bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonotypic VDJ Rearrangements in Mixed Phenotype Acute Leukemia can be Successfully Utilized to Track Minimal Residual Disease
Authors: Hennawi Marah , Quadeer Faatima , Pakasticali Nagehan , Osman Sami , Tashkandi Hammad , Hussaini Mohammad Omar
Published: May 2024

Introduction:

Multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) can both be used to identify a neoplastic clonotype by targeting CDR3 and assessing rearrangements in IgH, IgK, IgL, TCR-β, and TCR-gamma loci. The clonotypic sequence can be robustly used to track minimal residual disease (MRD). The ability to track MRD by NGS in mixed phenotype acute leukemia (MPAL) is unknown and warrants investigation.

Methods:

Institutional Review Board (IRB) approval was obtained. Central Moffitt Cancer Center (MCC) database was searched to locate any patients with MPAL from over 600,000 entries. Patient charts were manually curated to identify those with clonoSEQ data, and clinical data was procured from the electronic medical record (EMR).

Results:

Twenty-nine patients with MPAL were identified. Only 2 patients with clonoSEQ testing were found. Both demonstrated a B/myeloid phenotype, and both were bilineal. NGS (clonoSEQ) identified 4 dominant (IGH) (patient A; 8/2019) and 2 dominant sequences (patient B; 10/2019), respectively. In both patients, clonoSEQ testing successfully tracked minimal residual disease and mirrored clinical disease burden.

Conclusions:

This report is the first to confirm the utility of NGS-based MRD tracking in patients with MPAL and shows increased sensitivity of NGS over MRD flow cytometry.
Safety and Efficacy of Ethanol for Catheter Salvage and Central Line-Associated Bloodstream Infection Prophylaxis in Polyurethane Catheters in the PICU
Authors: Weber Mark D. , Woods-Hill Charlotte , Resendiz Karla , Nelson Eileen , Ryan Monica , Brennan Lauren , Srinivasan Abhay , Conlon Thomas
Published: May 2024

OBJECTIVES:

Ethanol lock therapy (ELT) is a potential method of central catheter salvage following central line-associated bloodstream infection (CLABSI) although there is potential risk of catheter damage in polyurethane catheters. Further, there is limited efficacy data across the spectrum of common pediatric catheters, and published ELT protocols describe dwell times that are not feasible for critically ill children. We sought to evaluate the safety and efficacy of ELT in polyurethane catheters using brief (30 min to 2 hr) dwell times in our PICU.

DESIGN:

Investigational pilot study using historical control data.

SETTING:

PICU in quaternary care, free-standing children’s hospital.

INTERVENTIONS:

ELT in polyurethane central venous catheters for catheter salvage.

RESULTS:

ELT with brief dwell times was used in 25 patients, 22 of whom were bacteremic. Ultimately 11 patients, comprising 14 catheters, were diagnosed with a primary CLABSI. The catheter salvage rate in primary CLABSI patients receiving ELT was 92% (13/14) and significantly higher than the salvage rate in patients receiving antibiotics alone (non-ELT) (62%, 39/64; mean difference 0.32, 95% CI [0.14–0.50], p = 0.03). The rate of catheter fracture in all patients receiving ELT was 8% (2/25) while the rate of fracture in the non-ELT group was 13% (8/64; mean difference –0.05, 95% CI [–0.18 to 0.09], p = 0.72). The rate of tissue plasminogen activator (tPA) use in the ELT group was 8% (2/25), whereas the rate of tPA use in the non-ELT group was significantly higher at 42% (26/64; mean difference –0.34, 95% CI [–0.49 to –0.17], p = 0.002).

CONCLUSIONS:

The use of ELT for catheter salvage and prophylaxis in the PICU is safe in a variety of polyurethane catheters. Dwell times ranging from 30 minutes to 2 hours were effective in sterilizing the catheters while allowing other therapies to continue. This approach may decrease the need for frequent line changes in a medically fragile pediatric population.
ICTV Virus Taxonomy Profile: Fimoviridae 2024
Authors: Digiaro Michele , Elbeaino Toufic , Kubota Kenji , Ochoa-Corona Francisco M. , von Bargen Susanne
Published: May 2024

An erratum of this article has been published full details can be found at 10.1099/jgv.0.001992

Members of the family Fimoviridae are plant viruses with a multipartite negative-sense enveloped RNA genome (−ssRNA), composed of 4–10 segments comprising 12.3–18.5 kb in total, within quasi-spherical virions. Fimoviruses are transmitted to plants by eriophyid mites and induce characteristic cytopathologies in their host plants, including double membrane-bound bodies in the cytoplasm of virus-infected cells. Most fimoviruses infect dicotyledonous plants, and many cause serious disease epidemics. This is a summary of the ICTV Report on the family Fimoviridae, which is available at ictv.global/report/fimoviridae.
Iceland: an underestimated hub for the spread of high-pathogenicity avian influenza viruses in the North Atlantic
Authors: Ahrens Ann Kathrin , Jónsson Stefán Ragnar , Svansson Vilhjálmur , Brugger Brigitte , Beer Martin , Harder Timm C. , Pohlmann Anne
Published: May 2024

