bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Willingness to Receive COVID-19 Vaccine and Associated Factors among Teachers in Dambi Dollo Town, Qellem Wallaga Zone, Oromia Regional State, Ethiopia: Institution based cross sectional study
Authors: Shiferaw Desalegn , Melaku Chara , Assefa Lamessa , Kinati Tadele
Published: January 2023

Background

COVID-19 devastated the routine life of all human kind since its discovery in Wuhan, China in 2019 and caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infections. Vaccination is an effective means for controlling the communicability of the disease and every effort has to be done to increase the proportion of vaccinated people against COVID-19.

Objective

The main objective of this study was to assess the willingness of teachers to receive COVID-19 vaccine and its associated factors in dambi dollo town, 2022.

Methods

School based cross sectional study design was applied. The data were collected self-administered questionnaire and analysed by SPSS version 23.0. Variables which showed association with dependent variable in the bivariate analyses at 0.25 were entered into multiple stepwise logistic regression model. P-Value 0.05 was considered statistically significant in this study. Adjusted Odds ratios together with corresponding 95% confidence intervals was used to interpret the findings.

Results

About 92% of the teachers in dambi dollo town have heard covid-19 vaccine and 67.2% of them know that the vaccine can prevent the COVID-19 disease. On the other hand 51 %(95%CI: 44.8, 57.2) of the respondents had good knowledge about COVID-19 vaccine. From the total 247 participants who have responded to our inquiry on their willing to receive the COVID-19 vaccine, 68.4% (95%CI: 62.5, 74.3) of them were willing to receive the vaccine immediately while the remaining were either not willing or not ready at the time of data collection. Those participants having good knowledge of the vaccine were about six times more willing to get vaccinated, (AOR=5.85, 95%CI: 2.74, 12.47) in comparison with those having poor knowledge of the vaccine.

Conclusion

In conclusion, the level of willingness to receive the COVID-19 Vaccine was 68.4% and relatively low in the current study population and participants’ religion and knowledge status are the two variables significantly associated with willingness to receive the vaccine.
Biochemical and structural characterisation of a family GH5 cellulase from endosymbiont of shipwormP. megotara
Authors: Junghare Madan , Manavalan Tamilvendan , Fredriksen Lasse , Leiros Ingar , Altermark Bjørn , Eijsink Vincent G.H. , Vaaje-Kolstad Gustav
Published: January 2023

Cellulases play a key role in enzymatic conversion of plant cell-wall polysaccharides into simple and economically relevant sugars. The discovery of novel cellulases from exotic biological niches is of interest as they may present properties that are valuable in biorefining of lignocellulose. We have characterized a glycoside hydrolase 5 (GH5) domain of a bi-catalytic GH5-GH6 multidomain enzyme from the unusual bacterial endosymbiontTeredinibacter waterburyiof the wood-digesting shipwormPsiloteredo megotara. The cellulase enzyme,TwCel5, was produced with and without a native C-terminal family 10 carbohydrate-binding module belongs to GH5, subfamily 2. Both variants showed hydrolytic endo-activity on soluble substrates such as, β-glucan, carboxymethylcellulose and konjac glucomannan. However, low activity was observed towards a crystalline form of cellulose. Interestingly, when co-incubated with a cellulose active LPMO, a clear synergy was observed that boosted hydrolysis of crystalline cellulose. The crystal structure of the GH5 catalytic domain was solved to 1.0 Å resolution and revealed a substrate binding cleft containing a putative +3 subsite, which is uncommon in this enzyme family. The enzymeTwCel5 was active in a wide range of pH and temperatures and showed high tolerance for NaCl. This study provides an important advance on discovery new enzymes from shipworm and shed new light on biochemical and structural characterization of cellulolytic cellulase and showed boost in hydrolytic activity of cellulase on crystalline cellulose when co-incubated with cellulose active LPMO. These findings will be relevant for the development of future enzyme cocktail that may be useful for the biotechnological conversion of lignocellulose.
The telegraph process is not a subordinator
Authors: Gorin Gennady , Pachter Lior
Published: January 2023

Investigations of transcriptional models by Amrhein et al. outline a strategy for connecting steady-state distributions to process dynamics. We clarify its limitations: the strategy holds for a very narrow class of processes, which excludes an example given by the authors.
Early β-amyloid accumulation in the brain is associated with peripheral T cell alterations
Authors: Gericke Christoph , Kirabali Tunahan , Flury Roman , Mallone Anna , Rickenbach Chiara , Kulic Luka , Tosevski Vinko , Hock Christoph , Nitsch Roger M. , Treyer Valerie , Ferretti Maria Teresa , Gietl Anton
Published: January 2023

