bluuebunny/crossref_metadata_2025 huggingface dataset:
Concurrent Cervical and Anal High-Risk Human Papillomavirus Infection in Women Living With HIV: An Observational Case–Control Study
Authors: Gupta Ruchika , Hussain Showket , Hariprasad Roopa , Dhanasekaran Kavitha , Verma Sheel , Agarwal Vineeta , Das Pradeep K. , Singh Sompal , Gupta Sanjay
Published: August 2022

Background:

To evaluate the prevalence and correlates of concurrent uterine cervical and anal HR-HPV infections in women living with HIV (WLHIV).

Setting:

A cross-sectional study was undertaken at a tertiary care hospital and linked ART center.

Methods:

One hundred and forty-one WLHIV and 161 HIV-negative women were enrolled for cervical and anal cytology as well as HR-HPV testing using the HC2 method. Screen-positive women were followed-up with colposcopy/anoscopy and/or repeat cytology. Appropriate statistical tests were applied to assess the association of concurrent HR-HPV with various parameters.

Results:

Concurrent cervical and anal HR-HPV infection was detected in 22 WLHIV (16.3%) and 5 HIV-negative women (3.1%), the difference being statistically significant (P < 0.001). Among WLHIV, concurrent HR-HPV was associated with tobacco use (P < 0.001), receptive anal intercourse (P = 0.02), low CD4 counts (P = 0.001), and negatively with ART intake (P = 0.004) on bivariate analysis. Multivariate logistic regression analysis showed a positive association of concurrent HR-HPV positivity with tobacco use (P = 0.02) and low nadir CD4 counts (P = 0.03).

Conclusions:

WLHIV, especially those with CD4 counts less than 200/µL, should be offered HR-HPV screening and follow-up to detect cervical and anal lesions.
A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation
Authors: Pinto-Marques Hugo , Cardoso Joana , Silva Sílvia , Neto João L. , Gonçalves-Reis Maria , Proença Daniela , Mesquita Marta , Manso André , Carapeta Sara , Sobral Mafalda , Figueiredo Antonio , Rodrigues Clara , Milheiro Adelaide , Carvalho Ana , Perdigoto Rui , Barroso Eduardo , Pereira-Leal José B.
Published: August 2022

Objective:

To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT).

Background:

Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation.

Methods:

A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict.

Results:

HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%–24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%–94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term.

Conclusions:

HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.
Time is Tissue: Barriers to Timely Transfusion after Pediatric Injury
Authors: Sullivan Travis M. , Gestrich-Thompson Waverly V. , Milestone Zachary P. , Burd Randall S.
Published: August 2022

Strategies to improve outcomes among children and adolescents in hemorrhagic shock have primarily focused on component resuscitation, pharmaceutical coagulation adjuncts, and hemorrhage control techniques. Many of these strategies have been associated with better outcomes in children, but the barriers to their use and the impact of timely use on morbidity and mortality has received little attention. Because transfusion is uncommon in injured children, few studies have identified and described barriers to the processes of using these interventions in bleeding patients, processes that move from the decision to transfuse, to obtaining the necessary blood products and adjuncts, and to delivering them to the patient. In this review, we identify and describe the steps needed to ensure timely blood transfusion and propose practices to minimize barriers in this process. Given the potential impact of time on hemorrhage associated outcomes, ensuring timely intervention may have a similar or greater impact than the interventions themselves.

Level of Evidence:

Regular Review: Level III and IV
Era, a GTPase-like protein of the Ras family, does not control ribosome assembly in Mycobacterium tuberculosis
Authors: Agarwal Nisheeth , Sharma Shivani , Pal Pramila , Kaushal Prem S. , Kumar Naresh
Published: August 2022

Era GTPase is universally present in microbes including

Mycobacterium tuberculosis

(Mtb) complex bacteria. While Era is known to regulate ribosomal assembly in

Escherichia coli

and predicted to be essential for in vitro growth, its function in mycobacteria remains obscured. Herein, we show that Era ortholog in the attenuated Mtb H37Ra strain, MRA_2388 (annotated as EraMT) is a cell envelope localized protein harbouring critical GTP-binding domains, which interacts with several envelope proteins of Mtb. The purified Era from

M. smegmatis

(annotated as EraMS) exhibiting ~90 % sequence similarity with EraMT, exists in monomeric conformation. While it is co-purified with RNA upon overexpression in

E. coli

, the presence of RNA does not modulate the GTPase activity of the EraMS as against its counterpart from other organisms. CRISPRi silencing of eraMT
does not show any substantial effect on the in vitro growth of Mtb H37Ra, which suggests a redundant function of Era in mycobacteria. Notably, no effect on ribosome assembly, protein synthesis or bacterial susceptibility to protein synthesis inhibitors was observed upon depletion of EraMT in Mtb H37Ra, further indicating a divergent role of Era GTPase in mycobacteria.
Microbe Profile: Pectobacterium atrosepticum: an enemy at the door
Authors: Toth Ian K.
Published: August 2022

