Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Features of Nucleoprotein CST/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations

Telomere comprises the ends of eukaryotic linear chromosomes and is composed of G-rich (TTAGGG) tandem repeats which play an important role in maintaining genome stability, premature aging and onsets of many diseases. Majority of the telomere are replicated by conventional DNA replication, and only the last bit of the lagging strand is synthesized by telomerase (a reverse transcriptase). In addition to replication, telomere maintenance is principally carried out by two key complexes known as shelterin (TRF1, TRF2, TIN2, RAP1, POT1, and TPP1) and CST (CDC13/CTC1, STN1, and TEN1). Shelterin protects the telomere from DNA damage response (DDR) and regulates telomere length by telomerase; while, CST govern the extension of telomere by telomerase and C strand fill-in synthesis. We have investigated both structural and biochemical features of shelterin and CST complexes to get a clear understanding of their importance in the telomere maintenance. Further, we have analyzed ~115 clinically important mutations in both of the complexes. Association of such mutations with specific cellular fault unveils the importance of shelterin and CST complexes in the maintenance of genome stability. A possibility of targeting shelterin and CST by small molecule inhibitors is further investigated towards the therapeutic management of associated diseases. Overall, this review provides a possible direction to understand the mechanisms of telomere borne diseases, and their therapeutic intervention.
Circulating Levels of PD-L1 in Mesothelioma Patients from the NIBIT-MESO-1 Study: Correlation with Survival

Targeting of the programmed cell death protein (PD)-1/programmed death-ligand 1 (PD-L1) axis has shown a significant clinical impact in several tumor types. Accordingly, our phase II NIBIT-MESO-1 study demonstrated an improved clinical efficacy in mesothelioma patients treated with the anti-PD-L1 durvalumab combined with the anti-cytotoxic T-lymphocyte antigen (CTLA)-4 tremelimumab, as compared to tremelimumab alone. Due to the promising therapeutic activity of immune check-point inhibitors (ICIs) in mesothelioma patients, the identification of biomarkers predictive of response to treatment is of crucial relevance. The prognostic role of soluble PD-L1 (sPD-L1) proposed in cancer patients prompted us to investigate this protein in sera from mesothelioma patients (n = 40) enrolled in the NIBIT-MESO-1 study. A significant (p < 0.001) increase in sPD-L1 levels was detected in patients after the first cycle and during therapy vs. baseline. A longer overall survival (OS) was observed in patients with sPD-L1 concentrations below (at baseline, d1C2, d1C5 (p < 0.01)) or FC values above (p < 0.05 at d1C2, d1C3, d1C5) their statistically calculated optimal cut-offs. On the basis of these initial results, the specific role of CTLA-4-, PD-L1-, or PD-1-targeting on sPD-L1 release was then investigated in sera from 81 additional ICI-treated solid cancer patients. Results showed a significant (p < 0.001) increase of sPD-L1 levels during therapy compared to baseline only in anti-PD-L1-treated patients, supporting the specific involvement of PD-L1 targeting in the release of its soluble form. Our findings suggest that sPD-L1 represents a predictive biomarker of clinical response to anti-PD-L1 cancer immunotherapy.
Geoacumulation of Heavy Metals in Sediment of the Fluvial–Lagoon–Deltaic System of the Palizada River, Campeche, Mexico

The fluvial–lagoon–deltaic system of the Palizada River in Campeche is an ecosystem of socioeconomic and ecological importance. It is justifiable to carry out studies in this system due to its connection with another larger ecosystem called the Términos Lagoon. The objective of this investigation was to analyze the concentration of Pb and Cd in sediments of the fluvial–lagoon–deltaic system of the Palizada River and to determine, with this, the contamination index of these metals. Cd showed the highest concentration in sampling sites and climatic seasons with respect to Pb, with a maximum value of 53.9 ± 5.0, while the Pb concentration was 10.4 ± 0.2 μg∙g−1. The same tendency was present with pollution and geoaccumulation indexes; here, the Cd index stands out. The enrichment of heavy metals was identified through the accumulation of Cd and Pb; such a process was evaluated through the geoacumulation index (Igeo). The results of this indicated that the contamination of these elements is mainly of anthropogenic origin. This element represents an ecological toxic risk due to the chronic presence of heavy metals in a priority area for the conservation of aquatic and terrestrial biota such as the Palizada system, owing to its high toxicity even at low concentrations. Thus, it is important to evaluate its sublethal effects in the organisms that inhabit this system, which requires the implementation of integral monitoring.
The Effectiveness of Attachment Security Priming in Improving Positive Affect and Reducing Negative Affect: A Systematic Review

