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Plant species identification by genome skimming across the vascular plant tree of life.

Accurate species identification is essential for biodiversity conservation and sustainable use, yet standard plant DNA barcoding often fails to achieve species-level resolution. We present a large-scale empirical evaluation of genome skimming as a tool to improve plant species discrimination. Using standardised data from 1969 individuals representing 475 species from 32 genera across major lineages of the vascular plant tree of life, we compare conventional plastid + internal transcribed spacer (ITS) barcodes with genome skimming approaches. Standard barcoding using rbcL, matK, trnH-psbA and ITS resolved about half of species (49.3%), with six genera showing <&#x2009;25% species discrimination. By contrast, genome skimming enabled the recovery of complete plastid genomes, yielding 57.6% species discrimination. It also generated sufficient nuclear genomic data for additional resolution from k-mer analysis, achieving 66.8% species discrimination - an average gain of 17.5% over standard barcodes - while eliminating cases of extreme failure (<&#x2009;25% resolution). The recovery of complete plastomes and ribosomal DNAs from genome skims also ensures backward compatibility with existing barcode datasets. Our results demonstrate that genome skimming provides data that substantially improves species-level resolution across diverse plant lineages and offers a scalable, high-throughput approach for building comprehensive reference resources to support global biodiversity initiatives.

DNA Barcoding, Taxonomic

Divergent trajectories of genome architecture and chromosome evolution in ferns and angiosperms.

Ferns and angiosperms represent the two largest vascular plant lineages but exhibit striking genomic and ecological contrasts. We investigated whether differences in genome size, chromosome architecture, GC content, and stomatal traits reveal divergent evolutionary trajectories between these lineages. We assembled the most comprehensive dataset to date, integrating genome size, chromosome number and size, GC content, and stomatal traits for over 1100 fern species and compared it with an extensive angiosperm dataset. Ferns exhibited markedly lower variability and c. 16-fold slower rates of chromosome size evolution than angiosperms. A persistent positive relationship between genome size and chromosome number in ferns suggests limited cytological post-polyploid diploidization. While ferns generally possess larger stomata, this difference disappears after accounting for genome size, indicating that nucleotypic constraints, rather than lineage-specific physiology, dictate stomatal dimensions. Both groups share a unimodal GC-genome size relationship peaking at c. 14 Gbp. Larger fern chromosomes imply lower genome-wide recombination rates, potentially limiting genetic reshuffling and adaptive potential. Our results highlight fundamentally divergent evolutionary trajectories, likely shaped by meiotic symmetry in ferns and meiotic asymmetry, possibly centromere drive, and post-polyploid diploidization in angiosperms, defining the functional and genomic landscapes of these lineages across deep evolutionary timescales.

Genome, Plant

Blue light therapy delivered through light glasses improves sleep quality and daytime sleepiness in Parkinson's disease: A randomized trial.

BackgroundSleep disturbances, including excessive daytime sleepiness (EDS) and fragmented nocturnal sleep, are common in Parkinson's disease (PD) and significantly reduce quality of life. This pilot study evaluated the efficacy of a novel approach using blue light, delivered via dedicated glasses with integrated LED lights, to improve sleep and non-motor symptoms.MethodsRandomised, placebo-controlled, single-blind pilot study with a 2-week light intervention. Participants were assessed at baseline, two weeks, and five weeks. The study was designed to evaluate between- and within-group changes. Participants were randomly allocated to receive blue light therapy (n&#x2009;=&#x2009;15) or red light placebo (n&#x2009;=&#x2009;15), delivered via LED-integrated glasses for one hour, twice daily, given for a 2-week period. Primary outcome was improvement in sleep quality, assessed via the Pittsburgh Sleep Quality Index. Secondary outcomes included diary-based sleep outcomes, excessive daytime sleepiness, mood, anxiety, and motor symptoms.ResultsThere was a significant group&#x2009;&#xd7;&#x2009;time effect with blue light therapy leading to better Pittsburgh Sleep Quality Index scores (p&#x2009;=&#x2009;0.021). Between-group analyses showed that at two weeks a trend toward significance was observed (p&#x2009;=&#x2009;0.065), while sleep quality significantly improved at five weeks compared to placebo (p&#x2009;=&#x2009;0.029) with a large effect size (0.896). Excessive sleepiness improved in the blue light group (p&#x2009;<&#x2009;0.001), with a reduction in clinically relevant sleepiness from 50.0% to 6.7% (p&#x2009;=&#x2009;0.005).ConclusionsBlue light therapy delivered through dedicated glasses appeared to show an improvement in sleep quality and daytime sleepiness in individuals with PD. Blue light therapy offers a promising alternative to traditional light therapy utilising lower light intensities and eliminating the need for light boxes.