Pectobacterium atrosepticum

is part of a larger family of soft rot bacteria (

Pectobacteriaceae

) that cause disease on a wide range of crops worldwide. They are closely related to members of the

Enterobacteriaceae

and, as the plant pathogens and plant associated members of the group, form part of a continuum towards opportunistic and more devastating animal and human pathogens. Many of the horizontally acquired islands present in the genome of

P. atrosepticum

are directly responsible for life on plants. These include genes for a plethora of plant cell wall degrading enzymes, plant toxins, siderophores etc., which are exported by multiple secretion systems under a highly coordinated regulation system.
PEMT: A patent enrichment tool for drug discovery
Authors: Gadiya Yojana , Zaliani Andrea , Gribbon Philip , Hofmann-Apitius Martin
Published: August 2022

Motivation

Drug discovery practitioners in industry and academia use semantic tools to extract information from online scientific literature to generate new insights into targets, therapeutics and diseases. However, due to complexities in access and analysis, patent-based literature is often overlooked as a source of information. As drug discovery is a highly competitive field, naturally, tools that tap into patent literature can provide any actor in the field an advantage in terms of better informed decision making. Hence, we aim to facilitate access to patent literature through the creation of an automatic tool for extracting information from patents described in existing public resources.

Results

Here, we present PEMT, a novel patent enrichment tool, that takes advantage of public databases like ChEMBL and SureChEMBL to extract relevant patent information linked to chemical structures and/or gene names described through FAIR principles and metadata annotations. PEMT aims at supporting drug discovery and research by establishing a patent landscape around genes of interest. The pharmaceutical focus of the tool is mainly due to the subselection of International Patent Classification (IPC) codes, but in principle, it can be used for other patent fields, provided that a link between a concept and chemical structure is investigated. Finally, we demonstrate a use-case in rare diseases by generating a gene-patent list based on the epidemiological prevalence of these diseases and exploring their underlying patent landscapes.

Availability and implementation

PEMT is an open-source Python tool and its source code and PyPi package are available athttps://github.com/Fraunhofer-ITMP/PEMTandhttps://pvpi.org/project/PEMT/respectively.

Contact

yojana.gadiya@itmp.fraunhofer.de

Supplementary information

Supplementary data are available atBioinformaticsonline.
A measure of the somatosensory blink reflex to parametric variation of mechanical stimulation
Authors: Kaiser Eric A , Haggery Edda B , Garner Dena P , Bunya Vatinee Y , Aguirre Geoffrey K
Published: August 2022

The primary goal of this study was to develop a parametric model that relates variation in stimulation of the trigeminal nerve to properties of the blink response. We measured blink responses in 17 healthy, adult participants to air puffs directed at the lateral canthus of the eye at five different, log-spaced intensities (3.5 - 60 PSI). Lid position over time was decomposed into amplitude and velocity components. We found that blink amplitude was systematically related to log stimulus intensity, with the relationship well described by a sigmoidal function. The parameters of the model fit correspond to the slope of the function and the stimulus intensity required to produce half of a maximal blink response (the half-response threshold). There was a reliable decrease in the half-response threshold for the contralateral as compared to the ipsilateral blink response. This decrease was consistent across participants despite substantial individual differences in the half-response threshold and slope parameters of the overall sensitivity function, suggesting that the laterality effect arises in the neural circuit subsequent to individual differences in sensitivity. Overall, we find that graded mechanical stimulation of the somatosensory trigeminal afferents elicits a graded response that is well described by a simple parametric model. We discuss the application of parametric measurements of the blink response to the detection of group differences in trigeminal sensitivity.

Impact statement

There has been limited study of how variation in stimulus intensity influences the cutaneous blink response. We describe how variation in the intensity of an air-puff stimulus relates to the amplitude of the blink response using a two-parameter model. The parameters of the model capture individual differences in response, which may be used in future studies to identify population differences in trigeminal sensitivity.
SVR-based Multimodal Active Subspace Analysis for the Brain using Neuroimaging Data
Authors: Batta Ishaan , Abrol Anees , Calhoun Vince D. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2022

