Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the Interference of Solvents Used in the Evaluation of Antimicrobial Activity of Liposoluble Natural Compounds

Because it is an activity already consolidated throughout the ages, the use of compounds from plants has been well studied and tested for definition or proof of its antibacterial activity. Despite the difficulties encountered as the solubility of essential oils, there are compounds that help in experiments, they are called solvents and emulsifiers and the most used in phytotherapeutic tests are: ethyl acetate, acetone, ethyl alcohol, methyl alcohol, neutral detergent (phosphates free), dimethylsulfoxide (DMSO), triton X-I00 and polysorbate 80 (tween 80). In view of this fact, the present work seeks to identify concentrations of polysorbate 80 (Tween 80) and dimethylsulfoxide (DMSO) capable of performing an antibacterial activity, due to its wide use in the scientific environment, against the following bacterial strains: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 25922 and Enterococcus faecalis ATCC 29212. The evaluation of the activity of the compounds was performed by the diffusion disc method. This method is the one recommended by the Clinical and Laboratory Standards Institute and is based on the diffusion through the agar of a reagent impregnated in a disc of filter paper and the diffusion of the same leads to the formation of a halo of inhibition of growth of the micro- organisms whose diameter is inversely proportional to the minimum inhibitory concentration. This method is qualitative, that is, it allows to classify the bacterial sample as susceptible, intermediate or resistant to antimicrobial. The tests were carried out with different concentrations of the reagents to determine the antimicrobial effect of the studied solvents. The experiments were run in triplicate at all concentrations using the compounds in combination (DMSO + Tween). The incubation was done in a greenhouse at 35 ± 2 ° C, for a period of 24 hours. The tests were performed and the results expressed in mm by the arithmetic mean of the diameter of the inhibition halos, formed around the discs. As results, no values ​​were determined that determined antimicrobial activity, and it is not possible to determine MIC when the formed halo is equal to or less than 6 mm or when there is no formation thereof. In view of the results, it can be observed that the compounds may not present activities against the microorganisms tested or, due to their physico-chemical characteristics, suffer some interference, such as the diffusion difficulty in the agar, its insolubility in water and chemical complexity.
Epigallocatechin gallate (EGCG) attenuates myocardial hypertrophy and fibrosis induced by transverse aortic constriction via inhibiting the Akt/mTOR pathway

Abstract Context Epigallocatechin gallate (EGCG) is the most abundant catechin from tea. Previous studies have indicated EGCG has a cardioprotective effect. Objective This manuscript mainly explores the role of EGCG in pressure-overload cardiac hypertrophy and its mechanism related to the Akt/mTOR pathway. Methods and methods Transverse aortic constriction (TAC) was utilized to establish the cardiac hypertrophy mice model. C57BL/6 mice were assigned into 6 groups. Starting from the first day after surgery, mice received different doses of EGCG (20, 40, 80 mg/kg) or vehicle orally for four weeks. Heart weight to body weight (HW/BW) ratio and heart weight to tibia length (HW/TL) ratio as well as hematoxylin-eosin staining were utilized to evaluate cardiac hypertrophy. Masson’s trichrome and Sirius red staining were used to depict cardiac fibrosis. The expressions of fibrosis and hypertrophy-related markers and Akt/mTOR pathway were quantified by western blot and qRT-PCR. Results EGCG significantly attenuated cardiac function shown by decreased HW/BW (TAC, 6.82 ± 0.44 vs. 20 mg/kg EGCG, 5.53 ± 0.45; 40 mg/kg EGCG, 4.79 ± 0.32; 80 mg/kg EGCG, 4.81 ± 0.38) and HW/TL (TAC, 11.94 ± 0.69 vs. 20 mg/kg EGCG, 11.44 ± 0.49; 40 mg/kg EGCG, 8.83 ± 0.58; 80 mg/kg EGCG, 8.98 ± 0.63) ratios as well as alleviated cardiac histology. After treatment, hemodynamics was improved, cardiac fibrosis was attenuated. The activated Akt/mTOR pathway was inhibited by EGCG. Discussion and conclusions EGCG plays a protective role in the TAC model by regulating the Akt/mTOR pathway, which provides a theoretical basis for its clinical treatment.
MRI, Big Data, and Artificial Intelligence

Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative condition of the CNS characterized by highly variable clinical features. This variability makes it difficult for neurologists to predict the clinical course in each individual and, as a result, results in significant uncertainty for patients. Disease variability also makes prediction of treatment response a challenge, posing a major barrier to implementation of personalized medicine approaches in MS. These are major issues, as there are up to 3 million people with MS worldwide and approximately 1 million in the United States,1 and many go on to develop significant physical disability or disabling symptoms. We have an incomplete understanding of the reasons for this heterogeneity and variability. The pathology of MS is heterogeneous and involves inflammatory and neurodegenerative processes.2 In MS lesions, there are varying amounts of myelin content, with some patients and lesions demonstrating little demyelination.3 Similarly, the inflammatory profiles of patients with MS show significant heterogeneity, with T cells,4 B cells,5 and microglial cells6 involved. To gain further understanding, we need tools that help us understand the disease process, improve our diagnostic accuracy, better predict disease course, and select optimal treatments.
Regulating the starting location of front-gradient enabled highly efficient Cu(In,Ga)Se2 solar cells via a facile thiol–amine solution approach

The introduction of a double-gallium (Ga) gradient plays a key role in pushing the performance of Cu(In,Ga)Se2 (CIGSe) solar cells to a more competitive level. In particular, the location of the front-gradient starting position strongly affects the barrier of the electron transport path, and this is not based on either significantly reducing the electron collection or decreasing the fill factor. Here we present and implement a double-Ga gradient design for CIGSe absorber layers using a diamine–dithiol solution approach. By regulating the front-gradient starting location, three CIGSe absorber layers with different Ga gradients were successfully constructed; these materials maximize solar spectrum absorption and improve the charge collection efficiency. Moreover, this facile solution-process approach does not require expensive vacuum equipment and can be applied to roll-to-roll printing technology. By combining optimal front-gradients with the back gradient, the short-circuit current has been increased by 17% and a maximum improvement in CIGSe efficiency to 13.12% achieved through adjusting the front-gradient to an optimum location.
CASANOVA: Permutation inference in factorial survival designs

We propose inference procedures for general factorial designs with time‐to‐event endpoints. Similar to additive Aalen models, null hypotheses are formulated in terms of cumulative hazards. Deviations are measured in terms of quadratic forms in Nelson–Aalen‐type integrals. Different from existing approaches, this allows to work without restrictive model assumptions as proportional hazards. In particular, crossing survival or hazard curves can be detected without a significant loss of power. For a distribution‐free application of the method, a permutation strategy is suggested. The resulting procedures' asymptotic validity is proven and small sample performances are analyzed in extensive simulations. The analysis of a data set on asthma illustrates the applicability.
Fecal Putative Uropathogen Abundance and Antibiotic Resistance Gene Carriage in Women With Refractory Recurrent Urinary Tract Infection Treated With Fecal Microbiota Transplantation

Objective The aims of this study were to describe the fecal relative abundance of potentially uropathogenic bacteria and to analyze antibiotic resistance genes before and after fecal microbiota transplantation in women with recurrent urinary tract infection (UTI). Methods Shotgun sequencing was performed on fecal samples from 3 donors and 4 women with recurrent UTI who underwent transplantation. Recipient samples were sequenced at baseline and at 4 time points through 6 months postintervention. Relative fecal uropathogen abundance was analyzed by species and participant using descriptive statistics. Antibiotic resistance gene abundance was assigned, normalized, and compared between donors and recipients at baseline and postintervention using an abundance bar plot, nonmetric multidimensional scaling, and pairwise permutational multivariate analysis of variance. Results The median (range) relative abundance of Escherichia coli in all fecal samples from women with recurrent UTI was 0% (0%–5.10%); Enterococcus faecalis, 0% (0%–0.20%); Enterococcus faecium, 0% (0%–1.90%); Klebsiella pneumoniae, 0% (0%–0.10%); and Pseudomonas aeruginosa, 0% (0%–0.10%). Gut microbes carried genes conferring resistance to antibiotics used for UTI. No significant difference was seen in antibiotic resistance gene carriage after transplantation compared with baseline (P=0.22, R2=0.08 at 3 months). Antibiotic gene composition and abundance were significantly associated with the individual from whom the sample came (P=0.004, R2=0.78 at 3 months). Conclusions Exploratory analysis of gut microbiomes in women with recurrent UTI identifies no or low relative putative uropathogen abundance for all species examined. Antibiotic resistance gene carriage persisted after fecal microbiota transplantation, although conclusions are limited by small sample size.
A multi-state Markov model using notification data to estimate HIV incidence, number of undiagnosed individuals living with HIV, and delay between infection and diagnosis: Illustration in France, 2008–2018

