julilili42/papers huggingface dataset:
The COVID-19 Data Exchange Platform of the German University Medicine
2022-05-25

COVID-19 has challenged the healthcare systems worldwide. To quickly identify successful diagnostic and therapeutic approaches large data sharing approaches are inevitable. Though organizational clinical data are abundant, many of them are available only in isolated silos and largely inaccessible to external researchers. To overcome and tackle this challenge the university medicine network (comprising all 36 German university hospitals) has been founded in April 2020 to coordinate COVID-19 action plans, diagnostic and therapeutic strategies and collaborative research activities. 13 projects were initiated from which the CODEX project, aiming at the development of a Germany-wide Covid-19 Data Exchange Platform, is presented in this publication. We illustrate the conceptual design, the stepwise development and deployment, first results and the current status.
Could a Lower Toll-like Receptor (TLR) and NF-κB Activation Due to a Changed Charge Distribution in the Spike Protein Be the Reason for the Lower Pathogenicity of Omicron?
2022-05-25

The novel SARS-CoV-2 Omicron variant B.1.1.529, which emerged in late 2021, is currently active worldwide, replacing other variants, including the Delta variant, due to an enormously increased infectivity. Multiple substitutions and deletions in the N-terminal domain (NTD) and the receptor binding domain (RBD) in the spike protein collaborate with the observed increased infectivity and evasion from therapeutic monoclonal antibodies and vaccine-induced neutralizing antibodies after primary/secondary immunization. In contrast, although three mutations near the S1/S2 furin cleavage site were predicted to favor cleavage, observed cleavage efficacy is substantially lower than in the Delta variant and also lower compared to the wild-type virus correlating with significantly lower TMPRSS2-dependent replication in the lungs, and lower cellular syncytium formation. In contrast, the Omicron variant shows high TMPRSS2-independent replication in the upper airway organs, but lower pathogenicity in animal studies and clinics. Based on recent data, we present here a hypothesis proposing that the changed charge distribution in the Omicron’s spike protein could lead to lower activation of Toll-like receptors (TLRs) in innate immune cells, resulting in lower NF-κB activation, furin expression, and viral replication in the lungs, and lower immune hyper-activation.
Mitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination
2022-05-25

Dysfunctional mitochondria are linked to several neurodegenerative diseases. Metabolic defects, a symptom which can result from dysfunctional mitochondria, are also present in spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, the most frequent, dominantly inherited neurodegenerative ataxia worldwide. Mitochondrial dysfunction has been reported for several neurodegenerative disorders and ataxin-3 is known to deubiquitinylate parkin, a key protein required for canonical mitophagy. In this study, we analyzed mitochondrial function and mitophagy in a patient-derived SCA3 cell model. Human fibroblast lines isolated from SCA3 patients were immortalized and characterized. SCA3 patient fibroblasts revealed circular, ring-shaped mitochondria and featured reduced OXPHOS complexes, ATP production and cell viability. We show that wildtype ataxin-3 deubiquitinates VDAC1 (voltage-dependent anion channel 1), a member of the mitochondrial permeability transition pore and a parkin substrate. In SCA3 patients, VDAC1 deubiquitination and parkin recruitment to the depolarized mitochondria is inhibited. Increased p62-linked mitophagy, autophagosome formation and autophagy is observed under disease conditions, which is in line with mitochondrial fission. SCA3 fibroblast lines demonstrated a mitochondrial phenotype and dysregulation of parkin-VDAC1-mediated mitophagy, thereby promoting mitochondrial quality control via alternative pathways.
Never Gonna Give You Up – Current Developments in Covalent Protein Kinase Inhibitors
2022-05-25

Covalent inhibitors have recently seen a revival in medicinal chemistry. Inhibitors addressing non-catalytic cysteine residues with weakly reactive electrophiles have been very successfully employed to target protein kinases, one of the major druggable protein families. Here we provide an overview of irreversible and reversible covalent protein kinase inhibitors in clinical development and beyond. We further spotlight recent advances in targeting amino acids other than cysteine and the reactive groups utilized in covalent protein kinase inhibitors.
Duration of Treatment for Pseudomonas aeruginosa Bacteremia: a Retrospective Study
2022-05-25

