bluuebunny/crossref_metadata_2025_split huggingface dataset:
Counterproductive effects of Daratumumab and checkpoint inhibitor for the treatment of patients with relapsing NK/T lymphoma
Authors: Lee Wendy W.L. , Lim Jing Quan , Tang Tiffany P.L , Tan Daryl , Joo Puan Kia , Tan Kim Peng , Wang Liang Wei , Koh Ser Mei , Ong Choon Kiat , Rotzschke Olaf 
Published: March 2021

ABSTRACTNatural killer/T cell lymphoma (NK/T L) is an aggressive malignancy associated with poor prognosis in relapsed patients. Although L-asparaginase based treatments are recommended as first-line treatment in relapsed patients, advances in immunotherapies such as checkpoint inhibitions have provided new therapeutic alternatives. However, as clinical outcomes for checkpoint inhibitors seemed to vary between NK/T L patients, combination therapies have been suggested to improve treatment efficacy. Here, we compared the effects of Daratumumab (anti-CD38)/anti-PD-1 combination therapy versus anti-PD-1 monotherapy on two relapsed NK/T L patients. Anti-PD-1 triggered an upregulation of CD38 on activated T cells, leading to depletion by Daratumumab. Concomittantly, EBV-specific antibody titer was also reduced alongside with depletion of CD38+ B cells and antibody-producing plasmablasts. Taken together, combining anti-CD38 and anti-PD-1 is likely to be antithetic.
Risk, clinical course and outcome of ischemic stroke in patients hospitalized with COVID-19: a multicenter cohort study
Authors: Sluis Wouter M. , Linschoten Marijke , Buijs Julie E. , Biesbroek J. Matthijs , Hertog Heleen M. den , Ribbers Tessa , Nieuwkamp Dennis , Houwelingen Reinier C. van , Dias Andreas , Uden Ingeborg W.M. van , Kerklaan Joost P. , Bienfait H. Paul , Vermeer Sarah E. , de Jong Sonja W. , Ali Mariam , Wermer Marieke J.H. , de Graaf Marieke T. , Brouwers Paul J.A.M. , Asselbergs Folkert W. , Kappelle L. Jaap , van der Worp H. Bart , Algra Annemijn M. 
Published: March 2021

AbstractBackground and purposeThe frequency of ischemic stroke in patients with COVID-19 varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.MethodsWe included patients with a laboratory confirmed SARS-CoV-2 infection admitted in 16 hospitals participating in the international CAPACITY-COVID registry between March 1st and August 1st, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.ResultsWe included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit (ICU). Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older, but did not differ in sex or cardiovascular risk factors. Median time between onset of COVID-19 symptoms and diagnosis of stroke was two weeks. The incidence of ischemic stroke was higher among patients who were treated at an ICU (16/586; 2.7% versus 22/1561; 1.4%; p=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted RR: 2.08; 95%CI:1.52-2.84). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functional dependent at discharge and in-hospital mortality. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted RR 1.56; 95%CI:1.13-2.15) than patients without stroke.ConclusionsIn this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was approximately 2%, with a higher risk in patients treated at an ICU. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.
Predicting the onset of freezing of gait in de novo Parkinson’s disease
Authors: Wang Fengting , Pan Yixin , Zhang Miao , Hu Kejia 
Published: March 2021

