Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of the Roles of Vimentin in Regulating the Proliferation and Migration of HSCs during Hepatic Fibrogenesis

The activation of hepatic stellate cells (HSCs) manifested as proliferation and migration is the pivotal event involved in liver fibrogenesis. The vimentin network, an intermediate filament (IF) system, is one of the critical cascades by which the cell morphology, growth, and motility are modulated. However, the vimentin-mediated cytoskeletal cross talk, as well as the signaling transduction, which further coordinates the cellular responses during hepatic fibrogenesis, is poorly understood. In the current study, both messenger RNA (mRNA) and the vimentin protein were significantly increased in a time-dependent manner in the dimethylnitrosamine (DMN)-exposed liver. In particular, vimentin was highly expressed in the activated HSCs. Again, the overexpressed vimentin was observed in the plasma samples derived from patients with hepatic fibrosis/cirrhosis, suggesting that vimentin may be a key factor in regulating the progression of liver fibrosis. Meanwhile, vimentin knockdown suppressed the migratory propensity, provoked morphological changes, and disturbed the focal adhesions in the HSCs due to the breakdown of associated cytoskeletal proteins. Western blotting showed that vimentin deletion inhibited proliferating cell nuclear antigen (PCNA) and arrested the Rho GTPase family, thereby impairing the HSCs’ growth as well as motility. The phosphorylated extracellular-signal regulated kinase (ERK) and AKT signals were also notably reduced in response to the silence of vimentin. Inhibitors of selected signaling pathways suppressed the migration and differentiation of activated HSCs by regulating specific serine phosphorylated sites on vimentin. Taken together, these findings revealed a novel mechanism of vimentin through which various signaling pathways controlled the proliferation, differentiation, and movement of the HSCs via the ERK/AKT and Rho cascades.
Measuring delay discounting in a crowdsourced sample: An exploratory study.

Delay discounting is a measure of preferences for smaller immediate rewards over larger delayed rewards. Discounting has been assessed in many ways; these methods have variably and inconsistently involved measures of different lengths (single vs. multiple items), forced-choice methods, self-report methods, online and laboratory assessments, monetary and non-monetary compensation. The majority of these studies have been conducted in laboratory settings. However, over the past 20 years, behavioral data collection has increasingly shifted online. Usually, these experiments involve completing short tasks for small amounts of money, and are thus qualitatively different than experiments in the lab, which are typically more involved and in a strongly controlled environment. The present study aimed to determine how to best measure future discounting in a crowdsourced sample using three discounting measures (a single shot measure, the 27-item Kirby Monetary Choice Questionnaire, and a one-time Matching Task). We examined associations of these measures with theoretically related variables, and assessed influence of payment on responding. Results indicated that correlations between the discounting tasks and conceptually related measures were smaller than in prior laboratory experiments. Moreover, our results suggest providing monetary compensation may attenuate correlations between discounting measures and related variables. These findings suggest that incentivizing discounting measures changes the nature of measurement in these tasks.
Targeted High-Throughput Sequencing Identifies Predominantly Fungal Pathogens in Patients with Clinically Infectious, Culture-Negative Endophthalmitis in South India

