julilili42/papers huggingface dataset:
Evaluation of the Tobacco Heating System (THS) During Closed Lower Limb Fracture Healing in Trauma Smokers’ Patients
2024-11-12

BACKGROUND: Since 1976, it has been recognized that increased cigarette consumption correlates with decreased bone density, hindering fracture healing and leading to prolonged hospitalization. Although prior research has shown the relatively less harmful effects of electronic nicotine delivery systems (ENDS) on bone cells in lab settings and animal models, clinical evidence regarding their impact on fracture healing remains scarce. This study aims to investigate whether switching to a tobacco heating system (THS) post-orthopedic surgery improves outcomes for smoking patients during tibia or femur fracture healing over a 6-month period. METHODS: The study is a prospective, open-label, non-parallel, single-center trial involving 150 patients from a Level 1 Trauma center in Germany, diagnosed and treated for closed tibia, closed femur shaft, or closed distal femur fractures (according to AO/OTA: 41A2-41C3, 42A-C, 43A-C, 32A-C, 33A2-3, 33B-C). Participants will be categorized into three groups based on smoking behavior: smokers (no intervention), THS (participants switching from cigarettes to THS), and ex-smokers (participants abstaining from cigarettes or ENDS during the study). Clinical, radiological, and laboratory data will be collected during preoperative and postoperative assessments at 6, 12, 18, and 24 weeks. The primary outcome will be the serum concentration of N-terminal propeptide procollagen type 1, a bone formation marker. Secondary outcomes include bone metabolism, healing, immunological, blood count, and clinical parameters. Approval for the study protocol and consent declarations was obtained from the ethics committee of the medical faculty of Eberhard Karls University (724/2022BO1). DISCUSSION: The study results will provide evidence that switching to THS after previous orthopedic intervention improves clinical outcomes during closed tibia or femur fracture healing in smoking patients due to a reduced bone resorption rate consequent to the diminished activity of cigarette smoke-activated osteoclasts.
INTEGRAL Observations of Magnetars
2024-11-12

ABSTRACT The INTEGRAL satellite has collected a large amount of data on magnetars in our Galaxy, spanning more than 20 years starting from 2003. The large data set obtained with the IBIS/ISGRI instrument at energies above 20 keV allows us to study both the properties and long‐term evolution of their persistent hard X‐ray emission and the population characteristics of the short bursts emitted during active periods. We are carrying out a comprehensive analysis of the observed magnetars, exploiting the most recent calibrations and analysis software. Here we report on the long term evolution of the hard X‐ray flux of the magnetars detected with ISGRI and the results of a sensitive search for short bursts in SGR J1935+2154.
Cognitive reserve against Alzheimer’s pathology is linked to brain activity during memory formation
2024-11-13

Abstract The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer’s Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.
Environmental DNA barcoding reveals general biodiversity patterns in the large tropical rift Lake Albert
2024-11-13

Lake Albert, Africa's seventh-largest lake and a biodiversity hotspot, faces significant environmental challenges, including unregulated anthropogenic pressure and a lack of comprehensive biological studies. To address the scarcity of biodiversity data, we utilized environmental DNA (eDNA) metabarcoding to assess the lake's eukaryotic and metazoan communities. Surface water samples were collected at three distinct locations: close to the southern inflow of the Semliki River, the central part of the lake, and close to the northern inflow of the Victoria Nile and outflow of the Albert Nile. We aimed to study ecological patterns across the lake, focusing on sequence variant richness and community composition, testing for differences among locations and between shoreline and pelagic zones. Consistent with previous morphology-based observations, our results revealed differences in community composition among the three sites, with cyclopoid copepods dominating the communities. Distance from shore was a significant factor influencing community composition, confirming expectations about the effects of nutrient and oxygen availability gradients. However, the lack of comprehensive reference sequence data limited accurate taxonomic assignments. Despite these limitations, our study demonstrates that eDNA metabarcoding is highly useful for assessing biodiversity in underexplored tropical freshwater ecosystems. We advocate for urgent efforts to generate reference sequences from tropical regions to enhance the utility of eDNA for biodiversity monitoring and conservation. Our findings underscore the potential of eDNA in providing insights into ecological patterns of entire communities and emphasize the need for comprehensive studies addressing the full taxonomic spectrum in tropical freshwater ecosystems.
ATP1A3 dysfunction causes motor hyperexcitability and afterhyperpolarization loss in a dystonia model
2024-11-13