Aged

Evaluating the Efficacy of Electronic Screening, Brief Intervention, and Referral to Treatment (e-SBIRT) for Gambling: An Online Pilot Randomised Trial.

OBJECTIVES: To investigate the efficacy of electronic screening, brief intervention, and referral to treatment (e-SBIRT) at improving gambling outcomes and increasing help-seeking. METHODS: We conducted a two-arm, randomised online pilot trial (n&#x2009;=&#x2009;83) comparing an e-SBIRT intervention with an active control over 12 weeks. The brief intervention was informed by motivational interviewing and incorporated personalised normative feedback, information provision, and relapse-prevention components. Eligible participants were aged 18 or older, resided in the UK and had scores indicating at least moderate severity gambling. RESULTS: Participants (54 [65.1%] male; mean [SD] age&#x2009;=&#x2009;40.58 [12.75] years, mean [SD] PGSI&#x2009;=&#x2009;7.16 [5.58]) in the e-SBIRT and control conditions showed improvements in gambling harms (p&#x2009;=&#x2009;0.033) and perceived ability to control gambling (p&#x2009;=&#x2009;0.029). No significant effects of condition assignment or condition x time interactions were observed. However, exploratory analyses of individual model coefficients suggested greater improvement in perceived ability to control gambling among participants receiving e-SBIRT at 12 weeks (p&#x2009;=&#x2009;0.043). Exploratory analyses also suggested higher rates of help-seeking at 12-week follow-up among participants receiving e-SBIRT. CONCLUSION: Overall, e-SBIRT did not demonstrate clear advantages over assessment and information provision alone. Further research should prioritise refining intervention components and evaluating SBIRT approaches in settings that better reflect its opportunistic delivery model.

Humans

Frequency of Human Brucellosis Complications in West Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Brucellosis is a multi-systemic zoonotic infection. The West Asia/Middle East region is an important global hotspot for brucellosis. This systematic review and meta-analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region. METHODS: PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched. Selection of studies, data extraction, and the risk of bias assessment were performed in duplicate. Data extraction was performed for 254 complications. Meta-analysis was performed using a random-effects model with Freeman-Tukey double arcsine transformation. Where applicable small-study effects was assessed using funnel plots and Egger's test. Separate by-country, by-age, and by-publication-decade subgroup analyses were performed if feasible. RESULTS: Out of 9518 results, 240 studies (260 references) were included. The majority of the included studies were conducted in Turkey (n&#x2009;=&#x2009;177). The reported complications varied and different complication categorization systems were detected. The highest pooled estimate was observed for musculoskeletal involvement (50%, 95%CI: 39%-61%, I2&#x2009;=&#x2009;96.63%). The evidences is up-to-date until March 4, 2024. CONCLUSIONS: Some complications such as the complications of the eye were not reported in all the countries. Therefore, it's recommended to determine the relative frequency of those complications in regions without such reports. The pooled estimates of different complications of brucellosis were different. There's a need for the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.

Brucellosis

Molecular Diagnostics for WHO Priority Bacterial Pathogens: A Bibliometric Mapping of Diagnostic Platforms, Resistance Markers, and Antimicrobial Resistance Research Trends.

Antimicrobial resistance (AMR) constrains effective treatment and carries implications for infection control, surveillance, and public health. The World Health Organization (WHO) priority bacterial pathogen framework has intensified the need for diagnostic innovation by redefining research priorities around organisms combining high disease burden with complex resistance profiles. Molecular diagnostics have accordingly moved beyond culture-based workflows, integrating rapid pathogen identification, resistance-marker detection, genomic surveillance, and clinical decision support. The present study conducted a bibliometric mapping of the literature on WHO priority pathogens. Rather than addressing resistance at a general level or a single pathogen or technology, it integrates priority pathogens, molecular platforms, and resistance markers within a single framework, tracing their joint thematic and temporal evolution along an explicit pathogen-platform-marker axis. Scopus-indexed articles and reviews (2000-2025) were retrieved, yielding 1746 publications after screening adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analyses used Bibliometrix/Biblioshiny, R, and VOSviewer. The literature expanded markedly after 2018, led by China and the United States. Methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, Enterococcus faecium, and the Enterobacterales-carbapenemase axis constituted the principal thematic cores, whereas conventional polymerase chain reaction (PCR)/nucleic acid amplification testing (NAAT) and whole-genome sequencing were the dominant platforms. Overall, the field has evolved from pathogen detection into an AMR-centered translational domain encompassing resistance prediction, genomic epidemiology, surveillance, and clinical decision support. Diagnostic development, stewardship, and surveillance depend on hybrid workflows coupling rapid marker-targeted assays with genome-based characterization, delivering actionable resistance within clinically meaningful timeframes, and extending coverage to underrepresented pathogens and platforms.