Fast and minimally invasive approaches for early, preclinical diagnosis of neurodegenerative Alzheimer’s disease (AD) are highly anticipated. Evidence of adaptive immune cells responding to cerebral β-amyloidosis, one of the pathological hallmarks of AD, has raised the question of whether immune markers could be used as proxies for β-amyloid accumulation in the brain. Here, we deploy multidimensional mass cytometry combined with unbiased machine learning techniques to immunophenotype peripheral blood mononuclear cells from study participants in cross-sectional and longitudinal cohorts. We show that increases in antigen-experienced adaptive immune cells in the blood, particularly CD45RA-reactivated T effector memory (TEMRA) cells, are associated with early accumulation of brain β-amyloid and with changes in plasma AD biomarkers in still cognitively healthy subjects. Our results suggest that preclinical AD pathology is linked to systemic alterations of the adaptive immune system. These immunophenotype changes may help in the future to identify and develop novel diagnostic tools for early AD assessment and to better understand clinical outcomes.
A hybrid approach for predicting multi-label subcellular localization of mRNA at genome scale
Authors: Choudhury Shubham , Bajiya Nisha , Patiyal Sumeet , Raghava Gajendra P. S.
Published: January 2023

In the past, number of methods have been developed for predicting single label subcellular localization of mRNA in a cell. Only limited methods had been built to predict multi-label subcellular localization of mRNA. Most of the existing methods are slow and cannot be implemented at transcriptome scale. In this study, a fast and reliable method had been developed for predicting multi-label subcellular localization of mRNA that can be implemented at genome scale. Firstly, deep learning method based on convolutional neural network method have been developed using one-hot encoding and attained an average AUROC - 0.584 (0.543 – 0.605). Secondly, machine learning based methods have been developed using mRNA sequence composition, our XGBoost classifier achieved an average AUROC - 0.709 (0.668 - 0.732). In addition to alignment free methods, we also developed alignment-based methods using similarity and motif search techniques. Finally, a hybrid technique has been developed that combine XGBoost models and motif-based searching and achieved an average AUROC 0.742 (0.708 - 0.816). Our method – MRSLpred, developed in this study is complementary to the existing method. One of the major advantages of our method over existing methods is its speed, it can scan all mRNA of a transcriptome in few hours. A publicly accessible webserver and a standalone tool has been developed to facilitate researchers (Webserver:https://webs.iiitd.edu.in/raghava/mrslpred/).

Key Points

Prediction of Subcellular localization of mRNA

Classification of mRNA based on Motif and BLAST search

Combination of alignment based and alignment free techniques

A fast method for subcellular localization of mRNA

A web server and standalone software
Comparison of cell response to chromatin and DNA damage
Authors: Luzhin Artyom , Rajan Priyanka , Safina Alfiya , Leonova Katerina , Stablewski Aimee , Wang Jianmin , Pal Mahadeb , Kantidze Omar , Gurova Katerina
Published: January 2023

DNA-targeting drugs may damage DNA or chromatin. Many anti-cancer drugs damage both, making it difficult to understand their mechanisms of action. Using molecules causing DNA breaks without altering nucleosome structure (bleomycin) or destabilizing nucleosomes without damaging DNA (curaxin), we investigated the consequences of DNA or chromatin damage in normal and tumor cells. As expected, DNA damage caused p53-dependent growth arrest followed by senescence. Chromatin damage caused higher p53 accumulation than DNA damage; however, growth arrest was p53-independent and did not result in senescence. Chromatin damage activated the transcription of multiple genes, including classical p53 targets, in a p53-independent manner. Although these genes were not highly expressed in basal conditions, they had chromatin organization around the transcription start sites (TSS) characteristic of most highly expressed genes and the highest level of paused RNA polymerase. We hypothesized that nucleosomes around the TSS of these genes were the most sensitive to chromatin damage. Therefore, nucleosome loss upon curaxin treatment would enable transcription without the assistance of sequence-specific transcription factors. We confirmed this hypothesis by showing greater nucleosome loss around the TSS of these genes upon curaxin treatment and activation of a p53-specific reporter in p53-null cells by chromatin-damaging agents but not DNA-damaging agents.
Insulin-mediated endothelin signaling is antiviral during West Nile virus infection
Authors: Trammell Chasity E. , Rowe Evelyn H. , Jones Brianne J. , Char Aditya B. , Fawcett Stephen , Ahlers Laura R.H. , Goodman Alan G.
Published: January 2023

West Nile virus (WNV) is the most prevalent mosquito-borne virus in the United States with approximately 2,000 cases each year. There are currently no approved human vaccines and a lack of prophylactic and therapeutic treatments. Understanding host responses to infection may reveal potential intervention targets to reduce virus replication and disease progression. The use ofDrosophila melanogasteras a model organism to understand innate immunity and host antiviral responses is well established. Previous studies revealed that insulin-mediated signaling regulates WNV infection in invertebrates by regulating canonical antiviral pathways. Because insulin signaling is well-conserved across insect and mammalian species, we sought to determine if results usingD. melanogastercan be extrapolated for the analysis of orthologous pathways in humans. Here, we identify insulin-mediated endothelin signaling using theD. melanogastermodel and evaluate an orthologous pathway in human cells during WNV infection. We demonstrate that endothelin signaling reduces WNV replication through the activation of canonical antiviral signaling. Taken together, our findings show that endothelin-mediated antiviral immunity is broadly conserved across species and reduces replication of viruses that can cause severe human disease.