To evaluate the clinical utility of high-throughput sequencing (HTS) approach-based analysis of the bacterial and fungal genome in vitreous fluids from patients clinically diagnosed as endophthalmitis, we subjected 75 vitreous fluids from clinically presumed infectious endophthalmitis patients to high-throughput sequencing (Illumina HiSeq 2500) after DNA extraction and amplification of the 16S rRNA for the detection of bacteria, and ITS 2 region for detection of fungal pathogens. As controls, we included vitreous biopsies from 70 patients diagnosed with other non-infectious retinal disorders. Following the construction of the curated microbial genome database and filtering steps to reduce ambiguousness/contaminants from the environment, the paired reads were analyzed. Our HTS reads revealed in almost all cases the same organism that was grown in culture (bacterial-14/15, fungal 3/3) by conventional microbiological workup. HTS additionally diagnosed the presence of microbes in 42/57 (73.7%) patients who were conventionally negative (fungal pathogens in 36/57, bacterial pathogens in 11/57, including five cases that showed the presence of both bacterial and fungal organisms). Aspergillus sp. , Fusarium sp. , Exserohilum sp. , and Candida sp. were the most predominant genera in our cohort of culture-negative endophthalmitis cases. Heat map based microbial clustering analysis revealed that these organisms were taxonomically similar to the species identified by conventional culture methods. Interestingly, 4/70 control samples also showed the presence of bacterial reads, although their clinical significance is uncertain. HTS is useful in detecting pathogens in endophthalmitis cases that elude conventional attempts at diagnosis and can provide actionable information relevant to management, especially where there is a high index of suspicion of fungal endophthalmitis, particularly in tropical countries. Outcome analyses and clinical trials addressing the success and cost savings of HTS for the diagnosis of endophthalmitis are recommended.
Layer-By-Layer: The Case for 3D Bioprinting Neurons to Create Patient-Specific Epilepsy Models

The ability to create three-dimensional (3D) models of brain tissue from patient-derived cells, would open new possibilities in studying the neuropathology of disorders such as epilepsy and schizophrenia. While organoid culture has provided impressive examples of patient-specific models, the generation of organised 3D structures remains a challenge. 3D bioprinting is a rapidly developing technology where living cells, encapsulated in suitable bioink matrices, are printed to form 3D structures. 3D bioprinting may provide the capability to organise neuronal populations in 3D, through layer-by-layer deposition, and thereby recapitulate the complexity of neural tissue. However, printing neuron cells raises particular challenges since the biomaterial environment must be of appropriate softness to allow for the neurite extension, properties which are anathema to building self-supporting 3D structures. Here, we review the topic of 3D bioprinting of neurons, including critical discussions of hardware and bio-ink formulation requirements.
Learning Collaboratives in Medical Education: Exploring the Impact of Collaboratives’ Structure and Resources and Teams’ Experience

The Alliance of Independent Academic Medical Centers (AIAMC) organized and coordinated a multicenter learning collaborative, National Initiative V (NI V), focused on community health and health inequity. A pre–post descriptive study was designed to examine the outcomes of the AIAMC NI V. Data were collected from pre- and post-assessment surveys as well as a project milestone self-assessment survey. Twenty-nine institutions participated. By the conclusion of the NI, the majority of institutions had completed at least 1 of the milestones in each of the pre-work/background (65.52%), measurement (62.07%), methods (62.07%), and implement/sustain (20.69%) domains. Institutions reported a significant association between their readiness assessments prior to the start of the NI compared with their status of activities on completion. Milestone achievement is significantly associated with 3 of the assessment items. Learning collaboratives with thoughtfully integrated structure and support can be impactful on topic readiness for the participating organizations.
The Multisensor Array Based on Grown-On-Chip Zinc Oxide Nanorod Network for Selective Discrimination of Alcohol Vapors at Sub-ppm Range

We discuss the fabrication of gas-analytical multisensor arrays based on ZnO nanorods grown via a hydrothermal route directly on a multielectrode chip. The protocol to deposit the nanorods over the chip includes the primary formation of ZnO nano-clusters over the surface and secondly the oxide hydrothermal growth in a solution that facilitates the appearance of ZnO nanorods in the high aspect ratio which comprise a network. We have tested the proof-of-concept prototype of the ZnO nanorod network-based chip heated up to 400 °C versus three alcohol vapors, ethanol, isopropanol and butanol, at approx. 0.2–5 ppm concentrations when mixed with dry air. The results indicate that the developed chip is highly sensitive to these analytes with a detection limit down to the sub-ppm range. Due to the pristine differences in ZnO nanorod network density the chip yields a vector signal which enables the discrimination of various alcohols at a reasonable degree via processing by linear discriminant analysis even at a sub-ppm concentration range suitable for practical applications.
Early mobilization of critically ill patients in the intensive care unit: A systematic review and meta-analysis

