bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits and Challenges of Transitioning Occupational Health to an Enterprise Electronic Health Record
Authors: Isakari Marcia , Sanchez Arthur , Conic Rosalynn , Peretti Jacqueline , Saito Kenji , Sitapati Amy M. , Millen Marlene , Longhurst Christopher
Published: April 2023

Objective

Occupational health (OH) documentation has traditionally been separate from health system electronic health records (EHRs), but this can create patient safety and care continuity challenges. Herein, we describe outcomes and challenges of such integration including how one health system managed compliance with laws, regulations, and ethical principles concerning digital privacy.

Methods

Occupational health integration with the enterprise EHR at the University of California San Diego Health was started in June 2021 and completed in December 2021.

Results

Integrating with the enterprise EHR allowed for a secure telehealth system, faster visit times, digitization of questionnaires medical clearance forms, and improved reporting capabilities.

Conclusions

Integration and interoperability are fundamental building blocks to any OH EHR solution and will allow for evaluation of worker population trends, and targeted interventions to improve worker health status.
Interventions for sustainable surgery: a systematic review
Authors: Lam Kyle , Gadi Nishita , Acharya Amish , Winter Beatty Jasmine , Darzi Ara , Purkayastha Sanjay
Published: April 2023

Objective:

To systematically evaluate interventions designed to improve the sustainability of surgical practice with respect to their environmental and financial impact.

Background:

Surgery contributes significantly to emissions attributed to healthcare due to its high resource and energy use. Several interventions across the operative pathway have, therefore, been trialed to minimize this impact. Few comparisons of the environmental and financial effects of these interventions exist.

Materials and methods:

A search of studies published up to 2nd February 2022 describing interventions to increase surgical sustainability was undertaken. Articles regarding the environmental impact of only anesthetic agents were excluded. Data regarding environmental and financial outcomes were extracted with a quality assessment completed dependent upon the study design.

Results:

In all, 1162 articles were retrieved, of which 21 studies met inclusion criteria. Twenty-five interventions were described, which were categorized into five domains: ‘reduce and rationalize’, ‘reusable equipment and textiles’, ‘recycling and waste segregation’, ‘anesthetic alternatives’, and ‘other’. Eleven of the 21 studies examined reusable devices; those demonstrating a benefit reported 40–66% lower emissions than with single-use alternatives. In studies not showing a lower carbon footprint, the reduction in manufacturing emissions was offset by the high environmental impact of local fossil fuel-based energy required for sterilization. The per use monetary cost of reusable equipment was 47–83% of the single-use equivalent.

Conclusions:

A narrow repertoire of interventions to improve the environmental sustainability of surgery has been trialed. The majority focuses on reusable equipment. Emissions and cost data are limited, with longitudinal impacts rarely investigated. Real-world appraisals will facilitate implementation, as will an understanding of how sustainability impacts surgical decision-making.
Predicting necrotising soft tissue infections in people who inject drugs: poor performance of the Laboratory Risk Indicator for Necrotising Fasciitis score and development of a novel clinical predictive nomogram in a retrospective cohort with internal validation
Authors: MacLeod Caitlin S. , O’Neill Hannah L. , Shaalan Ramy , Nagy John , Flett Murray M. , Guthrie Graeme J.K. , McLeod Graeme , Suttie Stuart A. ,   on behalf of the East of Scotland Vascular Network (ESVN)
Published: April 2023

Introduction:

Necrotising soft tissue infections (NSTI) can threaten life and limb. Early identification and urgent surgical debridement are key for improved outcomes. NSTI can be insidious. Scoring systems, like the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC), exist to aid diagnosis. People who inject drugs (PWID) are high risk for NSTI. This study aimed to assess the utility of the LRINEC in PWID with lower limb infections and develop a predictive nomogram.

Methods:

A retrospective database of all hospital admissions due to limb-related complications secondary to injecting drug use between December 2011 and December 2020 was compiled through discharge codes and a prospectively maintained Vascular Surgery database. All lower limb infections were extracted from this database, dichotomised by NSTI and non-NSTI with the LRINEC applied. Specialty management times were evaluated. Statistical analyses involved: chi-square; Analysis of “variance”; Kaplan–Meier, and receiver operating characteristic curves. Nomograms were developed to facilitate diagnosis and predict survival.

Results:

There were 557 admissions for 378 patients, with 124 (22.3%; 111 patients) NSTI. Time from admission to: theatre and computed tomography imaging respectively varied significantly between specialties (P=0.001). Surgical specialties were faster than medical (P=0.001). Vascular surgery received the most admissions and had the quickest time to theatre. During follow-up there were 79 (20.9%) deaths: 27 (24.3%) NSTI and 52 (19.5%) non-NSTI. LRINEC ≥6 had a positive predictive value of 33.3% and sensitivity of 74% for NSTI. LRINEC <6 had a negative predictive value of 90.7% and specificity of 63.2% for non-NSTI. Area under the curve was 0.697 (95% CI: 0.615–0.778). Nomogram models found age, C-reactive protein, and non-linear albumin to be significant predictors of NSTI, with age, white cell count, sodium, creatinine, C-reactive protein, and albumin being significant in predicting survival on discharge.

