bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors supporting the primary care physicians’ performance in Benin: a multiple case study
Authors: Bello Kéfilath , Lepeleire Jan De , Zannou Djimon Marcel , Criel Bart
Published: March 2024

Introduction

In Benin, as in many African countries, there is a gradual increase in physicians practising at the primary care level. A literature review showed that these primary care physicians (PCPs) have great potential for improving the quality of care. However, several conditions are necessary for this potential to be unlocked and for the PCPs to contribute effectively to strengthen their local health system. This study aims to understand the factors that underpin the performance of PCPs in Benin.

Methods

We conducted a multiple case study in which we analysed eight contrasting PCP practices spread across five health districts in Benin. The study used a combination of quantitative and qualitative methods. We collected quantitative data through direct observations of the services provided by the PCPs. A descriptive statistical analysis of these data helped to assign performance scores to each PCP’s practices (for the technical quality of services and communication with patients). For the qualitative data collection, we conducted 40 in-depth interviews and 16 focus group discussions with PCPs, other health workers, health authorities, local authorities and other community members. This qualitative data was subjected to thematic content analysis to identify the factors that might explain the observed performances. We then constructed a matrix presenting all the cases studied and the potential performance factors. Finally, we carried out a cross-case analysis to identify the most critical factors supporting the performance of PCPs in Benin.

Results

The PCPs’ performance scores ranged from 14.7 to 19.3 (out of 20) for communication and from 68% to 88% (out of 100%) for technical quality of care. Out of 14 potential performance factors retained after the first phase of the qualitative analysis, cross-analysis revealed nine factors that appeared to be essential in supporting the performance of PCPs in Benin in both the public and private sectors. These were (i) the values supporting the PCPs’ practices, (ii) the PCPs’ preparation to practice at first-line, (iii) the support provided to the PCPs from the hierarchy, peers or professional associations, (iv) the leadership mandate given to the PCPs and the degree of autonomy allocated to exert it, (v) the modalities of the financing of the PCPs’ practices, (vi) the accountability mechanisms in place to support the PCPs’ practices, (vii) the PCPs’ relationship with the rest of the primary care team and their leadership style, (viii) the PCPs’ collaboration with community leaders and other public officials, and (ix) the context in which the PCP’s practices are embedded.

Conclusion

This study has enabled the identification of a series of factors that could act as levers for improving the practice of PCPs in Benin.
Definition of sinonasal and otologic exacerbation in patients with primary ciliary dyskinesia - an expert consensus
Authors: Goutaki Myrofora , Lam Yin Ting , Anagiotos Andreas , Armengot Miguel , Burgess Andrea , Campbell Raewyn , Carlier Mathilde , Caversaccio Nathalie , Chadha Neil K. , Demir Berat , Dheyauldeen Sinan Ahmed D. , Gunaydin Onder , Harris Amanda , Hayn Isolde , Inal-Ince Deniz , Levi Eric , Fernandez Trini Lopez , Lucas Jane S. , Maitre Bernard , Poirrier Anne-Lise ML , Schofield Lynne , Takeuchi Kazuhiko , van Gogh Christine , Wolter Nikolaus E. , Papon Jean-François
Published: March 2024

Background

Recurrent infections of the nose, sinuses, and ears are common problems for people with primary ciliary dyskinesia (PCD). While pulmonary exacerbations in PCD are defined, there is no definition for Ear-Nose-Throat (ENT) exacerbations, a potential outcome for research and clinical trials.

Methods

We set up an expert panel of 24 ENT specialists, respiratory physicians, other healthcare professionals, and patients to develop consensus definitions of sinonasal and otologic exacerbations in children and adults with PCD for research settings. We reviewed the literature and used a modified Delphi approach with four electronic surveys.

Results

Both definitions are based on a combination of major and minor criteria, requiring three major or two major and at least two minor criteria each. Major criteria for a sinonasal exacerbation are: 1) reported acute increase in nasal discharge or change in colour; 2) reported acute pain or sensitivity in the sinus regions; 3) mucopurulent discharge on examination. Minor criteria include: reported symptoms; examination signs; doctoŕs decision to treat; improvement after at least 14-days. Major criteria for the otologic exacerbation are: 1) reported acute ear pain or sensitivity, 2) reported acute ear discharge, 3) ear discharge on examination, 4) signs of otitis media in otoscopy. Minor criteria are: reported acute hearing problems; signs of acute complication; doctoŕs decision to treat.

Conclusion

These definitions might offer a useful outcome measure for PCD research in different settings. They should be validated in future studies and trials together with other potential outcomes, to assess their usability.
A Systematic Review and Meta-Analysis: Research Using the Autism Polygenic Score
Authors: de Wit M.M. , Morgan M.J. , Libedinsky I. , Austerberry C. , Begeer S. , Abdellaoui A. , Ronald A. , Polderman T.J.C.
Published: March 2024

Objective

Genetic factors play a substantial role in the etiology of autism and its co-occurrence with other conditions and traits. The autism polygenic score, derived from the latest autism case-control meta-genome-wide association studies, captures some of the accumulated influence of common genetic variants on autism. We reviewed and meta-analyzed published studies that assessed the relationship between this autism polygenic score and autism diagnosis, and autistic, behavioral and neurobiological traits.

Method

Systematically searching public databases, we identified 72 studies and > 750 outcome measures. Included studies received a quality assessment.

