Miracle-dz/UniFAR-FTUs huggingface dataset:
Obstacles against the Marketing of Curcumin as a Drug

Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb Curcuma longa, has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it’s interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug.
Management of Pediatric Post-Endoscopy Fever: Reducing Unnecessary Healthcare Utilization with a Clinical Care Guideline.

OBJECTIVES To validate rates of fever after pediatric gastrointestinal endoscopy, to describe clinical outcomes of post-endoscopy fever (PEF) cases, and to assess the effect of a PEF Clinical Care Guideline (CCG) on hospital utilization. METHODS Episodes of PEF were reviewed from a large prospective database of all adverse events following pediatric gastrointestinal endoscopy at an academic children's hospital. A CCG was implemented to standardize care of children with reported fever after endoscopy and reduce unnecessary resource utilization. Chi-squared analysis was performed to compare rates of hospital use for evaluation of PEF before and after implementation of the CCG. RESULTS PEF occurred in 0.55% of the 27,100 endoscopies performed during this study period. In the 150 cases of reported fever, the rate of identified endoscopy-related infection was low (4.0%). The rate of PEF was significantly higher in patients who underwent interventional procedures (0.81%) than those who underwent diagnostic endoscopy (0.51%, p = 0.02). In patients who experienced PEF, the CCG significantly reduced hospital utilization, decreasing Emergency Department visits and hospital admissions by 52.1% (p < 0.0001) without leading to negative patient outcomes. CONCLUSION PEF in children rarely represents clinically significant infection and may be due in part to inflammation from tissue damage and/or physiologic stress. This study shows that implementation of a PEF CCG may reduce unnecessary care while maintaining patient safety. Further multi-center studies are required to confirm the overall safety of similar clinical algorithms.
A Peripheral CB1R Antagonist Increases Lipolysis, Oxygen Consumption Rate, and Markers of Beiging in 3T3-L1 Adipocytes Similar to RIM, Suggesting that Central Effects Can Be Avoided

With the increased prevalence of obesity and related co-morbidities, such as type 2 diabetes (T2D), worldwide, improvements in pharmacological treatments are necessary. The brain- and peripheral-cannabinoid receptor 1 (CB1R) antagonist rimonabant (RIM) has been shown to induce weight loss and improve glucose homeostasis. We have previously demonstrated that RIM promotes adipose tissue beiging and decreased adipocyte cell size, even during maintenance on a high-fat diet. Given the adverse side-effects of brain-penetrance with RIM, in this study we aimed to determine the site of action for a non-brain-penetrating CB1R antagonist AM6545. By using in vitro assays, we demonstrated the direct effects of this non-brain-penetrating CB1R antagonist on cultured adipocytes. Specifically, we showed, for the first time, that AM6545 significantly increases markers of adipose tissue beiging, mitochondrial biogenesis, and lipolysis in 3T3-L1 adipocytes. In addition, the oxygen consumption rate (OCR), consisting of baseline respiratory rate, proton leak, maximal respiratory capacity, and ATP synthase activity, was greater for cells exposed to AM6545, demonstrating greater mitochondrial uncoupling. Using a lipolysis inhibitor during real-time OCR measurements, we determined that the impact of CB1R antagonism on adipocytes is driven by increased lipolysis. Thus, our data suggest the direct role of CB1R antagonism on adipocytes does not require brain penetrance, supporting the importance of focus on peripheral CB1R antagonism pharmacology for reducing the incidence of obesity and T2D.
Systemic amyloidosis from A (AA) to T (ATTR): a review

Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues. Symptoms are usually insidious and nonspecific resulting in diagnostic delay. The field of amyloidosis has seen significant improvements over the past decade in diagnostic accuracy, prognosis prediction and management. The advent of mass spectrometry‐based shotgun proteomics has revolutionized amyloid typing and has led to the discovery of new amyloid types. Accurate typing of the precursor protein is of paramount importance as the type dictates a specific management approach. In this article, we review each type of systemic amyloidosis to provide the practitioner with practical tools to improve diagnosis and management of these rare disorders.
A Review on Ecotoxicology of Veterinary Pharmaceuticals to Plants and Soil Microbes

