julilili42/papers huggingface dataset:
Tundra Nenets: A Heritage Language in Its Own Land? Linguistic Identity and Language Loss
2024-11-14

Through fieldwork conducted between 2014 and 2016 in Arkhangelsk, Naryan-Mar, Krasnoye, and Saint Petersburg, this paper investigates the endangered status of Tundra Nenets, an underrepresented and understudied Samoyedic minority language in northern Russia. Criteria for assessing language endangerment are applied to Tundra Nenets while also taking into consideration the interplay between language identity, reactive ethnicity, negative attitudes, and state politics. The personal story of NC, a Tundra Nenets woman, serves as a case study and exemplifies the impact of decades of marginalization, stigmatization, and discrimination on the cultural and linguistic identity. NC’s narrative illustrates how negative attitudes are exacerbating the decline of Tundra Nenets, further threatening its survival. Because of its absence from schools and institutions, Tundra Nenets seems to be turning into a heritage language in its own homeland. This paper studies the complex interplay between identity, language, and societal pressures, illustrating the broader challenges faced by the Tundra Nenets and other minority communities in maintaining their linguistic and cultural heritage. While the situation remains dire and political action is called for, efforts in boosting language awareness, documentation, and revitalization offer potential pathways for the preservation of Tundra Nenets, drawing on successful examples from other endangered language communities.
CHANGES IN STIFFNESS OF THE EXTRACELLULAR AND PERICELLULAR MATRIX IN THE ANULUS FIBROSUS OF LUMBAR INTERVERTEBRAL DISCS OVER THE COURSE OF DEGENERATION
2024-11-14

Introduction Analogous to articular cartilage, changes in spatial chondrocyte organisation have been proposed to be a strong indicator for local tissue degeneration and destruction in the intervertebral disc (IVD). While a progressive structural and functional degradation of the extracellular (ECM) and pericellular (PCM) matrix occurs in osteoarthritic cartilage, these processes have not yet been biomechanically elucidated in the IVD. We aimed to evaluate the local stiffness of the ECM and PCM in the anulus fibrosus of the IVD on the basis of local cellular spatial organisation. Method Using atomic force microscopy, we measured the elastic modulus of the local ECM and PCM in human disc samples using the spatial chondrocyte patterns as an image-based biomarker. Result By measuring tissue from 30 patients, we found a significant difference in the elastic moduli of the PCM in clusters when compared to the healthy patterns single cells (p=0.029), pairs (p=0.016), and string formations (p=0.010) whereas the values of the elastic moduli of the ECM only reached statistical significance when clusters were compared with string formations. The ECM/PCM ratio ranged from 0.62 to 0.89. Overall, the reduced elastic moduli in clusters demonstrates that cluster formation is not only a morphological phenomenon describing disc degeneration, but it marks a compromised biomechanical functioning. Conclusion This study is the first to describe and quantify the differences in the elastic moduli of the ECM in relation to the PCM in the anulus fibrosus of the IVD by means of atomic force microscopy on the basis of spatial chondrocyte organisation. Advanced disc degeneration is accompanied by a biomechanically compromised tissue functioning.
Slowing myopia progression with cylindrical annular refractive elements (CARE) spectacle lenses—Year 1 results from a 2‐year prospective, multi‐centre trial
2024-11-15

