bluuebunny/crossref_metadata_2025_split huggingface dataset:
MoaB2, a newly identified transcription factor, binds to σ
A
in
Mycobacterium smegmatis
Authors: Brezovská Barbora , Narasimhan Subhash , Šiková Michaela , Šanderová Hana , Kovaľ Tomáš , Borah Nabajyoti , Shoman Mahmoud , Pospíšilová Debora , Vaňková Hausnerová Viola , Tužinčin Dávid , Černý Martin , Komárek Jan , Janoušková Martina , Kambová Milada , Halada Petr , Křenková Alena , Hubálek Martin , Trundová Mária , Dohnálek Jan , Hnilicová Jarmila , Žídek Lukáš , Krásný Libor 
Published: November 2024

ABSTRACT

In mycobacteria, σ
A
is the primary sigma factor. This essential protein binds to RNA polymerase (RNAP) and mediates transcription initiation of housekeeping genes. Our knowledge about this factor in mycobacteria is limited. Here, we performed an unbiased search for interacting partners of
Mycobacterium smegmatis
σ
A
. The search revealed a number of proteins; prominent among them was MoaB2. The σ
A
-MoaB2 interaction was validated and characterized by several approaches, revealing that it likely does not require RNAP and is specific, as alternative σ factors (
e.g.
, closely related σ
B
) do not interact with MoaB2. The structure of MoaB2 was solved by X-ray crystallography. By immunoprecipitation and nuclear magnetic resonance, the unique, unstructured N-terminal domain of σ
A
was identified to play a role in the σ
A
-MoaB2 interaction. Functional experiments then showed that MoaB2 inhibits σ
A
-dependent (but not σ
B
-dependent) transcription and may increase the stability of σ
A
in the cell. We propose that MoaB2, by sequestering σ
A
, has a potential to modulate gene expression. In summary, this study has uncovered a new binding partner of mycobacterial σ
A
, paving the way for future investigation of this phenomenon.

IMPORTANCE

Mycobacteria cause serious human diseases such as tuberculosis and leprosy. The mycobacterial transcription machinery is unique, containing transcription factors such as RbpA, CarD, and the RNA polymerase (RNAP) core-interacting small RNA Ms1. Here, we extend our knowledge of the mycobacterial transcription apparatus by identifying MoaB2 as an interacting partner of σ
A
, the primary sigma factor, and characterize its effects on transcription and σ
A
stability. This information expands our knowledge of interacting partners of subunits of mycobacterial RNAP, providing opportunities for future development of antimycobacterial compounds.
Effect of wild-type vaccine doses on BA.5 hybrid immunity, disease severity, and XBB reinfection risk
Authors: Chen Daxiang , Zhang Weihong , Xiao Bin , Xu Banglao , Yang Xiaoyun , Deng Shidong , Li Guichang , Yang Gang , Cao Jinpeng , Mei Xinyue , Luo Qi , Huang Peiyu , Sun Xi , su Jie , Zhong Nanshan , Zhao Zhuxiang , Wang Zhongfang 
Published: November 2024

ABSTRACT

Vaccination against the wild-type (WT) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus did not produce detectable levels of neutralizing antibodies (NAbs) against the BA.5 strain before it emerged. However, coronavirus disease-2019 (COVID-19) severity varied highly between unvaccinated, partially vaccinated, and fully vaccinated individuals, for unknown reasons. We assessed the severity of BA.5 infection and the risk of XBB strain reinfection and measured serum levels of NAbs against WT, BA.5, and XBB.1.9.1 SARS-CoV-2 strains at varying time points in 1,373 individuals who received zero, one, two, or three WT vaccine doses. We found that two to three WT doses significantly increased WT and BA.5 NAb levels and reduced the incidence of COVID-19-associated pneumonia upon BA.5 strain infection compared to zero to one dose. Regarding XBB reinfection, those who received two to three doses and were infected with the BA.5 variant exhibited a significantly lower reinfection risk compared to those who received zero to one dose. RNA analysis revealed that the differentially expressed genes between the two to three dose and unvaccinated groups were enriched in B cell activation, cytokine-cytokine receptor interaction, complement, and monocyte activation functions—indicating that vaccination increased the antibody response and reduced inflammation. Our results suggest that multiple antigen exposures to either matched or unmatched SARS-COV-2 variants, through vaccination or infection, may be necessary to achieve significant immune imprinting.

