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Event management systems (EMS) are key tools for epidemic intelligence, integrating surveillance signals and incident response, although international standards to inform development are lacking. We describe the Nigeria Centre for Disease Control and Prevention (NCDC) SITAware, a software capable of operating with low internet bandwidth to generate notifications, reports, and spatiotemporal dashboards and provide event-level data for real-time accountability and postevent learning. SITAware was enabled by local institutional ownership, co-created at low cost, and integrated into existing workflows. In 2022, SITAware was used to manage ≈300 incidents, and NCDC implemented it subnationally. NCDC’s experience may inform EMS development and implementation in similar settings.

Mitochondrial membranes are defined by their diverse functions, complex geometries, and unique lipidomes. In the inner mitochondrial membrane, highly curved membrane folds known as cristae house the electron transport chain and are the primary sites of cellular energy production. The outer mitochondrial membrane is flat by contrast, but is critical for the initiation and mediation of processes key to mitochondrial physiology: mitophagy, interorganelle contacts, fission and fusion dynamics, and metabolite transport. While the lipid composition of both the inner mitochondrial membrane and outer mitochondrial membrane have been characterized across a variety of cell types, a mechanistic understanding for how individual lipid classes contribute to mitochondrial structure and function remains nebulous. In this review, we address the biophysical properties of mitochondrial lipids and their related functional roles. We highlight the intrinsic curvature of the bulk mitochondrial phospholipid pool, with an emphasis on the nuances surrounding the mitochondrially-synthesized cardiolipin. We also outline emerging questions about other lipid classes — ether lipids, and sterols — with potential roles in mitochondrial physiology. We propose that further investigation is warranted to elucidate the specific properties of these lipids and their influence on mitochondrial architecture and function.

Abstract Health care workers (HCWs) experienced greater risk of SARS-CoV-2 infection during the COVID-19 pandemic. This study applies a cost-of-illness (COI) approach to model the economic burden associated with SARS-CoV-2 infections among HCWs in five low- and middle-income sites (Kenya, Eswatini, Colombia, KwaZulu-Natal province, and Western Cape province of South Africa) during the first year of the pandemic. We find that not only did HCWs have a higher incidence of COVID-19 than the general population, but in all sites except Colombia, viral transmission from infected HCWs to close contacts resulted in substantial secondary SARS-CoV-2 infection and death. Disruption in health services as a result of HCW illness affected maternal and child deaths dramatically. Total economic losses attributable to SARS-CoV-2 infection among HCWs as a share of total health expenditure ranged from 1.51% in Colombia to 8.38% in Western Cape province, South Africa. This economic burden to society highlights the importance of adequate infection prevention and control measures to minimize the risk of SARS-CoV-2 infection in HCWs.

Abstract Background Health workers (HWs) in Africa face challenges accessing and learning from existing online training opportunities. To address these challenges, we developed a modular, self-paced, mobile-ready and work-relevant online course covering foundational infection prevention and control (IPC) concepts. Here, we evaluate the first pilot of this course, conducted with HWs in Nigeria. Methods We used a learner-centered design and prototyping process to create a new approach to delivering online training for HWs. The resulting course comprised 10 self-paced modules optimized for use on mobile devices. Modules presented IPC vignettes in which learning was driven by short assessment questions with feedback. Learners were recruited by distributing a link to the training through Nigeria-based email lists, WhatsApp groups and similar networks of HWs, managers and allied professionals. The course was open to learners for 8 weeks. We tracked question responses and time on task with platform analytics and assessed learning gains with pre- and post-testing. Significance was evaluated with the Wilcoxon signed-rank test, and effect size was calculated using Cohen’s d. Results Three hundred seventy-two learners, with roles across the health system, enrolled in the training; 59% completed all 10 modules and earned a certificate. Baseline knowledge of foundational IPC concepts was low, as measured by pre-test scores (29%). Post-test scores were significantly higher at 54% (effect size 1.22, 95% confidence interval 1.00-1.44). Learning gains were significant both among learners with low pre-test scores and among those who scored higher on the pre-test. We used the Net Promoter Score (NPS), a common user experience metric, to evaluate the training. The NPS was + 62, which is slightly higher than published scores of other self-paced online learning experiences. Conclusions High completion rates, significant learning gains and positive feedback indicate that self-paced, mobile-ready training that emphasizes short, low-stakes assessment questions can be an effective, scalable way to train HWs who choose to enroll. Low pre-test scores suggest that there are gaps in IPC knowledge among this learner population.

