Miracle-dz/UniFAR-FTUs huggingface dataset:
Glacier Mass Changes of Lake-Terminating Grey and Tyndall Glaciers at the Southern Patagonia Icefield Derived From Geodetic Observations and Energy and Mass Balance Modeling

In this study we demonstrate how energy and mass fluxes vary in space and time for Grey and Tyndall glaciers at the Southern Patagonia Icefield (SPI). Despite the overall glacier retreat of most Patagonian glaciers, a recent increase in mass loss has been observed, but individual glaciers respond differently in terms of spatial and temporal changes. In this context, the detailed investigation of the effect of mass balance processes on recent glacier response to climate forcing still needs refinement. We therefore quantify surface energy-fluxes and climatic mass balance of the two neighboring glaciers, Grey and Tyndall. The COupled Snow and Ice energy and MAss balance model COSIMA is applied to assess recent surface energy and climatic mass balance variability with a high temporal and spatial resolution for a 16-year period between April 2000 to March 2016. The model is driven by downscaled 6-hourly atmospheric data derived from ERA-Interim reanalysis and MODIS/Terra Snow Cover and validated against ablation measurements made in single years. High resolution precipitation fields are determined by using an analytical orographic precipitation model. Frontal ablation is estimated as residual of climatic mass balance and geodetic mass balance derived from TanDEM-X/SRTM between 2000 and 2014. We simulate a positive glacier-wide mean annual climatic mass balance of +1.02$\pm$0.52\,m\,w.e. a$^{-1}$ for Grey Glacier and of +0.68$\pm$0.54\,m\,w.e. a$^{-1}$ for Tyndall Glacier between 2000 and 2014. Climatic mass balance results show a high year to year variability. Comparing climatic mass balance results with previous studies underlines the high uncertainty in climatic mass balance modeling with respect to accumulation on the SPI. Due to the lack of observations accumulation estimates differ from previous studies based on the methodological approaches. Mean annual ice loss by frontal ablation is estimated to be 2.07$\pm$0.70\,m\,w.e. \,a$^{-1}$ for Grey Glacier and 3.26$\pm$0.82\,m\,w.e. \,a$^{-1}$ for Tyndall Glacier between 2000 and 2014. Ice loss by surface ablation exceeds ice loss by frontal ablation for both glaciers. The overall mass balance of Grey and Tyndall glaciers are clearly negative with -1.05$\pm$0.18\,m\,w.e. \,a$^{-1}$ and -2.58$\pm$0.28\,m\,w.e. \,a$^{-1}$ respectively.
Pharmacogenetic of voriconazole antifungal agent in pediatric patients.

AIM We explored the role of SNPs within the SLCO1B3, SLCO1B1, SLC22A6, ABCB1, ABCG2, SLCO3A1, CYP2C19, ABCC2, SLC22A1, ABCB11 and NR1I2 genes on voriconazole pharmacokinetics. PATIENTS & METHODS 233 pediatric patients were enrolled. Drug plasma Ctrough was measured by a HPLC-MS method. Allelic discrimination was performed by qualitative real-time PCR. RESULTS SLCO1B3 rs4149117 c.334 GT/TT (p = 0.046), ABCG2 rs13120400 c.1194 + 928 CC (p = 0.029) and ABCC2 rs717620 c. -24 GA/AA (p = 0.025) genotype groups significantly influenced Ctrough. ethnicity (p = 0.042), sex (p = 0.033), SLCO1B3 rs4149117 c.334 GT/TT (p = 0.041) and ABCB1 rs1045642 c.3435 TT (p = 0.016) have been retained in linear regression model as voriconazole predictor factors. CONCLUSION Understanding how some gene polymorphisms affect the voriconazole pharmacokinetic is essential to optimally dose this agent.
Elevated levels of vitamin B12 in chronic stable heart failure: a marker for subclinical liver damage and impaired prognosis

