Miracle-dz/UniFAR-FTUs huggingface dataset:
Healthcare resource utilization and costs among nonalcoholic fatty liver disease patients in Germany

Background Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are associated with progression to advanced liver diseases that include compensated cirrhosis, decompensated cirrhosis, liver transplantation, and hepatocellular carcinoma (HCC). This study characterized comorbidities, healthcare resource utilization (HRU), and associated costs among NAFLD patients in Germany. Methods German healthcare claims data between 2011 and 2016 were analyzed retrospectively. Adult patients diagnosed with NAFLD and/or NASH were categorized as NAFLD, NAFLD non-progressors, compensated cirrhosis, decompensated cirrhosis, liver transplant, or HCC. Within each stage, annual all-cause HRU and costs were measured during the pre- and post-index periods. Results Among 4,580,434 patients in the database, proportion of NAFLD was 4.7% (n=215,655). Of them, 36.8% were non-progressors, 0.2% compensated cirrhosis, 9.6% decompensated cirrhosis, 0.0005% liver transplant, and 0.2% HCC. Comorbidity rates were significantly higher in compensated cirrhosis, decompensated cirrhosis, and HCC compared with non-progressors (52.07%, 56.46%, 57.58% vs. 27.49% for cardiovascular disease; 77.13%, 76.61%, 83.47% vs. 54.89% for hypertension; 47.20%, 53.81%, 52.89% vs. 35.21% for hyperlipidemia; 49.88%, 36.67%, 48.21% vs. 20.38% for type 2 diabetes mellitus). The mean annual numbers of post-index outpatient visits and inpatient hospitalizations were significantly higher in patients with advanced liver diseases versus non-progressors. Mean annual costs were significantly higher among patients with advanced liver diseases (compensated cirrhosis, €10,291; decompensated cirrhosis, €22,561; liver transplant, €34,089; HCC, €35,910) than non-progressors (€3,818, P<0.001, except liver transplant cohort). This trend remained consistent after adjusting for baseline demographics and comorbidities. Conclusions NAFLD patients in Germany are grossly underdiagnosed and exert substantial healthcare resource use and economic burden, particularly those with advanced liver diseases. Optimal strategies for early identification and management are needed to prevent disease progression and limit the rising costs.
Stroke outcome assessment: Optimizing cutoff scores for the Longshi Scale, modified Rankin Scale and Barthel Index

The Longshi Scale, a visual-based scale, is reliable and valid in activity assessment, but lacks cutoff definition corresponding to classical scales such as the modified Rankin Scale and Barthel Index. Therefore, this study aimed to investigate the relationships of the Longshi Scale with the modified Rankin Scale and Barthel Index and optimize cutoff scores of these scales in stroke outcomes assessment. This is a cross-sectional study. Stroke patients were measured concurrently by the Longshi scale, modified Rankin Scale and Barthel Index. Kruskal-Wallis test and Spearman correlation analysis were used to analyze the differences and associations among the three scales. The receiver operating characteristic curve was performed to determine the optimal cutoff scores. A total of 5475 stroke patients (67.3% ischemic) were included in this study. There are close relationships of the Longshi Scale with adjusted modified Rankin Scale and Barthel Index (r = -0.861, 0.922; p<0.001, <0.001; respectively). The activity levels assessed by adjusted modified Rankin Scale and Barthel Index among different Longshi scale grades were significantly different (χ2:4217.27, 4676.55; p<0.001, <0.001; respectively). The optimal cutoff scores were adjusted modified Rankin Scale 4, 3, 3, 3, 2 for Longshi scale grade 2 to 6 (sensitivity%: 96.12, 70.24, 89.10, 96.80, 86.23, specificity%: 72.72, 98.29, 93.81, 79.82, 92.89, respectively), and Barthel Index 15, 45, 60, 75, 80 for Longshi scale grade 2 to 6 (sensitivity%: 92.54, 89.28, 91.32, 90.30, 95.65, specificity%: 95.48, 89.51, 94.02, 90.41, 90.62, respectively). In conclusion, the classification of Longshi Scale is consistent with those of modified Rankin Scale and Barthel Index. We recommend the Longshi Scale as an effective supplement for modified Rankin Scale and Barthel Index in assessing the outcome in acute stroke patients.
The Ayeyarwady River (Myanmar): Washload transport and its global role among rivers in the Anthropocene

