bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening instruments for cognitive impairment in older patients in the Emergency Department: a systematic review and meta-analysis
Authors: Calf Agneta H , Pouw Maaike A , van Munster Barbara C , Burgerhof Johannes G M , de Rooij Sophia E , Smidt Nynke 
Published: August 2020

Abstract

Background
cognitive impairment is highly prevalent among older patients attending the Emergency Department (ED) and is associated with adverse outcomes.

Methods
we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of cognitive screening instruments to rule out cognitive impairment in older patients in the ED. A comprehensive literature search was performed in MEDLINE, EMBASE, CINAHL and CENTRAL. A risk of bias assessment using QUADAS-2 was performed.

Results
23 articles, examining 18 different index tests were included. Only seven index tests could be included in the meta-analysis. For ruling out cognitive impairment irrespective of aetiology, Ottawa 3 Day Year (O3DY) (pooled sensitivity 0.90; (95% CI) 0.71–0.97) had the highest sensitivity. Fourteen articles focused on screening for cognitive impairment specifically caused by delirium. For ruling out delirium, the 4 A’s Test (4AT) showed highest sensitivity (pooled sensitivity 0.87, 95% confidence interval (95% CI) 0.74–0.94).

Conclusions
high clinical and methodological heterogeneity was found between included studies. Therefore, it is a challenge to recommend one diagnostic test for use as a screening instrument for cognitive impairment in the ED. The 4AT and O3DY seem most promising for ruling out cognitive impairment in older patients attending the ED.
The review protocol was registered in PROSPERO (CRD42018082509).
The unique disarticulation layer formed in the rachis of Aegilops longissima probably results from the spatial co-expression of Btr1 and Btr2
Authors: Zeng Xiaoxue , Chen Gang , Wang Lei , Tagiri Akemi , Kikuchi Shinji , Sassa Hidenori , Komatsuda Takao 
Published: August 2020

Abstract

Background and Aims
The brittle rachis trait is a feature of many wild grasses, particularly within the tribe Triticeae. Wild Hordeum and Triticum species form a disarticulation layer above the rachis node, resulting in the production of wedge-type dispersal units. In Aegilops longissima, only one or two of the nodes in the central portion of its rachis are brittle. In Triticeae species, the formation of a disarticulation layer above the rachis node requires the co-transcription of the two dominant and complementary genes Btr1 and Btr2. This study aims to establish whether homologues of Btr1 and/or Btr2 underlie the unusual brittle rachis phenotype observed in Ae. longissima.

Methods
Scanning electron microscopy was used to examine the disarticulation surfaces. Quantitative RT-PCR and RNA in situ hybridization experiments were used to identify gene expression in the immature inflorescence.

Key Results
Analysis based on scanning electron microscopy was able to demonstrate that the disarticulation surfaces formed in the Ae. longissima rachis are morphologically indistinguishable from those formed in the rachises of wild Hordeum and Triticum species. RNA in situ hybridization showed that in the immature Ae. longissima inflorescence, the intensity of Btr1 transcription varied from high at the rachis base to low at its apex, while that of Btr2 was limited to the nodes in the central to distal portion of the rachis.

Conclusions
The disarticulation pattern shown by Ae. longissima results from the limitation of Btr1 and Btr2 co-expression to nodes lying in the centre of the rachis.
The Association Between Functional Assessment and Structural Brain Biomarkers in an Ethnically Diverse Sample With Normal Cognition, Mild Cognitive Impairment, or Dementia
Authors: Arruda Fernanda , Rosselli Mónica , Greig Maria T , Loewenstein David A , Lang Merike , Torres Valeria L , Vélez-Uribe Idaly , Conniff Joshua , Barker Warren W , Curiel Rosie E , Adjouadi Malek , Duara Ranjan 
Published: August 2020

Abstract

Objective
To investigate the association between the functional activities questionnaire (FAQ) and brain biomarkers (bilateral hippocampal volume [HV], bilateral entorhinal volume [ERV], and entorhinal cortical thickness [ERT]) in cognitively normal (CN) individuals, mild cognitive impairment (MCI), or dementia.

