julilili42/papers huggingface dataset:
5-Year Outcomes with Cobimetinib plus Vemurafenib in BRAFV600 Mutation–Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study
2021-06-22

Abstract Purpose: The randomized phase III coBRIM study (NCT01689519) demonstrated improved progression-free survival (PFS) and overall survival (OS) with addition of cobimetinib to vemurafenib compared with vemurafenib in patients with previously untreated BRAFV600 mutation–positive advanced melanoma. We report long-term follow-up of coBRIM, with at least 5 years since the last patient was randomized. Patients and Methods: Eligible patients were randomized 1:1 to receive either oral cobimetinib (60 mg once daily on days 1–21 in each 28-day cycle) or placebo in combination with oral vemurafenib (960 mg twice daily). Results: 495 patients were randomized to cobimetinib plus vemurafenib (n = 247) or placebo plus vemurafenib (n = 248). Median follow-up was 21.2 months for cobimetinib plus vemurafenib and 16.6 months for placebo plus vemurafenib. Median OS was 22.5 months (95% CI, 20.3–28.8) with cobimetinib plus vemurafenib and 17.4 months (95% CI, 15.0–19.8) with placebo plus vemurafenib; 5-year OS rates were 31% and 26%, respectively. Median PFS was 12.6 months (95% CI, 9.5–14.8) with cobimetinib plus vemurafenib and 7.2 months (95% CI, 5.6–7.5) with placebo plus vemurafenib; 5-year PFS rates were 14% and 10%, respectively. OS and PFS were longest in patients with normal baseline lactate dehydrogenase levels and low tumor burden, and in those achieving complete response. The safety profile remained consistent with previously published reports. Conclusions: Extended follow-up of coBRIM confirms the long-term clinical benefit and safety profile of cobimetinib plus vemurafenib compared with vemurafenib monotherapy in patients with BRAFV600 mutation–positive advanced melanoma.
Transdiagnostic efficacy of a group exercise intervention for outpatients with heterogenous psychiatric disorders: a randomized controlled trial
2021-06-22

Abstract Background Exercise efficaciously reduces disorder-specific symptoms of psychiatric disorders. The current study aimed to examine the efficacy of a group exercise intervention on global symptom severity and disorder-specific symptoms among a mixed outpatient sample. Methods Groups of inactive outpatients, waiting for psychotherapy, with depressive disorders, anxiety disorders, insomnia, and attention-deficit/hyperactivity disorders were randomized to a manualized 12-week exercise intervention, combining moderate to vigorous aerobic exercise with techniques for sustainable exercise behaviour change ( n = 38, female = 71.1% ( n = 27), M age = 36.66), or a passive control group ( n = 36, female = 75.0% ( n = 27), M age = 34.33). Primary outcomes were global symptom severity and disorder-specific symptoms, measured with the Symptom Checklist-90-Revised and Pittsburgh Sleep Quality Index pre- and post-treatment. Secondary outcome was the self-reported amount of exercise (Physical Activity, Exercise, and Sport Questionnaire), measured pre-treatment, intermediate-, and post-treatment. Intention-to-treat analyses were conducted using linear mixed models. Linear regressions were conducted to examine the effect of the change of exercise behaviour on the change of symptoms. Results The intervention significantly improved global symptom severity ( d = 0.77, p = .007), depression ( d = 0.68, p = .015), anxiety ( d = 0.87, p = .002), sleep quality ( d = 0.88, p = .001), and increased the amount of exercise ( d = 0.82, p &lt; .001), compared to the control group. Post-treatment differences between groups were significant for depression ( d = 0.63, p = .031), sleep quality ( d = 0.61, p = .035) and the amount of exercise ( d = 1.45, p &lt; .001). Across both groups, the reduction of global symptom severity was significantly predicted by an increase of exercise ( b = .35, p = .012). Conclusions The exercise intervention showed transdiagnostic efficacy among a heterogeneous clinical sample in a realistic outpatient setting and led to sustained exercise behaviour change. Exercise may serve as an efficacious and feasible transdiagnostic treatment option improving the existing treatment gap within outpatient mental health care settings. Trial registration The study was registered on ClinicalTrials.gov (ID: NCT03542396 , 25/04/2018).
Comparison of Risk Factors, Safety, and Efficacy Outcomes of Mechanical Thrombectomy in Posterior vs. Anterior Circulation Large Vessel Occlusion
2021-06-22