Abstract Purpose To evaluate the effectiveness of 12 months of spectacle lens wear incorporating cylindrical annular refractive elements (CARE) in slowing myopia progression compared to single vision (SV) spectacle wear. Methods In an ongoing 2‐year prospective, double‐masked, multi‐centre clinical trial, 240 Chinese children aged 6–13 years, spherical equivalent refractive error (SE) −0.75 D to −5.00 D were randomised to one of three groups of 80 participants each to wear: SV spectacle lens ( N = 80), CARE spectacles (7 mm central clear zone surrounded by treatment zone incorporating CARE with mean surface power of +4.6 D) and CARE S (9 mm central clear zone surrounded by treatment zone comprising CARE with mean surface power of +3.8 D). Cycloplegic SE and axial length (AL) were measured at 6‐month intervals. Results Compared to baseline, changes in SE and AL were significantly different between the groups at both 6 and 12 months ( p &lt; 0.001, linear mixed model). Adjusting for site, group, parental myopia and age, at 12 months, the estimated change in SE and AL with 95% CI with SV was −0.65 D (CI: −0.56 to −0.74 D)/0.32 mm (CI: 0.29–0.36 mm). In comparison, the estimated change in SE/AL at 12 months with CARE was −0.35 D (−0.26 to −0.44 D)/0.19 mm (0.15–0.22 mm) and with CARE S was −0.36 D (−0.27 to −0.46 D)/0.21 mm (0.18–0.25 mm) at 12 months. Progression was slower with CARE and CARE S compared to SV ( p &lt; 0.05) but did not differ from each other ( p = 0.793 and 0.336 for SE and AL, respectively). Conclusions In children with myopia, after 12 months of lens wear, both CARE and CARE S spectacle lenses significantly slowed myopia progression compared to SV lenses.
Utilization of Psychiatric Hospital Services Following Intensive Home Treatment
2024-11-15

Importance Home treatment (HT) has been associated with fewer inpatient treatment (IT) readmission days but lacks evidence on reducing combined psychiatric hospital service use (IT, HT, day clinic). Objective To assess the association of intensive home treatment (IHT) compared with IT regarding readmission rate, social outcomes, and clinical outcomes. Design, Setting, and Participants This quasi-experimental, nonrandomized trial was conducted from 2020 to 2022 in 10 psychiatric hospitals in Germany. Propensity score (PS) matching was used to compare both treatment models at the 12-month follow-up using standardized instruments and routine hospital data. All patients were screened until the target sample size was reached, based on these criteria: stable residence with privacy for sessions, no child welfare risk, primary diagnosis within International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F0X to F6X, residence in the catchment area, no commitment order, no acute suicidality or severe aggression requiring hospitalization, capacity to consent, not participating in other interventional studies, sufficient German language skills, no substantial cognitive deficits or intellectual impairment, and no more than 7 days in IHT or IT before recruitment. Statistical analysis was performed from February to November 2023. Intervention IHT provided daily acute psychiatric treatment at home, while IT was psychiatric inpatient treatment as usual. The mean treatment duration of the index treatment was 37.2 days for IHT and 28.2 days for IT. Main Outcomes and Measures The inpatient readmission rate was the primary outcome. Secondary outcomes were combined readmission rate, total inpatient days, job integration, quality of life, psychosocial functioning, symptom severity, and recovery. Results Of 1396 individuals, 200 patients receiving IHT and 200 patients receiving IT were included (264 female [65%]; mean [SD] age, 45.45 [15.83] years [range, 18-88 years]). Baseline sociodemographic and psychometric characteristics did not differ significantly between the groups. At 12-month follow-up, patients in the IHT group had lower inpatient readmission rate (IHT vs IT: 31.12% vs 49.74% IT; mean difference, 18% [95% CI, 9%-28%; P &amp;amp;lt; .001), combined readmission rate (mean difference, 13% [95% CI, 4%-24%; P &amp;amp;lt; .001), and fewer inpatient days (mean difference, 6.82 days; P &amp;amp;lt; .001) than the IT group. Conclusions and Relevance This nonrandomized clinical trial found that patients receiving IHT had a lower likelihood of utilizing hospital-based psychiatric services and spent fewer inpatient days, suggesting that IHT is a viable alternative to IT. Trial Registration ClinicalTrials.gov Identifier: NCT04745507
The T4bSS of Legionella features a two-step secretion pathway with an inner membrane intermediate for secretion of transmembrane effectors
2024-11-15