Background Physical therapy can prevent functional impairments and improve the quality of life of patients after hospital discharge. However, the effect of early mobilization on patients with a critical illness remains unclear. This study was performed to assess the evidence available regarding the effect of early mobilization on critically ill patients in the intensive care unit (ICU). Methods Electronic databases were searched from their inception to March 21, 2019. Randomized controlled trials (RCTs) comprising critically ill patients who received early mobilization were included. The methodological quality and risk of bias of each eligible trial were assessed using the Cochrane Collaboration tool. Data were extracted using a standard collection form each included study, and processed using the Mantel-Haenszel (M-H) or inverse-variance (I-V) test in the STATA v12.0 statistical software. Results A total of 1,898 records were screened. Twenty-three RCTs comprising 2,308 critically ill patients were ultimately included. Early mobilization decreased the incidence of ICU-acquired weakness (ICU-AW) at hospital discharge (three studies, 190 patients, relative risk (RR): 0.60, 95% confidence interval (CI) [0.40, 0.90]; p = 0.013, I2 = 0.0%), increased the number of patients who were able to stand (one study, 50 patients, 90% vs. 62%, p = 0.02), increased the number of ventilator-free days (six studies, 745 patients, standardized mean difference (SMD): 0.17, 95% CI [0.02, 0.31]; p = 0.023, I2 = 35.5%) during hospitalization, increased the distance the patient was able to walk unassisted (one study, 104 patients, 33.4 (0–91.4) meters vs. 0 (0–30.4) meters, p = 0.004) at hospital discharge, and increased the discharged-to-home rate (seven studies, 793 patients, RR: 1.16, 95% CI [1.00, 1.34]; p = 0.046). The mortality (28-day, ICU and hospital) and adverse event rates were moderately increased by early mobilization, but the differences were statistically non-significant. However, due to the substantial heterogeneity among the included studies, and the low quality of the evidence, the results of this study should be interpreted with caution. Publication bias was not identified. Conclusions Early mobilization appears to decrease the incidence of ICU-AW, improve the functional capacity, and increase the number of ventilator-free days and the discharged-to-home rate for patients with a critical illness in the ICU setting.
Conflicting selection on Cneorum tricoccon (Rutaceae) seed size caused by native and alien seed dispersers

The disappearance of native seed dispersers due to anthropogenic activities is often accompanied by the introduction of alien species, which may to some extent replace the ecological service provided by the extinct ones. Yet, little empirical evidence exists demonstrating the evolutionary consequences of such alien “replacement. ” Here, we document the conflicting selection exerted on seed size by two native lizards (Podarcis lilfordi and P. pityusensis) and an alien mammal species (Martes martes), all acting as legitimate seed dispersers of the Mediterranean relict Cneorum tricoccon. While lizards mostly exerted a negative directional selection on seed diameter, especially P. pityusensis, the much larger pine marten exerted positive selection on seed size. Our findings suggest that this among‐disperser variation in the selection regimes, together with the occurrence of spatial variation in the presence of each seed disperser, help to create the geographical variation observed for seed size of C. tricoccon. To our knowledge, this is the first empirical evidence showing opposing selective pressures between native and alien species in the seed dispersal process in an invaded ecosystem.
Spatial Compounding of Volumetric Data Enables Freehand Optoacoustic Angiography of Large-Scale Vascular Networks