Background and Purpose: It is believed that stroke occurring due to posterior circulation large vessel occlusion (PCLVO) and that occurring due to anterior circulation large vessel occlusion (ACLVO) differ in terms of their pathophysiology and the outcome of their acute management in relation to endovascular mechanical thrombectomy (MT). Limited sample size and few randomized controlled trials (RCTs) with respect to PCLVO make the safety and efficacy of MT, which has been confirmed in ACLVO, difficult to assess in the posterior circulation. We therefore conducted a meta-analysis to study to which extent MT in PCLVO differs from ACLVO. Materials and Methods: We searched the databases PubMed, Cochrane, and EMBASE for studies published between 2010 and January 2021, with information on risk factors, safety, and efficacy outcomes of MT in PCLVO vs. ACLVO and conducted a systematic review and meta-analysis; we compared baseline characteristics, reperfusion treatment profiles [including rates of intravenous thrombolysis (IVT) and onset-to-IVT and onset-to-groin puncture times], recanalization success [Thrombolysis In Cerebral Infarction scale (TICI) 2b/3], symptomatic intracranial hemorrhage (sICH), and favorable functional outcome [modified Rankin Score (mRS) 0–2] and mortality at 90 days. Results: Sixteen studies with MT PCLVO (1,172 patients) and ACLVO (7,726 patients) were obtained from the search. The pooled estimates showed higher baseline National Institutes of Health Stroke Scale (NIHSS) score (SMD 0.32, 95% CI 0.15–0.48) in the PCLVO group. PCLVO patients received less often IVT (OR 0.65, 95% CI 0.53–0.79). Onset-to-IVT time (SMD 0.86, 95% CI 0.45–1.26) and onset-to-groin puncture time (SMD 0.59, 95% CI 0.33–0.85) were longer in the PCLVO group. The likelihood of obtaining successful recanalization and favorable functional outcome at 90 days was comparable between the two groups. PCLVO was, however, associated with less sICH (OR 0.56, 95% CI 0.37–0.85) but higher mortality (OR 1.92, 95% CI 1.46–2.53). Conclusions: This meta-analysis indicates that MT in PCLVO may be comparably efficient in obtaining successful recanalization and 90 day favorable functional outcome just as in ACLVO. Less sICH in MT-treated PCLVO patients might be the result of the lower IVT rate in this group. Higher baseline NIHSS and longer onset-to-IVT and onset-to-groin puncture times may have contributed to a higher 90 day mortality in PCLVO patients.
Further evidence for de novo variants in SYNCRIP as the cause of a neurodevelopmental disorder
2021-06-22

SYNCRIP encodes for the Synaptotagmin-binding cytoplasmic RNA-interacting protein, involved in RNA-binding and regulation of multiple cellular pathways. It has been proposed as a candidate gene for neurodevelopmental disorders (NDDs) with autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. We ascertained genetic, clinical, and neuroradiological data of three additional individuals with novel de novo SYNCRIP variants. All individuals had ID. Autistic features were observed in two. One individual showed myoclonic-atonic epilepsy. Neuroradiological features comprised periventricular nodular heterotopia and widening of subarachnoid spaces. Two frameshift variants in the more severely affected individuals, likely result in haploinsufficiency. The third missense variant lies in the conserved RNA recognition motif (RRM) 2 domain likely affecting RNA-binding. Our findings support the importance of RRM domains for SYNCRIP functionality and suggest genotype-phenotype correlations. Our study provides further evidence for a SYNCRIP-associated NDD characterized by ID and ASD sporadically accompanied by malformations of cortical development and myoclonic-atonic epilepsy.
Effects of the Antidepressants Citalopram and Venlafaxine on the Big Ramshorn Snail (Planorbarius corneus)
2021-06-22