Conclusion:

There was reduced performance of the LRINEC in this PWID cohort. Diagnosis may be enhanced through use of this predictive nomogram.
“I Am a Human”
Authors: Lusaka Joseph , Kpoeh Julius D.N. , Crowell Jacqueline P. , Gowa Martha Sekey , Hardy Dehcontee M. , Karanja Viola , Rosa William E.
Published: April 2023

Liberia is a postwar, post-Ebola, and low-income nation in West Africa with minimal to no palliative care access. In 2017, Partners In Health in collaboration with the Liberian Ministry of Health invested in the development of a nurse-led, community-based palliative care team in southeastern Maryland County at JJ Dossen Memorial Hospital. Between 2017 and 2022, the 9-member team (8 nurses, 1 physician assistant) has enrolled 142 patients under their care. This is a qualitative process evaluation eliciting the experiences, perspectives, and attitudes of patients with cancer to inform future palliative care program delivery improvement and development. Using an exploratory design, n = 8 participants were interviewed using a semi-structured guide. The sample had a mean age of 48 years with an average palliative care clinic enrollment period of 22.5 weeks at the time of interview. The interdisciplinary coding team used an applied thematic text analysis approach and identified 5 themes: history and disease progression, follow-up clinic services, psychological distress and its sources, social support, and spiritual and cultural beliefs. Implications emphasize the need for increased community engagement, primary palliative care capacity development of clinical colleagues in the region, and the support of local and national decision-makers to prioritize palliative care service expansion.
Brain Science Learning Guides
Authors: Onello Rachel
Published: April 2023

Background:

Students often struggle with how to synthesize course content during independent learning outside of class.

Problem:

Study strategies may be entrenched in ineffective methods that reinforce misperceptions of learning and undermine the development of metacognitive thinking.

Approach:

To promote the development of effective study skills, a scaffolded approach was developed to facilitate students actively engaging with course content outside of class time, based on best practices of brain science–based learning.

Outcomes:

Using evidence in the brain science of teaching and learning, Learning Guides were developed to shift the focus of study outside of class time from the “what” to the “how.” Preliminary feedback from students in multiple core nursing courses suggests that these guides are an effective tool for student learning.

Conclusion:

This brain science–based approach to learning can provide a road map for students to build the essential skills for effective study habits that can lead to durable learning.
Planetary Health
Authors: Vandenberg Shannon Y.
Published: April 2023

Background:

Climate change around the globe is impacting human and planetary health at unprecedented rates. Nurses are well positioned to act as climate leaders, given their critical role globally.

Problem:

Current and future nurses must work to mitigate climate-related health effects. It is necessary that a planetary health approach is integrated into nursing education.

Approach:

Curricular modifications, using the Planetary Health Education Framework, are presented, which will promote awareness and understanding of climate health among future nurses. The framework is grounded in equity, which is well suited to nursing education, and can be readily adapted into current nursing curricula.

Outcomes:

Recommendations for nursing education are presented within the 5 domains of the framework.

Conclusions:

Future nurses are called on to be exemplary planetary health communicators, educators, advocates, and leaders. The Planetary Health Education Framework promotes nursing leadership in practice and in advocating for a climate-resistant future.
Measuring Nursing Student Development Through Computer-Based Simulation Activities
Authors: Aller Loretta , Shelestak Deb , Phillips Lynette , Reed Janet , Allen Betty
Published: April 2023

Background:

New nurse attrition jeopardizes patient safety, devastates career plans, and negatively impacts costs to hospitals and patients. Employers and educators recognize the widening transition-to-practice gap in meeting expectations for practice-ready, resilient nurses.

Purpose:

The purpose of this study was to test the use of computer-based simulation activities (CBSAs) to measure processes in Aller's Development of Decision-Making and Self-Efficacy Model (ADD-SEM).

Methods:

BSN students (N = 50) in a multisite, cross-sectional study used CBSAs to provide data on decision making (Virtual Patient Lasater's Clinical Judgment Rubric), psychological capital (Nursing Anxiety and Self-Confidence in Decision-Making Scale©), and reflection.

Results:

Repeated-measures analysis of variance and reflexive thematic analysis revealed that decision-making (DM) scores were highest in noticing and lowest in interpreting with significant differences in cohorts (DM) (juniors: P < .001; seniors: P = .013) and self-confidence/anxiety (P < .001).

