bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of finger control complexity and intrusion of flexor biases are dissociable in finger individuation impairment after stroke
Authors: Xu Jing , Ma Timothy , Kumar Sapna , Olds Kevin , Brown Jeremy , Carducci Jacob , Forrence Alex , Krakauer John
Published: September 2023

The ability to control each finger independently is an essential component of human hand dexterity. A common observation of hand function impairment after stroke is the loss of this finger individuation ability, often referred to as enslavement, i.e., the unwanted coactivation of non-intended fingers in individuated finger movements. In the previous literature, this impairment has been attributed to several factors, such as the loss of corticospinal drive, an intrusion of flexor synergy due to upregulations of the subcortical pathways, and/or biomechanical constraints. These factors may or may not be mutually exclusive and are often difficult to tease apart. It has also been suggested, based on a prevailing impression, that the intrusion of flexor synergy appears to be an exaggerated pattern of the involuntary coactivations of task-irrelevant fingers seen in a healthy hand, often referred to as a flexor bias. Most previous studies, however, were based on assessments of enslavement in a single dimension (i.e., finger flexion/extension) that coincide with the flexor bias, making it difficult to tease apart the other aforementioned factors. Here, we set out to closely examine the nature of individuated finger control and finger coactivation patterns in all dimensions. Using a novel measurement device and a 3D finger-individuation paradigm, we aim to tease apart the contributions of lower biomechanical, subcortical constraints, and top-down cortical control to these patterns in both healthy and stroke hands. For the first time, we assessed all five fingers’ full capacity for individuation. Our results show that these patterns in the healthy and paretic hands present distinctly different shapes and magnitudes that are not influenced by biomechanical constraints. Those in the healthy hand presented larger angular distances that were dependent on top-down task goals, whereas those in the paretic hand presented larger Euclidean distances that arise from two dissociable factors: a loss of complexity in finger control and the dominance of an intrusion of flexor bias. These results suggest that finger individuation impairment after stroke is due to two dissociable factors: the loss of finger control complexity present in the healthy hand reflecting a top-down neural control strategy and an intrusion of flexor bias likely due to an upregulation of subcortical pathways. Our device and paradigm are demonstrated to be a promising tool to assess all aspects of the dexterous capacity of the hand.
OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology
Authors: Heinson Yuli W. , Han Julie L. , Entcheva Emilia
Published: September 2023

We present a simple low-cost system for comprehensive functional characterization of cardiac function under spontaneous and paced conditions, in standard 96 and 384-well plates. This full-plate actuator/imager, OptoDyCE-plate, uses optogenetic stimulation and optical readouts of voltage and calcium from all wells in parallel. The system is validated with syncytia of human induced pluripotent stem cell derived cardiomyocytes, iPSC-CMs, grown as monolayers, or in quasi-3D isotropic and anisotropic constructs using electrospun matrices, in 96 and 394-well format. Genetic modifications, e.g. interference CRISPR (CRISPRi), and nine compounds of acute and chronic action were tested, including five histone deacetylase inhibitors (HDACis). Their effects on voltage and calcium were compared across growth conditions and pacing rates. We also demonstrated deployment of optogenetic cell spheroids for point pacing to study conduction in 96-well format, and the use of temporal multiplexing to register voltage and calcium simultaneously on a single camera in this stand-alone platform. Opto-DyCE-plate showed excellent performance even in the small samples in 384-well plates, in the various configurations. Anisotropic structured constructs may provide some benefits in drug testing, although drug responses were consistent across tested configurations. Differential voltage vs. calcium responses were seen for some drugs, especially for non-traditional modulators of cardiac function, e.g. HDACi, and pacing rate was a powerful modulator of drug response, highlighting the need for comprehensive multiparametric assessment, as offered by OptoDyCE-plate. Increasing throughput and speed and reducing cost of screening can help stratify potential compounds early in the drug development process and accelerate the development of safer drugs.
The Link Between Atrial Fibrillation And Cognitive Impairment: A Systematic Review And Meta-Analysis
Authors: Agarwal Abhimanyu , Mostafa Mohamed A. , Ahmad Muhammad Imtiaz , Soliman Elsayed Z.
Published: September 2023

Atrial fibrillation (AF) affects a substantial population of individuals aged ≥55 years globally and has been associated with an increased risk of cognitive impairment (CImp) due to the shared risk factors such as aging, obesity, and diabetes. It is essential to comprehend their unique relationship to manage them effectively to reduce its impact on public health systems. We performed a PubMed search of English language papers published till 31 May 2023. Data was extracted and effect measures were calculated. Meta-analysis of 33 studies revealed a significant association between AF and CImp after adjusting for comorbidities, with considerable between-study heterogeneity (pooled OR: 1.62; 95% CI: 1.43, 1.81, I2= 94.143). Prospective and cross-sectional studies revealed substantial associations. CImp in AF may be mediated through silent brain infarctions, microemboli, brain atrophy, and inflammation. Future research should prioritize investigating the mechanisms and etiology of this association, as well as potential treatment options.
Ultrasound-guided bleomycin sclerotherapy for Warthin’s tumor: preliminary results of a prospective study
Authors: Castren Eeva , Sirviö Minna , Aro Katri , Lappalainen Kimmo , Lindén Riikka , Kurdo Goran , Tarkkanen Jussi , Mäkitie Antti , Atula Timo
Published: September 2023

Background

Warthin’s tumor (WT) is the second most common parotid gland neoplasm with rising incidence. As some WT patients are not suitable for surgery, non-surgical treatment options are needed. This is the first study to evaluate the feasibility of ultrasound-guided bleomycin sclerotherapy (UGBS) for WT.

