Miracle-dz/UniFAR-FTUs huggingface dataset:
RMDisease: a database of genetic variants that affect RNA modifications, with implications for epitranscriptome pathogenesis

Abstract Deciphering the biological impacts of millions of single nucleotide variants remains a major challenge. Recent studies suggest that RNA modifications play versatile roles in essential biological mechanisms, and are closely related to the progression of various diseases including multiple cancers. To comprehensively unveil the association between disease-associated variants and their epitranscriptome disturbance, we built RMDisease, a database of genetic variants that can affect RNA modifications. By integrating the prediction results of 18 different RNA modification prediction tools and also 303,426 experimentally-validated RNA modification sites, RMDisease identified a total of 202,307 human SNPs that may affect (add or remove) sites of eight types of RNA modifications (m6A, m5C, m1A, m5U, Ψ, m6Am, m7G and Nm). These include 4,289 disease-associated variants that may imply disease pathogenesis functioning at the epitranscriptome layer. These SNPs were further annotated with essential information such as post-transcriptional regulations (sites for miRNA binding, interaction with RNA-binding proteins and alternative splicing) revealing putative regulatory circuits. A convenient graphical user interface was constructed to support the query, exploration and download of the relevant information. RMDisease should make a useful resource for studying the epitranscriptome impact of genetic variants via multiple RNA modifications with emphasis on their potential disease relevance. RMDisease is freely accessible at: www.xjtlu. edu.cn/biologicalsciences/rmd.
Older adult participation in cancer clinical trials: A systematic review of barriers and interventions

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence‐based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real‐world data.
Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.
Application of herb chronology: Annual fertilization and climate reveal annual ring signatures within the roots of US tallgrass prairie plants

The relatively new field of herbaceous root chronology (“herb chronology”) uses the annual rings of secondary xylem in roots of perennial forbs to analyze belowground secondary growth as a function of annual growth environment. By using three tallgrass forb species from long-term experiments within Konza prairie of northeastern Kansas (USA), we aimed to find the effects of fertilization, growing season temperature, and precipitation on annual secondary growth. For two of the three species, we found annual rings were significantly larger among plots that were fertilized annually with phosphorus or nitrogen + phosphorus in contrast to unfertilized control plots. Rings also had significant variation with climatic variables. We found a consistent negative correlation with early season temperature for each species. However, early growing season precipitation proved to be far less consistent, with positive correlations only found in a few cases between species. Overall, we conclude that annual rings in these se.
Effects of descending or ascending stair exercise on body composition, insulin sensitivity, and inflammatory markers in young Chinese women with obesity: A randomized controlled trial

ABSTRACT We examined the effects of descending (DSE) or ascending (ASE) stair exercise on body composition, insulin sensitivity, and inflammatory markers in young Chinese women with obesity. Thirty-six participants were randomly assigned into three groups DSE, ASE and a control group. The DSE and ASE groups performed three sessions of stair walking per week for 12 weeks with a gradual increase in repetitions. Following the exercise interventions, body composition related variables obtained by Dual-energy X-ray absorptiometry scans significantly decreased. Abdominal fat decreased in the DSE group only. Moreover, Insulin sensitivity improved significantly 3.5-fold in the DSE group compared with ASE group (insulin: −33.2% vs. −9.8%, homoeostasis model assessment for insulin resistance: −35.6% vs. −10.8%). Pro-inflammatory factors showed significant decreases in tumour necrosis factor-α (TNF-α) (−39.9% vs. −23.2%) for both intervention groups. The reduction in TNF-α concentrations in the DSE group was significantly different compared to the other two groups. Interleukin-6 significantly decreased in both exercise protocols. Our results show that 12-weeks induced stair walking improved body composition parameters in Chinese females with obesity. The results also demonstrate the superiority of the DSE protocol for improving insulin sensitivity. These findings may be attributable to the decreases observed in TNF- α levels.
Exploiting Replication Stress as a Novel Therapeutic Intervention

