bluuebunny/crossref_metadata_2025 huggingface dataset:
Propensity-Score Matched Analysis of Three Years Survival of Trans Carotid Artery Revascularization Versus Carotid Endarterectomy in the Vascular Quality Initiative Medicare-Linked Database
Authors: Zarrintan Sina , Elsayed Nadin , Patel Rohini J. , Clary Bryan , Goodney Philip P. , Malas Mahmoud B.
Published: July 2023

Objective:

Carotid endarterectomy (CEA) remains the gold standard procedure for carotid revascularization. Transfemoral carotid artery stenting (TFCAS) was introduced as a minimally invasive alternative procedure in patients who are at high risk for surgery. However, TFCAS was associated with an increased risk of stroke and death compared to CEA.

Background:

Transcarotid artery revascularization (TCAR) has outperformed TFCAS in several prior studies and has shown similar perioperative and 1-year outcomes compared with CEA. We aimed to compare the 1-year and 3-year outcomes of TCAR versus CEA in the Vascular Quality Initiative (VQI)-Medicare-Linked [Vascular Implant Surveillance and Interventional Outcomes Network (VISION)] database.

Methods:

The VISION database was queried for all patients undergoing CEA and TCAR between September 2016 to December 2019. The primary outcome was 1-year and 3-year survival. One-to-one propensity-score matching (PSM) without replacement was used to produce 2 well-matched cohorts. Kaplan-Meier estimates, and Cox regression was used for analyses. Exploratory analyses compared stroke rates using claims-based algorithms for comparison.

Results:

A total of 43,714 patients underwent CEA and 8089 patients underwent TCAR during the study period. Patients in the TCAR cohort were older and were more likely to have severe comorbidities. PSM produced two well-matched cohorts of 7351 pairs of TCAR and CEA. In the matched cohorts, there were no differences in 1-year death [hazard ratio (HR)=1.13; 95% CI, 0.99–1.30; P=0.065]. At 3-years, TCAR was associated with slight increased risk of death (HR=1.16; 95% CI, 1.04–1.30; P=0.008). When stratifying by initial symptomatic presentation, the increased 3-year death associated with TCAR persisted only in symptomatic patients (HR=1.33; 95% CI, 1.08–1.63; P=0.008). Exploratory analyses of postoperative stroke rates using administrative sources suggested that validated measures of claims-based stroke ascertainment are necessary.

Conclusions:

In this large multi-institutional PSM analysis with robust Medicare-linked follow-up for survival analysis, the rate of death at 1 year was similar in TCAR and CEA regardless of symptomatic status. The slight increase in the risk of 3-year death in symptomatic patients undergoing TCAR is likely confounded by more severe comorbidities despite matching. A randomized controlled trial comparing TCAR to CEA is necessary to further determine the role of TCAR in standard-risk patients requiring carotid revascularization.
Astrocyte endfeet may theoretically act as valves to convert pressure oscillations to glymphatic flow
Authors: Bork Peter A. R. , Ladrón-de-Guevara Antonio , Christensen Anneline H. , Jensen Kaare H. , Nedergaard Maiken , Bohr Tomas
Published: July 2023

The glymphatic system of cerebrospinal fluid transport through the perivascular spaces of the brain has been implicated in metabolic waste clearance, neurodegenerative diseases and in acute neurological disorders such as stroke and cardiac arrest. In other biological low-pressure fluid pathways such as in veins and the peripheral lymphatic system, valves play an important role in ensuring the flow direction. Though fluid pressure is low in the glymphatic system and directed bulk flow has been measured in pial and penetrating perivascular spaces, no valves have yet been identified. Valves, which asymmetrically favour forward flow to backward flow, would imply that the considerable oscillations in blood and ventricle volumes seen in magnetic resonance imaging could cause directed bulk flow. Here, we propose that astrocyte endfeet may act as such valves using a simple elastic mechanism. We combine a recent fluid mechanical model of viscous flow between elastic plates with recent measurements of
in vivo
elasticity of the brain to predict order of magnitude flow-characteristics of the valve. The modelled endfeet are effective at allowing forward while preventing backward flow.
Cooperative melting in double-stranded peptide chains through local mechanical interactions
Authors: Bellino Luca , Florio Giuseppe , Goriely Alain , Puglisi Giuseppe
Published: July 2023

The separation of double-stranded peptide chains can occur in two ways: cooperatively or non-cooperatively. These two regimes can be driven either by chemical or thermal effects, or through non-local mechanical interactions. Here, we show explicitly that local mechanical interactions in biological systems may regulate the stability, the reversibility, and the cooperative/non-cooperative character of the debonding transition. We show that this transition is characterized by a single parameter depending on an internal length scale. Our theory describes a wide range of melting transitions found in biological systems such as protein secondary structures, microtubules and tau proteins, and DNA molecules. In these cases, the theory gives the critical force as a function of the chain length and its elastic properties. Our theoretical results provide quantitative predictions for known experimental effects that appear in different biological and biomedical fields.
Surface texture heterogeneity in maculated bird eggshells
Authors: Attard Marie R. G. , Bowen James , Portugal Steven J.
Published: July 2023