AbstractFreezing of gait (FoG) is a debilitating symptom of Parkinson’s disease (PD) related to higher risks of falls and poor quality of life. In this study, we predicted the onset of FoG in PD patients using a battery of risk factors from patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI) cohort. The endpoint was the presence of FoG, which was assessed every year during the five-year follow-up visit. Overall, 212 PD patients were included in analysis. Seventy patients (33.0%) developed FoG during the visit (pre-FoG group). Age, bradykinesia, TD/PIGD classification, fatigue, cognitive impairment, impaired autonomic functions and sleep disorder were found to be significantly different in patients from pre-FoG and non-FoG groups at baseline. The logistic regression model showed that motor factors such as TD/PIGD classification (OR = 2.67, 95% CI = 1.41-5.09), MDS-UPDRS part III score (OR = 1.05, 95% CI = 1.01-1.09) were associated with FoG occurrence. Several indicators representing non-motor symptoms such as SDMT total score (OR = 0.95, 95% CI = 0.91-0.98), HVLT immediate/Total recall (OR = 0.91, 95% CI = 0.86-0.97), MOCA (OR = 0.87, 95% CI = 0.76-0.99), Epworth Sleepiness Scale (OR = 1.13, 95% CI = 1.03-1.24), fatigue(OR = 1.98, 95% CI = 1.32-3.06), SCOPA-AUT gastrointestinal score (OR = 1.27, 95% CI = 1.09-1.49) and SCOPA-AUT urinary score (OR = 1.18, 95% CI = 1.06-1.32) were found to have the predictive value. PD patients that developed FoG showed a significant reduction of DAT uptake in the striatum. However, no difference at baseline was observed in genetic characteristics and CSF biomarkers between the two patient sets. Our model indicated that TD/PIGD classification, MDS-UPDRS total score, and Symbol Digit Modalities score were independent risk factors for the onset of FoG in PD patients. In conclusion, the combination of motor and non-motor features including the akinetic subtype and poor cognitive functions should be considered in identifying PD patients with high risks of FoG onset.
Analysis of Accumulated SARS-CoV-2 Seroconversion in North Carolina: The COVID-19 Community Research Partnership
Authors: Williamson John C. , Wierzba Thomas F , Santacatterina Michele , Munawar Iqra , Seals Austin L , Ballard Christine Ann Pittman , Alexander-Miller Martha , Runyon Michael S , McCurdy Lewis H , Gibbs Michael A , Ahmed Amina , Lagarde William H , Maguire Patrick D , King-Thiele Robin , Hamrick Terri , Ihmeidan Abdalla , Henderson Shakira , Uschner Diane , Herrington David M , Sanders John W 
Published: March 2021

AbstractIntroductionThe COVID-19 Community Research Partnership is a population-based longitudinal syndromic and sero-surveillance study. The study includes over 17,000 participants from six healthcare systems in North Carolina who submitted over 49,000 serology results. The purpose of this study is to use these serology data to estimate the cumulative proportion of the North Carolina population that has either been infected with SARS-CoV-2 or developed a measurable humoral response to vaccination.MethodsAdult community residents were invited to participate in the study between April 2020 and February 2021. Demographic information was collected and daily symptom screen was completed using a secure, HIPPA-compliant, online portal. A portion of participants were mailed kits containing a lateral flow assay to be used in-home to test for presence of anti-SARS-CoV-2 IgM or IgG antibodies. The cumulative proportion of participants who tested positive at least once during the study was calculated. A standard Cox proportional hazards model was constructed to illustrate the probability of seroconversion over time up to December 20, 2020 (before vaccines available). A separate analysis was performed to describe the influence of vaccines during an extended period through February 15, 2021.Results17,688 participants contributed at least one serology result. Approximately two-thirds of the population were female and almost three-quarters were between 30 and 64 years of age. The average number of serology test results submitted per participant was 3.0 (±1.9). At December 20, 2020, the overall probability of seropositivity in the CCRP population was 32.6%. At February 15, 2021 the probability among healthcare workers and non-healthcare workers was 83% and 49%, respectively. An inflection upward in the probability of seropositivity was demonstrated around the end of December, suggesting an influence of vaccinations, especially for healthcare workers. Among healthcare workers, those in the oldest age category (60+ years) were 38% less likely to have seroconverted by February 15, 2021.ConclusionsResults of this study suggest more North Carolina residents may have been infected with SARS-CoV-2 than the number of documented cases as determined by positive RNA or antigen tests. The influence of vaccinations on seropositivity among North Carolina residents is also demonstrated. Additional research is needed to fully characterize the impact of seropositivity on immunity and the ultimate course of the pandemic.
COVID-19 and Medical Education in Ghana: Assessing the Impact
Authors: Asumanu Edward , Tsevi Linda 
Published: March 2021

