Miracle-dz/UniFAR-FTUs huggingface dataset:
Harnessing the patient voice in prostate cancer research: Systematic review on the use of patient‐reported outcomes in randomized controlled trials to support clinical decision‐making

Given the growing importance of patient‐reported outcomes (PROs) as part of “big data” in improving patient care, there is a need to provide a state‐of‐the‐art picture of the added value of using PROs in prostate cancer (PCa) randomized controlled trials (RCTs). We aimed to synthetize the most recent high‐quality PRO evidence‐based knowledge from PCa RCTs and to examine whether quality of PRO reporting in PCa research improved over time.
Links between the rumen microbiota, methane emissions and feed efficiency of finishing steers offered dietary lipid and nitrate supplementation

Ruminant methane production is a significant energy loss to the animal and major contributor to global greenhouse gas emissions. However, it also seems necessary for effective rumen function, so studies of anti-methanogenic treatments must also consider implications for feed efficiency. Between-animal variation in feed efficiency represents an alternative approach to reducing overall methane emissions intensity. Here we assess the effects of dietary additives designed to reduce methane emissions on the rumen microbiota, and explore relationships with feed efficiency within dietary treatment groups. Seventy-nine finishing steers were offered one of four diets (a forage/concentrate mixture supplemented with nitrate (NIT), lipid (MDDG) or a combination (COMB) compared to the control (CTL)). Rumen fluid samples were collected at the end of a 56 d feed efficiency measurement period. DNA was extracted, multiplexed 16s rRNA libraries sequenced (Illumina MiSeq) and taxonomic profiles were generated. The effect of dietary treatments and feed efficiency (within treatment groups) was conducted both overall (using non-metric multidimensional scaling (NMDS) and diversity indexes) and for individual taxa. Diet affected overall microbial populations but no overall difference in beta-diversity was observed. The relative abundance of Methanobacteriales (Methanobrevibacter and Methanosphaera) increased in MDDG relative to CTL, whilst VadinCA11 (Methanomassiliicoccales) was decreased. Trimethylamine precursors from rapeseed meal (only present in CTL) probably explain the differences in relative abundance of Methanomassiliicoccales. There were no differences in Shannon indexes between nominal low or high feed efficiency groups (expressed as feed conversion ratio or residual feed intake) within treatment groups. Relationships between the relative abundance of individual taxa and feed efficiency measures were observed, but were not consistent across dietary treatments.
Three-dimensional, printed water-filtration system for economical, on-site arsenic removal

The threat of arsenic contamination to public health, particularly in developing countries, has become a serious problem. Millions of people in their daily lives are still highly dependent on groundwater containing high levels of arsenic, which causes excessive exposure to this toxic element, due to the high cost and lack of water-treatment infrastructures. Therefore, a technique for large-scale treatment of water in rural areas to remove arsenic is needed and should be low-cost, be easily customized, and not rely on electrical power. In this study, in an effort to fulfill those requirements, we introduce a three-dimensional (3D), printed water-filtration system for arsenic removal. Three-dimensional printing can provide a compact, customized filtration system that can fulfill the above-mentioned requirements and that can be made from plastic materials, which are abundant. Armed with the versatility of 3D printing, we were able to design the internal surface areas of filters, after which we modified the surfaces of the 3D, printed filters by using iron (III) oxide as an adsorbent for arsenite. We investigated the effects of the controlled surface area on the flow rate and the deposition of the adsorbent, which are directly related to the adsorption of arsenic. We conducted isotherm studies to quantify the adsorption of arsenic on our 3D, printed filtration system.
Expression of Nik-related kinase in smooth muscle cells attenuates vascular inflammation and intimal hyperplasia

