bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance evaluation of the Xpert MTB/XDR test for the detection of drug resistance to
Mycobacterium tuberculosis
among people diagnosed with tuberculosis in South Africa
Authors: Omar Shaheed Vally , Louw Gail , Ismail Farzana , Liu Xiaohong , Ngcamu Dumsani , Gwala Thabisile , van der Meulen Minty , Joseph Lavania 
Published: July 2024

ABSTRACT

Drug-resistant tuberculosis (TB) poses a significant public health concern in South Africa due to its complexity in diagnosis, treatment, and management. This study assessed the diagnostic performance of the Xpert MTB/XDR test for detecting drug resistance in patients with TB by using archived sputum sediments. This study analyzed 322 samples collected from patients diagnosed with TB between 2016 and 2019 across South Africa, previously characterized by phenotypic and genotypic methods. The Xpert MTB/XDR test was evaluated for its ability to detect resistance to isoniazid (INH), ethionamide (ETH), fluoroquinolones (FLQ), and second-line injectable drugs (SLIDs) compared with phenotypic drug susceptibility testing (pDST) and whole-genome sequencing (WGS). Culture, Xpert MTB/RIF Ultra, and Xpert MTB/RIF (G4) tests were performed to determine sensitivity and agreement with this test for TB detection. The sensitivities using a composite reference standard, pDST, and sequencing were >90% for INH, FLQ, amikacin (AMK), kanamycin (KAN), and capreomycin (CAP) resistance, meeting the WHO target product profile criteria for this class. A lower sensitivity of 65.9% (95% CI: 57.1–73.6) for ETH resistance was observed. The Xpert MTB/XDR showed a sensitivity of 98.3% (95% CI: 96.1–99.3) and specificity of 100% (95% CI: 86.7–100) compared with culture, a positive percent agreement (PPA) of 98.8% (95% CI: 93.7–99.8) and negative percent agreement (NPA) of 100.0% (95% CI: 78.5–100.0) compared with G4, and a PPA of 99.5% (95% CI: 97.3–99.9) and NPA of 100.0% (95% CI: 78.5–100.0) compared with Xpert MTB/RIF Ultra for detecting
Mycobacterium tuberculosis
. The test offers a promising solution for the rapid detection of drug-resistant TB and could significantly enhance control efforts in this setting.
Regulatory complexity of cellular differentiation in
Candida albicans
revealed through systematic screening of protein kinase mutants
Authors: Lorenz Michael C. 
Published: July 2024

ABSTRACT

A recent study in
mBio
reports the construction and preliminary screening of a library containing mutants of 99 of the 119 predicted protein kinases in
Candida albicans
(the majority of the remaining 20 are probably essential) (J. Kramara, M.-J. Kim, T. L. Ollinger, L. C. Ristow, et al., mBio e01249-24, 2024,
https://doi.org/10.1128/mbio.01249-24
). Using a quantitative competition assay in 10 conditions that represent nutritional, osmotic, cell wall, and pH stresses that are considered to model various aspects of the host environment allowed them to phenotypically cluster kinases, which highlight both the integration and specialization of signaling pathways, suggesting novel functions for many kinases. In addition, they tackle two complex and partially overlapping differentiation events, hyphal morphogenesis and biofilm formation. They find that a remarkable 88% of the viable kinase mutants in
C. albicans
affect hyphal growth, illustrating how integrated morphogenesis is in the overall biology of this organism, and begin to dissect the regulatory relationships that control this key virulence trait.
Mobile genetic elements define the non-random structure of the
Salmonella enterica
serovar Typhi pangenome
Authors: Peñil-Celis Arancha , Tagg Kaitlin A. , Webb Hattie E. , Redondo-Salvo Santiago , Francois Watkins Louise , Vielva Luis , Griffin Chelsey , Kim Justin Y. , Folster Jason P. , Garcillan-Barcia M. Pilar , de la Cruz Fernando 
Published: July 2024

