Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and molecular characterization of seven patients with Danon disease

Danon disease is an X-linked glycogen storage disease characterized by skeletal myopathy, cardiomyopathy and intellectual impairment. It is caused by a loss-of-function mutation in the lysosome-associated membrane protein-2 (LAMP2) gene. In the present study, exon and boarding intron analysis of 96 cardio disease-associated genes was performed in 770 patients with hypertrophic cardiomyopathy (HCM) using second-generation sequencing. Next, the identified mutations were confirmed in family members of the patients and 300 healthy controls. Detailed clinical, electrocardiographic (ECG) and echocardiographic findings were recorded. A pathogenic mutation in LAMP2 was identified in 7 patients who phenotypically presented with HCM. A total of four patients had a fragmented QRS complex (fQRS) on surface ECG. In addition, two patients presented with ventricular preexcitation with a short PR interval. Compared with the patients with protein kinase AMP-activated non-catalytic subunit γ2 syndrome and Fabry disease, the 7 patients with Danon disease presented at an earlier age, had a smaller left atrial size, a thinner maximal left ventricular wall thickness and a lower probability of pacemaker implantation. Compared with 12 sex- and age-matched patients with sarcomere-protein mutations, the 4 patients with Danon disease had a lower left ventricular outflow tract gradient and worse diastolic function. The present study provided a comprehensive comparison of different pathologies presenting with HCM and reported on features of early-onset Danon disease, including the characteristic preexcitation and fQRS on ECG. This may provide valuable information that may be utilized for the early diagnosis and treatment of patients with Danon disease. The present study was registered as a clinical trial with ClinicalTrials.gov (Sep. 2, 2016; registry no. NCT02888132).
Effects of Self-Identification as a Caregiver on Expectations of Public Stigma of Alzheimer’s Disease

Background: As a result of caring for a person with dementia, caregivers of persons with Alzheimer’s disease (AD) may be uniquely aware of public stigma for persons with AD. Objective: The purpose of this study was to compare self-identified caregivers and non-caregivers’ expectations of public stigma experienced by persons living with dementia. Methods: Analysis of data from a survey of 910 adults (median age = 49 years) who read a vignette about a man with mild stage dementia. Multivariable ordered logistic regression was used to examine how AD caregiver status associated with responses on a modified Family Stigma in Alzheimer’s Disease Scale (FS-ADS). Results: 9%(n = 82) of respondents self-identified as a current or former primary caregiver of a person with AD, about the same as the national estimate of informal caregivers (8.8%). Compared to non-caregivers, AD caregivers were more likely to report stronger reactions on all seven domains of the FS-ADS (all p < 0.05). As compared to AD caregivers with less factual knowledge about caregiving, AD caregivers with more knowledge expected the person with dementia to experience less social distance (p < 0.05). In addition, female AD caregivers reported fewer negative aesthetic attributions than male AD caregivers (p < 0.05). Conclusion: Compared to non-caregivers, respondents who self-identified as an AD caregiver gave responses that suggest they perceived more stigma of dementia among members of the public. Their reactions were attenuated by AD knowledge and being female. The findings have key implications for interventions to reduce AD stigma.
Diurnal variations in the expression of core-clock genes correlate with resting muscle properties and predict fluctuations in exercise performance across the day

