bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing Practice: Clinical Application of Resistance Training Evidence for Children With Cerebral Palsy
Authors: Hedgecock James B. , Harris Nicole M. , Rapport Mary Jane
Published: June 2023

Purpose:

Describe the development and application of a progressive resistance exercise (PRE) program for children with cerebral palsy (CP), which became a standard care model at an urban specialty hospital network.

Summary of Key Points:

Muscle structure and performance have been shown to impact function and participation in children with CP. Use of PRE to achieve function and participation goals is supported by a growing body of evidence. A novel guideline, focused on individualized, goal-focused PRE dosing, professional development, program monitoring, and outcome measures use, facilitated application of a new clinical practice.

Conclusions:

Practice change was accomplished by translating evidence using a clinical guideline resulting in positive child function and participation outcomes.

Recommendations for Clinical Practice:

This Special Communication provides an example of addressing goal-related muscle performance impairments in children with CP. Clinicians should consider updating long-standing physical therapy intervention strategies by incorporating goal-specific PRE into practice.
Integrating Contact Tracers Into Point-of-Care Testing Workflow to Accelerate the Tracing of People With Exposure to COVID-19, August-December 2020, New York City
Authors: Udeagu Chi-Chi N. , Gbedemah Misato , Pitiranggon Masha , Feldman Samantha , Cordoba Evette , Goldenberg Shifra , Keeley Chris , Blaney Kathleen , Vora Neil M. , Long Theodore
Published: June 2023

Objectives:

We assessed the timeliness of contact tracing following rapid-positive COVID-19 test result at point-of-care testing (POCT) sites in New York City (NYC).

Design:

Interviewed case-patients to elicit exposed contacts and conducted COVID-19 exposure notifications.

Settings:

Twenty-two COVID-19 POCT sites in NYC, the 2 NYC international airports, and 1 ferry terminal.

Participants:

Case-patients with rapid-positive COVID-19 test results and their named contacts.

Main Outcome Measures:

We quantified the proportions of interviewed individuals with COVID-19 and notified contacts and assessed the timeliness between the dates of the rapid-positive COVID-19 test results and the interviews or notifications.

Results:

In total, 11 683 individuals with rapid-positive COVID-19 test results were referred for contact tracing on the day of their diagnosis; 8878 (76) of whom were interviewed within 1 day of diagnosis, of whom 5499 (62%) named 11 486 contacts. A median of 1.24 contacts were identified from each interview. The odds of eliciting contacts were significantly higher among individuals reporting COVID-19 symptoms than among persons with no symptoms (51% vs 36%; adjusted odds ratio [aOR] = 1.37; 95% confidence interval [CI], 1.11-1.70) or living with 1 or more persons than living alone (89% vs 38%; aOR = 12.11; 95% CI, 10.73-13.68). Among the 8878 interviewed case-patients, 8317 (94%) were interviewed within 1 day of their rapid-positive COVID-19 test results and 91% of contact notifications were completed within 1 day of contact identification. The median interval from test result to interview date and from case investigation interview to contact notification were both 0 days (IQR = 0).

Conclusions:

The integration of contact tracers into COVID-19 POCT workflow achieved timely case investigation and contact notification. Accelerated contact tracing can be used to curb COVID-19 transmission during local outbreaks.
The Emerging Leaders in Public Health Initiative: Individual Leadership Transformation
Authors: Orton Stephen , Schenck Anna P. , Suttie Janet , Carter-Edwards Lori , Herrick Jeannine , Dinkin Donna R. , Meadows Phyllis
Published: June 2023

The Emerging Leaders in Public Health (ELPH) Initiative, sponsored by The Kresge Foundation, provided leadership development to local governmental public health leaders. An adaptive leadership framework was used to shape the curriculum. The coleads attended multiday convenings and webinars over a 16- to 18-month period. Key components of the initiative included using applied learning to solidify their leadership skills as they worked to develop a new role for their agencies provision of a resource grant from The Kresge Foundation to support agency transformation and technical assistance and consultation provided by a National Program Office.

An external evaluator conducted a multicomponent evaluation of individual leadership skill change. Graduates assessed change in their own leadership and change in their colead. Colleagues of ELPH participants were surveyed about their observed changes in the leadership actions of the program graduates.

One hundred four leaders from 30 states participated in the initiative in 3 successive cohorts. Leaders demonstrated improvement as shown by self-report and external observation. Improved ability to communicate in a way that inspires others was one of the most significant changes in leadership behaviors. Additional leadership actions were strengthened including the ability to create and maintain high-performing teams, the ability to ask transformational questions, and the ability to actively listen to understand.

The pandemic has shown the importance of developing the field, starting with leadership. Leadership development and agency transformation are synergistic; they depend on each other and support each other.
Payment Methods and Demographics Influence Patterns of Dental Service Utilization
Authors: Pendleton Matthew , Moss Mark E. , Wu Qiang , Tempel Rob , Garcia Raul , Al-Dajani Mahmoud
Published: June 2023

Objective:

To describe the patterns of specific dental service utilization among the various sociodemographic groups in North Carolina served by the East Carolina University School of Dental Medicine (ECU SoDM).

