julilili42/papers huggingface dataset:
Additional file 24 of Canalization of genome-wide transcriptional activity in Arabidopsis thaliana accessions by MET1-dependent CG methylation
2023-04-13

Additional file 24: Table S4. (1) Frameshifted oligonucleotides (forward and reverse primers) used for amplicon-sequencing of multiple samples. (2) List of individual samples analyzed for each mutant line.
Additional file 1 of Molecular characterisation of 36 multilocus imprinting disturbance (MLID) patients: a comprehensive approach
2023-04-13

Additional file 1. Table S1 Studies reporting on screening for MLID in ImpDis cohorts. Table S2 MS-MLPA results in the study population. DNA methylation alterations of 13 imprinted DMRs in 25 BWS/MLID and eleven SRS/MLID patients are shown. Oocyte-derived gDMRs are marked in red, sperm-derived gDMRs in blue. Table S3 ImprintSeq results. Mean methylation levels (MMLs) per locus and patient. The extent of methylation is shown by a colour gradient (red = high MML; green = low MML). The mean MML of the BWS/MLID and SRS/MLID group and its standard deviation from the control’s MML as well as the frequency of LOMs/GOMs per iDMR are listed below. Table S4 Application of the molecular MLID criteria proposed by Ochoa et al. (9) in the 27 patients examined by ImprintSeq. Table S5 Physical positions (CGRCh37/hg19) of the iDMRs analysed by MS-MLPA and ImprintSeq. Table S6 Discrepancy findings between MS-MLPA and ImprintSeq. In five iDMRs, discrepant results were examined by pyrosequencing. Table S7 WES results in our cohort. Pathogenic variants detected in NLRP2, NLRP5, and PADI6 in the six families for which data from NGS approaches have been published previously (14-16). The yet unpublished variant in NLRP7 is marked in red. Table S8 Clinical scores of the BWS/MLID (a) and SRS/MLID (b) patients, leaned on the BWS spectrum (BWSp)-scoring system suggested by Brioude et al. (17) and the Netchine-Harbison clinical scoring system (NH-CSS)(18). The frequency of clinical features of MLID patients is compared with those of single-locus patients of previously published studies (36, 38). Table S9 Birth parameters of the BWS/MLID and SRS/MLID patients, compared with those of single-locus patients from previously published studies (36, 38). Table S10 Reproductive history of the MLID mothers. Table S11 Functional properties of iDMRs with currently unknown clinical relevance but often affected in BWS/MLID or SRS/MLID patients.
Additional file 1 of Canalization of genome-wide transcriptional activity in Arabidopsis thaliana accessions by MET1-dependent CG methylation
2023-04-13

Additional file 1: Table S1. (1) CRISPR guide-RNA design for MET1 knockout, primers used for PCR-based genotyping of frameshift mutations. (2) List of accessions used in this study. (3) List of mutants in each accession and identified mutations.
Additional file 10 of Constructing a novel mitochondrial-related gene signature for evaluating the tumor immune microenvironment and predicting survival in stomach adenocarcinoma
2023-04-13

Additional file 10: Tables S1–S14. Table S1. The list of mitochondrial-related genes. Table S2. The list of carcinoma associated fibroblast up signatures (n=24). Table S3. The list of carcinoma associated fibroblast down signatures (n=24). Table S4. The list of ECM and Collagen signatures (n=225). Table S5. The list of matrisome signatures (1026). Table S6. The primer sequences. Table S7. The list of all DEGs in tumor and normal groups (n=2381). Table S8. The list of protein-coding DEGs in tumor and normal groups (n=2145). Table S9. The list of mitochondrial-related DEGs (n=183). Table S10. GO terms in tumor and normal groups. Table S11. KEGG terms in tumor and normal groups. Table 12. The list of DEGs in high and low risk groups (n=298). Table S13. GO terms in high and low risk groups. Table S14. KEGG terms in high and low risk groups .
Additional file 2 of Canalization of genome-wide transcriptional activity in Arabidopsis thaliana accessions by MET1-dependent CG methylation
2023-04-13

