julilili42/papers huggingface dataset:
Management of Cerebral Venous Thrombosis Due to Adenoviral COVID‐19 Vaccination
2022-06-11

Objective Cerebral venous thrombosis (CVT) caused by vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus‐based severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non‐heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods We used data from an international prospective registry of patients with CVT after the adenovirus‐based SARS‐CoV‐2 vaccination. We analyzed possible, probable, or definite VITT‐CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results Ninety‐nine patients with VITT‐CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in‐line with VITT recommendations ( p &lt; 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16–1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06–0.58). Treatment with non‐heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24–2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74–6.54). Conclusions In patients with VITT‐CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT‐CVT. ANN NEUROL 2022;92:562–573
A Closer Look at the Sleep/Wake Habits and Dark Triad Traits
2022-06-11

In this study, we sought to explore the association between sleep/wake habits and the Dark Triad (DT) traits. The sample consisted of 637 university students who filled out the measures of the Dark Triad, sleep quality, daytime sleepiness, and sleep timing. There was a positive relationship between the Dark Triad composite and eveningness, and a negative relationship between the DT and circadian distinctness was observed. Psychopathy appeared as the most sleep-related DT trait, and narcissism appeared as the least sleep-related one. Psychopathy and Machiavellianism predicted bedtime prior to free days stronger than the other sleep variables. This study suggests that both sleep timing and sleep stability are influenced by higher DT traits. As sleep disturbances go along with some other comorbid mental problems, looking for the possible underlying factors such as biological markers or psychological traits is warranted.
A Platform of Patient-Derived Microtumors Identifies Individual Treatment Responses and Therapeutic Vulnerabilities in Ovarian Cancer
2022-06-12

In light of the frequent development of therapeutic resistance in cancer treatment, there is a strong need for personalized model systems representing patient tumor heterogeneity, while enabling parallel drug testing and identification of appropriate treatment responses in individual patients. Using ovarian cancer as a prime example of a heterogeneous tumor disease, we developed a 3D preclinical tumor model comprised of patient-derived microtumors (PDM) and autologous tumor-infiltrating lymphocytes (TILs) to identify individual treatment vulnerabilities and validate chemo-, immuno- and targeted therapy efficacies. Enzymatic digestion of primary ovarian cancer tissue and cultivation in defined serum-free media allowed rapid and efficient recovery of PDM, while preserving histopathological features of corresponding patient tumor tissue. Reverse-phase protein array (RPPA)-analyses of &gt;110 total and phospho-proteins enabled the identification of patient-specific sensitivities to standard, platinum-based therapy and thereby the prediction of potential treatment-responders. Co-cultures of PDM and autologous TILs for individual efficacy testing of immune checkpoint inhibitor treatment demonstrated patient-specific enhancement of cytotoxic TIL activity by this therapeutic approach. Combining protein pathway analysis and drug efficacy testing of PDM enables drug mode-of-action analyses and therapeutic sensitivity prediction within a clinically relevant time frame after surgery. Follow-up studies in larger cohorts are currently under way to further evaluate the applicability of this platform to support clinical decision making.
Another way to implement complex computations
2022-06-12

Whenever data-intensive computation gets so complex that it requires the use of iteration or recursion, SQL developers turn towards recursive common table expressions (CTEs). We present the results of a user study that shows how developers struggle with the unusual fixpoint semantics and awkward monolithic syntactic structure of CTEs. The study suggests that recursive user-defined functions (UDFs)---written in a style much like regular functional programs---are less prone to errors, significantly more readable, and can be authored more quickly. Since such recursive UDFs can be automatically compiled into efficiently executable CTEs, we put functional-style UDFs forward as another promising pillar to express complex computation close to the data.
Mitochondrial and autophagy-lysosomal pathway polygenic risk scores predict Parkinson's disease
2022-06-13

Polygenic Risk Scores (PRS), which allow assessing an individuals' genetic risk for a complex disease, are calculated as the weighted number of genetic risk alleles in an individual's genome, with the risk alleles and their weights typically derived from the results of genome-wide association studies (GWAS). Among a wide range of applications, PRS can be used to identify at-risk individuals and select them for further clinical follow-up. Pathway PRS are genetic scores based on single nucleotide polymorphisms (SNPs) assigned to genes involved in major disease pathways. The aim of this study is to assess the predictive utility of PRS models constructed based on SNPs corresponding to two cardinal pathways in Parkinson's disease (PD) including mitochondrial PRS (Mito PRS) and autophagy-lysosomal PRS (ALP PRS). PRS models were constructed using the clumping-and-thresholding method in a German population as prediction dataset that included 371 cases and 249 controls, using SNPs discovered by the most recent PD-GWAS. We showed that these pathway PRS significantly predict the PD status. Furthermore, we demonstrated that Mito PRS are significantly associated with later age of onset in PD patients. Our results may add to the accumulating evidence for the contribution of mitochondrial and autophagy-lysosomal pathways to PD risk and facilitate biologically relevant risk stratification of PD patients.
Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Multicenter Randomized Phase II Trial
2022-06-13