To promote intracellular survival and infection, Legionella spp . translocate hundreds of effector proteins into eukaryotic host cells using a type IV b protein secretion system (T4bSS). T4bSS are well known to translocate soluble as well as transmembrane domain-containing effector proteins (TMD-effectors) but the mechanisms of secretion are still poorly understood. Herein we investigated the secretion of hydrophobic TMD-effectors, of which about 80 were previously reported to be encoded by L . pneumophila . A proteomic analysis of fractionated membranes revealed that TMD-effectors are targeted to and inserted into the bacterial inner membranes of L . pneumophila independent of the presence of a functional T4bSS. While the T4bSS chaperones IcmS and IcmW were critical for secretion of all tested TMD-effectors, they did not influence inner membrane targeting of these proteins. As for soluble effector proteins, translocation of all investigated TMD-effectors depended on a C-terminal secretion signal. A deeper analysis of the TMD-effector SidF showed that this signal needed to be presented towards the cytoplasmic side of the inner membrane and that a small periplasmic loop was required for efficient translocation. We propose that strongly hydrophobic TMD-effectors are secreted in a two-step secretion process: Initially, an inner membrane intermediate is formed, that is extracted towards the cytoplasmic side, possibly by the help of the type IV coupling protein complex and subsequently secreted into eukaryotic host cells by the T4bSS core complex. Overall, our study highlights the amazing versatility of T4bSS to secrete soluble and TMD-effectors from different subcellular locations of the bacterial cell.
Alterations in Glucagon Levels and the Glucagon-to-Insulin Ratio in Response to High Dietary Fat or Protein Intake in Healthy Lean Adult Twins: A Post Hoc Analysis
2024-11-15

Background/Objectives: Emerging data support evidence of the essential role of glucagon for lipid metabolism. However, data on the role of dietary fat intake for glucagon secretion is limited. This analysis investigated whether altering nutritional fat intake affects glucagon levels in healthy subjects. Methods: A total of 92 twins (age: 31 ± 14 years, BMI: 23 ± 3 kg/m2) consumed two 6-week diets: first a low-fat, high-carbohydrate diet (LFD) followed by an isocaloric high-fat, low-carbohydrate diet (HFD). In total, 24 twins (age: 39 ± 15 years, BMI: 24 ± 2 kg/m2) continued with a high-protein diet (HPD). Clinical investigations were performed after 6 weeks of the LFD, after 1 and 6 weeks of the HFD and after 6 weeks of the HPD. Results: The LFD caused a significant decrease in fasting glucagon (−27%, p &lt; 0.001) compared to baseline. After 6 weeks of the HFD, glucagon increased (117%, p &lt; 0.001 vs. LFD), while free fatty acids decreased. Six weeks of the HPD further increased glucagon levels (72%, p = 0.502 vs. HFD), although fasting amino acid levels remained constant. Fasting insulin and HOMA-IR moderately increased after one week of the HFD, while six weeks of the HPD significantly decreased both. The fasting glucagon-to-insulin ratio decreased during the LFD (p &lt; 0.001) but increased after the HFD (p &lt; 0.001) and even further increased after the HPD (p = 0.018). Liver fat, triglycerides and blood glucose did not increase during the HFD. The heritability of glucagon levels was 45% with the LFD. Conclusions: An HFD increases glucagon levels and the glucagon-to-insulin ratio under isocaloric conditions compared to an LFD in healthy lean subjects. This rise in glucagon may represent a metabolic response to prevent hepatic steatosis, as glucagon increases have been previously shown to induce hepatic fat oxidation.
Single-cell transcriptomics link gene expression signatures to clinicopathological features of gonadotroph and lactotroph PitNET
2024-11-15

Abstract Background Pituitary neuroendocrine tumors (PitNET) are among the most common intracranial tumors. Despite a frequent benign course, aggressive behavior can occur. Tumor behavior is known to be under the influence of the tumor microenvironment (TME). However, the relationship between TME cells and aggressive tumor behavior has not been adequately explored in PitNET. Methods We performed differential expression analysis as well as gene expression program identification based on single-cell RNA sequencing to comparatively characterize the transcriptome of seven gonadotroph and three lactotroph PitNET and correlate it with clinical features using bulk RNA-seq data from an independent cohort of 134 PitNET. Tumor immune infiltration was quantified via immunostaining on tissue sections of gonadotroph and lactotroph PitNET. Results In lactotroph PitNET, we detect a highly proliferative gene profile with significantly increased expression levels in aggressively growing tumors within bulk RNA-seq data of an independent cohort of 134 PitNET samples. We also report high intratumoral heterogeneity in gonadotroph PitNET (GoPN) and lactotroph PitNET (LaPN) and identify signatures of epithelial, endocrine, and immunological gene networks in both subtypes. A comparison of their TME composition shows enrichment of SPP1 + macrophages and CD4 + T cells in GoPN, as well as enrichment of CD4/CD8 double-negative T cells (DN) and natural killer cells (NK) in LaPN. Also notable is the presence of proliferative lymphocytes, the occurrence of which positively correlates with more aggressive tumor behavior in the bulk RNA-seq cohort. However, increased CD8 + T and NK cell abundances correlate significantly with reduced aggressiveness indicating potential anti-tumoral effects. Conclusions Our study expands the knowledge of the differences in cellular composition of gonadotroph and lactotroph PitNET subtypes. It lays the foundation for further studies on the influence of lymphoid cells on the variable aggressive behavior of PitNET. Regarding the treatment of drug-resistant lactotroph PitNET, proliferative lymphocytes, CD8 + T, and NK cells could represent potentially valuable targets for developing new cancer immunotherapies.
Unveiling novel conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling
2024-11-15

