bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organoid Medicine for Inflammatory Bowel Disease
Authors: Wakisaka Yusuke , Sugimoto Shinya , Sato Toshiro 
Published: January 2022

AbstractInflammatory bowel disease (IBD) is a chronic relapsing-remitting inflammatory disease of the gastrointestinal tract with an unknown etiology, and its incidence is increasing worldwide. Recent advances in immunomodulatory therapeutic agents such as biologics and small-molecule inhibitors have improved the prognosis of patients with IBD. However, some patients are refractory and resistant to these immunomodulatory therapies, and new therapies are needed. Given the importance of the intestinal epithelium in IBD pathogenesis, the difficulty of culturing intestinal epithelial cells (IECs) for long periods remains an obstacle in IBD research. Over the past 15 years, intestinal stem cells have been identified, and the in vivo microenvironment, called the niche, required for their maintenance has been elucidated, making the permanent culture of IECs possible. Recapitulating the niche in vitro, the intestinal epithelium forms 3-dimensional structures called organoids that simulate the intestinal epithelium in vivo. The intestinal epithelium plays an important role in the intestinal barrier and immunomodulatory functions and serves as a physical structure that separates the intestinal lumen from the body. Recent studies have revealed that functional disruption of the intestinal epithelium is closely related to the pathogenesis of IBD, and IBD research using organoids has attracted attention. In this review, we discuss the application of adult tissue-derived organoids culture technology to elucidate the pathogenesis of IBD and to develop novel therapies, including regenerative treatments.
Performance of a Multisensor Smart Ring to Evaluate Sleep: In-Lab and Home-Based Evaluation Relative to Polysomnography and Actigraphy: Importance of Generalized Versus Personalized Scoring
Authors: Grandner Michael A. , Bromberg Zohar , Hadley Aaron , Morrell Zoe , Graf Arnulf , Hutchison Stephen , Freckleton Dustin 
Published: January 2022

ABSTRACTStudy ObjectivesWearable sleep technology has rapidly expanded across the consumer market due to advances in technology and increased interest in personalized sleep assessment to improve health and mental performance. In this study, we tested the performance of a novel device, the Happy Ring, alongside other commercial wearables, against in-lab polysomnography (PSG) and an at-home EEG-derived sleep monitoring device, the Dreem 2 Headband.Methods36 healthy adults with no diagnosed sleep disorders and no recent use of medications or substances known to affect sleep pattern were assessed across 77 nights while wearing the Happy Ring, as well as a set of other consumer wearable devices. Subjects participated in a single night of in-lab PSG and 2 nights of at-home data collection. The Happy Ring includes sensors for skin conductance, movement, heart rate, and skin temperature. The Happy Ring utilized two machine-learning derived scoring algorithms: a “generalized” algorithm that applied broadly to all users, and a “personalized” algorithm that adapted to individual subjects’ data. Epoch-by-epoch analyses compared the wearable devices to both in-lab PSG and to the Dreem 2 EEG Headband (“Dreem 2 Headband”) at home.ResultsCompared to in-lab PSG, the “generalized” and “personalized” algorithms demonstrated good sensitivity (94% and 93%, respectively) and specificity (70% and 83%, respectively). Accuracy was 91% for “generalized” and 92% for “personalized” algorithms. The generalized algorithm demonstrated an accuracy of 67%, 85%, and 85% for light, deep, and REM sleep, respectively. The personalized algorithm was 81%, 95%, and 92% accurate for light, deep, and REM sleep, respectively.ConclusionsThe Happy Ring performed well at home and in the lab, especially regarding sleep detection. The personalized algorithm demonstrated improved detection accuracy over the generalized approach and other devices, suggesting that adaptable, dynamic algorithms can enhance sleep detection accuracy.
Longitudinal serologic and viral testing post–SARS-CoV-2 infection and post-receipt of mRNA COVID-19 vaccine in a nursing home cohort—Georgia, October 2020‒April 2021
Authors: Tobolowsky Farrell A. , Waltenburg Michelle A. , Moritz Erin D. , Haile Melia , DaSilva Juliana C. , Schuh Amy J. , Thornburg Natalie J. , Westbrook Adrianna , McKay Susannah L. , LaVoie Stephen P. , Folster Jennifer M. , Harcourt Jennifer L. , Tamin Azaibi , Stumpf Megan M. , Mills Lisa , Freeman Brandi , Lester Sandra , Beshearse Elizabeth , Lecy Kristin D. , Brown Laura G. , Fajardo Geroncio , Negley Jeanne , McDonald L. Clifford , Kutty Preeta K. , Brown Allison C. ,   for the CDC Infection Prevention and Control Team
Published: January 2022

