bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regenerative medicine for radiation emergencies
Authors: Higashi Yukihito , Yusoff Farina Mohamad , Kishimoto Shinji , Maruhashi Tatsuya 
Published: September 2020

ABSTRACT
Hiroshima University is a ‘medical institution for tertiary radiation emergencies’ and a ‘medical support organization as a part of the International Atomic Emergency Agency Emergency Preparedness Response–Response and Assistance Network (IAEA EPR-RANET)’. To establish a system of regenerative medicine for radiation emergencies with treatment by implantation of various types of cells derived from induced pluripotent stem (iPS) cells, it is necessary to establish methods of defense against and treatment for radiation-induced damage from nuclear power plant accidents and nuclear terrorism. It is also necessary to develop cell therapy, cellular repair technology and regenerative biotechnology as regenerative medicine for radiation emergencies. Such applications have not been established yet. To develop a regenerative medical system, by using the existing one, for radiation emergencies, we will attempt to manage the cell-processing center to establish a safe and secured iPS cell bank for radiation medicine. By using this iPS cell bank as the central leverage, we will develop an education program for radiation emergency medicine and construct a network of regenerative medicine for radiation emergency medicine.
An Efficient Bedside Measure Yields Prognostic Implications for Language Recovery in Acute Stroke Patients
Authors: Keator Lynsey M. , Faria Andreia V. , Kim Kevin T. , Saxena Sadhvi , Wright Amy E. , Sheppard Shannon M. , Breining Bonnie L. , Goldberg Emily , Tippett Donna C. , Meier Erin , Hillis Argye E. 
Published: September 2020

Background:
It is estimated that ∼30% of stroke survivors have aphasia, a language disorder resulting from damage to left-hemisphere language networks. In acute care settings, efficient identification of aphasia is critical, but there is a paucity of efficient bedside assessments.

Objective:
To determine whether objective measures on a picture description task administered within 48 hours post stroke (a) predict language recovery, (b) estimate left-hemisphere lesion volume and location, and (c) correlate with other bedside language assessments.

Method:
Behavioral data were scored at acute and chronic time points. Neuroimaging data were used to determine associations between the picture description task, other language assessments, and lesion volume and location.

Results:
Acute content units, age, and total lesion volume predicted communication recovery; F
3,18 = 3.98, P = 0.024; r
2 = 0.40. Significant correlations were found between the picture description task and lesion volume and location. Picture description outcomes were also associated with other clinical language assessments.

Discussion:
This picture description task quickly predicted the language performance (communication recovery and outcome) for patients who suffered a left-hemisphere stroke. Picture description task measures correlated with damage in the left hemisphere and with other, more time-consuming and cumbersome language assessments that are typically administered acutely at bedside.

Conclusion:
The predictive value of this picture description task and correlations with existing language assessments substantiate the clinical importance of a reliable yet rapid bedside measure for acute stroke patients that can be administered by a variety of health care professionals.
Investigations of Memory Monitoring in Individuals With Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment
Authors: Yu Hui , Wang Kai , Zhong Ping , Cheng Huai-Dong , Lv Xin-Yi , Yuan Li-Li 
Published: September 2020

Background:
Subjective cognitive decline (SCD) has been called the prodromal stage of amnestic mild cognitive impairment (aMCI); however, further investigation is needed to confirm this observation.

Objective:
To define the relationship between SCD and aMCI.

Method:
In this case-control study, we used the feeling-of-knowing in episodic memory (FOK–EM) test to measure the memory-monitoring function of 40 adults with aMCI, 60 with SCD, and 55 healthy controls.

Results:
The recognition rates of FOK–EM (53.53% ± 7.82%; 55.12% ± 6.08%) and judgment accuracy of the aMCI and SCD groups (γ values 0.21 ± 0.11; 0.30 ± 0.16) were significantly lower than those of the control group (72.32% ± 5.14%; 0.57 ± 0.16) (F = 116.24, P < 0.01; F = 128.57, P < 0.01; F = 73.33, P < 0.01). The scores for correct decision/correct recognition (RR; 27.2 ± 6.43; 29.36 ± 5.16) and correct decision/false recognition (RF; 30.41 ± 5.06; 27.26 ± 4.37) of the aMCI and SCD groups were also significantly lower than those of the control group (49.35 ± 7.13; 11.16 ± 4.35) (F
RR = 132.67, P < 0.01; F
RF = 131.8, P < 0.01).