Understanding the patterns of changes in brain function and structure due to various disorders and diseases is of utmost importance. There have been numerous efforts toward successful biomarker discovery for complex brain disorders by evaluating neuroimaging datasets with novel analytical frameworks. However, due to the multi-faceted nature of the disorders involving a wide and overlapping range of symptoms as well as complex changes in structural and functional brain networks, it is increasingly important to devise computational frameworks that can consider the underlying patterns of heterogeneous changes with specific target assessments, at the same time producing a summarizing output from the high-dimensional neuroimaging data. While various machine learning approaches focus on diagnostic prediction, many learning frameworks analyze important features at the level of brain regions involved in prediction using supervised methods. Unsupervised learning methods have also been utilized to break down the neuroimaging features into lower dimensional components. However, most learning frameworks either do not consider the target assessment information while extracting brain subspaces, or can extract only higher dimensional importance associations as an ordered list of involved features, making manual interpretation at the level of subspaces difficult. We present a novel multimodal active subspace learning framework to understand various subspaces within the brain that are associated with changes in particular biological and cognitive traits. For a given cognitive or biological trait, our framework performs a decomposition of the feature importances to extract robust multimodal subspaces that define the most significant change in the given trait. Through a rigorous cross-validation procedure on an Alzheimer’s disease (AD) dataset, we show that our framework can extract subspaces covering both functional and structural modalities, which are specific to a given clinical assessment (like memory and other cognitive skills) and also retain predictive performance in standard machine learning algorithms. We show that our framework not only uncovers AD-related brain regions (e.g., hippocampus, entorhinal cortex) in the associated brain subspaces, but also enables an automated identification of multiple underlying structural and functional sub-systems of the brain that collectively characterize changes in memory and cognitive skill proficiency related to brain disorders like AD.
Spatial Scale of Non-Target Effects of Cotton Insecticides
Authors: Bordini Isadora , Naranjo Steven E. , Fournier Alfred , Ellsworth Peter C.
Published: August 2022

Plot size is of practical importance in any integrated pest management (IPM) study that has a field component. Such studies need to be conducted at a scale relevant to species dynamics because their abundance and distribution in plots might vary according to plot size. An adequate plot size is especially important for researchers, technology providers and regulatory agencies in understanding effects of various insect control technologies on non-target arthropods. Plots that are too small might fail to detect potential harmful effects of these technologies due to arthropod movement and redistribution among plots, or from untreated areas and outside sources. The Arizona cotton system is heavily dependent on technologies for arthropod control, thus we conducted a 2-year replicated field experiment to estimate the optimal plot size for non-target arthropod studies in our system. Experimental treatments consisted of plot sizes and insecticides in a full factorial. We established three plot sizes that measured 144 m2, 324 m2 and 576 m2. For insecticides, we established an untreated check, a positive control insecticide with known negative effects on the arthropod community and a selective insecticide. We investigated how plot size impacts the estimation of treatment effects relative to community structure (27 taxa), community diversity, individual abundance, effect sizes, biological control function and success of arthropod taxa with a wide range of mobility, including Collops spp., Orius tristicolor, Geocoris spp., Misumenops celer, Drapetis nr. divergens and Chrysoperla carnea. The 144 m2 plots supported similar results for all parameters compared to larger plots, thus being sufficiently large to measure insecticidal effects on non-target arthropods in Arizona cotton. Though results might be system-specific, they point to a scale of testing that should be considered when developing any IPM guidelines, especially for systems that share a similar fauna of predators and pests.
Multidimensional topography of memory revealed from thousands of daily documented memories
Authors: Bainbridge Wilma A. , Baker Chris I.
Published: August 2022

Our memories form a rich, colorful tapestry of emotions, events, people, and places, woven across the decades of our lives. However, research has typically been limited in its ability to assess the multidimensional nature of episodic memory, given the short time scales and artificial stimulus sets often required in experiments. In an era when people are constantly recording their lives through social media, we can now examine key questions about the behavioral and neural underpinnings of diverse and extensive real-world memories. Here, we tested the neural representations of episodic memory in a naturalistic setting, specifically focusing on the age, location, subjective memory strength, and emotional content of memories. We recruited 23 users of a video diary app (“1 Second Everyday”), who had recorded a total of 9,266 daily memory videos spanning up to 7 years prior to our study. During a 3T fMRI scan, participants viewed a set of 300 of their own memory videos intermixed with 300 videos from another individual. We identified key areas specifically engaged for one’s own memories versus another’s. Delving into the multidimensional nature of these memories, we find that their features are tightly interrelated, highlighting the need to consider these features in conjunction when conducting memory research. Importantly, when looking at the distinct contributions of these features, we find a topography of memory content extending across the medial parietal lobe with separate representations of a memory’s age, it’s strength, and the familiarity of the people and places involved.
A chromosome-level genome resource for studying virulence mechanisms and evolution of the coffee rust pathogen Hemileia vastatrix
Authors: Tobias Peri A , Edwards Richard J. , Surana Priyanka , Mangelson Hayley , Inácio Vera , do Céu Silva Maria , Várzea Vitor , Park Robert F. , Batista Dora
Published: August 2022

