Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary Choline Supplementation Attenuates High-Fat-Diet-Induced Hepatocellular Carcinoma in Mice.

BACKGROUND Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death in the world. Choline deficiency has been well studied in the context of liver disease; however, less is known about the effects of choline supplementation in HCC. OBJECTIVE The objective of this study was to test whether choline supplementation could influence the progression of HCC in a high-fat-diet (HFD)-driven mouse model. METHODS Four-day-old male C57BL/6J mice were treated with the chemical carcinogen, 7,12-dimethylbenz[a]anthracene, and were randomly assigned at weaning to a cohort fed an HFD (60% kcal fat) or an HFD with supplemental choline (60% kcal fat, 1.2% choline; HFD+C) for 30 wk. Blood was isolated at 15 and 30 wk to measure immune cells by flow cytometry, and glucose-tolerance tests were performed 2 wk prior to killing. Overall tumor burden was quantified, hepatic lipids were measured enzymatically, and phosphatidylcholine species were measured by targeted MS methods. Gene expression and mitochondrial DNA were quantified by quantitative PCR. RESULTS HFD+C mice exhibited a 50-90% increase in both circulating choline and betaine concentrations in the fed state (P ≤ 0.05). Choline supplementation resulted in a 55% decrease in total tumor numbers, a 67% decrease in tumor surface area, and a 50% decrease in hepatic steatosis after 30 wk of diet (P ≤ 0.05). Choline supplementation increased the abundance of mitochondria and the relative expression of β-oxidation genes by 21% and ∼75-100%, respectively, in the liver. HFD+C attenuated circulating myeloid-derived suppressor cells at 15 wk of feeding (P ≤ 0.05). CONCLUSIONS Choline supplementation attenuated HFD-induced HCC and hepatic steatosis in male C57BL/6J mice. These results suggest a therapeutic benefit of choline supplementation in blunting HCC progression.
Spinal cord stimulation modulates complexity of neural activities in patients with disorders of consciousness

Abstract Objective: Spinal cord stimulation (SCS) is a valuable treatment for patients with disorders of consciousness (DOC). This study used permutation entropy (PeEn) of neural activities to quantify brain responses to SCS. Method: We recruited 14 patients with DOC, including seven patients in minimally conscious state (MCS) and seven patients in vegetative state/unawareness state (VS/UWS). All patients received a single session of 20 min’ continuous SCS. We recorded resting state EEG before, during and after SCS. In this study, PeEn was first calculated to describe overall neural activities changes in SCS. The brain was then divided into frontal, central, parietal and occipital regions to explore spatial SCS modulation effects. Finally, a correlation analysis was conducted between CRS-R values and changes in PeEn on each of the four regions. Results: SCS was associated with short-term changes in neural activities in DOC. When SCS was on, PeEn increased as compared to the baseline. When SCS was shut off, PeEn decreased. The PeEn of all patients after SCS was higher than before SCS, and changes of PeEn for MCS were more significant than those for VS, especially in the frontal region. Conclusion: PeEn from EEG data could be used to evaluate SCS modulation effects, and EEG complexity might be a critical index to describe brain responses to SCS in DOC.
Association between Monocyte Chemoattractant Protein-1 -2518 (A/G) Single Nucleotide Polymorphism and Chronic Periodontitis in End-stage Renal Disease Patients – A Case–control Study