High-pathogenicity avian influenza viruses (HPAIVs) of the goose/Guangdong lineage are enzootically circulating in wild bird populations worldwide. This increases the risk of entry into poultry production and spill-over to mammalian species, including humans. Better understanding of the ecological and epizootiological networks of these viruses is essential to optimize mitigation measures. Based on full genome sequences of 26 HPAIV samples from Iceland, which were collected between spring and autumn 2022, as well as 1 sample from the 2023 summer period, we show that 3 different genotypes of HPAIV H5N1 clade 2.3.4.4b were circulating within the wild bird population in Iceland in 2022. Furthermore, in 2023 we observed a novel introduction of HPAIV H5N5 of the same clade to Iceland. The data support the role of Iceland as an utmost northwestern distribution area in Europe that might act also as a potential bridging point for intercontinental spread of HPAIV across the North Atlantic.
Comparative genomics of the world’s smallest mammals reveals links to echolocation, metabolism, and body size plasticity
Authors: Cossette Marie-Laurence , Stewart Donald T. , Shafer Aaron B.A.
Published: May 2024

Originating 30 million years ago, shrews (Soricidae) have diversified into around 400 species worldwide. Shrews display a wide array-array of adaptations, with some species having developed distinctive traits such as echolocation, underwater diving, and venomous saliva. Accordingly, these tiny insectivores are ideal to study the genomic mechanisms of evolution and adaptation. We conducted a comparative genomic analysis of four shrew species and 16 other mammals to identify genomic variations unique to shrews. Using two existing shrew genomes andde novoassemblies for the maritime (Sorex maritimensis) and smoky shrew (S. fumeus), we identified mutations in conserved regions of the genomes, also known as accelerated regions, gene families undergoing significant expansion, and positively selected genes. Our analyses unveiled shrew-specific genomic variants in genes associated with the nervous, metabolic, and auditory systems, which can be linked to unique traits in shrews. Notably, genes suggested to be under convergent evolution in echolocating mammals exhibited accelerated regions in shrews, and pathways linked to putative body size plasticity were detected. These findings provide insight into the evolutionary mechanisms shaping shrew species, shedding light on their adaptation and divergence over time.
RSV-Related Healthcare Burden: A Prospective Observational Study in a Resource-Constrained Setting
Authors: Saha Senjuti , Sudipta Saha SM , Kanon Naito , Hooda Yogesh , Islam Mohammad Shahidul , Islam Shuborno , Ahmed Zabed Bin , Rahman Sheikh Wasik , Alam Md Jahangir , Anik Ataul Mustufa , Sarkar Probir K , Ahsan Mohammed Rizwanul , Amin Md. Ruhul , Saha Samir K
Published: May 2024

Background

Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations worldwide, straining health systems. Data gaps in resource-limited settings and limited RSV immunization impact estimates hinder policymaking.

Methods

From January to December 2019, we conducted a prospective study at Bangladesh’s largest pediatric hospital to assess RSV’s burden on the health system. Outcomes for RSV-positive under-five children were analyzed. We followed outcomes of children denied hospitalization due to bed shortages. Adjusted hazard ratios for children denied admission versus admitted were estimated using survival analysis. Monte Carlo simulations with a queuing model were used to estimate effects of RSV interventions on admission denials and mortality.

Findings

Of 40,664 children admitted, 31,692 were under-five; 19,940 were in study wards. Among 7,191 admitted with possible respiratory infections, 6,149 (86%) had samples taken, with 1,261 (21%) testing RSV-positive. Median age of RSV cases was 3 months, with a median hospital-stay of 5 days; 24 (1.9%) died in hospital. RSV cases accounted for 8,274 of 151,110 bed days. Additionally, of 9,169 children denied admission, outcomes were tracked for 3,928 and compared with 2,845 admitted. The hazard ratio for death was 1.56 [95%CI:1.34-1.81] for children denied versus admitted, highest within neonates at 2.27 [95%CI:1.87-2.75]. RSVpreF maternal vaccine or Nirsevimab could have reduced denials by 677 [95%PI:63-1347] and 1,289 [95%PI:684-1865], respectively, potentially preventing 130 [95%PI:-60-322] and 258 [95%PI:32-469] deaths.

Interpretation

RSV strains healthcare in Bangladesh, increasing mortality risks. Preventive interventions could lessen its impact, boosting healthcare capacity and child health in resource-limited settings.
Altered brain glucose metabolism in nicotine use but not in hazardous alcohol consumption or problem gambling of healthy middle-aged adults
Authors: Shin Seunghyeon , Kim Keunyoung , Kim Jihyun , Nam Hyun-Yeol , Seok Ju Won , Pak Kyoungjune
Published: May 2024

Objectives

We aimed to determine whether chronic nicotine use, alcohol consumption, and gambling alters brain glucose metabolism.

Methods

We retrospectively analyzed data from 473 healthy men who participated in health checkups at Samsung Changwon Hospital Health Promotion Center during 2013 (baseline) and 2018 (follow-up). The health checks included a brain18F-fluorodeoxyglucose positron emission tomography (PET), a questionnaire of tobacco use, the Alcohol Use Disorders Identification Test (AUDIT; Korean version), and the Problem Gambling Severity Index (PGSI). From brain PET scans, the mean uptake in regions-of-interest was scaled to the mean global cortical uptake by each individual, defining the standardized uptake value ratio. We established a model for tobacco use, AUDIT, and PGSI with regional SUVR as a dependent variable and tobacco use, AUDIT, and PGSI as predictors adjusted for age using Bayesian hierarchical modelling. Bayesian models were estimated using four Markov chains, each of which had 4,000 iterations including 1,000 warm-ups, thus totaling 12,000 post-warmup samples. The sampling parameters were slightly modified to facilitate convergence (max tree depth = 20). All data were analyzed using R (The R Foundation for Statistical Computing, Vienna, Austria).

