bluuebunny/crossref_metadata_2025 huggingface dataset:
Voluntary co-contraction of ankle muscles alters motor unit discharge characteristics and reduces estimates of persistent inward currents
Authors: Gomes Matheus M. , Jenz Sophia T. , Beauchamp James A. , Negro Francesco , Heckman C.J. , Pearcey Gregory E.P.
Published: March 2024

Motoneuronal persistent inward currents (PICs) are both facilitated by neuromodulatory inputs and highly sensitive to local inhibitory circuits (e.g., Ia reciprocal inhibition). Methods aimed to increase group Ia reciprocal inhibition from the antagonistic muscle have been successful in decreasing PICs, and the diffuse actions of neuromodulators released during activation of remote muscles have increased PICs. However, it remains unknown how motoneurons function in the presence of simultaneous excitatory and inhibitory commands. To probe this topic, we investigated motor unit (MU) discharge patterns and estimated PICs during voluntary co-contraction of ankle muscles, which simultaneously demands the contraction of agonist-antagonist pairs. Twenty young adults randomly performed triangular ramps (10s up and down) of both co-contraction (simultaneous dorsiflexion and plantarflexion) and isometric dorsiflexion to a peak of 30% of their maximum muscle activity from a maximal voluntary contraction. Motor unit spike trains were decomposed from high-density surface electromyography recorded over the tibialis anterior (TA) using blind source separation algorithms. Voluntary co-contraction altered motor unit discharge rate characteristics, decreasing estimates of PICs by 20% (4.47 pulses per second (pps) vs 5.57 pps during isometric dorsiflexion). These findings suggest that, during voluntary co-contraction, the inhibitory input from the antagonist muscle overcomes the additional excitatory and neuromodulatory drive that may occur due to the co-contraction of the antagonist muscle, which constrains PIC behavior.

KEY POINTS

Voluntary co-contraction is a unique motor behavior that concurrently provides increases in excitatory and inhibitory inputs to motoneurons.

During co-contraction of agonist-antagonist pairs, agonist motor unit discharge characteristics are altered, consistent with reductions in persistent inward current magnitude.

Reciprocal inhibition from the antagonist likely becomes proportional to the increase in neural drive to the agonist, dampening the magnitude of persistent inward currents.
“Identification of microRNAs regulated by E2F transcription factors in human pluripotent stem cells”
Authors: Rodríguez-Varela María Soledad , Vautier Mercedes Florencia , Mucci Sofía , Isaja Luciana , Fernández Elmer , Sevlever Gustavo Emilio , Scassa María Elida , Romorini Leonardo
Published: March 2024

Human pluripotent stem cells (hPSCs), which include embryonic and induced pluripotent stem cells (hESCs and hiPSCs, respectively), have an unusual cell cycle structure which consists of a short G1 phase and the absence of the G1/S checkpoint regulation. E2F transcription factors (E2Fs) play an important role in the G1/S transition. G1 duration contributes to hPSC fate determination, and microRNAs (miRNAs) play critical roles in this commitment. As little is known about the interplay between E2Fs and miRNAs in hPSCs, we aimed to identify miRNAs that are regulated by E2Fs in these cells. We first found that mRNA expression levels of canonical E2F repressors were more expressed than most E2F activators in G1-arrested hPSCs. Moreover, we observed higher mRNA and protein expression levels of canonicalE2F2,E2F3A,andE2F5in G1 synchronized hPSCs compared to human fibroblasts (HF). However,E2F1andE2F4protein expression levels were higher in HF. We next found that E2F inhibition with HLM006474 induced an increase in the G1 cell population without affecting hPSC viability, concomitantly with a decrease inOCT-4mRNA levels and the percentage of OCT-4+hPSCs. Next, by RNA-seq analysis we found 52 differentially expressed (DEGs) miRNAs in HLM006474-treated hESCs. RT-qPCR validation of some of the DEGs let us conclude that miR-19a-3p, miR-19b-3p, miR-4454, miR-1260a, miR-1260b, miR-454-3p and miR-301a-3p are regulated by E2Fs in hPSCs. Interestingly, gene target and ontology analysis of these miRNAs revealed a possible implication in proliferation and cell cycle regulation, development, and neural differentiation.
Latest RNA and DNA nanopore sequencing allows for rapid avian influenza profiling
Authors: Perlas Albert , Reska Tim , Croville Guillaume , Tarrés-Freixas Ferran , Guérin Jean-Luc , Majó Natàlia , Urban Lara
Published: March 2024

Avian influenza virus (AIV) currently causes a panzootic with extensive mortality in wild birds, poultry, and wild mammals, thus posing a major threat to global health and underscoring the need for efficient monitoring of its distribution and evolution. Here, we utilized a well-defined AIV strain to systematically investigate AIV characterization through rapid, portable nanopore sequencing by (i) benchmarking the performance of fully portable RNA extraction and viral detection; (ii) comparing the latest DNA and RNA nanopore sequencing approaches for in-depth AIV profiling; and (iii) evaluating the performance of various computational pipelines for viral consensus sequence creation and phylogenetic analysis. Our results show that the latest RNA-specific nanopores can accurately genomically profile AIV from native RNA while additionally detecting RNA epigenetic modifications. We further identified an optimal laboratory and bioinformatic pipeline for reconstructing viral consensus genomes from nanopore sequencing data at various rarefaction thresholds, which we validated by application to real-world environmental samples for AIV monitoring in livestock.

