Miracle-dz/UniFAR-FTUs huggingface dataset:
Fermented Maillard reaction products attenuate stress-induced testicular dysfunction.

Chronic stress can cause psychological diseases and affect male fertility and the reproductive system. Maillard reaction of milk proteins improves their functional and nutritional properties through modification of proteins. Previously, we determined that Maillard reaction product (MRP) from milk casein and MRP fermented (FMRP) with Lactobacillus rhamnosus 4B15 (4B15) had anti-anxiolytic effects in mice under chronic stress. Therefore, we aimed to investigate the effects of MRP and FMRP on chronic stress-induced testicular dysfunction in mice through quantitative real-time PCR (qRT-PCR) and in situ hybridization analysis. Mice were pretreated with MRP and FMRP for 10 wk; simultaneously, from the third week of the experimental period, they were exposed to unpredictable chronic mild stress (UCMS) for 7 wk. The expression levels of the luteinizing hormone subunit β (Lhb) and follicle-stimulating hormone subunit β (Fshb) were remarkably reduced after exposure to UCMS. However, treatment with MRP and FMRP inhibited the UCMS-induced reduction, with FMRP showing especially significant inhibition. Moreover, the expression of steroidogenesis-related genes [luteinizing hormone receptor (Lhr), follicle-stimulating hormone (Fshr), 3-β hydroxysteroid dehydrogenase 2 (Hsd3b2), and steroidogenic acute regulatory protein (StAR)] were significantly reduced in response to UCMS. In contrast, the transcript levels of these genes were highest in the MRP-treated mice. Mice pretreated with FMRP also exhibited higher levels of gene expression compared with the nonstressed mice. Moreover, UCMS significantly downregulated the expression of genes associated with testicular function [i.e., a disintegrin and metallopeptidase domain 5 (Adam5), Adam29, bone morphogenetic protein 2 (Bmp2), tektin 3 (Tekt3), and sperm adhesion molecule 1 (Spam1)]. However, the administration of MRP and FMRP prevented the UCMS-induced reduction in the expressions of above genes. The localization of Lhr, Srd5a2, Adam29, and Spam1 was confirmed by in situ hybridization analysis and the results were consistent with those of qRT-PCR. Consequently, these results indicated that MRP and FMRP, manufactured by the heat treatment of milk casein and fermentation with probiotic 4B15, have the potential to prevent chronic stress-induced testicular dysfunction.
Ostracism Disrupts Self-Continuity

We conducted six studies to test our hypotheses that ostracism disrupts self-continuity and that self-affirmation counters ostracism’s negative influence on self-continuity. Participants who experienced more ostracism in their daily lives (Study 1), imagined being ostracized (Studies 2 and 5), recalled a past ostracism experience (Studies 3 and 6), and were ostracized in a ball-tossing game (Study 4) reported lower levels of self-continuity than their counterparts. Moreover, neither violations of expectation nor negativity of the experience was sufficient in decreasing self-continuity (Study 5). Finally, self-affirmation weakened the negative effect of ostracism on self-continuity (Study 6). Taken together, our findings provide converging causal evidence for our hypotheses and provide novel insights for the literature on how daily interpersonal interactions influence individuals’ sense of an enduring self. In addition, the moderation of self-affirmation reported in our research indicates an effective approach to diminishing the negative influence of ostracism.
Crystal structure of carbon dioxide at high pressure : "Superhard" polymeric carbon dioxide

The crystal structures of two molecular phases (I and III) and a polymeric phase (V) of CO2 have been investigated to 60 GPa. CO2-1 (Pa3) transforms to CO2-III (Cmca) at 12 GPa with almost no change of density. Although CO2-III persists in Cmca to at least 60 GPa at ambient temperature, it transforms when heated to 1800 K above 40 GPa to tridymite (P212121) CO2-V with 15.3% volume change. Each carbon atom of CO2-V is tetrahedrally bonded to four oxygen atoms. CO2-V is likely superhard with low compressibility B0 = 365 GPa, similar to cubic BN.
Normal pressure hydrocephalus: Diagnostic delay

