Miracle-dz/UniFAR-FTUs huggingface dataset:
The general mRNA exporters Mex67 and Mtr2 play distinct roles in nuclear export of tRNAs in Trypanosoma brucei

Abstract Transfer RNAs (tRNAs) are central players in protein synthesis, which in Eukarya need to be delivered from the nucleus to the cytoplasm by specific transport receptors, most of which belong to the evolutionarily conserved beta-importin family. Based on the available literature, we identified two candidates, Xpo-t and Xpo-5 for tRNA export in Trypanosoma brucei. However, down-regulation of expression of these genes did not disrupt the export of tRNAs to the cytoplasm. In search of alternative pathways, we tested the mRNA export complex Mex67-Mtr2, for a role in tRNA nuclear export, as described previously in yeast. Down-regulation of either exporter affected the subcellular distribution of tRNAs. However, contrary to yeast, TbMex67 and TbMtr2 accumulated different subsets of tRNAs in the nucleus. While TbMtr2 perturbed the export of all the tRNAs tested, silencing of TbMex67, led to the nuclear accumulation of tRNAs that are typically modified with queuosine. In turn, inhibition of tRNA nuclear export also affected the levels of queuosine modification in tRNAs. Taken together, the results presented demonstrate the dynamic nature of tRNA trafficking in T. brucei and its potential impact not only on the availability of tRNAs for protein synthesis but also on their modification status.
Risk factors for Neospora caninum, bovine viral diarrhoea virus, and Leptospira interrogans serovar Hardjo infection in smallholder cattle and buffalo in Lao PDR

Smallholder large ruminant production in Lao People’s Democratic Republic (Laos) is characterised by low reproductive efficiency. To determine if common abortifacient bovid infectious diseases are involved, a serological investigation was conducted. Sera was collected from stored and fresh cattle (n = 390) and buffalo (n = 130) samples from 2016–18 from, and then examined for associations in a retrospective risk factor study of 71 herds. The sera were assayed for antibodies to Neospora caninum, bovine viral diarrhoea virus (BVDV), Leptospira interrogans serovar Hardjo and Brucella abortus using commercially available enzyme-linked immunosorbent assay kits. These pathogens were detected in buffalo samples at 78.5% (95% CI 71.4–85.6), 0%, 2.3% (95% CI 0–4.9) and 0%, respectively, and in cattle at 4.4% (95% CI 2.4–6.4), 7.7% (95% CI 3.1–12.3), 12.8% (95% CI 9.5–16.1) and 0.26% (95% CI 0–0.8), respectively. Exposure of buffalo to N. caninum was positively associated with buffalo age, with a predicted seropositivity at birth of 52.8%, increasing to 97.2% by 12 years of age (p = 0.037). Exposure of cattle to L. interrogans serovar Hardjo was more prevalent in females compared to males, was associated with higher titres of BVDV, and was more prevalent in the wet season compared to the dry season. Exposure of cattle to BVDV was more prevalent in males compared to females, the wet and dry seasons were comparable, and was associated with rising antibody titres against N. caninum and L. interrogans serovar Hardjo. The risk factor survey identified that the probability of herds being N. caninum positive increased with farmer age, if farmers believed there were rodents on farm, and if farmers weren’t aware that canids or rodents could contaminate bovid feed on their farm. The probability of a herd being positive to L. interrogans serovar Hardjo increased on farms where multiple cows shared the same bull, where farmers had lower husbandry knowledge, and on farms that used water troughs. The probability of a herd being BVDV seropositive increased with increasing herd size and increasing titres to N. caninum. The benchmarking of bovid exposure to emerging abortifacient pathogens and identification of their risk factors potentially informs disease prevention strategies, supporting efforts to establish a biosecure beef supply for enhanced smallholder livestock productivity, public health and food security in Laos and surrounding countries.
Artificial intelligence using a convolutional neural network for automatic detection of small‐bowel angioectasia in capsule endoscopy images

Although small‐bowel angioectasia is reported as the most common cause of bleeding in patients and frequently diagnosed by capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding, a computer‐aided detection method has not been established. We developed an artificial intelligence system with deep learning that can automatically detect small‐bowel angioectasia in CE images.
J-Wave Elevation in the Inferior Leads Predicts Lethal Ventricular Arrhythmia Initiated by Premature Ventricular Contractions With Right Bundle Branch Block and Superior Axis.

