julilili42/papers huggingface dataset:
GH Responsiveness Is not Correlated to IGF1 P2 Promoter Methylation in Children With Turner Syndrome, GHD and SGA Short Stature
2022-06-13

Background The methylation of IGF1 promoter P2 was reported to negatively correlate with serum IGF-1 concentration and rhGH treatment response in children with idiopathic short stature. These findings have not yet been confirmed. Objective This study aimed to determine IGF1 promoter P2 methylation in short children treated with rhGH and correlate clinical parameters with the methylation status. In addition, long-term stability of methylation during rhGH treatment was studied. Design This was a single tertiary center study analyzing clinical GH response and IGF-1 serum concentration changes in patients with GHD (n=40), SGA short stature (n=36), and Turner syndrome (n=16) treated with rhGH. Data were correlated to the methylation of two cytosine residues (-137, +97) of the P2 promoter of IGF1 in blood cells measured by pyrosequencing in 443 patient samples. Results Basal and stimulated IGF-1 concentrations, first year increment in height velocity and studentized residuals of a prediction model did not correlate to the methylation of -137 und +97 in IGF1 P2 promoter. The methylation of these two sites was relatively stable during treatment. Conclusions This study did not confirm IGF1 P2 promotor being a major epigenetic locus for GH responsiveness in patients treated with a normal dose of rhGH. Additional studies are warranted.
Static and dynamic transport properties of multi-terminal, multi-junction microSQUIDs realized with Nb/HfTi/Nb Josephson junctions
2022-06-13

Abstract The progressive miniaturization of superconducting quantum interference devices (SQUIDs) used, e.g. for magnetic imaging on the nanoscale or for the detection of the magnetic states of individual magnetic nanoparticles causes increasing problems in realizing a proper flux-bias scheme for reading out the device. To overcome the problem, a multi-terminal, multi-junction layout has been proposed and realized recently for the SQUID-on-tip configuration, which uses constriction-type Josephson junctions (JJ). This geometry is also interesting for SQUIDs based on overdamped superconductor—normal metal—superconductor (SNS) JJ. We fabricated four-terminal, four-junction SQUIDs based on a trilayer Nb/HfTi/Nb process and study their static and dynamic transport properties in close comparison with numerical simulations based on the resistively and capacitively shunted junction model. Simulations and measurements are in very good agreement. However, there are large differences to the transport properties of conventional two-junction SQUIDs, including unusual phase-locked and chaotic dynamic states which we describe in detail. We further extract the current-phase relation of our SNS junctions, which turns out to be purely sinusoidal within the experimental error bars.
Edge-based growth control inArabidopsisinvolves two cell wall-associated Receptor-Like Proteins
2022-06-13

Summary Morphogenesis of multicellular organs requires coordination of cellular growth. In plants, 3D growth is driven by undirected turgor pressure, whereas growth directionality is controlled by cell wall mechanical properties at 2D cell faces. Their shared cell wall also fixes cells in their position, and plants thus have to integrate tissue-scale mechanical stresses arising due to growth in a fixed tissue topology. This implies a need to monitor cell wall mechanical and biochemical status and to adapt growth accordingly. Here, we propose that plant cells use their 1D cell edges to monitor cell wall status. We describe two Receptor-Like Proteins, RLP4 and RLP4-L1, which occupy a unique polarity domain at cell edges established through a targeted secretory transport pathway. We show that at cell edges, RLP4s associate with the cell wall via their extracellular domain, and contribute to directional growth control in Arabidopsis .
One bound to rule them all: from Adiabatic to Zeno
2022-06-14