Abstract Introduction: Normotensive hydrocephalus is a differential diagnosis in the evaluation of the dementia syndrome. The diagnostic protocols would allow detecting this pathology that has more effective treatment than other dementias. Objective: To describe a population with clinical suspicion of normal pressure hydrocephalus evaluated in a Colombian psychiatric hospital and discuss the possible reasons for its diagnostic and therapeutic delay. Materials and methods: We conducted a retrospective study of medical records to identify patients with suspected normal pressure hydrocephalus during a 5-year period. Results: Thirty-five patients with suspected normal pressure hydrocephalus underwent diagnostic lumbar puncture and five of them were considered candidates for a peritoneal-venous shunt, but none underwent this surgical procedure. After three to six months of the lumbar puncture, the gait pattern improved in 22.8% of the patients, cognition in 22.8%, and sphincter control in 11.4%. Improvement was not sustained in the long term (1 year) in any of them. Conclusion: This study suggests the poor implementation of the protocols for evaluating patients with cognitive deficits and delays in the diagnosis of normal pressure hydrocephalus. A small number of patients were identified as candidates for treatment. Normal pressure hydrocephalus is a potentially reversible clinical entity with the placement of a peritoneal ventricular shunt, but delays in diagnosis and treatment have deleterious consequences for patients and their families.
Patterns of Human Leukocyte Antigen Class I and Class II Associations and Cancer

GWAS of >71,000 individuals across 27 cancer types suggest that patterns of HLA Class I and Class II associations may provide etiologic insights for cancer. Human leukocyte antigen (HLA) gene variation is associated with risk of cancers, particularly those with infectious etiology or hematopoietic origin, given its role in immune presentation. Previous studies focused primarily on HLA allele/haplotype-specific associations. To answer whether associations are driven by HLA class I (essential for T-cell cytotoxicity) or class II (important for T-cell helper responses) genes, we analyzed GWAS from 24 case–control studies and consortia comprising 27 cancers (totaling >71,000 individuals). Associations for most cancers with infectious etiology or of hematopoietic origin were driven by multiple HLA regions, suggesting that both cytotoxic and helper T-cell responses are important. Notable exceptions were observed for nasopharyngeal carcinoma, an EBV-associated cancer, and CLL/SLL forms of non-Hodgkin lymphomas; these cancers were associated with HLA class I region only and HLA class II region only, implying the importance of cytotoxic T-cell responses for the former and CD4+ T-cell helper responses for the latter. Our findings suggest that increased understanding of the pattern of HLA associations for individual cancers could lead to better insights into specific mechanisms involved in cancer pathogenesis. Significance: GWAS of >71,000 individuals across 27 cancer types suggest that patterns of HLA Class I and Class II associations may provide etiologic insights for cancer.
Effect of antimicrobial use and production system on Campylobacter spp., Staphylococcus spp. and Salmonella spp. resistance in Spanish swine: A cross‐sectional study

Antimicrobial resistance is a worldwide public health threat; hence, current trends tend to reduce antimicrobial use in food‐producing animals and to monitor resistance in primary production. This study aimed at evaluating the impact of antimicrobial use and production system on swine farms in the antimicrobial resistance of Campylobacter, Salmonella and Staphylococcus, the main zoonotic pathogens in pig herds, in order to assess their potential value as sentinel microorganisms in antimicrobial resistance surveillance schemes. A total of 37 Spanish swine farms, 18 intensive and 19 organic/extensive farms, were included in the study. The antimicrobial resistance of 104 Campylobacter, 84 Staphylococcus and 17 Salmonella isolates was evaluated using Sensititre plates following the EUCAST guidelines. Mixed‐effects logistic regression was used to evaluate the influence of production system and antimicrobial use in resistant and multidrug‐resistant (MDR) phenotypes to the antimicrobials tested. The results showed that antimicrobial use was higher (p < .001) on intensive farms than on organic/extensive farms. MDR in Campylobacter and Staphylococcus was lower on organic/extensive farms (OR < .01p < .001). Antimicrobial resistance in Campylobacter and Staphylococcus isolates was, also for most of the antimicrobials studied, significantly higher in intensive than organic/extensive pig herds. Tetracycline resistance was associated with total antimicrobial consumption in both microbial species (p < .05), and some cross‐associations between distinct antimicrobial substances were established, for instance resistance to erythromycin was associated with macrolide and phenicol consumption. No significant associations could be established for Salmonella isolates. The results demonstrate the link between antimicrobial consumption and resistance in zoonotic bacteria and evidence the potential value of using Campylobacter and Staphylococcus species in monitoring activities aimed at determining the impact of antimicrobials use/reduction on the occurrence and spread of antimicrobial resistance.
A High Q-Factor Outer-Frame-Anchor Gyroscope Operating at First Resonant Mode