AbstractImportanceThere are limited data describing SARS-CoV-2–specific immune responses and their durability following infection and vaccination in nursing home residents.ObjectiveTo evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination.DesignA prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW™ COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture.SettingA nursing home during and after a SARS-CoV-2 outbreak.Participants11 consenting SARS-CoV-2–positive nursing home residents.Main Outcomes and MeasuresSARS-CoV-2 testing (BinaxNOW™, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series).ResultsOf 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR–positive but none were culture positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation ≤90 days post-first dose. Post-vaccination geometric means of IgG titers were 10–200-fold higher than post-infection.Conclusions and RelevanceNursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.
Exome sequencing of 628,388 individuals identifies common and rare variant associations with clonal hematopoiesis phenotypes
Authors: Kessler Michael D. , Damask Amy , O’Keeffe Sean , Van Meter Michael , Banerjee Nilanjana , Semrau Stefan , Li Dadong , Watanabe Kyoko , Horowitz Julie , Houvras Yariv , Gillies Christopher , Mbatchou Joelle , White Ryan R. , Kosmicki Jack A. , LeBlanc Michelle G. , Jones Marcus ,   Regeneron Genetics Center,   GHS-RGC DiscovEHR Collaboration, Glass David J. , Lotta Luca A. , Cantor Michael N. , Atwal Gurinder S. , Locke Adam E. , Ferreira Manuel A. R. , Deering Raquel , Paulding Charles , Shuldiner Alan R. , Thurston Gavin , Salerno Will , Reid Jeffrey G. , Overton John D. , Marchini Jonathan , Kang Hyun M. , Baras Aris , Abecasis Gonçalo R. , Jorgenson Eric 
Published: January 2022

AbstractClonal hematopoiesis (CH) refers to the expansion of certain blood cell lineages and has been associated with aging and adverse health outcomes. Here, we use exome sequence data on 628,388 individuals to identify 40,208 carriers of clonal hematopoiesis of indeterminate potential (CHIP). Using genome-wide and exome-wide association analyses, we identify 27 loci (24 novel) where germline genetic variation influences CH/CHIP predisposition, including missense variants in the DNA-repair gene PARP1 and the lymphocytic antigen coding gene LY75 that are associated with reduced incidence of CH/CHIP. Analysis of 5,194 health traits from the UK Biobank (UKB) found relationships between CHIP and severe COVID outcomes, cardiovascular disease, hematologic traits, malignancy, smoking, obesity, infection, and all-cause mortality. Longitudinal analyses revealed that one of the CHIP subtypes, DNMT3A-CHIP, is associated with the subsequent development of myeloid but not lymphoid leukemias, and with solid cancers including prostate and lung. Additionally, contrary to previous findings from the initial 50,000 UKB exomes, our results in the full sample do not support a role for IL-6 inhibition in reducing the risk of cardiovascular disease among CHIP carriers. Our findings demonstrate that CHIP represents a complex set of heterogenous phenotypes with shared and unique germline genetic causes and varied clinical implications.
COVIDFast™: A high-throughput and RNA extraction-free method for SARS-CoV-2 detection in swab (SwabFAST™) or saliva (SalivaFAST™)
Authors: Qiu Yue , Lu Ling , Halven Amanda , Terrio Rachel , Yuldelson Sydney , Dougal Natalie , Galbo Filippo , Lu Andrew , Gao Dexiang , Blomquist Bob , Zevallos Jose P. , Harry Brian L. , Yao Xin , Lu Shi-Long 
Published: January 2022

