bluuebunny/crossref_metadata_2025_split huggingface dataset:
Findings from Cardiovascular Evaluation of NCAA Division I Collegiate Student-Athletes after Asymptomatic or Mildly Symptomatic SARS-CoV-2 Infection
Authors: Hwang Calvin E , Kussman Andrea , Christle Jeffrey W , Froelicher Victor , Wheeler Matthew T , Moneghetti Kegan J 
Published: January 2021

ABSTRACTObjectivesThe risk of myocardial damage after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been controversial. There is an urgent need for data to support the appropriate level of cardiovascular screening for safe return-to-play. The purpose of this study is to report the incidence of abnormal cardiovascular findings in National Collegiate Athletic Association (NCAA) Division I student-athletes with a history of SARS-CoV-2 infection.MethodsThis is a case series of student-athletes at a single NCAA Division I institution who tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) or antibody testing (IgG) from 4/15/2020 to 10/31/2020. From 452 athletes who were screened, 5,124 PCR and 452 antibody tests were completed. Student-athletes were followed through 12/31/2020 (median 104 days, range 64-182 days). Cardiac work-up included clinical evaluation, troponin level, electrocardiogram (ECG), and echocardiogram. Additional work-up was ordered as clinically indicated.Results55 student-athletes tested positive for SARS-CoV-2. Of these, 38 (69%) had symptoms of Coronavirus Disease (COVID-19), 14 (26%) had a positive IgG test, and 41 (74%) had a positive PCR test. Eight abnormal cardiovascular screening evaluations necessitated further testing including cardiac magnetic resonance imaging (cMRI). Two athletes received new cardiac diagnoses, one probable early cardiomyopathy and one pericarditis, while the remaining six had normal cardiac MRIs.ConclusionThese data support recent publications which recommend the de-escalation of cardiovascular testing for athletes who have recovered from asymptomatic or mildly symptomatic SARS-CoV-2 infection. Continued follow-up of these athletes for sequelae of SARS-CoV-2 is critical.
Center-Based Experiences Implementing Strategies to Reduce Risk of Horizontal Transmission of SARS-Cov-2: Potential for Compromise of Neonatal Microbiome Assemblage
Authors: Romano-Keeler Joann , Fiszbein Dana , Zhang Jilei , Horowitz Joseph , Hayani Karen , Buhimschi Irina , Lopez Christina , Kadhem Zaynab , Berman James , Rasamimari Phornphat , Raghavan Aarti , Pillers De-Ann M. , Sun Jun 
Published: January 2021

AbstractPerinatal transmission of COVID-19 is poorly understood and many neonatal intensive care units’ (NICU) policies minimize mother-infant contact to prevent transmission. We present our unit’s approach and ways it may impact neonatal microbiome acquisition. We attended COVID-19 positive mothers’ deliveries from March-August 2020. Delayed cord clamping and skin-to-skin were avoided and infants were admitted to the NICU. No parents’ visits were allowed and discharge was arranged with COVID-19 negative family members. Maternal breast milk was restricted in the NICU. All twenty-one infants tested negative at 24 and 48 hours and had average hospital stays of nine days. 40% of mothers expressed breastmilk and 60% of infants were discharged with COVID-19 negative caregivers. Extended hospital stays, no skin-to-skin contact, limited maternal milk use, and discharge to caregivers outside primary residences, potentially affect the neonatal microbiome. Future studies are warranted to explore how ours and other centers’ similar policies influence this outcome.
Compartmentalized three-dimensional human neuromuscular tissue models fabricated on a well-plate-format microdevice
Authors: Yamamoto Kazuki , Yamaoka Nao , Imaizumi Yu , Nagashima Takunori , Furutani Taiki , Ito Takuji , Okada Yohei , Honda Hiroyuki , Shimizu Kazunori 
Published: January 2021

