bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Ankle and Foot Exercises on Ankle Strength, Balance, and Falls in Older People: A Systematic Review and Meta-Analysis
Authors: Liang Sam Guoshi , Chow Joman Chung Man , Leung Nga Ming , Mo Yee Nok , Ng Thomas Ming Hin , Woo Christy Lok Ching , Lam Freddy Man Hin
Published: December 2024

Objective

Ankle-foot control is essential to maintain balance and gait stability. However, there has been limited evidence on the effect of ankle-foot exercises on balance and falls in older people. This study aimed to summarize the effects of ankle-foot exercises on ankle flexibility and strength, balance, mobility, and falls in older people and to identify determining factors for ankle-foot exercises to improve balance and mobility.

Methods

Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, and Physiotherapy Evidence Database (PEDro) were searched to identify randomized controlled trials that studied the effects of ankle-foot exercises on ankle control, balance, and falls in older people. The PEDro scale was used to evaluate the methodological quality of the studies. Meta-analyses were done for similar outcomes. The quality of evidence was rated by GRADE.

Results

Sixteen papers (n = 651) were included. Meta-analyses showed that ankle-foot exercises significantly improved ankle plantarflexion strength (SMD = 0.35, 95% CI = 0.04 to 0.65, low-quality evidence), ankle flexibility (SMD = 0.48, 95% CI = −0.01 to 0.96, low-quality evidence), and balance in an eyes-open condition (SMD = 0.41, 95% CI = 0.19 to 0.70, low-quality evidence). There was no significant change in ankle dorsiflexion strength (SMD = 0.29, 95% CI = −0.24 to 0.82, very low-quality evidence), balance under eyes-closed condition (SMD = 0.41, 95% CI = −0.1 to 0.92, very low-quality evidence), and gait speed (SMD = 0.36, 95% CI = −0.24 to 0.96, very low-quality evidence). Two studies reported insignificant findings on fear of falling, fall incidence, and risk of falls.

Conclusions

Very low– to low-quality evidence showed that ankle-foot exercises effectively improve ankle plantarflexion strength, flexibility, and balance with eyes open, whereas no effect on falls was found. Improvements in balance and gait tend to be associated with improvements in ankle strength and flexibility. Toe-strengthening exercise and training 3 times per week appear to be important for improving balance.

Impact

This review suggested that ankle-foot exercises might improve balance in older people. Determining factors leading to improvement in balance and mobility were identified. It paves the ground for further research to study the effect of ankle-foot exercises on fall prevention.

Lay Summary

Ankle and foot exercises appear to be effective in improving ankle plantarflexion strength, flexibility, and balance performance in an eye-open condition. If you are an older adult who wants to improve your balance, your physical therapist may prescribe ankle and foot exercises as a supplemental component in a fall prevention program due to the observed improvements in balance and the safety and ease of the exercise.
Association of validated patient reported outcome measures with patients’ self-reported disease status in axial spondyloarthritis
Authors: Redeker Imke , Tsiami Styliani , Klavdianou Kalliopi , Oezdemir Yaren Elif , Sewerin Philipp , Kiefer David , Andreica Ioana , Kernder Anna , Vossen Diana , Kiltz Uta , Baraliakos Xenofon
Published: December 2024

Objective

In axSpA, validated PROs are well-established in clinical trials, but it remains unclear whether they comprehensively reflect patients’ discomfort and disease status. We aimed to investigate how patients’ self-reported disease status compares with validated clinical trial measures during routine clinical visits.

Methods

Data from axSpA patients’ initial and last five visits were retrospectively analysed. ASDAS, BASDAI, ASAS20, ASAS40 and ASAS partial remission were assessed at each visit and compared with patients’ self-reported disease status, categorized into very good (status satisfaction), mild, severe and very severe based on patients’ self-reported opinion on the level of severity of symptom burden related to axSpA. The association of these PROs with patients’ self-reported disease status was analysed using mixed models.

Results

A total of 3,120 visits over a median follow-up of 4.7 years from 557 axSpA patients were analyzed. Very good or mild self-reported disease status was reported in 98.7% of visits with inactive and 90.9% of visits with low ASDAS compared to 67.9% with high and 39.3% with very high ASDAS. Severe or very severe self-reported disease status was reported in 15.1% of visits with ASAS20 achievement, in 7.2% with ASAS40 achievement, and in 0.6% with achievement of ASAS partial remission, compared with 26.0% without ASAS20 achievement, 25.1% without ASAS40 achievement, and 30.1% without achievement of ASAS partial remission.

Conclusions

Patients’ self-reported disease status was well captured by ASDAS and BASDAI in most clinical visits. Other investigated measures used in clinical trials failed to capture patients’ self-reported disease status in a large proportion of visits.
Synovial transcriptome-wide association study implicates novel genes underlying rheumatoid arthritis risk
Authors: Hu Shou-Ye , Jiang Feng , Song Hui-Miao , Wang Ya-Kang , Tian Wen , Wu Hao , Yao Shi , He Chang-Yi , Gao Hui-Wu , Yang Tie-Lin , Yang Zhi , Guo Yan
Published: December 2024

Objectives

This study aimed to address the lack of gene expression regulation data in synovial tissues and to identify genes associated with rheumatoid arthritis (RA) in the synovium, a primary target tissue for RA.