ABSTRACT Monocyte chemoattractant protein 1 (MCP-1) plays an important role in the development of periodontitis. The purpose of this investigation was to evaluate association of the MCP-1 gene polymorphism with chronic periodontitis in patients with end-stage renal disease (ESRD). One hundred fifty ESRD patients with chronic periodontitis (CP), 100 without CP and 190 healthy controls were included in this study. Genomic DNA from all participants was genotyped for the –2518 (A/G) polymorphism by a polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) assay. Significant differences were observed in the genotype and allele frequencies between patients with ESRD and CP and controls. The G allele frequency was significantly higher in patients than in control subjects, with odds ratio 1.77 (95 % CI 1.2–2.5), p = 0.0014. For the GG genotype the OR was 3.63 (95 % CI 1.5–8.76), p = 0.041. No significant differences in the polymorphism distribution were observed between ESRD patients without CP and control subjects. Comparison of the MCP-1 gene polymorphism distribution in ESRD patients with various primary diseases leading to ESRD did not show any significant differences. The mean MCP-1 serum levels were compared between subgroups. They were significantly higher in ESRD patients with CP (582 ± 112 pg/ml) than in patients without CP (309 ± 103 pg/ml) and controls (265 ± 85 pg/ml). Our results suggest that the MCP-1-2518 A/G polymorphism might be a novel risk factor for developing chronic periodontitis in patients with ESRD.
Irradiated Human Fibroblasts as a Substitute Feeder Layer to Irradiated Mouse 3T3 for the Culture of Human Corneal Epithelial Cells: Impact on the Stability of the Transcription Factors Sp1 and NFI

Because of the worldwide shortage of graftable corneas, alternatives to restore visual impairments, such as the production of a functional human cornea by tissue engineering, have emerged. Self-renewal of the corneal epithelium through the maintenance of a sub-population of corneal stem cells is required to maintain the functionality of such a reconstructed cornea. We previously reported an association between stem cell differentiation and the level to which they express the transcription factors Sp1 and NFI. In this study, we investigated the impact of replacing irradiated 3T3 (i3T3) murine fibroblast feeder cells by irradiated human corneal fibroblasts (iHFL) on the expression of Sp1 and NFI and evaluated their contribution to the proliferative properties of human corneal epithelial cells (hCECs) in both monolayer cultures and human tissue engineered corneas (hTECs). hCECs co-cultured with iHFL could be maintained for up to two more passages than when they were grown with i3T3. Western Blot and electrophoretic mobility shift assays (EMSAs) revealed no significant difference in the feeder-layer dependent increase in Sp1 at both the protein and DNA binding level, respectively, between HCECs grown with either i3T3 or iHFL. On the other hand, a significant increase in the expression and DNA binding of NFI was observed at each subsequent passage when hCECs were co-cultured along with i3T3. These changes were found to result from an increased expression of the NFIA and NFIB isoforms in hCECs grown with i3T3. Exposure of hCECs to cycloheximide revealed an increased stability of NFIB that likely resulted from post-translational glycosylation of this protein when these cells were co-cultured with i3T3. In addition, iHFL were as efficient as i3T3 at preserving corneal, slow-cycling, epithelial stem cells in the basal epithelium of the reconstructed hTECs. Furthermore, we observed an increased expression of genes whose encoded products promote hCECs differentiation along several passages in hCECs co-cultured with either type of feeder layer. Therefore, the iHFL feeder layer appears to be the most effective at maintaining the proliferative properties of hCECs in culture most likely by preserving high levels of Sp1 and low levels of NFIB, which is known for its gene repressor and cell differentiation properties.
Optical coherence tomography findings in patients with alcohol use disorder and their relationship with clinical parameters

Abstract Purpose: In our study, we aimed to investigate the ganglion cell-inner plexiform layer thickness (GCIPL), retinal nerve fibre layer thickness (RNFL), mean macular volume (MMV), central macular thickness (CMT), mean macular thickness (MMT), and choroidal thickness (CT) values with optical coherence tomography (OCT) in patients who are diagnosed with alcohol use disorder (AUD). Materials and methods: The study included 43 patients who were diagnosed with AUD, and 43 healthy controls. Detailed biomicroscopic examinations of all the participants, visual acuity, intraocular pressure, anterior and posterior segment examinations, and then, OCT measurements were carried out. Results: Although the measured values for RNFL in the superior and temporal quadrant are within normal limits, they were slightly higher compared to those in the control group (p values 0.127 and 0.191 for superior quadrant and temporal quadrant, respectively). The CT measurements in all quadrants were higher than the control group; however, these measurements were not statistically significant (p > 0.05). When the relation between clinical features and OCT findings of the patients were examined, it was determined that the ages of the patients were statistically significantly and inversely correlated with the temporal CT and also the nasal and temporal quadrants of RNFL. Conclusions: Our study is the first study that examines the retinal GCIPL and CT with OCT in patients who are diagnosed with AUD. In our results, it was determined that there were no statistically significant differences between the participants in terms of OCT parameters. Further studies with larger sampling groups evaluating neurotransmission findings may provide wider results.
The Microbiome–Estrogen Connection and Breast Cancer Risk