AbstractEngineered three-dimensional models of neuromuscular tissues are promising for use in mimicking their disorder states in vitro. Although several models have been developed, it is still challenging to mimic the physically separated structures of motor neurons (MNs) and skeletal muscle (SkM) fibers in the motor units in vivo. In this study, we aimed to develop microdevices for precisely compartmentalized coculturing of MNs and engineered SkM tissues. The developed microdevices, which fit a well of 24 well plates, had a chamber for MNs and chamber for SkM tissues. The two chambers were connected by microtunnels for axons, permissive to axons but not to cell bodies. Human iPSC (hiPSC)-derived MN spheroids in one chamber elongated their axons into microtunnels, which reached the tissue-engineered human SkM in the SkM chamber, and formed functional neuromuscular junctions with the muscle fibers. The cocultured SkM tissues with MNs on the device contracted spontaneously in response to spontaneous firing of MNs. The addition of a neurotransmitter, glutamate, into the MN chamber induced contraction of the cocultured SkM tissues. Selective addition of tetrodotoxin or vecuronium bromide into either chamber induced SkM tissue relaxation, which could be explained by the inhibitory mechanisms. We also demonstrated the application of chemical or mechanical stimuli to the middle of the axons of cocultured tissues on the device. Thus, compartmentalized neuromuscular tissue models fabricated on the device could be used for phenotypic screening to evaluate the cellular type specific efficacy of drug candidates and would be a useful tool in fundamental research and drug development for neuromuscular disorders.
An awareness-dependent saliency map in the human visual system
Authors: Wang Lijuan , Huang Ling , Li Mengsha , Wang Xiaotong , Wang Shiyu , Lin Yuefa , Zhang Xilin 
Published: January 2021

AbstractThe bottom-up contribution to the allocation of exogenous attention is a saliency map. However, how the saliency map is distributed when multiple salient stimuli are presented simultaneously and how this distribution interacts with awareness remain unclear. These questions were addressed here using visible and invisible stimuli that consisting of two salient foregrounds: the high one served as the target and the low one served as the distractor, which did or did not interfere the target’ saliency, indicating a gradient or winner-take-all manner, respectively. By combining psychophysics, fMRI, and effective connectivity analysis, we found that the saliency map was distributed as a gradient or winner-take-all manner with and without awareness, respectively. Crucially, we further revealed that the gradient manner was derived by feedback from pIPS, whereas the winner-take-all manner was constructed in V1. Together, our findings indicate an awareness-dependent saliency map and reconcile previous, seemingly contradictory findings on the saliency map.
Free Energy Landscape and Rate Estimation of the Aromatic Ring Flips in Basic Pancreatic Trypsin Inhibitor Using Metadynamics
Authors: Kulkarni Mandar , Söderhjelm Pär 
Published: January 2021

ABSTRACTAromatic side-chains (phenylalanine and tyrosine) of a protein flip by 180° around theCβ− Cγaxis (χ2dihedral of side-chain) producing two symmetry-equivalent states. The ring-flip dynamics act as an NMR probe to understand local conformational fluctuations. Ring-flips are categorized as slow (ms onwards) or fast (ns to near ms) based on timescales accessible to NMR experiments. In this study, we investigated the ability of the infrequent metadynamics approach to discriminate between slow and fast ring-flips for eight individual aromatic side-chains (F4, Y10, Y21, F22, Y23, F33, Y35, F45) of basic pancreatic trypsin inhibitor (BPTI). Well-tempered metadynamics simulations were performed to observe ring-flipping free energy surfaces for all eight aromatic residues. The results indicate thatχ2as a standalone collective variable (CV) is not sufficient to classify fast and slow ring-flips. Most of the residues neededχ1(N − Cα) as a complementary CV, indicating the importance of librational motions in ring-flips. Multiple pathways and mechanisms were observed for residues F4, Y10, and F22. Recrossing events are observed for residues F22 and F33, indicating a possible role of friction effects in the ring-flipping. The results demonstrate the successful application of the metadynamics based approach to estimate ring-flip rates of aromatic residues in BPTI and identify certain limitations of the approach.
Coordinated overexpression ofOsSUT1, OsSWEET11andOsSWEET14in rice impairs carbohydrate metabolism that has implications in plant growth, yield and susceptibility toXanthomonas oryzae pv oryzae (Xoo)
Authors: Singh Jitender , James Donald , Murali Achary V Mohan , Patel Manish Kumar , Thakur Jitendra Kumar , Reddy M K , Tripathy Baishnab Charan 
Published: January 2021

