bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of BA.1/BA.2 subvariant, vaccination, and prior infection on infectiousness of SARS-CoV-2 Omicron infections
Authors: Qassim Suelen H. , Chemaitelly Hiam , Ayoub Houssein H. , AlMukdad Sawsan , Tang Patrick , Hasan Mohammad R. , Yassine Hadi M. , Al-Khatib Hebah A. , Smatti Maria K. , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed Ghaith , Al-Khal Abdullatif , Coyle Peter , Kaleeckal Anvar Hassan , Shaik Riyazuddin Mohammad , Latif Ali Nizar , Al-Kuwari Einas , Jeremijenko Andrew , Butt Adeel A. , Bertollini Roberto , Al-Romaihi Hamad Eid , Al-Thani Mohamed H. , Abu-Raddad Laith J. 
Published: March 2022

AbstractBACKGROUNDQatar experienced a large SARS-CoV-2 Omicron (B.1.1.529) wave that started on December 19, 2021 and peaked in mid-January, 2022. We investigated effects of Omicron subvariant (BA.1 and BA.2), previous vaccination, and prior infection on infectiousness of Omicron infections, between December 23, 2021 and February 20, 2022.METHODSUnivariable and multivariable regression analyses were conducted to estimate the association between the RT-qPCR cycle threshold (Ct) value of PCR tests (a proxy for SARS-CoV-2 infectiousness) and each of the Omicron subvariants, mRNA vaccination, prior infection, reason for RT-qPCR testing, calendar week of RT-qPCR testing (to account for phases of the rapidly evolving Omicron wave), and demographic factors.RESULTSCompared to BA.1, BA.2 was associated with 3.53 fewer cycles (95% CI: 3.46-3.60), signifying higher infectiousness. Ct value decreased with time since second and third vaccinations. Ct values were highest for those who received their boosters in the month preceding the RT-qPCR test—0.86 cycles (95% CI: 0.72-1.00) higher than for unvaccinated persons. Ct value was 1.30 (95% CI: 1.20-1.39) cycles higher for those with a prior infection compared to those without prior infection, signifying lower infectiousness. Ct value declined gradually with age. Ct value was lowest for those who were tested because of symptoms and was highest for those who were tested for travel-related purposes. Ct value was lowest during the exponential-growth phase of the Omicron wave and was highest after the wave peaked and was declining.CONCLUSIONSThe BA.2 subvariant appears substantially more infectious than the BA.1 subvariant. This may reflect higher viral load and/or longer duration of infection, thereby explaining the rapid expansion of this subvariant in Qatar.
Prevalence of Bacterial Coinfection and Patterns of Antibiotics Prescribing in Patients with COVID-19: A Systematic review and Meta-Analysis
Authors: Alshaikh Faisal Salman , Sindi Oula Nawaf , Godman Brian , Seaton R Andrew , Kurdi Amanj 
Published: March 2022

AbstractBackgroundEvidence around prevalence of bacterial coinfection and pattern of antibiotic use in COVID-19 is controversial although high prevalence rates of bacterial coinfection have been reported in previous similar global viral respiratory pandemics. Early data on the prevalence of antibiotic prescribing in COVID-19 indicates conflicting low and high prevalence of antibiotic prescribing which challenges antimicrobial stewardship programmes and increases risk of antimicrobial resistance (AMR).AimTo determine current prevalence of bacterial coinfection and antibiotic prescribing in COVID-19 patientsData SourceOVID MEDLINE, OVID EMBASE, Cochrane and MedRxiv between January 2020 and June 2021.Study EligibilityEnglish language studies of laboratory-confirmed COVID-19 patients which reported (a) prevalence of bacterial coinfection and/or (b) prevalence of antibiotic prescribing with no restrictions to study designs or healthcare settingParticipantsAdults (aged ≥ 18 years) with RT-PCR confirmed diagnosis of COVID-19, regardless of study setting.MethodsSystematic review and meta-analysis. Proportion (prevalence) data was pooled using random effects meta-analysis approach; and stratified based on region and study design.ResultsA total of 1058 studies were screened, of which 22, hospital-based studies were eligible, compromising 76,176 of COVID-19 patients. Pooled estimates for the prevalence of bacterial co-infection and antibiotic use were 5.62% (95% CI 2.26 – 10.31) and 61.77% (CI 50.95 – 70.90), respectively. Sub-group analysis by region demonstrated that bacterial co-infection was more prevalent in North American studies (7.89%, 95% CI 3.30-14.18).ConclusionPrevalence of bacterial coinfection in COVID-19 is low, yet prevalence of antibiotic prescribing is high, indicating the need for targeted COVID-19 antimicrobial stewardship initiatives to reduce the global threat of AMR.
Identifying SARS-CoV-2 Variants of Concern through saliva-based RT-qPCR by targeting recurrent mutation sites
Authors: Ham Rachel E. , Smothers Austin R. , Che Rui , Sell Keegan J. , Peng Congyue Annie , Dean Delphine 
Published: March 2022