Thirty-five years since the discovery of the human immunodeficiency virus (HIV), the epidemic is still ongoing in France. To guide HIV prevention strategies and monitor their impact, it is essential to understand the dynamics of the HIV epidemic. The indicator for reporting the progress of new infections is the HIV incidence. Given that HIV is mainly transmitted by undiagnosed individuals and that earlier treatment leads to less HIV transmission, it is essential to know the number of infected people unaware of their HIV-positive status as well as the time between infection and diagnosis. Our approach is based on a non-homogeneous multi-state Markov model describing the progression of the HIV disease. We propose a penalized likelihood approach to estimate the HIV incidence curve as well as the diagnosis rates. The HIV incidence curve was approximated using cubic M-splines, while an approximation of the cross-validation criterion was used to estimate the smoothing parameter. In a simulation study, we evaluate the performance of the model for reconstructing the HIV incidence curve and diagnosis rates. The method is illustrated in the population of men who have sex with men using HIV surveillance data collected by the French Institute for Public Health Surveillance since 2004.
Immunohistochemical evaluation of D2-40, Galectin-3, Maspin and MCM7 expression in palate squamous cell carcinomas

Squamous cell carcinoma (SCC) is the most frequent cancer in oral cavity and its prognosis has exhibited little improvement in the last decades. Although much less common palate SCCs manifests a higher local aggression invading very quickly the adjacent muscles and jawbones, thus being able frequently to lead to dysfunctions in chewing, swallowing, and speech. To elucidate what underlies such local aggression, we investigated the immunohistochemical expression in palate SCCs of Podoplanin (D2-40), Galectin-3 (Gal-3), mammary serine protease inhibitor (Maspin) and minichromosome maintenance complex component 7 (MCM7), markers that are known to be involved in tumor invasiveness. We found a progressive increase in reactivity for D2-40 and MCM7 from the normal epithelium toward dysplastic epithelium and respectively to SCC, which suggests the intervention of these markers in the early stages of squamous cell carcinogenesis in the palate. The highest D2-40, Gal-3 and MCM7 reactivity was observed in basaloid and in poorly differentiated (G3) palate SCCs, while for Maspin the well-differentiated (G1) palate SCCs were the most reactive. The first three markers mentioned above were most intensely expressed at the invasion front, while the Maspin reactivity was low or absent at this level. Statistically, we found significant stratification on localization, grading, muscle invasion, and survival for all investigated markers, but with very high direct correlations between D2-40, Gal-3, and MCM7 immunoreactive score (IRS) values, while between the Maspin and each of the previous markers there were very high inverse correlations. Overall, all these investigate markers proved to be responsible for the local invasiveness and regional lymph node metastasis, thus allowing a prognostic and therapeutic stratification of patients with palate SCCs.
Burnout and well-being in young doctors in Hong Kong: a territory-wide cross-sectional survey.