Results

This study included 131 healthy males (mean age at baseline and follow-up: 43.0 ± 3.4, 48.1 ± 3.3 years, respectively). Tobacco use was negatively associated with glucose metabolism in the caudate, thalamus, cingulate, and frontal lobe, and positively associated with the cerebellum, whereas AUDIT or PGSI were not associated.

Conclusion

Tobacco use was associated with altered brain glucose metabolism in the caudate, thalamus, cingulate, frontal lobe, and the cerebellum. However, neither hazardous alcohol consumption, nor problem gambling showed any association with brain glucose metabolism. Our findings might provide new insights into the neural mechanisms of chronic nicotine use.
A Seven-Year Retrospective Assessment Evaluating the Effectiveness of Electronic Consultation (e-Consult) Service in Genetics
Authors: Biswas Sawona , So Joyce , Wallerstein Robert , Gonzales Ralph , Tout Delphine , DeAngelis Lisa , Rajkovic Aleksandar
Published: May 2024

Electronic consultation (e-Consult) programs serve as a conduit between healthcare providers and specialized genetic experts. This retrospective chart review and summary report presents the experience of implementing a Genetics e-Consult Service at the University of California San Francisco (UCSF) from 2016 through 2024 across multiple disciplines. The study examines 622 requests managed by the Genetics team, resulting in the completion of 360 e-Consults (57.8%) and the decline of 262 e-Consults (42.1%). Provider-to-provider consultations, conducted by board-certified geneticists, were completed within 3 days (83.9%), with consultation times ranging from 5 to 20 minutes in most cases (67%). Most requests originated from general practitioners in primary care, pediatrics, and family medicine (48.1%). Analysis of a subset of e-Consults (n=144) revealed that diagnostic queries accounted for 50.6% of requests, followed by management of symptoms (17%) and test interpretation (11%). Providers adhered to geneticists’ recommendations in 84% of cases. These findings underscore the potential of e-Consult frameworks as a viable strategy to enhance accessibility to genetic healthcare services.
Misleading and avoidable: design-induced biases in observational studies evaluating cancer screening -- the example of site-specific effectiveness of screening colonoscopy
Authors: Braitmaier Malte , Schwarz Sarina , Didelez Vanessa , Haug Ulrike
Published: May 2024

Observational studies evaluating the effectiveness of cancer screening are often biased due to non-alignment at time zero, which can be avoided by target trial emulation (TTE). We aimed to illustrate this by evaluating site-specific effectiveness of screening colonoscopy regarding colorectal cancer (CRC) incidence. Based on a German health care database, we assessed the effect of screening colonoscopy vs. no screening colonoscopy in preventing CRC in the distal and the proximal colon over 12 years of follow-up in 55-69-year-old persons. We compared four different study designs: cohort and case-control study, each with/without alignment at time zero. In both analyses with time zero-alignment, screening colonoscopy showed a rather similar effectiveness in reducing the incidence of distal and proximal CRC (cohort analysis: 32% (95% CI: 27-37%) vs. 28% (20-35%); case-control analysis: 27% vs. 33%). Both analyses without alignment suggested a difference by site: Incidence reduction regarding distal and proximal CRC, respectively, was 65% (61-68%) vs. 37% (31-43%) in the cohort analysis and 77% (67- 84%) vs. 46% (25-61%) in the case-control analysis. Violations of basic design principles can substantially bias the results of observational studies. In our example, it falsely suggested a much stronger preventive effect of colonoscopy in the distal vs. the proximal colon. Our study illustrates that TTE avoids such design-induced biases.
Genome-wide study of half a million individuals with major depression identifies 697 independent associations, infers causal neuronal subtypes and biological targets for novel pharmacotherapies
Authors: McIntosh Andrew M , Lewis Cathryn M ,   Mark J Adams for the Psychiatric Genomics Consortium Major Depressive Disorder Working Group
Published: May 2024

In a genome-wide association study (GWAS) of 685,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries and across diverse and admixed ancestries, we identify 697 independent associations at 636 genetic loci, 293 of which are novel. Using fine-mapping and functional genomic datasets, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. Leveraging new single-cell gene expression data, we conducted a causal neural cell type enrichment analysis that implicated excitatory and inhibitory midbrain and forebrain neurons, peptidergic neurons, and medium spiny neurons in MD. Critically, our findings are enriched for the targets of antidepressants and provide potential antidepressant repurposing opportunities (e.g., pregabalin and modafinil). Polygenic scores (PGS) from European ancestries explained up to 5.7% of the variance in liability to MD in European samples and PGS trained using either European or multi-ancestry data significantly predicted case control status across all four diverse ancestries. These findings represent a major advance in our understanding of MD across global populations. We provide evidence that MD GWAS reveals known and novel biological targets that may be used to target and develop pharmacotherapies addressing the considerable unmet need for effective treatment.
A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth
Authors: Mostafa Ishita , Hibberd Matthew C. , Hartman Steven J. , Rahman Md Hasan Hafizur , Mahfuz Mustafa , Hasan S. M. Tafsir , Ashorn Per , Barratt Michael J. , Ahmed Tahmeed , Gordon Jeffrey I.
Published: May 2024

Background

Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches.

Methods

124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma.

Findings

Children who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, βtreatmentgroupxstudyweek(95% CI) = 0.002 (0.001, 0.003);P=0.004]. They also had elevated fecal abundances ofAgathobacter faecis,Blautia massiliensis,LachnospiraandDialister, plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjustedP<0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention.