Patients and methods

WT patients with concordant clinical, imaging, and cytology data were included. UGBS was proposed for patients who desired non-surgical intervention and fulfilled the inclusion criteria. Tumor volume and tumor-related symptoms were registered before UGBS and six months after.

Results

Nine patients underwent UGBS between September 2021 and September 2022. In seven of the nine patients (78%), the tumor volume had diminished on average by 34% at six-month follow-up. Also, tumor-related pain, and cosmetic and functional discomfort decreased during the follow-up. One patient was later referred to partial parotidectomy.

Conclusion

UGBS could be an alternative non-surgical treatment for WT, especially for patients with risk factors for surgery.
Characterizing the Extended Language Network in Individuals with Multiple Sclerosis
Authors: Ratzan Alexander S. , Simani Leila , Dworkin Jordan D. , Buyukturkoglu Korhan , Riley Claire S. , Leavitt Victoria M.
Published: September 2023

Background

Cognitive impairment is a pervasive, functionally limiting symptom of multiple sclerosis (MS), a disease of the central nervous system that is the most common non-traumatic cause of neurologic disability in young adults. Recently, language dysfunction has received increased attention as a prevalent and early affected cognitive domain in individuals with MS.

Objectives

To establish a network-level model of language dysfunction in MS.

Methods

Cognitive data and 3T structural and functional brain magnetic resonance imaging (MRI) scans were acquired from 54 MS patients and 54 healthy controls (HCs). Summary measures of the extended language network (ELN) and structural imaging metrics were calculated. Group differences in ELN summary measures were evaluated. Associations between ELN summary measures and language performance were assessed in both groups; in the MS group, a two-step regression analysis was applied to assess relationships between additional language-specific imaging measures and language performance.

Results

In comparison to the HC group, the MS group performed significantly worse on the semantic fluency and rapid automized naming tests (p< 0.005). Concerning the ELN summary measures, the MS group exhibited higher within-ELN connectivity than the HCs (0.11 ± 0.02 vs. 0.10 ± 0.01,p< 0.05, respectively). While no significant relationships between ELN summary measures and language function were observed in either group, the regression analysis identified a set of 17 imaging features that predicted performance on the rapid automized naming test (p< 0.05) and identified key white matter tracts predicting language function in individuals with MS.

Conclusion

The derived functional network-level measures, combined with the identified structural neuroimaging metrics, constitute a comprehensive set of imaging features to characterize language dysfunction in MS. Further studies leveraging these features may uncover underlying mechanisms and clinically relevant predictors of language dysfunction, potentially leading to improved precision treatment strategies for cognitively impaired patients with multiple sclerosis.
The pivotal role of the X-chromosome in the genetic architecture of the human brain
Authors: Jiang Zhiwen , Sullivan Patrick F. , Li Tengfei , Zhao Bingxin , Wang Xifeng , Luo Tianyou , Huang Shuai , Guan Peter Y. , Chen Jie , Yang Yue , Stein Jason L. , Li Yun , Liu Dajiang , Sun Lei , Zhu Hongtu
Published: September 2023

Genes on the X-chromosome are extensively expressed in the human brain. However, little is known for the X-chromosome’s impact on the brain anatomy, microstructure, and functional network. We examined 1,045 complex brain imaging traits from 38,529 participants in the UK Biobank. We unveiled potential autosome-X-chromosome interactions, while proposing an atlas outlining dosage compensation (DC) for brain imaging traits. Through extensive association studies, we identified 72 genome-wide significant trait-locus pairs (including 29 new associations) that share genetic architectures with brain-related disorders, notably schizophrenia. Furthermore, we discovered unique sex-specific associations and assessed variations in genetic effects between sexes. Our research offers critical insights into the X-chromosome’s role in the human brain, underscoring its contribution to the differences observed in brain structure and functionality between sexes.