Recurrent epidemics of coffee leaf rust, caused by the fungal pathogen Hemileia vastatrix, have constrained the sustainable production of Arabica coffee for over 150 years. The ability of H. vastatrix to overcome resistance in coffee cultivars and evolve new races is inexplicable for a -pathogen that supposedly only utilizes clonal reproduction. Understanding the evolutionary complexity between H. vastatrix and its only known host, including determining how the pathogen evolves virulence so rapidly is crucial for disease management. Achieving such goals relies on the availability of a comprehensive and high-quality genome reference assembly. To date, two reference genomes have been assembled and published for H. vastatrix that, while useful, remain fragmented and do not represent chromosomal scaffolds. Here, we present a complete scaffolded pseudochromosome-level genome resource for H. vastatrix strain 178a (Hv178a). Our initial assembly revealed an unusually high degree of gene duplication (over 50% BUSCO basidiomycota_odb10 genes). Upon inspection, this was predominantly due to a single scaffold that itself showed 91.9% BUSCO Completeness. Taxonomic analysis of predicted BUSCO genes placed this scaffold in Exobasidiomycetes and suggests it is a distinct genome, which we have named Hv178a associated fungal genome (Hv178a AFG). The high depth of coverage and close association with Hv178a raises the prospect of symbiosis, although we cannot completely rule out contamination at this time. The main Ca. 546 Mbp Hv178a genome was primarily (97.7%) localised to 11 pseudochromosomes (51.5 Mb N50), building the foundation for future advanced studies of genome structure and organization.
Spatial attention in perceptual decision making as revealed by response-locked classification image analysis
Authors: Sano Hironobu , Ueno Natsuki , Maruyama Hironori , Motoyoshi Isamu
Published: August 2022

In many situations, humans serially sample information from many locations in an image to make an appropriate decision about a visual target. Spatial attention plays a crucial role in this serial vision process. To investigate the effect of spatial attention in such dynamic decision making, we applied a classification image (CI) analysis locked to the observer’s reaction time (RT). We asked human observers to detect as rapidly as possible a target whose contrast gradually increased on the left or right side of dynamic noise, with the presentation of a spatial cue. The analysis revealed a spatiotemporally biphasic profile of the CI which peaked at ∼350 ms before the observer’s response. We found that a valid cue presented at the target location shortened the RT and increased the overall amplitude of the CI, especially when the cue appeared 500-1250 ms before the observer’s response. The results were quantitatively accounted for by a simple perceptual decision mechanism that accumulates the outputs of the spatiotemporal contrast detector, whose gain is increased by sustained attention to the cued location.
Absorbable Conductive Electrotherapeutic Scaffolds (ACES) for Enhanced Peripheral Nerve Regeneration and Stimulation
Authors: Srinivasan Shriya , Gfrerer Lisa , Karandikar Paramesh , Som Avik , Alshareef Amro , Liu Sabrina , Higginbotham Haley , Ishida Keiko , Hayward Alison , Kalva Sanjeeva P. , Langer Robert , Traverso Giovanni
Published: August 2022

While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration after injury to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. Here, we describe the design and validation of a new platform for nerve regeneration and interfacing: Absorbable, Conductive, Electrotherapeutic Scaffolds (ACES). ACES are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open and minimally invasive percutaneous approaches. In a rodent model of sciatic nerve repair, ACES significantly improved motor and sensory recovery (p< 0.05), increased muscle mass (p< 0.05), and increased axonogenesis (p< 0.05). Triggered dissolution of ACES enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p< 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p< 0.05). Overall, ACES facilitated lead placement, stabilization, stimulation and atraumatic removal enabling therapeutic PNS as demonstrated in small and large animal models.
Magnetique: An interactive web application to explore transcriptome signatures of heart failure
Authors: Britto-Borges Thiago , Ludt Annekathrin , Boileau Etienne , Gjerga Enio , Marini Federico , Dieterich Christoph
Published: August 2022

Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. We present Magnetique (https://shiny.dieterichlab.org/app/magnetique), an interactive web application to explore the transcriptional signatures of heart failure. We reanalyzed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts from organ donors and patient characteristics that allowed us to model confounding factors. Focusing on the DCM versus HCM contrast, we identified 201 differentially expressed genes and associated pathway signatures. Moreover, we predict underlying signaling networks based on inferred transcription factor activities. To the best of our knowledge, Magnetique is the first online application to provide an interactive view of the HF transcriptome by analyzing differential transcript isoform usage. Finally, another graphical view on statistically predicted RNA-binding protein to target transcript interactions complements the Magnetique web application.

The source code for both the analyses (https://github.com/dieterich-lab/magnetiqueCode2022) and the web application (https://github.com/AnnekathrinSilvia/magnetique) is available to the public. We hope that our application will help users to uncover the molecular basis of heart failure.
Notch Signaling and Fluid Shear Stress in Regulating Osteogenic Differentiation
Authors: Zhao Yuwen , Richardson Kiarra , Yang Rui , Bousraou Zoe , Lee Yoo Kyoung , Fasciano Samantha , Wang Shue
Published: August 2022

