bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ionic liquids: prospects for nucleic acid handling and delivery
Authors: Egorova Ksenia S , Posvyatenko Alexandra V , Larin Sergey S , Ananikov Valentine P 
Published: January 2021

Abstract
Operations with nucleic acids are among the main means of studying the mechanisms of gene function and developing novel methods of molecular medicine and gene therapy. These endeavours usually imply the necessity of nucleic acid storage and delivery into eukaryotic cells. In spite of diversity of the existing dedicated techniques, all of them have their limitations. Thus, a recent notion of using ionic liquids in manipulations of nucleic acids has been attracting significant attention lately. Due to their unique physicochemical properties, in particular, their micro-structuring impact and tunability, ionic liquids are currently applied as solvents and stabilizing media in chemical synthesis, electrochemistry, biotechnology, and other areas. Here, we review the current knowledge on interactions between nucleic acids and ionic liquids and discuss potential advantages of applying the latter in delivery of the former into eukaryotic cells.
A novel all-in-one conditional knockout system uncovered an essential role of DDX1 in ribosomal RNA processing
Authors: Suzuki Teruhiko , Katada Eiji , Mizuoka Yuki , Takagi Satoko , Kazuki Yasuhiro , Oshimura Mitsuo , Shindo Mayumi , Hara Takahiko 
Published: January 2021

Abstract
Generation of conditional knockout (cKO) and various gene-modified cells is laborious and time-consuming. Here, we established an all-in-one cKO system, which enables highly efficient generation of cKO cells and simultaneous gene modifications, including epitope tagging and reporter gene knock-in. We applied this system to mouse embryonic stem cells (ESCs) and generated RNA helicase Ddx1 cKO ESCs. The targeted cells displayed endogenous promoter-driven EGFP and FLAG-tagged DDX1 expression, and they were converted to Ddx1 KO via FLP recombinase. We further established TetFE ESCs, which carried a reverse tetracycline transactivator (rtTA) expression cassette and a tetracycline response element (TRE)-regulated FLPERT2 cassette in the Gt(ROSA26)Sor locus for instant and tightly regulated induction of gene KO. By utilizing TetFE Ddx1F/F ESCs, we isolated highly pure Ddx1F/F and Ddx1−/− ESCs and found that loss of Ddx1 caused rRNA processing defects, thereby activating the ribosome stress–p53 pathway. We also demonstrated cKO of various genes in ESCs and homologous recombination-non-proficient human HT1080 cells. The frequency of cKO clones was remarkably high for both cell types and reached up to 96% when EGFP-positive clones were analyzed. This all-in-one cKO system will be a powerful tool for rapid and precise analyses of gene functions.
Matched Cohort Study of Convalescent COVID-19 Plasma Treatment in Severely or Life Threateningly Ill COVID-19 Patients
Authors: Klapholz Marc , Pentakota Sri Ram , Zertuche Juan-Pablo , McKenna Marshall , Roque Willy , Forsberg Mark , Packer Johnathan , Lal Devika S , Dever Lisa 
Published: January 2021

Abstract

Background
The utility of convalescent coronavirus disease 2019 (COVID-19) plasma (CCP) in the current pandemic is not well defined. We sought to evaluate the safety and efficacy of CCP in severely or life threateningly ill COVID-19 patients when matched with a contemporaneous cohort.

Methods
Patients with severe or life-threatening COVID-19 were treated with CCP according to Food and Drug Administration criteria, prioritization by an interdisciplinary team, and based on CCP availability. Individual-level matched controls (1:1) were identified from patients admitted during the prior month when no CCP was available. The safety outcome was freedom from adverse transfusion reaction, and the efficacy outcome was a composite of death or worsening O2 support. Demographic, clinical, and laboratory data were analyzed by univariate and multivariable regression analyses accounting for matched design.

Results
Study patients (n = 94, 47 matched pairs) were 62% male with a mean age of 58, and 98% (90/94) were minorities (53% Hispanic, 45% Black, non-Hispanic) in our inner-city population. Seven-day composite and mortality outcomes suggested a nonsignificant benefit in CCP-treated patients (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.23–2.12; P = .52; aHR, 0.23; 95% CI, 0.04–1.51; P = .13, respectively). Stratification by pretransfusion mechanical ventilation status showed no differences between groups. No serious transfusion reactions occurred.

