julilili42/papers huggingface dataset:
Phase-specific signatures of wound fibroblasts and matrix patterns define cancer-associated fibroblast subtypes
2022-11-20

ABSTRACT Healing wounds and cancers present remarkable cellular and molecular parallels, but the specific roles of the healing phases are largely unknown. We developed a bioinformatics pipeline to identify genes and pathways that define distinct phases across the time course of healing. Their comparison to cancer transcriptomes revealed that a resolution-phase wound signature is associated with increased severity in skin cancer and enriches for extracellular matrix-related pathways. Comparisons of transcriptomes of early- and late-phase wound fibroblasts vs skin cancer-associated fibroblasts (CAFs) identified an “early-wound” CAF subtype, which localizes to the inner tumor stroma and expresses collagen-related genes that are controlled by the RUNX2 transcription factor. A “late-wound” CAF subtype localizes to the outer tumor stroma and expresses elastin-related genes. Matrix imaging of primary melanoma tissue microarrays validated these matrix signatures and identified collagen- vs elastin-rich niches within the tumor microenvironment, whose spatial organization predicts survival and recurrence. These results identify wound-regulated genes and matrix patterns with prognostic potential in skin cancer.
Current Issues in Sport Science
2022-11-21

CISS welcomes and encourages articles addressing a broad range of topics across sport science which include but is not limited to genetic, biological, physical, physiological, psychological, pedagogical, sociological, environmental, policy among other aspects. In this editorial, we highlight several topics of interest for each of our sections within CISS: biology &amp; medicine, biomechanics &amp; informatics, movement &amp; exercise science, pedagogy &amp; history, psychology &amp; philosophy, public health, sociology &amp; economics and technology. We hope to motivate you and your colleagues to join us in advancing the field of sport science.
How error-prone bioaccumulation experiments affect the risk assessment of hydrophobic chemicals and what could be improved
2022-11-21

Abstract Bioaccumulation is one of the three criteria for the PBT assessment of chemicals, where P stands for persistence, B for bioaccumulation, and T for toxicity, which is a cornerstone for the “Registration, Evaluation, Authorization, and Restriction of Chemicals” (REACH) in the EU. Registrants are required by REACH to submit data on bioaccumulation if the chemical is manufactured in and/or imported to the European Economic Area at more than 100 t/year. Most of the experimental bioaccumulation studies submitted were on the bioconcentration factor (BCF) and were conducted prior to 2012, before the OECD Test Guideline 305 on Bioaccumulation in Fish was updated. An analysis of the submitted data revealed that many of the experimental data, but also the data from QSARs and other calculation methods, underestimate the actual bioaccumulation potential of hydrophobic substances considerably. One of the main reasons in the nonexperimental studies is that the BCF is related there to the total concentration of the chemical in water and not to the dissolved chemical concentration. There is therefore an urgent need to reassess the bioaccumulation potential of the hydrophobic substances registered under REACH. Based on the model calculations in the present study, between 332 and 584 substances that are registered under REACH are likely to bioaccumulate in the aquatic environment—many more than have so far been identified in the B assessment. Integr Environ Assess Manag 2023;19:792–803. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology &amp; Chemistry (SETAC).
Millennial-timescale quantitative estimates of climate dynamics in central Europe from earthworm calcite granules in loess deposits
2022-11-21

Abstract Ice core and marine archives provide detailed quantitative records of last glacial climate changes, whereas comparable terrestrial records from the mid-latitudes remain scarce. Here we quantify warm season land-surface temperatures and precipitation over millennial timescales for central Europe for the period spanning 45,000–22,000 years before present that derive from two temporally overlapping loess-palaeosol-sequences, dated at high resolution by radiocarbon on earthworm calcite granules. Interstadial temperatures were 1–4 °C warmer than stadial climate, a temperature difference which is strongly attenuated compared to Greenland records. We show that climate in the Rhine Valley was significantly cooler during the warm season and overall drier with annual precipitation values reduced by up to 70% compared to the present day. We combine quantitative estimates with mesoscale wind and moisture transport modelling demonstrating that this region was dominated by westerlies and thereby inextricably linked to North Atlantic climate forcing, although ameliorated.
Exome-based gene panel analysis in a cohort of acute juvenile ischemic stroke patients:relevance of NOTCH3 and GLA variants
2022-11-21

