bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual Recruitment is Here to Stay: 2020 ID Fellowship Program and Matched Applicant Recruitment Experiences
Authors: Rockney Danica , Benson Constance A. , Blackburn Brian G. , Chirch Lisa M. , Konold Victoria J. L. , Luther Vera P. , Razonable Raymund R. , Tackett Sean , Melia Michael T. 
Published: May 2021

BackgroundGraduate Medical Education training programs transitioned to all-virtual recruitment in 2020. Few data have been published regarding the consequences of this transition. We desired to understand (1) infectious diseases (ID) fellowship programs’ recruitment efforts and the effect of virtual recruitment on application and interview numbers, and (2) the number of programs to which matched applicants applied and interviewed, and their perspectives on virtual recruitment.MethodsIn 2020-21 we surveyed all United States ID fellowship program directors (PDs) and matched applicants. Descriptive data analysis was performed on quantitative survey items. Free-text responses were analyzed through a quantitative content analysis approach.ResultsPD response rate was 68/158 (43%); applicant response rate was at least 23% (85/365). PDs reported a 27% increase in mean number of applications received and a 45% increase in mean number of applicants interviewed. Applicants especially valued online program structure information, PD program overview videos, fellow testimonials, didactic and curriculum content, and current fellow profiles. Most applicants preferred interviews lasting no more than 40 minutes and interview days lasting no more than 5 hours. Nearly all (60/64, 94%) PDs adequately learned about candidates; most (48/64, 75%) felt unable to showcase their program as well as when in-person. Most PDs (54/64, 84%) and applicants (56/73, 77%) want at least an option for virtual recruitment moving forward.ConclusionsVirtual recruitment enabled programs to accommodate more applicants and highlighted applicants’ preferences for programs’ augmented online presences and time-limited interview days. Most programs and applicants want the option for virtual interviews.Main PointsVirtual recruitment enables programs to accommodate more applicants. Applicants value programs’ augmented online presences and favor time-limited interview days. Most programs and applicants prefer in-person interviews and want at least an option for virtual interviews.
Changes in wheat rhizosphere microbiota in response to chemical inputs, plant genotype and phenotypic plasticity
Authors: Jacquiod Samuel , Raynaud Tiffany , Pimet Eric , Ducourtieux Chantal , Casieri Leonardo , Wipf Daniel , Blouin Manuel 
Published: May 2021

ABSTRACTSince modern wheat varieties are grown with chemical inputs, we ignore if changes observed in rhizosphere microorganisms between ancient and modern varieties are due to i) breeding-induced changes in plant genotype, ii) modifications of the environment via synthetic chemical inputs, or (iii) phenotypic plasticity, defined as the interaction between the genotype and the environment. In the field, we evaluated the effects of various wheat varieties (modern and ancient) grown with or without chemical inputs (N-fertilizer, fungicide and herbicide together) in a crossed factorial design. We analysed rhizosphere bacteria and fungi by amplicons sequencing and mycorrhizal association by microscopic observations. When considered independently of plant genotype, chemical inputs were responsible for an increase in dominance for bacteria and decrease in evenness for bacteria and fungi. Independently of inputs, modern varieties had richer and more even bacterial communities compared to ancient varieties. Phenotypic plasticity had a significant effect: bacterial and fungal diversity decreased when inputs were applied in ancient varieties but not in modern ones. Mycorrhiza were more abundant in modern than ancient varieties, and less abundant when using chemical inputs. Although neglected, phenotypic plasticity is important to understand the evolution of plant-microbiota associations and a relevant target in breeding programs.
Long-term stress and trait anxiety alter brain network balance in dynamic decisions during working memory
Authors: Liu Liangying , Wu Jianhui , Geng Haiyang , Liu Chao , Luo Yuejia , Luo Jing , Qin Shaozheng 
Published: May 2021