Attachment security priming has been extensively used in relationship research to explore the contents of mental models of attachment and examine the benefits derived from enhancing security. This systematic review explores the effectiveness of attachment security priming in improving positive affect and reducing negative affect in adults and children. The review searched four electronic databases for peer-reviewed journal articles. Thirty empirical studies met our inclusion criteria, including 28 adult and 2 child and adolescent samples. The findings show that attachment security priming improved positive affect and reduced negative affect relative to control primes. Supraliminal and subliminal primes were equally effective in enhancing security in one-shot prime studies (we only reviewed repeated priming studies using supraliminal primes so could not compare prime types in these). Global attachment style moderated the primed style in approximately half of the studies. Importantly, repeated priming studies showed a cumulative positive effect of security priming over time. We conclude that repeated priming study designs may be the most effective. More research is needed that explores the use of attachment security priming as a possible intervention to improve emotional wellbeing, in particular for adolescents and children.
Impact Mineralization of Chokeberry and Cranberry Fruit Juices Using a New Functional Additive on the Protection of Bioactive Compounds and Antioxidative Properties

Chicken eggshells can be used as an attractive dietary source of mineral compounds, including calcium (Ca). However, the effects of chicken eggshell powder (CESP) on berry fruit juices have not been studied to date. Therefore, the objective of this study was to evaluate the effect of its addition to juices from chokeberry and cranberry on their phytochemical properties. The juices were determined for contents of polyphenols (determined by ultra-efficient liquid chromatography coupled with a mass detector (UPLC-PDA-ESI-MS/MS)), macro- and microelements (by inductively coupled plasma - optical emission spectrometry (ICP-OES)), and organic acids (by high-performance liquid chromatography (HPLC-PDA)) as well as for their antioxidative activity by radical scavenging capacity (ABTS) and ferric reducing antioxidative power (FRAP) assay, color profile (CIE L* a* b* system), and sensory attributes. The study results demonstrate that CESP addition to chokeberry and cranberry juices enriched them with minerals and increased their Ca content 25.7 times and 66.3 times, respectively, compared to the control samples. Juices supplementation with CESP significantly decreased their acidity and total organic acids content as well as increased their pH value. Chokeberry and cranberry juices supplementation with 1% CESP caused no significant changes in the amount of precipitate and their color, but it significantly improved their taste. For this reason, CESP addition in the amount of up to 1% can be suggested as the optimal supplementation of berry fruit juices. The study also demonstrated that CESP addition in the amount of up to 1% caused no significant differences in the content of polyphenolic compounds and in the antioxidative activity of juices, which can be deemed important from the viewpoint of their putative health benefits. In addition, the heat treatment of juices contributed to only a 4% loss of polyphenolic compounds from the CESP-supplemented juices compared to the 6% loss from the non-supplemented juices.
A Cohort Study of Antihyperglycemic Medication Exposure and Gastric Cancer Risk

