julilili42/papers huggingface dataset:
Quantitative Metabolomics and Lipoprotein Analysis of PDAC Patients Suggests Serum Marker Categories for Pancreatic Function, Pancreatectomy, Cancer Metabolism, and Systemic Disturbances
2024-02-26

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in the early stages and lacks reliable biomarkers. The scope of this project was to establish quantitative nuclear magnetic resonance (NMR) spectroscopy to comprehensively study blood serum alterations in PDAC patients. Serum samples from 34 PDAC patients obtained before and after pancreatectomy as well as 83 age- and sex-matched control samples from healthy donors were analyzed with <i>in vitro</i> diagnostics research (IVDr) proton NMR spectroscopy at 600 MHz. Uni- and multivariate statistics were applied to identify significant biofluid alterations. We identified 29 significantly changed metabolites and 98 lipoproteins when comparing serum from healthy controls with those of PDAC patients. The most prominent features were assigned to (i) markers of pancreatic function (e.g., glucose and blood triglycerides), (ii) markers related to surgery (e.g., ketone bodies and blood cholesterols), (iii) PDAC-associated markers (e.g., amino acids and creatine), and (iv) markers for systemic disturbances in PDAC (e.g., gut metabolites DMG, TMAO, DMSO<sub>2</sub>, and liver lipoproteins). Quantitative serum NMR spectroscopy is suited as a diagnostic tool to investigate PDAC. Remarkably, 2-hydroxybutyrate (2-HB) as a previously suggested marker for insulin resistance was found in extraordinarily high levels only after pancreatectomy, suggesting this metabolite is the strongest marker for pancreatic loss of function.
Levels and facets of university students' stress during the COVID‐19 pandemic: Longitudinal evidence from the first two academic years in Germany and the U.S.
2024-02-26

Abstract Following its outbreak, the COVID‐19 pandemic had strong negative effects on university students' stress and mental health worldwide. Using two longitudinal datasets from Germany ( N = 504) and the U.S. ( N = 893), we investigated how students' stress developed over the first two academic years during the pandemic. In both studies, we found elevated levels of students' stress at the beginning of the pandemic. In Germany, we found a significant intraindividual decrease in students' general stress experiences even before universities had returned to in‐person classes. When examining specific stress facets in the U.S., we found that students' academic stress increased during the first pandemic year with remote teaching and decreased significantly after the university resumed normal operations, that is, in‐person classes and on‐campus residence. Students' practical stress decreased towards all later time points compared to the onset of the pandemic, whereas health stress continuously increased until the university resumed normal operations. We report differences by students' demographic backgrounds (gender, college generation status, childcare status, ethnicity, academic year) and discuss our findings against the background of the course of the pandemic in the particular context in which both studies were conducted.
The role of information presentation for wildlife knowledge, attitude, and risk perception
2024-02-26

Abstract Public opinion can have a decisive influence on conservation actions leading to a need to understand how public opinion is formed. In a survey with a representative sample of the German population, participants answered questions about foxes in two consecutive years. Different versions of a leaflet about foxes were distributed to 2448 participants before the second interview. We compared a narrative text presentation to a non‐narrative list of facts and examined the use of photographs and schematic graphs. We assessed how the presentation format and socio‐demographic factors affected the probability that participants read the leaflet. Using a before‐after/control‐impact design, we examined whether the leaflet affected people's fox‐related knowledge, attitude, and risk perception. The results show that participants were more likely to read the leaflet with increasing age and a higher educational level. Reading probability also increased with attitude toward foxes. Participants who read the leaflet completely gained more knowledge about foxes than those who read it only partly. Photographs also contributed to a higher knowledge gain, but schematic graphs did not. Moreover, participants who read a fact list gained more knowledge compared to the control condition. Furthermore, the combination of visual and textual features had an effect on attitude toward foxes. However, we found no evidence that any treatment affected risk perception. We discuss implications and derivations for science communication to improve conservation actions.
An Illustrated Review of the Recent 2019 World Health Organization Classification of Neuroendocrine Neoplasms: A Radiologic and Pathologic Correlation
2024-02-26

