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One in three patients with positional obstructive sleep apnea does not benefit from positional therapy: Insights from a home-based trial.

PURPOSE: Positional obstructive sleep apnea (POSA) is the most common phenotype of obstructive sleep apnea, yet patient selection for positional therapy (PT) remains suboptimal. With this analysis we aimed to clarify how many patients with POSA may not require PT because they do not habitually sleep supine at home, and how many fail vibrotactile PT despite appropriate indication. METHODS: We conducted a retrospective observational study of consecutive adults with POSA evaluated at a tertiary sleep center between 2021 and 2024. All patients underwent a home-based trial with a neck-based vibrotactile positional therapy device (Night Shift™), consisting of monitoring mode followed by therapy mode. Outcomes included the proportion of non-supine sleepers at home, failure rate of vibrotactile PT, device compliance and differences in supine sleep time between diagnostic testing and home monitoring. RESULTS: Of 92 screened patients, 74 met inclusion criteria (mean age 60.3 ± 13.2 years; mean AHI 22.9 ± 13.3 events/h). Fifteen percent (11/74) did not habitually sleep supine at home, indicating no clinical need for PT, and an additional 14.8% (11/74) failed vibrotactile PT. Overall, 30% of patients were either unlikely to benefit from PT or failed therapy. Non-response was frequently associated with psychotropic or sedative medication use and neurological or sleep-related comorbidities. CONCLUSION: A substantial proportion of patients diagnosed with POSA either do not require or fail vibrotactile treatment in real-world conditions. Incorporating a brief home monitoring and therapy trial into routine clinical practice may optimize patient selection, reduce unnecessary costs, and improve personalized management of POSA.

Humans

Anabolic androgen therapy in critically ill adults: A systematic review and meta-analysis.

Critical illness is characterized by a catabolic, proinflammatory state. Anabolic agents, such as testosterone, have therefore been proposed as therapeutic targets. Our objectives were to assess the effects of testosterone in critically ill populations on patient-important outcomes and identify design limitations to inform future studies. We searched for randomized control trials (RCTs) through Medline, Embase, and EBM Reviews databases from inception through February 24, 2026, including English language articles enrolling adults (≥18 years) admitted to ICU where anabolic androgen therapies (AAT) were compared with placebo or standard of care. Studies had to report at least one of: mortality, ICU and hospital lengths of stay, or duration of mechanical ventilation. We extracted data independently using a standardized data extraction tool, and feedback was received from all co-authors to ensure agreement. For each outcome, we performed meta-analyses using a random-effects model with inverse variance weighting in RevMan. We used the GRADE approach to assess certainty in pooled estimates of effect. Of 1325 screened articles, we found 4 that fit our inclusion criteria. Together, we judged risk of bias as 'some concerns' in 3 trials and 'high' in the final trial, and ultimately found that the effects of anabolic-androgen therapy on patient-important outcomes uncertain. With the uncertainty of current evidence for the effects of anabolic-androgen therapy in critically ill adults, there is insufficient support for its routine use. Future randomized evidence is needed to determine whether anabolic-androgen therapy improves clinically-important outcomes and better define its safety profile in critically ill adults.

Humans

Theta-range SEEG stimulation for intracranial mapping: extending conventional 1-Hz and 50-Hz protocols.

OBJECTIVE: Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7 Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS: We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS: At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50 Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS: EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE: These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

Humans

Molecular adaptation of caspase genes to salinity stress in the tropical sea cucumber Stichopus monotuberculatus: A comparative analysis across echinoderms.

Apoptosis is an essential physiological process that plays a critical role in development and tissue homeostasis. Caspases, as central regulators of apoptosis, are crucial in controlling inflammation and cell death. In this study, we investigated the caspase gene family in Stichopus monotuberculatus to explore their potential roles in salinity stress adaptation. Five caspase genes were identified from the genome of S. monotuberculatus, including Smcaspase3, Smcaspase6, Smcaspase8a, Smcaspase8b, and Smcaspase8c. Phylogenetic analysis revealed that these Smcaspase genes clustered into distinct caspase subfamilies and showed high conservation with homologs from other echinoderms and representative vertebrates. Conserved motif and gene structure analyses showed relatively similar structural patterns within each clade, whereas divergence was observed among different subfamilies. Promoter analysis identified numerous cis-acting elements related to gene regulation, immune response, and growth and development. Expression profiling under salinity stress showed that Smcaspase8a was significantly upregulated, particularly under prolonged stress, whereas the other genes exhibited limited transcriptional responses. Our findings highlight caspase function in salinity stress and provide the foundation of molecular salinity adaptation mechanisms in S. monotuberculatus.