ABSTRACTThere is an urgent need of having a rapid, high throughput, yet accurate SARS-COV-2 PCR testing to control the COVID19 pandemic. However, the RNA extraction step in conventional PCR creates a major bottle neck in the diagnostic process. In this paper we modified the CDC COVID-19 assay and developed an RNA-extraction free RT-qPCR assay for SARS-CoV-2, i.e. COVIDFast™. Depending on sample types, the assay is further divided into SwabFAST™, which uses anterior nares nasal swab, and SalivaFAST™, which uses saliva. By utilizing the proprietary buffer for either swab or saliva samples, the performance of SwabFAST or SalivaFAST is equivalent to RNA-extraction SARS-CoV-2 RT-qPCR in both contrived and clinical samples. The limit of detection of either assay is 4 copies/μL. We further developed a semi-automatic system, which is easy to adapt by clinical lab for implementation of a high-throughput SARS-CoV-2 test. Working together with the COVIDCheck Colorado, we have tested over 400,000 samples using COVIDFast (83.62% SwabFAST and 16.38% SalivaFAST) in less than a year, resulting in significant clinical contribution in the battle against COVID-19 during the pandemic.
P-TEFb is degraded by Siah1/2 in quiescent cells
Authors: Huang Fang , Feng Yongmei , Peterlin B. Matija , Fujinaga Koh 
Published: January 2022

AbstractP-TEFb, composed of CycT1 and CDK9, regulates the elongation of transcription by RNA polymerase II. In proliferating cells, it is regulated by 7SK snRNA in the 7SK snRNP complex. In resting cells, P-TEFb is absent, because CycT1 is dephosphorylated, released from CDK9 and rapidly degraded. In this study, we identified the mechanism of this degradation. We mapped the ubiquitination and degradation of free CycT1 to its N-terminal region from positions 1 to 280. This region is ubiquitinated at six lysines, where E3 ligases Siah1 and Siah2 bind and degrade these sequences. Importantly, the inhibition of Siah1/2 rescued the expression of free CycT1 in proliferating as well as resting primary cells. We conclude that Siah1/2 are the E3 ligases that bind and degrade the dissociated CycT1 in resting, terminally differentiated, anergic and/or exhausted cells.
Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels
Authors: Cecon Erika , Fernandois Daniela , Renault Nicolas , Coelho Caio Fernando Ferreira , Wenzel Jan , Bedart Corentin , Izabelle Charlotte , Wimez Sarah Gallet , Poder Sophie Le , Klonjkowski Bernard , Schwaninger Markus , Prevot Vincent , Dam Julie , Jockers Ralf 
Published: January 2022

ABSTRACTCOVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post COVID condition. Brain infection is particularly pronounced in the K18-hACE2 mouse model of COVID-19. Here, we show that treatment of K18-hACE2 mice with melatonin and two melatonin-derived marketed drugs, agomelatine and ramelteon, prevent SARS-CoV-2 entry in the brain thereby reducing virus-induced damage of small cerebral vessels, immune cell infiltration and brain inflammation. Brain entry of SARS-CoV-2 through endothelial cells is prevented by melatonin through allosteric binding to human angiotensin-converting enzyme 2 (ACE2), which interferes with the cell entry receptor function of ACE2 for SARS-CoV-2. Our findings open new perspectives for the repurposing of melatonergic drugs in the prevention of brain infection by SARS-CoV-2 and COVID-19-related long-term neurological symptoms.
THE RHIZOSPHERE BACTERIAL COMMUNITIES DIFFER AMONG DOMESTICATED MAIZE LANDRACES – AN EXPERIMENTAL CONFIRMATION
Authors: Lund Mads , Rasmussen Jacob Agerbo , Ramos-Madrigal Jazmín , Gilbert M. Thomas P. , Barnes Christopher James 
Published: January 2022

AbstractThe plant-associated microbiome has been shown to vary considerably between species and across environmental gradients. The effects of genomic variation on the microbiome within single species are less clearly understood, with results often confounded by the larger effects of climatic and edaphic variation.In this study, the effect of genomic variation on the rhizosphere bacterial communities of maize was investigated by comparing different genotypes grown within controlled environments. Rhizosphere bacterial communities were profiled by metabarcoding the universal bacterial 16S rRNA v3-v4 region. Initially, plants from the inbred B73 line and the Ancho - More 10 landrace were grown for 12- weeks and compared. The experiment was then repeated with an additional four Mexican landraces (Apachito - Chih 172, Tehua - Chis 204, Serrano - Pueb 180 and Hairnoso de Ocho) that were grown alongside additional B73 and Ancho – More 10 genotypes.In both experiments there were significant genotypic differences in the rhizosphere bacteria. Additionally, the bacterial communities were significantly correlated with genomic distance between genotypes, with the more closely related landraces being more similar in rhizosphere bacterial communities.Despite limited sampling numbers, here we confirm that genomic variation in maize landraces is associated with differences in the rhizosphere bacterial communities. Further studies that go beyond correlations to identify the mechanisms that determine the genotypic variation of the rhizosphere microbiome are required.
SARS-CoV-2 entry sites are present in all structural elements of the human glossopharyngeal and vagal nerves: clinical implications
Authors: Vitale-Cross L. , Szalayova I , Scoggins A , Palkovits M. , Mezey E 
Published: January 2022