AbstractEnhancing carbohydrate export to sink tissues is considered as a feasible approach for improving photosynthetic efficiency and crop yield. InOryza sativaSucrose Transporter OsSUT1 located in companion cells and Sugars Will Eventually be Exported Transporters (SWEETs); OsSWEET11 and OsSWEET14 present in phloem parenchyma mesophyll cell plasma membranes are involved in long distance sucrose transport.OsSWEET11andOsSWEET14also play important role in host-pathogen interaction of rice plants andXanthomonas oryzaepvoryzae(Xoo) that causes bacterial leaf blight. Three genes,OsSUT1, OsSWEET11, andOsSWEET14were overexpressed under the control of their native promoters in rice to modulate long distance sugar transport and disease resistance. The transgenics displayed several phenotypic aberrations such as reduced plant height and seed weight due to altered sucrose transport and metabolism. Lower sucrose transport rate in transgenics than the WT resulted in reduced sucrose, fructose and glucose and increased starch accumulation in their leaves at the end of dark period. Transcriptional analysis revealed a reduction in the expression of genes involved in sucrose synthesis pathway in transgenics. Normal growth and development of transgenic seedlings were restored in growth media supplemented with 3% sucrose demonstratingin plantasucrose limitation. Remarkably, transgenic lines had diminished susceptibility toXoothan the WTs due to low sugar content in the leaves demonstrating that rice plants maintain an optimum level of SWEETs for proper plant growth and development, and upregulation of theseSWEETsin rice mimicksXooattack impelling plants to reduce sugar content in the apoplasm to inhibit pathogen growth.
Mapping cellular subpopulations within triple negative breast cancer tumors provides a tool for cancer sensitization to radiotherapy
Authors: Alkhatib Heba , Rubinstein Ariel M. , Vasudevan Swetha , Flashner-Abramson Efrat , Stefansky Shira , Oguche Solomon , Peretz-Yablonsky Tamar , Granit Avital , Granot Zvika , Ben-Porath Ittai , Sheva Kim , Meirovitz Amichay , Kravchenko-Balasha Nataly 
Published: January 2021

SummaryTriple negative breast cancer (TNBC) is an aggressive type of cancer that is known to be resistant to radiotherapy (RT). Evidence is accumulating that is indicative of the plasticity of TNBC, where one cancer subtype switches to another in response to various treatments, including RT. In this study we aim to overcome tumor resistance by designing TNBC-sensitizing targeted therapies that exploit the plasticity occurring due to radiation exposure. Using single cell analysis of molecular changes occurring in irradiated TNBC tumors, we identified two initially undetected distinct subpopulations, represented by overexpressed Her2 and cMet, expanding post-RT and persisting in surviving tumors. Using murine cancer models and patient-derived TNBC tumors, we showed that only simultaneous targeting of Her2 and cMet was successful in sensitizing TNBC to RT and preventing its regrowth. The strategy presented herein holds the potential to be broadly applicable in clinical use.HighlightsSensitization of TNBC to radiotherapy (RT) is a clinically unmet needSingle cell strategy creates a precise map of subpopulations expanding post-RTEvolution of intra-tumor heterogeneity is turned into a therapeutic advantageSimultaneous targeting of expanding subpopulations sensitizes TNBC to radiotherapy
A mammalian methylation array for profiling methylation levels at conserved sequences
Authors: Arneson Adriana , Haghani Amin , Thompson Michael J. , Pellegrini Matteo , Kwon Soo Bin , Vu Ha , Yao Mingjia , Li Caesar Z. , Lu Ake T. , Barnes Bret , Hansen Kasper D. , Zhou Wanding , Breeze Charles E. , Ernst Jason , Horvath Steve 
Published: January 2021

AbstractInfinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures 36k CpGs that are well conserved across mammalian species. We designed a set of probes on the array that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others.
The impact of PNPLA3 and TM6SF2 in cirrhosis related complications
Authors: Shao Xue , Uojima Haruki , Arai Taeang , Ogawa Yuji , Setsu Toru , Atsukawa Masanori , Furuichi Yoshihiro , Arase Yoshitaka , Horio Kazue , Hidaka Hisashi , Nakazawa Takahide , Kako Makoto , Kagawa Tatehiro , Iwakiri Katsuhiko , Nakajima Atsushi , Terai Shuji , Tanaka Yasuhito , Koizumi Wasaburo 
Published: January 2021

AbstractPatatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6-superfamily member 2 (TM6SF2) polymorphisms have major impact for fibrosis due to steatohepatitis. However, there are scant data about correlations between cirrhosis-related complications and the polymorphisms of these genes. Therefore, we aimed to determine the role of the PNPLA3 and TM6SF2 polymorphisms in fibrosis progression for patients with liver cirrhosis. A multicenter study was performed at six hospitals in Japan enrolling 400 patients with liver cirrhosis caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33). These cirrhotic patients included those with complications of variceal bleeding, hepatic ascites, and/or hepatic encephalopathy and those without. To assess the role of the PNPLA3 and TM6SF2 polymorphisms in patients with cirrhosis related complications, we calculated the odds ratio and relative risk for the rs738409 and rs58542926 polymorphisms. We also accessed whether or not the interaction between these two polymorphisms contributed to cirrhosis related complications. As a result, the odds ratio for complications in the NAFLD group significantly increased in the presence of the rs738409 GG genotype when the CC genotype was used as the reference. There were no significant risks between complications and the presence of the rs738409 G allele in the virus or alcohol groups. There were no significant risks of complications in the frequency of the rs58542926 T polymorphism regardless of the etiology of liver cirrhosis. The interaction between the rs738409 and rs58542926 polymorphisms had the highest odds ratio of 2.415 for complications in the rs738409 GG + rs58542926 (CT+TT) group when rs738409 (CC+CG) + TM6SF2 CC was used as the reference in the NAFLD group although there was no statistically interaction between these gene polymorphisms (P=0.085).
Concentration-dependent duality of bFGF in regulation of barrier properties of human brain endothelial cells
Authors: Kriaučiūnaitė Karolina , Pociūtė Agnė , Kaušylė Aida , Pajarskienė Justina , Verkhratsky Alexei , Pivoriūnas Augustas 
Published: January 2021

AbstractMultiple paracrine factors regulate barrier properties of human brain capillary endothelial cells (BCECs). Understanding precise mode of action of these factors remains a challenging task because of the limited availability of functionally competent BCECs and use of serum-containing medium. In the present study we employed defined protocol for producing BCECs from human inducible pluripotent stem cells. We found that autocrine secretion of basic fibroblast growth factor (bFGF) is necessary for the establishment a tight BCECs barrier, as revealed by measurements of trans-endothelial electric resistance (TEER). In contrast, exogenous bFGF in concentrations exceeding 4 ng/ml inhibited TEER and proliferation of BCECs in a concentration-dependent manner. Exogenous bFGF did not significantly affect expression and distribution of tight junction proteins claudin-5, occludin and ZO-1. Treatment with FGF receptor blocker PD173074 (15 μM) suppressed inhibitory effects of bFGF and induced nuclear translocation of protein ZO-1. Inhibition of phosphoinositide 3-Kinase (PI-3K) with LY294002 (25 μM) significantly potentiated inhibitory effect of bFGF on TEER indicating that PI-3K signalling pathway partially suppress inhibitory effects of bFGF on TEER. In conclusion we show that autocrine bFGF secretion is necessary for the proper barrier function of BCECs, whereas exogenous bFGF suppresses barrier resistance in a concentration-dependent manner. Our findings demonstrate a dual role for bFGF in the regulation of BCEC barrier function.
Transcriptomic profiles ofPlasmodium falciparumandPlasmodium vivax-infected individuals in Indonesia
Authors: Bobowik Katalina , Syafruddin Din , Darusallam Chelzie Crenna , Sudoyo Herawati , Wells Christine , Romero Irene Gallego 
Published: January 2021

