bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased functional connectivity of amygdala subregions in patients with drug-naïve panic disorder and without comorbidities
Authors: Zhang Ping , Yang Xiangyun , Wang Yun , Liu Huan , Meng Limin , Yan Zijun , Zhou Yuan , Li Zhanjiang 
Published: May 2023

Abstract

Background:
Amygdala plays an important role in the neurobiological basis of panic disorder (PD), and the amygdala contains different subregions, which may play different roles in PD. The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest (ROIs) and the clinical symptoms of PD patients.

Methods:
Fifty-three drug-naïve, non-comorbid PD patients and 70 healthy controls (HCs) were recruited. Seed-based resting-state functional connectivity (rsFC) analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed. Two samples t test was performed for the seed-based Fisher's z-transformed correlation maps. The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis.

Results:
PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group (left amygdala [lAMY]: t = 4.84, P <0.001; right amygdala [rAMY]: t = 4.55, P <0.001; left centromedial amygdala [lCMA]: t = 3.87, P <0.001; right centromedial amygdala [rCMA]: t = 3.82, P = 0.002; left laterobasal amygdala [lBLA]: t = 4.33, P <0.001; right laterobasal amygdala [rBLA]: t = 4.97, P <0.001; left superficial amygdala [lSFA]: t = 3.26, P = 0.006). The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group (t = 3.70, P = 0.003). And most of the altered rsFCs were located in the default mode network (DMN). A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients (r = 0.285, P = 0.039).

Conclusions:
Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD. Future studies may further explore whether the rsFC of amygdala subregions, especially with the regions in DMN, can be used as a biological marker of PD.
Microblading-Induced Granulomatous Reaction: Case Report and Review of the Literature
Authors: Ibraheim Marina Kristy , Desai Mansee , Tawfik Melanie , Elsensohn Ashley , Furukawa Betsy 
Published: May 2023

Abstract:Microblading is a common cosmetic procedure that can modify the appearance of one's eyebrows. Although generally well-tolerated, the procedure can cause a number of dermatologic issues; on rare occasions, granulomatous reactions can manifest. We use this case to highlight a presentation of a nonsarcoidal granulomatous dermatitis and review the literature on granulomatous reactions secondary to microblading. Of the 21 cases included in our review, approximately half (10/21) were diagnosed with foreign-body granulomas and the other half with sarcoidosis (7 of 21 with systemic sarcoidosis and 4 of 21 with cutaneous sarcoidosis). Although microblading remains a commonplace cosmetic technique, it is not without risk. Much like other types of tattoos, microblading can cause granulomatous reactions for which we must be vigilant, and further workup for sarcoidosis might be considered in select patients.
Setting Observers Up for Success in Simulation
Authors: Johnson Brandon Kyle , Fey Mary 
Published: May 2023

Background:
The assignment to be an observer in simulation is common. Despite evidence that learning outcomes are similar for participants and observers, there is uncertainty among simulation facilitators about how to create a valuable learning experience for learners in observer roles.

Problem:
The prebriefing practices of establishing a fiction contract and orienting learners to their role are frequently centered on learners in participant roles.

Approach:
Tailoring a fiction contract to the opportunities and challenges that observers experience as well as the use of feedforward to provide specific objectives to learners in observer roles is discussed.

Conclusions:
Including specific strategies in the prebriefing for learners in observer roles sets observers up for success in simulation learning experiences.
Using Artificial Intelligence to Identify Sources and Pathways of Lead Exposure in Children
Authors: Sambanis Apostolis , Osiecki Kristin , Cailas Michael , Quinsey Logan , Jacobs David E. 
Published: May 2023

Context:
Sources and pathways of lead exposure in young children have not been analyzed using new artificial intelligence methods.

Objective:
To collect environmental, behavioral, and other data on sources and pathways in 17 rural homes to predict at-risk households and to compare urban and rural indicators of exposure.

Design:
Cross-sectional pilot study.

Setting:
Knox County, Illinois, which has a high rate of childhood lead poisoning.

Participants:
Rural families.

Methods:
Neural network and K-means statistical analysis.

Main Outcome Measure:
Children's blood lead level.

