Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of CYP3A5 Polymorphism on Rapid Progression of Chronic Kidney Disease: A Prospective, Multicentre Study

Personalised medicine is potentially useful to delay the progression of chronic kidney disease (CKD). The aim of this study was to determine the effects of CYP3A5 polymorphism in rapid CKD progression. This multicentre, observational, prospective cohort study was performed among adult CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, who had ≥4 outpatient, non-emergency eGFR values during the three-year study period. The blood samples collected were analysed for CYP3A5*3 polymorphism. Rapid CKD progression was defined as eGFR decline of >5 mL/min/1.73 m2/year. Multiple logistic regression was then performed to identify the factors associated with rapid CKD progression. A total of 124 subjects consented to participate. The distribution of the genotypes adhered to the Hardy–Weinberg equilibrium (X2 = 0.237, p = 0.626). After adjusting for potential confounding factors via multiple logistic regression, the factors associated with rapid CKD progression were CYP3A5*3/*3 polymorphism (adjusted Odds Ratio [aOR] 4.190, 95% confidence interval [CI]: 1.268, 13.852), adjustments to antihypertensives, young age, dyslipidaemia, smoking and use of traditional/complementary medicine. CKD patients should be monitored closely for possible factors associated with rapid CKD progression to optimise clinical outcomes. The CYP3A5*3/*3 genotype could potentially be screened among CKD patients to offer more individualised management among these patients.
Associations between Parental Stress and Subsequent Changes in Dietary Intake and Quality among Preschool Children Susceptible to Obesity

Background: Cross-sectional studies indicate that parental stress may be a barrier for healthy dietary behaviours among children. However, there is a lack of evidence from longitudinal studies on the association between parental stress and changes in dietary intake among toddlers. The aim of this study was to examine the association between parental stress and changes in dietary intake and quality among preschool children susceptible to obesity. Methods: In the Healthy Start study, parents to 250 preschool children had completed a modified version of the Parental Stress Index and assessed the dietary intake of their children at baseline and after 15 months of follow up. The association between parental stress and changes in dietary intake and quality was examined using multiple linear regression analyses with adjustment for potential confounders. We tested for potential effect modification by group allocation and sex. Results: There were no significant associations between parental stress and subsequent changes in child total energy intake, intake of macronutrients or intake of fruit, vegetables, sugar sweetened beverages, fish or starch, or dietary quality. Conclusion: This study provides no evidence to support an association between parental stress and subsequent change in dietary intake and quality of their children. Trial registration: ClinicalTrials.gov, Trial number: NCT01583335, Registered: 31 March 2012, retrospectively registered.
Fungal Melanin and the Mammalian Immune System

Melanins are ubiquitous complex polymers that are commonly known in humans to cause pigmentation of our skin. Melanins are also present in bacteria, fungi, and helminths. In this review, we will describe the diverse interactions of fungal melanin with the mammalian immune system. We will particularly focus on Cryptococcus neoformans and also discuss other major melanotic pathogenic fungi. Melanin interacts with the immune system through diverse pathways, reducing the effectiveness of phagocytic cells, binding effector molecules and antifungals, and modifying complement and antibody responses.
The association between ozone and fine particles and mental health-related emergency department visits in California, 2005–2013