Background Elevated vitamin B12 is a sign for liver damage, but its significance in chronic stable heart failure (HF) is less known. The present study investigated the clinical correlates and prognostic significance of vitamin B12 levels in stable systolic HF. Methods A total of 129 consecutive patients with HF and 50 control subjects were enrolled. Data regarding demographics, clinical signs, therapeutic and conventional echocardiographic measurements were recorded for all patients. Right-sided HF was defined as the presence of at least one of the typical symptoms (ankle swelling) or specific signs (jugular venous distention or abdominojugular reflux) of right HF. Cox proportional hazards regression analyses were performed to determine the independent prognostic determinants of mortality. Results Baseline B12 levels in HF patients (n=129) with and without right sided HF were significantly higher compared to healthy controls (n=50): Median 311 pg/mL and 235 pg/mL vs 198 pg/mL, respectively (P=0.005). Folic acid levels were similar between the study groups. Age, ejection fraction, left atrial size, estimated glomerular filtration rate, and direct and indirect bilirubin levels were significantly correlated to serum B12 level in univariate analysis. In multivariate analysis, independent correlates of B12 were direct bilirubin (R=0.51, P<0.001) and age (R=0.19, P=0.028). Patients with HF were followed-up for a median period of 32 months. Median B12 levels were significantly higher in patients who subsequently died (n=35) compared to survivors, but folic acid was not different between the two groups. ROC analysis showed that B12 values ≥270 pg/mL had 80% sensitivity and 58% specificity for predicting all-cause mortality (area under the curve=0.672, 95% CI=0.562−0.781; P=0.003). However, in Cox regression analysis, only left atrial diameter, level of direct bilirubin, and the presence of abdominojugular reflux were independent predictors of death. Conclusion Increased B12 in stable HF patients is associated with increased direct bilirubin due to right HF, indicating a cardiohepatic syndrome, but neither B12 nor folic acid are independently associated with mortality.
Differential characteristics of Acinetobacter baumannii colonization and infection: risk factors, clinical picture, and mortality

Objectives The objectives of this study were to detect those characteristics that were specifically associated with infection or colonization by Acinetobacter baumannii, describe the clinical manifestations of those patients in whom the infection was detected in intensive care unit (ICU) or non-ICU wards, and analyze the prognosis-associated factors in patients from whom A. baumannii was isolated. Patients and methods A sample of 122 patients from whom A. baumannii was recovered during an endemic period in a teaching hospital was included. Only those cases in which A. baumannii was recovered as the unique microbe were considered. Demographic data; ward of admission; intrinsic and extrinsic risk factors for infection or colonization; chronic underlying condition severity, as evaluated by the McCabe classification or Charlson index and Acute Physiology and Chronic Health Evaluation (APACHE) II score; and clinical manifestations were analyzed to differentiate specific characteristics of colonized or infected patients. Factors independently associated with the mortality at 30 days were also analyzed by Cox regression. Results A total of 73 (60%) patients were colonized and 49 (40%) individuals were infected with A. baumannii. A non-fatal McCabe class (when compared to ultimately and rapidly fatal), days of hospitalization prior to isolation of A. baumannii, and present ICU admission were associated with the diagnosis of infection. The more frequent clinical picture was respiratory infection (tracheobronchitis, 16 [33%] cases; pneumonia, 27 [55%] cases). Mortality at 30 days was 24% (n=29). A non-fatal McCabe class (Exp[B] 2.44, 95% confidence interval [CI] 1.05–5.66, p=0.039) and the absence of infection (Exp[B] 2.75, 95% CI 1.18–6.38, p=0.019) were independently associated with survival. Conclusion Parameters associated with infection by A. baumannii in an endemic situation are the admission at ICU and the number of days of hospitalization. Mortality of patients from whom A. baumannii was isolated was independently influenced by the chronic underlying basal state and the presence of infection by A. baumannii.
The Modulatory Properties of Li-Ru-Kang Treatment on Hyperplasia of Mammary Glands Using an Integrated Approach

