julilili42/papers huggingface dataset:
Diagnosis and treatment of venous leg ulcers: S2k Guideline of the German Society of Phlebology and Lymphology (DGPL) e.V.
2024-06-28

Summary This S2k guideline on venous leg ulcers was created on the initiative and under the leadership of the German Society of Phlebology and Lymphology (DGPL). The guideline group also consisted of representatives from the German Society for Phlebology and Lymphology, German Dermatological Society, German Society for General Medicine, German Society for Angiology, German Society for Vascular Surgery and Vascular Medicine, German Society for Surgery, German Society for Dermatosurgery, German Society for Wound Healing and Wound Treatment, Professional Association of Phlebologists and Lymphologists and Initiative Chronische Wunden. The aim of this guideline is to combine the different approaches and levels of knowledge of the respective professional groups on the basis of consensus, so that a basic concept for the best possible treatment of patients with venous leg ulcers can be provided. A total of 70 specific recommendations were formulated and agreed upon, divided into the subject areas of diagnostics, therapy, prevention of recurrences, and everyday challenges. The guideline thus reflects the current state of scientific knowledge and is intended to be widely used as the best available document for the treatment of patients with venous leg ulcers in everyday clinical practice.
From adsorption to crystallization of proteins: Evidence for interface-assisted nucleation
2024-06-28

Protein crystallization is among the key processes in biomolecular research, but the underlying mechanisms are still elusive. Here, we address the role of inevitable interfaces for the nucleation process. Quartz crystal microbalance with dissipation monitoring (QCM-D) with simultaneously optical microscopy, confocal microscopy, and grazing-incidence small angle X-rays scattering (GISAXS) were employed to investigate the temporal behavior from the initial stage of protein adsorption to crystallization. Here we studied the crystallization of the Human Serum Albumin (HSA), the most abundant blood protein, in the presence of a charged surface and a trivalent salt. We found evidence for interface-assisted nucleation of crystals. The kinetic stages involved are initial adsorption followed by enhanced adsorption after longer times, subsequent nucleation, and finally crystal growth. The results highlight the importance of interfaces for protein phase behavior and in particular for nucleation.
Large Deviation Full Counting Statistics in Adiabatic Open Quantum Dynamics
2024-06-28

The state of an open quantum system undergoing an adiabatic process evolves by following the instantaneous stationary state of its time-dependent generator. This observation allows one to characterize, for a generic adiabatic evolution, the average dynamics of the open system. However, information about fluctuations of dynamical observables, such as the number of photons emitted or the time-integrated stochastic entropy production in single experimental runs, requires controlling the whole spectrum of the generator and not only the stationary state. Here, we show how such information can be obtained in adiabatic open quantum dynamics by exploiting tools from large deviation theory. We prove an adiabatic theorem for deformed generators, which allows us to encode, in a biased quantum state, the full counting statistics of generic time-integrated dynamical observables. We further compute the probability associated with an arbitrary "rare" time history of the observable and derive a dynamics which realizes it in its typical behavior. Our results provide a way to characterize and engineer adiabatic open quantum dynamics and to control their fluctuations.
THE CARNIVORAN RECORD FROM THE NEOGENE OF EASTERN ROMANIA
2024-06-28

The present work deals with the carnivorans found in five Neogene localities in eastern Romania: the Vallesian locality of Păun, the Turolian localities of Pogana 1 and Creţeşti 1, and the Ruscinian localities of Bereşti and Măluşteni. The presented material includes cranial and postcranial specimens, some of which are herein described for the first time. This study includes a re-description and re-depiction of the type material of Lutra rumana Simionescu, 1922 and Promephitis malustenensis Simionescu, 1930, in order to clarify the taxonomic position of these two enigmatic taxa. The carnivoran faunal lists of all five localities are reviewed offering interesting insights into the temporospatial range of the discovered forms. Most localities have only yielded a limited number of species, except from Măluşteni, which shows evidence of at least nine different coexisting forms. Notable occurrences in terms of biostratigraphy include Paludolutra sp. in Pogana 1, Protictitherium crassum (Depéret, 1892) in Creţeşti 1, and a phocid from Măluşteni. This review aims to aid the understanding of the Neogene ecosystems in the north of the Paratethys in terms of faunal contents, biostratigraphy and palaeoecology.
Numerical modeling and simulation of microbially induced calcite precipitation on a cement surface at the pore scale
2024-06-28

