bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Schema Method: Using Quantified Learning to Innovate, Augment, Assess and Analyze Learning in Medicine
Authors: Sebin Deepu , Doda Vishwin , Balami Skanthvelan 
Published: September 2022

AbstractIntroductionThe predominant method of learning Medicine at its core has remained unchanged for decades. This stagnancy creates a need for making learning more effective, insightful, and quantified. ‘Schema’ achieves this through e-learning, active feedback, and quantified learning by granulating the medical curriculum into specific subtopics selected based on the crucial knowledge that a competent medical learner must possess, hereafter referred to as ‘yield.’ This particular study aims to analyze medical students’ multidimensional competency in solving clinical scenario-based MCQs pertaining to vertically integrated topics derived from the ‘Schema.’MethodsA retrospective study was conducted by analyzing the user data of a leading e-learning platform for medical students. For the purposes of this study, twenty such “high-yield” Schema topics were shortlisted as being the most crucial knowledge areas. Students’ performance in solving a fixed set of SOC-MCQs of these Schema topics was used to gauge their competence. Performance variation over five years (2018-2022) was also analyzed to study the changing patterns in topic-specific performance.ResultsA total of 20 Schema topics were shortlisted, consisting of 128 MCQs. The number of participants solving each Single Option Correct Multiple Choice Question (SOC-MCQ) ranged from 60,080 to 2,06,672. A significant improvement in the Net Delta was observed in 9 topics. Performance in other topics showed either no significant change or a significant downtrend.ConclusionA significant performance uptrend (ND = 128%) was observed in Anaphylaxis, Basic Lifesaving Skills, ST-Elevated Myocardial Infarction, Glasgow Coma Scale, and subdural hemorrhage & Syndromic management of Sexually Transmitted Infections, most of which are either acute or emergency conditions. A significant downtrend in performance was seen in Schema topics such as Asthma management, Hypertension management, Diabetic Ketoacidosis, and Subarachnoid hemorrhage pertaining to chronic conditions. Several hypotheses for these findings can be derived, the validities and collective impacts of which can be explored in more in-depth and broader studies in the future.
The establishment ofPopulusxLaccaria bicolorectomycorrhiza requires the inactivation of MYC2 coordinated defense response with a key role for root terpene synthases
Authors: Marqués-Gálvez José Eduardo , Basso Veronica , Kohler Annegret , Barry Kerrie , Keymanesh Keykhosrow , Johnson Jenifer , Singan Vasanth , Grigoriev Igor V. , Vilgalys Rytas , Martin Francis , Veneault-Fourrey Claire 
Published: September 2022

AbstractThe jasmonic acid (JA) signaling pathway plays an important role in the establishment of the ectomycorrhizal symbiosis (ECM) betweenLaccaria bicolorand poplar. We previously showed that theL. bicoloreffector MiSSP7 induces the stabilization of the poplar JAZ6, a JA co-repressor protein that binds toPopulusMYC2.1 and MYC2.2, orthologs of theArabidopsisMYC2 transcription factor (TF), blocking their activity. Here we showed that both TFs play a central role in root colonization byL. bicolormycelium, since their overexpression decreased the formation of the Hartig net, the hyphal network involved in symbiotic nutrient exchanges. By combining RNA sequencing and DNA Affinity Purification sequencing (DAP-seq) analysis, we identified a core set of JA-responsive genes directly activated by poplar MYC2.1 and MYC2.2, that need to be bypassed by the fungi to colonize root apoplastic spaces. These genes encode for other TFs, receptor-like kinases and many defense-related proteins, including terpene synthases (TPS). Monoterpenes produced by some of these TPS impactL. bicolorgrowth and ECM formation, suggesting a role for poplar root monoterpenes as negative regulators ofin plantafungal growth and ECM symbiosis.Significance statementThe ectomycorrhizal symbiosis is a predominant mutualistic plant-fungus interaction occurring in forests, sustaining tree health. Ectomycorrhizal fungi colonize the root intercellularly establishing the symbiotic interface required for bidirectional nutrients exchanges, the Hartig net. During root colonization, the fungusL. bicolorproduces the effector protein MiSSP7 that binds to the jasmonate co-receptor PtJAZ6, maintaining the repression of MYC2-targeted genes. Here we showed that defensive genes are major targets of MYC2, suggesting that their strict control is required to allow fungal colonization, with special emphasis on the host root monoterpene synthesis. Future research will focus on how root terpene defenses mediate belowground mutualistic interactions and how they can be manipulated to engineer plants with enhanced disease resistance but stable mutualistic interactions.
Viral infection impacts the 3D subcellular structure of the abundant marine diatomGuinardia delicatula
Authors: Walde Marie , Camplong Cyprien , de Vargas Colomban , Baudoux Anne-Claire , Simon Nathalie 
Published: September 2022