One-sentence Summary

We investigated the genetic impact of the X-chromosome and the sex differences in the human brain.
Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium
Authors: Lin Keshuo , Wen Wei , Lipnicki Darren M. , Mewton Louise , Chen Rory , Du Jing , Wang Dadong , Skoog Ingmar , Sterner Therese Rydberg , Najar Jenna , Kim Ki Woong , Han Ji Won , Kim Jun Sung , Ng Tze Pin , Ho Roger , Chua Denise Qian Ling , Anstey Kaarin J. , Cherbuin Nicolas , Mortby Moyra E. , Brodaty Henry , Kochan Nicole , Sachdev Perminder S. , Jiang Jiyang ,   Cohort Studies of Memory in an International Consortium (COSMIC)
Published: September 2023

INTRODUCTION

White matter hyperintensities (WMH) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well-documented in populations of different ethnicities and/or from different geographical regions.

METHOD

Magnetic resonance imaging data of five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their associations with vascular risk factors and cognition.

RESULT

Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake and insufficient physical activity. Participants with moderate or higher physical activity had less WMH than those who never exercised, but the former two groups did not differ. Hypertension and stroke had stronger associations with WMH volumes in the White, compared to Asian subsample.

DISCUSSION

The current study highlighted the ethnic differences in the contributions of vascular risk factors to WMH.
XBB.1.5 Spike Protein COVID-19 Vaccine Induces Broadly Neutralizing and Cellular Immune Responses Against EG.5.1 and Emerging XBB Variants
Authors: Patel Nita , Trost Jessica F. , Guebre-Xabier Mimi , Zhou Haixia , Norton Jim , Jiang Desheng , Cai Zhaohui , Zhu Mingzhu , Marchese Anthony M. , Greene Ann M. , Mallory Raburn M. , Kalkeri Raj , Dubovsky Filip , Smith Gale
Published: September 2023

Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against SARS-CoV-2 Omicron XBB sub-variants. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces cross-neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4+ T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023-2024 COVID-19 vaccination campaign.
Online Bayesian Optimization of Nerve Stimulation
Authors: Wernisch Lorenz , Edwards Tristan , Berthon Antonin , Tessier-Lariviere Olivier , Sarkans Elvijs , Stoukidi Myrta , Fortier-Poisson Pascal , Pinkney Max , Thornton Michael , Hanley Catherine , Lee Susannah , Jennings Joel , Appleton Ben , Garsed Phillip , Patterson Bret , Buttinger Will , Gonshaw Samuel , Jakopec Matjaž , Shunmugam Sudhakaran , Mamen Jorin , Tukiainen Aleksi , Lajoie Guillaume , Armitage Oliver , Hewage Emil
Published: September 2023

Objective

In bioelectronic medicine, neuromodulation therapies induce neural signals to the brain or organs modifying their function. Stimulation devices, capable of triggering exogenous neural signals using electrical wave forms, require a complex and multi-dimensional parameter space in order to control such wave forms. Determining the best combination of parameters (wave form optimization, or dosing) for treating a particular patient’s illness is therefore challenging. Comprehensive parameter searching for an optimal stimulation effect is often infeasible in a clinical setting, due to the size of the parameter space. Restricting this space, however, may lead to sub-optimal therapeutic results, reduced responder rates, and adverse effects.

Approach

As an alternative to a full parameter search, we present a flexible machine learning, data acquisition and processing framework for optimizing neural stimulation parameters requiring as few steps as possible using Bayesian optimization. Such optimization builds a model of the neural and physiological responses to stimulations enabling it to optimize stimulation parameters and to provide estimates of the accuracy of the response model. The vagus nerve innervates, among other thoracic and visceral organs, the heart, thus controlling heart rate and is therefore ideal for demonstrating the effectiveness of our approach.Main results.The efficacy of our optimization approach was first evaluated on simulated neural responses, then applied to vagus nerve stimulation intraoperatively in porcine subjects. Optimization converged quickly on parameters achieving target heart rates and optimizing neural B-fibre activations despite high intersubject variability.

Significance

An optimized stimulation waveform was achieved in real time with far fewer stimulations than required by alternative optimization strategies, thus minimizing exposure to side effects. Uncertainty estimates helped avoiding stimulations outside a safe range. Our approach shows that a complex set of neural stimulation parameters can be optimized in real-time for a patient to achieve a personalized precision dosing.
Regulating Cell Orientation with a Femtosecond Laser-Induced Macro Stripe Design on Metallic Culture Surfaces
Authors: Imashiro Chikahiro , Ezura Atsushi , Yamada Takahiro G. , Akiyama Yoshikatsu , Komotori Jun
Published: September 2023

Controlling cell orientation is paramount in bioengineering processes. While several surface modification techniques have emerged to guide cell alignment, they often involve complex, repetitive procedures for each experiment. A streamlined approach for cell orientation is thus necessary. In this study, we present a reusable metallic culture surface that induces an anisotropic cell orientation, attributed to its unique geometric morphology. By employing a femtosecond laser, periodic nanostructures were produced on the metallic culture surface, leading to a distinctive macro-stripe design composed of both laser-treated and mirrored areas. Myoblast cells cultured on this surface displayed a pronounced orientation. Initial random cell adherence was followed by migration towards the mirror surface, culminating in the desired orientation. This shift can be credited to the mirrored sections offering superior cell adhesion and reduced wettability compared to the laser-treated sections. This innovative culture surface holds significant potential for advancing bioengineering endeavors, especially in the realm of tissue engineering.
All-optical reporting of inhibitory receptor driving force in the nervous system
Authors: Selfe Joshua S. , Steyn Teresa J. S. , Shorer Eran F. , Burman Richard J. , Düsterwald Kira M. , Abdelfattah Ahmed S. , Schreiter Eric R. , Newey Sarah E. , Akerman Colin J. , Raimondo Joseph V.
Published: September 2023