Disc gyroscope manufactured through microelectromechanical systems (MEMS) fabrication processes becomes one of the most critical solutions for achieving high performance. Some reported novel disc constructions acquire good performance in bias instability, scale factor nonlinearity, etc. However, antivibration characteristics are also important for the devices, especially in engineering applications. For multi-ring structures with central anchors, the out-of-plane motions are in the first few modes, easily excited within the vibration environment. The paper presents a multi-ring gyro with good dynamic characteristics, operating at the first resonant mode. The design helps obtain better static performance and antivibration characteristics with anchor points outside of the multi-ring resonator. According to harmonic experiments, the nearest interference mode is located at 30,311 Hz, whose frequency difference is 72.8% far away from working modes. The structures were fabricated with silicon on insulator (SOI) processes and wafer-level vacuum packaging, where the asymmetry is 780 ppm as the frequency splits. The gyro also obtains a high Q-factor. The measured value at 0.15 Pa was 162 k, which makes the structure have sizeable mechanical sensitivity and low noise.
DeepA-RBPBS: A hybrid convolution and recurrent neural network combined with attention mechanism for predicting RBP binding site

Abstract It’s important to infer the binding site of RNA-binding proteins (RBP) for understanding the interaction between RBP and its RNA targets and decipher the mechanisms of transcriptional regulation. However, experimental detection of RBP binding sites is still time-intensive and expensive. Algorithms based on machine learning can speed up detection of RBP binding sites. In this article, we propose a new deep learning method, DeepA-RBPBS, which can use RNA sequences and structural features to predict RBP binding site. DeepA-RBPBS uses CNN and BiGRU to extract sequences and structural features without long-term dependence issues. It also utilizes an attention mechanism to enhance the contribution of key features. The comparison shows that the performance of DeepA-RBPBS is better than that of the state-of-the-art predictors. In the testing on 31 datasets of CLIP-seq experiments over 19 proteins, MCC (AUC) is 8% (5%) higher than those of the latest method based on deep learning, iDeepS. We also apply DeepA-RBPBS to the target RNA data of RBPs related to diabetes (LIN28, RBFOX2, FTO, IGF2BP2, CELF1 and HuR). The results show that DeepA-RBPBS correctly predicted 41,693 samples, where iDeepS predicted 31,381 samples. Communicated by Ramaswamy H. Sarma
An Implementation Science Approach to Promote Optimal Implementation, Adoption, Use, and Spread of Continuous Clinical Monitoring System Technology

Supplemental digital content is available in the text. Objectives This study aimed to apply implementation science tenets to guide the deployment and use of in-hospital Clinical Monitoring System Technology (CMST) and to develop a toolkit to promote optimal implementation, adoption, use, and spread of CMST. Methods Six steps were carried out to (1) establish leadership support; (2) identify, educate, and sustain champions; (3) enlist clinical staff users to learn barriers and facilitators; (4) examine initial qualitative data from 11 clinician group interviews; (5) validate barriers/facilitators to CMST use and toolkit content; and (6) propose a toolkit to promote utilization. Clinical Monitoring System Technology output before and after implementation were compared. Results The top 3 barriers to effective CMST use were as follows: (1) inadequate education/training/support, (2) clinical workflow challenges, and (3) lack of communication. Facilitators to CMST implementation and adoption included the following: (1) providing comprehensive and consistent CMST education, (2) presenting evidence early and often, (3) tailoring device and usage expectations to individual environments, and (4) providing regular feedback about progress. Empirical data drove the development of a CMST implementation toolkit covering 6 areas: (1) why, (2) readiness, (3) readiness and implementation, (4) patient/family introduction, (5) champions, (6) care team saves, and (7) troubleshooting. Clinical Monitoring System Technology positively impacted failure to rescue events. Monthly median cardiac alert responses decreased from 30 to 3.64 minutes (87.9%), and respiratory alert responses decreased from 26 to 4.85 minutes (81.4%). Conclusions Using implementation science tenets to concurrently guide deployment and study performance of 2 CMST devices and impact on workload was effective for both learning CMST efficacy at 2 hospital systems and developing a toolkit to promote optimal implementation, adoption, use, and spread.
LANGUAGE DISCRIMINATION BY LARGE-BILLED CROWS