Interpretation

MDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development.

Funding

This work was supported by the BMGF (Grants OPP1134649/INV-000247).ClinicalTrials.govidentifier:NCT04015999
Protocol on an Integrative review on nomenclature and outcomes in children with complex critical illness in Paediatric Intensive Care - The basis for consensus definition
Authors: Cuevas-Asturias Sofia , Tremlett Will , Mitchell Hannah K , Rafferty Claire , Ramnarayan Padmanabhan , Pattison Natalie
Published: May 2024

Paediatric Critical Care (PCC) supports the recovery of children with severe illness. Nationally, there are 30 PCC units with a total of approximately four hundred beds. There is constant demand for these beds with a mean five-day length of stay and admissions increasing at a greater rate than age-specific population growth [1, 2]. Prolonged stay patients account for approximately half of all PCC patient bed days [3].

Children with complex critical illness (CCI) need input from multiple different teams alongside support for their family [4, 5]. CCI often become prolonged PCC-stay patients too [6]. Internationally, there is variation in the definition of CCI [4, 8], this creates service variation and tensions around what resources can be provided including discharge planning, provision, and support.

Objective

The face of Paediatric Critical Care, in the UK and internationally has changed over the course of the last ten years with a growing cohort of complex critically ill patients. This integrative review aims to look at current nomenclature, definitions, and outcome measures of priority in this undefined patient population.

Inclusion criteria

All types of studies looking at children with complex critical illness (age <18 years) admitted to any paediatric intensive care unit (PICU).

Methods

The review is registered on Prospero. Medline, Embase, Maternity and Infant care, The Cochrane library, the Cumulative Index to Nursing and Allied Health literature (CINAHL) and Trip database will be searched from 2014 to May 2024.

Search limits will include all languages, exclude the setting of neonatal intensive care and age>18 years old. Four independent reviewers will screen citations for eligible studies and perform data extraction. The final search strategy will be developed in Medline and peer-reviewed by a health research librarian not involved in the study. This will be translated to other databases as appropriate.

Author approval

All authors have seen and approved the manuscript.
Exercise Training Improves Cognitive Function and Neurovascular Control in Patients With Heart Failure and Atrial Fibrillation: A Randomized Clinical Trial
Authors: Guimarães Guilherme Veiga , Chizzola Paulo Roberto , D’Avila Veridiana Moraes , Santo-Silva Paulo Roberto , Grohes Miranda Raphaela Villar , Alves Leandro Silva , Bocchi Edimar Alcides
Published: May 2024

Background

Atrial fibrillation (AF) may be linked to cognitive impairment in heart failure (HF) patients. Regular exercise training has numerous benefits, including improving adults’ overall health and cognitive function. However, the effects of exercise training on cognitive function in heart failure patients with reduced ejection fraction and permanent atrial fibrillation (HFAF) are not well understood.

Objective

To test the hypothesis that exercise training improves cognitive function and neurovascular control in patients with HFAF.

Methods

This randomized clinical trial included patients with HFAF, LVEF ≤40%, and resting HR ≤80 bpm. Montreal Cognitive Assessment score (MoCA), muscle sympathetic nerve activity (MSNA), and forearm blood flow (FBF) assessment were performed before and after the 12-week protocol period.

Results

Twenty-six patients were randomized to exercise training (HFAF-trained, n=13) or no training (HFAF-untrained, n=13). At baseline, no differences between groups were found. Exercise significantly improved the MoCA score from 14.85 to 22.62 (P<0.0001), as well as those measuring processing visuospatial, memory, and attention function from 2.23 to 3.31 (P=0.02); from 1.92 to 2.69 (P=0.01); and from 2.62 to 3.85 (P=0.002), respectively. HFAF-training significantly decreased MSNA from 49.6±9.5 to 32.0±7.2 burst/min (P<0.0001) and forearm vascular resistance from 48.8±13.1 to 28.1±7 units (P<0.0001). Concomitantly, FBF increased from 1.9±0.5 to 3.0±0.7 mL/min/100mL (P<0.0001). The untrained group increased MSNA from 50.9±10.6 to 57.6±9.2 burst/min (P=0.004). No significant changes were found in the other variables in untrained patients.

Conclusion

Exercise training improves cognitive function and neurovascular control in patients with heart failure with reduced ejection fraction and permanent atrial fibrillation.
Intensity of habitual physical activity and maintenance of normal blood pressure – findings from the SUN longitudinal cohort study
Authors: Gribble Anne Katherine , Hershey Maria S. , López-Gil José Francisco , Lan Fan-Yun , Kales Stefanos N. , Martínez-González Miguel Ángel , Bes-Rastrollo Maira , Fernandez-Montero Alejandro
Published: May 2024

(2)

Background

Physical activity (PA) is a modifiable protective factor against hypertension, but the optimum intensity of PA for prevention of hypertension remains unknown. It has been suggested that total energy expenditure is the crucial factor while intensity is non-differential provided it is moderate or above. Yet it is possible that higher intensity PA may produce a distinct effect.

Methods

We used data from theSeguimiento Universidad de Navarra(SUN) cohort – a large prospective longitudinal cohort study in Spain - to investigate how intensity of habitual PA may affect hypertension incidence. Average intensity of PA was calculated incorporating incidental walking and stairclimbing in addition to leisure-time PA (LTPA). Hazard ratios (HRs) for incident hypertension and their 95% confidence intervals (CI) were estimated using Cox regression analyses, and modelling adjusted for EE and body mass index (BMI) as well as other important covariables. Comparative models investigated how time spent in PA and EE in PA relate to hypertension incidence.

