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Base editing reversal of radiation sensitivity in NHEJ1 immunodeficiency.
Inherited defects of DNA double-stranded break (DSB) repair can result in radiosensitive/radiation-sensitive (RS) SCID (RS-SCID). We applied base editing to reverse NHEJ1 mutations in patient fibroblasts, exemplifying how this technology can help interrogate RS sequence variants.
Advanced/Novel Stenting for Pediatric Dynamic Airway Collapse.
Pediatric dynamic airway collapse is a complex condition that can impact all levels of the pediatric airway. These conditions can pose life threatening risk to pediatric patients and carry lasting impacts. While traditionally, tracheostomy has been used to address all levels of dynamic collapse, recent advances have allowed for more individualized, anatomy-specific stenting and splinting strategies for treatment. This article covers pathophysiology and the latest evidence on strategies to address nasopharyngeal, oropharyngeal, proximal trachea, and tracheobronchial dynamic collapse.
Risk factors for leg wound infection after conventional and no-touch vein harvesting: insights from a multicentre randomised trial.
ClinicalTrials.gov: ID NCT03501303.
Psychotherapy training in psychiatry: a systematic review and narrative synthesis on the supervision experiences of early-career psychiatrists.
BACKGROUND: Supervision is a fundamental component of psychotherapy training, transforming theoretical knowledge into clinical skills through real-world practice. Psychotherapy training practices vary widely between countries, training programs, and over time, including supervision. Our systematic review aimed to investigate and describe the experiences of psychotherapy supervision through early-career psychiatrists' (ECPs) views. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and PubPsych for survey-based studies on ECPs' experiences of psychotherapy supervision during or after their psychiatry training and reported our findings according to the PRISMA guidelines. Of 32,877 articles screened, 29 articles were included. Each article underwent quality assessment, and results were synthesized narratively. RESULTS: Included articles published between 2000 and 2025, were from Europe (N = 16, 55.1%), the Americas (N = 5, 17.2%), Western Pacific (N = 4, 13.7%), South-East Asia (N = 2, 7%), Eastern Mediterranean (N = 1, 3.5%), and Africa (N = 1, 3.5%), with a total of 4691 participants. Supervision access rates ranged from 26.2% in Nigeria to 85.5% in Russia, with significant variation across countries and psychotherapy modalities. Most ECPs received 50-100 total hours of supervision, frequently delivered in weekly sessions. While formats, individual, group, or mixed, varied by country and training scheme, supervision was generally provided by a psychiatrist-psychotherapist. Common learning techniques included oral consultations and case discussions, followed by audio recordings or transcripts. The need to self-fund psychotherapy supervision costs was identified as a prominent barrier. CONCLUSIONS: Psychotherapy supervision is inconsistent globally, with barriers including supervisor availability and cost. There is a large implementation gap between recommendations and evaluated practice. Digital tools and competency-based frameworks may improve access and quality.
Overcoming the hurdles: A systematic review of barriers to self-initiated exercise in trauma recovery.
There is substantial quantitative evidence in support of exercise as beneficial for trauma recovery, particularly in targeting the neurobiological mechanisms disrupted by trauma. It is therefore important to understand the circumstances under which individuals may avoid exercise, ultimately preventing them from accessing the wellbeing benefits. Some qualitative articles have identified the factors which may prevent an individual from choosing to engage in exercise outside of a structured intervention (self-initiated exercise), but there lacks a synthesis across these differing articles. This systematic review aimed to synthesise qualitative evidence on trauma survivors' experience of barriers to self-initiated exercise. A systematic search of six databases was conducted to identify peer-reviewed qualitative findings on the perceived barriers to self-initiated exercise engagement, with six articles meeting the inclusion criteria. Thematic synthesis revealed three key themes: Searching for Safety, Staying With The Trauma, and Costs of Exercise and Trauma. In their decision to exercise, trauma survivors negotiate many barriers: the physiological, social, and environmental threats to their safety, trauma-related dissociation, and the costs of both exercise and trauma weighed against competing recovery needs. The small number of included studies reflects the emerging nature of research in this area, but it may limit the transferability of the findings. Nonetheless, as the first of its kind, this systematic review collates the experience of barriers as a first meaningful, exploratory step towards addressing them in future research. Taken together, the findings underscore the importance of a trauma-informed approach to ensure exercise remains unimpeded for trauma survivors.
Rare clinical complications following scorpion envenomation worldwide: A systematic review.