AbstractLong-term stress has a profound impact on the human brain and cognition, and trait anxiety influences stress-induced adaptive and maladaptive effects. However, the neurocognitive mechanisms underlying long-term stress and trait anxiety interactions remain elusive. Here we investigated how long-term stress and trait anxiety interact to affect dynamic decisions during working-memory (WM) by altering functional brain network balance. In comparison to controls, male participants under long-term stress experienced higher psychological distress and exhibited faster evidence accumulation but had a lower decision-threshold during WM. This corresponded with hyper-activation in the anterior insula, less WM-related deactivation in the default-mode network, and stronger default-mode network decoupling with the frontoparietal network. Critically, high trait anxiety under long-term stress led to slower evidence accumulation through higher WM-related frontoparietal activity, and increased decoupling between the default-mode and frontoparietal networks. Our findings provide neurocognitive evidence for long-term stress and trait anxiety interactions on executive functions with (mal)adaptive changes.
Effects ofPlatycodon grandiflorumon Gut Microbiota and Immune System of Immunosuppressed Mouse
Authors: Jhang So Yun , Lee Sung-Hyen , Lee Eun-Byeol , Choi Ji-Hye , Bang Sohyun , Jeong Misun , Jang Hwan-Hee , Kim Hyun-Ju , Lee Hae-Jeung , Jeong Hyun Cheol , Lee Sung Jin 
Published: May 2021

ABSTRACTPlatycodon grandiflorum(PG) has been used as a traditional remedy to control immune related diseases. However, there is limited information about its immune stimulating effects on the immunosuppressed model. The main bioactive components such as saponins are known to con-tribute to controlling immune activity. Thus, we developed an aged red PG (PGS) with 2.6 times of platycodin D, one of the saponins. We treated PG and PGS (PG-diets) to immunosuppressed mice via cyclophosphamide (CPA) injection. After 2weeks of the supplement, 16S rRNA sequencing was performed to investigate the effects of PG-diets on the gut microbiota and immune system in the immune suppressed model. PG-diets groups showed an increased abundance of microorganism in immune-deficient mice compared to the control NC group, indicating PG-diets have a distinct effect on microbial communities. Detection of specific genera related to the immune related biomarkers in PG-diets groups can support their effects on the immune system. Especially, theAkkermansiashowed a significant decrease of abundance in response to the CPA treatment in the NC group at the genus level, but its abundance increased in response to the PG-diets treatment in the PG-diets groups. We also found that the modulation of gut microbiome by PG-diets was correlated with body weight as one of important immune biomarkers, though not much difference was found between PG and PGS effects. The results demonstrate that PG-diets may improve the health benefits of immune suppressed mice by altering the gut microbiome.
Reversion of antibiotic resistance in drug-resistant bacteria using non-steroidal anti-inflammatory drug benzydamine
Authors: Liu Yuan , Tong Ziwen , Shi Jingru , Deng Tian , Li Ruichao , Xiao Xia , Wang Zhiqiang 
Published: May 2021

AbstractAntimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimen. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing previously approved drugs as potent antibiotic adjuvants offers a cost-effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug-resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non-steroidal anti-inflammatory drug in clinic, remarkably potentiated broad-spectrum antibiotic-tetracyclines activity against a panel of clinical important resistant pathogens, including MRSA, VRE, MCRPEC andtet(X)-positive Gram-negative bacteria. Further mechanistically experiments showed that benzydamine dissipated membrane potential (ΔΨ) in both Gram-positive and negative bacteria, which in turn upregulated the transmembrane proton gradient (ΔpH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system-mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline-benzydamine combination against different metabolic states of bacteria including persister cells. As a proof-of-concept, thein vivoefficacy of this combination therapy was evidenced in multiple animal infection models. These findings revealed that benzydamine is a promising tetracycline antibiotics adjuvant and has the potential to address life-threatening infections by MDR bacteria.
Hepatitis B virus polymerase restricts LINE-1 retrotransposition
Authors: Ariumi Yasuo 
Published: May 2021

AbstractLong interspersed element-1 (LINE-1, L1) retrotransposon composes about 17% of the human genome. However, genetic and biochemical interactions between L1 and hepatitis B virus (HBV) remain poorly understood. In this study, we found that HBV restricts L1 mobility without inhibiting the L1 promoter activity. Notably, HBV polymerase (Pol) strongly inhibited L1 retrotransposition in a reverse transcriptase (RT)-independent manner. Indeed, the ribonuclease H (RNase H) domain was essential for inhibition of L1 retrotransposition. L1 ORF1p RNA-binding protein predominantly localized into cytoplasmic RNA granule termed P-body. However, HBV Pol sequestered L1 ORF1p from P-body and colocalized with L1 ORF1p in cytoplasm, when both proteins were co-expressed. Altogether, HBV Pol seems to restrict L1 mobility through a sequestration of L1 ORF1p from P-body. Thus, these results suggest a novel function or activity of HBV Pol in regulation of L1 retrotransposition.
Spatial point pattern analysis identifies mechanisms shaping the skin parasite landscape inLeishmania donovaniinfection
Authors: Doehl Johannes S. P. , Ashwin Helen , Brown Najmeeyah , Romano Audrey , Carmichael Samuel , Pitchford Jon W. , Kaye Paul M. 
Published: May 2021