AbstractSARS-CoV-2 variants of concern (VOCs) continue to pose a public health threat which necessitates a real-time monitoring strategy to compliment whole genome sequencing. Thus, we investigated the efficacy of competitive probe RT-qPCR assays for six mutation sites identified in SARS-CoV-2 VOCs and, after validating the assays with synthetic RNA, performed these assays on positive saliva samples. When compared with whole genome sequence results, the SΔ69-70 and ORF1aΔ3675-3677 assays demonstrated 93.60% and 68.00% accuracy, respectively. The SNP assays (K417T, E484K, E484Q, L452R) demonstrated 99.20%, 96.40%, 99.60%, and 96.80% accuracies, respectively. Lastly, we screened 345 positive saliva samples from December 7-22, 2021 using Omicron-specific mutation assays and were able to quickly identify rapid spread of Omicron in Upstate South Carolina. Our workflow demonstrates a novel approach for low-cost, real-time population screening of VOCs.ImportanceSARS-CoV-2 variants of concern and their many sublineages can be characterized by mutations present within their genetic sequences. These mutations can provide selective advantages such as increased transmissibility and antibody evasion, which influences public health recommendations such as mask mandates, quarantine requirements, and treatment regimens. Our real-time RT-qPCR workflow allows for strain identification of SARS-CoV-2 positive saliva samples by targeting common mutation sites shared between VOCs and detecting single nucleotides present at the targeted location. This differential diagnostic system can quickly and effectively identify a wide array of SARS-CoV-2 strains, which can provide more informed public health surveillance strategies in the future.
Deep Sequence Modeling for Pressure Controlled Mechanical Ventilation
Authors: Belgaid Abdelghani 
Published: March 2022

AbstractThis paper presents a deep neural network approach to simulate the pressure of a mechanical ventilator. The traditional mechanical ventilator has a control pressure monitored by a medical practitioner, which could behave inaccurately by missing the proper pressure. This paper exploits recent studies and provides a simulator based on a deep sequence model to predict the airway pressure in the respiratory circuit during the inspiratory phase of a breath given a time series of control parameters and lung attributes. This approach demonstrates the effectiveness of neural network-based controllers in tracking pressure waveforms significantly better than the current industry standard and provides insights to build effective and robust pressure-controlled mechanical ventilators.
Deep sequencing of early T stage colorectal cancers reveals disruption of homologous recombination repair in microsatellite stable tumours with high mutational burdens
Authors: Li Jun , Steffen Pascal , Tse Benita C. Y. , Ahadi Mahsa S. , Gill Anthony J , Engel Alexander F. , Molloy Mark P. 
Published: March 2022

AbstractEarly T stage colorectal cancers (CRC) that invade lymph nodes (Stage IIIA) are greatly under-represented in large-scale genomic mapping projects such as TCGA datasets. We retrieved 10 Stage IIIA CRC cases, matched these to 16 Stage 1 CRC cases (T1 depth without lymph node metastasis) and carried out deep sequencing of 409 genes using the IonTorrent system. Tumour mutational burdens (TMB) ranged from 2.4-77.2/Mb sequenced. Using mean TMB as a cut-point to define groups, TMB-low (TMB-L) specimens showed higher frequency of KRAS and TP53 mutations in Stage IIIA compared to Stage I, consistent with TCGA data. TMB-High (TMB-H) specimens consisted of both microsatellite instable high (MSI-H) and microsatellite stable (MSS) genotypes. Comparison of TMB-H with TMB-L groups revealed clear differences in mutations of ATM, KDM5C, PIK3CA and APC. APC was less frequently mutated in the TMB-H group although variant composition was more diverse. Variants in ATM were restricted to the TMB-H group, and in four of five MSS specimens we observed the co-occurrence of mutations in homologous recombination repair (HRR) genes in either two of ATM, CDK12, PTEN or ATR, with at least one of these being a truncating mutation. No MSI-H specimens carried nonsense mutations in these genes. These findings add to our knowledge of early T stage CRC and highlight a potential therapeutic vulnerability in the HRR pathway of TMB-H MSS CRC.
Class-Controlled Copy-Paste Based Cell Segmentation for CoNIC Challenge
Authors: Ahn Heeyoung , Hong Yiyu 
Published: March 2022