Method
In total, 226 participants (137 females; mean age = 71.76, SD = 7.93; Hispanic Americans = 137; European Americans = 89) were assessed with a comprehensive clinical examination, a neuropsychological battery, a structural magnetic resonance imaging, and were classified as CN or diagnosed with MCI or dementia. Linear regression analyses examined the association between functional activities as measured by the FAQ on brain biomarkers, including HV, ERV, and ERT, controlling for age, education, global cognition, gender, and ethnicity.

Results
The FAQ significantly predicted HV, ERV, and ERT for the entire sample. However, this association was not significant for ERV and ERT when excluding the dementia group. The FAQ score remained a significant predictor of HV for the non-dementia group. Age, education, gender, ethnicity, Montreal Cognitive Assessment score, and FAQ were also significant predictors of HV for the overall sample, suggesting that younger Hispanic females with fewer years of education, higher global mental status, and better functioning, were more likely to have larger HV.

Conclusion
FAQ scores were related to HV in older adults across clinical groups (CN, MCI, and dementia), but its association with the entorhinal cortex was driven by individuals with dementia. Demographic variables, including ethnicity, additionally influenced these associations.
Home-Based Pediatric Teleneuropsychology: A validation study
Authors: Harder Lana , Hernandez Ana , Hague Cole , Neumann Joy , McCreary Morgan , Cullum C Munro , Greenberg Benjamin 
Published: August 2020

Abstract

Objective
To evaluate home-based teleneuropsychology in a pediatric cohort to determine if assessment via in-person and home-based videoconference yield similar results. The second objective was to determine the level of satisfaction with videoconference-based assessment among participants and caregivers.

Method
Fifty-eight participants, aged 6–20 years, were recruited through specialty programs for pediatric demyelinating disorders. Each participant was administered the same brief neuropsychological battery of common measures twice, once during an in-person session and once during a remote home-based videoconference session. Order of sessions was counterbalanced and time between assessments ranged from 1 to 50 days. It was hypothesized that results obtained through in-person vs. remote videoconference sessions would not be significantly different and that most participants and caregivers would rate the experience with teleneuropsychology as satisfactory.

Results
Mann–Whitney U tests showed no significant differences in results obtained in the in-person first vs. remote videoconference first sessions or the change in performance across sessions. Satisfaction ratings by participants and caregivers were largely favorable for the use of the videoconference testing format.

Conclusions
The current study is the first to validate home-based teleneuropsychology and is the first to validate teleneuropsychological assessment in a pediatric sample. Future studies should replicate these findings as well as expand on sample size, diversity of populations evaluated, and the assessment tools administered. Careful consideration of ethical and practical factors should be given before providing pediatric teleneuropsychology services.
BSAseq: an interactive and integrated web-based workflow for identification of causal mutations in bulked F2 populations
Authors: Wang Liya , Lu Zhenyuan , Regulski Michael , Jiao Yinping , Chen Junping , Ware Doreen , Xin Zhanguo 
Published: August 2020

Abstract

Summary
With the advance of next-generation sequencing technologies and reductions in the costs of these techniques, bulked segregant analysis (BSA) has become not only a powerful tool for mapping quantitative trait loci but also a useful way to identify causal gene mutations underlying phenotypes of interest. However, due to the presence of background mutations and errors in sequencing, genotyping, and reference assembly, it is often difficult to distinguish true causal mutations from background mutations. In this study, we developed the BSAseq workflow, which includes an automated bioinformatics analysis pipeline with a probabilistic model for estimating the linked region (the region linked to the causal mutation) and an interactive Shiny web application for visualizing the results. We deeply sequenced a sorghum male-sterile parental line (ms8) to capture the majority of background mutations in our bulked F2 data. We applied the workflow to 11 bulked sorghum F2 populations and 1 rice F2 population and identified the true causal mutation in each population. The workflow is intuitive and straightforward, facilitating its adoption by users without bioinformatics analysis skills. We anticipate that the BSAseq workflow will be broadly applicable to the identification of causal mutations for many phenotypes of interest.

Availability and implementation
BSAseq is freely available on https://www.sciapps.org/page/bsa.

Supplementary information
Supplementary data are available at Bioinformatics online.
CONAN: a web application to detect specificity determinants and functional sites by amino acids co-variation network analysis
Authors: Fonseca N J , Afonso M Q L , Carrijo L , Bleicher L 
Published: August 2020

Abstract

Summary
CONAN is a web application developed to detect specificity determinants and function-related sites by amino acids co-variation networks analysis, emphasizing local coevolutionary constraints. The software allows the characterization of structurally and functionally relevant groups of residues and their relationship with subsets of sequences by automatic cross-referencing with GO terms, UniprotKb annotations and INTERPRO.