Objectives In this study, we investigated daily fluctuations in molecular (gene expression) and physiological (biomechanical muscle properties) features in human peripheral cells and their correlation with exercise performance. Methods 21 healthy participants (13 men and 8 women) took part in three test series: for the molecular analysis, 15 participants provided hair, blood or saliva time-course sampling for the rhythmicity analysis of core-clock gene expression via RT-PCR. For the exercise tests, 16 participants conducted strength and endurance exercises at different times of the day (9h, 12h, 15h and 18h). Myotonometry was carried out using a digital palpation device (MyotonPRO), five muscles were measured in 11 participants. A computational analysis was performed to relate core-clock gene expression, resting muscle tone and exercise performance. Results Core-clock genes show daily fluctuations in expression in all biological samples tested for all participants. Exercise performance peaks in the late afternoon (15–18 hours for both men and women) and shows variations in performance, depending on the type of exercise (eg, strength vs endurance). Muscle tone varies across the day and higher muscle tone correlates with better performance. Molecular daily profiles correlate with daily variation in exercise performance. Conclusion Training programmes can profit from these findings to increase efficiency and fine-tune timing of training sessions based on the individual molecular data. Our results can benefit both professional athletes, where a fraction of seconds may allow for a gold medal, and rehabilitation in clinical settings to increase therapy efficacy and reduce recovery times.
The metabolic signature of cardiorespiratory fitness: a protocol for a systematic review and meta-analysis

Introduction A low cardiorespiratory fitness (CRF) is a strong and independent predictor of cardiometabolic, cancer and all-cause mortality. To date, the mechanisms linking CRF with reduced mortality remain largely unknown. Metabolomics, which is a powerful metabolic phenotyping technology to unravel molecular mechanisms underlying complex phenotypes, could elucidate how CRF fosters human health. Methods and analysis This study aims at systematically reviewing and meta-analysing the literature on metabolites of any human tissue sample, which are positively or negatively associated with CRF. Studies reporting estimated CRF will not be considered. No restrictions will be placed on the metabolomics technology used to measure metabolites. PubMed, Web of Science and EMBASE will be searched for relevant articles published until the date of the last search. Two authors will independently screen full texts of selected abstracts. References and citing articles of included articles will be screened for additional relevant publications. Data regarding study population, tissue samples, analytical technique, quality control, data processing, metabolites associated to CRF, cardiopulmonary exercise test protocol and exercise exhaustion criteria will be extracted. Methodological quality will be assessed using a modified version of QUADOMICS. Narrative synthesis as well as tabular/charted presentation of the extracted data will be included. If feasible, meta-analyses will be used to investigate the associations between identified metabolites and CRF. Potential sources of heterogeneity will be explored in meta-regressions. Ethics and dissemination No ethics approval is required. The results will be published in a peer-reviewed journal and as conference presentation. PROSPERO registration number CRD42020214375.
Accurate classification of COVID‐19 patients with different severity via machine learning

Dear Editor, Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could cause dramatic response in coronavirus disease 2019 (COVID-19) patients at multi-omics level,1–3 thus it is essential to systematically assess the pathogenesis of COVID-19. In our previous study, we presented the first trans-omics landscape of 236 COVID-19 patients with 4 clinical severity groups (including asymptomatic, mild, severe and critically ill cases) and found that the mild and severe COVID-19 patients shared several similar characteristics.4 However, it is crucial to discriminate mild from severe COVID-19 patients to prevent the latter from the progression of disease by facilitating early intervention. Herein, we developed an extreme gradient boosting (XGBoost)machine-learningmodel to predict the COVID-19 severities by leveraging multi-omics data. Briefly, we randomly stratified samples for the training set (80%) and the independent testing set (20%) (Figure 1A, seeMethods in the Supporting Information). After normalization, a total of 297 multi-omics features were preliminarily selected by applying a hybrid method (see Methods in the Supporting Information). The XGBoost model was trained on the training set with the preliminarily selected features, achieving mean micro-average AUROC (area under the receiver operating characteristic curve) and mean micro-average AUPR (area under the precisionrecall curve) of 0.9715 (95% CI, 0.9497–0.9932) and 0.9495 (95% CI, 0.9086–0.9904), respectively (Figure 1B and C). This showed strong generalizable discrimination among the four severities based on fivefold cross-validation over 100 iterations. The multi-omics features were prioritized and ranked by the XGBoost model and the SHAP (SHapley Additive exPlanations, see Methods in the Supporting Information) value. Top 60 important features were further selected consisting of 19 proteins, 11 metabolites, 7 lipids, and 23 mRNAs (Figure 1D, Figures S1-S4). With the top 60 features, the XGBoost model was re-trained and val-
Hepatitis B-related hepatocellular carcinoma and stress: untangling the host immune response from clinical outcomes