Design:

This was a descriptive study utilizing self-reported patients' sociodemographic information, payment method history, and CDT codes of procedures performed. Deidentified clinical data recorded for 26 710 patients and 534 983 procedures from 2011 to 2020 were extracted from a centralized axiUm database. Data were analyzed using IBM SPSS Statistics, version 25.0. Cross-tabulations between dental service utilizations, patients' demographics, and payment method were performed using chi-square analysis.

Setting:

Nine dental clinic sites across the state of North Carolina.

Participants:

In total, 26 710 adults 23 years to older than 65 years were included in the sample for this study.

Main Outcome Measures:

In total, 534 983 procedure codes completed for the eligible patients were cross-tabulated with payment method.

Results:

Payment method was significantly related to individual characteristics including location of service, age, race, ethnicity, and untreated decay (P < .001). Payment method is associated with the dental service type utilized by an individual (P < .001). Patients who received Medicaid benefits were more likely to receive restorative procedures, removable prosthetics, or oral surgery. Despite NC Medicaid covering preventive procedures, patients who received Medicaid benefits showed lower utilization of preventive procedures than expected. Privately insured or self-paying individuals demonstrated a greater variety of service option utilization, as well as more frequent usage of more specialized procedure options such as endodontics, periodontics, fixed prosthodontics, and implants.

Conclusions:

Payment method was found to be related to patients' demographics and type of dental service utilized. Adults older than 65 years demonstrated a higher proportion of self-payment for dental care, indicating a lack of payment options for this population. In the interest of providing care for underserved populations in North Carolina, policy makers should consider expanding dental coverage for adults older than 65 years.
A randomized clinical trial of on-demand oral pre-exposure prophylaxis does not modulate lymphoid/myeloid HIV target cell density in the foreskin
Authors: Rametse Cosnet L. , Webb Emily L. , Herrera Carolina , Alinde Berenice , Besethi Asiphe , Motaung Bongani , Mbangiwa Tshepiso , Leach Lloyd , Sebaa Shorok , Pillay Azure-Dee A.P. , Seiphetlo Thabiso B. , Malhangu Boitshoko , Petkov Stefan , Else Laura , Mugaba Susan , Namubiru Patricia , Odoch Geoffrey , Opoka Daniel , Serwanga Jennifer , Ssemata Andrew S. , Kaleebu Pontiano , Khoo Saye , Lebina Limakatso , Martinson Neil , Chiodi Francesca , Fox Julie , Gray Clive M.
Published: June 2023

Objectives:

As topical Pre-Exposure Prophylaxis (PrEP) has been shown to cause immune modulation in rectal or cervical tissue, our aim was to examine the impact of oral PrEP on lymphoid and myeloid changes in the foreskin in response to dosing and timing of drug administration.

Design:

HIV-negative males (n = 144) were recruited in South Africa and Uganda into an open-label randomised controlled trial in a 1:1:1:1:1:1:1:1:1 ratio to control arm (with no PrEP) or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) at one of two different doses, 5 h or 21 h before undergoing voluntary medical male circumcision (VMMC).

Methods:

After dorsal-slit circumcision, foreskin tissue-sections were embedded into Optimal Cutting Temperature media and analysed, blinded to trial allocation, to determine numbers of CD4+CCR5+, CD1a+ cells and claudin-1 expression. Cell densities were correlated with tissue-bound drug metabolites and p24 production after ex vivo foreskin challenge with HIV-1bal.

Results:

There was no significant difference in CD4+CCR5+ or CD1a+ cell numbers in foreskins between treatment arms compared with the control arm. Claudin-1 expression was 34% higher (p = 0.003) in foreskin tissue from participants receiving PrEP relative to controls. There was no correlation of CD4+CCR5+, CD1a+ cell numbers, or claudin-1 expression with tissue-bound drug metabolites, nor with p24 production after ex vivo viral challenge.

Conclusion:

Oral doses and timing of on-demand PrEP and in situ drug metabolite levels in tissue have no effect on numbers or anatomical location of lymphoid or myeloid HIV target cells in foreskin tissue.
Network typologies predict future molecular linkages in the network of HIV transmission in Florida
Authors: Rich Shannan N. , Cook Robert L. , Mavian Carla N. , Garrett Karen , Spencer Emma C. , Salemi Marco , Prosperi Mattia
Published: June 2023

Objective:

HIV molecular transmission network typologies have previously demonstrated associations to transmission risk; however, few studies have evaluated their predictive potential in anticipating future transmission events. To assess this, we tested multiple models on statewide surveillance data from the Florida Department of Health.

Design:

This was a retrospective, observational cohort study examining the incidence of new HIV molecular linkages within the existing molecular network of persons with HIV (PWH) in Florida.

Methods:

HIV-1 molecular transmission clusters were reconstructed for PWH diagnosed in Florida from 2006–2017 using the HIV-TRAnsmission Cluster Engine (HIV-TRACE). A suite of machine-learning models designed to predict linkage to a new diagnosis were internally and temporally externally validated using a variety of demographic, clinical, and network-derived parameters.

Results:

Of the 9,897 individuals who received a genotype within 12 months of diagnosis during 2012–2017, 2,611 (26.4%) were molecularly linked to another case within 1 year at 1.5% genetic distance. The best performing model, trained on two years of data, was high performing (area under the receiving operating curve = 0.96, sensitivity = 0.91, and specificity = 0.90) and included the following variables: age group, exposure group, node degree, betweenness, transitivity, and neighborhood.