Abstract Mutations in the gene encoding the alpha3 Na+/K+-ATPase isoform (ATP1A3) lead to movement disorders that manifest with dystonia, a common neurological symptom with many different origins, but for which the underlying molecular mechanisms remain poorly understood. We have generated an ATP1A3 mutant mouse that displays motor impairments and a hyperexcitable motor phenotype compatible with dystonia. We show that neurons harbouring this mutation are compromised in their ability to extrude raised levels of intracellular sodium, highlighting a profound deficit in neuronal sodium homeostasis. We show that the spinal motor network in ATP1A3 mutant mice has a reduced responsiveness to activity-dependent rises in intracellular sodium and that this is accompanied by loss of the Na+/K+-ATPase-mediated afterhyperpolarization in motor neurons. Taken together, our data support that the alpha3 Na+/K+-ATPase is important for cellular and spinal motor network homeostasis. These insights suggest that it may be useful to consider ways to compensate for this loss of a critical afterhyperpolarization-dependent control of neuronal excitability when developing future therapies for dystonia.
Longitudinal Follow-up Reveals Peripheral Immunological Changes Upon Tick Bite in α-Gal–Sensitized Individuals
2024-11-13

Background: α-Gal syndrome is characterized by specific IgE (sIgE) antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal) and delayed onset of allergic symptoms after ingestion of mammalian meat. While tick bites are assumed to mediate sensitization, the immune response to tick bites has not yet been investigated. Objective: To investigate the peripheral immune response to tick bites in humans over time. Methods: In a longitudinal cohort study, immunological reactions associated with tick bites (Ixodes species) were analyzed within 1 day (V1), 2 weeks (V2), 1 month (V3), and 3 months (V4) after the occurrence of a bite. sIgE, sIgG, and sIgG subclass levels, as well as 10 cytokines, were quantified. Deep immune phenotyping was performed using mass cytometry. Results: A total of 4 controls and 10 patients were bitten by a tick and followed up over 3 months. None of the controls developed sIgE to α-Gal, and sIgE increased in all patients from V1 until V2/V3, as did IL-8 levels. We noted a significant increase in CD19+ B cells and B-cell subpopulations, as well as a decrease in γδ CD56+ T cells in patients between V0 and V1. At V1, frequencies of plasmacytoid dendritic cells (pDCs) and γδ CD56+ T cells were lower in patients than in controls. Conclusion: Our study provides evidence of significant changes in several immune cell populations in α-Gal–sensitized patients, along with increased levels of IL-8 and sIgE. This is the first exploratory study to investigate longitudinal peripheral immune profiles in patients and controls bitten by ticks.
Mutations in mitochondrial ATAD3 gene and disease, lessons from in vivo models
2024-11-13

Pathogenic variants in the ATAD3 gene cluster have been associated with different neurodevelopmental disorders showing clinical symptoms like global developmental delay, muscular hypotonia, cardiomyopathy, congenital cataracts, and cerebellar atrophy. ATAD3A encodes for a mitochondrial ATPase whose function is unclear and has been considered one of the five most common nuclear genes associated with mitochondrial diseases in childhood. However, the mechanism causing ATAD3- associated disorders is still unknown. In vivo models have been used to identify ATAD3 function. Here we summarize the features of mouse models with ATAD3 loss of function and Drosophila models overexpressing pathogenic ATAD3 variants. We discuss how these models have contributed to our understanding of ATAD3 function and the pathomechanism of the ATAD3- associated disease.
Indecision and recency-weighted evidence integration in non-clinical and clinical settings
2024-11-13

