Miracle-dz/UniFAR-FTUs huggingface dataset:
The risk of infective endocarditis among people who inject drugs: a retrospective, population-based time series analysis

BACKGROUND: Infective endocarditis is an increasingly common complication among people who inject drugs. We conducted this study to determine whether the removal of traditional controlled-release oxycodone from the Canadian market would be associated with an increase in the use of hydromorphone and an increased risk of infective endocarditis. METHODS: We conducted a retrospective, population-based time series analysis using the linked health administrative databases of Ontario, Canada. We measured the quarterly risk of admissions for infective endocarditis related to injection drug use and changes in opioid prescription rates from 2006 to 2015. We set the intervention point at the fourth quarter of 2011, when traditional controlled-release oxycodone was removed from the Canadian market. RESULTS: We observed an increase in the risk of admissions for infective endocarditis related to injection drug use during the study period. Before the intervention point, we observed a mean of 13.4 admissions per quarter, and after the intervention, we observed a mean of 35.1 admissions per quarter. However, no significant change in this risk occurred at the intervention point. Rather, the risk of infectious endocarditis appeared to have increased earlier and in parallel with the rise in hydromorphone prescriptions. Hydromorphone represented 16% of all opioid prescriptions at the start of the observation period and 53% by the end. INTERPRETATION: The risk of infective endocarditis related to injection drug use is increasing and is temporally associated with increasing prescriptions for hydromorphone. This relation warrants further exploration.
Mixture Proportion Design Method of Steel Fiber Reinforced Recycled Coarse Aggregate Concrete

Steel fiber reinforced recycled coarse aggregate concrete (SFRCAC) is an impact minimisation building material. Mixture proportion design method of SFRCAC is developed in this paper to obtain concrete with target strength and workability, which can be used in structural members. Four key parameters of mixture proportioning, steel fiber content, water-cement ratio, water content and sand ratio are discussed through the mixture design tests. The formula for calculating the four key parameters of mixture proportions for SFRCAC are established through the statistical analysis of test results, which mainly consider the influences of recycled coarse aggregate (RCA) replacement ratio and steel fiber characteristic coefficient. The detailed procedure by using the new mixture proportion design method is illustrated with examples. The formulas established have the simple form, reflect the properties of RCA and steel fibers, enhance the mixture proportion design accuracy, and provide the reference for the mix proportion design of SFRCAC.
Pneumococcal Colonization in Healthy Adult Research Participants in the Conjugate Vaccine Era, United Kingdom, 2010–2017

Abstract Pneumococcal colonization is rarely studied in adults, except as part of family surveys. We report the outcomes of colonization screening in healthy adults (all were nonsmokers without major comorbidities or contact with children aged <5 years) who had volunteered to take part in clinical research. Using nasal wash culture, we detected colonization in 6.5% of volunteers (52 of 795). Serotype 3 was the commonest serotype (10 of 52 isolates). The majority of the remaining serotypes (35 of 52 isolates) were nonvaccine serotypes, but we also identified persistent circulation of serotypes 19A and 19F. Resistance to at least 1 of 6 antibiotics tested was found in 8 of 52 isolates.
Transcriptome Analysis Clarified Genes Involved in Betalain Biosynthesis in the Fruit of Red Pitayas (Hylocereus costaricensis)

The red flesh trait gives red pitayas more healthful components and a higher price, while the genetic mechanism behind this trait is unknown. In this manuscript, transcriptome analysis was employed to discover the genetic differences between white and red flesh in pitayas. A total of 27.99 Gb clean data were obtained for four samples. Unigenes, 79,049 in number, were generated with an average length of 1333 bp, and 52,618 Unigenes were annotated. Compared with white flesh, the expression of 10,215 Unigenes was up-regulated, and 4853 Unigenes were down-regulated in red flesh. The metabolic pathways accounted for 64.6% of all differentially expressed Unigenes in KEGG pathways. The group with high betalain content in red flesh and all structural genes, related to betalain biosynthesis, had a higher expression in red flesh than white flesh. The expression of the key gene, tyrosine hydroxylase CYP76AD1, was up-regulated 245.08 times, while 4,5-DOPA dioxygenase DODA was up-regulated 6.46 times. Moreover, the special isomers CYP76AD1α and DODAα were only expressed in red flesh. The competitive anthocyanin biosynthesis pathway had a lower expression in red flesh. Two MYB transcription factors were of the same branch as BvMYB1, regulating betalain biosynthesis in beet, and those transcription factors had expression differences in two kinds of pitayas, which indicated that they should be candidate genes controlling betalain accumulation in red pitayas. This research would benefit from identifying the major gene controlling red flesh trait and breed new cultivars with the red flesh trait. Future research should aim to prove the role of each candidate gene in betalain biosynthesis in red pitayas.
Clinicopathological study of malignant melanoma in a regional cancer center.