Conclusion:

The CBSAs are an effective means of measuring student development of DM and psychological capital needed to retain resilient nurses.
AORR DM Manuscript_MDC-D-23-00156.docx
Authors: Reddy Shivani M. , Kugley Shannon , Booth Graham , Dalton Jennie , Rodriguez Borja Ivette , Coker-Schwimmer Manny , Patel Sheila V. , Bonds Denise , Prum Soknorntha , Fujita Miku , Philbrick Sarah , Ruwala Richa , Albritton Jordan A. , Crotty Karen
Published: April 2023

  

We compared the effectiveness of audio care, as a replacement or a supplement to usual care, for managing diabetes.
Hospital Fire Outbreaks Before and During the COVID-19 Pandemic in Low- and Middle-Income Settings
Authors: Bayuo Jonathan , Duodu Precious Adade
Published: April 2023

Objective

The aim of the study is to identify and synthesize existing published and gray literature reporting on hospital fire outbreaks before and during the coronavirus disease 2019 (COVID-19) pandemic.

Methods

A 2-phase narrative review approach was used. The search covered peer-reviewed, gray literature sources, and news outlets. The pre-COVID-19 hospital fire outbreak search period was January 2000–December 2019 while that for during COVID-19 was December 2019–July 2021 (repeated in December 2021).

Results

Thirteen and 24 media reports were identified for the pre-COVID-19 and during COVID-19 periods, respectively. Although varied fire risks existed before the emergence of the COVID-19, this article demonstrates that the incidence of hospital fires has increased more than two-folds in recent times in COVID-19 wards and intensive care units causing death, injuries, and extensive damage to properties. The main risk in the pre-COVID-19 era was identified as electrical faults. During the pandemic, other issues such as oxygen explosions, inefficient cooling systems, and lack of fire control measures in makeshift pre-COVID-19 centers were identified as additional risks/causes of the hospital fire outbreaks.

Conclusions

Additional risks have emerged during the COVID-19 era, which increased the occurrence of hospital fire outbreaks. Guidelines, protocols, and policies regarding the prevention of hospital fire outbreaks and strategies for attenuating its effects need to be highlighted across settings and adhered to. Existing policies need to evolve to help resolve these risks. Beyond the preventive strategies, context-specific psychosocial support is also required for healthcare staff, families, and patients who survive episodes of hospital fire outbreaks.
Influence of Perioperative COVID-19 Infection on Surgical Outcomes and Risk Adjustment for Quality Assessment in the American College of Surgeons NSQIP
Authors: Peters Xane D , Cohen Mark E , Meng Xiangiu , Hall Bruce L , Ko Clifford Y
Published: April 2023

Background:

Surgical patients with perioperative COVID-19 infection experience higher rates of adverse events than those without COVID, which may lead to imprecision in hospital-level quality assessment. Our objectives were to quantify differences in COVID-19 associated adverse events in a large national sample and examine distortions in surgical quality benchmarking if COVID status is not considered.

Study Design:

Data included 793,280 patient records from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from April 1, 2020 to March 31, 2021. Models predicting 30-day Mortality, Morbidity, Pneumonia, Ventilator Dependency > 48 hours, and unplanned intubation were constructed. Risk adjustment variables were selected for these models from standard NSQIP predictors and perioperative COVID status.

Results:

5,878 (0.66%) had preoperative COVID and 5,215 (0.58%) had postoperative COVID. COVID rates demonstrated some consistency across hospitals (median preoperative 0.84%, IQR=0.14%-0.84%; median postoperative 0.50%, IQR=0.24%-0.78%). Postoperative COVID was always associated with increased adverse events. For postoperative COVID among all cases, there was nearly a six-fold increase in Mortality (1.07% to 6.37%) and15-fold increase in Pneumonia (0.92% to 13.57%), excluding the diagnosis of COVID itself. The effects of preoperative COVID were less consistent. Inclusion of COVID in risk-adjustment models had minimal effects on surgical quality assessments.

Conclusion:

Perioperative COVID was associated with a dramatic increase in adverse events. However, quality benchmarking minimally affected. This may be the result of low overall COVID rates or balance in rates established across hospitals over the 1-year observational period. There remains limited evidence for restructuring ACS NSQIP risk-adjustment for the time-limited effects of the COVID pandemic.
A novel constitutive model considering the role of elastic lamellae’ structural heterogeneity in homogenizing transmural stress distribution in arteries
Authors: Sigaeva Taisiya , Zhang Yanhang
Published: April 2023

Understanding how the homeostatic stress state can be reached in arterial tissues can provide new insights into vascular physiology. Even though the function of maintaining homeostasis is often linked to the concentric layers of medial elastic lamellae, how the lamellae are capable of evenly distributing the stress transmurally remains to be understood. The recent microstructural study by Yu
et al.
(2018
J. R. Soc. Interface
15
, 20180492) revealed that, circumferentially, lamellar layers closer to the lumen are wavier than the ones further away from it and, thus, experience more unfolding when subjected to blood pressure. Motivated by this peculiar finding, the current study, for the first time, proposes a novel approach to model elastic lamellae and such structural heterogeneity using the extensible worm-like chain model. When implemented into the material description of the conventional two-layer artery model, in which adventitial collagen is modelled using the inextensible worm-like chain model, it is demonstrated that structural heterogeneity in elastic lamellae plays an important role in dictating transmural stress distribution and, therefore, the homeostasis of the arterial wall.
The CpxRA two-component system represses gene expression of the heat-labile toxin of enterotoxigenic Escherichia coli
Authors: Rodríguez-Valverde Diana , León-Montes Nancy , Siqueiros-Cendón Tania , Rivera-Gutiérrez Sandra , Ares Miguel A. , De la Cruz Miguel A.
Published: April 2023