Abstract Recent advances in molecular pathology and an improved understanding of the etiology of neuroendocrine neoplasms (NENs) have given rise to an updated World Health Organization classification. Since gastroenteropancreatic NENs (GEP-NENs) are the most common forms of NENs and their incidence has been increasing constantly, they will be the focus of our attention. Here, we review the findings at the foundation of the new classification system, discuss how it impacts imaging research and radiological practice, and illustrate typical and atypical imaging and pathological findings. Gastroenteropancreatic NENs have a highly variable clinical course, which existing classification schemes based on proliferation rate were unable to fully capture. While well- and poorly differentiated NENs both express neuroendocrine markers, they are fundamentally different diseases, which may show similar proliferation rates. Genetic alterations specific to well-differentiated neuroendocrine tumors graded 1 to 3 and poorly differentiated neuroendocrine cancers of small cell and large-cell subtype have been identified. The new tumor classification places new demands and creates opportunities for radiologists to continue providing the clinically most relevant report and on researchers to design projects, which continue to be clinically applicable.
Correlation of fetal heart rate dynamics to inflammatory markers and brain-derived neurotrophic factor during pregnancy
2024-02-26

Abstract Objectives This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. Methods Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. Results Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (−0.309; −0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. Conclusions In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population.
Occupying Shops to Defend Spaces of Livelihoods: From Tenant Shopkeepers’ Fragmentation to Collective Consciousness in Urban Korea
2024-02-26

Abstract When commercial real estate becomes a highly coveted investment commodity, tensions intensify between those whose interest lies in extracting maximum profits from their properties and those who utilize the very same spaces for making a livelihood. Through ethnographic research with a tenant shopkeepers’ social movement organization (SMO) in Korea, I analyze the new collective consciousness forming among tenant shopkeepers who are defending their livelihoods against their landlords’ rapacious use of rent hikes and evictions to fully realize the speculative potential of their properties. Examining how the SMO brings together geographically scattered tenant shopkeepers based primarily in the larger metropolitan area of Seoul, I ask, more broadly: How can the self-employed facing precaritization overcome their fragmentation and generate a new collective consciousness based on a politics of solidarity? Drawing from my case study of tenant shopkeepers and the literature on livelihood struggles elsewhere around the globe, I identify the practice of occupying livelihood spaces as playing a pivotal role in the development of a sense of collective among those previously atomized in their struggles. I advance existing scholarship by scrutinizing both the challenges and the transformative potential of the solidarity cultivated through the occupy sites in bridging divergent interests, cultural sensibilities, and political beliefs of the previously unorganized.
Leveraging the Potential of Large Language Models in Education Through Playful and Game-Based Learning
2024-02-27

Abstract This perspective piece explores the transformative potential and associated challenges of large language models (LLMs) in education and how those challenges might be addressed utilizing playful and game-based learning. While providing many opportunities, the stochastic elements incorporated in how present LLMs process text, requires domain expertise for a critical evaluation and responsible use of the generated output. Yet, due to their low opportunity cost, LLMs in education may pose some risk of over-reliance, potentially and unintendedly limiting the development of such expertise. Education is thus faced with the challenge of preserving reliable expertise development while not losing out on emergent opportunities. To address this challenge, we first propose a playful approach focusing on skill practice and human judgment. Drawing from game-based learning research, we then go beyond this playful account by reflecting on the potential of well-designed games to foster a willingness to practice, and thus nurturing domain-specific expertise. We finally give some perspective on how a new pedagogy of learning with AI might utilize LLMs for learning by generating games and gamifying learning materials, leveraging the full potential of human-AI interaction in education.
Tumor-Stroma Proportion to Predict Chemoresistance in Patients With Ovarian Cancer
2024-02-27