Recent studies suggest that air pollutant exposure may increase the incidence of mental health conditions, however research is limited. We examined the association between ozone (O3) and fine particles (PM2.5) and emergency department (ED) visits related to mental health outcomes, including psychosis, neurosis, neurotic/stress, substance use, mood/affective, depression, bipolar, schizotypal/delusional, schizophrenia, self-harm/suicide, and homicide/inflicted injury, from 2005 through 2013 in California. Air monitoring data were provided by the U.S. EPA’s Air Quality System Data Mart and ED data were provided by the California Office of Statewide Health Planning and Development. We used the time-series method with a quasi-Poisson regression, controlling for apparent temperature, day of the week, holidays, and seasonal/long-term trends. Per 10 parts per billion increase, we observed significant cumulative 7-day associations between O3 and all mental health [0.64%, 95% confidence interval (CI): 0.21, 1.07], depression [1.87%, 95% CI: 0.62, 3.15], self-harm/suicide [1.43%, 95% CI: 0.35, 2.51], and bipolar [2.83%, 95% CI: 1.53, 4.15]. We observed 30-day lag associations between O3 and neurotic disorder [1.22%, 95% CI: 0.48, 1.97] and homicide/inflicted injury [2.01%, 95% CI: 1.00, 3.02]. Same-day mean PM2.5 was associated with a 0.42% [95% CI: 0.14, 0.70] increase in all mental health, 1.15% [95% CI: 0.62, 1.69] increase in homicide/inflicted injury, and a 0.57% [95% CI: 0.22, 0.92] increase in neurotic disorders per 10 μg/m3 increase. Other outcomes not listed here were not statistically significant for O3 or PM2.5. Risk varied by age group and was generally greater for females, Asians, and Hispanics. We also observed seasonal variation for outcomes including but not limited to depression, bipolar, schizophrenia, self-harm/suicide, and homicide/inflicted injury. Ambient O3 or PM2.5 may increase the risk of mental health illness, though underlying biological mechanisms remain poorly understood. Findings warrant further investigation to better understand the impacts of air pollutant exposure among vulnerable groups.
Chronic–Progressive Dopaminergic Deficiency Does Not Induce Midbrain Neurogenesis

Background: Consecutive adult neurogenesis is a well-known phenomenon in the ventricular–subventricular zone of the lateral wall of the lateral ventricles (V–SVZ) and has been controversially discussed in so-called “non-neurogenic” brain areas such as the periventricular regions (PVRs) of the aqueduct and the fourth ventricle. Dopamine is a known modulator of adult neural stem cell (aNSC) proliferation and dopaminergic neurogenesis in the olfactory bulb, though a possible interplay between local dopaminergic neurodegeneration and induction of aNSC proliferation in mid/hindbrain PVRs is currently enigmatic. Objective/Hypothesis: To analyze the influence of chronic–progressive dopaminergic neurodegeneration on both consecutive adult neurogenesis in the PVRs of the V–SVZ and mid/hindbrain aNSCs in two mechanistically different transgenic animal models of Parkinson´s disease (PD). Methods: We used Thy1-m[A30P]h α synuclein mice and Leu9′Ser hypersensitive α4* nAChR mice to assess the influence of midbrain dopaminergic neuronal loss on neurogenic activity in the PVRs of the V–SVZ, the aqueduct and the fourth ventricle. Results: In both animal models, overall proliferative activity in the V–SVZ was not altered, though the proportion of B2/activated B1 cells on all proliferating cells was reduced in the V–SVZ in Leu9′Ser hypersensitive α4* nAChR mice. Putative aNSCs in the mid/hindbrain PVRs are known to be quiescent in vivo in healthy controls, and dopaminergic deficiency did not induce proliferative activity in these regions in both disease models. Conclusions: Our data do not support an activation of endogenous aNSCs in mid/hindbrain PVRs after local dopaminergic neurodegeneration. Spontaneous endogenous regeneration of dopaminergic cell loss through resident aNSCs is therefore unlikely.
Forgetting Unwanted Memories: Active Forgetting and Implications for the Development of Psychological Disorders

Intrusive memories are a common feature of many psychopathologies, and suppression-induced forgetting of unwanted memories appears as a critical ability to preserve mental health. In recent years, biological and cognitive studies converged in revealing that forgetting is due to active processes. Recent neurobiological studies provide evidence on the active role of main neurotransmitter systems in forgetting, suggesting that the brain actively works to suppress retrieval of unwanted memories. On the cognitive side, there is evidence that voluntary and involuntary processes (here termed “intentional” and “incidental” forgetting, respectively) contribute to active forgetting. In intentional forgetting, an inhibitory control mechanism suppresses awareness of unwanted memories at encoding or retrieval. In incidental forgetting, retrieval practice of some memories involuntarily suppresses the retrieval of other related memories. In this review we describe recent findings on deficits in active forgetting observed in psychopathologies, like post-traumatic stress disorder, depression, schizophrenia, and obsessive-compulsive disorder. Moreover, we report studies in which the role of neurotransmitter systems, known to be involved in the pathogenesis of mental disorders, has been investigated in active forgetting paradigms. The possibility that biological and cognitive mechanisms of active forgetting could be considered as hallmarks of the early onset of psychopathologies is also discussed.
Effectiveness of Epidemic Preventive Policies and Hospital Strategies in Combating COVID-19 Outbreak in Taiwan