Enterotoxigenic

Escherichia coli

(ETEC) strains produce at least one of two types of enterotoxins: the heat-labile (LT) and heat-stable (ST) toxins, which are responsible for the watery secretory diarrhoea that is a hallmark of the human ETEC infection. One regulatory system that controls the transcription of virulence genes in pathogenic bacteria is the CpxRA two-component system (TCS). We reported that the eltAB bicistronic operon, which encodes for the A and B subunits of LT, was repressed for the CpxRA TCS by direct binding of CpxR-P from −12 to +6 bp with respect to the transcription start site of eltAB. Moreover, the Cpx-response activation down-regulated the transcription of eltAB genes, and this negative effect was CpxRA-dependent. Our data show that CpxRA TCS is a negative regulator of the LT, one of the main virulence determinants of ETEC.
Comparison of two measures of cognitive impairment on the 2015 Behavioral Risk Factor Surveillance System
Authors: Adams Mary
Published: April 2023

Only selected states have used an optional module to address subjective cognitive decline (SCD) on the Behavioral Risk Factor Surveillance System (BRFSS). This study compares SCD with a core measure of cognitive disability (CDis) that has been included on the BRFSS since 2013. Using 2015 BRFSS data from 35 states that asked the module we report the weighted prevalence of SCD and CDis by demographics, chronic conditions, and risk factors among 150,981 respondents ages 45 years or older. We also compare adults with SCD only, CDis only, both, or neither, plus all those reporting either measure on similar health related measures. In addition, results of logistic regression are presented. Weighted prevalence rates and 95% confidence intervals were 11.5% (11.1%-12.0%) for SCD and 10.6% (10.2%-11.0%) for CDis. Approximately half of those reporting one measure reported the other and about one-third of those reporting either fell into each of the 3 mutually exclusive groups. Comparisons indicated a consistent progression from SCD only, to CDis only, to those with both, for measures of chronic conditions, number of SCD-related risk factors, and poorer health status. Logistic regression results for CDis were more like those for adults with SCD who also reported functional difficulties than for all adults with SCD. Conclusion: Although it does not include a timeframe or capture the exact same respondents as SCD, the core measure of CDis appears to be a useful measure of cognitive impairment and may represent adults more adversely affected than those reporting SCD.
Knowledge, attitudes and practices towards antibiotic use and resistance in Kyegegwa district, Uganda – a questionnaire study
Authors: Kahunde Mary Ann , Odoch Terence , Owiny David Okello , Kankya Clovice , Kaelin Marisa B. , Hartnack Sonja
Published: April 2023

Background

Antimicrobials are widely used to protect human and animal health. Wide scale misuse can lead to the development and spread of antimicrobial resistance (AMR). In low and middle-income countries, knowledge, attitudes and practices are assumed to contribute to AMR.

Objective

To provide empirical data on knowledge and attitudes towards antibiotic use and resistance in livestock farmers, human and animal health professionals in Kyegegwa district, Uganda. To assess which factors (farming, education, affiliation with health-related ministries, gender, keeping cattle, goats, pigs, poultry or sheep) are associated with poor knowledge.

Methods

A questionnaire related to antibiotic usage (AMU) and AMR, as well as demographic data was developed and administered to health practitioners of both the humanmedical and the livestock sector, and (semi)-intensive livestock farmers. Polytomous latent class analysis was used to cluster respondents - based on their responses - in different classes of knowledge and attitudes. The association between the probability of belonging to latent classes and demographic data was assessed by multinomial regression models and conditional inference trees.

Results

In total 1022 responses were available (response rate 68.1%). More than 50% of the cattle received antibiotics at least three times during the last six months and in 39.1% members of the respondents’ households of this study were on antibiotics. Three latent classes related to attitude towards antibiotic access, usage and disposal; and two classes regarding resistance have been revealed. Class membership was associated with a number of socio-demographic factors.

Conclusion

Inadequate knowledge and inappropriate practices as evidenced in this study should support further policy formulations and strategies to regulate AMU. It will also be useful in refining the implementation of local and national action plans and efforts to control AMR. A key component of this will require promotion of One Health approach and effective communication to tackle prevailing misconceptions.
“A System Dynamics Model for Long-term Aspect of Caries Preventive Interventions”
Authors: Oo Tin Htet , Tianviwat Sukanya , Thitasomakul Songchai , Sontamino Phongpat
Published: April 2023

Objective

The purpose of the study is to appraise the long-term effects of caries preventive interventions of the Ministry of Public Health (MOPH), Thailand: supervised toothbrushing (STB), dental sealant, and combined STB+sealant that are implemented for 6- to 15-year-olds by comparing with the base case using the System Dynamics Model (SDM).