Many of the world's 10 000 bird species lay coloured or patterned eggs. The large diversity of eggshell patterning among birds, achieved through pigment, has been attributed to a few selective agents such as crypsis, thermoregulation, egg recognition, mate signalling, egg strength and protecting the embryo from UV. Pigmentation may influence the texture of eggshells, which in turn may be important for dealing with water and microbes. We measured surface roughness (Sa, nm), surface skewness (Ssk) and surface kurtosis (Sku), which describe different aspects of surface texture, across 204 bird species with maculated (patterned) eggs and 166 species with immaculate (non-patterned) eggs. Using phylogenetically controlled analyses, we tested whether maculated eggshells have different surface topography between the foreground colour and background colour, and between the background colour of maculated eggshells and the surface of immaculate eggshells. Secondly, we determined to what extent variation in eggshell pigmentation of the foreground and background colour is determined by phylogenetic relatedness, and whether certain life-history traits are important predictors of eggshell surface structure. We show that the surface of maculated eggs consists of a rougher foreground pigment compared to the background pigment across 71% of the 204 bird species (54 families) investigated. Species that lay immaculate eggs showed no difference in surface roughness, kurtosis or skewness compared to background pigment of maculated eggs. The difference in eggshell surface roughness between foreground and background pigmentation was greater among species that occupied dense habitats, such as forests with closed canopies, compared to those that nest in open and semi-open habitats (e.g. cities, deserts, grasslands, open shrubland and seashores). Among maculated eggs, foreground texture was correlated with habitat, parental care, diet, nest location, avian group and nest type, while background texture was correlated with clutch size, annual temperature, development mode and annual precipitation. Surface roughness among immaculate eggs was greatest for herbivores, and species that have larger clutch sizes. Together, this suggests that multiple life-history traits have influenced the evolution of eggshell surface textures in modern birds.
Animalistic slurs increase harm by changing perceptions of social desirability
Authors: Enock Florence E. , Over Harriet
Published: July 2023

In propaganda and hate speech, target groups are often compared to dangerous and disgusting animals. Exposure to these animalistic slurs is thought to increase endorsement of intergroup harm but the mechanism by which this happens remains unclear. Across two pre-registered and highly powered studies, we examined how animalistic language influences the cultural transmission of beliefs about target groups. In line with previous work, we found that describing a novel political group with animalistic slurs increased the extent to which participants endorsed harm towards them. Importantly, reading animalistic slurs did not influence the extent to which participants believed the target group possessed uniquely human qualities. Rather, the animalistic slurs influenced endorsement of harm by making the target group appear more undesirable. These findings offer a novel perspective into the nature of dehumanization and new insights into how hate speech functions.
The swim-and-sink behaviour of copepods: a revisit to mechanical power requirement and a new hypothesis on function
Authors: Jiang Houshuo
Published: July 2023

Many copepods display a swim-and-sink behaviour, which is not energetically efficient but probably aids in perceiving and capturing diatom chains. Here, computational fluid dynamics was employed to calculate the mechanical power required by a negatively buoyant, self-propelled copepod in swim-and-sink versus hovering. The results show that upward swim-and-sink about a fixed depth always demands more power than hovering. Subsequently, high-speed microscale imaging was employed to observe the copepod
Centropages
sp. in swim-and-sink, specifically its encounter and handling of diatom chains for capture, along with the measured alternating swimming and sinking currents imposed by the swim-and-sink copepod. The findings suggest that during upward swimming, the copepod uses its swimming current to scan the fluid for detecting embedded diatom chains, presumably through chemoreception. Once a diatom chain is perceived, the copepod sinks and uses its sinking current to manipulate the orientation of the diatom chain before swimming upward to capture it. Overall, these results propose a hypothesis that swim-and-sink is an innate behaviour that assists copepods in perceiving and manoeuvring diatom chains for capture. In contrast with near-spherical algae, diatom chains predominately exhibit a horizontal orientation in the ocean, necessitating vertically oriented copepods to possess a handling behaviour that manoeuvres diatom chains for capture.
Distillation of non-locality in porous solids
Authors: Patnaik Sansit , Jokar Mehdi , Ding Wei , Semperlotti Fabio
Published: July 2023

Non-local interactions are intrinsic to multiscale heterogeneous solids. The strength of the interactions exhibits a position-dependent character whose spatial distribution strongly correlates with the underlying microstructure. In this work, a variable-order fractional calculus-based framework to distill the position-dependent non-local effects is developed. By considering the example of porous plates, theoretical and numerical analyses will illustrate the ability of variable-order mechanics to enable parsimonious and causal models via a synthetic variable-order map that naturally measures the heterogeneous non-locality induced by the microstructure; in other terms, the non-classical role of the microstructure in determining the macroscopic response. The characteristic measure for non-locality, different from the local entanglement resulting from the porosity map, allows distillation of the macroscopic non-locality, analogous to quantum non-locality distillation. The macroscopic distillation also enables the additivity of the order map, that is the ability of assembled order maps to capture the response of combined porous plates.
Viscous froth model applied to multiple topological transformations of bubbles flowing in a channel: three-bubble case
Authors: Torres-Ulloa Carlos , Grassia Paul
Published: July 2023