Background: Li-Ru-Kang (LRK) has been used in the treatment of hyperplasia of mammary glands (HMG) for several decades and can effectively improve clinical symptoms. This study aims to investigate the mechanism by which LRK intervenes in HMG based on an integrated approach that combines metabolomics and network pharmacology analyses. Methods: The effects of LRK on HMG induced by estrogen-progesterone in rats were evaluated by analyzing the morphological and pathological characteristics of breast tissues. Moreover, UPLC-QTOF/MS was performed to explore specific metabolites potentially affecting the pathological process of HMG and the effects of LRK. Pathway analysis was conducted with a combination of metabolomics and network pharmacology analyses to illustrate the pathways and network of LRK-treated HMG. Results: Li-Ru-Kang significantly improved the morphological and pathological characteristics of breast tissues. Metabolomics analyses showed that the therapeutic effect of LRK was mainly associated with the regulation of 10 metabolites, including prostaglandin E2, phosphatidylcholine, leukotriene B4, and phosphatidylserine. Pathway analysis indicated that the metabolites were related to arachidonic acid metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Moreover, principal component analysis showed that the metabolites in the model group were clearly classified, whereas the metabolites in the LRK group were between those in the normal and model groups but closer to those in the normal group. This finding indicated that these metabolites may be responsible for the effects of LRK. The therapeutic effect of LRK on HMG was possibly related to the regulation of 10 specific metabolites. In addition, we further verified the expression of protein kinase C alpha (PKCα), a key target predicted by network pharmacology analysis, and showed that LRK could significantly improve the expression of PKCα. Conclusion: Our study successfully explained the modulatory properties of LRK treatment on HMG using metabolomics and network pharmacology analyses. This systematic method can provide methodological support for further understanding the complex mechanism underlying HMG and possible traditional Chinese medicine (TCM) active ingredients for the treatment of HMG.
The impact of signal crayfish (Pacifastacus leniusculus) on the recruitment of salmonid fish in a headwater stream in Yorkshire, England

Signal crayfish (Pacifastacus leniusculus) have become increasingly widespread in rivers in Great Britain since their introduction in the late 1970s, causing extensive losses of indigenous white-clawed crayfish and negative impacts on communities of aquatic plants, invertebrates and benthic fish. Angling interests are increasingly concerned about possible impacts of signal crayfish on brown trout, sea trout (Salmo trutta) and Atlantic salmon (S. salar). This study of a limestone headwater stream in the Pennine uplands, Yorkshire, compares density of fish and two species of crayfish in two years. Signal crayfish are progressively replacing white-clawed crayfish. Surveys showed a significant negative relationship between the fish and signal crayfish. Sites with white-clawed crayfish (1-2 crayfish/trap night) had abundant juvenile trout (> 47.100 m(-2)). Signal crayfish reached higher abundance (4-8 crayfish/trap night) and those sites had fewer fish (0-18.8.100 m(-2)). The signal crayfish population will expand to other tributaries over time. If similar reduction of salmonid recruitment occurs in those streams, there is potential for significant impacts on an important recreational fishery. leniusculus)
On Cell Loss and Selective Vulnerability of Neuronal Populations in Parkinson's Disease

Significant advances have been made uncovering the factors that render neurons vulnerable in Parkinson's disease (PD). However, the critical pathogenic events leading to cell loss remain poorly understood, complicating the development of disease-modifying interventions. Given that the cardinal motor symptoms and pathology of PD involve the loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc), a majority of the work in the PD field has focused on this specific neuronal population. PD however, is not a disease of DA neurons exclusively: pathology, most notably in the form of Lewy bodies and neurites, has been reported in multiple regions of the central and peripheral nervous system, including for example the locus coeruleus, the dorsal raphe nucleus and the dorsal motor nucleus of the vagus. Cell and/or terminal loss of these additional nuclei is likely to contribute to some of the other symptoms of PD and, most notably to the non-motor features. However, exactly which regions show actual, well-documented, cell loss is presently unclear. In this review we will first examine the strength of the evidence describing the regions of cell loss in idiopathic PD, as well as the order in which this loss occurs. Secondly, we will discuss the neurochemical, morphological and physiological characteristics that render SNc DA neurons vulnerable, and will examine the evidence for these characteristics being shared across PD-affected neuronal populations. The insights raised by focusing on the underpinnings of the selective vulnerability of neurons in PD might be helpful to facilitate the development of new disease-modifying strategies and improve animal models of the disease.
Intravenous Versus Topical Tranexamic Acid in Total Knee Arthroplasty: Both Effective in a Randomized Clinical Trial of 640 Patients