Osteoporosis is a common bone and metabolic disease that is characterized by bone density loss and microstructural degeneration. Human bone marrow-derived mesenchymal stem cells (hMSCs) are multipotent progenitor cells with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes, which have been utilized extensively in the field of bone tissue engineering and cell-based therapy. Although fluid shear stress plays an important role in bone osteogenic differentiation, the cellular and molecular mechanisms underlying this effect remain poorly understood. Here, an LNA/DNA nanobiosensor was exploited to monitor mRNA gene expression of hMSCs that were exposed to physiologically relevant fluid shear stress to examine the regulatory role of Notch signaling during osteogenic differentiation. First, the effects of fluid shear stress on cell viability, proliferation, morphology, and osteogenic differentiation were investigated and compared. Our results showed shear stress modulates hMSCs morphology and osteogenic differentiation depending on the applied shear and duration. By incorporating this LNA/DNA nanobiosensor and alkaline phosphatase (ALP) staining, we further investigated the role of Notch signaling in regulating osteogenic differentiation. Pharmacological treatment is applied to disrupt Notch signaling to investigate the mechanisms that govern shear stress induced osteogenic differentiation. Our experimental results provide convincing evidence supporting that physiologically relevant shear stress regulates osteogenic differentiation through Notch signaling. Inhibition of Notch signaling mediates the effects of shear stress on osteogenic differentiation, with reduced ALP enzyme activity and decreased Dll4 mRNA expression. In conclusion, our results will add new information concerning osteogenic differentiation of hMSCs under shear stress and the regulatory role of Notch signaling. Further studies may elucidate the mechanisms underlying the mechanosensitive role of Notch signaling in stem cell differentiation.
Surgical techniques and tips for a reliable murine model of primary and metastatic pancreatic cancer
Authors: Hue Jonathan J. , Zarei Mehrdad , Graor Hallie J. , Hajihassani Omid , Katayama Erryk S. , Loftus Alexander W. , Vaziri-Gohar Ali , Winter Jordan M.
Published: August 2022

For patients with pancreatic cancer, survival rates lag behind other common cancers. This is in part due to the relative resistance to conventional chemotherapeutics and novel immune- or targeted-therapies. Ongoing research efforts are needed to identify and validate effective therapies. It is the unfortunate reality that a significant proportion of pre-clinical success does not translate into improved patient outcomes, likely due to a multitude of factors. In the current research landscape, flank xenograft models are commonly utilized to study pancreatic cancer, as this technique is fast, fairly non-invasive, and reliable. However, this model is not anatomically or physiologically accurate, does not impact other intra-abdominal organs, and experiments are often ended based on tumor size rather than systemic illness. Orthotopic injections of cancer cells directly into the pancreas for study of localized disease or into the spleen for study of hepatic metastases can be performed via a quick, reliable, minimally invasive surgical procedure with minimal morbidity and mortality. Existing methodologic reports are often sparse. Thus, there are significant knowledge and technical gaps for researchers attempting these techniques for the first time. In the current report, details of orthotopic pancreatic injections and splenic injections for metastatic disease are provided. Details of commonly encountered operative issues and mistakes are presented with suggestions to improve performance are described. A summary of expected outcomes is also provided herein.
Appetitive and aversive cue reactivities differentiate biotypes of alcohol drinkers
Authors: Chen Yu , Li Chiang-Shan R.
Published: August 2022

Craving reflects the subjective urge to use drugs and can be triggered by both positive and negative emotional states. However, no studies have systematically investigated the relative roles of these mechanisms in the pathophysiology of substance misuse or distinguished the mechanisms in individual vulnerability to substance use disorders. In the current study, we performed meta-analyses of drug cue-elicited reactivity and win and loss processing in the monetary incentive delay task to identify distinct neural correlates of appetitive and aversive responses during cue exposure. We then characterized the appetitive and aversive cue responses in seventy-six alcohol drinkers performing a cue craving task during fMRI. Imaging data were processed according to published routines. The appetitive circuit involved medial cortical regions and the ventral striatum, and the aversive circuit involved the insula, caudate and mid-cingulate cortex. We observed a significant correlation ofβestimates of cue-elicited activity of the appetitive and aversive circuit. However, individuals varied in appetitive and aversive cue responses. From the regression of appetitive (y) vs. aversive (x)β, we identified participants in the top 1/3 each of those with positive (n = 15) and negative (n = 11) residuals as “approach” and “avoidance” biotype, with the others as the “mixed” biotype (n = 50). For clinical characteristics, the avoidance biotype showed higher sensitivity to punishment. In contrast, the approach biotype showed higher levels of sensation seeking and alcohol expectancy for social and physical pressure. The findings highlighted distinct neural underpinnings of appetitive and aversive components of cue-elicited reactivity and substantiated the importance of biotyping substance misuse.
IGF-1 therapy improves muscle size and function in experimental peripheral arterial disease
Authors: Dong Gengfu , Moparthy Chatick , Thome Trace , Kim Kyoungrae , Ryan Terence E.
Published: August 2022