Animals

Perspectives of participating neurologists and study nurses - Mixed-methods process evaluation of a web-based program for relapse management in multiple sclerosis (POWER@M2).

BACKGROUND: Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system and the leading cause of disability in young adults. In Germany, 90% of relapses are treated with high-dose intravenous glucocorticoids, despite limited evidence for long-term benefit and international preference for oral administration. Time constraints often hinder informed decision-making. The multicentre Randomized Controlled Trial (RCT) POWER@MS2 (N = 160, 2020-2023), conducted at 18 German MS-centres, aimed to promote self-determined relapse management through a complex intervention (dialogue-based decision aid, nurse-led webinar, online-chat). OBJECTIVE: While RCTs demonstrate effectiveness, process evaluations are essential to understand implementation, mechanisms of impact and contextual factors. This study explored healthcare professionals' experiences and attitudes toward implementing relapse self-management and self-medication in clinical practice. METHODS: A mixed-methods process evaluation followed the UK Medical Research Council- framework. Quantitative data were collected via validated questionnaires at up to three time points and analysed descriptively. Interview guides were developed based on these results. Qualitative data from neurologist and study nurse interviews were thematically analysed. Results were triangulated using a joint display. RESULTS: Data were collected from 55 neurologists and 17 study nurses (quantitative) and from 7 neurologists and 4 nurses (qualitative) (2020-2024). Most neurologists opposed routine steroid use, reserving it for severe relapses. Some voiced concerns about self-management, but informed patients were generally viewed as capable of safe self-medication. Study nurses gave mixed feedback on the intervention, citing overload and improved guidance. CONCLUSION: Clinicians showed openness toward implementing the intervention. Enhancing accessibility and addressing specific concerns may support broader adoption.

Humans

Prognostic Value of Frailty in Aortic Surgery: A Systematic Review and Meta-Analysis Comparing Frailty Assessment Tools.

BACKGROUND: Frailty is increasingly recognized as an important determinant of outcomes after aortic vascular surgery, but assessment methods vary substantially and the optimal tool for risk stratification remains uncertain. This systematic review and meta-analysis evaluated the prognostic value of preoperative frailty and compared the predictive performance of different frailty instruments in aortic surgery. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to April 27, 2026. Eligible studies included patients undergoing open, endovascular, or hybrid aortic procedures involving abdominal, thoracic, thoracoabdominal, arch, and proximal aortic diseases, including aneurysms and dissections, assessed frailty preoperatively, and reported postoperative outcomes. RESULTS: Thirty studies comprising 419,459 patients were included. Frailty was associated with higher early mortality (odds ratio [OR] 2.20; 95% confidence interval [CI] 1.54-3.14) and late mortality (hazard ratio 2.18; 95% CI 1.64-2.90). Frail patients also had increased risks of major complications (OR 2.52; 95% CI 1.22-5.19), acute kidney injury (OR 1.64; 95% CI 1.34-2.02), and nonhome discharge (OR 5.50; 95% CI 3.05-9.92). Associations were consistent across surgical approaches and aortic segments. Judgment-based or phenotype-like tools yielded higher effect estimates than deficit-accumulation indices, although differences were not statistically significant; among index-based tools, Modified Frailty Index (mFI)-11 outperformed mFI-5. CONCLUSION: Preoperative frailty strongly predicts mortality, morbidity, and loss of functional independence after open, endovascular, and hybrid aortic surgery across different aortic segments and pathologies, including aneurysmal and dissecting aortic disease. Routine frailty assessment may improve risk stratification and perioperative decision-making.

Humans

Recurrent myocardial infarction identified by centralized troponin review: Insights from the MINT trial.