Conclusions:

In the molecular network of HIV transmission in Florida, individuals’ network position and connectivity predicted future molecular linkages. Machine-learned models using network typologies performed superior to models using individual data alone. These models can be used to more precisely identify subpopulations for intervention.
Shaken or Stirred? The Inconsistencies of Manual Contrast Media Dilution in Endovascular Interventions
Authors: McDermott Michael C. , Hendriks Babs M.F. , Wildberger Joachim E. , de Boer Sanne W.
Published: June 2023

Objective

The growing need to reduce administered contrast media (CM) volumes for patient, economic, and sustainability reasons has led to clinics manually diluting with saline. The efficacy of this practice is not robustly explored in literature. The objective of this study was to determine the concentration accuracy and homogeneity of manually diluted CM in endovascular procedures.

Materials and Methods

Phase I: Eleven radiological technologists were asked to fill a CM injector 3 times with 50% diluted CM (iopromide 300 mg I/mL). The dilution was injected (12 mL/s) through a Coriolis flowmeter, with CM concentration and total volume calculated. Interoperator, intraoperator, and intraprocedural variations were calculated as coefficients of variability. Contrast media dose reporting accuracy was determined. Phase II: The study was repeated after implementation of a standardized dilution protocol with 5 representative operators.

Results

Phase I: The average injected concentration among 11 operators was 68% ± 16% CM (n = 33; range, 43%–98%), as compared with the target of 50% CM. The interoperator variability was 16%, the intraoperator variability was 6% ± 3%, and the intraprocedural variability was 23% ± 19% (range, 5%–67%). This led to overdelivery of CM compared with intended patient dose by 36% on average. Phase II: After standardization, injections averaged 55% ± 4% CM (n = 15; range, 49%–62%), with interoperator variability of 8%, intraoperator variability of 5% ± 1%, and intraprocedural variability of 1.6% ± 0.5% (range, 0.4%–3.7%).

Conclusions

Manual CM dilution can lead to substantial interoperator and intraoperator, as well as intraprocedural variability in injected concentration. This can result in underreporting of administered CM doses to patients. It is recommended that clinics assess their current standard of care regarding CM injections for endovascular interventions and evaluate potential corrective actions if appropriate.
International Liver Transplantation Society Global Census: First Look at Pediatric Liver Transplantation Activity Around the World
Authors: Rodriguez-Davalos Manuel I. , Lopez-Verdugo Fidel , Kasahara Mureo , Muiesan Paolo , Reddy Mettu S. , Flores-Huidobro Martinez Angel , Xia Qiang , Hong Johnny C. , Niemann Claus U. , Seda-Neto Joao , Miloh Tamir A. , Yi Nam-Joon , Mazariegos George V. , Ng Vicky L. , Esquivel Carlos O. , Lerut Jan , Rela Mohamed ,   for the Pediatric Liver Transplantation Global Census Group
Published: June 2023

Background.

Over 16 000 children under the age of 15 died worldwide in 2017 because of liver disease. Pediatric liver transplantation (PLT) is currently the standard of care for these patients. The aim of this study is to describe global PLT activity and identify variations between regions.

Methods.

A survey was conducted from May 2018 to August 2019 to determine the current state of PLT. Transplant centers were categorized into quintile categories according to the year they performed their first PLT. Countries were classified according to gross national income per capita.

Results.

One hundred eight programs from 38 countries were included (68% response rate). 10 619 PLTs were performed within the last 5 y. High-income countries performed 4992 (46.4%) PLT, followed by upper-middle- (4704 [44·3%]) and lower-middle (993 [9·4%])-income countries. The most frequently used type of grafts worldwide are living donor grafts. A higher proportion of lower-middle-income countries (68·7%) performed ≥25 living donor liver transplants over the last 5 y compared to high-income countries (36%; P = 0.019). A greater proportion of programs from high-income countries have performed ≥25 whole liver transplants (52.4% versus 6.2%; P = 0.001) and ≥25 split/reduced liver transplants (53.2% versus 6.2%; P < 0.001) compared to lower-middle-income countries.

Conclusions.

This study represents, to our knowledge, the most geographically comprehensive report on PLT activity and a first step toward global collaboration and data sharing for the greater good of children with liver disease; it is imperative that these centers share the lead in PLT.
The Association Between Frailty and Chronic Lung Allograft Dysfunction After Lung Transplantation
Authors: Singer Jonthan P. , Gao Ying , Huang Chiung-Yu , Kordahl Rose C. , Sriram Anya , Hays Steven R. , Kukreja Jasleen , Venado Aida , Calabrese Daniel R. , Greenland John R.
Published: June 2023

Background.

After lung transplantation, both frailty and chronic lung allograft dysfunction (CLAD) commonly develop, and when they do, are associated with poorer outcomes. Given their potential shared mechanisms, we sought to explore the temporal relationship between frailty and CLAD onset.

Methods.

In a single center, we prospectively measured frailty by the short physical performance battery (SPPB) repeatedly after transplant. Because of the nature of the relationship between frailty and CLAD is unknown, we tested the association between frailty, modeled as a time-dependent predictor, and CLAD development as well as CLAD development, modeled as a time-dependent predictor, and frailty development. To do so, we used Cox proportional cause-specific hazards and conditional logistic regression models adjusted for age, sex, race, diagnosis, cytomegalovirus serostatus, posttransplant body mass index, and acute cellular rejection episodes as time-dependent covariates. We tested SPPB frailty as a binary (≤9 points) and continuous predictor (12-point scale); as an outcome, we defined frailty as SPPB ≤9.