Additional file 2: Table S2. (1) Numbers of DEGs, DMRs and HV-dACRs identified across all samples. (2) Numbers of DEGs identified across all contrasts. (3) Numbers of unique genes identified in intersections between DEGs, DMRs and HV-dACRs. (4) Intersections between DMR and HV-dACRs with TEs and genes.
PFAS-Contaminated Soil Site in Germany: Nontarget Screening before and after Direct TOP Assay by Kendrick Mass Defect and FindPFΔS
2023-04-14

Soil contaminations with per- and polyfluoroalkyl substances (PFAS) are of great concern due to their persistence, leading to continuous, long-term groundwater contamination. A composite sample from contaminated agricultural soil from northwestern Germany (Brilon-Scharfenberg, North Rhine-Westphalia) was investigated in depth with nontarget screening (NTS) (Kendrick mass defect and MS<sup>2</sup> fragment mass differences with FindPFΔS). Several years ago, selected PFCAs and PFSAs were identified on this site by detection in nearby surface and drinking water. We identified 10 further PFAS classes and 7 C<sub>8</sub>-based PFAS (73 single PFAS) previously unknown in this soil including some novel PFAS. All PFAS classes except for one class comprised sulfonic acid groups and were semi-quantified with PFSA standards from which ∼97% were perfluorinated and are not expected to be degradable. New identifications made up >75% of the prior known PFAS concentration, which was estimated to >30 μg/g. Pentafluorosulfanyl (-SF<sub>5</sub>) PFSAs are the dominant class (∼40%). Finally, the soil was oxidized with the direct TOP (dTOP) assay, revealing PFAA precursors that were covered to a large extent by identified H-containing PFAS and additional TPs (perfluoroalkyl diacids) were detected after dTOP. In this soil, however, dTOP + target analysis covers <23% of the occurring PFAS, highlighting the importance of NTS to characterize PFAS contaminations more comprehensively.
IgG-based B7-H3xCD3 bispecific antibody for treatment of pancreatic, hepatic and gastric cancer
2023-04-14

T cell-based immunotherapy has significantly improved treatment options for many malignancies. However, despite these and other therapeutic improvements over the last decades, gastrointestinal cancers, in particular pancreatic, hepatic and gastric cancer, are still characterized by high relapse rates and dismal prognosis, with an accordingly high unmet medical need for novel treatment strategies. We here report on the preclinical characterization of a novel bispecific antibody in an IgG-based format termed CC-3 with B7-H3xCD3 specificity. In many cancer entities including pancreatic, hepatic and gastric cancers, B7-H3 (CD276) is overexpressed on tumor cells and also on the tumor vasculature, the latter allowing for improved access of immune effector cells into the tumor site upon therapeutic targeting. We demonstrate that CC-3 induces profound T cell reactivity against various pancreatic, hepatic and gastric cancer cell lines as revealed by analysis of activation, degranulation and secretion of IL2, IFNγ as well as perforin, resulting in potent target cell lysis. Moreover, CC-3 induced efficient T cell proliferation and formation of T cell memory subsets. Together, our results emphasize the potential of CC-3, which is presently being GMP-produced to enable clinical evaluation for treatment of pancreatic, hepatic and gastric cancer.
A Multicenter, Propensity Score–Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas
2023-04-14

BACKGROUND AND OBJECTIVES: There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery. METHODS: To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score–matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed. RESULTS: Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P &lt; .01). However, microscopic surgery also had a 7.82 OR ( P &lt; .01) for intensive care unit stay, 2.08 OR ( P &lt; .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (β = 2.01, P &lt; .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach. CONCLUSION: Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices.
The dark side of detracking: Mixed-ability classrooms negatively affect the academic self-concept of students with low academic achievement
2023-04-14

