bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-population genome-wide association study implicates both immune and non-immune factors in the etiology of pediatric steroid sensitive nephrotic syndrome
Authors: Barry Alexandra , McNulty Michelle T. , Jia Xiaoyuan , Gupta Yask , Debiec Hanna , Luo Yang , Nagano China , Horinouchi Tomoko , Jung Seulgi , Colucci Manuela , Ahram Dina F. , Mitrotti Adele , Sinha Aditi , Teeninga Nynke , Jin Gina , Shril Shirlee , Caridi Gianluca , Bodria Monica , Lim Tze Y , Westland Rik , Zanoni Francesca , Marasa Maddalena , Turudic Daniel , Giordano Mario , Gesualdo Loreto , Magistroni Riccardo , Pisani Isabella , Fiaccadori Enrico , Reiterova Jana , Maringhini Silvio , Morello William , Montini Giovanni , Weng Patricia L. , Scolari Francesco , Saraga Marijan , Tasic Velibor , Santoro Domenica , van Wijk Joanna A.E. , Milošević Danko , Kawai Yosuke , Kiryluk Krzysztof , Pollak Martin R. , Gharavi Ali , Lin Fangmin , Simœs e Silva Ana Cristina , Loos Ruth J.F. , Kenny Eimear E. , Schreuder Michiel F. , Zurowska Aleksandra , Dossier Claire , Ariceta Gema , Drozynska-Duklas Magdalena , Hogan Julien , Jankauskiene Augustina , Hildebrandt Friedhelm , Prikhodina Larisa , Song Kyuyoung , Bagga Arvind , Cheong Hae Il , Ghiggeri Gian Marco , Vachvanichsanong Prayong , Nozu Kandai , Vivarelli Marina , Raychaudhuri Soumya , Tokunaga Katsushi , Sanna-Cherchi Simone , Ronco Pierre , Iijima Kazumoto , Sampson Matthew G. 
Published: September 2022

ABSTRACTPediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional signals. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. We conducted a multi-population GWAS meta-analysis in 38,463 participants (2,440 cases) and population specific GWAS, discovering twelve significant associations (eight novel). Fine-mapping implicated specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk signal. Non-HLA loci colocalized with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs was lacking, but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associated with earlier disease onset in two independent cohorts. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cellspecific insights into its molecular drivers.
Internet Delivered Sexually Transmitted Infection and Teen Pregnancy Prevention Program: A Randomized Trial
Authors: Kissinger Patricia J. , Green Jakevia , Latimer Jennifer , Schmidt Norine , Ratnayake Aneeka , Madkour Aubrey Spriggs , Clum Gretchen , Wingood Gina M , DiClemente Ralph J. , Johnson Carolyn 
Published: September 2022

AbstractImportanceBlack teenaged women have disproportionately high rates of unintended pregnancy (UTP) and sexually transmitted infections (STI). Internet-based interventions can be delivered to large groups of people in a relatively inexpensive manner.ObjectiveThe purpose of this randomized trial was to examine the efficacy of an adaptation of a theory- and evidence-based UTP/STI prevention intervention for older teens and for internet delivery.DesignA randomized, attention-controlled trial.SettingParticipants were recruited from minority-serving institutions and community events in New Orleans, Louisiana.ParticipantsBlack women aged 18-19 who were not pregnant nor seeking to become pregnant were enrolled (n=637).Main outcomes and measuresParticipants were randomized to an 8-session intervention or attention control and were followed at 6- and 12-months post-intervention to determine if the use of reliable contraception, dual methods, intention to use condoms, and intention to use reliable contraception were higher among women in the intervention arm compared to controls. Pregnancy and STI rates were also compared.ResultsOverall, at baseline, reliable contraception was 54.8% and dual protection was 29.4% and the prevalence of STI was 11.1%. Participants were similar by arm. Participation and follow-up rates were excellent (60.9% and 80.3%). At 6 months, all outcomes were improved in intervention compared to control, but this effect waned by 12 months.Conclusion and RelevanceThe intervention was efficacious for increasing self-reported pregnancy and STI prevention behavior and intentions and lower trends for pregnancy and STIs were observed in this group which decreased over time suggesting the need for a booster.Trial RegistrationClinicalTrial.govNCT01579617
Histology of type 3 macular neovascularization and microvascular anomalies in treated age-related macular degeneration: a case study
Authors: Berlin Andreas , Cabral Diogo , Chen Ling , Messinger Jeffrey D , Balaratnasingam Chandrakumar , Mendis Randev , Ferrara Daniela , Freund K. Bailey , Curcio Christine A 
Published: September 2022