Thousands of tons of pharmaceutically active substances are used in veterinary medicines in intensive animal and poultry production, and most of the drugs are poorly absorbed by animals after intake. The animal excrements containing unchanged drugs and temporarily inactivated forms are either directly or indirectly released into soils and other environments by spreading animal excrements from animal husbandry as fertilizer into agricultural soils. Resulting residual concentrations ranges from a few μg up to g·kg-1. Effects of veterinary pharmaceuticals on plants and soil microbial community function and structure are diverse, mainly depending on veterinary antibiotic characteristics and soil factors including soil organic matter content, soil and clay types. Possibly, antibiotic uptake by plant is an energy-dependent process, which cause potential problems to human health. It is likely that pollution induced community resistance(PICT)can be provoked greatly by veterinary pharmaceuticals and can be affected by diverse soil factors, which is a great risk to ecosystem health including human beings.
Effective Masking Levels for Bone Conduction Auditory Brainstem Response Stimuli in Infants and Adults with Normal Hearing

Objective: The purpose of the present study was to investigate effective masking levels (EMLs) for bone conduction (BC) auditory brainstem response (ABR) testing in infants and adults. Early hearing detection and intervention programs aim to limit delays in identifying ear-specific type/degree of hearing loss in infants using the ABR. Ear-specific assessment poses challenges as sound delivered to one ear can travel across the skull and activate the contralateral cochlea. Wave V amplitude and latency measures ipsilateral and contralateral to the bone oscillator can be compared to isolate the test cochlea in some cases; however, when these findings are equivocal, clinical masking is required. This study aims to determine EMLs for ABRs elicited to 500- and 2000-Hz BC stimuli for normal-hearing infants (0 to 18 months) and adults. Design: Participants were 21 adults (18 to 54 years) and 24 infants (5 to 47 weeks) with normal hearing. BC 500- and 2000-Hz brief tonal stimuli at intensities approximating normal levels were presented via a B-71 oscillator (infants: 20 dB nHL at 500 Hz and 30 dB nHL at 2000 Hz; adults: 500 and 2000 Hz at 20 and 30 dB nHL, respectively). White noise masking was presented binaurally via ER-3A earphones (22 to 82 dB SPL; 10-dB steps). The lowest level of masking to eliminate a BC response was deemed the EML. Results: For stimuli presented at 20 dB nHL, adult mean (1 SD) EMLs for 500 and 2000 Hz were 65 (9) and 53 (6) dB SPL, respectively. Mean EMLs for infants were 80 (6) dB SPL for 500 Hz at 20 dB nHL and 64 (9) dB SPL for 2000 Hz at 30 dB nHL. Compared to adults, infants required approximately 13 dB more masking at 500 Hz but a similar amount of masking at 2000 Hz. Infants required 26 dB more masking at 500 versus 2000 Hz, whereas, adults required only 12 dB more masking. Conclusions: Maximum binaural EMLs for infant BC responses elicited to 500 Hz at 20 dB nHL are 82 dB SPL, and for 2000 Hz at 30 and 40 dB nHL, respectively, are 72 and 82 dB SPL. Monaural masking levels for the nontest ear (assuming 10 dB of interaural attenuation) recommended clinically are as follows: (1) 500 Hz: 72 and 82 dB SPL at 20 and 30 dB nHL, respectively; and (2) 2000 Hz: 62, 72, and 82 dB SPL at 30, 40, and 50 dB nHL, respectively. Unsafe levels of white noise would be needed to effectively mask at greater stimulus levels.
Mild neonatal complications following guideline-compliant vacuum-assisted delivery in Japan: improvements still needed