Results.

The 231 participants were a mean age of 55.7 y (SD 12.1). After adjusting for covariates, the development of frailty within 3 y after lung transplant was associated with cause-specific CLAD risk (adjusted cause-specific hazard ratio: 1.76; 95% confidence interval [CI], 1.05-2.92 when defining frailty as SPPB ≤9 and adjusted cause-specific hazard ratio: 1.10, 95% CI, 1.03-1.18 per 1-point worsening in SPPB). CLAD onset did not appear to be a risk factor for subsequent frailty (odds ratio, 4.0; 95% CI, 0.4-197.0).

Conclusions.

Studying the mechanisms underlying frailty and CLAD could provide new insights into the pathobiology of both and potential targets for intervention.
Recurrence-free Survival After Liver Transplantation Versus Surgical Resection for Hepatocellular Carcinoma: Role of High-risk MRI Features
Authors: Cha Dong Ik , Kim Jong Man , Jeong Woo Kyoung , Yi Nam-Joon , Choi Gyu-Seong , Rhu Jinsoo , Lee Kwang-Woong , Sinn Dong Hyun , Hwang Jeong Ah , Lee Won Jae , Kim Kyunga , Suh Kyung-Suk , Joh Jae-Won
Published: June 2023

Background.

This study aimed to evaluate recurrence-free survival (RFS) and overall survival (OS) after liver transplantation (LT) or liver resection (LR) for hepatocellular carcinoma (HCC) and perform subgroup analysis for HCC with high-risk imaging findings for recurrence on preoperative liver magnetic resonance imaging (MRI; high-risk MRI features).

Methods.

We included patients with HCC eligible for both LT and LR and received either of the treatments between June 2008 and February 2021 from 2 tertiary referral medical centers after propensity score-matching. RFS and OS were compared between LT and LR using Kaplan-Meier curves with the log-rank test.

Results.

Propensity score-matching yielded 79 patients in the LT group and 142 patients in the LR group. High-risk MRI features were noted in 39 patients (49.4%) in the LT group and 98 (69.0%) in the LR group. The Kaplan-Meier curves for RFS and OS were not significantly different between the 2 treatments among the high-risk group (RFS, P = 0.079; OS, P = 0.755). Multivariable analysis showed that treatment type was not a prognostic factor for RFS and OS (P = 0.074 and 0.937, respectively).

Conclusions.

The advantage of LT over LR for RFS may be less evident among patients with high-risk MRI features.
Differentiating Urgent from Elective Cases Matters in Minority Populations: Developing an Ordinal “Desirability of Outcome Ranking” to Increase Granularity and Sensitivity of Surgical Outcomes Assessment
Authors: Jacobs Michael A , Schmidt Susanne , Hall Daniel E , Stitzenberg Karyn B , Kao Lillian S , Wang Chen-Pin , Manuel Laura S , Shireman Paula K
Published: June 2023

BACKGROUND:

Surgical analyses often focus on single or binary outcomes; we developed an ordinal Desirability of Outcome Ranking (DOOR) for surgery to increase granularity and sensitivity of surgical outcome assessments. Many studies also combine elective and urgent procedures for risk adjustment. We used DOOR to examine complex associations of race/ethnicity and presentation acuity.

STUDY DESIGN:

NSQIP (2013 to 2019) cohort study assessing DOOR outcomes across race/ethnicity groups risk-adjusted for frailty, operative stress, preoperative acute serious conditions, and elective, urgent, and emergent cases.

RESULTS:

The cohort included 1,597,199 elective, 340,350 urgent, and 185,073 emergent cases with patient mean age of 60.0 ± 15.8, and 56.4% of the surgeries were performed on female patients. Minority race/ethnicity groups had increased odds of presenting with preoperative acute serious conditions (adjusted odds ratio [aORs] range 1.22 to 1.74), urgent (aOR range 1.04 to 2.21), and emergent (aOR range 1.15 to 2.18) surgeries vs the White group. Black (aOR range 1.23 to 1.34) and Native (aOR range 1.07 to 1.17) groups had increased odds of higher/worse DOOR outcomes; however, the Hispanic group had increased odds of higher/worse DOOR (aOR 1.11, CI 1.10 to 1.13), but decreased odds (aORs range 0.94 to 0.96) after adjusting for case status; the Asian group had better outcomes vs the White group. DOOR outcomes improved in minority groups when using elective vs elective/urgent cases as the reference group.

CONCLUSIONS:

NSQIP surgical DOOR is a new method to assess outcomes and reveals a complex interplay between race/ethnicity and presentation acuity. Combining elective and urgent cases in risk adjustment may penalize hospitals serving a higher proportion of minority populations. DOOR can be used to improve detection of health disparities and serves as a roadmap for the development of other ordinal surgical outcomes measures. Improving surgical outcomes should focus on decreasing preoperative acute serious conditions and urgent and emergent surgeries, possibly by improving access to care, especially for minority populations.
Prevalence and Outcome of Adults with Congenital Heart Disease and Coronary Artery Disease
Authors: Li Haiyang , Yan Yan , Wang Shipan , Sun Mingyu , Qian Sichong , Xue Yuan , Zhang Hongjia
Published: June 2023

BACKGROUND

Little is known about the prevalence of outcome in patients with coronary artery disease (CAD) among adults with congenital heart disease (ACHD). The objectives of this study were to determine rates of ACHD and factors associated with outcomes among adults with CAD in a contemporary cohort within the China.