CONDENSED ABSTRACT

Lower extremity peripheral arterial disease (PAD) has continued to increase in prevalence over the past several decades, yet therapeutic development has remained stagnant. Skeletal muscle health and function has been strongly linked to quality of life and medical outcomes in PAD patients. Using a rodent model of PAD, this study demonstrates that treatment of the ischemic limb with adeno-associated virus-mediated expression of insulin-like growth factor 1 (IGF1) significantly increases muscle size and strength, without improving limb hemodynamics. Interestingly, the effect size of IGF1 therapy was larger in female mice compared to their male counterparts, where substantial improvements in muscle specific force and a reduction in the progression of limb necrosis were observed. These findings indicate that clinical trials should carefully examine sex-dependent effects in experimental PAD therapies.
Precise targeting for 3D cryo-correlative light and electron microscopy volume imaging of tissues using a FinderTOP
Authors: de Beer Marit , Daviran Deniz , Roverts Rona , Rutten Luco , Sánchez Elena Macías , Metz Jurriaan R. , Sommerdijk Nico , Akiva Anat
Published: August 2022

Cryo-correlative light and electron microscopy (cryoCLEM) is a powerful strategy to high resolution imaging in the unperturbed hydrated state. In this approach fluorescence microscopy aids localizing the area of interest, and cryogenic focused ion beam/scanning electron microscopy (cryoFIB/SEM) allows preparation of thin cryo-lamellae for cryoET. However, the current method cannot be accurately applied on bulky (3D) samples such as tissues and organoids. 3D cryo-correlative imaging of large volumes is needed to close the resolution gap between cryo-light microscopy and cryoET, placing sub-nanometer observations in a larger biological context. Currently technological hurdles render 3D cryoCLEM an unexplored approach.

Here we demonstrate a cryoCLEM workflow for tissues, correlating cryo-Airyscan confocal microscopy with 3D cryoFIB/SEM volume imaging. Accurate correlation is achieved by imprinting a FinderTOP pattern in the sample surface during high pressure freezing, and allows precise targeting for cryoFIB/SEM volume imaging.
An Integrative Approach to Dissect the Drug Resistance Mechanism of the H172Y Mutation of SARS-CoV-2 Main Protease
Authors: Clayton Joseph , de Oliveira Vinicius Martins , Ibraham Mohamed Fouad , Sun Xinyuanyuan , Mahinthichaichan Paween , Shen Mingzhe , Hilgenfeld Rolf , Shen Jana
Published: August 2022

Nirmatrelvir is an orally available inhibitor of SARS-CoV-2 main protease (Mpro) and the main ingredient of PAXLOVID, a drug approved by FDA for high-risk COVID-19 patients. Recently, a rare natural mutation, H172Y, was found to significantly reduce nirmatrelvir’s inhibitory activity. As the COVID-19 cases skyrocket in China and the selective pressure of antiviral therapy builds up in the US, there is an urgent need to characterize and understand how the H172Y mutation confers drug resistance. Here we investigated the H172Y Mpro’s conformational dynamics, folding stability, catalytic efficiency, and inhibitory activity using all-atom constant pH and fixed-charge molecular dynamics simulations, alchemical and empirical free energy calculations, artificial neural networks, and biochemical experiments. Our data suggests that the mutation significantly weakens the S1 pocket interactions with the N-terminus and perturbs the conformation of the oxyanion loop, leading to a decrease in the thermal stability and catalytic efficiency. Importantly, the perturbed S1 pocket dynamics weakens the nirma-trelvir binding in the P1 position, which explains the decreased inhibitory activity of nirmatrelvir. Our work demonstrates the predictive power of the combined simulation and artificial intel-ligence approaches, and together with biochemical experiments they can be used to actively surveil continually emerging mutations of SARS-CoV-2 Mpro and assist the discovery of new antiviral drugs. The presented workflow can be applicable to characterize mutation effects on any protein drug targets.
Relative changes in the cochlear summating potentials to paired-clicks predict speech-in-noise perception and subjective hearing acuity
Authors: Lai Jesyin , Bidelman Gavin M.
Published: August 2022

Objective assays of human cochlear synaptopathy (CS) have been challenging to develop. It’s suspected if relative summating potential (SP) changes are different in CS listeners. In this proof-of-concept study, young, normal-hearing adults were recruited and assigned to a low/high-risk group for having CS based on their audiograms at 9-16 kHz. SPs to paired-clicks with varying inter-click intervals isolated non-refractory receptor components of cochlear activity. Abrupt increases in SPs to paired- vs. single-clicks were observed in high-risk listeners. Critically, overexaggerated SPs predicted speech-in-noise and subjective hearing abilities, suggesting relative SP changes to rapid clicks might help identify putative synaptopathic listeners.
ZmWRKY82-ZmSLG regulate seed development by modulating brassionsteroid homeostasis in maize
Authors: Li Hui , Wang Yayun , Luo Li , Hu Yufeng , Li Yangping , Zhang Junjie , Huang Yubi
Published: August 2022

