bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 Omicron Variant Wave in India: Advent, Phylogeny and Evolution
Authors: Singh Urvashi B. , Deb Sushanta , Chaudhry Rama , Bala Kiran , Rani Lata , Gupta Ritu , Kumari Lata , Ahmed Jawed , Gaurav Sudesh , Perumalla Sowjanya , Nizam Md. , Mishra Anwita , Stephenraj J. , Shukla Jyoti , Bhardwaj Deepika , Nayer Jamshed , Aggarwal Praveen , Kabra Madhulika , Ahuja Vineet , Sinha Subrata , Guleria Randeep 
Published: May 2022

AbstractSARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was responsible for disease in patients without comorbidity(97%), while Omicron BA.2 caused disease primarily in those with comorbidity(77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could possibly be due to evolutionary trade-off and explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2.
COVID-19 vaccines effectiveness against SARS-CO-V-2 infection among persons attending RT-PCR centre at a Medical College Hospital in Telangana: A case control study
Authors: Veerapu Nagapraveen , Inmdar Dhanashree P , Ravi Kumar Baer P , Anuradha Basavaraju , Guddanti Pavitra , Issapuri Sree D , Ganta Nikhita S , Gopi Arun 
Published: May 2022

AbstractBackgroundIn January 2021, India drug regulator issued restricted emergency approval for COVAXIN and COVISHIELD which were manufactured in India. On mid-January 2021, in India, there were 10.5million confirmed cases and 0.15 million deaths.ObjectivesThe objectives were to evaluate vaccine effectiveness (VE) of India made Covid-19 vaccines against SARS-CoV-2 infection.MethodsA test negative case control study was conducted from May 2021 to December 2021 for duration of 8months among people attending an RT-PCR centre at a medical college Hospital for RT-PCR test. The baseline characteristics and RT-PCR report; and preliminary data about vaccine status were collected from the RT-PCR centre. The exposure to vaccination was enquired via Phone call or was checked with data available with the health authorities.ResultsAfter applying inclusion exclusion criteria, case and control definitions, a total of 380 participants (95cases and 285 controls) were included. The adjusted VE of two doses of COVISHIED vaccine against symptomatic SARS-CoV-2 infection was 52.2% (95% CI, 41.7 to 62.1) and single dose was 40.88% (95% CI, 31.26 to 51.29). The adjusted VE of two doses of COVAXIN vaccine against SARS-CoV-2 infection was 39% (95% CI, 29.40 to 49.27). The overall VE was 48.20% (95% CI, 37.90 to 58.22) for two doses of any vaccines.ConclusionsIndia made vaccines were nearly 50% effective. Similar results show by different studies with a margin of 10-25% difference. Further new studies should be conducted as new variants of SARS-CoV-2 are emerging, and we don’t know how the vaccine works against the variants and booster doses were required or not.
Altered Regulation of Ia Afferent Input during Voluntary Activity after Human Spinal Cord Injury
Authors: Chen Bing , Perez Monica A. 
Published: May 2022

AbstractSensory input converging on the spinal cord contributes to the control of voluntary activity. Although sensory pathways reorganize following spinal cord injury (SCI), the extent to which sensory input from Ia afferents is regulated during voluntary activity after the injury remains largely unknown. To address this question, we examined the soleus H-reflex and conditioning of the H-reflex by stimulating homonymous and heteronymous nerves [depression of the soleus H-reflex evoked by common peroneal nerve stimulation (D1 inhibition) and the monosynaptic Ia facilitation of the soleus H-reflex evoked by femoral nerve stimulation (FN facilitation)] at rest, and during tonic voluntary activity in humans with and without chronic incomplete SCI. We found that during voluntary activity the soleus H-reflex size increased in both groups compared with rest, but to a lesser extent in SCI participants. Compared with rest, the D1 inhibition decreased during voluntary activity in controls but it was still present in SCI participants. Further, the FN facilitation increased in controls but remained unchanged in SCI participants during voluntary activity compared with rest. Changes in the D1 inhibition and FN facilitation were correlated with changes in the H-reflex during voluntary activity, suggesting an association between outcomes. These findings provide the first demonstration that the regulation of Ia afferent input from homonymous and heteronymous nerves is altered during voluntary in humans with SCI, resulting in lesser facilitatory effect on motor neurons.
Linked selection and the evolution of altruism in family-structured populations
Authors: Thomson Lia , Priego Espinosa Daniel , Brandvain Yaniv , Van Cleve Jeremy 
Published: May 2022