IMPORTANCE
The administration of coronavirus disease-2019 (COVID-19) vaccines that do not perfectly match the viral strains that individuals become infected with has been found to impact the resultant illness severity—although the precise mechanism underlying this phenomenon remains unclear. We assessed viral clearance, as well as serum levels of inflammatory cytokines and neutralizing antibodies (NAbs) against wild-type, BA.5, and XBB.1.9.1 variants of the severe acute respiratory syndrome coronavirus 2 among individuals who received varying doses of such strain-mismatched vaccines. Notably, vaccination with ≥2 doses of strain-mismatched COVID-19 vaccines appeared to stimulate the production of specific NAbs during infection with new variants, as well as attenuate the inflammatory response and enhance viral clearance. Such vaccination regimens can also reduce the risk of reinfection. These findings may be important for guiding the development of future COVID-19 vaccination strategies that target both matched and mismatched viral variants.
Age-specific dynamics of neutralizing antibodies, cytokines, and chemokines in response to La Crosse virus infection in mice
Authors: Alatrash Reem , Vaidya Varun , Herrera Bobby Brooke 
Published: November 2024

ABSTRACT

La Crosse virus (LACV) is a primary cause of pediatric arboviral encephalitis in the United States, particularly affecting children aged 16 years or younger. This age-related susceptibility extends to murine models, where weanling mice (3 weeks old) succumb to LACV infection, while adults (≥6 weeks old) demonstrate resistance. Despite its clinical relevance, the host immune response to LACV is not fully understood. In this study, we investigated the roles of neutralizing antibodies (nAbs), cytokines, and chemokines in weanling and adult mice following infection with 5 × 10
5
plaque-forming units (PFU) of LACV. Weanling mice demonstrated early disease onset with elevated peripheral viremia, but passive transfer of adult serum, confirmed to have nAbs, to naïve weanlings prior to infection completely rescued them from death. Moreover, adult mice had increased Th1 cytokines, Th9/Th17/Th22/Treg cytokines, and many chemokines. In contrast, weanlings had higher Th2 cytokines, correlating with symptoms onset. Flow cytometry and intracellular cytokine staining further demonstrated that weanling mice produced higher levels of IL-4 by CD4
+
and CD8
+
T cells compared to adults, regardless of infection status. Conversely, LACV-infected adult mice had increased IFN-γ production by CD8
+
T cells compared to uninfected controls. Finally, the adoptive transfer of splenocytes from immune adult mice to naïve weanlings delayed neurological symptoms and improved survival. In conclusion, this study links nAbs and cytokine and chemokine responses to protective immunity in adult mice, contrasting with the pathogenesis seen in weanlings. These findings underscore the importance of further research into innate and adaptive immune mechanisms during LACV infection.

IMPORTANCE
La Crosse virus (LACV) is a primary cause of pediatric encephalitis in the United States, with an impact on children aged 16 years or younger. This age-related susceptibility is recapitulated in mouse models, where young mice succumb to LACV-induced disease, while adults demonstrate resistance. Our understanding of host responses to LACV remains underexplored. This study sheds light on the dynamics of neutralizing antibodies (nAbs), cytokines, and chemokines following LACV infection in both adult and weanling mice. Our study reveals age-specific variations in viremia, neutralizing antibody titers, survivability, and levels of cytokines and chemokines. Adult mice exhibit significantly elevated levels of Th1 cytokines, contrasting with elevated levels of Th2 cytokines observed in weanling mice, often coinciding with the onset of symptoms. These data reveal age-specific dynamics in cytokines and chemokines associated with protective versus pathogenic immunity, emphasizing the need for further studies on innate and adaptive immunity.
Metagenomic analysis reveals higher
Coriobacteriia
abundance in mare’s milk consumers
Authors: Mukhanbetzhanov Nurislam , Jarmukhanov Zharkyn , Kozhakhmetov Samat , Kushugulova Almagul 
Published: November 2024

ABSTRACT

Our study reveals increased gut
Coriobacteriia
among mare’s milk consumers; metagenomic analysis showed a higher prevalence of genera belonging to class
Coriobacteriia
in consumers vs non-consumers. This suggests interactions between traditional dairy practices and gut microbiome composition, indicating potential for microbiota modulation through dietary interventions.
Cost-effectiveness of psychological and psychosocial interventions for adults, children and young people who have self-harmed
Authors: Mavranezouli Ifigeneia , Pelone Ferruccio , Connolly Rachel , Mughal Faraz , Witt Katrina G , Hawton Keith , Lascelles Karen , Wildgoose Amanda , Childs Angela , Pilling Stephen , Kapur Navneet 
Published: November 2024