Background: Patients with symptomatic internal carotid artery (ICA) stenosis are at high risk of recurrent ischemic stroke and require early interventional treatment and antiplatelet therapy. Increased bleeding rates might counterbalance the periprocedural efficacy of intensified platelet inhibition. We aim to investigate, whether Revacept, a competitive antagonist of glycoprotein VI, adjunct to standard antiplatelet therapy reduces the occurrence of ischemic lesions in patients with symptomatic ICA stenosis. Methods: International, multicenter (16 sites), 3-arm, randomized (1:1:1), double-blind, and placebo-controlled study with parallel groups, including patients with symptomatic ICA stenosis. A single infusion over 20 minutes of either placebo, 40 mg or 120 mg Revacept in addition to guideline-conform antiplatelet therapy was evaluated with regard to the exploratory efficacy end point: Number of new ischemic lesions on diffusion-weighted magnetic resonance imaging after treatment initiation. Main clinical outcome was the combined safety and efficacy end point including any stroke or death, transient ischemic attack, myocardial infarction, coronary intervention, and bleeding complications during follow-up. Results: Out of 160 randomized patients, 158 patients (68±10.1 years, 24% female) received study medication (51 patients placebo, 54 patients 40 mg Revacept and 53 patients 120 mg Revacept) and were followed for 11.2±2.3 months. A total of 1.16 (95% CI, 0.88–1.53)/1.05 (95% CI, 0.78–1.42; P =0.629)/0.63 (95% CI, 0.43–0.93) new diffusion-weighted magnetic resonance imaging lesions per patient were detected in the placebo/40 mg/120 mg Revacept groups, without statistical evidence of a difference. A reduction of the combined safety and efficacy end point during the study period was observed in patients who received 120 mg (HR, 0.46 [95% CI, 0.21–0.99]; P =0.047), but not 40 mg Revacept compared with placebo (HR, 0.72 [95% CI, 0.37–1.42]; P =0.343). Conclusions: Revacept 120 mg reduced the combined safety and efficacy end point in patients with symptomatic ICA stenosis. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01645306.
Long‐term fallows rate best among agri‐environment scheme effects on farmland birds—A meta‐analysis
2022-06-13

Abstract Agri‐environment schemes (AES) serve to counteract the ongoing decline of farmland bird populations, but their success remains controversial. We conducted a meta‐analysis to compare standardized effect size estimates among European AES options—classified into 15 categories that capture relevant management practices—for farmland bird abundance and species richness. Effect strengths varied substantially between AES categories. Long‐term fallows, nonproductive crops such as wild bird seed mixtures, artificial food supply, and winter cover yielded the strongest positive associations with farmland bird abundance. Average effect sizes were larger but also more variable in cropland compared to grassland‐dominated farming systems. This observation highlights the need to develop more effective conservation schemes for grassland inhabitants, which face similarly severe population declines as cropland inhabitants. Schemes that provided large ecological contrasts between treatment and control sites yielded particularly strong relative benefits, but AES‐specific effect sizes further varied with foraging and nesting site guilds of the target species. Our study confirms that the AES that is currently implemented can benefit farmland birds. However, clear improvements require AES to focus on options with maximal improvements in habitat quality and to locally implement sufficiently diverse AES options to serve the often‐incongruent needs of several bird guilds and species.
Flares and rotation of M dwarfs with habitable zones accessible to TESS planet detections
2022-06-13