AbstractMuch research on the evolution of altruism via kin selection, group selection, and reciprocity focuses on the role of a single locus or quantitative trait. Very few studies have explored how linked selection, or selection at loci neighboring an altruism locus, impacts the evolution of altruism. While linked selection can decrease the efficacy of selection at neighboring loci, it might have other effects including promoting selection for altruism by increasing relatedness in regions of low recombination. Here, we used population genetic simulations to study how negative selection at linked loci, or background selection, affects the evolution of altruism. When altruism occurs between full siblings, we found that background selection interfered with selection on the altruistic allele, increasing its fixation probability when the altruistic allele was disfavored and reducing its fixation when the allele was favored. In other words, background selection has the same effect on altruistic genes in family-structured populations as it does on other, nonsocial, genes. This contrasts with prior research showing that linked selective sweeps can favor the evolution of cooperation, and we discuss possibilities for resolving these contrasting results.
Effects of Robotic-Assisted Gait at Different Levels of Guidance and Body Weight Support on Lower Limb Joint Angles, Angular Velocity, and Inter-Joint Coordination
Authors: Cherni Yosra , Blache Yoann , Begon Mickaël , Ballaz Laurent , Maso Fabien Dal 
Published: May 2022

AbstractThe Lokomat provides task-oriented therapy for patients with gait disorders. This robotic technology drives the lower limbs in the sagittal plane. However, unconstrained gait involves motions also in the coronal and transverse planes. This study aimed to compare the Lokomat with Treadmill gait through 3D-joint kinematics and inter-joint coordination. Lower limb kinematics was recorded in 18 healthy participants who walked at 3 km/h on a Treadmill or in a Lokomat with nine combinations of Guidance (30, 50, 70%) and body-weight-support (30, 50,70%). Compared to Treadmill, the Lokomat altered pelvis rotation, decreased pelvis obliquity and hip adduction, and increased ankle rotation. Moreover, the Lokomat resulted in a significantly slower velocity at the hip, knee, and ankle flexion compared to the treadmill condition. Moderate to strong correlations were observed between the Treadmill and Lokomat conditions in terms of inter-joint coordination between hip-knee (r=0.67-0.91), hip-ankle (r=0.66-0.85), and knee-ankle (r=0.90-0.95). In conclusion, this study showed that some gait determinants such as pelvis obliquity and rotation, and hip adduction are altered when walking with Lokomat in comparison to Treadmill. Kinematic deviations induced by the Lokomat were most prominent at high levels of body-weight-support. Interestingly, different levels of Guidance did not affect gait kinematics.
Unmet dental needs in children following suspension of school-based oral health services due to COVID-19
Authors: Ruff Ryan Richard , Godín Tamarinda Barry , Whittemore Rachel , Small Topaz Murray , Santiago-Galvin Nydia , Sharma Priyanka 
Published: May 2022

AbstractBackgroundDental caries (tooth decay) is the world’s most prevalent noncommunicable disease and can lead to pain, infection, and edentulism. Many children with caries lack access to traditional dental services. School-based caries prevention can increase access to care and reduce health inequities. Disruptions in school-based care due to pandemic control policies may result in children losing access to their primary dental care option.MethodsThe CariedAway project was a school-based caries prevention program in operation from 2019-2023 in urban schools with a high proportion of low-income, minority students. Program operations were suspended for two years due to the COVID-19 pandemic. We estimated the prevalence of untreated decay, swelling, fistula, and pulpal involvement in participants at baseline and again after restrictions were lifted.Results2998 children between the ages of 5 and 13 years were enrolled and received preventive care prior to pandemic shutdowns, and 1398 (47%) completed their first follow-up observation after two years. At baseline, approximately 30% had untreated caries on any dentition, 11% of children presented with evidence of having received preventive dental sealants, and no participants had swelling, fistula, or pulpal involvement. After 24 months, 12% of participants had swelling fistula, or pulpal involvement that was not treated during the pandemic period.ConclusionThere are considerable unmet dental needs in high-risk children that may be further exacerbated by a lack of access to care during disease outbreaks.
Pulmonary function among rural residents in high air pollution area in northern Thailand
Authors: Ruchiwit Pitchayapa , Saiphoklang Narongkorn , Leelasittikul Kanyada , Pugongchai Apiwat , Poachanukoon Orapan 
Published: May 2022