Method

The System Dynamics Model (SDM) was analyzed to compare the interventions, supervised toothbrushing (STB), sealant, and combined STB+sealant as intervention scenarios with the base case scenario. The effectiveness data of interventions set in the model were retrieved from meta-analyses and experts’ opinions.

Results

The model established that the no caries population increased by 36.2%, 25.5%, and 18.6% while the caries population decreased by 8.1%, 5.6%, and 3.3% under combined STB+sealant, sealant, and supervised toothbrushing (STB) respectively compared to the base case at the age of 15 years old. From the above 20 years old to the elderly age, both individual and combined interventions have no favorable effect on reducing caries. On the other hand, the no caries population under the interventions is not significantly different from the base case during the elderly age.

Conclusion

Combined STB+sealant is the most effective intervention among the interventions that are administered during the age of 6-15 years. The interventions given during these ages have effectiveness in caries reduction by about 15 years from when they are started. In addition, System Dynamics Model (SDM) would assist in comparing the interventions or policies as scenarios to indicate the most opportune one for the population.
Qualitative feasibility study of the mobile app Destroke for clinical stroke monitoring based on the NIH Stroke Scale
Authors: Noch Evan K , Pham Dan , Kitago Tomoko , Wuennemann Marissa , Wortman-Jutt Susan , Falo M. Cristina
Published: April 2023

Background

Stroke is a leading cause of severe disability in the United States, but there is no effective method for patients to accurately detect the signs of stroke at home. We developed a mobile app, Destroke, that allows remote performance of a modified NIH stroke scale (NIHSS) by patients.

Aims

To assess the feasibility of a mobile app for stroke monitoring and education by patients with a history of stroke

Materials and Methods

We enrolled 25 patients with a history of stroke in a prospective open-label study to evaluate the feasibility of the Destroke app in patients with stroke. Nineteen patients completed all study assessments, with a median time from stroke onset to enrollment of 5.6 years (range 0.1-12 years). We designed a modified NIHSS that assessed 12 out of 16 tasks on the NIHSS. Patients completed this test eight times over a 28-day period. We conducted pre-study surveys that assessed demographic information, stroke and cardiovascular history, baseline NIHSS, and experience using mobile technologies, and mid- and post-study surveys that assessed patient satisfaction on app usage and confidence in stroke detection.

Results

Ten men and nine women participated in this study (median age of 64 (33-76)), representing ten US states and Washington D.C. Median baseline NIHSS was 0 (0-4). 15 patients reported using health apps. On a 5-point Likert scale, patients rated the app as 4.2 on being able to understand and use the app and 4.3 on using the app when instructed by their doctor. For eight patients with poor confidence in detecting the signs of a stroke before the study, six showed higher confidence after the study.

Conclusions

The use of an at-home stroke monitoring app is feasible by patients with a history of stroke and improves confidence in detecting the signs of stroke.
How do People with Multimorbidity Prioritise Healthcare when Faced with Financial Constraints? A Choice Experiment
Authors: Larkin James , Foley Louise , Timmons Shane , Hickey Tony , Clyne Barbara , Harrington Patricia , Smith Susan M.
Published: April 2023

Multimorbidity is associated with increased out-of-pocket healthcare costs, making people with multimorbidity more vulnerable to cost-related non-adherence to recommended treatment. This study aimed to understand how people with multimorbidity would prioritise different healthcare services and chronic conditions when faced with potential budget constraints. A cross-sectional online survey incorporating a choice experiment was conducted in Ireland (December 2021 to March 2022). Participants were adults aged 40 years or over with at least one chronic condition. They were asked how they would prioritise their real-world healthcare utilisation if their monthly personal healthcare budget were reduced by 25%. The survey also included questions about real-life experiences of cost-related non-adherence and financial burden. Among the 962 participants, 64.9% (n=624) had multimorbidity. When presented with the hypothetical budget constraint, participants reduced expenditure on ‘other healthcare (hospital visits, specialist doctors, etc.)’, by the greatest percentage (50.2%), and medicines by the lowest percentage (24.5%). Participants with multimorbidity tended to have a condition they prioritised over others. On average, they reduced expenditure for their top-priority condition by 69% less than would be expected if all conditions were valued equally, compared to a reduction in expenditure of 59% more than expected for their least prioritised condition. Participants were asked how important several areas were when making their decisions (scale of 1 – ‘not important at all’ to 5 – ‘very important’). Independence, symptom control and staying alive were rated as the most important decision factors (median=5). Over one third (34.5%, n=332) of participants reported cost-related non-adherence as they had either not attended a healthcare professional or not paid for medication or both in the last year due to cost. Research and clinical care must take greater consideration of the different ways people with multimorbidity respond to high healthcare costs and the impact this has on treatment adherence and health outcomes.
The landscape of biomedical research
Authors: González-Márquez Rita , Schmidt Luca , Schmidt Benjamin M. , Berens Philipp , Kobak Dmitry
Published: April 2023