The labeling hypothesis argues that mixed-ability classrooms foster the academic self-concept of students with low academic achievement because they lose their negative track branding. The contrast hypothesis presents the opposing view that mixed-ability classrooms expose students with low academic achievement to higher achieving peers, thus harming their self-concept due to social comparisons. The present study used data from two detracking school reforms (NStudy1 = 78,330 students, NStudy2 = 2,202 students) and employed a cohort-control design to compare cohorts before detracking with cohorts after detracking. In both studies, students with low academic achievement had a lower self-concept in untracked cohorts than in the tracked ones. However, the self-concept of students with high academic achievement did not differ between the cohorts. Our study highlights potential side effects of detracking school reforms that might result from students with low academic achievement being exposed to unfavorable social comparison processes.
DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
2023-04-14

Abstract Purpose: Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in head and neck squamous cell carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. Experimental Design: A DNA-methylome–based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA (The Cancer Genome Atlas)-HNSCC cohort based on matched assignments using gene expression–based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of human papillomavirus (HPV)–negative patients with HNSCC treated with primary radiochemotherapy (RCHT). Results: Although hypoxia-GES failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (HR, 4.3; P = 0.001) and overall survival (HR, 2.34; P = 0.03) but not distant metastasis after RCHT in both cohorts. Hypoxia-M status was inversely associated with CD8 T-cell infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR, 1.83; P = 0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status. Conclusions: Our findings highlight an unexplored avenue for DNA methylation–based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors. See related commentary by Heft Neal and Brenner, p. 2954
Whole genome analysis of two sympatric human Mansonella: Mansonella perstans and Mansonella sp “DEUX”
2023-04-14

Introduction Mansonella species are filarial parasites that infect humans worldwide. Although these infections are common, knowledge of the pathology and diversity of the causative species is limited. Furthermore, the lack of sequencing data for Mansonella species, shows that their research is neglected. Apart from Mansonella perstans, a potential new species called Mansonella sp “DEUX” has been identified in Gabon, which is prevalent at high frequencies. We aimed to further determine if Mansonella sp “DEUX” is a genotype of M. perstans , or if these are two sympatric species. Methods We screened individuals in the area of Fougamou, Gabon for Mansonella mono-infections and generated de novo assemblies from the respective samples. For evolutionary analysis, a phylogenetic tree was reconstructed, and the differences and divergence times are presented. In addition, mitogenomes were generated and phylogenies based on 12S rDNA and cox1 were created. Results We successfully generated whole genomes for M. perstans and Mansonella sp “DEUX”. Phylogenetic analysis based on annotated protein sequences, support the hypothesis of two distinct species. The inferred evolutionary analysis suggested, that M. perstans and Mansonella sp “DEUX” separated around 778,000 years ago. Analysis based on mitochondrial marker genes support our hypothesis of two sympatric human Mansonella species. Discussion The results presented indicate that Mansonella sp “DEUX” is a new Mansonella species. These findings reflect the neglect of this research topic. And the availability of whole genome data will allow further investigations of these species
Barriers and enabling factors for workplace integration of internationally qualified nurses: A qualitative study of perceptions of German nurses
2023-04-14

Abstract Aim Examine perceptions of nurses who obtained a recognised nursing qualification in Germany about the integration of internationally qualified nurses (IQN) in the German nursing workforce. Design Qualitative interview study. Methods Semi‐structured interviews with 21 state‐qualified nurses who had graduated from a German nursing program were conducted either face‐to‐face or by telephone. Nurses were selected using the purposive sampling method. Additionally, to reach a sufficient sample size, snowball sampling was applied. Each interview was pseudonymized and transcribed. Transcripts were coded according to Qualitative Content Analysis with data structured into themes and sub‐themes. The study was reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist for qualitative research. Results Two main themes including sub‐themes were identified: (a) Enabling Factors to Workplace Integration: motivated nursing team, structured orientation program, support by a preceptor, additional practical skills and specific language training and (b) Barriers to Workplace Integration: lack of language proficiency, cultural differences, othering and racism/discrimination. The findings of the study suggest that working in a diverse workplace can be challenging, it is therefore important for successful integration to recognise not only the experiences of IQN but also the perceptions of nurses who work with internationally qualified peers. No patient or public contribution. Registration number The study has been prospectively registered (27 June 2019) at the German Clinical Trial Register (REDACTED).
Different components of cognitive-behavioural therapy affect specific cognitive mechanisms
2023-04-14