Conclusion:
Mild clinical impairments in memory-monitoring function may precede clinically confirmed objective memory impairment in individuals with SCD.
The Unease When Using Anesthetics for Treatment-Refractory Status Epilepticus: Still Far Too Many Questions
Authors: Opić Petra , Sutter Raoul 
Published: September 2020

Summary:
Status epilepticus (SE), treatment-refractory status epilepticus (RSE), and super-treatment-refractory status epilepticus (SRSE) are associated with increased morbidity, mortality, and high socioeconomic burden and pose significant treatment challenges for intensivists and neurologists. To optimize and streamline emergency treatment, current practice guidelines recommend the use of continuously delivered intravenous anesthetic drugs such as midazolam, propofol, or barbiturates as the third-line therapy after first-line and second-line treatments have failed. Although the rationale for these third-line drugs seems intuitive at first glance, there is a clear paucity of evidence-based data on risks, benefits, and even on the choice of a third-line agent. Recent studies into safety and efficacy reveal disturbing results, such as a poor outcome and higher mortality associated with the use of intravenous anesthetic drugs, especially in patients with nonconvulsive SE without coma and in patients with out-of-hospital SE onset. Clinicians should deliberately weigh the advantages and disadvantages of intravenous anesthetic drug therapy in patients with different types of SE usually linked to a favorable outcome (i.e., simple partial, complex partial, or absence seizures). The lack of data to support evidence-based medicine prompts a careful balance of individual risks and benefits of intravenous anesthetic drug therapy in patients with SE, treatment-refractory SE, and super-RSE.
Drug Trials in Status Epilepticus: Current Evidence and Future Concepts
Authors: Mandge Vishal , Husain Aatif M. 
Published: September 2020

Summary:
Status epilepticus (SE) is a neurologic emergency with high morbidity and mortality. After many advances in the field, several unanswered questions remain for optimal treatment after the early stage of SE. This narrative review describes some of the important drug trials for SE treatment that have shaped the understanding of the treatment of SE. The authors also propose possible clinical trial designs for the later stages of SE that may allow assessment of currently available and new treatment options. Status epilepticus can be divided into four stages for treatment purposes: early, established, refractory, and superrefractory. Ongoing convulsive seizures for more than 5 minutes or nonconvulsive seizure activity for more than 10 to 30 minutes is considered early SE. Failure to control the seizure with first-line treatment (usually benzodiazepines) is defined as established SE. If SE continues despite treatment with an antiseizure medicine, it is considered refractory SE, which is usually treated with additional antiseizure medicines or intravenous anesthetic agents. Continued seizures for more than 24 hours despite use of intravenous anesthetic agents is termed superrefractory SE. Evidence-based treatment recommendations from high-quality clinical trials are available for only the early stages of SE. Among the challenges for designing a treatment trial for the later stages SE is the heterogeneity of semiology, etiology, age groups, and EEG correlates. In many instances, SE is nonconvulsive in later stages and diagnosis is possible only with EEG. EEG patterns can be challenging to interpret and only recently have consensus criteria for EEG diagnosis of SE emerged. Despite having these EEG criteria, interrater agreement in EEG interpretation can be challenging. Defining successful treatment can also be difficult. Finally, the ethics of randomizing treatment and possibly using a placebo in critically ill patients must also be considered. Despite these challenges, clinical trials can be designed that navigate these issues and provide useful answers for how best to treat SE at various stages.
Mendelian pathway analysis of laboratory traits reveals distinct roles for ciliary subcompartments in common disease pathogenesis
Authors: Drivas Theodore George , Lucas Anastasia , Zhang Xinyuan , Ritchie Marylyn DeRiggi 
Published: September 2020

