bluuebunny/crossref_metadata_2025_split huggingface dataset:
Packaging defects in pestiviral NS4A can be compensated by mutations in NS2 and NS3
Authors: Fellenberg Jonas , Dubrau Danilo , Isken Olaf , Tautz Norbert 
Published: September 2023

ABSTRACTThe non-structural (NS) proteins of theFlaviviridaemembers play a dual role in genome replication and virion morphogenesis. For pestiviruses, like bovine viral diarrhea virus, the NS2-3 region and its processing by the NS2 autoprotease is of particular importance. While uncleaved NS2-3 in complex with NS4A is essential for virion assembly, it cannot replace free NS3/4A in the viral replicase. Furthermore, surface interactions between NS3 and the C-terminal cytosolic domain of NS4A were shown to serve as a molecular switch between RNA replication and virion morphogenesis. To further characterize the functionality of NS4A, we performed an alanine-scanning mutagenesis of two NS4A regions, a short highly conserved cytoplasmic linker downstream of the transmembrane domain and the C-terminal domain. NS4A residues critical for polyprotein processing, RNA replication, and/or virion morphogenesis were identified. Three double-alanine mutants, two in the linker region and one close to the C-terminus of NS4A, showed a selective effect on virion assembly. All three packaging defective mutants could be rescued by a selected set of two second-site mutations, located in NS2 and NS3, respectively. This phenotype was additionally confirmed by complementation studies providing the NS2-3/4A packaging molecules containing the rescue mutations intrans. This indicates that the linker region and the cytosolic C-terminal part of NS4A are critical for the formation of protein complexes required for virion morphogenesis. The ability of the identified sets of second-site mutations in NS2-3 to compensate for diverse NS4A defects highlights a surprising functional flexibility for pestiviral NS proteins.IMPORTANCEPositive-strand RNA viruses have a limited coding capacity due to their rather small genome size. To overcome this constraint, viral proteins often exhibit multiple functions that come into play at different stages during the viral replication cycle. The molecular basis for this multifunctionality is often unknown. For the bovine viral diarrhea virus, the non-structural protein (NS) 4A functions as an NS3 protease cofactor, a replicase building block, and a component in virion morphogenesis. Here, we identified the critical amino acids of its C-terminal cytosolic region involved in those processes and show that second-site mutations in NS2 and NS3 can compensate for diverse NS4A defects in virion morphogenesis. The ability to evolve alternative functional solutions by gain-of-function mutations highlights the astounding plasticity of the pestiviral system.
New Data on the Age of Magmatic Rocks in the Alpha–Mendeleev Rise (Arctic Ocean) Based on the Results of Isotope U/Pb Dating of Zircons
Authors: Skolotnev S. G. , Fedonkin M. A. , Korniychuk A. V. 
Published: September 2023

Abstract
The age of magmatic rocks of basic composition sampled at the Alpha–Mendeleev Rise in the Arctic Ocean by a research submarine was studied based on the measurement of the U/Pb age of zircons separated from them. Early Cretaceous rocks of the moderately alkaline series, which had been formed at the turn of 112 million years, are most common on the Rise. These rocks contain a large number of ancient xenogenic zircons the age analysis of which shows that the subalkaline melts interacted with the crust at two levels including the horizon of Early Cretaceous sandstones and with rocks of the Late Archean crystalline basement aged 2675.1 ± 11.6 Ma. They also contain a small number of younger zircons aged 83 to 87 Ma, which probably arose during the recrystallization of Early Cretaceous zircons under the influence of Late Cretaceous magmatism.
ViSHWaS: Violence Study of Healthcare Workers and Systems—a global survey
Authors: Banga Akshat , Mautong Hans , Alamoudi Razan , Faisal Umme Habiba , Bhatt Gaurang , Amal Tanya , Mendiratta Ayushi , Bollu Bhaswanth , Kutikuppala L V Simhachalam , Lee Joanna , Simadibrata Daniel Martin , Huespe Ivan , Khalid Aisha , Rais Mohammed Amir , Adhikari Ramesh , Lakhani Alisha , Garg Piyush , Pattnaik Harsha , Gandhi Raghu , Pandit Ramesh , Ahmad Faizan , Camacho-Leon Genesis , Ciza N Pierre , Barrios Nimsi , Meza Kelly , Okonkwo Susan , Dhabuliwo Amuza , Hamza Hafeez , Nemat Arash , Essar Mohammad Yasir , Kampa Anne , Qasba Rakhtan K , Sharma Pranjal , Dutt Taru , Vekaria Pratikkumar , Bansal Vikas , Nawaz Faisal A , Surani Salim , Kashyap Rahul 
Published: September 2023