(1) Background: The implementation of effective control measures in a timely fashion is crucial to control the epidemic outbreak of COVID-19. In this study, we aimed to analyze the control measures implemented during the COVID-19 outbreak, as well as evaluating the responses and outcomes at different phases for epidemic control in Taiwan. (2) Methods: This case study reviewed responses to COVID-19 and the effectiveness of a range of control measures implemented for epidemic control in Taiwan and assessed all laboratory-confirmed cases between 11 January until 20 December 2020, inclusive of these dates. The confirmation of COVID-19 infection was defined as the positive result of a reverse-transcriptase–polymerase-chain-reaction test taken from a nasopharyngeal swab. Test results were reported by the Taiwan Centers for Disease Control. The incidence rate, mortality rate, and testing rate were compiled, and the risk ratio was provided to gain insights into the effectiveness of prevention measures. (3) Results and Discussion: This study presents retrospective data on the COVID-19 incidence rate in Taiwan, combined with the vital preventive control measures, in a timeline of the early stage of the epidemic that occurred in Taiwan. The implementation of multiple strategy control measures and the assistance of technologies to control the COVID-19 epidemic in Taiwan led to a relatively slower trend in the outbreak compared to the neighboring countries. In Taiwan, 766 confirmed patients were included, comprised of 88.1% imported cases and 7.2% local transmission cases, within the studied period. The incidence rate of COVID-19 in Taiwan during the studied period was 32 per million people, with a mortality rate of 0.3 per million people. Our analysis showed a significantly raised incidence risk ratio in the countries of interest in comparison to Taiwan during the study period; in the range of 1.9 to 947.5. The outbreak was brought under control through epidemic policies and hospital strategies implemented by the Taiwan Government. (4) Conclusion: Taiwan’s preventive strategies resulted in a drastically lower risk for Taiwan nationals of contracting COVID-19 when new pharmaceutical drug or vaccines were not yet available. The preventive strategies employed by Taiwan could serve as a guide and reference for future epidemic control strategies.
Structural Characterization, Antimicrobial Activity and BSA/DNA Binding Affinity of New Silver(I) Complexes with Thianthrene and 1,8-Naphthyridine

Three new silver(I) complexes [Ag(NO3)(tia)(H2O)]n (Ag1), [Ag(CF3SO3)(1,8-naph)]n (Ag2) and [Ag2(1,8-naph)2(H2O)1.2](PF6)2 (Ag3), where tia is thianthrene and 1,8-naph is 1,8-naphthyridine, were synthesized and structurally characterized by different spectroscopic and electrochemical methods and their crystal structures were determined by single-crystal X-ray diffraction analysis. Their antimicrobial potential was evaluated against four bacterial and three Candida species, and the obtained results revealed that these complexes showed significant activity toward the Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and the investigated Candida species with minimal inhibitory concentration (MIC) values in the range 1.56–7.81 μg/mL. On the other hand, tia and 1,8-naph ligands were not active against the investigated strains, suggesting that their complexation with Ag(I) ion results in the formation of antimicrobial compounds. Moreover, low toxicity of the complexes was detected by in vivo model Caenorhabditis elegans. The interaction of the complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate their binding affinity towards these biomolecules for possible insights into the mode of antimicrobial activity. The binding affinity of Ag1–3 to BSA was higher than that for DNA, indicating that proteins could be more favorable binding sites for these complexes in comparison to the nucleic acids.
Development of an assessment measure for sexual disinhibition in dementia

Sexual disinhibition (SD), a neuropsychiatric symptom characterized by sexually inappropriate comments and/or behaviors, remains under identified in dementia, possibly due to a lack of standardized assessment methods. A recent systematic review of measures used to assess SD proposed four behavioral domains and identified the need for a population‐specific measure. The present study addressed this by examining the underlying factor structure of SD to create a new caregiver‐report measure.
Mechanosensitive Pathways in Heart Development: Findings from Chick Embryo Studies

