Miracle-dz/UniFAR-FTUs huggingface dataset:
Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Although the global prevalence of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs’ entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.
Comparative efficacy of bariatric endoscopic procedures in the treatment of morbid obesity: a systematic review and network meta-analysis

Abstract Background The comparative efficacy of bariatric endoscopic procedures has not been completely elucidated. We aimed to comprehensively evaluate the efficacy of bariatric endoscopic procedures. Methods We searched for randomized controlled trials investigating the efficacy of bariatric endoscopic procedures, including the use of an intragastric balloon, duodenal-jejunal bypass liner (DJBL), aspiration therapy, primary obesity surgery endoluminal (POSE) procedure, and botulinum toxin injection to the stomach. Network meta-analyses were performed to determine the percentage of weight loss (%weight loss) and percentage of excess weight loss (%EWL). Results 22 studies with 2141 patients were included in the meta-analysis. Most endoscopic procedures showed superior efficacy in terms of %weight loss compared with the control (mean difference [MD] [95 % confidence interval (CI)]: aspiration therapy 10.4 % [7.0 % to 13.7 %]; fluid-filled balloon 5.3 % [3.4 % to 7.2 %]; POSE 4.9 % [1.7 % to 8.2 %]; and DJBL 4.5 % [1.4 % to 7.7 %]). In terms of %EWL, aspiration therapy, fluid-filled balloon, POSE, and DJBL were superior to the control (MD [95 %CI]: 27.3 % [15.3 % to 39.3 %]; 22.4 % [15.4 % to 29.4 %]; 15.3 % [2.5 % to 28.0 %]; and 13.0 % [4.9 % to 21.2], respectively). The gas-filled balloon and botulinum toxin injection did not show a significant difference in %weight loss or %EWL compared with the control. For the fluid-filled balloon, the %EWL and %weight loss tended to decrease after balloon removal at 6 months after the procedure. Conclusion All bariatric endoscopic procedures, except for gas-filled balloon and botulinum toxin injection to the stomach, showed superior short-term efficacy in terms of %weight loss or %EWL compared with lifestyle modification.
Ancient Genomes Reveal the Evolutionary History and Origin of Cashmere-Producing Goats in China

Abstract Goats are one of the most widespread farmed animals across the world; however, their migration route to East Asia and local evolutionary history remain poorly understood. Here, we sequenced 27 ancient Chinese goat genomes dating from the Late Neolithic period to the Iron Age. We found close genetic affinities between ancient and modern Chinese goats, demonstrating their genetic continuity. We found that Chinese goats originated from the eastern regions around the Fertile Crescent, and we estimated that the ancestors of Chinese goats diverged from this population in the Chalcolithic period. Modern Chinese goats were divided into a northern and a southern group, coinciding with the most prominent climatic division in China, and two genes related to hair follicle development, FGF5 and EDA2R, were highly divergent between these populations. We identified a likely causal de novo deletion near FGF5 in northern Chinese goats that increased to high frequency over time, whereas EDA2R harbored standing variation dating to the Neolithic. Our findings add to our understanding of the genetic composition and local evolutionary process of Chinese goats.
Oncogenic gene RGC‐32 is a direct target of miR‐26b and facilitates tongue squamous cell carcinoma aggressiveness through EMT and PI3K/AKT signalling

Growing data have recognized the significance of Response Gene to Complement (RGC)‐32 in numerous tumour developments. Notwithstanding, the functional role and underlying mechanism of it in tongue squamous cell carcinoma (TSCC) remain enigmatic. Here, to identify the impact of RGC‐32 in TSCC, its expression in multiple TSCC cells was measured and loss‐of‐function experiments in cell lines were performed to illuminate the function of it induced TSCC progression, via si‐RNA knockdown, CCK‐8, colony formation, wound‐healing, transwell, flow cytometry and western blot assays. To clarify potential mechanism, expressions of hallmarks in epithelial‐mesenchymal transition (EMT) process and PI3K/AKT signalling were assessed, and the upstream miR regulator of RGC‐32 was predicted and verified by applying bioinformatic approaches and dual‐luciferase reporter assay, respectively. Finally, the rescue experiments were applied to better elucidate the effect of miR‐26b/RGC‐32 axis in TSCC behaviours. As a result, RGC‐32 was upregulated in TSCC cells and knocking down of it abrogated cell proliferation, trans‐migration and invasion, whilst promoted apoptosis in TSCC, which was regulated through repressing EMT and inactivation of PI3K/AKT signalling. Subsequently, miR‐26b was predicted and identified as an upstream regulator of RGC‐32, and the pro‐tumorigenic effect of RGC‐32 was reversed by miR‐26b overexpression. Collectively, our results demonstrated that RGC‐32 facilitated TSCC progression, which was modulated by activations of PI3K/AKT pathway and EMT process, and reduction of its negative regulator of miR‐26b. These findings highlight a novel role of miR‐26b/RGC‐32 axis in TSCC and underlying mechanism, encouraging a potent usage in TSCC treatment.
Discovery of Cephalosporin-3´-Diazeniumdiolates that show Dual Antibacterial and Antibiofilm Effects against Pseudomonas aeruginosa Clinical Cystic Fibrosis Isolates and Efficacy in a Murine Respiratory Infection Model.

