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Cranial sutures separate neighboring skull bones and are sites of bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Using single-cell transcriptomics, lineage tracing, and mutant analysis in zebrafish, we uncover key developmental transitions regulating bone formation at sutures during skull expansion. In particular, we identify a subpopulation of mesenchyme cells in the mid-suture region that upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. Moreover, combinatorial mutation of BMP antagonists enriched in this mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data reveal establishment of a non-osteogenic mesenchyme population in the mid-suture region that restricts bone formation through local BMP antagonism, thus ensuring proper suture morphology.

Developing and adopting strategies that preserve soil health from degradation due to drastic changes in climate is critical for securing sustainable viticulture. For example, healthy soils promote water infiltration, nutrient cycling, and retention functions that support grape production. However, little research has evaluated drivers of growers' decision-making processes and actions towards soil management practices that impact soil health in vineyards. The objective of this study was to assess wine grape growers' perceptions and attitudes of soil health to identify grower's most important soil health functions and definition, and to understand how these might influence behavior related to soil management practices. Therefore, we conducted semi-structured interviews with 16 wine grape growers understand current barriers, motivations, and opportunities for adopting and/or maintaining practices for building soil health in vineyards. Most growers described healthy vineyard soils as balanced, biodiverse, self-sustaining, and resilient systems that provide nutrient, and water cycling functions and support high-quality wine grape production. Three categories of growers emerged based on soil health attitudes including Early Adopter (n = 3), Early Majority (n = 4) and Late Majority (n = 9) groups. The main barriers for adoption and maintenance of soil health practices were high costs, potential economic risks, and lack of information on how these practices influence grape production especially for the Late Majority group. Most growers were willing to adopt more soil heath practices if additional specific, practical information could be provided on outcomes of soil health practices for wine grape production systems—especially economic benefits. The outcomes of this study guide future soil health research and outreach activities to better support growers in building and protecting vineyard soil health while achieving viticultural goals.

Campylobacter jejuni and C. coli are causes of foodborne enteric infection worldwide (1). Campylobacter spp. are among the most frequent pathogens identified in diarrheal samples from persons in Africa, particularly [...]

Bacterial zoonoses cause severe febrile illness in East Africa (2). Patients with bacterial zoonotic diseases can have nonspecific febrile illnesses that are difficult to diagnose clinically or in the laboratory [...]

This is a large-scale, multi-author collaborative autoethnographic study exploring the concept of building a tangible teaching commons on the example of the Scholarship of Teaching and Learning (SoTL) Commons Conference. The project organizers sought to provide a big tent and extended an invitation to attendees to respond to a series of writing prompts about their conference experience. Collaborative writing took place asynchronously over an approximately 60-day period following the close of the conference and generated ˜ 20,000 words. This corpus became the basis for a three-stage emergent coding process, conducted by the four-member steering committee, which led to the identification of three primary themes from the collective experiences of the 2023 SoTL Commons Conference attendees: SoTL as pedagogy, SoTL as a community of scholars, and SoTL as scholarship. Despite some limitations to what the sense of commons represents, the project highlighted the respondents' spirit of appreciative inquiry, a signature mindset of SoTL and engaged participants who were new to the field. We argue that it acted as a form of academic hospitality itself; enabling the sharing of practice, deepening of reflection, strengthening of research skills, fostering of social connections, and, by extension, the advancement of the field as a community of scholars.

Abstract Four distinct species of human coronaviruses (HCoVs) circulate in humans. Despite the recent attention due to SARS-CoV-2, a comprehensive understanding of the molecular epidemiology and genomic evolution of HCoVs remains unclear. Here, we employed primary differentiated human nasal epithelial cells for the successful isolation and genome sequencing of HCoVs derived from two retrospective cohorts in Singapore and Tanzania. Phylodynamic inference shows that HCoV-229E and HCoV-OC43 were subject to stronger genetic drift and reduced purifying selection from the early 2000s onwards, primarily targeting spike Domain A and B. This resulted in increased lineage diversification, coinciding with a higher effective reproductive number (Re>1.0). However, HCoV-NL63 and HCoV-HKU1 experienced weaker genetic drift and selective pressure with prolonged regional persistence. Our findings suggest that HCoV-229E and HCoV-OC43 viruses are adept at generating new variants and achieving widespread intercontinental dissemination driven by continuous genetic drift, recombination, and complex migration patterns.