AbstractBackgroundAir pollution has become a serious environmental and health issue in several countries. This condition leads to respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). This study aimed to determine pulmonary functions and prevalence of respiratory diseases among rural residents in an area in northern Thailand with a high concentration of air pollution.MethodsA cross-sectional study was conducted in people aged 18 years or older, living in Lamphun, Thailand in December 2021. Demographics, pre-existing diseases, respiratory symptoms, and pulmonary functions by spirometry including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiration flow (PEF), forced expiration flow rate at 25-75% of FVC (FEF25-75), and bronchodilator responsiveness (BDR; FEV1 improvement after BDR test >12% and 200 mL) were collected.ResultsA total of 127 people (78.7%male) were included. Mean age was 43.76±11.32 years. Smoking was 52.0% and 4.44±5.45 pack-years. Self-reported respiratory diseases were allergic rhinitis (7.1%), asthma (0.8%), and COPD (0.8%). Respiratory symptoms were presented in 33.1% (14.2% runny nose, 10.2% nasal obstruction, 9.4% cough, 7.9% sputum production, and 6.3% breathlessness). Lung functions showed FVC in 96.74±12.91%, FEV1 in 97.52±12.99%, PEF in 102.46±19.18%, and FEF25-75 in 96.77±29.88%. Abnormal lung functions were found in 15.7%. Small airway disease (FEF25-75<65%) was 7.1%. Restrictive defect (FVC<80%) was 6.3%. Airway obstruction (FEV1/FVC<70%) was 2.4%. There was no BDR. Compared to people with normal lung functions, the abnormal lung function group was older (48.00±8.68 years vs 42.96±11.61 years, P=0.036), and had a higher proportion of breathlessness (20.0% vs 3.7%, P=0.021).ConclusionsAbnormal pulmonary functions, especially small airway disease, were relatively common in rural residents in a polluted air area in northern Thailand. These abnormal pulmonary functions were associated with more respiratory symptoms.Clinicaltrials.in.th numberTCTR20211223001
Therapeutic neutralizing monoclonal antibody administration protects against lethal Yellow Fever infection
Authors: Ricciardi Michael J. , Rust Lauren N. , Pedreño-Lopez Nuria , Yusova Sofiya , Biswas Sreya , Webb Gabriela M. , Gonsales-Nieto Lucas , Voigt Thomas B. , Louw Johan J. , Laurino Fernanda D. , DiBello John R. , Raué Hans-Peter , Barber-Axthelm Aaron M. , Uttke Samantha , Raphael Lidiane M.S. , Yrizarry-Medina Aaron , Rosen Brandon C. , Agnor Rebecca , Gao Lina , Labriola Caralyn , Axthelm Michael , Smedley Jeremy , Julander Justin G. , Bonaldo Myrna C. , Walker Laura M. , Messaoudi Ilhem , Slifka Mark K. , Burton Dennis R. , Kallas Esper G. , Sacha Jonah B. , Watkins David I. , Burwitz Benjamin J. 
Published: May 2022

ABSTRACTFew countermeasures to treat Yellow Fever virus (YFV) infection are under development, because vaccines have helped to limit new infections. Unfortunately, vaccine hesitancy, supply deficits, and a paucity of therapeutic options have left individuals at risk. Here, we tested potent YFV-specific neutralizing monoclonal antibodies in rodents and non-human primates. We administered antibodies during acute pathogenic YFV infection and demonstrate that we can prevent severe disease and death. Given the severity of YFV-induced disease, our results show that these antibodies could be effective in saving lives and fill a much-needed void in managing Yellow Fever cases during outbreaks around the world.One Sentence SummaryTherapeutic monoclonal antibodies prevent death from YFV infection.
Sex differences in coronary artery disease and diabetes revealed by scRNA-Seq and CITE-Seq of human CD4+ T cells
Authors: Saigusa Ryosuke , Vallejo Jenifer , Gulati Rishab , Suthahar Sujit Silas Armstrong , Suryawanshi Vasantika , Alimadadi Ahmad , Markings Jeff , Durant Christopher P. , Freuchet Antoine , Roy Payel , Ghosheh Yanal , Pandori William , Pattarabanjird Tanyaporn , Drago Fabrizio , McNamara Coleen A. , Shemesh Avishai , Lanier Lewis L. , Hedrick Catherine C. , Ley Klaus 
Published: May 2022