Author Summary

We tested portable, rapid, and easy-to-use technology to obtain more information about the potentially zoonotic RNA virus avian influenza virus, or AIV. AIV has spread globally via the migratory paths of wild birds, and endangers domestic birds, mammals, and human populations given past evidence of infections of different animal species. We here used novel genomic technology that is based on nanopores to explore the genomes of the virus; we established optimized ways of creating the viral genome by comparing different laboratory and computational approaches and the performance of nanopores that either sequence the viral RNA directly or the converted DNA. We then applied the optimized protocol to dust samples which were collected from a duck farm in France during an AIV outbreak. We showed that we were able to use the resulting data to reconstruct the relationship between the virus responsible for the outbreak and previously detected AIV. Altogether, we showed how novel easy-to-use genomic technology can support the surveillance of potentially zoonotic pathogens by accurately recreating the viral genomes to better understand evolution and transmission of these pathogens.
On the Evolution of Chromosomal Regions with High Gene Strand Bias in Bacteria
Authors: Tomasch Jürgen , Kopejtka Karel , Shivaramu Sahana , Mujakic Izabela , Koblížek Michal
Published: March 2024

On circular bacterial chromosomes, the majority of genes are coded on the leading strand. This gene strand bias (GSB) ranges from up to 85% in some Bacillota to little more than 50% in other phyla. The factors defining the extent of the GSB remain to be found. Here, we report that species in the phylum Gemmatimonadota share a unique chromosome architecture, distinct from neighboring phyla: In a conserved 600 kb region around the terminus of replication, almost all genes were located on the leading strands while on the remaining part of the chromosome the strand preference was more balanced. The high strand bias (HSB) region harbors the rRNA clusters, core, and highly expressed genes. Selective pressure for reduction of collisions with DNA replication to minimize detrimental mutations can explain the conservation of essential genes in this region. Repetitive and mobile elements are underrepresented, suggesting reduced recombination frequency by structural isolation from other parts of the chromosome. We propose that the HSB region forms a distinct chromosomal domain. Gemmatimonadota chromosomes evolved mainly by expansion through horizontal gene transfer and duplications outside of the ancient HSB region. In support of our hypothesis, we could further identify two Spiroplasma strains on a similar evolutionary path.

Importance

On bacterial chromosomes, a preferred location of genes on the leading strand has evolved to reduce conflicts between replication and transcription. Despite a vast body of research, the question why bacteria show large differences in their GSB is still not solved. The discovery of ‘hybrid’ chromosomes in different phyla, including Gemmatimonadota, in which a conserved high GSB is found exclusively in a region atter, points towards a role of nucleoid structure, additional to replication, in the evolution of strand preferences. A fine-grained structural analysis of the ever-increasing number of available bacterial genomes could help to better understand the forces that shape the sequential and spatial organization of the cell’s information content.
Ultrasonic Cigarettes: Chemicals and Cytotoxicity are Similar to Heated-Coil Pod-Style Electronic Cigarettes
Authors: Omaiye Esther E. , Luo Wentai , McWhirter Kevin J. , Pankow James F. , Talbot Prue
Published: March 2024

Our purpose was to test the hypothesis that ultrasonic cigarettes (u-cigarettes), which operate at relatively low temperatures, produce aerosols that are less harmful than heated-coil pod-style electronic cigarettes (e-cigarettes). The major chemicals in SURGE u-cigarette fluids and aerosols were quantified, their cytotoxicity and cellular effects were assessed, and a Margin of Exposure risk assessment was performed on chemicals in SURGE fluids. Four SURGE u-cigarette flavor variants (“Watermelon Ice,” “Blueberry Ice,” “Green Mint,” and “Polar Mint”) were evaluated. Flavor chemicals were quantified in fluids and aerosols using gas chromatography/mass spectrometry. Cytotoxicity and cell dynamics were assessed using the MTT assay, live-cell imaging, and fluorescent microscopy. WS-23 (a coolant) and total flavor chemical concentrations in SURGE were similar to e-cigarettes, while SURGE nicotine concentrations (13 - 19 mg/mL) were lower than many 4thgeneration e-cigarettes. Transfer efficiencies of dominant chemicals to aerosols in SURGE ranged from 44 - 100%. SURGE fluids and aerosols had four dominant flavor chemicals (> 1 mg/mL). Toxic aldehydes were usually higher in SURGE aerosols than in SURGE fluids. SURGE fluids and aerosols had aldehyde concentrations significantly higher than pod-style e-cigarettes. Chemical constituents, solvent ratios, and aldehydes varied among SURGE flavor variants. SURGE fluids and aerosols inhibited cell growth and mitochondrial reductases, produced attenuated and round cells, and depolymerized actin filaments, effects that depended on pod flavor, chemical constituents, and concentration. The MOEs for nicotine, WS-23, and propylene glycol were < 100 based on consumption of 1 - 2 SURGE cigarettes/day. Replacing the heating coil with a sonicator did not eliminate chemicals, including aldehydes, in aerosols or diminish toxicity in comparisons between SURGE and other pod products. The high concentrations of nicotine, WS-23, flavor chemicals, and aldehydes and the cytotoxicity of SURGE aerosols do not support the hypothesis that aerosols from u-cigarettes are less harmful than those from e-cigarettes.
SARS-CoV-2 diversity and transmission on a university campus across two academic years during the pandemic
Authors: Casto Amanda M , Paredes Miguel I , Bennett Julia Catherine , Luiten Kyle G , O'Hanlon Jessica A. , Han Peter D. , Gamboa Luis , McDermot Evan , Truong Melissa , Gottlieb Geoffrey S , Acker Zack , Wolf Caitlin R , Magedson Ariana , Lo Natalie K. , McDonald Devon , Wright Tessa C , McCaffrey Kathryn , Figgins Marlin D , Englund Janet A , Boeckh Michael , Lockwood Christina M , Nickerson Deborah A. , Shendure Jay , Uyeki Timothy M , Starita Lea M , Bedford Trevor , Chu Helen Y , Weil Ana A
Published: March 2024

