Miracle-dz/UniFAR-FTUs huggingface dataset:
GRACy: A tool for analysing human cytomegalovirus sequence data

Abstract Modern DNA sequencing has instituted a new era in human cytomegalovirus (HCMV) genomics. A key development has been the ability to determine the genome sequences of HCMV strains directly from clinical material. This involves the application of complex and often non-standardized bioinformatics approaches to analysing data of variable quality in a process that requires substantial manual intervention. To relieve this bottleneck, we have developed GRACy (Genome Reconstruction and Annotation of Cytomegalovirus), an easy-to-use toolkit for analysing HCMV sequence data. GRACy automates and integrates modules for read filtering, genotyping, genome assembly, genome annotation, variant analysis, and data submission. These modules were tested extensively on simulated and experimental data and outperformed generic approaches. GRACy is written in Python and is embedded in a graphical user interface with all required dependencies installed by a single command. It runs on the Linux operating system and is designed to allow the future implementation of a cross-platform version. GRACy is distributed under a GPL 3.0 license and is freely available at https://bioinformatics.cvr. ac.uk/software/ with the manual and a test dataset.
Assessment of Internet Hospitals in China During the COVID-19 Pandemic: National Cross-Sectional Data Analysis Study

Background Internet hospitals in China are being rapidly developed as an innovative approach to providing health services. The ongoing COVID-19 pandemic has triggered the development of internet hospitals that promote outpatient service delivery to the public via internet technologies. To date, no studies have assessed China's internet hospitals during the COVID-19 pandemic. Objective This study aimed to elucidate the characteristics of China's internet hospitals and assess the health service capacity of these hospitals. Methods Data on 711 internet hospitals were collected from official websites, the WeChat (Tencent Inc) platform, smartphone apps, and the Baidu search engine until July 16, 2020. Results As of July 16, 2020, 711 internet hospitals were developed in mainland China. More than half of these internet hospitals (421/711, 59.2%) were established during 2019 (206/711, 29%) and 2020 (215/711, 30.2%). Furthermore, about one-third (215/711, 30.2%) of internet hospitals were established at the beginning of 2020 as an emergency response to the COVID-19 epidemic. The 711 internet hospitals consisted of the following 3 types of hospitals: government-oriented (42/711, 5.91%), hospital-oriented (143/711, 20.11%), and enterprise-oriented internet hospitals (526/711, 73.98%). The vast majority of internet hospitals were traditional hospitals (526/711, 74%). Nearly 46.1% (221/711) of internet hospitals requested doctors to provide health services at a specific web clinic. Most patients (224/639, 35.1%) accessed outpatient services via WeChat. Internet hospitals’ consulting methods included SMS text messaging consultations involving the use of graphics (552/570, 96.8%), video consultations (248/570, 43.5%), and telephone consultations (238/570, 41.8%). The median number of available web-based doctors was 43, and the median consultation fees of fever clinics and other outpatient clinics were ¥0 (US $0) per consultation and ¥6 (US $0.93) per consultation, respectively. Internet hospitals have provided various services during the COVID-19 pandemic, including medical prescription, drug delivery, and medical insurance services. Conclusions The dramatic increase of internet hospitals in China has played an important role in the prevention and control of COVID-19. Internet hospitals provide different and convenient medical services for people in need.
Active Glucose Transport 2020 and Beyond

As a concept, active transport emerged from early studies of intestinal glucose absorption and renal glucose reabsorption. Transport requires energy and is blocked by the natural glucoside phlorizin. Bob Crane proposed in 1960 that the energy comes directly from the Naþ gradient across the membrane. The sodium–glucose cotransport hypothesis has been tested, confirmed, and extended to the active transport of molecules into cells throughout the body, eg, neurotransmitter uptake into neurons. The intestinal glucose cotransporter (SGLT1) was the first to be identified, cloned, and studied in heterologous expression systems such as Xenopus oocytes and cultured cells. SGLT1 is the founding member of the SLC5 human gene family and the large APC superfamily found throughout all life forms (www.tcdb.org). Extensive functional, biochemical, biophysical, and molecular genetic studies have resulted in kinetic and structural models for the mechanism of active glucose transport (Figure 1). SGLT1 is an integral membrane protein with a core of 10 transmembrane helices arranged in an inverted repeat in common with the APC superfamily members. The glucose-binding site is in the middle of the protein and access is via aqueous channels with outer and inner gates. Functionally, the driving cation, Naþ, binds to the apoprotein to open the external channel and
Two Cases of anti–PIT-1 Hypophysitis Exhibited as a Form of Paraneoplastic Syndrome not Associated With Thymoma