Abstract Background The Sequence Alignment/Map Format Specification (SAM) is one of the most widely adopted file formats in bioinformatics and many researchers use it daily. Several tools, including most high-throughput sequencing read aligners, use it as their primary output and many more tools have been developed to process it. However, despite its flexibility, SAM encoded files can often be difficult to query and understand even for experienced bioinformaticians. As genomic data are rapidly growing, structured, and efficient queries on data that are encoded in SAM/BAM files are becoming increasingly important. Existing tools are very limited in their query capabilities or are not efficient. Critically, new tools that address these shortcomings, should not be able to support existing large datasets but should also do so without requiring massive data transformations and file infrastructure reorganizations. Results Here we introduce SamQL, an SQL-like query language for the SAM format with intuitive syntax that supports complex and efficient queries on top of SAM/BAM files and that can replace commonly used Bash one-liners employed by many bioinformaticians. SamQL has high expressive power with no upper limit on query size and when parallelized, outperforms other substantially less expressive software. Conclusions SamQL is a complete query language that we envision as a step to a structured database engine for genomics. SamQL is written in Go, and is freely available as standalone program and as an open-source library under an MIT license, https://github.com/maragkakislab/samql/ .

Biomembranes adopt varying morphologies that are vital to cellular functions. Many studies use computational modeling to understand how various mechanochemical factors contribute to membrane shape transformations. Compared with approximation-based methods (e.g., finite element method [FEM]), the class of discrete mesh models offers greater flexibility to simulate complex physics and shapes in three dimensions; its formulation produces an efficient algorithm while maintaining coordinate-free geometric descriptions. However, ambiguities in geometric definitions in the discrete context have led to a lack of consensus on which discrete mesh model is theoretically and numerically optimal; a bijective relationship between the terms contributing to both the energy and forces from the discrete and smooth geometric theories remains to be established. We address this and present an extensible framework, Mem3DG, for modeling 3D mechanochemical dynamics of membranes based on discrete differential geometry (DDG) on triangulated meshes. The formalism of DDG resolves the inconsistency and provides a unifying perspective on how to relate the smooth and discrete energy and forces. To demonstrate, Mem3DG is used to model a sequence of examples with increasing mechanochemical complexity: recovering classical shape transformations such as 1) biconcave disk, dumbbell, and unduloid; and 2) spherical bud on spherical, flat-patch membrane; investigating how the coupling of membrane mechanics with protein mobility jointly affects phase and shape transformation. As high-resolution 3D imaging of membrane ultrastructure becomes more readily available, we envision Mem3DG to be applied as an end-to-end tool to simulate realistic cell geometry under user-specified mechanochemical conditions.