Conclusions
In this short-term matched cohort study, transfusion with CCP was safe and showed a nonsignificant association with study outcomes. Randomized and larger trials to identify appropriate timing and dosing of CCP in COVID-19 are warranted.

Trial Registration
ClinicalTrials.gov Identifier: NCT04420988.
Manifesting the Consistency in the Application of ‘Manifest Arbitrariness Doctrine’
Authors: Aggarwal Vasu 
Published: January 2021

Abstract
Manifest Arbitrariness Doctrine is perhaps the most important legal development of the decade for India. It is a standard that includes anything done by the legislature capriciously, irrationally and/or without adequate determining principle, excessively or disproportionately. It is being increasingly used to strike down plenary legislation under Article 14. However, there is no clarity on its application, and no literature addressing the same. Without this clarity, law-makers may inadvertently pass legislations that fail the test; and adjudicators may fail to determine when the legislations fail the test. More importantly, the Doctrine may empower judges to substitute legislative wisdom for their own. This paper alleviates these concerns by finding consistency in its application while restricting the scope of judicial scrutiny. By employing the framework of “Rules versus Standard”, this paper analyses six instances of application of the Doctrine and develops a four-step test. It evinces that the Doctrine has been used in a restrictive sense to strike down plenary legislation only when first, the legislation in question is a rule as against a standard; second, it is overinclusive/underinclusive; third, due to overinclusive/underinclusive nature, it yields socially undesirable results; and fourth, these socially undesirable results are worse than the competing social results.
Cloth Lanyards as a Source of Intermittent Transmission of Candida auris on an ICU*
Authors: Patterson Charlotte A. , Wyncoll Duncan , Patel Amita , Ceesay Yusupha , Newsholme William , Chand Meera , Mitchell Hannah , Tan Mark , Edgeworth Jonathan D. 
Published: January 2021

OBJECTIVES:

Candida auris has been implicated in ICU outbreaks worldwide and is notable for being difficult to identify and treat, its resilience in the environment, and significant patient mortality associated with invasive disease. Here, we describe a small C. auris outbreak and how it was terminated.

DESIGN:
Single-center, observational.

SETTING:
Two general adult ICUs at an urban U.K. teaching hospital.

PATIENTS:
All patients positive for C. auris during the 5-month outbreak were included (n = 7).

INTERVENTIONS:
Stepwise implementation of enhanced infection prevention and control precautions was introduced including twice-weekly screening, contact tracing, isolation precautions, and environmental decontamination. A detailed environmental screen was performed to identify potential reservoirs. This included the patient bed space and clinical equipment and a frequently handled cloth lanyard attached to a key used to access controlled drugs. Personal possessions such as mobile phones, lanyards, and identification badges were also screened.

MEASUREMENTS AND MAIN RESULTS:
The index case and six linked acquisitions were identified. Four of six (67%) patients were identified after discharge of all known previous C. auris cases from ICU, highlighting potential for an environmental reservoir. Environmental screening identified C. auris from a patient bed space following deep cleaning, prompting review and enhancement of cleaning procedures. The controlled drug cloth lanyard was positive for C. auris, which prompted removal and culture of all staff lanyards. C. auris was identified on 1/100 staff lanyards (1%). No mobile phones or identification badges were positive for C. auris. The outbreak terminated following withdrawal of lanyards from ICU.

CONCLUSIONS:
This outbreak further implicates environmental reservoirs as sustaining C. auris ICU outbreaks. Identification of C. auris on cloth lanyards highlights the need to identify commonly handled moveable objects during an outbreak. We suggest that ICUs with a C. auris outbreak should investigate similar infrequently cleaned items as potential reservoirs and review their policies on lanyard use.
Effect of Scenario-Based Simulation Training on the Obstetrics and Gynecology Nursing Clinical Practicum
Authors: ŞENTÜRK ERENEL Ayten , YAMAN SÖZBİR Şengül , UZUN AKSOY Mehtap , ARSLAN GÜRCÜOĞLU Esra , PELİT AKSU Sıdıka , ÜNAL TOPRAK Filiz , UÇAKCI ASALIOĞLU Canan 
Published: January 2021

ABSTRACT

Background
Simulation practices in obstetrics and gynecology (OB-GYN) nursing are used in education, practice, assessment, and the investigation of interventional and behavioral skills related to both routine and emergency conditions.