Methods

Gene expression prediction models were built for synovial tissue using matched genotype and gene expression data from 202 subjects. Using this model, we conducted a transcriptome-wide association study (TWAS), utilizing the largest rheumatoid arthritis (RA) genome-wide association study (GWAS) meta-analysis data (n = 276 020). Further analyses, including conditional and joint analysis, causal analysis, differential expression analysis and gene-set enrichment analysis, were conducted to deepen our understanding of genetic architecture and comorbidity aetiology of RA.

Results

Our analysis identified eight genes associated with rheumatoid arthritis (RA), including three novel genes: TPRA1 (PTWAS = 9.59 × 10−6), HIP1 (PTWAS = 1.47 × 10−5) and RP11-73E17.2 (PTWAS = 3.32 × 10−7). These genes differed from those identified in previous TWAS studies using alternative tissues and may play a crucial role in the target synovial tissue. We found four genes exhibited significant causal relationships with RA and were differentially expressed in RA patients. Furthermore, we explored potential drug repurposing opportunities for these genes.

Conclusions

Our study is the first to model gene expression in synovial tissue, uncovering novel genetic determinants of rheumatoid arthritis (RA). This advancement not only deepens our understanding of RA's genetic architecture, but also offers promising avenues for targeted therapies and drug repurposing.
Effects of extremely low-frequency (50 Hz) electromagnetic fields on vital organs of adult Wistar rats and viability of mouse fibroblast cells
Authors: Tekam Chandra Kant Singh , Majumdar Shreyasi , Kumari Pooja , Prajapati Santosh Kumar , Sahi Ajay Kumar , Singh Richa , Krishnamurthy Sairam , Mahto Sanjeev Kumar
Published: December 2024

In recent years, scientific communities have been concerned about the potential health effects of periodic electromagnetic field exposure (≤1 h/d). The objective of our study is to determine the impact of extremely low-frequency pulsed electromagnetic fields (ELF-PEMF) (1–3 mT, 50 Hz) on mouse fibroblast (red fluorescent protein (RFP)-L929) cells and adult Wistar rats to gain a comprehensive understanding of biological effects. We observed that RFP-L929 exhibits no significant changes in cell proliferation and morphology but mild elevation in aspartate aminotransferases, alanine aminotransferases, total bilirubin, serum creatinine, and creatine kinase-myocardial band levels in ELF-PEMF exposed groups under in vitro and in vivo conditions. However, the histological examination showed no significant alterations in tissue structure and morphologies. Our result suggests that 50-Hz ELF-PEMF exposure (1–3 mT, 50 Hz) with duration (<1 h/d) can trigger mild changes in biochemical parameters, but it is insufficient to induce any pathological alterations.
Altered neural response to social awkwardness in schizophrenia spectrum disorders
Authors: Przysinda Emily , Shovestul Bridget , Saxena Abhishek , Dong Xiaoyu , Reda Stephanie , Dudek Emily , Lamberti J. Steven , Lalor Edmund , Dodell-Feder David
Published: December 2024

Individuals with a schizophrenia spectrum disorder (SSD) have difficulties with social information processing, including mental state attribution, or “theory of mind” (ToM). Prior work has shown that these difficulties are related to disruption to the neural network subserving ToM. However, few such studies utilize naturalistic stimuli that are more representative of daily social interaction. Here, SSD and non-SSD individuals underwent fMRI while watching The Office to better understand how the ToM network responds to dynamic and complex social information, such as socially awkward moments. We find that medial prefrontal cortex tracks less with moment-to-moment awkwardness in SSD individuals. We also find a broad decrease in functional connectivity in the ToM network in SSD. Furthermore, neural response during awkward moments and functional connectivity was associated with psychotic experiences and social functioning. These results suggest that during naturalistic, socially awkward moments where mental state attribution is critical, individuals with SSD fail to recruit key regions of the ToM network, possibly contributing to decreased social understanding and impaired functioning.
P023 A Longitudinal Analysis of the Sleep Health of Neurodivergent and Neurotypical Children in Aotearoa
Authors: Dore L , Signal L , Muller D , Paine S , Fletcher B , Waldie K
Published: December 2024

Healthy sleep promotes physical, mental and neurobehavioural well-being, however it is widely acknowledged that neurodivergent children often experience sleep difficulties. We aimed to investigate the sleep health of neurodivergent (ND) children and neurotypical (NT) children in the Growing Up in New Zealand study over time.

Methods

Sleep duration, night wakings, and maternally reported sleep problems at 45-months, 2-years and 8-years were examined. Children were categorised into four groups based on Age-8 neurotype (ND/NT) and ethnicity (Māori/non-Māori) data and analysed using one-way ANOVA and chi square.

Results

Eight-year-old ND Māori had shorter average (mean [SD] hours) sleep (9.52 [1.30]) than NT non-Māori (9.76 [1.15], p=.016). At 2- and 8-years, a smaller proportion (% [95% CI]) of ND Māori (2-years 79.5% [72.6-85.2]; 8-years 77.0% [69.8-83.2]) and NT Māori (2-years 83.2% [80.6-85.6]; 8-years 80.0% [77.2-82.8]) had recommended sleep durations compared to NT non-Māori (2-years 87.2% [86.0-88.3]; 8- years 86.1% [84.9-87.3]). Similar patterns were observed for the other sleep measures, whereby a smaller proportion of ND children had an ‘appropriate’ number of night awakenings at 45-months and 8-years (Māori and non-Māori) compared to NT non-Māori. A larger proportion of ND children (Māori and non-Māori) had problematic sleep at 45-months and 8-years than NT children (Māori and non-Māori).