IMPORTANCE

Arboviruses, particularly those transmitted by mosquitoes, pose a significant threat to humans and are an increasing concern because of climate change, human activity, and expanding vector-competent populations. West Nile virus is of significant concern as the most frequent mosquito-borne disease transmitted annually within the continental United States. Here, we identify a previously uncharacterized signaling pathway that impacts West Nile virus infection, namely endothelin signaling. Additionally, we demonstrate that we can successfully translate results obtained fromD. melanogasterinto the more relevant human system. Our results add to the growing field of insulin-mediated antiviral immunity and identifies potential biomarkers or intervention targets to better address West Nile virus infection and severe disease.
Human-derived cortical neurospheroids coupled to passive, high-density and 3D MEAs: a valid platform for functional tests
Authors: Muzzi L. , Di Lisa D. , Falappa M. , Pepe S. , Maccione A. , Pastorino L. , Martinoia S. , Frega M.
Published: January 2023

With the advent of human-induced pluripotent stem cells (hiPSCs) differentiation protocols, different methods to createin-vitrohuman-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality would make them more representative of anin-vivoenvironment. Thus, human-derived neurospheroids and brain-organoids are becoming increasingly used forin-vitrodisease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapid generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by presenting for the first-time results from the main micro-electrodes arrays (MEAs) types available on the market (passive electrode, C-MOS electrodes, 3D electrodes). Neurospheroids grown in free culture and transferred on MEA exhibited functional activity that can be chemically and electrically modulated. Our results indicates that this model holds great potential for in-depth study of signal transmission to drug screening, disease modeling and offers a reproducible and stable platform forin-vitrofunctional testing.
A standardised test to evaluate audio-visual speech intelligibility in French
Authors: Rhun Loïc Le , Llorach Gerard , Delmas Tanguy , Suied Clara , Arnal Luc H , Lazard Diane S
Published: January 2023

Objective

Lipreading, which plays a major role in the communication of the hearing impaired, lacked a French standardised tool. Our aim was to create and validate an audio-visual (AV) version of the French Matrix Sentence Test (FrMST).

Design

Video recordings were created by dubbing the existing audio files.

Sample

Thirty-five young, normal-hearing participants were tested in auditory and visual modalities alone (Ao, Vo) and in AV conditions, in quiet, noise, and open and closed-set response formats.

Results

Lipreading ability (Vo) varied from 1% to 77%-word comprehension. The absolute AV benefit was 9.25ℒdB SPL in quiet and 4.6ℒdB SNR in noise. The response format did not influence the results in the AV noise condition, except during the training phase. Lipreading ability and AV benefit were significantly correlated.

Conclusions

The French video material achieved similar AV benefits as those described in the literature for AV MST in other languages. For clinical purposes, we suggest targeting SRT80 to avoid ceiling effects, and performing two training lists in the AV condition in noise, followed by one AV list in noise, one Ao list in noise and one Vo list, in a randomised order, in open or close set-format.
Investigating associations of omega-3 fatty acids, lung function decline, and airway obstruction
Authors: Patchen Bonnie K. , Balte Palavi , Bartz Traci M. , Barr R. Graham , Fornage Myriam , Graff Mariaelisa , Jacobs David R , Kalhan Ravi , Lemaitre Rozenn N. , O’Connor George , Psaty Bruce , Seo Jungkyun , Tsai Michael Y. , Wood Alexis C. , Xu Hanfei , Zhang Jingwen , Gharib Sina A. , Manichaikul Ani , North Kari , Steffen Lyn M. , Dupuis Josée , Oelsner Elizabeth , Hancock Dana B. , Cassano Patricia A.
Published: January 2023

Rationale

Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have anti-inflammatory properties and may benefit lung health.

Objectives

Investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in adults of diverse races/ethnicities from general population cohorts.

Methods

Complementary study designs: (1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV1and FVC measures in the National Heart, Lung, and Blood Institute Pooled Cohorts Study, and (2) two-sample Mendelian Randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters.

Measurements and Main Results

The longitudinal study found that higher omega-3 fatty acid concentrations were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for docosahexaenoic acid (DHA). One standard deviation higher DHA was associated with an attenuation of 1.8 mL/year for FEV1(95% confidence interval [CI] 1.3–2.2) and 2.4 mL/year for FVC (95% CI 1.9–3.0). One standard deviation higher DHA was also associated with a 9% lower incidence of spirometry-defined airway obstruction (95% CI 0.86–0.97). DHA associations persisted across sexes, smoking histories, and Black, white and Hispanic participants, with the largest magnitude associations in former smokers and Hispanics. The MR study showed positive associations of genetically predicted omega-3 fatty acids with FEV1and FVC, with statistically significant findings across multiple MR methods.