BACKGROUND: The utility of routine troponin testing to identify recurrent myocardial infarction (MI) after an incident MI is unclear. We assessed the incidence and prognosis of recurrent MIs identified from centralized troponin review in patients from the Myocardial Ischemia and Transfusion (MINT) trial. METHODS: The MINT trial randomized patients with acute MI and anemia to a liberal vs restrictive red blood cell transfusion strategy. Suspected recurrent MIs were identified through both site-report and centralized review of troponin levels collected for 3 days following randomization. Differences in cardiac, noncardiac, and all-cause death at 30 and 180 days were compared across patients with any site-reported MI, only centrally identified MI, and no recurrent MI. RESULTS: Among 3,504 patients, 275 (7.8%) had a recurrent MI within 30 days; 119 (43.3%) by site-report, and 156 (56.7%) by central troponin review only. Rates of cardiac and all-cause death at 30 and 180 days were highest for patients with site-reported MI, intermediate for centrally identified MI, and lowest for no recurrent MI; rates of noncardiac death did not vary. Patients with only centrally identified recurrent MI had an increased risk of cardiac death at 30 days (RR 1.9, 95% CI 1.0-3.4) and 180 days (RR 1.7, 95% CI 1.1-2.7) compared to those without recurrent MI. CONCLUSIONS: In patients with acute MI and anemia, centralized troponin review identified more than half of all recurrent MI events. Patients with centrally identified MI had a higher risk of cardiac death than those with no recurrent MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02981407 https://clinicaltrials.gov/study/NCT02619136.

Humans

Mobile health apps improve Health-Related Quality of Life in Type 2 Diabetes Mellitus by enhancing medication adherence: A multicentre randomised controlled trial with mediation analysis.

AIMS: This study evaluated whether a gamified mHealth application (CareAide&#xae;) improves Health-Related Quality of Life (HRQoL) in Type 2 Diabetes Mellitus (T2DM) and whether this effect is mediated by medication adherence. METHODS: Prespecified secondary analysis of the T2DM cohort from a 6-month multicentre RCT (NCT06068309; N&#x202f;=&#x202f;663; three Malaysian hospitals). Participants were randomised 1:1 to standard care or CareAide&#xae;. Adherence (MMAS-8), EQ-5D-5L utility (Malaysian value set), and AQoL-6D were assessed at baseline and 6 months. Simple mediation analysis (PROCESS Model 4; 5000 bootstraps) adjusted for baseline HRQoL. RESULTS: CareAide&#xae; significantly predicted higher MMAS-8 scores (mean difference +1.756; d = 1.638; p&#x202f;<&#x202f;0.001). Higher MMAS-8 scores significantly predicted improved AQoL-6D utility (b = 0.024; p&#x202f;<&#x202f;0.001). The direct effect on AQoL-6D was non-significant (p&#x202f;=&#x202f;0.248). Bootstrapped indirect effect confirmed full mediation via AQoL-6D (0.042; 95% CI [0.024, 0.060]). A sensitivity analysis adjusting for baseline HbA1c confirmed full mediation (indirect = 0.034; 95% CI [0.015, 0.052]; n&#x202f;=&#x202f;563). EQ-5D-5L utility showed a significant direct between-group difference at 6 months (p&#x202f;=&#x202f;0.012) but did not operate as a mediation outcome. CONCLUSIONS: Medication adherence fully mediates the AQoL-6D HRQoL benefit of a gamified mHealth intervention in T2DM, as confirmed by both the primary and HbA1c-adjusted sensitivity analyses. These findings support integration of behaviourally informed digital adjuncts into routine primary diabetes care.

Humans

Clinical and genetic features of Ph-negative myeloproliferative neoplasms with dual-driver gene positivity.

