bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete sequencing of expandedSAMD12repeats by long-read sequencing and Cas9-mediated enrichment
Authors: Mizuguchi Takeshi , Toyota Tomoko , Miyatake Satoko , Mitsuhashi Satomi , Doi Hiroshi , Kudo Yosuke , Kishida Hitaru , Hayashi Noriko , Tsuburaya Rie S , Kinoshita Masako , Fukuyama Tetsuhiro , Fukuda Hiromi , Koshimizu Eriko , Tsuchida Naomi , Uchiyama Yuri , Fujita Atsushi , Takata Atsushi , Miyake Noriko , Kato Mitsuhiro , Tanaka Fumiaki , Adachi Hiroaki , Matsumoto Naomichi 
Published: January 2021

AbstractA pentanucleotide TTTCA repeat insertion into a polymorphic TTTTA repeat element in SAMD12 causes benign adult familial myoclonic epilepsy. Although the precise determination of the entire SAMD12 repeat sequence is important for molecular diagnosis and research, obtaining this sequence remains challenging when using conventional genomic/genetic methods, and even short-read and long-read next-generation sequencing technologies have been insufficient. Incomplete information regarding expanded repeat sequences may hamper our understanding of the pathogenic roles played by varying numbers of repeat units, genotype–phenotype correlations, and mutational mechanisms. Here, we report a new approach for the precise determination of the entire expanded repeat sequence and present a workflow designed to improve the diagnostic rates in various repeat expansion diseases. We examined 34 clinically diagnosed benign adult familial myoclonic epilepsy patients, from 29 families using repeat-primed PCR, Southern blot, and long-read sequencing with Cas9-mediated enrichment. Two cases with questionable results from repeat-primed PCR and/or Southern blot were confirmed as pathogenic using long-read sequencing with Cas9-mediated enrichment, resulting in the identification of pathogenic SAMD12 repeat expansions in 76% of examined families (22/29). Importantly, long-read sequencing with Cas9-mediated enrichment was able to provide detailed information regarding the sizes, configurations, and compositions of the expanded repeats. The inserted TTTCA repeat size and the proportion of TTTCA sequences among the overall repeat sequences were highly variable, and a novel repeat configuration was identified. A genotype–phenotype correlation study suggested that the insertion of even short (TTTCA)14 repeats contributed to the development of benign adult familial myoclonic epilepsy. However, the sizes of the overall TTTTA and TTTCA repeat units are also likely to be involved in the pathology of benign adult familial myoclonic epilepsy. Seven unsolved SAMD12-negative cases were investigated using whole-genome long-read sequencing, and infrequent, disease-associated, repeat expansions were identified in two cases. The strategic workflow resolved two questionable SAMD12-positive cases and two previously SAMD12-negative cases, increasing the diagnostic yield from 69% (20/29 families) to 83% (24/29 families). This study indicates the significant utility of long-read sequencing technologies to explore the pathogenic contributions made by various repeat units in complex repeat expansions and to improve the overall diagnostic rate.
Acute Systemic Experimental Inflammation Does Not Reduce Human Odor Identification Performance
Authors: Tognetti Arnaud , Sarolidou Georgia , Lasselin Julie , Lekander Mats , Olsson Mats J , Lundström Johan N 
Published: January 2021