Conclusions

The longitudinal and MR studies provide evidence supporting beneficial effects of higher circulating omega-3 fatty acids, especially DHA, on lung health.
Suicide deaths during the COVID-19 pandemic in the United States, by region, March 1, 2020-June 30, 2022
Authors: Faust Jeremy Samuel , Renton Benjamin , Du Chengan , Shah Sejal B. , Chen Alexander Junxiang , Li Shu-Xia , Krumholz Harlan M.
Published: January 2023

Introduction

There were concerns that suicide deaths might increase due to Covid-19 pandemic-related stressors. Previous research demonstrated that suicide deaths actually decreased in 2020 in the US. An update covering 2021-2022 with regional data is warranted.

Methods

Observational cohort, US and regional data. Expected monthly deaths were modeled using pre-pandemic US and regional data (2015-2020). Mortality data was accessed from CDC public reporting.

Results

We find that suicide deaths in the United States were below expected levels throughout the pandemic period (March 1, 2020-June 30,2022) with >4,100 fewer suicide deaths than would have been expected to occur during the study period. Stratifying suicide mortality by US Census Bureau region yielded statistically significant decreases from expected suicide deaths in all regions except the Midwest, (which recorded no significant change in suicide deaths during the overall pandemic period).

Conclusion

Suicide mortality is down in the US since the pandemic began, through June 30, 2022. Possible explanations include an early “coming together” effect; Later, increased access to mental health resources and a greater focus on mental health in the media may have reduced stigma and barriers in seeking necessary psychiatric care.
Biomarkers’ performance in the SEPSIS-3 era
Authors: de la Fuente Amanda , López-Sánchez Jaime , Vaquero-Roncero Luis Mario , Merino García María , Sánchez Barrado María Elisa , Sánchez-Hernández Miguel Vicente , Rico-Feijoo Jesús , Muñoz-Bellvís Luis , de Castro Rafael González , Tedim Ana P. , Ortega Alicia , Fernández Omar Abdel-lah , Suárez-de-la-Rica Alejandro , Maseda Emilio , González Ignacio Trejo , García Carrera Geovanna Liszeth , Marcos-Vidal José Miguel , Nieto Arranz Juan Manuel , Esteban-Velasco Carmen , Aldecoa César , Bermejo-Martin Jesús F
Published: January 2023

Objective

the biomarkers’ performance for diagnosis and severity stratification of sepsis has not been properly evaluated anew using the SEPSIS-3 criteria introduced in 2016. We evaluated the accuracy of 21 biomarkers classically tested in sepsis research to identify infection, sepsis, and septic shock in surgical patients classified using SEPSIS-3.

Methods

four groups of adult surgical patients were compared: post-surgical patients with no infection, patients with infection but no sepsis, patients with sepsis, and patients with septic shock were recruited prospectively from the surgery departments and surgical ICUs from four Spanish hospital. The area under the curve (AUC) to differentiate between groups was calculated for each biomarker.

Results

A total of 187 patients were recruited (50 uninfected post-surgery controls, 50 patients with infection, 47 with sepsis and 40 with septic shock). The AUCs indicated that none of the biomarkers tested was accurate enough to differentiate those patients with infection from the uninfected controls. In contrast, procalcitonin, lipocalin 2, pentraxin 3, IL-15, TNF-α, IL-6, angiopoietin 2, TREM-1, D-dimer and C-reactive protein yielded AUCs > 0.80 to discriminate the patients with sepsis or septic shock from those with no infection. C-reactive protein and IL-6 were the most accurate markers to differentiate plain infection from sepsis (AUC = 0.82). Finally, our results revealed that sepsis and septic shock shared similar profiles of biomarkers.

Conclusion

Revaluation in the “SEPSIS-3 era” identified the scenarios where biomarkers do and do not provide useful information to improve the management of surgical patients with infection or sepsis.
Understanding how a digital mental health intervention can be optimised to ensure effectiveness in the longer-term: findings from a causal mediation analyses of the CONEMO trials
Authors: Seward Nadine , Loh Wen Wei , Miranda J. Jaime , Diez-Canseco Francisco , Claro Heloisa Garcia , Menezes Paulo Rossi , de Almeida Lopes Fernandes Ivan Filipe , Araya Ricardo
Published: January 2023

Background

Two CONEMO trials in Lima, Peru and São Paulo, Brazil evaluated a digital mental health intervention (DMHI) based on behavioural activation (BA) that demonstrated improvements in symptoms of depression between trial arms at three-months, but not at six-months. To understand how we can optimize CONEMO in the longer-term, we therefore aim to investigate mediators through which the DMHI improved symptoms of depression at six-months, separately for the two trials and then using a pooled dataset.

Methods

We used data that included adults with depression (Patient Health Questionnaire – 9 (PHQ-9) score ≥10) and comorbid hypertension and/or diabetes. Interventional effects were used to decompose the total effect of DMHI on symptoms of depression at six months into indirect effects via: understanding the content of the sessions without difficulty; number of activities completed that were self-selected to improve levels of BA; and levels of activation measured using the Behavioural Activation for Depression Short Form (BADS-SF).

