bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arrhythmic Outcomes in Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Lee Sharen , Zhou Jiandong , Jeevaratnam Kamalan , Lakhani Ishan , Wong Wing Tak , Kei Wong Ian Chi , Mak Chloe , Mok Ngai Shing , Liu Tong , Zhang Qingpeng , Tse Gary 
Published: January 2021

AbstractIntroductionCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare cardiac ion channelopathy. The aim of this study is to examine the genetic basis and identify pre-dictive factors for arrhythmic outcomes in CPVT patients from Hong Kong.MethodsThis was a territory-wide retrospective cohort study of consecutive patients diagnosed with CPVT at public hospitals or clinics in Hong Kong. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF).ResultsA total of 16 (mean presentation age=11±4 years old) patients were included. All patients presented at or before 19 years of age. Fifteen patients (93.8%) were initially symptomatic. Ten patients had both premature ventricular complexes (PVCs) and VT/VF, whereas one patient had PVCs without VT/VF. Genetic tests were performed in 14 patients (87.5%). Eight (57.1%) tested positive for the RyR2 gene. Seven variants have been described else-where (c.14848G>A, c.12475C>A, c.7420A>G, c.11836G>A, c.14159T>C, c.10046C>T and c.7202G>A). c.14861C>G is a novel RyR2 variant that has not been reported outside this cohort. All patients were treated with beta-blockers, three patients received amiodarone and two received verapamil. Sympathectomy (n=8), ablation (n=1) and implantable-cardioverter defibrillator implantation (n=3) were performed. Over a median follow-up of 127 (IQR: 97-143) months, six patients suffered from incident VT/VF. No significant predictors were identified on Cox regression. Nevertheless, a random survival forest model identified initial VT/VF/sudden cardiac death, palpitations, QTc, initially symptomatic and heart rate as important variables for estimating the probability of developing incident VT/VF.ConclusionAll CPVT patients who are from Hong Kong presented at or before 19 years of age. Clinical and electrocardiographic findings can be used to predict arrhythmic outcomes. A nonparametric machine learning survival analysis achieved high accuracy for predicting the probability of incident VT/VF.
Family physicians supporting patients with palliative care needs within the Patient Medical Home in the community: An Appreciative Inquiry qualitative study
Authors: Tan Amy , Spice Ronald , Sinnarajah Aynharan 
Published: January 2021

ABSTRACTObjectivesCanadians want to live and die in their home communities. Unfortunately, Canada has the highest proportion of deaths in acute care facilities as compared to other developed nations. This study aims to identify the essential components required to best support patients and families with palliative care needs in their communities to inform system changes and empower family physicians (FPs) in providing community-based palliative care for patients.DesignAppreciative Inquiry (AI) methodology with individual interviews. Interview transcripts were analyzed iteratively for emerging themes and used to develop “possibility statements” to frame discussion in subsequent focus groups. A conceptual framework emerged to describe the “destiny” state as per AI methods.SettingFamily physicians, palliative home care providers, patients and bereaved caregivers were recruited in the urban and surrounding rural health authority zones of Calgary, Canada.Participants9 females and 9 males FPs (range of practice years 2-42) in interviews; 8 bereaved caregivers, 1 patient, 26 Palliative Home Care team members in focus groups. Interviews and focus groups were recorded digitally and transcribed with consent.ResultsThe identified themes that transcended all three groups created the foundation for the conceptual framework. Enhanced communication and fostering team relationships between all care providers with the focus on the patient and caregivers was the cornerstone concept. The family physician/patient relationship must be protected and encouraged by all care providers, while more system flexibility is needed to respond more effectively to patients. These concepts must exist in the context that patients and caregivers need more education regarding the benefits of palliative care, while increasing public discourse about mortality.ConclusionsKey areas were identified for how the patient’s team can work together effectively to improve the patient and caregiver palliative care journey in the community with the cornerstone element of building on the trusting FP-patient longitudinal relationship.Strengths and limitations of this studyThis study uses Appreciative Inquiry qualitative methods to identify the essential components required to best support patients and families with palliative care needs in their communities.Multiple perspectives recruited including: community-based family physicians, palliative home care clinicians, patients, and bereaved caregivers.Analysis was focused on the family physicians’ interviews to derive “possibility statements” and used to frame the focus groups with the other groups of participants.Generalisability may be limited due to the lack of diversity in participants recruited for the patients and bereaved caregivers in terms of ethnicity, age, and gender.Patients and caregivers may have been reluctant to volunteer for this study as it involved discussing palliative care.
IgA Potentiates NETosis in Response to Viral Infection
Authors: Stacey Hannah D. , Golubeva Diana , Posca Alyssa , Ang Jann C. , Novakowski Kyle E. , Zahoor Muhammad Atif , Kaushic Charu , Cairns Ewa , Bowdish Dawn M. E. , Mullarkey Caitlin E. , Miller Matthew S. 
Published: January 2021