Results

17,146 normotensive participants (63.6% female, mean age 36.7 years, mean BMI 23.2kg/m2) were followed for 204,677 person-years. 2,495 cases of incident hypertension emerged. After adjustment for covariables, including EE, intensity of PA was monotonically associated with decreased risk for incident hypertension (aHR for Q5 vs Q1: 0.81, 95% CI 0.71-0.93). In comparison, increasing time in PA was associated with increasing risk for incident hypertension following adjustment for EE (aHR for Q5 vs Q1: 1.60, 95% CI 1.10- 2.32).

Conclusion

Intensity of habitual PA is independently and inversely associated with incidence of hypertension.
Influenza vaccine effectiveness against hospital-attended influenza infection in 2023/24 season in Hangzhou, China
Authors: Lei Hao , Niu Beidi , Sun Zhou , Wang Yaojing , Che Xinren , Du Shengqiang , Liu Yan , Zhang Ke , Zhao Shi , Yang Shigui , Wang Zhe , Zhao Gang
Published: May 2024

Background

From 2020, influenza activities were largely affected by the coronavirus disease (COVID-19) pandemic at the global scale. The B/Yamagata lineage has become extinct since 2020, raising concerns regarding the quadrivalent influenza vaccine. Evaluating vaccine effectiveness (VE) against influenza infections is important to guide future influenza vaccine programs.

Methods

A test-negative case-control study was conducted in five tertiary hospitals in Hangzhou, the capital city of Zhejiang province, China. Hospital-attended patients aged >6 months who presented with influenza-like illness (ILI) from October 1, 2023 to March 31, 2024 were enrolled in this study. The VE was estimated using multivariate logistic regression models, adjusted by sex, age, influenza detection methods and influenza testing timing.

Results

In total, 157291 hospital-attended ILI participants were enrolled. 56704 (36%) were tested positive for influenza virus. The adjusted estimates of overall VE against any hospital-attended influenza infection was 48% (95% Confidence interval [CI]: 46%-51%). The overall VE of trivalent inactivated influenza vaccine (IIV3) was 59% (95% CI: 50%-66%), followed by trivalent live attenuated vaccine (LAIV3) (VE=53%, 95% CI: 42%-62%) and quadrivalent inactivated influenza vaccine (IIV4) (VE=47%, 95% CI: 45%-50%). IIV3 provided even much better protection against hospital-attended influenza B infection than IIV4 (VE=87% (95% CI: 81%-92%) for IIV3 versus VE=53%, 95% CI: 50%-57% for IIV4).

Conclusions

The influenza vaccine provided moderate protection against influenza infection in the 2023/24 season in Hangzhou, China, during a massive epidemic. The results supported the World Health Organization recommendation regarding the exclusion of B/Yamagata lineage antigen in quadrivalent influenza vaccines in 2023.
Identification and validation of drugs for repurposing in Glioblastoma: a computational and experimental workflow
Authors: Gonzalez Nazareno , Pérez Küper Melanie , Garcia Fallit Matías , Peña Agudelo Jorge A. , Nicola Candia Alejandro J. , Suarez Velandia Maicol , Videla-Richardson Guillermo A. , Candolfi Marianela
Published: May 2024

Purpose

Glioblastoma (GBM) remains a formidable challenge in oncology due to its invasiveness and resistance to treatment, i.e. surgery, radiotherapy, and chemotherapy with temozolomide. This study aimed to develop and validate an integrated model to predict the sensitivity of GBM to alternative chemotherapeutics and to identify novel candidate drugs and combinations for the treatment of GBM.

Patients and Methods

We utilized the drug sensitivity response data of 272 compounds from CancerRxTissue, a validated predictive model, to identify drugs with therapeutic potential for GBM. Using the IC50, we selected ’potentially effective’ drugs among those predicted to be blood-brain barrier permeable viain silicoalgorithms. We ultimately selected drugs with targets overexpressed and associated with worse prognosis in GBM for experimentalin vitrovalidation.

Results

The workflow proposed predicted that GBM is more sensitive to Etoposide and Cisplatin, in comparison with Temozolomide, effects that were validatedin vitroin a set of GBM cellular models. Using this workflow, we identified a set of 5 novel drugs to which GBM would exhibit high sensitivity and selected Daporinad, a blood-brain barrier permeant NAMPT inhibitor, for further preclinicalin vitroevaluation, which aligned with thein silicoprediction.

Conclusion

Our results suggest that this workflow could be useful to select potentially effective drugs and combinations for GBM, according to the molecular characteristics of the tumor. This comprehensive workflow, which integrates computational prowess with experimental validation, could constitute a simple tool for identifying and validating compounds with potential for drug reporpusing in GBM and other tumors.
The effect of head orientation on vestibular signal-based modulation of paraspinal muscle activity during walking
Authors: Li Yiyuan C. , Lemaire Koen K. , Bruijn Sjoerd M. , Brumagne Simon , van Dieën Jaap H.
Published: May 2024