Abstract Introduction Neonatal cephalohematoma and hyperbilirubinemia are often encountered after vacuum-assisted delivery. For safe obstetric practice, guidelines for vacuum procedure were published in 2014 in Japan. We aimed to identify the risk of mild neonatal complications since guideline introduction. Methods This retrospective observational study included singleton deliveries at term gestation from 2015 to 2019 at a single perinatal center in Japan. Incidences of neonatal jaundice requiring phototherapy, cephalohematoma, and umbilical artery pH <7.10 were determined and risk factors relevant to the development of hyperbilirubinemia were evaluated. Results Of 1010 deliveries during the study period, vacuum procedures were attempted in 183 (18%). Guideline recommendations were fully adhered to in over 98% of vacuum procedures. Phototherapy for neonatal hyperbilirubinemia was performed in 75 (41%) of 183 deliveries with vacuum procedure, cephalohematoma occurred in 35 (19%), and umbilical artery pH <7.10 was observed in 10 (5.5%), all of which were significantly higher than without vacuum procedure, such as hyperbilirubinemia (11%, risk ratio [RR] = 3.8, 95% confidence interval [CI] = 2.9 − 4.9, p < .0001), cephalohematoma (1.0%, RR = 19.8, 95%CI = 9.3 − 41.9, p < .0001), and umbilical artery pH <7.10 (0.6%, RR = 9.0, 95%CI = 3.1 − 26.1, p < .0001). Multiple logistic regression analysis demonstrated that vacuum procedure was the factor most strongly associated with neonatal hyperbilirubinemia (odds ratio = 3.5, 95%CI = 2.2 − 5.5, p < .0001). Discussion Vacuum procedure is an important option for the safe vaginal delivery. However, neonates should be observed for development of jaundice to prevent kernicterus even after optimally performed vacuum-assisted delivery.
Association between single nucleotide polymorphism at miR-191 target site and susceptibility to gastric cancer

Objective The study aims to investigate the association between SNP at miR-191 target site and the susceptibility to gastric cancer. Methods Bioinformatics survey was used to explore SNPs within miR-191 binding sites. A case-control study and genotypes assay using PCR-RFLP method were conducted to explore the relationship between SNPs and gastric cancer. Results Three SNPs(rs1327552、 rs433402、 rs4245739) of target genes within miR-191 binding sites were selected by using bioinformatics survey and genotyped. The casecontrol study found that only G allele genotypes(rs1327552 AG and GG) of shoc2 were found to be associated with significantly increased GC risk. After gastric cancer cases were stratified according to age 、 sex、 smoking and drinking or clinic stage, they showed that the frequencies of shoc2 genotypes(rs1327552 AG and GG) were found to be significantly associated with a later stage of GC. Conclusion The polymorphism of rs1327552 in SHOC2 is associated with GC. Thus, the G allele may be an inherited risk factor for GC development.
Swimming through parameter subspaces of a simple anguilliform swimmer.

Computational scientists have investigated swimming performance across a multitude of different systems for decades. Most models depend on numerous model parameters and performance is sensitive to those parameters. In this paper, parameter subspaces are qualitatively identified in which there exists enhanced swimming performance for an idealized, simple swimming model that resembles a C. elegan, an organism that exhibits an anguilliform mode of locomotion. The computational model uses the immersed boundary method to solve the fluid-interaction system. The 1D swimmer propagates itself forward by dynamically changing its preferred body curvature. Observations indicate that the swimmer's performance appears more sensitive to fluid scale and stroke frequency, rather than variations in the velocity and acceleration of either its upstroke or downstroke as a whole. Pareto-like optimal fronts were also identified within the data for the cost of transport and swimming speed. While this methodology allows one to locate robust parameter subspaces for desired performance in a straight-forward manner, it comes at the cost of simulating orders of magnitude more simulations than traditional fluid-structure interaction studies.
RNA-activated protein kinase differentially modulates innate immune response mediated by supraphysiological concentrations of thyroid hormone