BACKGROUND Lethal ventricular arrhythmia (VA) can be initiated by idiopathic premature ventricular contractions (PVCs) originating from the left ventricular (LV) inferior wall. Furthermore, J-wave elevation in the inferior leads on ECG is sometimes associated with lethal VA. However, the relationship between these PVCs and J-wave elevation in patients with lethal VA is unclear, so we investigated it in the present study.Methods and Results:We studied 32 consecutive patients who underwent radiofrequency (RF) ablation of idiopathic PVCs with right bundle branch block (RBBB) and superior axis. Thee PVCs were originating from the inferior wall of the LV. Lethal VA was defined as ventricular fibrillation (VF) or ventricular tachycardia (VT) with loss of consciousness (LOC). Among 32 patients, 3 had VF and 2 had VT with LOC. Other 27 had non-lethal VA. Baseline clinical characteristics were not significantly difference between lethal and non-lethal VA. The ratio of J-wave elevation in lethal VA was significantly higher as compared with non-lethal VA (100% vs. 11.1%, P<0.0001). Furthermore, no patients with J-wave elevation in the inferior leads had recurrence of lethal VA after RF ablation of the PVCs. CONCLUSIONS We speculate that J-wave elevation in the inferior leads might be a predictor of lethal VA initiated by PVCs with RBBB and superior axis. RF ablation of these PVCs was a useful method of treating lethal VA.
Botulinum toxin type A as an alternative way to treat trigeminal neuralgia: a systematic review.

INTRODUCTION Trigeminal neuralgia (TN) is one of the most common neurological diseases involving the orofacial region. It affects mainly the older population, usually after the age of 60, and more commonlywomen. It involves the fifth cranial nerve and manifests as paroxysmal, unilateral, severe, shock-like or knife-like pain of from a second to two minutes' duration. Usually pain attacks arise spontaneously, but they can also be precipitated by triggers such as cold weather, brushing teeth or shaving. The ICHD-3 classification divides TN into classical, secondary and idiopathic. Current treatment includes pharmacological and surgical methods. Anticonvulsants, such as carbamazepine and oxcarbazepine, are the first line therapy. Microvascular decompression is the most common and most effective way to treat TN surgically. However, none of these methods is free from complications. Moreover, 25-50% of patients became refractory to drug therapy. Some studies have shown that a new therapy that uses a Botulinum toxin type A can be a safe and effective way to treat trigeminal neuralgia. METHODS Literature from the PubMed base and the Main Medical Library from the last 18 years was analysed. Forty-three items were obtained; after verification, seven articles were included. AIM OF THE STUDY To look at current guidelines about treating trigeminal neuralgia with Botulinum Toxin type A in patients who are refractory to drug therapy or who do not want to undergo surgical treatment. CONCLUSION BoNT-A therapy is a safe and effective method of treating trigeminal neuralgia.
Factors associated with rehoming and time until rehoming for horses listed with an equine charity

The number of unwanted horses in the UK has increased in recent years. It is therefore important to identify factors that indicate whether a horse can be rehomed and how long it takes to be rehomed. Data from 1 January 2013 until 30 March 2014 were extracted from an equine rehoming charity’s database. Exposure variables were examined using multivariable logistic and Cox regression. In total, 791 horses were included in the study and 410 (51.8%) were rehomed during the study period. Median time until rehomed was 39 days (IQR 24–75). Horses whose owner was prepared to transfer ownership were nearly three times more likely to be rehomed than those available for loan. Horses deemed suitable for beginner riders had higher odds of finding a new home, compared with those needing an advanced rider. Horses that were only suitable as unridden companions took longer to find a new home than rideable horses. A restricted rehoming radius (<50 miles) also resulted in longer time to rehoming. Findings from this study can be used to inform rehoming strategies but also to identify horses less likely to be rehomed, and thus where alternative options should be considered.
Effects of stock, sex, and muscle type on carcass characteristics and meat quality attributes of parent broiler breeders and broiler chickens