We assessed gastric cancer risk in type 2 diabetes mellitus patients. Gastric cancer patients with diabetes between 2001–2012 were identified. Four groups were analysed: combination therapy with metformin users; insulin and other medication users; metformin and insulin users; and sulfonylurea users. Standardised incidence ratios (SIRs) for gastric cancers as a ratio of the observed number of cancer cases in people with diabetes to the expected number of cancer cases in the underlying general population were calculated. A total of 99,992 patients with diabetes were analysed and 337 gastric cancer cases in patients with diabetes were observed when compared to the expected number of 400.54 gastric cancer cases, according to the cancer rates of the general population (SIR 0.84, 95% confidence interval (CI): 0.76–0.94). Lower risk of gastric cancer was found both in male and female patients with diabetes, however, risk among females was insignificantly lower. Higher gastric cancer risk was found in the group of diabetic patients treated with sulfonylureas (SIR 1.31, 95% CI: 1.04–1.65) and significantly lower risk than expected from the general population was found in the group of metformin users (SIR 0.75, 95% CI: 0.66–0.86). Type 2 diabetes mellitus was not associated with increased risk of gastric cancer. Metformin might decrease the risk of gastric cancer in patients with diabetes, while sulfonylureas may increase gastric cancer risk.
On the usefulness of parental lines GWAS for predicting low heritability traits in tropical maize hybrids

Genome-wide association studies (GWAS) is one of the most popular methods of studying the genetic control of traits. This methodology has been intensely performed on inbred genotypes to identify causal variants. Nonetheless, the lack of covariance between the phenotype of inbred lines and their offspring in cross-pollinated species (such as maize) raises questions on the applicability of these findings in a hybrid breeding context. To address this topic, we incorporated previously reported parental lines GWAS information into the prediction of a low heritability trait in hybrids. This was done by marker-assisted selection based on significant markers identified in the lines and by genomic prediction having these markers as fixed effects. Additive-dominance GWAS of hybrids, a non-conventional procedure, was also performed for comparison purposes. Our results suggest that incorporating information from parental inbred lines GWAS led to decreases in the predictive ability of hybrids. Correspondingly, inbred lines and hybrids-based GWAS yielded different results. These findings do not invalidate GWAS on inbred lines for selection purposes, but mean that it may not be directly useful for hybrid breeding.
Differences in ultrasound‐derived arterial wall stiffness parameters and noninvasive blood pressure between Friesian horses and Warmblood horses

Abstract Background Aortic rupture is more common in Friesians compared to Warmbloods, which might be related to differences in arterial wall composition and, as such, arterial wall stiffness (AWS). Currently, nothing is known about differences in AWS between these breeds. Objectives Comparison of AWS parameters and noninvasive blood pressure between Friesians and Warmbloods. Animals One hundred one healthy Friesians and 101 age‐matched healthy Warmbloods. Methods Two‐dimensional and pulsed‐wave Doppler ultrasound examination was performed of the aorta, common carotid artery, and external iliac artery to define local and regional AWS parameters. Regional aortic AWS was estimated using aortic‐to‐external iliac artery pulse wave velocity (PWVa‐e) and carotid‐to‐external iliac artery pulse wave velocity (PWVc‐e). Noninvasive blood pressure and heart rate were recorded simultaneously. Results Systolic, diastolic, and mean arterial blood pressure and pulse pressure were significantly higher in Friesians compared to Warmbloods. No significant difference in heart rate was found. Most local AWS parameters (diameter change, compliance coefficient, distensibility coefficient) were significantly lower in Friesians compared to Warmbloods, indicating a stiffer aorta in Friesians. This difference could be confirmed by the regional stiffness parameters. A higher PWVa‐e and PWVc‐e was found in Friesians. For the cranial and caudal common carotid artery and external iliac artery, most local AWS parameters were not significantly different. Conclusions and clinical importance Results indicate that aortic AWS differs between Friesian and Warmblood horses. Friesians seem to have a stiffer aorta, which might be related to the higher incidence of aortic rupture in Friesians.
Distribution of Head Acceleration Events Varies by Position and Play Type in North American Football