AbstractObjective/PurposeTo investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient.DesignA case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation).ParticipantsA white woman in her 90’s treated with numerous intravitreal anti-vascular endothelial growth factor (VEGF) injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).Intervention(s)/ MethodsClinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain optical coherence tomography (OCT), OCT angiography, and fluorescein angiography. Eye tracking, applied to the two preserved donor eyes, enabled correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy.Main Outcome(s) and Measure(s)Histologic/ ultrastructural descriptions and diameters of vessels seen in clinical imaging.ResultsSix vascular lesions were histologically confirmed (type 3 MNV, n=3; deep retinal age-related microvascular anomalies (DRAMA), n=3). Pyramidal (n=2) or tangled (n=1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the sub-retinal pigment epithelium (RPE)-basal laminar space or cross Bruch’s membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and non-fenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. DRAMA lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers, without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMA lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes.ConclusionsType 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMA are part of the type 3 MNV progression sequence.
Azithromycin alters spatial and temporal dynamics of airway microbiota in idiopathic pulmonary fibrosis
Authors: Gijs Pieter-Jan , Daccord Cécile , Bernasconi Eric , Brutsche Martin , Clarenbach Christian , Hostettler Katrin , Guler Sabina A. , Mercier Louis , Ubags Niki , Funke-Chambour Manuela , Garnier Christophe von 
Published: September 2022

AbstractBackgroundHigh bacterial burden in lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases and observational studies have shown a positive effect of azithromycin on mortality and hospitalization rate in IPF. However, the effect of AZT on lung microbiota in IPF remain unknown.MethodsWe sought to determine the impact of a three-month course of azithromycin on lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomized controlled cross-over trial of a thrice-weekly 500 mg oral azithromycin. 16S rRNA sequencing and quantitative polymerase chain reaction (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARG) were assessed using real-time qPCR.ResultsAzithromycin significantly decreased community diversity with a stronger and more persistent effect in lower airways. During treatment, turnover of airway microbiota decreased in upper and lower airways, resulting in greater similarity between microbiota of the two sites persisting one month after macrolide cessation.Patients with increased expression of ARG had a lower bacterial load and an enrichment of the genus Streptococcus. In contrast, patients without increased in ARG expression had a higher bacterial load and an enrichment in Prevotella.ConclusionsWe observed that AZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.
Viroscope: plant viral diagnosis from NGS data using biologically-informed genome assembly coverage
Authors: Valenzuela Sandro L. , Norambuena Tomás , Morgante Verónica , García Francisca , Jiménez Juan C. , Núñez Carlos , Fuentes Ignacia , Pollak Bernardo 
Published: September 2022

ABSTRACTNext-generation sequencing (NGS) methods are transforming our capacity to detect pathogens and perform disease diagnosis. Although sequencing advances have enabled accessible and point-of-care NGS, data analysis pipelines have yet to provide robust tools for precise and certain diagnosis, particularly in cases of low sequencing coverage. Lack of standardized metrics and harmonized detection thresholds confound the problem further, impeding the adoption and implementation of these solutions in real-world applications. In this work, we tackle these issues and propose biologically-informed viral genome assembly coverage as a method to improve diagnostic certainty. We use the identification of viral replicases, an essential function of viral life cycles, to define genome coverage thresholds in which biological functions can be described. We validate the analysis pipeline, Viroscope, using field samples, synthetic and published datasets and demonstrate that it provides sensitive and specific viral detection. Furthermore, we developed Viroscope.io a web-service to provide on-demand NGS data viral diagnosis to facilitate adoption and implementation by phytosanitary agencies to enable precise viral diagnosis.
Molecular engineering of a cryptic epitope in Spike RBD improves manufacturability and neutralizing breadth against SARS-CoV-2 variants
Authors: Rodriguez-Aponte Sergio A. , Dalvie Neil C. , Wong Ting Y. , Johnston Ryan S. , Naranjo Christopher A. , Bajoria Sakshi , Kumru Ozan S. , Kaur Kawaljit , Russ Brynnan P. , Lee Katherine S. , Cyphert Holly A. , Barbier Mariette , Rao Harish D. , Rajurkar Meghraj P. , Lothe Rakesh R. , Shaligram Umesh S. , Batwal Saurabh , Chandrasekaran Rahul , Nagar Gaurav , Kleanthous Harry , Biswas Sumi , Bevere Justin R. , Joshi Sangeeta B. , Volkin David B. , Damron F. Heath , Love J. Christopher 
Published: September 2022