Vestibulospinal reflexes play a role in maintaining the upright posture of the trunk. Head orientation has been shown to modify the vestibulospinal reflexes during standing. This study investigated how vestibular signals affect paraspinal muscle activity during walking, and whether head orientation changes these effects. Sixteen participants were instructed to walk on a treadmill for 8 min at 78 steps/min and 2.8 km/h in four conditions defined by the presence of electrical vestibular stimulation (EVS) and by head orientation (facing forward and facing leftward), while bipolar electromyography (EMG) was recorded bilaterally from the paraspinal muscles from cervical to lumbar levels. In both head orientations, significant phasic EVS-EMG coherence (p< 0.01) in the paraspinal muscles was observed at ipsilateral and/or contralateral heel strikes. Compared to walking with the head forward, a significant decrease (p< 0.05) was found in EVS evoked responses (i.e., EVS-EMG coherence and gain) when participants walked with the leftward head orientation, with which EVS induced disturbance in the sagittal plane. This overall decrease may be explained by less need of feedback control for walking stabilization in the sagittal plane compared to in the frontal plane. The decrease in coherence was only significant at the left lower vertebral levels and at the right upper vertebral levels around left heel strikes (p< 0.05). Together, these findings confirm the contribution of the vestibular afferent signals to the control of paraspinal muscle activity during walking and indicate that this control is changed in response to different head orientations.

Key Point Summary

Vestibulospinal reflexes simultaneously contribute to stabilizing the centre of mass trajectory and to maintaining an upright posture of the trunk.

Head orientation, which challenges stability via altered visual, vestibular and proprioceptive signals, modifies vestibulospinal reflexes during standing.

To explore the impact of head orientation during walking, we recorded bilateral surface EMG of cervical to lumbar paraspinal muscles, and characterized coherence, gain and delay between EMG and electrical vestibular stimulation, during walking with head facing forward and leftward.

When walking with head facing leftward, vestibular stimulation caused disturbance in sagittal plane. Phasic response in paraspinal muscles with a significant smaller magnitude was found compared to facing forward.

Our results agree with the idea that less feedback control is required for walking stabilization in the sagittal plane and confirm that vestibular afference modulates paraspinal muscle activity for trunk control during walking, and this modulation is changed in response to head orientation.
Histological and gene-expression analyses of pyloric sphincter formation during stomach metamorphosis inXenopus laevis
Authors: Nagura Kei , Ikeda Takafumi , Hasebe Takashi , Satou-Kobayashi Yumeko , Udagawa Sumio , Shigenobu Shuji , Ishizuya-Oka Atsuko , Taira Masanori
Published: May 2024

During anuran metamorphosis from herbivorous tadpoles to carnivorous frogs, the gastrointestinal (GI) tract undergoes drastic remodeling, such as the formation of the stomach-intestine boundary and the development of the pyloric sphincter at the posterior end of the stomach. However, the morphogenetic process and molecular mechanisms of how the pyloric sphincter is formed during metamorphosis, instead of during embryogenesis as in amniotes, are largely uninvestigated. Using the African clawed frogXenopus laevis, we histologically examined the development of the pylorus region from embryonic to froglet stages and performed spatiotemporal gene expression analyses. We found that the pyloric sphincter is formed at a flexure within the pyloric region during metamorphic climax, and that the pyloric and duodenal epithelia, which are morphologically indistinguishable before sphincter formation, become clearly demarcated by the sphincter at the end of metamorphosis. Consistent with these morphological changes, expression domains of a stomach markerbarx1and an intestine markercdx2overlapped until late metamorphic climax, but became separated after metamorphosis. Despite the absence of the sphincter before metamorphosis, various genes crucial for sphincter formation in amniotes were already expressed in the pylorus region ofXenopusembryos. RNA-sequencing analysis at pre-metamorphic and metamorphic-climax stages suggest unappreciated roles of genes, such as those for retinoic acid signaling and various transcription factors, in suppressing or promoting sphincter formation. These data provide histological and molecular insights into the heterochrony of the pyloric sphincter formation in amniotes and anurans.
Exploring Neuroscience Researchers’ Trust in Preprints through Citation Analysis
Authors: Rasuli Behrooz , Seyfzadehdarabad Fatemeh , Cardone Paolo , Thibaut Aurore , Gosseries Olivia
Published: May 2024

Preprints have emerged as efficient tools for fast and free dissemination of scientific findings. The present study explores the evolving landscape of preprints among the field of neuroscience and examines patterns and evolution of citations to preprints over time in this field. Leveraging bibliometric methods, we identified over 33,000 citations (1993-2022) to preprints within neuroscience publications indexed in Scopus. The findings elucidate a significant temporal increase in the number of documents citing preprints, reaching a peak of around 60 per 1,000 Scopus documents in 2021. Diverse document types, particularly reviews, exhibit a growing reliance on preprints as references. The most frequently cited preprint servers include bioRxiv, ArXiv, medRxiv, and PsyArXiv. Leading journals such as eLife and PLOS Computational Biology have cited preprints more than others. The United States takes the lead in citing preprints, followed by the United Kingdom and Germany. Using Scite.ai, motivations underlying preprint citations and the context in which they were cited were explored and the results are indicative of the “mentioning” nature of 93% of citations to preprints. Furthermore, the introduction and discussion sections have shown to include the highest number of citations to preprints. The findings highlight the dynamic transformation of preprints in neuroscience field.
Time-restricted feeding prevents memory impairments induced by obesogenic diet consumption in mice, in part through hippocampal thyroid hormone signaling
Authors: Helbling Jean-Christophe , Ginieis Rachel , Mortessagne Pierre , Ruiz-Gayo Mariano , Ducourneau Eva Gunnel , Ciocca Dominique , Boulete Illona-Marie , Favereaux Alexandre , Ces Aurélia , Montalban Enrica , Capuron Lucile , Jeanneteau Freddy , Ferreira Guillaume , Challet Etienne , Moisan Marie-Pierre
Published: May 2024