The number of publications in biomedicine and life sciences has rapidly grown over the last decades, with over 1.5 million papers now being published every year. This makes it difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here we present a 2D map of the entire corpus of biomedical literature, and argue that it provides a unique and useful overview of the life sciences research. We based our atlas on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we used the large language model PubMedBERT, combined witht-SNE tailored to handle samples of our size. We used our atlas to study the emergence of the Covid-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, the distribution of gender imbalance in academic authorship, and the distribution of retracted paper mill articles. Furthermore, we present an interactive web version of our atlas that allows easy exploration and will enable further insights and facilitate future research.
Intravital Two-Photon Microscopy of the Native Thymus
Authors: Seyedhassantehrani N. , Burns C. S. , Verrinder R. , Okafor V. , Abbasizadeh N. , Spencer J. A.
Published: April 2023

The thymus, a key organ involved in the adaptive immune system, is damaged by a variety of insults including cytotoxic preconditioning. This damage can lead to atrophy and potentially to changes in the hemodynamics of the thymic blood vascular system. Although the thymus has an innate ability to regenerate, the production of T cells relies on the trafficking of lymphoid progenitors from the bone marrow through the altered thymic blood vascular system. Our understanding of thymic blood vascular hemodynamics is limited due to technical challenges associated with accessing the native thymus in live mice. To overcome this challenge, we developed an intravital two-photon imaging method to visualize the native thymus in vivo and investigated functional changes to the vascular system following sublethal irradiation. We were able to quantify blood flow velocity and shear rate in cortical blood vessels and identified a subtle but significant increase in vessel diameter and barrier function ~24 hrs post-sublethal irradiation. Ex vivo whole organ imaging of optically cleared thymus lobes confirmed a disruption of the thymus vascular structure, resulting in an increase in blood vessel diameter and vessel area, and concurrent thymic shrinkage. This novel two-photon intravital imaging method enables a new paradigm for directly investigating the thymic microenvironment in vivo.
Mutation signature filtering enables high-fidelity RNA structure probing at all four nucleobases with DMS
Authors: Mitchell David , Cotter Jennifer , Saleem Irfana , Mustoe Anthony M.
Published: April 2023

Chemical probing experiments have transformed RNA structure analysis, enabling high-throughput measurement of base-pairing in living cells. Dimethyl sulfate (DMS) is one of the most widely used structure probing reagents and has played a prominent role in enabling next-generation single-molecule probing analyses. However, DMS has traditionally only been able to probe adenine and cytosine nucleobases. We previously showed that, using appropriate conditions, DMS can also be used to interrogate base-pairing of uracil and guaninesin vitroat reduced accuracy. However, DMS remained unable to informatively probe guanines in cells. Here, we develop an improved DMS mutational profiling (MaP) strategy that leverages the unique mutational signature of N1-methylguanine DMS modifications to enable robust, high-fidelity structure probing at all four nucleotides, including in cells. Using information theory, we show that four-base DMS reactivities convey greater structural information than comparable two-base DMS and SHAPE probing strategies. Four-base DMS experiments further enable improved direct base-pair detection by single-molecule PAIR analysis, and ultimately support RNA structure modeling at superior accuracy. Four-base DMS probing experiments are easily performed and will broadly facilitate improved RNA structural analysis in living cells.
Programmed ribosomal frameshifts, and how to find them
Authors: McNair Katelyn , Salamon Peter , Edwards Robert A. , Segall Anca M.
Published: April 2023

One of the stranger phenomena that can occur during gene translation is where, as a ribosome reads along the mRNA, various cellular and molecular properties contribute to stalling the ribosome on a slippery sequence, shifting the ribosome into one of the other two alternate reading frames. The alternate frame has different codons, so different amino acids are added to the peptide chain, but more importantly, the original stop codon is no longer in-frame, so the ribosome can bypass the stop codon and continue to translate the codons past it. This produces a longer version of the protein, a fusion of the originalin-frameamino acids, followed by all the alternate frame amino acids. There is currently no automated software to predict the occurrence of these programmed ribosomal frameshifts (PRF), and they are currently only identified by manual curation. Here we present the first machine-learning based method to detect and predict the presence of PRFs in all types of coding genes and taxa with an accuracy exceding 90%.
Is neglect of self-clearance biassing TB vaccine impact estimates?
Authors: Scarponi Danny , Clark Rebecca A , Weerasuriya Chathika , Emery Jon C , Houben Rein MGJ , White Richard G , McCreesh Nicky
Published: April 2023

Background

Mathematical modelling has been used extensively to estimate the potential impact of new tuberculosis vaccines, with the majority of existing models assuming that individuals with Mycobacterium tuberculosis (Mtb) infection remain at lifelong risk of tuberculosis disease. Recent research provides evidence that self-clearance of Mtb infection may be common, which may affect the potential impact of new vaccines that only take in infected or uninfected individuals. We explored how the inclusion of self-clearance in models of tuberculosis affects the estimates of vaccine impact in China and India.