SummaryRare monogenic disorders of the primary cilium, termed ciliopathies, are characterized by extreme presentations of otherwise-common diseases, such as diabetes, hepatic fibrosis, and kidney failure. However, despite a revolution in our understanding of the cilium’s role in rare disease pathogenesis, the organelle’s contribution to common disease remains largely unknown. We hypothesized that common genetic variants affecting Mendelian ciliopathy genes might also contribute to common complex diseases pathogenesis more generally. To address this question, we performed association studies of 16,875 common genetic variants across 122 well-characterized ciliary genes with 12 quantitative laboratory traits characteristic of ciliopathy syndromes in 378,213 European-ancestry individuals in the UK BioBank. We incorporated tissue-specific gene expression analysis, expression quantitative trait loci (eQTL) and Mendelian disease information into our analysis, and replicated findings in meta-analysis to increase our confidence in observed associations between ciliary genes and human phenotypes. 73 statistically-significant gene-trait associations were identified across 34 of the 122 ciliary genes that we examined (including 8 novel, replicating associations). With few exceptions, these ciliary genes were found to be widely expressed in human tissues relevant to the phenotypes being studied, and our eQTL analysis revealed strong evidence for correlation between ciliary gene expression levels and patient phenotypes. Perhaps most interestingly our analysis identified different ciliary subcompartments as being specifically associated with distinct sets of patient phenotypes, offering a number of testable hypotheses regarding the cilium’s role in common complex disease. Taken together, our data demonstrate the utility of a Mendelian pathway-based approach to genomic association studies, and challenge the widely-held belief that the cilium is an organelle important mainly in development and in rare syndromic disease pathogenesis. The continued application of techniques similar to those described here to other phenotypes/Mendelian diseases is likely to yield many additional fascinating associations that will begin to integrate the fields of common and rare disease genetics, and provide insight into the pathophysiology of human diseases of immense public health burden.Contacttheodore.drivas@gmail.com
Clinical evaluation of BD Veritor™SARS-CoV-2 point-of-care test performance compared to PCR-based testing and versus the Sofia®2 SARS Antigen point-of-care test
Authors: Young Stephen , Taylor Stephanie N. , Cammarata Catherine L. , Roger-Dalbert Celine , Montano Amanda , Griego-Fullbright Christen , Burgard Cameron , Fernandez Catherine , Eckert Karen , Andrews Jeffrey C. , Ren Huimiao , Allen Joseph , Ackerman Ronald , Cooper Charles K. 
Published: September 2020

ABSTRACTObjectivesThe clinical performance of the BD Veritor™ System for Rapid Detection of SARS-CoV-2 antigen (Veritor), a chromatographic immunoassay that detects the SARS-CoV-2 nucleocapsid antigen as a point-of-care test, was evaluated on nasal specimens from individuals with COVID-19 symptoms.Methods and MaterialsTwo studies were completed to determine clinical performance. In the first study, nasal specimens and either nasopharyngeal or oropharyngeal specimens from 251 participants with COVID-19 symptoms (≤7 days from symptom onset [DSO]), ≥18 years of age, were utilized to compare Veritor with the Lyra®SARS-CoV-2 PCR Assay (Lyra). In the second study, nasal specimens from 361 participants with COVID-19 symptoms (≤5 DSO), ≥18 years of age, were utilized to compare performance of Veritor to that of the Sofia®2 SARS Antigen FIA test (Sofia 2). Positive, negative, and overall percent agreement (PPA, NPA, and OPA, respectively) were the primary outcomes.ResultsIn study 1, PPA for Veritor, compared to Lyra, ranged from 81.8%-87.5% for 0-1 through 0-6 DSO ranges. In study 2, Veritor had a PPA, NPA, and OPA of 97.4%, 98.1%, and 98.1%, respectively, with Sofia 2. Discordant analysis showed one Lyra positive missed by Veritor and five Lyra positives missed by Sofia 2; one Veritor positive result was negative by Lyra.ConclusionsVeritor met FDA-EUA acceptance criteria for SARS-CoV-2 antigen testing (≥80% PPA point estimate) for the 0-5 and 0-6 DSO ranges. Veritor and Sofia 2 showed a high degree of agreement for SARS-CoV-2 detection. The Veritor test should facilitate rapid and reliable results for COVID-19 diagnosis utilizing easy-to-collect nasal swabs.SummaryThe BD Veritor SARS-CoV-2 antigen test met FDA-EUA acceptance criteria for SARS-CoV-2 antigen testing for subjects with COVID-19 symptoms (0-5 days post-onset). BD Veritor and Quidel Sofia 2 antigen tests had good agreement for SARS-CoV-2 detection; discordant analysis favored Veritor.
The impact of hypertension and use of calcium channel blockers on tuberculosis treatment outcomes
Authors: Chidambaram Vignesh , Gupte Akshay , Wang Jann-Yuan , Golub Jonathan E. , Karakousis Petros C. 
Published: September 2020