Seed development is a crucial biological process affecting crop yield. Brassionsteroids (BRs) plays essential role in seed development. Although part of genes participated in BR regulate seed development have been cloned in maize, their genetic and mechanisms are still unclear. In the previous experiment, we found that exogenous spray BL promote seed development. Here, RNA-sequence analysis of BL treated seeds revealed that 12 candidate function genes and 62 candidate transcription factors among the differentially expressed genes (DEGs) were regulated by BL. Combining with previous QTL and GWAS research results in maize and homologous gene analysis, ZmSLG1 was screened out from 12 candidate function genes for further study. Overexpression of ZmSLG1 displayed round seed and delayed embryo development in maize. Moreover, overexpression of ZmSLG1 decreased BR content and increased expression of BR synthesis related genes in seed. To understand the mechanism of BL regulating ZmSLG1 expression, ZmWRKY82 was identified from 62 candidate transcription factors and examined its function. Transient expression, EMSA and ChIP analysis showed ZmWRKY82 can directly bind to the ZmSLG1 promoter to regulate ZmSLG1 expression. Collectively, exogenous BL regulate the ZmSLG1 gene expression through ZmWRKY82 transcription factor, and ZmSLG1 negatively regulates the endogenous BR contents in seed.

Highlight

We conclude that ZmWRKY82-ZmSLG1 is required for BR homeostasis and that modification of ZmSLG1 expression to an appropriate level may provide a way to increase yield.
Phylophenomic and Phylogenomic analysis for Ovis aries reveals distinct identity of newly reported breed
Authors: Pal Aruna , Banerjee Samiddha , karmakar Prabir
Published: August 2022

Domestication and phylogenetics for Ovis aries is an important species to study, since there exists enormous biodiversity in terms of habitat and utility of sheep. The present study aimed at identification of the biodiversity existing within sheep breeds reared in different agroclimatic zones of the state West Bengal (Garole, Birbhum, Bonpala and Chotanagpuri) through phylogenetic analysis of phenotypic traits as growth and biomorphometric traits through principal component analysis, factor analysis, genetic correlation, multivariate cluster analysis through Hierarchial classification and k-means cluster analysis. Confirmation of the phylophenomic studies were later on carried out with phylogenomic analysis with microsatellite markers for sheep. Birbhum sheep from dry arid region of West Bengal is reported as the newly reported breed of sheep with distinct genetic identity.
EVALUATION OF THE PERFORMANCE OF THE ROUTINE EPIDEMIOLOGICAL SURVEILLANCE SYSTEM IN THE HEALTH DISTRICT OF TAMBACOUNDA (SENEGAL) IN 2020
Authors: Gadiaga Tidiane , Ba Mouhamadou Faly , Sagna Siré , Cissé Bayal , Diallo Amadou , Ndiaye Samba , Diop Boly , Ndiaye Mbouna , Ndoye Babacar , Ba Mamadou Sarifou , Sall Yoro , Sougou Ndeye Mareme , Tine Jean Augustin Diégane , Leye Mamadou Makhtar Mbacké
Published: August 2022

Introduction

Epidemiological surveillance (ES) which is a continuous systematic process of data collection, analysis and interpretation for decision-making is of paramount importance for a good health system. Thus, to contribute to the improvement of the health system in Senegal, a study of the functioning of the routine epidemiological surveillance system was conducted in Tambacounda from S1 to S53 of the year 2020.

Methodology

A descriptive and analytical cross-sectional study was conducted from 1 to 17 July 2021. Comprehensive recruitment of the district’s 44 health care points was carried out. Data collection was carried out through a questionnaire prepared, pre-tested and administered to the 44 heads of public and non-public health facilities. The analyses were carried out with R software version 4.0.5.

Results

Of the 44 health facilities surveyed, 64% were public and 36% were non-public. The completeness and timeliness of the data were 100% and 97.5%, respectively. Suspected cases of tuberculosis were the most reported. For the providers surveyed (n=44), only 65.9% had knowledge of disease under epidemiological surveillance (DUES) and 93.2% managed suspected cases. On-site data analysis is only performed by 20.5% of providers. Only 38.6% of the service delivery point (SDP) had a health area card and the ES was under the responsibility of 77.3% of the paramedics. The training of ES officials was effective for only 45.5% of them. Despite the availability of dry tubes (69.8%), only 29.5% of PSD had COVID sampling equipment. The contribution of local authorities and technical and financial partners (TFP) to the SE was 22.7% and 29.5% respectively.

There was a statistically significant link between public SDP with knowledge of DUES (p <0.001), display of case definitions (p <0.001), feedback of reported cases, knowledge of indicators (p<0.001), existence of a health area map (p <0.001), advocacy with authorities (p=0.003), staff training (p=0.002), availability of DUES vaccines (p <0.001), availability of notification form (p<0.001) and partner contribution to ES activities.