Humans

Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in HARS1-Related Autosomal Recessive Disorder Associated With Usher-Like Symptoms.

Autosomal recessive HARS1-related disorder (originally described as Usher syndrome type 3B) caused by a homozygous Y454S variant in the histidyl-tRNA synthetase gene (HARS1) is characterized by progressive sensorineural hearing and vision loss and respiratory deterioration with risk for sudden death following febrile illnesses. In-vitro studies have previously shown that histidine can rescue a humanized yeast model for pathogenic HARS alleles. Fourteen children homozygous for HARS Y454S were treated with supplemental oral histidine (50 mg/kg BID) and monitored with bloodwork and physical, visual, and audiometry assessments during a 3-year clinical trial, then followed for more than 4&#x2009;years on histidine in the post-trial period. Patient fibroblasts were assessed for response to histidine. Hearing and vision remained stable, and growth improved significantly. Children remained healthy, with no severe deteriorations despite exposure to bacterial and viral infections, including COVID-19. Gains in growth were maintained in the post-trial period on varying levels of histidine supplementation. Daily oral histidine supplementation in children with autosomal recessive HARS1-related disorder can ameliorate or slow the progression of disease and is safe, inexpensive, and well tolerated. This study adds to the growing list of autosomal recessive ARSopathies (aminoacyl-tRNA synthetase disorders) that are amenable to amino acid supplementation.

Humans

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p&#x2009;<&#x2009;0.001), PVAS (p&#x2009;<&#x2009;0.001), TEWL (p&#x2009;=&#x2009;0.014), IgE (p&#x2009;<&#x2009;0.001) and QoL scores (p&#x2009;<&#x2009;0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p&#x2009;<&#x2009;0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals

Intraskeletal Variation in Cortical Bone Quantity in a Medieval Italian Sample: A Multivariate Exploratory Approach.

Bioarcheologists interpret skeletal health by examining variability within and between individuals. Studies of bone loss have generated contradictory and conflicting results regarding the onset and severity of age-related bone loss on a global and temporal scale, perhaps due to mismatched methodologies. Intraskeletal comparisons of bone tissue prove challenging precisely because of heterogeneous baselines in quantity and remodeling of cortical bone throughout the skeleton, as well as evolutionary histories and environmental impacts on growth and development. Here we analyze cortical bone indicators from the rib, metacarpal, and femoral cortical bone in a subset of individuals (n&#x2009;=&#x2009;72) regions from the medieval Italian archaeological site of Pieve di Pava. To facilitate intraskeletal comparisons across elements with different biological baselines, we standardize cortical bone parameters using z-scores. Variation in relative intraskeletal cortical bone was assessed using accessible multivariate methods (principal component analysis and hierarchical cluster analysis). Results suggest an association between femoral and metacarpal cortical bone values, with stochastic trends in metacarpal and femoral relative bone quantity in relation to the rib bone quantity at the sample level. Our study demonstrates that while intraskeletal analyses are challenging, they are made more robust by synthesizing multivariate methods alongside exploratory data analysis (EDA) methods to tack between sample-level and individual-level scales and variability. Ultimately, we advocate for leveraging multivariate techniques not as a final step, but rather as a means of generating new hypotheses and challenging tendencies to a priori establish typological groups in the research process.

Skeleton

Safety and Stability of a Combined C2 Screw Placement Strategy With Vertebral Artery Mobilization.

