Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of cardiovascular diseases mortality- and disability-adjusted life-years attributed to modifiable dietary risk factors from 1990 to 2030 among East Asian countries and the world

Background Unhealthy eating habits are a significant modifiable risk factor for cardiovascular diseases (CVDs); nevertheless, no evidence of their impact on the CVD burden has been reported in East Asian countries. We aimed to determine the trend and predict the future CVDs burden attributed to modifiable dietary risk factors in the East Asian countries (China, Japan, South Korea, and North Korea) and the world. Methods The Global Burden of Disease (GBD) 2019 data were used to find the trend of CVDs [ischemic heart disease (IHD) and ischemic stroke (IS)] mortality- and disability-adjusted life-years (DALYs) attributed to dietary risk factors in the East Asian countries and the world (1990–2019) and its prediction from 2020 to 2030. We used the joinpoint regression model and the autoregressive integrated moving average (ARIMA) model for trend and future forecast, respectively. Results From 1990 to 2019, regardless of sex, the age-standardized mortality rate (ASMR) and DALYs of IHD attributed to dietary risk factors significantly decreased in Japan, South Korea, and the world. However, the ASMR of IHD significantly increased in Chinese males and for both sexes in North Korea. The ASMR and DALYs of IHD and IS due to dietary risk factors were higher in males than in females in the world. From 2020 to 2030, the ASMR of IHD is predicted to increase in South Korean females and Japanese males. Globally, a diet low in whole grains was the top risk factor for the highest IHD mortality and DALYs in 2019, followed by a diet low in legumes and a diet high in sodium. A diet low in whole grains, a diet high in sodium, and a diet low in legumes were the leading risk factors for high IHD mortality in East Asian countries. Conclusion The trend of IHD and IS burden due to dietary risk factors varies substantially across the East Asian countries compared to the trend of CVDs burden in the world. The study findings may help the public health policymakers to design proper strategies for improvement of the quality of life to combat the CVDs burden in the future for the East Asian countries.
Systematic review and meta-analysis on the therapeutic reference range for escitalopram: Blood concentrations, clinical effects and serotonin transporter occupancy

Introduction A titration within a certain therapeutic reference range presupposes a relationship between the blood concentration and the therapeutic effect of a drug. However, this has not been systematically investigated for escitalopram. Furthermore, the recommended reference range disagrees with mean steady state concentrations (11–21 ng/ml) that are expected under the approved dose range (10–20 mg/day). This work systematically investigated the relationships between escitalopram dose, blood levels, clinical effects, and serotonin transporter occupancy. Methods Following our previously published methodology, relevant articles were systematically searched and reviewed for escitalopram. Results Of 1,032 articles screened, a total of 30 studies met the eligibility criteria. The included studies investigated escitalopram blood levels in relationship to clinical effects (9 studies) or moderating factors on escitalopram metabolism (12 studies) or serotonin transporter occupancy (9 studies). Overall, the evidence for an escitalopram concentration/effect relationship is low (level C). Conclusion Based on our findings, we propose a target range of 20–40 ng/ml for antidepressant efficacy of escitalopram. In maintenance treatment, therapeutic response is expected, when titrating patients above the lower limit. The lower concentration threshold is strongly supported by findings from neuroimaging studies. The upper limit for escitalopram’s reference range rather reflects a therapeutic maximum than a tolerability threshold, since the incidence of side effects in general is low. Concentrations above 40 ng/ml should not necessarily result in dose reductions in case of good clinical efficacy and tolerability. Dose-related escitalopram concentrations in different trials were more than twice the expected concentrations from guideline reports. Systematic review registration [https://www.crd. york.ac. uk/PROSPERO/display_record. php? RecordID=215873], identifier [CRD42020215873].
Clinical characteristics and prognosis of patient with leptospirosis: A multicenter retrospective analysis in south of China