Background: Tranexamic acid (TXA) reduces bleeding and the need for transfusion after total knee arthroplasty. Most literature has focused on intravenous (IV) administration of TXA, with less data available on the efficacy of topically administered TXA. This multicenter randomized clinical trial specifically assessed the efficacy of topical TXA compared with IV TXA as measured by calculated blood loss, drain output, and transfusion rates. Complications, including venous thromboembolism (VTE), were reported. Methods: A total of 640 patients who underwent primary unilateral total knee arthroplasty for osteoarthritis at 2 large academic centers were randomized to receive 1 g of IV TXA prior to tourniquet inflation and 1 g at closure, or 3 g of TXA diluted in 45 mL of normal saline solution (total volume of 75 mL) and topically applied after cementation. Age, sex, body mass index, American Society of Anesthesiologists (ASA) score, and preoperative hemoglobin level were similar between the groups. Univariate, multiple linear regression, and multiple logistic regression analyses were performed. Results: Patients who received topical TXA had significantly greater calculated blood loss compared with those who received IV TXA (mean of 324 compared with 271 mL; p = 0.005). Drain output was significantly higher in the topical TXA group compared with the IV TXA group (mean of 560 compared with 456 mL; p < 0.0001). The rate of transfusion was low in the topical and IV groups, with no significant difference on univariate analysis (1.6% compared with 0.6%, respectively; p = 0.45); however, on multiple logistic regression analysis, patients who received topical TXA were 2.2-fold more likely to receive a transfusion (p < 0.0001). The topical and IV TXA groups did not differ significantly with respect to the rate of thrombotic events (0.6% compared with 1.6%, respectively; p = 0.45). Conclusions: In this large, randomized clinical trial involving patients undergoing total knee arthroplasty, both IV and topical TXA were associated with a low rate of transfusion. While IV TXA was associated with less calculated blood loss, lower drain output, and fewer transfusions, the small differences between the groups may not be clinically important. Given the low prevalence of thrombotic complications, the relative safety of one formulation of TXA over the other cannot be definitely established. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Segmentation of Dilated Hemorrhoidal Veins in Hemorrhoidal Disease

Vein segmentation is a vascular remodeling process mainly studied in experimental conditions and linked to hemodynamic factors, with clinical implications. The aim of this work is to assess the morphologic characteristics, associated findings, and mechanisms that participate in vein segmentation in humans. To this end, we examined 156 surgically obtained cases of hemorrhoidal disease. Segmentation occurred in 65 and was most prominent in 15, which were selected for serial sections, immunohistochemistry, and immunofluorescence procedures. The dilated veins showed differently sized spaces, separated by thin septa. Findings associated with vein segmentation were: (a) vascular channels formed from the vein intima endothelial cells (ECs) and located in the vein wall and/or intraluminal fibrin, (b) vascular loops formed by interconnected vascular channels (venous-venous connections), which encircled vein wall components or fibrin and formed folds/pillars/papillae (FPPs; the encircling ECs formed the FPP cover and the encircled components formed the core), and (c) FPP splitting, remodeling, alignment, and fusion, originating septa. Thrombosis was observed in some nonsegmented veins, while the segmented veins only occasionally contained thrombi. Dense microvasculature was also present in the interstitium and around veins. In conclusion, the findings suggest that hemorrhoidal vein segmentation is an adaptive process in which a piecemeal angiogenic mechanism participates, predominantly by intussusception, giving rise to intravascular FPPs, followed by linear rearrangement, remodeling and fusion of FPPs, and septa formation. Identification of other markers, as well as the molecular bases, hemodynamic relevance, and possible therapeutic implications of vein segmentation in dilated hemorrhoidal veins require further studies.
Glutathione metabolism in cancer progression and treatment resistance