OBJECTIVES: To investigate the clinical laboratory characteristics and gene mutation features of dual-driver gene positivity in patients with Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-negative MPN). METHODS: We conducted a retrospective analysis of clinical data and genetic test results from 203 newly diagnosed patients with Ph-negative MPN. Of these, 194 had single-driver gene positivity and 9 had dual-driver gene positivity. High-throughput sequencing was used to detect mutations in JAK2, CALR, and MPL. Clinical characteristics and gene mutation profiles were compared between the two patient groups. RESULTS: The incidence of dual-driver gene positivity was 4.4% (9/203), with the most common combinations being JAK2 with CALR (4 patients) and JAK2 with MPL (4 patients). Compared with the single-driver group, the dual-driver group had a significantly higher risk of bleeding [4.1% (8/194) vs. 33.3% (3/9), P&#x2009;=&#x2009;0.008] and a higher proportion of uncommon mutations [3.6% (7/194) vs. 33.3% (3/9), P&#x2009;=&#x2009;0.006]. No statistically significant differences were observed between the two groups regarding age, thrombosis incidence, splenomegaly, or routine blood test indicators. During follow-up, 1 patient in the dual-driver group died from cerebrovascular disease. No leukaemia transformation or disease-related deaths occurred among the remaining patients. DISCUSSION: The increased bleeding risk in dual-driver patients may be related to a higher proportion of CALR mutations, elevated platelet counts, and higher variant allele frequencies, though these findings require validation in larger cohorts due to the small sample size. The higher prevalence of uncommon mutations suggests a more complex mutational landscape in this subgroup. CONCLUSION: Patients with Ph-negative MPN and dual-driver gene positivity may have a higher risk of bleeding and a more complex gene mutation profile.

Humans

Sleep disturbances in children and adolescents with iron deficiency: Questionnaire-based and actigraphic findings.

OBJECTIVE: Iron deficiency (ID), without or with anemia (IDA), has been linked to restless sleep and sleep-related movement disorders in childhood, but objective correlates are incompletely defined. We aimed to describe caregiver-reported sleep disturbances, restless legs syndrome (RLS) - related symptoms, and actigraphic sleep patterns in children and adolescents with ID/IDA, and to compare these findings with available sleep-asymptomatic control datasets. We finally explored short-term changes after iron supplementation. METHODS: In this single-center pilot observational study, 31 children with ID/IDA underwent baseline clinical/laboratory assessment and caregiver-reported sleep evaluation with the Sleep Disturbance Scale for Children (SDSC) plus RLS-oriented items. Sixteen also completed home actigraphy, and 8 had follow-up after iron treatment prescribed in routine care. Baseline findings were compared with historical healthy control datasets without reported sleep disturbances; iron-status data were not available for the questionnaire control group; within-subject changes were explored in the follow-up subgroup. RESULTS: Compared with healthy controls, the ID/IDA cohort had higher SDSC total scores (43.97&#x202f;&#xb1;&#x202f;9.63 vs 34.61&#x202f;&#xb1;&#x202f;7.50; p&#x202f;<&#x202f;0.001), with significant differences in the subscales difficulty in initiating and maintaining sleep (DIMS), sleep-wake transition disorders (SWTD), and sleep hyperhidrosis (SHY). Ten of 31 screened children (32.25%) had clinically plausible RLS-related symptoms and higher SWTD scores. Actigraphy showed shorter sleep duration, lower sleep efficiency, longer wake after sleep onset, and greater fragmentation. After iron treatment, parent reported restlessness improved, whereas actigraphic parameters showed only partial normalization. CONCLUSIONS: Pediatric ID/IDA was associated with caregiver-reported and actigraphic sleep disruption, characterized by restless and fragmented sleep. These findings support systematic sleep assessment in children with low iron stores and consideration of iron status in the work-up of restless or nonrestorative sleep.

Humans

Factors associated with successful integration of pharmacists into residential aged care teams: A qualitative study.

BACKGROUND: Australia's Aged Care Onsite Pharmacist program aims to support quality use of medicines in residential aged care homes. This is a novel role introduced into existing teams in a complex environment. Factors associated with successful integration since implementation are currently unknown. AIM: This study aims to explore the perspectives of pharmacists and other stakeholders within aged care homes regarding successful integration of the novel aged care pharmacist service into healthcare teams. METHODS: A qualitative approach, using interpretive descriptive methodology, was used to explore perspectives. Semi-structured focus groups and interviews with pharmacists, nursing and care staff, allied health professionals, general practitioners, residents, and family members were undertaken. Data were collected via Zoom&#x2122;, audio- and video-recorded, and transcribed verbatim. Two researchers undertook inductive thematic analysis to identify key themes. RESULTS: 30 participants across focus groups, focus-group interviews, interviews, and member-checking processes contributed. An overarching theme of proactivity and showing a genuine interest in others underpinned three key themes. Theme 1: Pharmacists needed to be seen, through physical presence and availability, as well as developing a distinct identity. Theme 2: Pharmacists needed to build trust, through collaboration in real time and demonstrating value. Theme 3: Pharmacists needed to develop an understanding of the aged care home environment, including social and contextual norms, as well as procedures, routines and roles. DISCUSSION: This research complements existing understandings of interprofessional collaboration and teamwork amongst healthcare professionals. Themes were interlinked; we used a sensitising framework, social cognitive theory, to present and explain the findings and interactions that can support pharmacist integration into existing teams. Aged care services should structure onboarding to prioritise early visibility, clarify roles and organisational needs, and foster in-person collaboration. Pharmacists should demonstrate proactivity and an authentic interest in all staff, residents and families.

