Miracle-dz/UniFAR-FTUs huggingface dataset:
Is the Phenylalanine-Restricted Diet a Risk Factor for Overweight or Obesity in Patients with Phenylketonuria (PKU)? A Systematic Review and Meta-Analysis

Although there is a general assumption that a phenylalanine (Phe)-restricted diet promotes overweight in patients with phenylketonuria (PKU), it is unclear if this presumption is supported by scientific evidence. This systematic review aimed to determine if patients with PKU are at a higher risk of overweight compared to healthy individuals. A literature search was carried out on PubMed, Cochrane Library, and Embase databases. Risk of bias of individual studies was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and the quality of the evidence for each outcome was assessed using the NutriGrade scoring system. From 829 articles identified, 15 were included in the systematic review and 12 in the meta-analysis. Body mass index (BMI) was similar between patients with PKU and healthy controls, providing no evidence to support the idea that a Phe-restricted diet is a risk factor for the development of overweight. However, a subgroup of patients with classical PKU had a significantly higher BMI than healthy controls. Given the increasing prevalence of overweight in the general population, patients with PKU require lifelong follow-up, receiving personalised nutritional counselling, with methodical nutritional status monitoring from a multidisciplinary team in inherited metabolic disorders.
Secular Trends in Dietary Intake over a 20-Year Period in People with Type 2 Diabetes in Japan: A Comparative Study of Two Nationwide Registries; Japan Diabetes Complications Study (JDCS) and Japan Diabetes Clinical Data Management Study (JDDM)

Background: In order to provide effective dietary guidance, it is necessary to consider dietary intake, which can change over time. This study analyzed changes in the diet of Japanese patients with type 2 diabetes over a 20-year period. Methods: We compared the results of two dietary surveys that used the food frequency questionnaire format. The first was conducted in 1996 by the Japan Diabetes Complications Study (JDCS) (n = 1509; males 53.3%), and the second in 2014–2018 by the Japan Diabetes Clinical Data Management Study (JDDM) (n = 1145; males 65.6%). Both are nationwide representative registries of outpatients with type 2 diabetes in Japan. Results: Over a 20-year period, both men and women with type 2 diabetes had a significant increase in body mass index (BMI). Nonetheless, there was only a small change in energy intake. Conversely, there was a significant increase in fat intake and thus in the fat-to-energy ratio. With regard to food groups, there was a significant increase in meat intake and a decrease in the intake of fish, soybeans/soy products, vegetables, and fruits, with a particularly significant decrease in vegetables. Conclusions: Even in Japan, an industrialized country with a stable socioeconomic environment, there were many significant changes in the dietary intake of patients with type 2 diabetes over the 20-year period.
Waning of Maternal Antibodies against Measles Suggests a Large Window of Susceptibility in Infants in Lao People’s Democratic Republic

Introduction: Measles is an endemic but largely neglected disease in Lao People’s Democratic Republic. New-borns are protected by maternal antibodies, but antibody waning before measles vaccination at 9 months of age leaves infants susceptible to infection. In this study, the susceptibility window of infants was determined to generate scientific evidence to assess the national measles immunization strategy. Methods: Between 2015 and 2016, demographic data, medical history, and blood samples were collected from 508 mother-child pairs at the provincial hospital in Vientiane. The samples were screened with a commercial kit detecting anti-measles IgG antibodies. Results: The large majority (95.7%) of the mothers were seropositive for anti-measles IgG and antibody titers of the mothers and infants were highly correlated (p < 0.01). While at birth 97.7% of the infants were seropositive, seropositivity rates decreased to 74.2% two months later to reach only 28.2% four months after birth (p < 0.01). Just before the first dose of the measles-rubella vaccine, scheduled at 9 months of age, was actually given, less than 14% of the infants were seropositive. Conclusion: This alarmingly wide susceptibility gap due to rapid maternal antibody decay leaves infants at risk of measles infection and serious disease complications. A high herd immunity is crucial to protect young infants and can be achieved through improved routine vaccination coverage and (expanded age group) supplementary immunization activities.
Inhibition of Autophagy In Vivo Extends Methamphetamine Toxicity to Mesencephalic Cell Bodies