INTRODUCTION This territory-wide study evaluated the level of burnout and health status among young doctors in Hong Kong. METHODS All young doctors in Hong Kong, defined as residents-in-training or doctors within 10 years of their specialist registration, were invited to participate in an online cross-sectional survey. This survey used standardised questionnaires including the Copenhagen Burnout Inventory (CBI) for burnout, Patient Health Questionnaire-9 for depression, and general health questionnaires. RESULTS In total, 514 doctors completed the survey; 284 were doctors within 10 years of their specialist registration, while 230 were residents-in-training. There were 277 women (54%); among all respondents, the mean age was 33.7 ± 6.1 years. Using a CBI subscale cut-off score of ≥50 (moderate and higher), 72.6% (n=373) of respondents reported personal burnout; 70.6% (n=363) of respondents reported work-related burnout; and 55.4% (n=285) of respondents reported client-related burnout. Furthermore, 24% (n=125) of respondents were "somewhat dissatisfied" with their present job position; 4% (n=19) of respondents were "very dissatisfied" with their present job position. The prevalence of depression among respondents was 21% (n=110). CONCLUSIONS In this territory-wide cross-sectional survey of young doctors in Hong Kong, a high prevalence of burnout was identified among young doctors; respondents exhibited a considerable level of depression and substantial dissatisfaction with their current positions. Strategies to address these problems must be formulated to ensure the future well-being of the medical and dental workforce in Hong Kong.
Raman Spectroscopy Coupled with Reflectance Spectroscopy as a Tool for the Characterization of Key Hydrothermal Alteration Minerals in Epithermal Au–Ag Systems: Utility and Implications for Mineral Exploration

Raman spectroscopy of fine-grained hydrothermal alteration minerals, and phyllosilicates in particular, presents certain challenges. However, given the increasingly widespread recognition of field portable visible–near infrared–shortwave infrared (Vis-NIR-SWIR) spectroscopy as a valuable tool in the mineral exploration industry, Raman microspectroscopy has promise as an approach for developing detailed complementary information on hydrothermal alteration phases in ore-forming systems. Here we present exemplar high-quality Raman and Vis-NIR-SWIR spectra of four key hydrothermal alteration minerals (pyrophyllite, white mica, chlorite, and alunite) that are common in precious metal epithermal systems, from deposits on the island of Newfoundland, Canada. The results reported here demonstrate that Raman microspectroscopy can accurately characterize pyrophyllite, white mica, chlorite, and alunite and provide details on their compositional variation at the microscale. In particular, spectral differences in the 1000–1150 cm−1 white mica Raman band allows the distinction between low-Tschermak phases (muscovite, paragonite) and phases with higher degrees of Tschermak substitution (phengitic white mica composition). The peak position of the main chlorite Raman band shifts between 683 cm−1 for Mg-rich chlorite and 665 cm−1 for Fe-rich chlorite and can be therefore used for semiquantitative estimation of the Fe2+ content in chlorite. Furthermore, while Vis-NIR-SWIR macrospectroscopy allows the rapid identification of the overall composition of the most abundant hydrothermal alteration mineral in a given sample, Raman microspectroscopy provides an in-depth spectral and chemical characterization of individual mineral grains, preserving the spatial and paragenetic context of each mineral and allowing for the distinction of chemical variation between (and within) different mineral grains. This is particularly useful in the case of alunite, white mica, and chlorite, minerals with extensive solid solution, where microscale characterization can provide information on the alteration zonation useful for mineral exploration and provide insight into mineral deposit genesis. Graphical Abstract
Increased Plasma Hyaluronan Levels are Associated With Acute Traumatic Coagulopathy

Supplemental Digital Content is available in the text ABSTRACT Introduction: Acute traumatic coagulopathy (ATC) is an endogenous impairment in hemostasis that often contributes to early mortality after trauma. Endothelial glycocalyx damage is associated with trauma-induced coagulation abnormalities; however, the specific relationship between hyaluronan (HA), a key glycocalyx constituent, and ATC has not been evaluated. Methods: We performed a secondary analysis of prospectively collected data from a recent study in which trauma patients (>18 years) admitted to our Level I trauma center with an ABC Score≥2 were enrolled. Partial thromboplastin time (PTT), international normalized ratio (INR), and thromboelastography (TEG) parameters were recorded at arrival. Injury characteristics and clinical outcomes were obtained. Plasma HA levels were measured in healthy controls (HC) and in trauma subjects at arrival (t = 0 h) and 12, 24, and 48 h. ATC was defined as admission INR>1.2 or PTT≥36.5 s. Comparisons of HA levels were assessed, and Spearman's correlations were performed between 0 h and 24 h HA levels, coagulation measures and clinical outcomes. P values < 0.05 were considered significant. Results: Forty-eight trauma patients and 22 controls were enrolled for study. Sixteen trauma subjects were coagulopathic at admission. HA levels in subjects with ATC were higher than non-coagulopathic subjects at all time points and elevated above HC levels at 24 and 48 h. At arrival, HA levels correlated with TEG R-time, PTT, and INR. HA levels at 24 h correlated with increased transfusion requirements and intensive care unit and hospital lengths of stay. Conclusion: Shed HA is associated with early coagulation abnormalities in trauma patients, which may contribute to worse outcomes. These findings highlight the need for additional studies to evaluate the mechanistic role of HA in ATC.
Prevalence of adenomatous polyposis in a fecal immunochemical test-based colorectal cancer screening program and risk of advanced neoplasia during follow-up