The formation of biofilms provides a formidable defense for many bacteria against antibiotics and host immune responses. As a consequence, biofilms are thought to be the root cause of most chronic infections, including those occurring on medical indwelling devices, endocarditis, urinary tract infections, diabetic and burn wounds and bone and joint infections. In cystic fibrosis (CF), chronic Pseudomonas aeruginosa respiratory infections are the leading cause of morbidity and mortality in adults. Previous studies have shown that many bacteria can undergo a coordinated dispersal event in the presence of low concentrations of nitric oxide (NO), suggesting that NO could be used to trigger biofilm dispersal in chronic infections and enable clearance of the more vulnerable planktonic cells. In this proof-of-principle study, we describe efforts to create 'all-in-one' cephalosporin-based NO donor prodrugs (cephalosporin-3´-diazeniumdiolates, C3Ds) that show both direct beta-lactam mediated antibacterial activity and NO-induced antibiofilm effects. Twelve novel C3Ds were synthesized and screened against a panel of P. aeruginosa CF clinical isolates and other human pathogens. The most active compound, AMINOPIP2-ceftazidime 12, showed higher antibacterial potency than its parent cephalosporin and front-line antipseudomonal antibiotic ceftazidime, good stability against beta-lactamases, activity against ceftazidime-resistant P. aeruginosa in vitro biofilms and efficacy equivalent to ceftazidime in a murine P. aeruginosa respiratory infection model. The results support further evaluation of AMINOPIP2-ceftazidime 12 for P. aeruginosa lung infections in CF and broader study of 'all-in-one' C3Ds for other chronic infections.
CEREALES ENTIERES POUR LES POULETS DE CHAIR : LE RETOUR ?

Successes encountered in some northern European poultry farms raise interest for the use of whole cereals grains distributed with a protein concentrate in broiler chicken feeding. The three main types of distribution of whole grains are compared splitted diets, loose-mix and sequential feeding. Loose-mix and sequential feeding techniques are efficient. These feeding systems allow to control partly the whole cereal and protein concentrate proportions actually ingested by chickens. On the other hand, splitted diets favour the expression of individual factors of food selection, and does not always allow to get growth and body composition as expected by poultry farmers. Broilers digest whole grain as efficiently as ground cereals. Broilers are able to quickly adapt to a diet including a whole cereal grain, by adjustment of their feeding behaviour. The proportion of cereal grain ingested depends on the physical form and composition of the protein concentrate. Whole cereal grains induce a larger development of gizzard whose effects on digestion and on natural resistance of the birds towards coccidiosis require further research. The system of loose-mix feeding is mastered and applied in some northern European poultry farms by computer monitored distribution. Sequential feeding is less expensive than loose-mix feeding but remains to be validated in practise. Economical interest of this feeding method for French farmers requires further evaluation.
The Role of Physical Activity as Conservative Treatment for Hip and Knee Osteoarthritis in Older People: A Systematic Review and Meta-Analysis

The aim of this systematic review and meta-analysis is to determine the role of physical activity as a conservative treatment for older people with knee or hip osteoarthritis. The effect on pain, physical function, stiffness, quality of life, and dynamic balance of Aquatic Exercise, Land-based Exercise, and Sports were compared in a specific population composed of osteoarthritic patients aged 65 or over. A systematic search using Pubmed-Medline, Google Scholar, and the Cochrane Library was carried out to select randomized clinical trials, observational studies, or case series that evaluated outcome measures after physical activity. Twenty randomized controlled trials (RCTs) and two case series were included in this review. Four trials were at low risk of bias (A), 12 at unclear risk of bias (B), and four at high risk of bias (C). Compared to controls, Aquatic Exercise, Land-based Exercise, Tai Chi, and Yoga showed a small to high effect for improving pain, physical function, quality of life, and stiffness. Active exercise and sport are effective to improve pain and physical function in elderly people with osteoarthritis. Nevertheless, further studies are required to validate the use of land-based exercise, aquatic exercise, or sport to treat the symptoms of older adults that suffer from knee and hip osteoarthritis.
Incorporating Noise Robustness in Speech Command Recognition by Noise Augmentation of Training Data