Psychological therapies are among the most effective treatments for a range of common mental health problems – however, we still know relatively little about how exactly they improve symptoms. Here, we demonstrate the power of combing theory with computational methods to parse effects of different components of cognitive-behavioural therapies on to underlying mechanisms. Specifically, we present data from a series of randomized-controlled experiments testing the effects of brief components of behavioural and cognitive therapies on different cognitive processes, using well-validated behavioural measures and associated computational models (total N=807). We found that a goal-setting intervention, based on behavioural activation therapy materials, reliably and selectively reduced sensitivity to effort when deciding how to act to gain reward. By contrast, we found that a cognitive restructuring intervention, based on cognitive therapy materials, reliably and selectively reduced the tendency to attribute negative everyday events to self-related causes. Importantly, the effects of each intervention were specific to these respective measures. Our approach provides a basis for beginning to understand how different elements of common psychotherapy programs work, from which we may be able to work towards theoretically-informed treatment targeting in the future.
Extensive remodelling of the cell wall during the development of Staphylococcus aureus bacteraemia
2023-04-14

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.
Miniaturization and microfluidic devices: an overview of basic concepts, fabrication techniques, and applications
2023-04-14

Abstract Miniaturization brings along significant advantages in the development, optimization, and implementation of chemical, biochemical, and related fields processes and assays. Given the reduced footprint, miniaturization allows a significant reduction in volumes to be processed while providing conditions for several conditions to be evaluated simultaneously. Accordingly, work can be performed timely in a space efficient manner, with significant costs savings. Microfluidics is the pinnacle of miniaturization, where the previous advantageous aspects are taken to the limit, with the added features of operation under well-defined and highly efficient mass and heat transfer environment. Additionally, microfluidic environment fosters process integration, monitoring, and control in a single framework. The present chapter aims to provide an overview of diverse applications of miniaturized devices, fabrication methods, and key issues in fluid dynamics that characterize a microfluidic environment.
Synthetic curcumin analogues present antiflavivirus activity in vitro with potential multiflavivirus activity from a thiazol-ylhydrazone moiety
2023-04-14

Those files comprise trajectories of MD simulations of protein E dimers in presence of ligands of interest (see below). We also provide the data for the simulation interactions and RMSD/RMSF as raw data here enclosed. Methods and ligand specifications are provided in the respective manuscript.Trajectories were generated in Desmond and are provided in this format, alternative formats or specific frames are available upon request. a = apo x = lig xtal 6 = cpd6 7 = cpd7
Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia
2023-04-14

Introductory Paragraph / Abstract The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of this protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.
Dynamic fluctuations in a bacterial metabolic network
2023-04-15

Abstract The operation of the central metabolism is typically assumed to be deterministic, but dynamics and high connectivity of the metabolic network make it potentially prone to generating fluctuations. However, time-resolved measurements of metabolite levels in individual cells that are required to characterize such fluctuations remained a challenge, particularly in small bacterial cells. Here we use single-cell metabolite measurements based on Förster resonance energy transfer, combined with computer simulations, to explore the real-time dynamics of the metabolic network of Escherichia coli . We observe that steplike exposure of starved E. coli to glycolytic carbon sources elicits large periodic fluctuations in the intracellular concentration of pyruvate in individual cells. These fluctuations are consistent with predicted oscillatory dynamics of E. coli metabolic network, and they are primarily controlled by biochemical reactions around the pyruvate node. Our results further indicate that fluctuations in glycolysis propagate to other cellular processes, possibly leading to temporal heterogeneity of cellular states within a population.