AbstractMuti-class cell segmentation in histopathology images is a challenging task. Here, we propose a copy-paste augmentation-based method for CoNIC challenge. As the challenge train data is severely class imbalanced. To deal with it, we copy all cell objects of train data and paste them to the train image on the fly while training model. The paste strategy is that we paste more cell objects of the insufficient classes and paste less cell objects for the sufficient classes. We experimented the method by stratified splitting train data in 4:1 ratio, the result shows the copy paste method can reach PQ 64.84 and mPQ 53.72, which improved and 0.66 compared to without copy pasted. Moreover, the improvements in those insufficient classes is more obvious.
Apical constriction induces tissue rupture in a proliferative epithelium
Authors: Osswald Mariana , Barros-Carvalho André , Carmo Ana M , Loyer Nicolas , Gracio Patricia C , Sunkel Claudio , Homem Catarina C , Januschke Jens , Morais-de-Sá Eurico 
Published: March 2022

AbstractApical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Deregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncovered howDrosophilaaPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries culturedex vivo. We show that fast aPKC perturbation in the proliferative follicular epithelium produces large epithelial gaps that result from increased apical constriction, rather than loss of apical-basal polarity. Accordingly, we could modulate the incidence of epithelial gaps by increasing and decreasing actomyosin-driven contractility. We traced the origin of epithelial gaps to tissue rupture next to dividing cells. Live imaging shows that aPKC perturbation rapidly induces apical constriction in non-mitotic cells, producing pulling forces that ultimately detach dividing and neighbouring cells. We further demonstrate that epithelial rupture requires a global increase of apical constriction, since it was prevented by the presence of non-constricting cells. Conversely, a global induction of apical tension through light-induced recruitment of RhoGEF2 to the apical side was sufficient to produce tissue rupture. Hence, our work reveals that the roles of aPKC in polarity and actomyosin regulation are separable and provides the firstin vivoevidence that excessive tissue stress can break the epithelial barrier during proliferation.
Target isoforms are an overlooked challenge and opportunity in chimeric antigen receptor cell therapy
Authors: Barnkob Mike Bogetofte , Vitting-Seerup Kristoffer , Olsen Lars Rønn 
Published: March 2022

AbstractThe development of novel chimeric antigen receptor (CAR) cell therapies is rapidly growing, with 299 new agents being reported and 109 new clinical trials initiated so far this year. One critical lesson from approved CD19-specific CAR therapies is that target isoform switching has been shown to cause tumor relapse, but little is known about the isoforms of CAR targets in solid cancers. Here we assess the protein isoform landscape and identify both the challenges and opportunities protein isoform switching present as CAR therapy is applied to solid cancers.
Engineering bacterial blight-resistant plants through CRISPR/Cas9-targeted editing of theMeSWEET10apromoter in cassava
Authors: Wang Yajie , Geng Mengting , Pan Ranran , Zhang Tong , Lu Xiaohua , Zhen Xinghou , Che Yannian , Li Ruimei , Liu Jiao , Chen Yinhua , Guo Jianchun , Yao Yuan 
Published: March 2022

