bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of the gut microbial community structure and function with aging in the spontaneously hypertensive stroke prone rat
Authors: Shi Huanan , Nelson James W. , Phillips Sharon , Petrosino Joseph F. , Bryan Robert M. , Durgan David J. 
Published: May 2022

AbstractGut dysbiosis, a pathological imbalance of bacteria, has been shown to contribute to the development of hypertension (HT), systemic- and neuro-inflammation, and blood–brain barrier (BBB) disruption in spontaneously hypertensive stroke prone rats (SHRSP). However, to date individual species that contribute to HT in the SHRSP model have not been identified. One potential reason, is that nearly all studies of the SHRSP gut microbiota have analyzed samples from rats with established HT. The goal of this study was to examine the SHRSP gut microbiota before, during, and after the onset of hypertension, and in normotensive WKY control rats over the same age range. We hypothesized that we could identify key microbes involved in the development of HT by comparing WKY and SHRSP microbiota during the pre-hypertensive state and longitudinally. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and fecal microbiota analyzed by16S rRNA gene sequencing. SHRSP showed significant elevations in SBP, as compared to WKY, beginning at 8 weeks of age (p < 0.05 at each time point). Bacterial community structure was significantly different between WKY and SHRSP as early as 4 weeks of age, and remained different throughout the study (p = 0.001–0.01). At the phylum level we observed significantly reduced Firmicutes and Deferribacterota, and elevated Bacteroidota, Verrucomicrobiota, and Proteobacteria, in pre-hypertensive SHRSP, as compared to WKY. At the genus level we identified 18 bacteria whose relative abundance was significantly different in SHRSP versus WKY at the pre-hypertensive ages of 4 or 6 weeks. In an attempt to further refine bacterial candidates that might contribute to the SHRSP phenotype, we compared the functional capacity of WKY versus SHRSP microbial communities. We identified significant differences in amino acid metabolism. Using untargeted metabolomics we found significant reductions in metabolites of the tryptophan-kynurenine pathway and increased indole metabolites in SHRSP versus WKY plasma. Overall, we provide further evidence that gut dysbiosis contributes to hypertension in the SHRSP model, and suggest for the first time the potential involvement of tryptophan metabolizing microbes.
Proof of concept for multiplex amplicon sequencing for mutation identification using the MinION nanopore sequencer
Authors: Whitford Whitney , Hawkins Victoria , Moodley Kriebashne S. , Grant Matthew J. , Lehnert Klaus , Snell Russell G. , Jacobsen Jessie C. 
Published: May 2022

AbstractRapid, cost-effective identification of genetic variants in small candidate genomic regions remains a challenge, particularly for less well equipped or lower throughput laboratories. The application of Oxford Nanopore Technologies’ MinION sequencer has the potential to fulfil this requirement. We demonstrate a proof of concept for a multiplexing assay that pools PCR amplicons for MinION sequencing to enable sequencing of multiple templates from multiple individuals, which could be applied to gene-targeted diagnostics. A combined strategy of barcoding and sample pooling was developed for simultaneous multiplex MinION sequencing of 100 PCR amplicons. The amplicons are family-specific, spanning a total of 30 loci in DNA isolated from 82 human neurodevelopmental cases and family members. The target regions were chosen for further interrogation because a potentially disease-causative variant had been identified in affected individuals following Illumina exome sequencing. The pooled MinION sequences were deconvoluted by aligning to custom references using the minimap2 aligner software. Our multiplexing approach produced an interpretable and expected sequence from 29 of the 30 targeted genetic loci. The sequence variant which was not correctly resolved in the MinION sequence was adjacent to a five nucleotide homopolymer. It is already known that homopolymers present a resolution problem with the MinION approach. Interestingly despite equimolar quantities of PCR amplicon pooled for sequencing, significant variation in the depth of coverage (127×–19,626×; mean = 8321×, std err = 452.99) was observed. We observed independent relationships between depth of coverage and target length, and depth of coverage and GC content. These relationships demonstrate biases of the MinION sequencer for longer templates and those with lower GC content. We demonstrate an efficient approach for variant discovery or confirmation from short DNA templates using the MinION sequencing device. With less than 130 × depth of coverage required for accurate genotyping, the methodology described here allows for rapid highly multiplexed targeted sequencing of large numbers of samples in a minimally equipped laboratory with a potential cost as much 200 × less than that from Sanger sequencing.
Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements
Authors: Ueo Hiroki , Minoura Itsushi , Ueo Hiroaki , Gamachi Ayako , Kai Yuichiro , Kubota Yoko , Doi Takako , Yamaguchi Miki , Yamashita Toshinari , Tsuda Hitoshi , Moriya Takuya , Yamaguchi Rin , Kozuka Yuji , Sasaki Takeshi , Masuda Takaaki , Urano Yasuteru , Mori Masaki , Mimori Koshi 
Published: May 2022