Ewing sarcoma is an aggressive pediatric tumor of the bone and soft tissue. The current standard of care is radiation and chemotherapy, and patients generally lack targeted therapies. One of the defining molecular features of this tumor type is the presence of significantly elevated levels of replication stress as compared with both normal cells and many other types of cancers, but the source of this stress is poorly understood. Tumors that harbor elevated levels of replication stress rely on the replication stress and DNA damage response pathways to retain viability. Understanding the source of the replication stress in Ewing sarcoma may reveal novel therapeutic targets. Ewing sarcomagenesis is complex, and in this review, we discuss the current state of our knowledge regarding elevated replication stress and the DNA damage response in Ewing sarcoma, one contributor to the disease process. We will also describe how these pathways are being successfully targeted therapeutically in other tumor types, and discuss possible novel, evidence-based therapeutic interventions in Ewing sarcoma. We hope that this consolidation will spark investigations that uncover new therapeutic targets and lead to the development of better treatment options for patients with Ewing sarcoma. Implications: This review uncovers new therapeutic targets in Ewing sarcoma and highlights replication stress as an exploitable vulnerability across multiple cancers.
A Method for the Validation of Simulated Mixing Characteristics of Two Dynamic Mixers in Single-Screw Extrusion

The field of simulation and optimisation of dynamic mixing elements (‘mixers’) is lacking good methods for spatially resolved validation and flow visualisation. For this reason, the authors present an experimental setup that gives better insight into the thermal, distributive and dispersive mixing process by measuring melt temperatures upstream of the mixer and injecting a secondary, visually distinguishable stream of melt upstream. Running extrusion trials for a polyethylene on both a rhomboidal and a Maddock mixer, temperatures, gray scale distribution of images of extrudates and size of dispersed domains in incompatible polystyrene were measured. It was found that temperatures upstream and downstream of the mixer can be quantified. This was used to validate a simulation of thermal mixing. In distributive mixing, good agreement with simulation and an excellent spatial resolution were observed, thereby identifying an area of the rhomboidal mixer in need of geometric improvement. For dispersive mixing, a trend coherent with extrusion theory was found.
Risk factors for central retinal vein occlusion in young adults

Purpose: Several risk factors have been identified for central retinal vein occlusion (CRVO) in older population. CRVO in young is uncommon, and the risk factors for this group are unclear. This large retrospective, cross-sectional study used the National Inpatient Sample (NIS) database to evaluate the risk factors for CRVO in patients 18 to 40 years of age. Methods: The 2002 to 2014 NIS database was used. All patients 18 to 40 years of age with a primary diagnosis of CRVO were identified. Age- and gender-matched non-CRVO controls were randomly selected. The primary outcome was identification of risk factors for CRVO. Chi-square analysis and Firth logistic regression were performed with IBM SPSS 23 and R packages versions 3.4. 3, respectively. p < 0.05 was considered significant. Results: A total of 95 weighted young CRVO patients were identified. The average age was 31.44 ± 6.41 years with no gender predilection. Systemic and ocular conditions found to have statistically significant associations with CRVO included primary open-angle glaucoma (POAG) (OR 836.72, p < 0.001), retinal vasculitis (OR 705.82, p < 0.001), pseudotumor cerebri (OR 35.94, p < 0.001), hypercoagulable state (OR 25.25, p < 0.001), history of deep vein thrombosis/pulmonary embolism (DVT/PE) (OR 21.88, p < 0.001), and hyperlipidemia (OR 3.60, p = 0.003). Conclusion: The most significant risk factors for CRVO in young adults were POAG, retinal vasculitis, and pseudotumor cerebri. Hypercoagulable states and DVT/PE were also associated with CRVO in this population. Systemic inflammatory conditions were not associated with CRVO. Traditional risk factors such as hypertension and diabetes did not pose significant risks, whereas hyperlipidemia was deemed a significant risk factor.
Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer’s disease