Results

The majority of included studies were rated as good quality. The autism polygenic score was most strongly associated with autism diagnosis (meta-analyticr= .162, 95% CI .066 – .258). The autism polygenic score was also significantly associated with autistic traits but to a lesser degree than for autism (meta-analyticr= .042 (95% CI .004 – .081). Associations with other outcomes were inconsistent and meta-analytic effect sizes were generally small (medianr= .03).

Conclusion

We conclude that the current autism polygenic score is consistently associated with autism diagnostic status and autistic traits, but overlap between autism and other traits and conditions is not, from publications to date, explained significantly by the autism polygenic score. When compared to other mental conditions, autism is phenotypically and etiologically heterogeneous, which might drive the relatively modest associations observed with the autism polygenic score to date.
Prevalence and seroprevalence of COVID-19 infection among older people: A scoping review based on population-based studies in 2020-2022
Authors: Lei Jingxin , Soe Phyumar
Published: March 2024

Background

Accurate estimates of the prevalence of infections play an important role in COVID-19 surveillance. Older people are known to have higher risks of severe outcomes after infection, but whether they also have a higher infection rate remains unclear. To obtain estimates of COVID-19 prevalence among older people, we synthesized evidence from RT-PCR-based prevalence and serological studies.

Methods

We conducted a scoping review using a comprehensive search of MEDLINE (Ovid), Embase (Ovid), Europe PMC,ClinicalTrials.gov, and the WHO COVID-19 Research Database from December 2019 to Oct 2022. We included population-based cross-sectional (sero)prevalence studies among older people (i.e., people aged >= 65 +/-5 years) who were tested for SARS-CoV-2 infection using RT-PCR tests, antigen tests, or serological tests. Studies that were conducted solely in institutional housing were excluded. Eligible studies were extracted and critically appraised. We described and mapped the prevalence (tested by RT-PCR or antigen tests) and seroprevalence (tested by serological tests) by geographical area and time. We then compared the estimated prevalence with WHO-reported prevalence and the prevalence among younger age groups from the same study.

Results

We identified 202 (sero)prevalence estimates from 126 studies, covering 50 countries up to October 2022. Of the 126 studies, 28 studies estimated RT-PCR-based prevalence; 104 studies estimated seroprevalence, ranging from 0% in Jordan to 22.5% in the United States in 2020, from 0.41% in Brazil to 98% in Chile in 2021. In the year 2020, prevalence of COVID-19 ranged from 0.0006% in China, to 52.8% in Brazil, while in 2021, prevalence ranged from 0.06% in England to 41.1% in Brazil. The ratio of the reported prevalence to estimated prevalence ranged from <0.01 to 77.50, where 86% (24/28) studies estimated a higher prevalence than WHO reported and half of them estimated >10 times higher prevalence. One third of studies (32%, 9/28) estimated a higher prevalence in older people compared with younger people.

Conclusions

Our findings suggest that underreporting of COVID-19 cases among older people may exist extensively worldwide. Compared with younger groups, older people were less likely to be infected with COVID-19 in two thirds of the studies through the first two years of the pandemic.
The Sexual and Reproductive Health needs and preferences of youths in sub-Saharan Africa: A meta-synthesis
Authors: Uka Victoria Kalu , White Helen , Smith Debbie M.
Published: March 2024

The sexual and reproductive health (SRH) needs of youths in sub-Saharan Africa are not being fully met, as evidenced by high rates of unintended pregnancies and sexually transmitted infections in this population. Understanding service needs and preferences of sub-Saharan African youths aged 10-24 years is critical for improving access and SRH outcomes and the focus of this systematic review of qualitative research. Four databases were searched with key words to identify relevant studies, supplemented by citation search, with an update in June 2023. The eligibility criteria were clear and developed a priori. Twenty included studies from seven countries underwent quality appraisal using CASP. A meta-ethnographic approach was used to synthesise concepts across studies by the researchers. Four key themes were generated:information needs; service needs; social needs; and delivery preferences. Information needs encompassed desires for age-appropriate education on contraception, safer sex, bodily changes, and healthy relationships to fill knowledge gaps. Social needs consisted of life skills training, vocational development, substance use rehabilitation, and support systems to foster healthy behaviours. Service needs included accessible youth-friendly sexual health services, preventative care, sexually transmitted Infections (STI) management, and contraception; and delivery preferences including competent providers who maintain privacy and confidentiality, convenient youth-oriented settings, free or low-cost provisions, and youth involvement in service design. In conclusion, the identified themes emphasise the diverse nature of SRH needs and preferences among sub-Saharan African youths. Insights from their unique priorities and unmet needs inform policy development and intervention strategies. Tailored awareness campaigns, youth-centred training for providers, youth-friendly and confidential SRH models, comprehensive education, and engaging youth in developing relevant solutions may improve acceptability, access, and health outcomes. These efforts could address barriers around stigma, costs, and lack of knowledge, contributing to enhanced SRH and wellbeing. Fulfilling youth SRH needs in sub-Saharan Africa requires commitment across sectors to evidence-based, youth-focused strategies placing their perspectives at the centre
Optimal waist circumference cut-off points for predicting Metabolic Syndrome among females of reproductive age in Wakiso district, central Uganda
Authors: Lubogo David , Wamani Henry , Mayega Roy William , Orach Christopher Garimoi
Published: March 2024

Background

Metabolic Syndrome (MetS) poses a significant challenge to global public health, due to its strong association with Type 2 diabetes and cardiovascular disease. Waist circumference (WC) is a convenient metric for diagnosing MetS. Our study sought to establish waist circumference cut-offs that predict MetS in females of reproductive age residing in Wakiso district in central Uganda.

