Miracle-dz/UniFAR-FTUs huggingface dataset:
MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters

Abstract With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites. org/.
Epidemiology of primary shoulder dislocations requiring surgery: A cohort study from a major trauma center during 7 years

Purpose The epidemiology of shoulder instability in the general population is lacking. The aim of the current study was to determine the incidence rate of primary shoulder dislocations requiring surgical interventions in a major trauma center within a large maintenance organization. Methods A retrospective cohort analysis of electronic health records database from 1 January 2014 and 31 December 2020 was conducted in major rural trauma center. This study included all patients aged 10 years or older with a primary shoulder dislocation that were treated with closed reduction in the emergency room department. An overall incidence density rates (IDR) (per 100,000 person-years) of primary shoulder dislocations and stabilization surgeries were determined for the entire cohort. The data was used to evaluate the age-specific and gender-specific epidemiology. Results During the study period of 7 years there were 1,302 patients who underwent closed reduction after a primary shoulder dislocation (mean age 45 years). Of those, a total of 106 shoulder stabilization surgeries (8%) were performed. The IDR of primary shoulder dislocations was 179 per 100,000 person-years. The IDR of primary shoulder stabilizations was 15 per 100,000 person-years. The peak in number of dislocations was observed in the age groups of 20–29 years and over 60 years. In the age groups under 59 years dislocations were more common in men while in ages over 60 years dislocations were more common in women. The vast majority of shoulder stabilization surgeries were performed in young patients (age under 39 years). Conclusion The IDR of primary shoulder dislocations calculated from a major trauma center of the largest health maintenance organization in Israel was 179 per 100,000 person-years. Shoulder dislocations had bimodal age distribution. Overall, eight percent of the patients (mainly young) with shoulder dislocations underwent shoulder stabilization surgery during the study period.
Studies on the sensory sensilla on the tarsi and external genitalia of the Asian tiger mosquito, Aedes albopictus (Skuse)

Dengue fever is a worldwide health problem transmitted mainly by Aedes albopictus. The ability of female mosquitoes to transmit disease depends on their behavioral responses to locate their host. The presence of different types of sensory sensilla with different morphological characteristics is the most distinctive feature of Ae. albopictus, in addition to the main sensory organs. The sensory sensilla are chemosensory contacts that Ae. albopictus uses to locate long‐distance hosts and oviposition sites by receiving well‐defined cues such as changes in temperature and humidity, mechanical impact, and odors. As a result, it is crucial to study the sensory sensilla of Ae. albopictus. Although the sensory sensilla of Ae. aegypti have been extensively studied, but there is still a lack of knowledge about the sensory sensilla of the Asian tiger mosquito, Ae. albopictus. This study aimed to investigate the different types of sensory sensilla on the tarsi and external genitalia of both sexes of Ae. albopictus and their morphological features using a scanning electron microscope. The results demonstrated that the tarsi have five types of sensory sensilla: sensilla chaetica, grooved pegs, sensilla campaniform, sensilla basiconica, and sensilla coeloconica. There are two thick, grooved sensilla on the tarsal joints. Sensilla coeloconica on the tarsus are hidden under scales in a raised pit and have a diameter of 13.69 ± 0.071 μm, which is significantly larger than those on the external genitalia of males, which have a diameter of 7.65 ± 0.065 μm. Sensilla coeloconica is absent from the external genitalia of females. Two types of senillae chaetica are found on the tarsomeres, near the claws, and on the joints, which differ significantly in morphology and morphometric parameters. The ovulation‐supporting cerci are provided with three pairs of long sensilla chaetica at the apex, measuring 111.36 ± 0.020 μm in length. Two groups of four apical sensilla and short spiny subapical sensilla are randomly distributed on the ovipositor. The female external genitalia have two types of sensilla chaetica, which are arranged in rows and are significantly smaller than those of the male external genitalia.
Influence of glimepiride plus sitagliptin on treatment outcome, blood glucose, and oxidative stress in diabetic patients.