Abstract The development of ribosomal profiling (Riboseq) revealed the immense coding capacity of human and viral genomes. Here, we used Riboseq to delineate the first translatome of HIV-1 in infected CD4 + T cells. In addition to canonical viral protein coding sequences (CDSs), we identify 98 alternative open reading frames (ARFs), corresponding to small Open Reading Frames (sORFs) that are distributed across the HIV genome including the UTR regions. Using a database of HIV genomes, we observed that most ARF amino-acid sequences are likely conserved among clade B and C of HIV-1, with 8 ARF-encoded amino-acid sequences being more conserved than the overlapping CDSs. Using T cell-based assays and mass spectrometry-based immunopeptidomics, we demonstrate that ARFs encode viral polypeptides. In the blood of HIV-infected individuals, ARF-derived peptides elicit potent poly-functional T cell responses mediated by both CD4 + and CD8 + T cells. Our discovery expands the list of conserved viral polypeptides that are targets for vaccination strategies and might reveal the existence of viral microproteins or pseudogenes.
Evidence of Middle Palaeolithic human occupation in south-central Oman
2024-11-15

Abstract Debate surrounds the early peopling of the Arabian Peninsula. The first evidence of the Levallois lithic technology in the Huqf area of south-eastern Arabia now extends the Middle Palaeolithic record of hominin activity into central Oman and helps to diversify the picture of Arabian prehistory.
Comparative Multi‐Omics Survey Reveals Novel Specialized Metabolites and Biosynthetic Gene Clusters Under GacS Control in Pseudomonas donghuensis Strain SVBP6
2024-11-15

ABSTRACT In Pseudomonas donghuensis SVBP6, isolated from an agricultural field, the well‐conserved Gac‐Rsm pathway upregulates biosynthesis of the antifungal compound 7‐hydroxytropolone (7‐HT). However, 7‐HT does not fully explain the strain's Gac‐Rsm‐dependent antimicrobial activity. Here, we combined comparative transcriptomic, proteomic, and metabolomic approaches to identify novel GacS‐dependent biosynthetic gene clusters (BGC) and/or extracellular specialized metabolites. Our data revealed a broad impact of GacS on gene expression and extracellular metabolite profile of SVBP6. At both the mRNA and polypeptide levels, specialized metabolism was the main affected functional category in the gacS mutant. The major extracellular MS/MS spectral families promoted by GacS were fatty acid amides, fatty acids, and alkaloids. GacS was required for the production of the antimicrobial compound pseudoiodinine and to activate expression of the corresponding BGC. We also detected GacS‐dependent production of 2,3,4‐trihydro‐β‐carboline‐1‐one, which may add to the antimicrobial arsenal of SVBP6. Furthermore, transcriptomics and proteomics pinpointed several GacS‐activated BGCs that had escaped in silico genome mining tools. Altogether, comparative multi‐omics analyses of gacS loss‐of‐function mutants in Pseudomonas isolates are a promising strategy to uncover bioactive metabolites and/or their BGCs. Discovery of novel natural products is important for harnessing the potential of microbiota to improve crop plant growth and health.
Complexes R₂Sn(IV)L with Tridentate O,N,O΄-Donor Schiff Bases: Photophysical Properties and Biological Activity
2024-11-15