Abstract Anti–pituitary-specific transcription factor 1 (PIT-1) hypophysitis (anti–PIT-1 antibody syndrome) is a thymoma-associated autoimmune disease characterized by acquired growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) deficiencies due to autoimmunity against PIT-1. Ectopic expression of PIT-1 in the thymoma plays a causal role in development of the disease. Here, we report 2 cases of anti–PIT-1 hypophysitis exhibiting as a form of paraneoplastic syndrome with conditions other than thymoma. A 79-year-old woman (case 1) and an 86-year-old man (case 2) were referred with a suspicion of anti–PIT-1 hypophysitis because of acquired GH, PRL, and TSH deficiencies. Case 1 was complicated by diffuse large B-cell lymphoma (DLBCL) of the bladder and case 2 was diagnosed with malignancy with multiple metastases of unknown origin. Because circulating anti–PIT-1 antibody was detected, both patients were diagnosed with anti–PIT-1 hypophysitis. Circulating PIT-1–reactive T cells were detected in case 1 via enzyme-linked immunospot (ELISPOT) assay. Interestingly, the PIT-1 protein was ectopically expressed in the DLBCL cells of case 1, whereas DLBCL tissues derived from patients without anti–PIT-1 hypophysitis were negative for PIT-1. In case 2, the materials were not available because of best supportive care was under way. These data show that anti–PIT-1 hypophysitis is associated not only with thymoma but also with other malignancies. Additionally, the ectopic expression of PIT-1 in the DLBCL tissues and presence of PIT-1–reactive T cells suggested that the underlying mechanisms were similar to those observed in thymoma. Thus, anti–PIT-1 hypophysitis is defined as a form of paraneoplastic syndrome.
Community Parameters and Genome-Wide RAD-Seq Loci of Ceratothoa oestroides Imply Its Transfer between Farmed European Sea Bass and Wild Farm-Aggregating Fish

Wild fish assemblages that aggregate within commercial marine aquaculture sites for feeding and shelter have been considered as a primary source of pathogenic parasites vectored to farmed fish maintained in net pens at an elevated density. In order to evaluate whether Ceratothoa oestroides (Isopoda, Cymothoidae), a generalist and pestilent isopod that is frequently found in Adriatic and Greek stocks of farmed European sea bass (Dicentrarchus labrax), transfers between wild and farmed fish, a RAD-Seq (restriction-site-associated DNA sequencing)-mediated genetic screening approach was employed. The double-digest RAD-Seq of 310 C. oestroides specimens collected from farmed European sea bass (138) and different wild farm-aggregating fish (172) identified 313 robust SNPs that evidenced a close genetic relatedness between the “wild” and “farmed” genotypes. ddRAD-Seq proved to be an effective method for detecting the discrete genetic structuring of C. oestroides and genotype intermixing between two populations. The parasite prevalence in the farmed sea bass was 1.02%, with a mean intensity of 2.0 and mean abundance of 0.02, while in the wild fish, the prevalence was 8.1%; the mean intensity, 1.81; and the mean abundance, 0.15. Such differences are likely a consequence of human interventions during the farmed fish’s rearing cycle that, nevertheless, did not affect the transfer of C. oestroides.
Umbilical cord blood metabolome differs in relation to delivery mode, birth order and sex, maternal diet and possibly future allergy development in rural children

Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Available umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 3 years and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though there was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and biosynthetic pathways, including glutamate and aspartic acid—histidine metabolism (p = 0.004) and the tricarboxylic acid cycle (p = 0.006) for birth order; branched chain amino acid metabolism (p = 0.0009) and vitamin B6 metabolism (p = 0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p = 0.005) for mode of delivery. Maternal diet was also related to some of the metabolites associated with allergy. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies.
Isolating, identifying and evaluating of oil degradation strains for the air-assisted microbial enhanced oil recovery process