AbstractSevere acute respiratory syndrome coronavirus (SARS-CoV-2) infections result in the temporary loss of smell and taste (anosmia and dysgeusia) in about one third of confirmed cases. Several investigators have reported that the viral spike protein receptor is present in olfactory neurons. However, no study has been published to date showing the presence of viral entry sites angiotensin-converting enzyme 2 (ACE2), neuropilin1 (NRP1), and TMPRSS2, the serine protease necessary for priming the viral proteins, in human nerves that are responsible for taste sensation (cranial nerves: VII, IX and X). We used immunocytochemistry to examine three postmortem donor samples of the IXth (glossopharyngeal) and Xth (vagal) cranial nerves where they leave/join the medulla from three donors to confirm the presence of ACE2, NRP1 and TMPRSS2. Two samples were paraffin embedded; one was a frozen sample. In addition to staining sections from the latter, we isolated RNA from it, made cDNA, and performed PCR to confirm the presence of the mRNAs that encode the proteins visualized. All three of the proteins required for SARS-CoV-2 infections appear to be present in the human IXth and Xth nerves near the medulla. Direct infection of these nerves by the COVID-19 virus is likely to cause the loss of taste experienced by many patients. In addition, potential viral spread through these nerves into the adjacent brainstem respiratory centers might also aggravate the respiratory problems patients are experiencing.
V1 receptive field structure contributes to neuronal response latency
Authors: Vafaei Amin , Mohammadi Milad , Khadir Alireza , Zabeh Erfan , YazdaniBanafsheDaragh Faraz , Khorasani Mehran , Lashgari Reza 
Published: January 2022

AbstractThe timing of neuronal responses is considered to be important for information transferring and communication across individual neurons. However, the sources of variabilities in the timing of neuronal responses are not well understood and sometimes over-interpreted. A systematic variability in the response latencies of the primary visual cortex has been reported in presence of drifting grating stimulus. Whereas the response latencies are systematically dependent on stimulus orientation. To understand the underlying mechanism of these systematic latencies, we recorded the neuronal response of the cat visual cortex, area 17, and simulated the response latency of V1 neurons, with two geometric models. We showed that outputs of these two models significantly predict the response latencies of the electrophysiology recording during orientation tasks. The periodic patterns created in the raster plots were dependent on the relative position of the stimulus rotation center and the receptive-field sub-regions. We argue the position of stimulus is contributing to systematic response latencies, dependent on drifting orientation. Therefore, we provide a toolbox based on our geometrical model for determining the exact location of RF sub-regions. Our result indicates that a major source of neuronal variability is the lack of fine-tuning in the task parameters. Considering the simplicity of the orientation selectivity task, we argue fine-tuning of stimulus properties is crucial for deduction of neural variability in higher-order cortical areas and understanding their neural dynamics.
Superficial white matter microstructure affects processing speed in cerebral small vessel disease
Authors: Wang Shuyue , Zhang Fan , Huang Peiyu , Hong Hui , Jiaerken Yeerfan , Yu Xinfeng , Zhang Ruiting , Zeng Qingze , Zhang Yao , Kikinis Ron , Rathi Yogesh , Makris Nikos , Lou Min , Pasternak Ofer , Zhang Minming , O’Donnell Lauren J. 
Published: January 2022