ABSTRACT

Bacterial relatedness measured using select chromosomal loci forms the basis of public health genomic surveillance. While approximating vertical evolution through this approach has proven exceptionally valuable for understanding pathogen dynamics, it excludes a fundamental dimension of bacterial evolution—horizontal gene transfer. Incorporating the accessory genome is the logical remediation and has recently shown promise in expanding epidemiological resolution for enteric pathogens. Employing
k
-mer-based Jaccard index analysis, and a novel genome length distance metric, we computed pangenome (i.e., core and accessory) relatedness for the globally important pathogen
Salmonella enterica
serotype Typhi (Typhi), and graphically express both vertical (homology-by-descent) and horizontal (homology-by-admixture) evolutionary relationships in a reticulate network of over 2,200 U.S. Typhi genomes. This analysis revealed non-random structure in the Typhi pangenome that is driven predominantly by the gain and loss of mobile genetic elements, confirming and expanding upon known epidemiological patterns, revealing novel plasmid dynamics, and identifying avenues for further genomic epidemiological exploration. With an eye to public health application, this work adds important biological context to the rapidly improving ways of analyzing bacterial genetic data and demonstrates the value of the accessory genome to infer pathogen epidemiology and evolution.

IMPORTANCE

Given bacterial evolution occurs in both vertical and horizontal dimensions, inclusion of both core and accessory genetic material (i.e., the pangenome) is a logical step toward a more thorough understanding of pathogen dynamics. With an eye to public, and indeed, global health relevance, we couple contemporary tools for genomic analysis with decades of research on mobile genetic elements to demonstrate the value of the pangenome, known and unknown, annotated, and hypothetical, for stratification of
Salmonella enterica
serovar Typhi (Typhi) populations. We confirm and expand upon what is known about Typhi epidemiology, plasmids, and antimicrobial resistance dynamics, and offer new avenues of exploration to further deduce Typhi ecology and evolution, and ultimately to reduce the incidence of human disease.
Multilocus sequence typing database for
Streptococcus agalactiae
contains a spurious allele of the transketolase gene
Authors: Chen Swaine L. , Tiruvayipati Suma , Tang Wen Ying , M. S. Barkham Timothy 
Published: July 2024

ABSTRACT

The
tkt
(transketolase) gene is one of the seven gene fragments used in the multilocus sequence typing (MLST) system for
Streptococcus agalactiae
. We discovered that the tkt_134 allele is derived from a homologous gene (which we designate
tktX
) that is not present in all
S. agalactiae
; all known strains that contain a match to the tkt_134 allele also contain a gene sequence that is much closer in sequence identity to the other non-tkt_134 alleles (i.e., the canonical tkt gene) in the database. Based on these data, the tkt_134 allele has been removed from the MLST database as of September 2021, and all sequence types containing tkt_134 have also been removed.

IMPORTANCE

Multilocus sequence typing (MLST) databases are a common good and remain important for research, medical, and epidemiological purposes. This remains true even in the context of widespread whole-genome sequencing. We discovered a contaminating allele of the
tkt
gene in the
S. agalactiae
MLST database that led to unstable, ambiguous, or erroneous MLST assignment. The allele has since been removed from the public database based on the results presented in this manuscript.
Collision structures of the Prince William terrane and Chugach terrane docking along the Shumagin and Unimak convergent margins, Alaska, USA
Authors: von Huene Roland , Miller John J. 
Published: July 2024

Abstract
Western Alaska's convergent margins are composed of tectonostratigraphic terranes. On land, terrane assembly is recognized along boundaries or sutures between neighboring geologic elements with distinctly different origins. In marine areas where rock outcrops are covered by sediment, recognizing terrane sutures is problematic. A fault in seismic dip line 5 of the ALEUT project has been interpreted as a terrane suture. It is imaged intermittently down to the 30+-km-deep plate interface. Processing of ALEUT strike line 7 revealed the suture at ~18 km depths extending 300 km along the margin. Upper structures in line 5 are like the structures of adjacent seismic transects where imaging is only 8−10 km deep. They were previously not recognized as the upper reaches of terrane sutures and show structural details obscured at greater depths. The composite data are the basis for a simple tectonic model of terrane docking.
Health system responsiveness and its associated factors for intrapartum care in conflict affected areas in Amhara region, Ethiopia: a cross-sectional study
Authors: Atnafu Asmamaw , Dellie Endalkachew , Kebede Adane , Fetene Samrawit Mihret , Haile Tsegaye G. , Alemu Melaku Birhanu , Park Jinha , Tefera Selamawit , Alene Bruhtesfa Mouhabew , Negash Wubshet Debebe 
Published: July 2024