Methamphetamine (METH) is a widely abused psychostimulant and a stress-inducing compound, which leads to neurotoxicity for nigrostriatal dopamine (DA) terminals in rodents and primates including humans. In vitro studies indicate that autophagy is a strong modulator of METH toxicity. In detail, suppressing autophagy increases METH toxicity, while stimulating autophagy prevents METH-induced toxicity in cell cultures. In the present study, the role of autophagy was investigated in vivo. In the whole brain, METH alone destroys meso-striatal DA axon terminals, while fairly sparing DA cell bodies within substantia nigra pars compacta (SNpc). No damage to either cell bodies or axons from ventral tegmental area (VTA) is currently documented. According to the hypothesis that ongoing autophagy prevents METH-induced DA toxicity, we tested whether systemic injection of autophagy inhibitors such as asparagine (ASN, 1000 mg/Kg) or glutamine (GLN, 1000 mg/Kg), may extend METH toxicity to DA cell bodies, both within SNpc and VTA, where autophagy was found to be inhibited. When METH (5 mg/Kg × 4, 2 h apart) was administered to C57Bl/6 mice following ASN or GLN, a frank loss of cell bodies takes place within SNpc and a loss of both axons and cell bodies of VTA neurons is documented. These data indicate that, ongoing autophagy protects DA neurons and determines the refractoriness of cell bodies to METH-induced toxicity.
Stabilizing Fe–N–C Catalysts as Model for Oxygen Reduction Reaction

The highly efficient energy conversion of the polymer‐electrolyte‐membrane fuel cell (PEMFC) is extremely limited by the sluggish oxygen reduction reaction (ORR) kinetics and poor electrochemical stability of catalysts. Hitherto, to replace costly Pt‐based catalysts, non‐noble‐metal ORR catalysts are developed, among which transition metal–heteroatoms–carbon (TM–H–C) materials present great potential for industrial applications due to their outstanding catalytic activity and low expense. However, their poor stability during testing in a two‐electrode system and their high complexity have become a big barrier for commercial applications. Thus, herein, to simplify the research, the typical Fe–N–C material with the relatively simple constitution and structure, is selected as a model catalyst for TM–H–C to explore and improve the stability of such a kind of catalysts. Then, different types of active sites (centers) and coordination in Fe–N–C are systematically summarized and discussed, and the possible attenuation mechanism and strategies are analyzed. Finally, some challenges faced by such catalysts and their prospects are proposed to shed some light on the future development trend of TM–H–C materials for advanced ORR catalysis.
Impact of COVID-19 on the Mental Health of Medical Students in Portugal

(1) Background: The purpose of this article is to assess the impact of the COVID-19 pandemic on the mental health of medical students in Portugal in the period after returning to face-to-face classes during the COVID-19 pandemic, in the 2020/2021 academic year. (2) Methods: We conducted an observational, descriptive, and cross-sectional study, between December 2020 and February 2021 with a representative sample of Portuguese medical students (n = 649), applying an anonymous questionnaire which was composed by a sociodemographic characterization, The Brief Symptoms Inventory–18, The Fear of COVID-19 Scale and the Negative Impact Assessment Scale. For statistical processing, Statistical Package for Social Sciences (SPSS ©) was used. (3) Results: 65.3% of participants said that self-perceived relevant anxiety symptoms, and around 10% said that they had a physical or a mental illness diagnosis. Significant differences (p < 0.05) were found for Fear of COVID-19, Somatization, Anxiety and Overall Mental Health, indicating that women, students from the 1st and last years of training had higher scores. Age, year of training, Fear of COVID-19 and Negative Impact of COVID-19 were significant predictors of overall mental health. (4) Conclusion: In our sample of Portuguese medical students, age, year of training, but mostly fear of COVID-19 and the negative impact of COVID-19 contributed to mental health symptoms.
Emergence and Characterization of a Novel Reassortant Canine Influenza Virus Isolated from Cats