Inflammation of the vascular microenvironment modulates distinct types of vascular cells, and plays important roles in promoting atherosclerosis, stenosis/restenosis, and vascular-related diseases. Nik-related kinase (Nrk), a member of the Ste20-type kinase family, has been reported to be selectively expressed in embryonic skeletal muscle. However, whether Nrk is expressed in adult vascular smooth muscle, and if it influences intimal hyperplasia is unclear. Here, we found that Nrk is abundantly expressed in cultured vascular smooth muscle cells (VSMC) and mouse arterial intima. Treatment of mouse VSMCs with lipopolysaccharide (LPS) or platelet-derived growth factor significantly reduced Nrk expression. In addition, expression of Nrk was significantly reduced in regions of neointimal formation caused by guide-wire carotid artery injuries in mice, as well as in human atherosclerotic tissues, when compared to normal vessels. We identified that expression of matrix metalloproteinases (MMP3, MMP8 and MMP12) and inflammatory cytokines/chemokines (CCL6, CCL8, CCL11, CXCL1, CXCL3, CXCL5 and CXCL9) are synergistically induced by Nrk siRNA in LPS-treated mouse VSMCs. Moreover, we found that resveratrol significantly impaired LPS- and Nrk siRNA-induced expression of MMP3, CCL8, CCL11, CXCL3 and CXCL5. These results suggested that Nrk may play important roles in regulating pathological progression of atherosclerosis or neointimal- hyperplasia-related vascular diseases.
Development of Ophthalmic Microsurgery Training in Augmented Reality

Abstract Background Using a group of 23 physician trainees, we investigated whether microsurgery training in an augmented reality (AR) training simulator improves motor skills and whether an intelligent tutoring system (ITS) improves training efficiency. Methods Characteristic motor skill steps involved in the peeling of an internal limiting membrane (ILM) were identified and implemented in the AR simulation. For training, implemented steps were either presented in the natural sequence, as in a real ILM surgery, or administered according to the ITS. Participants underwent the training over 5 days for 10 minutes per day. A subgroup of 11 participants performed the 5 microsurgical steps in a natural sequence. The other 12 participants used the ITS method. Motor skill performance was recorded before and after each training session with the AR simulator, and before the first and after the last training session using a method that did not rely on AR. Results Five steps of the ILM peeling procedure were identified and implemented: insertion of the instrument, flap creation, clockwise peeling, counterclockwise peeling, and retraction of the instrument. Both training methods significantly improved the motor skills of the participants. In both methods, steep learning progress was found within the first three training sessions. In both methods, motor skills continued to improve on days 4 and 5, but at a slower rate. After the 5 training days, performance was significantly improved, but improvement did not depend significantly on the training method. However, within the first 3 days of training, ITS led to steeper training progress than the natural sequence method. Conclusion It is possible to improve microsurgical motor skills using the implemented AR simulation. Some technical limitations, such as system lag, deserve further improvements. However, the proposed AR solution was highly appreciated by the participants and could help overcome constraints of practice in microsurgical training, such as limited availability of training opportunities or a standardized assessment of motor skill performance.
Genetic diversity of the green turtle nesting populations in Yaeyama Archipelago, Japan

ABSTRACT Patterns of mitochondrial DNA (mtDNA) variation were used to analyze the genetic diversity and population genetic structure of green turtle ( Chelonia mydas ) populations in Yaeyama Archipelago, southwestern Japan. Six mtDNA haplotypes were observed among 42 nesting green turtles. Nucleotide diversities at Yaeyama populations are higher than other sea turtle populations, reflecting all rookeries are comprised of a mixture of divergent haplotypes. Because genetic diversity is believed to represent the ability of populations to adapt or respond to environmental changes, it is important to protect Yaeyama nesting colonies for conserving this endangered species. KEYWORDS: Chelonia mydas , mitochondrial DNA, genetic analysis, conservation genetics INTRODUCTION Information on the genetic diversity and population structure of female green turtle, Chelonia mydas , is necessary to define conservation priorities for this highly endangered species. In recent reports, mitochondrial DNA (mtDNA) assays have proven useful for resolving divergence within a gene phylogeny and migratory behavior in female sea turtles (Bass et al., 1996; Bourjea et al., 2007; Encalada et al., 1996). However, the geographical specificity of genetic diversity and population structure apparently varies widely (Bass et al., 1996; Chassin-Noria et al., 2004). Therefore, it is necessary to study the local nesting populations for proper management strategies. In this study, mtDNA control region sequences were analyzed to resolve the genetic diversity and population genetic structure of Yaeyama Archipelago nesting populations of green turtle. Yaeyama Archipelago, located in southwestern Japan, has major nesting sites for green turtle which is a northern limit of green turtle nesting in the Pacific Ocean.
Physician Assistant Students' Competency to Identify and Diagnose Autism Spectrum Disorder.