AbstractBreast-conserving surgery has become the preferred treatment method for breast cancer. Surgical margin assessment is performed during surgery, as it can reduce local recurrence in the preserved breast. Development of reliable and lower-cost ex vivo cancer detection methods would offer several benefits for patient care. Here, a practical and quantitative evaluation method for the ex vivo fluorescent diagnosis of breast lesions was developed and confirmed through a three-step clinical study. Gamma-glutamyl-hydroxymethyl rhodamine green (gGlu-HMRG) has been reported to generate fluorescence in breast lesions. Using this probe, we constructed a reliable and reproducible procedure for the quantitative evaluation of fluorescence levels. We evaluated the reliability of the method by considering reproducibility, temperature sensitivity, and the effects of other clinicopathological factors. The results suggest that the fluorescence increase of gGlu-HMRG is a good indicator of the malignancy of breast lesions. However, the distributions overlapped. A 5 min reaction with this probe could be used to distinguish at least part of the normal breast tissue. This method did not affect the final pathological examination. In summary, our results indicate that the methods developed in this study may serve as a feasible intraoperative negative-margin assessment tool during breast-conserving surgery.
Contributing factors for acute stress in healthcare workers caring for COVID-19 patients in Argentina, Chile, Colombia, and Ecuador
Authors: Martin-Delgado Jimmy , Poblete Rodrigo , Serpa Piedad , Mula Aurora , Carrillo Irene , Fernández Cesar , Vicente Ripoll María Asunción , Loudet Cecilia , Jorro Facundo , Garcia Elorrio Ezequiel , Guilabert Mercedes , Mira José Joaquín 
Published: May 2022

AbstractThis study analyzed the frequency and intensity of acute stress among health professionals caring for COVID-19 patients in four Latin American Spanish-speaking countries during the outbreak. A cross-sectional study involved a non-probability sample of healthcare professionals in four Latin American countries. Participants from each country were invited using a platform and mobile application designed for this study. Hospital and primary care workers from different services caring for COVID-19 patients were included. The EASE Scale (SARS-CoV-2 Emotional Overload Scale, in Spanish named Escala Auto-aplicada de Sobrecarga Emocional) was a previously validated measure of acute stress. EASE scores were described overall by age, sex, work area, and experience of being ill with COVID-19. Using the Mann–Whitney U test, the EASE scores were compared according to the most critical moments of the pandemic. Univariate and multivariate analysis was performed to investigate associations between these factors and the outcome ‘acute stress’. Finally, the Kruskal–Wallis was used to compare EASE scores and the experience of being ill. A total of 1372 professionals responded to all the items in the EASE scale: 375 (27.3%) Argentines, 365 (26.6%) Colombians, 345 (25.1%) Chileans, 209 (15.2%) Ecuadorians, and 78 (5.7%) from other countries. 27% of providers suffered middle-higher acute stress due to the outbreak. Worse results were observed in moments of peak incidence of cases (14.3 ± 5.3 vs. 6.9 ± 1.7, p < 0.05). Higher scores were found in professionals in COVID-19 critical care (13 ± 1.2) than those in non-COVID-19 areas (10.7 ± 1.9) (p = 0.03). Distress was higher among professionals who were COVID-19 patients (11.7 ± 1) or had doubts about their potential infection (12 ± 1.2) compared to those not infected (9.5 ± 0.7) (p = 0.001). Around one-third of the professionals experienced acute stress, increasing in intensity as the incidence of COVID-19 increased and as they became infected or in doubt whether they were infected. EASE scale could be a valuable asset for monitoring acute stress levels among health professionals in Latin America.ClinicalTrials: NCT04486404.
Building digital twins of the human immune system: toward a roadmap
Authors: Laubenbacher R. , Niarakis A. , Helikar T. , An G. , Shapiro B. , Malik-Sheriff R. S. , Sego T. J. , Knapp A. , Macklin P. , Glazier J. A. 
Published: May 2022