Scorpion envenomation is an important public health problem in many tropical and subtropical regions and may result in rare but life-threatening grade III complications involving multiple organ systems. This systematic review synthesizes published articles from 2000 to 2025 that describe uncommon, severe clinical manifestations following scorpion stings. A total of 71 rare clinical complications were identified, encompassing cardiovascular, neurological, respiratory, renal, hematological, ocular, dermatological, and other systemic manifestations. Cardiovascular complications were the most frequently reported, whereas neurological complications exhibited the greatest clinical diversity. Mesobuthus tamulus and Hemiscorpius lepturus were most commonly associated with severe complications, and children younger than 10 years appeared to be at increased risk of serious neurological involvement. These findings highlight the remarkable clinical heterogeneity of grade III scorpion envenomation and emphasize the importance of early recognition, species-specific clinical awareness, and timely management to reduce severe outcomes in endemic regions.
Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis.
BACKGROUND: No systematic review has evaluated the existing evidence regarding the association between packed red blood cell (pRBC) transfusion and clinical worsening of necrotizing enterocolitis (NEC) in neonates. This systematic review and meta-analysis was conducted to address this knowledge gap. MATERIALS AND METHODS: We searched the Cochrane Library, EBSCO, Embase, Web of Science, Google Scholar, and PubMed for studies on pRBC transfusion and NEC published before May 10, 2025. Relevant articles were selected through title, abstract, and full-text screening. English-language case-control studies or cohort studies, or randomized controlled trials involving newborns with NEC that compared pRBC transfusion with no transfusion and reported changes in NEC clinical status were included. Review articles, systematic reviews, case reports, editorials, animal studies, duplicate publications, and studies with incomplete data were excluded. RESULTS: Five studies involving 971 neonates with NEC were included. The pooled analysis demonstrated a potential association between pRBC transfusion and clinical deterioration of NEC in neonates (odds ratio: 6.05, 95% confidence interval: 3.02-12.14). CONCLUSIONS: pRBC transfusion was associated with an exacerbation of NEC in neonates. However, these findings should be interpreted cautiously because of the small number of eligible studies included in this meta-analysis, and future large-scale, well-designed studies are needed to confirm the observed association.
A systematic literature review of cultural concepts taught by pharmacist preceptors during pharmacy student experiential placements.
BACKGROUND: Cultural concepts such as cultural intelligence, awareness, competency and safety are essential in guiding culturally responsive care in health professional practice. Pharmacist preceptors play a pivotal role in sharing both clinical and cultural safe practice with pharmacy students. Culturally responsive care can contribute to achieving health equity, which is especially important for Indigenous communities. AIM: To review literature on cultural concepts in pharmacist preceptorship practices, and how these concepts are taught and communicated to pharmacy students during experiential learning. METHOD: The systematic review followed the PRISMA 2020 guideline. Scopus, PubMed, and Google Scholar were used to identify articles specific to pharmacist preceptors and pharmacy students published between 2015 and 2025, and available in English. RESULTS: Three full-text articles met the inclusion criteria. Major themes and subthemes were identified; pharmacist preceptors lacked preparedness to teach cultural concepts, resulting in variability in preceptors' understanding of cultural concepts and confidence in fulfilling preceptor responsibilities, underutilised structured frameworks to guide students' learning, challenges with preceptorship due to limited resources and support, and the influence of preceptorship on student learning, which impacted students' learning and competency. CONCLUSION: Pharmacy students had minimal exposure to culturally informed pharmacist preceptorship. It is likely that pharmacist preceptors require country-specific educational resources to support culturally safe preceptorship. Future research is required to substantiate these findings, and to guide culturally responsive practice and promote equitable health outcomes in diverse populations.
Utility of hearing aid use on neurocognitive functions and auditory processing: A systematic review.
PURPOSE: Hearing loss not only affects the peripheral auditory system but also leads to changes in central auditory pathways and neurocognitive skills. The use of hearing aids has shown potential benefits in mitigating the adverse effects of hearing loss. Earlier literature showed various studies assessing the impact of hearing aid use on cognitive functions and auditory processing, a comprehensive review of the existing literature is warranted. Existing literature showed heterogeneous outcomes among studies investigated the effect of Hearing aid use in combating the adverse effects of hearing loss on neurocognitive functions and auditory processing. METHOD: Databases including PubMed, SciELO, Cochrane Library, PsycINFO, Web of Science, and Index Copernicus were searched (2005-2025) using English keywords on hearing aid effects on neurocognition and auditory processing in individuals with hearing loss. Studies on effect of hearing aid use on neurocognition and auditory processing were included, while those involving cochlear implant users or other neurological disorders unrelated to hearing loss were excluded. Titles, authors and publication years were examined, and duplicates were removed. RESULTS: Total of 61 research papers were found on specific area and were included in the present review. Findings of these 61 articles have been analysed and are reported in this article. The outcome of the present study showed usefulness of hearing aid use on neurocognitive functions and auditory processing. CONCLUSION: The present literature review emphasized the importance of early rehabilitation through hearing aid use to alleviate the adverse effects of hearing loss on neurocognitive function and auditory processing.