Nuclear hormone receptor ligands are known to modulate innate immunity by dampening the immune response induced by pathogens. Here, we report that unlike other ligands, 3,3′,5-triiodo-l-thyronine (T3) induced the type 1 IFN response and expression of IFN-stimulated genes (ISGs). T3 action was found to be significantly amplified at supraphysiological concentrations (SPC) and in combination with double-stranded RNA mimic polyinosinic–polycytidylic acid. Induction by T3 was due to non-genomic mechanisms involving integrin binding, calcium mobilization, and phosphatidyl-inositol 3-kinase–AKT pathways, but was independent of TLR3, RIG-I, and IFN-β1 pathways. Whereas siRNA-induced knockdown of RNA-activated protein kinase (PKR) was found to abrogate the T3-induced expression of select ISGs, expression of other T3-induced ISGs was strongly induced by PKR knockdown, indicating the differential role of PKR in modulating T3 action. Together, we describe a novel role of T3 in modulating the innate immune response and identify the importance of PKR in regulating T3-induced immune activation. These findings have important implications in the basic understanding of the mechanisms of T3 function at SPCs and crosstalk involved in the thyroid hormone function and the innate immune response.
Social Capital in Bahia Clusters

This paper aimed to assess the impact of social capital on the performance of clusters in the state of Bahia, Brazil. Through bibliographic and documentary research, it was possible to achieve the desired objective. It was evident that the most developed clusters in Bahia are found in regions with good levels of social capital. The operationalization of social capital results in cooperation processes that have a direct influence on the performance of the agglomerations of companies. It is concluded that social capital is a decisive factor for the development of clusters.
Muscle activity of the Lumbo-pelvic-hip complex in three isometric exercises using TRX ® rip trainer™ (Actividad muscular del complejo Lumbo-Pelvis-Cadera en tres ejercicios isométricos usando TRX® rip trainer™)

Abstract. One of the tools currently used for strengthening the lumbo-pelvic-hip complex (LPHC) is the TRX ® Rip Trainer™. This device produces asymmetric destabilizing forces by means of an elastic resistance (ER) cord. This study aimed to compare the level of muscle activity of LPHC, during the performance of three isometric exercises using TRX ® Rip Trainer™. Twenty-two healthy, physically active men (mean age 23 ± 2.35 years) were evaluated during the performance of “Drag” (anterior), "Drive" (posterior) and “Stack” (rotation) isometrically resisted exercises, performed using TRX ® Rip Trainer ™. The muscle activity of longissimus, external oblique, gluteus medius, and biceps femoris was recorded by means of surface electromyography. There were differences regarding the side of the ER location in most of the evaluated muscles (p <.05). In addition, a Friedman test revealed differences between the exercises in relation to the evaluated muscle (p<.05). Usually, Stack exercise produces a higher level of activity in these muscles. The findings of this study describe the behavior of LPHC muscles during the use of TRX ® Rip Trainer ™. Resumen. Una de las herramientas actualmente utilizadas para el fortalecimiento del complejo lumbo-pelvis-cadera (CLPC) es el TRX® Rip Trainer ™. Este dispositivo produce una fuerza desestabilizadora asimétrica por medio de un cordón de resistencia elástica (RE). Este estudio tuvo como objetivo comparar el nivel de actividad muscular de CLPC, durante la realización de tres ejercicios isométricos utilizando TRX® Rip Trainer ™. Veintidós hombres sanos, físicamente activos (edad media de 23 ± 2,35 años) se evaluaron durante la realización de los ejercicios de resistencia a la isometría “Drag” (anterior), "Drive" (posterior) y "Stack" (rotación), realizados con TRX® Rip Trainer ™. Mediante electromiografía de superficie, se registró la actividad muscular de longissimus, oblicuo externo, glúteo medio y bíceps femoral. Hubo diferencias en relación con el lado de la ubicación de RE, en la mayoría de los músculos evaluados (p <.05). Además, un test de Friedman reveló diferencias entre los ejercicios en relación con el músculo evaluado (p <.05). Por lo general, el ejercicio Stack produce un mayor nivel de actividad en estos músculos. Los resultados indicados en este estudio describen el comportamiento de los músculos CLPC durante el uso de TRX® Rip Trainer ™.
Comparison of clinical outcomes of implantable collamer lens implantation with and without use of an ophthalmic viscosurgical device.

