bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR-guided programmable self-assembly of artificial virus-like nucleocapsids
Authors: Calcines-Cruz Carlos , Finkelstein Ilya J. , Hernandez-Garcia Armando 
Published: October 2020

AbstractDesigner virus-inspired proteins drive the manufacturing of more effective and safer gene-delivery systems as well as simpler models to study viral assembly. However, the self-assembly of engineered viromimetic proteins on specific nucleic acid templates, a distinctive viral property, has proved difficult. Inspired by viral packaging signals, we harness the programmability of CRISPR-Cas12a to direct the nucleation and growth of a self-assembling synthetic polypeptide into virus-like particles (VLP) on specific DNA molecules. Positioning up to ten nuclease-dead Cas12a (dCas12a) proteins along a 48.5 kbp DNA template triggers particle growth and full DNA encapsidation at limiting polypeptide concentrations. Particle growth rate was further increased when dCas12a was dimerized with a polymerization silk-like domain. Such improved self-assembly efficiency allows for discrimination between cognate versus non-cognate DNA templates by the synthetic polypeptide. Our CRISPR-guided VLPs could help develop programmable bio-inspired nanomaterials with applications in biotechnology as well as viromimetic scaffolds to improve our understanding of viral self-assembly.
Causal discovery identifies posttraumatic stress as a driver of internalizing symptoms across independent veteran and civilian populations
Authors: Pierce Benjamin , Kirsh Thomas , Ferguson Adam R. , Neylan Thomas C. , Ma Sisi , Kummerfeld Erich , Cohen Beth E. , Nielson Jessica L. 
Published: October 2020

ABSTRACTBackgroundApproximately half of patients with posttraumatic stress disorder (PTSD) also meet criteria for internalizing disorders, yet few studies assess reciprocal longitudinal relations among these symptoms.MethodsWe used longitudinal causal discovery in a veteran cohort for hypothesis-generation about PTSD and internalizing symptom drivers (n=240), followed by hypothesis-testing in two independent civilian cohorts with similar symptom assessments over time (n=79 and n=116).ResultsIn the veteran cohort, causal discovery revealed PTSD symptoms drove internalizing symptoms, which subsequently impacted social functioning; all independent of problematic alcohol use. This replicated in treatment-seeking anxiety disorders (AD, n = 79) and substance abuse (SA, n = 116) samples with significantly better model fit for PTSD symptoms driving internalizing symptoms, versus internalizing symptoms driving PTSD symptoms (BIC change for AD sample = 175.1, p<.001; BIC change for SA sample = 571.6, p<.001). We also found better model fit with PTSD symptoms driving anxiety symptoms, versus anxiety symptoms driving PTSD symptoms (BIC change for AD sample = 71.8, p < .001; BIC change for SA sample = 568.9, p < .001). Posthoc analysis in the veteran sample revealed that hyperarousal and cognitive and affective disturbance bridged between other PTSD symptoms and internalizing symptoms.ConclusionsOur findings suggest that internalizing symptoms that emerge in the context of PTSD are more likely to be driven by PTSD symptoms. These results highlight the need for a PTSD- and trauma-informed approach to treating internalizing symptoms, and provide preliminary evidence for cognition and mood disruption as a factor driving comorbidity.
Systematic analysis of short tandem repeats in 38,095 exomes provides an additional diagnostic yield
Authors: van der Sanden Bart P.G.H. , Corominas Jordi , de Groot Michelle , Pennings Maartje , Meijer Rowdy P.P. , Verbeek Nienke , van de Warrenburg Bart , Schouten Meyke , Yntema Helger G. , Vissers Lisenka E.L.M. , Kamsteeg Erik-Jan , Gilissen Christian 
Published: October 2020

