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PubMed2026

Type, severity, frequency and management of adverse reactions associated with ultrasound contrast agents: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis are aimed at evaluating the incidence of adverse drug reactions (ADRs) following administration of clinically approved ultrasound contrast agents (UCAs) in adults and children, to assess risks in patients with cardiovascular disease and in pregnancy, and to evaluate the effectiveness of emergency management of severe ADRs. MATERIALS AND METHODS: A PRISMA 2020 systematic review was conducted searching PubMed, Scopus, and Embase. Two reviewers independently screened, extracted data, and assessed quality. Incidence estimates were pooled when feasible, stratified by age group, contrast agent, and administration route. RESULTS: Seventy-four studies encompassing > 1 million adults and > 36,000 children were included, contributing multiple analytic cohorts to the quantitative synthesis. Severe acute ADRs were extremely rare (6 and 16 cases per 100,000 in adults and children, respectively) and absent following endocavitary administration in children. Non-severe acute ADRs occurred in 11 and 8 cases per 10,000 adults and children, respectively. Delayed reactions were very rare (< 1 case per million in adults). No significant safety differences emerged between UCA products. The incidence of ADRs in patients with cardiovascular disease was analogous to the general population. No ADRs were reported in pregnant women. Standard emergency management was effective in almost all serious cases, though rare fatalities occurred. CONCLUSION: UCAs show an excellent safety profile in adults and children, with very rare severe ADRs and few non-severe, typically self-limiting reactions. Strict adherence to recommended emergency management protocols mitigates the remaining risks, supporting safe use across a broad range of clinical indications. PROSPERO REGISTRATION: CRD42023432668. KEY POINTS: Question What is the incidence, type, and severity of acute and delayed ADRs associated with clinically approved UCAs across different patient populations? Findings Severe acute adverse reactions are very rare, and non-severe reactions are rare and self-limiting, with no significant safety differences between adults, children, or patients with cardiovascular disease. Clinical relevant UCAs show an excellent safety profile across populations. These findings support their safe clinical use as reliable alternatives to iodine-based and gadolinium-based contrast agents in routine diagnostic imaging.

Contrast Media↗

PubMed2026

What's the meta now? More updates on the problems with systematic reviews.

BACKGROUND: Systematic reviews are intended to provide trustworthy evidence synthesis, yet previous iterations of this living review have identified numerous recurring problems in their conduct and reporting. This article presents the third version and second update of the living systematic review examining issues raised across the academic literature. METHODS: Using consistent eligibility criteria and methods from earlier versions, literature searches were updated to May 2025. Eligible meta-research and editorial articles describing problems with systematic reviews were analyzed to identify emerging themes. Additionally, four basic indicators of methodological quality of the included meta-research were presented across review versions. RESULTS: The update included 209 additional articles. Critically low methodological quality and absence of protocols remained among the most frequently reported issues in systematic reviews across disciplines and journals but notably in evidence underpinning clinical practice guidelines. Spin in abstracts and conflicts of interest continued to be common. Apparent improvements in reporting quality were inconsistent, with modest gains in some full-text reporting but persistent deficiencies in abstracts. Authorship diversity of systematic reviews improved in gender representation but remained geographically concentrated in high-income countries, and primary research included in reviews similarly lacked global representativeness. The issue of misalignment between systematic review evidence bases and global burden of disease bring the total number of problems with systematic reviews to 69. Emerging use of automation and artificial intelligence was variably reported. Descriptive comparison of meta-research articles over the three versions of this living review suggests a greater proportion meeting basic quality indicators in more recent updates. CONCLUSION: Across successive updates, problems with systematic reviews remain widespread and consistent rather than isolated. Incremental reporting improvements coexist with persistent concerns about transparency, bias, and representativeness. Future efforts should prioritize evaluating interventions and aligning research incentives to support genuinely trustworthy evidence synthesis.

Humans↗

PubMed2026

Infra-low-frequency neurofeedback alters EEG network efficiency: exploratory evidence from healthy volunteers.