ObjectiveIn Ethiopia, information about health system responsiveness (HSR) in conflict-affected areas is limited. No previous local study was conducted on the assessment of HSR at the community level. Hence, the study assessed HSR for intrapartum care in conflict-affected areas in Amhara region, Ethiopia.DesignCommunity-based cross-sectional study design.SettingWadila, Gayint and Meket districts, Amhara region, Ethiopia.ParticipantsThe participants were 419 mothers who gave birth in conflict-affected areas within the last 6 months. The study included all mothers who gave birth at health facilities but excluded those who delivered at home, critically ill or unable to hear.OutcomeHSR was the outcome variable. In this regard, the study assessed how mothers were treated and the situation in which they were cared for in relation to their experience during the conflict.MethodsWe conducted the study in the community, where we analysed eight domains of HSR to identify 30 measurement items related to intrapartum care responsiveness. The domains we looked at were dignity (4), autonomy (4), confidentiality (2), communication (5), prompt attention (5), social support (3), choice (3) and basic amenities (4). We used a multiple linear regression model to analyse the data, and in this model, we used an unstandardized β coefficient with a 95% CI and a p value of less than 0.05 to determine the factors significantly associated with HSR.ResultsThe findings of our study revealed that the overall proportion of HSR in intrapartum care was 45.11% (95% CI: 40.38 to 49.92). The performance of responsiveness was the lowest in the autonomy, choice and prompt attention domains at 35.5%, 49.4% and 52.0%, respectively. Mothers living in urban areas (β=4.28; 95% CI: 2.06 to 6.50), government employees (β=4.99; 95% CI: 0.51 to 9.48), those mothers stayed at the health facilities before delivery/during conflict (β=0.22; 95% CI: 0.09 to 0.35), those who were satisfied with the healthcare service (β=0.69; 95% CI: 0.08 to 1.30) and those who perceived the quality of healthcare favourable (β=0.96; 95% CI: 0.72 to 1.19) were more likely to rate HSR positively. On the other hand, joint decision-making for health (β=−2.46; 95% CI: −4.81 to –0.10) and hospital delivery (β=−3.62; 95% CI: −5.60 to –1.63) were negatively associated with HSR.ConclusionIn the Amhara region of Ethiopia, over 50% of mothers living in areas affected by conflict reported that health systems were not responsive with respect to intrapartum care. Therefore, all stakeholders should work together to ensure that intrapartum care is responsive to conflict-affected areas, with a focus on providing women autonomy and choice.
How should non-emergency EMS presentations be managed? A thematic analysis of politicians’, policymakers’, clinicians’ and consumers’ viewpoints
Authors: Wilkinson-Stokes Matt , Yap Celene , Crellin Di , Bange Ray , Braitberg George , Gerdtz Marie 
Published: July 2024

ObjectiveIn 2023, Australian government emergency medical services (EMS) responded to over 4 million consumers, of which over 56% were not classified as an ‘emergency’, at the cost of AU$5.5 billion. We explored the viewpoints of politicians, policymakers, clinicians and consumers on how these non-emergency requests should be managed.DesignA realist framework was adopted; a multidisciplinary team (including paramedicine, medicine and nursing) was formed; data were collected via semistructured focus groups or interviews, and thematic analysis was performed.Setting and participants56 participants were selected purposefully and via open advertisement: national and state parliamentarians (n=3); government heads of healthcare disciplines (n=3); government policymakers (n=5); industry policymakers in emergency medicine, general practice and paramedicine (n=6); EMS chief executive officers, medical directors and managers (n=7); academics (n=8), frontline clinicians in medicine, nursing and paramedicine (n=8); and consumers (n=16).ResultsThree themes emerged: first, the reality of the EMS workload (theme titled ‘facing reality’); second, perceptions of what direction policy should take to manage this (‘no silver bullet’) and finally, what the future role of EMS in society should be (‘finding the right space’). Participants provided 16 policy suggestions, of which 10 were widely supported: increasing public health literacy, removing the Medical Priority Dispatch System, supporting multidisciplinary teams, increasing 24-hour virtual emergency departments, revising undergraduate paramedic university education to reflect the reality of the contemporary role, increasing use of management plans for frequent consumers, better paramedic integration with the healthcare system, empowering callers by providing estimated wait times, reducing ineffective media campaigns to ‘save EMS for emergencies’ and EMS moving away from hospital referrals and towards community care.ConclusionsThere is a need to establish consensus on the role of EMS within society and, particularly, on whether the scope should continue expanding beyond emergency care. This research reports 16 possible ideas, each of which may warrant consideration, and maps them onto the standard patient journey.
Development of a core data set for describing, measuring and reporting the learning curve in studies of novel invasive procedures: study protocol
Authors: Ramirez Jozel , Hoffmann Christin , Corrigan Neil , Kobetic Matthew , Macefield Rhiannon , Elliott Daisy , Blazeby Jane , Potter Shelley , Stocken Deborah D , Avery Kerry , Blencowe Natalie S 
Published: July 2024