Ionic driving forces provide the net electromotive force for ion movement across receptors, channels, and transporters, and are a fundamental property of all cells. In the brain for example, fast synaptic inhibition is mediated by chloride permeable GABAA receptors, and single-cell intracellular recordings have been the only method for estimating driving forces across these receptors (DFGABAA). Here we present a new tool for quantifying inhibitory receptor driving force named ORCHID: all-Optical Reporting of CHloride Ion Driving force. We demonstrate ORCHID’s ability to provide accurate, high-throughput measurements of resting and dynamic DFGABAA from genetically targeted cell types over multiple timescales. ORCHID confirms theoretical predictions about the biophysical mechanisms that establish DFGABAA, reveals novel differences in DFGABAA between neurons and astrocytes, and affords the firstin vivomeasurements of intact DFGABAA. This work extends our understanding of inhibitory synaptic transmission and establishes a precedent for all-optical methods to assess ionic driving forces.
Growth/differentiation factor 15 controls primary cilia morphology in the murine ventricular-subventricular zone thereby affecting progenitor proliferation
Authors: Baur Katja , Şan Şeydanur , Hölzl-Wenig Gabriele , Mandl Claudia , Hellwig Andrea , Ciccolini Francesca
Published: September 2023

Growth/differentiation factor 15 (GDF15) and its receptor GDNF Family Receptor Alpha-Like (GFRAL) are expressed from embryonic development onwards in the germinal epithelium of the ganglionic eminence (GE), regulating proliferation and number of apical progenitors. However, the mechanisms underlying this regulation are not yet clear. We here show that GDF15 exerts this regulation by affecting ciliary signalling. Not only was GFRAL localized to primary cilia but, constitutive GDF15 ablation also led to shorter and thicker primary cilia. Lack of GDF15 affected the expression of histone deacetylase 6 (HDAC6) and ciliary adenylate cyclase 3 (ADCY3), thereby modifying acetylation of microtubules and endogenous Sonic Hedgehog (SHH) activation in neural progenitors. Application of exogenous GDF15 or pharmacological antagonism of HDAC6 or ADCY3 all increased cilia length and rescued proliferation and SHH signalling in mutant but not WT progenitors. Notably, HDAC6 expression and cilia length were changed only in the GE, were ciliary GFRAL localization was observed. In contrast, GFRAL was absent from primary cilia of hippocampal progenitors where GDF15 affected ADCY3 and SHH signalling, but not HDAC6 expression or cilia morphology. We conclude that ciliary GDF15 signalling regulates HDAC6 thereby affecting primary cilia elongation and proliferation in apical progenitors.
How antisense transcripts can evolve to encode novel proteins
Authors: Iyengar Bharat Ravi , Grandchamp Anna , Bornberg-Bauer Erich
Published: September 2023

Protein coding features can emergede novoin non coding transcripts, resulting in emer- gence of new protein coding genes. Studies across many species show that a large frac- tion large fraction of evolutionarily novel non-coding RNAs have an antisense overlap with protein coding genes. The open reading frames (ORFs) in these antisense RNAs could also overlap with existing ORFs. In this study, we investigate how the evolution an ORF could be constrained by its overlap with an existing ORF in three different read- ing frames. Using a combination of mathematical modeling and genome/transcriptome data analysis in two different model organisms, we show that antisense overlap can increase the likelihood of ORF emergence and reduce the likelihood of ORF loss, es- pecially in one of the three reading frames. In addition to rationalising the repeatedly reported prevalence ofde novoemerged genes in antisense transcripts, our work also provides a generic modeling and an analytical framework that can be used to under- stand evolution of antisense genes.
Role of NUMTs (Nuclear mitochondrial DNA) genes in affecting disease resistance in duck against Pasteurellosis
Authors: Sahu Jyoti , Pal Aruna , Chakraborty Argha , Banerjee Samiddha , Debnath Manti , Samanta Rajarshi
Published: September 2023