Abstract Background Genetic variants are considered to have a crucial impact on the occurrence of ischemic stroke. In clinical routine, the diagnostic value of next-generation sequencing (NGS) in the medical clarification of acute juvenile stroke has not been investigated so far. Material and methods We analyzed an exome-based gene panel of 349 genes in 172 clinically well-characterized patients with magnetic resonance imaging (MRI)-proven, juvenile (age ≤ 55 years), ischemic stroke admitted to a single comprehensive stroke center. Results Monogenetic diseases causing ischemic stroke were observed in five patients (2.9%): In three patients with lacunar stroke (1.7%), we identified pathogenic variants in NOTCH3 causing cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Hence, CADASIL was identified at a frequency of 12.5% in the lacunar stroke subgroup. Further, in two male patients (1.2%) suffering from lacunar and cardioembolic stroke, pathogenic variants in GLA causing Fabry’s disease were present. Additionally, genetic variants in monogenetic diseases lacking impact on stroke occurrence, variants of unclear significance (VUS) in monogenetic diseases, and (cardiovascular-) risk genes in ischemic stroke were observed in a total of 15 patients (15.7%). Conclusion Genetic screening for Fabry’s disease in cardioembolic and lacunar stroke as well as CADASIL in lacunar stroke might be beneficial in routine medical work-up of acute juvenile ischemic stroke.
Ovarian tissue cryopreservation for a 3-year-old girl with Mosaic Turner syndrome in China: First case report and literature review
2022-11-21

Background Although it cannot be predicted accurately which young females will develop premature ovarian insufficiency (POI) following chemotherapy or irradiation, patients at high risk of POI should be offered ovarian tissue cryopreservation (OTC). Our ovarian tissue cryobank is the first center in China. OTC was firstly performed on a 3-year-old girl with mosaic Turner syndrome (TS) in China. We report this case and present a literature review about TS girls’ fertility preservation (FP). Case presentation Karyotype analysis of umbilical cord blood showed that the girl was diagnosed with TS, 45,X [19]/46,XX [81]. The girl was a 3-year-old girl when her parents would like OTC to preserve fertility. No abnormality was found in the reproductive system, abdominal and cardiac ultrasound, spinal X-ray, and bone age. She was treated with growth hormone (GH) one year ago because of her short stature. GH has been discontinued now. Because of the high risk of POI, OTC was planned. The hormone level before OTC was FSH 4.27 IU/L, LH 0.00 IU/L, E2 &amp;lt; 11.80 pg/ml, AMH 1.06 ng/ml. Pelvic ultrasound showed that the size of the bilateral ovaries was 1.6 cm×0.7-0.8 cm, no enlarged follicles were found, and the maximum diameter of follicles was 0.2-0.37 cm. Ovarian tissue for OTC was taken from the whole right ovary by laparoscopic surgery, and the antral follicles could be seen in ovarian tissue preparation. Sixteen ovarian cortical slices were cryopreserved by slow freezing, with an average of 1380 follicles in round cortical tissue with a diameter of 2 mm, and the follicular density was about 440/mm 3 . The ovarian tissue from 10 children with non-TS was cryopreserved in our center, the median age was 5 (range 2-8) years old, and the median number of follicles was 766 (range 163-2250) per 2 mm biopsy. The follicles number in this girl were within normal range. Conclusion TS patients should be evaluated early in childhood to benefit from FP. For highly selected young females with mosaic TS, if the endocrine evaluation does not indicate POI and other health problems do not rule out future pregnancy, it seems reasonable to consider OTC as an FP option.
Clinical, genetic, and epidemiological survey of Polish children and adolescents with severe obesity: A study protocol of the Polish–German study project on severe early-onset obesity
2022-11-21

Severe early-onset obesity (SEOO) in children is a common feature of monogenic obesity. Nowadays, mutations in at least 50 genes are known to be related to monogenic obesity, and many others are tested. Part of them is involved in the leptin–proopiomelanocortin pathway. The aim of the project is to establish the Polish database of severely obese children and adolescents and to evaluate the prevalence of monogenic forms of obesity in this cohort, with a special focus on leptin–proopiomelanocortin pathway abnormalities. The secondary project aim is to identify new population-specific mutations in obesity-related genes in severely obese Polish children and adolescents. This is a prospective multi-center clinical study performed in four Polish centers. The estimated sample size is 500 patients aged 1–18 years, with severe obesity, hyperphagia, and food-seeking behaviors. In each patient, the medical history regarding the obesity duration in the patient and obesity and its complication existence in the family will be taken. Next, the questionnaire regarding the symptom characteristic of specific mutations, which we are going to test, will be performed. Hyperphagia will be assessed on the basis of age-specific questionnaires. The physical examination with anthropometric measurement, basic biochemical and hormonal tests, and leptin and biologically active leptin measurements will be performed. Finally, genetic analysis will be performed using next-generation sequencing with sequencing libraries prepared to include obesity-related genes. The genotyping findings will be confirmed with the use of classic sequencing (Sanger’s method). In the future, the pathogenicity of new mutations in obesity-related genes identified in our cohort is planned to be confirmed by functional testing in vitro . Nowadays, there are no data regarding the prevalence of severe obesity or monogenic obesity in Polish children. This project has the potential to improve understanding of obesity etiology and may contribute to implementing attribute mutation-specific treatment. Moreover, it may lead to a finding of new, population-specific mutations related to SEOO.
What Happens With Comparison Processes When “the Other” is Very Similar? Academic Self-Concept Formation in Twins
2022-11-21