Purpose
This study was conducted in an OB-GYN nursing course to determine the effect of simulation practices on clinical practice satisfaction, clinical stress, and self-confidence in nursing students.

Methods
A cluster randomized controlled experimental trial was conducted on 122 students (experimental group, n = 58; control group, n = 64). After theoretical training, all of the students applied six scenarios in the OB-GYN nursing simulation laboratory. The students in the experimental group began clinical practice after simulation training, whereas their peers in the control group began clinical practice without prior simulation training. Data in this study were collected using a personal information form, the Pagana Clinical Stress Questionnaire, a self-confidence scale, and a satisfaction subscale from the Clinical Learning Environment Scale on, respectively, the first day and final day of clinical practice.

Results
At the end of the clinical practice, average clinical stress in the control group was higher than that in the experimental group (p = .001). No intergroup difference was found in self-confidence levels (p > .05). For the control group, at posttest, the average satisfaction with the clinical learning environment was higher (p = .046) and the average satisfaction with the clinical learning environment was lower (p = .05). In contrast, no mean pretest–posttest differences were found in clinical stress and self-confidence levels in the experimental group (p > .05). In the control group, no mean pretest–posttest difference was found for the clinical learning environment (p > .05), whereas mean clinical stress (p < .001) and self-confidence (p = .012) levels were higher at posttest (p < .05).

Conclusions/Implications for Practice
The findings of this study indicate that simulation training interventions reduce clinical satisfaction and stress in students but do not influence self-confidence. Nursing educators may provide scenario-based simulation training to students taking OB-GYN courses to enhance their preparedness for clinical practice.
Validity and Reliability of the Instruments to Measure Colorectal Cancer Screening Benefits and Barriers—Turkish Version
Authors: Dönmez Elif , Nahcivan Nursen O. , Rawl Susan M. 
Published: January 2021

Background
Perceptions of benefits and barriers are important determinants in understanding colorectal cancer screening (CRCS) behaviors. There is a need for standardized Turkish tools that measure the benefits and barriers of fecal occult blood test (FOBT) and colonoscopy (COL).

Objective
The aim of this study was to assess the validity and reliability of the Turkish version of the “Instruments to Measure CRCS Benefits and Barriers.”

Methods
This methodological study was carried out in 2 stages in primary care and in 394 adults between the ages of 50 and 70 years. In the first stage, some items of the scales demonstrated low/unacceptable corrected item-total and factor loadings, and in the second stage, it was decided to add emoji-based facial scales, which include emoji expressions.

Results
Results with the emoji-based facial scales included internal consistency coefficients of 0.85 for FOBT benefits, 0.79 for FOBT barriers, 0.84 for COL benefits, and 0.86 for COL barriers; the item-total correlations of FOBT varied between 0.39 and 0.73, whereas those of COL varied between 0.38 and 0.76. The factor loadings of all items were higher than 0.40.

Conclusions
The emoji-based facial scale for CRC Screening Benefits and Barriers is a valid and reliable tool for measuring the benefits and barriers perceptions of 50- to 70-year-old Turkish adults.

Implications for Practice
The Instruments to Measure CRCS Benefits and Barriers–Turkish version can provide insights for nurses and healthcare professionals to understand individuals’ perceived FOBT and COL benefits and barriers and to develop effective interventions to increase CRCS rates.
Paired heavy and light chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses
Authors: Banach Bailey B. , Cerutti Gabriele , Fahad Ahmed S. , Shen Chen-Hsiang , de Souza Matheus Oliveira , Katsamba Phinikoula S. , Tsybovsky Yaroslav , Wang Pengfei , Nair Manoj S. , Huang Yaoxing , Urdániz Irene M. Francino , Steiner Paul J. , Gutiérrez-González Matias , Liu Lihong , López Acevedo Sheila N. , Nazzari Alexandra , Wolfe Jacy R. , Luo Yang , Olia Adam S. , Teng I-Ting , Yu Jian , Zhou Tongqing , Reddem Eswar R. , Bimela Jude , Pan Xiaoli , Madan Bharat , Laflin Amy D. , Nimrania Rajani , Yuen Kwon-Tung , Whitehead Timothy A. , Ho David D. , Kwong Peter D. , Shapiro Lawrence , DeKosky Brandon J. 
Published: January 2021