IntroductionThe introduction of novel surgical techniques and procedures remains poorly regulated and standardised. Although the learning curve associated with invasive procedures is a critical part of innovation, it is currently inconsistently defined, measured and reported. This study aims to develop a core data set that can be applied in all studies describing or measuring the learning curve in novel invasive procedures.MethodsA core data set will be developed using methods adapted from the Core Outcome Measures in Effectiveness Trials initiative. The study will involve three phases: (1) Identification of a comprehensive list of data items through (a) an umbrella review of existing systematic reviews on the learning curve in surgery and (b) qualitative interviews with key stakeholders. (2) Key stakeholders (eg, clinical innovators, clinicians, patients, methodologists, statisticians, journal editors and governance representatives) will complete a Delphi survey to score the importance of each data item, generating a shortened list. (3) Consensus meeting(s) with stakeholders to discuss and agree on the final core data set.Ethics and disseminationThe study is approved by an Institutional Ethics Committee at the University of Bristol (ref: 111362). Participants will complete written informed consent to participate. Dissemination strategies include scientific meeting presentations, peer-reviewed journal publications, patient engagement events, use of social media platforms, workshops and other events.
General practitioners retiring or relocating and its association with healthcare use and mortality: a cohort study using Norwegian national data
Authors: Vinjerui Kristin Hestmann , Asheim Andreas , Sarheim Anthun Kjartan , Carlsen Fredrik , Mjølstad Bente Prytz , Nilsen Sara Marie , Pape Kristine , Bjørngaard Johan Håkon 
Published: July 2024

BackgroundContinuity in the general practitioner (GP)-patient relationship is associated with better healthcare outcomes. However, few studies have examined the impact of permanent discontinuities on all listed patients when a GP retires or relocates.AimTo investigate changes in the Norwegian population’s overall healthcare use and mortality after discontinuity due to Regular GPs retiring or relocating.MethodsLinking national registers, we compared days with healthcare use and mortality for matched individuals affiliated with Regular GPs who retired or relocated versus continued. We included list patients 3 years prior to exposure and followed them up to 5 years after. We assessed changes over time employing a difference-in-differences design with Poisson regression.ResultsFrom 2011 to 2020, we identified 819 Regular GPs retiring and 228 moving, affiliated with 1 165 295 people. Relative to 3 years before discontinuity, the rate ratio (RR) of daytime GP contacts, increased 3% (95% CI 2 to 4) in year 1 after discontinuity, corresponding to 148 (95% CI 54 to 243) additional contacts per 1000 patients. This increase persisted for 5 years. Out-of-hours GP contacts increased the first year, RR 1.04 (95% CI 0.99 to 1.09), corresponding to 16 (95% CI −5 to 37) contacts per 1000 patients. Planned hospital contacts increased 3% (95% CI 2 to 4) in year 1, persisting into year 5. Acute hospital contacts increased 5% (95% CI 3 to 7), primarily in the first year. These 1-year effects corresponded to 51 (95% CI 18 to 83) planned and 13 (95% CI 7 to 18) acute hospital contacts per 1000 patients. Mortality was unchanged up to 5 years after discontinuity.ConclusionRegular GPs retirement and relocation were associated with small to moderate increases in healthcare use among listed patients, while mortality was unaffected.
Firearm ownership for protection in the USA, 2023: results from a nationally representative survey
Authors: Degli Esposti Michelle , Sokol Rebeccah L , Lee Daniel B , Wiebe Douglas J , Cunningham Rebecca M , Hawryszkiewycz Alice , Carter Patrick M 
Published: July 2024