Campylobacteriosis and antimicrobial resistance (AMR) are global public health concerns. Africa is estimated to have the world’s highest incidence of campylobacteriosis and a relatively high prevalence of AMR in Campylobacter spp. from humans and animals. Few studies have compared Campylobacter spp. isolated from humans and poultry in Africa using whole-genome sequencing and antimicrobial susceptibility testing. We explored the population structure and AMR of 178 Campylobacter isolates from East Africa, 81 from patients with diarrhea in Kenya and 97 from 56 poultry samples in Tanzania, collected during 2006–2017. Sequence type diversity was high in both poultry and human isolates, with some sequence types in common. The estimated prevalence of multidrug resistance, defined as resistance to >3 antimicrobial classes, was higher in poultry isolates (40.9%, 95% credible interval 23.6%–59.4%) than in human isolates (2.5%, 95% credible interval 0.3%–6.8%), underlining the importance of antimicrobial stewardship in livestock systems.

This study investigates the impact of in-person professional development (PD) with ongoing emailed practice-based feedback (EPF) on teacher correct implementation of a multicomponent shared reading intervention for students with extensive support needs (ESN) embedded within general education (GE) instruction within three multiple baseline across skills designs. Skills within the shared reading intervention included (a) student engagement, reinforcement, and redirection, (b) planned questioning with wait time and error correction, and (c) in the moment data collection. A functional relation between PD with EPF package and teacher correct implementation of the multicomponent shared reading intervention was established for all three teachers. Teachers reported the experience was positive and felt comfortable delivering the small group shared reading intervention. No negative impact on student comprehension occurred. Findings show general and special educators can embed individualized shared reading using modified grade-level books and collect data on literacy skills for students with ESN in GE instruction with fidelity. This successfully implemented specialized instruction and data collection on the individualized educational goals of students with ESN provides more evidence that GE settings are an effective location for individualized service delivery and progress monitoring. Further implications for research and practice are shared.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal sentinel surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortiums aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

Abstract Cranial sutures separate neighboring skull bones and are sites of bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Using single-cell transcriptomics, lineage tracing, and mutant analysis in zebrafish, we uncover key developmental transitions regulating bone formation at sutures during skull expansion. In particular, we identify a subpopulation of mesenchyme cells in the mid-suture region that upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. Moreover, combinatorial mutation of BMP antagonists enriched in this mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data reveal establishment of a non-osteogenic mesenchyme population in the mid-suture region that restricts bone formation through local BMP antagonism, thus ensuring proper suture morphology.

Abstract Background Sleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans. Methods Using modelling, we explore how cryptic (undetected) transmission impacts the monitoring of progress towards and the achievement of the EoT goal. We have developed gHAT models that include either asymptomatic or animal transmission, and compare these to a baseline gHAT model without either of these transmission routes, to explore the potential role of cryptic infections on the EoT goal. Each model was independently calibrated to five different health zones in the Democratic Republic of the Congo (DRC) using available historical human case data for 2000–2020 (obtained from the World Health Organization’s HAT Atlas). We applied a novel Bayesian sequential updating approach for the asymptomatic model to enable us to combine statistical information about this type of transmission from each health zone. Results Our results suggest that, when matched to past case data, we estimated similar numbers of new human infections between model variants, although human infections were slightly higher in the models with cryptic infections. We simulated the continuation of screen-confirm-and-treat interventions, and found that forward projections from the animal and asymptomatic transmission models produced lower probabilities of EoT than the baseline model; however, cryptic infections did not prevent EoT from being achieved eventually under this approach. Conclusions This study is the first to simulate an (as-yet-to-be available) screen-and-treat strategy and found that removing a parasitological confirmation step was predicted to have a more noticeable benefit to transmission reduction under the asymptomatic model compared with the others. Our simulations suggest vector control could greatly impact all transmission routes in all models, although this resource-intensive intervention should be carefully prioritised. Graphical Abstract

Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007–April 2009. Among 788 participants, median age was 20 (interquartile range 2–38) years. We performed PCR amplification of V1–V2 variable region 16S rRNA on cell pellet DNA, then metagenomic deep-sequencing and pathogenic taxonomic identification. We detected bacterial zoonotic pathogens in 10 (1.3%) samples: 3 with Rickettsia typhi, 1 R. conorii, 2 Bartonella quintana, 2 pathogenic Leptospira spp., and 1 Coxiella burnetii. One other sample had reads matching a Neoerhlichia spp. previously identified in a patient from South Africa. Our findings indicate that targeted 16S metagenomics can identify bacterial zoonotic pathogens causing severe febrile illness in humans, including potential novel agents.

Abstract Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition leading to progressive muscle weakness, atrophy, and ultimately death. Traditional ALS clinical evaluations often depend on subjective metrics, making accurate disease detection and monitoring disease trajectory challenging. To address these limitations, we developed the nQiALS toolkit, a machine learning-powered system that leverages smartphone typing dynamics to detect and track motor impairment in people with ALS. The study included 63 ALS patients and 30 age- and sex-matched healthy controls. We introduce the three core components of this toolkit: the nQiALS-Detection, which differentiated ALS from healthy typing patterns with an AUC of 0.89; the nQiALS-Progression, which separated slow and fast progression at specific thresholds with AUCs ranging between 0.65 and 0.8; and the nQiALS-Fine Motor, which identified subtle progression in fine motor dysfunction, suggesting earlier prediction than the state-of-the-art assessment. Together, these tools represent an innovative approach to ALS assessment, offering a complementary, objective metric to traditional clinical methods and which may reshape our understanding and monitoring of ALS progression.

Predicting elemental cycles and maintaining water quality under increasing anthropogenic influence requires understanding the spatial drivers of river microbiomes. However, the unifying microbial processes governing river biogeochemistry are hindered by a lack of genome-resolved functional insights and sampling across multiple rivers. Here we employed a community science effort to accelerate the sampling, sequencing, and genome-resolved analyses of river microbiomes to create the Genome Resolved Open Watersheds database (GROWdb). This resource profiled the identity, distribution, function, and expression of thousands of microbial genomes across rivers covering 90% of United States watersheds. Specifically, GROWdb encompasses 1,469 microbial species from 27 phyla, including novel lineages from 10 families and 128 genera, and defines the core river microbiome for the first time at genome level. GROWdb analyses coupled to extensive geospatial information revealed local and regional drivers of microbial community structuring, while also presenting a myriad of foundational hypotheses about ecosystem function. Building upon the previously conceived River Continuum Concept 1 , we layer on microbial functional trait expression, which suggests the structure and function of river microbiomes is predictable. We make GROWdb available through various collaborative cyberinfrastructures 2, 3 so that it can be widely accessed across disciplines for watershed predictive modeling and microbiome-based management practices.

Summary: Background: Clinical severity scores can identify patients at risk of severe disease and death, and improve patient management. The modified early warning score (MEWS), the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), and the Universal Vital Assessment (UVA) were developed as risk-stratification tools, but they have not been fully validated in low-resource settings where fever and infectious diseases are frequent reasons for health care seeking. We assessed the performance of MEWS, qSOFA, and UVA in predicting mortality among febrile patients in the Lao PDR, Malawi, Mozambique, and Zimbabwe. Methods: We prospectively enrolled in- and outpatients aged ≥ 15 years who presented with fever (≥37.5 °C) from June 2018–March 2021. We collected clinical data to calculate each severity score. The primary outcome was mortality 28 days after enrolment. The predictive performance of each score was determined using area under the receiver operating curve (AUC). Findings: A total of 2797 participants were included in this analysis. The median (IQR) age was 32 (24–43) years, 38% were inpatients, and 60% (1684/2797) were female. By the time of follow-up, 7% (185/2797) had died. The AUC (95% CI) for MEWS, qSOFA and UVA were 0.67 (0.63–0.71), 0.68 (0.64–0.72), and 0.82 (0.79–0.85), respectively. The AUC comparison found UVA outperformed both MEWS (p