The Ayeyarwady (Irrawaddy) is the second largest river of Southeast Asia and one of the rivers with the highest load of suspended sediment delivered to the sea in the world. The Ayeyarwady is the lifeline of Myanmar which concentrates the majority of the population and GDP of the country. It is the main way of transport, a source of fluvial aggregates for development projects, hydropower, and the basin plays a major role in food supply and irrigation. Despite the Ayeyarwady ranking amongst the world’s largest rivers and its vital importance to Myanmar, scarce research has been undertaken to understand its morphodynamics and sediment transport regime. Current load estimates still heavily rely on the only systematic study of sediment transport dating back to the 19th century. Here, we provide a novel estimate for the recent washload sediment transport based on a field calibrated remote sensing model of surface suspended sediments concentrations. We show that the Ayeyarwady has likely become the river with the second or third largest delivery of washload to the sea in the world since it has so far been much less affected by damming compared to the vast majority of other rivers.
Late post-injection of biofuel blends in an optical diesel engine: Experimental and theoretical discussion on the inevitable wall-wetting effects on oil dilution

In a diesel engine, diesel particulate filter is used to reduce particle matter emissions. Diesel particulate filter requires periodic regenerations under high-temperature conditions in the exhaust pipe in order to oxidize the accumulated soot. A common strategy to produce high exhaust gas temperature is to inject late post-injections after the main injection. However, this practice may dilute the engine oil, causing engine wear. Biofuel addition to petroleum diesel may increase oil dilution even more. This is related to the fuel spray characteristics, the post-injection control and the vaporization process of fuel in engine oil. In this study, spray properties of late post-injection were studied with petroleum diesel and two types of transport biofuel blends containing 30% either fatty acid methyl ester or hydro-treated vegetable oil. Three different late post-injection timings were investigated. Image sequences of the main spray flame as well as the non-combusting late post-injection spray were extracted. In order to verify oil dilution during regeneration cycle and late post-injection, oil samples from six-cylinder test engine were analyzed. According to the present experiments, differences in the spray characteristics are not significant with the tested fuels. However, higher oil dilution rates were observed with fuel blend composed of 30% fatty acid methyl ester. All the studied late post-injection timings were noted to lead to the unwanted cylinder spray/wall interaction and wall-wetting consequently diluting the engine oil. The spray/wall interaction is thoroughly explained by introducing a theoretical/computational framework which characterizes any spray/wall interaction in terms of a phase diagram for any considered operation conditions. The novelty of this study arises from (1) first comparison of fatty acid methyl ester and hydro-treated vegetable oil blends in an optical engine, (2) strong evidence on the phenomena related to post-injection phase in six-cylinder and single-cylinder optical engine configurations and (3) the development of a single-droplet model showing inevitable wall-wetting.
Risk factors and protective factors of depression in older people 65+. A systematic review

Objectives Identifying risk factors of depression can provide a better understanding of the disorder in older people. However, to minimize bias due to the influence of confounders and to detect reverse influence, a focus on longitudinal studies using multivariate analysis is required. Design A systematic literature search was conducted by searching the databases MEDLINE, Cochrane, PsycINFO and Web of Science for all relevant articles published from January 2000 to the end of March 2020. The following inclusion criteria were used: prospective design, nationally or regionally representative sample, published in English or German, analyzed risk factors for depression of individuals 65+ identified by multivariate analysis, and provided validity of diagnostic instrument. All results of multivariate analysis were reported and summarized. Results Thirty articles were identified. Heterogeneous results were found for education, female gender, self-rated health, cognitive impairment and older age, although significant in several studies. Findings hinted at a protective quality of physical activity. In terms of physical health, chronic disease and difficulty initiating sleep homogeneously increased risk of depression. Mobility impairment resulted as a risk factor in three studies. IADL impairment and vision impairment were mostly identified as significant risk factors. Alcohol consumption and smoking behavior yielded heterogenous results. Psychosocial factors were assessed similarly in multiple studies and yielded heterogenous results. Limitations Research was limited to articles published in English or German. Length of follow up was not considered for the presentation of results. Adjustments for and inclusion of different variables in the studies may distort results. Conclusion Our findings demonstrate the necessity of refined, more comparable assessment tools for evaluating potential risk factors.
Determination of organochlorine pesticides in leather by solid-phase microextraction and gas chromatography-mass spectrometry