Accurate estimation of contaminant transport in cementitious material using numerical tools plays a key role in the risk assessments of nuclear waste disposal. At the pore scale, the increase of microbial activity, such as microbially induced calcite precipitation on cementitious material, causes changes in solid surface topography, pore network geometry, and pore water chemistry, which affect contaminant transport at the core scale and beyond. Consequently, a meaningful estimation of contaminant migration in the subsurface requires a pore-scale investigation of the influence of microbial activity on transport processes. In this study, a pore-scale reactive transport model is presented to simulate the physicochemical processes resulting from microbially induced calcite precipitation on a cement surface. Numerical investigations focus on modeling the reactive transport in a two-dimensional flow-through cell. The model results are validated by experimental data showing an increase in pH and a decrease in calcium concentration due to microbially induced calcite precipitation. Our results show heterogeneous calcite precipitation under transport-limited conditions and homogeneous calcite precipitation under reaction-limited conditions, resulting in non-uniform and uniform changes in the material surface topography. Moreover, power spectral density analysis of the surface data demonstrates that microbially induced calcite precipitation affects the surface topography via both general changes over the entire frequency and local modifications in the high-frequency region. The sensitivity studies provide a comprehensive understanding of the evolution of surface topography due to the microbially induced calcite precipitation at the pore scale, thus contributing to an improved predictability of contaminant transport at the core scale and beyond.
Pulmonary function in patients with ANCA-associated vasculitis.
2024-06-28

AAV patients presented with characteristic alterations in PFTs according to their respective pulmonary and/or airway manifestations. These results did not change over time and were independent from vasculitis activity.
Freedom and Sustainability
2024-06-28

This article examines the perceived conflict between freedom and sustainability, proposing that a qualitative understanding of freedom can integrate liberal and ecological interests. It critiques the notion of quantitative freedom, focused on maximizing individual choices without considering their content or purpose, for ignoring essential aspects such as the rights of future generations and ecological sustainability. In contrast, it argues that qualitative freedom, which values options based on their contribution to human autonomy and dignity, offers a more comprehensive solution. This perspective prioritizes options that promote the freedom of all, including future generations, and suggests that some restrictions may be necessary to enhance sustainable life opportunities. The conclusion asserts that qualitative freedom should precede the quantitative consideration of options, allowing sustainability policies to be viewed not as limitations on freedom but as qualitative improvements that ensure better opportunities for all, both now and in the future.
Effect of Crocus sativus Extract Supplementation in the Metabolic Control of People with Diabetes Mellitus Type 1: A Double-Blind Randomized Placebo-Controlled Trial
2024-06-29

Introduction–Background: Data from experimental trials show that Crocus sativus L. (saffron) is considered to improve glycemia, lipid profile, and blood pressure and reduce oxidative stress. So far, clinical trials have been conducted in individuals with metabolic syndrome and Diabetes Mellitus type 2 (DMT-2). The purpose of this study is to assess the effectiveness of saffron in individuals with Diabetes Mellitus type 1 (DMT-1). Patients–Methods: 61 individuals with DMT-1, mean age 48 years old (48.3 ± 14.6), 26 females (42.6%) were randomized to receive a new oral supplement in sachets containing probiotics, prebiotics, magnesium, and Crocus sativus L. extract or placebo containing probiotics, prebiotics and magnesium daily for 6 months. Glycemic control was assessed with a continuous glucose monitoring system and laboratory measurement of HbA1c and lipid profile was also examined. Blood pressure at baseline and end of intervention was also measured. Individuals were either on a continuous subcutaneous insulin infusion with an insulin pump or in multiple daily injection regimens. Diabetes distress and satiety were assessed through a questionnaire and body composition was assessed with bioelectrical impedance. Results: At the end of the intervention, the two groups differed significantly only in serum triglycerides (p = 0.049). After 6 months of treatment, a significant reduction in the active group was observed in glycated hemoglobin (p = 0.046) and serum triglycerides (p = 0.021) compared to baseline. The other primary endpoints (glycemic control, lipid profile, blood pressure) did not differ within the groups from baseline to end of intervention, and there was no significant difference between the two groups. Diabetes distress score improved significantly only in the active group (p = 0.044), suggesting an overall improvement in diabetes disease burden in these individuals but that was not significant enough between the two groups. Conclusions: A probiotic supplement with saffron extract improves serum triglycerides in well-controlled people with DMT-1 and may potentially be a valuable adjunct for enhancing glycemic control.
Likelihood-of-harm/help of microsurgery compared to radiosurgery in large vestibular schwannoma
2024-06-29