Results:
Lead paint on doors, lead dust, residential property assessed tax, and median interior paint lead level were the most important predictors of children's blood lead level.

Conclusions:
K-means analysis confirmed that settled house dust lead loadings, age of housing, concentration of lead in door paint, and geometric mean of interior lead paint samples were the most important predictors of lead in children's blood. However, assessed property tax also emerged as a new predictor. A sampling strategy that examines these variables can provide lead poisoning prevention professionals with an efficient and cost-effective means of identifying priority homes for lead remediation. The ability to preemptively target remediation efforts can help health, housing, and other agencies to remove lead hazards before children develop irreversible health effects and incur costs associated with lead in their blood.
Understanding Disparities in Antiretroviral Therapy Adherence and Sustained Viral Suppression Among Black, Hispanic/Latina, and White Women in the United States – Medical Monitoring Project, United States, 2015–2019
Authors: Raiford Jerris L. , Yuan Xin , Carree Tamara , Beer Linda 
Published: May 2023

Background:
Racial and ethnic disparities in antiretroviral therapy (ART) adherence and sustained viral suppression (SVS) have been documented among women with HIV. We examined factors that may account for these racial/ethnic differences among women to inform interventions that increase health equity.

Methods:
We used data from the 2015–2019 cycles of the Medical Monitoring Project, a probability sample of U.S. adults with diagnosed HIV. Using logistic regression with predicted marginal means, we calculated weighted prevalence differences (PDs) of ART adherence and SVS among Black, Hispanic/Latina, and White women taking ART. Using modeling with forward stepwise selection, we adjusted PDs for selected variables, including social and structural determinants of health (SDOH) factors, to examine whether magnitude of PDs was attenuated by their inclusion. We assessed relative changes between unadjusted and adjusted PDs.

Results:
After adjusting for poverty, transportation needs, health literacy, and gap in health insurance/coverage, the Black–White PD in adherence decreased by 11% (−16.0% to −14.2%). After adjusting for adherence, poverty, type of health insurance, and gap in health insurance/coverage, the Black–White PD in SVS reduced 37% (−7.9% to −5.0%) and was no longer statistically different. The Hispanic/Latina–White PD in adherence reduced 24% (−12.7% to −9.6%) after adjusting for poverty, health literacy, and transportation needs. The unadjusted Hispanic/Latina–White PD in SVS was not significantly different.

Conclusion:
Racial/ethnic disparities in HIV outcomes among women taking ART were substantially reduced after accounting for SDOH and other factors although differences remained. Structural interventions to improve SDOH are needed to improve health equity for women with HIV.
Comparison of Anatomical and Diffusion MRI for detecting Parkinson’s Disease using Deep Convolutional Neural Network
Authors: Chattopadhyay Tamoghna , Singh Amit , Laltoo Emily , Boyle Christina P. , Owens-Walton Conor , Chen Yao-Liang , Cook Philip , McMillan Corey , Tsai Chih-Chien , Wang J-J , Wu Yih-Ru , van der Werf Ysbrand , Thompson Paul M. 
Published: May 2023

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disease that affects over 10 million people worldwide. Brain atrophy and microstructural abnormalities tend to be more subtle in PD than in other age-related conditions such as Alzheimer’s disease, so there is interest in how well machine learning methods can detect PD in radiological scans. Deep learning models based on convolutional neural networks (CNNs) can automatically distil diagnostically useful features from raw MRI scans, but most CNN-based deep learning models have only been tested on T1-weighted brain MRI. Here we examine the added value of diffusion-weighted MRI (dMRI) - a variant of MRI, sensitive to microstructural tissue properties - as an additional input in CNN-based models for PD classification. Our evaluations used data from 3 separate cohorts - from Chang Gung University, the University of Pennsylvania, and the PPMI dataset. We trained CNNs on various combinations of these cohorts to find the best predictive model. Although tests on more diverse data are warranted, deep-learned models from dMRI show promise for PD classification.Clinical RelevanceThis study supports the use of diffusion-weighted images as an alternative to anatomical images for AI-based detection of Parkinson’s disease.
Mechanisms of Resistance to CAR-T cell Immunotherapy: Insights from a Mathematical Model
Authors: Santurio Daniela S. , Paixão Emanuelle A. , Barros Luciana R.C. , Almeida Regina C. , Fassoni Artur C. 
Published: May 2023