Objective: The goal of this pilot study was to evaluate the number of head acceleration events (HAEs) based on position, play type, and starting stance. Design: Prospective cohort study. Setting: Postcollegiate skill development camp during practice sessions and 1 exhibition game. Participants: Seventy-eight male adult North American football athletes. Independent Variables: A position was assigned to each participant, and plays in the exhibition game were separated by play type for analysis. During the exhibition game, video data were used to determine the effects of the starting position (“up” in a 2-point stance or “down” in a 3- or 4-point stance) on the HAEs experienced by players on the offensive line. Main Outcome Measures: Peak linear acceleration and number of HAEs greater than 20 g (g = 9.81 m/s2) were measured using an xPatch (X2 Biosystems, Seattle, WA). Results: Four hundred thirty-seven HAEs were recorded during practices and 272 recorded during the exhibition game; 98 and 52 HAEs, the greatest number of HAEs by position in the game, were experienced by the offensive and defensive linemen, respectively. Linebackers and tight ends experienced high percentages of HAEs above 60 g. Offensive line players in a down stance had a higher likelihood of sustaining a HAE than players in an up stance regardless of the type of play (run vs pass). Conclusions: Changing the stance of players on the offensive line and reducing the number of full-contact practices will lower HAEs.
Practitioner perceptions regarding the practices of soccer substitutes

Despite empirical observations suggesting that practitioners value the use of substitutions during soccer match-play, limited research has sought to substantiate such claims. This study used online surveys to assess the perceptions of practitioners within professional soccer about the use and practices of substitutes. Thirty-three practitioners completed one of two surveys (each requiring both open and closed questions to be answered), depending upon whether their primary role related mostly to tactical (‘tactical practitioners’; n = 7) or physical (‘physical practitioners’; n = 26) aspects of player/team management. Thematic content analysis of responses identified four higher-order themes: ‘impact of substitutions’, ‘planning and communication’, ‘player preparation and recovery’ and ‘regulations’. Eighty-five percent of practitioners believed that substitutes are important in determining success during soccer match-play, with the primary justification being the perceived ability of such players to provide a physical and/or tactical impact. However, contextual factors such as the match situation, timing of introduction, and players undergoing adequate pre-pitch-entry preparation, may be important for realising such aims. Although many practitioners believed that there was a need for substitutes to engage in bespoke non-match-day preparations and recovery strategies that differ from starting players, logistical considerations, such as scarcity of resources, often limit their scope. Notwithstanding, 96% of respondents indicated that substitutes frequently perform extra conditioning sessions to account for deficits in high-speed running loads compared with players exposed to a longer period of match-play. Substitutes’ pre-match warm-ups are typically led by team staff, however practitioners reported providing varying levels of input with regards to the practices adopted between kick-off and pitch-entry. Uncertainty exists as to the efficacy of current pre-pitch-entry practices, and 100% of practitioners highlighted ‘preparatory strategies’ as at least a ‘moderately important’ direction for future research. This study presents novel insights and highlights areas that are considered future research priorities amongst those working in the field.
Dentin Microhardness and Sealer Bond Strength to Root Dentin are Affected by Using Bioactive Glasses as Intracanal Medication

This study investigated the human dentin microhardness (MH) and the MTA Fillapex® (Fillapex) and AH Plus®(AH) bond strength (BS) to dentin after using calcium hydroxide (Ca(OH)2) and bioactive glasses (45S5 and an experimental niobium phosphate bioactive glass (NbG)) as intracanal medications. For the MH test dentin slices were filled with medications and were submitted to Knoop MH (KHN) test (at day-0 (baseline data/without medication) and at day-15 (after using medication)). For the BS test, after medications had remained for 15 days in the roots, dentin slices were obtained and filled with the sealers. Seven days later, sealer BS to dentin was measured by push-out test (MPa). Data were statistically analyzed. Failure mode was visually assessed. The use of NbG, 45S5 for 15 days, increased the dentin MH and reduced the BS between AH sealer and dentin, but did not interfere with the Fillapex BS.
Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments. This organelle organizes well-defined structures within neurons (cell bodies and axons), which allow their proper development and function through life. Here, we will provide an overview of both the basic and novel concepts related to those cytoskeletal proteins, which are emerging as potential targets in the study of the pathophysiological mechanisms underlying neurological disorders.
Human Long Noncoding RNA Interactome: Detection, Characterization and Function