Cats are susceptible to a wide range of influenza A viruses (IAV). Furthermore, cats can serve as an intermediate host, and transfer avian influenza virus (AIV) H7N2 to a veterinarian. In this report, a novel reassortant influenza virus, designated A/feline/Jiangsu/HWT/2017 (H3N2), and abbreviated as FIV-HWT-2017, was isolated from nasal swab of a symptomatic cat in Jiangsu province, China. Sequence analysis indicated that, whilst the other seven genes were most similar to the avian-origin canine influenza viruses (CIV H3N2) isolated in China, the NS gene was more closely related to the circulating human influenza virus (H3N2) in the region. Therefore, FIV-HWT-2017 is a reassortant virus. In addition, some mutations were identified, and they were similar to a distinctive CIV H3N2 clade. Whether these cats were infected with the reassortant virus was unknown, however, this random isolation of a reassortant virus indicated that domestic or stray cats were “mixing vessel” for IAV cannot be ruled out. An enhanced surveillance for novel influenza virus should include pet and stray cats.
Applying HPLC to Screening QTLs for BLB Resistance in Rice

Bacterial leaf blight (BLB) is caused by Xanthomonas oryzae pv. oryzae and is a major cause of rice yield reductions around the world. When diseased, plants produce a variety of metabolites to resist pathogens. In this study, the various defense metabolites were quantified using high-performance liquid chromatography (HPLC) after Xoo inoculation in a 120 Cheongcheong/Nagdong double haploid (CNDH) population. Quantitative trait locus (QTL) mapping was conducted using the concentration of the plant defense metabolites. HPLC analyzes the concentration of substances according to the severity of disease symptoms. Searching for BLB resistance candidate genes by applying this analysis method is very effective when mapping related genes. These resistance genes can be mapped directly to the causative pathogens. A total of 17 metabolites were detected by means of HPLC analysis after Xoo inoculation in the 120 CNDH population. QTL mapping of the metabolite concentrations resulted in the detection of the BLB resistance candidate gene, OsWRKYq6, in RM3343 of chromosome 6. OsWRKYq6 has a very high homology sequence with WRKY transcription factor 39, and when inoculated with Xoo, the relative expression level of the resistant population was higher than that of the susceptible population. Resistance genes have previously been detected using only phenotypic change data. In this study, resistance candidate genes were detected using the concentration of metabolites produced in plants after inoculation with pathogens. This newly developed analysis method can be used to effectively detect and identify genes directly involved in disease resistance for future studies.
Protective Effect of Natural Antioxidant Compounds on Methimazole Induced Oxidative Stress in a Feline Kidney Epithelial Cell Line (CRFK)

The treatment of choice for feline hyperthyroidism is the administration of the antithyroid drug methimazole. Both the endocrinopathy and the drug adverse reactions (e.g., hepatotoxicosis, gastrointestinal disorders, and renal injury) are partly due to oxidative stress and redox unbalance. This study investigated the free radical production and the impairment of the antioxidant barrier induced by methimazole in an in vitro model of feline renal epithelium. The protective effects of quercetin and resveratrol were also explored. CRFK cells were incubated with a methimazole concentration equivalent to the maximum plasma levels in orally treated cats (4 µM), in the presence or absence of either one of the two selected antioxidants at different time-points (up to 72 h). Cell viability, ROS production, GSH levels, and mRNA expression of antioxidant enzymes (i.e., CAT, SOD, GPx, and GST) were assessed. Methimazole impaired cell viability and increased ROS levels in a time-dependent manner. Similarly, GSH content and CAT, SOD, and GPx3 expression were higher compared with control cells. Such effects were significantly counteracted by quercetin. These results provide new insights about the mechanisms underlying the methimazole-related side effects frequently observed in hyperthyroid cats. They also support the use of quercetin in the management of feline hyperthyroidism.
Precise Characterization of Genetic Interactions in Cancer via Molecular Network Refining Processes