Context. More than 4000 exoplanets have been discovered to date, providing the search for a place capable of hosting life with a large number of targets. With the Transiting Exoplanet Survey Satellite (TESS) having completed its primary mission in July 2020, the number of planets confirmed by follow-up observations is growing further. Crucial for planetary habitability is not only a suitable distance of the planet to its host star, but also the star’s properties. Stellar magnetic activity, and especially flare events, expose planets to a high photon flux and potentially erode their atmospheres. Here especially the poorly constrained high-energy UV and X-ray domain is relevant. Aims. We characterize the magnetic activity of M dwarfs to provide the planet community with information on the energy input from the star; in particular, in addition to the frequency of optical flares directly observed with TESS, we aim at estimating the corresponding X-ray flare frequencies, making use of the small pool of known events observed simultaneously in both wavebands. Methods. We identified 112 M dwarfs with a TESS magnitude ≤11.5 for which TESS can probe the full habitable zone for transits. These 112 stars have 1276 two-minute cadence TESS LCs from the primary mission, which we searched for rotational modulation and flares. We study the link between rotation and flares and between flare properties, for example the flare amplitude-duration relation and cumulative flare energy frequency distributions (FFDs). Assuming that each optical flare is associated with a flare in the X-ray band, and making use of published simultaneous Kepler /K2 and XMM-Newton flare studies, we estimate the X-ray energy released by our detected TESS flare events. Our calibration also involves the relation between flare energies in the TESS and K2 bands. Results. We detected more than 2500 optical flare events on a fraction of about 32% of our targets and found reliable rotation periods only for 12 stars, which is a fraction of about 11%. For these 12 targets, we present cumulative FFDs and FFD power law fits. We construct FFDs in the X-ray band by calibrating optical flare energies to the X-rays. In the absence of directly observed X-ray FFDs for main-sequence stars, our predictions can serve for estimates of the high-energy input to the planet of a typical fast-rotating early- or mid-M dwarf.
ClinCNV: multi-sample germline CNV detection in NGS data
2022-06-13

Abstract Germline copy number variants (CNVs) are a common source of genomic variation involved in many genetic disorders, and their detection is crucial for clinical molecular diagnostics. Genomic microarrays, quantitative polymerase chain reaction (qPCR), and multiplex ligation-dependent probe amplification (MLPA) have been widely used for CNV detection in clinics for many years. Similarly, next-generation sequencing (NGS) applications such as whole-genome sequencing (WGS) and whole-exome sequencing (WES) are well-established, highly accurate techniques for the detection of single nucleotide variants (SNVs) and small insertions and deletions (indels). However, CNV detection using NGS remains challenging due to short read lengths, smaller than CNVs sizes. CNV detection using read coverage depths summarized in genomic regions is affected by various biases that arise during the library preparation and sequencing. We have developed a novel strategy for detecting CNVs, implemented in the tool ClinCNV (freely available on https://github.com/imgag/ClinCNV ). ClinCNV does multi-sample normalization and CNV calling, using an original algorithm taking the best from the circular binary segmentation method and Hidden Markov model-based approaches. Here, we describe the methods and discuss the results obtained by applying ClinCNV to thousands of clinical WES, WGS, and shallow-WGS samples in various clinical and research settings.
Quantum Efficiency Enhancement of Lead-Halide Perovskite Nanocrystal LEDs by Organic Lithium Salt Treatment
2022-06-13

Surface-defect passivation is key to achieving a high photoluminescence quantum yield in lead halide perovskite nanocrystals. However, in perovskite light-emitting diodes, these surface ligands also have to enable balanced charge injection into the nanocrystals to yield high efficiency and operational lifetime. In this respect, alkaline halides have been reported to passivate surface trap states and increase the overall stability of perovskite light emitters. On the one side, the incorporation of alkaline ions into the lead halide perovskite crystal structure is considered to counterbalance cation vacancies, whereas on the other side, the excess halides are believed to stabilize the colloids. Here, we report an organic lithium salt, viz. LiTFSI, as a halide-free surface passivation on perovskite nanocrystals. We show that treatment with LiTFSI has multiple beneficial effects on lead halide perovskite nanocrystals and LEDs derived from them. We obtain a higher photoluminescence quantum yield and a longer exciton lifetime and a radiation pattern that is more favorable for light outcoupling. The ligand-induced dipoles on the nanocrystal surface shift their energy levels toward a lower hole-injection barrier. Overall, these effects add up to a 4- to 7-fold boost of the external quantum efficiency in proof-of-concept LED structures, depending on the color of the used lead halide perovskite nanocrystal emitters.
Investigating Potential Links Between Fine-Grained Components in Loess and Westerly Airflow: Evidence From East and Central Asia
2022-06-13