ABSTRACTIgA is the second most abundant antibody present in circulation and is enriched at mucosal surfaces. As such, IgA plays a key role in protection against a variety of mucosal pathogens, including viruses. In addition to neutralizing viruses directly, IgA can also stimulate Fc-dependent effector functions via engagement of Fc alpha receptors (FcαRI) expressed on the surface of certain immune effector cells. Neutrophils are the most abundant leukocyte, express FcαRI, and are often the first to respond to sites of injury and infection. Here, we describe a novel function for IgA:virus immune complexes (ICs) during viral infections. We show that IgA:virus ICs potentiate NETosis – the programmed cell death pathway through which neutrophils release neutrophil extracellular traps (NETs). Mechanistically, IgA:virus ICs potentiated a suicidal NETosis pathway via engagement of FcαRI on neutrophils through a toll-like receptor (TLR)-independent, NADPH oxidase complex-dependent pathway. NETs also were capable of trapping and inactivating viruses, consistent with an antiviral function.
Error Prediction Determines the Coordinate System Used for Novel Dynamics Representation
Authors: Leib Raz , Franklin David W. 
Published: January 2021

AbstractSkillful object manipulation requires a representation of the object’s dynamics. Despite extensive research, previous studies have not been able to provide a consistent view of this representation in the motor system, with each study providing evidence favoring an extrinsic coordinate system, an intrinsic coordinate system, an object-based representation, or mixtures of these coordinate systems. In a series of experiments, we show that the motor system combines different representations based on their reliability. Specifically, since noise creates an error between planned and executed force production which depends on the arm state, the motor system will rely more on the representation for which the plan is less affected. In addition, we show that the error based weights predict the different results made about dynamics representation and thus explaining the discrepancy between influential past studies. Overall, we are able to reconcile all of the apparently disparate findings under a single cohesive model of dynamics representation.
An optimized ribodepletion approach forC. elegansRNA-sequencing libraries
Authors: Barrett Alec , McWhirter Rebecca , Taylor Seth R , Weinreb Alexis , Miller David M , Hammarlund Marc 
Published: January 2021

ABSTRACTA recent and powerful technique is to obtain transcriptomes from rare cell populations, such as single neurons inC. elegans,by enriching dissociated cells using fluorescent sorting. However, these cell samples often have low yields of RNA that present challenges in library preparation. This can lead to PCR duplicates, noisy gene expression for lowly expressed genes, and other issues that limit endpoint analysis. Further, some common resources, such as sequence specific kits for removing ribosomal RNA, are not optimized for non-mammalian samples. To optimize library construction for such challenging samples, we compared two approaches for building RNAseq libraries from less than 10 nanograms ofC. elegansRNA: SMARTSeq V4 (Takara), a widely used kit for selecting poly-adenylated transcripts; and SoLo Ovation (Tecan Genomics), a newly developed ribodepletion-based approach. For ribodepletion, we used a custom kit of 200 probes designed to matchC. elegansrRNA gene sequences. We found that SoLo Ovation, in combination with our customC. elegansprobe set for rRNA depletion, detects an expanded set of noncoding RNAs, shows reduced noise in lowly expressed genes, and more accurately counts expression of long genes. The approach described here should be broadly useful for similar efforts to analyze transcriptomics when RNA is limiting.
Cellular and Viral Determinants of HSV-1 Entry and Intracellular Transport towards Nucleus of Infected Cells
Authors: Musarrat Farhana , Chouljenko Vladimir , Kousoulas Konstantin G. 
Published: January 2021