METHODS

Using pragmatic data from the Prospective Registry of the Current Status of Care for Patients with Coronary Artery Disease database, between January and May 2022, we stratified all CAD patients with comorbid ACHD or not. Using logistic regression method, we explored the risk factors associated with lower risk of mortality and stroke. We constructed a matching sub-cohort as sensitive analysis.

RESULTS

Of 10,517 evaluable patients 189 (1.8%) were with a diagnosis of ACHD, and were more female, more frequent with a history of atrial fibrillation, had a lower hemoglobin level at admission but less likely to have hypertension or smoking history than those without ACHD. In-hospital mortality before discharge was higher in patients with ACHD compared with no ACHD in the whole population (1.06% vs. 0.28%, p=0.05) and matched population (1.06% vs. 0.13%, p=0.04). Acute myocardial infarction (54.8%) represented the most common cause of death among all cohort, whereas 100% deaths among ACHD were due to ischemic stroke (2 cases).

CONCLUSIONS

ACHD was associated with a higher rate of mortality, which stroke complications contribute most. Future studies are needed to improve the acknowledge of underlying stroke mechanisms and prognosis in this special population.
Integrative Multi-omic Profiling of Two Human Decedents Receiving Pig Heart Xenografts Reveals Strong Perturbations in Early Immune-Cell and Cellular Metabolism Responses
Authors: Schmauch Eloi , Piening Brian , Xia Bo , Zhu Chenchen , Stern Jeffrey , Zhang Weimin , Dowdell Alexa , Loza Bao-Li , Mohebnasab Maede , Gragert Loren , Khalil Karen , Camellato Brendan , de Oliveira Michelli Faria , O’Brien Darragh , Weldon Elaina , Lin Xiangping , Gao Hui , Kagermazova Larisa , Kim Jacqueline , Loupy Alexandre , Heguy Adriana , Taylor Sarah , Zhu Florrie , Gao Sarah , Gandla Divya , Reddy Kriyana , Chang Andrew , Michael Basil , Jiang Lihua , Jian Ruiqi , Narula Navneet , Linna-Kuosmanen Suvi , Kaikkonen-Määttä Minna , Lorber Marc , Kellis Manolis , Tatapudi Vasishta , Ayares David , Griesemer Adam , Mangiola Massimo , Pass Harvey , Snyder Michael P. , Montgomery Robert A. , Boeke Jef D. , Keating Brendan J.
Published: June 2023

Background

Recent advances in xenotransplantation in living and decedent humans using pig xenografts have laid promising groundwork towards future emergency use and first in human trials. Major obstacles remain though, including a lack of knowledge of the genetic incompatibilities between pig donors and human recipients which may led to harmful immune responses against the xenograft or dysregulation of normal physiology. In 2022 two pig heart xenografts were transplanted into two brain-dead human decedents with a minimized immunosuppression regime, primarily to evaluate onset of hyper-acute antibody mediated rejection and sustained xenograft function over 3 days.

Methods

We performed multi-omic profiling to assess the dynamic interactions between the pig and human genomes in the first two pig heart-xenografts transplants into human decedents. To assess global and specific biological changes that may correlate with immune-related outcomes and xenograft function, we generated transcriptomic, lipidomic, proteomic and metabolomics datasets, across blood and tissue samples collected every 6 hours over the 3-day procedures.

Results

Single-cell datasets in the 3-day pig xenograft-decedent models show dynamic immune activation processes. We observe specific scRNA-seq, snRNA-seq and geospatial transcriptomic changes of early immune-activation leading to pronounced downstream T-cell activity and hallmarks of early antibody mediated rejection (AbMR) and/or ischemia reperfusion injury (IRI) in the first xenograft recipient. Using longitudinal multiomic integrative analyses from blood in addition to antigen presentation pathway enrichment, we also observe in the first xeno-heart recipient significant cellular metabolism and liver damage pathway changes that correlate with profound physiological dysfunction whereas, these signals are not present in the other xenograft recipient.

Conclusions

Single-cell and multiomics approaches reveal fundamental insights into early molecular immune responses indicative of IRI and/or early AbMR in the first human decedent, which was not evident in the conventional histological evaluations.
Broca’s area, variation and taxic diversity in earlyHomofrom Koobi Fora (Kenya)
Authors: Beaudet Amélie , Jager Edwin de
Published: June 2023