Abstract
Olfactory dysfunction is a common symptom of various diseases, but the underlying pathophysiology has not been fully understood. Evidence from both animal and human studies suggests that local inflammation of the olfactory epithelium is linked to olfactory dysfunction. However, whether systemic inflammation causes olfactory dysfunction is yet to be determined. In the present behavioral study, we set out to test whether acute systemic inflammation impairs olfactory identification performance by inducing a transient and controlled state of systemic inflammation using an experimental endotoxemia model. We treated young healthy participants (N = 20) with a relatively high dose (2.0 ng/kg) of lipopolysaccharide (LPS) and a placebo treatment in a double-blind within-subject design, and assessed participants’ ability to identify odors using the MONEX-40, a reliable method for experimental assessment of odor identification ability in healthy and young individuals. Our results show that olfactory identification performance was not affected by the acute systemic inflammation triggered by the injection of LPS. Moreover, odor identification performance following the LPS injection was not associated with levels of circulating proinflammatory cytokines (interleukin-6, interleukin-8, and tumor necrosis factor-α). Because experimental LPS-induced systemic inflammation does not affect olfactory identification performance, our findings suggest that chronic, rather than transient, systemic inflammation is a more likely mechanism to explore in order to explain the olfactory deficits observed in inflammatory diseases.
Clinical Presentation of Incident Syphilis Among Men Who Have Sex with Men Taking HIV Pre-Exposure Prophylaxis in Melbourne, Australia
Authors: Peel Joanne , Chow Eric P F , Denham Ian , Schmidt Tina , Buchanan Andrew , Fairley Christopher K , Williamson Deborah A , Bissessor Melanie , Chen Marcus Y 
Published: January 2021

AbstractBackgroundCurrent international guidelines on human immunodeficieny virus (HIV) Pre-Exposure Prophylaxis (PrEP) recommend serological screening for syphilis at routine 3-monthly PrEP appointments. The aim of our study was to describe the pattern of clinical presentation of syphilis among men who have sex with men (MSM) taking PrEP. We were interested in whether syphilis is detected through screening at scheduled3-monthly PrEP clinic appointments or whether primary or secondary syphilis presented at unscheduled interval visits.MethodsThis was a retrospective study of MSM attending the PrEP clinic at the Melbourne Sexual Health Centre between February 2016 and March 2019. Serological screening for syphilis was routinely undertaken at 3-monthly PrEP clinic appointments. Diagnoses of early syphilis were identified from PrEP clinic visits and from interim walk-in STI clinic attendances.ResultsThere were 69 cases of early syphilis among 61 MSM taking PrEP during the study period. There were 24 (35%) primary, 16 (23%) secondary, and 29 (42%) early latent infections. The incidence of early syphilis was 8.6 per 100 person-years. A substantial proportion of primary (58%) and secondary (44%) syphilis diagnoses were made at interim STI clinic attendances, between PrEP appointments.ConclusionsSyphilis screening at routine 3-monthly PrEP visits alone fails to detect a proportion of primary and secondary syphilis infections and may be insufficient in preventing onward transmission. Education of MSM taking PrEP regarding the risk of syphilis and symptom recognition is necessary together with access to syphilis testing between PrEP visits.
Some additions and corrections for Sraffa on Ricardo in Business
Authors: Parys Wilfried 
Published: January 2021

Abstract
Sraffa’s Ricardo edition gained a well-deserved authoritative status and numerous authors have studied its first nine volumes. I concentrate on ‘Ricardo in Business’ in Volume 10, and I present some additions and corrections, with respect to, for example, Ricardo’s activities at the Stock Exchange, the 1811 incident about Wetenhall’s price lists and the 1814 Berenger fraud, the huge British Loan contracts of the Barnes-Steers-Ricardo consortium and the identity of its unknown fourth member, the timing and the effects of the news from the Battle of Waterloo, the financial hierarchy in the two (not four) consortia that contracted for the Waterloo Loan and earlier Loans. Silberling (1924) accused Ricardo of dishonest strategies against Goldsmid’s consortium. Sraffa destroyed Silberling’s arguments in 1955, 24 years after informing Cannan about his ‘ammunition’. Using newly discovered letters from Barnes, I suggest that Silberling even confused victims and perpetrators. I also examine the quality of quotations by Sraffa, Dobb and a few others.
Sixty-day consequences of COVID-19 in patients discharged from hospital: an electronic health records study
Authors: Islam Nazrul , Lewington Sarah , Kharbanda Rajesh K , Davies Jim , Várnai Kinga A , Lacey Ben 
Published: January 2021