Methods

The data collected were from a cross-sectional study conducted in Wakiso district, central Uganda, involving 697 randomly selected females aged 15 to 49 between June 9thand August 17th,2021. Data included MetS components: WC, High-Density Lipoprotein (HDL) Cholesterol, triglycerides, blood pressure, and fasting blood sugar. MetS status was identified based on two or more MetS components excluding WC. ROC analysis established the average optimal WC. The accuracy and performance of the cut-off points were evaluated through sensitivity, specificity, Positive likelihood ratio, and the Youden index.

Results

Of the 697 participants, 49.9% had two or more MetS risk factors. For females aged 15-49 years, the average optimal WC cut-off was 80.3 cm. Variations in optimal WC thresholds were observed across different age groups: 97.4 cm for (15-24 years), 79.9 cm (25-34 years), 85.6 cm (35-44 years), and 91.1 cm (45-54 years) respectively. The area under the ROC curve for these age groups ranged from 0.78 to 0.86, indicating good discriminatory capability. The sensitivity ranged from 85% to 97%, specificity from 58% to 88%, and the Youden Index from 0.557 to 0.729.

Conclusions

A waist circumference of 80.3 cm is the optimal threshold for identifying Metabolic Syndrome in females between the ages of 15 and 49 years in the setting. This finding concurs with the guidance set forth by the International Diabetes Federation. Additionally, study participants had varying WC cut-offs ranging from 79.4 cm to 91.1 cm, depending on their age.
Socio-economic determinants of early antenatal care visit among pregnant women in Zambia (2007-2019): Evidence from the Zambia Demographic and Health Surveys
Authors: Ng’ambi Wingston Felix , Zyambo Cosmas , Hazemba Alice Ngoma , Muula Adamson Sinjani , Nkhoma Dominic , Hamonga Twaambo , Mwiche Angel
Published: March 2024

INTRODUCTION

The timing of antenatal care (ANC) attendance may affect outcomes for mother and child health. Using the Zambia Demographic and Health Survey (ZDHS), we describe the adoption of at least four early ANC (ANC4+) visits and early uptake of ANC among women of reproductive age in Zambia between 2007 and 2019.

METHODS

We made use of ZDHS data gathered between 2007 and 2019. In this investigation, all women between the ages of 15 and 49 were taken into account. Early ANC4+ was the desired result, which was defined as having at least four ANC visits with the first ANC visit occurring during the first four months of pregnancy. In Stata v17, weighted univariate, bivariate, and multivariate logistic regression analyses were performed.

RESULTS

A total of 11633 (56%) of the 20661 women enrolled in our study had received early initiation of ANC4+. We saw an increase in the proportion of women who started ANC4+ early, from 55% in 2007 to 63% in 2018/19. There was a decreasing trend in the odds of early ANC4+ initiation with parity, but an increasing trend in the odds of early ANC4+ initiation with a higher level of education. Being a member of a wealthier household was associated with a lower risk of ANC4+ (OR= 0.81, 95%CI: 0.66-0.99, P=0.03). Twenty-seven percent of the 12,333 women who had at least four ANC visits, regardless of the timing of their first visit, reported being late for ANC.

CONCLUSION

Early ANC4+ uptake increased in Zambia between 2007 and 2019. There were, however, disparities due to wealth, education, and parity. We found that 27% of women who were misclassified as having at least ANC4+ using conventional analysis were actually late for ANC. We provide some key considerations for ensuring that Zambia and other similar settings achieve universal antenatal care coverage by 2030.
Economic determinants of county-level mental health – United States, 2019
Authors: Bolduc Michele , Saberi Parya , Neilands Torsten B , Mercado Carla I , Battle Johnson Shanice , Freggens Zoe R.F. , Banks Desmond , Njai Rashid , Bullard Kai McKeever
Published: March 2024

A better understanding of whether and how economic factors impact mental health can inform policy and program decisions to improve mental health. This study looked at the association between county-level economic factors and the prevalence of self-reported poor mental health among adults in US counties in 2019, overall and separately for urban and rural counties. General dominance analyses were completed to rank-order the relative importance of the selected variables in explaining county prevalence of adults reporting > 14 poor mental health days in the last 30 days (“poor mental health”). The highest weighted variables were assessed for the statistical significance of their relationships with county-level poor mental health through multiple linear regression. Across all models, the four highest-ranked economic factors were household income, receipt of Supplemental Security Income (SSI), population with a college degree, and receipt of Supplemental Nutrition Assistance Program (SNAP) benefits. The overall, rural, and urban models explained over 69% of the variation in poor mental health prevalence between counties. Urban and rural models also showed notable differences in the relationship between poor mental health and median home value and population with public insurance. The findings from this study indicate a significant association between several economic factors and poor mental health, which may inform decision makers in addressing mental health in the US.
Mitochondrial Raf1 Regulates Glutamine Catabolism
Authors: Shanderson Ronald L. , Ferguson Ian D. , Siprashvili Zurab , Ducoli Luca , Li Albert M. , Miao Weili , Srinivasan Suhas , Velasco Mary Grace , Li Yang , Ye Jiangbin , Khavari Paul
Published: March 2024

One-Sentence Summary

Raf1 is present within the mitochondrial matrix, where it binds GLS to regulate glutamine catabolism and tumorigenesis.