Genetic interactions (GIs), such as the synthetic lethal interaction, are promising therapeutic targets in precision medicine. However, despite extensive efforts to characterize GIs by large-scale perturbation screening, considerable false positives have been reported in multiple studies. We propose a new computational approach for improved precision in GI identification by applying constraints that consider actual biological phenomena. In this study, GIs were characterized by assessing mutation, loss of function, and expression profiles in the DEPMAP database. The expression profiles were used to exclude loss-of-function data for nonexpressed genes in GI characterization. More importantly, the characterized GIs were refined based on Kyoto Encyclopedia of Genes and Genomes (KEGG) or protein–protein interaction (PPI) networks, under the assumption that genes genetically interacting with a certain mutated gene are adjacent in the networks. As a result, the initial GIs characterized with CRISPR and RNAi screenings were refined to 65 and 23 GIs based on KEGG networks and to 183 and 142 GIs based on PPI networks. The evaluation of refined GIs showed improved precision with respect to known synthetic lethal interactions. The refining process also yielded a synthetic partner network (SPN) for each mutated gene, which provides insight into therapeutic strategies for the mutated genes; specifically, exploring the SPN of mutated BRAF revealed ELAVL1 as a potential target for treating BRAF-mutated cancer, as validated by previous research. We expect that this work will advance cancer therapeutic research.
Gryllus bimaculatus Extract Protects against Lipopolysaccharide-Derived Inflammatory Response in Human Colon Epithelial Caco-2 Cells

Simple Summary Inflammatory bowel disease (IBD), a potentially life-threatening disease, is characterized by increased tight junction permeability and overproduction of proinflammatory cytokines. The long-term administration of recognized chemotherapeutic agents can cause serious potential side effects. As such, increasing attention has been paid to natural, low-toxicity products with anti-inflammatory properties for treating IBD. We assessed the potential utility of the edible cricket species Gryllus bimaculatus for anti-inflammatory and cytoprotective effects in the human epithelial cell line Caco-2, following treatment with an inflammatory lipopolysaccharide stimulus. We found that aqueous ethanolic G. bimaculatus extract (AE-GBE) treatment increased cell viability and significantly reduced inflammatory mediators. Moreover, AE-GBE significantly reduced inflammatory cytokine expression levels, intestinal epithelial permeability, and related tight junction protein expression levels. In conclusion, AE-GBE can protect epithelial cells from lipopolysaccharide-induced impaired barrier integrity by increasing tight junction proteins and preventing various inflammatory mediators. These results may be used to pursue further use of natural insect extracts in treating IBD. Abstract Increased tight junction permeability and overproduction of proinflammatory cytokines are crucial pathophysiological mechanisms in inflammatory bowel disease (IBD). This study evaluated anti-inflammatory effects of aqueous ethanolic Gryllus bimaculatus extract (AE-GBE) against intestinal permeability on lipopolysaccharide (LPS)-treated Caco-2 cells. Treatment with AE-GBE increased cell viability and significantly reduced inflammatory mediators such as nitric oxide and LPS-induced reactive oxidative stress. LPS increased the expression levels of iNOS, Cox-2, and 4-hydroxylnonenal; however, these levels were attenuated by AE-GBE treatment. Moreover, the mRNA and protein expression levels of the inflammatory cytokines TNFα, IL-6, IL-1β, and IFNγ were increased by LPS, but were significantly reduced by AE-GBE treatment. Intestinal epithelial permeability and the related expression of the proteins Zoula ocludence-1, occludin, and claudin-1 was increased by LPS treatment, and this effect was significantly reduced by AE-GBE treatment. The reduction in AMPK phosphorylation in LPS-treated Caco-2 cells was reversed in activation by co-treatment with AE-GBE. In conclusion, AE-GBE can protect epithelial cells from LPS-induced impaired barrier integrity by increasing tight junction proteins and preventing various inflammatory mediators. Thus, AE-GBE has the potential to improve inflammation-related diseases, including IBD, by inhibiting excessive production of inflammation-inducing mediators.
Metal Cluster Size-Dependent Activation Energies of Growth of Single-Chirality Single-Walled Carbon Nanotubes inside Metallocene-Filled Single-Walled Carbon Nanotubes