Chronic hepatitis B virus (HBV) infection is a major public health challenge on the global scale. Affecting hundreds of millions worldwide, HBV is a leading risk factor for hepatocellular carcinoma (HCC). Clinical outcomes from chronic HBV infection are varied and appear to be influenced by a complex and dysregulated host immune response. In turn, much attention has been given to the immunologic response to HBV in an effort to identify host factors that lead to the development of HCC. However, the role of nonimmunologic host factors, such as chronic stress, in HBV-related HCC is poorly defined. Indeed, a growing appreciation for the effects of stress on chronic liver diseases raises the question of its role in chronic HBV infection. In this light, the present review will untangle the roles of key host factors in HBV-related HCC with an emphasis on chronic stress as a viable contributor. First discussed is the interplay of stress, inflammation and chronic liver disease. The host immune response’s role as a driver of HBV-related HCC is then reviewed, allowing for a close exploration of the effects of stress on immune function in chronic hepatitis B and as a potential risk factor for HBV-related HCC.
Adsorption of Methonine at Mercury/Aqueous Solution of Chlorate(VII) Interface; Dependence on the Supporting Electrolyte Concentration

Adsorption of methionine on the mercury electrode from 0.5 to 8 mol dm−3 chlorates(VII) was examined. In all the systems studied the relative surface excesses of methionine increase with the increase of electrode charge and adsorbate concentration, they depend also on chlorates(VII) concentration. The adsorption parameters were determined from the Frumkin and virial isotherms. It was stated that the adsorption parameters change together with the change of supporting electrolyte concentration, what points at competitive adsorption of methionine and ClO ions and electrostatic interactions between the water dipoles and methionine in the double layer.
Association between influenza vaccination and hospitalisation or all-cause mortality in people with COVID-19: a retrospective cohort study

Introduction Recent evidence suggests that influenza vaccination may offer protection against COVID-19 severity. Our aim was to quantify the association between influenza vaccination status and risk of hospitalisation or all-cause mortality in people diagnosed with COVID-19. Methods A retrospective cohort study using routinely collected health records from patients registered to a General Practitioner (GP) practice in South West England within the Electronic Care and Health Information Analytics database. The cohort included 6921 people with COVID-19 during the first wave of the pandemic (1 January–31 July 2020). Data on influenza vaccination, hospitalisation and all-cause mortality were ascertained through linked clinical and demographic records. We applied propensity score methods (stabilised inverse probability of treatment weight) to quantify the association between influenza vaccination status and COVID-19 outcomes (hospitalisation or all-cause mortality). Results 2613 (38%) participants received an influenza vaccination between 1 January 2019 and COVID-19 diagnosis. Receipt of influenza vaccination was associated with a significantly lower odds of hospitalisation or all-cause mortality (adjusted OR: 0.85, 95% CI 0.75 to 0.97, p=0.02), and 24% reduced odds of all-cause mortality (adjusted OR: 0.76, 95% CI 0.64 to 0.90). Discussion Influenza vaccination was associated with a 15%–24% lower odds of severe COVID-19 outcomes. The current UK influenza vaccination programme needs urgent expansion as an integral component of the ongoing response plans to the COVID-19 pandemic.
Endocrine Signals Altered by Heat Stress Impact Dairy Cow Mammary Cellular Processes at Different Stages of the Dry Period