Background: Marathon participation is becoming increasingly popular among individuals ≥40 years of age. Little is known about the prevalence of subclinical coronary artery disease (CAD) and corresponding ischemia in this patient population. The study objectives are: (1) to characterize the prevalence of silent CAD in marathoners ≥ 40 years old using cardiac computed tomography angiography (CCT); and (2) if subclinical CAD was detected, to determine the functional significance of occult lesions by stress echocardiography (SE). Methods: Marathoners aged ≥ 40 years who completed a full marathon between 2018 and 2019 were recruited to undergo a prospective CCT. Coronary artery stenosis was graded as zero, mild (1%-49%), moderate (50%-69%), or severe (> 70%). All study participants diagnosed with mild-to-severe atherosclerotic CAD on CCT further underwent functional imaging with exercise treadmill SE. Results: A total of 65 individuals (53 ± 7 years, 65% males, 24 ± 3 kg/m2) underwent a prospective CCT within 12 months of marathon completion. Of the total study population, 13 participants (20%) were diagnosed with CAD, of whom 10 (77%) had mild disease, 1 (8%) had moderate disease, and 2 (15%) had severe disease by CCT. Despite the identification of subclinical CAD on CCT, none of the 13 patients had any evidence of inducible ischemia on SE. Conclusions: This is the first study to incorporate both CCT and SE in the evaluation of subclinical CAD in marathoners ≥40 years old. Although the overall prevalence of anatomic CAD was 20%, there was no evidence of functional ischemia in this highly competitive cohort. Résumé: Contexte: Les marathons ont gagné en popularité auprès des individus âgés de 40 ans ou plus. On en sait toutefois peu sur la prévalence de la coronaropathie subclinique et de l’ischémie qui lui est associée dans cette population de patients. L’étude visait à 1) caractériser la prévalence de la coronaropathie silencieuse chez les marathoniens âgés de 40 ans ou plus à l’aide d’une angiographie cardiaque par tomodensitométrie (ACTDM) si une coronaropathie subclinique était détectée, à déterminer l’importance fonctionnelle des lésions occultes par une échocardiographie d’effort (EE). Méthodologie: Des marathoniens âgés de 40 ans ou plus ayant réalisé un marathon entre 2018 et 2019 ont été recrutés et soumis à une ACTDM prospective. Les sténoses des artères coronaires étaient classées selon une échelle allant de zéro, légère (1 à 49 %), modérée (50 à 69 %) à sévère (> 70 %). Tous les participants à l’étude ayant reçu un diagnostic de coronaropathie athéroscléreuse légère à sévère à la suite de l’ACTDM ont été soumis à une imagerie fonctionnelle avec EE sur tapis roulant. Résultats: Au total, 65 sujets (53 ± 7 ans, 65 % d’hommes, 24 ± 3 kg/m2) ont été soumis à une ACTDM prospective dans un délai de 12 mois à la suite de leur dernier marathon. Dans l’ensemble de la population à l’étude, 13 participants (20 %) ont reçu un diagnostic de coronaropathie; 10 (77 %) présentaient une maladie bénigne, 1 (8 %) présentait une maladie modérée et 2 (15 %) présentaient une maladie sévère selon l’ACTDM. Même si une coronaropathie subclinique a été diagnostiquée lors de l’ACTDM, aucun des 13 patients ne présentait de signe d’ischémie inductible à l’EE. Conclusions: Il s’agit de la première étude à utiliser l’ACTDM et l’EE pour évaluer la présence d’une coronaropathie chez des marathoniens âgés de 40 ou plus. Même si la prévalence globale de la coronaropathie anatomique était de 20 %, il n’y avait aucun signe d’ischémie fonctionnelle au sein de cette cohorte hautement compétitive.

It appears inevitable that severe acute respiratory syndrome coronavirus 2 will continue to spread. Although we still have limited information on the epidemiology of this virus, there have been multiple reports of superspreading events (SSEs), which are associated with both explosive growth early in an outbreak and sustained transmission in later stages. Although SSEs appear to be difficult to predict and therefore difficult to prevent, core public health actions can prevent and reduce the number and impact of SSEs. To prevent and control of SSEs, speed is essential. Prevention and mitigation of SSEs depends, first and foremost, on quickly recognizing and understanding these events, particularly within healthcare settings. Better understanding transmission dynamics associated with SSEs, identifying and mitigating high-risk settings, strict adherence to healthcare infection prevention and control measures, and timely implementation of nonpharmaceutical interventions can help prevent and control severe acute respiratory syndrome coronavirus 2, as well as future infectious disease outbreaks.