OBJECTIVE This research sets out to investigate the influence of glimepiride (GLIM) plus sitagliptin (SITA) on the treatment outcome, blood glucose (BG), and oxidative stress (OS) in diabetic patients. METHODS In this retrospective study, 189 patient cases of type 2 diabetes mellitus (T2DM) admitted from July 2017 to July 2021 to the Affiliated Hospital of Nantong University were selected, of whom 99 cases treated with GLIM + SITA were assigned to the research group (RG) and 90 cases receiving GLIM monotherapy were set as the control group (CG). The two cohorts of patients were compared in terms of treatment outcomes, BG, islet function, OS, inflammatory responses (IRs), and safety. The BG indexes detected mainly included fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPG) and glycosylated hemoglobin (HbA1c). Islet function was mainly measured by Homeostasis Model Assessment of β-cell Function (HOMA-β) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The OS parameters measured primarily included malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-18 were the inflammatory factors measured. RESULTS A statistically higher excellent or good rate of treatment was determined in the RG compared to the CG. After treatment, FBG, 2hPG, HbA1c, HOMA-IR, MDA, TNF-α, IL-6, and IL-18 were lower in the RG while HOMA-β, SOD, and GSH-PX were higher, compared to the levels before treatment and the CG. A non-significantly different incidence of adverse reactions between groups was determined. CONCLUSIONS Our findings demonstrated high efficacy of GLIM + SITA in the treatment of T2DM patients, which can effectively improve the BG and OS of patients and reduce inflammation without increasing the incidence of adverse reactions. This should have high clinical application value.
A critical review of adalimumab for the treatment of moderate-to-severe active ulcerative colitis in children

ABSTRACT Introduction Anti-tumor necrosis factor (TNF) antibodies play a major role in treating inflammatory bowel disease (IBD), both in adult and pediatric patients. While there is a large number of studies on efficacy and safety of infliximab in treating children and adolescents with ulcerative colitis (UC), data on adalimumab (ADA) are scarce. Areas covered Here, we review published case reports, cohort and real-time data, as well as the first randomized trial, ENVISION I, using ADA for treating pediatric UC. Available evidence confirms good efficacy in inducing and maintaining remission in children and adolescents with UC, with even higher response rates compared to adult UC. ENVISION I showed that in UC patients responding to ADA induction therapy, almost half of the patients remained in remission after 52 weeks of therapy on high-dosing ADA (weekly administration). As already well experienced with other biologics, dosing schemes are different between pediatric and adult patients, with children often requiring higher dosing. Expert opinion Further data are required to better understand how to optimize ADA therapy. The present and still-growing evidence places subcutaneous (sc.) anti-TNF-medication as alternative first-line therapy also for pediatric UC. This is also reflected by the preference for sc. medication of adolescent patients allowing less frequent and autonomous drug administration.
An Extended Theory of General Relativity Unifying the Matter-Antimatter States

This paper follows one of our earlier publications detailing an extended theory of General Relativity (GR) with two types of curvatures. In this framework, we first extend the Riemannian spinor theory in the formalism of A.Lichnerowicz. We then suggest that the non vanishing covariant derivative of the metric tensor linked to the extra curvature of our extended GR theory, be related to the trace of a specific Hermitean matrix. In the Riemannian theory, this matrix reduces to the classical gamma matrix that is precisely designed to distinguish the spin one half fields from its anti Fermionic counterpart. Our extended General Relativity theory therefore appears as unifying the Fermion-anti Fermion field states, and would legitimate the hidden medium concept introduced by Louis de Broglie in his attempt to explain the matter-antimatter symmetry.
Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021

The number of cases of Candida auris infection or carriage and of countries reporting cases and outbreaks increased in the European Union and European Economic Area during 2020 and 2021. Eight countries reported 335 such cases in 2020 and 13 countries 655 cases in 2021. Five countries experienced outbreaks while one country reported regional endemicity. These findings highlight the need for adequate laboratory capacity and surveillance for early detection of C. auris and rapid implementation of control measures.
California cannabis cultivation and processing workers: A qualitative analysis of physiological exposures and health effects.

INTRODUCTION Cannabis is a multi-billion-dollar California industry, but little is known about the occupational hazards or health experiences of cannabis cultivation workers. Respiratory and dermal exposures, musculoskeletal hazards, and other agricultural hazards have been identified in previous research. Even in a post-legalization framework, cannabis work is stigmatized and most cannabis is still produced illegally. Qualitative research is essential for establishing rapport with cannabis workers to understand their experiences and concerns. METHODS We conducted semi-structured discussions with four focus groups including 32 cannabis workers total, and 9 key informants who were workers, industry experts, and business owners or managers. Transcribed results were analyzed to identify key themes on physiological exposures and health effects. RESULTS The majority (81.3%) of focus group participants were seasonal migrant cannabis trimmers. Themes emerged of respiratory and dermal exposures and outcomes, musculoskeletal disorders, and physical hazards including living conditions. Workers reported respiratory symptoms and rashes from exposure to cannabis, mold, and pesticides. Musculoskeletal pain was ubiquitous due to inadequate seating and long shifts performing repetitive tasks. Seasonal workers experienced chronic exposure to cold conditions and unsanitary housing. Management-level interviewees and other industry stakeholders described concerns and experiences that differed from those of workers. DISCUSSION The results were consistent with existing research on cannabis worker health, with workers reporting respiratory and dermal exposure and symptoms, musculoskeletal hazards, and physical hazards associated with agricultural work. In addition, we found that workers were affected by substandard living conditions, remote and isolated work environments, and an absence of training.
MOSFiT: Modular Open Source Fitter for Transients