Abstract
Data on patients discharged following COVID-19 hospitalization is scarce. We conducted an electronic health records study of community-acquired COVID-19 patients discharged between 15 March and 14 July 2020 from hospitals in Oxfordshire, UK. Of 403 discharged patients, 114 (28%) were readmitted or died within 60 days (incidence rate 18/100 person-months). Rates of readmission or death were twice as high among those ≥ 65 years as those &lt; 65 years [standardized rate ratio: 2.21 (95% CI: 1.45–3.56)] and among women than men [2.25 (1.05–4.18)]. These findings suggest important sex differences in 60-day outcomes following COVID-19 hospitalization that have not previously been well described.
Voters and Foreign Policy: Evidence from a Conjoint Experiment in Pakistan
Authors: Clary Christopher , Siddiqui Niloufer 
Published: January 2021

AbstractHow much weight do voters place on foreign policy when deciding between electoral candidates? In traditional surveys in Pakistan, the vast majority of respondents identify India as an enemy and threat to Pakistan. What these studies do not assess is whether these beliefs affect voter preferences. Using a conjoint survey experiment conducted among 1,990 respondents in Pakistan, we find that respondents punish hypothetical politicians who advocate a friendly policy toward India, but only modestly. Candidate attitudes toward India were the least meaningful characteristic for voter choice among five characteristics tested, suggesting that attitudinal measurements of salience poorly predict candidate preference. Subgroup results are also instructive: younger and more educated respondents and those from Pakistan's largest province of Punjab were less likely to punish dovish politicians. We discuss implications of these findings and outline avenues for future research.
Specific collagens maintain the cuticle permeability barrier inCaenorhabditis elegans
Authors: Sandhu Anjali , Badal Divakar , Sheokand Riya , Tyagi Shalini , Singh Varsha 
Published: January 2021

AbstractCollagen-enriched cuticle forms the outermost layer of skin in nematode Caenorhabditis elegans. The nematode’s genome encodes 177 collagens, but little is known about their role in maintaining the structure or barrier function of the cuticle. In this study, we found six permeability determining (PD) collagens. Loss of any of these PD collagens—DPY-2, DPY-3, DPY-7, DPY-8, DPY-9, and DPY-10—led to enhanced susceptibility of nematodes to paraquat (PQ) and antihelminthic drugs- levamisole and ivermectin. Upon exposure to PQ, PD collagen mutants accumulated more PQ and incurred more damage and death despite the robust activation of antioxidant machinery. We find that BLMP-1, a zinc finger transcription factor, maintains the barrier function of the cuticle by regulating the expression of PD collagens. We show that the permeability barrier maintained by PD collagens acts in parallel to FOXO transcription factor DAF-16 to enhance survival of insulin-like receptor mutant, daf-2. In all, this study shows that PD collagens regulate cuticle permeability by maintaining the structure of C. elegans cuticle and thus provide protection against exogenous toxins.
Aerobic Exercise Improves Mitochondrial Function in Sarcopenia Mice Through Sestrin2 in an AMPKα2-Dependent Manner
Authors: Liu Sujuan , Yu Chunxia , Xie Lingjian , Niu Yanmei , Fu Li 
Published: January 2021

Abstract
Sarcopenia, the age-related loss of skeletal muscle mass and function, contributes to high morbidity and mortality in the older population. Regular exercise is necessary to avoid the initiation and progression of sarcopenia, in which the underlying molecular mechanism is still not clear. Our data revealed that the outcomes induced by sarcopenia, including muscle mass and strength loss, decreased cross-sectional area of gastrocnemius fiber, chronic inflammation, and increased dysfunctional mitochondria, were reversed by regulation exercise. Knockout or silencing of Sestrin2 (Sesn2) resulted in imbalanced mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy damage in vivo and in vitro, which was attenuated by aerobic exercise or overexpression of Sesn2. Moreover, we found that the effects of Sesn2 on mitochondrial function are dependent on AMP-activated protein kinase α2 (AMPKα2). This study indicates that aerobic exercise alleviates the negative effects resulting from sarcopenia via the Sesn2/AMPKα2 pathway and provides new insights into the molecular mechanism by which the Sesn2/AMPKα2 signaling axis mediates the beneficial impact of exercise on sarcopenia.
Measuring Caregiver Retention in Nursing Homes
Authors: Castle Nicholas G 
Published: January 2021

Abstract

Background and Objectives
Retention of nursing home caregivers is examined. This represents the concept of continuously employing the same caregivers in the same facility for a defined period of time. In this research, several measures of caregiver retention are examined and the utility of these measures for practitioners and policy makers is discussed.