The heart is the first organ that starts to function in a developing embryo. It continues to undergo dramatic morphological changes while pumping blood to the rest of the body. Genetic regulation of heart development is partly governed by hemodynamics. Chick embryo is a major animal model that has been used extensively in cardiogenesis research. To reveal mechanosensitive pathways, a variety of surgical interferences and chemical treatments can be applied to the chick embryo to manipulate the blood flow. Such manipulations alter expressions of mechanosensitive genes which may anticipate induction of morphological changes in the developing heart. This paper aims to present different approaches for generating clinically relevant disturbed hemodynamics conditions using this embryonic chick model and to summarize identified mechanosensitive genes using the model, providing insights into embryonic origins of congenital heart defects.
Granulibacter bethesdensis, a Pathogen from Patients with Chronic Granulomatous Disease, Produces a Penta-Acylated Hypostimulatory Glycero-D-talo-oct-2-ulosonic Acid–Lipid A Glycolipid (Ko-Lipid A)

Granulibacter bethesdensis can infect patients with chronic granulomatous disease, an immunodeficiency caused by reduced phagocyte NADPH oxidase function. Intact G. bethesdensis (Gb) is hypostimulatory compared to Escherichia coli, i.e., cytokine production in human blood requires 10–100 times more G. bethesdensis CFU/mL than E. coli. To better understand the pathogenicity of G. bethesdensis, we isolated its lipopolysaccharide (GbLPS) and characterized its lipid A. Unlike with typical Enterobacteriaceae, the release of presumptive Gb lipid A from its LPS required a strong acid. NMR and mass spectrometry demonstrated that the carbohydrate portion of the isolated glycolipid consists of α-Manp-(1→4)-β-GlcpN3N-(1→6)-α-GlcpN-(1⇿1)-α-GlcpA tetra-saccharide substituted with five acyl chains: the amide-linked N-3′ 14:0(3-OH), N-2′ 16:0(3-O16:0), and N-2 18:0(3-OH) and the ester-linked O-3 14:0(3-OH) and 16:0. The identification of glycero-d-talo-oct-2-ulosonic acid (Ko) as the first constituent of the core region of the LPS that is covalently attached to GlcpN3N of the lipid backbone may account for the acid resistance of GbLPS. In addition, the presence of Ko and only five acyl chains may explain the >10-fold lower proinflammatory potency of GbKo–lipidA compared to E. coli lipid A, as measured by cytokine induction in human blood. These unusual structural properties of the G.bethesdensis Ko–lipid A glycolipid likely contribute to immune evasion during pathogenesis and resistance to antimicrobial peptides.
Production of Pyracantha Polysaccharide-Iron(III) Complex and Its Biologic Activity

In this study, the optimum synthetic process of the Pyracantha polysaccharide-iron (PPI) complex was studied via response surface methodology (RSM). Its antioxidant and anti-cancer activities were also investigated. It was demonstrated that the optimal conditions for the synthetic process of the complex were as follows: a pH of 8.9, a reaction temperature of 70 °C and a trisodium citrate:polysaccharide ratio of 1:2. PPI were analysis by UV, FTIR, SEM, CD, XRD, TGA and NMR. PPI was able to scavenge the metal ion, ABTS and free radicals of the superoxide anion, demonstrating its potential antioxidant activity. PPI was found to display cytotoxicity to Skov3 cells, as shown by its ability to induce apoptosis and alter gene expression in Skov3 cells. These findings show than PPI may represent a novel antioxidant and chemotherapeutic drug.
Evaluation of muscle lipid extraction and non-lethal fin tissue use for carbon, nitrogen, and sulfur isotope analyses in adult salmonids.