AbstractViruses are key players in marine ecosystems where they infect abundant marine microbes. RNA viruses are emerging as key members of the marine virosphere. They have recently been identified as a potential source of mortality in diatoms, a group of microalgae that accounts for roughly 40% of the primary production in the ocean. Despite their likely importance, their impacts on host populations and ecosystems remain difficult to assess.In this study, we introduce an innovative tool approach that combines automated 3D confocal microscopy with quantitative image analysis and physiological measurements to expand our understanding of viral infection. We followed different stages of infection of the bloom-forming diatomGuinardia delicatulaby the RNA virus GdelRNAV-04 until the complete lysis of the host. From 20h after infection, we observed quantifiable changes in subcellular host morphology and biomass. Our microscopy monitoring also showed that viral infection ofG. delicatulainduced the formation of auxospores as a probable defense strategy against viruses. Our method enables the detection of discriminative morphological features on the subcellular scale and at high throughput for comparing populations, making it a promising approach for the detection quantification of viral infections in the field in the future.
Redefining normal breast cell populations using long noncoding RNAs
Authors: Bitar Mainá , Rivera Isela Sarahi , Pimentel de Almeida Isabela , Shi Wei , Ferguson Kaltin , Beesley Jonathan , Lakhani Sunil R , Edwards Stacey L , French Juliet D 
Published: September 2022

ABSTRACTSingle-cell RNAseq has allowed unprecedented insight into gene expression across different cell populations in normal tissue and disease states. However, almost all studies rely on annotated gene sets to capture gene expression levels and sequencing reads that do not align to known genes are discarded. Here, we discover thousands of long noncoding RNAs (lncRNAs) expressed in human mammary epithelial cells and analyze their expression in individual cells of the normal breast. We show that lncRNA expression alone can discriminate between luminal and basal cell types and define subpopulations of both compartments. Clustering cells based on lncRNA expression identified additional basal subpopulations, compared to clustering based on annotated gene expression, suggesting that lncRNAs can provide an additional layer of information to better distinguish breast cell subpopulations. In contrast, these breast-specific lncRNAs poorly distinguish brain cell populations, highlighting the need to annotate tissue-specific lncRNAs prior to expression analyses. We also identified a panel of 100 breast lncRNAs that could discern breast cancer subtypes better than protein-coding markers. Overall, our results suggest that lncRNAs are an unexplored resource for new biomarker and therapeutic target discovery in the normal breast and breast cancer subtypes.
Rapid and accurate discrimination of Mycobacterium abscessus subspecies based on matrix-assisted laser desorption ionization-time of flight spectrum and machine learning algorithms
Authors: Wang Hsin-Yao , Kuo Chi-Heng , Chung Chia-Ru , Lin Ting-Wei , Yu Jia-Ruei , Lu Jang-Jih , Wu Ting-Shu 
Published: September 2022

AbstractBackgroundMycobacterium abscessus complex (MABC) has been reported to cause considerable complicated infections. Subspecies identification of MABC is crucial for adequate treatment due to different antimicrobial resistance property amid the subspecies. However, long incubation days is needed for the traditional antibiotic susceptibility testing (AST) method. Effective antibiotics administration often delayed considerably and caused unfavorable outcomes. Thus, we proposed a novel and accurate method to identify subspecies and its potential antibiotics resistance, to guide clinical treatment within hours.MethodsSubspecies of the MABC isolates were determined by secA1, rpoB, and hsp65. AST was tested by using microdilution method, as well as sequencing of erm(41) and rrl genes. MALDI-TOF mass spectrometry (MS) spectra were analyzed. The informative peaks on MS spectra were detected by random forest (RF) importance. Machine learning (ML) algorithms were used to build models for classifying MABC subspecies based on MALDI-TOF spectrum. The models were developed and validated by nested five-fold cross-validation to avoid over-fitting.ResultsIn total, 102 MABC isolates (52 subspecies abscessus and 50 subspecies massiliense) were analyzed. Top informative peaks including m/z 6715, 4739, 2805, etc. were identified. RF model attained AUROC of 0.9166 (95% CI: 0.9072-0.9196) and outperformed other algorithms in discriminating subspecies abscessus from massiliense.ConclusionWe developed a MALDI-TOF based ML model for rapid and accurate MABC subspecies identification. The novel diagnostic tool would guide a more accurate and timely MABC subspecies-specific treatment.
ETV7 reduces inflammatory responses in breast cancer cells by repressing TNFR1/NF-κB axis
Authors: Meškytė Erna Marija , Pezzè Laura , Forcato Mattia , Bocci Irene Adelaide , Bisio Alessandra , Bicciato Silvio , Baltriukienė Daiva , Ciribilli Y. 
Published: September 2022