This study adds to our knowledge of differences in sleep between Māori and non-Māori children, and the timeframe for the emergence of differences in sleep between ND and NT children.
Prognostic factors of preterm neonates with gastrointestinal perforation: a retrospective cohort study from a tertiary neonatal center’s 13-year experience in China
Authors: Yuan Peng , Yao Huang , Feng Wei , Wang Yi
Published: December 2024

This study aimed to describe the clinical features of preterm neonatal gastrointestinal perforation (GIP) and evaluate the prognostic factors. This retrospective study comprised 191 preterm neonates diagnosed with GIP, who were categorized into survival and non-survival groups. Clinical and demographic data, laboratory and imaging features, and outcomes were retrospectively collected. Univariate and multivariate logistic regression analyses were conducted to identify independent prognostic factors. The median gestational age was 34 weeks, and the median birth weight was 2000 g. The overall mortality in the study cohort was 25.1%. The median age of onset of gastric perforation was 3 days (range: 1–11 days), while it was 7.5 days (range: 1–30 days) for intestinal perforation. Abdominal distension was the most common symptom in 184/191 (96.3%) subjects. Ninety-one (47.6%) neonates were diagnosed with a complication of necrotizing enterocolitis. Finally, three independent prognostic factors were identified: severe acidosis (OR: 7.604; 95% CI: 1.424–51.910; P = .025), shock (5.131; 2.419–11.266; P < .001), and coagulopathy (3.269; 1.511–7.431; P = .003). Severe acidosis, shock, and coagulopathy are independent prognostic factors in preterm neonates with GIP. Indexes of systemic status evaluation should be given more attention when treating GIP in premature infants.
Prevalence and associated factors of anaemia and iron-deficiency anaemia among adolescent Sudanese schoolchildren: a cross-sectional study
Authors: Osman Hiba M , Osman Almarwa A , Al-Nafeesah Abdullah , AlEed Ashwaq , Adam Ishag
Published: December 2024

Anaemia among adolescents is a worldwide health problem; however, data on anaemia among adolescents in Sudan are scarce. A cross-sectional study was conducted to investigate the prevalence and associated factors of anaemia and iron-deficiency anaemia among adolescent schoolchildren in northern Sudan. Socio-demographic information was collected using a questionnaire. A total of 309 adolescents (52.4% female and 47.6% male) were enrolled in the study. Seventy-five (24.3%) adolescents had anaemia, and none had severe anaemia. In the multivariate analysis, history of pica [adjusted odds ratio (AOR)  =  2.30, 95% confidence interval (CI) = 1.31–4.02] was associated with increased odds of anaemia, and an increased level of serum ferritin (AOR  =  0.97, 95% CI = 0.95–0.99) was associated with decreased odds of anaemia. Of the adolescents, 189 (61.2%) and 55 (17.8%) had iron deficiency and iron-deficiency anaemia, respectively. In the multivariate analysis, being female (AOR  =  3.13, 95% CI = 1.88–5.23) and having a history of pica (AOR  =  1.85, 95% CI = 1.03–3.31) were associated with increased odds of iron deficiency. This study showed a high prevalence of anaemia and iron-deficiency anaemia among adolescents in this part of Sudan, which was associated with a history of pica.
Wilms tumor and associated predisposing syndromes and conditions
Authors: Meni David
Published: December 2024

Wilms tumor, also known as nephroblastoma, is relatively rare but is the most common renal malignancy in children, accounting for about 5% of all childhood malignancies and 90% of all childhood renal malignancies. Advances in the understanding of the underlying cause and pathophysiology of Wilms tumor have significantly improved the prognosis and survival rates for children with Wilms tumor, but cases may occur sporadically and certain affected patients face higher rates of relapse and morbidity. The most common clinical presentation involves the identification of an abdominal mass or swelling without other signs or symptoms. The nonspecific nature of symptoms that can present can delay timely diagnosis and treatment. Numerous predisposing syndromes are associated with an increased risk for the development of Wilms tumor. Clinicians who recognize these syndromes and other conditions and understand the increased risk can provide the appropriate level of anticipatory guidance and use the optimal screening plan.
Developing a Nursing Workload Intensity Staffing Model
Authors: Bacon Cynthia Thornton , McCoy Thomas P. , Jenkins Marjorie , Gontarz JoAnna , Mittal Amita
Published: December 2024

OBJECTIVE

To explore a workload intensity staffing (WIS) model's effect on nurse and patient outcomes.

BACKGROUND

Little is known about the relationship between WIS and nurse and patient outcomes.

METHODS

A point-based workload intensity tool was developed and implemented to determine the level of care for adult inpatients. Before and after implementation, nurses provided feedback on staffing practices. Rates for catheter-associated urinary tract infections (CAUTIs), central line–associated bloodstream infections (CLABSI), and patient fall rates were collected.

RESULTS

Nurses indicated that patients were equally distributed among nurses (pre-score mean [M] = 3.7 vs post M = 3.6, P = 0.609) and that patient work intensity was incorporated into patient assignments (pre M = 3.4 vs post M = 3.5, P = 0.717). A significant negative trend was revealed for patient falls per 1000 patient-days (b = −0.063, P = 0.010) with fewer falls post-WIS implementation and a significant decrease in falls with injury (b = −0.085, P = 0.002). There was no significant difference in CAUTI and CLABSI rates for pre- versus post-WIS and WIS implementation.