ABSTRACTMedical education in Ghana has been affected in many ways by the onslaught of the COVID-19 pandemic. Though the pandemic has affected both preclinical and clinical segments of medical education, the effect has been felt more at the clinical stage. Medical students on vacation who started their clinical training abroad could not return to their destination of study to complete their programme because of COVID-19 linked travel restrictions. This qualitative study examined how COVID-19 impacted on teaching and learning at a public higher education institution offering clinical medical education in Ghana for over 200 medical students. These medical students were from three different higher education institutions with varied curriculum outcomes. Thus, for them to be considered as a single group required innovativeness on the part of administrators. Open-ended interviews were held with administrators and the outcome indicated that salient aspects of the clinical training process had been impacted. These included administration of clinical education, curriculum, student learning, student assessment and code of practice. As a result of the pandemic, student learning shifted from traditional face to face interaction to online learning at the beginning. Some of the administrative challenges that ensued included the need for reduced number of students per tutor and introduction of afternoon sessions with a limited budget. The paper concludes that COVID-19 has been disruptive to traditional medical education in Ghana. However, the novel learning processes may provide opportunities to increase access to medical education using a phased system of learning. The findings from this study should have implications for policy and contribute to the discourse on blended learning in medical education in Ghana while ensuring that quality is maintained in all instances.
Smartphone-based videoconference visits are easy to implement, effective, and feasible in Crohn’s Disease Patients: A prospective cohort study
Authors: Yilmaz Hasan , Duman Ali Erkan 
Published: March 2021

AbstractBackgroundCrohn’s Disease patients require life-long follow-up resulting frequent hospital visits. Usefulness of telehealth has been established in remote management of Crohn’s disease but mobile technology’s role is missing. We aimed to determine the feasibility and effectiveness of smartphone-based real-time video visits.MethodsWe prospectively studied 139 patients either at a traditional (FTF) or online clinic (OLV) in a university hospital between March 2020-September 2020. We measured patients’ satisfactions, disease activity, visit outcomes, socioeconomic parameters, and travel expenses to assess the effectiveness and acceptance of OLV.ResultsSatisfaction scores were significantly higher at OLV compared to FTF (89.58±9.93 vs 70.85±18.51, p<0.001). The Cronbach Alpha reliability coefficient of the VSQ9 scale was 0.878. Median 47km travel distance and 49 minutes travel time per visit saved with OLV. An average of US$12.24 potential travel costs were saved per appointment. Eighty-five per cent of the patients met the needs at online visits and did not require a face-to-face visit.ConclusionsSmartphone-based real-time video visit telehealth model for distant management of Crohn’ disease had high acceptance. The model was easy to implement, effective and saved travel cost and time.
Sleep quality mediates the relationship between risk of obstructive sleep apnea and acute stress in young adults
Authors: Aggarwal Kunal , Akhtar Nasreen , Mallick Hrudananda 
Published: March 2021

AbstractPurposeIntermittent hypoxia and transient arousals in obstructive sleep apnea (OSA) can lead to poor sleep quality and acute stress. Rising levels of obesity and increased incidence of OSA in young adults predisposes them to acute stress. We propose a mediation model to assess if risk of OSA is associated with acute stress and if the relationship between risk for OSA and acute stress is mediated by sleep quality.Methods493 healthy individuals (F=237, M=256) from 18-25 years of age (mean age=20.3±1.53 years) were screened for OSA, sleep quality and acute stress using STOP-BANG questionnaire, Pittsburg Sleep Quality Index and American Psychiatry Association’s National Stressful Events Survey Acute Stress Disorder Short Scale (NSESS-S) respectively. Binary and logistic regression were used establish the relationships between the variables. Sobel test for mediation analysis was conducted.Results73 participants (17.3%) were found at an intermediate and high risk of OSA by STOP BANG questionnaire. 79 (16%) participants reported level of stress as ‘None’. Mild, moderate and severe stress was present in 248 (50.3%), 109 (22.1%), 51 (10.3%) and 16 (3.2%) participants respectively. The odds of having severe and extreme stress among those at risk of sleep apnea is 2.18 times higher than that among those not at risk of sleep apnea (OR: 2.18, 95% Confidence Interval: 1.37-3.51). Sobel test established that the relationship between OSA and acute stress is mediated by sleep quality.ConclusionSleep quality mediates the relationship between risk for sleep apnea and acute stress. This highlights the importance of screening for OSA in young adults, particularly young men with high BMI, presenting with high stress levels.
Automated Production of Research Data Marts from a Canonical Fast Healthcare Interoperability Resource (FHIR) Data Repository: Applications to COVID-19 Research
Authors: Lenert Leslie A , Ilatovskiy Andrey V. , Agnew James , Rudsill Patricia , Jacobs Jeff , Weatherston Duncan , Deans Kenneth 
Published: March 2021