AbstractCassava starch is a widely used raw materials for industrial production. However, cassava bacterial blight (CBB) caused byXanthomonas axonopodispv.manihotis(Xam) results in severe yield losses and is the most destructive bacterial disease in all worldwide cassava planting regions. This study showed that editing of the promoter in the disease-susceptibility geneMeSWEET10aof SC8 cassava confers resistance to CBB. All mutated cassava lines had normal morphological and yield-related traits as the wild type. The results lay a research foundation for breeding cassava resistant to bacterial blight.HighlightsMeSWEET10agene in SC8 cultivar is hijacked by TALE20 fromXam11strain.Editing of theMeSWEET10apromoter in SC8 cultivar confers resistance to CBB.All the mutated cassava lines had similar yield-related traits compared to wild-type.
Critical role of PCYT2 in muscle health and aging
Authors: Cikes Domagoj , Elsayad Kareem , Sezgin Erdinc , Koitai Erika , Ferenc Torma , Orthofer Michael , Yarwood Rebecca , Heinz Leonhard X. , Sedlyarov Vitaly , Miranda Nasser Darwish , Taylor Adrian , Grapentine Sophie , al-Murshedi Fathiya , Abott Anne , Weidinger Adelheid , Kutchukian Candice , Sanchez Colline , Cronin Shane J.F. , Novatchkova Maria , Kavirayani Anoop , Schuetz Thomas , Haubner Bernhard , Haas Lisa , Hagelkruys Astrid , Jackowski Suzanne , Kozlov Andrey , Jacquemond Vincent , Knauf Claude , Superti-Furga Giulio , Rullman Eric , Gustafsson Thomas , McDermot John , Lowe Martin , Radak Zsolt , Chamberlain Jeffrey S. , Bakovic Marica , Banka Siddharth , Penninger Josef M. 
Published: March 2022

AbstractMuscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing, affecting hundreds of millions of people. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases represents an important goal in improving human health. Here, we show that phosphatidylethanolamine cytidyltransferase (PCYT2/ECT), the critical enzyme of the Kennedy branch of phosphatidylethanolamine (PE) synthesis pathway, has an essential role in muscle health. Human genetic deficiency inPCYT2causes a severe disease with failure to thrive and progressive muscle weakness.Pcyt2mutant zebrafish recapitulate the patient phenotypes, indicating that the role of PCYT2/PE in muscle is evolutionary conserved. Muscle specificPcyt2knockout mice exhibited failure to thrive, impaired muscle development, progressive muscle weakness, muscle loss, accelerated ageing, and reduced lifespan. Mechanistically, Pcyt2 deficiency affects mitochondrial bioenergetics and physicochemical properties of the myofiber membrane lipid bilayer, in particular under exercise strain. We also show that PCYT2 activity declines in the aging muscles of humans and mice. AAV-based delivery of PCYT2 rescued muscle weakness inPcyt2knock-out mice and, importantly, improved muscle strength in old mice, offering a novel therapeutic avenue for rare disease patients and muscle aging. Thus, PCYT2 plays a fundamental, specific, and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2 synthesized PE lipids to severe muscle dystrophy, exercise intolerance and aging.
Neovascularization and the recruitment of CD31+ cells from the bone marrow are unique under regenerative but not wound repair conditions
Authors: Bedelbaeva Kamila , Zhang Young , Azlanukov Azamat , Gourevitch Dmitri , Strehin Iossif , Messersmith Phillip , Heber-Katz Ellen 
Published: March 2022

ABSTRACTThe long-noted observation that endostatin is a potent inhibitor of tumor vasculature but has little or no effect on wound repair or pregnancy remains an “as of yet unexplained but remarkable phenomenon”(1). However, there is another path to wound healing, epimorphic regeneration, and here we present data in mice demonstrating that endostatin is, in fact, a potent inhibitor of epimorphic regeneration. In this study, we show that a rege nerative response seen in the spontaneously regenerating MRL mouse involves CD31+ endothelial precursors that migrate from the bone marrow into the wound site and form new vessels, unlike that seen in the non-regenerating C57BL/6 mouse injury site. Furthermore, this appears to relate to the induction of HIF-1a, an inducer of regeneration (2). Inducing epimorphic regeneration in otherwise non-regenerating mice via an enhanced HIF-1a response by employing the PHD inhibitor 1,4-DPCA/hydrogel, a HIF-1a stabilizer, results in the same increased bone marrow-derived CD31+ endothelial precursor response and increased vasculogenesis. This regenerative response is completely blocked by endostatin, supporting the notion that vascularization induced during regeneration shares similarities to the tumor vasculature.
Taxonomic and functional shifts in the perinatal gut microbiome of rhesus macaques
Authors: Rhoades Nicholas S. , Cinco Isaac R. , Hendrickson Sara M. , Slifka Mark K. , Messaoudi Ilhem 
Published: March 2022

ABSTRACTPregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal health. One of the factors believed to critically modulate these physiological changes is the maternal gut microbiome. However, the dynamic changes in this community during the perinatal period remain understudied. Clinical studies can be complicated by confounding variables such as diet and other drivers of heterogeneity in the human microbiome. Therefore, in this study, we conducted a longitudinal analysis of the fecal microbiome obtained during the perinatal and post-partum periods in 25 rhesus macaques using 16S rRNA gene amplicon sequencing and shotgun metagenomics. Shifts at both the taxonomic and functional potential level were detected when comparing pregnancy to postpartum samples. Taxonomically, Alloprevotella, Actinobacillus, and Anaerovibrio were enriched during pregnancy while Treponema, Lachnospiraceae, and Methanosphaera were more abundant post-partum. Functionally, pregnancy was associated with increased abundance in the pathway to produce the beneficial short chain fatty acid (SCFA), butyrate, while pathways associated with starch degradation and folate transformation were more abundant postpartum. These data demonstrate dramatic changes in the maternal gut even in the absence of dietary changes and suggest that rhesus macaques could provide a valuable model to determine how changes in the microbiome correlate to other physiological changes in pregnancy.
Simulating semantic dementia in a brain-constrained model of action and object words learning
Authors: Efremov Aleksei , Kuptsova Anastasia , Wennekers Thomas , Shtyrov Yury , Gutkin Boris , Garagnani Max 
Published: March 2022

The nature of semantic knowledge – conceptual information stored in the brain – is highly debated in the field of cognitive science. Experimental and clinical data specify various cortical regions involved in the processing of meaning. Those include semantic hubs that take part in semantic processing in general as well as sensorimotor areas that process specific conceptual categories according to their modality. Biologically inspired neurocomputational models can help adjudicate between different theories about the exact roles of those regions in the functioning of the semantic system.Here, we used an existing neuroanatomically constrained model of frontotemporal brain areas implicated in language acquisition and grounding. We adapted it to replicate and explain the effects of semantic dementia on word processing abilities. Semantic dementia is a disease characterized by semantic knowledge deterioration that correlates with neural damage in the anterior temporal lobe. The behavior of our model is in accordance with clinical data – namely, word recognition performance decreases as SD lesions progress, whereas word repetition abilities remain preserved, or are less affected. Furthermore, our model makes novel predictions about category-specific effects of SD – namely, our simulation results indicate that word processing should be more impaired for object-than for action-related words, and that white matter degradation should lead to more severe consequences than the same proportion of grey matter degradation.The present results provide a mechanistic, cortical-level explanatory account of a range of language impairments as observed in clinical populations during the onset and progress of semantic dementia.
Adaptive brain changes to virtual lesions interfering with visual processing
Authors: Raffin Estelle , Salamanca-Giron Roberto F. , Huxlin Krystel R. , Reynaud Olivier , Mattera Loan , Martuzzi Roberto , Hummel Friedhelm C. 
Published: March 2022

AbstractUnderstanding the causal relationship between a focal lesion and network (re)organization is crucial to accurately predict the resulting large-scale symptoms of a lesion. In this study, we applied short trains of 10 Hz TMS to healthy participants over the early visual areas (EVA) or the medio-temporal area (hMT+/MT) during a motion discrimination task and at rest, while concurrent fMRI was acquired. TMS applied in the early stage of motion processing induced a specific deficit in judging motion direction in both sites, while global motion perception was preserved. This was associated with a common suppression of local brain activity and network activity. In contrast, we report distinct topological network properties depending on the disrupted site. Networks associated with EVA perturbation displayed a more robust and efficient functional reorganization, suggesting that EVA might be more resilient to focal perturbations. While contributing to a better understanding of the impact and potential mechanisms of TMS perturbation, these results provide a model for focal lesions in the visual motion processing system.HighlightsTMS-induced perturbation of the early visual areas (EVA) or the mediotemporal area (hMT+/V5) area selectively impairs motion direction discrimination.The TMS perturbation is associated with a local down-scaling of BOLD activity in both areas, potentially specific to task-related neuronal populations during motion discrimination.The two visual areas display distinct topological networks’ adaptations in response to TMS, reflecting different levels of networks resilience to a focal lesion.TMS-fMRI coupling can be used to assess ‘disconnectomics’ and to precisely map how a local perturbation propagates to large-scale behavioural deficits.Graphical abstract