Language discrimination has previously been found in human infants, cotton-top tamarin monkeys, rats, and Java sparrows. This ability might also be relevant for the crow, a social passerine with extensive auditory perceptual skills living in close contact with humans. In this experiment we tested whether crows autonomously pay attention to spoken language, and whether they can discriminate a familiar, locally spoken language (Japanese) from an unfamiliar language (Dutch) without training. When presented with sentences spoken by multiple speakers, the crows showed significantly more responses to the Dutch than to the Japanese, which suggests that they discriminate two languages with distinctive linguistic features, and that they might also be more attentive to an unfamiliar language, Dutch, compared to a familiar one, Japanese. These results further extend the hypothesis that language discrimination is based on a general perceptual mechanism that predates the evolution of language and show that crows can voluntarily apply this mechanism to language outside of experimental set-ups.
Neonatal gut colonization by Bifidobacterium is associated with higher childhood cytokine responses

ABSTRACT The gut microbiota is a major stimulus for the immune system, and late acquisition of bacteria and/or reduced complexity of the gut flora may delay adaptive immune maturation. However, it is unknown how the gut bacterial colonization pattern in human infants is related to T cell activation during early childhood. We followed 65 Swedish children in the FARMFLORA cohort, from birth up to 3 years of age. In fecal samples collected at several time points during the first year of life, the gut colonization pattern was investigated with the use of both 16S rRNA next generation sequencing (NGS) and culture-based techniques. This was related to production of IL-13, IL-5, IL-6, TNF, IL-1β and IFN-γ by PHA-stimulated fresh mononuclear cells and to proportions of CD4+ T cells that expressed CD45RO at 36 months of age. Both NGS and culture-based techniques showed that colonization by Bifidobacterium at 1 week of age associated with higher production of IL-5, IL-6, IL-13, TNF and IL-1β at 36 months of age. By contrast, gut colonization by Enterococcus, Staphylococcus aureus or Clostridium in early infancy related inversely to induced IL-13, IL-5 and TNF at 3 years of age. Infants with elder siblings produced more cytokines and had a larger fraction of CD45RO+ T cells compared to single children. However, controlling for these factors did not abolish the effect of colonization by Bifidobacterium on immune maturation. Thus, gut colonization in early infancy affects T cell maturation and Bifidobacterium may be especially prone to induce infantile immune maturation.
Analysis of Tea Auction Prices Using Non-Cointegration Based Techniques

Favorable product prices act as a set off for any commercial activity normally and perhaps its sustainability. Tea is a significant commercial crop in Kenya and has contributed immensely to the economy’s Gross Domestic Product (GDP) through its export earnings. However, tea industry has gone through many phases of ups and downs, particularly in terms of its export performance recently. Therefore, there is need to study the behavior of tea auction prices to get a deeper perspective into the behavior of the tea prices and to develop a model that is suitable to forecast the tea auction prices precisely. The study aimed at analyzing the trend of tea auction prices in Kenya, fit a suitable model for forecasting tea auction prices and finally, forecast the future tea prices using the most optimal model. The findings of this study will therefore inform the government and other policy makers in terms of its policy formulation regarding the tea sector in order to accord it a competitive position in the global arena. The study used univariate and multivariate forecasting techniques which do not impose co-integration restrictions such as the Autoregressive Integrated Moving Average (ARIMA) and the Vector Autoregressive (VAR). The techniques used were chosen because of their flexibility, wide acceptability and they are also easy to utilize. The study used secondary data for the Mombasa Tea Auction Centre for a period of 2009 to 2018. Augmented Dicker-Fuller (ADF) test was performed for unit root tests to check for stationary of the price series. ACF and PACF functions were estimated to assist in deciding the most appropriate orders of AR (p) and MA (q) models. AIC test was used because were considering several ARIMA models and the model with the lowest AIC was chosen. VAR model showed a high forecasting error with MAPE of 85.64% compared to that ARIMA of 9.2% for tea prices. ARIMA model performed much better than VAR model because of its high forecasting accuracy.
Rhinologic disease and its impact on sleep: a systematic review