Purpose Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus Leptospira. However, there is currently no consensual definition or diagnostic criteria for severe and different forms of leptospirosis. Therefore, more insight on clinical manifestations, risk factors, and outcomes of leptospirosis is warranted. The identification of leptospirosis with distinct clinical manifestations and prognosis in our population. Methods Multiple correspondence analysis and hierarchical classification on principal components were presented to identify different clinical types of leptospirosis. The outcomes were clinical phenotypes, laboratory and imaging findings, and prognosis. Results The 95 enrolled patients had median values of 54.0 years (39.0-65.0) for age, 9.0 (7.0-14.0) for total hospital stay lengths, of whom 86.3% was male and 40.0% was transferred to ICU. Three clinical types were distinguished: mild leptospirosis (n=43, 45.3%) with less organ dysfunction and shorter hospital stays; respiratory leptospirosis (n=28, 29.5%) with hemoptysis, and respiratory and circulatory failure; and hepato-renal leptospirosis (n=24, 25.3%) with worst liver and kidney dysfunction. Total hospital mortality was 15.8% and was associated with dyspnea and high levels of neutrophil counts. Conclusions The identification of leptospirosis with distinct clinical manifestations and prognosis in our population may assist clinicians to distinguish leptospirosis-like disease. Moreover, dyspnea and neutrophil count were found to be independent risk factors for severe leptospirosis progression.
Developing and evaluating week 2 and weeks 3-4 outlook tools for extratropical storminess

Extratropical cyclones give rise to most of the high impact weather in the mid-to high-latitudes during the cool seasons, including heavy precipitation and strong winds. Thus it is important for stakeholders to be informed of approaching periods of increased or decreased cyclone activity. While individual cyclone tracks can be predicted out to about a week or so, from week 2 on, statistics summarizing cyclone activity, or storminess, are more useful. Storminess can be defined based on Lagrangian cyclone tracking or by Eulerian variance statistics. The outlook includes a combination of both methods. Lagrangian cyclone tracks provide information about where cyclones pass through and are more intuitive to users, while Eulerian variance statistics have been shown to be highly correlated with cyclone-related weather and are expected to be more predictable given that they are not as noisy. In this paper, we evaluate a storminess outlook tool developed based on dynamical model forecasts in the week-2 and weeks 3-4 time ranges. The outlook uses two 6-hourly subseasonal ensemble forecasts–the Global Ensemble Forecast System version 12 (GEFSv12), and the coupled Climate Forecast System version 2 (CFSv2). Hindcasts and operational forecasts from 1999–2016 are used to assess the prediction skill. Our results show that the GEFSv12 and CFSv2 combined ensemble has higher skill than either individual ensemble. The combined ensemble shows some skill in predicting cyclone amplitude and frequency out to weeks 3-4, with highest skill in winter, and lowest skill in summer. Models also show some skill in predicting the statistics of deep cyclones for week 2. The prediction skills for an Eulerian sea level pressure variance storminess metric is significantly higher than those for Lagrangian track statistics. Our results also show that GEFSv12 performs better than its predecessor GEFSv11. Correlations between the storminess indices and surface weather, including precipitation and high winds, are examined. A publicly accessible web page has been developed to display the subseasonal predictions in real time. The web page also contains information on climatology and forecast verification to enable users to make more informed use of the outlook.
Internet-based survey evaluating the impact of ground substrate on injury and performance in canine agility athletes

Agility is a rapidly growing canine performance sport worldwide, yet the literature is sparse regarding the impact of ground substrate on performance and injury. Approximately 1/3 of dogs participating in agility trials will experience a performance-related injury. The impact of ground material has been well-documented in racing greyhounds, equine athletes, and humans, but has been minimally investigated in agility dogs. In this retrospective, cross-sectional study, 300 respondents (handlers, owners, and trainers) of 308 agility dogs completed an online survey regarding their dog's training and competition regimen, history of injury, perceived association between injury and substrate and/or agility obstacle, markers of decreased performance (MDPs) observed on different substrates, and changes to routine following injury. 35.7% of dogs sustained a training injury (TI) and 11.2% sustained a competition injury (CI). The most commonly reported sites of injury were the shoulder (TI: 33.9%, CI: 25.4%), forelimb digits (TI: 14.7%, CI: 11.9%) and iliopsoas muscle (TI: 11.9%, CI: 13.6%). Dogs most commonly trained on natural grass (85.3%), artificial turf (50.8%), and dirt (34.5%). Significantly fewer MDPs were observed on natural grass than any other substrate except dirt. Significantly more MDPs were noted on rubber mat compared to natural grass, artificial turf, dirt, sand, or foam mat. Rubber mat had the highest Incidence Proportion (IP) (32.0%) of TI and was perceived to be related to TI in 87.5% of cases. Obstacles perceived to be associated with injuries included jumps (TI: 37.5%, CI: 27.8%), contacts (TI: 29.7%, CI: 22.2%), weaves (TI: 11.9%, CI: 13.9%), and tunnels (CI: 25.0%). Overall, agility dogs were perceived to perform best on natural grass and dirt, while rubber mat was associated with injury and decreased performance. Respondents were willing to make significant alterations to their dog's routine due to a perceived association between substrate, injury, and performance. Further prospective studies are needed to assess the impact of substrate composition and maintenance, and inform evidence-based recommendations to maximize performance and minimize performance-related injury in agility dogs.
Regulation of gut microbiome by ketogenic diet in neurodegenerative diseases: A molecular crosstalk