AbstractPurposeThe expansion of specific short tandem repeats (STRs) can lead to approximately 30 different human genetic disorders. Despite extensive application of exome sequencing (ES) in routine diagnostic genetic testing, STRs are not routinely identified from these data.MethodsWe assessed diagnostic utility by applying ExpansionHunter to 2,867 exomes from movement disorder patients and 35,228 other clinical exomes.ResultsWe identified 36 movement disorder patients with a possible aberrant STR length. Validation by PCR and/or repeat-primed PCR technologies confirmed the presence of aberrant expansion alleles for 11 (31%). For seven of these patients the genotype was compatible with the phenotypic description, and resulted in a molecular diagnosis. We subsequently tested the remainder of our diagnostic ES cohort, including over 30 clinically and genetically heterogeneous disorders. Optimized manual curation yielded 140 samples with a likely aberrant STR length. Validations confirmed 70/140 (50%) aberrant expansion alleles, of which 48 were in the pathogenic range and 22 in the premutation range.ConclusionsOur work provides guidance for the implementation of STR analysis in clinical ES. Our results show that systematic STR evaluation may increase diagnostic ES yield by 0.2%, and recommend to make STR evaluation a routine part of ES interpretation in genetic testing laboratories.
Separating Newborns from Mothers and Maternal Consent for Newborn Care and the Association with Health Care Satisfaction, Use and Breastfeeding: Findings from a longitudinal survey in Kenya
Authors: Nakphong Michelle K. , Sacks Emma , Opot James , Sudhinaraset May 
Published: October 2020

AbstractObjectivesDisrespectful and poor treatment of newborns such as unnecessary separation from parents or failure to obtain parental consent for medical procedures occurs at health facilities across contexts, but little research has investigated the prevalence, risk factors, or associated outcomes. This study aimed to examine these practices and associations with health care satisfaction, use, and breastfeeding.DesignProspective cohort studySettingHealth facilities in Nairobi and Kiambu counties in KenyaParticipantsData were collected from women who delivered in health facilities between September 2019 and January 2020. The sample included 1,014 women surveyed at baseline and at least one follow-up at 2-4 or 10 weeks postpartum.Primary and secondary outcome measures1) Outcomes related to satisfaction with care and care utilization, 2) Continuation of post-discharge newborn care practices such as breastfeeding.Results17.6% of women reported being separated from their newborns at the facility after delivery, of whom 71.9% were separated over 10 minutes. 44.9% felt separation was unnecessary and 8.4% reported not knowing the reason for separation. 59.9% reported consent was not obtained for procedures on their newborn. Women separated from their newborn (>10 minutes) were 44% less likely to be exclusively breastfeeding at 2-4 weeks (aOR=0.56, 95%CI: 0.40, 0.76). Obtaining consent for newborn procedures corresponded with 2.7 times greater likelihood of satisfaction with care (aOR=2.71, 95%CI: 1.67, 4.41), 27% greater likelihood of postpartum visit attendance for self or newborn (aOR=1.27, 95%CI: 1.05, 4.41), and 33% greater likelihood of exclusive breastfeeding at 10 weeks (aOR=1.33, 95%CI: 1.10, 1.62).ConclusionsNewborns, mothers, and families have a right to high quality, respectful care, including the ability to stay together, be informed and have proper consent for care. The implications of these practices on health outcomes a month or more after discharge illustrate the importance of a positive experience of postnatal care.Article SummaryStrengths and Limitations of the StudyThis is one of the first studies to include survey questions surrounding details of separation of newborns from mothers and maternal consent for care, including risk factors and reasons for separation.This study used longitudinal data collected over 10 weeks following delivery to assess associations with outcomes, including postpartum visit attendance and breastfeeding.Differences in participants who responded to the 2-4week and 10 week follow-up interviews may have introduced bias due to differences in composition, thus comparisons of associations with outcomes between these two points should be interpreted conservatively.Findings may have limited generalizability to other contexts, as the study sample included women who gave birth at facilities in Nairobi and Kiambu counties.
Accuracy of Healthcare Professionals’ Nasopharyngeal Swab Technique in SARS-CoV-2 Specimen Collection
Authors: Woods Robbie S. R. , Nwaokorie Kellie , Crowley Jana , Walsh Michael , de Barra Eoghan , Lacy Peter D. 
Published: October 2020