Much of the progress made in time-domain astronomy is accomplished by relating observational multiwavelength time-series data to models derived from our understanding of physical laws. This goal is typically accomplished by dividing the task in two: collecting data (observing), and constructing models to represent that data (theorizing). Owing to the natural tendency for specialization, a disconnect can develop between the best available theories and the best available data, potentially delaying advances in our understanding new classes of transients. We introduce MOSFiT: the Modular Open Source Fitter for Transients, a Python-based package that downloads transient data sets from open online catalogs (e.g., the Open Supernova Catalog), generates Monte Carlo ensembles of semi-analytical light-curve fits to those data sets and their associated Bayesian parameter posteriors, and optionally delivers the fitting results back to those same catalogs to make them available to the rest of the community. MOSFiT is designed to help bridge the gap between observations and theory in time-domain astronomy; in addition to making the application of existing models and creation of new models as simple as possible, MOSFiT yields statistically robust predictions for transient characteristics, with a standard output format that includes all the setup information necessary to reproduce a given result. As large-scale surveys such as that conducted with the Large Synoptic Survey Telescope (LSST), discover entirely new classes of transients, tools such as MOSFiT will be critical for enabling rapid comparison of models against data in statistically consistent, reproducible, and scientifically beneficial ways.
The Disks of Galaxies with Seyfert and Starburst Nuclei. II. Near-Infrared Structural Properties

We have derived the near-infrared structural components of a sample of Seyfert and starburst (SBN) host galaxies by fitting near-infrared images with a new two-dimensional decomposition algorithm. An analysis of the fitted parameters shows that Seyfert 1 and SBN bulges resemble normal early-type bulges in structure and color, with (J-K) about 0.1 mag redder than disk (J-K). Seyfert 2 bulges, on the other hand, are bluer than normal, with (J-K) ~ (J-K). Seyfert disks (especially type 1), but not those of SBNs, are abnormally bright (in surface brightness), significantly more so than even the brightest normal disks. Seyfert disks are also compact, but similar to those in normal early-type spirals. For a given mass, Seyfert and particularly SBN galaxies are abnormally rich in neutral hydrogen, and there is strong, albeit indirect, evidence for lower mass-to-light (M/L) ratios in Seyfert and SBN disks, but normal M/L ratios in their bulges. In Seyfert and SBN galaxies, H I mass fractions and M/L ratios are anticorrelated, and we attribute the high gas mass fractions and low M/L ratios in SBNs and several Seyfert galaxies to ongoing star formation. Such abundant gas in Seyfert galaxies would be expected to inhibit bar formation, which may explain why active galaxies are not always barred.
Same-Sex Marriage and Common Mental Health Diagnoses: A Sibling Comparison and Adoption Approach

ABSTRACT We aimed to test whether the association between same-sex marriage and common mental health diagnoses was explained by shared genetic and environmental familial influences using sibling comparison and adoption analyses. For the sibling comparison analysis, participants (1,177,712 men and 1,266,917 women) were individuals born in Sweden between 1932 and 1994 and had ever been recorded as married (in opposite-sex or same-sex marriages). For the adoption analysis, participants were 147,164 and 1,298 female–female full sibling and adoptive sibling pairs, respectively. Based on medical records, prescribed medication, and death certificates, depression, substance abuse, and suicide (completed and attempted) from age 18 years were identified. For both sexes, being in a same-sex marriage was associated with greater risk of depression, substance abuse, and suicide, compared with being in an opposite-sex marriage. Controlling for shared familial confounding reduced this difference by less than 20% in magnitude, but overall mental health disparities for individuals in same-sex marriages remained statistically significant. Among women, only the genetic correlation between same-sex marriage and depression was statistically significant (r = .33). Same-sex marriage, as a proxy for sexual orientation, was associated with increased risk of certain mental health diagnoses and shared familial confounding explained a small component of this association, depending on the diagnosis. The findings indicate that sexual orientation disparities in mental health outcomes may involve unmeasured factors, and a relatively small proportion should be considered that may be due to shared familial confounding relevant to both sexual orientation and psychopathology.
Ethnoracial Variation in Risk for Psychotic Experiences.

