bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bayesian approach to analysing cortico-cortical associative stimulation induced increases in the excitability of corticospinal projections in humans
Authors: Carson Richard G. , Capozio Antonio , McNickle Emmet , Sack Alexander T. 
Published: October 2020

AbstractRepeated pairing of transcranial magnetic stimulation (TMS) over left and right primary motor cortex (M1), at intensities sufficient to generate descending volleys, produces sustained increases in corticospinal excitability. In other paired associative stimulation (PAS) protocols, in which peripheral afferent stimulation is the first element, changes in corticospinal excitability achieved when the second stimulus consists of brief bursts of transcranial alternating current stimulation (tACS), are comparable to those obtained if TMS is used instead (McNickle and Carson 2015). The present aim was to determine whether associative effects are induced when the first stimulus of a cortico-cortical pair is tACS, or alternatively subthreshold TMS. Bursts of tACS (500 ms; 140 Hz; 1 mA) were associated (180 stimulus pairs) with single magnetic stimuli (120% resting motor threshold rMT) delivered over the opposite (left) M1. The tACS ended 6 ms prior to the TMS. In a separate condition, TMS (55% rMT) was delivered to right M1 6 ms before (120% rMT) TMS was applied over left M1. In a sham condition, TMS (120% rMT) was delivered to left M1 only. The limitations of null hypothesis significance testing are well documented. We therefore employed Bayes factors to assess evidence in support of experimental hypotheses—defined precisely in terms of predicted effect sizes, that these two novel variants of PAS increase corticospinal excitability. Although both interventions induced sustained (~ 20–30 min) increases in corticospinal excitability, the evidence in support of the experimental hypotheses (over specified alternatives) was generally greater for the paired TMS-TMS than the tACS-TMS conditions.
The incidence and influence of the donor corneas positive for herpesviridae DNA in keratoplasty
Authors: Qu Jing-hao , Peng Rong-mei , Xiao Ge-ge , Qu Hong-qiang , Yu Ting , Zhang Shuang , Hong Jing 
Published: October 2020

Abstract
Purpose
We detected the DNA of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in donor corneas and assessed the clinical outcomes of recipients who received virus-positive grafts.

Method
All donor corneas were analyzed for the presence of HSV-1, HSV-2, VZV, CMV, and EBV by real-time PCR from April 2017 to July 2019. The medical records of the transplant patients who received virus-positive grafts were reviewed.

Result
Twenty-three (2.44%) donor cornea buttons tested positive for herpesviridae DNA. The positivity rates of HSV-1, CMV, VZV, and EBV were 0.74%, 0.85%, 0.64%, and 0.21%, respectively.

Conclusion
We suggest that the corneas from donors who had cancer, donors who were inpatients, and donors who had immunodeficiency or who were on immunosuppressive therapy should be tested for herpesviridae DNA before transplantation. Finally, HSV-1 can be transmitted from graft to recipient, but that CMV cannot be transmitted according to our observations. The donor corneas found to be HSV-1-positive have to be discarded and not used for keratoplasty.
Disease-associated HCN4 V759I variant is not sufficient to impair cardiac pacemaking
Authors: Erlenhardt Nadine , Kletke Olaf , Wohlfarth Franziska , Komadowski Marlene A. , Clasen Lukas , Makimoto Hisaki , Rinné Susanne , Kelm Malte , Jungen Christiane , Decher Niels , Meyer Christian , Klöcker Nikolaj 
Published: October 2020

AbstractThe hyperpolarization-activated cation current If is a key determinant for cardiac pacemaker activity. It is conducted by subunits of the hyperpolarization-activated cyclic nucleotide–gated (HCN) channel family, of which HCN4 is predominant in mammalian heart. Both loss-of-function and gain-of-function mutations of the HCN4 gene are associated with sinus node dysfunction in humans; however, their functional impact is not fully understood yet. Here, we sought to characterize a HCN4 V759I variant detected in a patient with a family history of sick sinus syndrome. The genomic analysis yielded a mono-allelic HCN4 V759I variant in a 49-year-old woman presenting with a family history of sick sinus syndrome. This HCN4 variant was previously classified as putatively pathogenic because genetically linked to sudden infant death syndrome and malignant epilepsy. However, detailed electrophysiological and cell biological characterization of HCN4 V759I in Xenopus laevis oocytes and embryonic rat cardiomyocytes, respectively, did not reveal any obvious abnormality. Voltage dependence and kinetics of mutant channel activation, modulation of cAMP-gating by the neuronal HCN channel auxiliary subunit PEX5R, and cell surface expression were indistinguishable from wild-type HCN4. In good agreement, the clinically likewise affected mother of the patient does not exhibit the reported HCN4 variance. HCN4 V759I resembles an innocuous genetic HCN channel variant, which is not sufficient to disturb cardiac pacemaking. Once more, our work emphasizes the importance of careful functional interpretation of genetic findings not only in the context of hereditary cardiac arrhythmias.
A CRISPR and high-content imaging assay compliant with ACMG/AMP guidelines for clinical variant interpretation in ciliopathies
Authors: Nazlamova Liliya , Thomas N. Simon , Cheung Man-Kim , Legebeke Jelmer , Lord Jenny , Pengelly Reuben J. , Tapper William J. , Wheway Gabrielle 
Published: October 2020