New tin(IV) complexes (Ln)SnR2 (R = n-Bu (I, II), t-Bu (III–V), and Ph (VI)) with O,N,O ́-donor Schiff bases are synthesized. The molecular structures of compounds I and IV in the crystalline state are determined by XRD (CIF files CCDC nos. 2309864 (I) and 2309422 (IV)). The photophysical properties of the complexes are studied in comparison with the previously synthesized compounds containing phenyl or ethyl hydrocarbon groups at the tin atom. All compounds luminesce in chloroform: the emission bands are observed in the range from 580 to 638 nm. Both the groups at the tin atom and nature of the substituents in Schiff bases significantly affect the relative quantum yield. The anti/prooxidant activity of (Ln)SnR2 in the reactions with the ABTS (2,2 ́-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) radical cation and superoxide radical anion, in the oxidative DNA damage, and during lipid peroxidation in vitro is studied. A weak antibacterial activity against the bacterial strains Staphylococcus aureus ANCC 6538 and E. faecium ATCC 3576 are observed for some compounds. The in vitro antiproliferative properties for a number of the complexes are studied for the HTC-116 and А-549 cancer cell lines. The coordination of the organometallic fragment with the O,N,O ́-tridentate ligands is found to induce a pronounced decrease in the cytotoxicity of the complexes.
Application of quantitative histomorphometric features in computational pathology
2024-11-16

Abstract Computer vision has facilitated the execution of various computer‐aided diagnostic tasks. From a methodological perspective, these tasks are primarily implemented using two dominant strategies: end‐to‐end Deep learning (DL)‐based methods and traditional feature engineering‐based methods. DL methods are capable of automatically extracting, analyzing, and filtering features, leading to final decision‐making from whole slide images. However, these methods are often criticized for the “black box” issue, a significant limitation of DL. In contrast, traditional feature engineering‐based methods involve well‐defined quantitative input features. But it was considered as less potent than DL methods. Advances in segmentation technology and the development of quantitative histomorphometric (QH) feature representation have propelled the evolution of feature engineering‐based methods. This review contrasts the performance differences between the two methods and traces the development of QH feature representation. The conclusion is that, with the ongoing progress in QH feature representation and segmentation technology, methods based on QH features will leverage their advantages—such as explainability, reduced reliance on large training datasets, and lower computational resource requirements—to play a more significant role in some clinical tasks. They may even replace DL methods somewhat or be used in conjunction with them to achieve accurate and understandable results.
High p53 Protein Level Is a Negative Prognostic Marker for Pancreatic Adenocarcinoma
2024-11-16

Pancreatic adenocarcinoma is one of the most aggressive types of cancer. Among different mechanisms generally believed to be important for the development of cancer, aberrant regulation of the p53 protein is a well-known and common feature for many cancer entities. Our work aims to analyze the impact of p53 deregulation and proteins encoded by p53 target genes on the survival of patients suffering from pancreatic adenocarcinoma. We, therefore, focused on the analysis of the selected collective for the TP53 mutation status, the p53 protein level, their correlation, and possible impacts on the prognosis/survival. We compared and analyzed a set of 123 patients. We have extracted information regarding the TP53 mutation status, p53 protein levels, the level of proteins encoded by prominent p53 target genes, and information on the overall survival. Survival analyses were displayed by Kaplan–Meier plots, using the log-rank test, in order to check for statistical significance. Protein levels were compared using the Mann–Whitney Test. We did not find any statistically significant correlation between the TP53 mutation status and the survival of the patients. Moreover, we have not found any significant correlation between the protein amount of prominent p53 target genes and the patients’ survival. However, we see a significant correlation between the p53 protein level in cancer samples and the overall survival of pancreatic adenocarcinoma patients: patients having tumors with a p53 protein level within the upper quartile of all measured cases show a significantly reduced survival compared to the rest of the patients. Thus, in pancreatic adenocarcinoma, the p53 protein level is a relevant marker for prognosis, and cancers having a high p53 protein amount show a shortened patients’ survival. In contrast, for this cancer entity, the TP53 mutation status or the protein amount of prominent p53 target genes on their own seems not to have a significant impact on survival.