Similarities between stem cells and cancer cells have implicated mammary stem cells in breast carcinogenesis. Recent evidence suggests that normal breast stem cells exist in multiple phenotypic states: epithelial, mesenchymal, and hybrid epithelial/mesenchymal (E/M). Hybrid E/M cells in particular have been implicated in breast cancer metastasis and poor prognosis. Mounting evidence also suggests that stem cell phenotypes change throughout the life course, for example, through embryonic development and pregnancy. The goal of this study was to use single cell RNA-sequencing to quantify cell state distributions of the normal mammary (NM) gland throughout developmental stages and when perturbed into a stem-like state in vitro using conditional reprogramming (CR). Using machine learning based dataset alignment, we integrate multiple mammary gland single cell RNA-seq datasets from human and mouse, along with bulk RNA-seq data from breast tumors in the Cancer Genome Atlas (TCGA), to interrogate hybrid stem cell states in the normal mammary gland and cancer. CR of human mammary cells induces an expanded stem cell state, characterized by increased expression of embryonic stem cell associated genes. Alignment to a mouse single-cell transcriptome atlas spanning mammary gland development from in utero to adulthood revealed that NM cells align to adult mouse cells and CR cells align across the pseudotime trajectory with a stem-like population aligning to the embryonic mouse cells. Three hybrid populations emerge after CR that are rare in NM: KRT18+/KRT14+ (hybrid luminal/basal), EPCAM+/VIM+ (hybrid E/M), and a quadruple positive population, expressing all four markers. Pseudotime analysis and alignment to the mouse developmental trajectory revealed that E/M hybrids are the most developmentally immature. Analyses of single cell mouse mammary RNA-seq throughout pregnancy show that during gestation, there is an enrichment of hybrid E/M cells, suggesting that these cells play an important role in mammary morphogenesis during lactation. Finally, pseudotime analysis and alignment of TCGA breast cancer expression data revealed that breast cancer subtypes express distinct developmental signatures, with basal tumors representing the most “developmentally immature” phenotype. These results highlight phenotypic plasticity of normal mammary stem cells and provide insight into the relationship between hybrid cell populations, stemness, and cancer.

In this perspective, we examine three key aspects of an end-to-end pipeline for realistic cellular simulations: reconstruction and segmentation of cellular structures; generation of cellular structures; and mesh generation, simulation, and data analysis. We highlight some of the relevant prior work in these distinct but overlapping areas, with a particular emphasis on current use of machine learning technologies, as well as on future opportunities.

Healthcare workers (HCWs) are at increased risk of infection from SARS-CoV-2 and other disease pathogens, which take a disproportionate toll on HCWs, with substantial cost to health systems. Improved infection prevention and control (IPC) programmes can protect HCWs, especially in resource-limited settings where the health workforce is scarcest, and ensure patient safety and continuity of essential health services. In response to the COVID-19 pandemic, we collaborated with ministries of health and development partners to implement an emergency initiative for HCWs at the primary health facility level in 22 African countries. Between April 2020 and January 2021, the initiative trained 42 058 front-line HCWs from 8444 health facilities, supported longitudinal supervision and monitoring visits guided by a standardised monitoring tool, and provided resources including personal protective equipment (PPE). We documented significant short-term improvements in IPC performance, but gaps remain. Suspected HCW infections peaked at 41.5% among HCWs screened at monitored facilities in July 2020 during the first wave of the pandemic in Africa. Disease-specific emergency responses are not the optimal approach. Comprehensive, sustainable IPC programmes are needed. IPC needs to be incorporated into all HCW training programmes and combined with supportive supervision and mentorship. Strengthened data systems on IPC are needed to guide improvements at the health facility level and to inform policy development at the national level, along with investments in infrastructure and sustainable supplies of PPE. Multimodal strategies to improve IPC are critical to make health facilities safer and to protect HCWs and the communities they serve.

Recent advances in electron microscopy have enabled the imaging of single cells in 3D at nanometer length scale resolutions. An uncharted frontier for in silico biology is the ability to simulate cellular processes using these observed geometries. Enabling such simulations requires watertight meshing of electron micrograph images into 3D volume meshes, which can then form the basis of computer simulations of such processes using numerical techniques such as the finite element method. In this paper, we describe the use of our recently rewritten mesh processing software, GAMer 2, to bridge the gap between poorly conditioned meshes generated from segmented micrographs and boundary marked tetrahedral meshes which are compatible with simulation. We demonstrate the application of a workflow using GAMer 2 to a series of electron micrographs of neuronal dendrite morphology explored at three different length scales and show that the resulting meshes are suitable for finite element simulations. This work is an important step towards making physical simulations of biological processes in realistic geometries routine. Innovations in algorithms to reconstruct and simulate cellular length scale phenomena based on emerging structural data will enable realistic physical models and advance discovery at the interface of geometry and cellular processes. We posit that a new frontier at the intersection of computational technologies and single cell biology is now open.