Abstract Biases in information gathering are common in the general population and can reach pathological extremes in paralysing indecisiveness, as in obsessive-compulsive disorder (OCD). Here, we adopt a new perspective on information gathering and demonstrate an information integration bias where most recent information is over-weighted by means of evidence strength updates (ΔES). In a large, crowd-sourced sample (N=5,237), we find reduced ΔES-weighting drives indecisiveness along an OC spectrum. We replicate the attenuated ΔES- weighting in a second lab-based study (N=105) that includes a transdiagnostic OC spectrum encompassing OCD and generalised anxiety patients. Using magnetoencephalography (MEG), we trace ΔES signals to a late neural signal peaking around 920 ms. Critically, high-OC participants show an attenuated neural ΔES signal in medio-frontal areas while other decision- relevant processes remain intact. Our findings establish biased information-weighting as a key driver of information gathering, where attenuated ΔES can lead to indecisiveness across an OC spectrum.
Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer’s disease
2024-11-13

Abstract INTRODUCTION Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals. METHODS Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes. Sample sizes were computed for detecting a reduction of either absolute levels of AD-related pathology (amyloid, tau) or change over time in neurodegeneration (atrophy, hypometabolism, cognitive change). RESULTS Biomarkers measuring amyloid and tau pathology had required sample sizes below 200 participants per arm (examples CSF Aβ42/40: 47[95%CI 25,104], cortical PIB 49[28,99], CSF p-tau181 74[48,125]) for a four-year trial in presymptomatic individuals (CDR=0) to have 80% power (5% statistical significance) to detect a 25% reduction in absolute levels of pathology, allowing 40% dropout. For cognitive, MRI, and FDG, it was more appropriate to detect a 50% reduction in rate of change. Sample sizes ranged from 250-900 (examples hippocampal volume: 338[131,2096], cognitive composite: 326[157,1074]). MRI, FDG and cognitive outcomes had lower sample sizes when including indivduals with mild impairment (CDR=0.5 and 1) as well as presymptomatic individuals (CDR=0). DISCUSSION Despite the rarity of ADAD, presymptomatic clinical trials with feasible sample sizes given the number of cases appear possible.
PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes
2024-11-14

Abstract Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity of such pharmacogenetic variation differ drastically across human populations. Here, we present PharmFreq, a global repository of pharmacogenetic frequency information that aggregates frequency data of 658 allelic variants from over 10 million individuals collected from &amp;gt;1200 studies across 144 countries. Most investigations were conducted in East Asian and European populations, accounting for 29.4 and 26.6% of all studies, respectively. We find that the number of studies per country and aggregated cohort size correlated significantly with population size (R = 0.55, P= 3*10−9) and country gross domestic product (R = 0.43, P= 2*10−6) with overall population coverage varying between 5% in Estonia to &amp;lt; 0.001% in many countries in Sub-Saharan Africa and Asia. All frequency data are openly accessible via a web-based interactive dashboard at pharmfreq.com that facilitates the exploration, visualization and analysis of country- and population-specific data and their inferred phenotypic consequences. PharmFreq thus presents a comprehensive, freely available resource for pharmacogenetic variant frequencies that can inform about ethnogeographic pharmacogenomic diversity and reveal important inequities that help to focus future research efforts into underrepresented populations.
Enhancing patient activation: a controlled implementation study of an interprofessional evidence-based counseling program for complementary and integrative healthcare in cancer patients (‘CCC-Integrativ’)
2024-11-14

