Miracle-dz/UniFAR-FTUs huggingface dataset:
Gallstones and incident colorectal cancer in a large pan‐European cohort study

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self‐reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow‐up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99–1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63–1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.
Inter-Vehicle Communication at Intersections : An Evaluation of Ad-Hoc and Cellular Communication

This book evaluates the ability of ad-hoc and cellular communication to enable cross-traffic assistance at intersections. Potential issues like Non-Line-Of-Sight (NLOS) reception with ad-hoc and limited capacity, higher latency and costs with cellular technology are investigated in two individual evaluations. A method for efficient information delivery via cellular systems and an inter-vehicle NLOS radio propagation model are proposed. Finally, the suitability of both technologies is compared.
Basic auditory processing in the children with autistic features

Abstract This study aimed inhibition mechanisms of auditory processing in the group with autistic features. Thirty-two children (autistic group = 16, typically developing [TD] group = 16) received neuropsychological tests, IQ test and experimental tasks. Both groups showed similar performances except the processing speed index. The results showed that the group with autistic features had less inhibition of return (IOR) than the TD group. However, we did not get a statistically significant group difference in the auditory Go-NoGo task. These results might be attributed to a ceiling effect due to an adjustment failure of a difficulty level instead of showing that the group with autistic features would have intact inhibitory or pitch discriminative function problems. In conclusion, this study showed that the group with autistic features could have an inhibitory processing difficulty in both auditory and visual IOR tasks even when their general cognitive functions are relatively intact. This study presented a possibility that the group with autistic features might have a basic inhibitory function problem, but these findings should be investigated in the further study with enough samples. In addition, we are going to revise the auditory Go-NoGo task and verify the feasibility as a tool to detect ASD in an early stage in the following study.
Epigenetic Biomarkers in Cell-Free DNA and Applications in Liquid Biopsy

Cell-free circulating DNA (cfDNA) in plasma has gained global interest as a diagnostic material for noninvasive prenatal testing and cancer diagnosis, or the so-called “liquid biopsy”. Recent studies have discovered a great number of valuable genetic and epigenetic biomarkers for cfDNA-based liquid biopsy. Considering that the genetic biomarkers, e.g., somatic mutations, usually vary from case to case in most cancer patients, epigenetic biomarkers that are generalizable across various samples thus possess certain advantages. In this study, we reviewed the most recent studies and advances on utilizing epigenetic biomarkers for liquid biopsies. We first reviewed more traditional methods of using tissue/cancer-specific DNA methylation biomarkers and digital PCR or sequencing technologies for cancer diagnosis, as well as tumor origin determination. In the second part, we discussed the emerging novel approaches for exploring the biological basis and clinical applications of cfDNA fragmentation patterns. We further provided our comments and points of view on the future directions on epigenetic biomarker development for cfDNA-based liquid biopsies.
Recognizing psychiatric presentations of anti‐NMDA receptor encephalitis in children and adolescents: A synthesis of published reports

The aim of this study was to improve early recognition of anti‐N‐methyl‐d‐aspartate receptor encephalitis (anti‐NMDArE) in children and adolescents by identifying characteristic temporal patterns of clinical features in patients likely to be referred for psychiatric evaluation. In this form of autoimmune encephalitis, NMDAr hypofunction is caused by autoantibodies to receptor surface components. Clinical outcomes following prompt immunotherapy are usually good, but delayed treatment often results in a protracted course with significant residual disability or death. Anti‐NMDArE frequently mimics psychiatric disorders, so most patients are referred initially to a psychiatrist and treated for days or weeks before being correctly diagnosed.
Psychiatric in-patient audit — the patient's perspective

Consumer attitudes are of the utmost importance in achieving adequate care of a psychiatric population and may directly influence compliance with drug treatment, attendance at out-patient appointments and willingness to accept admission to a psychiatric unit. It is therefore surprising that despite the original Griffiths Report (1987) highlighting the need for consumer input into the psychiatric audit process, little research has been undertaken in this area and knowledge into the quality of inpatient care is especially sparse.
Comparison of Outcomes in Oncoplastic Pelvic Reconstruction with VRAM versus Omental Flaps: A Large Cohort Analysis