Infra-Low-Frequency Neurofeedback (ILF-NFB) combines classic frequency-band (FB) and infra-low-frequency (ILF) EEG components in implicit training protocols and is increasingly applied in clinical contexts. Yet, the neurophysiological mechanisms underlying ILF-NFB remain to be further elucidated. In this randomized, sham-controlled and double-blind study, we explored the online impact of a one-session ILF-NFB application on EEG correlates in healthy participants (39 analyzed datasets). Continuous 31-channel EEG was recorded during verum and sham feedback in a double-blind, randomized crossover design. In this exploratory analysis approach, functional connectivity was estimated using the debiased weighted phase-lag index (dwPLI) and analyzed with graph-theoretical measures. The results revealed higher global efficiency during verum compared to sham in the Beta1 band (12-15 Hz), reaching significance in the primary comparison but not surviving Bonferroni correction across the five tested bands; block-wise follow-ups showed a significant verum-sham difference in the first half of the neurofeedback session and a directionally consistent pattern in the second half. The Condition × Block interaction was not significant. No consistent differences were observed in other frequency bands, nor for betweenness centrality. While preliminary, these exploratory results point to possible network-level effects during ILF-NFB and motivate further confirmatory work in extended training protocols and clinical populations.

Humans↗

PubMed2026

Integration of ear and hearing care services in low- and middle-income health systems: a systematic review and qualitative synthesis.

Hearing loss is a global public health burden and mostly affects those living in low- and middle-income countries (LMICs). One approach to address ongoing challenges is the World Health Organization's recommendation for the integration of ear and hearing care (EHC) services into healthcare packages. However, little is known about EHC integration approaches, particularly in LMICs additionally, these approaches have not been investigated through a health systems lens. This qualitative review aimed to describe the various approaches to the EHC service integration in LMICs and to identify enabling and constraining factors. We reviewed 17 studies, with a focus on LMICs, using adaptations of the Valentijn integration and World Health Organization EHC frameworks, following the PRISMA guidelines. Our investigation showed that most integration approaches were at micro or individual level. Enabling factors for integration of EHC services were training, mentorship, collaboration, technology, inclusion of EHC in healthcare packages and investment in EHC services. Barriers were challenges with training, facilities and equipment, policy implementation and resourcing of EHC services. We further described factors influencing healthcare seeking behaviour and the use of integrated EHC services, such as access and ability to pay, referral systems and communication and awareness. This study describes the complex nature of EHC integration and ways to support integration. Key considerations are the level of integration, training to address workforce issues and factors influencing service utilisation as we work towards health system strengthening.

Humans↗

PubMed2026

Medication safety in older adults in India: an integrative PhD synthesis of direct evidence and contextual implementation evidence.

BACKGROUND: Unsafe medication practices among older adults are an important global health concern, particularly in low- and middle-income countries where multimorbidity, fragmented care, self-medication, and informal healthcare provision intersect. OBJECTIVE(S): To synthesize direct evidence on medication safety among older adults in India and contextual evidence on deprescribing and community-level provider interventions relevant to safer medication use. METHODS: This PhD synthesis integrates four studies: a record-based cross-sectional study on polypharmacy and cardiovascular autonomic function in Kolkata; a six-city community study of 600 Indian older adults; a systematic review and meta-analysis on deprescribing preventive medications in frail or end-of-life older adults; and a systematic review of informal healthcare provider interventions in low- and middle-income countries. Studies I-II provided direct Indian older-adult evidence, while Studies III-IV provided indirect contextual evidence for their optimization and implementation. RESULTS: Polypharmacy was associated with higher anticholinergic burden and numerically higher cardiac autonomic neuropathy although residual confounding limits causal interpretation. In the multicity study, one-third had polypharmacy, while potentially inappropriate medications, prescribing omissions, and self-medication were common. Risks were higher with multimorbidity, recent hospitalization, care transitions, or living alone. Deprescribing showed no statistically significant increase in mortality, hospitalization, or major cardiovascular events, but heterogeneity was high and certainty low to very low. Informal-provider interventions showed the potential to improve knowledge, referral, case management, and medication-related practices. CONCLUSIONS: Medication safety among older adults in India requires an integrated continuum approach, but direct evidence supports only some components and implementation strategies that need prospective evaluation.

Humans↗

PubMed2026

Early mobilization within 24 to 48 h improves postoperative clinical outcomes in older adults with hip fracture: A systematic review and meta-analysis.