SummaryUnderstanding protective mechanisms of antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We discovered a new antibody, 910-30, that targets the SARS-CoV-2 ACE2 receptor binding site as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. We performed sequence and structural analyses to explore how antibody features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer revealed its binding interactions and ability to disassemble spike. Despite heavy chain sequence similarity, biophysical analyses of IGHV3-53/3-66 antibodies highlighted the importance of native heavy:light pairings for ACE2 binding competition and for SARS-CoV-2 neutralization. We defined paired heavy:light sequence signatures and determined antibody precursor prevalence to be ~1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These data reveal key structural and functional neutralization features in the IGHV3-53/3-66 public antibody class to accelerate antibody-based medical interventions against SARS-CoV-2.HighlightsA molecular study of IGHV3-53/3-66 public antibody responses reveals critical heavy and light chain features for potent neutralizationCryo-EM analyses detail the structure of a novel public antibody class member, antibody 910-30, in complex with SARS-CoV-2 spike trimerCryo-EM data reveal that 910-30 can both bind assembled trimer and can disassemble the SARS-CoV-2 spikeSequence-structure-function signatures defined for IGHV3-53/3-66 class antibodies including both heavy and light chainsIGHV3-53/3-66 class precursors have a prevalence of 1:44,000 B cells in healthy human antibody repertoires
Cellular mechanisms of heterogeneity inNF2-mutant schwannoma
Authors: Chiasson-MacKenzie Christine , Vitte Jeremie , Liu Ching-Hui , Wright Emily A. , Flynn Elizabeth A. , Stott Shannon L. , Giovannini Marco , McClatchey Andrea I. 
Published: January 2021

AbstractSchwannomas are common sporadic nervous system tumors and diagnostic features of familial neurofibromatosis type 2 (NF2) that develop predominantly on cranial and spinal nerves and cause severe neurological deficits and significant morbidity. Virtually all schwannomas result from inactivation of theNF2tumor suppressor gene with few, if any, cooperating mutations. Despite their genetic uniformity schwannomas exhibit remarkable clinical and therapeutic heterogeneity, which has impeded the success of early rational therapies. An understanding of how heterogeneity develops inNF2-mutant schwannomas is critically needed to improve therapeutic options for these patients. We have found that loss of the membrane:actin cytoskeleton-associated NF2 tumor suppressor protein, merlin, yields unstable intrinsic polarity and enablesNf2-/-Schwann cells to adopt distinct programs of coordinated ErbB ligand production and polarized signaling, suggesting a self-generated model of schwannoma heterogeneity. We validated the heterogeneous distribution of biomarkers of these programs in human schwannoma tissue and took advantage of the synchronous development of multiple lesions in a well-studied mouse model to establish a quantitative pipeline that can be used to study how schwannoma heterogeneity evolves and impacts nerve function and therapeutic response in mouse, and ultimately human schwannomas. Our studies inform a mounting appreciation that intrinsic mechanisms are major contributors to heterogeneity across many human cancers.
Designing novel biochemical pathways to commodity chemicals using ReactPRED and RetroPath2.0
Authors: Vigrass Eleanor , Islam M. Ahsanul 
Published: January 2021

AbstractCommodity chemicals are high-demand chemicals, used by chemical industries to synthesise cocountless chemical products of daily use. For many of these chemicals, the main production process uses petroleum-based feedstocks. Concerns over these limited resources and their associated environmental problems, as well as mounting global pressure to reduce CO2emissions have motivated efforts to find biochemical pathways capable of producing these chemicals. Advances in metabolic engineering have led to the development of technologies capable of designing novel biochemical pathways to commodity chemicals. Computational software tools, ReactPRED and RetroPath2.0 were utilised to design 49 novel pathways to produce benzene, phenol, and 1,2-propanediol — all industrially important chemicals with limited biochemical knowledge. A pragmatic methodology for pathway curation was developed to analyse thousands and millions of pathways that were generated using the software. This method utilises publicly accessible biological databases, including MetaNetX, PubChem, and MetaCyc to analyse the generated outputs and assign EC numbers to the predicted reactions. The workflow described here for pathway generation and curation can be used to develop novel biochemical pathways to commodity chemicals from numerous starting compounds.
Spontaneous and deliberate modes of creativity: Multitask eigen-connectivity analysis captures latent cognitive modes during creative thinking
Authors: Xie Hua , Beaty Roger E. , Jahanikia Sahar , Geniesse Caleb , Sonalkar Neeraj S. , Saggar Manish 
Published: January 2021

