Miracle-dz/UniFAR-FTUs huggingface dataset:
Free abdominal gas on computed tomography in the emergency department: aetiologies and association between amount of free gas and mortality.

INTRODUCTION Free abdominal gas is an important finding with major clinical implications. However, data on the aetiologies and prognosis of patients with free gas are scarce. Our primary aim was to describe the sources of free abdominal gas on emergency department (ED) computed tomography (CT). The secondary aim was to evaluate the association between the amount of free gas and all-cause mortality. METHODS All patients who underwent CT in the ED between February 2012 and February 2019 with free abdominal gas were included in the study. A scoring system was used to assess the amount of free gas: small - gas bubbles; medium - any gas pocket ≤2cm in diameter; large - any gas pocket >2cm. Data were collected from laboratory and clinical assessment regarding the source of free gas and all-cause mortality. RESULTS A total of 372 patients had free abdominal gas. Colonic diverticulitis was the most common aetiology among those with a small or medium amount of free gas (81/250 [32.4%] and 12/71 [16.9%] respectively). For patients with a large amount of gas, peptic disease was the most common aetiology (11/51 [21.6%]). Three-quarters of the patients (280/372, 75.2%) had the source of free gas identified during ED admission. Ninety-day mortality rates were 7.2%, 9.9% and 21.6% for patients with small, medium and large amounts of gas respectively (p=0.007). CONCLUSIONS Colonic diverticulitis was the most common source of free abdominal gas and peptic disease was the most common cause of a large amount of free gas. Mortality rates correlated with the amount of gas and were significantly higher in patients with a large amount.
SCFA: mechanisms and functional importance in the gut

In recent years, the importance of the gut microbiota in human health has been revealed and many publications have highlighted its role as a key component of human physiology. Owing to the use of modern sequencing approaches, the characterisation of the microbiome in healthy individuals and in disease has demonstrated a disturbance of the microbiota, or dysbiosis, associated with pathological conditions. The microbiota establishes a symbiotic crosstalk with their host: commensal microbes benefit from the nutrient-rich environment provided by the gut and the microbiota produces hundreds of proteins and metabolites that modulate key functions of the host, including nutrient processing, maintenance of energy homoeostasis and immune system development. Many bacteria-derived metabolites originate from dietary sources. Among them, an important role has been attributed to the metabolites derived from the bacterial fermentation of dietary fibres, namely SCFA linking host nutrition to intestinal homoeostasis maintenance. SCFA are important fuels for intestinal epithelial cells (IEC) and regulate IEC functions through different mechanisms to modulate their proliferation, differentiation as well as functions of subpopulations such as enteroendocrine cells, to impact gut motility and to strengthen the gut barrier functions as well as host metabolism. Recent findings show that SCFA, and in particular butyrate, also have important intestinal and immuno-modulatory functions. In this review, we discuss the mechanisms and the impact of SCFA on gut functions and host immunity and consequently on human health.
Feasibility and Acceptability of Ecological Momentary Assessment with High-Risk Suicidal Adolescents Following Acute Psychiatric Care

ABSTRACT Objective: The study purpose was to examine the feasibility and acceptability of intensive ecological momentary assessment (EMA) among high-risk adolescents with suicidal thoughts and behaviors following discharge from acute psychiatric care. Method: Fifty-three adolescents, 12–18 years old, and their parents, were recruited following discharge from acute psychiatric care for suicide risk. The study included a baseline assessment (adolescent and parent), 28 days of EMA surveys (5x per day) and wrist actigraphy (adolescent), and an interview at the end of the 28-day monitoring period (adolescent). Adolescents’ outpatient clinicians were also surveyed about the study. Results: Study feasibility was indicated by a reasonable enrollment rate, high adherence to wearing the actigraphy device, and good adherence to EMA surveys (highest in the first week with significant drop-off in subsequent weeks). Adolescents reported their overall experience in the study was positive, the questions were understandable, their responses to questions were generally accurate, and the surveys were minimally burdensome. The study procedures did not appear to be iatrogenic; suicide attempts and rehospitalizations were not study related and occurred at a rate comparable to other adolescents at the recruitment site. Adolescents’ clinicians reported that the study was somewhat positive and minimally burdensome for them, and somewhat positive for their patients and families. Conclusions: This study demonstrated that intensive EMA designs are feasible and acceptable among high-risk suicidal youth following acute psychiatric care. Specific procedures are provided for keeping adolescents safe during intensive EMA studies, including detailed information about the risk and safety monitoring plan.
MYCN Silencing by RNA Interference Induces Neurogenesis and Suppresses Proliferation in Models of Neuroblastoma with Resistance to Retinoic Acid.

Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display MYCN amplification, which indicates a very poor prognosis. MYCN is a highly specific target for an NB tumor therapy as MYCN expression is absent or very low in most normal cells, while, as a transcription factor, it regulates many essential cell activities in tumor cells. We aim to develop a therapy for NB based on MYCN silencing by short interfering RNA (siRNA) molecules, which can silence target genes by RNA interference (RNAi), a naturally occurring method of gene silencing. It has been shown previously that MYCN silencing can induce apoptosis and differentiation in MYCN amplified NB. In this article, we have demonstrated that siRNA-mediated silencing of MYCN in MYCN-amplified NB cells induced neurogenesis in NB cells, whereas retinoic acid (RA) treatment did not. RA can differentiate NB cells and is used for treatment of residual disease after surgery or chemotherapy, but resistance can develop. In addition, MYCN siRNA treatment suppressed growth in a MYCN-amplified NB cell line more than that by RA. Our result suggests that gene therapy using RNAi targeting MYCN can be a novel therapy toward MYCN-amplified NB that have complete or partial resistance toward RA.
Long-term outcomes of the hip shelf arthroplasty in adolescents and adults with residual hip dysplasia: a systematic review

Background and purpose — The shelf arthroplasty was the regular treatment for residual hip dysplasia before it was substituted by the peri-acetabular osteotomy. Yet, evidence regarding the survival of shelf arthroplasty surgery has never been systematically documented. Hence, we investigated the survival time of the shelf procedure until revision to THA in patients with primary hip dysplasia. Factors that influenced survival and complications were also examined, along with the accuracy of correcting radiographic parameters to characterize dysplasia. Material and methods — The inclusion criteria were studies of human adolescents and adults (> 16 years) with primary or congenital hip dysplasia who were treated with a shelf arthroplasty procedure. Data were extracted concerning patient characteristics, survival time, complications, operative techniques, and accuracy of correcting radiographic parameters. Results — Our inclusion criteria were applicable to 9 studies. The average postoperative Center-Edge Angle and Acetabular Head Index were mostly within target range, but large variations were common. Kaplan–Meier curves (endpoint: conversion to THA) varied between 37% at 20 years’ follow-up and 72% at 35 years’ follow-up. Clinical failures were commonly associated with pain and radiographic osteoarthritis. Only minor complications were reported with incidences between 17% and 32%. Interpretation — The shelf arthroplasty is capable of restoring normal radiographic hip parameters and is not associated with major complications. When carefully selected on minimal osteoarthritic changes, hip dysplasia patients with a closed triradiate cartilage may benefit from the shelf procedure with satisfactory survival rates. The importance of the shelf arthroplasty in relation to peri-acetabular osteotomies needs to be further (re)explored.
Lung Cytokines and Systemic Inflammation in Patients with COPD

Chronic obstructive pulmonary disease (COPD) is a growing global epidemic condition with raising morbidity and mortality as population age. It has been projected that COPD, which ranked sixth as the cause of death in 1990, will become the third leading cause of death worldwide by 2020 [1]. Smoking is the most well-known risk factor for COPD; however, non-smokers may develop chronic airflow obstruction through occupational exposure to dust and chemicals and indoor pollution from biomass. Other recognized risk factors are genetic predisposition and low socioeconomic status [1].
Partnership Between Japan and the United States for Early Development of Pediatric Medical Devices　- Harmonization By Doing for Children.