This study aimed to investigate the effect of using breeder parents (434-days-old) and broiler chickens (37 D of age) from Ross 308 on meat quality parameters and carcass characteristics; sex and muscle type were also estimated. Carcass assessment involved hot carcass weight, carcass yield, and cuts (breast, legs, wings, back, and shoulder). A total of 120 birds were divided into 2 groups (60 birds from each stock), each stock contain equal number of sexes (30 males and 30 females), and further divided into 6 replicates, so that there were 5 birds in each replicate. The birds were fed ad libitum. A sample of 30 birds (male, n = 15 and female, n = 15) from each group was slaughtered for assessing carcass and physical characteristics. Sensory analysis was carried out on each group after boiling or roasting the bird. Live weight, carcass weight and yield, breast weight, legs, wings, and back weights and yield were higher (P < 0.001) for breeder parents when compared to broilers, with the exception of breast percentage. Moreover, better carcass characteristics were observed in males than in females. Parent stock had better water-holding capacity and myofibrillar fragmentation whereas broilers had more tender meat than breeders. Moreover, cooking loss and other sensory characters were not significant between the two groups; however, females had more tender pectoral muscles and more myofibrillar fragmentation than males. We concluded that parent breeders had better carcass characteristics than broiler chickens. The broiler chickens of Ross 308 and female birds had better meat quality than parent breeders.
Hot Water Extract of Curcuma longa L. Improves Serum Inflammatory Markers and General Health in Subjects with Overweight or Prehypertension/Mild Hypertension: A Randomized, Double-Blind, Placebo-Controlled Trial

To investigate the effect of a hot water extract of C. longa L. (WEC) containing anti-inflammatory agents, bisacurone, and turmeronol on chronic inflammation, a randomized double-blind placebo-controlled study was conducted in middle-aged and elderly subjects aged 50–69 years with overweight or prehypertension/mild hypertension. The subjects consumed 900 mg WEC tablets, containing 400 μg bisacurone, 80 μg turmeronol A and 20 μg turmeronol B (WEC group: n = 45), or placebo tablets without WEC (placebo group: n = 45) daily for 12 weeks. Serum inflammatory and metabolic markers were measured. The subjects also completed the MOS 36-item short-form health survey (SF-36) and the Profile of Mood States scale (POMS). In the WEC group, the serum levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and soluble vascular cell adhesion molecule-1 decreased significantly. Compared with the placebo group, the WEC group had significantly lower serum levels of glucose, hemoglobin A1c, and triglycerides, as well as higher serum levels of high-density lipoprotein cholesterol. The WEC group also showed significant improvement of SF-36 scores (for general health, vitality, mental health, and mental summary component) and POMS scores for positive mood states (vigor-activity and friendliness). In conclusion, WEC may ameliorate chronic low-grade inflammation, thus contributing to the improvement of associated metabolic disorders and general health.
Wisteria floribunda agglutinin-positive Mac-2-binding protein in the prediction of disease severity in chronic hepatitis B patients

Background Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) was a novel marker of liver fibrosis. We aimed to investigate WFA+-M2BP level in assessing liver fibrosis in patients with chronic hepatitis B (CHB) infection. Methods A total of 160 CHB patients, who received a liver biopsy, were consecutively recruited. Serum WFA+-M2BP level was quantified at the time point of biopsy. The results were compared with histopathological manifestations and clinical characteristics of the patients. Results The median WFA+-M2BP level, aspartate aminotransferase-to-platelet ratio (APRI) and Fibrosis-4 (FIB-4) index were 1.20 COI, 1.19, and 1.63, respectively. Fifty-one (31.9%) patients had advanced fibrosis. There was a significant increase of WFA+-M2BP levels in parallel to necroinflammation/fibrosis stages. The areas under the receiver operating characteristic curve (AUROC) of WFA+-M2BP level for predicting fibrosis stages were 0.780 of F2, 0.785 of F3, and 0.769 of F4, respectively (all p <0.001). The multivariate analysis identified age (Odds ratio [OR] 1.05, 95% confidence interval [CI]: 1.010–1.092, p = 0.014), platelet (OR: 0.99, 95%CI: 0.980–0.998, p = 0.013), and WFA+-M2BP level (OR: 1.97, 95% CI: 1.299–2.984, p = 0.001) as independent factors associated with advanced fibrosis. Combination of age, platelet and WFA+-M2BP level achieved a better diagnostic performance for advanced fibrosis (AUROC: 0.732, accuracy: 81.3%) than APRI (AUROC: 0.577, accuracy: 63.8%) or FIB-4 index (AUROC: 0.691, accuracy: 75.6%). Conclusion WFA+-M2BP had a good performance indistinguishing liver fibrosis in CHB patients. The combination of age, platelet, and WFA+-M2BPaddressed more accuracy in identifying patients with advanced fibrosis.
LncRNA MALAT1/miR-181a-5p affects the proliferation and adhesion of myeloma cells via regulation of Hippo-YAP signaling pathway