Abstract Complementary and integrative healthcare (CIH) is increasingly recognized as a valuable approach to empowering and activating cancer patients. Studies have shown that higher patient activation is positively associated with improved health outcomes and reduced healthcare costs. The CCC-Integrativ study aimed to assess the implementation of an evidence-based counseling service on CIH at four Comprehensive Cancer Centers (CCC) in Germany. In this controlled implementation study, the patient-level intervention included three CIH consultations within a 3-month period delivered by interprofessional teams of physicians and nurses. The primary endpoint was patient activation using the PAM-13 at baseline (T1) and post-intervention (T2), and compared between control (CO, receiving routine care) and the intervention group (IG) using an analysis of covariance. Missing data were handled with multiple imputations. Maintenance effects at 6-month follow-up (T3) were investigated using a linear mixed model. A total of n = 1128 oncology patients (CO = 443, IG = 685) with diverse tumor entities and cancer stages were included in the study. The overall mean baseline PAM-13 score was 69.74 (SD = 14.24) ( n = 959 (85.0%)). A statistically significant between-group difference in post-intervention PAM-13 scores was observed (F group (1, 1866.82) = 8.634, P = 0.003), with an adjusted mean difference of 2.22 PAM-points. Age, gender, tumor entity, disease stage, or CCC study site did not significantly predict post-treatment PAM-13 scores. The maintenance effect of the intervention was not statistically significant (F timeXgroup (1, 3316.04) = 2.337, P = 0.096). Individually tailored counseling on CIH, offered by specifically trained, interprofessional teams, significantly improved patient activation. Given the established positive effects of higher patient activation, the implementation of such a program at cancer centers may yield beneficial outcomes for both patients and the healthcare system.
Incretin-responsive human pancreatic adipose tissue organoids: A functional model for fatty pancreas research
2024-11-14

This novel adipose organoid model is a valuable tool to study the metabolic impact of incretin signalling in pancreatic adipose tissue, revealing potential therapeutic targets of incretins beyond islets. The donor-specific metabolic memory of these organoids enables examination of the pancreatic fat-islet crosstalk in a donor-related metabolic context.
Phosphorylation‐dependent activation of the bHLH transcription factor ICE1/SCRM promotes polarization of the Arabidopsis zygote
2024-11-14

Summary In Arabidopsis thaliana , the asymmetric cell division (ACD) of the zygote gives rise to the embryo proper and an extraembryonic suspensor, respectively. This process is controlled by the ERECTA‐YODA‐MPK3/6 receptor kinase‐MAP kinase‐signaling pathway, which also orchestrates ACDs in the epidermis. In this context, the bHLH transcription factor ICE1/SCRM is negatively controlled by MPK3/6‐directed phosphorylation. However, it is unknown whether this regulatory module is similarly involved in the zygotic ACD. We investigated the function of SCRM in zygote polarization by analyzing the effect of loss‐of‐function alleles and variants that cannot be phosphorylated by MPK3/6, protein accumulation, and target gene expression. Our results show that SCRM has a critical function in zygote polarization and acts in parallel with the known MPK3/6 target WRKY2 in activating WOX8. Our work further demonstrates that SCRM activity in the early embryo is positively controlled by MPK3/6‐mediated phosphorylation. Therefore, the effect of MAP kinase‐directed phosphorylation of the same target protein fundamentally differs between the embryo and the epidermis, shedding light on cell type‐specific, differential gene regulation by common signaling pathways.
Why Swipe Right? Career Interests and Aspirations of Incoming Statistics Majors
2024-11-14