Glutathione (GSH) is the most abundant antioxidant found in living organisms and has multiple functions, most of which maintain cellular redox homeostasis. GSH preserves sufficient levels of cysteine and detoxifies xenobiotics while also conferring therapeutic resistance to cancer cells. However, GSH metabolism plays both beneficial and pathogenic roles in a variety of malignancies. It is crucial to the removal and detoxification of carcinogens, and alterations in this pathway can have a profound effect on cell survival. Excess GSH promotes tumor progression, where elevated levels correlate with increased metastasis. In this review, we discuss recent studies that focus on deciphering the role of GSH in tumor initiation and progression as well as mechanisms underlying how GSH imparts treatment resistance to growing cancers. Targeting GSH synthesis/utilization therefore represents a potential means of rendering tumor cells more susceptible to different treatment options such as chemotherapy and radiotherapy.
A realist review to understand the efficacy and outcomes of interventions designed to minimise, reverse or prevent the progression of frailty

ABSTRACT Interventions to minimise, reverse or prevent the progression of frailty in older adults represent a potentially viable route to improving quality of life and care needs in older adults. Intervention methods used across European Innovation Partnership on Active and Healthy Ageing collaborators were analysed, along with findings from literature reviews to determine ‘what works for whom in what circumstances’. A realist review of FOCUS study literature reviews, ‘real-world’ studies and grey literature was conducted according to RAMESES (Realist and Meta-narrative Evidence Synthesis: Evolving Standards), and used to populate a framework analysis of theories of why frailty interventions worked, and theories of why frailty interventions did not work. Factors were distilled into mechanisms deriving from theories of causes of frailty, management of frailty and those based on the intervention process. We found that studies based on resolution of a deficiency in an older adult were only successful when there was indeed a deficiency. Client-centred interventions worked well when they had a theoretical grounding in health psychology and offered choice over intervention elements. Healthcare organisational interventions were found to have an impact on success when they were sufficiently different from usual care. Compelling evidence for the reduction of frailty came from physical exercise, or multicomponent (exercise, cognitive, nutrition, social) interventions in group settings. The group context appears to improve participants’ commitment and adherence to the programme. Suggested mechanisms included commitment to co-participants, enjoyment and social interaction. In conclusion, initial frailty levels, presence or absence of specific deficits, and full person and organisational contexts should be included as components of intervention design. Strategies to enhance social and psychological aspects should be included even in physically focused interventions.
Watching people fail: fostering diagnostic competences with peer feedback on erroneous cognitive modeling examples

II Acknowledgements and Dedication I would like to begin with expressing my deepest gratitude to my supervisors Prof. Martin Fischer and Prof. Jan-Willem Strijbos. They have been loyal, patient and supportive academic mentors throughout my work, making this dissertation possible. I would also like to emphasize my thankfulness for helping me with amazing support and input to Prof. Ingo Kollar and Dr. Nicole Heitzmann, as well as to Prof. Kevin Eva as my peer reviewer and to Prof. Birgit Neuhaus as my forth examination committee member. Thanks to the Elitenetwork of Bavaria for generously funding my position, conferences and stays abroad [Project Nr: K-GS-2012-209]. Further, I would like to thank Prof. Frank Fischer who believed in me as researcher and whose support enabled me to pursue my academic career until this PhD. Thanks to all the professors and colleagues from Lehrstuhl für Empirische Pädagogik und Pädagogische Psychologie and the Institut für Didaktik und Ausbildungsforschung in der Medizin at the LMU. Particular regards to Anja Härtl, Thomas Brendel, Diana Ouellette, Mia Wermelt and Benedikt Lenzer. I am grateful for my colleagues from the REASON doctoral program for being such a formidable, supportive and joyful company. Without the support of my family throughout my career, I would not have been able to pursue this endeavor. Therefore I would like to thank my granny Josefine for believing in me, my parents Klaus-Günther and Claudia for their proud words, my sister Iris for her emergency hotline as well as my aunt Birgit for her open ear and shoulder to lean on. Many thanks for their contributions to my student helpers Max Fink, Rebecca Thaller, Isabell Wenning, Ceyda Göcmen, Ina Bechter and Veronika Maricic. Lastly, thanks to my great friends Selcan Özbay, Christina Färber, Klaus Schmidt, Alejandro Mankowski, Leo Horsch, Dominik Hofmeister, Sarah Severin, Kati and Nils Ledig, Vanessa Middendorf, Malte and Felix Lachmann and especially Pezhman Nasirifard for the amazing encouragement through all phases of my PhD. You rock.