ObjectiveTo provide insights into the nature, risk factors, impact and existing measures for reporting and preventing violence in the healthcare system. The under-reporting of violence against healthcare workers (HCWs) globally highlights the need for increased public awareness and education.MethodsThe Violence Study of Healthcare Workers and Systems study used a survey questionnaire created using Research Electronic Data Capture (REDCap) forms and distributed from 6 June to 9 August 2022. Logistic regression analysis evaluated violence predictors, including gender, age, years of experience, institution type, respondent profession and night shift frequency. A χ2test was performed to determine the association between gender and different violence forms.ResultsA total of 5405 responses from 79 countries were analysed. India, the USA and Venezuela were the top three contributors. Female respondents comprised 53%. The majority (45%) fell within the 26–35 age group. Medical students (21%), consultants (20%), residents/fellows (15%) and nurses (10%) constituted highest responders. Nearly 55% HCWs reported firsthand violence experience, and 16% reported violence against their colleagues. Perpetrators were identified as patients or family members in over 50% of cases, while supervisor-incited violence accounted for 16%. Around 80% stated that violence incidence either remained constant or increased during the COVID-19 pandemic. Among HCWs who experienced violence, 55% felt less motivated or more dissatisfied with their jobs afterward, and 25% expressed willingness to quit. Univariate analysis revealed that HCWs aged 26–65 years, nurses, physicians, ancillary staff, those working in public settings, with >1 year of experience, and frequent night shift workers were at significantly higher risk of experiencing violence. These results remained significant in multivariate analysis, except for the 55–65 age group, which lost statistical significance.ConclusionThis global cross-sectional study highlights that a majority of HCWs have experienced violence, and the incidence either increased or remained the same during the COVID-19 pandemic. This has resulted in decreased job satisfaction.
Preconception contraceptive use and miscarriage: prospective cohort study
Authors: Yland Jennifer J , Wesselink Amelia K , Hernandez-Diaz Sonia , Huybrechts Krista , Hatch Elizabeth E , Wang Tanran R , Savitz David , Kuohung Wendy , Rothman Kenneth J , Wise Lauren A 
Published: September 2023

ObjectivesTo evaluate the association between preconception contraceptive use and miscarriage.DesignProspective cohort study.SettingResidents of the United States of America or Canada, recruited from 2013 until the end of 2022.Participants13 460 female identified participants aged 21-45 years who were planning a pregnancy were included, of whom 8899 conceived. Participants reported data for contraceptive history, early pregnancy, miscarriage, and potential confounders during preconception and pregnancy.Main outcome measureMiscarriage, defined as pregnancy loss before 20 weeks of gestation.ResultsPreconception use of combined and progestin-only oral contraceptives, hormonal intrauterine devices, copper intrauterine devices, rings, implants, or natural methods was not associated with miscarriage compared with use of barrier methods. Participants who most recently used patch (incidence rate ratios 1.34 (95% confidence interval 0.81 to 2.21)) or injectable contraceptives (1.44 (0.99 to 2.12)) had higher rates of miscarriage compared with recent users of barrier methods, although results were imprecise due to the small numbers of participants who used patch and injectable contraceptives.ConclusionsUse of most contraceptives before conception was not appreciably associated with miscarriage rate. Individuals who used patch and injectable contraceptives had higher rates of miscarriage relative to users of barrier methods, although these results were imprecise and residual confounding was possible.
Drivers of uptake of HIV testing services, a snapshot of barriers and facilitators among adolescent boys and young men in Lusaka: a qualitative study
Authors: Nyirenda Herbert Chabwera , Foloko Marksman , Bolton-Moore Carolyn , Vera Jaime , Sharma Anjali 
Published: September 2023