BACKGROUND: Hip fracture is a major public health concern among older adults, often resulting in prolonged disability, institutionalization, and increased healthcare burden. Early mobilization has been widely recommended to enhance postoperative recovery; however, there is a lack of consolidated evidence quantifying its impact on clinical and functional outcomes. This study aimed to synthesize and evaluate the impact of early mobilization following hip fracture surgery in older adults and to explore potential sources of heterogeneity to better inform clinical and nursing practice. METHODS: A comprehensive literature search was conducted across seven databases (PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Emcare) from inception to June 15, 2025. Eligible studies included randomized controlled trials and observational cohort studies comparing early mobilization (defined as ambulation within 24 to 48 h postoperatively) to delayed or usual mobilization in patients undergoing hip fracture surgery. Primary outcomes included mortality, discharge destination, and length of hospital stay. Secondary outcomes included postoperative complications, functional recovery, and readmission. Risk of bias was assessed using funnel plots and Egger's test. RESULTS: Twenty-six studies involving 297,435 patients were included. Compared with delayed mobilization, early mobilization significantly reduced 30-day mortality (relative risk = 0.40, 95% confidence interval: 0.25-0.64) and 1-year mortality (relative risk = 0.57, 95% confidence interval: 0.40-0.80) (both p < 0.05). In regional analyses of pooled mortality, similar reductions were observed across Asia-Pacific, North America, and Europe. Patients receiving early mobilization were more likely to be discharged home and had shorter hospital stays. Early mobilization also resulted in a reduced risk of postoperative complications (relative risk = 0.79, 95% confidence interval: 0.74-0.84, p < 0.05), with specific improvements in pneumonia and thromboembolism rates. Functional independence was significantly improved, as shown by higher Barthel Index scores and increased odds of achieving Functional Independence Measure ≥5 at discharge. No significant difference was observed in readmission rates. CONCLUSIONS: lization within 24 to 48 h following hip fracture surgery was associated with favorable outcomes, including reduced mortality, improved functional independence, higher rates of discharge to home, shorter hospital length of stay, and fewer postoperative complications. Although heterogeneity across studies and the predominance of observational evidence warrant cautious interpretation, these findings support current recommendations for early mobilization and highight the potential value of structured and standardized mobilization protocols in routine postoperative hip fracture care.

Humans↗

PubMed2026

Sex-stratified mortality trends in preterm birth complications in Sierra Leone: progress, persistence, and equity implications.

BACKGROUND: Preterm birth complications remain a leading cause of neonatal mortality in Sierra Leone, despite recent health system gains. Evidence on long-term sex-specific disparities in mortality due to preterm birth complications is limited, constraining equitable neonatal care planning. OBJECTIVE: To examine two‑decade trends in sex‑stratified mortality from preterm birth complications using standardized equity indicators. METHODS: We conducted a retrospective longitudinal analysis of sex-disaggregated mortality estimates from the World Health Organization (WHO) Global Health Estimates (GHE), accessed through the WHO Health Equity Assessment Toolkit (HEAT), Built-in Database Edition (Version 6.0). Mortality rates per 100,000 population were extracted for 2001, 2006, 2011, 2016, and 2021. Inequality was assessed using absolute difference (D), relative ratio (R), population attributable risk (PAR), and population attributable fraction (PAF). RESULTS: Mortality declined substantially between 2001 and 2021 for both males (85.1-49.3 per 100,000) and females (71.2-39.9 per 100,000). Male mortality remained consistently higher across all years, with relative ratios indicating approximately 20-25% excess mortality among male neonates. Absolute inequalities narrowed modestly over time, whereas relative inequalities remained largely unchanged. PAR and PAF remained close to zero throughout the study period. Wider uncertainty intervals in earlier years reflected limited empirical data availability. CONCLUSION: Although preterm mortality declined over two decades, a persistent male disadvantage remained in Sierra Leone. These findings highlight the importance of integrating sex-disaggregated equity monitoring into neonatal policies and programmes. Future research should evaluate strategies to reduce the persistent excess mortality among male neonates while sustaining overall improvements in neonatal survival and progress toward Sustainable Development Goal 3.2.