AbstractWhite matter hyperintensities (WMH) are a typical feature of cerebral small vessel disease (CSVD). This condition contributes to about 50% of dementias worldwide, a massive health burden in aging. Microstructural alterations in the deep white matter (DWM) have been widely examined in CSVD. However, little is known about abnormalities in the superficial white matter (SWM) and their relevance for processing speed, the main cognitive deficit in CSVD. In this paper, 141 patients with CSVD were studied. Processing speed was assessed by the completion time of the Trail Making Test Part A. White matter abnormalities were assessed by WMH burden (lesion volume on T2-FLAIR) and diffusion MRI, including DTI and free-water (FW) imaging microstructure measures. The results of our study indicate that the superficial white matter may play a particularly important role in cognitive decline in CSVD. SWM imaging measures resulted in a large contribution to processing speed, despite a relatively small WMH burden in the SWM. SWM FW had the strongest association with processing speed among all imaging markers and, unlike the other diffusion MRI measures, significantly increased between two patient subgroups with the lowest WMH burdens (possibly representing early stages of disease). When comparing two patient subgroups with the highest WMH burdens, the involvement of WMH in the SWM was accompanied by significant differences in processing speed and white matter microstructure. Given significant effects of WMH volume and regional FW on processing speed, we performed a mediation analysis. SWM FW was found to fully mediate the association between WMH volume and processing speed, while no mediation effect of DWM FW was observed. Overall, our findings identify SWM abnormalities in CSVD and suggest that the SWM has an important contribution to processing speed. Results indicate that FW in the SWM is a sensitive marker of microstructural changes associated with cognition in CSVD. This study extends the current understanding of CSVD-related dysfunction and suggests that the SWM, as an understudied region, can be a potential target for monitoring pathophysiological processes in future research.
Rsc3K, a SMV resistance gene localized on chromosome 2 in soybean cv. Kefeng No.1, interacts with virulence determinant P3
Authors: Jin Tongtong , Yin Jinlong , Xue Song , Li Bowen , Zong Tingxuan , Yang Yunhua , Liu Hui , Liu Mengzhuo , Xu Kai , Li Kai , Wang Liqun , Zhi Haijian 
Published: January 2022

ABSTRACTSoybean mosaic virus (SMV) is one of the most devastating viral pathogens in Glycine max (L.) Merr (soybean). Twenty-two SMV strains (SC1-SC22) isolated in China were identified based on their responses to ten soybean cultivars. By using the F2-derived F3 (F2:3) and recombinant inbred line (RIL) populations of resistant Soybean cultivar (cv.) Kefeng No.1 × susceptible cv. Nannong 1138-2, we localized the gene mediating resistant to SMV-SC3 strain to a 90 kb interval on chromosome 2 in Kefeng No.1. Bean pod mottle virus (BPMV)-induced gene silencing (VIGS) were used to study the gene function of candidate genes in the mapping interval and revealed that an recombinant gene, later named as Rsc3K, caused by internal deletion of a genomic DNA frag ement in Kefeng No.1, is the resistant gene to SMV-SC3. By shuffling genes between avirulent isolate SC3 and avirulent SMV isolate 1129, we found that P3 is the virulence determinant causing resistance on Kefeng No.1. We showed the interaction between Rsc3K and P3 by the yeast two-hybrid (Y2H) and bimolecular fluorescent complementation (BiFC) assays. In conclusion, this study demonstrated that Rsc3K plays a crucial role in resistance of Kefeng No.1 to SMV-SC3 by direct interaction with viral protein P3.HighlightRsc3K resistant to SMV-SC3 by interacting with P3.
In silico Elucidation of Dihydroquinine Mechanism of Action against Toxoplasma gondii
Authors: Ayariga Joseph A. , Huffman Aarin M. , Napier Audrey , Robertson BK , Abugri Daniel A. 
Published: January 2022

AbstractDihydroquinine (DHQ), is a quinine-based compound with anti-malarial properties. However, little is known about its mechanism of action against T. gondii inhibition, which shares similar biology with Plasmodium spp. In order to explore DHQ activity as an inhibitor of T. gondii using in vitro assays, we first used an in silico approach to decipher its mechanisms of action based on previous knowledge about its disruption of nucleic acid and protein synthesis. An in silico study was performed on T. gondii parasite replication, transcriptional and translational machinery to decipher the binding potentials of DHQ to some top selected enzymes. We report for the first time, using an in silico analysis that showed that DHQ binds strongly to DNA gyrase, Calcium Dependent Protein Kinase 1 (CDPK 1), and prolyl tRNA synthetase and thus could affect DNA replication, transcriptional and translational activities in T. gondii. Also, we found DHQ to effectively bind to mitochondria detoxifying enzymes (i.e., superoxide dismutase (SOD), peroxidoxin, and Catalase (CAT)). In conclusion, DHQ could be a lead compound for the treatment of toxoplasmosis when successfully evaluated using in vitro and in vivo models to confirm its effectiveness and safety.