BackgroundStriking gender and rural–urban disparities highlight the need to redesign HIV services to improve HIV testing and linkage by adolescent boys and young men (ABYM) in sub-Saharan African cities.PurposeWe sought to understand drivers of HIV testing among ABYM living in urban Lusaka in order to design a targeted intervention that may increase their entry into the HIV prevention and treatment cascade.MethodsIn May and June 2019, two male moderators conducted three focus group discussions lasting 1.25 hours with seven to nine ABYM per group and six in-depth interviews with healthcare providers (HCPs) working with adolescents. ABYM were conveniently selected from first aid training, sports and youth-friendly sites in three settlement areas. We purposefully selected HCP from community, facility and district levels. Thematic analyses using inductive reasoning were applied.ResultsThe 24 ABYM were 18–24 years old (median 21 years), single, from 11 different neighbourhoods and 79% had 9–12 years of education. Facilitators of HIV testing uptake included the importance ABYM placed on good health and planning their future in order to fulfil their masculine identity and societal roles. Barriers included peer norms, life-long treatment along with anticipated changes to sexual life and alcohol use, fear of results and judgement and disappointment among HCP. HCPs agreed that masculine roles (‘many things to do’) and arduous clinical processes deterred ABYM from accessing testing services. They suggested that ABYM were prone to depression which both caused and resulted from behavioural issues such as alcohol use and risk-taking, which prevented uptake of HIV testing services. Both parties agreed that ABYM needed services specifically designed for them and that offered convenient, private, swift and non-judgemental services.ConclusionsABYM disillusioned by standard counselling procedures, systemic barriers and stigma, avoid HIV test and treat services. Innovative ways and youth-specific spaces are needed to increase access to non-judgemental services that facilitate entry into the HIV prevention and treatment cascade in this population.
Prevalence of comorbidities and its associated factors among type-2 diabetes patients: a hospital-based study in Jashore District, Bangladesh
Authors: Shuvo Suvasish Das , Hossen Md Toufik , Riazuddin Md , Hossain Md Sakhawot , Mazumdar Sanaullah , Parvin Rashida , Elahi Md Toufiq 
Published: September 2023

ObjectiveThis study aimed to estimate the prevalence of comorbidity and its associated factors among Bangladeshi type-2 diabetes (T2D) patients.DesignA hospital-based cross-sectional study.SettingThis study was conducted in two specialised diabetic centres residing in the Jashore District of Bangladesh. A systematic random sampling procedure was applied to identify the T2D patients through a face-to-face interview.ParticipantsA total of 1036 patients with T2D were included in this study. A structured questionnaire was administered to collect data on demographic, lifestyle, medical and healthcare access-related data through face-to-face and medical record reviews.Outcome measures and analysesThe main outcome variable for this study was comorbidities. The prevalence of comorbidity was measured using descriptive statistics. A logistic regression model was performed to explore the factors associated with comorbidity among Bangladeshi T2D patients.ResultsThe overall prevalence of comorbidity was 41.4% and the most prevalent conditions were hypertension (50.4%), retinopathy (49.6%), obesity (28.7%) and oral problem (26.2). In the regression model, the odds of comorbidities increased with gender (male: OR: 1.27, 95% CI 1.12 to 1.87), age (50–64 years: OR: 2.14, 95% CI 1.32 to 2.93; and above 65 years: OR: 2.96, 95% CI 1.83 to 4.16), occupation (unemployment: OR: 3.32, 95% CI 1.92 to 6.02 and non-manual worker: OR: 2.31, 95% CI 1.91 to 5.82), duration of diabetes (above 15 years: OR: 3.28, 95% CI 1.44 to 5.37), body mass index (obese: OR: 2.62, 95% CI 1.24 to 4.26) of patients. We also found that individuals with recommended moderate to vigorous physical activity levels (OR: 0.41, 95% CI 0.25 to 0.74) had the lowest odds of having comorbidity. Meanwhile, respondents with limited self-care practice, unaffordable medicine and financial problems had 1.82 times, 1.94 times and 1.86 times higher odds of developing comorbidities.ConclusionThe findings could be useful in designing and implementing effective intervention strategies and programmes for people with T2D to reduce the burden of comorbidity.
EyeCee One preloaded intraocular lens: are patients with glaucoma more at risk?
Authors: Jones Ruth K , Jong Joel Lee Zher , Ramjiani Vipul , Tan Jennifer H Y 
Published: September 2023