Institutions of higher education (IHEs) have been a focus of SARS-CoV-2 transmission studies but there is limited information on how viral diversity and transmission at IHEs changed as the pandemic progressed. Here we analyze 3606 viral genomes from unique COVID-19 episodes collected at a public university in Seattle, Washington (WA) from September 2020 to September 2022. Across the study period, we found evidence of frequent viral transmission among university affiliates with 60% (n=2153) of viral genomes from campus specimens genetically identical to at least one other campus specimen. Moreover, viruses from students were observed in transmission clusters at a higher frequency than in the overall dataset while viruses from symptomatic infections were observed in transmission clusters at a lower frequency. Though only a small percentage of community viruses were identified as possible descendants of viruses isolated in university study specimens, phylodynamic modelling suggested a high rate of transmission events from campus into the local community, particularly during the 2021-2022 academic year. We conclude that viral transmission was common within the university population throughout the study period but that not all university affiliates were equally likely to be involved. In addition, the transmission rate from campus into the surrounding community may have increased during the second year of the study, possibly due to return to in-person instruction.
Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder
Authors: Sudnawa Khemika K. , Li Wenxing , Calamia Sean , Kanner Cara H. , Bain Jennifer M. , Abdelhakim Aliaa H. , Geltzeiler Alexa , Mebane Caroline M. , Provenzano Frank A. , Sands Tristan T. , Fee Robert J. , Montes Jacqueline , Shen Yufeng , Chung Wendy K.
Published: March 2024

Purpose

Pathogenic variants in Kinesin Family Member 1A (KIF1A) are associated withKIF1A-associated neurological disorder (KAND). We report the clinical phenotypes and correlate genotypes of individuals with KAND.

Methods

Medical history and adaptive function were assessed longitudinally. In-person evaluations included neurological, motor, ophthalmologic and cognitive assessments.

Results

We collected online data on 177 individuals. Fifty-seven individuals were also assessed in-person. Most individuals hadde novoheterozygous missense likely pathogenic/pathogenicKIF1Avariants. The most common characteristics were hypotonia, spasticity, ataxia, seizures, optic nerve atrophy, cerebellar atrophy, and cognitive impairment. Mean Vineland Adaptive Behavior Composite score (VABS-ABC) was low (M=62.9,SD=19.1). The mean change in VABS-ABC over time was -3.1 (SD=7.3). The decline in VABS-ABC was associated with the age at first assessment and abnormal electroencephalogram/seizure. There was a positive correlation between Evolutionary Scale Model (ESM) score for the variants and final VABS-ABC (p=0.003). Abnormal electroencephalogram/seizure, neuroimaging result, and ESM explain 34% of the variance in final VABS-ABC (p<0.001).

Conclusion

In-person assessment confirmed caregiver report and identified additional visual deficits. Adaptive function declined over time consistent with both the neurodevelopmental and neurodegenerative nature of the condition. Using ESM score assists in predicting phenotype across a wide range of unique variants.
Predicting Patient Weight from Intracardiac Electrograms: A Study in Electrophysiological Signal Analysis
Authors: Alagöz Celal
Published: March 2024

The analysis of electrophysiological signals from the human body has become increasingly crucial, especially given the widespread adoption of wearable technologies and the growing trend of remote and online monitoring. In situations where demographic patient data is unavailable, the evaluation of such information from electrophysiological signals becomes imperative for making well-informed diagnostic and therapeutic decisions, particularly in ambulatory and urgent cases. This study underscores the significance of this necessity by utilizing intracardiac electrograms to predict patient weight.

Intracardiac electrograms were recorded from 44 patients (14 female, with an average age of 59.2±11.5 years) using a 64-pole basket catheter over a duration of 60 seconds. A dataset comprising 2,816 unipolar electrogram signal segments, each lasting 4 seconds, was utilized. Weight, considered as a continuous variable, underwent discretization into k bins with uniformly distributed widths, where various values of k were experimented with. As the value of k increases, class imbalance also increases.