Humans

Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has emerged as a promising gene-editing platform for genetic disorders; however, its in vivo application remains limited by low delivery efficiency and biological barriers. Many CRISPR payloads fail to reach target sites due to extracellular degradation, immune clearance, and intracellular trafficking limitations. This review examines the interplay between biological barriers and nanoparticle engineering strategies for CRISPR/Cas9 delivery. A barrier-oriented engineering approach is proposed as a central framework, encompassing ligand-based surface modification for enhanced targeting and uptake, improved circulation stability via PEGylation and biomimetic coatings, and optimized payload release through endosomal escape strategies. Stimulus-responsive nanoparticle systems further enable spatiotemporal control over payload release. Nuclear targeting strategies, including optimization of nuclear localization signals (NLS) and exploitation of endogenous trafficking pathways, are highlighted as key factors for improving genome-level editing efficiency. Despite these advances, major challenges-including limited intracellular delivery efficiency, insufficient targeting precision, and safety concerns-continue to hinder clinical translation. Future directions highlight artificial intelligence-driven nanoparticle design, personalized delivery systems, and next-generation CRISPR platforms. Overall, an integrated, barrier-oriented engineering strategy is essential for advancing CRISPR/Cas9 delivery toward clinical applications, ultimately advancing global good health and well-being.

CRISPR/Cas9

Liver Cancer Risk and Incidence Attributable to Human Immunodeficiency Virus: A Meta-Analysis and Population-Attributable Modeling Study of Over 1.2 Million Individuals.

HIV-induced immune suppression and chronic inflammation elevate the risk of cancer progression. We conducted a systematic review and meta-analysis of studies published between January 1, 1984 and October 13, 2023 to assess the association between HIV infection and liver cancer. People living with HIV (PLHIV) had a higher risk (pooled relative risk&#x2009;=&#x2009;3.36, 95% CI: 2.72-4.15). The global PAF for HIV-attributed liver cancer was 1.43% in 2019, with a three-fold increase over the past 30&#x2009;years. The Asia-Pacific region recorded the second highest new cases of HIV-attributed liver cancer in 2019, and the highest age-standardized incidence rate (ASIR) in Eastern and Southern Africa. Particularly, the ASIR of HIV-attributed liver cancer increased rapidly in Eastern Europe and Central Asia, with the highest estimated annual percentage change reaching 22.98%. PLHIV have an increased risk and incidence of liver cancer. In regions with high burden of HIV-attributed liver cancer, it is essential to integrate prevention and effective treatment for HIV, viral hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis, and liver cancer.

Humans

Zinc status following different bariatric procedures: systematic review and meta-analysis.

INTRODUCTION: This study evaluated perioperative changes in serum zinc levels following different bariatric procedures and provided evidence-based recommendations for postoperative monitoring and supplementation. METHODS: PubMed, Embase, the Cochrane Library, Web of Science and CNKI were systematically searched from inception to July 2025. Eligible studies compared pre- and postoperative serum zinc levels in individuals with obesity undergoing bariatric surgery. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and the certainty of evidence was graded using the GRADE approach. Pooled analyses were conducted with StataSE 17.0. RESULTS: Twelve studies including 2,529 participants were analysed, with overall quality rated as high. Compared with baseline, pooled standardized mean differences (SMDs) in serum zinc at 3&#x2009;months, 6&#x2009;months, 1&#x2009;year, and 2&#x2009;years postoperatively were -0.12 (95% CI: -0.27 to 0.04, I2&#xa0;= 57.9%, &#x3c4;2 = 0.0265, p&#x2009;=&#x2009;0.149), -0.36 (95% CI: -0.58 to -0.14, I2&#xa0;= 82.2%, &#x3c4;2 = 0.1043, p&#x2009;=&#x2009;0.001), -0.35 (95% CI: -0.53 to -0.16, I2&#xa0;= 81.9%, &#x3c4;2 = 0.0769, p&#x2009;=&#x2009;0.001), and -0.36 (95% CI: -0.95 to 0.24, I2&#xa0;= 97.2%, &#x3c4;2 = 0.3515, p&#x2009;=&#x2009;0.240), respectively. Subgroup analysis showed no significant changes at 3&#x2009;months across procedures. However, zinc levels significantly decreased at 6 and 12&#x2009;months after Roux-en-Y gastric bypass (RYGB) and mini-gastric bypass (MGB), but not after sleeve gastrectomy (SG). At 2&#x2009;years, no significant reduction was observed in any group. The certainty of evidence for zinc changes was rated as moderate. CONCLUSION: Serum zinc levels decline significantly during the first postoperative year, particularly after RYGB and MGB, while SG shows minimal impact. Routine zinc monitoring and individualized supplementation are recommended within the first year after surgery to prevent deficiency-related complications. REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251138846.