ObjectiveThe Medicine and Healthcare products Regulatory Agency reported links of raised intraocular pressure (IOP) with recently implanted EyeCee One intraocular lens (IOL). This work investigates if glaucomatous eyes were more susceptible to these postoperative IOP rises and if they required more intensive management.MethodsRetrospective observational study of all phacoemulsification surgery with implanted EyeCee One IOL, performed between 1 October 2022 and 26 January 2023 inclusive.AnalysisA significant IOP elevation was defined as an IOP rise of 10 mm Hg or more from preoperative to maximal postoperative IOP reading. The management of all patients who had a significant IOP elevation was reviewed. Glaucoma/ocular hypertension cases were identified and analysed against non-glaucomatous eyes and statistical analysis performed.Results112 glaucoma and 671 non-glaucoma cases identified; 19.6% of the glaucoma cohort had a significant postoperative IOP rise compared with 8.9% of patients without glaucoma (OR 2.49 (95% CI 1.45 to 4.20) p=0.0014). In the glaucoma cohort, 12.5% had an increase in the number of topical IOP-lowering agents (mean increase 1.65±1.58), 6.3% required systemic treatment and 2.7% surgical intervention. In the non-glaucoma group, 3.3% required topical treatment (mean number of agents 0.88±1.34), 0.8% required systemic treatment and 0.2% surgical intervention.ConclusionThis study shows that during the time frame in question, patients with glaucoma or ocular hypertension who had an EyeCee One IOL were almost two and a half times more likely to have a postoperative rise of 10 mm Hg or more in IOP following routine cataract surgery, requiring more aggressive management.
PAX5 and CD70 are expressed in thymic carcinoma but not in atypical thymoma (WHO type B3 thymoma): an immunohistochemical analysis of 60 cases
Authors: Weissferdt Annikka , Moran Cesar 
Published: September 2023

AimsThymic carcinoma and atypical thymoma (WHO type B3 thymoma) are unusual tumours the separation of which may be challenging in small biopsies. Both tumours consist of epithelioid tumour cells that share similar morphology and immunophenotype with conventional markers. Therefore, additional antibodies are needed to differentiate between these tumours.MethodsFor this purpose, a panel of immunohistochemical stains including PAX2, PAX5, PAX8 (all monoclonal) and CD70 was used on whole tumour sections of 30 thymic carcinomas and 30 atypical thymomas to determine the expression pattern of these antibodies. In addition, all tumours were stained with markers that are well known to be expressed in both tumours, including pancytokeratin and cytokeratin 5/6. The percentage of positive tumour cells as well as the intensity of staining were evaluated and scored.ResultsPAX5 stained close to 70% of thymic carcinomas while all atypical thymomas were negative for this marker. CD70 was expressed in 18 thymic carcinomas (60%) and in 1 case of atypical thymoma (3%). On the other hand, monoclonal PAX8 was negative in all cases while PAX2 was positive in a single thymic carcinoma. Of the established stains, pancytokeratin and cytokeratin 5/6 were equally positive in both tumours.ConclusionsAmong the markers explored, only PAX5 and CD70 appear to be differentially expressed and are predominantly restricted to thymic carcinomas. Therefore, in small biopsy specimens and in resections in which the morphological features remain equivocal, application of these particular stains may facilitate separation of thymic carcinoma and atypical thymoma.
Association between genetic polymorphisms and risk of adolescent idiopathic scoliosis in case-control studies: a systematic review
Authors: Terhune Elizabeth , Heyn Patricia , Piper Christi , Wethey Cambria , Monley Anna , Cuevas Melissa , Hadley Miller Nancy 
Published: September 2023

BackgroundAdolescent idiopathic scoliosis (AIS) is a structural lateral spinal curvature of ≥10° with rotation. Approximately 2%–3% of children across populations are affected with AIS, and this condition is responsible for ~$3 billion in costs within the USA. Although AIS is believed to have a strong genetic contribution, clinical translation of identified genetic variants has stalled.MethodsThe databases MEDLINE (via PubMed), Embase, Google Scholar and Ovid MEDLINE were searched and limited to articles in English. Title and abstract, full-text and data extraction screening was conducted through Covidence, followed by data transfer to a custom REDCap database. Studies containing variant-level data using genome-wide methodology as well as validation studies of genome-wide methods were considered. Quality assessment was conducted using Q-Genie.Results33 studies were included, including 9 genome-wide association studies, 4 whole exome sequencing and 20 validation studies. Combined, these studies included data from >35,000 cases and >67,000 controls, not including validation cohorts. Additionally, results from six meta-analyses containing novel cohorts were also reported. All included study cohorts were from populations of primarily East Asian or Caucasian descent. Quality assessment found that overall study quality was high and control group selection was moderate. The highest number of reported associations were in single nucleotide polymorphisms (SNPs) in or nearLBX1, LBX1-AS1, GPR126/ADGRG6orBNC2.ConclusionAIS risk may be influenced by specific SNPs, particularly those in/nearLBX1andGPR126. Translatability of study findings is unknown due to an underrepresentation of most ethnic groups as well as few identified genome-wide studies. Further studies may benefit from increased cohort diversity and thorough evaluation of control cohort groups.
Incidence of acute compartment syndrome with routine use of regional anesthesia for patients with long bone fractures: a large single-center retrospective review from a level I trauma tertiary academic institution
Authors: Chembrovich Svetlana , Ihnatsenka Barys , Smith Cameron , Zasimovich Yury , Gunnett Amy , Petersen Timothy R , Le-Wendling Linda 
Published: September 2023