The gut taxonomical profile is one of the contributory factors in maintaining homeostasis within the central nervous system (CNS). Of late, the efficacy of diet as a target of treatment, and how various dietary interventions may modulate gut microbiota differently have been an area of focus in research. The role of ketogenic diet (KD) in particular has been well-established in other diseases like intractable epilepsy due to its postulated effects on gut microbiome modulation, resulting in neuronal stability and prevention of epileptogenesis. Therefore, this systematic review aimed to critically evaluate the current available literature investigating the interplay between the three distinct entities: ketogenic diet, neurodegeneration, and gut microbiota, which may serve as a focus guide for future neurodegenerative diseases (ND) therapeutic research. A comprehensive literature search was performed on three databases; PubMed, Scopus, and Ovid Medline. A total of 12 articles were selected for critical appraisal, after subjecting to the inclusion and exclusion criteria in this study. The selected articles revealed that the hopes of KD as a treatment modality for ND are being ventured into as these individuals are said to acquire gut dysbiosis, primarily through increased colonization of phyla Proteobacteria and Firmicutes. Although positive effects including restoration of healthy gut microbes such as Akkermansia Muciphilia sp. , improvement in cognitive functioning and decline in neuro-inflammatory markers were noted, this systematic review also depicted conflicting results such as decrease in alpha and beta species diversity as well as diminution of healthy gut commensals such as Bifidobacteriace. In addition, positive neuromodulation were also observed, notably an increase in cerebral blood perfusion to ventromedial hippocampal region via increased expression of eNOS and clearance of amyloid-beta proteins across the blood-brain-barrier via expression of p-glycoprotein. Neuroprotective mechanisms of ketogenic diet also included downregulation of mTOR expression, to prevention acceleration of pathological diseases such as Alzheimer's. Thus due to this conflicting/contrasting results demonstrated by ketogenic diet, such as a decline in gut species richness, diminution in beneficial microbes and decline cognition unless delivered in an intermittent fasting pattern, further studies may still be required before prior recommendation of a ketogenic diet therapeutic regime in ND patients.
Big contributions of the little brain for precision psychiatry

Our previous work using 3T functional Magnetic Resonance Imaging (fMRI) parcellated the human dentate nuclei (DN), the primary output of the cerebellum, to three distinct functional zones each contributing uniquely to default-mode, salience-motor, and visual brain networks. In this perspective piece, we highlight the possibility to target specific functional territories within the cerebellum using non-invasive brain stimulation, potentially leading to the refinement of cerebellar-based therapeutics for precision psychiatry. Significant knowledge gap exists in our functional understanding of cerebellar systems. Intervening early, gauging severity of illness, developing intervention strategies and assessing treatment response, are all dependent on our understanding of the cerebello-cerebral networks underlying the pathology of psychotic disorders. A promising yet under-examined avenue for biomarker discovery is disruptions in cerebellar output circuitry. This is primarily because most 3T MRI studies in the past had to exclude cerebellum from the field of view due to limitations in spatiotemporal resolutions. Using recent technological advances in 7T MRI (e.g., parallel transmit head coils) to identify functional territories of the DN, with a focus on dentato-cerebello-thalamo-cortical (CTC) circuitry can lead to better characterization of brain-behavioral correlations and assessments of co-morbidities. Such an improved mechanistic understanding of psychiatric illnesses can reveal aspects of CTC circuitry that can aid in neuroprognosis, identification of subtypes, and generate testable hypothesis for future studies.
The effect of COVID-19 on the presentation of thyroid disease in children