We derive a universal nonperturbative bound on the distance between unitary evolutions generated by time-dependent Hamiltonians in terms of the difference of their integral actions. We apply our result to provide explicit error bounds for the rotating-wave approximation and generalize it beyond the qubit case. We discuss the error of the rotating-wave approximation over long time and in the presence of time-dependent amplitude modulation. We also show how our universal bound can be used to derive and to generalize other known theorems such as the strong-coupling limit, the adiabatic theorem, and product formulas, which are relevant to quantum-control strategies including the Zeno control and the dynamical decoupling. Finally, we prove generalized versions of the Trotter product formula, extending its validity beyond the standard scaling assumption.
Adult‐Onset Neurodegeneration in Nucleotide Excision Repair Disorders (NERDND): Time to Move Beyond the Skin
2022-06-14

ABSTRACT Background Variants in genes of the nucleotide excision repair (NER) pathway have been associated with heterogeneous clinical presentations ranging from xeroderma pigmentosum to Cockayne syndrome and trichothiodystrophy. NER deficiencies manifest with photosensitivity and skin cancer, but also developmental delay and early‐onset neurological degeneration. Adult‐onset neurological features have been reported in only a few xeroderma pigmentosum cases, all showing at least mild skin manifestations. Objective The aim of this multicenter study was to investigate the frequency and clinical features of patients with biallelic variants in NER genes who are predominantly presenting with neurological signs. Methods In‐house exome and genome datasets of 14,303 patients, including 3543 neurological cases, were screened for deleterious variants in NER‐related genes. Clinical workup included in‐depth neurological and dermatological assessments. Results We identified 13 patients with variants in ERCC4 (n = 8), ERCC2 (n = 4), or XPA (n = 1), mostly proven biallelic, including five different recurrent and six novel variants. All individuals had adult‐onset progressive neurological deterioration with ataxia, dementia, and frequently chorea, neuropathy, and spasticity. Brain magnetic resonance imaging showed profound global brain atrophy in all patients. Dermatological examination did not show any skin cancer or pronounced ultraviolet damage. Conclusions We introduce NERD ND as adult‐onset neurodegeneration ( ND ) within the spectrum of autosomal recessive NER disorders (NERD). Our study demonstrates that NERD ND is probably an underdiagnosed cause of neurodegeneration in adulthood and should be considered in patients with overlapping cognitive and movement abnormalities. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Evaluation of a laboratory-based high-throughput SARS-CoV-2 antigen assay
2022-06-14

Abstract Objectives Antigen tests are an essential part of SARS-CoV-2 testing strategies. Rapid antigen tests are easy to use but less sensitive compared to nucleic acid amplification tests (NAT) and less suitable for large-scale testing. In contrast, laboratory-based antigen tests are suitable for high-throughput immunoanalyzers. Here we evaluated the diagnostic performance of the laboratory-based Siemens Healthineers SARS-CoV-2 Antigen (CoV2Ag) assay. Methods In a public test center, from 447 individuals anterior nasal swab specimens as well as nasopharyngeal swab specimens were collected. The nasal swab specimens were collected in sample inactivation medium and measured using the CoV2Ag assay. The nasopharyngeal swab specimens were measured by RT-PCR. Additionally, 9,046 swab specimens obtained for screening purposes in a tertiary care hospital were analyzed and positive CoV2Ag results confirmed by NAT. Results In total, 234/447 (52.3%) participants of the public test center were positive for SARS-CoV-2-RNA. Viral lineage B1.1.529 was dominant during the study. Sensitivity and specificity of the CoV2Ag assay were 88.5% (95%CI: 83.7–91.9%) and 99.5% (97.4–99.9%), respectively. Sensitivity increased to 93.7% (97.4–99.9%) and 98.7% (97.4–99.9%) for swab specimens with cycle threshold values &lt;30 and &lt;25, respectively. Out of 9,046 CoV2Ag screening tests from hospitalized patients, 21 (0.2%) swab specimens were determined as false-positive by confirmatory NAT. Conclusions Using sample tubes containing inactivation medium the laboratory-based high-throughput CoV2Ag assay is a very specific and highly sensitive assay for detection of SARS-CoV-2 antigen in nasal swab specimens including the B1.1.529 variant. In low prevalence settings confirmation of positive CoV2Ag results by SARS-CoV-2-RNA testing is recommended.
Scientific Inference With Interpretable Machine Learning: Analyzing Models to Learn About Real-World Phenomena
2022-06-14