Scientia Chromatographica 2015; 7(2) 117 Abstract An analytical procedure based on the solid-phase microextraction technique (SPME) combined with gas chromatography-selected ion monitoring-mass spectrometry (GC-SIM-MS) for the determination of organochlorine pesticides (OCPs) extracted directly from leather samples is proposed. The extraction conditions for the headspace SPME (HS-SPME) procedure were optimized using experimental designs. The fibers and the ionic strength were optimized by the univariate procedure, while a Doehlert matrix was used to optimize the extraction time and temperature. The best extraction conditions were obtained using a PDMS/DVB fiber with extraction time and temperature of 35 min and 80 oC, respectively. No salt addition was necessary. Detection limits ranging from 3.3 to 11 ng g and relative standard deviations (RSD, n = 5) lower than 14.2% were obtained. The recovery was studied at three concentration levels by adding different amounts of organochlorine pesticides to the leather samples (600, 900 and 1500 ng g) and excellent recoveries ranging from 93.7 to 107.3% were obtained.
Correlation between serum lipid and prognosis of idiopathic sudden sensorineural hearing loss: a prospective cohort study

Background To investigate the correlation between blood lipids and the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL). Methods We included 232 patients with ISSNHL at the Second Affiliated Hospital of Shanghai University from June 2015 to March 2017 using a prospective cohort study design. We collected information including age, gender, hypertension, diabetes, mellitus, vertigo, as well as the levels of blood total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL-C). We also recorded the ratio between the levels of low-density lipoproteins and the levels of high-density lipoproteins (LDL-C/HDL-C ratio). Correlations between the prognosis of ISSNHL and TC, TG, LDL-C, and LDL-C/HDL-C ratio were analyzed by univariable and multivariable logistic regression analyses. Results The clinical effectiveness rate of patients with TC ranging from 5.2 to 6.2 mmol/L was significantly higher than that of patients with TC <5.2 mmol/L (P<0.001). No notable difference was found between patients with TC <5.2 mmol/L and patients with TC ≥6.2 mmol/L. The clinical effectiveness rate of patients in TG ranging from 1.7 mmol/L to 2.3 mmol/L was markedly higher than those in TG <1.7 mmol/L (P<0.001). No significant difference was found between patients with TG ranging from 2.3 to 5.6 mmol/L, TG ≥5.6 mmol/L, and TG <1.7 mmol/L. The clinical effectiveness rate of patients in LDL-C/HDL-C <1.5 was considerably higher than those in LDL-C/HDL-C ranging from 1.5 to 2.5, 2.5 to 3.5, and ≥3.5 (P<0.001). Conclusions Our findings indicated that TC, TG, and the LDL-C/HDL-C ratio are strongly associated with the prognosis of ISSNHL. These three indices could be recommended as independent markers to predict outcomes.
Revisiting density-dependent fecundity in schistosomes using sibship reconstruction