In this retrospective study, 6-10 days of antibiotic course for P. aeruginosa bacteremia were as effective as longer courses in terms of survival and recurrence. Shorter therapy was associated with reduced length of stay and less drug discontinuation.
Gibberellin and abscisic acid transporters facilitate endodermal suberin formation in Arabidopsis
2022-05-25

<title>Abstract</title> The plant hormone gibberellin (GA) regulates multiple developmental processes. It accumulates in the root elongating endodermis, but how it moves into this cell file and the significance of this accumulation are unclear. Here, we identified a monophyletic clade of NPF transporters required for GA and abscisic acid (ABA) translocation. We demonstrate that NPF2.14 is a subcellular GA/ABA transporter, the first to be identified in plants, facilitating GA and ABA accumulation in the root endodermis to regulate suberization. Further, NPF2.12 and NPF2.13, closely related proteins, are plasma membrane-localized GA and ABA importers that facilitate shoot-to-root GA<sub>12</sub> translocation, regulating endodermal hormone accumulation. This work reveal that GA promotes root suberization and that GA and ABA can act non-antagonistically. We demonstrated how a clade of transporters mediates hormone flow while utilizing defined cell-file-specific vacuolar storage at the phloem unloading zone, allowing a hormone slow-release mechanism required for suberin formation in the maturation zone.
Metadata Definition in Registries: What Is a Data Element?
2022-05-25

Observational research benefits from a rich methodological foundation of registry development and operation published in international and national guidelines. Metadata management is an essential part of registry implementation based on concepts of data elements and value sets. The metadata from six German registries revealed vastly divergent interpretations of the concept of data elements. The different perspectives of research questions, data acquisition and data storage were all represented in the registries’ catalogs of data elements. Consequently, the whole life cycle of a registry needs to be accompanied by a catalog of data elements, which has to be continuously adapted to the changing perspectives. A standard for the representation of those metadata is still missing. The FAIR Guiding Principles introduce important methodological requirements, but the tools for their fulfillment in respect to the management of metadata are still in its infancy.
Anderson and many-body localization in the presence of spatially\\n correlated classical noise
2022-05-25

We study the effect of spatially correlated classical noise on both Anderson\\nand many-body localization of a disordered fermionic chain. By analyzing the\\nevolution of the particle density imbalance following a quench from an initial\\ncharge density wave state, we find prominent signatures of localization also in\\nthe presence of the time-dependent noise, even though the system eventually\\nrelaxes to the infinite temperature state. In particular, for sufficiently\\nstrong static disorder we observe the onset of metastability, which becomes\\nmore prominent the stronger the spatial correlations of the noise. In this\\nregime we find that the imbalance decays as a stretched-exponential - a\\nbehavior characteristic of glassy systems. We identify a simple scaling\\nbehavior of the relevant relaxation times in terms of the static disorder and\\nof the noise correlation length. We discuss how our results could be exploited\\nto extract information about the localization length in experimental setups.\\n
Seeing the World More Clearly
2022-05-25

In this paper, I discuss the effects of using thought experiments for the purpose of conceptual clarification of students’ hermeneutical abilities. On the one hand, by providing opportunities to explore the scope of normatively loaded concepts, thought experiments can effectively help students to interpret their social and moral reality more adequately, which in some cases might even help to reduce existing hermeneutical injustices. On the other hand, given their notorious susceptibility to distorting factors that are philosophically irrelevant, they can also push students into accepting idiosyncratic intuitions that they don’t really share and thereby further impair their hermeneutical abilities. After setting out this dilemma in more detail, I will propose various strategies for facilitating the safe use of thought experiments that instructors can use to effectively exploit the empowering potential of thought experiments.
Genetic diversity of Staphylococcus aureus wall teichoic acid glycosyltransferases affects immune recognition
2022-05-25