Ducks are mostly resistant to common avian diseases, but frequent occurrence of duck pasteurellosis, commonly kown as Duck Cholera, caused byPasteurella multocidamay cause a loss. In our earlier studies, we have identified certain immune response genes of nuclear origin as well as mitochondrial genes in duck, conferring resistance against duck cholera. In our current study, we have detected certain NUMT (Nuclear mitochondrial) genes in duck with certain role in disease resistance in case of duck cholera. NUMT genes are basically nuclear genes, but they act through mitochondria. Identified NUMT genes (Thymidine phosphorylase/ endothelial cell growth factor1 gene, TFAM Transcription factor A, mitochondrial, TK2 Thymidine kinase 2) were characterized and certain important domains were identified. Differential mRNA expression profiling revealed upregulation of the genes in healthy ducks compared to that of infected ducks. Exploitation of the identified genes may lead to development of ducks resistant to duck Cholera.
Machine learning general transcriptional predictors of plant disease
Authors: Sia Jayson , Zhang Wei , Cheng Mingxi , Bogdan Paul , Cook David E.
Published: September 2023

Plants utilize an innate immune system to defend against all classes of microbial invaders. While we understand specific genetic determinants of host-pathogen interactions, it remains less clear how generalized the immune response is to diverse pathogens. Using a data-driven approach, and utilizing feature selection based on network science and topology, we developed machine learning models that could predict host disease development across diverse pathosystems. These machine learning models identified early transcriptional responses predictive of later disease development, regardless of pathogen class, using a fraction of the host transcriptome. The identified gene sets were not enriched for canonical defense genes, but where statistically enriched for genes previously identified from independent data sets, including those described as representing a general plant stress response. These results highlight novel components of a general plant immune response, and demonstrate the application of machine learning to address biological hypotheses of a complex multigenic outcome.

Teaser

A machine learning approach can predict plant disease development caused by diverse microbial invaders, and newly identified genes may represent novel components of a general plant response to infection.
SenePy: Unveiling the Cell-Type Specific Landscape of Cellular Senescence through Single-Cell Analysis in Living Organisms
Authors: Sanborn Mark A. , Wang Xinge , Gao Shang , Dai Yang , Rehman Jalees
Published: September 2023

Senescent cells accumulate in tissues with organismal age and contribute causally to multiple chronic diseases.In vivosenescent cell phenotypes are heterogeneous because cellular context and stressors vary by cell type and tissue. Due to the variability of senescence programs, there is no universal method to identify senescent cells and even widely used markers, such asCDKN2A, are not ubiquitous. Therefore, we interrogated theTabula Muris Senismouse single-cell aging atlas and an array of single-cell datasets from human donors that spanned many ages to find cell-specific signatures of cellular senescence. We derived 75 mouse and 65 human senescence signatures from individual cell populations.CDKN2Aand other markers of senescence were overrepresented in these signatures but there were many novel senescence genes present at higher rates. Within individual cell populations, we observed multiple programs of senescence with distinct temporal and transcriptional characteristics. We packaged the signatures along with a single-cell scoring method into an open-source package:SenePy. SenePysignatures better recapitulate cellular senescence than available methods when tested on multiplein vivoRNA-seq datasets and a p16ink4areporter single-cell dataset. We usedSenePyto map the kinetics of senescent cell accumulation across 97 cell types from humans and mice.SenePyalso generalizes to disease-associate senescence and we used it to identify an increased burden of senescent cells in COVID-19 and myocardial infarction. This work provides a significant advancement towards our ability to identify and characterizein vivocellular senescence.
Genomic Epidemiologic Investigation of a Multispecies Hospital Outbreak of NDM-5-Producing Enterobacterales Infections
Authors: Raabe Nathan J. , Valek Abby L. , Griffith Marissa P. , Mills Emma , Waggle Kady , Srinivasa Vatsala Rangachar , Ayres Ashley M. , Bradford Claire , Creager Hannah , Pless Lora L. , Sundermann Alexander J. , Tyne Daria Van , Snyder Graham M. , Harrison Lee H.
Published: September 2023

Background

New Delhi metallo-β-lactamase (NDM) represents an emergent mechanism of carbapenem resistance associated with high mortality and limited antimicrobial treatment options. Because theblaNDMresistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods like speciation, antimicrobial resistance testing, and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks.

Methods

Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance, which was performed weekly using the Illumina platform. To resolve NDM-encoding plasmids, we performed long-read Oxford Nanopore sequencing and constructed hybrid assemblies using Illumina and Nanopore sequencing data. Reports of relatedness between NDM-producing organisms and reactive WGS for suspected outbreaks were shared with the IP&C team for assessment and intervention.

Findings

We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included seven bacterial species and each encoded the same NDM-5 plasmid, which showed high homology to NDM plasmids previously observed in Asia. WGS surveillance and epidemiologic investigation characterized ten horizontal plasmid transfer events and six bacterial transmission events between patients housed in varying hospital units. Transmission prevention focused on enhanced observation and adherence to basic infection prevention measures.

Interpretation

Our investigation revealed a complex, multispecies outbreak of NDM that involved multiple plasmid transfer and bacterial transmission events, increasing the complexity of outbreak identification and transmission prevention. Our investigation highlights the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks.

Funding

This work was funded in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (R01AI127472) (R21AI1783691).

5.