ABSTRACTBackgroundDespite the decades-old knowledge that diabetes mellitus (DM) is a major risk factor for cardiovascular disease (CVD), the reasons for this association are only partially understood. Among the immune cells involved in CVD development, accumulating evidence supports the critical role of T cells as drivers and modifiers of this condition. CD4+ T cells are commonly found in atherosclerotic plaques. The activity and distribution of CD4+ T cell subsets differs between the sexes.MethodsPeripheral blood mononuclear cells (PBMCs) of 61 men and women who underwent cardiac catheterization were interrogated by single cell RNA sequencing (scRNA-Seq, ∼200,000 cells) combined with 49 protein markers (CITE-Seq). Coronary artery disease (CAD) was quantified using Gensini scores, with scores above 30 considered CAD+ and below 6 considered CAD-. Four pairs of groups were matched for clinical and demographic parameters. To test how DM changed cell proportions and gene expression, we compared matched groups of diabetic and non-diabetic subjects. We analyzed 41,782 single CD4+ T cell transcriptomes for sex differences in 61 mostly statin-treated coronary artery disease patients with and without DM.ResultsWe identified 16 clusters in CD4 T cells. The proportion of cells in CD4 cluster 8 (CD4T8, CCR2+ Em) was significantly decreased in CAD+, especially among DM+ participants. The proportions of cells in CD4T2, CD4T11, CD4T16 were increased and CD4T13 was decreased in CAD+ among DM+Statin+ participants. CD4T12 was increased in DM+ participants. In female participants, CD4T8, 12, and 13 were decreased compared to in male participants. In CD4 T cells, 31 genes showed significant and coordinated upregulation in both CAD and DM. The DM gene signature was partially additive to the CAD gene signature.ConclusionsWe conclude that CAD and DM are clearly reflected in PBMC transcriptomes and that significant differences exist between women and men and between subjects treated with statins or not.
Parallel clonal and molecular profiling of hematopoietic stem cells using RNA barcoding
Authors: Wojtowicz Edyta E. , Mistry Jayna , Uzun Vladimir , Scoones Anita , Chin Desmond W. , Kettyle Laura , Grasso Francesca , Lord Allegra M. , Etherington Graham , Hellmich Charlotte , Woll Petter S. , Belderbos Mirjam E. , Bowles Kristian M. , Nerlov Claus , Haerty Wilfried , Bystrykh Leonid V. , Jacobsen Sten Eirik W. , Rushworth Stuart A. , Macaulay Iain C. 
Published: May 2022

AbstractAnucleate cells - platelets and erythrocytes - constitute over 95% of all hematopoietic stem cell (HSC) output, but the clonal dynamics of HSC contribution to these lineages remains largely unexplored. Here, we use lentiviral RNA cellular barcoding and transplantation of HSCs, combined with single-cell RNA-seq, for quantitative analysis of clonal behavior with a multi-lineage readout - for the first time including anucleate and nucleate lineages. We demonstrate that most HSCs steadily contribute to hematopoiesis, but acute platelet depletion shifts the output of multipotent HSCs to the exclusive production of platelets, with the additional emergence of new myeloid-biased clones. Our approach therefore enables comprehensive profiling of multi-lineage output and transcriptional heterogeneity of individual HSCs, giving insight into clonal dynamics in both steady state and under physiological stress.
Expanding EMC Foldopathies: Topogenesis Deficits Alter the Neural Crest
Authors: Marquez Jonathan , Khokha Mustafa K. 
Published: May 2022