Targeting SIRT6: the design and therapeutic implications of activators and inhibitors.
Sirtuin 6 (SIRT6) is an NAD+-dependent deacylase that maintains genomic stability, regulates metabolism, and influences aging, making it an attractive but challenging therapeutic target. Pharmacological modulation of SIRT6 holds promise for cancer and metabolic disorders, yet its context-dependent functions demand precise intervention strategies. Potent, selective, and drug-like chemical probes are therefore essential to dissect SIRT6 biology and to validate its therapeutic potential. This review critically evaluates recent medicinal chemistry advances in SIRT6 modulation. We focus on structure-guided design strategies and structure-activity relationships (SAR) that have transformed initial hits into optimized leads for both activators and inhibitors, highlighting the remaining challenges in achieving isoform selectivity and drug-like properties.
Efficacy of current approaches to non-invasive diagnosis of skin cancer and the potential impact of artificial intelligence: A systematic review and meta-analysis.
BACKGROUND: Skin cancer is one of the most prevalent malignancies worldwide, particularly within Caucasian populations. This systematic review and meta-analysis aimed to quantitatively review the current literature on non-invasive diagnosis of skin cancer and evaluate the current evidence to support the use of tools in addition to, or in replacement of clinician face-to-face assessment. METHODS: A literature search was conducted for publications in PubMed, Medline and Embase databases. Articles describing accuracy, sensitivity, specificity and outcomes of their mode of assessment were included. A total of 208 articles met the inclusion criteria. RESULTS AND CONCLUSION: This systematic review and meta-analysis showed that the diagnostic performance of artificial intelligence (AI) in the interpretation of dermatoscopic images was high for melanoma diagnosis, basal cell carcinoma or malignancy, in comparison to dermatoscopic assessment alone by clinicians and experts. Although AI interpretation of images demonstrated higher sensitivity for melanoma diagnosis in comparison to clinical assessment combined with dermatoscopic assessment, it is unclear if this is also the case for basal cell carcinoma and squamous cell carcinoma diagnosis. Reflectance confocal microscopy, a non-invasive high resolution imaging technique, is known to have a high sensitivity for diagnosing cutaneous malignancy, and this may have applications within secondary care. Therefore, AI could help reduce resource burden and aid in clinical assessment, particularly within primary care settings.
Transverse Tibial Transport for Limb Salvage in Ischemic Lower Extremity Disease: Technique, Mechanisms, and Clinical Outcomes-A Systematic Review.
Transverse tibial transport (TTT) is a surgical technique derived from Ilizarov's distraction osteogenesis principles that stimulates angiogenesis and microcirculatory regeneration in the ischemic lower limb without directly manipulating macrovascular anatomy. By creating a proximal tibial cortical bone window and distracting it transversely using an external fixator, TTT triggers converging cascades of growth factor release, endothelial progenitor cell mobilization, and immunomodulation that translate into improved distal limb perfusion and wound healing. Combined TTT plus endovascular therapy improves amputation-free survival versus endovascular therapy alone. Prospective randomized trials and standardized international protocols are needed to consolidate TTT's role in multidisciplinary limb salvage pathways.
Multi-omics panorama of glaucoma: Pathogenesis, biomarkers, and novel therapeutic strategies.
Glaucoma is a group of irreversible, blinding eye diseases characterized by progressive loss of retinal ganglion cells, leading to gradual visual field defects that severely impact patients' quality of life. Its complex pathophysiological mechanisms remain incompletely understood, limiting the development of early diagnostic and effective therapeutic strategies. Advances in omics technologies have provided new insights into elucidating the pathophysiology of glaucoma. We summarize specific alterations in genomics, transcriptomics, proteomics, metabolomics, epigenomics, and microbiomics associated with glaucoma. We emphasize the systematic analysis of disease mechanisms, identification of clinically applicable biomarkers, and discovery of novel therapeutic targets through the integration of these data. This approach paves new pathways for glaucoma subtype diagnosis and personalized treatment, while also outlining future research directions and challenges.