Due to the inefficient reproduction of microorganisms in oxygen-deprived environments of the reservoir, the applications of microbial enhanced oil recovery (MEOR) are restricted. To overcome this problem, a new type of air-assisted MEOR process was investigated. Three compounding oil degradation strains were screened using biochemical experiments. Their performances in bacterial suspensions with different amounts of dissolved oxygen were evaluated. Water flooding, microbial flooding and air-assisted microbial flooding core flow experiments were carried out. Carbon distribution curve of biodegraded oil with different oxygen concentration was determined by chromatographic analysis. The long-chain alkanes are degraded by microorganisms. A simulation model was established to take into account the change in oxygen concentration in the reservoir. The results showed that the optimal dissolved oxygen concentration for microbial growth was 4.5~5.5mg/L. The main oxygen consumption in the reservoir happened in the stationary and declining phases of the microbial growth systems. In order to reduce the oxygen concentration to a safe level, the minimum radius of oxygen consumption was found to be about 145m. These results demonstrate that the air-assisted MEOR process can overcome the shortcomings of traditional microbial flooding techniques. The findings of this study can help for better understanding of microbial enhanced oil recovery and improving the efficiency of microbial oil displacement.
Genetic and Environmental Factors Influence the Pleomorphy of LRRK2 Parkinsonism

Missense mutations in the LRRK2 gene were first identified as a pathogenic cause of Parkinson’s disease (PD) in 2004. Soon thereafter, a founder mutation in LRRK2, p.G2019S (rs34637584), was described, and it is now estimated that there are approximately 100,000 people worldwide carrying this risk variant. While the clinical presentation of LRRK2 parkinsonism has been largely indistinguishable from sporadic PD, disease penetrance and age at onset can be quite variable. In addition, its neuropathological features span a wide range from nigrostriatal loss with Lewy body pathology, lack thereof, or atypical neuropathology, including a large proportion of cases with concomitant Alzheimer’s pathology, hailing LRRK2 parkinsonism as the “Rosetta stone” of parkinsonian disorders, which provides clues to an understanding of the different neuropathological trajectories. These differences may result from interactions between the LRRK2 mutant protein and other proteins or environmental factors that modify LRRK2 function and, thereby, influence pathobiology. This review explores how potential genetic and biochemical modifiers of LRRK2 function may contribute to the onset and clinical presentation of LRRK2 parkinsonism. We review which genetic modifiers of LRRK2 influence clinical symptoms, age at onset, and penetrance, what LRRK2 mutations are associated with pleomorphic LRRK2 neuropathology, and which environmental modifiers can augment LRRK2 mutant pathophysiology. Understanding how LRRK2 function is influenced and modulated by other interactors and environmental factors—either increasing toxicity or providing resilience—will inform targeted therapeutic development in the years to come. This will allow the development of disease-modifying therapies for PD- and LRRK2-related neurodegeneration.
Characteristics of Salmonella Recovered From Stools of Children Enrolled in the Global Enteric Multicenter Study

Abstract Background The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of nontyphoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. Methods Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole-genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk-diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing, and whole-genome sequencing was performed to assess the phylogeny of ST313. Results Of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java, and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar among both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone, but African isolates were susceptible to these antibiotics. Conclusions Our data confirm that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multidrug-resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa.
Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways

Background and Aims: The disease progression of nonalcoholic fatty liver disease (NAFLD) from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is driven by multiple factors. Berberine (BBR) is an ancient Chinese medicine and has various beneficial effects on metabolic diseases, including NAFLD/NASH. However, the underlying mechanisms remain incompletely understood due to the limitation of the NASH animal models used. Methods: A high-fat and high-fructose diet-induced mouse model of NAFLD, the best available preclinical NASH mouse model, was used. RNAseq, histological, and metabolic pathway analyses were used to identify the potential signaling pathways modulated by BBR. LC–MS was used to measure bile acid levels in the serum and liver. The real-time RT-PCR and Western blot analysis were used to validate the RNAseq data. Results: BBR not only significantly reduced hepatic lipid accumulation by modulating fatty acid synthesis and metabolism but also restored the bile acid homeostasis by targeting multiple pathways. In addition, BBR markedly inhibited inflammation by reducing immune cell infiltration and inhibition of neutrophil activation and inflammatory gene expression. Furthermore, BBR was able to inhibit hepatic fibrosis by modulating the expression of multiple genes involved in hepatic stellate cell activation and cholangiocyte proliferation. Consistent with our previous findings, BBR’s beneficial effects are linked with the downregulation of microRNA34a and long noncoding RNA H19, which are two important players in promoting NASH progression and liver fibrosis. Conclusion: BBR is a promising therapeutic agent for NASH by targeting multiple pathways. These results provide a strong foundation for a future clinical investigation.
Factors Associated with Symptoms of Depression and Psychological Distress during the COVID-19 Pandemic