The stability of parasite populations is regulated by density-dependent processes occurring at different stages of their life cycle. In dioecious helminth infections, density-dependent fecundity is one such regulatory process that describes the reduction in egg production by female worms in high worm burden within-host environments. In human schistosomiasis, the operation of density-dependent fecundity is equivocal and investigation is hampered by the inaccessibility of adult worms that are located intravascularly. Current understanding is almost exclusively limited to data collected from two human autopsy studies conducted over 40 years ago, with subsequent analyses having reached conflicting conclusions. Whether egg production is regulated in a density-dependent manner is key to predicting the effectiveness of interventions targeting the elimination of schistosomiasis and to the interpretation of parasitological data collected during monitoring and evaluation activities. Here, we revisit density-dependent fecundity in the two most globally important human Schistosoma spp. using a statistical modelling approach that combines molecular inference on the number of parents/adult worms in individual human hosts with parasitological egg count data from mainland Tanzania and Zanzibar. We find a non-proportional relationship between S. haematobium egg counts and inferred numbers of female worms, providing the first clear evidence of density-dependent fecundity in this schistosome species. We do not find robust evidence for density-dependent fecundity in S. mansoni because of high sensitivity to some modelling assumptions and the lower statistical power of the available data. We discuss the strengths and limitations of our model-based analytical approach and its potential for improving our understanding of density dependence in schistosomiasis and other human helminthiases earmarked for elimination.
The emerging role of microRNA in regulating the mTOR signaling pathway in immune and inflammatory responses

The mechanistic/mammalian target of rapamycin (mTOR) is considered to be an atypical protein kinase that plays a critical role in integrating different cellular and environmental inputs in the form of growth factors, nutrients and energy and, subsequently, in regulating different cellular events, including cell metabolism, survival, homeostasis, growth and cellular differentiation. Immunologically, mTOR is a critical regulator of immune function through integrating numerous signals from the immune microenvironment, which coordinates the functions of immune cells and T cell fate decisions. The crucial role of mTOR in immune responses has been lately even more appreciated. MicroRNAs (miRNAs) are endogenous, small, noncoding single‐stranded RNAs that act as molecular regulators involved in multiple processes during immune cells development, homeostasis, activation and effector polarization. Several studies have recently indicated that a range of miRNAs are involved in regulating the phosphoinositide 3‐kinase/protein kinase B/mTOR (PI3K/AKT/mTOR) signaling pathway by targeting multiple components of this signaling pathway and modulating the expression and function of these targets. Current evidence has revealed the interplay between miRNAs and the mTOR pathway circuits in various immune cell types. The expression of individual miRNA can affect the function of mTOR signaling to determine the cell fate decisions in immune responses through coordinating immune signaling and cell metabolism. Dysregulation of the mTOR pathway/miRNAs crosstalk has been reported in cancers and various immune‐related diseases. Thus, expression profiles of dysregulated miRNAs could influence the mTOR pathway, resulting in the promotion of aberrant immunity. This review summarizes the latest information regarding the reciprocal role of the mTOR signaling pathway and miRNAs in orchestrating immune responses.
GCN2 Regulates ATF3-p38 MAPK Signaling Transduction in Pulmonary Veno-Occlusive Disease

Pulmonary veno-occlusive disease (PVOD) is a fatal disease of pulmonary vascular lesions leading to right heart failure. Heritable PVOD (hPVOD) is related to biallelic mutation of EIF2AK4 (encoding GCN2), but its molecular mechanism remains unclear. In this study, we aimed to investigate the pathogenesis of PVOD and to find potential drug targets for PVOD. GCN2 dysfunction led to an enhanced transcription of collagen I gene (col1a1 and col1a2) through decreasing ATF3-dependent p38 phosphorylation inhibition in PVOD, which promotes the collagen I synthesis in pulmonary arterial smooth muscle cells (PASMCs) and eventually leads to increased collagen deposition in pulmonary artery. Four GCN2 knockout (KO) cell lines (exon 15 or 33 mutation) were successfully constructed by epiCRISPR system. Two induced pluripotent stem cells (iPSCs) were generated by reprogramming peripheral blood mononuclear cells (PBMCs) of PVOD patient. It was also comfirmed that GCN2 dysfunction could lead to increased expression of collagen I in lateral plate mesoderm lineage-smooth muscle cells (LM-SMCs) differentiated from both GCN2 KO cell lines and iPSCs. SB203580 (a specific inhibitor of p38) improved hemodynamics and pulmonary vascular remodeling in mitomycin C (MMC)-induced PVOD rats by right ventricle echocardiography. On the whole, we proposed that GCN2 deficiency decreased ATF3-dependent p38 phosphorylation inhibition in PVOD development and suggested a potential therapeutic reagent of SB203580 for the treatment of the disease.
Sample Selection Bias Due to Differential Mortality: A Supplementary Measure of Old-Age Poverty