Optoacoustic tomography systems have attained unprecedented volumetric imaging speeds, thus enabling insights into rapid biological dynamics and marking a milestone in the clinical translation of this modality. Fast imaging performance often comes at the cost of limited field-of-view, which may hinder potential applications looking at larger tissue volumes. The imaged field-of-view can potentially be expanded via scanning and using additional hardware to track the position of the imaging probe. However, this approach turns impractical for high-resolution volumetric scans performed in a freehand mode along arbitrary trajectories. We have developed an accurate framework for spatial compounding of time-lapse optoacoustic data. The method exploits the frequency-domain properties of vascular networks in optoacoustic images and estimates the relative motion and orientation of the imaging probe. This allows rapidly combining sequential volumetric frames into large area scans without additional tracking hardware. The approach is universally applicable for compounding volumetric data acquired with calibrated scanning systems but also in a freehand mode with up to six degrees of freedom. Robust performance is demonstrated for whole-body mouse imaging with spiral volumetric optoacoustic tomography and for freehand visualization of vascular networks in humans using volumetric imaging probes. The newly introduced capability for angiographic observations at multiple spatial and temporal scales is expected to greatly facilitate the use of optoacoustic imaging technology in pre-clinical research and clinical diagnostics. The technique can equally benefit other biomedical imaging modalities, such as scanning fluorescence microscopy, optical coherence tomography or ultrasonography, thus optimizing their trade-offs between fast imaging performance and field-of-view.
Clinical and postmortem findings of pentalogy of Fallot in an 18-month-old Holstein heifer

An 18-month-old female Holstein Friesian heifer presented with a history of stunted growth and a recent onset of anorexia; she presented with cyanosis and eventually died. A postmortem examination revealed obstruction of the right ventricular outflow tract, ventricular septal defect, overriding aortic root, right ventricular hypertrophy, and an atrial septal defect, indicating a pentalogy of Fallot (POF). In addition to POF, the heifer also had pulmonary artery dilatation, although she did not present with patent ductus arteriosus. This heifer had the longest lifespan among the Holstein cattle reported to have POF, which may be secondary to delayed pulmonary obstruction due to deformation of one of the pulmonary valves.
Latent variable models for harmonization of test scores: A case study on memory

Combining data from different studies has a long tradition within the scientific community. It requires that the same information is collected from each study to be able to pool individual data. When studies have implemented different methods or used different instruments (e.g., questionnaires) for measuring the same characteristics or constructs, the observed variables need to be harmonized in some way to obtain equivalent content information across studies. This paper formulates the main concepts for harmonizing test scores from different observational studies in terms of latent variable models. The concepts are formulated in terms of calibration, invariance, and exchangeability. Although similar ideas are present in measurement reliability and test equating, harmonization is different from measurement invariance and generalizes test equating. In addition, if a test score needs to be transformed to another test score, harmonization of variables is only possible under specific conditions. Observed test scores that connect all of the different studies, are necessary to be able to test the underlying assumptions of harmonization. The concepts of harmonization are illustrated on multiple memory test scores from three different Canadian studies.
Galectin-13/placental protein 13: redox-active disulfides as switches for regulating structure, function and cellular distribution.

Galectin-13 (Gal-13) plays numerous roles in regulating the relationship between maternal and fetal tissues. Low expression levels or mutations of the lectin can result in pre-eclampsia. The previous crystal structure and gel filtration data show that Gal-13 dimerizes via formation of two disulfide bonds formed by Cys136 and Cys138. In the present study, we mutated them to serine (C136S, C138S and C136S/C138S), crystalized the variants and solved their crystal structures. All variants crystallized as monomers. In the C136S structure, Cys138 formed a disulfide bond with Cys19, indicating that Cys19 is important for regulation of reversible disulfide bond formation in this lectin. Hemagglutination assays demonstrated that all variants are inactive at inducing erythrocyte agglutination, even though gel filtration profiles indicate that C136S and C138S could still form dimers, suggesting that these dimers do not exhibit the same activity as wild type Gal-13. In HeLa cells, the three variants were found to be distributed the same as with wild type Gal-13. However, a Gal-13 variant truncated at T221 could not be transported into the nucleus, possibly explaining why women having this variant get pre-eclampsia. Considering the normally high concentration of glutathione in cells, wild type Gal-13 should exist mostly as a monomer in cytoplasm, consistent with the monomeric variant C136S/C138S which has a similar ability to interact with HOXA1 as wild type Gal-13.
Measurements of the Vertical Displacements of a Railway Bridge Using TLS Technology in the Context of the Upgrade of the Polish Railway Transport