AbstractIncreasing evidence suggests that infectiousness of hosts carrying parasites of theLeishmania donovanicomplex, the causative agents of visceral leishmaniasis, is linked to parasite repositories in the host skin. However, a detailed understanding of the dispersal and dispersion of these obligatory-intracellular parasites and their host phagocytes in the skin is lacking. Using endogenously fluorescent parasites as a proxy, we apply image analysis combined with spatial point pattern models borrowed from ecology to characterize dispersion of parasitized myeloid cells (including ManR+and CD11c+cells) and predict dispersal mechanisms in a previously described immunodeficient model ofL. donovaniinfection. Our results suggest that after initial seeding of infection in the skin, heavily parasite-infected myeloid cells are found in patches that resemble innate granulomas. Spread of parasites from these initial patches subsequently occurs through infection of recruited myeloid cells, ultimately leading to self-propagating networks of patch clusters. This combination of imaging and ecological pattern analysis to identify mechanisms driving the skin parasite landscape offers new perspectives on myeloid cell behavior following parasitism byL. donovaniand may also be applicable to elucidating the behavior of other intracellular tissue-resident pathogens and their host cells.
Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2
Authors: Laiton-Donato Katherine , Franco-Muñoz Carlos , Álvarez-Díaz Diego A. , Ruiz-Moreno Hector Alejandro , Usme-Ciro José A. , Andrés Prada Diego , Reales-González Jhonnatan , Corchuelo Sheryll , Herrera-Sepúlveda María T. , Naizaque Julian , Santamaría Gerardo , Rivera Jorge , Rojas Paola , Hernández Ortiz Juan , Cardona Andrés , Malo Diana , Prieto-Alvarado Franklin , Gómez Fernando Ruiz , Wiesner Magdalena , Ospina Martínez Martha Lucia , Mercado-Reyes Marcela 
Published: May 2021

SummaryThe genetic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to impact the virus transmissibility and the escape from natural infection- or vaccine-elicited neutralizing antibodies. Here, representative samples from circulating SARS-CoV-2 in Colombia between January and April 2021, were processed for genome sequencing and lineage determination following the nanopore amplicon ARTIC network protocol and PANGOLIN pipeline. This strategy allowed us to identify the emergence of the B.1.621 lineage, considered a variant of interest (VOI) with the accumulation of several substitutions affecting the Spike protein, including the amino acid changes T95I, Y144T, Y145S and the insertion 146N in the N-terminal domain, R346K, E484K and N501Y in the Receptor-binding Domain (RBD) and P681H1 in the S1/S2 cleavage site of the Spike protein. The rapid increase in frequency and fixation in a relatively short time in Magdalena, Atlántico, Bolivar, Bogotá D.C, and Santander that were near the theoretical herd immunity suggests an epidemiologic impact. Further studies will be required to assess the biological and epidemiologic roles of the substitution pattern found in the B.1.621 lineage.HighlightsMonitoring the emergence of new variants of SARS-CoV-2 in real time is a worldwide priority.Emerging variants of SARS-CoV-2 may have high impact biological implications for public healthThe SARS-CoV-2 B.1.621 variant of interest was characterized by several substitutions: T95I, Y144T, Y145S, ins146N, R346K, E484K, N501Y and P681H in spike protein.
In vivoimaging of cannabinoid type 2 receptors, functional and structural alterations in mouse model of cerebral ischemia by PET and MRI
Authors: Ni Ruiqing , Müller Herde Adrienne , Haider Ahmed , Keller Claudia , Louloudis Georgios , Vaas Markus , Schibli Roger , Ametamey Simon M. , Klohs Jan , Mu Linjing 
Published: May 2021