Findings

Using the pooled dataset, understanding the content of the sessions without difficulty mediated a 10% [0.10: 95% CI: 0.03 to 0.15] improvement in PHQ-9 scores at six months; completing self-selected activities mediated a 12% improvement [0.12: 0.01 to 0.23]; and, lastly, BA mediated a 2% [0.02: 0.01, 0.05] improvement.

Conclusions

Our findings suggest that targeting participants to complete activities they find enjoyable will help to improve levels of activation and maintain the effect of the CONEMO intervention in the longer-term. Improving the content of the sessions to facilitate understanding can also help to maintain improvements.
Knowledge, attitudes, and practices associated with Vitamin D supplementation: A cross-sectional online community survey of adults in the UK
Authors: Tanna Nuttan , Karki Manisha , Webber Iman , Alaa Aos , El-Osta Austen , Blair Mitch
Published: January 2023

Objective

Assess knowledge, attitudes, and practices (KAPs) of a diverse population. Identify barriers and facilitators that inform routine vitamin D supplementation and self-care in the community setting.

Design

Cross-sectional online voluntary survey. Electronic survey link published on college Qualtrics platform and advertised widely. Study information provided with Participant Information Sheet.

Setting and Participants

556 community dwelling adults across the UK.

Methods

The overarching study included two phases, incorporating quantitative and qualitative methodologies. This paper reports findings from the first phase of the FABCOM-D (Facilitators and Barriers to Community (Healthy) Vitamin D status) study. Online survey questions were iteratively developed after background literature searches and piloted to ensure clarity and ease of understanding. Survey responses summarised using frequencies and percentages, and univariable and multivariable logistic regression models explored for any association. A p-value less than 0.05 was considered statistically significant. The Checklist for Reporting Results of Internet E-Surveys guided reporting. Statistical analysis performed using IBM SPSS software.

Main outcome measures

Awareness of vitamin D information sources, health benefits and testing. Attitudes to supplementation, sun exposure and fortification.

Results

Three quarters of the community had some awareness of vitamin D and around half were taking supplements. The two most trusted sources of information included health professionals and the NHS website. Participants were willing to pay for supplements, supporting a self-care agenda. With increasing age, there was significant reduced intake of vitamin D supplements. This aspect needs to be explored further as this could be a concern in deficiency status in the elderly. There was acceptance of food fortification but uncertainty on how to balance food intake with supplementation

Conclusion

We were successful in eliciting views on KAPs around vitamin D from a community population including a large proportion of Black and Minority Ethnic individuals. The community wanted information and guidance to help manage individual vitamin D status, especially for high-risk groups, and on balancing supplementation, food fortification and sun exposure.
Impact of statin withdrawal on perceived and objective muscle function
Authors: Peyrel Paul , Mauriège Pascale , Frenette Jérôme , Laflamme Nathalie , Greffard Karine , Dufresne Sébastien S. , Huth Claire , Bergeron Jean , Joanisse Denis R.
Published: January 2023

Background and Aims

Statin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters.

Methods

Patients (59 men, 33 women, 50.3±9.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n=61) or without symptoms (No SAMS, n=15), and controls (n=16). Force (FO), endurance (EN) and power (PO) of the leg extensors (EXT) and flexors (FLE) and handgrip strength (FOHG) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal.

Results

Following withdrawal, repeated-measures analyses show improvements for the entire cohort in ENEXT, ENFLE, FOFLE, POEXT and POFLE (range +7.2 to +13.3%, all p≤0.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). FOHG was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (−1.7 to -4.2%) (all p=0.02).

Conclusions

Whether suffering from “true” SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted.
Information Sharing through Digital Service Agreement
Authors: Elvas Luis B , Helgheim Berit , Ferreira João CA
Published: January 2023

Data sharing and services reuse in the health sector is a significant problem due to privacy, and security issues. The European Commission has classified health data as a unique resource owing to the ability to do both prospective and retrospective research at a low cost. Similarly, the OECD encourages member nations to create and implement health data governance systems that protect individual privacy while allowing data sharing. This paper aimed to describe a conceptual framework to allow medical information sharing among health entities in a secure environment. A framework of shared Artificial Intelligent services is proposed to provide a safe environment for information sharing based on digital services agreements (DSA) and a shared services infrastructure for artificial intelligence (AI) and knowledge creation: From the collaborative platform with privacy, health data can be shared, and shared analytics services will allow an easy and fast application of AI algorithms. The framework allows data prosumers (producers/consumers) to easily express their preferences on sharing their data, which analytics operations can be performed on such data, and by whom the resulting data can be shared, among other relevant aspects. This entails a framework that combines several technologies for expressing and enforcing data-sharing agreements and technologies to perform data analytics operations compliant. Among these technologies, we can mention data-centric policy enforcement mechanisms and data analysis operations directly performed on encrypted data provided by multiple prosumers. The framework is mainly based on an Information Sharing Infrastructure (ISI) and an Information Analysis Infrastructure (IAI) that can be deployed in several ways and on several devices (from cloud to mobile devices).
Telehealth-supported exercise/physical activity programs for knee osteoarthritis: A systematic review and meta-analysis
Authors: Xiang Xiao-Na , Wang Ze-Zhang , Zhang Jiang-yin , Li Ke , Chen Qi-Xu , Xu Fa-Shu , Zhang Yue-Wen , He Hong-Chen , He Cheng-Qi , Zhu Si-Yi
Published: January 2023