AbstractChimeric Antigen Receptor (CAR)-T cell therapy long-term follow-up studies revealed non-durable remissions in a significant number of patients. Some of the mechanisms underlying these relapses include poor CAR T cell cytotoxicity or persistence, as well as antigen loss or lineage switching in tumor cells. In order to investigate how antigen-mediated resistance mechanisms affect therapy outcomes, we develop a mathematical model based on a set of integral-partial differential equations. Using a continuous variable to describe the level of antigen expression of tumor cells, we recapitulated important cellular mechanisms across patients with different therapeutic responses. Fitted with clinical data, the model successfully captured the dynamics of tumor and CAR-T cells for several hematological cancers. Furthermore, the role played by these mechanisms are explored with regard to different biological scenarios, such as pre-existing or acquired mutations, providing a deeper understanding of key factors underlying resistance to CAR-T cell immunotherapy.Statement of significanceOur study introduces the first mathematical model to characterize the influence of a continuous level of antigen expression on the interplay between Chimeric Antigen Receptor (CAR)-T cells and cancer cells. We examine various cellular mechanisms across different hematologic cancers, taking into account both antigen-positive and antigen-negative relapses. Our findings shed light on the role of antigen density in CAR-T cell therapies and provide a valuable framework to investigate resistance with potential to improve patient’s outcomes.
Probing macromolecular crowding at the lipid membrane interface with genetically-encoded sensors
Authors: Löwe Maryna , Hänsch Sebastian , Hachani Eymen , Schmitt Lutz , Weidtkamp-Peters Stefanie , Kedrov Alexej 
Published: May 2023

AbstractBiochemical processes within the living cell occur in a highly crowded environment. The phenomenon of macromolecular crowding is not an exclusive feature of the cytoplasm and can be observed in the densely protein-packed, nonhomogeneous cellular membranes and at the membrane interfaces. Crowding affects diffusional and conformational dynamics of proteins within the lipid bilayer, and modulates the membrane organization. However, the non-invasive quantification of the membrane crowding is not trivial. Here, we developed the genetically- encoded fluorescence-based sensor for probing the macromolecular crowding at the membrane interfaces. Two sensor variants, both composed of fluorescent proteins and a membrane anchor, but differing by the flexible linker domains were characterizedin vitro, and the procedures for the membrane reconstitution were established. Lateral pressure induced by membrane-tethered synthetic and protein crowders altered the sensors’ conformation, causing increase in the intramolecular Förster’s resonance energy transfer. The effect of protein crowders only weakly correlated with their molecular weight, suggesting that other factors, such as shape and charge play role in the quinary interactions. Upon their expression, the designed sensors were localized to the inner membrane ofE. coli, and measurements performed in extracted membrane vesicles revealed low level of interfacial crowding. The sensors offer broad opportunities to study interfacial crowding in a complex environment of native membranes, and thus add to the toolbox of methods for studying membrane dynamics and proteostasis.
Detection and Molecular Characterization of Animal Adenovirus and Astrovirus from Western Maharashtra, India
Authors: Sawant PM , Waghchaure RB , Shinde PA , Palikondawar AP , Lavania M 
Published: May 2023

AbstractBackgroundAstroviruses (AstV) and adenoviruses (AdV) are associated with diarrhoea in young ones of animals. However, the epidemiology and genetic diversity of AstVs and AdVs in animals are not well studied. Hence the present study was conducted to detect and characterize AstVs and AdVs in calves, piglets and puppies in India.FindingsOut of the processed porcine (48), canine (80), and bovine (65) faecal samples from Western Maharashtra, India, the porcine AstV (PAstV), bovine AstV (BAstV), canine AstV (CAstV), and porcine AdV (PAdV) were detected in 12.5%, 7.69%, 3.75% and 4.1% of samples, respectively. In the RNA-dependent RNA polymerase region-based phylogenetic analysis the detected BAstV strains grouped with MAstV-28, MAstV-33, and MAstV-35, CAstV strains belonged to MAstV-5, PAstV strains belonged to MAstV-24, MAstV-26, and MAstV-31. Both the detected PAdV were of genotype 3, exhibiting 91.9-92.5% nucleotide identity with Ivoirian and Chinese strains. The study reports first-time BAstVs from calves and PAdV-3 from piglets in India.ConclusionThe study revealed diversity in the circulation of AstVs and AdVs in young ones of dogs, pigs and calves. Therefore, extensive epidemiological investigations of AstV and AdV are necessary to confirm their association with diarrhoea and to develop diagnostic tools and control measures.
Tetraspanin CD82 maintains HTLV-1 biofilm polarization and is required for efficient viral transmission
Authors: Arone Coline , Martial Samuel , Burlaud-Gaillard Julien , Thoulouze Maria-Isabel , Roingeard Philippe , Dutartre Hélène , Muriaux Delphine 
Published: May 2023