Abstract Background Current guidelines recommend genetic counseling and intensive colonoscopy surveillance for patients with ≥ 10 colorectal adenomas based on scarce data. We investigated the prevalence of this condition in a fecal immunochemical test (FIT)-based colorectal (CRC) screening program, and the incidence of metachronous lesions during follow-up. Methods We retrospectively included all FIT-positive participants with ≥ 10 adenomas at index colonoscopy between 2010 and 2018. Surveillance colonoscopies were collected until 2019. Patients with inherited syndromes, serrated polyposis syndrome, total colectomy, or lacking surveillance data were excluded. The cumulative incidence of CRC and advanced neoplasia were analyzed by Kaplan–Meier analysis. Risk factors for metachronous advanced neoplasia were investigated by multivariable logistic regression analysis. Results 215 of 9582 participants (2.2 %) had ≥ 10 adenomas. Germline genetic testing was performed in 92 % of patients with ≥ 20 adenomas, identifying two inherited syndromes (3.3 %). The 3-year cumulative incidence of CRC and advanced neoplasia were 1 % and 16 %, respectively. In 39 patients (24.2 %), no polyps were found on first surveillance colonoscopy. The presence of an advanced adenoma was independently associated with a higher risk of advanced neoplasia at first surveillance colonoscopy (odds ratio 3.91, 95 %CI 1.12–13.62; P = 0.03). Beyond the first surveillance colonoscopy, the risk of metachronous advanced neoplasia was lower. Conclusions The prevalence of ≥ 10 adenomas in a FIT-based CRC screening program was 2.2 %; a small proportion of inherited syndromes were detected, even amongst those with ≥ 20 adenomas. A low rate of post-colonoscopy CRC was observed and the risk of advanced neoplasia beyond the first surveillance colonoscopy tended to progressively decrease throughout successive follow-ups.
Getting immunosuppression just right: the role of clinical biomarkers in predicting patient response post solid organ transplantation

ABSTRACT Introduction Actually, immunosuppression selection isn't based on individual immune alloreactivity, and immunosuppressive drug dosing is mainly based on the development of toxicity and the achievement of specific target concentrations. Since a successful outcome requires optimal patient risk stratification and treatment, several groups have evaluated candidate biomarkers that have shown promise in the assessment of individual immune responses, the prediction of personal pharmacodynamic effects of immunosuppressive drugs and the prognosis and diagnosis of graft outcomes. Areas covered This review includes biomarkers that the Scientific Community in Solid Organ Transplantation currently considers to have potential as diagnostic and prognostic biomarkers of graft evolution. We have focused on recent scientific advances and expert recommendations regarding the role of specific and non-specific pharmacodynamic biomarkers that are mainly involved in the T-cell-mediated response. Expert opinion Integral pharmacologic monitoring that combines pharmacokinetics, pharmacogenetics and predictive pharmacodynamic biomarkers may provide crucial information and allow personal adjustment of immunosuppressive drugs at an early stage before severe adverse events ensue. Multicentre, randomized, prospective and interventional trials are needed to fine tune the established cut-off values for each biomarker and the optimal monitoring frequency for each biomarker and to accurately evaluate possible clinical confounding factors to enable correct clinical qualification.