Humans

Enhancing Hemoglobin Bart's hydrops fetalis syndrome prevention: a single-tube multiplex real-time PCR assay for the comprehensive detection of four significant &#x3b1;0-thalassemia deletions (--SEA, --THAI, --CR, and --SA) found in Thailand.

BACKGROUND: Hemoglobin (Hb) Bart's hydrops fetalis is a major public health concern in Southeast Asia, particularly in Thailand. Current screening strategies target the two most common &#x3b1;0 -thalassemia deletions (--SEA and --THAI). METHOD: In this study, we developed a single-tube multiplex real-time PCR assay for the simultaneous detection of four clinically relevant &#x3b1;0-thalassemia deletions (--SEA, --THAI, --CR, and --SA). The assay was validated using 538 clinical samples with diverse thalassemia genotypes and compared against conventional gap-PCR as the reference method. Analytical performance, including sensitivity, specificity, and limit of detection (LOD), was evaluated. In addition, clinical utility was assessed in 22 prenatal diagnosis cases at risk of Hb Bart's hydrops fetalis. RESULTS: The study cohort demonstrated substantial genetic heterogeneity, comprising 43 distinct genotypes. The developed assay achieved 100% sensitivity and specificity for all targeted deletions, with complete concordance with gap-PCR results. No cross-reactivity was observed with &#x3b1;+-thalassemia. The assay demonstrated a high analytical sensitivity with a LOD of 9.76&#x2009;&#xd7;&#x2009;10-3&#x2009;ng per reaction. Whereas in prenatal diagnosis, all 22 fetal genotypes were accurately identified, including five cases of homozygous --SEA and one rare compound heterozygous --SEA/--CR fetus. CONCLUSIONS: This study presents a rapid, accurate, and cost-effective multiplex real-time PCR assay capable of detecting both common and rare &#x3b1;0-thalassemia deletions in a single reaction. The assay demonstrates strong potential for implementation in routine clinical laboratories and large-scale population screening, contributing to improved prevention and control of severe thalassemia syndromes in high-prevalence regions.

Humans

Oro-esophageal feeding for tracheostomized patients with severe traumatic brain injury: a randomized controlled trial.

BACKGROUND: This study reports the clinical effects of intermittent oro-esophageal tube feeding (IOE) versus nasogastric tube feeding (NGT) on nutritional status, aspiration pneumonia, decannulation, and level of consciousness in tracheostomized patients with severe traumatic brain injury (sTBI). METHODS: A randomized controlled trial was conducted between March 2024 and October 2025 in China and included tracheostomized patients with sTBI. Participants were randomized 1:1 to the intervention and control groups for 28-day interventions. IOE or NGT was used for nutritional supports, respectively. The primary outcome was nutritional status, including hemoglobin, albumin, prealbumin and body mass index. The secondary outcomes included aspiration pneumonia, decannulation, and level of consciousness assessed using the Glasgow Coma Scale (GCS). Generalized linear mixed-effects models, generalized estimating equations, and Cox regression were used for data analyze. RESULTS: A total of 104 participants were included in the analysis. After intervention, significant interaction effects were observed in hemoglobin (&#x3b2;&#x2009;=&#x2009;5.272, 95% CI: 2.707, 7.837), albumin (&#x3b2;&#x2009;=&#x2009;3.675, 95% CI: 1.854, 5.496), prealbumin (&#x3b2;&#x2009;=&#x2009;11.835, 95% CI: 6.623, 17.047), body mass index (&#x3b2;&#x2009;=&#x2009;1.719, 95% CI: 0.868, 2.569), the GCS (&#x3b2;&#x2009;=&#x2009;0.981, 95% CI: 0.572, 1.390), and aspiration pneumonia (OR= 0.304, 95% CI: 0.133, 0.693). The Cox model revealed that group significantly influenced the decannulation outcomes [HR (95% CI) =5.556 (3.197, 9.657), p&#x2009;<&#x2009;0.001]. CONCLUSIONS: In tracheostomized patients with sTBI who received routine treatment, IOE is more conducive to decannulation and the improvement in nutritional status, aspiration pneumonia, and level of consciousness than NGT. CLINICAL TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT06328985, 03/18/2024, clinicaltrials.gov/study/NCT06328985).