In cancer, Raf1 activation occurs via mechanisms that include mutation of upstream regulators, such as receptor tyrosine kinases and Ras GTPases, as well as by mutations that affectRAF1itself, including via gene amplification (1–4). Once recruited to the plasma membrane (PM) Raf1 can engage downstream mitogen-activated protein kinase (MAPK) pathway signaling through phosphorylation of the MEK kinases (5). In addition to Raf1, A-Raf and B-Raf can also activate MEK and these other two Raf isoforms can compensate for MAPK activation in the event of Raf1 loss (6,7). Despite this, Raf1 remains essential for the development and maintenance of some tumors through mechanisms independent of MAPK activity (7,8). In this regard, Raf1 has well-described interactions outside the canonical MAPK pathway, including several with outer mitochondrial membrane (OMM) proteins (9,10), although Raf1 has not been previously identified inside mitochondria. Mitochondria comprise a hub for various metabolic processes modulated in cancer cells to accommodate rapid proliferation. One such process is glutaminolysis, which involves the catabolism of glutamine to generate both ATP as well as precursors for the synthesis of fatty acids, nucleotides, and nonessential amino acids (11–13). Glutaminase (GLS) proteins, which catalyze the first and rate-limiting step of this process by converting glutamine to glutamate, are often upregulated in cancer (14–16). GLS activation has been previously associated with tumors driven by Ras, upstream regulators of Raf kinases (13,17). Here we identify Raf1 protein inside mitochondria where Raf1 associates with GLS in the mitochondrial matrix to enable glutamine catabolism and tumorigenic growth.

Raf kinases play vital roles in normal mitogenic signaling and cancer, however, the identities of functionally important Raf-proximal proteins throughout the cell are not fully known. Raf1 proximity proteomics/BioID in Raf1-dependent cancer cells unexpectedly identified Raf1-adjacent proteins known to reside in the mitochondrial matrix. Inner-mitochondrial localization of Raf1 was confirmed by mitochondrial purification and super-resolution microscopy. Inside mitochondria, Raf1 associated with glutaminase (GLS) in diverse human cancers and enabled glutaminolysis, an important source of biosynthetic precursors in cancer. These impacts required Raf1 kinase activity and were independent of canonical MAP kinase pathway signaling. Kinase-dead mitochondrial matrix-localized Raf1 impaired glutaminolysis and tumorigenesis in vivo. These data indicate that Raf1 localizes inside mitochondria where it interacts with GLS to engage glutamine catabolism and support tumorigenesis.
Molecular Mimicry as a Mechanism of Viral Immune Evasion and Autoimmunity
Authors: Maguire Cole , Wang Chumeng , Ramasamy Akshara , Fonken Cara , Morse Brinkley , Lopez Nathan , Wylie Dennis , Melamed Esther
Published: March 2024

Mimicry of host protein structures (“molecular mimicry”) is a common mechanism employed by viruses to evade the host’s immune system. To date, studies have primarily evaluated molecular mimicry in the context of full protein structural mimics. However, recent work has demonstrated that short linear amino acid (AA) molecular mimics can elicit cross-reactive antibodies and T-cells from the host, which may contribute to development and progression of autoimmunity. Despite this, the prevalence of molecular mimics throughout the human virome has not been fully explored. In this study, we evaluate 134 human infecting viruses and find significant usage of linear mimicry across the virome, particularly those in the herpesviridae and poxviridae families. Furthermore, we identify that proteins involved in cellular replication and inflammation, those expressed from autosomes, the X chromosome, and in thymic cells are over-enriched in viral mimicry. Finally, we demonstrate that short linear mimicry from Epstein-Barr virus (EBV) is significantly higher in auto-antibodies found in multiple sclerosis patients to a greater degree than previously appreciated. Our results demonstrate that human-infecting viruses frequently leverage mimicry in the course of their infection, point to substantial evolutionary pressure for mimicry, and highlight mimicry’s important role in human autoimmunity. Clinically, our findings could translate to development of novel therapeutic strategies that target viral infections linked to autoimmunity, with the goal of eliminating disease-associated latent viruses and preventing their reactivation.
Highly Dynamic and Sensitive NEMOer Calcium Indicators for Imaging ER Calcium Signals in Excitable Cells
Authors: Gu Wenjia , Chen Jia-Hui , Zhang Yiyin , Wang Zhirong , Li Jia , Wang Sijia , Zhang Hanhan , Jiang Amin , Zhong Ziyi , Zhang Jiaxuan , Xi Chao , Hou Tingting , Gill Donald L. , Li Dong , Mu Yu , Wang Shi-Qiang , Tang Ai-Hui , Wang Youjun
Published: March 2024