Methods

For both countries, we calibrated a tuberculosis model to a scenario without self-clearance and to various scenarios with self-clearance. To account for the current uncertainty in self-clearance properties, we varied the rate of self-clearance, and the level of protection against reinfection in self-cleared individuals. We introduced potential new vaccines in 2025, exploring vaccines that work in uninfected or infected individuals only, or that are effective regardless of infection status, and modelling scenarios with different levels of vaccine efficacy in self-cleared individuals. We then estimated the relative incidence reduction in 2050 for each vaccine compared to the no vaccination scenario.

Findings

The inclusion of self-clearance increased the estimated relative reductions in incidence in 2050 for vaccines effective only in uninfected individuals, by a maximum of 12% in China and 8% in India. The inclusion of self-clearance increased the estimated impact of vaccines only effective in infected individuals in some scenarios and decreased it in others, by a maximum of 14% in China and 15% in India. As would be expected, the inclusion of self-clearance had minimal impact on estimated reductions in incidence for vaccines that work regardless of infection status.

Interpretations

Our work suggests that the neglect of self-clearance in mathematical models of tuberculosis vaccines does not result in substantially biased estimates of tuberculosis vaccine impact. It may, however, mean that we are slightly underestimating the relative advantages of vaccines that work in uninfected individuals only compared to those that work in infected individuals.
Qualitative evaluation of the use of modelling in resource allocation decisions for HIV and TB
Authors: Bowring Anna L , ten Brink Debra , Martin-Hughes Rowan , Fraser-Hurt Nicole , Cheikh Nejma , Scott Nick
Published: April 2023

Introduction

Globally, resources for health spending, including HIV and tuberculosis (TB), are constrained, and a substantial gap exists between spending and estimated needs. Optima is an allocative efficiency modeling tool that has been used since 2010 in over 50 settings to generate evidence for country-level HIV and TB resource allocation decisions. This evaluation assessed the utilization of modeling to inform financing priorities from the perspective of country stakeholders and their international partners.

Methods

In October-December 2021, the World Bank and Burnet Institute led 16 semi-structured small-group virtual interviews with 54 representatives from national governments and international health and funding organizations. Interviews probed participants’ roles and satisfaction with Optima analyses and how model findings have had been used and impacted resource allocation. Interviewed stakeholders represented nine countries and 11 different disease program-country contexts with prior Optima modeling analyses. Interview notes were thematically analyzed to assess factors influencing the utilization of modeling evidence in health policy and outcomes.

Results

Common influences on utilization of Optima findings encompassed the perceived validity of findings, health system financing mechanisms, the extent of stakeholder participation in the modeling process, engagement of funding organization, socio-political context, and timeliness of the analysis. Utilizing workshops can facilitate effective stakeholder engagement and collaboration.

Model findings were often used conceptually to localize global evidence and facilitate discussion. Secondary outputs included informing strategic and financial planning, funding advocacy, grant proposals, and influencing investment shifts.

Conclusion

Allocative efficiency modeling has supported evidence-informed decision making in numerous contexts and enhanced the conceptual and practical understanding of allocative efficiency. Most immediately, greater involvement of country stakeholders in modeling studies and timing studies to key strategic and financial planning decisions may increase the impact on decision making. Better consideration for integrated disease modeling, equity goals, and financing constraints may improve relevance and utilization of modeling findings.
Targeting ABCB4 using mRNA-LNP for the treatment of rare liver diseases
Authors: Alsuraih Mohammed , LaViolette Brianna , Lin Guan-Yu , Kovi Ramesh , Daurio Natalie , Cheng Congsheng , Ahn Youngwook , Jiang Zhihua , Ortiz Roberto , Li Shangzhong , Cheng Yuxing , Wang Ye , Fan Xiaoyu , Haskins Jessica , Sun Xiuhua , Hunter Abigail , Hirenallur Shanthapa Dinesh , Wu Ying , Holsti Matthew , Stewart Morag , Tadin-Strapps Marija , Chiang Shian-Huey
Published: April 2023

Mutations in the ABCB4 gene lead to a wide-spectrum of rare liver diseases including progressive familial intrahepatic cholestasis type 3 (PFIC3) and low-phospholipid associated cholelithiasis (LPAC) syndrome. PFIC3 patients develop symptoms during late infancy, including severe itching, jaundice, and failure to thrive. The condition may progress to liver failure during childhood or adulthood. This is a highly unmet medical condition where liver transplantation is the only option to correct this disease. Recently, exciting data suggested that restoration of the ABCB4 function via gene replacement could rescue liver phenotypes associated with ABCB4 dysfunction in a preclinical PFIC3 mouse model. Here, we used mRNA LNP platform to determine expression and durability of ABCB4 in the liver of wildtype mice. In addition, we generated Abcb4-/-mice to study the efficacy of systemic delivery of ABCB4 mRNA LNP. We observed a robust and durable expression of hABCB4 up to 72 hours post systemic dosing in the liver of wild-type mice. Systemic administration of hABCB4 mRNA achieved a remarkable restoration of phosphatidylcholine levels in bile, a significant decrease in liver stiffness as measured by shear wave elastography, and amelioration of liver histopathology including fibrosis and ductular reaction. We conclude that administration of hABCB4 mRNA LNPs was sufficient to ameliorate fibrosis markers in the PFIC3 mouse model. Our data suggests that gene replacement using mRNA LNP modality could provide an excellent opportunity for patients with biliary diseases.
Divergent pattern of development in rats and humans
Authors: campos Wanda , Iorri Tomas , Presti Antonella , Grimson Rafael , Vázquez-Borsetti Pablo
Published: April 2023