A two-dimensional foam system comprised of three bubbles is studied via dynamic simulations with the viscous froth model. The bubbles are arranged in a staircase configuration and move along a channel due to an imposed driving back pressure. Depending on the bubble size relative to channel size, the three-bubble system can undergo topological transformations (as for a simpler staircase structure, known as the simple lens) or it can reach a geometrically invariant migrating state (as for an infinite staircase structure). A methodology used previously determined the system evolution up to the first topological transformation, but evolution beyond this was not studied before. To address this, unsteady state three-bubble simulations are realized here, extending beyond the first transformation. For sufficiently high imposed back pressures, a sequence of topological transformations occurs before a steadily migrating shape is reached, typically in a topology such that an equal number of films connect to both channel walls.
The density and pressure of helium nano-bubbles encapsulated in silicon
Authors: Pyper N. C. , Thom A. J. W. , Whelan Colm T.
Published: July 2023

The

1

s
2

→
1
s
2
p

(
1

P
)

excitation in compressed helium atoms in either the bulk material or encapsulated in a bubble is shifted to energies higher than in the free atom. For bulk helium, energy shifts predicted from non-empirical electronic structure computations are in excellent agreement with experimentally determined values. However, there are significant discrepancies both between the results of experiments on different bubbles and between these and the well established descriptions of the bulk. A critique is presented of previous analyses of earlier scanning transmission electron microscope measurements that are untrustworthy because the density dependence of the electron impact excitation cross section was neglected. Experimental electron energy loss data from an earlier study of helium encapsulated in silicon are reanalysed and it is shown that the properties of the helium in these bubbles do not differ significantly from those in the bulk, thereby enabling the densities in the bubbles to be determined. These enable bubble pressures to be deduced from a well established experimentally derived equation of state. It is shown that the errors of up to 80% in the incorrectly determined densities are greatly magnified in the predicted pressures which can be too large by factors of over seven.
Confusion will be my epitaph: genome-scale discordance stifles phylogenetic resolution of Holothuroidea
Authors: Mongiardino Koch Nicolás , Tilic Ekin , Miller Allison K. , Stiller Josefin , Rouse Greg W.
Published: July 2023

Sea cucumbers (Holothuroidea) are a diverse clade of echinoderms found from intertidal waters to the bottom of the deepest oceanic trenches. Their reduced skeletons and limited number of phylogenetically informative traits have long obfuscated morphological classifications. Sanger-sequenced molecular datasets have also failed to constrain the position of major lineages. Noteworthy, topological uncertainty has hindered a resolution for Neoholothuriida, a highly diverse clade of Permo-Triassic age. We perform the first phylogenomic analysis of Holothuroidea, combining existing datasets with 13 novel transcriptomes. Using a highly curated dataset of 1100 orthologues, our efforts recapitulate previous results, struggling to resolve interrelationships among neoholothuriid clades. Three approaches to phylogenetic reconstruction (concatenation under both site-homogeneous and site-heterogeneous models, and coalescent-aware inference) result in alternative resolutions, all of which are recovered with strong support and across a range of datasets filtered for phylogenetic usefulness. We explore this intriguing result using gene-wise log-likelihood scores and attempt to correlate these with a large set of gene properties. While presenting novel ways of exploring and visualizing support for alternative trees, we are unable to discover significant predictors of topological preference, and our efforts fail to favour one topology. Neoholothuriid genomes seem to retain an amalgam of signals derived from multiple phylogenetic histories.
Are non-lactose-fermenting Escherichia coli important diarrhoeal pathogens in children and adults?
Authors: Sharma Bhawna , Modgil Vinay , Mahindroo Jaspreet , Kumar Ajay , Kaur Varpreet , Narayan Chandradeo , Verma Ritu , Mohan Balvinder , Taneja Neelam
Published: July 2023

Introduction. Diarrhoeagenic

Escherichia coli

(DEC) remains one of the major causes of acute diarrhoea episodes in developing countries. The percentage of acute diarrhoea cases caused by DEC is 30–40 % in these countries. Approximately 10% of

E. coli

isolates obtained from stool specimens have been reported to be non-lactose-fermenting (NLF). The available literature is sparse regarding the pathogenicity of NLF

E. coli

causing infectious diarrhoea.

Aim. We aimed to elucidate the importance of NLF

E. coli

in causing diarrhoea in both adults and children by detecting various DEC pathotypes among NLF

E. coli

in stool samples taken from gastroenteritis cases.

Material and Methods. A total of 376 NLF

E. coli

isolates from 3110 stool samples from diarrhoea/gastroenteritis patients were included in the study. Up to three NLF colonies that were not confirmed as

Vibrio cholerae

,

Aeromonas

spp.,

Salmonella

spp. or

Shigella

spp., but were identified as

E. coli

using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), were carefully picked up from each MacConkey agar plate and then meticulously streaked onto freshly prepared, sterilized nutrient agar plates, and biochemical reactions were conducted. Multiplex PCR was conducted for the EAEC, EPEC, ETEC and EHEC pathotypes and PCR for the ipaH gene was conducted for EIEC. The disc diffusion method was used for antibiotic sensitivity testing.