The microbiome is undoubtedly the second genome of the human body and has diverse roles in health and disease. However, translational progress is limited due to the vastness of the microbiome, which accounts for over 3.3 million genes, whose functions are still unclear. Numerous studies in the past decade have demonstrated how microbiome impacts various organ-specific cancers by altering the energy balance of the body, increasing adiposity, synthesizing genotoxins and small signaling molecules, and priming and regulating immune response and metabolism of indigestible dietary components, xenobiotics, and pharmaceuticals. In relation to breast cancer, one of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism since endogenous estrogens are the most important risk factor in breast cancer development especially in postmenopausal women. Intestinal microbes encode enzymes capable of deconjugating conjugated estrogen metabolites marked for excretion, pushing them back into the enterohepatic circulation in a biologically active form. In addition, the intestinal microbes also break down otherwise indigestible dietary polyphenols to synthesize estrogen-like compounds or estrogen mimics that exhibit varied estrogenic potency. The present account discusses the potential role of gastrointestinal microbiome in breast cancer development by mediating metabolism of steroid hormones and synthesis of biologically active estrogen mimics.
External validation of clinical prediction rules for complications and mortality following Clostridioides difficile infection

Background Several clinical prediction rules (CPRs) for complications and mortality of Clostridioides difficile infection (CDI) have been developed but only a few have gone through external validation, and none is widely recommended in clinical practice. Methods CPRs were identified through a systematic review. We included studies that predicted severe or complicated CDI (cCDI) and mortality, reported at least an internal validation step, and for which data were available with minimal modifications. Data from a multicenter prospective cohort of 1380 adults with confirmed CDI were used for external validation. In this cohort, cCDI occurred in 8% of the patients and 30-day all-cause mortality occurred in 12%. The performance of each tool was assessed using individual outcomes, with the same cut-offs and standard parameters. Results Seven CPRs were assessed. Three predictive scores for cCDI showed low sensitivity (25–61%) and positive predictive value (PPV; 9–31%), but moderate specificity (54–90%) and negative predictive value (NPV; 82–95%). One model [using age, white blood cell count (WBC), narcotic use, antacids use, and creatinine ratio > 1.5× the normal level as covariates] showed a probability of 25% of cCDI at the optimal cut-off point with 36% sensitivity and 84% specificity. Two scores for mortality had low sensitivity (4–55%) and PPV (25–31%), and moderate specificity (71–78%) and NPV (87–92%). One predictive model for 30-day all-cause mortality [Charlson comorbidity index, WBC, blood urea nitrogen (BUN), diagnosis in ICU, and delirium] showed an AUC-ROC of 0.74. All other CPRs showed lower AUC values (0.63–0.69). Errors in calibration ranged from 12%- 27%. Conclusions Included CPRs showed moderate performance for clinical use in a large validation cohort with a majority of patients infected with ribotype 027 strains and a low rate of cCDI and mortality. These data show that better CPRs need to be developed and validated.
Snagfall the first decade after severe bark beetle infestation of high-elevation forests in Colorado, USA.