ABSTRACTThe human T-lymphotropic virus type-1 (HTLV-1) is an oncogenic retrovirus whose transmission relies primarily on cell-to-cell contacts as cell-free viruses are poorly infectious. Among the intercellular transmission routes described, HTLV-1 biofilms are adhesive structures polarized at the cell surface that confine virions in a protective environment, which is believed to promote their simultaneous delivery during infection. Here, we show that several tetraspanins are enriched in HTLV-1 biofilms and incorporated into the viral envelope. However, we report that only tetraspanin CD82 interacts with HTLV-1 Gag which initiates its polarization into viral biofilms. Also, we demonstrate that CD82 maintains HTLV-1 biofilm polarization and favors viral transmission, as its silencing induces a complete reorganization of viral clusters at the cell surface and reduces the ability of infected T-cells to transmit the virus. Our results highlight the crucial role of CD82 in the architectural organization of HTLV-1 biofilms and their transfer through intercellular contacts.
Both stimulus-specific and configurational features of multiple visual stimuli shape the spatial ventriloquism effect
Authors: Kayser Christoph , Debats Nienke , Heuer Herbert 
Published: May 2023

AbstractStudies on multisensory perception often focus on simplistic conditions in which one single stimulus is presented per modality. Yet, in everyday life we usually encounter multiple signals per modality. To understand how multiple signals within and across the senses are combined we extended the classical audio-visual spatial ventriloquism paradigm to combine two visual stimuli with one sound. The individual visual stimuli presented in the same trial differed in their relative timing and spatial offsets to the sound, allowing us to contrast their individual and combined influence on sound localization judgements. We find that the ventriloquism bias is not dominated by a single visual stimulus but rather is shaped by the collective multisensory evidence. In particular, the contribution of an individual visual stimulus to the ventriloquism bias depends not only on its own relative spatio-temporal alignment to the sound but also the spatio-temporal alignment of the other visual stimulus. We propose that this pattern of multi-stimulus multisensory integration reflects the evolution of evidence for sensory causal relations during individual trials, calling for the need to extend established models of multisensory causal inference to more naturalistic conditions. Our data also suggest that this pattern of multisensory interactions extends to the ventriloquism aftereffect, a bias in sound localization observed in unisensory judgements following a multisensory stimulus.
mTOR Inhibition Suppresses Salinomycin-Induced Ferroptosis in Breast Cancer Stem Cells by Ironing Out Mitochondrial Dysfunctions
Authors: Cosialls Emma , Pacreau Emeline , Ceccacci Sara , Elhage Rima , Duruel Clémence , Desterke Christophe , Roger Kevin , Guerrera Chiara , Ducloux Romane , Souquere Sylvie , Pierron Gérard , Nemazanyy Ivan , Kelly Mairead , Dalmas Elise , Chang Yunhua , Goffin Vincent , Mehrpour Maryam , Hamaï Ahmed 
Published: May 2023