BACKGROUND: Although C2 pedicle screws are considered the gold standard for atlantoaxial fixation, the optimal fixation strategy for patients with high-riding vertebral arteries (HRVA) or narrow C2 pedicles (NC2P) remains controversial because of the increased risk of vertebral artery injury and the limitations of alternative fixation techniques. OBJECTIVE: To evaluate the safety, stability, and clinical efficacy of an individualized C2 screw fixation strategy incorporating vertebral artery mobilization for complex upper cervical anatomy. METHODS: A retrospective study was conducted in 312 patients who underwent C2 fixation between 2017 and 2025. Patients were categorized according to fusion method, screw laterality, and VA transposition requirement. Bone fusion rates and screw accuracy (Gertzbein-Robbins grading) were compared across groups using &#x3c7;2, Fisher's exact, and multivariate logistic regression analyses to control confounders. RESULTS: All procedures were successfully completed without permanent neurovascular injury. At 6&#x2009;months, the fusion rate with an atlantoaxial fusion cage was significantly higher than with interlaminar bone grafting (92.3% vs. 51.0%, p&#x2009;<&#x2009;0.001). Unilateral C2 pedicle screw fixation combined with a contralateral alternative screw achieved comparable stability to bilateral fixation (p&#x2009;>&#x2009;0.05). Screw placement accuracy was 100% clinically acceptable in normal anatomy and 60% in cases requiring VA mobilization, with no VA injury or blood flow compromise. CONCLUSION: The proposed multi-strategy C2 screw placement protocol-integrating fusion cage support and VA mobilization-achieves superior fusion, reliable fixation, and high safety, even in anatomically challenging conditions. This approach provides a reproducible and versatile solution for C2 instrumentation in complex craniovertebral junction surgery.

Humans

Screening of Estrogenic and Antiestrogenic Effects of Estradiol, Bisphenol A, and Fulvestrant Using 2D and 3D Breast Cancer Cell Systems With a Luciferase Reporter Gene Assay.

Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) pose health risks by interfering with hormones. This study develops and utilizes in&#xa0;vitro 2D and 3D cell models to evaluate the estrogenic and antiestrogenic properties of compounds. Human breast cancer cell lines T47D and MCF7, stably transfected with a luciferase reporter gene (ERE-LUC), were first compared in 2D. Due to the significantly higher sensitivity and responsiveness observed in the T47D line during preliminary 2D screenings, this cell line was exclusively selected for the development of the 3D spheroid model. Cells were treated with 17&#x3b2;-estradiol (E2), BPA, and Fulvestrant (FUL) to assess cell viability and luciferase activity. In 2D models, T47D ERE-LUC cells showed higher responsiveness than MCF7 ERE-LUC, which failed to show significant luciferase induction with E2. In the 3D T47D model, cells exhibited significant and robust changes in luciferase activity in response to E2 and BPA, highlighting the enhanced fidelity of 3D cultures in replicating tissue conditions compared to their 2D counterparts. The study highlights the effectiveness of 3D models over 2D in evaluating estrogenic activity. Specifically, the 3D T47D ERE-LUC system serves as a superior, sensitive, and reliable platform for screening EDCs, offering benefits in cost, data speed, and reduced in&#xa0;vivo reliance.

Humans

Assessing the Concurrent Validity of the Australian Treatment Outcomes Profile in a Methamphetamine Dependent Treatment-Seeking Population.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool assessing substance use, health and well-being used in Australian alcohol and other drug treatment services. It is validated for use with clients using alcohol, opioids and cannabis, but not yet for clients who primarily use methamphetamine. METHODS: An embedded validation study was undertaken in treatment-seeking adults enrolled in a randomised double-blind placebo-controlled trial of lisdexamfetamine for methamphetamine dependence with sites in New South Wales, South Australia and Victoria. Participant demographics were collected during study screening. The ATOP and comparators (Time Line Follow Back, Opiate Treatment Index, Depression Anxiety Stress Scale, WHOQOL-BREF and Personal Wellbeing Index) were collected at baseline. Continuous ATOP items were analysed using Pearson's correlation coefficient, and dichotomous items were analysed using Fleiss's &#x3ba;. Agreement was rated as strong where measures were &#x2265;&#x2009;0.50, moderate where agreement was 0.30-0.49, and weak where <&#x2009;0.30. RESULTS: One hundred and eighteen study participants (2018-2020) had data for concurrent validity analysis. Strong validity was demonstrated for physical health, psychological health, quality of life, injecting drug use and crime items, and for days of use for amphetamines, alcohol, cannabis and cocaine. There was weak validity for days of use for benzodiazepines. Heroin use days and other opioid use days were endorsed by fewer than five participants and were therefore unable to be assessed. DISCUSSION AND CONCLUSIONS: The ATOP is valid for use in a treatment-seeking methamphetamine-dependent population, expanding the range of tools for assessment and standardised outcome monitoring across different settings and services.