AbstractCiliopathies are a broad range of inherited developmental and degenerative diseases associated with structural or functional defects in motile or primary non-motile cilia. There are around 200 known ciliopathy disease genes and whilst genetic testing can provide an accurate diagnosis, 24–60% of ciliopathy patients who undergo genetic testing do not receive a genetic diagnosis. This is partly because following current guidelines from the American College of Medical Genetics and the Association for Molecular Pathology, it is difficult to provide a confident clinical diagnosis of disease caused by missense or non-coding variants, which account for more than one-third of cases of disease. Mutations in PRPF31 are the second most common cause of the degenerative retinal ciliopathy autosomal dominant retinitis pigmentosa. Here, we present a high-throughput high-content imaging assay providing quantitative measure of effect of missense variants in PRPF31 which meets the recently published criteria for a baseline standard in vitro test for clinical variant interpretation. This assay utilizes a new PRPF31+/– human retinal cell line generated using CRISPR gene editing to provide a stable cell line with significantly fewer cilia in which novel missense variants are expressed and characterised. We show that high-content imaging of cells expressing missense variants in a ciliopathy gene on a null background can allow characterisation of variants according to the cilia phenotype. We hope that this will be a useful tool for clinical characterisation of PRPF31 variants of uncertain significance, and can be extended to variant classification in other ciliopathies.
Managing groundwater supplies subject to drought: perspectives on current status and future priorities from England (UK)
Authors: Ascott M. J. , Bloomfield J. P. , Karapanos I. , Jackson C. R. , Ward R. S. , McBride A. B. , Dobson B. , Kieboom N. , Holman I. P. , Van Loon A. F. , Crane E. J. , Brauns B. , Rodriguez-Yebra A. , Upton K. A. 
Published: October 2020

AbstractEffective management of groundwater resources during drought is essential. How is groundwater currently managed during droughts, and in the face of environmental change, what should be the future priorities? Four themes are explored, from the perspective of groundwater management in England (UK): (1) integration of drought definitions; (2) enhanced fundamental monitoring; (3) integrated modelling of groundwater in the water cycle; and (4) better information sharing. Whilst these themes are considered in the context of England, globally, they are relevant wherever groundwater is affected by drought.
A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI)
Authors: Shinozaki Katsunori , Yamada Takeshi , Nasu Junichiro , Matsumoto Toshihiko , Yuasa Yasuhiro , Shiraishi Takeshi , Nagano Hiroaki , Moriyama Ichiro , Fujiwara Toshiyoshi , Miguchi Masashi , Yoshida Ryosuke , Nozaka Kimiyasu , Tanioka Hiroaki , Nagasaka Takeshi , Kurisu Yasuro , Kobayashi Michiya , Tsuchihashi Kenji , Inukai Michio , Kikuchi Takashi , Nishina Tomohiro 
Published: October 2020

Abstract
Purpose
FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes.

Methods
Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR).

Results
Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8–77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively.

Conclusions
FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.
Generative Learning: Which Strategies for What Age?
Authors: Brod Garvin 
Published: October 2020

AbstractGenerative learning strategies are intended to improve students’ learning by prompting them to actively make sense of the material to be learned. But are they effective for all students? This review provides an overview of six popular generative learning strategies: concept mapping, explaining, predicting, questioning, testing, and drawing. Its main purpose is to review for what ages the effectiveness of these strategies has been demonstrated and whether there are indications of age-related differences in their effectiveness. The description of each strategy covers (1) how it is supposed to work, (2) the evidence on its effectiveness in different age groups, and (3) if there are age-related differences in its effectiveness. It is found that while all six generative learning strategies reviewed have proven effective for university students, evidence is mixed for younger students. Whereas some strategies (practice testing, predicting) seem to be effective already in lower-elementary-school children, others (drawing, questioning) seem to be largely ineffective until secondary school. The review closes with a call for research on the cognitive and metacognitive prerequisites of generative learning that can explain these differences.
High power and stable P-doped yolk-shell structured Si@C anode simultaneously enhancing conductivity and Li+ diffusion kinetics
Authors: Chen Ming , Zhou Qinnan , Zai Jiantao , Iqbal Asma , Tsega TsegayeTadesse , Dong Boxu , Liu Xuejiao , Zhang Yuchi , Yan Changyu , Zhao Liang , Nazakat Ali , E SharelPeisan , Low CheeTongJohn , Qian Xuefeng 
Published: October 2020