ObjectiveThis study aims to characterise the motivations of firearm owners and examine whether firearm ownership motivations and carriage varied by state stand your ground law status. MethodsUsing a nationally representative survey of US adults in 2023, we asked firearm owners (n=2477) about their firearm motivations and behaviours, including reason(s) for ownership.ResultsOf all firearm owners, 78.8% (95% CI 76.0% to 81.0%) owned a firearm for protection, and 58.1% (95% CI 54.3% to 62.0%) carried a firearm outside their home in the last 12 months. Firearm ownership for protection was not significantly associated with stand your ground laws, but firearm carriage was more prevalent in states with stand your ground laws (50.1% (95% CI 47.0% to 53.0%) vs 34.9% (95% CI 25.0% to 46.0%)). Gender (women) and race (minority groups) emerged as key correlates for firearm ownership for protection (vs other ownership motivations). For example, black and Asian women (98.8%) almost exclusively owned firearms for protection.ConclusionsProtection was the dominant reason for firearm ownership in 2023, motivating 65 million Americans to own firearms and appealing to different strata of the population.
Phase I study of the safety and clinical activity of the interleukin-8 inhibitor AMY109 combined with atezolizumab in patients with advanced solid cancers
Authors: Yamamoto Noboru , Kitano Shigehisa , Koyama Takafumi , Ikeda Masafumi , Mizugaki Hidenori , Narikiyo Takatsugu , Yamaguchi Yuki , Ishida Takaaki , Takubo Ryoko , Ogami Chika , Sekiya Mayuko , Nakagawa Yuki , Kuboki Yasutoshi 
Published: July 2024

BackgroundImmunosuppressive conditions within the tumor microenvironment (TME) can allow tumors to evade the immune system, including by hampering programmed death ligand 1 (PD-L1) inhibitor activity. Interleukin (IL)-8 contributes to immunosuppression and fibrosis in the TME. AMY109, a humanized anti-IL-8 monoclonal antibody, reduced fibrosis and decreased immunosuppressive cells in tumor tissue in animals. Combining AMY109 with atezolizumab (anti-PD-L1 antibody) may enhance its antitumor effects by making the TME more favorable to PD-L1 inhibition.MethodsThis multicenter, open-label, dose-escalation study evaluated the safety, pharmacokinetics, and clinical activity of AMY109 plus atezolizumab in patients with previously treated advanced solid tumors and Eastern Cooperative Oncology Group performance status 0 or 1. Patients received AMY109 (2–45 mg/kg) plus atezolizumab (1200 mg) intravenously every 3 weeks in part 1, and AMY109 (15–45 mg/kg) plus atezolizumab (1200 mg) in part 2. Primary endpoints were the dose-limiting toxicity (DLT), safety, and pharmacokinetics of AMY109 and atezolizumab in Part 1, and safety and antitumor activity per investigator-assessed Response Evaluation Criteria in Solid Tumors 1.1 in part 2. Exploratory analyses of peripheral and tumor biomarker were conducted.ResultsOverall, 38 patients (18 in part 1 and 20 in part 2) were enrolled. Part 1 showed no DLTs and a dose-proportional increase in AMY109 exposure over 2–45 mg/kg, with no apparent change in mean atezolizumab serum concentrations across AMY109 dosing. Plasma IL-8 concentration accumulation was seen in all dose cohorts after AMY109 initiation. Grade 1–3 treatment-related adverse events (AEs) occurred in 21 of 38 patients (55%). Treatment-related serious AEs occurred in two patients (5%). No AEs led to treatment withdrawal. Partial responses (PRs) occurred in 2 of 38 patients; the confirmed objective response rate was 5%. These patients had uterocervical and pancreatic cancer, respectively, and had been treated for >500 days at the cut-off date: one had received 45 mg/kg of AMY109 throughout, and the other received 30 mg/kg of AMY109 until cycle 5, then 45 mg/kg thereafter.ConclusionsWith no DLTs, AMY109 plus atezolizumab was well tolerated in patients with advanced solid tumors, with no new safety signals. AMY109 showed a dose-proportional increase in exposure. The PRs in two patients were durable.