AbstractObjectiveObjective: The COVID-19 pandemic has enhanced the need for timely real-world data (RWD) for research. To meet this need, several large clinical consortia have developed networks for access to RWD from electronic health records (EHR), each with its own common data model (CDM) and custom pipeline for extraction, transformation, and load operations for production and incremental updating. However, the demands of COVID-19 research for timely RWD (e.g., 2-week delay) make this less feasible.Methods and MaterialsWe describe the use of the Fast Healthcare Interoperability Resource (FHIR) data model as a canonical model for representation of clinical data for automated transformation to the Patient-Centered Outcomes Research Network (PCORnet) and Observational Medical Outcomes Partnership (OMOP) CDMs and the near automated production of linked clinical data repositories (CDRs) for COVID-19 research using the FHIR subscription standard. The approach was applied to healthcare data from a large academic institution and was evaluated using published quality assessment tools.ResultsSix years of data (1.07M patients, 10.1M encounters, 137M laboratory results), were loaded into the FHIR CDR producing 3 linked real-time linked repositories: FHIR, PCORnet, and OMOP. PCORnet and OMOP databases were refined in subsequent post processing steps into production releases and met published quality standards. The approach greatly reduced CDM production efforts.ConclusionsFHIR and FHIR CDRs can play an important role in enhancing the availability of RWD from EHR systems. The above approach leverages 21st Century Cures Act mandated standards and could greatly enhance the availability of datasets for research.
Two Genomic Loci Control Three Eye Colors in the Domestic Pigeon (Columba livia)
Authors: Maclary Emily T. , Phillips Bridget , Wauer Ryan , Boer Elena F. , Bruders Rebecca , Gilvarry Tyler , Holt Carson , Yandell Mark , Shapiro Michael D. 
Published: March 2021

ABSTRACTThe iris of the eye shows striking color variation across vertebrate species, and may play important roles in crypsis and communication. The domestic pigeon (Columba livia)has three common iris colors, orange, pearl (white), and bull (dark brown), segregating in a single species, thereby providing a unique opportunity to identify the genetic basis of iris coloration. We used comparative genomics and genetic mapping in laboratory crosses to identify two candidate genes that control variation in iris color in domestic pigeons. We identified a nonsense mutation in the solute carrierSLC2A11Bthat is shared among all pigeons with pearl eye color, and a locus associated with bull eye color that includesEDNRB2, a gene involved in neural crest migration and pigment development. However, bull eye is likely controlled by a heterogeneous collection of alleles across pigeon breeds. We also found that theEDNRB2region is associated with regionalized plumage depigmentation (piebalding). Our results establish a genetic link between iris and plumage color, two traits that were long known by pigeon breeders to co-occur, and demonstrate the importance of gene duplicates in establishing possibilities and constraints in the evolution of color and color pattern among vertebrates.
Whole-organism 3D Quantitative Characterization of Zebrafish Melanin by Silver Deposition Micro-CT
Authors: Katz Spencer R. , Yakovlev Maksim A. , Vanselow Daniel J. , Ding Yifu , Lin Alex Y. , Parkinson Dilworth Y. , Wang Yuxin , Canfield Victor A. , Ang Khai C. , Cheng Keith C. 
Published: March 2021

AbstractMelanin-rich zebrafish melanophores are used to study pigment development, human skin color, and as a large-scale screening phenotype. To facilitate more detailed whole-body, computational analyses of melanin content and morphology, we have combined X-ray microtomography (micro-CT), a non-destructive, full-volume imaging modality, with a novel application of ionic silver staining to characterize melanin distribution in whole zebrafish larvae. Normalized micro-CT reconstructions of silver-stained fish consistently reproduced pigment patterns seen by light microscopy, and allowed direct quantitative comparisons of melanin content across wild-type and mutant samples, for both dramatic and subtle phenotypes not previously described. Silver staining of melanin for micro-CT provides proof-of-principle for whole-body, three-dimensional computational phenomic analysis of a particular cell type at cellular resolution, with potential applications in other model organisms and human melanoma biopsies. Whole-organism, high-resolution phenotyping is a challenging ideal, but provides superior context for functional studies of mutations, diseases, and environmental influences.
A cell-ECM mechanism for connecting the ipsilateral eye to the brain
Authors: Su Jianmin , Liang Yanping , Sabbagh Ubadah , Olejníková Lucie , Russell Ashley L. , Chen Jiang , Pan Yuchin Albert , Triplett Jason W. , Fox Michael A. 
Published: March 2021