To learn about real world phenomena, scientists have traditionally used models with clearly interpretable elements. However, modern machine learning (ML) models, while powerful predictors, lack this direct elementwise interpretability (e.g. neural network weights). Interpretable machine learning (IML) offers a solution by analyzing models holistically to derive interpretations. Yet, current IML research is focused on auditing ML models rather than leveraging them for scientific inference. Our work bridges this gap, presenting a framework for designing IML methods-termed 'property descriptors' -- that illuminate not just the model, but also the phenomenon it represents. We demonstrate that property descriptors, grounded in statistical learning theory, can effectively reveal relevant properties of the joint probability distribution of the observational data. We identify existing IML methods suited for scientific inference and provide a guide for developing new descriptors with quantified epistemic uncertainty. Our framework empowers scientists to harness ML models for inference, and provides directions for future IML research to support scientific understanding.
Assay validity of point-of-care platelet function tests in thrombocytopenic blood samples
2022-06-14

Point-of-care (POC) platelet function tests are faster and easier to perform than in-depth assessment by flow cytometry. At low platelet counts, however, POC tests are prone to assess platelet function incorrectly. Lower limits of platelet count required to obtain valid test results were defined and a testing method to facilitate comparability between different tests was established. We assessed platelet function in whole blood samples of healthy volunteers at decreasing platelet counts (&gt; 100, 80-100, 50-80, 30-50 and &lt; 30 x109/L) using two POC tests: impedance aggregometry and in-vitro bleeding time. Flow cytometry served as the gold standard. The number of platelets needed to reach 50% of the maximum function (ED50) and the lower reference limit (EDref) were calculated to define limits of test validity. The minimal platelet count required for reliable test results was 100 x109/L for impedance aggregometry and in-vitro bleeding time but only 30 x109/L for flow cytometry. Comparison of ED50 and EDref showed significantly lower values for flow cytometry than either POC test (P value &lt; 0.05) but no difference between POC tests nor between the used platelet agonists within a test method. Calculating the ED50 and EDref provides an effective way to compare values from different platelet function assays. Flow cytometry enables correct platelet function testing as long as platelet count is &gt; 30 x109/L whereas impedance aggregometry and in-vitro bleeding time are inconsistent unless platelet count is &gt; 100 x109/L.
Lessons learned after one year of COVID-19 from a urologist and radiotherapist view: A German survey on prostate cancer diagnosis and treatment
2022-06-14

Introduction Since the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines. Materials and methods To longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses. Results A total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate. Conclusion While the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.
Traces of impaired social communication and cognitive ability in the youth brain are shared across diagnostic boundaries
2022-06-14

Background: Despite longstanding effort, psychopathology etiology remains elusive. Identification of shared and distinct traits across clinical groups may illuminate the structure of psychopathology. A multitude of factors is likely involved; however, most studies have investigated one or a few factors at a time. Methods: In a clinical youth sample (n=1732, 64% male, age range: 5-21 years), we used canonical correlation and independent component analysis to estimate modes of covariation between structural neuroimaging measures with clinical, cognitive, and psychosocial variables. Out-of-sample validations of brain patterns were conducted in an independent population-based sample (n=1253, 54% female, age range: 8-21 years). Brain patterns in the independent sample were then correlated with clinical, and cognitive variables to test their predictive ability.Results: We identified two significant modes of brain-behavior covariation: the first linked age, physical and cognitive maturation to lower cortical thickness and gyrification (r=.92, p=.005). The second mode linked lower academic performance, trouble with social communication and psychological difficulties, with lower white matter surface area and gyrification (r=.92, p=.006). Diagnosed youth showed elevated mode 2 scores compared to undiagnosed peers. Out-of-sample validation replicated the covariation pattern across brain features. Mode 1 correlated highly with age (r [95% CI]; .7 [.68-.71]) and age-related cognitive maturation (.36 [.33-.38]), while mode 2 correlated with deviations from normative cognitive development (-.24 [-.27--.21]).Conclusion: Our results link maturation and socio-cognitive difficulties to brain structure across diagnostic boundaries, suggesting disorder-general effects as the most prominent. This emphasises transdiagnostic approaches in the identification of traits relevant for psychopathology.
Targeting new N-furfurylated 4-chlorophenyl-1,2,4-triazolepropionamide hybrids as potential 15-lipoxygenase inhibitors supported with in vitro and in silico studies
2022-06-14