BACKGROUND & HYPOTHESIS Psychotic disorders are inequitably distributed by race in the United States, although it is not known whether this is due to assessment biases or inequitable distributions of risk factors. Psychotic experiences are subclinical hallucinations and delusions used to study the etiology of psychosis, which are based on self-report and therefore not subject to potential clinician biases. In this study, we test whether the prevalence of psychotic experiences (PE) varies by race and if this variance is explained by socioenvironmental risk factors. STUDY DESIGN Data on demographics, PE, and socioenvironmental risk factors were collected through the National Survey of Poly-victimization and Mental Health, a national probability sample of US young adults. Logistic regression analyses were used to determine whether PE prevalence varied by race/ethnicity and, if so, whether this was attenuated with inclusion of indicators of income, education, urban/rural living, discrimination, and trauma exposure. STUDY RESULTS Black and Hispanic respondents reported PE at significantly greater rates than White or "other" ethnoracial groups, with hallucinations more commonly reported by Hispanic respondents. PE were significantly associated with police violence exposure, discrimination, adverse childhood experiences, and educational attainment. These factors statistically explained ethnoracial differences in the likelihood of overall PE occurrence and of nearly all PE subtypes. CONCLUSIONS Previously observed racial differences in psychosis extend beyond clinical schizophrenia, and therefore, are unlikely to be explained entirely by clinician biases. Instead, racial disparities in PE appear to be driven by features of structural racism, trauma, and discrimination.
Alcohol and Atrial Fibrillation: A Pathophysiologic Perspective

Atrial fibrillation (AF) is the most common cardiac arrhythmia responsible for significant morbidity and mortality. Its burden on patients and the health care system is only expected to increase. Several studies have established a dose-response relationship between the amount and frequency of alcohol consumption and the incidence of new onset AF independent of sex, age, and other risk factors. This causal relationship is mediated by the impact alcohol consumption has on conduction properties of the atrium, structural and cellular effect on cardiac myocytes, and dysregulation of the autonomic nervous system. This article reviews the current literature supporting the link between alcohol consumption and AF while attempting to provide an insight into pathophysiological mechanisms.
Relationship of binding-site occupancy, transthyretin stabilisation and disease modification in patients with tafamidis-treated transthyretin amyloid cardiomyopathy

Abstract Background Tafamidis inhibits progression of transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) by binding TTR tetramer and inhibiting dissociation to monomers capable of denaturation and deposition in cardiac tissue. While the phase 3 ATTR-ACT trial demonstrated the efficacy of tafamidis, the degree to which the approved dose captures the full potential of the mechanism has yet to be assessed. Methods We developed a model of dynamic TTR concentrations in plasma to relate TTR occupancy by tafamidis to TTR stabilisation. We then developed population pharmacokinetic–pharmacodynamic models to characterise the relationship between stabilisation and measures of disease progression. Results Modelling individual patient data of tafamidis exposure and increased plasma TTR confirmed that single-site binding provides complete tetramer stabilisation in vivo. The approved dose was estimated to reduce unbound TTR tetramer by 92%, and was associated with 53%, 56% and 49% decreases in the rate of change in NT-proBNP, KCCQ-OS, and six-minute walk test disease progression measures, respectively. Simulating complete TTR stabilisation predicted slightly greater reductions of 58%, 61% and 54%, respectively. Conclusions These findings support the value of TTR stabilisation as a clinically beneficial treatment option in ATTR-CM and the ability of tafamidis to realise nearly the full therapeutic benefit of this mechanism. Clinicaltrials.gov identifier NCT01994889
Oxidative damage induced by combined exposure of titanium dioxide nanoparticles and cypermethrin in rats for 90 days

Titanium dioxide nanoparticles (TiO2NPs) and cypermethrin (CPM) are widely used in various fields, and they can enter the environment in different ways. Combined exposure of TiO2NPs and CPM may increase the accumulation of pollutants in organisms and affect human health. This study was undertaken to evaluate the oxidative and inflammatory parameters associated with the combined exposure of TiO2NPs and CPM in rats. Twenty-four healthy male adult SD rats were randomly divided into four groups. The first group served as the control, while groups 2, 3, and 4 were treated with TiO2NPs (450 mg/m3); CPM (6.67 mg/m3) or combined exposure of TiO2NPs and CPM by inhalation for 90 days. We investigated the oxidative damage induced through combined exposure of TiO2NPs and CPM in rats by evaluating hematology of the rats and determining the blood biochemical index. Our results demonstrated that inhalation of TiO2NPs and CPM increased the levels of oxidative stress markers such as malondialdehyde and alkaline phosphatase in the serum of rats. These were accompanied by a decreased glutathione peroxidase and total superoxide dismutase levels. Furthermore, the level of glutathione peroxidase was further decreased while malondialdehyde was increased in the combined exposure of TiO2NPs and CPM. Interestingly, pathological sections showed that different degrees of tissue injury could be seen in the liver and lung tissues of each exposure group. In summary, the combined exposure of TiO2NPs and CPM can cause increased oxidative damage in rats and damage the tissue structure of the liver and lung.