Humans

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2&#xa0;with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p&#x2009;<&#x2009;0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43&#x2009;months, p&#x2009;<&#x2009;0.0001; 9.46 vs. 14.44&#x2009;months, p&#x2009;=&#x2009;0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans

Chemotherapy-Induced Nausea and Vomiting in Early Breast Cancer Patients Receiving Adjuvant Chemotherapy With Fluorouracil, Epirubicin, Cyclophosphamide Followed by Docetaxel Versus an Anthracycline-Free Regimen With Docetaxel, Cyclophosphamide-Results From a Randomized Clinical Trial.

Chemotherapy-induced nausea and vomiting (CINV) remains an important side effect despite new antiemetic drugs. This study tried to understand the occurrence of CINV in patients receiving two different chemotherapy regimens. As part of the randomized controlled clinical trial SUCCESS C (NCT00847444), 1582 of the 3463 patients completed CINV diaries. Patients were randomized to receive either chemotherapy with FEC (5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel) or TC (docetaxel, cyclophosphamide). CINV was evaluated hourly using a specially designed questionnaire. Endpoints of the study were complete response (no emesis) and total control (no nausea and no emesis) and were assessed with Kaplan-Meier curves and Cox regression analyses over three chemotherapy cycles. Eight hundred fourteen patients received FEC and 768 received TC; patients and tumor characteristics were similar in both groups. Patients receiving FEC had significantly more nausea and vomiting, with the main difference in the first 12&#x2009;h. In the first cycle, the 0-12-h nausea/emesis-free rates were 70%/41% for FEC and 91/76% for TC. By 24&#x2009;h after chemotherapy, the rates were 65%/33% (FEC) and 85%/60% (TC). The differences were similar in cycles 2 and 3. The detailed analysis of CINV in the study is unique and paves the way for modern CINV analysis of new therapeutics such as antibody-drug conjugates.

Adult

Pharmacokinetic and Pharmacodynamic Bio-Similarity of ADL-018 to Innovator Omalizumab: A Randomized Study in Healthy Adults.

Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC(0-last), AUC(0-&#x221e;), and Cmax, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80-1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n&#xa0;=&#xa0;102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC(0-last)-1.08, AUC(0-&#x221e;)-1.07, Cmax-1.05; GMRs of ADL-018 vs EU-OMA: AUC(0-last)-1.06, AUC(0-&#x221e;)-1.06, Cmax - 1.05; and GMRs of US-OMA vs EU-OMA: AUC(0-last)-0.99, AUC(0-&#x221e;)-0.99, Cmax-1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC &#x223c;30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC &#x223c;29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n&#xa0;=&#xa0;6; US-OMA, n&#xa0;=&#xa0;5; EU-OMA, n&#xa0;=&#xa0;4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.

Humans

Putting Globus Into Context: Prevalence, Characteristics, and Overlap With Other Disorders of Gut-Brain Interaction.

OBJECTIVE: Globus is characterized by the sensation of a lump in the throat without dysphagia or underlying structural abnormality or major motility disorder. Reported prevalences vary considerably across studies. Globus has been linked to both heartburn and affective disorders. This study aims to determine the global prevalence of globus, its association with heartburn, overlap with disorders of gut-brain interaction (DGBI) and psychosocial disorders, and its impact on health-related quality of life (HRQOL). METHODS: Internet surveys from the Rome Foundation Global Epidemiology study were used (N&#xa0;=&#xa0;54,127). Rome IV criteria were used to identify globus and concurrent DGBI. Heartburn was defined as symptoms &#x2265; 2-3&#xa0;days/week. Psychosocial co-morbidity and somatic symptom severity were assessed with PHQ-4 and PHQ-15, and HRQOL by PROMIS-10. RESULTS: The global prevalence of globus according to Rome IV criteria was 0.75%, representing 12.8% of esophageal DGBI and 1.86% of all DGBI. Prevalence was highest in Western Europe (0.94%) and Asia (0.90%), and lowest in the Middle East (0.31%). Globus was slightly more common in females (55.4%), and most affected individuals were aged between 40 and 64&#xa0;years (46.6%). Coexisting heartburn was reported in 17.4% of cases, esophageal DGBI in 9.1%, and non-esophageal DGBI in 49.0%. Anxiety and/or depression was present in 60.5%. CONCLUSION: Global prevalence of globus is 0.75%, with a slight female predominance, and is most prevalent below 65&#xa0;years. Overlap with non-esophageal DGBI was greater than with heartburn symptoms or esophageal DGBI, and most patients had anxiety and/or depressive symptoms.

