Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysregulated Long Non-coding RNAs in Parkinson’s Disease Contribute to the Apoptosis of Human Neuroblastoma Cells

The molecular mechanism underlying Parkinson’s disease (PD), an increasingly common neurodegenerative disease, remains unclear. Long non-coding RNA (lncRNA) plays essential roles in gene expression and human diseases. We hypothesize that lncRNAs are involved in neuronal degeneration of PD. Using microarray, we identified 122 differentially expressed (DE) lncRNAs and 48 DE mRNAs between the circulating leukocytes from PD patients and healthy controls. There were 714 significant correlations (r ≥ 0.8 or ≤−0.8, p < 0.05) among the DE lncRNAs and mRNAs. Gene function and pathway analysis of the 48 DE mRNAs revealed biological pathways related to PD pathogenesis, including immune response, inflammatory response, MAPK, and Jak-STAT pathway. In a cohort of 72 PD patients and 22 healthy controls, the upregulation of four lncRNAs (AC131056.3-001, HOTAIRM1, lnc-MOK-6:1, and RF01976.1-201) in circulating leukocytes of PD patients were further confirmed. These lncRNAs were also upregulated in THP-1 cells, a human monocytic cell line, after inflammatory stimulation. Interestingly, the conditioned culture medium of THP-1 cells or 6-OHDA significantly increased the expression of these lncRNAs in SH-SY5Y cells, a human neuroblastoma cell line expressing dopaminergic markers. Importantly, overexpression of AC131056.3-001 or HOTAIRM1 increased baseline and 6-OHDA-induced apoptosis of SH-SY5Y cells. Taken together, we identified distinct expression profiles of lncRNA and mRNA in circulating leukocytes between PD patients and healthy controls. Dysregulated lncRNAs such as HOTAIRM1 and AC131056.3-001 may contribute to PD pathogenesis by promoting the apoptosis of dopaminergic neuron.
Religious Affiliation and Marital Satisfaction: Commonalities Among Christians, Muslims, and Atheists

Scientists have long been interested in the relationship between religion and numerous aspects of people’s lives, such as marriage. This is because religion may differently influence one’s level of happiness. Some studies have suggested that Christians have greater marital satisfaction, while others have found evidence that Muslims are more satisfied. Additionally, less-religious people have shown the least marital satisfaction. In the present study, we examined marital satisfaction among both sexes, and among Muslims, Christians, and atheists, using a large, cross-cultural sample from the dataset in Sorokowski et al. (2017). Our results show that men have higher marital satisfaction ratings than women, and that levels of satisfaction do not differ notably among Muslims, Christians, and atheists. We discuss our findings in the context of previous research on the association between marriage and religion.
The relationship between weight gain in exclusively breastfed babies and maternal diet

Objectives: To determine the relationship between maternal nutrition and their breastfed infants' anthropometric measures during the first 14 weeks after delivery. Methods: A prospective, observational study, comprising 200 mothers and their infants. The weight, length, and head circumference of the infants and the weight and dietary intake of the mothers were recorded at 6, 10, and 14 weeks. Results: The relationship between weight gain in babies and calorie intake at 6, 10, and 14 weeks were significant (P value < 0.05). The relationship between weight gain in babies and protein intake at 6 and 10 weeks was not significant (P value at 6 weeks = 0.896, P value at 10 weeks = 0.127) but was significant at 14 weeks (<0.05). Mothers' weight gain during 14 weeks was significant (P value < 0.05). When mothers were distributed into four groups according to their calorie and protein intake for comparison (median value: calorie-2034 kilocalorie, protein- 78.7 grams), the weight, length and head circumference gain in infants and mothers' weight were significantly higher in Group I and Group II compared to Group III and Group IV with P value < 0.05 at 6, 10, and 14 weeks. Conclusions: Calorie intake was low in mothers when compared to RDA recommendations. Infants showed lower weight, length, and head circumference gain than WHO Child Growth Standards. There is a direct relationship between the maternal diet and anthropometric measures of their infants. During postnatal period, mothers showed an increase in weight, rather than the decrease that is usually expected.
Effects of regional differences and demography in modelling foot-and-mouth disease in cattle at the national scale