ABSTRACT Gender Differences in Planned Retirement Age Among Medical Students: Are Changes On the Horizon? Purpose Planned age of retirement has an important effect on the physician workforce. Earlier studies of practicing physicians have reported that the planned as well as actual retirement age was significantly younger for women. Also, previous reports had shown that rural physicians tended to retire earlier. This paper offers a view earlier in the physician pipeline and reports surveys of medical students and pre-medical college students concerning their retirement plans. Methods During 2015-2019, 70 college students and 41 medical students at a regional rural medical campus completed a career eulogy that included their planned retirement age. Results Combining both groups of students, women planned to retire at a mean age of 61.9 and men at 59.1, P=0.048. A longitudinal comparison of just medical students showed that prematriculation students just before starting medical school had the oldest planned age of 66.9, compared to college students (57.4 to 58.9) and medical students (64.0 to 64.6), P=0.049. There was no difference in planned retirement age in rural vs urban upbringing. Conclusions In this group of pathways students, women planned to retire almost 3 years later than men, which differs from earlier reports of physicians in practice. The men planned retirement almost 5 years earlier than in previous reports of planned retirement age. There was no difference in rural vs urban upbringing. Whether this is a generalizable finding will require similar studies in different student populations on other campuses, and our survey instrument is available for others to look deeper into the process of professional identity formation that may explain any differences in planned retirement age.

IntroductionThere are multiple ongoing outbreaks of carbapenem resistant Acinetobacter baumannii (CRAb) infection in Fiji’s hospitals. CRAb is able to colonize and persist on various hospital surfaces for extended periods. We conducted a study to understand the extent of hospital environmental contamination and phylogenetic links with clinical isolates.MethodsSwabs were collected from high-touch surfaces at Colonial War Memorial Hospital (CWMH) September 2021 and December 2022; Lautoka Hospital (LTKH) August 2022; and Labasa Hospital (LBSH) November 2022. All bacterial isolates were identified, and antimicrobial susceptibility testing (AST) performed; isolates resistant to carbapenems and producing a carbapenemase underwent whole genome sequencing. Comparison was made to clinical isolates obtained from CWMH in 2016–2017 and 2019–2021 and from LTKH and LBSH from 2020–2021.ResultsFrom the 180 environmental samples collected, ten (5.6%) CRAb were isolated; no other carbapenem-resistant gram-negative organisms were isolated. Seven (70%) of the CRAb were isolated from CWMH and three (30%) from LTKH; no CRAb were isolated from LBSH. Of the seven CWMH CRAb, two were sequence type 2 (ST2), three ST25, and two ST499. All LTKH isolates were ST499. The two environmental CRAb ST2 isolates were closely genetically linked to isolates obtained from patients in CWMH, LTKH, and LBSH 2020–2021. Similarly, the three environmental CRAb ST25 isolates were closely genetically linked to isolates obtained from patients admitted to CWMH in 2019–2021 and LBSH in 2020. The environmental CRAb ST499 isolates represented two distinct clones, with clone 1 comprising two genetically identical isolates from CWMH and clone 2 the three isolates from LTKH. Although no genetic linkages were observed when comparing environmental ST499 isolates to those from CWMH patients in 2020–2021, both clone 1 isolates were genetically identical to an isolate obtained from a patient admitted during the sampling period.ConclusionOur study highlights the contamination of high-touch surfaces within Fiji hospitals with CRAb, suggesting that these may serve as important sources for CRAb. Phylogenetic linkages to CRAb isolated from patients since 2019 underscores the persistence of this resistant pathogen in hospital settings and the ongoing risk for hospital-acquired infections.