The consumption of calorie-rich diet has adverse effects on short and long-term memory, especially when introduced early in life when the brain is still maturing. Time-restricted feeding (TRF) without calorie restriction has proven to be an efficient strategy to reduce the deleterious effects of diet-induced obesity on metabolism. TRF was also shown to be beneficial to restore long-term memory in Alzheimer rodent models. Here, we provide evidence that four weeks of TRF restore the rhythmicity of some metabolic parameters together with short and long-term memory in mice fed a high fat-high sucrose (HFS) diet since weaning. Hippocampal translatome analyses indicated that impaired memory of mice underad libitumHFS diet is accompanied by changes in genes associated with thyroid hormone signaling and astrocytic genes involved in the regulation of glutamate neurotransmission. TRF restored the diurnal expression variation of part of these genes and intra-hippocampal infusion of T3, the active form of thyroid hormone, rescued the memory performances ofad libitumHFS diet-fed mice. Thus, TRF demonstrates positive effects on both metabolism and memory in mice fed an obesogenic diet, highlighting this nutritional approach as a powerful tool in addressing obesity and its related comorbidities in mice. The analogous time-restricted eating in humans is an easy to implement lifestyle intervention that should now be tested in obese adolescents with memory alterations.
Biocompatibility of KAPs-Depleted Residual Hair
Authors: Meer Allison , Mathews Aidan , Cabral Mariana , Tarabokija Andrew , Carroll Evan , Chaudhry Henna , Paszek Michelle , Radecker Nancy , Palaia Thomas , de Guzman Roche C.
Published: May 2024

This work is an in-depth investigation of thein vitroandin vivobiocompatibility of processed and treated residual human hair samples with intact cuticle layers. The specimens included oxidized hair with no melanin (BLH) and hair with medium-(M-KAP) and low-(L-KAP) levels of keratin associated proteins (KAPs), confirmed through gel electrophoresis, electron microscopy, and trichrome histological staining, in comparison to the untreated regular hair (REG) control. All hair groups, high KAPs (H-KAPs: REG and BLH), M-KAP, and L-KAP, were found to be non-cytotoxic in the adipose fibroblast cell line’s response to their extracts based on the ISO 10993-5 medical device biomaterial testing standard.In vivomouse subcutaneous implantation (ISO 10993-6, local effects) at 2 weeks showed that the samples caused a foreign body response (FBR) with a thin fibrous encapsulation at a mean value of 28% relative skin dermis thickness; but notably, the L-KAP implant mitigated a statistically significant decrease in FBR area compared to H-KAP’s (REG and/or BLH) and a lower number of cells, including immune cells of mostly macrophages and mast cells on the biomaterial’s surface, normalized to implant and tissue coverage. In the bulk of the capsules, blood vessels and collagen extracellular matrix densities were similar among groups. These findings suggest that small globular KAPs diffuse out of the cortex to the host-biomaterial interface which induce a slightly elevated FBR but limited to the implant’s surface vicinity. On-going follow-up research focuses on purer keratin-based macromolecularly organized residual hair biomaterials, those with depleted KAPs, for drug-delivery gel implants as they are deemed the most biocompatible.

Statement of Significance

Human hair is an abundant biological product that is regularly discarded and wasted but has the potential to be a clinical implantable allograft biomaterial. There are currently just two FDA class II-510(k)-approved medical devices from hair, limited to surface / skin wound care use, and no class III-PMA or biologics-BLA implants. Also, these products and those in research and development phases are based on soluble keratin and KAPs extracts utilizing tedious processing conditions and requiring oxidation reaction for reassembly into gels and scaffolds. Here we describe that the insoluble residual hair biomaterials with organized keratin structure, higher-degree of disulfide crosslinks, and particularly those with depleted KAPs have increased biocompatibility based on pre-clinical ISO 10993 standards. This novel natural biomaterials are now being developed as drug-delivery implantable gels for clinical applications.
Neuronal downregulation ofPLCG2impairs synaptic function and elicits Alzheimer disease hallmarks
Authors: Coulon Audrey , Rabiller Florian , Takalo Mari , Roy Avishek , Martiskainen Henna , Siedlecki-Wullich Dolores , Mendes Tiago , Lemeu Celia , Carvalho Lukas-Iohan , Ehrardt Anaël , Melo de Farias Ana Raquel , Hulsman Marc , Najdek Chloé , Lannette-Weimann Nina , Freire-Regatillo Alejandra , Amouyel Philippe , Charbonnier Camille , Dols-Icardo Orio , Jeskanen Heli , Willman Roosa-Maria , Kuulasmaa Teemu , Kurki Mitja , Hardy John , Wagner Richard , Heikkinen Sami , Holstege Henne , Mäkinen Petra , Nicolas Gaël , Mead Simon , Wagner Michael , Ramirez Alfredo , Rauramaa Tuomas , Palotie Aarno , Sims Rebecca , Soininen Hilkka , van Swieten John , Williams Julie , Bellenguez Céline , Grenier-Boley Benjamin , Gelle Carla , Lambert Erwan , Ayral Anne-Marie , Demiautte Florie , Costa Marcos R. , Deforges Séverine , Kilinc Devrim , Mulle Christophe , Chapuis Julien , Hiltunen Mikko , Dumont Julie , Lambert Jean-Charles
Published: May 2024