Foot-and-mouth disease (FMD) is a fast-spreading viral infection that can produce large and costly outbreaks in livestock populations. Transmission occurs at multiple spatial scales, as can the actions used to control outbreaks. The US cattle industry is spatially expansive, with heterogeneous distributions of animals and infrastructure. We have developed a model that incorporates the effects of scale for both disease transmission and control actions, applied here in simulating FMD outbreaks in US cattle. We simulated infection initiating in each of the 3049 counties in the contiguous US, 100 times per county. When initial infection was located in specific regions, large outbreaks were more likely to occur, driven by infrastructure and other demographic attributes such as premises clustering and number of cattle on premises. Sensitivity analyses suggest these attributes had more impact on outbreak metrics than the ranges of estimated disease parameter values. Additionally, although shipping accounted for a small percentage of overall transmission, areas receiving the most animal shipments tended to have other attributes that increase the probability of large outbreaks. The importance of including spatial and demographic heterogeneity in modelling outbreak trajectories and control actions is illustrated by specific regions consistently producing larger outbreaks than others.
Coupling and Regulation of Porous Carriers Using Plasma and Amination to Improve the Catalytic Performance of Glucose Oxidase and Catalase

Multiple enzyme systems are being increasingly used for their high-efficiency and co-immobilization is a key technology to lower the cost and improve the stability of enzymes. In this study, poly glycidyl methacrylate (PGMA) spheres were synthesized using suspension polymerization, and were used as a support to co-immobilize glucose oxidase (GOx) and catalase (CAT). Surface modification was carried out via a combination of plasma and amination to promote the properties of the catalyzer. The co-immobilized enzymes showed a more extensive range of optimum pH and temperature from 5.5 to 7.5 and 25 to 40°C, respectively, compared to free enzymes. Furthermore, the maximum activity and protein adsorption quantity of the co-immobilized enzymes reached 25.98 U/g and 6.07 mg/g, respectively. The enzymatic activity of the co-immobilized enzymes was maintained at ~70% after storage for 5 days and at 82% after three consecutive cycles, indicating that the immobilized material could be applied industrially.
Baroreflex Sensitivity Predicts Response to Metoprolol in Children With Vasovagal Syncope: A Pilot Study

Objective: To explore the role of baroreflex sensitivity (BRS) in the head-up tilt test (HUTT) in predicting the therapeutic response of vasovagal syncope (VVS) patients to metoprolol. Materials and Methods: Vasovagal syncope patients treated with metoprolol were enrolled in this study and were classified as responders or non-responders according to changes in their symptom scores before and after metoprolol treatment. Values of BRS in the supine position and at positive response occurrence in the HUTT were obtained, and BRS changes from supine to positive response occurrence were calculated. Differences between responders and non-responders were analyzed. Receiver operating characteristic curve analysis was performed to assess the value of BRS for predicting the therapeutic efficacy of metoprolol in pediatric patients with VVS. Results: Forty patients (14 boys; 11.8 ± 2.5 years) diagnosed with VVS were recruited in the study, 28 of whom were verified to be responders to metoprolol and 12 of whom were verified as non-responders. They did not show any differences in baseline characteristics and hemodynamics in the HUTT (p > 0.05). However, the responders had an obviously increased supine BRS value compared to the non-responders (16.9 ± 7.7 ms/mmHg vs. 7.6 ± 3.8 ms/mmHg; p < 0.01). No difference in BRS at positive response occurrence was observed between the two groups (8.9 ± 8.5 ms/mmHg vs. 10.6 ± 9.8 ms/mmHg; p > 0.05). Accordingly, the changes in the BRS of responders were more obvious than in non-responders (8.0 ± 7.8 ms/mmHg vs. −3.0 ± 10.4 ms/mmHg; p < 0.01). The area under the receiver operating characteristic curve for the predictive value of supine BRS was 0.887 (95% CI, 0.779–0.995; p < 0.01). A cut-off value of 10 ms/mmHg yielded a sensitivity and specificity of 82 and 83%, respectively, in predicting the therapeutic efficacy of metoprolol in pediatric VVS patients. The area under the receiver operating characteristic curve for the predictive value of BRS changes was 0.827 (95% CI, 0.693–0.962; p < 0.01). A cut-off value of 4 ms/mmHg yielded a sensitivity and specificity of 71 and 83%, respectively. Conclusion: Baroreflex sensitivity may predict the response of children with VVS to metoprolol.
Do Stretch-Shortening Cycles Really Occur in the Medial Gastrocnemius? A Detailed Bilateral Analysis of the Muscle-Tendon Interaction During Jumping