AbstractBackground and purposeBrain ischemia is one of the most important pathologies of the central nervous system. Non-invasive molecular imaging methods have the potential to provide critical insights into the temporal dynamics and follow alterations of receptor expression and metabolism in ischemic stroke. The aim of this study was to assess the cannabinoid type 2 receptors (CB2R) levels in transient middle cerebral artery occlusion (tMCAO) mouse models at subacute stage using positron emission tomography (PET) with our novel tracer [18F]RoSMA-18-d6, and structural imaging by magnetic resonance imaging (MRI).MethodsOur recently developed CB2R PET tracer [18F]RoSMA-18-d6 was used for imaging the neuroinflammation at 24 h after reperfusion in tMCAO mice. The RNA expression levels of CB2R and other inflammatory markers were analyzed by quantitative real-time polymerase chain reaction using brain tissues from tMCAO (1 h occlusion) and sham-operated mice. [18F]fluorodeoxyglucose (FDG) was included for evaluation of the cerebral metabolic rate of glucose (CMRglc). In addition, diffusion-weighted imaging and T2-weighted imaging were performed for anatomical reference and delineating the lesion in tMCAO mice.ResultsmRNA expressions of inflammatory markersTNF-α,Iba1, MMP9andGFAP, CNR2were increased at 24 h after reperfusion in the ipsilateral compared to contralateral hemisphere of tMCAO mice, while mRNA expression of the neuronal markerMAP-2was markedly reduced. Reduced [18F]FDG uptake was observed in the ischemic striatum of tMCAO mouse brain at 24 h after reperfusion. Although higher activity of [18F]RoSMA-18-d6 inex-vivobiodistribution studies and higher standard uptake value ratio (SUVR) were detected in the ischemic ipsilateral compared to contralateral striatum in tMCAO mice, thein-vivospecificity of [18F]RoSMA-18-d6 was confirmed only in the CB2R-rich spleen.ConclusionsThis study revealed an increased [18F]RoSMA-18-d6 measure of CB2R and a reduced [18F]FDG measure of CMRglc in ischemic striatum of tMCAO mice at subacute stage. [18F]RoSMA-18-d6 might be a promising PET tracer for detecting CB2R alterations in animal models of neuroinflammation without neuronal loss.
AutoVEM2: a flexible automated tool to analyze candidate key mutations and
epidemic trends for virus
Authors: Xi Binbin , Li Shuhua , Liu Wei , Jiang Dawei , Bai Yunmeng , Qu Yimo , Lon Jerome Rumdon , Huang Lizhen , Du Hongli 
Published: May 2021

Abstract
In our previous work, we developed an automated tool, AutoVEM, for real-time
monitoring the candidate key mutations and epidemic trends of SARS-CoV-2. In
this research, we further developed AutoVEM into AutoVEM2. AutoVEM2 is composed
of three modules, including call module, analysis module, and plot module, which
can be used modularly or as a whole for any virus, as long as the corresponding
reference genome is provided. Therefore, it’s much more flexible than AutoVEM.
Here, we analyzed three existing viruses by AutoVEM2, including SARS-CoV-2, HBV
and HPV-16, to show the functions, effectiveness and flexibility of AutoVEM2. We
found that the N501Y locus was almost completely linked to the other 16 loci in
SARS-CoV-2 genomes from the UK and Europe. Among the 17 loci, 5 loci were on the
S protein and all of the five mutations cause amino acid changes, which may
influence the epidemic traits of SARS-CoV-2. And some candidate key mutations of
HBV and HPV-16, including T350G of HPV-16 and C659T of HBV, were detected. In
brief, we developed a flexible automated tool to analyze candidate key mutations
and epidemic trends for any virus, which would become a standard process for
virus analysis based on genome sequences in the future.

Highlights

An automatic tool to quickly analyze candidate key mutations and
epidemic trends for any virus was developed.

Our integrated analysis method and tool could become a standard
process for virus mutation and epidemic trend analysis based on
genome sequences in the future.

N501Y with the other 16 highly linked mutation sites of
SARS-CoV-2 in the UK and Europe were further confirmed, and some
valuable mutation sites of HBV and HPV-16 were detected.
Clone decomposition based on mutation signatures provides novel insights into mutational processes
Authors: Matsutani Taro , Hamada Michiaki 
Published: May 2021