Telehealth-supported program has been increasingly integrated into chronic disease management, but it is unknown if this benefit applies to populations with knee osteoarthritis. This study aimed to assess the effectiveness of telehealth-supported exercise/physical activity programs in individuals with knee osteoarthritis. A comprehensive literature search was conducted in September 2022 on randomized controlled trials investigating the effects compared to a control condition. Twenty-three studies met eligibility criteria, of which 20 studies included in meta-analysis. Telehealth-supported exercise/physical activity programs resulted in reduced pain (g = −0.39, CI −0.67 to −0.11, I2= 83%), better physical activity (g = 0.13, CI 0.03 to 0.23, I2= 0%) and better physical function (g = −0.51, CI −0.98 to −0.05, I2= 87%). In addition, better improvements in quality of life, self-efficacy for pain, and global improvement were observed, but with non-significant improvements for self-efficacy for physical function. These findings suggested that telehealth-supported exercise/physical activity program might be an effective treatment for knee osteoarthritis. Future research with standardized components and wearables should evaluate the effects.
Evaluating pregnant women’s selenium intake through dietary assessment in Accra, Ghana: a feasibility study
Authors: Amuquandoh Amy , Aluko Marie , Ebenezer Ofori-Attah , Egbi Godfred , Adu-Bonsaffoh Kwame
Published: January 2023

Objective

Dietary selenium (Se) deficiency is associated adverse pregnancy outcomes. We sought to determine the feasibility of: (1) assessing dietary Se consumption via administration of a food frequency questionnaire (FFQ) to pregnant women attending the antenatal clinic of Korle Bu Teaching Hospital (KBTH) in Accra, Ghana and (2) quantifying total Se intake.

Methods

In this prospective observational cohort study, participants were recruited via purposive sampling and face-to-face data collection was undertaken using structured FFQs. English-speaking pregnant women who were ≥ 18 years old were eligible to participate. Questions of feasibility were assessed and the average total Se intake in the population was analyzed.

Results

One hundred study participants met the inclusion criteria out of 117 eligible. It was feasible to administer the surveys in the clinic waiting room. The average total Se intake in this population of pregnant women was 90.4 μg/day ±50.0 μg, which is higher than the National Institute of Health recommended dietary allowance (RDA) of 60μg/day for pregnant women.

Conclusion

FFQ assessment of Se consumption and resource evaluation were deemed feasible in the KBTH setting. Participants reported an average Se intake above the RDA. Future studies can examine the influence of Se intake on pregnancy outcomes.
Extensive characterization of a Williams Syndrome murine model showsGtf2ird1-mediated rescue of select sensorimotor tasks, but no effect on enhanced social behavior
Authors: Nygaard Kayla R. , Maloney Susan E. , Swift Raylynn G. , McCullough Katherine B. , Wagner Rachael E. , Fass Stuart B. , Garbett Krassimira , Mirnics Karoly , Veenstra-VanderWeele Jeremy , Dougherty Joseph D.
Published: January 2023

Williams Syndrome is a rare neurodevelopmental disorder exhibiting cognitive and behavioral abnormalities, including increased social motivation, risk of anxiety and specific phobias along with perturbed motor function. Williams Syndrome is caused by a microdeletion of 26-28 genes on chromosome 7, includingGTF2IRD1, which encodes a transcription factor suggested to play a role in the behavioral profile of Williams Syndrome. Duplications of the full region also lead to frequent autism diagnosis, social phobias, and language delay. Thus, genes in the region appear to regulate social motivation in a dose-sensitive manner. A ‘Complete Deletion’ mouse, heterozygously eliminating the syntenic Williams Syndrome region, has been deeply characterized for cardiac phenotypes, but direct measures of social motivation have not been assessed. Furthermore, the role ofGtf2ird1in these behaviors has not been addressed in a relevant genetic context. Here, we have generated a mouse overexpressingGtf2ird1, which can be used both to model duplication of this gene alone and to rescueGtf2ird1expression in the Complete Deletion mice. Using a comprehensive behavioral pipeline and direct measures of social motivation, we provide evidence that the Williams Syndrome Critical Region regulates social motivation along with motor and anxiety phenotypes, but thatGtf2ird1complementation is not sufficient to rescue most of these traits, and duplication does not decrease social motivation. However,Gtf2ird1complementation does rescue light-aversive behavior and performance on select sensorimotor tasks, perhaps indicating a role for this gene in sensory processing or integration.
Ciliopathy-associated missense mutations in IFT140 are hypomorphic and have edgetic effects on protein interaction networks
Authors: Leonhard Tobias , Diwan Gaurav D. , Klose Franziska , Stehle Isabel F. , Junger Katrin , Seda Marian , Bolz Sylvia , Woerz Franziska , Russell Robert B. , Boldt Karsten , Jenkins Dagan , Ueffing Marius , Beyer Tina
Published: January 2023