Because brain tissues rarely fossilize, pinpointing when and how modern human cerebral traits emerged in the hominin lineage is particularly challenging. The fragmentary nature of the fossil material, coupled with the difficulty of characterizing such a complex organ, have been the source of long-standing debates. Prominent among them is the uncertainties around the derived or primitive state of the brain organization in the earliest representatives of the genusHomo, more particularly in key areas such as the Broca’s area. By revisiting a particularly well-preserved fossil endocast from the Turkana basin (Kenya) attributed to earlyHomo, here we confirm that humans in Africa had a primitive organization of the Broca’s area ca. 1.9 million years ago. Additionally, our description of KNM-ER 3732 adds further information about the variation pattern of the inferior frontal gyrus in fossil hominins, with implications for earlyHomotaxic diversity (i.e., one or twoHomospecies at Koobi Fora) and the nature of the mechanisms involved in the emergence of derived cerebral traits.
Finding and exploring reproducible cell phenotypes with the Stemformatics data portal
Authors: Choi Jarny , Butcher Suzanne , Angel Paul , Bransfield Jack , Barry Jake , Faux Noel , Shaban Bobbie , Pillai Priyanka , Michalewicz Aleks , Wells Christine
Published: June 2023

Stemformatics is an established online data portal which hosts hundreds of curated gene expression datasets. It has been serving the stem cell research community for over a decade, by hosting transcriptional profiles of pluripotent and adult stem cells and their progeny from multiple tissues and derivation methods. The portal provides easy-to-use online tools to explore gene expression patterns in published data. In recent years, Stemformatics has shifted its focus from curation to collation and integration of public data with shared phenotypes. It now hosts several integrated expression atlases based on human myeloid cells, which allow for easy cross-dataset comparisons and discovery of emerging cell subsets and activation properties. The inclusion of laboratory-derived cell types enables users to benchmark their own data, to assist with cell-type standardisation or improve cell-derivation methods. The sample annotations have been greatly improved to enable better data integration, and the website has also undergone a major upgrade to modernise its visualisation tools. An application programming interface server also provides the data directly for computational users. Stemformatics is an open-source project and readily available at stemformatics.org.
Bacteriophage diet breadth is impacted by interactions between bacteria
Authors: Bisesi Ave T. , Möbius Wolfram , Nadell Carey , Hansen Eleanore G. , Bowden Steven D. , Harcombe William R.
Published: June 2023

Predators play a central role in shaping community structure, function, and stability. The degree to which bacteriophage predators (viruses that infect bacteria) evolve to be specialists with a single bacterial prey species versus generalists able to consume multiple types of prey has implications for their effect on microbial communities. The presence and abundance of multiple bacterial prey types can alter selection for phage generalists, but less is known about how interactions between prey shapes diet breadth in microbial systems. Using a phenomenological mathematical model of phage and bacterial populations, we find that the dominant phage strategy depends on prey ecology. Given a fitness cost for generalism, generalist predators maintain an advantage when prey species compete, while specialists dominate when prey are obligately engaged in cross-feeding interactions. We test these predictions in a synthetic microbial community with interacting strains ofEscherichia coliandSalmonella entericaby competing a generalist T5-like phage able to infect both prey against P22vir, anS. enterica-specific phage. Our experimental data conform to our modeling expectations when prey are competing or obligately mutualistic, although our results suggest that thein vitrocost of generalism is caused by a biological mechanism not represented in our model. Our work demonstrates that interactions between bacteria play a role in shaping ecological selection on diet breadth in bacteriophage and emphasizes the diversity of ways in which fitness trade-offs can manifest.
SPIDR: a highly multiplexed method for mapping RNA-protein interactions uncovers a potential mechanism for selective translational suppression upon cellular stress
Authors: Wolin Erica , Guo Jimmy K. , Blanco Mario R. , Perez Andrew A. , Goronzy Isabel N. , Abdou Ahmed A. , Gorhe Darvesh , Guttman Mitchell , Jovanovic Marko
Published: June 2023

RNA binding proteins (RBPs) play crucial roles in regulating every stage of the mRNA life cycle and mediating non-coding RNA functions. Despite their importance, the specific roles of most RBPs remain unexplored because we do not know what specific RNAs most RBPs bind. Current methods, such as crosslinking and immunoprecipitation followed by sequencing (CLIP-seq), have expanded our knowledge of RBP-RNA interactions but are generally limited by their ability to map only one RBP at a time. To address this limitation, we developed SPIDR (Split and Pool Identification of RBP targets), a massively multiplexed method to simultaneously profile global RNA binding sites of dozens to hundreds of RBPs in a single experiment. SPIDR employs split-pool barcoding coupled with antibody-bead barcoding to increase the throughput of current CLIP methods by two orders of magnitude. SPIDR reliably identifies precise, single-nucleotide RNA binding sites for diverse classes of RBPs simultaneously. Using SPIDR, we explored changes in RBP binding upon mTOR inhibition and identified that 4EBP1 acts as a dynamic RBP that selectively binds to 5’-untranslated regions of specific translationally repressed mRNAs only upon mTOR inhibition. This observation provides a potential mechanism to explain the specificity of translational regulation controlled by mTOR signaling. SPIDR has the potential to revolutionize our understanding of RNA biology and both transcriptional and post-transcriptional gene regulation by enabling rapid,de novodiscovery of RNA-protein interactions at an unprecedented scale.
Imidacloprid disrupts larval molting regulation and nutrient energy metabolism, causing developmental delay in honey beeApis mellifera
Authors: Li Zhi , Wang Yuedi , Qin Qiqian , Chen Lanchun , Dang Xiaoqun , Ma Zhengang , Zhou Zeyang
Published: June 2023