We investigated a multispecies outbreak of Enterobacterales harboring the same New-Delhi metallo-β-lactamase-encoding plasmid using both traditional infection prevention and genomic approaches. Our investigation revealed a complex outbreak involving 7 bacterial species, including both bacterial transmission and plasmid transfer events.
Patterns of Crimean-Congo haemorrhagic fever virus seroprevalence in human and livestock populations in northern Tanzania
Authors: Hughes Ellen C , de Glanville William , Kibona Tito , Mmbaga Blandina Theophil , Rostal Melinda K , Swai Emanuel , Cleaveland Sarah , Lankester Felix , Willett Brian J , Allan Kathryn J
Published: September 2023

Results from a cross-sectional study of Crimean-Congo haemorrhagic fever virus (CCHFV) in northern Tanzania demonstrated high seroprevalence in humans and ruminant livestock with high levels of spatial heterogeneity. CCHFV may represent an unrecognised human health risk in this region and drivers of exposure need further investigation.
Systematic review of genome wide association studies (GWAS) of epilepsy identifies common risk variants and associated genes
Authors: Jacobs S. , Wootton O. , Ives-Deliperi V , Tucker L.M , Stein D.J , Dalvie S.
Published: September 2023

Background

Epilepsy is one of the most prevalent neurological disorders, affecting 50 million individuals worldwide. The aetiology of epilepsy is known to have genetic contributions, yet headline results obtained from genome-wide association studies (GWAS) of epilepsy have not always been consistent. We undertook a systematic review of all the findings from this work in order to identify risk variants for epilepsy.

Methods

This systematic review was conducted in accordance with the updated PRISMA protocol. EbscoHost, PubMed, Scopus, Web of Science and Primo were searched between the years 2010 – 2024. The quality of each of the studies was evaluated using the Q-Genie tool.

Results

11 studies were included for full extraction, analysis, and quality assessment. Across the identified studies, 79 SNPs, located in 64 genes, were significantly associated with epilepsy at the genome-wide level. The majority of the variants were intronic and intergenic, with the well documentedSCN1Athe most widely reported gene involved across studies. Two SNPs, rs2292096 and rs149212747, linked respectively to focal epilepsy (FE) and status epilepticus, were exclusively identified in individuals of Asian ancestry, alongside an Asian-exclusive synonymous variant (rs3782886) inBRAPand a missense variant (rs671) inALDH2.

Conclusions

Genes which encode for ion and transport channels, transcription factors, ubiquitin ligase and transporter proteins were identified as potentially involved in the aetiology of epilepsy disorders. The review identified one missense and one synonymous variant which deserve further exploration. Future research should also include populations of more diverse ancestries as this may reveal unique and important epilepsy-associated genes.
Impact of health systems interventions in primary health settings on type 2 diabetes care and health outcomes among adults in West Africa: a systematic review protocol
Authors: Bondzie Eugene Paa Kofi , Jahan Yasmin , Balabanova Dina , Danso-Appiah Tony , Mirzoev Tolib , Antwi Edward , Ayepong Irene
Published: September 2023

Type 2 diabetes remains a major global public health challenge particularly in the African region. Though evidence exists on pharmacological agents and non-pharmacological interventions in maintaining blood glucose concentration, the health systems ability in meeting patients’ needs may be inadequate. However, the management of non-communicable diseases particularly diabetes, have been postulated to depend largely on functioning health systems. This systematic review will therefore, summarize the current evidence on existing health systems interventions in primary health settings for type 2 diabetes care and health outcomes in West Africa and would explore the impact of these system-level interventions on service availability, accessibility and quality, as well as individualized outcomes such as glycemic control, disease awareness and treatment adherence.

The review will be conducted in accordance with the reporting guidance provided in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). The health system framework by Witter et al, 2019 will guide the system-level interventions and the search strategy to be explored in this review. This framework was designed to integrate the six building blocks of the World health’s organization (WHO) health systems framework and delineates how they work synergistically to improve specific health outcomes. We will search the following databases PubMed, Google scholar and Cumulated Index to Nursing and Allied Health Literature (CINAHL) between January 2000 to June 2023 and Car.info from inception to June 2023. The Cochrane Collaboration tool for assessing Risk of Bias will be implemented on each included study to assess for risk of bias.

We will conduct a narrative synthesis and make comparisons across findings using Excel generated tables.

The main limitation of this study is that we are likely to miss out on studies not conducted in English or French since our search would be conducted in English and French only.