AbstractThe transcription factor ETV7 is an oncoprotein that is up-regulated in all breast cancer (BC) types. We have recently demonstrated that ETV7 promoted breast cancer progression by increasing cancer cell proliferation and stemness and was also involved in the development of chemo- and radio-resistance. However, the roles of ETV7 in breast cancer inflammation have yet to be studied. Gene ontology analysis previously performed on BC cells stably over-expressing ETV7 demonstrated that ETV7 was involved in the suppression of innate immune and inflammatory responses. To better decipher the involvement of ETV7 in these signaling pathways, in this study, we identified TNFRSF1A, encoding for the main receptor of TNF-α, TNFR1, as one of the genes down-regulated by ETV7. We demonstrated that ETV7 directly binds to the intron I of this gene, and we showed that the ETV7-mediated down-regulation of TNFRSF1A reduced the activation of NF-κB signaling. Furthermore, in this study, we unveiled a potential crosstalk between ETV7 and STAT3, another master regulator of inflammation. While it is known that STAT3 directly up-regulates the expression of TNFRSF1A, here we demonstrated that ETV7 reduces the ability of STAT3 to bind to the TNFRSF1A gene via a competitive mechanism, leading to the repression of its transcription. These results suggest that ETV7 can reduce the inflammatory responses in breast cancer through the down-regulation of TNFRSF1A.
Investigating the risk of cardiac fibrosis due to heat-not-burn cigarettes through human cardiac stromal cells
Authors: Picchio Vittorio , Pagano Francesca , Carnevale Roberto , D’Amico Alessandra , Cozzolino Claudia , Floris Erica , Bordin Antonella , Schirone Leonardo , Saade Wael , Miraldi Fabio , De Falco Elena , Sciarretta Sebastiano , Peruzzi Mariangela , Biondi-Zoccai Giuseppe , Frati Giacomo , Chimenti Isotta 
Published: September 2022

ABSTRACTBackgroundThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain.ObjectiveTo investigate the effects of circulating molecules in HNBC chronic smokers on the fibrotic specification and paracrine function of cardiac stromal cells (CSCs).MethodsResident CSCs were isolated from the atrial tissue of patients with cardiovascular diseases, and exposed to the serum of 60 young healthy subjects, stratified in exclusive HNBC smokers, traditional combustion cigarette (TCC) smokers, or non-smokers (NS) as reference.ResultsCSCs treated with TCC serum displayed impaired 3D growth and migration, as well as increased expression and/or release of pro-inflammatory and pro-fibrotic cytokines. Cells cultured with HNBC serum showed increased mRNA levels of pro-fibrotic genes, and reduced expression of the gap junction protein CX43. Nonetheless, both TCC and HNBC sera reduced the release of angiogenic and protective factors from CSCs. In fact, their paracrine support to tube-formation by endothelial cells and to preserved cell viability of cardiomyocytes in culture was significantly impaired. Treatment with the sera of both types of smokers also increased the expression of NOX isoforms and the release of H2O2by CSCs.ConclusionThe circulating molecules in the serum of chronic HNBC smokers induce fibrotic specification in CSCs. They also reduce the beneficial paracrine effects of stromal cells on endothelial cells and cardiomyocytes, albeit to a reduced extent for some features. These results point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.CONDENSED ABSTRACTThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. We isolated human stromal cells from the atrial tissue of patients with cardiovascular diseases, and exposed them to the serum of young healthy subjects, that are exclusive HNBC smokers. Results showed significant alterations in the phenotype of CSCs exposed to HNBC serum, suggesting a specification towards fibrosis, reduced support to parenchymal cells, and increased oxidative stress production. Data point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.
GDF15 antagonism limits severe heart failure and prevents cardiac cachexia in mice
Authors: Takaoka Minoru , Tadross John A. , Al-Hadithi Ali , Villena-Gutiérrez Rocío , Tromp Jasper , Absar Shazia , Au Marcus , Harrison James , Coll Anthony P. , Marciniak Stefan J. , Rimmington Debra , Oliver Eduardo , Ibáñez Borja , Voors Adriaan A. , O’Rahilly Stephen , Mallat Ziad , Goodall Jane C. 
Published: September 2022

AbstractHeart failure and associated cachexia is an unresolved and important problem. We report a new model of severe heart failure that consistently results in cachexia. Mice lacking the integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A, exhibit a dilated cardiomyopathy and severe weight loss following irradiation, whilst wildtype mice are unaffected. This is associated with increased expression of Gdf15 in the heart and increased levels of GDF15 in the circulation. We provide evidence that blockade of GDF15 activity prevents cachexia and slows the progression of heart failure. Our data suggests that cardiac stress mediates a GDF15 dependent pathway that drives weight loss and worsens cardiac function. We show relevance of GDF15 to lean mass and protein intake with patients with heart failure. Blockade of GDF15 could constitute a novel therapeutic option to limit cardiac cachexia and improve clinical outcomes in patients with severe systolic heart failure.
Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
Authors: Martinez-Riano Ana , Wang Shenshen , Boeing Stefan , Minoughan Sophie , Casal Antonio , Spillane Katelyn M , Ludewig Burkhard , Tolar Pavel 
Published: September 2022