Abstract Purpose It has been shown that in large vestibular schwannomas (VS), radiosurgery ( SRS ) is inferior with respect to tumor control compared to microsurgical resection ( SURGERY ). However, SURGERY poses a significantly higher risk of facial-function deterioration (FFD). The aim of this study was to illustrate the effectiveness in terms of number-needed-to-treat/operate (NNO), number-needed-to-harm (NNH), and likelihood-of-harm/help (LHH) by comparing both treatment modalities in large VS. Methods This was a retrospective, dual-center cohort study. Tumor size was classified by Hannover Classification. Absolute risk reduction and risk increase were used to derive additional estimates of treatment effectiveness, namely NNO and NNH. LHH was then calculated by a quotient of NNH/NNO to illustrate the risk–benefit-ratio of SURGERY . Results Four hundred and forty–nine patients treated met the inclusion criteria. The incidence of tumor recurrence was significantly higher in SRS (14%), compared to SURGERY (3%) resulting in ARR of 11% and NNO of 10. At the same time, SURGERY was related to a significant risk of FFD resulting in an NNH of 12. Overall, the LHH calculated at 1.20 was favored SURGERY, especially in patients under the age of 40 years (LHH = 2.40), cystic VS (LHH = 4.33), and Hannover T3a (LHH = 1.83) and T3b (LHH = 1.80). Conclusions Due to a poorer response of large VS to SRS , SURGERY is superior with respect to tumor control. One tumor recurrence can be prevented, when 10 patients are treated by SURGERY instead of SRS . Thus, LHH portrays the benefit of SURGERY in large VS even when taking raised FFD into account.
PhyloFusion- Fast and easy fusion of rooted phylogenetic trees into rooted phylogenetic networks
2024-06-29

Abstract Unrooted phylogenetic networks are often used to represent evolutionary data when incompatibilities are present. Although rooted phylogenetic networks are better suited for explicitly depicting evolutionary histories that involve reticulate events, they have been rarely used in practice, due to a lack of appropriate methods for their calculation. Here we present PhyloFusion, a fast and easily-applicable method for calculating rooted phylogenetic networks on sets of rooted phylogenetic trees. The algorithm can handle trees with unresolved nodes (which arise when edges with low support are contracted) and missing taxa. We illustrate how to use the algorithm to explore different groups of functionally-related genes and report that the algorithm can be applied to datasets containing tens of trees and hundreds of taxa. Availability An open source implementation of PhyloFusion is available in SplitsTree, https://www.github.com/husonlab/splitstree6 (GPLv3 license)
My friend MIROSLAV: A Hackable Open-Source Hardware and Software Platform for High-Throughput Rodent Activity Monitoring in the Home Cage
2024-06-29

Abstract While conventional behavioural tests offer valuable insight into rodent behaviour in specific paradigms, rodents spend most of their time in a safe, undisturbed environment – their home cage. However, home cage monitoring (HCM) is often impractical at scale over prolonged periods of time without significant loss of data. To achieve this, we developed MIROSLAV, the Multicage InfraRed Open Source Locomotor Activity eValuator, a home cage activity and environmental monitoring device designed to be open, adaptable, and robust. Its transparent and modular design allows the device to be tailored to varying experimental requirements and environmental conditions, while its wireless operation and multiple redundancies minimise loss of data and animal disturbance. Data quality is maintained by a modular software workflow for data preparation (Prepare-a-SLAV) and cleaning (TidySLAV), followed by exploratory (MIROSine – MIRO The Explorer) and statistical (MIROSine – StatistiSLAV) analysis of circadian periodicity. Here, using MIROSLAV, we demonstrate circadian dysrhythmia and a disrupted response to regular stimuli (e.g. behavioural testing, bedding change) in a rat model of sporadic Alzheimer’s disease, showcasing MIROSLAV’s utility in a typical animal study of disease. In accordance with the 3Rs, every rodent study and laboratory performing them can benefit from HCM, provided the existence of transparent and customisable tools which allow robust deployment to tens or hundreds of cages in various conditions. MIROSLAV provides this opportunity to researchers in a cost-effective manner.
Altered thymic niche synergistically drives the massive proliferation of malignant thymocytes
2024-06-29