According to the internal/external frame of reference (I/E) model (Marsh, 1986), individuals' academic self-concept is strongly influenced by comparing their achievement in one domain with their achievement in other domains and with the achievement of others. Research has typically found contrast effects such that high-achieving others have a negative effect on students' academic self-concept. Yet, what happens if the "other" is somebody very similar to oneself as in the case of monozygotic twins? We postulate and examine the mirror effect, which means that rather than serving as a contrast, the effect of the co-twin's achievement parallels the effect of a monozygotic twin's own achievement on academic self-concept. We used data from two school-aged cohorts (11- and 17-year-olds) from a representative sample (N = 4,202) of monozygotic and dizygotic twins in Germany. We regressed twins' math and German self-concepts on their own and their co-twins' mathematics and German achievement. Internal and external comparison effects as postulated in the I/E model were replicated for both monozygotic and dizygotic twins across both age groups. In line with our hypothesis, the mirror effect was found in monozygotic twins only: Co-twins' achievement and twins' own achievement showed a parallel pattern of positive effects on academic self-concept within each domain and negative effects on academic self-concept between domains, duplicating the I/E pattern. The mirror effect tended to be more pronounced for older monozygotic twins. We argue that the mirror effect is likely caused by high interpersonal similarity and constitutes a rare exception to the broad generalizability of contrast effects as assumed in the I/E model.
Schlenk's Legacy—Methyllithium Put under Close Scrutiny
2022-11-21

Abstract Commercially available stock solutions of organolithium reagents are well‐implemented tools in organic and organometallic chemistry. However, such solutions are inherently contaminated with lithium halide salts, which can complicate certain synthesis protocols and purification processes. Here, we report the isolation of chloride‐free methyllithium employing K[N(SiMe 3 ) 2 ] as a halide‐trapping reagent. The influence of distinct LiCl contaminations on the 7 Li‐NMR chemical shift is examined and their quantification demonstrated. The structural parameters of new chloride‐free monomeric methyllithium complex [(Me 3 TACN)LiCH 3 ], ligated by an azacrown ether, are assessed by comparison with a halide‐contaminated variant and monomeric lithium chloride [(Me 3 TACN)LiCl], further emphasizing the effect of halide impurities.
Return of individual genomic research results within the PRAEGNANT multicenter registry study
2022-11-21

Abstract Purpose The PRAEGNANT study is a registry study for metastatic breast cancer patients, focusing on biomarker detection. Recently, within this study, genetic alterations in 37 breast cancer predisposition genes were analyzed and genetic findings were detected for 396 participants. The aim of this project was to return genetic results to the physicians and to analyze actions taken (e.g., disclosure of results to patients, validation of results, clinical impact, and impact on the patient’s quality of life) using a questionnaire. Methods 235 questionnaires were sent out to the study centers, with each questionnaire representing one patient with a genetic finding. The questionnaire consisted of twelve questions in the German language, referring to the disclosure of results, validation of test results, and their impact on treatment decisions and on the patient’s quality of life. Results 135 (57.5%) questionnaires were completed. Of these, 46 (34.1%) stated that results were returned to the patients. In 80.0% ( N = 36) of cases where results were returned, the patient had not been aware of the finding previously. For 27 patients (64.3%), genetic findings had not been validated beforehand. All validation procedures ( N = 15) were covered by the patients’ health insurance. For 11 (25.0%) patients, physicians reported that the research results influenced current or future decision-making on treatment, and for 37.8% ( N = 17) the results influenced whether family members will be genetically tested. Conclusion This study provides novel insights into the return of research results and into clinical and personal benefits of disclosure of genetic findings within a German registry.
How Flexible is Cognitive Control? (Mouse)Tracking Conflict Adaptation Across Context Similarities
2022-11-21

Exerting cognitive control to remain on-task and reach our goals is a crucial skill, as is the ability to flexibly adapt our responding in rapidly changing environments. The dynamics of cognitive control are typically studied by examining how participants process stimuli that contain competing relevant and irrelevant information in so-called conflict tasks. Adjustments in performance following the experience of conflict, also termed conflict adaptation, suggests a certain degree of flexibility in the deployment of cognitive control. The present study investigated to what extent conflict adaptation effects transfer across trials of the same and different tasks in three online mouse-tracking experiments. Adaptations of the Simon and Stroop tasks were combined to create different levels of context similarity between the paired tasks. Based on a previous literature review (Braem et al. 2014, Frontiers in Psychology), across-task conflict adaptation was expected only in the most and least similar contexts. In contrast to our hypothesis, conflict adaptation effects were observed in at least one measure in all three experiments. To our surprise, task order also seemed to impact the size of across-task conflict adaptation effects. The heterogeneity in the current results highlight the importance of applying sensitive measurement tools to evaluate conflict adaptation and suggest that the occurrence of across-task conflict adaptation may be conditional on more than just shared relevant and irrelevant dimensions.
Redox control and substrate specificity of the glycogen catabolic isoenzymes in Synechocystis sp. PCC 6803
2022-11-21