Lipoxygenases (LOXs) are a group of enzymes that catalyze the oxidation of polyunsaturated fatty acids and initiate the biosynthesis of secondary metabolites that are involved to control inflammation. In search of new and more potent LOX inhibitors, a series of new 3-(5-(4-chlorophenyl)-4-(2-furylmethyl)-1,2,4-triazole hybrids was prepared and screened for its LOX inhibitory potential. 4-Chlorobenzoic acid (<b>a</b>) was metamorphosed into <i>N</i>-furfuryl-5-(4-chlorophenyl)-4-(2-furylmethyl)-1,2,4-triazole (<b>4</b>) via intermediates like benzoate (<b>1</b>), hydrazide (<b>2</b>) and semicarbazide (<b>3</b>). Finally, triazole (<b>4</b>) was fused with propionamides (<b>6a-o</b>) and transformed it into the aimed derivatives (<b>7a-o</b>). The structural interpretations of the prepared derivatives (<b>7a-o</b>) were accomplished via FTIR, <sup>1</sup>H-, <sup>13</sup>C-NMR spectroscopy, EI-MS and HR-EI-MS spectrometry. The inhibitory potency of the compounds against soybean 15-LOX was determined by <i>in vitro</i> assay using chemiluminescence method. Compounds <b>7a</b> and <b>7f</b> exhibited potent LOX inhibitory profiles with IC<sub>50</sub> 21.83 ± 0.56 and 25.72 ± 0.51 μM, whereas <b>7d</b> and <b>7e</b> showed comparable inhibitory potential with IC<sub>50</sub> values of 34.52 ± 0.39 and 39.12 ± 0.46 μM, respectively. Compounds <b>7a</b>, <b>7f</b>, <b>7d</b> and <b>7e</b> exhibited 65.58 ± 1.4%, 54.72 ± 1.3%, 58.52 ± 1.2% and 63.56 ± 1.4% blood mononuclear cells viability, respectively. Density functional theory and molecular docking studies further strengthened the studies of the synthesized compounds and these derivatives perceived to be potential 'lead' compounds in drug discovery as anti-LOX.Communicated by Ramaswamy H. Sarma.
Resolving the fate of trace metals during microbial remineralization of phytoplankton biomass in precursor banded iron formation sediments
2022-06-14

Abstract Banded Iron Formations (BIFs) have long been considered a sedimentary record of seawater trace metal composition during the Precambrian. However, recent work has suggested that the trace metal composition of BIFs was derived from phytoplankton biomass, not seawater. In this model, phytoplankton biomass settles from the photic zone to the seafloor sediments, where it is then oxidized by heterotrophic microbes, such as dissimilatory Fe(III) reducing (DIR) bacteria, for energy generation. Remineralization of this biomass released the trace metals associated with organic molecules from phytoplankton ( i . e ., in metalloproteins), allowing these metals to be captured by Fe (oxyhydr)oxides and preserved in BIFs. While there is compelling evidence that the phytoplankton biomass served as a trace metal shuttle to precursor BIF sediments, it is unclear whether the degradation of biomass by DIR bacteria would liberate the biogenic trace metals as the model proposes. This work tests this hypothesis by using anoxic incubations of a model DIR bacterium ( Shewanella oneidensis MR-1) with phytoplankton biomass as energy and carbon sources and ferrihydrite, a poorly crystalline Fe(III) oxyhydroxide (Fe(OH) 3 ), as electron acceptor. Our results show that while S. oneidensis MR-1 can consume some of the carbon substrates found in phytoplankton biomass, there is no evidence that S. oneidensis MR-1 degraded metalloproteins which would have liberated trace metals. In the context of the Precambrian, these data imply that other heterotrophic bacteria, such as fermenters, may have had a larger role in the liberation of trace metals from dead biomass during early BIF development. Highlights Phytoplankton are the proposed source of trace metals to banded iron formations Iron reducers are hypothesized to release metals from phytoplankton biomass Experiments show that iron reducers do not liberate metals when degrading biomass Other microbial heterotrophs must have liberated the biogenic trace metals
Spesolimab Treatment for People with Flares of Generalized Pustular Psoriasis: A Plain Language Summary of the Effisayil™ 1 Study
2022-06-14