Results. Using multiplex PCR and ipaH PCR, a total of 63 pathotypes of DEC were obtained, with EAEC being the most predominant (n=31) followed by EIEC (n=22), EPEC (n=8) and ETEC (n=2). To further differentiate EIEC from

Shigella

, additional biochemical tests were performed, including acetate utilization, mucate and salicin fermentation, and aesculin hydrolysis. Antimicrobial susceptibility testing (AST) showed that maximum resistance was seen against ciprofloxacin (82.5 %) followed by ampicillin (77.8 %) and cotrimoxazole (68.2 %), and minimum resistance was seen against ertapenem (4.8 %).

Conclusion. In our study two pathotypes (EAEC, EIEC) were predominant among NLF

E. coli

and these were not only important aetiological agents in children, but also in adults. Our study also sheds light on the epidemiology of EIEC, which is one of the most neglected DEC pathotypes, as hardly any microbiological laboratories process NLF

E. coli

for EIEC.
Holtiella tumoricola gen. nov. sp. nov., isolated from a human clinical sample
Authors: Allen-Vercoe Emma , Daigneault Michelle C. , Vancuren Sarah J. , Cochrane Kyla , O’Neal Lindsey L. , Sankaranarayanan Krithivasan , Lawson Paul A.
Published: July 2023

The diversity of bacteria associated with biopsy material obtained from patients with colorectal cancer was investigated using culture techniques. A novel bacterium, strain CC70AT, was isolated by diluting a sample of homogenized tissue in anaerobic medium, and then plating to yield a pure culture. Strain CC70AT was a Gram-positive, strictly anaerobic, motile, rod-shaped bacterium. Formate, but not acetate, was a fermentative end-product from growth in peptone–yeast extract and peptone–yeast–glucose broth. The G+C content of DNA from strain CC70AT was 34.9 mol%. 16S rRNA gene sequence analysis revealed that the isolate was part of the phylum

Bacillota

. The closest described relatives of strain CC70AT were

Cellulosilyticum lentocellum

(93.3 %) and

Cellulosilyticum ruminicola

(93.3 and 91.9% sequence similarity across 16S rRNA gene, respectively). According to the data obtained in this work, strain CC70AT represents a novel bacterium belonging to a new genus for which the name Holtiella tumoricola gen. nov., sp. nov. is proposed. The type strain for our described novel species is CC70AT (=DSM 27931T= JCM 30568T).
A highly discriminatory RNA strand-specific assay to facilitate analysis of the role of cis-acting elements in foot-and-mouth disease virus replication
Authors: Dobson Samuel J. , Ward Joseph C. , Herod Morgan R. , Rowlands David J. , Stonehouse Nicola J.
Published: July 2023

A corrigendum of this article has been published full details can be found at https://doi.org/10.1099/jgv.0.001993

Foot-and-mouth-disease virus (FMDV), the aetiological agent responsible for foot-and-mouth disease (FMD), is a member of the genus Aphthovirus within the family Picornavirus. In common with all picornaviruses, replication of the single-stranded positive-sense RNA genome involves synthesis of a negative-sense complementary strand that serves as a template for the synthesis of multiple positive-sense progeny strands. We have previously employed FMDV replicons to examine viral RNA and protein elements essential to replication, but the factors affecting differential strand production remain unknown. Replicon-based systems require transfection of high levels of RNA, which can overload sensitive techniques such as quantitative PCR, preventing discrimination of specific strands. Here, we describe a method in which replicating RNA is labelled in vivo with 5-ethynyl uridine. The modified base is then linked to a biotin tag using click chemistry, facilitating purification of newly synthesised viral genomes or anti-genomes from input RNA. This selected RNA can then be amplified by strand-specific quantitative PCR, thus enabling investigation of the consequences of defined mutations on the relative synthesis of negative-sense intermediate and positive-strand progeny RNAs. We apply this new approach to investigate the consequence of mutation of viral cis-acting replication elements and provide direct evidence for their roles in negative-strand synthesis.
Nasopharyngeal competition dynamics are likely to be altered following vaccine introduction: bacteriocin prevalence and diversity among Icelandic and Kenyan pneumococci
Authors: Butler Madeleine E. B. , Jansen van Rensburg Melissa J. , Karani Angela , Mvera Benedict , Akech Donald , Akter Asma , Forrest Calum , van Tonder Andries J. , Quirk Sigríður J. , Haraldsson Gunnsteinn , Bentley Stephen D. , Erlendsdóttir Helga , Haraldsson Ásgeir , Kristinsson Karl G. , Scott J. Anthony G. , Brueggemann Angela B.
Published: July 2023

Bacteriocins are antimicrobial peptides produced by bacteria to inhibit other bacteria in the surrounding environment.