Abstract Background The purpose of this study is to describe our experience and outcomes in oncoplastic pelvic reconstruction for patients who underwent either vertical rectus abdominis musculocutaneous (VRAM) or omental flap following abdominoperineal resection (APR) at a single tertiary care institution. Methods All patients who underwent pelvic reconstruction following APR with either VRAM or omental flaps from January 1992 to January 2017 were retrospectively reviewed. Patient demographics and relevant comorbidities including chemotherapy and radiation therapy data were collected and analyzed. In addition, margin status at the time of oncologic resection was analyzed. Flap-specific data were collected for each approach. Oncologic data collected included cancer type, stage at time of APR, and rate of tumor recurrence within the flap. Results A total of 562 patients were identified who underwent pelvic reconstruction with either VRAM or omental pedicle flaps. Of these, 274 (48.8%) underwent VRAM reconstruction and 288 (51.2%) underwent omental flap reconstruction. All margins were negative at time of cancer ablation surgery. Complications data included: seroma (VRAM = 2 [0.36%]; omentum = 32 [5.69%], p < 0.0001), wound dehiscence (VRAM = 31 [5.52%]; omentum = 17 [3.02%], p = 0.022), abscess (VRAM = 4 [0.71%]; omentum = 27 [4.8%], p < 0.0001), cellulitis (VRAM = 2 [0.36%]; omentum = 10 [1.78%], p = 0.025). Statistical comparison of tumor recurrence between these two reconstructive approaches showed a significantly higher recurrence rate in omental flaps compared with VRAM flaps (p = 0.000127). Conclusion The results of this study suggest a significantly higher tumor recurrence rate in omental flap pelvic reconstruction compared with VRAM flaps. This knowledge has the potential to influence surgical planning and flap selection in pelvic reconstruction.
Towards Wearable Comprehensive Capture and Analysis of Skeletal Muscle Activity during Human Locomotion

Background: Motion capture and analyzing systems are essential for understanding locomotion. However, the existing devices are too cumbersome and can be used indoors only. A newly-developed wearable motion capture and measurement system with multiple sensors and ultrasound imaging was introduced in this study. Methods: In ten healthy participants, the changes in muscle area and activity of gastrocnemius, plantarflexion and dorsiflexion of right leg during walking were evaluated by the developed system and the Vicon system. The existence of significant changes in a gait cycle, comparison of the ankle kinetic data captured by the developed system and the Vicon system, and test-retest reliability (evaluated by the intraclass correlation coefficient, ICC) in each channel’s data captured by the developed system were examined. Results: Moderate to good test-retest reliability of various channels of the developed system (0.512 ≤ ICC ≤ 0.988, p < 0.05), significantly high correlation between the developed system and Vicon system in ankle joint angles (0.638R ≤ 0.707, p < 0.05), and significant changes in muscle activity of gastrocnemius during a gait cycle (p < 0.05) were found. Conclusion: A newly developed wearable motion capture and measurement system with ultrasound imaging that can accurately capture the motion of one leg was evaluated in this study, which paves the way towards real-time comprehensive evaluation of muscles and joint motions during different activities in both indoor and outdoor environments.
Molecular network of miR-1343 regulates the pluripotency of porcine pluripotent stem cells via repressing OTX2 expression

ABSTRACT Porcine OTX2 was found to be highly activated in porcine iPS cells (piPSCs) that were reported by different laboratories worldwide. To reveal the regulatory function of OTX2 in porcine reprogrammed cells, we screened porcine miRNA-seq databases and found two miRNAs, miR-1343 and miR-545, that could specifically bind to 3ʹUTR of OTX2 and suppress endogenous OTX2 expression in piPSCs. Knockdown of OTX2 by miR-1343 and miR-545 could significantly increase the expression of SOX2 and ESRRB, but did not alter the expressions of OCT4 and KLF4, and improve the pluripotency of piPSCs. The promoter-based assays showed that OTX2 potentially bound to the promoter region of SOX2 and ESRRB and suppressed their expression. On the other hand, SOX2 could interact with OTX2 promoter. Ectopic expression of SOX2 could significantly decrease OTX2 promoter activity, showing that there is a negative feedback loop between SOX2 and OTX2. Additionally, SOX2 and ESRRB significantly stimulated miR-1343 expression in piPSCs, but OTX2 down regulated the expression of miR-1343 in either direct or indirect manners. In summary, this study demonstrates that there is a regulatory network mediated by miR-1343, in which downregulation of OTX2 by miR-1343 can elevate the expression of pluripotent genes that were then sustain the pluripotency of piPSCs.
MiR‐552 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells by inhibiting AJAP1 expression