The mechanisms underlying recessive Mendelian diseases and the interplay between genotype and phenotype still need to be better understood. It is therefore necessary to characterise the functional effects of missense mutations at the protein level. Here we focus on missense mutations in the intraflagellar transport protein IFT140, which forms part of the IFT complex A (IFT-A), a crucial component of the ciliary machinery. Mutations in IFT140 can cause a vast spectrum of diseases belonging to the group of ciliopathies, reaching from isolated retinal dystrophy to severe skeletal abnormalities and multi-organ diseases such as Mainzer-Saldino and Jeune syndrome. We hypothesise that missense mutations in IFT140 are hypomorphic leading to quantitative effects on a subset of protein-protein interactions. This may affect complex stability as well as perturbations of protein interaction networks. In this work we assessed how 24 missense mutations in IFT140 affect interactions with other IFT and effector proteins using affinity purification coupled to mass spectrometry. Our data reveals that several mutations in IFT140 are hypomorphic and disrupt the stability of the IFT-A complex to varying degrees in a quantitative way. Allelic combination and the degree of IFT-A complex disruption in analysed missense mutations correlates with the severity of the observed phenotype in a subset of patients. In addition, we show that a distinct subset of mutations in IFT140 shows edgetic effects by disrupting specific PPIs rather than causing a total loss of IFT-A binding. This is the case e.g. with the disease-associated protein TULP3 which is involved in cilia-dependent sonic hedgehog signalling.
Preserved functional organization of human auditory cortex in individuals missing one temporal lobe from infancy
Authors: Regev Tamar I , Lipkin Benjamin , Boebinger Dana , Paunov Alexander , Kean Hope , Norman-Haignere Sam , Fedorenko Evelina
Published: January 2023

Human cortical responses to natural sounds, measured with fMRI, can be approximated as the weighted sum of a small number of canonical response patterns (components), each having interpretable functional and anatomical properties. Here, we asked whether this organization is preserved in cases where only one temporal lobe is available due to early brain damage by investigating a unique family: one sibling born without a left temporal lobe, another without a right temporal lobe, and a third anatomically neurotypical. We analyzed fMRI responses to diverse natural sounds within the intact hemispheres of these individuals and compared them to 12 neurotypical participants. All siblings manifested the neurotypical auditory responses in their intact hemispheres. These results suggest that the development of the auditory cortex in each hemisphere does not depend on the existence of the other hemisphere, highlighting the redundancy and equipotentiality of the bilateral auditory system.
Tau tubulin kinase 1 and 2 regulate ciliogenesis and human pluripotent stem cells–derived neural rosettes
Authors: Binó Lucia , Čajánek Lukáš
Published: January 2023

Primary cilia are key regulators of embryo development and tissue homeostasis. However, their mechanisms and functions, particularly in the context of human cells, are still unclear. Here, we analyzed the consequences of primary cilia modulation for human pluripotent stem cells (hPSCs) proliferation and differentiation. We show that neither activation of the cilia-associated Hedgehog signaling pathway nor ablation of primary cilia by CRISPR gene editing to knockout Tau Tubulin Kinase 2 (TTBK2), a crucial ciliogenesis regulator, affects the selfrenewal of hPSCs. In addition, we demonstrate that TTBK1, a closely related kinase without previous links to ciliogenesis, is upregulated during hPSCs-derived neural rosette differentiation to regulate primary cilia formation together with TTBK2. Finally, we show that TTBK1/2 and primary cilia are implicated in the regulation of the size of hPSCs-derived neural rosettes.
The Shot CH1 domain recognises a distinct form of F-actin duringDrosophilaoocyte determination
Authors: Nashchekin D. , Squires I. , Prokop A. , St Johnston D.
Published: January 2023

As in mammals, only one cell in aDrosophilamulticellular female germline cyst is specified as an oocyte. The symmetry-breaking cue for oocyte selection is provided by the fusome, a tubular structure connecting all cells in the cyst. TheDrosophilaspectraplakin Shot localises to the fusome and translates its asymmetry into a polarised microtubule network that is essential for oocyte specification, but how Shot recognises the fusome is unclear. Here we demonstrate that Shot’s actin-binding domain (ABD) is necessary and sufficient to localise Shot to the fusome and mediates Shot function in oocyte specification together with the microtubule-binding domains. The calponin homology domain 1 (CH1) of Shot’s ABD recognises fusomal F-actin and requires CH2 to distinguish it from other forms of F-actin in the cyst. By contrast, the ABDs of Utrophin, Fimbrin, Filamin, Lifeact and F-tractin do not recognise fusomal F-actin. We therefore propose that Shot propagates fusome asymmetry by recognising a specific conformational state of F-actin on the fusome.
High-throughput sequencing of macaque basolateral amygdala projections reveals dissociable connectional motifs with frontal cortex
Authors: Zeisler Zachary R , London Liza , Janssen William G , Fredericks J Megan , Elorette Catherine , Fujimoto Atsushi , Zhan Huiqing , Russ Brian E , Clem Roger L , Hof Patrick R , Stoll Frederic M , Rudebeck Peter H
Published: January 2023