Streptococcus pneumoniae

is a leading cause of disease worldwide and colonises the healthy human nasopharynx, where it competes for space and nutrients. Pneumococcal conjugate vaccines have reduced the incidence of disease, but they also restructure the bacterial population, and this restructuring likely alters the nasopharyngeal competition dynamics. Here, the distribution of bacteriocins was examined in over 5000 carriage and disease-causing pneumococci from Iceland and Kenya, recovered before and after the introduction of pneumococcal vaccination. Overall, up to eleven different bacteriocin gene clusters were identified per pneumococcus. Significant differences in the prevalence of bacteriocins were observed before and after vaccine introduction, and among carriage and disease-causing pneumococci, which were largely explained by the bacterial population structure. Genetically similar pneumococci generally harboured the same bacteriocins although sometimes different repertoires of bacteriocins were observed, which suggested that horizontal transfer of bacteriocin clusters had occurred. These findings demonstrated that vaccine-mediated changes in the pneumococcal population altered the prevalence and distribution of bacteriocins. The consequences of this for pneumococcal colonisation and disease remain to be determined.
The ratio between SARS-CoV-2 RNA viral load and culturable viral titer differs depending on stage of infection
Authors: Porter Michael K. , Viloria Winnett Alexander , Hao Linhui , Shelby Natasha , Reyes Jessica A. , Schlenker Noah W. , Romano Anna E. , Tognazzini Colton , Feaster Matthew , Goh Ying-Ying , Gale Michael , Ismagilov Rustem F.
Published: July 2023

Analysis of incident, longitudinal RNA viral loads in saliva and nasal swabs and culturable viral titers in nasal swabs collected twice-daily by a tricenarian male infected with SARS-CoV-2 revealed the ratio between viral load and viral titer can be five orders of magnitude higher during early infection than late infection.
Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 93 risk genes for Alzheimer’s disease dementia
Authors: Guo Shuyi , Yang Jingjing
Published: July 2023

Background

Transcriptome-wide association study (TWAS) is an influential tool for identifying novel genes associated with complex diseases, where their genetic effects may be mediated through transcriptome. TWAS utilizes reference genetic and transcriptomic data to estimate genetic effect sizes on expression quantitative traits of target genes (i.e., effect sizes of a broad sense of expression quantitative trait loci, eQTL). These estimated effect sizes are then employed as variant weights in burden gene-based association test statistics, facilitating the mapping of risk genes for complex diseases with genome-wide association study (GWAS) data. However, most existing TWAS of Alzheimer’s disease (AD) dementia have primarily focused oncis-eQTL, disregarding potentialtrans-eQTL. To overcome this limitation, we applied the Bayesian Genome-wide TWAS (BGW-TWAS) method which incorporated bothcis- andtrans-eQTL of brain and blood tissues to enhance mapping risk genes for AD dementia.

Methods

We first applied BGW-TWAS to the Genotype-Tissue Expression (GTEx) V8 dataset to estimatecis- andtrans-eQTL effect sizes of the prefrontal cortex, cortex, and whole blood tissues. Subsequently, estimated eQTL effect sizes were integrated with the summary data of the most recent GWAS of AD dementia to obtain BGW-TWAS (i.e., gene-based association test) p-values of AD dementia per tissue type. Finally, we used the aggregated Cauchy association test to combine TWAS p-values across three tissues to obtain omnibus TWAS p-values per gene.

Results

We identified 37 genes in prefrontal cortex, 55 in cortex, and 51 in whole blood that were significantly associated with AD dementia. By combining BGW-TWAS p-values across these three tissues, we obtained 93 significant risk genes including 29 genes primarily due totrans-eQTL and 50 novel genes. Utilizing protein-protein interaction network and phenotype enrichment analyses with these 93 significant risk genes, we detected 5 functional clusters comprised of both known and novel AD risk genes and 7 enriched phenotypes.

Conclusion

We applied BGW-TWAS and aggregated Cauchy test methods to integrate bothcis- andtrans-eQTL data of brain and blood tissues with GWAS summary data to identify risk genes of AD dementia. The risk genes we identified provide novel insights into the underlying biological pathways implicated in AD dementia.
The Implementation and Evaluation of the James Hakim Leadership Development Program in Africa: process, lessons Learned, and Feedback from the Participants
Authors: Mubuuke Aloysius Gonzaga , Bercasio Alyssa , Yeboah Georgina , Kiguli-Malwadde Elsie , Kazembe Abigail , Forster Maeve , von Zinkernagel Deborah , Anderson Ellie , Sam-Woode Clara E. , Nkomazana Oathokwa , Mukwato Patricia Katowa , Reid Michael J A , de Villiers Marietjie
Published: July 2023

Background

Effective leadership is crucial for improving the quality of health professionals trained in Sub-Saharan Africa (SSA). However, many health professions training institutions lack formal faculty mentorship programs for leaders, leaving faculty to learn on the job without formal support. To address this gap, the African Forum for Research and Education in Health (AFREhealth) developed an innovative leadership capacity-strengthening program, named after the late educator and research, James Hakim. Objective: This article describes the design and implementation of the AFREhealth leadership training program and how it could bridge the leadership skills gap in health professions education in SSA. The objective of the article is to describe the program’s implementation process, share the experiences of participants, and discuss lessons learned.

Methods

The AFREhealth leadership training program was developed through consultative meetings, after a landscape review of existing leadership training programs. The program was designed to be delivered virtually over a 12-week period, and the curriculum included modules on leadership styles and personality, mentorship, change management, conflict management, budgeting, resource mobilization, building partnerships, inter-professional education & collaborative practice, and working on inter-professional teams. Training activities included weekly workshops, small group discussions, readings, reflective sessions with senior health leaders/experts, focused mentorship sessions, and a guided project design capstone. Surveys were conducted to obtain feedback from participants and assess the program’s impact on their ongoing leadership roles in their institutions.