AbstractBackgroundThe COVID-19 pandemic has caused huge pressure on healthcare systems worldwide. Public health measures to control the virus are reliant on testing, including appropriate collection of specimens for analysis.MethodsA prospective study of nasopharyngeal swab technique by staff in an academic tertiary referral centre was carried out. Nasopharyngeal swab technique was evaluated by a novel design of a navigated swab on a three-dimensional model head.ResultsSwab technique of 228 participants was assessed. Technique was poor, with a success rate of nasopharyngeal swabbing at 38.6%. Angle and length of insertion were significantly different between those with successful and unsuccessful technique. Doctors were significantly more accurate than nurses and non-healthcare professionals (p<0.01).ConclusionInaccurate specimen collection from poor swab technique could contribute to a false negative rate of testing for SARS-CoV-2. Specific training in nasopharyngeal anatomy and swab technique may improve the accuracy of nasopharyngeal swabbing.
Percentage HScore confirms low incidence of secondary haemophagocytic lymphohistiocytosis in hospitalised COVID-19 patients
Authors: Ardern-Jones Michael R , Stammers Matt , Phan Hang T.T. , Borca Florina , Koutalopoulou Anastasia , Teo Ying , Batchelor James , Smith Trevor , Duncombe Andrew S 
Published: October 2020

AbstractObjectiveIt has been assumed that a significant proportion of COVID-19 patients show evidence of hyperinflammation of which secondary haemophagocytic lymphohistiocytosis (sHLH) is the most severe manifestation. To facilitate diagnosis of sHLH the HScore has been developed and validated. We set out to examine the prevalence of sHLH-like hyperinflammation in COVID-19.MethodsWe retrospectively examined HScore parameters in 626 COVID-19 cases admitted to our institute of which 567 were suitable for analysis and compared these to a cohort of confirmed infection associated sHLH cases. To account for missing data, we calculated the maximum possible HScore of the recorded parameters (%HScore).ResultsEarly measurement of HScore parameters (day -1 to 4 from diagnosis) strongly predicted the %HScore over the course of the admission (p <0.0001). The retrospective cohort of sHLH showed significantly higher %HScores as compared to COVID-19 (median 73.47 vs 18.13 respectively, p <0.0001). The overall prevalence of individuals with an 80% probability of sHLH in our COVID-19 cohort was 1.59% on admission and only rose to 4.05% during the whole disease course. In the small cohort with scores suggestive of sHLH, there was no excess mortality compared with the whole cohort. %HScores were higher in younger patients (p<0.0001) and did not reliably predict outcome at any cut-off value (AUROC 0.533, p=0.211; OR 0.99).ConclusionSurprisingly, these findings show that sHLH-type hyperinflammation is not prevalent in COVID-19, and %HScores do not predict outcome. Therefore, new algorithms are required to optimise case selection for clinical trials of targeted anti-inflammatory interventions.
Could nutrition modulate COVID-19 susceptibility and severity of disease? A systematic review
Authors: James Philip T. , Ali Zakari , Armitage Andrew E. , Bonell Ana , Cerami Carla , Drakesmith Hal , Jobe Modou , Jones Kerry S. , Liew Zara , Moore Sophie E. , Morales-Berstein Fernanda , Nabwera Helen M. , Nadjm Behzad , Pasricha Sant-Rayn , Scheelbeek Pauline , Silver Matt J. , Teh Megan R. , Prentice Andrew M. 
Published: October 2020

ABSTRACTBackgroundMany nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to COVID-19 infection, progression to symptoms, likelihood of severe disease and survival. The pandemic has fostered many nutrition-related theories, sometimes backed by a biased interpretation of evidence.ObjectivesTo provide a systematic review of the latest evidence on how malnutrition across all its forms (under- and over-nutrition and micronutrient status) may influence both susceptibility to, and progression and severity of, COVID-19.MethodsWe synthesised information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity and diabetes; protein-energy malnutrition; anaemia; vitamins A, C, D, and E; poly-unsaturated fatty acids; iron; selenium; zinc; anti-oxidants, and nutritional support. For each section we provide: a) a landscape review of pertinent material; b) a systematic search of the literature in PubMed and EMBASE databases, including a systematic search of a wide range of pre-print servers; and c) a screen of six clinical trial registries. Two reviewers were assigned per section for data extraction. All original research was considered, without restriction to study design, and included if it covered: 1) SARS-CoV-2, MERS-CoV or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16thMay and 11thAugust, 2020. PROSPERO registration CRD42020186194.ResultsAcross the 13 searches, a total of 2732 articles from PubMed and EMBASE, 4164 articles from the pre-print servers, and 433 trials were returned. A total of 288 published articles and 278 pre-print articles were taken to full text screening. In the final narrative synthesis, we cover 22 published articles, 39 pre-print articles and 79 trials. The review highlights a range of mechanistic and observational evidence to highlight the role nutrition can play in susceptibility and progression of COVID-19. However, to date, there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery, although results of clinical trials are eagerly awaited.ConclusionsTo date there is no conclusive evidence supporting adoption of novel nutritional therapies. However, given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. There is strong evidence that prevention of obesity, and its consequent type-2 diabetes, will reduce the risk of serious COVID-19 outcomes.
A Multidisciplinary Approach: Teaching Medical Spanish to Medical Students Using Role-play
Authors: Mozaffari Khashayar , Kolodner Rebecca , Chalif Eric , Ruiz Victor Valdivia , Blatt Benjamin 
Published: October 2020