Difficulty performing activities of daily living ("functional impairment") is common in homeless adults aged 50 and older. However, little is known about the trajectory of these impairments, nor the extent to which these trajectories are similar to those of older adults in the general population. We identified trajectories of functional impairment in homeless adults aged 50 and older, and risk factors for differing trajectories. We conducted a prospective cohort study of 350 homeless adults, aged 50 and older, recruited via population-based sampling in Oakland, California and interviewed at 6-month intervals for up to 3 years. We assessed functional trajectories based on self-reported difficulty performing 5 activities of daily living. We used multivariable multinomial logistic regression to identify baseline risk factors for each trajectory. At baseline, participants' mean age was 58 years (SD, 5.3), 24.1% were women, 80.9% were African American, and 38.6% had difficulty performing 1 or more activities of daily living. We identified 4 distinct functional trajectories: minimal impairment in 136 participants (41.1%); persistent impairment in 81 (25.4%); partial improvement in 74 (23.5%); and decline in 28 (10.0%). Risk factors for persistent impairment included falls in the 6 months before baseline, depressive symptoms, and low physical performance. Although functional impairment improved in some homeless adults, it persisted or worsened in many others. These findings suggest that, similar to older adults in the general population, functional impairment among older homeless persons is not a transient phenomenon, but instead a chronic issue requiring long-term solutions.

The Joint External Evaluation tool is a World Health Organization-recommended method for evaluating countries' capacities under the International Health Regulations (2005) (IHR). It encompasses a national preparedness assessment process for public health threats and offers a structured framework for planning and implementing effective response measures. A tailored approach is necessary for Nigeria's federated system of government, in which most constitutional requirements for public health and associated issues are decentralized to the state level. The Nigeria Centre for Disease Control and Prevention (NCDC) developed an assessment tool to identify state-level health security gaps and support the development of improvement plans. With input from state and national public health leaders and legal experts, a legislative evaluation was conducted to determine specific IHR activities that could be implemented within the state's legal framework to accelerate the implementation of the Integrated Disease Surveillance and Response strategy and IHR. The resulting assessment instrument was piloted in Kano, Enugu, and Kebbi states, followed by a consensus meeting to identify additional areas for improvement. The revised tool contains 14 technical areas and 35 indicators tailored to implementing improvement plans. By recognizing the unique characteristics of subnational entities and their implications for pandemic preparedness, the tool provides an innovative approach to health security for countries with multilayered governance structures or geographic diversity. Conducting a subnational health security assessment is a crucial step in ensuring preparedness for public health threats and enhancing health security in Nigeria's federated system of government.

Uganda established a National Action Plan for Health Security in 2019, following a Joint External Evaluation (JEE) of International Health Regulations (2005) capacities in 2017. The action plan enhanced national health security awareness, but implementation efforts were affected by limited funding, excess of activities, and challenges related to monitoring and evaluation. To improve implementation, Uganda conducted a multisectoral health security self-assessment in 2021 using the second edition of the JEE tool and developed a 1-year operational plan. From 2017 to 2021, Uganda's composite ReadyScore improved by 20%, with improvement in 13 of the 19 technical areas. Indicator scores showing limited capacity declined from 30% to 20%, and indicators with no capacity declined from 10% to 2%. More indicators had developed (47% vs 40%), demonstrated (29% vs 20%), and sustained (2% vs 0%) capacities in 2021 compared with 2017. Using the self-assessment JEE scores, 72 specific activities from the International Health Regulations (2005) benchmarks tool were selected for inclusion in a 1-year operational plan (2021-2022). In contrast to the 264 broad activities in the 5-year national action plan, the operational plan prioritized a small number of activities to enable sectors to focus limited resources on implementation. While certain capacities improved before and during implementation of the action plan, countries may benefit from using short-term operational planning to develop realistic and actionable health security plans to improve health security capacities.