Introduction Although studies suggest a potential link between COVID-19 and thyroid dysfunction in adults, there are insufficient data to confirm that association in children, and whether there is any effect on presentation to healthcare services. Aims To identify whether presentations of thyroid dysfunction in children to a tertiary paediatric hospital changed as a result of the COVID-19 pandemic. Methods A retrospective case note review was conducted of all children with abnormal thyroid function tests between 1st January 2016 and 31st December 2021 at a tertiary paediatric endocrine centre in the United Kingdom. Results Overall, 244 children whose first presentation was within the timeframe of interest were included in this study, with a median age (range) of 11.5 (6.1, 16.8) years. Of these, 43 (18%) were hyperthyroid and 201 (82%) were hypothyroid. The greatest number of thyroid presentations occurred in 2021 (n=60, 25% of total over time period) and the fewest in 2020 (n=10, 4% of total over time period). Prior to this, the median (range) number of presentations per year was 34 (28, 39). There were no statistically significant differences in biochemistry, antibody status or other clinical characteristics between those who presented with hyperthyroidism prior to the pandemic or after. In those with hypothyroidism, baseline biochemistry was similar between the 2 groups, but the presence of other autoimmune conditions was greater pre-pandemic (17.2% vs 15.0%, p=0.03). In addition, patients were more likely to have transient thyroid dysfunction, which did not require treatment post-pandemic (70.0% vs 49.6%, p=0.0086). Conclusions Although overall rates of presentation with thyroid dysfunction have not altered since the first wave of the COVID-19 pandemic, presentations with transient thyroid dysfunction, not requiring ongoing treatment have increased. Further research regarding the relationship between COVID-19 and thyroid function in children and young people, is needed.
Oxysterols in catfish skin secretions (Arius bilineatus, Val.) exhibit anti-cancer properties

The edible catfish Arius bilineatus, (Valenciennes) elaborates a proteinaceous gel-like material through its epidermis when threatened or injured. Our on-going studies on this gel have shown it to be a complex mixture of several biologically active molecules. Anti-cancer studies on lipid fractions isolated from the gel-like materials showed them to be active against several cancer cell lines. This prompted us to investigate further the lipid composition of the catfish epidermal gel secretions (EGS). Analysis of the lipid fraction of EGS resulted in identification of 12 oxysterols including cholesterol and 2 deoxygenated steroids i.e., 7α-hydroxy cholesterol, 7β-hydroxycholesterol, 5,6 epoxycholesterol, 3β-hydroxycholest-5-ene-7-one and cholesta-3,5-dien-7-one. Progesterone, cholest-3,5-diene, cholesta-2,4-diene, cholest-3,5,6-triol and 4-cholesten-3-one were found as minor components, and were identified through their MS, 1HNMR and FTIR spectral data and were compared with those of the standards. Cholest-3,6-dione, cholesta-4,6-diene-3-one, cholesta-2,4-diene, and cholesta-5,20(22)-dien-3-ol were found only in trace amounts and were identified by GC/MS/MS spectral data. Since cholesterol is the major component of EGS, the identified oxysterols (OS) are presumably cholesterol oxidation products. Many of the identified OS are known important biological molecules that play vital physiological role in the producer and recipient organisms. We report herein the effects of these sterols on three human cancer cell lines in vitro, i.e., K-562 (CML cell line), MDA MB-231 (estrogen positive breast cancer cell line) and MCF-7 (estrogen negative breast cancer cell line). Interestingly significant (p < 0.05) dose differences were observed between tested OS on cell types used. The presence of these sterols in EGS may help explain some aspects of the physiological activities of fraction B (FB) prepared from EGS, such as enhanced wound and diabetic ulcer healing, anti-inflammatory action and cytotoxic activities reported in our previous studies. The anti-proliferative actions of some of these oxysterols especially the cholesterol 3,5,6-triol (#5) as established on selected cancer cell lines in this study support our previous studies and make them candidates for research for human application.
Six-month humoral immune response to inactivated COVID-19 vaccine among people living with HIV