Exploring determinants of vaccine hesitancy among healthcare professionals: a systematic literature review.
INTRODUCTION: This systematic review aims to assess determinants of vaccine hesitancy (VH) among healthcare professionals, to identify knowledge gaps and inform targeted training programs. RESEARCH DESIGN AND METHODS: A systematic search of PubMed and Scopus was conducted in February 2024. PRISMA criteria were applied, and methodological quality was assessed using a cross-sectional study evaluation tool. Studies addressing HCWs' VH determinants, including knowledge, attitudes, communication, and organizational factors, were included. RESULTS: Out of 1394 records, 221 articles were included. Reported prevalence of VH among HCWs varied across studies, reflecting differences in professional roles, settings, and vaccines studied. Key determinants included gaps in knowledge, personal beliefs, organizational barriers, and communication skills. The review highlights the importance of evidence-based information, continuing education, and effective communication in addressing VH among HCWs. CONCLUSIONS: Educational and organizational interventions are essential to improve HCWs' knowledge, attitudes, and practices regarding vaccination. Strengthening vaccine education, fostering effective communication, and addressing organizational challenges can reduce hesitancy and support HCWs in promoting vaccination among patients. Future initiatives should consider the diversity of educational settings, professional roles, and training requirements across healthcare systems.
Assessing the threat of Bacillus cereus: From toxin characterization to modern detection strategies.
Bacillus cereus is a spore-forming pathogen responsible for both diarrheal and emetic foodborne illnesses worldwide. Its significance in food safety has received growing attention. Recent advances, including the discovery of novel virulence factors and the development of emerging detection technologies, have provided new insights into its pathogenic mechanisms and surveillance strategies. This review critically examines the global burden of B. cereus infections, and molecular mechanisms of its major virulence factors, and the performance characteristics of current detection knowledge gaps such as the viable-but-non-culturable state and regulatory blind spots for emetic toxins, and discuss unresolved challenges in clinical management. By integrating epidemiological, microbiological, and technological perspectives with critical lens, this review aims to provide a valuable reference for future research and food safety practices.
Decoding the spatiotemporal patterns of food spoilage microbial communities: Integrating multi-omics and artificial intelligence to enable precision preservation.
In the global food supply chain, food wastage caused by spoilage has resulted in significant economic losses, food shortages, and environmental pressure. This process is fundamentally driven by the spatiotemporal dynamics of microbial communities. However, traditional research methods struggle to elucidate the complex mechanisms of spatial heterogeneity, interspecies interactions, and functional succession. This limits the development of effective preservation strategies. This review systematically reviews the cutting-edge progress of integrating multi-omics technologies and artificial intelligence (AI) to study food spoilage microbial communities, breaking through this bottleneck. We propose an intelligent theoretical framework that could potentially analyze microbial metabolic activities and predict dynamic shelf life if implemented. The conceptual framework integrates multidimensional data, including spatial metabolomics, temporal metatranscriptomics, single-cell transcriptomics, and longitudinal metagenomics. It can also be combined with AI models, such as graph neural networks. The article elaborates on the principles and applications of spatio-temporal monitoring technologies, such as nano secondary ion mass spectrometry, hyperspectral imaging, and the Internet of Things sensing. Through illustrative cases of typical perishable foods, it also explores how such a multi-omics - AI system might be applied to spoilage warning and precise intervention. Additionally, the article addresses the current challenges in data coverage, model generalization, and federated learning implementation. Then the research further explores emerging areas such as engineered probiotics, edge AI, and microfluidic sensing. These areas are targeted at transforming food preservation from an empirical control approach to a data-driven, precise regulatory framework. This transformation provides theoretical support and technical approaches for developing a smart, sustainable food preservation system.
First insights into the role of evolutionary history in shaping venom composition of Vipera ammodytes.
Understanding intraspecific venom variation requires distinguishing the contributions of neutral population history from natural selection. This study aims to determine whether venom variation in Vipera ammodytes species complex is structured across eight phylogenetic groups. Despite a complex evolutionary history, venom composition did not differ among phylogenetic groups within the analytical framework used, suggesting that shared ancestry alone does not explain venom variation. Whether local adaptation to environmental conditions explains the observed variation remains an open question for future studies.