We developed a high content screening to investigate how Alzheimer disease (AD) genetic risk factors may impair synaptic mechanisms in rat primary neuronal cultures. Out of the gene targets identified, we found that shRNA-mediated downregulation ofPlcg2in mouse dentate gyrus neurons consistently impaired dendritic morphology and synaptic function. In human neuronal cultures (hNCs),PLCG2downregulation also impaired synaptic function and was associated with increased levels of Aβ and Tau phosphorylation, potentiallyviathe AKT/GSK3β axis. Very rarePLCG2loss-of-function (LoF) variants were associated with a 10-fold increased AD risk.PLCG2LoF carriers exhibit low mRNA/proteinPLCG2/PLCγ2 levels, consistent with nonsense-mediated mRNA decay mechanisms. Restoring PLCγ2 levels in shPLCG2-hNCs fully reversed the disease-related phenotypes. Our findings indicate that the downregulation of PLCγ2 increases the risk of AD by impairing synaptic function and increasing the levels of Aβ and Tau phosphorylation in neurons.
A first insight into the developability of an IgG3: A combined computational and experimental approach
Authors: Armstrong Georgina B. , Lewis Alan , Shah Vidhi , Taylor Paul , Jamieson Craig J. , Burley Glenn A. , Lewis Will , Rattray Zahra
Published: May 2024

Immunoglobulin G 3 (IgG3) monoclonal antibodies (mAbs) are high value scaffolds for developing novel therapies. Despite their wide-ranging therapeutic potential, IgG3 physicochemical properties and developability characteristics remain largely under-characterised. Protein-protein interactions elevate solution viscosity in high-concentration formulations impacting physico-chemical stability, manufacturability, and injectability of mAbs. Therefore, in this manuscript, the key molecular descriptors and biophysical properties of a model anti-IL-8 IgG1 and its IgG3 ortholog are characterised. A computational and experimental framework was applied to measure molecular descriptors impacting on their downstream developability. Findings from this approach underpin a detailed understanding of the molecular characteristics of IgG3 mAbs as potential therapeutic entities. This work is the first report examining the manufacturability of IgG3 for high concentration mAb formulations. While poorer conformational and colloidal stability, and elevated solution viscosity was observed for IgG3, future efforts controlling surface potential through sequence-engineering of solvent-accessible patches can be used to improve biophysical parameters that dictate mAb developability.
Magnesium hydroxide nanoneedles derived fromAnthocleista schweinfurthiiGilg (Loganiaceae) support mesenchymal stromal cell proliferation and wound healing
Authors: Eya’ane Meva Francois , Pereira Rita , Ngnihamye Sandrine Elodie , Armel Florian Tchangou Njiemou , Ntoumba Agnes Antoinette , Hzounda Fokou jean Batiste , Beglau Thi Hai Yen , Fetzer Marcus N. A. , Kaul Marilyn , Schlierf Bianca , Mintang Fongang Ulrich Armel , Belle Ebanda Kedi Phillipe , Fannang Simone Veronique , Herrmann Marietta , Janiak Christoph
Published: May 2024

Multiple metallic nanoparticles are able to promote cellular and tissue health, but these nanoparticles can be difficult to synthesize and can also cause unintended side-effects. Here, we study the effects on wounds healing and bone reparation of Mg(OH)2fromAnthocleista schweinfurthiiGilg (Loganiaceae) leaves (AS), which are local to the Africa region and have been used in traditional medicine to treat injuries. Mg(OH)2nanoneedles were synthesized from aqueous extracts ofAnthocleista schweinfurthiiGilg (Loganiaceae) leaves (AS) and magnesium nitrate. The quick polydispersing and crystallized Mg(OH)2-metal interface was found to be covered in plant secondary metabolites. We call this compound Mg(OH)2-AS. Using an acute dermal toxicity experiment on animal model, we determined that Mg(OH)2-AS is safe for topical application.In vitroexperiments suggest that Mg(OH)2-AS has anti-inflammatory potential, andin vivowound healing assays in Wistar rats indicate that Mg(OH)2-AS can enhance wound healing. To investigate Mg(OH)2-AS effects on the cellular level, we used bone marrow mesenchymal stromal cells (BM-MSCs). In contrast to pure Mg(OH)2or AS, cell viability and proliferation were not impaired by Mg(OH)2-AS. Cell morphology remained unchanged upon media supplementation with Mg(OH)2-AS. Preliminary results further indicate enhanced osteogenic differentiation of BM-MSCs in media supplied with ascorbic acid, β-glycerophosphate and dexamethasone and addition of Mg(OH)2-AS. These findings motivate further research towards the inclusion of the material in implants for bone fracture healing.
Nanomotif: Leveraging DNA Methylation Motifs for Genome Recovery and Host Association of Plasmids in Metagenomes from Complex Microbial Communities
Authors: Heidelbach Søren , Dall Sebastian Mølvang , Bøjer Jeppe Støtt , Nissen Jacob , van der Maas Lucas N.L. , Sereika Mantas , Kirkegaard Rasmus H. , Jensen Sheila I. , Kousgaard Sabrina Just , Thorlacius-Ussing Ole , Hose Katja , Nielsen Thomas Dyhre , Albertsen Mads
Published: May 2024

DNA methylation is found across all domains of life but is a rarely used feature in recovery of metagenome-assembled genomes (MAGs). Recently, Oxford Nanopore introduced all context methylation detection models. We leveraged this to develop Nanomotif, which identifies and exploits methylation motifs for enhanced MAG recovery. We demonstrate how Nanomotif enables database-independent contamination removal from high-quality MAGs and host association of plasmids directly from Nanopore sequencing data in complex metagenomes.