AbstractIntroductionThe Hispanic community is the most rapidly growing minority group in the United States, making up 18.1% of the population, with 40% reporting limited English proficiency. To address this need, many health sciences institutions have implemented medical Spanish courses to increase Spanish proficiency among future healthcare providers. Although interactive courses have shown efficacy in teaching field-related terminology, barriers to medical Spanish curriculum implementation persist. Our study investigated the benefit of role-play, an underutilized teaching modality, in a medical Spanish course.Methods19 second year medical students were recruited to participate. Based on their placement test performance, students were assigned to a beginner or intermediate group and met weekly for one-hour sessions over five consecutive weeks. Students assumed the roles of Spanish-speaking patient, English-speaking provider, and interpreter to practice various medical scenarios. Students completed pre- and post-course examinations to assess Spanish proficiency improvement. Statistical significance was determined using a p-value < 0.05.ResultsSeven students, all members of the intermediate group, completed the course. Attendance among this group was 77.4%. When comparing examination scores, there was statistically significant improvement in oral translation of phrases from Spanish to English (p-value= 0.03).DiscussionStatistically significant improvement in oral translation of phrases from Spanish to English was accomplished through a minimal time requirement of one hour per week utilizing role-play. Given the fact that limited time poses a barrier to implementing medical Spanish curricula, our findings highlight the potential benefit of this teaching methodology and call for further evaluation.
The cross-sectional area of the vagus nerve is not reduced in Parkinson’s Disease patients
Authors: Sijben Laura C.J. , Mess Werner H. , Walter Uwe , Janssen A. Miranda L. , Kuijf Mark , Oosterloo Mayke , Weber Wim M. , Janssen Marcus L.F. 
Published: October 2020

AbstractObjectiveRecent studies have revealed the importance of the gut brain axis in the development of Parkinson’s disease (PD). It has also been suggested that the cross-sectional area (CSA) of the vagus nerve can be used in the diagnosis of PD. Here, we hypothesize that the CSA of the vagus nerve is decreased in PD patients compared to control subjects.MethodsIn this study we measured the CSA of the vagus nerve on both sides in 31 patients with PD and 51 healthy controls at the level of the common carotid artery using high-resolution ultrasound.ResultsThe CSA of the vagus nerve was not reduced in PD patients compared to controls (p = 0.391. The mean CSA of the left vagus nerve was significantly smaller than the right (p < 0.001). There was no significant correlation between age, gender and autonomic symptoms with the CSA of the left (p = 0.128) and right vagus nerve (p = 0.166).ConclusionThese findings show that the CSA of the vagus nerve using ultrasonography is not a reliable diagnostic tool in the diagnosis of PD.HighlightsThe cross-sectional area of the vagus nerve is not decreased in Parkinson disease patients.The cross-sectional area of the vagus nerve does not correlate with autonomic symptoms.Measurement of the vagus nerve cross-sectional area has a high inter-observer correlation.
Spatiotemporal Response Heterogeneity Across Metastatic Lesions Informs Drug Efficacy and Patient Survival in Colorectal Cancer
Authors: Zhou Jiawei , Li Quefeng , Cao Yanguang 
Published: October 2020