Results

The leadership training program was implemented twice in a 20-month period, with 68 trainees completing the program. Participants reported increased knowledge, skills, and confidence in attaining key leadership competencies. The virtual delivery of the training allowed for a wide pool of applicants to participate, and the curriculum was designed to be adaptable for other institutions.

Conclusion

The AFREhealth leadership development program demonstrated the need for mentoring health professions education leaders in Africa and the effectiveness of virtual training methods. The innovative curriculum and delivery model provide a valuable resource for other institutions seeking to build leadership capacity in health professions education.
Towards Medical Billing Automation: NLP for Outpatient Clinician Note Classification
Authors: Crowson Matthew G. , Alsentzer Emily , Fiskio Julie , Bates David W.
Published: July 2023

Objectives

Our primary objective was to develop a natural language processing approach that accurately predicts outpatient Evaluation and Management (E/M) level of service (LoS) codes using clinicians’ notes from a health system electronic health record. A secondary objective was to investigate the impact of clinic note de-identification on document classification performance.

Methods

We used retrospective outpatient office clinic notes from four medical and surgical specialties. Classification models were fine-tuned on the clinic notes datasets and stratified by subspecialty. The success criteria for the classification tasks were the classification accuracy and F1-scores on internal test data. For the secondary objective, the dataset was de-identified using Named Entity Recognition (NER) to remove protected health information (PHI), and models were retrained.

Results

The models demonstrated similar predictive performance across different specialties, except for internal medicine, which had the lowest classification accuracy across all model architectures. The models trained on the entire note corpus achieved an E/M LoS CPT code classification accuracy of 74.8% (CI 95: 74.1-75.6). However, the de-identified note corpus showed a markedly lower classification accuracy of 48.2% (CI 95: 47.7-48.6) compared to the model trained on the identified notes.

Conclusion

The study demonstrates the potential of NLP-based document classifiers to accurately predict E/M LoS CPT codes using clinical notes from various medical and procedural specialties. The models’ performance suggests that the classification task’s complexity merits further investigation. The de-identification experiment demonstrated that de-identification may negatively impact classifier performance. Further research is needed to validate the performance of our NLP classifiers in different healthcare settings and patient populations and to investigate the potential implications of de-identification on model performance.
Fully Automated Sequential Immunofluorescence (seqIF) for Hyperplex Spatial Proteomics
Authors: Rivest François , Eroglu Deniz , Pelz Benjamin , Kowal Joanna , Kehren Alexander , Procopio Maria Giuseppina , Bordignon Pino , Pérès Emilie , Ammann Marco , Dorel Emmanuel , Scalmazzi Sylvain , Bruno Lorenzo , Ruegg Matthieu , Campargue Gabriel , Casqueiro Gilles , Arn Lionel , Fischer Jérôme , Brajkovic Saska , Joris Pierre , Cassano Marco , Dupouy Diego
Published: July 2023

Tissues are complex environments where different cell types are in constant interaction with each other and with non-cellular components. Preserving the spatial context during proteomics analyses of tissue samples has become an important objective for different applications, one of the most important being the investigation of the tumor microenvironment. Here, we describe a multiplexed protein biomarker detection method on the COMET instrument, coined sequential ImmunoFluorescence (seqIF). The fully automated method uses successive applications of antibody incubation and elution, and in-situ imaging enabled by an integrated microscope and a microfluidic chip that provides optimized optical access to the sample. We show seqIF data on different sample types such as tumor and healthy tissue, including 40-plex on a single tissue section that is obtained in less than 24 hours, using off-the-shelf antibodies. We also present extensive characterization of the developed method, including elution efficiency, epitope stability, repeatability and reproducibility, signal uniformity, and dynamic range, in addition to marker and panel optimization strategies. The streamlined workflow using off-the-shelf antibodies, data quality enabling quantitative downstream analysis, and ease of reaching hyperplex levels make seqIF suitable for immune-oncology research and other disciplines requiring spatial analysis, paving the way for its adoption in clinical settings.
Incorporating photosynthetic acclimation improves stomatal optimisation models
Authors: Flo Victor , Joshi Jaideep , Sabot Manon , Sandoval David , Prentice Iain Colin
Published: July 2023

Stomatal opening in plant leaves is regulated through a balance of carbon and water exchange under different environmental conditions. Accurate estimation of stomatal regulation is crucial for understanding how plants respond to changing environmental conditions, particularly under climate change. A new generation of optimality-based modelling schemes determines instantaneous stomatal responses from a balance of trade-offs between carbon gains and hydraulic costs, but most such schemes do not account for biochemical acclimation in response to drought. Here, we compare the performance of seven instantaneous stomatal optimisation models with and without accounting for photosynthetic acclimation. Using experimental data from 38 plant species, we found that accounting for photosynthetic acclimation improves the prediction of carbon assimilation in a majority of the tested models. Non-stomatal mechanisms contributed significantly to the reduction of photosynthesis under drought conditions in all tested models. Drought effects on photosynthesis could not accurately be explained by the hydraulic impairment functions embedded in the stomatal models alone, indicating that photosynthetic acclimation must be considered to improve estimates of carbon assimilation during drought.