Humans↗

PubMed2026

Ultra-high-frequency ECG quantifies residual electrical dyssynchrony during left bundle branch area pacing in patients with wide QRS: a paired within-patient study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may restore a more physiological pattern of ventricular activation in patients with conduction delay; however, QRS narrowing alone may incompletely characterize electrical resynchronization. Ultra-high-frequency ECG (UHF-ECG) provides quantitative markers of ventricular activation timing and dyssynchrony. OBJECTIVE: To quantify paired OFF-to-ON changes in conventional ECG and UHF-ECG metrics during LBBAP in patients with baseline wide QRS and to assess the relationship between paced R-wave peak time (RWPT) and residual UHF-ECG dyssynchrony. METHODS: In this prospective single-center paired study, 21 patients with bradycardia and baseline wide QRS underwent standard ECG and UHF-ECG assessment during intrinsic rhythm (pacing OFF) and during LBBAP (pacing ON). Endpoints included QRS duration, signed VED16, absolute VED16 (|VED16|), mean ventricular delay (meanVD), and a clinically interpretable distance-to-normal metric defined as dist = max(|VED16|-20, 0). Paired changes were summarized as medians with bootstrap 95% confidence intervals and tested using the Wilcoxon signed-rank test. Associations between paced RWPT and residual dyssynchrony during pacing were evaluated using Pearson and Spearman correlation coefficients. RESULTS: LBBAP significantly narrowed QRS duration from 136.8 [130.2-153.6] ms during intrinsic rhythm to 116.0 [107.8-125.6] ms during pacing (median Δ -21.0 ms; 95% CI -33.9 to -18.6; p < 0.001). Signed VED16 did not change significantly (median Δ 0.4 ms; p = 1.000), consistent with the mixed conduction-phenotype composition of the cohort. In contrast, severity-oriented UHF-ECG endpoints improved: |VED16| decreased numerically (median Δ -5.2 ms; p = 0.070), whereas dist decreased significantly (median Δ -0.7 ms; 95% CI -14.4 to 0.0; p = 0.015). The proportion of patients within the normal dyssynchrony band (|VED16| ≤ 20 ms) increased from 7/21 (33.3%) to 12/21 (57.1%). Median paced RWPT was 66.6 [58.6-74.6] ms, and shorter RWPT correlated with lower residual |VED16| during pacing (Pearson r = -0.45, p = 0.038). CONCLUSIONS: In patients with baseline wide QRS, LBBAP produces marked QRS narrowing, whereas UHF-ECG provides complementary quantification of residual electrical dyssynchrony. Severity-oriented UHF-ECG endpoints, particularly a distance-to-normal metric, may offer an interpretable mechanistic framework beyond conventional ECG alone. Shorter paced RWPT was associated with lower residual dyssynchrony during pacing, supporting physiological coherence between procedural and high-resolution electrocardiographic markers.

Humans↗

PubMed2026

Access to maternity services for women asylum seekers and refugees: A transnational document analysis of international, European regional, and United Kingdom governance.

Women asylum seekers and refugees face persistent barriers to maternity care (antenatal, intrapartum and postnatal care) across high-income countries, yet the upstream governance shaping access remains under-examined. Although legally distinct, both groups share protection-seeking experiences and are addressed jointly in governance documents. This study examined and synthesised how international (macro), European regional (meso), and United Kingdom (UK, micro) governance documents frame and operationalise maternity service access. Sixty-four documents were analysed using the READ framework. Inductive analysis of macro and meso documents identified six access dimensions: universal coverage; cultural and linguistic adaptation; rights-based approaches; multi-agency collaboration; data, monitoring and accountability; and quality of care. These dimensions structured assessment of UK governance, with jurisdictions rated strong, moderate or weak. Alignment was fragmented: Wales, Scotland and Northern Ireland exempted asylum seekers from charging, whereas England retained charging provisions. Multi-agency collaboration was consistently articulated, yet none of the 35 UK government documents focused on maternity access for this population, and none required outcome monitoring disaggregated by asylum or refugee status. UK governance appears coordinated in form but fragmented in substance. UK-wide minimum standards and routine recording of these data, with safeguards against immigration-related use, could strengthen coherence and accountability and improve visibility of inequities.

Refugees↗

PubMed2026

Vitamin B12 Deficiency in Sickle Cell Disease: Method-Driven Estimates and Systematic Diagnostic Misclassification.