BACKGROUND : Malignant melanoma is a tumor of melanocytic origin. Although uncommon in India as compared with the west, its prevalence is increasing. OBJECTIVES To document the pattern of clinicopathological features of malignant melanoma cases attending in a regional cancer center in eastern India. MATERIAL AND METHODS The present study was a retrospective study of 182 cases diagnosed histopathologically as malignant melanoma during 2011-2016. RESULTS Out of the total cases, 170 (93.4%) were cutaneous and 12 (6.6%) were noncutaneous melanoma. The most common age group was sixth decade with a male predominance. Conventional melanotic melanomas were 176 (96.70%), and only 6 cases (3.30%) were amelanotic melanoma. Among noncutaneous melanomas, 6 were in anorectum, 2 in conjunctiva, and 1 case each in nasal cavity, palate, gingivo-buccal sulcus, and vagina. The acrallentigenous type was the most common variety, and the mixed epithelioid and spindle cell type was the most common histopathological pattern. Clark's level III was the most common level of invasion. CONCLUSION The lower extremity is the most common site for melanoma, whereas extracutaneous melanomas are exceedingly rare and aggressive neoplasms. Melanoma can metastasize to regional lymph nodes, however, visceral metastasis to liver can also occur. In the absence of pigment in amelanotic melanoma, immunohistochemical markers such as HMB 45 can be used for definitive diagnosis.
A new machine learning model based on induction of rules for autism detection

Autism spectrum disorder is a developmental disorder that describes certain challenges associated with communication (verbal and non-verbal), social skills, and repetitive behaviors. Typically, autism spectrum disorder is diagnosed in a clinical environment by licensed specialists using procedures which can be lengthy and cost-ineffective. Therefore, scholars in the medical, psychology, and applied behavioral science fields have in recent decades developed screening methods such as the Autism Spectrum Quotient and Modified Checklist for Autism in Toddlers for diagnosing autism and other pervasive developmental disorders. The accuracy and efficiency of these screening methods rely primarily on the experience and knowledge of the user, as well as the items designed in the screening method. One promising direction to improve the accuracy and efficiency of autism spectrum disorder detection is to build classification systems using intelligent technologies such as machine learning. Machine learning offers advanced techniques that construct automated classifiers that can be exploited by users and clinicians to significantly improve sensitivity, specificity, accuracy, and efficiency in diagnostic discovery. This article proposes a new machine learning method called Rules-Machine Learning that not only detects autistic traits of cases and controls but also offers users knowledge bases (rules) that can be utilized by domain experts in understanding the reasons behind the classification. Empirical results on three data sets related to children, adolescents, and adults show that Rules-Machine Learning offers classifiers with higher predictive accuracy, sensitivity, harmonic mean, and specificity than those of other machine learning approaches such as Boosting, Bagging, decision trees, and rule induction.
Cumulative Risk of End-Stage Renal Disease Among Patients With Type 2 Diabetes: A Nationwide Inception Cohort Study