Conclusion

Staff training, regular monitoring of ES activities with greater involvement of non-public structures, and the availability of inputs applied to the six pillars of the health system, are essential elements on which action must be taken. for an efficient ES system in the Tambacounda health district for the benefit of the country’s health system.
Does Influenza vaccination reduce the risk of contracting COVID-19?
Authors: Alòs Francesc , Zaldúa Yoseba Cánovas , Feijóo M Victoria , Del-Val José Luís , Sanchez-Callejas Andrea , Colomer MA
Published: August 2022

The concurrent timing of the COVID-19 pandemic and the seasonal occurrence of influenza, makes it especially important to analyze the possible effect of the influenza vaccine on the risk of contracting COVID-19, or in reducing the complications caused by both diseases, especially in vulnerable populations. There is very little scientific information on the possible protective role of the influenza vaccine against the risk of contracting COVID-19, particularly in groups at high-risk of influenza complications. Reducing the risk of contracting COVID-19 in high-risk patients (those with a higher risk of infection, complications, and death) is essential to improve public well-being and to reduce hospital pressure and the collapse of primary health centers. Apart from overlapping in time, COVID-19 and flu share common aspects of transmission, so that measures to protect against flu might be effective in reducing the risk of contracting COVID-19.

In this study, we conclude that the risk of contracting COVID-19 is reduced if patients are vaccinated against flu, but the reduction is small (0.22%) and therefore not clinically important. When this reduction is analysed based on the risk factor suffered by the patient, statistically significant differences have been obtained for patients with cardiovascular problems, diabetics, chronic lung and chronic kidney, in all four cases the reduction in the risk of contagion does not reach 1%.

It is worth highlighting the behaviour that is completely different from the rest of the data for institutionalized patients. The data for these patients does not suggest a reduction in the risk of contagion for patients vaccinated against the flu, but rather the opposite, a significant increase of 6%.

Socioeconomic conditions, as measured by the MEDEA deprivation index, explain increases in the risk of contracting COVID-19, and awareness campaigns should be increased to boost vaccination programs.
Intermediate levels of asymptomatic transmission can lead to the highest levels of epidemic fatalities
Authors: Park Sang Woo , Dushoff Jonathan , Grenfell Bryan T. , Weitz Joshua S.
Published: August 2022

Asymptomatic infections have hampered the ability to characterize and prevent the transmission of SARS-CoV-2 throughout the ongoing pandemic. Even though asymptomatic infections reduce severity at the individual level, they can make population-level outcomes worse if asymptomatic individuals—unaware they are infected—transmit more than symptomatic individuals. Using an epidemic model, we show that intermediate levels of asymptomatic infection lead to the highest levels of epidemic fatalities when the increase in asymptomatic transmission, due either to individual behavior or mitigation efforts, is strong. We generalize this result to include presymptomatic transmission, showing how intermediate levels of non-symptomatic transmission can lead to the highest levels of fatalities. Finally, we extend our framework to illustrate how the intersection of asymptomatic spread and immunity profiles determine epidemic trajectories, including population-level severity, of future variants.
The role of motion in the neural representation of social interactions in the posterior temporal cortex
Authors: Landsiedel Julia , Daughters Katie , Downing Paul E. , Koldewyn Kami
Published: August 2022

Humans are an inherently social species, with multiple focal brain regions sensitive to various visual social cues such as faces, bodies, and biological motion. More recently, research has begun to investigate how the brain responds to more complex, naturalistic social scenes, identifying a region in the posterior superior temporal sulcus (SI-pSTS; i.e., social interaction pSTS), among others, as an important region for processing social interaction. This research, however, has presented images or videos, and thus the contribution of motion to social interaction perception in these brain regions is not yet understood. In the current study, 22 participants viewed videos, image sequences, scrambled image sequences and static images of either social interactions or non-social independent actions. Combining univariate and multivariate analyses, we confirm that bilateral SI-pSTS plays a central role in dynamic social interaction perception but is much less involved when ‘interactiveness’ is conveyed solely with static cues. Regions in the social brain, including SI-pSTS and extrastriate body area (EBA), showed sensitivity to both motion and interactive content. While SI-pSTS is somewhat more tuned to video interactions than is EBA, both bilateral SI-pSTS and EBA showed a greater response to social interactions compared to non-interactions and both regions responded more strongly to videos than static images. Indeed, both regions showed higher responses to interactions than independent actions in videos and intact sequences, but not in other conditions. Exploratory multivariate regression analyses suggest that selectivity for simple visual motion does not in itself drive interactive sensitivity in either SI-pSTS or EBA. Rather, selectivity for interactions expressed in point-light animations, and selectivity for static images of bodies, make positive and independent contributions to this effect across the LOTC region. Our results strongly suggest that EBA and SI-pSTS work together during dynamic interaction perception, at least when interactive information is conveyed primarily via body information. As such, our results are also in line with proposals of a third visual stream supporting dynamic social scene perception.