AbstractMalaria is one of the leading causes of illness and death globally. The vast majority of transcriptomic studies of the impact of malaria on human hosts have been conducted on populations of African ancestry suffering fromPlasmodium falciparuminfection, making it unclear whether biological responses observed in these studies can be generalised to other populations. Here, we perform differential expression analysis between healthy controls and malaria-infected patients within Indonesia, a country of over 260 million people which has substantial morbidity due to endemic malaria. We find that in samples infected withP. falciparumandP. vivax, there is an upregulation of genes involved in inflammation, the immediate early immune response, translation, and apoptosis. When comparing these findings to transcriptomic studies conducted in Africa (onP. falciparum) and South America (onP. vivax), we find that many pathways are shared. This is particularly apparent for receptor recognition and inflammation-related genes inP. falciparumand innate immune and chemokine-related genes inP. vivaxinfection. However, we also find that many genes are unique to the Indonesian population, particularly those involved in RNA processing, splicing, and cell surface receptor genes. This study provides a more comprehensive view of malaria infection outside of Africa and contributes to a better characterisation of malaria pathogenesis within humans across a range of genetic architectures.
Increasing calling accuracy, coverage, and read depth in sequence data by the use of haplotype blocks
Authors: Pook Torsten , Nemri Adnane , Segovia Eric Gerardo Gonzalez , Simianer Henner , Schoen Chris-Carolin 
Published: January 2021

AbstractHigh-throughput genotyping of large numbers of lines remains a key challenge in plant genetics, requiring geneticists and breeders to find a balance between data quality and the number of genotyped lines under a variety of different existing technologies when resources are limited. In this work, we are proposing a new imputation pipeline (“HBimpute”) that can be used to generate high-quality genomic data from low read-depth whole-genome-sequence data. The key idea of the pipeline is the use of haplotype blocks from the software HaploBlocker to identify locally similar lines and merge their reads locally. The effectiveness of the pipeline is showcased on a dataset of 321 doubled haploid lines of a European maize landrace, which were sequenced with 0.5X read-depth. Overall imputing error rates are cut in half compared to the state-of-the-art software BEAGLE, while the average read-depth is increased to 83X, thus enabling the calling of structural variation. The usefulness of the obtained imputed data panel is further evaluated by comparing the performance in common breeding applications to that of genomic data from a 600k array. In particular for genome-wide association studies, the sequence data is shown to be performing slightly better. Furthermore, genomic prediction based on the overlapping markers from the array and sequence is leading to a slightly higher predictive ability for the imputed sequence data, thereby indicating that the data quality obtained from low read-depth sequencing is on par or even slightly higher than high-density array data. When including all markers for the sequence data, the predictive ability is slightly reduced indicating overall lower data quality in non-array markers.Author summaryHigh-throughput genotyping of large numbers of lines remains a key challenge in plant genetics and breeding. Cost, precision, and throughput must be balanced to achieve optimal efficiencies given available technologies and finite resources. Although genotyping arrays are still considered the gold standard in high-throughput quantitative genetics, recent advances in sequencing provide new opportunities for this. Both the quality and cost of genomic data generated based on sequencing are highly dependent on the used read depth. In this work, we are proposing a new imputation pipeline (“HBimpute”) that uses haplotype blocks to detect individuals of the same genetic origin and subsequently uses all reads of those individuals in the variant calling. Thus, the obtained virtual read depth is artificially increased, leading to higher calling accuracy, coverage, and the ability to all copy number variation based on relatively cheap low-read depth sequencing data. Thus, our approach makes sequencing a cost-competitive alternative to genotyping arrays with the additional benefit of the potential use of structural variation.