Undergraduate statistics programs can help students hone a wide range of quantitative, computational, and communicative skills as they prepare for a fruitful career. In this article, we explore what motivates students to choose a major in statistics and to what extent incoming statistics majors recognize these wider skills as part of doing statistics. To build theories regarding what motivates students toward statistics, we interviewed nine first-year statistics majors at a large public university and analyzed their responses using a grounded theory approach. Each student shared their views of “who” statistics is to them, what kind of career they aspired to, and what prior experiences oriented them toward studying statistics. A strong, cross-cutting theme that emerged was that of balance. For example, statistics appeared as a safe and lucrative career choice that catered to their mathematical strengths, but it could also be an exciting career choice that stoked their imaginations. We also found that students had different perspectives and expectations about the role of mathematics and coding that may impact their experience in the major. Implications for introductory course curricula, the importance of projects, and outreach programs are discussed.
MATRIX MAYHEM: INVESTIGATING THE EFFECTS OF PERICELLULAR PROTEOLYSIS ON BIOMECHANICAL PROPERTIES AND CALCIUM SIGNALLING IN ARTICULAR CARTILAGE
2024-11-14

Introduction Within articular cartilage, chondrocytes reside within the pericellular matrix (PCM), collectively constituting the microanatomical entity known as a chondron. The PCM functions as a pivotal protective shield and mediator of biomechanical and biochemical cues. In the context of Osteoarthritis (OA), enzymatic degradation of the PCM is facilitated by matrix metalloproteinases (MMPs). This study delves into the functional implications of PCM structural integrity decline on the biomechanical properties of chondrons and impact on Ca 2+ signaling dynamics. Method Chondrons isolated from human cartilage explants were incubated with activated MMP-2, -3, or -7. Structural degradation of the pericellular matrix (PCM) was assessed by immunolabelling (collagen type VI and perlecan, n=5). Biomechanical properties of chondrons (i.e. elastic modulus (EM)) were analyzed using atomic force microscopy (AFM). A fluorescent calcium indicator (Fluo-4-AM) was used to record and quantify the intracellular Ca 2+ influx of chondrons subjected to single cell mechanical loading (500nN) with AFM (n=7). Result Each of the three MMPs disrupted the structural integrity of the PCM, leading to attenuated fluorescence intensity for both perlecan and collagen VI. A significant decrease of EM was observed for all MMP groups (p&lt;0.005) with the most notable decrease observed for MMP-2 and MMP-7 (p&lt;0.001). In alignment with the AFM results, there was a significant alteration in Ca 2+ influx observed for all MMP groups (p&lt;0.05), in particular for MMP-2 and MMP-7 (p&lt;0.001). Conclusion Proteolysis of the PCM by MMP-2, -3, and -7 not only significantly alters the biomechanical properties of articular chondrons but also affects their mechanotransduction profile and response to mechanical loading, indicating a close interconnection between these processes. These findings underscore the influence of an intact pericellular matrix (PCM) in protecting cells from high stress profiles and carry implications for the transmission of mechanical signaling during OA onset and progression.
Inferring social signals from the eyes in male schizophrenia
2024-11-14

Abstract Nonverbal communication habitually leaks out in ways that expose underlying thoughts, true feelings, and integrity of a counterpart. Social cognition is deficient in a wide range of mental disorders, including schizophrenia (SZ). Inferring social signals through the eyes is pivotal for social interaction but remains poorly investigated. The present work aims to fill this gap by examining whether and, if so, how reading language of the eyes is altered in SZ. We focused on male SZ, primarily because the disorder manifests a gender-specific profile. Patients and matched typically developing (TD) individuals were administered the Reading the Mind in the Eyes Test-Modified (RMET-M) and Emotions in Masked Faces (EMF) task that provide comparable visual information. The findings indicate that in SZ, the emotion recognition profile is similar to TD, with a more accurate recognition of some emotions such as fear, neutral expressions, and happiness than the others (sadness and disgust). In SZ, however, this profile is shifted down: all emotions are recognized less accurately than in TD. On the RMET-M, patients are also less precise, albeit they perform better on items with positive valence. In SZ only, recognition accuracy on both tasks is tightly linked to each other. The outcome reveals global challenges for males with SZ in inferring social information in the eyes and calls for remediation programs to shape social cognition. This work offers novel insights into the profiles of social cognitive deficits in mental disorders that differ in their gender prevalence.