AbstractIntra-tumor heterogeneity is a phenomenon in which mutation profiles differ from cell to cell within the same tumor and is observed in almost all tumors. Understanding intra-tumor heterogeneity is essential from the clinical perspective. Numerous methods have been developed to predict this phenomenon based on variant allele frequency. Among the methods, CloneSig models the variant allele frequency and mutation signatures simultaneously and provides an accurate clone decomposition. However, this method has limitations in terms of clone number selection and modeling. We propose SigTracer, a novel hierarchical Bayesian approach for analyzing intra-tumor heterogeneity based on mutation signatures to tackle these issues. We show that SigTracer predicts more reasonable clone decompositions than the existing methods that use artificial data that mimic cancer genomes. We applied SigTracer to whole-genome sequences of blood cancer samples. The results were consistent with past findings that single base substitutions caused by a specific signature (previously reported as SBS9) related to the activation-induced cytidine deaminase intensively lie within immunoglobulin-coding regions for chronic lymphocytic leukemia samples. Furthermore, we showed that this signature mutates regions responsible for cell-cell adhesion. Accurate assignments of mutations to signatures by SigTracer can provide novel insights into signature origins and mutational processes.
The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases
Authors: Gorodetska Ielizaveta , Offermann Anne , Püschel Jakob , Lukiyanchuk Vasyl , Gaete Diana , Kurzyukova Anastasia , Labitzky Vera , Schwarz Franziska , Lange Tobias , Knopf Franziska , Wielockx Ben , Krause Mechthild , Perner Sven , Dubrovska Anna 
Published: May 2021

AbstractCancer stem cells (CSC) are characterized by high self-renewal capacity, tumor-initiating potential, and therapy resistance. Aldehyde dehydrogenase (ALDH)+ cell population serves as an indicator of prostate CSCs with increased therapy resistance, enhanced DNA double-strand break repair, and activated epithelial-mesenchymal transition (EMT) and migration. Numerous ALDH genes contribute to ALDH enzymatic activity; however, only some of them showed clinical relevance. We found that ALDH1A1 and ALDH1A3 genes functionally regulate CSC properties and radiation sensitivity of PCa. We revealed a negative correlation between ALDH1A1 and ALDH1A3 expression in publicly available prostate cancer (PCa) datasets and demonstrated that ALDH1A1 and ALDH1A3 have opposing predictive value for biochemical recurrence-free survival. Our data suggest an association of ALDH1A1 with the metastatic burden, elucidating the role of ALDH genes in the metastatic spread and homing to the bone, which can be, at least partially, attributed to regulating the transforming growth factor beta 1 (TGFB1) and matrix metalloproteinases (MMPs). ALDH genes play a diverse role in PCa development under AR and β-catenin-dependent regulation, with ALDH1A1 becoming dominant in later stages of tumor development when PCa cells gain androgen independence. Taken together, our results indicate that ALDH1A1 and ALDH1A3 modulate PCa radiosensitivity, regulate CSCs phenotype, and spread of PCa cells to the bone, therefore having clinical implication for identifying patients at high risk for progression to metastatic disease.
Osteoblast cell death triggers a pro-osteogenic inflammatory response regulated by reactive oxygen species and glucocorticoid signaling in zebrafish
Authors: Geurtzen Karina , Duseja Ankita , Knopf Franziska 
Published: May 2021

AbstractIn zebrafish, transgenic labeling approaches, robust regenerative responses and excellentin vivoimaging conditions enable precise characterization of immune cell behavior in response to injury. Here, we monitored osteoblast-immune cell interactions in bone, a tissue which is particularly difficult toin vivoimage in tetrapod species. Ablation of individual osteoblasts leads to recruitment of neutrophils and macrophages in varying numbers, depending on the extent of the initial insult, and initiates generation ofcathepsinK+ osteoclasts from macrophages. Induced osteoblast death triggers the production of pro-inflammatory cytokines and reactive oxygen species, which are needed for successful macrophage recruitment. Excess glucocorticoid signaling as it occurs during the stress response inhibits macrophage recruitment, maximum speed and changes the macrophages’ phenotype. While osteoblast loss is compensated for within a day by contribution of committed osteoblasts, macrophages continue to populate the region. Their presence is required for osteoblasts to fill the lesion site. Our model enables visualization of homeostatic bone repair after microlesions at single cell resolution and demonstrates a pro-osteogenic function of tissue-resident macrophages in non-mammalian vertebrates.Summary statementLaser-mediated osteoblast ablation induces recruitment of tissue-resident macrophages by a release of reactive oxygen species. The presence of macrophages is required for osteoblasts to repopulate the lesion site and can be modulated by glucocorticoids.