IMPORTANCE Platinum-based chemotherapy is the backbone of standard-of-care treatment for patients with advanced-stage, high-grade serous carcinoma (HGSC), the most common form of ovarian cancer; however, one-third of patients have or acquire chemoresistance toward platinum-based therapies. OBJECTIVE To demonstrate the utility of tumor-stroma proportion (TSP) as a predictive biomarker of chemoresistance of HGSC, progression-free survival (PFS), and overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS This prognostic study leveraged tumors from patients with HGSC in The Cancer Genome Atlas (TCGA) cohort (1993-2013) and an independent cohort of resected clinical specimens from patients with HGSC (2004-2014) available in diagnostic and tissue microarray formats from the University of Tübingen in Germany. Data analysis was conducted from January 2021 to January 2024. EXPOSURE Diagnosis of HGSC. MAIN OUTCOMES AND MEASURES Principal outcome measures were the ability of TSP to predict platinum chemoresistance, PFS, and OS. Using hematoxylin and eosin–stained slides from the Tübingen cohort (used for routine diagnostic assessment from surgical specimens) as well as tissue microarrays, representative sections of tumors for scoring of TSP were identified using previously evaluated cutoffs of 50% stroma or greater (high TSP) and less than 50% stroma (low TSP). Digitized slides from the TCGA Cohort were analyzed and scored in a similar fashion. Kaplan-Meier time-to-event functions were fit to estimate PFS and OS. RESULTS The study included 103 patients (mean [SD] age, 61.6 [11.1] years) from the TCGA cohort and 192 patients (mean [SD] age at diagnosis, 63.7 [11.1] years) from the Tübingen cohort. In the TCGA cohort, there was no significant association of TSP levels with chemoresistance, PFS, or OS. However, in the Tübingen cohort, high TSP was associated with significantly shorter PFS (HR, 1.586; 95% CI, 1.093-2.302; P = .02) and OS (hazard ratio [HR], 1.867; 1.249-2.789; P = .002). Patients with chemoresistant tumors were twice as likely to have high TSP as compared to patients with chemosensitive tumors (HR, 2.861; 95% CI, 1.256-6.515; P = .01). In tissue microarrays from 185 patients from the Tübingen cohort, high TSP was again associated with significantly shorter PFS (HR, 1.675; 95% CI, 1.012-2.772 P = .04) and OS (HR, 2.491; 95% CI, 1.585-3.912; P &amp;amp;lt; .001). CONCLUSIONS AND RELEVANCE In this prognostic study, TSP was a consistent and reproducible marker of clinical outcome measures of HGSC, including PFS, OS, and platinum chemoresistance. Accurate and cost-effective predictive biomarkers of platinum chemotherapy resistance are needed to identify patients most likely to benefit from standard treatments, and TSP can easily be implemented and integrated into prospective clinical trial design and adapted to identify patients who are least likely to benefit long-term from conventional platinum-based cytotoxic chemotherapy treatment at the time of initial diagnosis.
Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA‐Epilepsy study
2024-02-27

Abstract Objective The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross‐sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA‐Epilepsy working group. Methods A state‐of‐the‐art deep learning‐based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results Across all epilepsies, reduced total cerebellar volume was observed ( d = .42). Maximum volume loss was observed in the corpus medullare ( d max = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB ( d max = .47), crus I/II ( d max = .39), VIIIA ( d max = .45), and VIIIB ( d max = .40). Earlier age at seizure onset ( = .05) and longer epilepsy duration ( = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE‐HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.
Mott transition and pseudogap of the square-lattice Hubbard model: Results from center-focused cellular dynamical mean-field theory
2024-02-27

The recently proposed center-focused post-processing procedure [Phys. Rev. Res. 2, 033476 (2020)] of cellular dynamical mean-field theory suggests that central sites of large impurity clusters are closer to the exact solution of the Hubbard model than the edge sites. In this paper, we systematically investigate results in the spirit of this center-focused scheme for several cluster sizes up to 8×8 in and out of particle-hole symmetry. First we analyze the metal-insulator crossovers and transitions of the half-filled Hubbard model on a simple square lattice. We find that the critical interaction of the crossover is reduced with increasing cluster sizes and the critical temperature abruptly drops for the 4×4 cluster. Second, for this cluster size, we apply the center-focused scheme to a system with more realistic tight-binding parameters, investigating its pseudogap regime as a function of temperature and doping, where we find doping dependent metal-insulator crossovers, Lifshitz transitions and a strongly renormalized Fermi-liquid regime. Additionally to diagnosing the real space origin of the suppressed antinodal spectral weight in the pseudogap regime, we can infer hints towards underlying charge ordering tendencies.
Blood and cerebellar abundance of ATXN3 splice variants in spinocerebellar ataxia type 3/Machado-Joseph disease
2024-02-27

Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD) is a heritable proteinopathy disorder, whose causative gene, ATXN3, undergoes alternative splicing. Ataxin-3 protein isoforms differ in their toxicity, suggesting that certain ATXN3 splice variants may be crucial in driving the selective toxicity in SCA3. Using RNA-seq datasets we identified and determined the abundance of annotated ATXN3 transcripts in blood (n = 60) and cerebellum (n = 12) of SCA3 subjects and controls. The reference transcript (ATXN3-251), translating into an ataxin-3 isoform harbouring three ubiquitin-interacting motifs (UIMs), showed the highest abundance in blood, while the most abundant transcript in the cerebellum (ATXN3-208) was of unclear function. Noteworthy, two of the four transcripts that encode full-length ataxin-3 isoforms but differ in the C-terminus were strongly related with tissue expression specificity: ATXN3-251 (3UIM) was expressed in blood 50-fold more than in the cerebellum, whereas ATXN3-214 (2UIM) was expressed in the cerebellum 20-fold more than in the blood. These findings shed light on ATXN3 alternative splicing, aiding in the comprehension of SCA3 pathogenesis and providing guidance in the design of future ATXN3 mRNA-lowering therapies.
Insights into Gastrointestinal Redox Dysregulation in a Rat Model of Alzheimer’s Disease and the Assessment of the Protective Potential of D-Galactose
2024-02-27