AbstractThere is a continued need for sarbecovirus vaccines that can be manufactured and distributed in low- and middle-income countries (LMICs). Subunit protein vaccines are manufactured at large scales at low costs, have less stringent temperature requirements for distribution in LMICs, and several candidates have shown protection against SARS-CoV-2. We previously reported an engineered variant of the SARS-CoV-2 Spike protein receptor binding domain antigen (RBD-L452K-F490W; RBD-J) with enhanced manufacturability and immunogenicity compared to the ancestral RBD. Here, we report a second-generation engineered RBD antigen (RBD-J6) with two additional mutations to a hydrophobic cryptic epitope in the RBD core, S383D and L518D, that further improved expression titers and biophysical stability. RBD-J6 retained binding affinity to human convalescent sera and to all tested neutralizing antibodies except antibodies that target the class IV epitope on the RBD core. K18-hACE2 transgenic mice immunized with three doses of a Beta variant of RBD-J6 displayed on a virus-like particle (VLP) generated neutralizing antibodies (nAb) to nine SARS-CoV-2 variants of concern at similar levels as two doses of Comirnaty. The vaccinated mice were also protected from challenge with Alpha or Beta SARS-CoV-2. This engineered antigen could be useful for modular RBD-based subunit vaccines to enhance manufacturability and global access, or for further development of variant-specific or broadly acting booster vaccines.
Leishmania amazonensiscontrols macrophage-regulated cell death to establish chronic infectionin vitroandin vivo
Authors: Lecoeur Hervé , Zhang Sheng , Varet Hugo , Legendre Rachel , Proux Caroline , Granjean Capucine , Bousso Philippe , Prina Eric , Späth Gerald F. 
Published: September 2022

SummaryPathogenic protists of the genusLeishmaniahave evolved various strategies to exploit macrophages as host cells and subvert their immuno-metabolic functions to favour intracellular parasite survival. Surprisingly little is known on howLeishmaniaaffects regulated cell death (RCD) pathways of its host cell, even though increased survival ofin vitroinfected macrophages has been reported, and chronic macrophage infectionin vivocauses the devastating immunopathologies of leishmaniasis. To overcome this limitation and gain first systems-level insight into the interaction between intracellularLeishmaniaand the host cell RCD pathways, including apoptosis, pyroptosis and necroptosis, we applied transcriptomic analyses onL. amazonensis-infected, primary macrophages (termed LIMs) and used YO-PRO-1 to monitor cell death by fluorescent microscopy. RNAseq analyses at day 3 post-infection (PI) revealed dichotomic dysregulation of more than 60% of RCD-related genes in LIMs, characterized by up-regulation of anti-RCD and down-regulation of pro-RCD markers, including key regulators common to the three forms of cell death such ascasp8, fadd, tradd, tnfaip3, tax1bp1, birc3, anditch. This profile correlated with expression changes of transcription factors known to regulate RCD, including AP1 and NF-κB family members,pparγandcebpβ. Consequently, LIMs showed remarkable longevity in culture for at least 50 days, despite a constant increase of parasite burden to about 100 parasites per cell, while non-infected cells were cleared from the culture in just a few days. Longitudinal expression analysis of LIMs at days 0, 3, 15, and 30 PI by RT-qPCR confirmed stable maintenance of this high longevity profile with the dichotomic decrease and increase of RCD-activators and -inhibitors, respectively. LIMs further showed significant resistance to RCD-inducing signals compared to non-infected cells, including CSF-1 deprivation (intrinsic apoptosis), actinomycin D treatment (extrinsic apoptosis), LPS/ATP stimulation (pyroptosis). Significantly, we extended the anti-RCD expression pattern and RCD resistance phenotype toL. amazonensis-infected macrophages recovered from lesions, thus validating our long-termin vitroinfection system as an easily accessible model to study chronic macrophage infection. In conclusion, our analyses firmly document the pan-anti RCD effect ofL. amazonensison its macrophage host cellin vitroandin vivoand shed important new light on mechanisms underlyingLeishmaniachronic infection.
The Diversity and Ubiquity of Antibiotic Resistance Genes in Finfish Culture Ponds in Bangladesh
Authors: Bell Ashley G. , Thornber Kelly , Chaput Dominique L. , Hasan Neaz A. , Alam Md. Mehedi , Haque Mohammad Mahfujul , Cable Jo , Temperton Ben , Tyler Charles R. 
Published: September 2022