AbstractHSV-1 employs cellular motor proteins and modulates kinase pathways to facilitate intracellular virion capsid transport. Previously, we and others have shown that the Akt inhibitor miltefosine inhibited virus entry. Herein, we show that the protein kinase C inhibitors staurosporine (STS) and gouml inhibited HSV-1 entry into Vero cells, and that miltefosine prevents HSV-1 capsid transport toward the nucleus. We have reported that the HSV-1 UL37 tegument protein interacts with the dynein motor complex during virus entry and virion egress, while others have shown that the UL37/UL36 protein complex binds dynein and kinesin causing a saltatory movement of capsids in neuronal axons. Co-immoprecipitation experiments confirmed previous findings from our laboratory that the UL37 protein interacted with the dynein intermediate chain (DIC) at early times post infection. This UL37-DIC interaction was concurrent with DIC phosphorylation in infected, but not mock-infected cells. Miltefosine inhibited dynein phosphorylation when added before, but not after virus entry. Inhibition of motor accessory protein dynactins (DCTN2, DCTN3), the adaptor proteins EB1 and the Bicaudal D homolog 2 (BICD2) expression using lentiviruses expressing specific shRNAs, inhibited intracellular transport of virion capsids toward the nucleus of human neuroblastoma (SK-N-SH) cells. Co-immunoprecipitation experiments revealed that the major capsid protein Vp5 interacted with dynactins (DCTN1/p150 and DCTN4/p62) and the end-binding protein (EB1) at early times post infection. These results show that Akt and kinase C are involved in virus entry and intracellular transport of virion capsids, but not in dynein activation via phosphorylation. Importantly, both the UL37 and Vp5 viral proteins are involved in dynein-dependent transport of virion capsids to the nuclei of infected cells.ImportanceHerpes simplex virus type-1 enter either via fusion at the plasma membranes or endocytosis depositing the virion capsids into the cytoplasm of infected cells. The viral capsids utilize the dynein motor complex to move toward the nuclei of infected cells using the microtubular network. This work shows that inhibitors of the Akt kinase and kinase C inhibit not only viral entry into cells but also virion capsid transport toward the nucleus. In addition, the work reveals that the virion protein ICP5 (VP5) interacts with the dynein cofactor dynactin, while the UL37 protein interacts with the dynein intermediate chain (DIC). Importantly, neither Akt nor Kinase C was found to be responsible for phosphorylation/activation of dynein indicating that other cellular or viral kinases may be involved.
Associations between Stress and Child Verbal Abuse and Corporal Punishment during the COVID-19 Pandemic and Potential Effect Modification by Lockdown Measures
Authors: Jeharsae Rohani , Jae-noh Manusameen , Jae-a-lee Haneefah , Waeteh Suhaida , Nimu Nisuraida , Chewae Corliyoh , Yama Malinee , Dureh Nurin , Wichaidit Wit 
Published: January 2021

AbstractBackgroundChild abuse appears to be on the increase during the COVID-19 pandemic, but the extent that lockdown measures modified the association between stress and abuses has not been systematically assessed.ObjectivesTo assess: 1) the association between caregiver’s stress and self-reported verbal abuse and corporal punishment of a child in the household, and; 2) modification of the stated association by experienced COVID-19 lockdown measures.Participants and settingsCaregivers residing in villages on lockdown in the Deep South of Thailand (n=466 participants)MethodsWe randomly sampled 12 villages in the study area, and 40 households per village. Trained enumerators who were residents of the sampled villages collected the data using phone-based interview. We measured stress level using the standard ST-5 questionnaire. We developed and pilot-tested questions for measurement of child abuse and lockdown experiences specifically for this study.ResultsCaregivers with moderate and higher levels of stress were more likely than caregivers with low level of stress to report verbal abuse (48% vs. 23%, respectively; Adj. OR = 3.12, 95% CI = 1.89, 5.15) and corporal punishment (28% vs. 8%, respectively; Adj. OR = 2.76, 95% CI = 1.41, 5.42). We found that COVID-19 lockdown experiences modified the associations between stress and verbal abuse and corporal punishment.ConclusionThere were associations between stress and abuses, which were modified by lockdown experiences. However, social desirability, lack of details in the answers, and potential confounding by mental illness co-morbidities were notable limitations of the study. Caveat is advised in the interpretation of the study findings.
Analysis of 200,000 exome-sequenced UK Biobank subjects illustrates the contribution of rare genetic variants to hyperlipidaemia
Authors: Curtis David 
Published: January 2021