Depression is a serious health issue and, being such, treatment for it has become a topic of increasing concern. Consequently, the prescription rates of antidepressants have increased by about 50% over the past decade. Among antidepressants, citalopram and venlafaxine are the most frequently prescribed in Germany. Due to the high consumption and low elimination rates of both antidepressants during wastewater purification, they are frequently found in surface waters, where they may pose a risk to the aquatic environment. For the present study, we conducted experiments with the big ramshorn snail, which we exposed to environmentally relevant and explicitly higher concentrations (1–1000 μg/L) of the antidepressants citalopram and venlafaxine. We investigated apical endpoints, such as weight, mortality, behavioural changes, B-esterase activity, Hsp70 stress protein level and superoxide dismutase activity, as well as the tissue integrity of the hepatopancreas in the exposed snails. Citalopram and venlafaxine had no effects on the B-esterase activity, Hsp70 level and superoxide dismutase activity. Citalopram exposure resulted in weight reduction and tissue reactions in the hepatopancreas of snails exposed to 1000 μg/L. In contrast, venlafaxine did not induce comparable effects, but impacted the behaviour (sole detachment) of snails exposed to 100 μg/L and 1000 μg/L of the antidepressant. These results revealed that venlafaxine can affect snails at concentrations 10 times lower than citalopram. For this, in 2020 venlafaxine was introduced in the “Surface Water Watch List”, a list of potential pollutants that should be carefully monitored in surface water by the EU Member States.
Transformation of organic micropollutants along hyporheic flow in bedforms of river-simulating flumes
2021-06-22

Abstract Urban streams receive increasing loads of organic micropollutants from treated wastewaters. A comprehensive understanding of the in-stream fate of micropollutants is thus of high interest for water quality management. Bedforms induce pumping effects considerably contributing to whole stream hyporheic exchange and are hotspots of biogeochemical turnover processes. However, little is known about the transformation of micropollutants in such structures. In the present study, we set up recirculating flumes to examine the transformation of a set of micropollutants along single flowpaths in two triangular bedforms. We sampled porewater from four locations in the bedforms over 78 days and analysed the resulting concentration curves using the results of a hydrodynamic model in combination with a reactive transport model accounting for advection, dispersion, first-order removal and retardation. The four porewater sampling locations were positioned on individual flowpaths with median solute travel times ranging from 11.5 to 43.3 h as shown in a hydrodynamic model previously. Highest stability was estimated for hydrochlorothiazide on all flowpaths. Lowest detectable half-lives were estimated for sotalol (0.7 h) and sitagliptin (0.2 h) along the shortest flowpath. Also, venlafaxine, acesulfame, bezafibrate, irbesartan, valsartan, ibuprofen and naproxen displayed lower half-lives at shorter flowpaths in the first bedform. However, the behavior of many compounds in the second bedform deviated from expectations, where particularly transformation products, e.g. valsartan acid, showed high concentrations. Flowpath-specific behavior as observed for metformin or flume-specific behavior as observed for metoprolol acid, for instance, was attributed to potential small-scale or flume-scale heterogeneity of microbial community compositions, respectively. The results of the study indicate that the shallow hyporheic flow field and the small-scale heterogeneity of the microbial community are major controlling factors for the transformation of relevant micropollutants in river sediments.
Characterization of Export Regimes in Concentration–Discharge Plots via an Advanced Time-Series Model and Event-Based Sampling Strategies
2021-06-22