Our goal was to explore the function of miR‐552 and its potential target AJAP1 in hepatocellular carcinoma (HCC) oncogenesis and progression. In this study, bioinformatics analysis was performed to detect abnormally expressed miRNAs. The relationship between miR‐552 and AJAP1 was validated using luciferase reporter assays. RT‐qPCR and Western blot assays were applied to explore the expression level of miR‐552, AJAP1 and epithelial‐mesenchymal transition (EMT) markers. HCC cell proliferation was examined using CCK8 assays, while migration and invasion were investigated using Transwell assays. Nude mouse tumourigenesis models were established to facilitate observation of HCC progression in vivo. Finally, prognostic analysis was performed to discover how the prognosis of HCC patients correlated with miR‐552 and AJAP1 expression. MiR‐552 overexpression in HCC cells promoted HCC cell migration, invasion and EMT by targeting/suppressing AJAP1. Poorer prognosis appeared in HCC patients with higher miR‐552 expression or lower AJAP1 levels. Our findings suggested that miR‐552 promotes HCC oncogenesis and progression by inhibiting AJAP1 expression.
Small Polar Molecules: A Challenge in Marine Chemical Ecology

Due to increasing evidence of key chemically mediated interactions in marine ecosystems, a real interest in the characterization of the metabolites involved in such intra and interspecific interactions has emerged over the past decade. Nevertheless, only a small number of studies have succeeded in identifying the chemical structure of compounds of interest. One reason for this low success rate is the small size and extremely polar features of many of these chemical compounds. Indeed, a major challenge in the search for active metabolites is the extraction of small polar compounds from seawater. Yet, a full characterization of those metabolites is necessary to understand the interactions they mediate. In this context, the study presented here aims to provide a methodology for the characterization of highly polar, low molecular weight compounds in a seawater matrix that could provide guidance for marine ecologists in their efforts to identify active metabolites. This methodology was applied to the investigation of the chemical structure of an algicidal compound secreted by the bacteria Shewanella sp. IRI-160 that was previously shown to induce programmed cell death in dinoflagellates. The results suggest that the algicidal effects may be attributed to synergistic effects of small amines (ammonium, 4-aminobutanal) derived from the catabolization of putrescine produced in large quantities (0.05–6.5 fmol/cell) by Shewanella sp. IRI-160.
Red meat and processed meat intake and risk of colorectal cancer: a population-based case–control study

Supplemental Digital Content is available in the text. To examine the association between red meat subtypes intake and risk of colorectal cancer (CRC) among Jewish and Arabs populations in a unique Mediterranean environment. The Molecular Epidemiology of Colorectal Cancer study (n=10 026) is a prospective population-based case–control study in northern Israel. Participants were interviewed in-person about their dietary intake and lifestyle using a questionnaire that included a food-frequency questionnaire. Red meat consumption in Israel was found to be especially low in the Jewish population (1.29±1.45 servings/week), but higher in Arabs (3.0±1.98 servings/week) (P<0.001). Beef was the most commonly consumed red meat by Jews (1.15/1.29 servings/week, 89%) and proportionally less so by Arabs (2.00/3.00, 67%). Processed meat consumption (mostly pork free) was lower among Arabs (0.9±1.56 servings/week) compared with Jews (1.97±2.97 servings/week) (P<0.001). The adjusted odds of CRC per one serving/week of red meat were 1.05 (95% confidence interval: 1.01–1.08) in Jews and 0.94 (0.88–1.01) in Arabs. Compared with no consumption, beef consumption was associated with odds ratio (OR)=0.96 (0.86–1.07) in Jews and 0.94 (0.61–1.45) in Arabs, lamb consumption with OR=1.28 (1.10–1.5) and 1.01 (0.75–1.37), pork consumption with OR=1.44 (1.24–1.67) and 1.07 (0.73–1.56), and processed meat consumption with OR=1.22 (1.10–1.35) and 1.04 (0.82–1.33) in Jews and Arabs, respectively. Overall red meat consumption was associated weakly with CRC risk, significant only for lamb and pork, but not for beef, irrespective of tumor location. Processed meat was associated with mild CRC risk.
The Go-VAR (Veterans Active Recovery): An Adjunctive, Exercise-Based Intervention for Veterans Recovering from Substance Use Disorders

ABSTRACT Substance use disorders (SUD) are prevalent among veterans, and the relapse rate is estimated at ≥60% within one year of treatment. Exercise’s broad health benefits make it an appealing adjunctive component to interventions preventing relapse among individuals with SUDs. After conducting formative research, we designed and conducted the Go-VAR! (Veterans Active Recovery) pilot study to examine the feasibility and acceptability of a multi-component exercise-based intervention for veterans seeking SUD treatment through the outpatient Alcohol & Drug Treatment Program (ADTP) at the VA San Diego Healthcare System (VASDHS). Participants (N = 15; mean age = 45 [SD = 9.7]; 13% Hispanic, 60% White) from the La Jolla VASDHS outpatient ADTP were enrolled in this 12-week one-arm pilot study. Feasibility and acceptability were established: 70% of participants attended weekly psychoeducation groups, wore their Fitbit Charge HR, increased their weekly physical activity, and used their study-provided YMCA memberships, group exercise training sessions, and Fit4Me personal training program. Lower use of both alcohol and drugs were reported at the end of the study (p < .0001). Significant increases in daily steps as measured by the Fitbit HR and improvements in measures of physical fitness were also achieved (p < .05). Future work should focus on potential integration within the VA system.
Carbon dioxide and retinopathy of prematurity in extremely low birth weight infants