ABSTRACT Multiple myeloma (MM) is a plasma cells malignant proliferative disease, especially in aged people. LncRNAs have been considered as important regulators in MM. This research was to study the effect of LncRNA MALAT1 on the proliferation and adhesion of myeloma cells and whether Long non-coding RNAs MALAT1(LncRNA MALAT1) plays its regulative role through Hippo-YAP signaling pathway by targeting miR-181a-5p. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect the LncRNA MALAT1/miR-181a-5p expression and improve the transfection efficiency. Western blot analysis was used to analyze the expression of proliferation and apoptosis related proteins and Hippo-Yes-associated protein (YAP) signaling pathway related proteins. Cell proliferative ability and cell apoptosis were respectively determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. ELISA assay was for the determination of adherence factors. Immunohistochemistry was to detect the expression of proliferation and adhesion related proteins. LncRNA MALAT1 targeting gene was determined by Dual-luciferase reporter assay. LncRNA MALAT1 was increased in MM cells and LncRNA MALAT1 interference could inhibit cell proliferation and promote cell apoptosis with the changes in the related proteins. Also, LncRNA MALAT1 interference could inhibit cell adhesion through Hippo-YAP signaling pathway. MiR-181a-5p was demonstrated to be a target of LncRNA MALAT1 and miR-181a-5p overexpression could also regulate the changes in cellular behavior in accordance with the LncRNA MALAT1 interference. In addition, LncRNA MALAT1 interference could decrease the expression of miR-181a-5p and inhibit the growth of tumor. In conclusion, this study showed that LncRNA MALAT1 interference inhibited the proliferation and adhesion of myeloma cells by the up-regulation of miR-181a-5p through activating the Hippo-YAP signaling pathway.
The sound of soft alcohol: Crossmodal associations between interjections and liquor

An increasing number of studies reveal crossmodal correspondences between speech sounds and perceptual features such as shape and size. In this study, we show that an interjection Koreans produce when downing a shot of liquor reliably triggers crossmodal associations in American English, German, Spanish, and Chinese listeners who do not speak Korean. Based on how this sound is used in advertising campaigns for the Korean liquor soju, we derive predictions for different crossmodal associations. Our experiments show that the same speech sound is reliably associated with various perceptual, affective, and social meanings. This demonstrates what we call the ‘pluripotentiality’ of iconicity, that is, the same speech sound is able to trigger a web of interrelated mental associations across different dimensions. We argue that the specific semantic associations evoked by iconic stimuli depend on the task, with iconic meanings having a ‘latent’ quality that becomes ‘actual’ in specific semantic contexts. We outline implications for theories of iconicity and advertising.
Visfatin Connection: Present and Future in Osteoarthritis and Osteoporosis

Musculoskeletal pathologies (MSPs) such as osteoarthritis (OA) and osteoporosis (OP), are a set of disorders that cause severe pain, motion difficulties, and even permanent disability. In developed countries, the current incidence of MSPs reaches about one in four adults and keeps escalating as a consequence of aging and sedentarism. Interestingly, OA and OP have been closely related to similar risk factors, including aging, metabolic alterations, and inflammation. Visfatin, an adipokine with an inflammatory and catabolic profile, has been associated with several OA and OP metabolic risk factors, such as obesity, insulin resistance, and type II diabetes. Furthermore, visfatin has been associated with the innate immune receptor toll-like receptor 4 (TLR4), which plays a key role in cartilage and bone inflammatory and catabolic responses. Moreover, visfatin has been related to several OA and OP pathologic features. The aim of this work is to bring together basic and clinical data regarding the common role of visfatin in these pathologies and their major shared risk factors. Finally, we discuss the pitfalls of visfatin as a potential biomarker and therapeutic target in both pathologies.
Paradoxical effects of optogenetic stimulation in mesial temporal lobe epilepsy