The objective of this study was to examine factors associated with symptoms of depression and psychological distress during the COVID-19 pandemic in China. Convenience sampling and snowball sampling were used to recruit a sample of adults in China (n = 2130) from 14 February 2020 to 3 March 2020 to complete an online survey. Linear regression was used to examine the predictors of symptoms of depression and psychological distress. Living in a non-urban area and the number of confirmed cases in their city of residence were positively associated with symptoms of depression. Female gender, not being married, practicing social distancing, the amount of time spent daily on social media searching for and reading information on COVID-19, the number of confirmed cases of COVID-19 in their city of residence, and having confirmed or suspected cases of COVID-19 in personal networks were positively associated with psychological distress. Social distancing is a widely used public health approach for population-wide virus-containment of COVID-19. However, reductions in population-wide psychological well-being are inadvertent consequences of social distancing. There is an emerging need to negate factors that increase adverse mental health vulnerabilities during the COVID-19 pandemic.
“Go To Travel” Campaign and Travel-Associated Coronavirus Disease 2019 Cases: A Descriptive Analysis, July–August 2020

The Japanese government initiated the Go To Travel campaign on 22 July 2020, offering deep discounts on hotel charges and issuing coupons to be used for any consumption at travel destinations in Japan. In the present study, we aimed to describe the possible epidemiological impact of the tourism campaign on increasing travel-associated cases of coronavirus disease 2019 (COVID-19) in the country. We compared the incidence rates of travel-associated and tourism-related cases prior to and during the campaign. The incidence of travel-associated COVID-19 cases during the tourism campaign was approximately three times greater than the control period 22 June to 21 July 2020 and approximately 1.5 times greater than the control period of 15 to 19 July. The incidence owing to tourism was approximately 8 times and 2–3 times greater than the control periods of 22 June to 21 July and 15 to 19 July, respectively. Although the second epidemic wave in Japan had begun to decline by mid-August, enhanced domestic tourism may have contributed to increasing travel-associated COVID-19 cases during 22 to 26 July, the early stage of the Go To Travel campaign.
Heterologous Expression of ethA and katG in Mycobacterium marinum Enables the Rapid Identification of New Prodrugs Active against Mycobacterium tuberculosis

Screening strategies for antituberculosis compounds using Mycobacterium tuberculosis are time consuming and require biosafety level 3 (BSL3) facilities, which makes the development of high-throughput assays difficult and expensive. Mycobacterium marinum, a close genetic relative of M. tuberculosis, possesses several advantages as a suitable model for tuberculosis drug screening. However, despite the high genetic similarity, there are some obvious differences in susceptibility to some tuberculosis drugs between these two species, especially for the prodrugs ethionamide and isoniazid. ABSTRACT Screening strategies for antituberculosis compounds using Mycobacterium tuberculosis are time consuming and require biosafety level 3 (BSL3) facilities, which makes the development of high-throughput assays difficult and expensive. Mycobacterium marinum, a close genetic relative of M. tuberculosis, possesses several advantages as a suitable model for tuberculosis drug screening. However, despite the high genetic similarity, there are some obvious differences in susceptibility to some tuberculosis drugs between these two species, especially for the prodrugs ethionamide and isoniazid. In this study, we aimed to improve M. marinum as a model for antituberculosis drug identification by heterologous expression of two common drug activators, EthA and KatG. These two activators were overexpressed in M. marinum, and the strains were tested against ethionamide, isoniazid, and a library of established antimycobacterial compounds from TB Alliance to compare drug susceptibility. Both in vitro and in vivo using zebrafish larvae, these genetically modified M. marinum strains showed significantly higher susceptibility against ethionamide and isoniazid, which require activation by EthA and KatG. More importantly, a strain overexpressing both ethA and katG was potentially more susceptible to approximately 20% of the antituberculosis hit compounds from the TB Alliance library. Most of these compounds were activated by EthA in M. marinum. Four of these compounds were selected for further analysis, and three of them showed obvious EthA-dependent activity against M. tuberculosis. Overall, our developed M. marinum strains are valuable tools for high-throughput discovery of potential novel antituberculosis prodrugs.