AbstractThe endoplasmic reticulum membrane protein complex (EMC) is essential for the insertion of a wide variety of transmembrane proteins into the plasma membrane across cell types. Each EMC is composed of Emc1-7, Emc10, and either Emc8 or Emc9. Recent human genetics studies have implicated variants in EMC genes as the basis for a group of human congenital diseases. The patient phenotypes are varied but appear to affect a subset of tissues more prominently than others. Namely, craniofacial development seems to be commonly affected. We previously developed an array of assays in Xenopus tropicalis to assess the effects of emc1 depletion on the neural crest, craniofacial cartilage, and neuromuscular function. We sought to extend this approach to additional EMC components identified in patients with congenital malformations. Through this approach we determine that EMC9 and EMC10 are important for neural crest development and the development of craniofacial structures. The phenotypes observed in patients and our Xenopus model were similar to EMC1 loss of function likely due to a similar mechanism of dysfunction in transmembrane protein topogenesis.
A CRISPR-screen in intestinal epithelial cells identifies novel factors for polarity and apical transport
Authors: Klee Katharina MC , Hess Michael W , Lohmüller Michael , Herzog Sebastian , Pfaller Kristian , Müller Thomas , Vogel Georg F , Huber Lukas A 
Published: May 2022

AbstractEpithelial polarization and polarized cargo transport are highly coordinated and interdependent processes. In our search for novel regulators of epithelial polarization and protein secretion, we used a genome-wide CRISPR/Cas9 screen and combined it with an assay based on fluorescence-activated cell sorting (FACS) to measure the secretion of the apical brush border hydrolase dipeptidyl peptidase 4 (DPP4). In this way, we performed the first CRISPR screen to date in human polarized epithelial cells. Using high-resolution microscopy, we detected polarization defects and mislocalization of DPP4 to late endosomes/lysosomes after knock-down of TM9SF4, anoctamin 8, and ARHGAP33, confirming the identification of novel factors for epithelial polarization and apical cargo secretion. Thus, we provide a powerful tool suitable for studying polarization and cargo secretion in epithelial cells. In addition, we provide a dataset that serves as a resource for the study of novel mechanisms for epithelial polarization and polarized transport and facilitates the investigation of novel congenital diseases associated with these processes.
Visual system hyperexcitability and compromised V1 receptive field properties in early-stage retinitis pigmentosa in mice
Authors: Leinonen Henri , Lyon David C , Palczewski Krzysztof , Foik Andrzej T 
Published: May 2022

AbstractInherited retinal degenerative diseases are a prominent cause of blindness. Even though mutations causing death of photoreceptors are mostly known, the pathophysiology downstream in the inner retina and along the visual pathway is incompletely characterized in the earliest disease stages. Here we investigated retinal, midbrain and cortical visual function using electroretinography (ERG), the optomotor response (OMR), visual evoked potentials (VEPs), respectively, and single unit electrophysiology at the primary visual cortex (V1) in light-adapted juvenile (∼ 1-month-old) and young adult (3-month-old)RhoP23H/WTmice, representative of early-stage retinitis pigmentosa (RP). Photopic ERG revealed up to ∼ 30 % hypersensitivity to light inRhoP23H/WTmice, as measured by the light intensity required to generate half-maximal b-wave (I50parameter).RhoP23H/WTmice also showed increased optomotor responses towards low spatial frequency drifting gratings, indicative of visual overexcitation at the midbrain level. At the V1 level, VEPs and single-cell recordings revealed prominent hyperexcitability in the juvenileRhoP23H/WTmice. Mean VEP amplitudes for light ON stimuli were nearly doubled in 1-month-oldRhoP23H/WTmice compared to controls, and more than doubled for light OFF. Single-cell recordings showed a significantly increased spontaneous V1 neuron firing in theRhoP23H/WTmice, and persistent contrast and temporal sensitivities. In contrast, direction selectivity was severely compromised. Our data suggest that during early RP, the visual pathway becomes hyperexcited. This could have both compensatory and deleterious consequences for visual behavior. Further studies on the mechanisms of hyperexcitability are warranted as this could lead to therapeutic interventions for RP.Significance statementLost retinal function in many blinding retinal degenerative disorders could soon be alleviated by advanced therapies that restore photoreception. However, it is unknown whether a visual system rewired downstream of the photoreceptors can process signals adequately. We studied the functional consequences of early rod death along the visual pathway in young retinitis pigmentosa (RP) mice. Photopic inner retina responses were moderately hypersensitized in the electroretinograms of RP mice. Reflex-based visual behavior and visual cortex electrophysiology showed hyperexcitability. Some aspects of complex visual processing were remarkably resistant to degeneration, whereas others were severely impacted. We conclude that the visual system adapts to lost photoreception by increasing sensitivity, but simultaneously becomes detrimentally hyperexcited. Mechanistic understanding could lead to therapeutic preservation and restoration of vision.