ABSTRACT Traditional “head count” measures of poverty at advanced older ages understate the risk of falling into poverty because of survivorship bias due to the income-mortality gradient, which indicates that people in poverty have higher mortality rates than people with higher income. Survivorship bias is a form of sample selection bias. This paper presents a supplementary measure for poverty at older ages, based on an adaption of a model for correcting survivorship bias in rate of return data for mutual funds. Using U.S. longitudinal data from the Health and Retirement Study (HRS) for 1996 and 2002–2012 for the same cohort, we develop a new estimate of poverty at older ages that suggests that traditional cross-sectional measures understate the risk of falling into poverty by roughly a quarter. This finding has important implications for social programs that relate to the causes and consequences of the selectivity bias.
Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression

Background Inositol-requiring enzyme 1 (IRE1) plays a critical role in attenuating endoplasmic reticulum (ER) stress associated with renal injury which may also be a factor in diabetic nephropathy (DN). Alcohol dehydrogenase type I (ADH1) activity is prominent in the kidney, ADH1 activity is also reported to exert protective effects against ER stress that are not caused by alcohol consumption. However, the role of IRE1 in DN and the correlation between IRE1 and ADH1 activity remain unclear. Methods IRE1α floxed mice (Ire1f/f) of C57BL/6J background were established and crossbred with Ire1αf/f mice to produce podocyte-specific IRE1α knockout mice. Male db/db mice (C57BLKS/J-leprdb/leprdb mice) were used as a DN model. Male mice were made diabetic by injection of streptozotocin. pLKO.1-based vectors encoding short hairpin RNA (shRNA) specific to the IRE1α gene were transfected into HEK293T cells to knockdown IRE1α in mouse podocytes. ELISA, Masson’s staining, and electron microscopy were performed to analyze the development of DN. The ADH1 expression was assayed by qPCR and western blot. Results We found that IRE activity was increased in the glomeruli of DN mouse models. In contrast, ADH1 expression was decreased in these models and mice with podocyte-specific disruption of IRE1 (PKO mice). PKO mice that were made diabetic using streptozotocin exhibited accelerated proteinuria, enhanced glomerular fibrosis, and podocyte cell death. In addition, in cultured podocytes, the knockdown of IRE1 downregulated the ADH1 mRNA expression and induced ER stress, consistent with the result of PKO mice, while its detrimental effects were reversed by ADH1 overexpression. Conclusions Activation of IRE1 in podocytes serves to limit the progress of DN. The dependence of kidney ADH1 expression on podocyte IRE1 further suggests that ADH1 activity may play an important role downstream of IRE1 in protecting against DN.
A family with partially penetrant multicentric carpotarsal osteolysis due to gonadal mosaicism: First reported case

Multicentric carpotarsal osteolysis (MCTO) is an autosomal dominant condition characterized by carpal–tarsal abnormalities; over half of affected individuals also develop renal disease. MCTO is caused by mutations of MAFB; however, there is no clear phenotype–genotype correlation. We describe the first reported family of variable MCTO phenotype due to mosaicism: the proband had classical skeletal features and renal involvement due to focal segmental glomerulosclerosis (FSGS), and the father had profound renal impairment due to FSGS, necessitating kidney transplantation. Mosaicism was first suspected in this family due to unequal allele ratios in the sequencing chromatograph of the initial blood sample of proband's father and confirmed by sequencing DNA extracted from the father's hair, collected from different bodily parts. This case highlights the need for a high index of clinical suspicion to detect low‐level parental mosaicism, as well as a potential role for MAFB mutation screening in individuals with isolated FSGS.