Summary Statement

Accounting for photosynthetic acclimation improves the predictions of carbon assimilation in all the stomatal optimization models evaluated. The influence of drought on photosynthesis cannot be fully explained by the hydraulic impairment function of the stomatal models alone.
Self-supervised Benchmarking for scRNAseq Clustering
Authors: Tyler Scott R , Schadt Eric E , Guccione Ernesto
Published: July 2023

Interpretation of single cell RNAseq (scRNAseq) data are typically built upon clustering results and/or cell-cell topologies. However, the validation process is often exclusively left to bench biologists, which can take years and tens of thousands of dollars. Furthermore, a lack of objective ground-truth labels in complex biological datasets, has resulted in difficulties when benchmarking single cell analysis methods. Here, we address these gaps with count splitting, creating a cluster validation algorithm, accounting for Poisson sampling noise, and benchmark 120 pipelines using an independent test-set for ground-truth assessment, thus enabling the firstself-supervisedbenchmark. Anti-correlation-based feature selection paired with locally weighted Louvain modularity on the Euclidean distance of 50 principal-components with cluster-validation showed the best performance of all tested pipelines for scRNAseq clustering, yielding reproducible biologically meaningful populations. These new approaches enabled the discovery of a novel metabolic gene signature associated with hepatocellular carcinoma survival time.
Sex-Specific Effects of Anxiety on Cognition and Activity-Dependent Neural Networks: Insights from (Female) Mice and (Wo)Men
Authors: Hunsberger Holly C. , Lee Seonjoo , Jin Michelle , Lanio Marcos , Whye Alicia , Cha Jiook , Scarlata Miranda , Jayaseelan Keerthana , Denny Christine. A.
Published: July 2023

INTRODUCTION

Neuropsychiatric symptoms (NPS), such as depression and anxiety, are observed in 90% of Alzheimer’s disease (AD) patients, two-thirds of whom are women. NPS usually manifest long before AD onset creating a therapeutic opportunity. Here, we examined the impact of anxiety on AD progression and the underlying brain-wide neuronal mechanisms.

METHODS

To gain mechanistic insight into how anxiety impacts AD progression, we performed a cross-sectional analysis on mood, cognition, and neural activity utilizing the ArcCreERT2x enhanced yellow fluorescent protein (eYFP) x APP/PS1 (AD) mice. The ADNI dataset was used to determine the impact of anxiety on AD progression in human subjects.

RESULTS

Female AD mice exhibited anxiety-like behavior and cognitive decline at an earlier age than control (Ctrl) mice and male mice. Brain-wide analysis of c-Fos+revealed changes in regional correlations and overall network connectivity in AD mice. Sex-specific memory trace changes were observed; female AD mice exhibited impaired memory traces in dorsal CA3 (dCA3), while male AD mice exhibited impaired memory traces in the dorsal dentate gyrus (dDG). In the ADNI dataset, anxiety predicted transition to dementia. Female subjects positive for anxiety and amyloid transitioned more quickly to dementia than male subjects.

CONCLUSIONS

While future studies are needed to understand whether anxiety is a predictor, a neuropsychiatric biomarker, or a comorbid symptom that occurs during disease onset, these results suggest that AD network dysfunction is sexually dimorphic, and that personalized medicine may benefit male and female AD patients rather than a one size fits all approach.
A novel naïve Bayes approach to identifying grooming behaviors in the force-plate actometric platform
Authors: Anderson Collin J , Cadeddu Roberto , Anderson Daria Nesterovich , Huxford Job A , VanLuik Easton R , Odeh Karen , Pittenger Christopher , Pulst Stefan M , Bortolato Marco
Published: July 2023

Background

Self-grooming behavior in rodents serves as a valuable model for investigating stereotyped and perseverative responses. Most current grooming analyses primarily rely on video observation, which lacks standardization, efficiency, and quantitative information about force. To address these limitations, we developed an automated paradigm to analyze grooming using a force-plate actometer.

New Method

Grooming behavior is quantified by calculating ratios of relevant movement power spectral bands. These ratios are then input into a naïve Bayes classifier, trained with manual video observations. To validate the effectiveness of this method, we applied it to the behavioral analysis of the early-life striatal cholinergic interneuron depletion (CIN-d) mouse, a model of tic pathophysiology recently developed in our laboratory, which exhibits prolonged grooming responses to acute stressors. Behavioral monitoring was simultaneously conducted on the force-place actometer and by video recording.

Results

The naïve Bayes approach achieved 93.7% accurate classification and an area under the receiver operating characteristic curve of 0.894. We confirmed that male CIN-d mice displayed significantly longer grooming durations compared to controls. However, this elevation was not correlated with increases in grooming force. Notably, haloperidol, a benchmark therapy for tic disorders, reduced both grooming force and duration.

Comparison with Existing Methods

In contrast to observation-based approaches, our method affords rapid, unbiased, and automated assessment of grooming duration, frequency, and force.