IntroductionTraditionally, using peripheral nerve blocks (PNBs) in patients with long bone fractures has been limited due to concerns that it may interfere with the timely diagnosis of acute compartment syndrome (ACS). However, our large academic institution and level I trauma center have been using regional anesthesia routinely for pain management of patients with long bone fractures for more than a decade, with strict adherence to a comprehensive management protocol. The aim of this retrospective review is to present our experience with this practice.MethodsFollowing Institutional Review Board approval, we performed a retrospective chart review of patients with long bone fractures and ACS over a 10-year period (2008–2018).Results26 537 patients were included in the review. Approximately 20% of these patients required surgery, and 91.5% of surgically treated patients received regional anesthesia. The incidence of ACS in our cohort was 0.1% or 1.017 per 1000 patients with long bone fractures.ConclusionCurrent recommendations on using PNBs in patients at risk for ACS have been mainly based on expert opinion and dated case reports. Due to the nature of the condition, prospective data are lacking. Our large observational dataset evaluated the risk of missing or delaying ACS diagnosis when PNBs were offered for trauma patients and demonstrated a relatively low incidence of ACS despite the routine use of PNBs under strictly protocolized conditions when patients were managed by a dedicated multidisciplinary care team.
Laryngeal widening and adequate ventilation by expiratory pressure load training improve aerobic capacity in COPD: a randomised controlled trial
Authors: Miki Keisuke , Tsujino Kazuyuki , Fukui Motonari , Miki Mari , Kitajima Takamasa , Sumitani Hitoshi , Hashimoto Kazuki , Yokoyama Masashi , Hashimoto Hisako , Nii Takuro , Matsuki Takanori , Kida Hiroshi 
Published: September 2023

RationaleDespite strategies acting on peripheral airway obstruction in chronic obstructive pulmonary disease (COPD), exercise intolerance remains inadequately improved. We hypothesised that laryngeal narrowing is a potential treatment target of expiratory pressure load training (EPT) to improve exercise intolerance in COPD.MethodsThe effect of 3-month EPT was assessed in 47 patients with COPD divided into Global Initiative for Chronic Obstructive Lung Disease (GOLD) mild-to-moderate (I–II) and severe-to-very severe (III–IV), randomly allocating 1:1 to EPT or control groups. The primary outcome was endurance time in the constant work rate exercise test in GOLD III–IV patients.ResultsCompared with controls, EPT increased: (1) endurance time, with estimated treatment effect: +703 (95% CI: 379 to 1031) s, p=0.0008 (GOLD I–II); +390 (95% CI: 205 to 574) s, p=0.0006 (GOLD III–IV); (2) peak oxygen uptake (p=0.0086 in GOLD I–II; p=0.0004 in GOLD III–IV); (3) glottic dilatation ratio at maximum collapse on laryngoscopy in the submaximal exercise (p=0.0062 in GOLD I–II; p=0.0001 in GOLD III–IV); and (4) the inflection point of expiratory tidal volume relative to minute ventilation during the incremental exercise (p=0.0015 in GOLD I–II; p=0.0075 in GOLD III–IV). Across GOLD grades, the responses of glottic dilatation ratio at maximum collapse and the expiratory tidal volume at the inflection point were selected as more influential variables correlating with the improvement in peak oxygen uptake and endurance time, respectively.ConclusionThese results show that EPT improved aerobic capacity and endurance time with larger laryngeal widening and adequate ventilation despite advanced COPD.Trial registration numberUMIN000041250.