RATIONALE Chemical lipid extraction or using alternative tissues such as fish fin as opposed to muscle may alter isotopic ratios and influence interpretations of δ13 C, δ15 N, and previously unassessed δ34 S values in stable isotope analyses (SIA). Our objectives were to determine if lipid extraction alters these isotope ratios in muscle, if lipid normalization models can be used for lipid rich salmonids, and if fin isotope ratios are comparable with those of muscle in adult salmonids. METHODS In six adult salmonid species (n = 106) collected from Lake Ontario, we compared three isotope ratios in lipid extracted (LE) muscle with bulk muscle, and LE muscle with fin tissue, with paired t-tests and linear regressions. We compared differences between δ13 C values in LE and bulk muscle with predicted values from lipid normalization models and the log-linear model of best fit and determined model efficiency. RESULTS The δ15 N values in LE muscle increased (<1 ‰) relative to bulk muscle for most salmonids, with relationships nearing 1:1. There were either no differences or strong 1:1 relationships in δ34 S values between species-specific bulk and LE muscle. One lipid normalization model had greater model efficiency (97%) than the model of best fit (94%). Fin had higher δ13 C values than LE muscle while δ15 N trends varied (<1 ‰); however, both isotope ratios had either no or weak linear relationships with fin and LE muscle within species. The δ34 S values in fin were similar to those in LE muscle and had strong, 1:1 relationships across species. CONCLUSIONS We recommend using the lipid normalization model to adjust for δ13 C values in lipid-rich muscle (C:N >3.4). LE muscle could be used without δ15 N or δ34 S adjustments, but the minimal increase in δ15 N values may affect SIA interpretation. With high unexplained variability among adult species in fin-muscle δ13 C and δ15 N relationships, species-specific fin-muscle adjustments are warranted. No fin-muscle tissue adjustment would be required for δ34 S values.
Effects of Early Rehydration on Brain Perfusion and Infarct Core after Middle Cerebral Artery Occlusion in Rats

Imaging evidence for the effect of rehydration on cerebral perfusion and brain ischemia has never been proposed in the literature. This study aimed to test the hypothesis that early rehydration treatment can improve cerebral perfusion and decrease infarct volume, consequently reducing mortality of dehydrated stroke animals. Methods: Thirty dehydrated experimental rats were randomly assigned to either a rehydration or control group after middle cerebral artery occlusion (MCAO). Diffusion-weighted imaging and dynamic contrast enhancement perfusion imaging were performed at 30 min and 6 h after MCAO using a 9.4T MR imaging scanner to measure the infarct volume and brain perfusion. Results: The survival rates after the first MRI scan were 91.7% for the rehydration group and 58.3% for the control group (p = 0.059). The survival rates after the second MRI scan were 66.7% for the rehydration group, and 8.3% of the control group survived (p = 0.003). The infarct volume of the rehydration group was significantly smaller than control group at 30 min after MCAO (p = 0.007). The delay time and time to maximum were significantly shorter in the rehydration group at 30 min (p = 0.004 and 0.035, respectively). Conclusions: The findings suggest that early rehydration therapy can decrease the infarct volume, shorten the delay time of cerebral perfusion, and increase survival of dehydrated ischemic-stroke rats. This preliminary study provided imaging evidence that more intensive early hydration therapies and reperfusion strategies may be necessary for acute stroke patients with dehydrated status.
MicroRNAs, Long Non-Coding RNAs, and Circular RNAs: Potential Biomarkers and Therapeutic Targets in Pheochromocytoma/Paraganglioma

Simple Summary Pheochromocytomas/paragangliomas (PPGL) are rare tumors originating from chromaffin tissues. Around 40% of pheochromocytomas/paragangliomas (PPGL) harbor germline mutations, representing the highest heritability among human tumors. Unfortunately, there are no available molecular markers for the metastatic potential of these tumors, and the prognosis of metastatic forms is rather dismal. In this review, we present the potential relevance of non-coding RNA molecules including microRNAs, long non-coding RNAs and circular RNAs in PPGL pathogenesis and diagnosis. The pathomechanisms presented might also represent potential novel therapeutic targets. Abstract Around 40% of pheochromocytomas/paragangliomas (PPGL) harbor germline mutations, representing the highest heritability among human tumors. All PPGL have metastatic potential, but metastatic PPGL is overall rare. There is no available molecular marker for the metastatic potential of these tumors, and the diagnosis of metastatic PPGL can only be established if metastases are found at “extra-chromaffin” sites. In the era of precision medicine with individually targeted therapies and advanced care of patients, the treatment options for metastatic pheochromocytoma/paraganglioma are still limited. With this review we would like to nurture the idea of the quest for non-coding ribonucleic acids as an area to be further investigated in tumor biology. Non-coding RNA molecules encompassing microRNAs, long non-coding RNAs, and circular RNAs have been implicated in the pathogenesis of various tumors, and were also proposed as valuable diagnostic, prognostic factors, and even potential treatment targets. Given the fact that the pathogenesis of tumors including pheochromocytomas/paragangliomas is linked to epigenetic dysregulation, it is reasonable to conduct studies related to their epigenetic expression profiles and in this brief review we present a synopsis of currently available findings on the relevance of these molecules in these tumors highlighting their diagnostic potential.