CONCLUSIONS

Although these initial results are promising, more research is needed on WIS and nurse and patient outcomes.
Clinical Manifestations of Semaglutide Overdose: A Case Study
Authors: Branch Matthew R. , Amador Isabella E. , Tardif Irina , Patel Kruti K. , Lewis Daniel A.
Published: December 2024

Intentional overdose with semaglutide is an infrequently reported phenomenon. We present the case of a 39-year-old transgender male-to-female who attempted suicide by an intentional overdose of semaglutide (Ozempic). Her symptoms after the overdose were mild and self-limiting in nature. This finding reflects positively on the safety profile of the frequently prescribed weight-loss and diabetes medication, Ozempic.
A new universal chimeric-antigen receptor (CAR)- fragment antibody binder (FAB) split system for cancer immunotherapy
Authors: Arina Ainhoa , Arauz Edwin , Warzecha Karolina , Masoumi Elham , Saaf Annika , Widło Łukasz , Slezak Tomasz , Zieminska Aleksandra , Dudek Karolina , Schaefer Zachary P. , Lecka Maria , Usatyuk Svitlana , Weichselbaum Ralph R. , Kossiakoff Anthony A.
Published: December 2024

Chimeric antigen receptor T (CAR-T) cell therapy has shown extraordinary results in treating hematological cancer. However, many patients relapse because of heterogeneous antigen expression and outgrowth of antigen lost variants. Other problems include on-target-off-tumor toxicity and the requirement for manufacturing of complex cellular products. Universal and modular CAR constructs offer significantly improved flexibility, safety and cost-effectiveness over conventional CAR constructs. Here we present a new chimeric-antigen receptor (CAR)-fragment antibody binder (Fab) platform based on an engineered protein G variant (GA1) and Fab scaffolds that present exquisite specificity and selectivity on antibody capture. The expression of GA1CAR on human CD8+T cells leads to antigen recognition and T cell effector function that can be modulated according to the affinity of the CAR for the Fab scaffold and of the Fab for the target. GA1CAR-T cells can recognize multiple Fab-antigen pairs on breast and ovarian cancer cell lines. Adoptive transfer of GA1CAR-T cells/Fabs in breast cancer xenograft models leads to effective tumor control. Rapid re-direction of the CAR-T cells to a new target can be achieved by using different Fabs. GA1CAR expression confers favorable phenotypic properties to T cells including a higher effector function upon exposure to antigen as compared to conventional scFv CAR-T cells. This highly versatile “plug and play” CAR-T platform has potential for application in personalized therapy, preventing antigen loss variant escape, decreasing toxicity and increasing access.
Improving design and normalization of multiplex proteomics study
Authors: Fang Huaying , Shih Mei-Chiung , Jiang Lihua , da Veiga Leprevost Felipe , Jian Ruiqi , Chan Joanne , Nesvizhskii Alexey I. , Snyder Michael P. , Tang Hua
Published: December 2024

Advances in multiplex mass spectrometry-based technologies have enabled high-throughput, quantitative proteome profiling of large cohort. However, certain experimental design configurations can amplify sample variability and introduce systematic biases. To address these challenges, we incorporated two novel features in a recent proteogenomic investigation: (1) the inclusion of two reference samples within each mass spectrometry run to serve as internal standards, and (2) the analysis of each specimen as technical replicates across two distinct mass spectrometry runs. Building on these enhancements, we present ProMix, a flexible analytical framework designed to fully leverage these supplementary experimental components. Using both simulated and real-world datasets, we demonstrate the improved performance of ProMix and highlight the advantages conferred by these refined experimental design strategies.
A Novel Bispecific Antibody CVL006 Superior to AK112 for Dual Targeting of PD-L1 and VEGF in Cancer Therapy
Authors: Wang Chunyan , Huang Hao , Song Zeng , Li Zhongyuan , Huang Jinwen , Cao Liang , Wu Ziai , Pan Junfang , Shen Xiaokun
Published: December 2024

Both preclinical and clinical studies have shown that combining anti-VEGF/VEGFR drugs with immune checkpoint inhibitors (ICIs) significantly enhances anticancer efficacy. Currently, PDL-1/ VEGF bispecific antibodies demonstrate superior antitumor activity compared to monotherapy or even the combination of PD-L1 inhibitors with anti-VEGF antibodies. This enhanced efficacy results from the simultaneous blockade of the PD-1/PD-L1 pathway and the inhibition of VEGF-driven angiogenesis. In this study, we developed a novel bispecific antibody, CVL006, by fusing an anti-PDL1 VHH domain with a humanized IgG1 anti-VEGF monoclonal antibody while retaining antibody-dependent cellular cytotoxicity (ADCC) functionality. CVL006 demonstrated high affinity and specificity for both human PD-L1 and VEGF, effectively blocking both the VEGF/VEGFR signaling pathway and the PD-L1/PD-1 axis. This dual blockade not only suppressed VEGF-induced angiogenesis but also reactivated T cells, increasing the secretion of cytokines essential for immune response. In vivo studies further indicated that CVL006 achieved superior antitumor efficacy compared to the PD-L1 inhibitor atezolizumab in mouse models, with greater tumor growth inhibition and reduced angiogenesis. To compare with approved bispecific antibody PD-1/VEGF AK112 (ivonescimab), CVL006 showed superior antitumor efficacy in vivo. These findings underscore the therapeutic potential of CVL006, which integrates immune checkpoint inhibition with disruption of tumor vascularization, offering a robust and comprehensive anticancer strategy.
Thesev-GAL4driver inDrosophila melanogasterdoes not express in the eight pairs of dorso-medial and some other neurons in larval ventral ganglia: A correction
Authors: Kaushik Vanshika , Lakhotia Subhash C.
Published: December 2024