ABSTRACT The discovery of genetic alterations in patient samples over the last decades has reinforced a cell-autonomous view of proliferative expansion during T- cell acute lymphoblastic leukemia (T-ALL) development in the thymus. However, the potential contribution of non-cell-autonomous factors, particularly the impact of thymic epithelial cells (TECs) within the thymic niche during the initiation phase, remains unexplored. In this study, we combine a cell-based computational model of the thymus with complementary in vivo experiments in medaka ( Oryzias latipes ) to systematically analyze the impact of 12 cell-autonomous and non- autonomous factors, individually and in combination, on the proliferation of normal and malignant thymocytes carrying interleukin-7 receptor (IL7R) gain-of-function mutations or elevated IL7R levels, as observed in T-ALL patients. By simulating over 1500 scenarios, we show that while a dense TEC network favored the proliferation of normal thymocytes, it inhibited the proliferation of malignant lineages, which achieved their maximal proliferative capacity when TECs were sparsely distributed. Our in silico model further predicts that specific mutations could accelerate proliferative expansion within a few days. This prediction was experimentally validated, revealing the rapid onset of thymic lymphoma and systemic infiltration of malignant T-cells within just 8 days of embryonic development. These findings demonstrate that synergistic interaction between oncogenic alterations and modifications in the thymic niche can significantly accelerate disease progression. Our results also suggest that negative feedback from the proliferative state suppresses thymocyte differentiation. Overall, this multidisciplinary work reveals the critical role of TEC-thymocyte interactions in both the initiation and progression of T-ALL, highlighting the importance of the thymic microenvironment in early leukemogenesis.
Who is We: Capturing (European) Identity Content by Integrating Qualitative Methods in Survey-Based Approaches
2024-06-29

European identity can mean different things to different people. Yet, past quantitative research has largely focused on the extent to which individuals identify with Europe, and only in a limited way on the meaning and content of that identity. This is problematic because depending on the content of European identity, it may be associated with varying positions towards issues like immigration or Euroscepticism. In this overview, we present two different methods how to assess identity content that can be implemented in survey research. These represent open-ended questions on what it means to be European and Q methodology, asking participants to sort different aspects of Europe according to whether they strengthen or weaken attachment. Different analytical methods exist to group participants’ answers, leading to different results. Drawing on four studies that have used these methods, participants displayed a variety of understandings of Europe and Europeanness, which tap into ethnic heritage, culture, civic institutions, and individual practices among others. These findings highlight the importance to assess identity content next to identity processes (e.g., identification).
Insights into interoceptive and emotional processing: Lessons from studies on insular HD‐tDCS
2024-06-30

Abstract Interoception, the processing of internal bodily signals, is proposed as the fundamental mechanism underlying emotional experiences. Interoceptive and emotional processing appear distorted in psychiatric disorders. However, our understanding of the neural structures involved in both processes remains limited. To explore the feasibility of enhancing interoception and emotion, we conducted two studies using high‐definition transcranial direct current stimulation (HD‐tDCS) applied to the right anterior insula. In study one, we compared the effects of anodal HD‐tDCS and sham tDCS on interoceptive abilities (sensibility, confidence, accuracy, emotional evaluation) in 52 healthy subjects. Study two additionally included physical activation through ergometer cycling at the beginning of HD‐tDCS and examined changes in interoceptive and emotional processing in 39 healthy adults. In both studies, HD‐tDCS was applied in a single‐blind cross‐over online design with two separate sessions. Study one yielded no significant effects of HD‐tDCS on interoceptive dimensions. In study two, significant improvements in interoceptive sensibility and confidence were observed over time with physical preactivation, while no differential effects were found between sham and insula stimulation. The expected enhancement of interoceptive and emotional processing following insula stimulation was not observed. We conclude that HD‐tDCS targeting the insula does not consistently increase interoceptive or emotional variables. The observed increase in interoceptive sensibility may be attributed to the activation of the interoceptive network through physical activity or training effects. Future research on HD‐tDCS involving interoceptive network structures could benefit from protocols targeting larger regions within the network, rather than focusing solely on insula stimulation.
Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta‐Blocker Therapy
2024-07-01

Beta‐blockers are widely used medications for a variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic (e.g., CYP2D6 ) and pharmacodynamic (e.g., ADRB1 , ADRB2 , ADRA2C , GRK4 , GRK5 ) genes have been studied in relation to beta‐blocker exposure and response. We searched and summarized the strength of the evidence linking beta‐blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regarding genetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendations for CYP2D6 and other beta‐blockers or for any beta‐blocker and the other five genes evaluated (updates at www.cpicpgx.org ).
Evaluation of a Covalent Library of Diverse Warheads (CovLib) Binding to JNK3, USP7, or p53
2024-07-01

The screening and target evaluation of the CovLib revealed first interesting hits. The highly cysteine-reactive fragments VS004, SN001, SN006, and SN007 covalently modify several target proteins and showed distinct shifts in the melting temperatures up to +5.1 °C and -9.1 °C.
Local neuronal sleep after stroke: The role of cortical bistability in brain reorganization
2024-07-01

In summary, we found evidence that transient effects of sleep-like slow waves and cortical bistability within ipsilesional M1 resulting in excessive inhibition may interfere with functional reorganization, leading to a less favorable functional outcome post-stroke, pointing to a new therapeutic target to improve recovery of function.