The railway system in Poland is undergoing technological transformation. The development of the Polish railway system concerns not only high-speed trains but also infrastructure. The steel bridge is the most popular type of railway bridge in Poland. Most of them were built in the 1950s and 1960s. According to the recommendations in place in Western Europe, such railway bridges should be reviewed in terms of their fitness for use with modern high-speed trains. The modern technological revolution affects not only the railway, but also developments in displacement and deformation measurement techniques. New technologies provide more objective measurement results and accelerate results processing. They also facilitate the non-contact measurement of bridge structure stability. The authors investigated the vertical displacement of an old steel railway bridge in three different, specific case studies of terrestrial laser scanning data application. Then, the results of 3D data were compared with traditional land surveying results. The scientific results led to a conclusion that a strictly determined methodology of the measurement and analysis of a terrestrial laser scanner results supported by traditional land surveying techniques facilitates the determination of the vertical displacement of bridges with acceptable accuracy.
Preexisting variation in DNA damage response predicts the fate of single mycobacteria under stress

Clonal microbial populations are inherently heterogeneous, and this diversification is often considered as an adaptation strategy. In clinical infections, phenotypic diversity is found to be associated with drug tolerance, which in turn could evolve into genetic resistance. Mycobacterium tuberculosis, which ranks among the top ten causes of mortality with high incidence of drug‐resistant infections, exhibits considerable phenotypic diversity. In this study, we quantitatively analyze the cellular dynamics of DNA damage responses in mycobacteria using microfluidics and live‐cell fluorescence imaging. We show that individual cells growing under optimal conditions experience sporadic DNA‐damaging events manifested by RecA expression pulses. Single‐cell responses to these events occur as transient pulses of fluorescence expression, which are dependent on the gene–network structure but are triggered by extrinsic signals. We demonstrate that preexisting subpopulations, with discrete levels of DNA damage response, are associated with differential susceptibility to fluoroquinolones. Our findings reveal that the extent of DNA integrity prior to drug exposure impacts the drug activity against mycobacteria, with conceivable therapeutic implications.
Serum C-Reactive Protein and Max Polyp Diameter Are Useful Markers of Complications of Small-Intestinal Polypectomy

Background This study aimed to identify the risk factors of complications after small-intestinal polypectomy by single-balloon enteroscopy (SBE), and to assess the value of serum C-reactive protein (CRP) and the max polyp diameter (Dmax) in predicting postoperative complications of small-intestinal polypectomy. Material/Methods Between April 2017 and April 2018, clinical data from 37 patients who underwent small-intestinal polypectomy were retrospectively analyzed. Results Thirty-seven small-intestinal polypectomy procedures (18 oral and 19 anal) were carried out in 37 patients (M: F 20: 17; age 35.6±13.0 years). A total of 1081 small-intestine polyps were removed. Three patients (8.1%) had bleeding and 3 patients (8.1%) had perforation after small-intestinal polypectomy. Based on multivariate logistic analysis, CRP [1.104 (95% CI 1.022–1.191)] was the only risk factor for complications among the patients. According to the area under the receiver operating characteristic (AUROC) curve, CRP (27.5 mg/L), Dmax (3.5 cm), and the combination of CRP + Dmax appear to be predictive factors for complications after small-intestinal polypectomy. Conclusions SBE is an effective endoscopic tool for patients with small-intestinal polyps. CRP, Dmax, and the combination of CRP+Dmax may be potential predictors of complications from small-intestinal polypectomy.