Endoplasmic/sarcoplasmic reticulum (ER/SR) sits at the heart of the calcium (Ca2+) signaling machinery, yet current genetically encoded Ca2+indicators (GECIs) lack the ability to detect elementary Ca2+release events from ER/SR, particularly in muscle cells. Here we report a set of organellar GECIs, termed NEMOer, to efficiently capture ER Ca2+dynamics with increased sensitivity and responsiveness. Compared to G-CEPIA1er, NEMOer indicators exhibit dynamic ranges that are an order of magnitude larger, which enables up to 5-fold more sensitive detection of Ca2+oscillation in both non-excitable and excitable cells. The ratiometric version further allows super-resolution monitoring of local ER Ca2+homeostasis and dynamics. Notably, the NEMOer-f variant enabled the inaugural detection of Ca2+blinks, elementary Ca2+releasing signals from the SR of cardiomyocytes, as well asin vivospontaneous SR Ca2+releases in zebrafish. In summary, the highly dynamic NEMOer sensors expand the repertoire of organellar Ca2+sensors that allow real-time monitoring of intricate Ca2+dynamics and homeostasis in live cells with high spatiotemporal resolution.
Combining Cell-Intrinsic and -Extrinsic Resistance to HIV-1 By Engineering Hematopoietic Stem Cells for CCR5 Knockout and B Cell Secretion of Therapeutic Antibodies
Authors: Feist William N. , Luna Sofia E. , Ben-Efraim Kaya , Filsinger Interrante Maria V. , Amorin Nelson A. , Johnston Nicole M. , Bruun Theodora U. J. , Ghanim Hana Y. , Lesch Benjamin J. , Dudek Amanda M. , Porteus Matthew H.
Published: March 2024

Autologous transplantation ofCCR5null hematopoietic stem and progenitor cells (HSPCs) is the only known cure for HIV-1 infection. However, this treatment is limited because of the rarity ofCCR5-null matched donors, the morbidities associated with allogeneic transplantation, and the prevalence of HIV-1 strains resistant to CCR5 knockout (KO) alone. Here, we propose a one-time therapy through autologous transplantation of HSPCs genetically engineeredex vivoto produce both CCR5 KO cells and long-term secretion of potent HIV-1 inhibiting antibodies from B cell progeny. CRISPR-Cas9-engineered HSPCs maintain engraftment capacity and multi-lineage potentialin vivoand can be engineered to express multiple antibodies simultaneously. Human B cells engineered to express each antibody secrete neutralizing concentrations capable of inhibiting HIV-1 pseudovirus infectionin vitro. This work lays the groundwork for a potential one-time functional cure for HIV-1 through combining the long-term delivery of therapeutic antibodies against HIV-1 and the known efficacy ofCCR5KO HSPC transplantation.
In vitroandin vivovalidation of cwlM and pbpB essentiality for viability and resistance to imipenem inMycobacterium abscessus
Authors: Lee Jin , Li Si-Yang , Rifat Dalin , Kurepina Natalia , Chen Liang , Kreiswirth Barry N. , Nuermberger Eric L.
Published: March 2024

Mycobacterium abscessuslung infection is notoriously difficult to treat due, in part, to the intrinsic resistance of this pathogen to most marketed antibiotics. β-Lactams, namely imipenem and cefoxitin, are first-line drugs in combination regimens used to treat this infection; and there is growing interest in dual-β-lactam-based regimens. Better understanding of the molecular basis of β-lactam activity through study of the genetic determinants of β-lactam susceptibility and tolerance would enable more rational drug combinations and guide discovery of novel drug targets to complement β-lactams. We recently used an inducible CRISPR interference (CRISPRi) system to silencecwlMandpbpBand confirm their essentiality forin vitrogrowth and resistance to sub-MIC concentrations of imipenem. Here, we extend those findings to show that silencing either gene alone is bactericidal and augments the bactericidal activity of imipenemin vitro. Furthermore, using CRISPRi in a mouse model ofM. abscessuslung infection for the first time, we confirm the essentiality of each gene forin vivosurvival. These results validatecwlMandpbpBas essential genes and promising drug targets in this pathogen, including for potentiation of carbapenem activity. The results further establish CRISPRi as a powerful method for validating drug targets and studying gene-gene and gene-drug interactionsin vitroandin vivo.
Antimicrobial Resistance in Diverse Urban Microbiomes: Uncovering Patterns and Predictive Markers
Authors: Toscan Rodolfo Brizola , Lesiński Wojciech , Stomma Piotr , Subramanian Balakrishnan , Łabaj Paweł P. , Rudnicki Witold R.
Published: March 2024

Antimicrobial resistance (AMR) poses a significant global health threat, exacerbated by urbanization and anthropogenic activities. This study investigates the distribution and dynamics of AMR within urban microbiomes from six major U.S. cities using metagenomic data provided by the CAMDA 2023 challenge. We employed a range of analytical tools to investigate sample resistome, virome, and mobile genetic elements (MGEs) across these urban environments. Our results demonstrate that AMR++ and Bowtie outperform other tools in detecting diverse and abundant AMR genes, with binarization of data enhancing classification performance. The analysis revealed that a portion of resistome markers is closely associated with MGEs, and their removal drastically impacts the resistome profile and the accuracy of resistome modeling. These findings highlight the importance of preserving key MGEs in resistome studies to maintain the integrity and predictive power of AMR profiling models. This study underscores the heterogeneous nature of AMR in urban settings and the critical role of MGEs, providing valuable insights for future research and public health strategies.
Interplay between ß-propeller subunits WDR26 and muskelin regulates the CTLH E3 ligase supramolecular complex
Authors: Maitland Matthew E.R. , Onea Gabriel , Owens Dominic D. G. , Gonga-Cavé Brianna C. , Wang Xu , Arrowsmith Cheryl H. , Barsyte-Lovejoy Dalia , Lajoie Gilles A. , Schild-Poulter Caroline
Published: March 2024