AbstractA few genes have previously been identified in which very rare variants can have major effects on lipid levels. Weighted burden analysis of rare variants was applied to exome sequenced UK Biobank subjects with hyperlipidaemia as the phenotype, of whom 44,050 were designated cases and 156,578 controls, with the strength of association characterised by the signed log 10 p value (SLP). With principal components included as covariates there was a tendency for genes on the X chromosome to produce strongly negative SLPs, and this was found to be due to the fact that rare X chromosome variants were identified less frequently in males than females. The test performed well when both principal components and sex were included as covariates and strongly implicatedLDLR(SLP = 50.08) andPCSK9(SLP = -10.42) while also highlighting other genes previously found to be associated with lipid levels. Variants classified by SIFT as deleterious have on average a two-fold effect and their cumulative frequency is such that they are present in approximately 1.5% of the population. These analyses shed further light on the way that genetic variation contributes to risk of hyperlipidaemia and in particular that there are very many protein-altering variants which have on average moderate effects and whose effects can be detected when large samples of exome-sequenced subjects are available. This research has been conducted using the UK Biobank Resource.
Use of the FebriDx point-of-care assay as part of a triage algorithm for medical admissions with possible COVID-19
Authors: Houston Hamish , Deas Gavin , Naik Shivam , Shah Kamal , Patel Shiras , Dottori Maria Greca , Tay Michael , Filson Sarah , Biggin-Lamming James , Ross John , Vaughan Natalie , Vaid Nidhi , Rao Guduru Gopal , Amin Amit K , Gupta-Wright Ankur , John Laurence 
Published: January 2021

ABSTRACTBackgroundPatients admitted to hospital with COVID-19 need rapid identification and isolation to prevent nosocomial transmission. However, isolation facilities are often limited, and SARS-CoV-2 RT-PCR results are often not available when discharged from the emergency department. We evaluated a triage algorithm to isolate patients with suspected COVID-19 using simple clinical criteria and the FebriDx assay.DesignRetrospective observational cohortSettingLarge acute care hospital in London, UKParticipantsAll medical admissions from the ED between 10th August 2020 and 4th November 2020 with valid SARS-CoV-2 RT-PCR.InterventionsMedical admissions were triaged as likely, possible or unlikely COVID-19 based on clinical criteria. Patients triaged as possible COVID-19 underwent FebriDx lateral flow assay on capillary blood, and those positive for MxA were managed as likely COVID-19.Primary Outcome measuresDiagnostic accuracy (sensitivity, specificity and predictive values) of the algorithm and the FebriDx assay compared to SARS-CoV-2 RT-PCR from nasopharyngeal swabs as the reference standard.Results4.0% (136/3,443) of medical admissions had RT-PCR confirmed COVID-19. Prevalence of COVID-19 was 45.7% (80/175) in those triaged as likely, 4.1% (50/1,225) in possible and 0.3% (6/2,033) in unlikely COVID-19. Compared to SARS-CoV-2 RT-PCR, clinical triage had sensitivity of 95.6% (95%CI: 90.5% - 98.0%) and specificity of 61.5% (95%CI: 59.8% - 63.1%), whilst the triage algorithm including FebriDx had sensitivity of 92.6% (95%CI: 86.8% - 96.0%) and specificity of 86.4% (95%CI: 85.2% - 87.5%). The triage algorithm reduced the need for 2,859 patients to be admitted to isolation rooms. Ten patients missed by the algorithm had mild or asymptomatic COVID-19.ConclusionsA triage algorithm including FebriDx assay had good sensitivity and was useful to ‘rule-out’ COVID-19 among medical admissions to hospital.STRENGTHS AND LIMITATIONS OF THIS STUDYPragmatic study including a large cohort of consecutive medical admissions providing routine clinical care.A single SARS-CoV-2 RT-PCR is an imperfect reference standard for COVID-19. Multiple RT-PCR platforms used, with different PCR targets and performance.A higher prevalence of COVID-19 or other respiratory pathogens might alter performance.Criteria for likely and possible COVID-19 groups changed subtly during the study period.
Acceptability and efficacy of vaginal self-sampling for genital infection and bacterial vaginosis: A large, cross-sectional, non-inferiority trial
Authors: Claire Camus , Guillaume Penaranda , Hacène Khiri , Sabine Camiade , Lucie Molet , Melissa Lebsir , Anne Plauzolles , Laurent Chiche , Bernard Blanc , Edwin Quarello , Philippe Halfon 
Published: January 2021