PURPOSE Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in communication and reciprocal social interactions. Little research has focused on the evaluation of developmental/behavioral pediatric education in the physician assistant (PA) curriculum. Therefore, the aims of this study were to evaluate whether PA students received training in identifying the red flags of ASD, using screening tests such as the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F). Additionally, the study sought to determine if PA students received education on the evaluation and management of children with ASD along with the methods to communicate effectively with their caretakers. METHODS A survey open to PA students was administered by the American Academy of PAs. Demographic information along with questions on knowledge and perceptions related to ASD were asked. Perceptions of preparation to discuss ASD with patient caregivers were assessed, along with vaccination beliefs, and training information was collected. RESULTS A total of 213 PA students answered the survey. Students received training regarding the red flags for ASD as well as ASD-related skills. Of note, 58.2% did not receive training on administration of the M-CHAT-(R/F) and 54.9% did not receive training to provide care to patients with ASD; 77.8% received training to understand pediatric developmental milestones. PA students overwhelmingly rejected the suggestion that there is a link between vaccines and ASD. CONCLUSION The importance of diagnosing ASD as early as possible has been demonstrated by years of research; yet, this study concludes that many students still do not feel comfortable recognizing the red flags or using screening tools. Although the majority of PA students received training to understand developmental milestones, many did not know how to administer the M-CHAT-(R/F), which is key to making an early diagnosis.
Decreased melatonin secretion in patients with glaucoma: quantitative association with glaucoma severity in the LIGHT study.

Glaucoma may be associated with circadian disruption due to its association with a loss of intrinsically photosensitive retinal ganglion cells. Clinical evidence demonstrating an association between glaucoma and circadian disruption is limited, and no large-scale studies have been performed. The purpose of this cross-sectional study was to determine whether the presence and severity of glaucoma is correlated with the urinary 6-sulfatoxymelatonin levels as a circadian rhythm parameter. We measured the level of urinary 6-sulfatoxymelatonin excretion (UME) in 118 glaucoma patients and 395 control participants without glaucoma. The UME in the glaucoma group was significantly lower than that of the control group without glaucoma (3.05 and 3.24 log ng/mg creatinine, respectively; P = 0.010). Next, we examined association of the severity of glaucoma and melatonin levels. In stratification analysis of the glaucoma groups, multivariable linear regression analyses adjusted for potential confounders indicated significantly lower UME by 0.30 log ng/mg creatinine in patients with functional severe glaucoma (visual field mean deviation ≤ -6 dB) compared with mild glaucoma (mean deviation > -6 dB; P = 0.040) and lower UME by 0.05 log ng/mg creatinine with each 10 μm thinning of the circumpapillary retinal nerve fiber layer thickness as the index of structural severity of glaucoma (P = 0.011). In conclusion, significant association between glaucoma and lower urinary 6-sulfatoxymelatonin was found. In addition, patients with functional and structural severe glaucoma were significantly associated with lower urinary 6-sulfatoxymelatonin levels. Our results indicate the possibility of a circadian disruption in patients with glaucoma.
Insights into P-Glycoprotein Inhibitors: New Inducers of Immunogenic Cell Death