Research Design and Methods
A survey of nursing home administrators conducted in 2016 was used to collect staffing data from 2,898 facilities. This was matched with Nursing Home Compare and the Certification and Survey Provider Enhanced Reporting data. The association of four measures of retention for each of three types of caregivers with six quality indicators was examined.

Results
The descriptive statistics show rates of retention at 5 years for nurse aides (NAs), registered nurses (RNs), and licensed practical nurses to be low. The regression estimates show some support for the relationship that high caregiver retention is associated with better overall quality. The relationship was strongest for NAs and RNs. Support was also found for the notion that different measures of retention were more/less associated with quality. The 3- and 5-year retention measures had the strongest associations with the quality indicators.

Discussion and Implications
The findings presented provide some evidence that caregiver retention may be an important metric that can be used as a means of improving quality of care in nursing homes. However, the findings also show practitioners and policy makers should be more nuanced in the use of caregiver retention metrics.
ChiRA: an integrated framework for chimeric read analysis from RNA-RNA interactome and RNA structurome data
Authors: Videm Pavankumar , Kumar Anup , Zharkov Oleg , Grüning Björn Andreas , Backofen Rolf 
Published: January 2021

Abstract

Background
With the advances in next-generation sequencing technologies, it is possible to determine RNA-RNA interaction and RNA structure predictions on a genome-wide level. The reads from these experiments usually are chimeric, with each arm generated from one of the interaction partners. Owing to short read lengths, often these sequenced arms ambiguously map to multiple locations. Thus, inferring the origin of these can be quite complicated. Here we present ChiRA, a generic framework for sensitive annotation of these chimeric reads, which in turn can be used to predict the sequenced hybrids.

Results
Grouping reference loci on the basis of aligned common reads and quantification improved the handling of the multi-mapped reads in contrast to common strategies such as the selection of the longest hit or a random choice among all hits. On benchmark data ChiRA improved the number of correct alignments to the reference up to 3-fold. It is shown that the genes that belong to the common read loci share the same protein families or similar pathways. In published data, ChiRA could detect 3 times more new interactions compared to existing approaches. In addition, ChiRAViz can be used to visualize and filter large chimeric datasets intuitively.

Conclusion
ChiRA tool suite provides a complete analysis and visualization framework along with ready-to-use Galaxy workflows and tutorials for RNA-RNA interactome and structurome datasets. Common read loci built by ChiRA can rescue multi-mapped reads on paralogous genes without requiring any information on gene relations. We showed that ChiRA is sensitive in detecting new RNA-RNA interactions from published RNA-RNA interactome datasets.
Histopathology of anastomotic stenosis after total anomalous pulmonary vein connection
Authors: Masaki Naoki , Mizumoto Masahiro , Adachi Osamu , Sai Sadahiro 
Published: January 2021

Abstract
We report a case of a 10-month-old girl who was diagnosed with pulmonary vein stenosis after total anomalous pulmonary vein connection repair and underwent release of an anastomotic stenosis. Histopathological examinations of the resected anastomotic tissue revealed intimal hyperplasia at the anastomotic site. Predominant lesion cells were identified as myofibroblasts and had the characteristics of fibroblasts and synthetic smooth muscle cells. These cells could be a useful target for preventing anastomotic stenosis after total anomalous pulmonary vein connection repair.
Early life exposure to tobacco smoke and ovarian cancer risk in adulthood
Authors: Wang Tianyi , Townsend Mary K , Vinci Christine , Jake-Schoffman Danielle E , Tworoger Shelley S 
Published: January 2021