The state-of-the-art time series classification algorithm, Minirocket, was employed alongside the popular machine learning algorithm eXtreme Gradient Boosting (XGBoost). Minirocket consistently demonstrates superior performance compared to XGBoost across all class number scenarios and across all evaluation metrics, such as accuracy, F1 score, and Area Under the Curve (AUC) values, achieving scores of approximately 0.96. Conversely, XGBoost shows signs of overfitting, particularly noticeable in scenarios with higher class imbalance. Tuning probability thresholds for classes could potentially mitigate this issue. Additionally, XGBoost’s performance improves with reduced bin numbers, emphasizing the importance of balanced classes. This study provides novel insights into the predictive capabilities of these algorithms and their implications for personalized medicine and remote health monitoring.
Evaluation of a Low-threshold Exercise And Protein supplementation intervention for Women (LEAP-W) experiencing homelessness and addiction: Protocol for a single-site intervention study.
Authors: Kennedy Fiona , Murray Deirdre , Ní Cheallaigh Clíona , Romero-Ortuno Roman , Broderick Julie
Published: March 2024

Background: Frailty is a complex multi-dimensional state of increased vulnerability to adverse health outcomes and is usually associated with older age but there is growing evidence of accelerated ageing and frailty in non-geriatric populations, including those experiencing socio-economic deprivation and extreme social exclusion, such as people experiencing homelessness. Addiction, as a coping mechanism for prior trauma, is common among people who are homeless and can have a gendered dimension. Women experiencing homelessness and addiction have unique needs which require a gendered approach. The aim of this study is to explore the effectiveness of an exercise intervention to target the known physical functioning deficits and frailty which this population experiences. Methods: This mixed-methods study will explore physical functioning deficits and frailty in women experiencing homelessness and addiction, using a bespoke test battery and an exercise intervention. Physical function (10m Walk Test, 2 Min Walk Test, Single Leg Stance, Chair Stand Test, hand grip dynamometry), frailty (Clinical Frailty Scale and the SHARE-Frailty Instrument) and nutritional status (Mini-Nutritional Status), pain (Numerical Pain Rating Scale) and quality of life (SF 12-V2) will be evaluated. The 10-week intervention will involve a 3-times weekly exercise programme with protein supplementation. Following this, qualitative interviews, which will be thematically analysed using Braun & Clarke methodology, will be conducted. This study will be conducted in Dublin from February to July 2024. Discussion: Little is known about frailty-focussed interventions in women experiencing homelessness and addiction. This proposed study will help to increase the knowledge base regarding the physical health burden and frailty experienced by this extremely vulnerable population and will deliver a targeted intervention with a gendered dimension to mitigate its affects. The findings of this research will help narrow this research gap and will guide clinicians and policy makers to implement unique gender-based treatment strategies for this population.
Improvement of Survival Outcomes of Cholangiocarcinoma by Ultrasonography Surveillance: Multicenter Retrospective Cohorts
Authors: Chamadol Nittaya , Laopaiboon Vallop , Jareanrat Apiwat , Thanasukarn Vasin , Srisuk Tharatip , Luvira Vor , Sarkhampee Poowanai , Ungpinitpong Winai , Khamvijite Phummarat , Chumnanua Yutthapong , Nethuwakul Nipath , Sodarat Passakorn , Thammarit Samrit , Techasen Anchalee , Thuanman Jaruwan , Tawarungruang Chaiwat , Thinkhamrop Bandit , Sa-Ngiamwibool Prakasit , Loilome Watcharin , Prajumwongs Piya , Titapun Attapol
Published: March 2024

Introduction

Most cholangiocarcinoma (CCA) patients present with late stage of disease because of the difficulty to diagnosis at an early stage, resulting in poor survival of CCA patients. The Cholangiocarcinoma Screening and Care Program showed that ultrasound screening was an effective tool for detecting early stage CCA. This study aims to evaluate the survival outcome of patients diagnosed by ultrasound screening (US) compared to walk-in symptomatic patients.

Methods

5-year survival rates (5-YSR) and median survival time (MST) of CCA were calculated using Log-Rank test. Multivariate analyses were performed for significant factors from univariate analyses.

Results

A total of 711 histologically proven CCA cases were examined including ultrasound screening and walk-in groups. The screening group having 5-YSR was 53.9%, and MST was of 67.2 months, while walk-in group, the 5-YSR was 21.9% and MST was 15.6 months (p<0.001). In addition, multivariate analyses revealed that screening program was an independent factor to predict a good outcome of CCA patients when compared with walk-in group (p= 0.014).

Conclusion

US is an effective tool for detecting early stage CCA leading to improve clinical outcome of CCA patients. Practically, US should be considered as a first tool for screening CCA in risk populations.

Author Summary

Most cholangiocarcinoma (CCA) patients in Thailand have poor survival due to late-stage detection and patients walk-in to hospital with any symptoms. This study purpose to evaluate the survival outcome of CCA patients diagnosed by ultrasound screening (US). We found that US provided early stage and improved survival of CCA patients.
Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19 A retrospective case-control study
Authors: Zaremba Solomiia , Miller Alex J. , Ovrom Erik A. , Senefeld Jonathon W. , Wiggins Chad C. , Dominelli Paolo B. , Ganesh Ravindra , Hurt Ryan T. , Bartholmai Brian J. , Welch Brian T. , Ripoll Juan G. , Joyner Michael J. , Ramsook Andrew H.
Published: March 2024

Background

Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10-30% of patients with acute COVID-19 infection, symptoms persist for more than 4 weeks (referred to as post-acute sequelae of COVID-19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate if luminal area of large conducting airways is different between PASC and COVID-19 patients, and healthy controls.