AbstractSilicon is a low price and high capacity anode material for lithium-ion batteries. The yolk-shell structure can effectively accommodate Si expansion to improve stability. However, the limited rate performance of Si anodes can’t meet people’s growing demand for high power density. Herein, the phosphorus-doped yolk-shell Si@C materials (P-doped Si@C) were prepared through carbon coating on P-doped Si/SiOx matrix to obtain high power and stable devices. Therefore, the as-prepared P-doped Si@C electrodes delivered a rapid increase in Coulombic efficiency from 74.4% to 99.6% after only 6 cycles, high capacity retention of ∼ 95% over 800 cycles at 4 A·g−1, and great rate capability (510 mAh·g−1 at 35 A·g−1). As a result, P-doped Si@C anodes paired with commercial activated carbon and LiFePO4 cathode to assemble lithium-ion capacitor (high power density of ∼ 61,080 W·kg−1 at 20 A·g−1) and lithium-ion full cell (good rate performance with 68.3 mAh·g−1 at 5 C), respectively. This work can provide an effective way to further improve power density and stability for energy storage devices.
Child murder in the Early Bronze Age: proteomic sex identification of a cold case from Schleinbach, Austria
Authors: Rebay-Salisbury Katharina , Janker Lukas , Pany-Kucera Doris , Schuster Dina , Spannagl-Steiner Michaela , Waltenberger Lukas , Salisbury Roderick B. , Kanz Fabian 
Published: October 2020

AbstractThe identification of sex-specific peptides in human tooth enamel by nanoflow liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) represents a quantum leap for the study of childhood and social relations more generally. Determining sex-related differences in prehistoric child rearing and mortality has been hampered by the insufficient accuracy in determining the biological sex of juveniles. We conducted mass spectrometric analysis to identify sex-specific peptides in the dental enamel of a child from a settlement pit of the Early Bronze Age settlement of Schleinbach, Austria (c. 1950–1850 bc). Four perimortal impression fractures on the skull of a 5–6-year-old child indicate an intentional killing, with a co-buried loom weight as possible murder weapon. Proteomic analysis, conducted for the first time on prehistoric teeth in Austria, determined the child’s sex as male. While we cannot conclusively determine whether the child was the victim of conflicts between village groups or was slain by members of his own community, we suggest that contextual evidence points to the latter. A possible trigger of violence was the follow-on effects of an uncontrolled middle ear infection revealed by an osteological analysis. The boy from Schleinbach highlights the potential for further investigation of gender-biased violence, infanticide and child murder based on the recently developed method of proteomic sex identification.
Perceived Adverse Effects of Separating Government Institutions for Disaster Risk Reduction and Climate Change Adaptation Within the Southern African Development Community Member States
Authors: Nemakonde Livhuwani D. , Van Niekerk Dewald , Becker Per , Khoza Sizwile 
Published: October 2020

AbstractIntegration of disaster risk reduction (DRR) and climate change adaptation (CCA) is widely recognized as a solution for reducing the risk and impacts of disasters. However, successful integration seems elusive, and the two goals continue to function in isolation and in parallel. This article provides empirical insights into the perceived effects of separating government institutions for DRR and CCA within the Southern African Development Community member states. A mixed method research design was applied to the study. A total of 40 respondents from Botswana, Eswatini (until April 2018 Swaziland), Madagascar, Malawi, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe participated in face-to-face interviews or an online survey. Five major effects of separating the organizations for DRR and CCA that impede efforts to reduce disaster risk coherently were identified: duplication of services, polarization of interventions, incoherent policies, competition for the same resources, and territorial contests. Given the continued fragmentation of institutions for DRR and CCA, highlighting these effects is important to emphasize the need for integrated approaches towards the reduction of disaster risk.
Using mobile technology in assessment of entrustable professional activities in undergraduate medical education
Authors: Duggan Norah , Curran Vernon R. , Fairbridge Nicholas A. , Diana Deacon Diana , Coombs Heidi , Stringer Katherine , Pennell Stephen 
Published: October 2020