OBJECTIVE To estimate long-term cumulative risk of end-stage renal disease (ESRD) after diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS This nationwide population-based inception cohort study included 421,429 patients with type 2 diabetes diagnosed in 1990–2011; patients were followed until the end of 2013. Data linkage between several national health care registers in Finland, covering 100% of the population, enabled the inclusion of almost all inhabitants who started taking diabetes medication or were hospitalized for diabetes. Cumulative risk of ESRD and hazard ratios [HR] for ESRD and death were estimated according to age, sex, and time period of diabetes diagnosis. RESULTS Among 421,429 patients with type 2 diabetes, 1,516 developed ESRD and 150,524 died during 3,458,797 patient-years of follow-up. Cumulative risk of ESRD was 0.29% at 10 years and 0.74% at 20 years from diagnosis of diabetes. Risk was higher among men than among women (HR 1.93 [95% CI 1.72–2.16]), decreased with older age at diagnosis (HR 0.70 [95% CI 0.60–0.81] for age 60–69 vs. 40–49 years), and was lower for those diagnosed in 2000–2011 than in 1990–1994 (HR 0.72 [95% CI 0.63–0.81]). Patients diagnosed with diabetes in 2000–2011 had lower risk of death during follow-up than those diagnosed in 1990–1994 (HR 0.64 [95% CI 0.63–0.65]). CONCLUSIONS Cumulative risk of ESRD is minimal among patients with type 2 diabetes compared with their risk of death. Patients diagnosed with diabetes at an older age have a lower risk of ESRD due to higher competing mortality.
Response to ‘Sex‐by‐formulation interaction in bioequivalence studies: the importance of formulations and experimental conditions’ by Ibarra et al.

We are glad to read in the previous commentary that Ibarra et al agree that studies suggesting the existence of sex‐by‐formulation interaction should not be considered as demonstration of such an interaction if the study was not designed for that purpose and the sample size was not designed for that investigation. As regulators and scientists, we investigated the existence of a sex‐by‐formulation interaction in efavirenz tablets, as suggested by Ibarra et al, because we also consider this topic of interest. If the interaction really exists, the present bioequivalence requirements in regulatory guidelines would need to be revised worldwide. However, only a few papers have addressed this topic, and these papers are observational in nature and subject to bias. Consequently, it would be necessary that Ibarra et al conduct a confirmatory study with the formulation that suggested the existence of a sex‐by‐formulation interaction to obtain evidence from a properly designed experiment. On our side, we will continue exploring critically this possibility on the available data in order to improve the existing evidence, although observational. As argued by Ibarra et al, males are more likely to be in fasted state because digestion in males is more rapid than in females. Therefore, this suggests the different discriminatory power is not related to sex but to fasting/fed state. Consequently, even assuming that a sex‐by‐formulation interaction may exist, there is no need to demonstrate bioequivalence separately in males and females if bioequivalence is shown separately in fasted and fed state, as it is required by the US‐FDA presently, since the underlying cause is the fasting/fed state of the study participants. Given there would be a wide range in “degree of digestion” in both the female and male populations at a time such as 2 hours after a meal, the continued study at the two ends of the range, under completely fasted conditions and immediately following a meal, seems like the best way to address the variability that would be observed in between. The influence of the extreme values was pointed out to illustrate that mean values of groups with less than 12 subjects are not reliable. We appreciate the notification of an error in subject #10 value, which is inconsequential in our view. After the exclusion of the extreme values, the means of the sex groups continue to be unreliable since the sample size is too small. Ibarra et al claim that a sex‐by‐formulation interaction arises only if the evaluated formulations are truly different and acknowledges that the suggested sex‐by‐formulation in our pilot study could have been an artefact because it was bioequivalent to the reference in
Enhancement of the effect of BCG vaccine against tuberculosis using DDA/TDB liposomes containing a fusion protein of HspX, PPE44, and EsxV

Abstract Tuberculosis has been a major health problem worldwide for years; therefore, it is important to develop and produce an effective vaccine against this disease. In this study, the immunogenicity of Mycobacterium tuberculosis fusion protein (FP) encapsulated in liposomes containing DDA/TDB was evaluated. The FP was expressed in E. coli BL21 and encapsulated in liposomal formulations. Three weeks after the last subcutaneous immunization, IFN-γ, IL-4, IL-17, and IL-12 in spleen cell culture supernatants, and IgG2a, IgG1, and IgG2b titres in sera were measured. The greatest IFN-γ and IL-12 interleukin concentrations were observed in the DDA/TDB/CHOL liposomes containing the FP. Initial injection with BCG improved the efficacy of the DDA/TDB/CHOL/FP vaccine. The IgG2a/IgG1 ratio was also high in the DDA/TDB/CHOL/FP group; furthermore, the IgG2a/IgG1 ratio was increased in the BCG-primed, DDA/TDB/CHOL/FP-boosted group, indicating induction of a cellular immune response. Our study showed that the FP-containing DDA/TDB/CHOL liposomes induced a Th1 response. However, the groups that first received BCG and then DDA/TDB/CHOL/FP had the greatest Th1 response in terms of IFN-γ and IL-12 production of all the groups. This suggests that these formulations enhance the BCG vaccine’s effectiveness.
Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Very Young Children: A Multicenter, 3-Week, Randomized Trial