Methods

In this retrospective case-control study seventy-five patients with PASC (48 females) were age-, height-, and sex-matched to 75 individuals with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi.

Findings

Airway luminal areas between COVID-19 and PASC groups were not different (p>0.66). There were no group differences in airway luminal area (PASC vs control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12% to 39% larger among PASC patients compared to controls (p<0.05).

Interpretation

Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared to healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for complete reversal of changes.

Funding

National Heart, Lung, and Blood Institute (F32HL154320 to JWS; 5R35HL139854 to MJJ); Postdoctoral Fellowship from the Natural Sciences and Engineering Research Council of Canada (AHR).
Patterns of mental disorders in a nationwide child psychiatric sample (N=67,815): A DREAMS study
Authors: van der Mheen Malindi , Zijlmans Josjan , van der Doelen Daniël , Klip Helen , van der Lans Rikkert M. , Ruisch I. Hyun , de Vries Ymkje Anna , Tieskens Jacintha M. , Wildschut Marleen , Buitelaar Jan K. , Hoekstra Pieter J. , Lindauer Ramón J.L. , Popma Arne , Vermeiren Robert R.J.M. , Staal Wouter ,   DREAMS consortium, Polderman Tinca J.C.
Published: March 2024

Objective

To provide a comprehensive overview of the prevalence and comorbidity patterns of mental disorders in a large, nationwide child and adolescent psychiatry sample.

Methods

We retrieved data on DSM diagnoses from medical records of children (0.5-23 years old) who received care at a DREAMS center between 2015 and 2019. DREAMS is a consortium of four academic centers for child and adolescent psychiatry in the Netherlands that provide both outpatient and inpatient care. Diagnoses were assigned in regular clinical practice.

Results

Between 2015 and 2019, 67,815 children received care at a DREAMS center (age at admissionM=11.0 years,SD=4.3; 59.7% male). Of these children, 48,342 (71.3%) had a registered DSM disorder. The most prevalent primary diagnoses were ASD (34.1%), ADHD (24.4%) and trauma and stressor-related disorders (8.7%). Approximately half of all children (47.4%) had at least one comorbid diagnosis, of which intellectual disabilities were the most prevalent (14.0%).

Conclusion

Diagnostic patterns across sex and age as well as comorbidity patterns were generally consistent with previous research, but the prevalence of ASD and ADHD was higher than in other studies. Real-world diagnostic information such as presented here is essential to understand the use of DSM-5 in clinical practice, put differences between contexts and countries into perspective, and ultimately improve our diagnostic protocols and treatments.
Effectiveness of physical activity in obese children and adolescents and serum interleukin-10 levels: A protocol for systematic review
Authors: Pascoal Andreza Gomes , de Souza Mendes Paula , Rodrigues Lima Luiz Eduardo , Mori Bruno
Published: March 2024

Background

Obesity is a global health problem that affects millions of people around the world, especially children and adolescents. The main causes of obesity are a sedentary lifestyle, unhealthy diet, and lack of reduction in the level of physical activity with negative consequences for physical and mental health, such as increased risk of cardiovascular diseases, diabetes, hypertension, dyslipidemia, and inflammation. Therefore, we will carry out a perform a systematic review to evaluate the effectiveness of physical activity in obese children and adolescents and serum interleukin-10 levels.

Methods

This protocol is based on recommendations from the Cochrane Collaboration on the steps of a systematic review. A literature search will be performed on the following database: PubMed, the Cochrane Library, LILACS (VHL), and Google Scholar. According to the Cochrane Risk of Bias Tool and the level of evidence for results, we will assess the quality of the included studies by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. The Review Manager (v5.3) software will be applied to statistical analysis.

Results

From the study, we will evaluate the effectiveness of physical activity in obese children and adolescents and serum IL-10 levels correlated with age, ethnicity, sex, and body mass index (BMI).PROSPERO registration number: CRD42022355721

Strengths and limitations of this study

This article emphasizes the importance of evaluating the effectiveness of physical activity in obese children and adolescents and provides methodological guidance for evaluating clinical evidence. This study 1)provides a research protocol, 2) facilitates reasonable assessment of physical activity in obese children and adolescents and serum IL-10 levels 3) increases the potential importance of recommending physical activity in obese children and adolescents to improve serum levels of IL-10, which in turn has an immunoprotective effect. The lack of reports of these effects may be limited by the small sample size.
Sex differences in symptomatology and immune profiles of Long COVID
Authors: Silva Julio , Takahashi Takehiro , Wood Jamie , Lu Peiwen , Tabachnikova Alexandra , Gehlhausen Jeff R. , Greene Kerrie , Bhattacharjee Bornali , Monteiro Valter Silva , Lucas Carolina , Dhodapkar Rahul M. , Tabacof Laura , Peña-Hernandez Mario , Kamath Kathy , Mao Tianyang , Mccarthy Dayna , Medzhitov Ruslan , van Dijk David , Krumholz Harlan M. , Guan Leying , Putrino David , Iwasaki Akiko
Published: March 2024

Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection1–7. However, whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling of 165 individuals8with and without LC in an exploratory, cross-sectional study to identify key immunological traits underlying biological sex differences in LC. We found that female and male participants with LC experienced different sets of symptoms, and distinct patterns of organ system involvement, with female participants suffering from a higher symptom burden. Machine learning approaches identified differential sets of immune features that characterized LC in females and males. Males with LC had decreased frequencies of monocyte and DC populations, elevated NK cells, and plasma cytokines including IL-8 and TGF-β-family members. Females with LC had increased frequencies of exhausted T cells, cytokine-secreting T cells, higher antibody reactivity to latent herpes viruses including EBV, HSV-2, and CMV, and lower testosterone levels than their control female counterparts. Testosterone levels were significantly associated with lower symptom burden in LC participants over sex designation. These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex-specific pathology.
Xylazine Awareness, Desire, Use and Exposure: Preliminary Findings from the Rhode Island CUTS Drug Checking Cohort
Authors: Park Ju Nyeong , Serafinski Rachel , Ujeneza Merci , McKenzie Michelle , Tardif Jessica , Krotulski Alex J. , Badea Adina , Grossman Elyse R. , Green Traci C.
Published: March 2024

Background

Xylazine, an α2 adrenergic receptor agonist, is a veterinary sedative that causes severe health complications yet interventions to detect, prevent and treat human exposure remain underdeveloped. Community-based drug checking services (DCS) involve the consensual collection and testing of small amounts of drugs to increase community awareness and reduce drug-related harms. This study characterized xylazine awareness, desire, use and exposure among people who use drugs (PWUD) in Rhode Island, USA.

Methods

We linked and analyzed DCS and survey data from an ongoing cohort of PWUD. Between February and August 2023, 125 PWUD were recruited and enrolled from harm reduction organizations and surveyed about xylazine awareness and use behaviors. Using point-of-care Fourier Transform infrared spectroscopy (FTIR-S), at least one drug sample was tested from each participant and confirmed offsite at a laboratory. Results were conveyed in real-time, along with harm reduction education, referrals to resources and care.

Results

Virtually all participants (99%) wanted to avoid xylazine exposure. Half (51%) knew what xylazine was, and a quarter (26%) suspected previous exposure. Xylazine exposure was primarily surmised through sedating (45%) and ulcerative (26%) effects. Only 9% of participants submitted a sample that they perceived to contain xylazine. Xylazine was detected in 14% of samples using FTIR-S and in 21% of samples using a dual laboratory approach of gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Participants thought that these xylazine-positive samples were fentanyl (77%), heroin (14%), or Percocet® (9%).

Conclusion

Implementing point-of-care DCS at harm reduction organizations could be useful in rapidly increasing xylazine awareness and engaging at-risk individuals in prevention, harm reduction, treatment, and rapid care for xylazine-related wounds.
Relation of frailty with depression among Colombian COPD adults aged over 60 years
Authors: Campo-Arias Adalberto , Pedrozo-Pupo John Carlos , Caballero-Domínguez Carmen Cecilia
Published: March 2024

Introduction

Frailty and depression risk are common in older adults undergoing chronic obstructive pulmonary disease (COPD) treatment. However, little is known about this association in people with COPD residing in low- and middle-income countries. The study aimed to o establish the relationship between frailty and depression among ambulatory adults over 60 years with COPD in Santa Marta, Colombia.

Methods

A cross-sectional study was designed in which consecutive patients from the pulmonology outpatient clinic were invited to participate. Frailty was quantified with the FiND (Frail Non-Disabled [FiND] Screening Tool) [Cronbach’s alpha 0.65] and depression with the Primary Care Screening Questionnaire for Depression (PSQD) [Cronbach’s alpha 0.73].

Results

Three-hundred forty-nine patients with COPD between 60 and 98 years participated (M=75.6, SD=8.4), 61.9% were males, and 19.8% presented a C or D combined evaluation. Two hundred eighty-six patients (76.8%) presented frailty with and without mobility disability, and 31.2% presented depression. The relationship of frailty with depression remained significant, even after adjusting for confounding variables (OR=2.80, 95%CI 1.42-5.51).

Conclusions

Frailty and depression are significantly associated after adjusting for confounding variables. More studies are welcome.
Low-intensity repetitive transcranial magnetic stimulation is safe and well tolerated by people living with MS - outcomes of the phase I randomised controlled trial (TAURUS)
Authors: Nguyen Phuong Tram , Zarghami Amin , Makowiecki Kalina , Stevens Natasha , Ezegbe Chigozie , Kyle Kain , Wang Chenyu , Ly Linda , De La Rue Katie , Hinder Mark R , Johnson Lewis , Rodger Jennifer , Cooper Samantha , Cullen Carlie L , Barnett Michael , Young Kaylene M , Taylor Bruce V
Published: March 2024

Background

Low-intensity repetitive transcranial magnetic stimulation (rTMS), delivered as a daily intermittent theta burst stimulation (iTBS) for 4 consecutive weeks, increases the number of new oligodendrocytes in the adult mouse brain. rTMS holds potential as a remyelinating intervention for people with MS.