Doxorubicin is a strong inducer of immunogenic cell death (ICD), but it is ineffective in P-glycoprotein (Pgp)-expressing cells. Indeed, Pgp effluxes doxorubicin and impairs the immunesensitizing functions of calreticulin (CRT), an “eat-me” signal mediating ICD. It is unknown if classical Pgp inhibitors, designed to reverse chemoresistance, may restore ICD. We addressed this question by using Pgp-expressing cancer cells, treated with Tariquidar, a clinically approved Pgp inhibitor, and R-3 compound, a N,N-bis(alkanol)amine aryl ester derivative with the same potency of Tariquidar as Pgp inhibitor. In Pgp-expressing/doxorubicin-resistant cells, Tariquidar and R-3 increased doxorubicin accumulation and toxicity, reduced Pgp activity, and increased CRT translocation and ATP and HMGB1 release. Unexpectedly, only R-3 promoted phagocytosis by dendritic cells and activation of antitumor CD8+T-lymphocytes. Although Tariquidar did not alter the amount of Pgp present on cell surface, R-3 promoted Pgp internalization and ubiquitination, disrupting its interaction with CRT. Pgp knock-out restores doxorubicin-induced ICD in MDA-MB-231/DX cells that recapitulated the phenotype of R-3-treated cells. Our work demonstrates that plasma membrane-associated Pgp prevents a complete ICD notwithstanding the release of ATP and HMGB1, and the exposure of CRT. Pharmacological compounds reducing Pgp activity and amount may act as promising chemo- and immunesensitizing agents.
Mucoadhesive Chitosan Delivery System with Chelidonii Herba Lyophilized Extract as a Promising Strategy for Vaginitis Treatment

Chelidonium majus (also known as celandine) contains pharmacologically active compounds such as isoquinoline alkaloids (e.g., chelidonine, sanguinarine), flavonoids, saponins, carotenoids, and organic acids. Due to the presence of isoquinoline alkaloids, Chelidonii herba extracts are widely used as an antibacterial, antifungal, antiviral (including HSV-1 and HIV-1), and anti-inflammatory agent in the treatment of various diseases, while chitosan is a biocompatible and biodegradable carrier with valuable properties for mucoadhesive formulations preparation. Our work aimed to prepare mucoadhesive vaginal drug delivery systems composed of Chelidonii herba lyophilized extract and chitosan as an effective way to treat vaginitis. The pharmacological safety of usage of isoquinoline alkaloids, based on MTT test, were evaluated for the maximum doses 36.34 ± 0.29 µg/mL and 0.89 ± 1.16 µg/mL for chelidonine and sanguinarine, respectively. Dissolution rate profiles and permeability through artificial membranes for chelidonine and sanguinarine after their introduction into the chitosan system were studied. The low permeability for used save doses of isoquinoline alkaloids and results of microbiological studies allow confirmation that system Chelidonii herba lyophilized extract chitosan 80/500 1:1 (w/w) is a promising strategy for vaginal use. Ex vivo studies of mucoadhesive properties and evaluation of tableting features demonstrated that the formulation containing Chelidonii herba lyophilized extract (120.0 mg) with chitosan (80/500—100.0 mg) and polymer content (HPMC—100.0 mg, microcrystalline cellulose—50.0 mg, lactose monohydrate—30.0 mg and magnesium stearate—4.0 mg) is a vaginal dosage form with prolonging dissolution profile and high mucoadhesion properties (up to 4 h).
Long-term outcomes of survivors of neonatal insults: A systematic review and meta-analysis