BackgroundSelf-harm is a major health issue resulting in high societal costs. Few psychological and psychosocial interventions have shown effectiveness in reducing repeat self-harm.ObjectiveTo assess the cost-effectiveness of psychological and psychosocial interventions that have shown evidence of effectiveness in adults and CYP (children and young people) who have self-harmed.MethodsUsing effectiveness data from Cochrane reviews, we developed two decision-analytical models to compare costs and quality-adjusted life years (QALYs) of cognitive behavioural therapy (CBT)-informed psychological therapy added to treatment as usual (TAU) versus TAU alone for adults who have self-harmed, and of dialectical behavioural therapy for adolescents (DBT-A) versus enhanced TAU for CYP who have self-harmed, respectively, from a National Health Service and personal social services perspective in England. Other model input parameters were obtained from published sources, supplemented by expert opinion.FindingsThe incremental cost-effectiveness ratio (ICER) of CBT-informed psychological therapy added to TAU versus TAU alone for adults who have self-harmed was £9088/QALY. The ICER of DBT-A versus enhanced TAU for CYP who have self-harmed was £268 601/QALY. Results were overall robust to the alternative scenarios tested.Conclusions and clinical implicationsCBT-informed psychological therapy appears to be cost-effective for adults who have self-harmed, which contributes to evidence for its implementation in services. Currently, DBT-A does not seem to be cost-effective for CYP who have self-harmed. The economic analyses were informed by clinical evidence of moderate-to-low (CBT) and low (DBT-A) quality. Further clinical and economic evidence for DBT-A and other psychological and psychosocial interventions for people who have self-harmed is required.
Efficacy of a computer vision-based system for exercise management in patients with knee osteoarthritis: a study protocol for a randomised controlled pilot trial
Authors: Xu Yang , Chen Xi , Wang Li , You Mingke , Deng Qian , Liu Di , Lin Ye , Liu Weizhi , Li Peng-Cheng , Li Jian 
Published: November 2024

IntroductionThis study aims to evaluate the efficacy of a computer vision system in guiding exercise management for patients with knee osteoarthritis (OA) by comparing functional improvement between a tele-rehabilitation versus an outpatient intervention program.Methods and analysisThis is a prospective, single-blind, randomised controlled trial of 60 patients with knee OA who will be randomly assigned to exercise therapy (n=30) or control (n=30) . Both groups will receive treatment two times per week for 12 weeks. The primary outcome of the study will be assessed using the University of Western Ontario and McMaster University Osteoarthritis Index (WOMAC). The Knee Injury and Osteoarthritis Outcome Score will be assessed, as well as the visual analogue scale, quality of life score and physical fitness score. All observations will be collected at baseline and at weeks 4, 8 and 12 during the intervention period, as well as at weeks 4, 8, 12 and 24 during the follow-up visits after the end of the intervention.Ethics and disseminationThis evaluator-blinded, prospective, randomised controlled study was approved by the Biomedical Ethics Review Committee of West China Hospital of Sichuan University.Trial registration numberChiCTR2300070319.
Patient-reported harm following cancellation of planned surgery at a Danish university hospital: a cross-sectional study
Authors: Viftrup Anette , Laustsen Sussie , Pahle Maria Levin , Dreyer Pia , Nikolajsen Lone 
Published: November 2024