Currently, the export regime of a catchment is often characterized by the relationship between compound concentration and discharge in the catchment outlet or, more specifically, by the regression slope in log-concentrations versus log-discharge plots. However, the scattered points in these plots usually do not follow a plain linear regression representation because of different processes (e.g., hysteresis effects). This work proposes a simple stochastic time-series model for simulating compound concentrations in a river based on river discharge. Our model has an explicit transition parameter that can morph the model between chemostatic behavior and chemodynamic behavior. As opposed to the typically used linear regression approach, our model has an additional parameter to account for hysteresis by including correlation over time. We demonstrate the advantages of our model using a high-frequency data series of nitrate concentrations collected with in situ analyzers in a catchment in Germany. Furthermore, we identify event-based optimal scheduling rules for sampling strategies. Overall, our results show that (i) our model is much more robust for estimating the export regime than the usually used regression approach, and (ii) sampling strategies based on extreme events (including both high and low discharge rates) are key to reducing the prediction uncertainty of the catchment behavior. Thus, the results of this study can help characterize the export regime of a catchment and manage water pollution in rivers at lower monitoring costs. We propose a simple stochastic time-series model to represent the export regime of a catchment beyond simple regression. We propose how to get the required data with the least effort when the use of high-frequency in situ analyzers is not feasible or restricted. Sampling strategies based on extreme events are essential for reducing the prediction uncertainty of the catchment behavior.
Case Report: Guillain–Barré Syndrome Associated With COVID-19
2021-06-22

Guillain–Barré syndrome (GBS) is a potentially fatal, immune-mediated disease of the peripheral nervous system that is usually triggered by infection. Only a small number of cases of GBS associated with COVID-19 infection have been published. We report here five patients with GBS admitted to the Neurology, Psychiatry, and Neurosurgery Hospital, Assiut University/Egypt from July 1 to November 20, 2020. Three of the five patients were positive for SARS-CoV-2 following polymerase chain reaction (PCR) of nasopharyngeal swabs on day of admission and another one had a high level of IgM and IgG; all had bilateral ground-glass opacities with consolidation on CT chest scan (GGO) and lymphopenia. All patients presented with two or more of the following: fever, cough, malaise, vomiting, and diarrhea with variable duration. However, there were some peculiarities in the clinical presentation. First, there were only 3 to 14 days between the onset of COVID-19 symptoms and the first symptoms of GBS, which developed into flaccid areflexic quadriplegia with glove and stocking hypoesthesia. The second peculiarity was that three of the cases had cranial nerve involvement, suggesting that there may be a high incidence of cranial involvement in SARS-CoV-2-associated GBS. Other peculiarities occurred. Case 2 presented with a cerebellar hemorrhage before symptoms of COVID-19 and had a cardiac attack with elevated cardiac enzymes following onset of GBS symptoms. Case 5 was also unusual in that the onset began with bilateral facial palsy, which preceded the sensory and motor manifestations of GBS (descending course). Neurophysiological studies showed evidence of sensorimotor demyelinating polyradiculoneuropathy, suggesting acute inflammatory polyneuropathy (AIDP) in all patients. Three patients received plasmapheresis. All of them had either full recovery or partial recovery. Possible pathophysiological links between GBS and COVID-19 are discussed.
Signposts for CLARIN
2021-06-22

An implementation of CMDI-based signposts and its use is presented in this paper. Arnold, Fisseni et al. (2020) present signposts as a solution to challenges in long-term preservation of corpora. Though applicable to digital resources in general, we focus on corpora, especially those that are continuously extended or subject to modification, e.g., due to legal injunctions, but also may overlap with respect to constituents, and may be subject to migrations to new data formats. We describe the contribution signposts can make to the CLARIN infrastructure, notably virtual collections, and document the design for the CMDI profile.
Rare Copy Number Variants (CNVs) and Breast Cancer Risk
2021-06-22

<title>Abstract</title> <bold>Background</bold>Copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data.<bold>Results</bold>Gene burden tests detected the strongest association for deletions in <italic>BRCA1</italic> (P= 3.7E-18). Nine other genes were associated with a p-value &lt; 0.01 including known susceptibility genes <italic>CHEK2</italic> (P= 0.0008), <italic>ATM</italic> (P= 0.002) and <italic>BRCA2</italic> (P= 0.008). Outside the known genes we detected associations with p-values &lt; 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci.<bold>Conclusions</bold>This is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
Extending the CMDI Universe
2021-06-22