Objective

Primarily to determine the safety and tolerability of our rTMS protocol in people with MS. Secondary objectives included feasibility, blinding, and an exploration of changes in magnetic resonance imaging (MRI) metrics, patient reported outcome measures (PROMs) and cognitive or motor performance.

Methods

A randomised (2:1), placebo controlled, single blind, parallel group, phase 1 trial of 20 rTMS sessions (600 iTBS pulses per hemisphere; 25% maximum stimulator output), delivered over 4-5 weeks, with the coil positioned at 90° (n=7, ‘sham’) or 0° (n=13, active rTMS).

Results

Five adverse events (AEs) including one serious AE reported. None were related to treatment. Protocol compliance was high (85%) and blinding successful. Within participant MRI metrics, PROMs and cognitive or motor performance were unchanged over time.

Conclusion

20 sessions of rTMS is safe and well tolerated in a small group of people with MS. The study protocol and procedures are feasible. Improvement of sham is warranted before further investigating safety and efficacy.

Trial registration

Australian New Zealand Clinical Trials Registry (ACTRN12619001196134).https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378010&isReview=true
Enhancer RNA transcriptome-wide association study reveals an atlas of pan-cancer susceptibility eRNAs
Authors: Chen Wenyan , Wang Zeyang , Lin Jianxiang , Chen Shuxin , Chen Hui , Ma Xuelian , Zou Xudong , Li Xing , Wang Yinuo , Qin Yangmei , Ma Xixian , Qiao Yunbo , Li Lei
Published: March 2024

Many cancer risk variants are located within enhancer regions and lack sufficient molecular interpretation. Here, we constructed the first comprehensive atlas of enhancer RNA (eRNA)- mediated genetic effects from 28,033 RNA sequencing samples across 11,606 individuals, identifying 11,757 eRNA quantitative trait loci (eRNA-QTLs) significantly associated with eRNA expression. Mechanistically, eRNA-QTLs frequently altered binding motifs of transcription factors. In addition, 28.48% of cancer risk variants were strongly colocalized with eRNA-QTLs. We further performed an eRNA-based transcriptome-wide association study and identified 626 cancer susceptibility eRNAs across 23 cancer types. 54.9% of the eRNA target genes were overlooked by traditional gene expression studies, and most are essential for cancer cell proliferation. To substantiate our findings, we confirmed the enhancer functionality of two newly identified susceptibility eRNAs,CCND1eandSNAPC1e, through CRISPR-based inhibition, resulting in a marked decrease in the expression of their respective target genes, consequently suppressing the proliferation of prostate cancer cells. Our study underscores the essential role of eRNA in unveiling new cancer susceptibility genes and establishes a strong framework for enhancing our understanding of human cancer etiology.
TEMPORAL SPATIALIZATION AS A STRATEGY FOR URBAN MANAGEMENT IN CONTROLLING DISEASES TRANSMITTED BY MOSQUITOES
Authors: de Almeida Márlon Luiz , Souza Fábio Teodoro de , Pontes Alzair Eduardo , Nogueira Rodrigo Sant’Ana , Baldini Raquel Ribeiro de Medeiros
Published: March 2024

Due to their ecophysiological ability to adapt to new environments, combined with climate change, mosquitoes that vector dengue fever and other arboviruses are increasingly expanding their areas of infestation. Dengue fever has shown growth across the planet, reaching countries and regions that were previously free of this disease. And urban management must find tools that help minimize or eradicate arbovirus vectors. This research aims to demonstrate how the temporal spatialization of diseases transmitted by mosquitoes can contribute to urban management in controlling these types of illnesses in small cities. Through a case study in a small town in the interior of Brazil, it was possible to accurately detect, through temporal spatialization, which neighborhoods were most prone to the disease from 2010 to 2020. Thus, urban management can develop public policies in these neighborhoods and improve their performance against the disease.
CZ ID: a cloud-based, no-code platform enabling advanced long read metagenomic analysis
Authors: Simmonds Sara E. , Ly Lynn , Beaulaurier John , Lim Ryan , Morse Todd , Thakku Sri Gowtham , Rosario Karyna , Perez Juan Caballero , Puschnik Andreas , Mwakibete Lusajo , Hickey Scott , Tato Cristina M. , Team CZ ID , Kalantar Katrina
Published: March 2024

Metagenomics has enabled the rapid, unbiased detection of microbes across diverse sample types, leading to exciting discoveries in infectious disease, microbiome, and viral research. However, the analysis of metagenomic data is often complex and computationally resource-intensive. CZ ID is a free, cloud-based genomic analysis platform that enables researchers to detect microbes using metagenomic data, identify antimicrobial resistance genes, and generate viral consensus genomes. With CZ ID, researchers can upload raw sequencing data, find matches in NCBI databases, get per-sample taxon metrics, and perform a variety of analyses and data visualizations. The intuitive interface and interactive visualizations make exploring and interpreting results simple. Here, we describe the expansion of CZ ID with a new long read mNGS pipeline that accepts Oxford Nanopore generated data (czid.org). We report benchmarking of a standard mock microbial community dataset against Kraken2, a widely used tool for metagenomic analysis. We evaluated the ability of this new pipeline to detect divergent viruses using simulated datasets. We also assessed the detection limit of a spiked-in virus to a cell line as a proxy for clinical samples. Lastly, we detected known and novel viruses in previously characterized disease vector (mosquitoes) samples.
Learning probability distributions of sensory inputs with Monte Carlo Predictive Coding
Authors: Oliviers Gaspard , Bogacz Rafal , Meulemans Alexander
Published: March 2024