By combining in situ annealing and Raman spectroscopy measurements, the growth dynamics of nine individual-chirality inner tubes (8,8), (12,3), (13,1), (9,6), (10,4), (11,2), (11,1), (9,3) and (9,2) with diameters from ~0.8 to 1.1 nm are monitored using a time resolution of several minutes. The growth mechanism of inner tubes implies two successive stages of the growth on the carburized and purely metallic catalytic particles, respectively, which are formed as a result of the thermally induced decomposition of metallocenes inside the outer SWCNTs. The activation energies of the growth on carburized Ni and Co catalytic particles amount to 1.85–2.57 eV and 1.80–2.71 eV, respectively. They decrease monotonically as the tube diameter decreases, independent of the metal type. The activation energies of the growth on purely metallic Ni and Co particles equal 1.49–1.91 eV and 0.77–1.79 eV, respectively. They increase as the tube diameter decreases. The activation energies of the growth of large-diameter tubes (dt = ~0.95–1.10 nm) on Ni catalyst are significantly larger than on Co catalyst, whereas the values of small-diameter tubes (dt = ~0.80–0.95 nm) are similar. For both metals, no dependence of the activation energies on the chirality of inner tubes is observed.
Rapid Accumulation of Proline Enhances Salinity Tolerance in Australian Wild Rice Oryza australiensis Domin

Proline has been reported to play an important role in helping plants cope with several stresses, including salinity. This study investigates the relationship between proline accumulation and salt tolerance in an accession of Australian wild rice Oryza australiensis Domin using morphological, physiological, and molecular assessments. Seedlings of O. australiensis wild rice accession JC 2304 and two other cultivated rice Oryza sativa L. cultivars, Nipponbare (salt-sensitive), and Pokkali (salt-tolerant), were screened at 150 mM NaCl for 14 days. The results showed that O. australiensis was able to rapidly accumulate free proline and lower osmotic potential at a very early stage of salt stress compared to cultivated rice. The qRT-PCR result revealed that O. australiensis wild rice JC 2304 activated proline synthesis genes OsP5CS1, OsP5CS2, and OsP5CR and depressed the expression of proline degradation gene OsProDH as early as 1 h after exposure to salinity stress. Wild rice O. australiensis and Pokkali maintained their relative water content and cell membrane integrity during exposure to salinity stress, while the salt-sensitive Nipponbare failed to do so. An analysis of the sodium and potassium contents suggested that O. australiensis wild rice JC 2304 adapted to ionic stress caused by salinity by maintaining a low Na+ content and low Na+/K+ ratio in the shoots and roots. This demonstrates that O. australiensis wild rice may use a rapid accumulation of free proline as a strategy to cope with salinity stress.
Network meta-analysis of 6 kinds of Chinese patent medicines combined with mifepristone in the treatment of uterine fibroids

Abstract Background: Uterine fibroids are benign. They belong to the category of “abdominal mass” in traditional Chinese medicine, and pathogenesis is mainly caused by weakness of the body, qi stagnation, and blood stasis. Drug therapy is the preferred treatment of uterine fibroids in clinical practice, and mifepristone is the most commonly used drug. In the past decade, a large number of clinical randomized controlled trials have proven that Chinese patent medicine combined with mifepristone in the treatment of uterine fibroids has a better curative effect, fewer adverse reactions, and higher safety than mifepristone alone. However, there is a lack of evidence-based research. This study aims to integrate clinical data through network meta-analysis to provide more evidence-based medical evidence for clinical medication. Methods: The comprehensive search included Chinese and other-language databases, such as MEDLINE (PubMed), Web of Science, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, and China Biomedical Literature Database. Clinical randomized controlled trials of 6 Chinese patent medicines combined with mifepristone for the treatment of uterine fibroids, including Guizhi Fuling Capsule, Gongliuxiao Capsule, Gongliuqing Capsule, Danbie Capsule, Gongliuning Capsule, and Xiaojiean Capsule were retrieved. The search period was from January 2010 to April 2021. Two researchers screened the literature through EndNote and used Excel to extract data. RevMan 5.3 was used to evaluate the quality of the literature. Treatment measures were analyzed in R language, and a forest map and probability ranking map of various interventions were drawn. The network evidence map and correction comparison funnel map of various interventions were drawn by STATA 14.0 software. Results: This study provides the clinical efficacy and safety of network meta-analysis of 6 kinds of Chinese patent medicines combined with mifepristone in the treatment of uterine fibroids will be systematically evaluated or descriptively analyzed. Conclusion: This study's purpose is to provide a reference for the clinical treatment of uterine fibroids to choose more effective intervention therapies.