Simple Summary Late-gestation heat stress increases blood prolactin and decreases oestrogen concentrations in dry cows. These hormonal alterations may disturb mammary gland remodelling during the dry period, thereby being potentially responsible for the observed production impairments during the subsequent lactation. This project aimed to better understand the molecular mechanisms underlying subsequent impairments in mammary performance after dry period heat stress. For this, we studied the expression of genes encompassing prolactin and oestrogen pathways and key cellular process pathways under different thermal environments and in vitro hormonal milieus. The results of this study revealed that late-gestation heat stress impacted the expression of genes in the mammary gland involved in key cellular processes occurring during the dry period. Furthermore, our results indicated that these modifications are in part modulated by alterations of oestrogen and prolactin signalling. Abstract Hormonal alterations occurring under late gestation heat stress may disturb mammary gland remodelling, resulting in a reduced milk yield during the subsequent lactation. We investigated the effects of an altered endocrine environment on mammary gene expression at different stages of the dry period. Mammary gland biopsies from in vivo-cooled (CL) or heat-stressed (HT) cows were collected at d 3 and 35 relative to dry-off and divided into explants. Explants were incubated in vitro for 24 h in one of three media: Basal: no prolactin or estrogen; CL-mimic: Basal + low prolactin + high 17β-estradiol, or HT-mimic: Basal + high prolactin + low 17β-estradiol. Real time qPCR was used to quantify gene expression. We established that late-gestation heat stress changes the expression of prolactin and oestrogen receptors, downregulates genes involved in apoptosis, autophagy and proliferation at d 3 and upregulates genes related to those cellular processes at d 35. Moreover, compared with in vivo treatments, we showed that the expression of fewer genes was impacted by in vitro treatments which aimed to mimic the hormonal response of cows exposed to a different environment. Further research will continue to uncover the mechanisms behind the production impairments caused by late-gestation heat stress.
Green Conversion of Saponins to Diosgenin in an Alcoholysis System Catalyzed by Solid Acid Derived from Phosphorus Tailings

This work proposed to prepare solid acid from phosphorus tailings and successfully convert Dioscorea zingiberensis C.H. Wright (DZW) into diosgenin from the perspective of solid waste resource reuse and clean production. The results showed that SiO2–SO3H solid acid could catalyze the production of diosgenin from total saponins under solvothermal reaction conditions. In addition, the parameters of a single factor, such as the amount of SiO2–SO3H, solvent volume, reaction temperature, and reaction time, were optimized to confirm the optimal range of reaction conditions, and the optimal process conditions were determined by the response surface method. The yield of diosgenin was 2.45 ± 0.17% under the optimum conditions, and the yield of diosgenin was increased by 12.90% compared with the traditional acid hydrolysis process. Except the relatively higher catalytic activity, the alcoholysis approach for the production of diosgenin has no waste liquid to discharge. The products were analyzed by high-performance liquid chromatography-mass spectrometry, and the pathway to convert total saponins into diosgenin under SiO2–SO3H has been proposed. Moreover, the adopted catalyst can be prepared with very low cost from phosphorus tailings. Considering the obvious superiorities, the alcoholysis approach in this work could be a promising strategy for green production of diosgenin as well as a possible utilization pathway of phosphorus tailings.
Proteomics analysis of the hypothalamus in spontaneously hypertensive rats treated with twirling reinforcing manipulation, twirling reducing manipulation or electroacupuncture

Hypertension is one of the primary risk factors for cardiovascular diseases. Numerous proteins serve a critical role in hypertension. Acupuncture has been widely used as a treatment for hypertension in China. The results of the current study suggested that electroacupuncture (EA), twirling reinforcing manipulation (TRFM) and twirling reducing manipulation (TRDM) may be useful in the treatment of hypertension. Additionally, proteome analysis of spontaneously hypertensive rats treated with EA, TRFM and TRDM was performed. There were 117 (EA group), 61 (TRFM group) and 86 (TRDM group) differentially expressed proteins (DEPs) identified in the respective experimental groups compared with the model group. Moreover, parallel reaction monitoring assays were used to validate the reliability of the DEPs. The majority of the results were consistent with previous proteomics results, in particular that for expression of neudesin neurotrophic factor (NENF). NENF may potentially represent an antihypertensive drug target.
A Method to Separate Lignoids fromVirolaLeaves