Longitudinal humoral immune response to inactivated COVID-19 vaccines among people living with HIV (PLWH) have not yet been systematically investigated. We conducted a 6-month longitudinal study among vaccinated PLWH and HIV-Negative Controls (HNC) to determine whether the humoral immune response effects of the inactivated COVID-19 vaccine are different between the two groups of people. Totally, 46 PLWH and 38 HNC who received the inactivated COVID-19 vaccine on days 0 and 28 were enrolled. The SARS-CoV-2 neutralizing antibodies (nAbs) and total specific IgM and IgG antibodies were examined on Day 0-Day190. The level and positive seroconversion rate of nAbs peaked on Day 42 in HNC while peaked on Day 70 in PLWH, then decreased gradually with the extension of the vaccination period after the peaks. The peak level of nAbs in PLWH on Day 70, (GMC 8.07 BAU/mL, 95% CI 5.67-11.48) was significantly lower than in HNC on Day 42 (GMC 18.28 BAU/mL, 95% CI 10.33-32.33, P =0.03). The decrease in the geometric mean concentrations (GMCs) of nAbs was observed as 42.9% in PLWH after peak level, which decreased from 8.07 BAU/mL [95% CI: 5.67-11.48] on Day 70 to 4.61 BAU/mL [95% CI: 3.35-6.34] on Day 190 (p = 0.02). On Day 190, only seven (18%, [95% CI: 6-40]) HNC and five (11%, [95% CI: 4-25]) PLWH maintained positive nAbs response respectively. The geometric mean ELISA units (GMEUs) and positive seroconversion rate of IgG in PLWH dropped significantly from Day 70 (GMEUs, 0.20 EU/mL, [95% CI: 0.13-0.34]; seroconversion, 52%, [95% CI: 34-69]) to Day 190 (GMEUs, 0.05 EU/mL, [95% CI: 0.03-0.08], P<0.001; seroconversion, 18%, [95% CI: 8-33], P<0.001). There was no significant difference in levels and seroconversion rates of nAbs and IgG between the two groups on Day 190. The peak immunogenicity of the inactivated COVID-19 vaccine was delayed and inferior in PLWH compared to HNC, while no significant difference was found in six-month immunogenicity between the two groups.
Combined analysis of transcriptome and metabolome reveals the molecular mechanism and candidate genes of Haloxylon drought tolerance

Haloxylon ammodendron and Haloxylon persicum, as typical desert plants, show strong drought tolerance and environmental adaptability. They are ideal model plants for studying the molecular mechanisms of drought tolerance. Transcriptomic and metabolomic analyses were performed to reveal the response mechanisms of H. ammodendron and H. persicum to a drought environment at the levels of transcription and physiological metabolism. The results showed that the morphological structures of H. ammodendron and H. persicum showed adaptability to drought stress. Under drought conditions, the peroxidase activity, abscisic acid content, auxin content, and gibberellin content of H. ammodendron increased, while the contents of proline and malondialdehyde decreased. The amino acid content of H. persicum was increased, while the contents of proline, malondialdehyde, auxin, and gibberellin were decreased. Under drought conditions, 12,233 and 17,953 differentially expressed genes (DEGs) were identified in H. ammodendron and H. persicum , respectively, including members of multiple transcription factor families such as FAR1, AP2/ERF, C2H2, bHLH, MYB, C2C2, and WRKY that were significantly up-regulated under drought stress. In the positive ion mode, 296 and 452 differential metabolites (DEMs) were identified in H. ammodendron and H. persicum, respectively; in the negative ion mode, 252 and 354 DEMs were identified, primarily in carbohydrate and lipid metabolism. A combined transcriptome and metabolome analysis showed that drought stress promoted the glycolysis/gluconeogenesis pathways of H. ammodendron and H. persicum and increased the expression of amino acid synthesis pathways, consistent with the physiological results. In addition, transcriptome and metabolome were jointly used to analyze the expression changes of the genes/metabolites of H. ammodendron and H. persicum that were associated with drought tolerance but were regulated differently in the two plants. This study identified drought-tolerance genes and metabolites in H. ammodendron and H. persicum and has provided new ideas for studying the drought stress response of Haloxylon.