AbstractDigital twins, customized simulation models pioneered in industry, are beginning to be deployed in medicine and healthcare, with some major successes, for instance in cardiovascular diagnostics and in insulin pump control. Personalized computational models are also assisting in applications ranging from drug development to treatment optimization. More advanced medical digital twins will be essential to making precision medicine a reality. Because the immune system plays an important role in such a wide range of diseases and health conditions, from fighting pathogens to autoimmune disorders, digital twins of the immune system will have an especially high impact. However, their development presents major challenges, stemming from the inherent complexity of the immune system and the difficulty of measuring many aspects of a patient’s immune state in vivo. This perspective outlines a roadmap for meeting these challenges and building a prototype of an immune digital twin. It is structured as a four-stage process that proceeds from a specification of a concrete use case to model constructions, personalization, and continued improvement.
Terrestrial and marine influence on atmospheric bacterial diversity over the north Atlantic and Pacific Oceans
Authors: Lang-Yona Naama , Flores J. Michel , Haviv Rotem , Alberti Adriana , Poulain Julie , Belser Caroline , Trainic Miri , Gat Daniella , Ruscheweyh Hans-Joachim , Wincker Patrick , Sunagawa Shinichi , Rudich Yinon , Koren Ilan , Vardi Assaf 
Published: May 2022

AbstractThe diversity of microbes and their transmission between ocean and atmosphere are poorly understood despite the implications for microbial global dispersion and biogeochemical processes. Here, we survey the genetic diversity of airborne and surface ocean bacterial communities sampled during springtime transects across the northwest Pacific and subtropical north Atlantic as part of the Tara Pacific Expedition. We find that microbial community composition is more variable in the atmosphere than in the surface ocean. Bacterial communities were more similar between the two surface oceans than between the ocean and the overlying atmosphere. Likewise, Pacific and Atlantic atmospheric microbial communities were more similar to each other than to those in the ocean beneath. Atmospheric community composition over the Atlantic was dominated by terrestrial and specifically, dust-associated bacteria, whereas over the Pacific there was a higher prevalence and differential abundance of marine bacteria. Our findings highlight regional differences in long-range microbial exchange and dispersal between land, ocean, and atmosphere.
A prospective matched case-control study on the genomic epidemiology of colistin-resistant Enterobacterales from Dutch patients
Authors: Vendrik Karuna E. W. , de Haan Angela , Witteveen Sandra , Hendrickx Antoni P. A. , Landman Fabian , Notermans Daan W. , Bijkerk Paul , Schoffelen Annelot F. , de Greeff Sabine C. , Wielders Cornelia C. H. , Goeman Jelle J. , Kuijper Ed J. , Schouls Leo. M. ,   ColRE survey consortium, Heemstra Karen , Vainio Saara , Ott Alewijn , de Jager Steve , Koene Fleur , Hira Vishal , van Burgel Nathalie , Muller Anouk , Nagtegaal-Baerveldt Karolien , van der Meer Coby , van den Biggelaar Rik , Pontesilli Oscar , van Mens Suzan , van den Bijllaardt Wouter , Kolwijck Eva , Bosboom Ron , Frénay Ine , van ’t Veen Annemarie , Troelstra Annet , Kampinga Greetje , van Dijk Karin 
Published: May 2022

Abstract
Background
Colistin is a last-resort treatment option for infections with multidrug-resistant Gram-negative bacteria. However, colistin resistance is increasing.

Methods
A six-month prospective matched case-control study was performed in which 22 Dutch laboratories with 32 associated hospitals participated. Laboratories were invited to send a maximum of five colistin-resistant Escherichia coli or Klebsiella pneumoniae (COLR-EK) isolates and five colistin-susceptible isolates (COLS-EK) to the reference laboratory, matched for patient location, material of origin and bacterial species. Epidemiological/clinical data were collected and included in the analysis. Characteristics of COLR-EK/COLS-EK isolates were compared using logistic regression with correction for variables used for matching. Forty-six ColR-EK/ColS-EK pairs were analysed by next-generation sequencing (NGS) for whole-genome multi-locus sequence typing and identification of resistance genes, including mcr genes. To identify chromosomal mutations potentially leading to colistin resistance, NGS reads were mapped against gene sequences of pmrAB, phoPQ, mgrB and crrB.