In Conclusion,this systematic review will outline the existing system-level interventions that aim to or already improve type 2 diabetes services in primary health facilities in West Africa and would allow for strengthening and co-production of successful interventions that can be generalized to the entire sub-region.
Efficient Edge-AI Models for Robust ECG Abnormality Detection on Resource-Constrained Hardware
Authors: Huang Zhaojing , Herbozo Contreras Luis Fernando , Leung Wing Hang , Yu Leping , Truong Nhan Duy , Nikpour Armin , Kavehei Omid
Published: September 2023

This study introduces two models, CLTC and CCfC, designed for abnormality identification using ECG data. Trained on the TNMG subset dataset, both models were evaluated for their performance, generative capacity, and resilience. They demonstrated comparable results in terms of F1 scores and AUROC values. The CCfC model achieved slightly higher accuracy, while the CLTC model showed better handling of empty channels. Remarkably, the models were successfully deployed on a resource-constrained microcontroller, proving their suitability for edge device applications. Generalization capabilities were confirmed through the evaluation of the CPSC dataset. The models’ efficient resource utilization, occupying 70.6% of total storage and 9.4% of flash memory, makes them promising candidates for real-world healthcare applications. Overall, this research advances abnormality identification in ECG data, contributing to the progress of AI in healthcare.
Improving split reporters of protein-protein interactions through orthology-based protein engineering
Authors: Rakotoarison Louise-Marie , Tebo Alison G. , Böken Dorothea , Gautier Arnaud
Published: September 2023

Protein-protein interactions (PPI) can be detected through selective complementation of split fluorescent reporters made of two complementary fragments that reassemble into a functional fluorescent reporter when in close proximity. We previously introduced splitFAST, a chemogenetic PPI reporter with rapid and reversible complementation. Here, we present the engineering of RspA-splitFAST, an improved reporter displaying higher brightness, lower self-complementation and higher dynamic range for optimal monitoring of PPI using an original protein engineering strategy that exploits proteins with orthology relationships. Our study allowed the identification of a system with improved properties and enabled a better understanding of the molecular features controlling the complementation properties. Because of the rapidity and reversibility of its complementation, its low self-complementation, high dynamic range, and improved brightness, RspA-splitFAST is well suited to study PPI with high spatial and temporal resolution, opening great prospects to decipher the role of PPI in various biological contexts.
Outer mitochondrial membrane E3 Ub ligase MARCH5 controls mitochondrial steps in peroxisome biogenesis
Authors: Verhoeven Nicolas , Oshima Yumiko , Cartier Etienne , Neutzner Albert , Boyman Liron , Karbowski Mariusz
Published: September 2023

Peroxisomede novobiogenesis requires yet unidentified mitochondrial proteins. We report that the outer mitochondrial membrane (OMM)-associated E3 Ub ligase MARCH5 is vital for generating mitochondria-derived pre-peroxisomes. MARCH5 knockout results in accumulation of immature peroxisomes and lower expression of various peroxisomal proteins. Upon fatty acid-induced peroxisomal biogenesis, MARCH5 redistributes to newly formed peroxisomes; the peroxisomal biogenesis under these conditions is inhibited in MARCH5 knockout cells. MARCH5 activity-deficient mutants are stalled on peroxisomes and induce accumulation of peroxisomes containing high levels of the OMM protein Tom20 (mitochondria-derived pre-peroxisomes). Furthermore, depletion of peroxisome biogenesis factor Pex14 leads to the formation of MARCH5- and Tom20-positive peroxisomes, while no peroxisomes are detected in Pex14/MARCH5 dko cells. Reexpression of WT, but not MARCH5 mutants, restores Tom20-positive pre-peroxisomes in Pex14/MARCH5 dko cells. Thus, MARCH5 acts upstream of Pex14 in mitochondrial steps of peroxisome biogenesis. Our data validate the hybrid, mitochondria-dependent model of peroxisome biogenesis and reveal that MARCH5 is an essential mitochondrial protein in this process.

The authors found that mitochondrial E3 Ub ligase MARCH5 controls the formation of mitochondria-derived pre-peroxisomes. The data support the hybrid, mitochondria-dependent model of peroxisome biogenesis and reveal that MARCH5 is an essential mitochondrial protein in this process.
Validation of Digital Pathology Platform for Metabolic-Associated Steatohepatitis for Clinical Trials
Authors: Pulaski Hanna , Mehta Shraddha S. , Manigat Laryssa C. , Kaufman Stephanie , Hou Hypatia , Nalbantoglu ILKe , Zhang Xuchen , Curl Emily , Taliano Ross , Kim Tae Hun , Torbenson Michael , Glickman Jonathan N , Resnick Murray B , Patel Neel , Taylor Cristin E. , Bedossa Pierre , Montalto Michael C , Beck Andrew H , Wack Katy E
Published: September 2023

Aims

Determine if pathologic assessment of disease activity in steatohepatitis, performed using Whole Slide Images (WSIs) on the AISight Clinical Trials platform, yields results that are comparable to those obtained from the analysis performed using glass slides.

Methods and Results

The accuracy of scoring for steatohepatitis (NAS ≥4 with ≥1 for each feature and absence of atypical features suggestive of other liver disease) performed on the WSI viewing platform was evaluated against scoring conducted on glass slides. Both methods were assessed for overall percent agreement (OPA) with a consensus ‘ground truth’ (GT) score, defined as the median score of a panel of 3 expert pathologists on glass slides. Each case was also read by 3 different pathologists, once on glass and once using WSIs with a minimum 2-week washout period between glass and WSI reads. It was demonstrated that the average OPA across 3 pathologists of WSI scoring with GT was non-inferior to the average OPA of glass scoring with GT (non-inferiority margin of -0.05, difference of -0.001, 95% CI of (−0.027,0.026), and p<0.0001). For each pathologist, there was a similar average OPA of WSI and glass reads with glass GT (pathologist A 0.843 and 0.849, pathologist B 0.633 and 0.605 and pathologist C 0.755 and 0.780), with intra-reader, inter-modality agreements per histologic feature being greater than published intra-reader agreements.