BACKGROUND The Harmonization By Doing (HBD) program was established in 2003 as a partnership among stakeholders of academia, industry and regulatory agencies in Japan and the United States, with a primary focus on streamlining processes of global medical device development for cardiovascular medical devices. While HBD has traditionally focused on development of devices intended to treat conditions prevalent in adults, in 2016, HBD established the "HBD-for-Children" program, which focuses on the development of pediatric devices as the development of medical devices for pediatric use lags behind that of medical devices for adults in both countries.Methods and Results:Activities of the program have included: (1) conducting a survey with industry to better understand the challenges that constrain the development of pediatric medical devices; (2) categorizing pediatric medical devices into five categories based on global availability and exploring concrete solutions for the early application and regulatory approval in both geographies; and (3) facilitating global clinical trials of pediatric medical devices in both countries. CONCLUSIONS The establishment of the HBD-for-Children program is significant because it represents a global initiative for the introduction of pediatric medical devices for patients in a timely manner. Through the program, academia, industry and regulatory agencies can work together to facilitate innovative pediatric device development from a multi-stakeholder perspective. This activity could also encourage industry partners to pursue the development of pediatric medical devices.
CT perfusion core and ASPECT score prediction of outcomes in DEFUSE 3

Background The role of Alberta Stroke Program Early CT Score (ASPECTS) for thrombectomy patient selection and prognostication in late time windows is unknown. Aims We compared baseline ASPECTS and core infarction determined by CT perfusion (CTP) as predictors of clinical outcome in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE) 3 trial. Methods We included all DEFUSE 3 patients with baseline non-contrast CT and CTP imaging. ASPECTS and core infarction were determined by the DEFUSE 3 core laboratory. Primary outcome was functional independence (modified Rankin Scale (mRS) ≤2). Secondary outcomes included ordinal mRS shift at 90 days and final core infarction volume. Results Of the 142 patients, 85 patients (60%) had ASPECTS 8–10 and 57 (40%) had ASPECTS 5–7. Thirty-one patients (36%) with ASPECTS 8–10 and 11 patients (19%) with ASPECTS 5–7 were functionally independent at 90 days (p = 0.03). In the primary and secondary logistic regression analysis, there was no difference in ordinal mRS shift (p = 0.98) or functional independence (mRS ≤ 2; p = 0.36) at 90 days between ASPECTS 8–10 and ASPECTS 5–7 patients. Similarly, primary and secondary logistic regression analyses found no difference in ordinal mRS shift (p = 1.0) or functional independence (mRS ≤ 2; p = 0.87) at 90 days between patients with baseline small core ( < 50 ml) versus medium core (50–70 ml). Conclusions Higher ASPECTS (8–10) correlated with functional independence at 90 days in the DEFUSE trial. ASPECTS and core infarction volume did not modify the thrombectomy treatment effect, which indicates that patients with a target mismatch profile on perfusion imaging should undergo thrombectomy regardless of ASPECTS or core infarction volume in late time windows.
Advanced Chronic Kidney Disease in Lupus Nephritis: Is Dialysis Inevitable?