OBJECTIVE We aimed to assess the feasibility and safety of hybrid closed-loop insulin delivery in children with type 1 diabetes aged 1–7 years as well as evaluate the role of diluted insulin on glucose control. RESEARCH DESIGN AND METHODS In an open-label, multicenter, multinational, randomized crossover study, 24 children with type 1 diabetes on insulin pump therapy (median age 5 years [interquartile range 3–6] and mean ± SD HbA1c 7.4 ± 0.7% [57 ± 8 mmol/mol] and total insulin 13.2 ± 4.8 units/day) underwent two 21-day periods of unrestricted living and we compared hybrid closed-loop with diluted insulin (U20) and hybrid closed-loop with standard strength insulin (U100) in random order. During both interventions, the Cambridge model predictive control algorithm was used. RESULTS The proportion of time that sensor glucose was in the target range between 3.9 and 10 mmol/L (primary end point) was not different between interventions (mean ± SD 72 ± 8% vs. 70 ± 7% for closed-loop with diluted insulin vs. closed-loop with standard insulin, respectively; P = 0.16). There was no difference in mean glucose levels (8.0 ± 0.8 vs. 8.2 ± 0.6 mmol/L; P = 0.14), glucose variability (SD of sensor glucose 3.1 ± 0.5 vs. 3.2 ± 0.4 mmol/L; P = 0.16), or the proportion of time spent with sensor glucose <3.9 mmol/L (4.5 ± 1.7% vs. 4.7 ± 1.4%; P = 0.47) or <2.8 mmol/L (0.6 ± 0.5% vs. 0.6 ± 0.4%; P > 0.99). Total daily insulin delivery did not differ (17.3 ± 5.6 vs. 18.9 ± 6.9 units/day; P = 0.07). No closed-loop–related severe hypoglycemia or ketoacidosis occurred. CONCLUSIONS Unrestricted home use of day-and-night closed-loop in very young children with type 1 diabetes is feasible and safe. The use of diluted insulin during closed-loop does not provide additional benefits compared with standard strength insulin.
Introduction to the Virtual Issue "Translational Studies in AUD: Liver Disease".

Recent high visibility publications raised the overall awareness of the importance of alcohol use disorders (AUD) and alcohol-associated liver disease as major health problems in the United States and worldwide. While this is not earth-shattering news to the alcohol-research community, it markedly enhances the level of public awareness of these important issues. An article in the Lancet involving a very large number of centers and authors generated estimates of alcohol use and alcohol-contributable deaths and disability in life years for 195 locations between 1990-2016 (Collaborators, 2018). This article is protected by copyright. All rights reserved.
3,5-Diiodo-L-Thyronine Exerts Metabolically Favorable Effects on Visceral Adipose Tissue of Rats Receiving a High-Fat Diet