Abstract Staphylococcus aureus ( S. aureus ) is a leading cause of skin and soft tissue infections and (hospital-acquired) systemic infections. Wall teichoic acids (WTAs) are cell wall-anchored glycopolymers that are important for S. aureus nasal colonization, endocarditis, and antibiotic resistance. WTAs consist of a polymerized ribitol phosphate (RboP) chain that can be glycosylated with N -acetylglucosamine (GlcNAc) by three glycosyltransferases: TarS, TarM, and TarP. TarS and TarP modify WTA with β-linked GlcNAc on the C-4 (β1,4-GlcNAc) and the C-3 position (β1,3-GlcNAc) of the RboP subunit, respectively, whereas TarM modifies WTA with α-linked GlcNAc at the C-4 position (α1,4-GlcNAc). Importantly, these WTA glycosylation patterns impact immune recognition and clearance of S. aureus . Previous studies suggest that tarS is near-universally expressed within the S. aureus population, whereas a smaller proportion co-express either tarM or tarP . To gain more insight in the presence and genetic variation of tarS, tarM , and tarP in the S. aureus population, we analyzed a collection of 25,652 S. aureus genomes within the PubMLST database. Over 99% of isolates contained tarS . Co-expression of tarS / tarM or tarS / tarP occurred in 37% and 7% of isolates, respectively, and was associated to specific S. aureus clonal complexes. We also identified 26 isolates (0.1%) that contained all three glycosyltransferase genes. At sequence level, we identified tar alleles with amino acid substitutions in critical enzymatic residues or with premature stop codons. Several tar variants were expressed in a S. aureus tar -negative strain. Analysis using specific monoclonal antibodies and human langerin showed that WTA glycosylation was severely attenuated or absent. Overall, our data provide a broad overview of the genetic diversity of the three WTA glycosyltransferases in the S. aureus population and the functional consequences for immune recognition.
Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder
2022-05-26

Abstract Biallelic variants of the gene encoding for the zinc‐finger protein 142 ( ZNF142 ) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders.
The effect of low-intensity exercise on emotional and cognitive engagement in the classroom
2022-05-26

Abstract This study examined whether engaging in physical exercise during a university class would have beneficial effect on students’ learning motivation. One hundred and forty-nine participants took part in a psychology class over nine weeks (one lesson per week); for each lesson, participants engaged in a three-minute physical activity (low-intensity aerobic exercise) or control activity (watching a video), about 20 min after the lesson started. Participants reported higher vigour and lower fatigue during the class when they exercised than when they engaged in control activities. These findings suggest the utility of incorporating a short exercise activity in university settings to enhance students’ classroom motivation.
Effect on the cardiovascular independent risk factor lipoprotein(a) in overweight or obese PCOS patients with ethinyl-estradiol/drospirenone alone or plus orlistat
2022-05-26

This is the first study found that EE/DRSP plus Orlistat could significantly decrease Lp(a) in overweight or obese PCOS patients. This result can be assessed as particularly important, because Lp(a) is well-known as an independent risk factor predicting an increased risk of cardiovascular diseases (CVDs).
Cellular and Molecular Mechanism of Cell Proliferation in Human Gastric Cancer Drug-Resistant Cells After Hyperthermia and Cisplatin: Role of mRNAs and Long-Non-coding RNAs
2022-05-26

Hyperthermia combined with cisplatin reversed the expression of a large number of mRNAs and long non-coding RNAs in human gastric cancer drug-resistant cells. The molecular mechanism of inhibiting the proliferation of human gastric cancer drug- resistant cells may be related to the upregulation of long non-coding RNAs and mRNAs contributed in CD95, mTOR, and TNF receptor signaling pathway.
Comparative outcome of different treatment options for fragility fractures of the sacrum
2022-05-26