Abstract Objective: To evaluate the relationship between partial pressure of carbon dioxide (PCO2) during the first 3 days of life and retinopathy of prematurity (ROP) in extremely low birthweight (ELBW) infants. Patients and methods: A retrospective evaluation of data on ELBW infants were collected over a period of 4 years. Data during the first 72 hours of life was divided into six, 12-hour epochs. The average highest and overall means of PCO2, PO2, FiO2, and glucose were calculated for each epoch. Logistic regression analysis was used to determine the association between PCO2 and ROP after controlling for covariables. Results: A total of 78 neonates were included: birth weight (BW) (703 ± 157 g) and gestational age (25 ± 1.4 weeks). A total of 45 out of 78 had ROP: stage 1 (N = 8), stage 2 (N = 26), stage 3 (N = 14), and plus (N = 4). The overall mean PCO2 correlated with ROP in the first 72 hours of life (R = 0.31, p = .0069). This correlation was significant in epochs 2 (p = .049), 4 (p = .008) and 6 (p = .038). The average of the highest PCO2 also correlated with ROP in the first 72 hours of life (R = 0.38, p = .0007). This correlation was significant in epochs 2 (p = .0115), 4 (p = .0011), 5 (p = .028) and 6 (p = .037). The correlation between the stage of ROP and PCO2 was significant after controlling for PO2 and glucose concentrations. Other variables that correlated with ROP were the overall means of FiO2 (R = 0.23, p = .04), PO2 (R = 0.39, p = .0005) and glucose (R = 0.39, p = .0004) as well as the average highest concentrations of FiO2 (R = 0.26, p = .025), PO2 (R = 0.38, p = .0008) and glucose (R = 0.34, p = .007). Conclusion: After controlling for confounding variables, ROP correlated with the overall means and average highest PCO2. ROP also correlated with FiO2, PO2 and glucose concentrations. Further studies are needed to define the safe PCO2 range and the effect of PCO2 on the normal development of the retina.
A Major Limitation of the Direction of Causation Model: Non-Shared Environmental Confounding

Abstract Determining (1) the direction of causation and (2) the size of causal effects between two constructs is a central challenge of the scientific study of humans. In the early 1990s, researchers in behavioral genetics invented what was termed the direction of causation (DoC) model to address exactly these two concerns. The model claims that for any two traits whose mode of inheritance is sufficiently different, the direction of causation can be ascertained using a sufficiently large genetically informative sample. Using a series of simulation studies, we demonstrate a major challenge to the DoC model, namely that it is extremely sensitive to even tiny amounts of non-shared confounding. Even under ideal conditions for the DoC model (a large sample, N = 10,000), a large causal relationship (e.g., a causal correlation of .50) with very different modes of inheritance between the two traits (e.g., a pure AE model for one trait and a pure CE model for another trait) and a modest degree (correlation of .10) of non-shared confounding between the two traits results in the choice of the wrong causal models and estimating the wrong causal effects.
Elevated pyrimidine dimer formation at distinct genomic bases underlies promoter mutation hotspots in UV-exposed cancers

Sequencing of whole cancer genomes has revealed an abundance of recurrent mutations in gene-regulatory promoter regions, in particular in melanoma where strong mutation hotspots are observed adjacent to ETS-family transcription factor (TF) binding sites. While sometimes interpreted as functional driver events, these mutations have also been suggested to be due to locally inhibited DNA repair or, alternatively, locally increased propensity for UV damage. Here, we provide evidence that base-specific elevations in the efficacy of UV lesion formation underlie these mutations. First, we find that low-dose UV light induces mutations preferably at a known ETS promoter hotspot in cultured cells even in the absence of global or transcription-coupled nucleotide excision repair (NER), ruling out inhibited repair. Further, by genome-wide mapping of cyclobutane pyrimidine dimers (CPDs) shortly after UV exposure and thus before DNA repair, we find that ETS-related mutation hotspots exhibit a strong base-specific increase in CPD formation frequency. Analysis of a large whole genome cohort illustrates the widespread contribution of this effect to recurrent mutations in melanoma. While inhibited NER underlies a general increase in somatic mutation burden in regulatory regions, we conclude that the most recurrently mutated individual DNA bases arise instead due to locally favorable conditions for UV damage formation, thus explaining a key phenomenon in whole-genome cancer analyses.