The persistence and fall rate of snags (standing dead trees) generated during bark beetle outbreaks have consequences for the behavior, effects and suppression of potential wildfires, hazard tree and timber salvage operations, wildlife habitat and numerous ecosystem processes. However, post-beetle snagfall dynamics are poorly understood in most forest types. We tagged standing live and dead lodgepole pine (Pinus contorta), subalpine fir (Abies lasiocarpa) and Engelmann spruce (Picea engelmannii), including beetle-killed pine snags following the peak of a recent mountain pine bark beetle outbreak in watersheds at the Fraser Experimental Forest in northcentral Colorado and sampled snagfall ten and twelve years later. Bark beetle attacks began in 2003, peaked by 2006 and killed 78% of overstory lodgepole pine in 133 plots distributed across a range of stand and site conditions. Of those snags, only 17% fell between 2007 and 2018. Most snags broke at ground level, due to butt rot, and were oriented downhill. In contrast, snags that tipped up or snapped off above the ground were oriented with the prevailing winds. Equal numbers of snags fell singly and in multiple tree groups, and equal numbers remained elevated rather than in contact with the ground. Lodgepole pine snagfall was 1.6-times higher on steep slopes (> 40%) where dead pine density was higher, compared to flatter sites. Based on our findings and previous research we estimate that half the beetle-killed lodgepole pine in high-elevation forests such as those at Fraser may fall within 15-20 years of beetle infestation, but that some pine snags are likely to persist for decades longer. Post-outbreak snagfall dynamics create a multiple-decade legacy of bark beetle outbreaks that will persist longer in high-elevation compared to lower-elevation forests.
Association Between Greenness Surrounding Schools and Kindergartens and Attention-Deficit/Hyperactivity Disorder in Children in China

Key Points Question Is greenness surrounding schools and kindergartens associated with symptoms of attention-deficit/hyperactivity disorder among children? Findings In this large cross-sectional study of 59 754 Chinese children, attendance at schools or kindergartens in greener areas was associated with lower odds of having attention-deficit/hyperactivity disorder symptoms. Meaning These findings may be useful for policy makers and health care professionals to develop strategies (eg, planning for green spaces around schools and kindergartens) to mitigate the attention-deficit/hyperactivity disorder burden.
Gaze and Eye Tracking: Techniques and Applications in ADAS

Tracking drivers’ eyes and gazes is a topic of great interest in the research of advanced driving assistance systems (ADAS). It is especially a matter of serious discussion among the road safety researchers’ community, as visual distraction is considered among the major causes of road accidents. In this paper, techniques for eye and gaze tracking are first comprehensively reviewed while discussing their major categories. The advantages and limitations of each category are explained with respect to their requirements and practical uses. In another section of the paper, the applications of eyes and gaze tracking systems in ADAS are discussed. The process of acquisition of driver’s eyes and gaze data and the algorithms used to process this data are explained. It is explained how the data related to a driver’s eyes and gaze can be used in ADAS to reduce the losses associated with road accidents occurring due to visual distraction of the driver. A discussion on the required features of current and future eye and gaze trackers is also presented.
Axillary Osmidrosis

Abstract Axillary osmidrosis is characterized by offensive odor resulting from bacterial decomposition of apocrine secretions in the axillae, and individuals with axillary osmidrosis suffer detrimental effects to their psychosocial functioning. We searched the literature in January 2019 for all English-language publications discussing axillary osmidrosis to identify previous reports, present trends, and emerging treatments. Studies were listed chronologically by the country of the first author's institution. Publications were also classified regarding the study type (literature review), pathophysiology, and treatments. We identified 133 publications on axillary osmidrosis, and of these, 120 were from East-Asian countries. Before 1990, there were only 9 publications, but after 2000, publications increased in number. One hundred of 133 reports discussed treatment, namely, 39 reports on suction curettage, 28 reports on open surgery, and 8 reports on subdermal laser. Other studies focused on the pathophysiology of axillary osmidrosis. This literature review revealed unique trends in the identified studies. Because control of axillary odor is a universal subject, the etiology and pathophysiology of axillary osmidrosis have been studied throughout the world and are clearly described. However, almost all studies of surgical treatments have been performed in East-Asian countries. After the year 2000, various surgical and nonsurgical treatments, namely, laser therapy and suction curettage, have been attempted. Emerging treatments for axillary osmidrosis include ethanol injections, microwave therapy, and microneedle radiofrequency technologies; however, further studies of these treatments are needed.
Development and evaluation of point-of-care testing recertification with e-learning