AbstractIn Bangladesh, fish provide over 60% of animal-source food with 56.2% of this coming from aquaculture produced predominantly in rural freshwater ponds. Increasing demand for fish products is driving intensification and resulting in higher disease prevalence, posing a risk to food security. Biosecurity is often absent in rural aquaculture practices in Bangladesh and antibiotics are commonly used to treat and prevent disease outbreaks. Antibiotics are often administered incorrectly - a key factor associated with the development of antimicrobial resistance (AMR). AMR can be disseminated rapidly within microbial ecosystems via mobile genetic elements, posing a risk for humans and animals infected with AMR pathogens as treatments with antibiotics become ineffective. Early AMR detection and understanding of the spread of antimicrobial resistant genes (ARGs) in rural aquaculture practices is critical for both food security and human health protection. Here, we apply a metagenomic approach to assess the ARG composition in pond water from six finfish (tilapia and pangasius) farms in the Mymensingh division of North-central Bangladesh. We found microbial communities within the ponds had similar alpha and beta diversities, with multiple ARGs predicted to confer resistance to eighteen different classes of antimicrobials. The most common ARGs conferred resistance to aminoglycosides and sulphonamides and were present in taxa associated with both fish and human pathogens. This ARG diversity potentially confers resistance to a wide variety of antibiotic classes and questions the effectiveness of current and future treatment of diseases with antibiotics in earthen aquaculture ponds. The microbial and ARG compositions between fish ponds within each farm were similar, which may relate to parallels in farming practices creating similar microbial selection pressures and thus comparable microbial populations. Without a more controlled approach towards antibiotic usage, will inevitably further exacerbate the challenges in treating and preventing disease outbreaks as aquaculture production intensifies in Bangladesh.HighlightsARGs in Bangladesh rural fishponds indicate resistance to 18 different antibioticsThe most common AMR were to aminoglycosides and sulphonamidesARGs were present in plasmids and taxa-associated pathogensFarming practices strongly influence microbial and ARG compositionsIdentified ARGs question antibiotic treatment of disease in rural aquaculture
The coarse mental map of the breast is anchored on the nipple
Authors: Long Katie H. , Fitzgerald Emily E. , Berger-Wolf Ev I. , Fawaz Amani , Lindau Stacy Tessler , Bensmaia Sliman J. , Greenspon Charles M. 
Published: September 2022

AbstractTouch plays a key role in our perception of our body and shapes our interactions with the world, from the objects we manipulate to the people we touch. While the tactile sensibility of the hand has been extensively characterized, much less is known about touch on other parts of the body. Despite the important role of the breast in lactation as well as in affective and sexual touch, relatively little is known about its sensory properties. To fill this gap, we investigated the spatial acuity of the breast and compared it to that of the hand and back, body regions that span the range of tactile spatial acuity. First, we found that the tactile acuity of the breast was even lower than that of the back, heretofore the paragon of poor acuity. Second, acuity was lower for larger breasts, consistent with the hypothesis that innervation capacity does not scale with body size. Third, touches to different regions of the nipple were largely indistinguishable, suggesting that the nipple is a sensory unit. Fourth, localization errors were systematically biased toward the nipple and more so at greater distances from the breast.SignificanceOur basic understanding of the tactile capabilities of the breast remains poorly understood in comparison to the hand or face despite the fact that the breast plays a major role in the lives of those with breasts. This paper establishes common methods for studying breast tactile sensation and presents the breast and nipple as two fundamentally discrete tactile units from the torso.
Effect of Methamphetamine on Ultraweak Photon Emission and Level of Reactive Oxygen Species in Male Rat Brain
Authors: Esmaeilpour Tahereh , Lotfealian Azam , Anvari Morteza , Namavar Mohammadreza , Karbalaei Narges , Shahedi Abbas , Bokkon Istvan , Zadeh-Haghighi Hadi , Simon Christoph , Salari Vahid , Oblak Daniel 
Published: September 2022

AbstractAll living cells, including neurons, generate ultra-weak photon emission (UPE) during biological activity, and in particular, in the brain, it has been shown that UPE is correlated with neuronal activity and associated metabolic processes. Various intracellular factors, as well as external factors, can reduce or increase the intensity of UPE. In this study, we have used Methamphetamine (METH) as one potentially effective external factor, which is a substance that has the property of stimulating the central nervous system. METH can impair mitochondrial function by causing toxicity via various pathways, including an increase in the number of mitochondria, hyperthermia, the increased metabolic activity of the brain, and the production of glutamate and excess calcium. In addition to mitochondrial dysfunction, METH alters cellular homeostasis, leading to cell damage and the production of excess ROS. The aim of this study is to measure and compare the UPE intensity and reactive oxygen species (ROS) levels of the prefrontal, motor, and visual cortex before and after METH administration. Twenty male rats were randomly assigned to two groups, the control, and METH groups. In the control group, 2 hours after injection of normal saline and without any intervention, and in the experimental group 2 hours after IP injection of 20 mg/kg METH, sections were prepared from three areas: prefrontal, motor, and V1-V2 cortex, which were used to evaluate the emission of UPE using a photomultiplier tube (PMT) device and to evaluate the amount of ROS. The results showed that the amount of ROS and UPE in the experimental group in all three areas significantly increased compared to the control group. So, METH increases UPE and ROS in the prefrontal, motor, and visual regions, and there is a direct relationship between UPE intensity and ROS production. Therefore, UPE can be used as a dynamic reading tool to monitor oxidative metabolism in physiological processes related to ROS. Also, the results of this experiment can support the hypothesis that the production of excess UPE may lead to the phenomenon of phosphene and visual hallucinations.