Objective. Advanced chronic kidney disease (CKD) carries an increased risk for progression to endstage renal disease (ESRD). We aimed to determine the rate of progression and the factors that drive the decline of renal function in lupus nephritis (LN). Methods. Patients with advanced LN-related CKD were identified from our longterm longitudinal cohort. Advanced CKD was defined as stage 3b [estimated glomerular filtration rate (eGFR) = 30–44 ml/min/1.73 m2] and stage 4 (eGFR = 15–29 ml/min/1.73 m2). All individuals were followed until progression to ESRD or the last visit and were divided into “progressors” and “non- progressors. ” Demographic, clinical, immunological, and therapeutic variables were compared at baseline. Multivariable Cox regression analysis (both time-dependent and independent) was performed to identify predictors for progression. Results. One hundred eighteen patients (74 CKD 3b and 44 CKD 4) were included. Forty-five patients progressed (29 to ESRD and 16 from CKD 3b to CKD 4) after 6 years on average. No significant decline in the renal function was observed in 73 patients (“non-progressors”) after 10 years on average. Active serology (high anti-dsDNA titers and low complements C3/C4) at the time of CKD diagnosis and any increase of the daily prednisone dose after baseline were strongly associated with progression. Treatment with renin angiotensin system (RAS) blockers was associated with less risk for progression. Conclusion. Dialysis is not inevitable in LN-related advanced CKD because 62% of our patients did not progress over 10 years of followup on average. Certain predictors were identified to affect progression to ESRD.
Effect of isoproturon on barbiturate induced hypnosis in mice

lsoproturon a herbicide produces a CNS depressant effect. Pretreatment of mice with isoproturon at different doses increased the duration of pentobarbitone induced sleep in mice and potentiated the effect of subhypnotic dose of pentobarbitone. lsoproturon also decreased the onset and increased the duration of barbitone induced sleep in mice. However, four days pretreatment with two divided doses of isoproturon significantly decreased the duration of sleep and increased the mean liver weight in mice. The results indicate that isoproturon might have direct CNS depressant action. Decrease in pentobarbitone sleeping time in isoproturon pretreated mice appears to be due to induction of hepatic microsomal enzymes.
Durability study of a gellan gum-based tissue-mimicking phantom for ultrasonic thermal therapy.

Stability and duration of ultrasonic phantoms are still subjects of research. This work presents a tissue-mimicking material (TMM) to evaluate high-intensity therapeutic ultrasound (HITU) devices, composed of gellan gum (matrix), microparticles (scatterers), and chemicals. The ultrasonic velocity and attenuation coefficient were characterized as a function of temperature (range 20 °C-85 °C). The nonlinear parameter B/A was determined by the finite amplitude insertion substitution (FAIS) method, and the shear modulus was determined by a transient elastography technique. The thermal conductivity and specific heat were determined by the line source method. The attenuation was stable for 60 days, and in an almost linear frequency dependence (0.51f0.96 dB cm-1), at 20 °C (1-10 MHz). All other evaluated physical parameters are also close to typical soft tissue values. Longitudinal ultrasonic velocities were between 1.49 and 1.75 mm μs-1, the B/A parameter was 7.8 at 30 °C, and Young's modulus was 23.4 kPa. The thermal conductivity and specific heat values were 0.7 W(m K)-1 and 4.7 kJ(kg K)-1, respectively. Consistent temperature increases and thermal doses occurred under identical HITU exposures. Low cost, longevity, thermal stability, and thermal repeatability make TMM an excellent material for ultrasonic thermal applications. The TMM developed has the potential to assess the efficacy of hyperthermia devices and could be used to adjust the ultrasonic emission of HITU devices.
Cost-effective Management of Severe Gastroesophageal Reflux Disease: Toward an Improved Understanding of Anti-reflux Surgery