Conclusions

Our novel approach enables fast and accurate automated detection of grooming behaviors. This method holds promise for high-throughput assessments of grooming stereotypies in animal models of tic disorders and other psychiatric conditions.
Discovery of novel G-quadruplex stabilizing compounds from medicinal plant & Evaluates their cellular toxicity
Authors: Neha  , Ranjan Prashant , Das Parimal
Published: July 2023

G-Quadruplexes (G4Q) are higher-order, four-stranded structures that can be formed by repeated guanine tracts in human genomes. In this study, we used a structure-based virtual screening of phytomolecules derived from medicinal plants in order to discover new natural DNA G4Q binders. The top 40 ligands were sorted out based on binding affinity values after completing a docking study on 314 phytomolecule samples with parallel and mixed hybrid structure. Further Thermal melting, circular dichroism, and fluorescence displacement experiment was used as a preliminary screening tool to determine the potential stabilizing properties of β-sitosterol-β-D-glucoside, and Glabrolide. The cytotoxicity experiments were conducted on HEK293T cells and found that both of the tested phyto molecules are non-toxic for up to 150 μM concentration. Based on their cytotoxic experiments at the suggested high concentration, these phyto molecules may potentially be employed as G-Quadruplex targets in future research or applications. These results suggest that the plant may be a “lead” in the future for the development of novel therapies for diseases.
Increasing adult-born neurons protects mice from epilepsy
Authors: Jain Swati , LaFrancois John J. , Gerencer Kasey , Botterill Justin J. , Kennedy Meghan , Criscuolo Chiara , Scharfman Helen E.
Published: July 2023

ABSTRACT

Neurogenesis occurs in the adult brain in the hippocampal dentate gyrus, an area that contains neurons which are vulnerable to insults and injury, such as severe seizures. Previous studies showed that increasing adult neurogenesis reduced neuronal damage after these seizures. Because the damage typically is followed by chronic life-long seizures (epilepsy), we asked if increasing adult-born neurons would prevent epilepsy. Adult-born neurons were selectively increased by deleting the pro-apoptotic geneBaxfrom Nestin-expressing progenitors. Tamoxifen was administered at 6 weeks of age to conditionally deleteBaxin Nestin-CreERT2Baxfl/flmice. Six weeks after tamoxifen administration, severe seizures (status epilepticus; SE) were induced by injection of the convulsant pilocarpine. After mice developed epilepsy, seizure frequency was quantified for 3 weeks. Mice with increased adult-born neurons exhibited fewer chronic seizures. Postictal depression was reduced also. These results were primarily in female mice, possibly because they were the more affected byBaxdeletion than males, consistent with sex differences inBax. The female mice with enhanced adult-born neurons also showed less neuronal loss of hilar mossy cells and hilar somatostatin-expressing neurons than wild type females or males, which is notable because these two hilar cell types are implicated in epileptogenesis. The results suggest that selectiveBaxdeletion to increase adult-born neurons can reduce experimental epilepsy, and the effect shows a striking sex difference. The results are surprising in light of past studies showing that suppressing adult-born neurons can also reduce chronic seizures.
Declining use of clean cooking fuels & food security in 2022: Downstream impact of the Russian-Ukrainian war in a Kenyan informal urban settlement
Authors: Shupler Matthew , Mwitari James , O’Keefe Mark , Lorenzetti Federico , Nabukwangwa Willah , Gohole Arthur , Perros Tash , Nix Emily , Puzzolo Elisa , Pope Daniel , Osiolo Helen Hoka
Published: July 2023

Energy market turmoil due to the Russian-Ukrainian war increased global fuel/food prices. While risks to energy and food security have been suggested, little research has documented impacts for the most vulnerable. During September-October 2022, surveys were administered to 701 households using pay-as-you-go liquefied petroleum gas (PAYG LPG) for clean cooking in an informal settlement in Nairobi, Kenya. Paired t-tests compared PAYG LPG consumption/payment behaviors before (July-October 2021) and during a >15% inflationary food price period (July-October 2022). Three-quarters (74%; %; n=520) of all households and 94% of food insecure households (n=393; 54% of sample) changed their dietary behavior (changed foods cooked, skipped more meals, and/or reduced PAYG LPG consumption) in 2022. Between July-October 2021 and 2022, PAYG LPG prices increased by 16% (214 Kenyan Shilling (KSh)/kg ($1.53USD/kg) to 249 KSh/kg ($1.78USD/kg) and households reduced their monthly PAYG LPG expenditure by 79% (856 KSh ($6.07USD) to 184 KSh ($1.31USD)). Although 97% of participants continued using PAYG LPG in July-October 2022, average consumption declined by two-thirds (0.82 to 0.27 kg/capita/month; difference(paired-t):-0.28 95%CI:[-0.36,-0.21]). Higher food and LPG prices in 2022 led to substantial declines in food security and LPG consumption in an informal urban settlement, highlighting increased obstacles to achieving the Sustainable Development Goals.

Highlights

67% reduction (0.82 to 0.27 kg/capita/month) in mean PAYG LPG use between 2021 and 2022

97% of homes continued using LPG but monthly fuel expenditure decreased 79% between 2021- 2022

56% of households were food insecure

94% of food insecure homes changed foods cooked, skipped meals or reduced LPG use in 2022

One of first studies linking rising food prices with declines in clean energy consumption

Synopsis

Using smart meter data, this study illustrates that LPG consumption for cooking dropped by two-thirds and food insecurity increased in an informal urban settlement due to higher food costs in 2022.