AbstractDespite substantial progress in the quest of demystifying the brain basis of creativity, several questions remain open. One such issue concerns the relationship between two latent cognitive modes during creative thinking, i.e., deliberate goal-directed cognition and spontaneous thought generation. Although an interplay between deliberate and spontaneous thinking is often indirectly implicated in the creativity literature (e.g., dual-process models), a bottom-up data-driven validation of the cognitive processes associated with creative thinking is still lacking. Here, we attempted to capture the latent modes of creative thinking by utilizing a data-driven approach on a novel continuous multitask paradigm (CMP) that widely sampled a hypothetical two-dimensional cognitive plane of deliberate and spontaneous thinking in a single fMRI session. The CMP consisted of eight task blocks ranging from undirected mind wandering to goal-directed working memory task, while also including two of the widely used creativity tasks, i.e., alternate uses task (AUT) and remote association task (RAT). Using data-driven eigen-connectivity (EC) analysis on the multitask whole-brain functional connectivity (FC) patterns, we embedded the multitask FCs into a low-dimensional latent space. The first two latent components, as revealed by the EC analysis, broadly mapped onto the two cognitive modes of deliberate and spontaneous thinking, respectively. Further, in this low-dimensional space, both creativity tasks were located in the upper right corner of high deliberate and spontaneous thinking (creative cognitive space). Neuroanatomically, the creative cognitive space was represented by not only increased intra-network connectivity within executive control and default mode networks, but also by a higher inter-network coupling between the two. Further, individual differences reflected in the low-dimensional connectivity embeddings were related to differences in deliberate and spontaneous thinking abilities. Altogether, using a continuous multitask paradigm and data-driven approach, we provide direct empirical evidence for the contribution of both deliberate and spontaneous modes of cognition during creative thinking.
Efficacy of B12 fortified nutrient bar and yogurt in improving plasma B12 concentrations – results from two double blind randomised placebo controlled trials
Authors: Yajnik Chittaranjan , Kasture Sonal , Kantikar Vaishali , Lubree Himangi , Bhat Dattatray , Raut Deepa , Memane Nilam , Bhalerao Aboli , Ladkat Rasika , Yajnik Pallavi , Tomar Sudhir , Limaye Tejas , Phatak Sanat 
Published: January 2021

AbstractBackgroundDietary vitamin B12 (B12) deficiency is common in Indians. It may affect hematologic and neurocognitive systems and maternal deficiency predisposes offspring to neural tube defects and non-communicable disease. Long-term tablet supplementation is not sustainable.ObjectiveTo study efficacy of B12 fortified nutrient bar and yogurt in improving plasma B12 concentrations in children and adults.MethodsTwo double-blind, placebo-controlled randomised directly observed therapy (DOT) trials were conducted: 1. Healthy children (10–13Y) were fed nutrient bar fortified with B12 (2 mcg), multiple micronutrients (B12 1.8 mcg) or placebo for 120 days. 2. Healthy adults (18–50Y) were fed yogurt fortified with B12 (2 mcg) or Propionibacterium (1×108cfu/g) or placebo for 120 days. B12, folate, homocysteine and hemoglobin concentrations and anthropometry were measured before and post intervention.ResultsWe randomised 164 children and 118 adults; adherence was 96% and 82% respectively. In children, B12 fortified bars increased B12 concentrations significantly above baseline (B12 alone: median +91 pmol/l, B12+ multiple micronutrients: +82 pmol/l) compared to placebo. In adults, B12 fortified yogurt increased B12 significantly (median +38 pmol/l) compared to placebo, but Propionibacterium did not. In both trials, homocysteine fell significantly with B12 supplementation. There was no significant difference in different groups in anthropometry and hemoglobin.ConclusionsB12 fortified foods are effective in improving B12 status in Indian children and adults. They could be used to improve vitamin B12 status in the national programs for children, adolescents and women of reproductive age. They could also be used as over the counter products.Brief HighlightsVitamin B12 deficiency is common in India. Culturally acceptable fortified foods will help reduce it. We performed two RCTs (children and adults) with B12 fortified nutrient bar and yogurt at near RDA doses and found significant improvement in B12 status. This has important implications for nutritional policy.