Imidacloprid is a global health threat that severely poisons the economically and ecologically important honeybee pollinator,Apis mellifera. However, its effects on developing bee larvae remain largely unexplored. Our pilot study showed that imidacloprid causes developmental delay in bee larvae, but the underlying toxicological mechanisms remain incompletely understood. In this study, we exposed bee larvae to imidacloprid at environmentally relevant concentrations of 0.7, 1.2, 3.1, and 377 ppb. There was a marked dose-dependent delay in larval development, characterized by reductions in body mass, width, and growth index. However, imidacloprid did not affect on larval survival and food consumption. The primary toxicological effects induced by elevated concentrations of imidacloprid (377 ppb) included inhibition of neural transmission gene expression, induction of oxidative stress, gut structural damage, and apoptosis, inhibition of developmental regulatory hormones and genes, suppression of gene expression levels involved in proteolysis, amino acid transport, protein synthesis, carbohydrate catabolism, oxidative phosphorylation, and glycolysis energy production. In addition, we found that the larvae may use antioxidant defenses and P450 detoxification mechanisms to mitigate the effects of imidacloprid. Ultimately, this study provides the first evidence that environmentally exposed imidacloprid can affect the growth and development of bee larvae by disrupting molting regulation and limiting the metabolism and utilization of dietary nutrients and energy. These findings have broader implications for studies assessing pesticide hazards in other juvenile animals.
Catalpol inhibits HHcy-induced EndMT in endothelial cells by modulating ROS/NF-κB signaling
Authors: Wu Chengyan , Zhao Rusheng , Li Yuanhao , Li Peixia , Liu Huibing , Wang Libo , Wang Xuehui
Published: June 2023

Background

Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis (AS), the molecular mechanisms of its pathogenesis are not fully understood. Endothelial dysfunction is the key initiating link in AS. However, whether endothelial-mesenchymal transition (EndMT) is involved in the regulation of HHcy-induced endothelial dysfunction and the role of catalpol in it remain unexplored.

Methods and Results

In vitroHHcy-treated primary human umbilical vein endothelial cells (HUVECs) were used to construct a model of endothelial dysfunction, and the antioxidants N-acetylcysteine (NAC) and catalase alcohol were administered. The endothelial dysfunction model was constructed by observing cell morphological changes, measuring intracellular reactive oxygen species (ROS) content, quantifying EndMT marker proteins (VE-cadherin, α-SMA, N-cadherin) and p-p65 and p65 protein expression by western blot, and detecting VE-cadherin and α-SMA fluorescence intensity by immunofluorescence.In vivoC57BL/6N mice were given a diet fed with 4.4% high methionine chow to construct a HHcy mice model and were treated with catalpol. The model was further validated by measuring the concentration of homocysteinemia (Hcy) in mice, HE and Masson staining to observe the pathological changes in the endothelium of aortic roots, immunohistochemistry to detect the expression of EndMT marker protein, immunofluorescence to detect the fluorescence intensity of p-p65, and fluorescent probe method to detect the content of ROS in the endothelium of aorta. The results showed that catalpol significantly inhibited HHcy-induced endothelial cell morphological transformation, reduced HHcy-induced increase in intracellular ROS content and α-SMA, N-cadherin, p-p65 protein expression, increased HHcy-induced decrease in VE-cadherin, CD31 protein expression, and was able to protect against endothelial pathological changes in the aortic root and reduce aortic endothelial ROS content.

Conclusions

Catalpol inhibits HHcy-induced EndMT, and the underlying mechanism may be related to the ROS/NF-κB signaling pathway. Catalpol may be a potential drug for the treatment of HHcy-related AS.
Multiple sex chromosomes ofYponomeutaermine moths suggest a role of sexual antagonism in sex chromosome turnover in Lepidoptera
Authors: Irena Provazníková , Martina Dalíková , Anna Voleníková , Peter Roessingh , Ken Sahara , Jan Provazník , František Marec , Petr Nguyen
Published: June 2023

Sex chromosome-autosome fusions give rise to neo-sex chromosomes, which provide an insight into early evolution of sex chromosomes and drivers of chromosomal fusions. While sex chromosome-autosome fusions are scarce in vertebrates with female heterogamety (♀ZW/♂ZZ), they are common in moths and butterflies (Lepidoptera), the most species rich group with heterogametic females. This contradicts theoretical model that assumes chromosome fusions to be random and predicts them to be rare in taxa with high chromosome number such as Lepidoptera. In the present study we analyzed sex chromosomes in nine ermine moths of the genusYponomeuta(Yponomeutidae) and their two outgroups,Teinoptila gutella(Yponomeutidae) andPlutella xylostella(Plutellidae). We employed genomicin situhybridization to identify sex chromosomes and used a custom designed microarray to identify Z-linked genes. Our results confirmed a multiple sex chromosome system Z1Z2W to be present inT. gutellaand allYponomeutaspp. except forY. tokyonella. The multiple sex chromosome system resulted from a fusion between the W chromosome and autosome homeologous to theBombyx morichromosome 2 (BmChr2). The BmChr2 bears a cluster of genes with ovary-specific expression which suggests that sexually antagonistic selection could have driven fixation of the fusion in a common ancestor ofYponomeutaandTeinoptilagenera. We hypothesize that sex chromosome turnover in Lepidoptera could be driven by sexual antagonism.
TaxaHFE: A machine learning approach to collapse microbiome datasets using taxonomic structure
Authors: Oliver Andrew , Kay Matthew , Lemay Danielle G.
Published: June 2023

Motivation

Biologists increasingly turn to machine learning models not just to predict, but to explain. Feature reduction is a common approach to improve both performance and interpretability of models. However, some biological data sets, such as microbiome data, are inherently organized in a taxonomy, but these hierarchical relationships are not leveraged during feature reduction. We sought to design a feature engineering algorithm to exploit relationships in hierarchically organized biological data.