Thesev-Gal4driver is widely used inDrosophilato express the target gene in specific subsets of cells in ommatidial units of developing eye. A 2015 report (Ray & Lakhotia, J Genet 94, 407-416) from our laboratory claimed that besides the eye disc cells, theSev-Gal4(Bloomington stock 5793) also expresses in 8 pairs of dorso-medial neurons and some other cells in larval and early pupal ventral ganglia. The current study reveals that this claim was incorrect since theUAS-GFPtransgene in Bloomington stock 1521 used as reporter in the 2015 study expresses in the 8 pairs of dorso-medial neurons and some other cells in larval and early pupal ventral ganglia even in undriven condition. TheUAS-eGFPreporter in the BL-5431 stock, however, does not express in these ganglia, neither in undriven nor insev-Gal4driven condition. This was also confirmed by the G-TRACE cell lineage study. Present results suggest that only four dorsal-midline cells in ventral ganglia and a cluster of cells in central region of brain hemisphere, besides the earlier known cells in eye disc and optic lobe of brain, express thesev-Gal4transgene in the stock 5793. The essentiality of examining undriven expression of a transgene cannot be under-emphasized.
Rapid kinetics of H+transport by membrane pyrophosphatase: evidence for a “direct-coupling” mechanism
Authors: Anashkin Viktor A. , Bogachev Alexander V. , Serebryakova Marina V. , Zavyalova Elena G. , Bertsova Yulia V. , Baykov Alexander A.
Published: December 2024

Stress resistance-conferring membrane pyrophosphatase (mPPase) found in microbes and plants couples pyrophosphate hydrolysis with H+transport out of the cytoplasm. There are two opposing views on the energy-coupling mechanism in this transporter: the pumping is associated with either pyrophosphate binding to mPPase or the hydrolysis step. We used our recently developed stopped-flow pyranine assay to measure H+transport into mPPase-containing inverted membrane vesicles on the timescale of a single turnover. The vesicles were prepared fromEscherichia colioverproducing the H+-translocating mPPase ofDesulfitobacterium hafniense. Pyrophosphate induced linear accumulation of H+in the vesicles, without evident lag or burst. In contrast, the binding of three nonhydrolyzable pyrophosphate analogs essentially induced no H+accumulation. These findings are inconsistent with the “pumping-before-hydrolysis” model of mPPase functioning and support the alternative model positing the hydrolysis reaction as the source of the transported H+ions. mPPase is thus a first “directly-coupled” proton pump.
West Nile Virus Neuroinvasive Disease in Patients Treated with anti-CD20 Therapies
Authors: Ardakani Rumyar V. , Crane Paul D. , Pastula Daniel M. , Chauhan Lakshmi , Matthews Elizabeth , Money Kelli M. , Shah Anna A. , Piquet Amanda L. , Gross Robert H. , Carlson Aaron M. , Tyler Kenneth L. , Corboy John R. , Alvarez Enrique , Wolf Andrew B.
Published: December 2024

Background and objectives

The literature on severe West Nile virus (WNV) neuroinvasive disease (WNND) in patients treated with anti-CD20 therapies is limited to case reports. We systematically characterize cases of WNND in the tertiary academic UCHealth system.

Methods

A retrospective cohort (January 2016 to January 2024) of patients with a validated diagnosis of WNND and anti-CD20 medication use was identified with electronic medical record (EMR) query followed by individual chart review.

Results

We identified 25 patients, of whom multiple sclerosis was the most common indication for anti-CD20 therapy in 13 patients (52%). 21 patients (84%) presented with meningoencephalitis. Cerebrospinal fluid (CSF) WNV IgM was positive in 5/21 patients (24%) who were tested, while 13/14 tested patients (93%) had positive RT-PCR findings in the CSF. MRI demonstrated anomalies associated with WNND in 12/23 patients (52%) with available imaging. ICU admission was required in 8 patients (32%) and 12 patients (48%) were treated with intravenous immunoglobulin. Worsening of ≥1 point from pre-WNV baseline modified Rankin scale (mRS) to the 90-day post-discharge mRS was seen in 18 patients (75%). Two patients (8%) died by 90-days.

Discussion

WNND leads to disability accrual in patients on B-cell depleting anti-CD20 therapies. Utilization of RT-PCR is important in optimizing diagnosis due to limited sensitivity of antibody testing.
Comprehensive Genetic Profiling of Sensorineural Hearing Loss Using an Integrative Diagnostic Approach
Authors: Lee Sang-Yeon , Lee Seungbok , Park Seongyeol , Jung Sung Ho , Yun Yejin , Choi Won Hoon , Cha Ju Hyuen , Yun Hongseok , Lee Sangmoon , Suh Myung-Whan , Park Moo Kyun , Song Jae-Jin , Choi Byung Yoon , Lee Jun Ho , Ju Young Seok , Koh June-Young , Chae Jong-Hee
Published: December 2024