Availability and implementation
CONAN is free and open-source, being distributed in the terms of the GPLV3 license. The software is available as a web application and python script versions and can be accessed at http://bioinfo.icb.ufmg.br/conan. We also provide running instructions, the source code and a user guide.
Mutation-Simulator: fine-grained simulation of random mutations in any genome
Authors: Kühl M A , Stich B , Ries D C 
Published: August 2020

Abstract

Summary
Mutation-Simulator allows the introduction of various types of sequence alterations in reference sequences, with reasonable compute-time even for large eukaryotic genomes. Its intuitive system for fine-grained control over mutation rates along the sequence enables the mimicking of natural mutation patterns. Using standard file formats for input and output data, it can easily be integrated into any development and benchmarking workflow for high-throughput sequencing applications.

Availability and implementation
Mutation-Simulator is written in Python 3 and the source code, documentation, help and use cases are available on the Github page at https://github.com/mkpython3/Mutation-Simulator. It is free for use under the GPL 3 license.
Social Work Research in Chile: Tensions and Challenges under the ‘Knowledge Economy’ and Managerialist Research Agendas
Authors: Muñoz-Arce Gianinna , Rubilar-Donoso Gabriela 
Published: August 2020

Abstract
Research has been a contested dimension of Chilean social work. An important turn occurred in 2008 when Chilean national research policies—highly influenced by managerialist approaches—increased opportunities for social workers to conduct research. Several efforts have been made by academics and professional social work organisations to encourage research as a means of gaining recognition as a discipline. Drawing upon a thematic literature review from a Chilean-based study on social workers’ research trajectories, this article contends that, despite the value of such efforts, there are some tensions related to the acritical adoption of such a managerialist approach on social work research that need further attention: (i) research does not have the same value for all social work sectors; (ii) social work research is mainly understood as ‘academic’ research; and (iii) social workers’ research does not necessarily have a ‘social work focus’. These findings are discussed in light of the historical background of Chilean social work and the insights provided by the international literature, from which we conclude that the creation of more inclusive and collaborative ways of conducting research is an urgent challenge. Findings are context-specific, yet, offer considerations for social work research seeking to counteract managerial approaches of knowledge production.
Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy
Authors: Lin Chin-Hsien , Tsai Pei-I , Lin Han-Yi , Hattori Nobutaka , Funayama Manabu , Jeon Beomseok , Sato Kota , Abe Koji , Mukai Yohei , Takahashi Yuji , Li Yuanzhe , Nishioka Kenya , Yoshino Hiroyo , Daida Kensuke , Chen Meng-Ling , Cheng Jay , Huang Cheng-Yen , Tzeng Shiou-Ru , Wu Yen-Sheng , Lai Hsing-Jung , Tsai Hsin-Hsi , Yen Ruoh-Fang , Lee Ni-Chung , Lo Wen-Chun , Hung Yu-Chien , Chan Chih-Chiang , Ke Yi-Ci , Chao Chi-Chao , Hsieh Sung-Tsang , Farrer Matthew , Wu Ruey-Meei 
Published: August 2020