Recent evidence suggests that the gut plays a vital role in the development and progression of Alzheimer's disease (AD) by triggering systemic inflammation and oxidative stress. The well-established rat model of AD, induced by intracerebroventricular administration of streptozotocin (STZ-icv), provides valuable insights into the GI implications of neurodegeneration. Notably, this model leads to pathophysiological changes in the gut, including redox dyshomeostasis, resulting from central neuropathology. Our study aimed to investigate the mechanisms underlying gut redox dyshomeostasis and assess the effects of D-galactose, which is known to benefit gut redox homeostasis and alleviate cognitive deficits in this model. Duodenal rings isolated from STZ-icv animals and control groups were subjected to a prooxidative environment using 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) or H<sub>2</sub>O<sub>2</sub> with or without D-galactose in oxygenated Krebs buffer ex vivo. Redox homeostasis was analyzed through protein microarrays and functional biochemical assays alongside cell survival assessment. Structural equation modeling and univariate and multivariate models were employed to evaluate the differential response of STZ-icv and control samples to the controlled prooxidative challenge. STZ-icv samples showed suppressed expression of catalase and glutathione peroxidase 4 (GPX4) and increased baseline activity of enzymes involved in H<sub>2</sub>O<sub>2</sub> and superoxide homeostasis. The altered redox homeostasis status was associated with an inability to respond to oxidative challenges and D-galactose. Conversely, the presence of D-galactose increased the antioxidant capacity, enhanced catalase and peroxidase activity, and upregulated superoxide dismutases in the control samples. STZ-icv-induced gut dysfunction is characterized by a diminished ability of the redox regulatory system to maintain long-term protection through the transcription of antioxidant response genes as well as compromised activation of enzymes responsible for immediate antioxidant defense. D-galactose can exert beneficial effects on gut redox homeostasis under physiological conditions.
Targeting Lewy body dementia with neflamapimod‐rasagiline hybrids
2024-02-27

Abstract Lewy body dementia (LBD) represents the second most common neurodegenerative dementia but is a quite underexplored therapeutic area. Nepflamapimod ( 1 ) is a brain‐penetrant selective inhibitor of the alpha isoform of the mitogen‐activated serine/threonine protein kinase (MAPK) p38α, recently repurposed for LBD due to its remarkable antineuroinflammatory properties. Neuroprotective propargylamines are another class of molecules with a therapeutical potential against LBD. Herein, we sought to combine the antineuroinflammatory core of 1 and the neuroprotective propargylamine moiety into a single molecule. Particularly, we inserted a propargylamine moiety in position 4 of the 2,6‐dichlorophenyl ring of 1 , generating neflamapimod‐propargylamine hybrids 3 and 4 . These hybrids were evaluated using several cell models, aiming to recapitulate the complexity of LBD pathology through different molecular mechanisms. The N ‐methyl‐ N ‐propargyl derivative 4 showed a nanomolar p38α‐MAPK inhibitory activity (IC 50 = 98.7 nM), which is only 2.6‐fold lower compared to that of the parent compound 1 , while displaying no hepato‐ and neurotoxicity up to 25 μM concentration. It also retained a similar immunomodulatory profile against the N9 microglial cell line. Gratifyingly, at 5 μM concentration, 4 demonstrated a neuroprotective effect against dexamethasone‐induced reactive oxygen species production in neuronal cells that was higher than that of 1 .
Computational Investigation of Carbon Based Anode Materials for Li‐ and Post‐Li‐ Ion Batteries
2024-02-27

Abstract Due to its negligible capacity with respect to sodium intercalation, graphite is not suited as anode material for sodium ion batteries. Hard carbon materials, on the other hand, provide reasonably high capacities at low insertion potential, making them a promising anode materials for sodium (and potassium) ion batteries. The particular nanostructure of these functionalized carbon‐based materials has been found to be crucially linked to the material performance. However, there is still a lack of understanding with respect to the functional role of structural units, such as defects, for intercalation and storage. To overcome these problems, the intercalation of Li, Na, and K in graphitic model structures with distinct defect configurations has been investigated by density functional theory. The calculations confirm that defects are able to stabilize intercalation of larger alkali metal contents. At the same time, it is shown that a combination of phonon and band structure calculations are able to explain characteristic Raman features typically observed for alkali metal intercalation in hard carbon, furthermore allowing for the quantification of the alkali metal intercalation inbetween the layers of hard carbon anodes.