ObjectivesTo estimate the prevalence and severity of patient-reported physical and non-physical harm following surgery cancellation.DesignCross-sectional study.SettingA large Danish university hospital.ParticipantsPatients (≥18 years) from various surgical specialities, such as orthopaedic, spinal, abdominal, gynaecological, thoracic, vascular and urological surgery whose surgery was cancelled <2 weeks prior to the scheduled date due to hospital-related causes.OutcomePatient-reported physical and non-physical harm, defined as physical worsening, emotional strain and other consequences, measured using a patient-reported survey.ResultsWe identified 785 patients whose surgery was cancelled from 1 December 2021 to 1 June 2022, of whom 436 (55.5%) responded to the electronic survey. Physical worsening was reported by 42% and emotional strain by 48% of patients. One-third of patients reported an inability to continue daily activities, and 28% reported a need for an increased dose of analgesics. Emotional strain included various negative feelings such as being disappointed (59%) and lonely (31%). Furthermore, 44% of the respondents feared deterioration of their disease and 9% experienced anxiety of dying. The relative risk of emotional strain was higher in females than in males (54% vs 41%, adjusted relative risk (RR)=1.32 (1.08; 1.63)). A waiting period >30 days compared with ≤30 days was associated with a higher risk of physical worsening (25.3% vs 48.9%, adjusted RR=1.93 (1.42; 2.63)).ConclusionsHarm, measured as physical worsening and emotional strain, is reported with severity by nearly half of respondents following cancellation.
Scoping review of enablers and challenges of implementing pharmacogenomics testing in the primary care settings
Authors: Mai Chun-Wai , Sridhar Sathvik B , Karattuthodi Mohammed Salim , Ganesan Perishithaa M , Shareef Javedh , Lee E Lyn , Armani Keivan 
Published: November 2024

IntroductionPharmacogenomic testing (PGx) plays a crucial role in improving patient medication safety, yet ethical concerns and limitations impede its clinical implementation in the primary care settings.AimsTo systematically review the current state of PGx in the primary care settings and determine the enablers and challenges of its implementation.DesignA scoping review was carried out by adhering to Arksey and O’Malley’s 6-stage methodological framework and the 2020 Joanna Briggs Institute and Levacet al.Data sourcesCochrane Library, EMBASE, Global Health, MEDLINE and PubMed were searched up to 17 July 2023.Eligibility criteriaAll peer-reviewed studies in English, reporting the enablers and the challenges of implementing PGx in the primary care settings were included.Date extraction and synthesisTwo independent reviewers extracted the data. Information was synthesised based on the reported enablers and the challenges of implementing PGx testing in the primary care settings. Information was then presented to stakeholders for their inputs.Results78 studies discussing the implementation of PGx testing are included, of which 57% were published between 2019 and 2023. 68% of the studies discussed PGx testing in the primary care setting as a disease-specific themes. Healthcare professionals were the major stakeholders, with primary care physicians (55%) being the most represented. Enablers encompassed various advantages such as diagnostic and therapeutic benefits, cost reduction and the empowerment of healthcare professionals. Challenges included the absence of sufficient scientific evidence, insufficient training for healthcare professionals, ethical and legal aspects of PGx data, low patient awareness and acceptance and the high costs linked to PGx testing.ConclusionPGx testing integration in primary care requires increased consumer awareness, comprehensive healthcare provider training on legal and ethical aspects and global feasibility studies to better understand its implementation challenges. Managing high costs entails streamlining processes, advocating for reimbursement policies and investing in research on innovation and affordability research to improve life expectancy.
Early Hearing Detection and Intervention programmes for neonates, infants and children in non-Asian low-income and middle-income countries: a systematic review
Authors: Rajanbabu Keerthana , Joshi B Deepashree , Ramkumar Vidya , Kuper Hannah , Vaidyanath Ramya 
Published: November 2024

IntroductionEarly Hearing Detection and Intervention (EHDI) programmes were established to reduce the impact of hearing loss on children. High-income countries (HICs) have resources and knowledge to execute these programmes. However, financial and other resource constraints limit the availability of these programmes to low-income and middle-income countries (LMICs). Yet, LMICs have explored strategies to implement EHDI programmes in their context; the outcomes are still largely unknown.The aim of this study is to identify the various models of the EHDI program implemented in non-Asian LMICs.AimMethodStudies published between 2010 and 2023 reporting EHDI programmes in non-Asian LMICs for children were considered. The primary databases searched were PubMed, Scopus, Web of Science, EBSCOHost, EBSCO-CINAHL and ProQuest dissertations. The search results are summarised using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses chart. Quality appraisal and risk-of-bias assessment were assessed. Using the retrieved data, a narrative synthesis of the identified methods and forest plots for the prevalence estimate was created.ResultsFifty-six studies from 16 LMICs were included. They were grouped into 29 hearing screening programmes for neonates and infants and 26 programmes for older children. Predominantly hospital-based screening was employed for neonates and infants and school-based screening for older children. Two-stage otoacoustic emissions screening was employed for neonates and infants, while single-stage pure tone audiometry with otoscopy screening was used for older children. Predominantly, audiologists performed screening and diagnostics for neonates/infants while community health workers performed screening for the older children. Screening aspects were reported predominantly and not diagnostic evaluation/intervention outcomes. Overall, the economics of EHDI was reported only anecdotally in a few studies.ConclusionThe screening strategies were not uniform among non-Asian LMICs. The protocols used were similar to HICs, yet few developed protocols adapting the Joint Committee of Infant Hearing. However, long-term outcomes such as rate of identification, suitable intervention and their outcomes are not known. EHDI programmes with successful outcomes of early intervention must be studied and reported with economic evaluations.
Attitudes towards the regulation and provision of abortion among healthcare professionals in Britain: cross-sectional survey data from the SACHA Study
Authors: Wellings Kaye , Scott Rachel H , Sheldon Sally , McCarthy Ona , Palmer Melissa J , Shawe Jill , Meiksin Rebecca , Lewandowska Maria , Cameron Sharon T , Reiter Jennifer , French Rebecca S 
Published: November 2024