OBJECTIVES: To determine whether the reported 0%-70% prevalence of vitamin B12 deficiency in sickle cell disease (SCD) reflects true population variation or diagnostic misclassification. METHODS: We conducted a PRISMA 2020-compliant systematic review of observational studies (January 1, 2000-May 13, 2026; PROSPERO CRD420251087800) assessing B12 status in SCD. PubMed, AJOL, and Google Scholar were searched with citation tracking and dual screening. Diagnostic validity was assessed across biomarker strategy, analytical platform, thresholds, and confounder control using a proposed context-integrated framework to classify methodological robustness and discordance. RESULTS: Fourteen studies were included (57% high-income; 43% LMIC). The evidence base was dominated by limited diagnostic approaches: 71% used immunoassays, over one-third relied on circulating B12 alone, and functional biomarkers were inconsistently applied without systematic confounder adjustment. Prevalence estimates were strongly influenced by diagnostic methods rather than underlying population biology, ranging from 0% to 70% in single-marker studies (mostly 0%-7.1%, with outliers ~50%-70%) and 6.9%-53% in multi-marker studies. Discordance was substantial and greater in LMIC settings than HIC. CONCLUSION: Current diagnostic approaches in SCD appear method-dependent, generating heterogeneous prevalence estimates with uncertain clinical validity. These findings challenge existing estimates and have implications for clinical practice, research design, and diagnostic equity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420251087800.

Humans↗

PubMed2026

How is goal setting used in interventions for chronic disease prevention and management in sub-Saharan Africa? A systematic review and narrative synthesis.

Non-communicable diseases are increasingly prevalent in sub-Saharan Africa, and goal setting is often used to promote healthy self-management behaviours. In this review, we aimed to synthesise literature around how goal setting is used, for application in future interventions in the region. A systematic search was conducted in six databases and results screened for eligibility. Study characteristics, intervention details, goal setting components, feedback from participants and facilitators were extracted. Data were analysed using narrative synthesis and thematic analysis. The Mixed Methods Appraisal Tool was used to assess study quality. We included 24 publications describing 18 unique interventions. Included studies were of high to moderate methodological quality. Goal setting intervention components were informed by a variety of frameworks and involved a range of tasks. Interventions were often facilitator-led; many were conducted in group settings. Participants reported goal setting as useful for putting self-management into practice but encountered challenges related to language and literacy levels. Adequate detail on goal setting intervention components was not always present. Through this review, we provide a comprehensive picture of the variability of goal setting approaches in chronic disease prevention and management in sub-Saharan Africa and recommend more standardised use and reporting of goal setting intervention components.

Humans↗

PubMed2026

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↗

PubMed2026

De Novo 2.2 Mb 19q13.42-q13.43 Microdeletion Encompassing U2AF2: Support for a Haploinsufficiency Model.

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor involved in the early stages of pre-mRNA splicing. To date, multiple individuals have been reported with predominantly heterozygous missense variants presenting intellectual disability, speech and motor delays, seizures, hypotonia, and thin or hypoplastic corpus callosum. Here, we describe a patient with a de novo 2.2 Mb interstitial deletion involving chromosome 19q13.42-q13.43, encompassing U2AF2, presenting with intellectual disability, epilepsy, corpus callosum hypoplasia, dysmorphic features, and congenital heart disease. The patient's clinical features overlap substantially with those reported in individuals harboring heterozygous U2AF2 variants, supporting haploinsufficiency as a plausible disease mechanism. To our knowledge, this represents the first postnatal report of complete U2AF2 gene deletion. In addition, this is the first detailed phenotypic characterization of a distal 19q chromosomal interstitial deletion, further delineating the clinical spectrum associated with this genomic region.

Humans↗

PubMed2026

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

Humans↗

PubMed2026

Determinants of private health insurance uptake and its association with healthcare utilization in Gulf Cooperation Council countries: a systematic review.

All Gulf Cooperation Council (GCC) countries have a multi-payer healthcare system that comprises governmental health coverage (GHC), funded by the government, and private health insurance (PHI), mainly sponsored by employers and purchased by individuals. Both are expected to influence healthcare utilization and contribute to system efficiency and patient well-being. This systematic review explored the determinants of PHI uptake and its association with healthcare service utilization in the presence of GHC in GCC countries. We systematically searched CINAHL, PubMed, Scopus, Web of Science, and Cochrane Library for peer-reviewed studies published between January 2012 and October 2022. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklists for both quantitative and qualitative studies, following PRISMA guidelines. Twenty-six studies met the inclusion criteria. Determinants of PHI uptake were mapped to Andersen's Behavioral Model of Health Services Use (BMHSU) and categorized into (1) predisposing factors (sex, age, marital status, and education), (2) enabling factors (employment/income and health system-related factors such as access and perceived service quality), and (3) need factors (health status, including chronic noncommunicable diseases). PHI uptake was positively associated with being male, married, highly educated, employed with a high income, and having chronic diseases. PHI was positively associated with healthcare utilization, particularly routine check-ups, preventive services, and the use of prescribed medicines. In GCC countries, PHI uptake is influenced by sociodemographic and socioeconomic characteristics, health status, and perceived service quality. PHI is also associated with higher healthcare utilization, underlining the need for evidence-informed policies that enhance equity and expand coverage.