To establish the effects induced by long‐term, unilateral stimulation of parvalbumin (PV)‐positive interneurons on seizures, interictal spikes, and high‐frequency oscillations (80–500Hz) occurring after pilocarpine‐induced status epilepticus (SE)—a proven model of mesial temporal lobe epilepsy (MTLE)—in transgenic mice expressing or not expressing ChR2.
Genomic analysis reveals association of specific SNPs with athletic performance and susceptibility to injuries in professional soccer players

The development of specific and individualized training programs is a possible way to improve athletic performance and minimize injuries in professional athletes. The information regarding the sport's physical demands and the athletes’ physical profile have been, so far, considered as exhaustive for the design of effective training programs. However, it is currently emerging that the genetic profile has to be also taken into consideration. By merging medical and genetic data, it is thus possible to identify the athlete's specific attitude to respond to training, diet, and physical stress. In this context, we performed a study in which 30 professional soccer players, subjected to standard sport medical evaluation and practices, were also screened for genetic polymorphism in five key genes (ACTN3, COL5A1, MCT1, VEGF, and HFE). This genetic analysis represents the central point of a multidisciplinary method that can be adopted by elite soccer teams to obtain an improvement in athletic performance and a concomitant reduction of injuries by tailoring training and nutritional programs. The genetic fingerprinting of single athletes led to the identification of two performance‐enhancing polymorphisms (ACTN3 18705C>T, VEGF‐634C>G) significantly enriched. Moreover, we derived a genetic model based on the gene set analyzed, which was tentatively used to reduce athletes’ predisposition to injuries, by dictating a personalized nutrition and training program. The potential usefulness of this approach is concordant with data showing that this team has been classified as the healthiest and least injured team in Europe while covering the highest distance/match with the highest number of high‐intensity actions/match.
Testotoxicosis without Testicular Mass: Revealed by Peripheral Precocious Puberty and Confirmed by Somatic LHCGR Gene Mutation

ABSTRACT Purpose: Testotoxicosis is an autosomal dominant form of limited gonadotropin-independent precocious puberty in boys. It is caused by a heterozygous constitutively activating mutation of the LHCGR gene encoding the luteinizing/hormone receptor (LHR). Some twenty mutations of the LHCGR gene have been reported. Most of them are constitutive mutations isolated from blood leukocyte DNA, although others are somatic, found only in testicular tumoural tissue. In all the previously reported cases of these somatic mutations, the tumour, whether a nodular Leydig cell adenoma or hyperplasia, was easily visible on testicular ultrasonography. The aim of this study was to describe an unusual presentation of a patient with the clinical and hormonal characteristics of testotoxicosis but no well-circumscribed lesion at testicular ultrasonography. Materials and Methods: Molecular analysis of the LHCGR gene was performed by direct sequencing of DNA extracted from peripheral leucocytes and testicular biopsy. Results: Molecular analysis didn’t find any LHR mutation in blood, whereas it revealed for the first time a somatic D578H mutation in testicular tissue despite no evidence of a nodular aspect at testis ultrasonography. Conclusions: This observation underlines the need to look for a somatic LHCGR gene mutation from the testicular biopsies of all boys with testotoxicosis with no constitutive LHCGR gene mutation identified from blood DNA, even in the absence of circumscribed testicular lesion at ultrasonography. In addition, based on the known link between LHR mutations and testicular tumourigenesis, yearly ultrasound monitoring of the testes should be considered for these patients.
Acid-Assisted Direct Olefin Metathesis of Unprotected Carbohydrates in Water.

The ability to use unprotected carbohydrates in olefin metathesis reactions in aqueous media is demonstrated. Using water-soluble amine-functionalized Hoveyda-Grubbs catalysts under mildly acidic aqueous conditions, the self-metathesis of unprotected alkene-functionalized α-D-manno- and α-D-galactopyranosides could be achieved through minimization of non-productive chelation and isomerization. Cross-metathesis with allyl alcohol could be also be achieved with reasonable selectivity. The presence of small quantities (2.5 vol%) of acetic acid increased the self-metathesis product formation while significantly reducing the alkene isomerization process. The catalytic activity was furthermore retained in the presence of large amounts (0.01 M) of protein (BSA), underlining the potential of this carbon-carbon bond forming reaction under biological conditions. These results demonstrate the potential of directly using unprotected carbohydrate structures in olefin metathesis reactions under mild conditions compatible with biological systems, thereby enabling their use in, e.g., drug discovery and protein derivatization.