The Pro/N-degron recognizing C-terminal to LisH (CTLH) complex is an E3 ligase of emerging interest in the developmental field and for targeted protein degradation (TPD) modalities. The human CTLH complex forms distinct supramolecular ring-shaped structures dependent on the multimerization of WDR26 or muskelin ß-propeller proteins. Here, we find that, in human cells, CTLH complex E3 ligase activity is dictated by a dynamic exchange between WDR26 and muskelin in tandem with muskelin autoregulation. Proteomic experiments revealed that complex-associated muskelin protein turnover is a major ubiquitin-mediated degradation event dependent on the CTLH complex in unstimulated HeLa cells. We observed that muskelin and WDR26 binding to the scaffold of the complex is interchangeable, indicative of the formation of separate WDR26 and muskelin complexes, which correlated with distinct proteomes in WDR26 and muskelin knockout cells. We found that mTOR inhibition-induced degradation of Pro/N-degron containing protein HMGCS1 is distinctly regulated by a muskelin-specific CTLH complex. Finally, we found that mTOR inhibition also activated muskelin degradation, likely as an autoregulatory feedback mechanism to regulate CTLH complex activity. Thus, rather than swapping substrate receptors, the CTLH E3 ligase complex controls substrate selectivity and its autoregulation through exchanging its β-propeller oligomeric subunits WDR26 and muskelin.
A low-footprint, fluorescence-based bacterial time-kill assay for estimating dose-dependent cell death dynamics
Authors: King Eshan S. , Stacy Anna E. , Scott Jacob G.
Published: March 2024

Dose-response curves that describe the relationship between antibiotic dose and growth rate in bacteria are commonly measured with optical density (OD) based assays. While being simple and high-throughput, any dose-dependent cell death dynamics are obscured, as OD assays in batch culture can only quantify a positive net change in cells. Time-kill experiments can be used to quantify cell death rates, but current techniques are extremely resource-intensive and may be biased by residual drug carried over into the quantification assay. Here, we report a novel, fluorescence-based time-kill assay leveraging resazurin as a viable cell count indicator. Our method improves upon previous techniques by greatly reducing the material cost and being robust to residual drug carry-over. We demonstrate our technique by quantifying a dose-response curve inEscherichia colisubject to cefotaxime, revealing dose-dependent death rates. We also show that our method is robust to extracellular debris and cell aggregation. Dose-response curves quantified with our method may provide a more accurate description of pathogen response to therapy, paving the way for more accurate integrated pharmacodynamic-pharmacokinetic studies.
Effect of pH on the thermostability and redox properties of cytochromec552fromWolinella succinogenes
Authors: Mordido Vitor H. , Carepo Marta S. P. , Cordas Cristina M. , Paul Navendu , Simon Jörg , Moura Isabel , Pauleta Sofia R.
Published: March 2024

Cytochromec552fromWolinella succinogenesis one of the few examples of a low reduction potential class Ic-type cytochrome with a mixture of high/low spin state populations observed in its visible spectrum. Analysis of its structural model suggests that the heme is Met/His coordinated and highly solvent-exposed. This supports the hypothesis that it is the solvent accessibility of the propionate groups that controls the reduction potential of smallc-type cytochromes. The visible spectra obtained at different pH values reveal the presence of a protonable group with a pKaof 7.3, which also influences the reduction potential of this small cytochromec552(Em0’of 97 ± 5 mV, pH 7.0) and can be either an H2O/OH-group distantly coordinating the heme iron, or one of the propionate groups. The thermostability of cytochromec552has been studied by circular dichroism and differential scanning calorimetry, indicating a highly stable protein at pH 5-7 (90 °C to 77 °C).
A matter of salt: global assessment of the effect of salt ionic composition as a driver of aquatic bacterial diversity
Authors: Szabó Attila , Székely Anna J. , Boros Emil , Márton Zsuzsanna , Csitári Bianka , Barteneva Natalie , Anda Dóra , Dobosy Péter , Eiler Alexander , Bertilsson Stefan , Felföldi Tamás
Published: March 2024

While the strong general effects of salinity on microbial diversity are well-known and described for marine and freshwater habitats, the impact of the specific composition of major inorganic ions remains largely unexplored. In this study, we assess how microbial community structure in inland saline aquatic habitats is influenced by ionic composition as compared to salinity, spatial factors, and other environmental parameters. We collected and analysed 16S rRNA gene V4 and V3-V4 amplicon datasets from freshwater to hypersaline aquatic environments worldwide (in total 375 samples from 130 lakes). With an emphasis on saline inland waters characterised by highly variable ionic composition, we demonstrated that the ionic composition of the major ions explained more variability in community composition than bulk salinity and that the geographic location of the sampling sites had only an ambiguous effect. We also identified the taxa contributing the most to the observed dissimilarity between communities from sites with different ionic composition and found mostly lineages known to be characteristic for a given habitat type, such as Actinobacteria acI in freshwater, Halomonadaceae in saline, or Nitriliruptorales in soda and soda-saline habitats. Many of these habitat type-specific indicator lineages were monophyletic, underpinning ionic composition as a crucial eco-evolutionary driver of aquatic microbial diversity.
Digitalization and Resource Mobilization
Authors: Inceoglu Ilke , Vanacker Tom , Vismara Silvio
Published: March 2024