AbstractInformation about features in the visual world are parsed by circuits in the retina and are then transmitted to the brain by distinct subtypes of retinal ganglion cells (RGCs). Axons from RGC subtypes are stratified in retinorecipient brain nuclei, such as the superior colliculus (SC), to provide a segregated relay of parallel and feature-specific visual streams. Here, we sought to identify the molecular mechanisms that direct the stereotyped laminar targeting of these axons. We focused on ipsilateral-projecting subtypes of RGCs (ipsiRGCs) whose axons target a deep SC sublamina. We identified an extracellular glycoprotein, Nephronectin (NPNT), whose expression is restricted to this ipsiRGC-targeted sublamina. SC-derived NPNT and integrin receptors generated by ipsiRGCs are both required for the targeting of ipsiRGC axons to the deep sublamina of SC. Thus, a cell-extracellular matrix (ECM) recognition mechanism specifies precise laminar targeting of ipsiRGC axons and the assembly of eye-specific parallel visual pathways.Significance StatementDistinct features of the visual world are transmitted from the retina to the brain through anatomically segregated circuits. Despite this being an organizing principle of visual pathways in mammals, we lack an understanding of the signaling mechanisms guiding axons of different types of retinal neurons into segregated layers of brain regions. We explore this question by identifying how axons from the ipsilateral retina innervate a specific lamina of the superior colliculus. Our studies reveal a unique cell-extracellular matrix (ECM) recognition mechanism that specifies precise targeting of these axons to the superior colliculus. Loss of this mechanism not only resulted in the absence of this eye-specific visual circuit, but it led to an impairment of innate predatory visual behavior as well.
A survey of the mouse hindbrain in the fed and fasted state using single-nucleus RNA sequencing
Authors: Dowsett Georgina K.C. , Lam Brian Y.H. , Tadross John , Cimino Irene , Rimmington Debra , Coll Anthony P. , Polex-Wolf Joseph , Knudsen Lotte Bjerre , Pyke Charles , Yeo Giles S.H. 
Published: March 2021

AbstractObjectiveThe area postrema (AP) and the nucleus tractus solitaris (NTS), located in the hindbrain, are key nuclei that sense and integrate peripheral nutritional signals and, consequently, regulate feeding behaviour. While single cell transcriptomics have been used in mice to reveal the gene expression profile and heterogeneity of key hypothalamic populations, similar in-depth studies have not yet been performed in the hindbrain.MethodsUsing single-nucleus RNA sequencing, we provide a detailed survey of 16,034 cells within the AP and NTS of the mouse, in the fed and fasted state.ResultsOf these, 8910 are neurons that group into 30 clusters, with 4289 coming from mice fedad libitumand 4621 from overnight fasted mice. 7124 nuclei are from non-neuronal cells, including oligodendrocytes, astrocytes and microglia. Interestingly, we identified that the oligodendrocyte population was particularly transcriptionally sensitive to an overnight fast. The receptors GLP1R, GIPR, GFRAL and CALCR, which bind GLP1, GIP, GDF15 and amylin respectively, are all expressed in the hindbrain and are major targets for anti-obesity therapeutics. We characterise the transcriptomes of these four populations and show that their gene expression profiles are not dramatically altered by an overnight fast. Notably, we find that roughly half of cells that express GIPR are oligodendrocytes. Additionally, we profile POMC expressing neurons within the hindbrain and demonstrate that 84% of POMC neurons express either PCSK1, PSCK2 or both, implying that melanocortin peptides are likely produced by these neurons.ConclusionWe provide a detailed single-cell level characterisation of AP and NTS cells expressing receptors for key anti-obesity drugs that are either already approved for human use or are in clinical trials. This resource will help delineate the mechanisms underlying the effectiveness of these compounds, and also prove useful in the continued search for other novel therapeutic targets.