AbstractBackgroundHypertension induces systemic inflammation, but its impact on the outcome of infectious diseases like tuberculosis (TB) is unknown. Calcium channel blockers (CCB) improve TB treatment outcomes in pre-clinical models, but their effect in patients with TB remain unclear.MethodsThis retrospective cohort study, including all patients > 18 years receiving treatment for culture-confirmed, drug-sensitive TB from 2000 to 2016 at the National Taiwan University Hospital, assessed the association of hypertension and CCB use with all-cause and infection-related mortality during the first 9 months of TB treatment, as well as sputum-smear microscopy and sputum-culture positivity at 2 and 6 months.Results1052 of the 2894 patients (36.4%) had hypertension. Multivariable analysis revealed that hypertension was associated with increased mortality due to all causes (HR 1.57, 95% confidence interval[CI], 1.23-1.99) and infections (HR 1.87, 95%CI, 1.34-2.6), but there was no statistical difference in microbiological outcomes when stratified based on hypertensive group. Dihydropyridine-CCB (DHP-CCB) use was associated with reduced all-cause mortality (HR 0.67, 95%CI: 0.45-0.98) only by univariate Cox regression. There was no association between DHP-CCB use and infection-related mortality (HR 0.78, 95%CI: 0.46-1.34) or microbiological outcomes in univariate or multivariate regression analyses.ConclusionsPatients with hypertension have increased all-cause mortality and infection-related mortality during the 9 months following TB treatment initiation. DHP-CCB use may lower all-cause mortality in TB patients with hypertension. The presence of hypertension or the use of CCB did not result in a significant change in microbiological outcomes.
Fine-scale spatial patterns of wildlife disease are common and understudied
Authors: Albery Gregory F , Sweeny Amy R , Becker Daniel J , Bansal Shweta 
Published: September 2020

AbstractAll parasites are heterogeneous in space, yet little is known about the prevalence and scale of this spatial variation, particularly in wild animal systems. To address this question, we sought to identify and examine spatial dependence of wildlife disease across a wide range of systems.Conducting a broad literature search, we collated 31 such datasets featuring 89 replicates and 71 unique host-parasite combinations, only 51% of which had previously been used to test spatial hypotheses. We analysed these datasets for spatial dependence within a standardised modelling framework using Bayesian linear models, and we then meta-analysed the results to identify generalised determinants of the scale and magnitude of spatial autocorrelation.We detected spatial autocorrelation in 48/89 model replicates (54%) across 21/31 datasets (68%), spread across parasites of all groups. Even some very small study areas (under 0.01km2) exhibited substantial spatial variation.Despite the common manifestation of spatial variation, our meta-analysis was unable to identify host-, parasite-, or sampling-level determinants of this heterogeneity across systems. Parasites of all transmission modes had easily detectable spatial patterns, implying that structured contact networks and susceptibility effects are potentially as important in spatially structuring disease as are environmental drivers of transmission efficiency.Our findings demonstrate that fine-scale spatial patterns of infection manifest frequently and across a range of wild animal systems, and many studies are able to investigate them whether or not the original aim of the study was to examine spatially varying processes. Given the widespread nature of these findings, studies should more frequently record and analyse spatial data, facilitating development and testing of spatial hypotheses in disease ecology. Ultimately, this may pave the way for ana prioripredictive framework for spatial variation in novel host-parasite systems.
Accurate transcription start sites enable mining for the cis-regulatory determinants of tissue specific gene expression
Authors: Ansariola Mitra , Fraser Valerie N. , Filichkin Sergei A. , Ivanchenko Maria G. , Bright Zachary A. , Gould Russell A. , Ozguc Olivia R. , O’Neil Shawn T. , Megraw Molly 
Published: September 2020