Digitalization can profoundly change resource mobilization, including the search, access and governance of resources. In this introductory paper to the Special Issue on Digitalization and Resource Mobilization, we review existing research to identify different approaches towards digitalization, different conceptualizations of what resources are in this context and different aspects of resource mobilization across studies and theories. Drawing on these insights, we illustrate contemporary research examples and outline the way forward for two research streams focusing on resource mobilization in a digital context – specifically, the crowdfunding and human resources literature. We conclude by proposing four new areas to further advance the field.
Investigating the economic impact of climate change on agriculture in Iran: Spatial spillovers matter
Authors: Malaekeh Sayed Morteza , Shiva Layla , Safaie Ammar
Published: March 2024

In this study, we enhance our understanding of the economic impacts of climate change on agriculture in Iran to provide further information for moving Iran's climate policy forward by linking farmland net revenue to novel climatic and non‐climatic variables. We take advantage of spatial panel econometrics to better circumvent omitted factors extraneous to the agricultural sector and to develop a more reliable and consistent model when data are inherently spatial. In contrast to conventional panel studies which relied on year‐to‐year weather observations, we exploit a hybrid approach to compromise between the disadvantages and advantages of longer‐term cross‐sectional analysis and shorter‐term panel models. We estimate the potential impacts of climate change on agriculture under several global warming scenarios based on the Sixth Phase of the Coupled Model Intercomparison Project (CMIP6). We find that (I) farmlands’ net revenues are projected to decline by 8%–19% and 14%–51% by 2050 and 2080; (II) the distributional impacts of climate change would highly depend on climate zones and geographical locations; (III) a few counties might benefit from climate changes; (IV) finally, failing to account for spatial spillovers when they are present leads to a misspecified model.
Great expectations: The effect of unmet labor market expectations after higher education on ideology
Authors: Cox Loreto
Published: March 2024

Higher education has massively expanded around the world, yet we know little about the political consequences of this expansion. Students generally have overly optimistic expectations about the returns to educational investment, and the effects of unmet expectations on graduates’ political behavior have been overlooked. I study this phenomenon in Chile with observational and experimental methods, using unique panel survey data collected from new graduates covering 72% of higher education enrollment. The survey tracks students before and after they enter the labor market and includes an experiment that induces variation in their expectations. The panel data reveals that 65% of students have unmet expectations, and both methods indicate that this induces a shift toward progovernment/proequality ideology. Overall, this study shows that the gap between aspirations and reality upon graduation can be an important driver of political attitudes.
Young people's alcohol use in and around water: A scoping review of the literature
Authors: Carey Renee N. , Crawford Gemma , Jancey Jonine , Lam Tina , Nimmo Lauren , Trapp Gina , Pollard Christina , Hooper Paula , Leavy Justine E.
Published: March 2024

Issues

The surrounding social and commercial context, including alcohol advertising, heavily influences alcohol consumption. Alcohol use is a major risk factor for both fatal and non‐fatal drowning, particularly for young people.

Approach

We conducted a scoping review to explore the peer‐reviewed literature on the use of alcohol by young people (aged 15–34 years) in the context of aquatic environments. Five electronic academic databases were searched for English‐language studies conducted in high‐income countries and published in the last 15 years (since 2008). The MetaQAT framework was used to assess methodological quality of included studies.

Key Findings

The review included a total of 24 studies, including those addressing the prevalence of and/or risk factors for alcohol use in aquatic environments among young people (n = 13); the epidemiology of alcohol‐related unintentional drowning in young people (n = 9); and interventions to reduce alcohol‐related harm around water (n = 3). Findings suggest that young people commonly consume alcohol around water, particularly young men. We found multiple influences on this behaviour, including the perception of risk, location of aquatic activity and presence of others, particularly peers.

Implications

Understanding the literature addressing alcohol use around water among young people will assist in identifying and setting priorities for drowning prevention, including the need to mitigate the effects of alcohol advertising which promotes drinking in and around water.

Conclusion

There is a clear imperative to address the use of alcohol by young people in aquatic environments. These findings have key implications for public health policy, advocacy and practice.
A flavonoid metabolon: cytochrome b5 enhances B‐ring trihydroxylated flavan‐3‐ols synthesis in tea plants
Authors: Ruan Haixiang , Gao Liping , Fang Zhou , Lei Ting , Xing Dawei , Ding Yan , Rashid Arif , Zhuang Juhua , Zhang Qiang , Gu Chunyang , Qian Wei , Zhang Niuniu , Qian Tao , Li Kongqing , Xia Tao , Wang Yunsheng
Published: March 2024