It has been suggested that the brain employs probabilistic generative models to optimally interpret sensory information. This hypothesis has been formalised in distinct frameworks, focusing on explaining separate phenomena. On one hand, predictive coding theory proposed how the probabilistic models can be learned by networks of neurons employing local synaptic plasticity. On the other hand, neural sampling theories have demonstrated how stochastic dynamics enable neural circuits to represent the posterior distributions of latent states of the environment. Here, we bring together these two lines of theoretic work by introducing Monte Carlo predictive coding (MCPC). We demonstrate that the integration of predictive coding with neural sampling results in a neural network that learns precise generative models using local computation and plasticity. The neural dynamics of MCPC infer the posterior distributions of the latent states in the presence of sensory inputs, and can generate likely inputs in their absence. Furthermore, MCPC captures the experimental observations on the variability of neural activity during perceptual tasks. By combining predictive coding and neural sampling, MCPC offers a unifying theory of cortical computation which can account for both sets of neural data that previously had been explained by these individual frameworks.
Variables affecting acquisition and maintenance of operant ethanol self-administration in male and female Long-Evans rats
Authors: Wheeler Shannon R , Pitock Joseph R , Ayala Arleen Perez , Hou Shikun , Soto Nathaly M Arce , Glover Elizabeth J
Published: March 2024

Aims

The goal of the present study was to determine the effect of prior experience with ethanol drinking and changes in session duration on the acquisition and maintenance of operant ethanol self-administration.

Methods

Adult male and female Long-Evans rats were trained to operantly self-administer ethanol. A subset of male rats underwent intermittent-access two-bottle choice drinking in the home cage prior to operant training. Controls were given access to two bottles of water. Once fully trained in 30-min operant sessions, session duration was reduced to 15 min for all male and female rats. Differences between 30- and 15-min sessions were also assessed in a separate group of male and female rats trained to self-administer sucrose.

Results

No differences were observed in acquisition rates, the magnitude of responding for ethanol, or total ethanol consumed between male rats allowed to drink ethanol in the home cage and those that remained ethanol naïve prior to operant training. A significant decrease in appetitive and consummatory behaviors was observed in males trained to lever press for either ethanol or sucrose. Females exhibited a similar decrease in operant performance for sucrose, but their behavior was largely unchanged in response to changes in session duration when ethanol was the reinforcer.

Conclusions

These data suggest that the use of prior home cage ethanol drinking as an initiation procedure offers little advantage over no initiation procedure at all. Moreover, reducing operant session duration from 30-min to 15-min has the potential to decrease, rather than increase, levels of ethanol intake.

Short summary

Intermittent-access two-bottle choice ethanol drinking offers no advantage as an initiation procedure for operant ethanol self-administration over animals that are ethanol-naïve prior to training. In addition, shortening the operant session duration does not increase overall intake or promote binge-like patterns of intake for either ethanol or sucrose reinforcer.
Nanogap Solid-State Single-Molecule Detection at Mars, Europa, and Microgravity Conditions
Authors: Ramírez-Colón José L. , Johnson Emma , Duzdevich Daniel , Lee Sam , Soderblom Jason , Zuber Maria T. , Taniguchi Masateru , Ohshiro Takahito , Komoto Yuki , Carr Christopher E.
Published: March 2024

Solid-state nanogap systems are an emerging technology forin-situlife detection due to their single-molecule resolution of a wide range of biomolecules, including amino acids and informational polymers, at the parts per billion to trillion level. By targeting the abundance distributions of organic molecules, this technology is a candidate for detecting ancient and extant life and discriminating between biotic and abiotic organics on future planetary missions to Mars and icy moons such as Enceladus and Europa. A benchtop system developed at Osaka University has a proven ability to detect and discriminate among single amino acids, RNA, and DNA using nanogap chips. The Electronic Life-detection Instrument for Enceladus/Europa (ELIE) prototype was subsequently developed to make this technology viable for space instrumentation through the simplification of electronics, reduction of size and weight, and automation of gap formation. Initial ground testing using a manually formed nanogap with the first ELIE prototype detected the amino acid L-proline. However, this manual adjustment approach posed limitations in maintaining a consistent gap size. To address this challenge, we integrated an automated piezo actuator to enable real-time gap control, permitting single-molecule identification of a target amino acid, L-proline, under reduced gravity (g), including Mars (g= 0.378), Europa or Lunar (g= 0.166), and microgravity conditions (g= 0.03-0.06), as validated through parabolic flight testing. Power supply noise and experimental constraints of the experiment design limited data collection to short segments of good-quality data. Nevertheless, the subsequent analysis of detected events within these segments revealed a consistent system performance and a controlled gap size across the different accelerations. This finding highlights the system’s resilience to physical vibrations. Future goals are to progress the instrument towards technology readiness level 4 with further reductions of size and mass, lower noise, and additional system automation. With further development, ELIE has the potential to be an autonomous and sensitive single-molecule detection instrument for deployment throughout the solar system.