The neurofibrillary tangles (NFT) and amyloid‐ß plaques (AP) that comprise Alzheimer’s disease (AD) neuropathology are associated with neurodegeneration and microglial activation. Activated microglia exist on a dynamic spectrum of morphologic subtypes that include resting, surveillant microglia capable of converting to activated, hypertrophic microglia closely linked to neuroinflammatory processes and AD neuropathology in amnestic AD. However, quantitative analyses of microglial subtypes and neurons are lacking in non‐amnestic clinical AD variants, including primary progressive aphasia (PPA‐AD). PPA‐AD is a language disorder characterized by cortical atrophy and NFT densities concentrated to the language‐dominant hemisphere. Here, a stereologic investigation of five PPA‐AD participants determined the densities and distributions of neurons and microglial subtypes to examine how cellular changes relate to AD neuropathology and may contribute to cortical atrophy. Adjacent series of sections were immunostained for neurons (NeuN) and microglia (HLA‐DR) from bilateral language and non‐language regions where in vivo cortical atrophy and Thioflavin‐S‐positive APs and NFTs were previously quantified. NeuN‐positive neurons and morphologic subtypes of HLA‐DR‐positive microglia (i.e., resting [ramified] microglia and activated [hypertrophic] microglia) were quantified using unbiased stereology. Relationships between neurons, microglia, AD neuropathology, and cortical atrophy were determined using linear mixed models. NFT densities were positively associated with hypertrophic microglia densities (P < 0.01) and inversely related to neuron densities (P = 0.01). Hypertrophic microglia densities were inversely related to densities of neurons (P < 0.01) and ramified microglia (P < 0.01). Ramified microglia densities were positively associated with neuron densities (P = 0.02) and inversely related to cortical atrophy (P = 0.03). Our findings provide converging evidence of divergent roles for microglial subtypes in patterns of neurodegeneration, which includes hypertrophic microglia likely driving a neuroinflammatory response more sensitive to NFTs than APs in PPA‐AD. Moreover, the accumulation of both NFTs and activated hypertrophic microglia in association with low neuron densities suggest they may collectively contribute to focal neurodegeneration characteristic of PPA‐AD.
Dynamics of microbial population in tea ecosystem

Seasonal variations in microbial population and relationship of microbes with some soil parameters were studied in tea ecosystem of Assam Agricultural University, Jorhat. Soil samples were drawn from three depths viz. 0–20, 20–40 and 40–60 cm in pre-monsoon, monsoon, post-monsoon and winter seasons. Populations of bacteria, fungi, phosphate solubilizers, ammonifiers and nitrifiers decreased significantly with depth. Seasonal variation was significant in case of bacteria, fungi, ammonifiers and Nitrosomonas. Except for nitrifiers, other microbes attained population peak in monsoon season. In case of soil physico-chemical parameters, organic C, available N, P, K and temperature showed significant depth-variation. After monsoon season, organic C, available P and K increased significantly. On the other hand, available N decreased markedly after monsoon to winter. Effect of depth and seasonal interaction on soil pH was found to be statistically insignificant. The highest moisture and temperature were recorded in monsoon season and were the lowest in winter. Soil CEC, bulk density and aggregation did not show any significant seasonal change. Microbial groups showed highly significant and positive correlation in pre-monsoon and monsoon seasons with soil parameters. The r-values were lower in post-monsoon and winter seasons.
Does 2D:4D predict fitness in a wild mammal?

Environmental pressures present during critical periods in fetal development can have a strong influence on the long-term fitness of an individual. Susceptibility to parasites, immune function, and future reproductive success are all vulnerable to stressful events in utero. The causes and consequences of prenatal environmental stress are often difficult (if not impossible) to evaluate, especially in wild populations. Digit ratio, the ratio of 2nd digit to 4th digit length (2D:4D) has been identified as an index of fetal androgen exposure. Current techniques for assessing digit ratio pose severe limitations to the accuracy of digit measurement of wild animals owing to the constant movement of the feet and inaccessibility of laboratory equipment. Our study attempts a new indirect technique wherein subjects had an imprint taken of each foot that was then photographed and scanned for digital measurement. Using red squirrels (Tamiasciurus hudsonicus (Erxleben, 1777)) as a model species, we hypothesized that higher degrees of fetal testosterone exposure (assumed from digit ratios) would result in reduced reproductive success and increased susceptibility to parasite infection. Digit ratio was negatively correlated with reproductive output and positively correlated with parasite loads. Although this may indicate that exposure to excess testosterone in utero may jeopardize future fitness, the relationships are inconsistent.
Post-competition recovery strategies in elite male soccer players. Effects on performance: A systematic review and meta-analysis