The effect of stretch-shortening cycles (SSCs) is often studied in laboratory settings, yet it remains unclear whether highly active muscle SSCs actually occur during in vivo movement. Nine highly trained jumping athletes performed single-leg pre-hop forward jumps at maximal effort. We hypothesized that these jumps would induce a SSC at the level of the muscle in the medial gastrocnemius. Kinematic and kinetic data were collected together with electromyography signals (EMG) and muscle fascicle length and pennation angle changes of the medial gastrocnemius of both legs and combined with a musculoskeletal model to calculate the stretch-shortening behavior of the muscle (fascicles) and tendon (series-elastic element). The length changes of the fascicles, longitudinal muscle displacement, series-elastic element, and whole muscle-tendon unit further allowed for a detailed analysis of the architectural gearing ratio between different phases of the SSC within a single movement. We found a SSC at the level of the joint, muscle-tendon unit and tendon but not at the muscle. We further found that the average architectural gearing ratio was higher during the stretching of the series-elastic element as compared to when the series-elastic element was shortening, yet this was not statistically tested because of low sample size for this parameter. However, we found no correlation when plotting the architectural gearing ratio as a function of the fascicle velocities at each instance in time. Despite the athletes having a clear preferred leg for jumping, we found no differences in any kinematic or kinetic parameter between the preferred and non-preferred leg or any parameter from the muscle-tendon interaction analysis other than a reduced longitudinal muscle shortening in the non-preferred leg (p = 0.008). We conclude that, although common at the level of the joints, MTUs, and tendon (series-elastic element), highly active SSCs very rarely occur in the medial gastrocnemius, even in movements that induce high loading. This has important implications for the translation of ex vivo findings on SSC effects, such as residual force enhancement, in this muscle. We further conclude that there is no precise tuning of the architectural gearing ratio in the medial gastrocnemius throughout the whole movement.
Curious case of primary pulmonary mucoepidermoid carcinoma

Pulmonary mucoepidermoid carcinoma (MEC) is an uncommon tumor constituting only 0.1% to 0.2% of all lung carcinoma. It is classified under “salivary gland type” tumors in the World Health Organization (WHO) classification of lung cancers. It generally carries a better prognosis than the more common small cell and nonsmall cell lung carcinomas. It is pathologically classified into high-grade and low-grade tumors. High-grade tumors are usually unresectable at presentation. However, surgery is the mainstay of treatment, which aims at surgically negative margins for a complete cure. In our patient, pulmonary MEC presented with intrathoracic mass with pericardial effusion. It came out to be low-grade neoplasm, which was treated with platinum-based doublet chemotherapy and responded well with near-total disappearance of tumor, like a vanishing lung tumor.
Population Structure and Genetic Diversity of Sheep Breeds in the Kyrgyzstan

