julilili42/papers huggingface dataset:
Outcome Analysis of Distal Radius Fracture with Orthosis Versus Cast Immobilization after Palmar Plate Osteosynthesis: A Randomized Controlled Study
2023-01-09

Although the benefits of hand orthoses were shown in previous studies, they have not been able to establish themselves in clinical routines. With a focus on patient satisfaction, this study aimed to evaluate the latest generation of hand orthoses after palmar plate osteosynthesis for isolated distal radius fractures in comparison with circular plaster casts. 50 patients (16% dropout rate) were randomly assigned to an orthotic group (immobilization by orthosis, OG) or a control group (immobilization by a plaster cast, CG). Intra-articular fractures were present in 74% of the cases, and unstable AO C3 fractures in 26%. Questionnaires on patient satisfaction, documentation of the time required, clinical scores (DASH, SF-36), range of motion, grip measurements and radiographs were used for evaluation. The OG proved to be equivalent to the plaster treatment in terms of patient satisfaction, and stability of the reduction, as well as clinical scores DASH and SF-36. The OG was even superior in terms of personal hygiene (p = 0.011), handling (p = 0.008) and better adaptability (p = 0.013). Significantly less time was required to apply the orthosis (p &lt; 0.001). In addition to the good results achieved so far, the study showed that the latest generation of orthoses has several advantages over plaster cast therapy, and could therefore become established in everyday clinical practice.
EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection
2023-01-10

Abstract The mainstay of treatment for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a part of the standard of care, however, the predictive significance of most of these targets in central nervous system (CNS) tumors remains less well-studied. Despite that, there is increasing use of advanced molecular diagnostics that identify potential targets, and tumor-agnostic regulatory approvals on targets also present in CNS tumors have been granted. This raises the question of when and for which targets it is meaningful to test in adult patients with CNS tumors. This evidence-based guideline reviews the evidence available for targeted treatment for alterations in the RAS/MAPK pathway (BRAF, NF1), in growth factor receptors (EGFR, ALK, fibroblast growth factor receptor (FGFR), neurotrophic tyrosine receptor kinase (NTRK), platelet-derived growth factor receptor alpha, and ROS1), in cell cycle signaling (CDK4/6, MDM2/4, and TSC1/2) and altered genomic stability (mismatch repair, POLE, high tumor mutational burden (TMB), homologous recombination deficiency) in adult patients with gliomas, glioneuronal and neuronal tumors. At present, targeted treatment for BRAF p.V600E alterations is to be considered part of the standard of care for patients with recurrent gliomas, pending regulatory approval. For approved tumor agnostic treatments for NTRK fusions and high TMB, the evidence for efficacy in adult patients with CNS tumors is very limited, and treatment should preferably be given within prospective clinical registries and trials. For targeted treatment of CNS tumors with FGFR fusions or mutations, clinical trials are ongoing to confirm modest activity so far observed in basket trials. For all other reviewed targets, evidence of benefit in CNS tumors is currently lacking, and testing/treatment should be in the context of available clinical trials.
Resolving colistin resistance and heteroresistance in Enterobacter species
2023-01-10

Abstract Species within the Enterobacter cloacae complex (ECC) include globally important nosocomial pathogens. A three-year study of ECC in Germany identified Enterobacter xiangfangensis as the most common species (65.5%) detected, a result replicated by examining a global pool of 3246 isolates. Antibiotic resistance profiling revealed widespread resistance and heteroresistance to the antibiotic colistin and detected the mobile colistin resistance ( mcr )−9 gene in 19.2% of all isolates. We show that resistance and heteroresistance properties depend on the chromosomal arnBCADTEF gene cassette whose products catalyze transfer of L-Ara4N to lipid A. Using comparative genomics, mutational analysis, and quantitative lipid A profiling we demonstrate that intrinsic lipid A modification levels are genospecies-dependent and governed by allelic variations in phoPQ and mgrB , that encode a two-component sensor-activator system and specific inhibitor peptide. By generating phoPQ chimeras and combining them with mgrB alleles, we show that interactions at the pH-sensing interface of the sensory histidine kinase phoQ dictate arnBCADTEF expression levels. To minimize therapeutic failures, we developed an assay that accurately detects colistin resistance levels for any ECC isolate.
Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer’s disease
2023-01-10