PURPOSE To compare the clinical efficacy of posterior chamber phakic implantable collamer lens (ICL) implantation with and without the use of an ophthalmic viscosurgical device (OVD). SETTING Onnuri Eye Hospital, Jeonju, Jeollabuk-do, Soth Korea. DESIGN Retrospective case series. METHODS Included were patients who underwent ICL implantation with the use of an OVD (OVD group), and patients who underwent ICL implantation without the use of an OVD (hydro group). Refractive error, endothelial cell density (ECD), intraocular pressure (IOP), vault and adverse events were evaluated at 1 day, 1 week, 1 month, and 3 months postoperatively. The IOP and vault were checked 1 h after surgery, and the surgical time was recorded. RESULTS The OVD group comprised 54 eyes of 27 patients; the hydro group 49 eyes of 25 patients. There were no significant preoperative differences between the two groups. At 1 h postoperatively, the IOP was significantly higher in the OVD group (p < 0.001); however, there was no significant difference in IOP between the two groups at other follow-up timepoints. Surgical time was significantly shorter for the hydro group (p = 0.032). There was no significant difference in vault, ECD, or refractive error between the two groups during the 3-month follow-up period. No adverse events were observed. CONCLUSIONS ICL implantation without the use of an OVD was safe and effective. The advantages of this technique included a short surgical time, prevention of early postoperative IOP spikes, and cost savings due to OVD elimination.
Community based hematological reference intervals among apparently healthy adolescents aged 12-17 years in Mekelle city, Tigrai, northern Ethiopia: A cross sectional study

Background Hematological reference intervals are important in clinical and diagnostic management for the assessment of health and disease conditions. Hematological reference intervals are better to be established based on gender and age differences as these are among the main affecting factors. Objective The aim of this study was to establish hematological reference intervals among apparently healthy adolescents aged 12–17 years in Mekelle City, Tigrai, Northern Ethiopia, 2019. Method A community-based cross-sectional study was conducted in 249 adolescents aged 12–17 years from December 2018 to May 2019. About 4ml of blood sample was collected from each study participant using vacutainer tube containing K2EDTA. Hematological parameters were analyzed using Sysmex KX-21N hematology analyzer (Sysmex Corporation Kobe, Japan). Data were entered and analyzed using SPSS version 23. Both parametric and non-parametric analyses were used to calculate the median and 95% of reference intervals. The 97.5th and 2.5th percentiles were calculated using descriptive statistics for the upper and lower reference limits of the study participants. Differences in reference intervals between male and female participants were evaluated using the Mann–Whitney U test. Result Among the 249 participants 122 (49%) were males and 127 (51%) were females with the median age of 14.5 (range 12 to 17) years were recruited in this study. The median and the 95% reference intervals of hematological parameters were determined. The 95% RIs were: Red blood cells (1012/Liter) 4.6–5.9 (Males) and 4.3–5.6 (Females), White blood cells (109/Liter) 2.9–9.6 (Males) and 3.4–10.2 (Females), Hemoglobin (g/dl) 12.6–17.1 (Males) and 12–15.4 (Females), Platelets (109/Liter) 138–364 (Males) and 151–462 (Females). Almost all of the hematological parameters showed significant differences (p<0.05) across gender. Conclusion The hematological reference intervals established in this study showed a difference based on gender. We suggest preparing and using distinct local reference intervals for males and females separately.