The basolateral amygdala (BLA) projects widely across the macaque frontal cortex1–4, and amygdalo-frontal projections are critical for optimal emotional responding5and decision- making6. Yet, little is known about the single-neuron architecture of these projections: namely, whether single BLA neurons project to multiple parts of the frontal cortex. Here, we use MAPseq7to determine the projection patterns of over 3000 macaque BLA neurons. We found that one-third of BLA neurons have two or more distinct targets in parts of frontal cortex and of subcortical structures. Further, we reveal non-random structure within these branching patterns such that neurons with four targets are more frequently observed than those with two or three, indicative of widespread networks. Consequently, these multi-target single neurons form distinct networks within medial and ventral frontal cortex consistent with their known functions in regulating mood and decision-making. Additionally, we show that branching patterns of single neurons shape functional networks in the brain as assessed by fMRI-based functional connectivity. These results provide a neuroanatomical basis for the role of the BLA in coordinating brain-wide responses to valent stimuli8and highlight the importance of high- resolution neuroanatomical data for understanding functional networks in the brain.
Continuous muscle, glial, epithelial, neuronal, and hemocyte cell lines for Drosophila research
Authors: Coleman-Gosser Nikki , Raghuvanshi Shiva , Stitzinger Shane , Hu Yanhui , Chen Weihang , Luhur Arthur , Mariyappa Daniel , Josifov Molly , Zelhof Andrew , Mohr Stephanie E. , Perrimon Norbert , Simcox Amanda
Published: January 2023

Expression of activated Ras, RasV12, provides Drosophila cultured cells with a proliferation and survival advantage that simplifies the generation of continuous cell lines. Here we used lineage restricted RasV12expression to generate continuous cell lines of muscle, glial, and epithelial cell type. Additionally, cell lines with neuronal and hemocyte characteristics were isolated by cloning from cell cultures established with broad RasV12expression. Differentiation with the hormone ecdysone caused maturation of cells from mesoderm lines into active muscle tissue and enhanced dendritic features in neuronal-like lines. Transcriptome analysis showed expression of key cell-type specific genes and the expected alignment with single cell sequencing data in several cases. Overall, the technique has produced in vitro cell models with characteristics of glia, epithelium, muscle, nerve, and hemocyte. The cells and associated data are available from the Drosophila Genomic Resource Center.
L-type Ca2+channels mediate regulation of glutamate release by subthreshold potential changes
Authors: Lee Byoung Ju , Lee Unghwi , Ryu Seung Hyun , Han Sukmin , Lee Seung Yeon , Lee Jae Sung , Ju Anes , Chang Sunghoe , Lee Suk-Ho , Kim Sung Hyun , Ho Won-Kyung
Published: January 2023

Subthreshold depolarization enhances neurotransmitter release evoked by action potentials and plays a key role in modulating synaptic transmission by combining analog and digital signals. This process is known to be Ca2+-dependent. However, the underlying mechanism of how small changes in basal Ca2+caused by subthreshold depolarization can regulate transmitter release triggered by a large increase in local Ca2+is not well understood. This study aimed to investigate the source and signaling mechanisms of Ca2+that couple subthreshold depolarization with the enhancement of glutamate release in hippocampal cultures and CA3 pyramidal neurons. Subthreshold depolarization increased presynaptic Ca2+levels, the frequency of spontaneous release, and the amplitude of evoked release, all of which were abolished by blocking L-type Ca2+channels. A high concentration of intracellular Ca2+buffer or blockade of calmodulin and phospholipase C abolished depolarization induced increases in transmitter release. Estimation of the readily releasable pool size using hypertonic sucrose showed depolarization induced increases in readily releasable pool size, and this increase was abolished by blockade of calmodulin or phospholipase C. Our results provide mechanistic insights into the modulation of transmitter release by subthreshold potential change and highlight the role of L-type Ca2+channels in coupling subthreshold depolarization to the activation of Ca2+-dependent signaling molecules that regulate transmitter release.

SIGNIFICANCE

Neuronal activities are encoded by action potentials, but subthreshold changes in resting membrane potentials also play important roles in regulating neuronal functions including synaptic transmission. It is, however, poorly understood how small changes in basal Ca2+induced by subthreshold depolarization regulate transmitter release triggered by a large increase in local Ca2+in presynaptic terminals. We demonstrate that L-type Ca2+channels are the major source of presynaptic Ca2+influx at basal state and during subthreshold depolarization, resulting in the activation of signaling molecules such as calmodulin and phospholipase C, which facilitate transmitter release by increasing both release probability and the readily releasable pool size. Our results provide mechanistic insight into how subthreshold potential changes contribute to regulating transmitter release.