AbstractThe sum of target lesions is routinely used to evaluate patient objective responses to treatment in the RECIST criteria, but it neglects the response heterogeneity across metastases. This study argues that the spatiotemporal response heterogeneity across metastases informs drug efficacy and patient survival. We analyzed the longitudinal data of 11,404 metastatic lesions in 2,802 colorectal cancer patients and examined their response heterogeneity. The response dynamics of metastatic lesions varied broadly across anatomical locations and therapies. High inter-lesion heterogeneity is associated with worse survival (p < 0.001), while targeted therapies (bevacizumab or panitumumab) reduced the inter-lesion heterogeneity (p < 0.05) and elicited more favorable effects on liver lesions (p < 0.001) than chemotherapy alone. The responses of liver lesions predicted patient survival more significantly than the lesions in the lungs and lymph nodes. Altogether, the high spatiotemporal heterogeneity across metastases should be integrated into current methods for treatment evaluation and patient prognosis.SignificanceThe spatiotemporal heterogeneity across metastases in response to first-line therapies in colorectal cancer is informative for drug efficacy and patient survival, particularly in targeted therapy. Our findings provide evidence to support the inclusion of individual lesion response in the RECIST to improve the assessment of drug efficacy and patient survival.
Low-Cost Manually Assembled Open Source Reader for Isothermal Pathogen Detection from Saliva using RT-LAMP: SARS-CoV-2 Use Case
Authors: Bramley John C. , Waligorski Jason E. , Kremitzki Colin L. , Liebeskind Mariel J. , Yenkin Alex L. , Xu Xinyuan E. , Lalli Matthew A. , O’Halloran Jane A. , Mudd Philip A. , House Stacey L. , Mitra Robi D. , Milbrandt Jeffrey D. , Buchser William J. 
Published: October 2020

AbstractDistributed “Point-of-Care” or “at-Home” testing is an important component for a complete suite of testing solutions. This manuscript describes the construction and operation of a platform technology designed to meet this need. The ongoing COVID-19 pandemic will be used as the proof-of-concept for the efficacy and deployment of this platform. The technology outlined consists of a one-pot, reverse-transcription loop-mediated isothermal amplification (RT-LAMP) chemistry coupled with a low-cost and user-assembled reader using saliva as input. This platform is readily adapted to a wide range of pathogens due to the genetic basis of the reaction. A complete guide to the construction of the reader as well as the production of the reaction chemistry are provided here. Additionally, analytical limit of detection data and the results from saliva testing of SARS-CoV-2, are presented. The platform technology outlined here demonstrates a rapid, distributed, molecular point-of-care solution for pathogen detection using crude sample input.
Prevalence of antibodies to SARS-CoV-2 in healthy blood donors in New York
Authors: Kamath Kathy , Baum-Jones Elisabeth , Jordan Gregory , Haynes Winston , Waitz Rebecca , Shon John , Kujawa Steve , Fitzgibbons Lyn , Kessler Debra , Luchsinger Larry ,   Yale IMPACT Team, Daugherty Patrick 
Published: October 2020

ABSTRACTDespite the high level of morbidity and mortality worldwide, there is increasing evidence for asymptomatic carriers of the novel coronavirus SARS-CoV-2. We analyzed blood specimens from 1,559 healthy blood donors, collected in the greater New York metropolitan area between the months of March and July 2020 for antibodies to SARS-CoV-2 virus. Using our proprietary technology, SERA (Serum Epitope Repertoire Analysis), we observed a significant increase in SARS-CoV-2 seropositivity rates over the four-month period, from 0% [95% CI: 0 - 1.5%] (March) to 11.6% [6.0 - 21.2%] (July). Follow-up ELISA tests using S1 and nucleocapsid viral proteins confirmed most of these results. Our findings are consistent with seroprevalence studies within the region and with reports that SARS-COV-2 infections can be asymptomatic or cause only mild symptoms.IMPORTANCEThe COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has caused vast morbidity and mortality worldwide, yet several studies indicate that there may be a significant number of infected people who are asymptomatic or exhibit mild symptoms. In this study, samples were collected from healthy blood donors in a region of rapidly increasing disease burden (New York metropolitan area) and we hypothesized that a subset would be seropositive to SARS-CoV-2. People who experienced mild or no symptoms during SARS-CoV-2 infection may represent a source for convalescent plasma donors.