Flavan‐3‐ols are prominent phenolic compounds found abundantly in the young leaves of tea plants. The enzymes involved in flavan‐3‐ol biosynthesis in tea plants have been extensively investigated. However, the localization and associations of these numerous functional enzymes within cells have been largely neglected. In this study, we aimed to investigate the synthesis of flavan‐3‐ols in tea plants, particularly focusing on epigallocatechin gallate. Our analysis involving the DESI‐MSI method to reveal a distinct distribution pattern of B‐ring trihydroxylated flavonoids, primarily concentrated in the outer layer of buds. Subcellular localization showed that CsC4H, CsF3′H, and CsF3′5′H localizes endoplasmic reticulum. Protein–protein interaction studies demonstrated direct associations between CsC4H, CsF3′H, and cytoplasmic enzymes (CHS, CHI, F3H, DFR, FLS, and ANR), highlighting their interactions within the biosynthetic pathway. Notably, CsF3′5′H, the enzyme for B‐ring trihydroxylation, did not directly interact with other enzymes. We identified cytochrome b5 isoform C serving as an essential redox partner, ensuring the proper functioning of CsF3′5′H. Our findings suggest the existence of distinct modules governing the synthesis of different B‐ring hydroxylation compounds. This study provides valuable insights into the mechanisms underlying flavonoid diversity and efficient synthesis and enhances our understanding of the substantial accumulation of B‐ring trihydroxylated flavan‐3‐ols in tea plants.
How diverse a monocentric chromosome can be? Repeatome and centromeric organization of Juncus effusus (Juncaceae)
Authors: Dias Yhanndra , Mata‐Sucre Yennifer , Thangavel Gokilavani , Costa Lucas , Báez Mariana , Houben Andreas , Marques André , Pedrosa‐Harand Andrea
Published: March 2024

Juncus is the largest genus of Juncaceae and was considered holocentric for a long time. Recent findings, however, indicated that 11 species from different clades of the genus have monocentric chromosomes. Thus, the Juncus centromere organization and evolution need to be reassessed. We aimed to investigate the major repetitive DNA sequences of two accessions of Juncus effusus and its centromeric structure by employing whole‐genome analyses, fluorescent in situ hybridization, CENH3 immunodetection, and chromatin immunoprecipitation sequencing. We showed that the repetitive fraction of the small J. effusus genome (~270 Mbp/1C) is mainly composed of Class I and Class II transposable elements (TEs) and satellite DNAs. Three identified satellite DNA families were mainly (peri)centromeric, with two being associated with the centromeric protein CENH3, but not strictly centromeric. Two types of centromere organization were discerned in J. effusus: type 1 was characterized by a single CENH3 domain enriched with JefSAT1‐155 or JefSAT2‐180, whereas type 2 showed multiple CENH3 domains interrupted by other satellites, TEs or genes. Furthermore, while type 1 centromeres showed a higher degree of satellite identity along the array, type 2 centromeres had less homogenized arrays along the multiple CENH3 domains per chromosome. Although the analyses confirmed the monocentric organization of J. effusus chromosomes, our data indicate a more dynamic arrangement of J. effusus centromeres than observed for other plant species, suggesting it may constitute a transient state between mono‐ and holocentricity.
Tranexamic acid in trauma: After 3 hours from injury, when is it safe and effective to use again?
Authors: Barrett Christopher D. , Neal Matthew D. , Schoenecker Jonathan G. , Medcalf Robert L. , Myles Paul S.
Published: March 2024

Tranexamic acid (TXA) has proven mortality benefit if used early after traumatic injury, likely related to a combination of bleeding reduction and other non‐bleeding effects. If TXA is given more than 3 h after traumatic injury, there is a significant and paradoxical increased risk of death due to bleeding. TXA has level 1 evidence for use as a bleeding reduction agent in isolated orthopedic operations, but in polytrauma patients undergoing orthopedic operations, it is not clear if and when TXA is safe or effective once outside the 3‐h window of proven trauma efficacy.
An interpolation inequality involving LlogL$L\log L$ spaces and application to the characterization of blow‐up behavior in a two‐dimensional Keller–Segel–Navier–Stokes system
Authors: Wang Yulan , Winkler Michael
Published: March 2024

In a smoothly bounded two‐dimensional domain and for a given nondecreasing positive unbounded , for each and the inequality
is shown to hold for any positive fulfilling
This is thereafter applied to nonglobal solutions of the Keller–Segel system coupled to the incompressible Navier–Stokes equations through transport and buoyancy, and it is seen that in any such blow‐up event the corresponding population density cannot remain uniformly integrable over near its explosion time.
A characterization of heaviness in terms of relative symplectic cohomology
Authors: Mak Cheuk Yu , Sun Yuhan , Varolgunes Umut
Published: March 2024

For a compact subset of a closed symplectic manifold , we prove that is heavy if and only if its relative symplectic cohomology over the Novikov field is nonzero. As an application, we show that if two compact sets are not heavy and Poisson commuting, then their union is also not heavy. A discussion on superheaviness together with some partial results is also included.
On fillings of contact links of quotient singularities
Authors: Zhou Zhengyi
Published: March 2024

We study several aspects of fillings for links of general isolated quotient singularities using Floer theory, including co‐fillings, Weinstein fillings, strong fillings, exact fillings and exact orbifold fillings, focusing on the non‐existence of exact fillings of contact links of isolated terminal quotient singularities. We provide an extensive list of isolated terminal quotient singularities whose contact links are not exactly fillable, including for , which settles a conjecture of Eliashberg, quotient singularities from general cyclic group actions and finite subgroups of , and all terminal quotient singularities in complex dimension 3. We also obtain uniqueness of the orbifold diffeomorphism type of exact orbifold fillings of contact links of some isolated terminal quotient singularities.