Abstract
Parkinson’s disease is a neurodegenerative disorder with a multifactorial aetiology. Nevertheless, the genetic predisposition in many families with multi-incidence disease remains unknown. This study aimed to identify novel genes that cause familial Parkinson’s disease. Whole exome sequencing was performed in three affected members of the index family with a late-onset autosomal-dominant parkinsonism and polyneuropathy. We identified a novel heterozygous substitution c.941A&gt;C (p.Tyr314Ser) in the mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene, which co-segregates with disease within the family. Additional analysis of 699 unrelated Parkinson’s disease probands with autosomal-dominant Parkinson’s disease and 1934 patients with sporadic Parkinson’s disease revealed another two variants in UQCRC1 in the probands with familial Parkinson’s disease, c.931A&gt;C (p.Ile311Leu) and an allele with concomitant splicing mutation (c.70-1G&gt;A) and a frameshift insertion (c.73_74insG, p.Ala25Glyfs*27). All substitutions were absent in 1077 controls and the Taiwan Biobank exome database from healthy participants (n = 1517 exomes). We then assayed the pathogenicity of the identified rare variants using CRISPR/Cas9-based knock-in human dopaminergic SH-SY5Y cell lines, Drosophila and mouse models. Mutant UQCRC1 expression leads to neurite degeneration and mitochondrial respiratory chain dysfunction in SH-SY5Y cells. UQCRC1 p.Tyr314Ser knock-in Drosophila and mouse models exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons. Furthermore, intraperitoneal injection of levodopa could significantly improve the motor dysfunction in UQCRC1 p.Tyr314Ser mutant knock-in mice. Taken together, our in vitro and in vivo studies support the functional pathogenicity of rare UQCRC1 variants in familial parkinsonism. Our findings expand an additional link of mitochondrial complex III dysfunction in Parkinson’s disease.
Quality by Design Approach to Develop Stability Indicating Method to Quantify Related Substances and Degradation Products of Sacubitril by High Performance Liquid Chromatography
Authors: Bommi Sivaganesh , Jayanty Subbalakshmi , Tirumalaraju Satyanarayana Raju , Bandaru Sivasankar 
Published: August 2020

Abstract
Sacubitril (SBT) is a neprilysin inhibitor, approved by food and drug administration (FDA) in 2015, under the FDA’s priority review process. In this work, we report the validated stability indicating method of SBT by employing quality by design (QbD) principles related to analytical method development, capable in separation of 11 impurities. Chromatographic separation was performed on an ascentis phenyl hexyl column using 10 mM KH2PO4 as a mobile phase-A and the pH adjusted to 2.1. Methanol: acetonitrile (70:30 v/v) solvent mixture was employed as the mobile phase-B in a gradient mode of elution at a flow rate 0.8 mL/min at 30°C. The column effluents were monitored by a photo diode array detector set at a wavelength of maximum absorption 254 nm noted for all the impurities and furthermore for SBT. This method was remarked to be accurate in the range from 92 to 116%, precise with relative standard deviation 0.9% for SBT (0.8 mg/mL) and 1.0 to 2.1% for its related impurities (0.0005 mg/mL) also linear with correlation coefficient r ≥ 0.9989. The limits of quantification for all impurities were 0.05% with respect to sample concentration 0.8 mg/mL. The developed method revealed a good method operable design range for the experimental chromatographic conditions. Forced degradation of SBT carried under acidic, basic and oxidative stressed conditions manifested that the method is stability indicating.
Are All Patients with Cancer at Heightened Risk for Severe Coronavirus Disease 2019 (COVID-19)?
Authors: Chamilos Georgios , Lionakis Michail S , Kontoyiannis Dimitrios P 
Published: August 2020

AbstractCancer patients are traditionally considered at high risk for complicated respiratory viral infections, due to their underlying immunosuppression. In line with this notion, early case series reported high mortality rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with malignancy. However, subsequent large, prospective, epidemiological surveys indicate that the risk for severe coronavirus disease 2019 (COVID-19) may be largely attributed to the multiple confounders operating in this highly heterogeneous population of patients, rather than the cancer or its treatment per se. We critically discuss the conundrums of SARS-CoV-2 infection in cancer patients and underscore mechanistic insights on the outcome of COVID-19 as it relates to cancer therapy and the type and status of the underlying malignancy. Not all cancer patients are similarly at risk for a complicated COVID-19 course. A roadmap is needed for translational and clinical research on COVID-19 in this challenging group of patients.
Clinical Characteristics and Predictors of Outcomes of Hospitalized Patients With Coronavirus Disease 2019 in a Multiethnic London National Health Service Trust: A Retrospective Cohort Study
Authors: Perez-Guzman Pablo N , Daunt Anna , Mukherjee Sujit , Crook Peter , Forlano Roberta , Kont Mara D , Løchen Alessandra , Vollmer Michaela , Middleton Paul , Judge Rebekah , Harlow Christopher , Soubieres Anet , Cooke Graham , White Peter J , Hallett Timothy B , Aylin Paul , Ferguson Neil , Hauck Katharina , Thursz Mark R , Nayagam Shevanthi 
Published: August 2020

Abstract

Background
Emerging evidence suggests ethnic minorities are disproportionately affected by coronavirus disease 2019 (COVID-19). Detailed clinical analyses of multicultural hospitalized patient cohorts remain largely undescribed.