Despite the advent of Next-Generation Sequencing (NGS), genetic diagnosis of genetic disorders remains challenging, with diagnostic rates plateauing at approximately 50%. We investigated sensorineural hearing loss (SNHL), a prevalent sensory disorder with substantial genetic heterogeneity, through a comprehensive genomic analysis of a homogeneous disease cohort. Leveraging 394 families (750 individuals), we implemented a systematic multi-tiered genomic approach encompassing single-gene analysis to whole-genome sequencing (WGS), integrated with functional assays and bioinformatic analysis. Our methodological framework revealed a cumulative diagnostic yield of 55.6% (219 families), with automated WGS bioinformatics pipeline uncovering an additional 20 families harboring pathogenic variants, predominantly structural variants. Notably, comparative genomic analysis unveiled a higher frequency of single pathogenic alleles in recessive genes within our SNHL cohort relative to control populations. Subsequent deep intronic region interrogation identified three pathogenic variants on the opposite allele, substantiating the diagnostic utility of comprehensive genomic profiling. Through this approach, we delineated a genome-phenome landscape of SNHL, elucidating molecular signatures and establishing genotype-phenotype correlations at the inner ear functional level. This study underscores the transformative potential of WGS as a robust molecular diagnostic modality, advancing precision medicine paradigms in genetic disease research.
An Annotated Multi-Site and Multi-Contrast Magnetic Resonance Imaging Dataset for the study of the Human Tongue Musculature
Authors: Ribeiro Fernanda L. , Zhu Xiangyun , Ye Xincheng , Tu Sicong , Ngo Shyuan T. , Henderson Robert D. , Steyn Frederik J. , Kiernan Matthew C. , Barth Markus , Bollmann Steffen , Shaw Thomas B.
Published: December 2024

This dataset provides the first fully annotated, openly available MRI-based imaging dataset for investigations of tongue musculature, including multi-contrast and multi-site MRI data from non-disease participants. The present dataset includes 47 participants collated from three studies: BeLong (four participants; T2-weighted images), EATT4MND (19 participants; T2-weighted images), and BMC (24 participants; T1-weighted images). We provide automatically generated and manually corrected segmentation of five key tongue muscles: the superior longitudinal, combined transverse/vertical, genioglossus, and inferior longitudinal muscles. Other phenotypic measures, including age, sex, weight, height, and tongue muscle volume, are also available for use. This dataset will benefit researchers across domains interested in the structure and function of the tongue in health and disease. For instance, researchers can use this data to train new machine learning models for tongue segmentation, which can be leveraged for segmentation and tracking of different tongue muscles engaged in speech formation in health and disease. Altogether, this dataset provides the means to the scientific community for investigation of the intricate tongue musculature and its role in physiological processes and speech production in health and disease.
Using Machine Learning and Electronic Health Record (EHR) Data for the Early Prediction of Alzheimer’s Disease and Related Dementias
Authors: Akter Sonia , Liu Zhandi , Simoes Eduardo J. , Rao Praveen
Published: December 2024

Objective

In the United States, over 6 million patients are affected by Alzheimer’s Disease and Related Dementias (ADRD). The study aims to develop and validate machine learning (ML) models for the early diagnosis and prediction of ADRD using de-identified Electronic Health Record (EHR) data from the University of Missouri (MU) Healthcare for different prediction windows.

Materials and Methods

The study used de-identified EHR data provided by the MU NextGen Biomedical Informatics (BMI). An initial cohort of 380,269 patients aged over 40 with at least two healthcare encounters was narrowed to a final dataset of 4,012 unique patients of ADRD cases and 119,723 unique patients of controls. We trained and evaluated six different ML classifier models: Gradient-Boosted Trees (GBT), Light Gradient-Boosting Machine (LightGBM), Random Forest (RF), eXtreme Gradient-Boosting (XGBoost), Logistic Regression (LR), and Adaptive Boosting (AdaBoost) using metrics such as Area Under the Receiver Operating Characteristic Curve (AUC-ROC) score, accuracy, sensitivity, specificity, and F1 score. SHAP (SHapley Additive exPlanations) analysis was used to interpret predictions.

Results

The GBT model achieved the best AUC-ROC scores of 0.809, 0.821, 0.822, 0.808, and 0.833 for 1-year, 2-year, 3-year, 4-year, and 5-year prediction windows, respectively. The SHAP analysis highlighted key risk factors for ADRD, including depressive disorder, heart disease, higher age, headache, anxiety, and insomnia.

Conclusion

This study demonstrates the potential of ML models using EHR data for early ADRD prediction, enabling timely interventions to delay progression and improve outcomes. These findings offer insights for future research and proactive care strategies.
Z-chromosome dosage compensation and a male-specific lncRNA in octopus
Authors: Papanicolaou Natali , Wettersten Sebastian , Kloosterman Alexander , Reinius Björn
Published: December 2024

Sex chromosomes typically present as two copies of a large, gene-rich differentiated chromosome in the homogametic sex (e.g. XX in female mammals, ZZ in male birds) but as a single copy in the heterogametic sex (XY in male mammals, ZW in female birds). This creates a significant gene-copy imbalance of the X and Z chromosomes between the sexes as well as between the single sex chromosome and the autosomes in the heterogametic sex, making its resolution essential. Dosage compensation and its molecular mechanisms have primarily been studied in select organisms, such as primates, rodents, birds, fruit flies, andC. elegans, while the extent and mechanisms of dosage compensation remain largely unexplored in the vast majority of animal taxa.