Results

We designed an algorithm, called TaxaHFE, to collapse information-poor features into their higher taxonomic levels. We applied TaxaHFE to six previously published datasets and found, on average, a 90% reduction in the number of features (s.d = 5.1%) compared to using the most complete taxonomy. Using machine learning to compare the most resolved taxonomic level (i.e., species) against TaxaHFE-preprocessed features, models based on TaxaHFE features achieved an average increase of 3.47% in receiver operator curve area under the curve (ROC-AUC). Compared to other hierarchical feature engineering implementations, TaxaHFE introduces the novel ability to consider both categorical and continuous response variables to inform the feature set collapse. Importantly, we find TaxaHFE’s ability to reduce hierarchically organized features to a more information-rich subset increases the interpretability of models.

Availability and Implementation

TaxaHFE is available as a Docker image and as R code athttps://github.com/aoliver44/taxaHFE.
Approximate Bayesian computational methods to estimate the strength of divergent selection in population genomics models
Authors: Lukaszewicz Martyna , Salia Ousseini Issaka , Hohenlohe Paul A. , Buzbas Erkan O.
Published: June 2023

Statistical estimation of parameters in large models of evolutionary processes using SNP data is often too computationally inefficient to pursue using exact model likelihoods. Approximate Bayesian Computation (ABC) to perform statistical inference about parameters of large models takes the advantage of simulations to bypass direct evaluation of model likelihoods. We use forward-in-time simulations of a mechanistic model of divergent selection with variable migration rates, modes of reproduction (sexual, asexual), length and number of migration-selection cycles, and investigate the computational feasibility of ABC to perform statistical inference and study the quality of estimates on the position of loci under selection and the strength of selection. We evaluate usefulness of summary statistics well-known to capture the strength of selection, and assess their informativeness under divergent selection. We also evaluate the effect of genetic drift with respect to an idealized deterministic model with single-locus selection. We discuss the role of the recombination rate as a confounding factor in estimating the strength of divergent selection, and we answer the question for which part of the parameter space of the model we recover strong signal for estimating the selection and make recommendations which summary statistics perform well in estimating selection.
Cleaving DNA with DNA: cooperative tuning of structure and reactivity driven by copper ions
Authors: Dantu Sarath Chandra , Khalil Mahdi , Bria Marc , Saint-Pierre Christine , Gasparutto Didier , Sicoli Giuseppe
Published: June 2023

Abstract/Summary

A copper-dependent self-cleaving DNA (DNAzyme or dexoxyribozyme) previously isolated byin vitroselection has been analyzed by a combination of Molecular Dynamics simulations and advanced EPR/ESR spectroscopy, providing insights on the structural and mechanistic features of the cleavage reaction at unprecedented resolution. The minimized 46-nucleotide deoxyribozyme forms duplex and triplex substructures that flank a highly conserved catalytic core. The self-cleaving construct forms a bimolecular complex that has a distinct substrate and enzyme domains. Cleavage of the substrate is directed at one of two adjacent nucleotides and proceedsviaan oxidative cleavage mechanism that is unique to the position cleaved. The use of isotopologues of nucleotides allowed us to provide atomic resolution for the copper-substrate complex. The spectroscopic analysis overcomes the major drawbacks related to the ‘metal-soup’ scenario, also known as ‘super-stoichiometric’ ratios of cofactorsversussubstrate, conventionally required for the cleavage reaction within those nucleic acids-based enzymes. Our results pave the way for analysis on mixtures where metals/lanthanides are used as cofactors, having demonstrated that our approach may reach resolution of single nucleotide and beyond. Furthermore, the insertion of cleavage reaction within more complex architectures is now a realistic option towards the applicability of spectroscopic studies, bothin vitroandin vivomatrices.
Effects of sequence-dependent non-native interactions in equilibrium and kinetic folding properties of knotted proteins
Authors: Especial João N. C. , Faísca Patrícia F. N.
Published: June 2023

Determining the role of non-native interactions in folding dynamics, kinetics and mechanisms is a classical problem in protein folding. More recently, this question has witnessed a renewed interest in light of the hypothesis that knotted proteins require the assistance of non-native interactions to fold efficiently. Here, we conducted extensive equilibrium and kinetic Monte Carlo simulations of a simple off-lattice C-alpha model to explore the role of non-native interactions in the thermodynamics and kinetics of three proteins embedding a trefoil knot in their native structure. We find that equilibrium knotted conformations are stabilized by non-native interactions that are non-local, and proximal to native ones, thus enhancing them. Additionally, non-native interactions increase the knotting frequency at high temperature, and in partially folded conformations below the transition temperature. While non-native interactions clearly enhance the efficiency of the transition from an unfolded conformation to a partially folded knotted one, they are not required to efficiently fold a knotted protein. Indeed, a native centric interaction potential drives the most efficient folding transition, provided that the simulation temperature is well below the transition temperature of the considered model system.