Methods
We performed regression, survival, and cumulative competing risk analyses to evaluate factors associated with mortality in patients admitted for COVID-19 in 3 large London hospitals between 25 February and 5 April, censored as of 1 May 2020.

Results
Of 614 patients (median age, 69 [interquartile range, 25] years) and 62% male), 381 (62%) were discharged alive, 178 (29%) died, and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (adjusted odds ratio [aOR], 4.25 [95% confidence interval {CI}, 2.36–7.64]), leukocytosis (aOR, 2.35 [95% CI, 1.35–4.11]), thrombocytopenia (aOR [1.01, 95% CI, 1.00–1.01], increase per 109 decrease), severe renal impairment (aOR, 5.14 [95% CI, 2.65–9.97]), and low albumin (aOR, 1.06 [95% CI, 1.02–1.09], increase per gram decrease) were associated with death. Forty percent (n = 244) were from black, Asian, and other minority ethnic (BAME) groups, 38% (n = 235) were white, and ethnicity was unknown for 22% (n = 135). BAME patients were younger and had fewer comorbidities. Although the unadjusted odds of death did not differ by ethnicity, when adjusting for age, sex, and comorbidities, black patients were at higher odds of death compared to whites (aOR, 1.69 [95% CI, 1.00–2.86]). This association was stronger when further adjusting for admission severity (aOR, 1.85 [95% CI, 1.06–3.24]).

Conclusions
BAME patients were overrepresented in our cohort; when accounting for demographic and clinical profile of admission, black patients were at increased odds of death. Further research is needed into biologic drivers of differences in COVID-19 outcomes by ethnicity.
Assessing the Potential for Unintended Microbial Consequences of Routine Chlorhexidine Bathing for Prevention of Healthcare-associated Infections
Authors: Babiker Ahmed , Lutgring Joseph D , Fridkin Scott , Hayden Mary K 
Published: August 2020

AbstractChlorhexidine gluconate (CHG) is an antiseptic that is widely used in healthcare due to its excellent safety profile and wide spectrum of activity. Daily bathing with CHG has proven to be effective in the prevention of healthcare-associated infections and multidrug-resistant pathogen decolonization. Despite the proven benefits of CHG use, there remain concerns and unanswered questions about the potential for unintended microbial consequences of routine CHG bathing. This review aims to explore some of these questions.
Plasma Chemokines Are Baseline Predictors of Unfavorable Treatment Outcomes in Pulmonary Tuberculosis
Authors: Kumar Nathella P , Moideen Kadar , Nancy Arul , Viswanathan Vijay , Thiruvengadam Kannan , Nair Dina , Banurekha Vaithilingam V , Sivakumar Shanmugam , Hissar Syed , Kornfeld Hardy , Babu Subash 
Published: August 2020

Abstract

Background
Plasma chemokines are biomarkers of greater disease severity, higher bacterial burden, and delayed sputum culture conversion in pulmonary tuberculosis (PTB). Whether plasma chemokines could also serve as biomarkers of unfavorable treatment outcomes in PTB is not known.

Methods
A cohort of newly diagnosed, sputum smear- and culture-positive adults with drug-sensitive PTB were recruited under the Effect of Diabetes on Tuberculosis Severity study in Chennai, India. Plasma chemokine levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death, or recurrence) and 136 control individuals who had recurrence-free cure. A second validation cohort comprising newly diagnosed, culture-positive adults with drug-sensitive TB was used to measure plasma chemokine levels in 20 cases and 40 controls.

Results
Six chemokines (CCL2, CCL3, CCL4, CXCL8, CXCL10, and CX3CL1) were associated with increased risk, while CXCL1 was associated with decreased risk of unfavorable outcomes in unadjusted and adjusted analyses in the test cohort. Similarly, CCL3, CXCL8, and CXCL10 were associated with increased risk of unfavorable treatment outcomes in the validation cohort. Receiver operating characteristic analysis revealed that combinations of CCL3, CXCL8, and CXCL10 exhibited very high sensitivity and specificity in differentiating cases vs controls.

Conclusions
Our study reveals a plasma chemokine signature that can be used as a novel biomarker for predicting adverse treatment outcomes in PTB.