The application of a new generation of sequencing techniques has revealed that most of the genome has already been transcribed. However, only a small part of the genome codes proteins. The rest of the genome “dark matter” belongs to divergent groups of non-coding RNA (ncRNA), that is not translated into proteins. There are two groups of ncRNAs, which include small and long non-coding RNAs (sncRNA and lncRNA respectively). Over the last decade, there has been an increased interest in lncRNAs and their interaction with cellular components. In this review, we presented the newest information about the human lncRNA interactome. The term lncRNA interactome refers to cellular biomolecules, such as nucleic acids, proteins, and peptides that interact with lncRNA. The lncRNA interactome was characterized in the last decade, however, understanding what role the biomolecules associated with lncRNA play and the nature of these interactions will allow us to better understand lncRNA’s biological functions in the cell. We also describe a set of methods currently used for the detection of lncRNA interactome components and the analysis of their interactions. We think that such a holistic and integrated analysis of the lncRNA interactome will help to better understand its potential role in the development of organisms and cancers.
Knowledge, Attitude, and Practice of Yoga in Rural and Urban India, KAPY 2017: A Nationwide Cluster Sample Survey

Background: To examine the knowledge, attitudes, and practice gap of yoga across India based on implicit perceptions. Methods: The present study is a nationwide door-to-door survey conducted using a questionnaire/screening form. The data were collected from a national survey conducted under the Niyantrit Madhumeh Bharat (NMB) program initiated by The Ministry of Ayurveda, Yoga, Unani, Siddha, Homeopathy (AYUSH), Government of India, from all major zones of the country. A total of 162,330 participants who joined the NMB program were recruited in our study. Results: Out of the total respondents to the survey, it was observed that 11.8% [13,336/112,735] practice yoga, which was highest in the north zone [4,567/112,735] and lowest in the east zone [971/112,735]. Out of 101,643 respondents, 94,135 of the individuals who participated in the survey believed that yoga improved their lifestyle, and 90,102/98,518 believed that yoga prevented diabetes, revealing a huge knowledge–practice gap. Conclusions: The scale of the knowledge–practice gap coupled with the general acceptability of yoga calls for a change in the conventional healthcare provisions by its integration with modern medicine. The population-wide positive perceptions about yoga as a preventive health tool can not only catalyze consensus disease-specific yoga modules but also bridge the knowledge–practice gap that exists because of limited yoga centers and professionals.
An Omnidirectional Assistive Platform Integrated With Functional Electrical Stimulation for Gait Rehabilitation: A Case Study

This paper presents a novel omnidirectional platform for gait rehabilitation of people with hemiparesis after stroke. The mobile platform, henceforth the “walker”, allows unobstructed pelvic motion during walking, helps the user maintain balance and prevents falls. The system aids mobility actively by combining three types of therapeutic intervention: forward propulsion of the pelvis, controlled body weight support, and functional electrical stimulation (FES) for compensation of deficits in angular motion of the joints. FES is controlled using gait data extracted from a set of inertial measurement units (IMUs) worn by the user. The resulting closed-loop FES system synchronizes stimulation with the gait cycle phases and automatically adapts to the variations in muscle activation caused by changes in residual muscle activity and spasticity. A pilot study was conducted to determine the potential outcomes of the different interventions. One chronic stroke survivor underwent five sessions of gait training, each one involving a total of 30 minutes using the walker and FES system. The patient initially exhibited severe anomalies in joint angle trajectories on both the paretic and the non-paretic side. With training, the patient showed progressive increase in cadence and self-selected gait speed, along with consistent decrease in double-support time. FES helped correct the paretic foot angle during swing phase, and likely was a factor in observed improvements in temporal gait symmetry. Although the experiments showed favorable changes in the paretic trajectories, they also highlighted the need for intervention on the non-paretic side.