c 2020 The Korean Society of Neurogastroenterology and Motility J Neurogastroenterol Motil, Vol. 26 No. 2 April, 2020 www.jnmjournal. org Gastroesophageal reflux disease (GERD) can generally be well-managed using proton pump inhibitors (PPI). Four weeks of PPI therapy can achieve about 70% of healing rate and 60-90% of complete symptom resolution. However, GERD is a great socioeconomic burden. In the United States, the direct cost of managing GERD exceeds $12 billion, which is higher than the overall direct cost from all digestive tract cancers ($8.4 billion). The significant cost involved in the management of patients with GERD is caused by a high prevalence in the population and the need for long-term medications. Recently, the interest in managing GERD surgically has increased. A recent randomized-controlled trial showed that laparoscopic Nissen fundoplication was superior to medication in reducing reflux-related heartburn. In the study, treatment success, which was defined as an improvement of 50% or more in the GERDHealth Related Quality of Life score, was achieved in 67% of patients who underwent surgery, while 28% of patients who received active medical therapy including omeprazole and baclofen achieved treatment success. In another recent study in an Asian population, laparoscopic Nissen fundoplication was shown to be effective in patients for whom medical treatment was ineffective or who were unable to discontinue medication due to symptom recurrence. Although medication should be the first-line treatment for patients with GERD and even though a large proportion of patients can be medically managed, anti-reflux surgery may offer an option for selected patients. The efficacy of anti-reflux surgery in the management of GERD patients is well-recognized. However, cost-effectiveness must be a primary consideration before recommending surgical treatment widely in clinical practice. In this issue of the Journal of Neurogastroenterology and Motility, Park et al reported a costeffective analysis between anti-reflux surgery and medication in patients with severe GERD in Korea. They showed that the surgical approach resulted in cost savings of $551 per patient and that the quality-adjusted life years had a gain of 1.18 compared to medication among patients with severe GERD over a 10-year period. JNM J Neurogastroenterol Motil, Vol. 26 No. 2 April, 2020 pISSN: 2093-0879 eISSN: 2093-0887 https://doi.org/10.5056/jnm20025 Editorial Journal of Neurogastroenterology and Motility
Work/study productivity gain and associated indirect cost savings with guselkumab compared with adalimumab in moderate-to-severe psoriasis: results from the VOYAGE 1 study

Abstract Background Work productivity loss (WPL) is a major contributor to the indirect costs of psoriasis. Newer biologic therapies are effective at reducing disease symptoms and improving quality of life, but their impact on WPL and associated indirect cost savings compared to previously approved biologic therapies is largely unknown. Objectives To compare the effects of guselkumab and adalimumab on WPL and associated indirect cost savings in patients with moderate-to-severe psoriasis. Methods Using data from the VOYAGE 1 (NCT02207231) trial, improvements from baseline in Dermatology Life Quality Index (DLQI) work/study domain scores were compared for patients receiving guselkumab or adalimumab at 24 and 48 weeks of treatment. Improvements in WPL and associated cost savings were calculated using a previously established DLQI-WPL algorithm. Results Among patients who could not work/study at baseline (DLQI work/study domain score = 3), a significantly greater proportion of guselkumab-treated patients could work/study without problems (DLQI work/study domain score = 0) than adalimumab-treated patients at Weeks 24 and 48. Improvements from baseline in WPL and associated cost savings were greater with guselkumab than with adalimumab at Week 48. Conclusions Guselkumab was superior to adalimumab for improvement in WPL and associated indirect cost savings, and its use may reduce the economic burden of psoriasis.
Accelerated Evolution of the Regulatory Sequences of Brain Development in the Human Genome

Genetic modifications in noncoding regulatory regions are likely critical to human evolution. Human-accelerated noncoding elements are highly conserved noncoding regions among vertebrates but have large differences across humans, which implies human-specific regulatory potential. In this study, we found that human-accelerated noncoding elements were frequently coupled with DNase I hypersensitive sites (DHSs), together with monomethylated and trimethylated histone H3 lysine 4, which are active regulatory markers. This coupling was particularly pronounced in fetal brains relative to adult brains, non-brain fetal tissues, and embryonic stem cells. However, fetal brain DHSs were also specifically enriched in deeply conserved sequences, implying coexistence of universal maintenance and human-specific fitness in human brain development. We assessed whether this coexisting pattern was a general one by quantitatively measuring evolutionary rates of DHSs. As a result, fetal brain DHSs showed a mixed but distinct signature of regional conservation and outlier point acceleration as compared to other DHSs. This finding suggests that brain developmental sequences are selectively constrained in general, whereas specific nucleotides are under positive selection or constraint relaxation simultaneously. Hence, we hypothesize that human- or primate-specific changes to universally conserved regulatory codes of brain development may drive the accelerated, and most likely adaptive, evolution of the regulatory network of the human brain.