Sheep are a main livestock species of Kyrgyzstan, a Central Asian country with predominating mountain terrain. The current gene pool of local sheep resources has been forming under diverse climate conditions from the era of the trading caravans of the Great Silk Road, through the Soviet period of large-scale livestock improvements, which was followed by the deep crisis at the end of the 20th century, up to now. However, not much is known about the genetic background and variability of the local sheep populations. Therefore, our aims were to provide a characterization of the population structure and genetic relations within the Kyrgyz sheep breeds and to study their genetic connections with the global sheep breeds using SNP analysis. Samples of the Alai (n = 31), Gissar (n = 30), Kyrgyz coarse wool (n = 13), Aykol (n = 31), and Tien-Shan (n = 24) breeds were genotyped with the OvineSNP50 BeadChip or the Ovine Infinium HD BeadChip (Illumina Inc., USA). The measure of inbreeding based on runs of homozygosity showed a minimum value in the Aykol breed (FROH = 0.034), while the maximum was found in the Alai breed (FROH = 0.071). Short ROH segments (ROH ≤ 4 Mb) were predominant in all breeds. Long ROH segments (ROH > 16 Mb) were absent in the Gissar breed. The Gissar and Aykol breeds had the highest values of the effective population sizes estimated for five generations ago (Ne5 = 660 and 563), whereas the Alai and Kyrgyz coarse wool displayed lower values (Ne5 = 176 and 128, respectively). The synthetic origin of the Aykol breed was clearly evidenced by all analyses applied. Based on the network and admixture analyses of the Kyrgyz and global sheep breeds, the Tien-Shan and the Russian semi-fine wool breeds demonstrated a common ancestry that most likely is due to a contribution of the Lincoln breed. The Gissar, Aykol, and Kyrgyz coarse wool breeds showed a genetic background predominating in sheep populations from Iran and China whereas the Alai demonstrated the different ancestry type. The revealed admixture patterns probably resulted from the exchange and trade during the era of the Great Silk Road, which partly overlapped with historical and archeological findings.
High-Throughput Screening of a 2-Keto-L-Gulonic Acid-Producing Gluconobacter oxydans Strain Based on Related Dehydrogenases

High-throughput screening is a powerful tool for discovering strains in the natural environment that may be suitable for target production. Herein, a novel enzyme-based high-throughput screening method was developed for rapid screening of strains overproducing 2-keto-L-gulonic acid (2-KLG). The screening method detects changes in the fluorescence of reduced nicotinamide adenine dinucleotide (NADH) at 340 nm using a microplate reader when 2-KLG is degraded by 2-KLG reductase. In this research, three different 2-KLG reductases were expressed, purified, and studied. The 2-KLG reductase from Aspergillus niger were selected as the best appropriate reductase to establishment the method for its high activity below pH 7. Using the established method, and coupled with fluorescence-activated cell sorting, we achieved a high 2-KLG-producing strain of Gluconobacter oxydans WSH-004 from soil. When cultured with D-sorbitol as the substrate, the 2-KLG yield was 2.5 g/L from 50 g/L D-sorbitol without any side products. Compared with other reported screening methods, our enzyme-based method is more efficient and accurate for obtaining high-producing 2-KLG strains, and it is also convenient and cost-effective. The method is broadly applicable for screening keto acids and other products that can be oxidized via nicotinamide adenine dinucleotide (NAD+) or nicotinamide adenine dinucleotide phosphate (NADP+).
Predisposition to Apoptosis in Hepatocellular Carcinoma: From Mechanistic Insights to Therapeutic Strategies

Hepatocellular carcinoma (HCC) ranks among the most rapidly evolving cancers in the Western world. The majority of HCCs develop on the basis of a chronic inflammatory liver damage that predisposes liver cancer development and leads to deregulation of multiple cellular signaling pathways. The resulting dysbalance between uncontrolled proliferation and impaired predisposition to cell death with consecutive failure to clear inflammatory damage is a key driver of malignant transformation. Therefore, resistance to death signaling accompanied by metabolic changes as well as failed immunological clearance of damaged pre-neoplastic hepatocytes are considered hallmarks of hepatocarcinogenesis. Hereby, the underlying liver disease, the type of liver damage and individual predisposition to apoptosis determines the natural course of the disease as well as the therapeutic response. Here, we will review common and individual aspects of cell death pathways in hepatocarcinogenesis with a particular emphasis on regulatory networks and key molecular alterations. We will further delineate the potential of targeting cell death-related signaling as a viable therapeutic strategy to improve the outcome of HCC patients.
A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD

Background: Individuals with post-traumatic stress disorder (PTSD) have a heightened sensitivity to subsequent stressors, addictive drugs, and symptom recurrence, a form of behavioral sensitization. N-methyl-D-aspartate receptors (NMDARs) are involved in the establishment and activation of sensitized behavior. Objective: We describe a protocol of a randomized placebo-controlled Phase 1b proof-of-mechanism trial to examine target engagement, safety, tolerability, and possible efficacy of the NMDAR antagonist lanicemine in individuals with symptoms of PTSD (Clinician Administered PTSD Scale [CAPS-5] score ≥ 25) and evidence of behavioral sensitization measured as enhanced anxiety-potentiated startle (APS; T-score ≥ 2.8). Methods: Subjects (n = 24; age range 21–65) receive three 60-min intravenous infusions of placebo or 100 mg lanicemine over 5 non-consecutive days. Primary endpoint is change in APS from pre-treatment baseline to after the third infusion. NMDAR engagement is probed with resting state EEG gamma band power, 40 Hz auditory steady state response, the mismatch negativity amplitude, and P50 sensory gating. Change in CAPS-5 scores is an exploratory clinical endpoint. Bayesian statistical methods will evaluate endpoints to determine suitability of this agent for further study. Conclusion: In contrast to traditional early-phase trials that use symptom severity to track treatment efficacy, this study tracks engagement of the study drug on expression of behavioral sensitization, a functional mechanism likely to cut across disorders. This experimental therapeutics design is consistent with recent NIMH-industry collaborative studies, and could serve as a template for testing novel pharmacological agents in psychiatry. Clinical Trial Registration: www.ClinicalTrials. gov, identifier NCT03166501.
Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: Towards an Individualized Approach

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder featuring repetitive intrusive thoughts and behaviors associated with a significant handicap. Of patients, 20% are refractory to medication and cognitive behavioral therapy. Refractory OCD is associated with suicidal behavior and significant degradation of social and professional functioning, with high health costs. Deep brain stimulation (DBS) has been proposed as a reversible and controllable method to treat refractory patients, with meta-analyses showing 60% response rate following DBS, whatever the target: anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), nucleus accumbens (NAcc), anteromedial subthalamic nucleus (amSTN), or inferior thalamic peduncle (ITP). But how do we choose the “best” target? Functional neuroimaging studies have shown that ALIC-DBS requires the modulation of the fiber tract within the ventral ALIC via the ventral striatum, bordering the bed nucleus of the stria terminalis and connecting the medial prefrontal cortex with the thalamus to be successful. VC/VS effective sites of stimulation were found within the VC and primarily connected to the medial orbitofrontal cortex (OFC) dorsomedial thalamus, amygdala, and the habenula. NAcc-DBS has been found to reduce OCD symptoms by decreasing excessive fronto-striatal connectivity between NAcc and the lateral and medial prefrontal cortex. The amSTN effective stimulation sites are located at the inferior medial border of the STN, primarily connected to lateral OFC, dorsal anterior cingulate, and dorsolateral prefrontal cortex. Finally, ITP-DBS recruits a bidirectional fiber pathway between the OFC and the thalamus. Thus, these functional connectivity studies show that the various DBS targets lie within the same diseased neural network. They share similar efficacy profiles on OCD symptoms as estimated on the Y-BOCS, the amSTN being the target supported by the strongest evidence in the literature. VC/VS-DBS, amSTN-DBS, and ALIC-DBS were also found to improve mood, behavioral adaptability and potentially both, respectively. Because OCD is such a heterogeneous disease with many different symptom dimensions, the ultimate aim should be to find the most appropriate DBS target for a given refractory patient. This quest will benefit from further investigation and understanding of the individual functional connectivity of OCD patients.