Conclusion

Accuracy of digital reads for steatohepatitis using WSIs is equivalent to glass reads in the context of a clinical trial for scoring using the Clinical Research Network scoring system.
Recombineering 101: Making an in-Frame Deletion Mutant
Authors: Figueroa-Bossi Nara , Balbontín Roberto , Bossi Lionello
Published: September 2023

DNA recombineering uses phage λ Red recombination functions to promote integration of DNA fragments generated by polymerase chain reaction (PCR) into the bacterial chromosome. The PCR primers are designed to have the last 18–22 nt anneal on either side of the donor DNA and to carry 40- to 50-nt 5′ extensions homologous to the sequences flanking the chosen insertion site. The simplest application of the method results in knockout mutants of nonessential genes. Deletions can be constructed by replacing a portion or the entirety of a target gene with an antibiotic-resistance cassette. In some commonly used template plasmids, the antibiotic-resistance gene can be coamplified with a pair of flanking FRT (Flp recombinase recognition target) sites that, following insertion of the fragment into the chromosome, allow excision of the antibiotic-resistance cassette via the activity of the site-specific Flp recombinase. The excision step leaves behind a “scar” sequence comprising an FRT site and flanking primer annealing sequences. Removal of the cassette minimizes undesired perturbations on the expression of neighboring genes. Even so, polarity effects can result from the occurrence of stop codons within, or downstream of, the scar sequence. These problems can be avoided by the appropriate choice of the template and by designing primers so that the reading frame of the target gene is maintained past the deletion end point. This protocol is optimized for use withSalmonella entericaandEscherichia coli.
Partnering for impact: unveiling the dynamics of collaboration between social enterprises and impact investors in emerging economies
Authors: Emmanuel Jeremiah Arigu , Wijewardena Chanaka , Rammal Hussain Gulzar , Khakhar Priyan Pravin
Published: September 2023

Purpose

This study empirically aims to examine the collaboration between social enterprises (SEs) and impact investors (IIs), which are organisations with similar interests but with distinct logics, and in high demand in emerging economies with complex problems. Despite the significant economic contributions of these organisations, there have been limited studies examining how they collaborate in different contexts, including theoretical insights explaining how they gain partner fit from resource synergy.

Design/methodology/approach

Mainstream businesses use the compatibility and complementarity concepts to examine buyer–supplier strategic alliances. Using similar concepts in the context of hybrid organisations, the authors interviewed six pairs of SEs and IIs with dyadic relations in Nigeria, aiming to deeply understand how they align dissimilar logics in pursuing common goals in emerging economies.

Findings

The authors’ findings revealed how compatibility criteria from the institutional logics perspective and complementarity from social exchange theory guide collaboration between SEs and IIs in an emerging economy. Using these theories provides new insights that distinguish SEs and IIs collaboration from conventional theories on the internationalisation of businesses, which remained insufficient for understanding the cross-border operations of SEs.

Practical implications

The study holds practical implications for organisations, regardless of their size, international investors, governments, organisations and individuals desiring to pursue sustainable business agendas in emerging economies with huge impact opportunities and the process involved.

Originality/value

The outcomes of this study extend knowledge of the theoretical lens examining collaborative entrepreneurship from the perspective of hybrid organisations. It also challenged existing knowledge on collaboration between SEs and IIs, often characterised by potential tensions due to the dissimilarity of institutional logics of actors.
How does compulsory citizenship behavior disturb police employees' psychological health? The roles of work–family conflict and putting family first
Authors: Chaudhary Arooba , Cheema Amna Umer , Sheikh Labiba , Islam Talat
Published: September 2023

Purpose

This study investigates how compulsory citizenship behavior (CCB) restricts police employees from fulfilling their family responsibilities [i.e. work–family conflict (WFC)] and affects their psychological health. The authors also examined putting family first (PFF) as a conditional variable on the association between CCB and WFC.

Design/methodology/approach

This quantitative study collected data from 341 police employees on convenience basis. Further, the authors tackled the issue of common method bias (CMB) by collecting data in two waves.

Findings

The data were analyzed through structural equation modeling (SEM), and the result revealed that WFC mediates the association between CCB and police employees' psychological health. In addition, the authors noted that individuals high in PFF were less likely to experience WFC in the presence of CCB.

Originality/value

This study contributes to the scant literature on police employees' psychological health. Specifically, this study is the first to investigate the mediating role of WFC between CCB and psychological health with the boundary condition of PFF.