Recently, coleoid cephalopods, including octopuses, squids, and cuttlefish, were reported to possess a ZZ/Z0 sex chromosome system1, where males carry two copies of the Z chromosome while females carry only one. However, whether dosage compensation occurs in these species remains unexplored. Here, we present evidence that Z-chromosome dosage compensation is achieved in octopus. In two species (Octopus vulgarisandOctopus sinensis), we observed male-to-female ratios of Z-chromosome expression exceeding 1 but significantly below 2, indicating partial dosage compensation, comparable to that achieved for the Z chromosome in birds. Additionally, Z-to-autosomal expression ratios were close to 1. Furthermore, we identified a Z-linked, male-specific long non-coding RNA (lncRNA) inO. vulgaris(“Zmast”), with conserved sequence in annotated Z-linked loci ofO. sinensis—notably expressed in a male-specific manner also in this species.

Our results provide the first evidence of sex chromosome dosage compensation in octopus and introduce the intriguing possibility of a long non-coding RNA playing a sex-specific role in gene regulating.
ATG16L1 WD domain regulates lipid trafficking to maintain plasma membrane integrity to limit influenza virus infection
Authors: Bone Benjamin , Griffith Luke , Jefferson Matthew , Yamauchi Yohei , Wileman Thomas , Powell Penny P.
Published: December 2024

The non-canonical functions of autophagy protein ATG16L1 are dependent on a C-terminal WD domain. Recent studies show that the WD domain is required for conjugation of LC3 to single membranes during endocytosis and phagocytosis, where it is thought to promote fusion with lysosomes. Studies in cells lacking the WD domain suggest additional roles in the regulation of cytokine receptor recycling and plasma membrane repair. The WD domain also protects mice against lethal influenza virusin vivo. Here, analysis of mice lacking the WD domain (ΔWD) shows enrichment of cholesterol in brain tissue suggesting a role for the WD domain in cholesterol transport. Brain tissue and cells from ΔWD mice showed reduced cholesterol and phosphatidylserine (PS) in the plasma membrane. Cells from ΔWD mice also showed an intracellular accumulation of cholesterol predominantly in late endosomes in cell culture. Infection studies using IAV suggest that the loss of cholesterol and PS from the plasma membrane in cells from ΔWD mice results in increased endocytosis and nuclear delivery of IAV, as well as increased IFNβ and ISG expression. Upregulation of IL-6, IFNβ and ISG mRNA were observed inex vivoprecision cut lung slices from ΔWD mice both at rest and in response to IAV infection. Overall, we present evidence that regulation of lipid transport by the WD domain of ATG16L1 may have downstream implications in attenuating viral infection and limiting lethal cytokine signaling.
Spatial organization of multisensory convergence in mouse isocortex
Authors: Patel Kinjal , Ryoo Avery Hee-Woon , Buice Michael , Mihalas Stefan , Tripp Bryan
Published: December 2024

1

The diverse functions of different cortical areas are thought to arise from their distinct groups of inputs. However, additional organizing principles may exist in the spatial structure of converging inputs. We investigated spatial convergence patterns of projections from primary sensory areas to other areas throughout the mouse isocortex. We used a large tract tracing dataset to estimate the dimension of the space into which topographical connections from multiple modalities converged within each other cortical area. We call this measure the topography dimension (TD). TD is higher for areas that receive inputs of similar strength from multiple sensory modalities, and lower when multiple inputs terminate in register with one another. Across the isocortex, TD varied by a factor of 4. TD was positively correlated with hierarchy score, an independent measure that is based on laminar connection patterns. Furthermore, TD (an anatomical measure) was significantly related to several measures of neural activity. In particular, higher TD was associated with higher neural activity dimension, lower population sparseness, and lower lifetime sparseness of spontaneous activity, independent of an area’s hierarchical position. Finally, we analyzed factors that limited TD and found that linear correlations among projections from different areas typically had little impact, while diversity of connection strengths, both between different projections onto the same area, and within projections across different parts of an area, limited TD substantially. This analysis revealed additional intricacy of cortical networks, beyond areas’ sets of connections and hierarchical organization. We propose a means of approximating this organization in deep-network models.
Optical spin initialization and readout with a cavity-coupled quantum dot in an in-plane magnetic field
Authors: Sheldon Samuel J. , Brash Alistair J. , Skolnick Maurice S. , Fox A. Mark , Iles-Smith Jake
Published: December 2024

The spin of a charged semiconductor quantum dot (QD) coupled to an optical cavity is a promising candidate for high-fidelity spin-photon interfaces; the cavity selectively modifies the decay rates of optical transitions such that spin initialization, manipulation, and readout are all possible in a single magnetic field geometry. By performing cavity QED calculations, we show that a cavity with a single, linearly polarized mode can simultaneously support both high-fidelity optical spin initialization and readout in a single, in-plane (Voigt geometry) magnetic field. Furthermore, we demonstrate that single-mode cavities always outperform bimodal cavities in experimentally favorable driving regimes. Our analysis, when combined with established methods of control in a Voigt geometry field, provides optimal parameter regimes for high-fidelity initialization and readout, and coherent control in both cavity configurations, providing insights for the design and development of QD spin-photon interfaces as the basis of quantum network nodes and for the generation of photonic graph states.