Abstract Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and CSF and is predictive of cognitive function in individuals with Alzheimer’s disease. There has been limited prior work linking neurofilament light and functional connectivity, and no prior work has investigated neurofilament light associations with functional connectivity in autosomal dominant Alzheimer’s disease. Here, we assessed relationships between blood neurofilament light, cognition, and functional connectivity in a cross-sectional sample of 106 autosomal dominant Alzheimer’s disease mutation carriers and 76 non-carriers. We employed an innovative network-level enrichment analysis approach to assess connectome-wide associations with neurofilament light. Neurofilament light was positively correlated with deterioration of functional connectivity within the default mode network and negatively correlated with connectivity between default mode network and executive control networks, including the cingulo-opercular, salience, and dorsal attention networks. Further, reduced connectivity within the default mode network and between the default mode network and executive control networks was associated with reduced cognitive function. Hierarchical regression analysis revealed that neurofilament levels and functional connectivity within the default mode network and between the default mode network and the dorsal attention network explained significant variance in cognitive composite scores when controlling for age, sex, and education. A mediation analysis demonstrated that functional connectivity within the default mode network and between the default mode network and dorsal attention network partially mediated the relationship between blood neurofilament light levels and cognitive function. Our novel results indicate that blood estimates of neurofilament levels correspond to direct measurements of brain dysfunction, shedding new light on the underlying biological processes of Alzheimer’s disease. Further, we demonstrate how variation within key brain systems can partially mediate the negative effects of heightened total serum neurofilament levels, suggesting potential regions for targeted interventions. Finally, our results lend further evidence that low-cost and minimally invasive blood measurements of neurofilament may be a useful marker of brain functional connectivity and cognitive decline in Alzheimer’s disease.
Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales
2023-01-10

Background Current clinical rating scales in frontotemporal dementia (FTD) often do not incorporate neuropsychiatric features and may therefore inadequately measure disease stage. Methods 832 participants from the Genetic FTD Initiative (GENFI) were recruited: 522 mutation carriers and 310 mutation-negative controls. The standardised GENFI clinical questionnaire assessed the frequency and severity of 14 neuropsychiatric symptoms: visual, auditory, and tactile hallucinations, delusions, depression, anxiety, irritability/lability, agitation/aggression, euphoria/elation, aberrant motor behaviour, hypersexuality, hyperreligiosity, impaired sleep, and altered sense of humour. A principal component analysis (PCA) was performed to identify key groupings of neuropsychiatric and behavioural items in order to create a new neuropsychiatric module that could be used as an addition to the Clinical Dementia Rating (CDR) plus National Alzheimer’s Coordinating Center Behaviour and Language Domains (NACC FTLD) rating scale. Results Overall, 46.4% of mutation carriers had neuropsychiatric symptoms (51.6% C9orf72 , 40.8% GRN , 46.6% MAPT ) compared with 24.5% of controls. Anxiety and depression were the most common in all genetic groups but fluctuated longitudinally and loaded separately in the PCA. Hallucinations and delusions loaded together, with the remaining neuropsychiatric symptoms loading with the core behavioural features of FTD. These results suggest using a single ‘psychosis’ neuropsychiatric module consisting of hallucinations and delusions. Adding this to the CDR plus NACC FTLD, called the CDR plus NACC FTLD-N, leads to a number of participants being scored more severely, including those who were previously considered asymptomatic now being scored as prodromal. Conclusions Neuropsychiatric symptoms occur in mutation carriers at all disease stages across all three genetic groups. However, only psychosis features provided additional staging benefit to the CDR plus NACC FTLD. Inclusion of these features brings us closer to optimising the rating scale for use in trials.
China’s environmental solutions
2023-01-10

Abstract China emits unproportionately high concentrations of CO 2 and, due to rapid population growth and industrialization, suffers from air, water, and soil pollution. However, many of these challenges for sustainable growth are being vigorously addressed, and China aims at a CO 2 emission peak by 2030 and carbon neutrality by 2060 (“dual carbon policy”). In addition, nation-wide programs attempt to achieve reforestation and ecological restoration. By 2025, core elements of a “bioeconomy” and a circular economy are expected to be ready. Many of these programs extend into China’s international “belt-and-road” initiative (BRI). In this article, we briefly describe the present achievements of China’s environmental solutions and the country’s visions for a “digital, eco-friendly civilization.” Key points • China’s steps towards environmental cleaning, eco-protection, and decarbonization. • Steps towards a future bioeconomy.
Experiencing COVID-19, home isolation and primary health care: A mixed-methods study
2023-01-10