Humans

Exercise prehabilitation in head and neck cancer patients proposed for definitive chemoradiotherapy: The FIT4TREAT randomized controlled trial.

BACKGROUND: Patients with head and neck cancer (HNC) initially scheduled for definitive chemoradiotherapy (CRT) often experience early functional decline and deterioration in health-related quality of life (HRQoL) even before treatment initiation. Evidence for prehabilitation in this non-surgical setting remains limited. This study evaluated whether exercise prehabilitation (EP) initiated before CRT improves functional capacity compared with usual care (UC). METHODS: FIT4TREAT (ClinicalTrials.gov: NCT05418842) was a prospective, single-center, randomized clinical trial. Adults with HNC proposed for definitive CRT were randomly assigned (1:1) to EP or UC. EP consisted of supervised combined aerobic and resistance exercise performed three times per week from baseline until radiotherapy initiation. The primary outcome was the six-minute walk distance (6MWD) at the end of the pre-treatment period. Secondary outcomes included muscle strength, lower-limb functionality, body composition, and HRQoL assessed using the EORTC QLQ-C30 and QLQ-HN43. RESULTS: Between May 2021 and February 2025, 47 patients were enrolled; 40 were included in the primary analysis. After adjustment for baseline 6MWD and the randomization stratification variables, EP resulted in a significantly greater pre-treatment 6MWD than UC (adjusted between-group difference, 28.6&#xa0;m; 95&#xa0;% CI, 4.1-53.1; P&#xa0;=&#xa0;0.023). EP also improved lower-limb functionality (P&#xa0;<&#xa0;0.001) and was associated with better preservation in the QLQ-C30 summary score (P&#xa0;=&#xa0;0.008), social functioning (P&#xa0;=&#xa0;0.038) and body image (P&#xa0;=&#xa0;0.011). CONCLUSION: EP before definitive CRT improves functional capacity and may help preserve HRQoL in patients with HNC, supporting its potential integration into routine oncology care.

Humans

Identification of aquaporin (AQP) genes in the noble scallop Chlamys nobilis and characterization of their expression under low-temperature stress.

Aquaporins (AQPs) are transmembrane channel proteins essential for water homeostasis and cellular stress responses. In marine bivalves, their roles in cold tolerance remain poorly understood despite frequent winter mortality events in aquaculture. Here, we identified nine AQP genes in the genome of the economically important noble scallop Chlamys nobilis. Phylogenetic analysis revealed strong conservation with other bivalve AQPs, and structural features, including conserved NPA motifs and ar/R selectivity filters, support their canonical water/glycerol transport functions. Tissue-specific expression profiling showed predominant enrichment in osmoregulatory tissues (gills, intestine) and gonads. Under both chronic and acute low-temperature stress from 23&#xa0;&#xb0;C to 9&#xa0;&#xb0;C, most CnAQP genes exhibited transient upregulation followed by suppression. Notably, CnAQP4 displayed sustained upregulation, implicating it as a key mediator of long-term cold adaptation. Promoter analysis further revealed abundant cis-elements linked to growth and development as well as immune regulation. Our findings provide the first comprehensive characterization of the AQP family in C. nobilis, highlighting its critical role in maintaining cellular integrity during cold stress and offering molecular targets for selective breeding of cold-tolerant scallop strains.

Animals