The advent of new devices, technology, machine learning techniques, and the availability of free large speech corpora results in rapid and accurate speech recognition. In the last two decades, extensive research has been initiated by researchers and different organizations to experiment with new techniques and their applications in speech processing systems. There are several speech command based applications in the area of robotics, IoT, ubiquitous computing, and different human-computer interfaces. Various researchers have worked on enhancing the efficiency of speech command based systems and used the speech command dataset. However, none of them catered to noise in the same. Noise is one of the major challenges in any speech recognition system, as real-time noise is a very versatile and unavoidable factor that affects the performance of speech recognition systems, particularly those that have not learned the noise efficiently. We thoroughly analyse the latest trends in speech recognition and evaluate the speech command dataset on different machine learning based and deep learning based techniques. A novel technique is proposed for noise robustness by augmenting noise in training data. Our proposed technique is tested on clean and noisy data along with locally generated data and achieves much better results than existing state-of-the-art techniques, thus setting a new benchmark.
A Novel Feature Selection Method for Uncertain Features: An Application to the Prediction of Pro-/Anti-Longevity Genes

Understanding the ageing process is a very challenging problem for biologists. To help in this task, there has been a growing use of classification methods (from machine learning) to learn models that predict whether a gene influences the process of ageing or promotes longevity. One type of predictive feature often used for learning such classification models is Protein-Protein Interaction (PPI) features. One important property of PPI features is their uncertainty, i.e., a given feature (PPI annotation) is often associated with a confidence score, which is usually ignored by conventional classification methods. Hence, we propose the Lazy Feature Selection for Uncertain Features (LFSUF) method, which is tailored for coping with the uncertainty in PPI confidence scores. In addition, following the lazy learning paradigm, LFSUF selects features for each instance to be classified, making the feature selection process more flexible. We show that our LFSUF method achieves better predictive accuracy when compared to other feature selection methods that either do not explicitly take PPI confidence scores into account or deal with uncertainty globally rather than using a per-instance approach. Also, we interpret the results of the classification process using the features selected by LFSUF, showing that the number of selected features is significantly reduced, assisting the interpretability of the results. The datasets used in the experiments and the program code of the LFSUF method are freely available on the web at http://github.com/pablonsilva/FSforUncertainFeatureSpaces.
Vigorous-Intensity Physical Activities Are Associated with High Brown Adipose Tissue Density in Humans

Brown adipose tissue (BAT) plays a role in adaptive thermogenesis in response to cold environments and dietary intake via sympathetic nervous system (SNS) activation. It is unclear whether physical activity increases BAT density (BAT-d). Two-hundred ninety-eight participants (age: 41.2 ± 12.1 (mean ± standard deviation), height: 163.6 ± 8.3 cm, weight: 60.2 ± 11.0 kg, body mass index (BMI): 22.4 ± 3.0 kg/m2, body fat percentage: 25.4 ± 7.5%) without smoking habits were categorized based on their physical activity levels (a group performing physical activities including walking and moderate physical activity (WM) and a group performing WM + vigorous-intensity physical activities (VWM)). We measured the total hemoglobin concentration ([Total-Hb]) in the supraclavicular region, an index of BAT-d, and anthropometric parameters. [Total-Hb] was significantly higher in VWM than WM for all participant groups presumably owing to SNS activation during vigorous-intensity physical activities, and unrelated to the amount of total physical activity levels. Furthermore, multiple regression analysis revealed that BAT-d was related to visceral fat area and VWM in men and related to body fat percentage in women. We conclude that vigorous-intensity physical activities are associated with high BAT-d in humans, especially in men.
A Clinical Investigation on Serum Amyloid A Concentration in Client-Owned Healthy and Diseased Cats in a Primary Care Animal Hospital

Although measurement of serum amyloid A (SAA) concentration in client-owned cats has already been shown to be clinically useful, limited data are available on common diseases at primary care hospitals. In this study, we measured the SAA concentration in cats with various diseases and investigated their clinical significance using a primary care hospital as a population. We measured the SAA concentrations in healthy cats (n = 98) and those with various clinical signs (n = 444). The SAA concentrations in healthy cats did not differ significantly by age, breed, sex, and presence/absence of neutering/spaying. The SAA concentrations were significantly higher in the diseased cat group than in the healthy cat group (p < 0.001). We observed significant increases in SAA concentrations in cats with confirmed diagnosis of inflammatory disease such as upper respiratory tract infections (p < 0.001), pneumonia (p < 0.001), pyometra (p = 0.001), and feline infectious peritonitis (p < 0.001), compared with those observed in healthy cats. Conversely, no increase was observed in cardiomyopathy, hyperthyroidism, and diabetes mellitus without systemic inflammation. In univariate analysis, survival at 30 days (p = 0.03) differed significantly between the low and high SAA concentration groups, but not at 180 days. In multivariate analysis, survival at 30 days did not significantly affect SAA concentration. Measurement of SAA concentration is a useful biomarker for detecting the presence or absence of inflammation in diseased cats. However, it may not be useful as a biomarker for determining the prognosis of the disease.
Comprehensive Evaluation of Fourteen Docking Programs on Protein-Peptide Complexes and A New Strategy for Improving the Performance of Global Docking.