Humans

Estrone disrupts early reproductive development in juvenile male Siniperca chuatsi and is associated with brain and gonadal responses.

Whether estrone (E1)-associated disruption of early reproductive development in fish is accompanied by brain responses in addition to direct gonadal effects remains unclear. Here, juvenile Siniperca chuatsi, a non-model but economically important freshwater species, were exposed for 60 d to 0, 0.01, 0.1, and 1.0&#xa0;&#x3bc;g/L E1, spanning environmentally reported and elevated concentrations. By integrating waterborne concentration monitoring, histopathology, transcriptomics, and quantitative real-time PCR (qPCR) validation, we evaluated E1-associated changes in brain and gonadal tissues during early reproductive development. Waterborne E1 concentrations remained generally stable throughout the exposure period. At the highest tested concentration (1.0&#xa0;&#x3bc;g/L), E1 caused neuronal vacuolation and pyknosis in the hypothalamic region and induced distinct ovarian-like structures in the gonads of genetic males. In the brain, cyp19a1, crhr1, and adcy2a were significantly upregulated, whereas egr1 was significantly downregulated, indicating transcriptional changes in genes associated with local estrogen conversion, stress-response/cAMP signaling, and neuronal activity-related regulation within a broader injury/stress-response background. In the gonad, RNA-seq analysis showed significant downregulation of star2, hsd3b1, cyp17a1, and cyp11b and significant upregulation of hsd17b1, suggesting alterations in steroidogenesis-related gene expression at the transcriptomic level. qPCR analysis of selected gonadal candidate genes showed expression directions generally consistent with the RNA-seq results, and these molecular patterns were consistent with the feminized histological phenotype. Together, these results indicate that E1 can disrupt early reproductive development in juvenile S. chuatsi and support a cautious working model in which E1 exposure is accompanied by concurrent brain and gonadal responses. This study provides new evidence for understanding the toxic effects and ecological risk implications of natural estrogen E1 during early fish development.

Animals

Effects of Dynamic Neck Sensorimotor Biofeedback Training in Individuals With Mechanical Neck Pain: A Pilot Randomized Controlled Trial.

Mechanical neck pain (MNP) is commonly accompanied by pain-related functional limitations, sensorimotor disturbances, and fear of movement, which together may contribute to persistent disability. This preliminary randomized controlled trial study investigated the short-term effects of dynamic neck sensorimotor-based biofeedback training in individuals with MNP. 20 MNP patients from outpatient clinics were assigned to a biofeedback training group or a control group. The training group underwent dynamic biofeedback exercises twice weekly for 2&#xa0;weeks, whereas the control group performed repeated cervical movements without biofeedback. Outcomes included cervical kinematics as repositioning errors (RPE), movement units (MU), maximal range of motion (ROM), and subjective measures, including pain intensity, Neck Disability Index (NDI), and Fear-Avoidance Beliefs Questionnaire (FABQ). All participants completed post-intervention assessments; adherence in the training group was 100%, with no missing data and no adverse events reported. Within the biofeedback training group, participants receiving biofeedback training demonstrated greater improvements in cervical repositioning accuracy during flexion (51.95%, p&#xa0;=&#xa0;0.04) and extension (46.67%, p&#xa0;=&#xa0;0.02), along with reductions in fear-avoidance beliefs related to physical activity and work (p&#xa0;<&#xa0;0.05); these changes were less apparent in the active control group. Exploratory regression analyses suggested associations between improvements in repositioning accuracy and pain reduction, and between increased cervical range of motion and improvements in fear-avoidance beliefs related to physical activity. These pilot findings suggest that dynamic sensorimotor biofeedback training may improve proprioceptive acuity and fear-avoidance beliefs in individuals with MNP, supporting further evaluation in an adequately powered randomized trial.

Humans