Published by the American Physical Society
2024
String-based parametrization of nucleon GPDs at any skewness: A comparison to lattice QCD
Authors: Mamo Kiminad A. , Zahed Ismail
Published: December 2024

We introduce a string-based parametrization for nucleon quark and gluon generalized parton distributions (GPDs) valid at all skewness values. The conformal moments of the GPDs are expressed as sums of the spin-j nucleon A-form factor and the skewness-dependent spin-j nucleon D-form factor. This representation, which fulfills the polynomiality condition (due to Lorentz invariance) and does not rely on model-specific assumptions, is derived from t-channel string exchanges in anti-de Sitter spaces. The spin-j nucleon D-form factor is closely related to the spin-j nucleon A-form factor. We use the Mellin moments from empirical parton distributions to model the spin-j nucleon A-form factors. Using only five Regge slope parameters, fixed from the electromagnetic and gravitational form factors, our string-based parametrization generates accurate singlet, nonsinglet, isovector, and flavor-separated nucleon quark GPDs, along with symmetric nucleon gluon GPDs from their Mellin-Barnes integral representations. Our isovector nucleon quark GPD is in agreement with existing lattice data. Our string-based parametrization should facilitate the empirical extraction and global analysis of nucleon GPDs in exclusive processes, bypassing the deconvolution challenge.

Published by the American Physical Society
2024
Parametrization of Generalized Parton Distributions from
t
-Channel String Exchange in AdS Spaces
Authors: Mamo Kiminad A. , Zahed Ismail
Published: December 2024

We introduce a string-based parametrization for nucleon quark and gluon generalized parton distributions (GPDs) that is valid for all skewness. Our approach leverages conformal moments, representing them as the sum of spin-j nucleon A-form factor and skewness-dependent spin-j nucleon D-form factor, derived from t-channel string exchange in AdS spaces consistent with Lorentz invariance and unitarity. This model-independent framework, satisfying the polynomiality condition due to Lorentz invariance, uses Mellin moments from empirical data to estimate these form factors. With just five Regge slope parameters, our method accurately produces various nucleon quark GPD types and symmetric nucleon gluon GPDs through pertinent Mellin-Barnes integrals. Our isovector nucleon quark GPD is in agreement with existing lattice data, promising to improve the empirical extraction and global analysis of nucleon GPDs in exclusive processes, by avoiding the deconvolution problem at any skewness, for the first time.

Published by the American Physical Society
2024
A systematic review of training for mainstream mental health professionals working with people with intellectual disabilities and mental health needs
Authors: Hunter Emma , Sunley Jade , Richardson Shauni , Hemm Cahley , Dagnan Dave
Published: December 2024

Purpose

Policy in the UK and many other countries states that mainstream mental health services should be accessible to people with intellectual disabilities (ID). The purpose of this paper is to systematically review training and development needs assessments and delivered training and development for professionals working in mainstream mental health services who may work with people with IQ.

Design/methodology/approach

A systematic search of four databases (Web of Science; PsychInfo; PubMed; CINAHL) over the period of 2011–2023 was used. Papers were included if they described training or development delivered to, or specific training or development needs analyses of, mainstream qualified staff to support working with adults who have an ID.

Findings

Two papers were found that described training and development initiatives and six that described training and development needs analysis, five of these papers originated from Australia and were part of the development of a comprehensive workforce competency framework.

Research limitations/implications

Training and development approaches for mainstream mental health services to facilitate the support of people with IQ should be systematically developed and trialled.

Originality/value

To the best of the authors’ knowledge, this is the first study to review training and training needs analysis in this area since 2012. The review finds only a small number of papers in what is an important area for service development.
The role of technology in tourist guiding: future career, service quality, marketing and tourist experiences
Authors: Seyitoğlu Faruk , Atsız Ozan , Akyuz Meral
Published: December 2024

Purpose

This study aims to investigate the perceptions of tourist guides in Türkiye regarding the role of technology in the tourist guiding profession.

Design/methodology/approach

This research adopted an exploratory qualitative case study approach, conducting semi-structured interviews with 29 professional tourist guides actively working in different regions of Türkiye.

Findings

The findings reveal the dual roles of technology in tourist guiding. While it can facilitate service quality and enhance experiences, technologies such as robot tourist guides, augmented reality and virtual reality are perceived as disruptive and potentially damaging service quality and tourist experiences.

Originality/value

The research offers unique insights into the facilitative and disruptive aspects of technological tools in the tourism industry. These findings have direct implications for destination managers, travel agencies and tourist guides worldwide, equipping them with a comprehensive understanding of the role of technology in tourist guiding and guiding their future actions, strategies and policies.
Leader emergence as mediator of the relationship between individual career management and career success: a perspective of implicit leadership theory
Authors: Liu Songbo , Cheng Jinkai , Wang Zhen , Wei Shilong
Published: December 2024

Purpose

This study aims to investigate how individual career management (ICM) affects career success in Chinese organizations. Leader emergence was examined through the theoretical lens of implicit leadership theory as a mediating mechanism of this relationship. In addition, leadership self-efficacy and organizational warmth were analyzed jointly as boundary conditions strengthening the relationship between ICM and leader emergence.

Design/methodology/approach

To avoid common method bias, the authors adopted a three-wave data collection with a one-month lagged design. A total of 765 questionnaires were distributed and 424 usable questionnaires were collected. Mplus version 8.3 was used to test the hypothesized relationships.

Findings

Findings indicated that ICM is positively related to subjective career success and objective career success via leader emergence. Moreover, leadership self-efficacy and organizational warmth jointly moderate the relationship between ICM and leader emergence.

Originality/value

Based on implicit leadership theory, this study identifies leader emergence as a critical mechanism explaining the positive impact of ICM on career success in the Chinese context. Lastly, results stress the simultaneous need for leadership self-efficacy and organization warmth, which can promote high-ICM employees to emerge as leaders.