When administered to rats receiving a high-fat diet (HFD), 3,5-diiodo-L-thyronine (3,5-T2) [at a dose of 25 μg/100 g body weight (BW)] is known to increase energy expenditure and to prevent HFD-induced adiposity. Here, we investigated which cellular and molecular processes in visceral white adipose tissue (VAT) contributed to the beneficial effect of 3,5-T2 over time (between 1 day and 4 weeks following administration). 3,5-T2 programmed the adipocyte for lipolysis by rapidly inducing hormone sensitive lipase (HSL) phosphorylation at the protein kinase A-responsive site Ser563, accompanied with glycerol release at the 1-week time-point, contributing to the partial normalization of adipocyte volume with respect to control (N) animals. After two weeks, when the adipocyte volumes of HFD-3,5-T2 rats were completely normalized to those of the controls (N), 3,5-T2 consistently induced HSL phosphorylation at Ser563, indicative of a combined effect of 3,5-T2-induced adipose lipolysis and increasing non-adipose oxidative metabolism. VAT proteome analysis after 4 weeks of treatment revealed that 3,5-T2 significantly altered the proteomic profile of HFD rats and produced a marked pro-angiogenic action. This was associated with a reduced representation of proteins involved in lipid storage or related to response to oxidative stress, and a normalization of the levels of those involved in lipogenesis-associated mitochondrial function. In conclusion, the prevention of VAT mass-gain by 3,5-T2 occurred through different molecular pathways that, together with the previously reported stimulation of resting metabolism and liver fatty acid oxidation, are associated with an anti adipogenic/lipogenic potential and positively impact on tissue health.
Age, Race, and At-Risk Drinking in an HIV-infected U.S. Military Cohort.

INTRODUCTION There is a high prevalence of at-risk drinking in the U.S. military. Among HIV-infected individuals, alcohol abuse confers additional risk for adverse health outcomes. In the military, however, the characteristics of HIV-infected individuals who engage in high-risk drinking are not well defined. The purpose of this study was to assess risk factors associated with at-risk drinking in an HIV-positive longitudinal cohort of DoD beneficiaries. MATERIALS AND METHODS Annual prevalence of at-risk drinking was calculated for members of the U.S. Military HIV Natural History Study who initiated highly active antiretroviral therapy (HAART) during or after January 2006 through May 2014; each participant completed at least one self-reported alcohol survey within a year of HAART initiation. Univariate and multivariable logistic regression was used to analyze factors associated with at-risk drinking. RESULTS Sixty-six percent of subjects (495/752) reported at-risk drinking on at least one survey after HAART initiation. At-risk drinkers were more likely to be Active Duty compared to Retired (OR 0.65 95% CI [0.46, 0.92]). In multivariate models, Caucasian race (OR 3.30 95% CI [2.31, 4.71]); Hispanic/other race (OR 2.17 95% CI [1.51, 3.14]) and younger age (OR 0.61 per 10 years older, [95%CI 0.49, 0.75]) were significantly associated with at-risk drinking. Single relationship status (OR 1.51 95% CI [1.08, 2.13]) was also associated with at-risk drinking. CONCLUSIONS Consistent with general alcohol consumption patterns in the military, we found a high prevalence of at-risk drinking among individuals with HIV infection, which was associated most closely with young, non-African Americans. Targeting interventions toward this group will be important to reduce at-risk drinking and its potential for HIV-related complications.
Millennials and contraception: why do they forget? An international survey exploring the impact of lifestyles and stress levels on adherence to a daily contraceptive regimen

Abstract Background: Rates of unintended pregnancies are particularly high in young women, a finding that may be associated with their tendency not to use contraceptives correctly and/or consistently. For millennial women, busy lifestyles and associated stress may impact on daily activities including taking an oral contraceptive pill. Methods: Contraceptive pill users aged 21–29 years (‘millennial’ women; N = 4500) from nine countries in Europe and North and South America completed an online questionnaire on their daily habits and activities, disruptions to their routine and associated stress levels. Results: Thirty-nine percent of surveyed participants had forgotten to take their contraceptive pill at least once in the past month; 39% also admitted not taking it at the same time each day. On average, participants had experienced two major disruptions to their daily lives in the past year, with three quarters (74%) believing these disruptions increased their stress levels. Of those who had missed at least one pill in the past year, 40% attributed it to a busy schedule and 21% to stress, among other reasons. Over half of respondents (55%) reported they were more likely to forget their pill when preoccupied. Conclusions: Times of stress may make it more likely for millennial women to forget to take their pill. Health care providers should be aware of typical contraceptive adherence rates among young women and ensure that contraceptive counselling sessions include discussion of lifestyle issues and potential barriers to adherence. Every woman should be counselled on all available methods, so that she can make an informed choice on what best suits her.