainty of evidence using the GRADE approach. The review was registered with PROSPERO (CRD42022352137). RESULTS: Eighty-four studies were included. The meta-analysis showed an incidence of 230.64 suicides per 100,000 participants (95% CI: 167.51 to 317.49) in pooled individual-level data and an incidence of 43.02 suicides per 100,000 person-years (95% CI: 32.49 to 56.97) in pooled person-year data. Evidence was low certainty or very low certainty. CONCLUSIONS: The average suicide incidence (231 per 100,000 people) in people with obesity who underwent MBS significantly exceeded the 2019 WHO global estimate for the general population (nine per 100,000 people). These findings underscore the need to incorporate structured psychological screening and follow-up into the perioperative management process of MBS, as patient mental health may play a pivotal role in postoperative adherence and long-term outcomes.

Humans

Willingness to switch to long-acting regimens among people with HIV: a systematic review and meta-analysis.

OBJECTIVES: Long-acting regimens (LARs) offer promising alternatives for people with HIV, enhancing autonomy and convenience. Understanding preferences for LAR is essential to guide policy and implementation. DESIGN: This systematic review and meta-analysis examined willingness among adults with HIV to switch from daily oral antiretroviral therapy (ART) to LAR. METHODS: Following PRISMA guidelines, we included studies of adults with HIV using daily oral ART reporting willingness to switch to existing or hypothetical LAR. The primary outcome was the proportion willing to switch. Articles were searched in PubMed and Embase up to October 2024. Risk of bias was assessed using the RoB-PrevMH tool. A random-effects meta-analysis with a generalized linear mixed model synthesized willingness for LAR. Subgroup analyses explored heterogeneity. Alternative LAR were summarized descriptively. RESULTS: Searches identified 2038 records, of which 22 studies were included. Most studies were conducted in Europe or North America (96%). Willingness to switch to any LAR was 70% [95% confidence interval (95% CI): 59-79; I2 &#x200a;=&#x200a;97.9%]. Furthermore, two-monthly intramuscular injections were the most frequently investigated LAR, with a pooled willingness of 60% (95%CI: 42-76; I2 &#x200a;=&#x200a;97.5%). No study-level characteristics explained heterogeneity. Limited studies investigated willingness for alternative LAR. CONCLUSION: The majority of people with HIV expressed willingness to switch to LAR, with two-monthly intramuscular injections being the most commonly investigated formulation. Substantial heterogeneity persisted, suggesting that LAR preferences are highly context dependent. Evidence on alternative LAR, including tablets, implants and intravenous infusions, is limited. Low and middle-income countries were underrepresented, highlighting the need for geographically diverse research to better understand context-specific preferences and thereby inform treatment policy.

Humans

Direct Initiation of Long-Acting Cabotegravir Plus Rilpivirine in People with HIV and Suboptimal Virologic Suppression: A Randomized Trial.

BACKGROUND: Long-acting injectable cabotegravir plus rilpivirine (LA CAB+RPV) is approved for virally suppressed people with human immunodeficiency virus (HIV), but evidence for its use in those with persistent viremia and adherence challenges remains limited. METHODS: We conducted a multicenter, open-label, randomized study involving oral antiretroviral therapy (ART)-experienced people with HIV who had been diagnosed with HIV for at least 12 months and a most recent HIV-1 RNA level of at least 200 copies per milliliter. Participants with resistance-associated mutations to CAB or RPV were excluded. Eligible participants were randomly assigned in a 1:1 ratio to receive immediate LA CAB+RPV or to continue standard oral therapy until Week 24 (delayed switch group). The primary endpoint was the proportion of participants with an HIV-1 RNA level of less than 200 copies per milliliter at Week 24. RESULTS: Of 61 randomized participants, 45 met eligibility criteria and were included in the analysis; 91% were male, and the median baseline HIV-1 RNA was 35,000 copies/mL. At Week 24, viral suppression was achieved in 88.0% (22/25) in the immediate LA group versus 55.0% (11/20) in the delayed switch group (relative risk for failure to achieve viral suppression, 0.27; 95% CI, 0.08-0.86; p = 0.026). The effect of LA CAB+RPV was sustained through Week 52. CONCLUSIONS: Among people with HIV and viremia associated with adherence challenges, immediate initiation of LA CAB+RPV resulted in higher rates of viral suppression than continued oral ART, supporting its use beyond populations with stable suppression.

HIV