Results
In total, 72 COLR-EK/COLS-EK pairs (75% E. coli and 25% K. pneumoniae) were included. Twenty-one percent of COLR-EK patients had received colistin, in contrast to 3% of COLS-EK patients (OR > 2.9). Of COLR-EK isolates, five contained mcr-1 and two mcr-9. One isolate lost mcr-9 after repeated sub-culturing, but retained colistin resistance. Among 46 sequenced COLR-EK isolates, genetic diversity was large and 19 (41.3%) isolates had chromosomal mutations potentially associated with colistin resistance.

Conclusions
Colistin resistance is present but uncommon in the Netherlands and caused by the mcr gene in a minority of COLR-EK isolates. There is a need for surveillance of colistin resistance using appropriate susceptibility testing methods.
Genetic suppressors of Δgrx3 Δgrx4, lacking redundant multidomain monothiol yeast glutaredoxins, rescue growth and iron homeostasis
Authors: Li Guichun , Nanjaraj Urs Ankanahalli N. , Dancis Andrew , Zhang Yan 
Published: May 2022

Abstract
Saccharomyces cerevisiae Grx3 and Grx4 are multidomain monothiol glutaredoxins that are redundant with each other. They can be efficiently complemented by heterologous expression of their mammalian ortholog, PICOT, which has been linked to tumor development and embryogenesis. PICOT is now believed to act as a chaperone distributing Fe-S clusters, although the first link to iron metabolism was observed with its yeast counterparts. Like PICOT, yeast Grx3 and Grx4 reside in the cytosol and nucleus where they form unusual Fe-S clusters coordinated by two glutaredoxins with CGFS motifs and two molecules of glutathione. Depletion or deletion of Grx3/Grx4 leads to functional impairment of virtually all cellular iron-dependent processes and loss of cell viability, thus making these genes the most upstream components of the iron utilization system. Nevertheless, the Δgrx3/4 double mutant in the BY4741 genetic background is viable and exhibits slow but stable growth under hypoxic conditions. Upon exposure to air, growth of the double deletion strain ceases, and suppressor mutants appear. Adopting a high copy-number library screen approach, we discovered novel genetic interactions: overexpression of ESL1, ESL2, SOK1, SFP1 or BDF2 partially rescues growth and iron utilization defects of Δgrx3/4. This genetic escape from the requirement for Grx3/Grx4 has not been previously described. Our study shows that even a far-upstream component of the iron regulatory machinery (Grx3/4) can be bypassed, and cellular networks involving RIM101 pH sensing, cAMP signaling, mTOR nutritional signaling, or bromodomain acetylation, may confer the bypassing activities.
Gaussian noise parameter estimation based on multiple singular value decomposition and non‐linear fitting
Authors: Qi Jinli , Sun Lei , Li Kengpeng , Wang Lingang 
Published: May 2022

AbstractNoise standard deviation (STD) is an important parameter in many digital image processing applications. This paper presents a Gaussian noise parameter estimation algorithm using multiple singular value decomposition (SVD) and non‐linear fitting. The proposed algorithm adds known noise to the original noise image many times to generate a noise‐corrupted image set and then performs SVD on each image. By analyzing the singular values of the noise‐corrupted images, an overdetermined equation system with respect to the noise STD is established. The Gauss–Newton iteration method and backtracking Armijo line search are used to solve the equations, which improve the convergence speed and reduce computational cost. Compared with other methods, the mean error of the proposed algorithm on the TID2008 dataset is 0.028, which is several times lower than other methods. This shows that the performance of our estimator is significantly improved.
The contribution of data-driven poverty alleviation funds in achieving mid-21st-Century multidimensional poverty alleviation planning
Authors: Yang Di , Luan Weixin , Yang Jun , Xue Bing , Zhang Xiaoling , Wang Hui , Pian Feng 
Published: May 2022

AbstractThe first Sustainable Development Goal (SDG) is intended to eradicate multi-dimensional poverty globally. The same multidimensional poverty indices for India and the Middle East/Africa in 2020 indicate that 10–14 years are still required to reach the level of China’s poverty eradication. Using machine learning, spatial statistics, and a scenario analysis, we demonstrate how a Monte Carlo simulation of poverty alleviation funds-guided shared socioeconomic pathways (PAFs-SSPs) in China reveals the necessity to adopt an integrated poverty alleviation strategy. This approach employs multi-dimensional development indicators to reduce wide regional differences. We developed the data-driven model framework of a PAFs-SSPs to analyze the multifaceted and long-term planning needs of poverty alleviation policies, which can be applied to the formulation of poverty alleviation policies in different developing countries. Our findings point to the importance of implementing multidimensional development policies in China to achieve the first SDG worldwide.
Evaluation of
Authors: Wegi Teklu , Hassen Abubeker , Bezabih Melkamu , Nurfeta Ajebu , Yigrem Sintayehu , Tolera Adugna 
Published: May 2022