Humans↗

PubMed2026

Identification of elements determining KIR gene demethylation at the CD56-bright stage of NK cell development.

The variegated expression of the KIR family of class I MHC receptors generates specialized natural killer (NK) cells capable of allele-specific HLA recognition. Understanding the mechanism of KIR gene activation will lead to improved methods for the generation of fully functional NK cells. A central RUNX-binding site in the KIR proximal promoter is required for gene activation. RUNX proteins recruit ten-eleven translocation (TET) proteins that generate 5-hydroxymethylcytosine (5hmC) and drive DNA demethylation. Assessment of 5-methylcytosine (5mC) and 5hmC residues at four stages of NK cell development reveals deposition of 5hmC primarily in a CREB site next to the RUNX site at the CD56Bright stage but not the subsequent CD56Dim stage representing fully mature NK cells. KIR promoter demethylation is delayed relative to other lineage-associated genes, indicating a high threshold for KIR gene demethylation in developing NK cells, and a window of opportunity for RUNX/TET-dependent KIR gene activation in CD56Bright NK cells.

6-base sequencing↗

PubMed2026

Cross-species variant-to-function analyses implicate MEIS1 in conferring sleep abnormalities and impaired cerebellar development.

Genome-wide association studies (GWAS) have identified numerous loci for insomnia, yet functional validation of effector genes remains limited because most risk variants lie in noncoding regions, and the true causal gene is not known. Here, we use prior human cell-based variant-to-gene mapping to nominate six insomnia effector genes and test them in zebrafish, a tractable diurnal vertebrate model well suited for sleep phenotyping. Our CRISPR-based behavioral screening identifies the MEIS1 ortholog, meis1b, as a regulator of sleep maintenance, with crispants displaying impaired nighttime-specific sleep maintenance and increased sleep latency. Comparative chromatin analyses reveal conserved regulatory architecture spanning the human insomnia-associated locus and selectively implicate meis1b, whereas the duplicated ohnolog meis1a was dispensable. Developmental profiling further shows that meis1b is expressed in cerebellar granule progenitors, paralleling human MEIS1 expression, and that its disruption impairs cerebellar development. Together, these findings establish zebrafish as an efficient vertebrate platform for functional interrogation of GWAS candidates and support an evolutionarily conserved cerebellar role for MEIS1 in sleep maintenance.

Animals↗

PubMed2026

Vaccine preferences and their role for vaccine confidence and uptake: a meta-ethnography.

Vaccine confidence and uptake are influenced by individuals' preferences regarding vaccine composition, quality, or administration pathways. However, literature synthesizing available qualitative insights into individuals' vaccine preferences remains limited. We therefore conducted a meta-ethnographic systematic review of the qualitative literature on vaccine preferences to identify opportunities for enhancing vaccine confidence and uptake. We implemented a comprehensive search strategy and screened 5,528 studies across seven research databases published between 2001 and 2023. We identified and synthesized 97 qualitative articles to delineate factors influencing consumers' vaccine preferences. Our findings revealed four primary domains shaping individuals' vaccine preferences: Product, Place, Price, and Promotion. First, individuals' preferences for vaccines often hinge on perceived quality and safety of the product itself, which can, for example, be associated with vaccine brand or origin, especially in the case of novel vaccines. Second, people prioritize convenience in terms of vaccination sites and delivery methods (wanting vaccinations offered at their doorstep or in local peripheral clinics); evidence regarding preferred groups to administer the vaccines was mixed. Third, the price of vaccines and the secondary costs associated with vaccination played a role in uptake considerations. Finally, both the sources of information (such as healthcare workers, community volunteers, and religious authorities) and the methods of promoting vaccine information (including face-to-face consultations during clinic visits and the distribution of leaflets or banners), emerged as crucial factors shaping decision-making processes. Overall findings highlight the importance of addressing multifaceted preferences to enhance vaccine confidence and uptake. By understanding individuals' vaccine preferences, strategic recommendations can be developed to optimize vaccination programs and ensure acceptability and utilization.

Humans↗