A large number of protein-protein interactions (PPIs) are mediated by the interactions between proteins and peptide segments in binding partners, and therefore determination of protein-peptide interactions (PpIs) is quite crucial to elucidate important biological processes and design peptides or peptidomimetic drugs that can modulate PPIs. Nowadays, as a powerful computation tool, molecular docking has been widely utilized to predict the binding structures of protein-peptide complexes. However, although a number of docking programs have been available, the systematic study on the assessment of their performance for PpIs has never been reported. In this study, a benchmark dataset consisting of 185 protein-peptide complexes with peptide length ranging from 5 to 20 residues was employed to evaluate the performance of fourteen docking programs, including three protein-protein docking programs (ZDOCK, FRODOCK, and HawkDock), three small molecule docking programs (GOLD, Surflex-Dock, and AutoDock Vina), and eight protein-peptide docking programs (GalaxyPepDock, MDockPeP, HPEPDOCK, CABS-dock, pepATTRACT, DINC, AutoDock CrankPep (ADCP), and HADDOCK peptide docking). A new evaluation parameter, named IL_RMSD, was proposed to measure the docking accuracy. In global docking, HPEPDOCK performs the best to the entire dataset and yields the success rates of 4.3%, 27.0% and 58.9% at the top 1, 10 and 100 levels, respectively. In local docking, overall, ADCP achieves the best predictions and reaches the success rates of 11.9%, 39.5% and 72.4% at the top 1, 10 and 100 levels, respectively. Furthermore, based on the assessment results, HAVM, a new global docking strategy that employed ADCP to optimize the conformations generated by HPEPDOCK and then re-ranked these conformations by VoroMQA (a scoring function for protein complexes) was presented, which shows significantly better performance than HPEPDOCK in our benchmark with the success rates of 9.7%, 39.5% and 65.9% at the top 1, 10, 100 levels, respectively. It is expected that our work can provide some helpful insights into the selection and development of improved docking programs for PpIs.
Complete Genome Sequence of a Virulent Leptospira interrogans Serovar Copenhageni Strain, Assembled with a Combination of Nanopore and Illumina Reads

Here, we present the complete genome sequence of a highly virulent Leptospira interrogans serovar Copenhageni strain isolated from a dog with severe leptospirosis. In this work, a gapless genome draft was assembled with a combination of Nanopore and Illumina data of relatively low coverage. ABSTRACT Here, we present the complete genome sequence of a highly virulent Leptospira interrogans serovar Copenhageni strain isolated from a dog with severe leptospirosis. In this work, a gapless genome draft was assembled with a combination of Nanopore and Illumina data of relatively low coverage.
Ospemifene efficacy and safety data in women with vulvovaginal atrophy

Abstract Vulvovaginal atrophy (VVA) is a frequent, underreported and underdiagnosed condition. Ospemifene is a third-generation Selective Estrogen Receptor Modulator (SERM) that has been shown to be effective in women with VVA and dyspareunia, vaginal dryness and vulvar vestibular symptoms. Some of the possible side effects included by FDA and EMA are hot flushes, headache, muscle spasms, vaginal bleeding and vaginal discharge. Ospemifene does not increase the incidence of endometrial cancer or hyperplasia. While the efficacy is comparable with that of estrogenic treatments, ospemifene is not only well tolerated and safe but also reduces bone turnover in postmenopausal women, and available data indicate no safety concerns for breast tissue.
Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies

Sweeteners that are a hundred thousand times sweeter than sucrose are being consumed as sugar substitutes. The effects of sweeteners on gut microbiota composition have not been completely elucidated yet, and numerous gaps related to the effects of nonnutritive sweeteners (NNS) on health still remain. The NNS aspartame and acesulfame-K do not interact with the colonic microbiota, and, as a result, potentially expected shifts in the gut microbiota are relatively limited, although acesulfame-K intake increases Firmicutes and depletes Akkermansia muciniphila populations. On the other hand, saccharin and sucralose provoke changes in the gut microbiota populations, while no health effects, either positive or negative, have been described; hence, further studies are needed to clarify these observations. Steviol glycosides might directly interact with the intestinal microbiota and need bacteria for their metabolization, thus they could potentially alter the bacterial population. Finally, the effects of polyols, which are sugar alcohols that can reach the colonic microbiota, are not completely understood; polyols have some prebiotics properties, with laxative effects, especially in patients with inflammatory bowel syndrome. In this review, we aimed to update the current evidence about sweeteners’ effects on and their plausible biological interactions with the gut microbiota.