The genus Virola (Myristicaceae) comprises approximately 35 species which are distributed in neotropical countries (Rodrigues, 1980). Their geographical and taxonomic distribution has been used in studies of chemical ecology (Paulino Filho, 1985), especially of the Amazon forest. The bark resin, derived from various Virola species, provides hallucinogenic snuff and an arrow poison, and the species has thus attracted phytochemical examination (Holmstedt et al., 1980). The genus is well known to be an abundant source of lignans and neolignans, and its important physiological actions have been reported (MacRae and Towers, 1985). A particularly striking finding is the observed high levels of lignoids found in human urine (enterolignans), following dietary intake of vegetable fibre and grain (Bannwart et al., 1989), which have been suggested to have cancer-protective effects (Adlercreutz et al., 1991). Investigations of lignoids in plants were mainly carried out with trunk wood (Fernandes, J. B. et al., 1980), bark, fruit (Lemus and Castro, 1989), fruit pericarp, aril, seed coat and kernel (Kato et al., 1990), while little is known of the distribution of these compounds in the leaves (Martinez et al., 1985). The apparent lack of phytochemical data may be due in part to the nature of the crude extracts of Virola leaves, which generally yield a sticky residue composed of chlorophylls and other colouring matters which are difficult to resolve by chromatographic methods. The general procedure for the removal of colouring matter from plant leaves includes the treatment of green extracts with freshly activated charcoal or by passing through a charcoal column (Nair et al., 1990), as well as by lead acetate adsorption. There are, however, disadvantages to these procedures: metabolite losses can occur through occlusion in the precipitate and a residuum of lead acetate remains in solution and can cause problems in subsequent stages. As part of our continuous research work on the Virola, we have examined the lignoid constituents of the leaves of V. surinamensis (Rol.) Warb. (Barata et al., 1978; Queiroz Paulo, 1982; Santos and Barata, 1990) of V. oleifera (Schott) A. C. Smith (Fernandes, A. M. A. P. et al., 1993, 1994) and of V. pavonis (A. DC.) A. C. Smith (Ferri and Barata, 1991, 1992). The crude extracts of the leaves were systematically submitted to chlorophyll elimination yielding purified fractions free of colouring matter and rich in lignoid mixtures. This resulted in the isolation of seventeen lignoids, including nine new compounds. The present work describes the use of this simplified methodology for an efficient separation of the lignans and neolignans from apolar and polar crude extracts of the leaves of V. oleifera and V. pavonis.
Graphene/carbon aerogels derived from graphene crosslinked polyimide as electrode materials for supercapacitors

Carbon aerogels with hierarchical porous structures are highly promising for developing novel electrode materials for supercapacitors due to their substantial active sites for ion and electron transfer. Herein, a new type of graphene/carbon aerogels with multimodal pores have been facilely synthesized via carbonization of graphene crosslinked polyimide aerogels. Compared to most carbon aerogels based on organic aerogels reported previously, this preparation process is facilitated by the exclusion of harmful formaldehyde. Moreover, graphene is demonstrated as a powerful crosslinking agent, allowing acceleration of the gelation process, improvement of the porous structures inside carbon aerogels, and enlargement of specific surface area and conductivity of carbon aerogels. SEM observation shows the multimodal pores and three-dimensional nano-network of carbon aerogels, which provide short diffusion lengths for both charge and ion transport and high electroactive regions. With graphene involved, the as-prepared carbon aerogels possess high specific surface area up to 998.7 m 2 g � 1 and specific capacitance up to 178.1 F g � 1 at a current density of 1 A g � 1 , which is much higher than that of pure carbon aerogels (193.6 m 2 g � 1 and 104.2 F g � 1 ). This work provides a new and facile avenue for