Glycogen serves as the main carbon storage polymer in many organisms and is widespread across all domains of life. In cyanobacteria, glycogen degradation is crucial for metabolic transitions during dark phases or during resuscitation from nitrogen starvation. Like many other cyanobacteria, Synechocystis sp. PCC 6803 possesses multiple homologues of glycogen catabolizing enzymes, though their specific roles and regulatory mechanisms are only partially understood. Here we demonstrate through biochemical analysis that the glycogen phosphorylase GlgP1, known to promote high temperature acclimation, is uniquely regulated by a C-terminal redox switch found certain cyanobacteria. This is the first evidence of redox regulation of a prokaryotic glycogen degrading enzyme. Notably, GlgP1 is activated via oxidation by reactive oxygen species and inactivated by reducing agents, with thioredoxin being the most effective inhibitor tested. The physiological implications of this redox regulation are discussed. Additionally, a biochemically characterization of the two glycogen debranching isoenzymes GlgX1 and GlgX2 revealed that only GlgX1 exhibits debranching activity, while GlgX2 does not. Mutant analysis confirmed that GlgX1 plays an essential role in glycogen mobilization, being crucial for resuscitation from chlorosis and survival during extended dark periods. In contrast the physiological function of GlgX2 remains unclear.
Issue Information
2022-11-21

Analysis (EPA) is a double-blind peer-reviewed journal addressing European perspectives on the study of public policy.Published on behalf of the Policy Studies Organization, the journal provides a platform for individually submitted articles and special foci of high quality.Both empirical and theoretical contributions are welcomed, but EPA prefers submissions that present new theoretical or methodological perspectives combined with current data.Likewise, EPA invites overviews of country and regional perspectives on the study of public policy
Identification of a DAMP receptor and its cognate peptide ligand in sweet potato (Ipomoea batatas)
2022-11-21

Abstract Sweet potato ( Ipomoea batatas ) is an important tuber crop, but also target of numerous insect pests. Intriguingly, the abundant storage protein in tubers, sporamin, has intrinsic trypsin protease inhibitory activity. In leaves, sporamin is induced by wounding or a volatile homoterpene and enhances insect resistance. While the signaling pathway leading to sporamin synthesis is partially established, the initial event, perception of a stress-related signal is still unknown. Here, we identified a leucine-rich repeat receptor kinase ( Ib LRR-RK1) that is induced upon wounding and herbivory, and related to peptide-elicitor receptors (PEPRs) from tomato and Arabidopsis. We also identified a gene encoding a precursor protein comprising a peptide ligand ( Ib Pep1) for Ib LRR-RK1. Ib Pep1 represents a distinct signal in sweet potato, which might work in a complementary and/or parallel pathway to the previously described HypSys peptides to strengthen insect resistance. Notably, an inter-family compatibility in the Pep/PEPR system from Convolvulaceae and Solanaceae was identified.
Dynamic of SOFA Score Predicts Functionality after ARDS Therapy
2022-11-21

Abstract Rationale : Health-related quality of life after surviving acute respiratory distress syndrome has come into focus in recent years, especially during the coronavirus disease 2019 pandemic. Objectives : A total of 143 patients with acute respiratory distress syndrome caused by COVID-19 or of other origin were recruited in a randomized multicenter trial. Methods : Clinical data during intensive care treatment and data up to 180 days after study inclusion were collected. Changes in the Sequential Organ Failure Assessment score were used to quantify disease severity. Disability was assessed using the Barthel index on days 1, 28, 90, and 180. Measurements : Mortality rate and morbidity after 180 days were compared between patients with and without COVID-19. Independent risk factors associated with high disability were identified using a binary logistic regression. Main Results : Mortality after 180 days and impairment measured by the Barthel index did not differ between patients with and without COVID-19. The SOFA score at day 5 was an independent risk factor for high disability in both groups, and score dynamic within the first 5 days significantly impacted disability in the non-COVID group. Conclusions : Acute respiratory distress syndrome caused by COVID-19 was not associated with increased mortality or morbidity. Resolution of organ dysfunction within the first 5 days significantly impacts long-term morbidity and emphasizes the importance of timely initiation of treatment in these critically ill patients.