Rhinologic disease can be responsible for systemic symptoms affecting mood, cognition, and sleep. It is unclear whether sleep disturbance in specific rhinologic disorders (chronic rhinosinusitis [CRS], rhinitis, and nasal septal deviation [NSD]) is an obstructive phenomenon or due to other mechanisms. In this review we examine the impact of CRS, rhinitis, and NSD on objective and subjective sleep outcome metrics and draw comparisons to normal controls and patients with known obstructive sleep apnea (OSA).
The Therapeutic Effects of Dodecaborate Containing Boronophenylalanine for Boron Neutron Capture Therapy in a Rat Brain Tumor Model

Simple Summary We have developed a new boron compound for application in boron neutron capture therapy (BNCT) named boronophenylalanine–amide alkyl dodecaborate (BADB). It is characterized by a larger amount of 10B per molecule, linking boronphenylalanine (BPA) and dodecaborate, and we conducted various experiments on its efficacy. Its high accumulation at the cellular level made it a promising novel drug, but it did not sufficiently accumulate in brain tumor tissue when intravenously administered. However, in neutron irradiation experiments, the drug showed remarkably high compound biological effectiveness and significantly prolonged the survival time in rat brain tumor models. We confirmed the antitumor efficacy of BADB in BNCT and its additional efficacy when administered in combination with BPA. Though this drug showed poor results when administered as a single agent, it was superior to BPA alone when administered in combination with BPA, making it a drug that we have been waiting for in our clinical practice. Abstract Background: The development of effective boron compounds is a major area of research in the study of boron neutron capture therapy (BNCT). We created a novel boron compound, boronophenylalanine–amide alkyl dodecaborate (BADB), for application in BNCT and focused on elucidating how it affected a rat brain tumor model. Methods: The boron concentration of F98 rat glioma cells following exposure to boronophenylalanine (BPA) (which is currently being utilized clinically) and BADB was evaluated, and the biodistributions in F98 glioma-bearing rats were assessed. In neutron irradiation studies, the in vitro cytotoxicity of each boron compound and the in vivo corresponding therapeutic effect were evaluated in terms of survival time. Results: The survival fractions of the groups irradiated with BPA and BADB were not significantly different. BADB administered for 6 h after the termination of convection-enhanced delivery ensured the highest boron concentration in the tumor (45.8 μg B/g). The median survival time in the BADB in combination with BPA group showed a more significant prolongation of survival than that of the BPA group. Conclusion: BADB is a novel boron compound for BNCT that triggers a prolonged survival effect in patients receiving BNCT.
Adenovirus vectored IFN-α protects mice from lethal challenge of Chikungunya virus infection

Chikungunya virus (CHIKV) is a mosquito-borne pathogen that is responsible for numerous large and geographical epidemics, causing millions of cases. However, there is no vaccine or therapeutics against CHIKV infection available. Interferon-alpha (IFN-α) has been shown to produce potent antiviral responses during viral infection. Herein we demonstrated the use of an adenovirus-vectored expressed mouse IFN-α (mDEF201) as a prophylactic and therapeutic treatment against CHIKV in vivo. 6-day-old BALB/c mice were pre- or post-treated intranasally with single dose of mDEF201 at 5 x 106 PFU per mouse and challenged with lethal dose of CHIKV. Complete survival protection was observed in mice upon a single dose of mDEF201 administration 1 days prior to virus challenge. Viral load in the serum and multiple organs were significantly reduced upon mDEF201 administration in a dose dependent manner as compare with adenovirus 5 vector placebo set. Histological analysis of the mice tissue revealed that mDEF201 could significantly reduce the tissue morphological abnormities, mainly infiltration of immune cells and muscle fibre necrosis caused by CHIKV infection. In addition, administration of mDEF201 at 6 hours post CHIKV challenge also showed promising inhibitory effect against viral replication and dissemination. In conclusion, single-dose of intranasal administration with mDEF201 as a prophylactic or therapeutic agent within 6 hours post CHIKV infection is highly protective against a lethal challenge of CHIKV in the murine model.