AbstractAcross tissues, gene expression is regulated by a combination of determinants, including the binding of transcription factors (TFs), along with other aspects of cellular state. Recent studies emphasize the importance of both genetic and epigenetic states – TF binding sites and binding site chromatin accessibility have emerged as potentially causal determinants of tissue specificity. To investigate the relative contributions of these determinants, we constructed three genome-scale datasets for both root and shoot tissues of the sameArabidopsis thalianaplants: TSS-seq data to identify Transcription Start Sites, OC-seq data to identify regions of Open Chromatin, and RNA-seq data to assess gene expression levels. For genes that are differentially expressed between root and shoot, we constructed a machine learning model predicting tissue of expression from chromatin accessibility and TF binding information upstream of TSS locations. The resulting model was highly accurate (over 90% auROC and auPRC), and our analysis of model contributions (feature weights) strongly suggests that patterns of TF binding sites within ∼500 nt TSS-proximal regions are predominant explainers of tissue of expression in most cases. Thus, in plants, cis-regulatory control of tissue-specific gene expression appears to be primarily determined by TSS-proximal sequences, and rarely by distal enhancer-like accessible chromatin regions. This study highlights the exciting future possibility of a native TF site-based design process for the tissue-specific targeting of plant gene promoters.
Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles
Authors: Koloteva-Levine Nadejda , Marchante Ricardo , Purton Tracey J. , Hiscock Jennifer R. , Tuite Mick F. , Xue Wei-Feng 
Published: September 2020

ABSTRACTAmyloid seeds are nanometre-sized protein particles that accelerate amyloid assembly, as well as propagate and transmit the amyloid protein conformation associated with a wide range of protein misfolding diseases. However, seeded amyloid growth through templated elongation at fibril ends cannot explain the full range of molecular behaviours observed during cross-seeded formation of amyloid by heterologous seeds. Here, we demonstrate that amyloid seeds can accelerate amyloid formation via a surface catalysis mechanism without propagating the specific amyloid conformation associated with the seeds. This type of seeding mechanism is demonstrated through quantitative characterisation of the cross-seeded assembly reactions involving two non-homologous and unrelated proteins: the human Aβ42 peptide and the yeast prion-forming protein Sup35NM. Our results suggest experimental approaches to differentiate seeding by templated elongation from non-templated amyloid seeding, and rationalise the molecular mechanism of the cross-seeding phenomenon as a manifestation of the aberrant surface activities presented by amyloid seeds as nanoparticles.
Response to Kozlovet al.: Inaccurate estimation of biases in herbarium specimen data
Authors: Meineke Emily K. , Davis Charles C. , Jonathan Davies T. 
Published: September 2020

SummaryKozlov and colleagues1call into question the application of herbarium specimens to quantify historical patterns of herbivory2–5. It is already widely appreciated that collectors of herbarium specimens may tend to avoid insect damage, thus making herbivory estimates from herbarium specimens potentially down-biased2. However, Kozlovet al.additionally suggest that variation in sampling selectivity among collectors and curators may lead herbarium specimens to misrepresent patterns of herbivory in nature. The authors sought to quantify these biases by collecting and contrasting insect herbivory data across 17 plant species from herbarium versus standard field ecological sampling procedures, and then assessed the selection of these specimens by curators. They concluded that herbivory estimates from herbarium specimens are highly variable, rendering them an inaccurate representation of herbivory in nature. Our re-analysis of Kozlovet al.’s data suggests that, in contrast with their results, herbarium specimens indeed provide a useful record of herbivory as long as sample sizes are appropriate. In addition, we assert that by arguing that herbarium specimens are “distorting mirrors”, Kozlovet al.’s conclusions fundamentally overstep their data, which narrowly assesses biases across species. Kozlovet al.argue that herbarium specimens are inaccurate data sources, but fail to characterize the specific circumstances under which assumed biases would apply. Thus, Kozlovet al.’s data do not support their main premise, and the authors extrapolate beyond the specific biases investigated in their study; we believe their contribution does a disservice to researchers interested in exploring the potential value of herbarium specimens for studying herbivory through time.