ObjectivesTo gather views of healthcare professionals on the regulation and provision of abortion in Britain.MethodsCross-sectional, stratified cluster sample survey of healthcare professionals working in a range of healthcare services including abortion services. Measures included knowledge of and attitudes towards the regulation and provision of abortion.ResultsA total of 771 healthcare professionals responded. More than nine in ten supported abortion being a woman’s choice and a clear majority favoured abortion being treated as a health rather than a legal issue. Some 6.2% saw abortion at any gestational age as contrary to personal beliefs and a similarly small minority (6.7%) opposed abortion after 12 weeks’ gestation. One in five of all healthcare professionals and a third of those aged under 30 years were unaware that the law in Britain requires two doctors to authorise an abortion. Free-text comments revealed opposition to the need for this legal requirement. Support for an extended role for nurses in abortion care was high; 65.3% agreed that nurses should be able to prescribe abortion medication. Little more than a third of all healthcare professionals (37.0%) agreed that abortion should be standard practice in their service; the proportion was highest among those in sexual and reproductive health services (58.4%) and lowest among those in general practice (18.7%).ConclusionsHealthcare professionals in Britain were generally supportive of abortion being treated in the same way as other health issues and would be likely to support any moves to decriminalise abortion.
Intratumoral and peritumoral radiomics of MRIs predicts pathologic complete response to neoadjuvant chemoimmunotherapy in patients with head and neck squamous cell carcinoma
Authors: Lin Peiliang , Xie Wenqian , Li Yong , Zhang Chenjia , Wu Huiqian , Wan Huan , Gao Ming , Liang Faya , Han Ping , Chen Renhui , Cheng Gui , Liu Xuekui , Fan Song , Huang Xiaoming 
Published: November 2024

BackgroundFor patients with locally advanced head and neck squamous cell carcinoma (HNSCC), combined programmed death receptor-1 inhibitor and chemotherapy improved response rate to neoadjuvant therapy. However, treatment response varies among patients. There is no tool to predict pathologic complete response (pCR) with high accuracy for now. To develop a tool based on radiomics features of MRI to predict pCR to neoadjuvant chemoimmunotherapy (NACI) may provide valuable assistance in treatment regimen determination for HNSCC.MethodsFrom January 2021 to April 2024, a total of 172 patients with HNSCC from three medical center, who received NACI followed by surgery, were included and allocated into a training set (n=84), an internal validation set (n=37) and an external validation set (n=51). Radiomics features were extracted from intratumoral and different peritumoral areas, and radiomics signature (Rad-score) for each area was constructed. A radiomics-clinical nomogram was developed based on Rad-scores and clinicopathological characteristics, tested in the validation sets, and compared with clinical nomogram and combined positive score (CPS) in predicting pCR.ResultsThe radiomics-clinical nomogram, incorporating peritumoral Rad-score, intratumoral Rad-score and CPS, achieved the highest accuracy with areas under the receiver operating characteristic curve of 0.904 (95% CI, 0.835 to 0.972) in the training cohort, 0.860 (95% CI, 0.722 to 0.998) in the internal validation cohort, and 0.849 (95% CI, 0.739 to 0.959) in the external validation cohort, respectively, which outperformed the clinical nomogram and CPS in predict pCR to NACI for HNSCC.ConclusionA nomogram developed based on intratumoral and peritumoral MRI radiomics features outperformed CPS, a widely employed biomarker, in predict pCR to NACI for HNSCC, which would provide incremental value in treatment regimen determination.