Background The Millennium Developmental Goals ensured a significant reduction in childhood mortality. However, this reduction simultaneously raised concerns about the long-term outcomes of survivors of early childhood insults. This systematic review focuses on the long-term neurocognitive and mental health outcomes of neonatal insults (NNI) survivors who are six years or older. Methods Two independent reviewers conducted a comprehensive search for empirical literature by combining index and free terms from the inception of the databases until 10th October 2019. We also searched for additional relevant literature from grey literature and using reference tracking. Studies were included if they: were empirical studies conducted in humans; the study participants were followed at six years of age or longer; have an explicit diagnosis of NNI, and explicitly define the outcome and impairment. Medians and interquartile range (IQR) of the proportions of survivors of the different NNI with any impairment were calculated. A random-effect model was used to explore the estimates accounted for by each impairment domain. Results Fifty-two studies with 94,978 participants who survived NNI were included in this systematic review. The overall prevalence of impairment in the survivors of NNI was 10.0% (95% CI 9.8–10.2). The highest prevalence of impairment was accounted for by congenital rubella (38.8%: 95% CI 18.8–60.9), congenital cytomegalovirus (23.6%: 95% CI 9.5–41.5), and hypoxic-ischemic encephalopathy (23.3%: 95% CI 14.7–33.1) while neonatal jaundice has the lowest proportion (8.6%: 95% CI 2.7–17.3). The most affected domain was the neurodevelopmental domain (16.6%: 95% CI 13.6–19.8). The frequency of impairment was highest for neurodevelopmental impairment [22.0% (IQR = 9.2–24.8)] and least for school problems [0.0% (IQR = 0.0–0.00)] in any of the conditions. Conclusion The long-term impact of NNI is also experienced in survivors of NNI who are 6 years or older, with impairments mostly experienced in the neurodevelopmental domain. However, there are limited studies on long-term outcomes of NNI in sub-Saharan Africa despite the high burden of NNI in the region. Trial registration Registration number: CRD42018082119.
Age-Related Changes in Synaptic Plasticity Associated with Mossy Fiber Terminal Integration during Adult Neurogenesis

Abstract Mouse hippocampus retains the capacity for neurogenesis throughout lifetime, but such plasticity decreases with age. Adult hippocampal neurogenesis (AHN) involves the birth, maturation, and synaptic integration of newborn granule cells (GCs) into preexisting hippocampal circuitry. While functional integration onto adult-born GCs has been extensively studied, maturation of efferent projections onto CA3 pyramidal cells is less understood, particularly in aged brain. Here, using combined light and reconstructive electron microscopy (EM), we describe the maturation of mossy fiber bouton (MFB) connectivity with CA3 pyramidal cells in young adult and aged mouse brain. We found mature synaptic contacts of newborn GCs were formed in both young and aged brains. However, the dynamics of their spatiotemporal development and the cellular process by which these cells functionally integrated over time were different. In young brain newborn GCs either formed independent nascent MFB synaptic contacts or replaced preexisting MFBs, but these contacts were pruned over time to a mature state. In aged brain only replacement of preexisting MFBs was observed and new contacts were without evidence of pruning. These data illustrate that functional synaptic integration of AHN occurs in young adult and aged brain, but with distinct dynamics. They suggest elimination of preexisting connectivity is required for the integration of adult-born GCs in aged brain.
Appendix S1 to “A stochastic and dynamical view of pluripotency in mouse embryonic stem cells”

Yen Ting Lin, 2 Peter G. Hufton, Esther J. Lee, and Davit A. Potoyan Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA School of Physics and Astronomy, The University of Manchester, Manchester, M13 9PL, UK Department of Bioengineering, Rice University, Houston, TX 77005, USA Department of Chemistry, Iowa State University, Ames, IA 50011, USA (Dated: February 1, 2018)
A Low-Rank Tensor Factorization Using Implicit Similarity in Trust Relationships

Low-rank tensor factorization can not only mine the implicit relationships between data but also fill in the missing data when working with complex data. Compared with the traditional collaborative filtering (CF) algorithm, the changes are essentially proposed, from traditional matrix analysis to three-dimensional spatial analysis. Based on low-rank tensor factorization, this paper proposes a recommendation model that comprehensively considers local information and global information, in other words, combining the similarity between trust users and low-rank tensor factorization. First, the similarity between trusted users is measured to capture local information between users by trusting similar preferences of users when selecting items. Then, the users’ similarity is integrated into the tensor, and the low-rank tensor factorization is used to better maintain and describe the internal structure of the data to obtain global information. Furthermore, based on the idea of the alternating least squares method, the conjugate gradient (CG) optimization algorithm for the model of this paper is designed. The local and global information is used to generate the optimal expected result in an iterative process. Finally, we conducted a large number of comparative experiments on the Ciao dataset and the FilmTrust dataset. Experimental results show that the algorithm has less precision loss under the data set with lower density. Thus, not only can a perfect compromise between accuracy and coverage be achieved, but also the computational complexity can be reduced to meet the need for real-time results.