ABSTRACTGerminal centers (GCs) require sustained availability of antigens to promote antibody affinity maturation against pathogens and vaccines. A key source of antigens for GC B cells are immune complexes (ICs) displayed on follicular dendritic cells (FDCs). Here we show that FDC spatial organization regulates antigen dynamics in the GC. We show the existence of two light zone (LZ) FDC populations, which differ in the duration of antigen retention. While the entire light zone (LZ) FDC network captures ICs initially, only the central cells of the network function as a long-term antigen reservoir, where different antigens arriving from subsequent immunizations co-localize. Mechanistically, central FDCs constitutively express subtly higher CR2 membrane densities than peripheral FDCs, which strongly increases the IC retention half-life. Even though repeated immunizations gradually saturate central FDCs, B cell responses remain efficient because new antigens partially displace old ones. These results reveal the principles shaping antigen display on FDCs during the GC reaction.
A double-spiral maze and hi-resolution tracking pipeline to study dispersal by groups of minute insects
Authors: Cointe M. , Burte V. , Perez G. , Mailleret L. , Calcagno V. 
Published: September 2022

AbstractMinute insects such as parasitic micro-wasps have high basic and applied importance, for their widespread use as biocontrol agents. Their dispersal is a phenotype of particular interest. Classically, it is evaluated using field releases, but those are time consuming, costly, and their results highly variable, preventing high-throughput and repeatability. Alternatively, dispersal can be studied using small-scale assays, but those neglect important higher-scale processes. Consequently, proper evaluation of dispersal is often complicated or lacking in academic studies and biocontrol breeding programs. Here we introduce a new method, the double-spiral maze, that allows the study of spatial propagation at relevant scales (several hours and meters), retaining high throughput and experimental power. The method records the location of every individual at every time, enabling accurate precise estimates of diffusion coefficients or other dispersal metrics. We describe this affordable, scalable, and easy-to-implement method, and illustrate its application with a species of agricultural interest.
Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine
Authors: Lu Changrui , Zhang Yuntao , Liu Xiaohu , Hou Fujun , Cai Rujie , Yu Zhibin , Liu Fei , Yang Guohuan , Ding Jun , Xu Jiang , Hua Xianwu , Pan Xinping , Liu Lianxiao , Lin Kang , Wang Zejun , Li Xinguo , Lu Jia , Zhang Qiu , Li Yuwei , Hu Chunxia , Fan Huifeng , Liu Xiaoke , Wang Hui , Jia Rui , Xu Fangjingwei , Wang Xuewei , Huang Hongwei , Zhao Ronghua , Li Jing , Cheng Hang , Jia William , Yang Xiaoming 
Published: September 2022

ABSTRACTThe coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants following an order of BA.1>BA.2>BA.4/5. In naïve animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccine’s targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection across all VOCs. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by “recall” and “reshape” the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine– primed populations.
Real time visualisation of conjugation reveals the molecular strategy evolved by the conjugative F plasmid to ensure the sequential production of plasmid factors during establishment in the new host cell
Authors: Couturier Agathe , Virolle Chloé , Goldlust Kelly , Berne-Dedieu Annick , Reuter Audrey , Nolivos Sophie , Yamaichi Yoshiharu , Bigot Sarah , Lesterlin Christian 
Published: September 2022

AbstractDNA conjugation is a contact-dependent horizontal gene transfer mechanism responsible for disseminating drug resistance among bacterial species. Conjugation remains poorly characterised at the cellular scale, particularly regarding the reactions occurring after the plasmid enters the new host cell. Here, we use live-cell microscopy to visualise the intracellular dynamics of conjugation in real time. We reveal that the transfer of the plasmid in single-stranded DNA (ssDNA) form followed by its conversion into double-stranded DNA (dsDNA) are fast and efficient processes that occur with specific timing and subcellular localisation. Notably, the ss-to-dsDNA conversion is the critical step that governs the timing of plasmid-encoded protein production. The leading region that first enters the recipient cell carries single-stranded promoters that allow the early and transient synthesis of leading proteins immediately upon entry of the ssDNA plasmid. The subsequent ss-to-dsDNA conversion turns off leading gene expression and licences the expression of the other plasmid genes under the control of conventional double-stranded promoters. This elegant molecular strategy evolved by the conjugative plasmid allows for the timely production of factors sequentially involved in establishing, maintaining and disseminating the plasmid.