Abstract Background Fragility fractures of the sacrum (FFS) have been detected more and more frequently in recent times, and the incidence will continue to increase due to increasing life expectancy. The aim of this study was to compare the feasibility and clinical outcome of conservative, interventional and surgical treatment of FFS. Methods Retrospectively, 292 patients (276 women, 16 men) with confirmed FFS were followed up over a period of 5 years. The age of the women was Ø 81.2 (58–99) and that of the men Ø 78.1 (76–85) years. The pain was quantified using a VAS. A fracture classification was carried out considering X-rays, CT and MRI examinations. A QCT of the lumbar spine was performed to quantify bone mineral density. Fractures were recorded, taking X-rays and medical history into account. An interdisciplinary case conference determined the individual treatment concept with classification into conservative, interventional or surgical treatment. Over the course pain and independence was measured, complications and patient satisfaction were documented. A vitamin D determination was done, and existing comorbidities were included. Results Patients with a pain level of &lt; / = 5 benefited from the conservative therapy measures, with pain levels &gt; 5 significantly delaying the development of mobility. After sacroplasty, the pain reduced significantly, which caused a rapid improvement in mobility without any significant difference being found between vertebro- (VSP), balloon (BSP), radiofrequency (RFS) and cement sacroplasty (CSP). The planned osteosynthesis was carried out as planned. In terms of pain reduction and mobilization, the patients benefited from osteosynthesis, although more complex fracture types with lumbopelvic stabilization took longer. Overall, there were no deaths during the hospital stay. Mortality after 12 months was 21.7% for the conservative, 8.4% for the interventional and 13.6% for the surgical therapy group; the differences are significant. For patients in the conservative therapy group who were difficult to mobilize due to pain, the mortality increased to 24.3%. Over 24 months, patients achieved the best independence after sacroplasty. At 12 and 24 months, subjective satisfaction with the therapies was best after sacroplasty, followed by osteosynthesis and conservative measures. All patients had a pronounced vitamin D deficiency and manifest osteoporosis. Cardiovascular pathologies were the main concomitant diseases. Conclusions Patients with FFS with a low level of pain benefit from conservative therapy measures, whereby complications and mortality increase significantly in the case of persistent immobilizing pain. Patients with an unacceptable level of pain resulting from non-dislocated fractures benefit significantly from sacroplasty. Patients with unstable and displaced fractures should be operated on promptly. Different techniques are available for sacroplasty and osteosynthesis, which lead to an improvement of independence and a reduction in mortality.
Inhaled Prostacyclin Improves Oxygenation in Patients with COVID-19-induced Acute Respiratory Distress Syndrome – a randomized controlled multicenter trial
2022-05-26

Abstract Background. Acute Respiratory Distress Syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS. Methods. We performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride. The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events. Results. Of 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline oxygenation index did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than NaCl (p = 0·17). Oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0·04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups. Conclusions. Although the primary result of our study was negative, our data suggest that inhaled prostacyclin might be a more beneficial treatment than standard care for patients with ARDS. Trial registration: The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016-003168-37) and registered at clinicaltrials.gov ( NCT03111212 ).
Additional file 2 of Comparison of survival between patients receiving general outpatient palliative care and patients receiving other palliative care - analysis of data of a statutory health insurance data
2022-05-26

Additional file 2: Appendix B. Kaplan-Meier Curve of palliative care oncology and non-oncology patients (12-month follow-up): Group A vs. Group B. Group A: patients who received only General Outpatient Palliative Care. Group B: patients who received also inpatient or Specialized Outpatient Palliative Care.
Additional file 3 of Comparison of survival between patients receiving general outpatient palliative care and patients receiving other palliative care - analysis of data of a statutory health insurance data
2022-05-26

Additional file 3: Appendix C. Kaplan-Meier Curve of palliative care oncology and non-oncology patients (12-month follow-up): Group A1 vs. Group A2 Group A1: patients receiving only General Outpatient Palliative Care, treatment = 1 day. Group A2: patients receiving only General Outpatient Palliative Care, treatment &gt; 1 day.
A global experiment on motivating social distancing during the COVID-19 pandemic
2022-05-27

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment ( n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
HPCGen: Hierarchical K-Means Clustering and Level Based Principal Components for Scan Path Genaration
2022-05-27

In this paper, we present a new approach for decomposing scan paths and its utility for generating new scan paths. For this purpose, we use the K-Means clustering procedure to the raw gaze data and subsequently iteratively to find more clusters in the found clusters. The found clusters are grouped for each level in the hierarchy, and the most important principal components are computed from the data contained in them. Using this tree hierarchy and the principal components, new scan paths can be generated that match the human behavior of the original data. We show that this generated data is very useful for generating new data for scan path classification but can also be used to generate fake scan paths. Code can be downloaded here https://atreus.informatik.uni-tuebingen.de/seafile/d/8e2ab8c3fdd444e1a135/?p=%2FHPCGen&mode=list.