The Component Metadata Infrastructure (CMDI) is a discipline independent metadata framework, though it is currently mainly used within CLARIN and by initiatives in the humanities and social sciences. CMDI allows flexible modelling of metadata schemas that are adjusted to the type of data. The model has built in functionality for semantic interoperability based on inventories providing persistent identifiers for definitions. In this paper we investigate, if and how CMDI can be used in bioinformatics for metadata modelling and describing the research data. For this purpose we embed CMDI based metadata in METS containers. Two sample schemas are developed the first based on a bottom up process and the second one takes the requirements of data publishing portals as the starting point of development.
Epicureans and the City’s Laws
2021-06-22

Abstract The article discusses the accusation advanced by Plutarch and Cicero, according to which the Epicureans are unjust, as they would break the law to pursue pleasure if certain of impunity, and deals with this criticism by analyzing the Epicurean theory of law and justice and comparing it with friendship. The article argues that, from a doctrinal standpoint, philia has a higher place in the Epicurean’s priorities and a stronger efficacy than positive law in serving the naturally just. It thus concludes that, as Plutarch and Cicero suspected, the Epicurean’s ultimate loyalty does not lie with positive law, in spite of its importance for social order, but rather with the naturally just ( dikaion ), better secured by friendship.
The Refractive Error and Vision Impairment Estimation With Spectacle data (REVIEWS) study
2021-06-22

Abstract Objective To investigate whether spectacle lens sales data can be used to estimate the population distribution of refractive error amongst ametropes and hence estimate the current and future risk of vision impairment. Design Cross Sectional Study Subjects A total 141,547,436 spectacle lens sales records from an international European lens manufacturer between the years 1998 and 2016. Methods Anonymized patient spectacle lens sales data including refractive error information was provided by a major European spectacle lens manufacturer. Data from the Gutenberg Health Survey was digitized to allow comparison of a representative, population-based sample to the spectacle lens sales data. A bootstrap analysis was completed to assess the comparability of both datasets. The expected level of vision impairment due to myopia at age 75 was calculated for both datasets using a previously published risk estimation equation combined with a saturation function. Main Outcome Measures Comparability of spectacle lens sales data on refractive error to typical population surveys of refractive error and its potential utility to predict vision impairment due to refractive error. Results Equivalent estimates of the population distribution of spherical equivalent refraction can be provided from spectacle lens data within limits. For myopia, the population distribution was equivalent to the Gutenberg Health Survey (≤ 5% deviation) for levels ≤-2.0 dioptres, while for hyperopia the distribution was equivalent (≤ 5% deviation) for levels ≥ +3.0 diopters. The estimated rates of vision impairment due to myopia were not statistically significantly different (χ 2 = 182, DoF = 169, p = 0.234) between the spectacle lens data and Gutenberg Health Survey data. Conclusions The distribution of refractive error and hence the risk of vision impairment due to refractive error within a population can be determined using spectacle lens sales data. Pooling this type of data from multiple industry sources could provide a cost effective, timely and globally representative mechanism for monitoring the evolving epidemiology of refractive error and associated vision impairment.
CMDI Explorer
2021-06-22

We present CMDI Explorer, a tool that empowers users to easily explore the contents of complex CMDI records and to process selected parts of them with little effort. The tool allows users, for instance, to analyse virtual collections represented by CMDI records, and to send collection items to other CLARIN services such as the Switchboard for subsequent processing. CMDI Explorer hence adds functionality that many users felt was lacking from the CLARIN tool space.
Daily weather data averages for Germany aggregated over official weather stations
2021-06-22

Daily data averaged across Germany for the period of 2016-01-01 till 2021-06-27: <strong>temperature_mean: </strong>mean daily temperature in degree Celsius averaged across all weather stations in Germany. <strong>temperature_max:</strong> maximum daily temperature in degree Celsius averaged across all weather stations in Germany. <strong>precipitation:</strong> daily precipitation sum in millimeter (equals liter per square meter) averaged across all weather stations in Germany. <strong>sunshine: </strong>sunshine duration per day averaged across all weather stations in Germany. gemittelte Werte basierende auf Daten des Deutschen Wetterdiensts, Vermessungsverwaltungen der Länder und BKG (https://gdz.bkg.bund.de/)