ABSTRACTFerroptosis constitutes a promising therapeutic strategy against cancer by efficiently targeting the highly tumorigenic and treatment-resistant cancer stem cells (CSCs). We previously showed that the lysosomal iron-targeting drug Salinomycin (Sal) was able to eliminate CSCs by triggering ferroptosis. Here, in a well-established breast CSCs model (human mammary epithelial HMLER CD24low/CD44high), we identified that pharmacological inhibition of mechanistic target of rapamycin (mTOR), suppresses Sal-induced ferroptosis. Mechanistically, mTOR inhibition modulates iron cellular flux and prevents the iron and ROS bursts induced by Sal. Besides, integration of multi-omics data identified mitochondria as a key target of Sal action. We demonstrated that mTOR inhibition prevents Sal-induced mitochondrial functional and structural alteration, and that Sal-induced metabolic plasticity is mainly dependent on the mTOR pathway. Overall, our findings provide experimental evidences on the detailed mechanisms of mTOR as a crucial effector of Sal-induced ferroptosis, and gives proof-of-concept that careful evaluation of such combination therapy (here mTOR and ferroptosis co-targeting) is required for effective treatment.GRAPHICAL ABSTRACT
Anin-silicoapproach to study the molecular interaction of the PINK1 kinase domain with Parkin Ubl domain
Authors: Biswas Sima , Roy Sreekanya , Bagchi Angshuman 
Published: May 2023

ABSTRACTParkinson’s Disease (PD) is the second most common neurodegenerative disorder which creates devastating effects on the neurons of the mid brain. PARK2 and PARK6 genes encode the E3 ubiquitin ligase Parkin and serine/threonine protein kinase PINK1 (PTEN-induced kinase 1), respectively. Mutations in these proteins are responsible for majority of the early onset of PD. PINK1 protein along with Parkin are known to participate in the mitochondrial mitophagy pathway which selectively removes damaged mitochondria. Parkin with the help of its intra-domain interactions goes to an autoinhibited inactive state. Parkin ubiquitin activity is suppressed in this condition. Phosphorylation of the Serine65 residue, present in the Ubl domain of Parkin, is required for its ubiquitin ligase activity. PINK1 protein phosphorylates the Serine65 residue after its self-phosphorylation. After activation, Parkin protein ubiquitinates other damaged mitochondrial proteins for their degradation. Therefore, PINK1-Parkin interaction is important for the proper maintenance of the mitochondrial and neuronal fidelity. In this present work, we are trying to find out how the mutations in the PINK1 kinase domain would affect the modes of its interaction with the Ubl domain of Parkin. We used the three dimensional coordinates of the PINK1 and Ubl domain of Parkin from our previous work and selected the mutations P296L and G309D which have the abilities to hamper the said interactions between PINK1 and the Ubl domain of Parkin. We used molecular docking followed by molecular dynamics simulations to study the nature and structural dynamics of the binding interactions. The results from our study could provide an insight into the PINK1 mediated Parkin activation and plausible biochemical mechanism behind the onset of PD.
A mysterious cloak: the peptidoglycan layer of algal and plant plastids
Authors: MacLeod Alexander I. , Knopp Michael R. , Gould Sven B. 
Published: May 2023

AbstractThe plastids of algae and plants originated on a single occasion from an endosymbiotic cyanobacterium at least a billion years ago. Despite the divergent evolution that characterizes the plastids of different lineages, many traits such as membrane organisation and means of fission are universal – they pay tribute to the cyanobacterial origin of the organelle. For one such trait, the peptidoglycan (PG) layer, the situation is more complicated, and little is known about its distribution and molecular relevance in green algae and land plants. Here, we investigate the extent of PG presence across the Chloroplastida using a phylogenomic approach. Our data support the view of a PG layer being present in the last common ancestor of land plants and its remarkable conservation across bryophytes that are otherwise characterized by gene loss. In embryophytes, the occurrence of the PG layer biosynthetic toolkit becomes patchier, but the availability of novel genome data questions previous predictions regarding a functional coevolution of the PG layer and the plastid division machinery-associated gene FtsZ3. Furthermore, our data confirm the presence of penicillin-binding proteins (PBPs) in seed plants, which were previously thought to be absent from this clade. The thicker and seemingly unchanged PG layer armouring the plastids of glaucophyte algae might still provide the original function of structural support, but the same can likely not be said about the only recently identified and ultrathin PG layer of bryophyte and tracheophyte plastids. In combination with the apparent lack of some genes thought critical for PG layer biosynthesis in land plants that, however, likely have a PG layer, this leaves many issues with respect to the composition, exact function, and biosynthesis in land plants to be explored.