Context Plant species exhibit different patterns of plant cuticular wax profiles, which can potentially be used as diet composition markers in free-grazing herbivores. Aims Evaluate the suitability of the plant cuticular n-alkanes, long-chain alcohol (LCOH) profiles and carbon stable isotope enrichment (δ13C) of n-alkanes as markers in the estimation of diet composition of grazing animals. Methods Forage samples were collected from 100 representative quadrats of 0.5 m × 0.5 m at 10 m transects and sorted by species and pooled from different quadrats to obtain enough quantities of representative individual species. In total, 10 dominant forage species were identified and analysed for n-alkanes and LCOH by gas chromatography, and the isotopic ratio by using gas chromatography–combustion–isotope ratio mass spectrometry. Principal component analysis (PCA) was used to identify inter-species differences in the concentration patterns of plant wax components. Key results Odd-chain n-alkanes comprised the highest proportion of the total n-alkane concentration, ranging from 79% in Ischaemum afrum to 95% in Haplocarpha hastata. n-Alkanes C31, C29 and C33 were the most abundant with an average of 167, 80 and 61 mg/kg DM, in that order, in all species. Even-chain LCOH comprised the highest proportion of the total LCOH concentration, accounting for 92% in Brachiaria scalaris to 97% in Ischaemum afrum. The dominant even-chain LCOH were C30OH, C32OH, C28OH and C26OH, with an average concentration of 362, 348, 266 and 237 mg/kg DM respectively, across species. The δ13C of n-alkanes showed large variations among forage species, ranging from −19.7‰ in Andropogon amethystinus to −40.6‰ in Trifolium mattirolianum. The result of the PCA showed that 81% of the variance in the pattern of concentrations of n-alkanes was explained by the first two principal components compared with 69.3% and 82.9% in the case of LCOH and δ13C of n-alkanes, respectively. Conclusions Noticeable variations were observed for forage species studied in the patterns of plant wax components. Implications The differences in the patterns of concentrations of n-alkanes, LCOH and δ13C of n-alkanes could be suitable as markers for diet composition estimation of grazing animals.
MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells
Authors: Comar Courtney E. , Otter Clayton J. , Pfannenstiel Jessica , Doerger Ethan , Renner David M. , Tan Li Hui , Perlman Stanley , Cohen Noam A. , Fehr Anthony R. , Weiss Susan R. 
Published: May 2022

Significance
Middle East respiratory syndrome coronavirus (MERS-CoV) causes highly lethal respiratory disease. MERS-CoV encodes innate immune antagonists, including accessory proteins NS4a and NS4b, unique to the merbeco lineage of betacoronaviruses, and the nsp15 protein endoribonuclease (EndoU), conserved among all coronaviruses. While mutation of each antagonist protein alone has little effect on innate immunity, infections with recombinant MERS-CoVs with mutations of EndoU in combination with either NS4a or NS4b activate innate signaling pathways and are attenuated for replication. Our data indicate that EndoU and accessory proteins NS4a and NS4b together suppress innate immunity during MERS-CoV infection, to optimize viral replication. This is in contrast to SARS-CoV-2 which activates these pathways and is thus more vulnerable to host innate immune responses.
Visualization of mutagenic nucleotide processing by
Escherichia coli
MutT, a Nudix hydrolase
Authors: Nakamura Teruya , Yamagata Yuriko 
Published: May 2022

Significance
Time-resolved X-ray crystallography has captured transient elements in enzymatic reactions and has advanced understanding regarding canonical mechanisms. Although Nudix hydrolases are involved in cellular metabolism via hydrolytic activities, the catalytic mechanisms remain elusive. This is because the Nudix hydrolases are defined only by a highly conserved short motif and because most mechanisms are based on the structures mimicking the reaction states. Time-resolved X-ray crystallography of MutT has followed the course of 8-oxo-dGTP hydrolysis and enabled visualization of the process of nucleophilic substitution by a water molecule that is synchronized with the sequential coordination of three metal ions. These observations are consistent with previous kinetic analysis and are indicative of a three-metal-ion mechanism.