Objectives Although the vast majority of COVID-19 cases are treated in primary care, patients' experiences during home isolation have been little studied. This study aimed to explore the experiences of patients with acute COVID-19 and to identify challenges after the initial adaptation of the German health system to the pandemic (after first infection wave from February to June 2020). Methods A mixed-method convergent design was used to gain a holistic insight into patients experience. The study consisted of a cross-sectional survey, open survey answers and semi-structured telephone interviews. Descriptive analysis was performed on quantitative survey answers. Between group differences were calculated to explore changes after the first infection wave. Qualitative thematic analysis was conducted on open survey answers and interviews. The results were then compared within a triangulation protocol. Results A total of 1100 participants from all German states were recruited by 145 general practitioners from August 2020 to April 2021, 42 additionally took part in qualitative interviews. Disease onset varied from February 2020 to April 2021. After the first infection wave, more participants were tested positive during the acute disease (88.8%; 95.2%; P &amp;lt; 0.001). Waiting times for tests (mean 4.5 days, SD 4.1; 2.7days, SD 2.6, P &amp;lt; 0.001) and test results (mean 2.4 days, SD 1.9; 1.8 days, SD 1.3, P &amp;lt; 0.001) decreased. Qualitative results indicated that the availability of repeated testing and antigen tests reduced insecurities, transmission and related guilt. Although personal consultations at general practices increased (6.8%; 15.5%, P &amp;lt; 0.001), telephone consultation remained the main mode of consultation (78.5%) and video remained insignificant (1.9%). The course of disease, the living situation and social surroundings during isolation, access to health care, personal resilience, spirituality and feelings of guilt and worries emerged as themes influencing the illness experience. Challenges were contact management and adequate provision of care during home isolation. A constant contact person within the health system helped against feelings of care deprivation, uncertainty and fear. Conclusions Our study highlights that home isolation of individuals with COVID-19 requires a holistic approach that considers all aspects of patient care and effective coordination between different care providers.
The Impact of Tissue Preparation on Salivary Gland Tumors Investigated by Fourier-Transform Infrared Microspectroscopy
2023-01-10

Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.
Infrared He I 10830 Å, ultra-violet Ca II, and Mg II chromosphere emissions in the spectra of classical Cepheid X Cyg
2023-01-10

Aims. In a previous publication, we reported the first detection of emission in the infrared (IR) triplet at 10 830 Å in the spectra of the classical Cepheid X Cyg. Emission is detectable at phases from approximately 0.25 to 0.90. We present and discuss further information on the chromosphere activity of this star, namely International Ultraviolet Explorer (IUE) archive data concerning the emission in the h and k Mg II doublet, and near-ultraviolet (NUV) spectra in the vicinity of the H and K Ca II doublet. We also present rough estimates of the chromosphere conditions and semi-empirical modelling of the observed emissions in He I triplet. Methods. A study of the emissions in UV lines of Ca II and Mg II , and IR lines of He I suggests that the emissions observed at certain phases can be explained within the framework of the Gillet's phenomenological model of shock waves in pulsating atmospheres, which was developed from a study of the H α behaviour in X Cyg spectra. We used the non-local thermodynamic equilibrium (NLTE) approximation and a simple model of this star's chromosphere for the analysis of the chromosphere indicator profiles. Results. We show that under certain assumptions about the properties of the chromosphere, it is possible to describe the presence or absence of emission in the IR lines of He I and Ca II , and UV lines of Ca II and Mg II .
Genetic architecture of brain age and its casual relations with brain and mental disorders
2023-01-10

Abstract The difference between chronological age and the apparent age of the brain estimated from brain imaging data — the brain age gap (BAG) — is widely considered a general indicator of brain health. Converging evidence supports that BAG is sensitive to an array of genetic and non-genetic traits and diseases, yet few studies have examined the genetic architecture and its corresponding causal relationships with common brain disorders. Here, we estimate BAG using state-of-the-art neural networks trained on brain scans from 53,542 individuals (age range 3-95 years). A genome-wide association analysis across 28,104 individuals (40-84 years) from the UK Biobank revealed eight independent genomic regions significantly associated with BAG (p&lt;5x10 -8 ) implicating neurological, metabolic, and immunological pathways – among which seven are novel. No significant genetic correlations or causal relationships with BAG were found for Parkinson’s disease, major depressive disorder, or schizophrenia, but two-sample Mendelian randomization indicated a causal influence of AD (p=7.9x10 -4 ) and bipolar disorder (p=1.35x10 -2 ) on BAG. These results emphasize the polygenic architecture of brain age and provide insights into the causal relationship between selected neurological and neuropsychiatric disorders and BAG.
The cortical dynamics of context-dependent language processing
2023-01-10