What is this study about?: Spesolimab is a drug developed to treat worsening disease (known as flares) of generalized pustular psoriasis (shortened to GPP). GPP is a rare disease in which pus-filled blisters or pustules suddenly form all over the body. Before a drug can be approved to treat the symptoms of a disease, clinical studies are performed to test how well it works and whether there are any side effects. This summary reports the results from a clinical study called EffisayilTM 1 that was performed to understand if spesolimab is effective at treating people with GPP flares. What were the results?: The study showed that a single dose of spesolimab rapidly cleared pustules and skin lesions (areas of skin affected by redness, pustules, and scaling) within 1 week of treatment, and continued to improve skin lesions for up to 12 weeks. Spesolimab also reduced pain and improved the quality of life of participants over time. Some participants experienced side effects, which were mostly mild or moderate. What do the results of the study mean?: The results indicate that spesolimab is an effective treatment for GPP flares. Although spesolimab is not yet available for doctors to prescribe as medication to their patients, the results of this study are currently under review by the official body that approves drugs for use in the USA.
Additional file 8 of A 13.42-kb tandem duplication at the ASIP locus is strongly associated with the depigmentation phenotype of non-classic Swiss markings in goats
2022-06-14

Additional file 8: Table S6. The genome-coverage analysis and predicted copy numbers of the 13,420-bp duplicated sequence in the total 70 goats with Swiss markings from four domestic goat populations.
Diabetes Distress, Depressive Symptoms, and Anxiety Symptoms in People With Type 2 Diabetes: A Network Analysis Approach to Understanding Comorbidity
2022-06-15

OBJECTIVE In this study, we aimed to explore interactions between individual items that assess diabetes distress, depressive symptoms, and anxiety symptoms in a cohort of adults with type 2 diabetes using network analysis. RESEARCH DESIGN AND METHODS Participants (N = 1,796) were from the Montreal Evaluation of Diabetes Treatment (EDIT) study from Quebec, Canada. A network of diabetes distress was estimated using the 17 items of the Diabetes Distress Scale (DDS-17). A second network was estimated using the DDS-17 items, the nine items of the Patient Health Questionnaire (PHQ-9), and the seven items of the Generalized Anxiety Disorder Assessment (GAD-7). Network analysis was used to identify central items, clusters of items, and items that may act as bridges between diabetes distress, depressive symptoms, and anxiety symptoms. RESULTS Regimen-related and physician-related problems were among the most central (highly connected) and influential (most positive connections) in the diabetes distress network. The depressive symptom of failure was found to be a potential bridge between depression and diabetes distress, being highly connected to diabetes distress items. The anxiety symptoms of worrying too much, uncontrollable worry, and trouble relaxing were identified as bridges linking both anxiety and depressive items and anxiety and diabetes distress items, respectively. CONCLUSIONS Regimen-related and physician-related diabetes-specific problems may be important in contributing to the development and maintenance of diabetes distress. Feelings of failure and worry are potentially strong candidates for explaining comorbidity. These individual diabetes-specific problems and mental health symptoms could hold promise for targeted interventions for people with type 2 diabetes.