ABSTRACTObjectiveScreening for genital infection (GI), bacterial vaginosis (BV), sexually transmitted infection (STI) and asymptomatic carriage of group B streptococcus (GBS) in pregnant women is a common reason for medical appointments. Objectives were first to determine the non-inferiority of vaginal self-sampling compared with vaginal/cervical classical sampling to screen for GIs, bacterial vaginosis (BV), STIs, and GBS asymptomatic carriage in pregnant women; second to determine the feasibility of vaginal self-sampling.MethodsVaginal self-sampling (VSS) and vaginal/cervical classical sampling (VCS) of 1027 women were collected by health care professionals and simultaneously carried out on each patient. Bacterial infection, yeast infection, Chlamydia trachomatis, Neisseria gonorrhoea, Mycoplasma genitalium, Trichomonas vaginalis and Herpes simplex virus types were systematically screened in both paired VSS and VCS samples.ResultsStatistical tests supported the non-inferiority of VSS compared with VCS. Agreements between VCS and VSS remained high regardless of the type of studied infection. VSS had successful diagnostic performances, especially for Predictive negative value (PNV) (over 90%) for all studied infections. Most participants (84%) recommended the use of VSS.ConclusionsThis study remains the most exhaustive in screening for GI, BV, STI agents and asymptomatic GBS carriage. Given its efficacy and acceptability, VSS seems to be a viable alternative to classic physician sampling among women in the general population. This study provides evidence that vaginal self-sampling can be used as a universal specimen for detection of lower genital tract infections in women.Study Identification numberID-RCB 2014-A01250-4
Immunogenicity of an AAV-based, room-temperature stable, single dose COVID-19 vaccine in mouse and non-human primates
Authors: Zabaleta Nerea , Dai Wenlong , Bhatt Urja , Chichester Jessica A , Sanmiguel Julio , Estelien Reynette , Michalson Kristofer T , Diop Cheikh , Maciorowski Dawid , Qi Wenbin , Hudspeth Elissa , Cucalon Allison , Dyer Cecilia D , Pampena M. Betina , Knox James J. , LaRocque Regina C , Charles Richelle C , Li Dan , Kim Maya , Sheridan Abigail , Storm Nadia , Johnson Rebecca I , Feldman Jared , Hauser Blake M , Zinn Eric , Ryan Aisling , Kobayashi Dione T , Chauhan Ruchi , McGlynn Marion , Ryan Edward T , Schmidt Aaron G , Price Brian , Honko Anna , Griffiths Anthony , Yaghmour Sam , Hodge Robert , Betts Michael R. , Freeman Mason W , Wilson James M , Vandenberghe Luk H 
Published: January 2021

SummaryThe SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 million deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological and logistical attributes of the vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity in mouse and nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained at 5 months and are complemented by functional memory T-cells responses. The AAVrh32.33 capsid of the AAVCOVID vaccine is an engineered AAV to which no relevant pre-existing immunity exists in humans. Moreover, the vaccine is stable at room temperature for at least one month and is produced at high yields using established commercial manufacturing processes in the gene therapy industry. Thus, this methodology holds as a very promising single dose, thermostable vaccine platform well-suited to address emerging pathogens on a global scale.