Background The adoption of competency-based medical education requires objective assessments of a learner’s capability to carry out clinical tasks within workplace-based learning settings. This study involved an evaluation of the use of mobile technology to record entrustable professional activity assessments in an undergraduate clerkship curriculum.
Approach A paper-based form was adapted to a mobile platform called eClinic Card. Students documented workplace-based assessments throughout core clerkship and preceptors confirmed accuracy via mobile phones. Assessment scores for the 2017–2018 academic year were collated and analyzed for all core rotations, and preceptors and students were surveyed regarding the mobile assessment experience.
Evaluation The mobile system enabled 80 students and 624 preceptors to document 6850 assessment submissions across 47 clinical sites over a 48-week core clerkship curriculum. Students’ scores demonstrated progressive improvement across all entrustable professional activities with stage-appropriate levels of independence reported by end of core clerkship. Preceptors and students were satisfied with ease of use and dependability of the mobile assessment platform; however, students felt quality of formative coaching feedback could be improved.
Reflection Our preliminary evaluation suggests the use of mobile technology to assess entrustable professional activity achievement across a core clerkship curriculum is a feasible and acceptable modality for workplace-based assessment. The use of mobile technology supported a programmatic assessment approach. However, meaningful coaching feedback, as well as faculty development and support, emerged as key factors influencing successful adoption and usage of entrustable professional activities within an undergraduate medical curriculum.
Alcohol-Induced Neuropathy in Chronic Alcoholism: Causes, Pathophysiology, Diagnosis, and Treatment Options
Authors: Dudek Iga , Hajduga Danuta , Sieńko Cezary , Maani Amr , Sitarz Elżbieta , Sitarz Monika , Forma Alicja 
Published: October 2020

AbstractPurpose of the ReviewAlcohol abuse causes a wide range of disorders that affect the nervous system. These include confusion, cerebellar ataxia, peripheral neuropathy, and cognitive impairment. Chronic and excessive alcohol consumption is the primary cause of peripheral neuropathy. It is worth noting that peripheral neuropathy has no reliable treatment due to the poor understanding of its pathology.Recent FindingsCoasting is a major feature of alcoholic neuropathy, largely due to chronic alcohol abuse. Its major features are hyperalgesia, allodynia, and burning pain. Even though much research was done in this area, still we do not have a full understanding of the mechanism of alcoholic neuropathy. However, some theories have been proposed. These include direct or indirect effects of alcohol metabolites, impaired axonal transport, suppressed excitatory nerve pathway activity, or imbalance in neurotransmitters. Activation of spinal cord microglia, mGlu5 spinal cord receptors, and hypothalamic-pituitary-adrenal axis also seem to be implicated in the pathophysiology of this alcoholic neuropathy. The goal of treatment is to impede further damage to the peripheral nerves while also restoring their normal physiology. Alcohol abstinence, intake of balanced diets, and treatment with medications are suggested including benfotiamine, alpha-lipoic acid, acetyl-l-carnitine, vitamin E, methylcobalamin, myo-inositol,N-acetylcysteine, capsaicin, tricyclic antidepressants, or antiepileptic drugs.SummaryThis review focuses on the many pathways that play a role in the onset and development of alcohol-induced neuropathy, as well as present the possible treatment strategies of this disorder, providing insights into a further search of new treatment modalities.
Immunomodulatory Therapies for COVID-19 in Solid Organ Transplant Recipients
Authors: Fernández-Ruiz Mario , Aguado José María 
Published: October 2020

Abstract
Purpose of Review
Severe coronavirus disease 2019 (COVID-19) is characterized by the development of a deleterious hyperinflammatory response, in which the pleiotropic cytokine interleukin (IL)-6 plays a pivotal role. The administration of immunomodulatory therapies has been proposed to revert the tissue damage induced by COVID-19-related cytokine release syndrome (CRS). The present review summarizes the biological rationale and available clinical experience with this therapeutic strategy in the specific scenario solid organ transplantation (SOT).

Recent Findings
A number of case reports, case series, and non-controlled cohort studies have assessed the efficacy and safety of the anti-IL-6-receptor monoclonal tocilizumab in SOT (namely kidney transplantation) recipients with COVID-19 pneumonia and CRS. Although the heterogeneity in patient management and the lack of a control group limit the interpretation of these results, tocilizumab therapy appears to provide some clinical benefit in post-transplant COVID-19 and to be reasonably safe in terms of bacterial superinfection. A large randomized clinical trial (RCT) has shown survival benefit with adjuvant corticosteroids in non-transplant patients, but supporting evidence is scarce for SOT recipients and confounded by the variable adjustment of baseline immunosuppression. Anecdotal experiences have been reported with the use of the anti-IL-1 agent anakinra and the NLRP3 inflammasome inhibitor colchicine in this population.

Summary
Immunomodulation has emerged as a promising option for SOT recipients with COVID-19-related CRS, with available experience mainly restricted to the anti-IL-6 agent tocilizumab. However, the supporting evidence is scarce and of low quality. In the absence of RCT, observational studies including well-matched control groups should be designed in future.