Aims The main aim of the present review was to update the available evidence on the value interest of post-competition recovery strategies in male professional or semi-professional soccer players to determine its effect on post-game performance outcomes, physiological markers, and wellness indicators. Methods A structured search was carried out following the PRISMA guidelines using six online databases: Pubmed, Scopus, SPORTDiscus, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials. The risk of bias was completed following the Cochrane Collaboration Guidelines. Meta-analyses of randomized controlled trials were conducted to determine the between and within-group effects of different recovery strategies on performance, physiological markers and wellness data. Final meta-analyses were performed using the random-effects model and pooled standardized mean differences (SMD). Results Five randomized controlled trials that used Compression Garments (n = 3), Cold Water Immersion (n = 1), and acute Sleep Hygiene Strategy (n = 1) were included. Greater CMJ values at 48h for the intervention group (SMD = 0.70; 95% CI 0.14 to 1.25; p = 0.001; I2 = 10.4%) were found. For the 20-m sprint and MVC, the results showed no difference either at 24h or 48h. For physiological markers (CK and CRP) and wellness data (DOMS), small to large SMD were present in favor of the intervention group both at 24h (-0.12 to -1.86) and 48h (-0.21 to -0.85). No heterogeneity was present, except for MVC at 24h (I2 = 90.4%; p = 0.0012) and CALF DOMS at 48h (I2 = 93.7%; p = 0.013). Conclusion The use of recovery strategies offers significant positive effects only in jumping performance (CMJ), with no effects on the 20-m sprint or MVC. Also, the use of recovery strategies offers greater positive effects on muscle damage (physiological markers and wellness data), highlighting the importance of post-match recovery strategies in soccer.
Effect of phosphorus, potassium, sulphur and boron on litchi

Plant receiving 400 g P2O5, 700 g K2O and 140 g S/plant/year caused earliest flower opening from panicle initiation while it delayed by about 4 days with recommended fertilizer doses in West Bengal. The duration of flowering and hermaphrodite flower production were found maximum in plants receiving 200 g P2O5, 700 g K2O, 140 g S and 7 g B/plant/year. Increasing the phosphorus level to 600 g along with 700 g K2O, 140 g S and 7 g B/plant/year showed the maximum flower sex ratio. The number of fruits increased with the increase in the level of potassium from 0 to 700 g/plant/year, but thereafter it decreased with 1050 g K2O/plant/year. Plants receiving 400 g P2O5, 700 g K2O and 7 g B/plant/year showed the maximum yield. The fruit yield showed a positive correlation (r = 0.5116) with first season vegetative flush appears between June and September. The aril weight of fruit was also highest with the same treatment while the maximum seed weight of 4.13 g fruit−1 was noted in the fruits from the plants fertilized with 400 g PO5, 350 g K2O, 140 g S and 7 g B/plant/year. The total soluble solids and reducing sugar contents of fruit were noted maximum by application of 600 g P2O5, 350 g K2O, 140 g S and 7 g B/plant/year while TSS/acid ratio and ascorbic acid content were noted highest in fruits from the plants receiving 400 g P2O5, 1050 g K2O, 140 g S and 7 g B/plant/year.
Automated Intensity Modulated Radiation Therapy Treatment Planning for Cervical Cancer Based on Convolution Neural Network

Purpose: To develop and evaluate an automatic intensity-modulated radiation therapy (IMRT) program for cervical cancer, including a Convolution Neural Network (CNN)-based prediction model and an automated optimization strategy. Methods: A CNN deep learning model was trained to predict a patient-specify set of IMRT objectives based on overlap volume histograms (OVH) and high-quality plan of previous patients. A total of 140 cervical cancer patients were enrolled in this study, including 100 patients in the training set, 20 patients in the validation set and 20 patients in the testing set. The input of this model was OVH data and the output were values of IMRT plan objectives. For patients in the testing set, the set of planning objectives were predicted by the CNN model and used to automatically generate IMRT plans. Meanwhile, manual plans of these patients were generated by 1 beginner planner and 1 senior planner respectively. Finally, dose distribution, dosimetric parameters and planning time were analyzed. In addition, the 3 types of plans were blinded compared and ranked by an experienced oncologist. Results: There were almost no statistically differences among these 3 types of plans in target coverage and dose conformity. Dose homogeneity were slightly decreased while the average dose and parameters for most organs-at-risk (OARs) were decreased in automatic plans. Especially in comparison with manual plans by the beginner planner, V40 of bladder and rectum decreased 6.3% and 12.3%, while mean dose of rectum and marrow were 1.1 Gy and 1.8 Gy lower with automatic plans (either P < 0.017). In the blinded comparison, automatic plans were chosen as best plan in 14 cases. Conclusions: For cervical cancer, automatic IMRT plans optimized from the CNN generated objectives have superior dose sparing without compromising of target dose. It significantly reduced the planning time.