A previous functional magnetic resonance imaging study (Dietrich et al. [2019]. Discourse management during speech perception: A functional magnetic resonance imaging (fMRI) study. NeuroImage, 202, 116047. ) showed a contribution by the pre-supplementary motor area (pre-SMA), the inferior frontal gyrus (IFG), and the basal ganglia (BG) in the processing of discourse structure. By applying dynamic causal modelling (DCM) to the data of this previous study, we aimed to shed further light on the functional interrelationships of these areas. Discourse coherence had been manipulated by using presupposition triggers in a test sentence that either corresponded or failed to correspond to a contextual item. We found connections from pre-SMA to IFG and from pre-SMA to BG. Additionally, participants' ability to accommodate violations modulated the coupling from the BG to the pre-SMA. We discuss this pattern in light of the aslant tract transmitting control signals from the pre-SMA to the IFG that slow down procedural processing in case of errors. The pre-SMA itself seems to be regulated by the BG depending on whether participants accommodate a violation.
Analyzing Sequential Data in Computer-Supported Collaborative Learning
2023-01-10

Representations and changes between them play a major role in cognitive development (e.g., Vosniadou, & Brewer, 1992) and education (e.g., Hewson, Beeth, & Thorley, 1998). By definition, change of representations is also indispensable for collaborative work since a common understanding or shared knowledge can only be achieved by a partial convergence of the knowledge structures of the collaborating subjects. This articles presents and discusses knowledge tracking (KT), viz., an approach to analyze cognition on the basis of symbolic sequential data. We present and discuss the methodological aspects of KT and delineate the Web-based computer program (knowledge tracking engine, KTE) set up to run KTanalyses (https://www.knowledge-tracking.com). An empirical study in collaborative learning is taken to exemplify the usage of KT in analysis of computer supported collaboration.
The FRISK (Fracture Risk)—A New Tool to Indicate the Probability of Fractures
2023-01-10

Increasing patient inflow into the emergency department makes it necessary to optimize triage management. The scope of this work was to determine simple factors that could detect fractures in patients without the need for specialized personnel. Between 2014 and 2015, 798 patients were admitted to an orthopedic emergency department and prospectively included in the study. The patients received a questionnaire before contacting the doctor. Objective and subjective data were evaluated to determine fracture risk for the upper and lower extremities. The highest risk for fractures in one region was the hip (73.21%; n = 56), followed by the wrist (60.32%; n = 63) and the femoral shaft (4 of 7, 57.14%; n = 7). The regions with the lowest risk were the knee (8.41%; n = 107), the ankle (18.29%; n = 164), and the forearm shaft (30.00%; n = 10). Age was a predictor for fracture: patients older than 59 years had a risk greater than 59.26%, and patients older than 90 years had a risk greater than 83.33%. The functional questions could exclude fractures. Three factors seem to be able to predict fracture risk: the injured region, the patient’s age, and a functional question. They can be used for a probatory heuristic that needs to be proven in a prospective way.
Cross‐Ancestry Genome‐Wide Association Study Defines the Extended CYP2D6 Locus as the Principal Genetic Determinant of Endoxifen Plasma Concentrations
2023-01-11

The therapeutic efficacy of tamoxifen is predominantly mediated by its active metabolites 4‐hydroxy‐tamoxifen and endoxifen, whose formation is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6). Yet, known CYP2D6 polymorphisms only partially determine metabolite concentrations in vivo . We performed the first cross‐ancestry genome‐wide association study with well‐characterized patients of European, Middle‐Eastern, and Asian descent ( n = 497) to identify genetic factors impacting active and parent metabolite formation. Genome‐wide significant variants were functionally evaluated in an independent liver cohort ( n = 149) and in silico . Metabolite prediction models were validated in two independent European breast cancer cohorts ( n = 287, n = 189). Within a single 1‐megabase (Mb) region of chromosome 22q13 encompassing the CYP2D6 gene, 589 variants were significantly associated with tamoxifen metabolite concentrations, particularly endoxifen and metabolic ratio (MR) endoxifen/ N ‐desmethyltamoxifen (minimal P = 5.4E−35 and 2.5E−65, respectively). Previously suggested other loci were not confirmed. Functional analyses revealed 66% of associated, mostly intergenic variants to be significantly correlated with hepatic CYP2D6 activity or expression ( ρ = 0.35 to −0.52), and six hotspot regions in the extended 22q13 locus impacting gene regulatory function. Machine learning models based on hotspot variants ( n = 12) plus CYP2D6 activity score (AS) increased the explained variability (~ 9%) compared with AS alone, explaining up to 49% (median R 2 ) and 72% of the variability in endoxifen and MR endoxifen/ N ‐desmethyltamoxifen, respectively. Our findings suggest that the extended CYP2D6 locus at 22q13 is the principal genetic determinant of endoxifen plasma concentration. Long‐distance haplotypes connecting CYP2D6 with adjacent regulatory sites and nongenetic factors may account for the unexplained portion of variability.