AbstractBackgroundOvarian cancer risk in adulthood may be affected by early life exposure to tobacco smoke. We investigated this relationship in two large prospective cohorts, the Nurses’ Health Study (NHS) and NHSII.MethodsIn total, analyses included 110 305 NHS participants (1976–2016) and 112 859 NHSII participants (1989–2017). Self-reported early life smoking exposures were queried at baseline or follow-up questionnaires. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of ovarian cancer overall and by tumour histotype.ResultsOverall, ovarian cancer risk was not different among participants whose mothers did versus did not smoke during pregnancy (HR = 1.05, 95% CI: 0.87–1.27); however, an increased risk was observed among women who themselves were never smokers (HR = 1.38, 95% CI: 1.05–1.81) but not among ever smokers (HR = 0.86, 95% CI: 0.66–1.14; Pheterogeneity = 0.02). Compared with women who never smoked, ovarian cancer risk was similar for women who started to smoke at age &lt;18 (HR = 0.98, 95% CI: 0.86–1.11) or ≥18 (HR = 1.02, 95% CI: 0.93–1.12). These associations did not differ by histotype (Pheterogeneity ≥0.35). Parental smoking in the home during childhood/adolescence was related to a 15% increased risk of ovarian cancer in adulthood (HR = 1.15, 95% CI: 1.04–1.27) and this association was suggestively stronger among women with non-serous/low-grade serous tumours (HR = 1.28, 95% CI: 1.02–1.61) versus high-grade serous/poorly differentiated tumours (HR = 1.09, 95% CI: 0.93–1.28; Pheterogeneity = 0.25).ConclusionsExposure to parental tobacco smoke in the home, but not early initiation of smoking, was associated with a modest elevated risk of ovarian cancer. Further investigations are required to confirm these findings and elucidate underlying mechanisms.
Development of a Novel Assay to Assess the Avidity of Dengue Virus-Specific Antibodies Elicited in Response to a Tetravalent Dengue Vaccine
Authors: Tsuji Isamu , Dominguez David , Egan Michael A , Dean Hansi J 
Published: January 2021

AbstractAntibody affinity maturation is a critical step in development of functional antiviral immunity; however, accurate measurement of affinity maturation of polyclonal serum antibody responses to particulate antigens such as virions is challenging. We describe a novel avidity assay employing biolayer interferometry and dengue virus-like particles. After validation using anti-dengue monoclonal antibodies, the assay was used to assess avidity of antibody responses to a tetravalent dengue vaccine candidate (TAK-003) in children, adolescents, and adults during two phase 2 clinical trials conducted in dengue-endemic regions. Vaccination increased avidity index and avidity remained high through 1 year postvaccination. Neutralizing antibody titers and avidity index did not correlate overall; however, a correlation was observed between neutralizing antibody titer and avidity index in those subjects with the highest degree of antibody affinity maturation. Therefore, vaccination with TAK-003 stimulates polyclonal affinity maturation and functional antibody responses, including neutralizing antibodies.Clinical Trials RegistrationNCT01511250 and NCT02302066.
The Chinese government’s management of anti-Japan nationalism during Hu-Wen era
Authors: Burcu Oana 
Published: January 2021

AbstractChina and Japan continue to partly live in the shadow of World War II (WWII) with recurrent expressions of anti-Japanese nationalism in China periodically ebbing bilateral relations. How does the Chinese government manage anti-Japan public manifestations of nationalism and what factors explain it? The government has to walk a fine line by managing the nationalism it has bred without undermining its own rule and considering elite divisions, heightened public nationalism, and the developments in its external environment. Six case studies from the Hu-Wen era provide a comprehensive understanding of what pertains to Chinese nationalism, the means used to express it, and more importantly the way the government chose to tackle them. While nationalism can be a mean of garnering legitimacy and exercising pressure on Japan to bend to its wishes, the Chinese government is embarked on the sinuous task of preventing an escalation beyond its control at both the domestic and international levels.