Timely access to emergency funding has been identified as a bottleneck for outbreak response in Nigeria. In February 2019, a new revolving outbreak investigation fund (ROIF) was established by the Nigeria Centre for Disease Control (NCDC). We abstracted the date of NCDC notification, date of verification, and date of response for 25 events that occurred prior to establishing the fund (April 2017 to August 2019) and for 8 events that occurred after establishing the fund (February to October 2019). The median time to notification (1 day) and to verification (0 days) did not change after establishing the ROIF, but the median time to response significantly decreased, from 6 days to 2 days ( P  = .003). Response to disease outbreaks was accelerated by access to emergency funding with a clear approval process. We recommend that the ROIF should be financed by the national government through budget allocation. Finally, development partners can provide financial support for the existing fund and technical assistance for protocol development toward financial accountability and sustainability.

Across the world, the level of pandemic preparedness varies and no country is fully prepared to respond to all public health events. The International Health Regulations 2005 require state parties to develop core capacities to prevent, detect, and respond to public health events of international concern. In addition to annual self-assessment, these capacities are peer reviewed once every 5 years through the voluntary Joint External Evaluation (JEE). In this article, we share Nigeria's experience of conducting a country-led midterm self-assessment using a slightly modified application of the second edition of the World Health Organization (WHO) JEE and the new WHO benchmarks tool. Despite more stringent scoring criteria in the revised JEE tool, average scoring showed modest capacity improvements in 2019 compared with 2017. Of the 19 technical areas assessed, 11 improved, 5 did not change, and 3 had lower scores. No technical area attained the highest-level scoring of 5. Understanding the level of, and gaps in, pandemic preparedness enables state parties to develop plans to improve health security; the outcome of the assessment included the development of a 12-month operational plan. Countries need to intentionally invest in preparedness by using existing frameworks (eg, JEE) to better understand the status of their preparedness. This will ensure ownership of developed plans with shared responsibilities by all key stakeholders across all levels of government.

The 2014-2016 West African Ebola epidemic was devastating in many respects, not least of which was the impact on healthcare systems and their health workforce. Healthcare workers-including physicians, clinical officers, nurses, midwives, and community health workers-serve on the front lines of efforts to detect, control, and stop the spread of disease. Risk mitigation strategies, including infection prevention and control (IPC) practices, are meant to keep healthcare workers safe from occupational exposure to disease and to protect patients from healthcare-associated infections. Despite ongoing IPC efforts, steady rates of both healthcare-associated and healthcare worker infections signal that these mitigation measures have been inadequate at all levels and present a potential critical point of failure in efforts to limit and control the spread of outbreaks. The fact that healthcare workers continue to be infected or are a source of infection during public health emergencies reveals a weakness in global preparedness efforts. Identification of key points of failure-both within the health system and during emergencies-is the first step to mitigating risk of exposure. A 2-pronged solution is proposed to address long-term gaps in the health system that impact infection control and emergency response: prioritization of IPC for epidemic preparedness at a global level and development and use of rapid risk assessments to prioritize risk mitigation strategies for IPC. Without global support, evidence, and systems in place to support the lives of healthcare workers, the lives of their patients and the health system in general are also at risk.

Multiple costing tools have been developed to understand the resources required to build and sustain implementation of the International Health Regulations (IHR), including a detailed costing tool developed by WHO ("WHO Costing Tool") and 2 action-based costing tools, Georgetown University's IHR Costing Tool and CDC's Priority Actions Costing Tool (PACT). The relative performance of these tools is unknown. Nigeria costed its National Action Plan for Health Security (NAPHS) using the WHO Costing Tool. We conducted a desktop review, using the other tools to compare the cost estimates generated using different costing approaches. Technical working groups developed activity plans and estimated component costs using the WHO Costing Tool during a weeklong workshop with approximately 60 participants from various ministries, departments, and federal agencies. We retrospectively applied the IHR Costing Tool and PACT to generate rapid cost estimates required to achieve a Joint External Evaluation (JEE) score of "demonstrated capacity" (level 4). The tools generated similar activities for implementation. Cost estimates varied based on the anticipated procurement and human resources requirements and by the level of implementation (eg, health facility-level versus local government area-level procurement). The desktop IHR Costing Tool and PACT tools required approximately 2 and 8 person-hours to complete, respectively. A strategic costing approach, wherein governments select from a menu of recommended and costed actions following the JEE to develop a NAPHS, could accelerate implementation of plans. Major cost drivers, including procurement and human resources, should be prioritized based on anticipated resource availability and countries' priorities.