Loess is a ubiquitous, silty aeolian sediment common across the semiarid to subhumid regions in the Northern Hemisphere. As such, the physical characteristics of loess sediment, such as modal grain size and quartz crystallinity index, have the potential to inform us about dust transport pathways and corresponding atmospheric circulation responsible for entrainment, transport, and deposition. In this article, we combine detailed granularity analyses and non-parametric end-member modeling with investigations of the quartz crystallinity index of three loess deposits, extending from East to Central Asia, with the aim of identifying dust transport processes and the climate subsystems responsible for them. We find marked differences in the grain size characteristics of Eastern and Central Asian loess. Given potential linkages of fine particles to the westerly jet stream, here we focused on the fine-grained end-members in the loess. The fine-grained components of the Central Asian Bishkek (BSK) and Chashmanigar (CMG) loess may be derived from individual particles carried at high altitude by major climate subsystems such as the westerlies. However, similar quartz crystallinity indexes of fine- and coarse-grained components in the Central Asian loess indicated that surface-level wind strength might influence the releases from proximal-sourced regions and abundances in the upper atmosphere for the fine particles. By contrast, the fine-grained component of the East Asian [Fanshan18 (FS18)] loess seems to yield physical similarities to the Tertiary Red Clays underlying many loess stratigraphies, and has been interpreted to relate to transport associated with the East Asian winter monsoon. It was further supported by quartz crystallinity indexes of the &amp;lt;16 μm fractions in the FS18 loess, basically consistent with those of the deserts in North China, highlighting the near-surface northwesterly winter monsoon as the dominant transport dynamics of fine-grained dust. In addition, comparisons of quartz crystallinity indexes of fine-grained components between the East and Central Asian loess also suggest that variations in fine particles within the loess might not be related to transport by the higher-level westerlies, which is in disagreement with the previous model. Therefore, our results indicate that variations in fine-grained end-members in loess are difficult to reliably document the variabilities of higher-level westerlies.
Implementation and evaluation of an individualized physical exercise promotion program in people with manifested risk factors for multimorbidity (MultiPill-Exercise): a study protocol for a pragmatic randomized controlled trial
2022-06-13

Abstract Background Multimorbidity is a major problem in Europe, increasing the need for prevention and rehabilitation programs. In Germany no guidelines have been developed that focus on patients with multiple chronic non-communicable diseases (NCDs). Benefits of physical activity (PA) and exercise in NCDs have been proven, but most interventions focus on single conditions. The evaluation of the effectiveness, efficiency and safety of PA programs in patients suffering from multiple NCDs and the feasibility of the implementation within the health care service remain open research questions. Methods The multi-site randomized controlled pragmatic trial includes 320 sedentary subjects with at least two of the following NCDs, either manifested or in a pre-stage with evident risk factors: Cardio-vascular disease, Diabetes mellitus type 2, knee/ hip osteoarthritis and obesity. Participants will be recruited from general practitioners and medical specialists and randomized to standard care of a statutory health insurance or MultiPill-Exercise . Standard care includes a choice of one or a maximum of two 8- to 12-week health programs, including nutrition, exercise, relaxation or special disease management programs. MultiPill-Exercise is based on the bio-psycho-social health model, considering a person-oriented perspective in light of given individual characteristics and context factors. The 24-weeks intervention focuses on aerobic and strengthening exercises in line with the WHO PA recommendations. Psychological and pedagogical elements along with behavior change techniques are implemented to ease the initiation and maintenance of exercise participation and lifestyle change, including nutrition. Primary outcome will be short- and long-term PA measured with the European Health Interview Survey-Physical Activity Questionnaire (EHIS-PAQ). Secondly, the effectiveness of the program on generic, disease specific, economic, and exercise behavioral parameters, as well as program adherence and safety will be evaluated. Discussion Results of this trial evaluate the PA intervention program in people with multiple NCDs in a real-life scenario. It will serve as a proof of concept with the opportunity of translation into routine practice. This approach, as a multi-site RCT with its rigorous methods and standardized operating procedures for the conduction of the intervention, will allow valid conclusions for the implementation of PA interventions in people with multimorbidity. Trial registration The trial was registered at www.drks.de (ID: DRKS00025033 ) on 30th September 2021.
Clinical and morphological characteristics of patients with idiopathic epiretinal membrane with foveal herniation
2022-06-13

Abstract Purpose To analyse the clinical and morphological characteristics of eyes with idiopathic epiretinal membrane (iERM) and foveal herniation (FH). Methods Clinical findings and OCT features of patients with iERM and FH were retrospectively analysed. Primary outcome were changes of the best-corrected-visual-acuity (BCVA) and OCT features from baseline to the last visit. FH patients were divided into two groups based on herniated layers: ganglion cell complex (GCC)-group and sub-GCC-group. Surgical outcome was also assessed. Results In this study, 3882 patients with iERM were screened, of whom 51 (1.3%) were identified with FH. The GCC-group ( n = 16) had a better baseline BCVA and thinner central foveal thickness (CFT) in comparison to the sub-GCC-group ( n = 35) but without statistical significance ( p = 0.330, p = 0.417, respectively). The postoperative BCVA-improvement was similar between the two groups ( p = 0.280). Fibrillary surface changes were detected in 42/51 (82.3%) patients, significantly more often in the sub-GCC group ( p = 0.020). The baseline BCVA was a predictive factor for the postoperative vision change. Conclusion FH presents with a unique macular morphology in eyes with iERM. Affected eyes experience varying visual disturbances based on the involvement of the inner retinal layers in the foveal herniation. Macular surgery is successful in restoring vision, even though foveal morphology does not fully recover.