Rattus norvegicusis the second most used laboratory species and the most widely used model in neuroscience. Nonetheless, there is still no agreement regarding the temporal relationship of development between humans and rats. We addressed this question by examining the time required to reach a set of homologous developmental milestones in both species. With this purpose, a database was generated with data collected through a bibliographic survey. This database was in turn compared with other databases about the same topic present in the literature. Finally, the databases were combined, covering for the first time the entire development of the rat including the prenatal, perinatal, and postnatal periods. This combined database includes 497 individual dates for both species. The developmental relationship between humans and rats was better fit by a logarithmic function than by a linear function. Also, an inflection point close to birth becomes evident after the logarithmic transformation of the data. The predictions of the proposed model were compared with other estimators historically used to calculate developmental relationships, such as growth in brain weight, finding a notorious discrepancy. As development progresses, an increase in the dispersion of the data is observed. Until now, developmental relationships have been interpreted as a univocal equivalence. In this work, is proposed an alternative interpretation where the age of one species is translated into a range of ages in the other.
A Shared Pathogenic Mechanism for Valproic Acid and SHROOM3 Knockout in a Brain Organoid Model of Neural Tube Defects
Authors: Takla Taylor N. , Luo Jinghui , Sudyk Roksolana , Huang Joy , Walker J. Clayton , Vora Neeta L. , Sexton Jonathan Z. , Parent Jack M. , Tidball Andrew M.
Published: April 2023

Neural tube defects (NTDs) including anencephaly and spina bifida are common major malformations of fetal development resulting from incomplete closure of the neural tube. These conditions lead to either universal death (anencephaly) or life-long severe complications (spina bifida). Despite hundreds of genetic mouse models having neural tube defect phenotypes, the genetics of human NTDs are poorly understood. Furthermore, pharmaceuticals such as antiseizure medications have been found clinically to increase the risk of NTDs when administered during pregnancy. Therefore, a model that recapitulates human neurodevelopment would be of immense benefit to understand the genetics underlying NTDs and identify teratogenic mechanisms. Using our self-organizing single rosette spheroid (SOSRS) brain organoid system, we have developed a high-throughput image analysis pipeline for evaluating SOSRS structure for NTD-like phenotypes. Similar to small molecule inhibition of apical constriction, the antiseizure medication valproic acid (VPA), a known cause of NTDs, increases the apical lumen size and apical cell surface area in a dose-responsive manner. This expansion was mimicked by GSK3β and HDAC inhibitors; however, RNA sequencing suggests VPA does not inhibit GSK3β at these concentrations. Knockout of SHROOM3, a well-known NTD-related gene, also caused expansion of the lumen as well as reduced f-actin polarization. The increased lumen sizes were caused by reduced cell apical constriction suggesting that impingement of this process is a shared mechanism for VPA treatment and SHROOM3-KO, two well-known causes of NTDs. Our system allows the rapid identification of NTD-like phenotypes for both compounds and genetic variants and should prove useful for understanding specific NTD mechanisms and predicting drug teratogenicity.
Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes
Authors: Zhou Xinrui , Seow Wan Yi , Ha Norbert , Cheng Teh How , Lingfan Jiang , Boonruangkan Jeeranan , Goh Jolene Jie Lin , Prabhakar Shyam , Chou Nigel , Chen Kok Hao
Published: April 2023

High-dimensional, spatially resolved analysis of intact tissue samples promises to transform biomedical research and diagnostics, but existing spatial omics technologies are costly and labor-intensive. We present FISHnCHIPs for highly sensitivein situprofiling of cell types and gene expression programs. FISHnCHIPs achieves this by simultaneously imaging ∼2-35 co-expressed genes that are spatially co-localized in tissues, resulting in similar spatial information as single-gene FISH, but at ∼2-20-fold higher sensitivity. Using FISHnCHIPs, we imaged up to 53 gene modules from the mouse kidney and mouse brain, and demonstrated high-speed, large field-of-view profiling of a whole tissue section. FISHnCHIPS also revealed spatially restricted localizations of cancer-associated fibroblasts in a human colorectal cancer biopsy. Overall, FISHnCHIPs enables robust and scalable spatial transcriptomics analysis of tissues with normal physiology or undergoing pathogenesis.