Abstract One of the main requirements in point-of-care testing (POCT) is efficient operator training to avoid diagnostic errors. Considering a variety of users and time-independent learning, e-learning is preferred. However, in our experience, e-learning is not always accepted by employees. After using a commercial e-learning program with little success, we developed a specific e-learning offer to achieve a better acceptance of online-based training. Herein our goal was to identify the most relevant aspects for better acceptance. The new e-learning modules were implemented with the learning management system ILIAS and dealt with typical sources of error. The implementation was accompanied by an anonymous online questionnaire within the POCT operators examining differences between the acceptance of the commercial e-learning and the hospital-specific. The results show higher acceptance for clinic-specific e-learning whereby online training of the POCT operators could successfully established. Most relevant aspects are the relevance of contents for the personal work and the working processes within the clinic as well as processing time. Thereby, the recertification of the POCT operators based on the successful completion of the learning modules was fully integrated in the POCT process. In respect to the need for regular recertification of POCT operators, our study shows that the acceptance of e-learning could be improved by adapting e-learning modules to the specific workflows in the hospital.
Structure-Activity Study of an All-d Antimicrobial Octapeptide D2D

The increasing emergence of multi-drug resistant bacteria is a serious threat to public health worldwide. Antimicrobial peptides have attracted attention as potential antibiotics since they are present in all multicellular organisms and act as a first line of defence against invading pathogens. We have previously identified a small all-d antimicrobial octapeptide amide kk(1-nal)fk(1-nal)k(nle)-NH2 (D2D) with promising antimicrobial activity. In this work, we have performed a structure-activity relationship study of D2D based on 36 analogues aimed at discovering which elements are important for antimicrobial activity and toxicity. These modifications include an alanine scan, probing variation of hydrophobicity at lys5 and lys7, manipulation of amphipathicity, N-and C-termini deletions and lys-arg substitutions. We found that the hydrophobic residues in position 3 (1-nal), 4 (phe), 6 (1-nal) and 8 (nle) are important for antimicrobial activity and to a lesser extent cationic lysine residues in position 1, 2, 5 and 7. Our best analogue 5, showed MICs of 4 µg/mL against A. baumannii, E. coli, P. aeruginosa and S. aureus with a hemolytic activity of 47% against red blood cells. Furthermore, compound 5 kills bacteria in a concentration-dependent manner as shown by time-kill kinetics. Circular dichroism (CD) spectra of D2D and compounds 1–8 showed that they likely fold into α-helical secondary structure. Small angle x-ray scattering (SAXS) experiments showed that a random unstructured polymer-like chains model could explain D2D and compounds 1, 3, 4, 6 and 8. Solution structure of compound 5 can be described with a nanotube structure model, compound 7 can be described with a filament-like structure model, while compound 2 can be described with both models. Lipid interaction probed by small angle X-ray scattering (SAXS) showed that a higher amount of compound 5 (~50–60%) inserts into the bilayer compared to D2D (~30–50%). D2D still remains the lead compound, however compound 5 is an interesting antimicrobial peptide for further investigations due to its nanotube structure and minor improvement to antimicrobial activity compared to D2D.
Fundamentals of Global Modeling for Polymer Extrusion

A review paper is presented on modeling for polymer extrusion for both single screw and twin-screw extrusion. An issue of global modeling is discussed, which includes modeling for solid conveying, melting, melt flow, and co-operation of the screw/die system. The classical approach to global modeling of the extrusion process, which is based on separate models for each section of the screw, i.e., solid transport section, melting and pre-melting sections, and the melt flow section is presented. In this case, the global model consists of the elementary models. A novel continuous concept of global modeling based on CFD (Computational Fluids Dynamics) computations is also presented, and a concept of using the DEM (Discrete Element Method) computation coupled with CFD computations is discussed.