Miracle-dz/UniFAR-FTUs huggingface dataset:
Deaths from novel psychoactive substances in England, Wales and Northern Ireland: Evaluating the impact of the UK psychoactive substances act 2016

Background: ‘Legal highs’ began appearing in the UK in the mid-2000s. Whilst many of these substances were controlled under the 1971 Misuse of Drugs Act, novel compounds and new variants of controlled compounds were continuously being introduced to the recreational drug market. The Psychoactive Substances Act (PSA) was therefore implemented in 2016 as a blanket ban on all novel psychoactive substances (NPS). Aim: To evaluate the impact of the PSA on deaths following NPS use in England, Wales and Northern Ireland. Methods: Cases reported to the National Programme on Substance Abuse Deaths where death had occurred 3 years pre- or post-implementation of the PSA were extracted. Cases with NPS detected at post-mortem were analysed and compared against cases non-NPS cases. Results: 293 deaths with NPS detected were identified; 91 occurring before the PSA and 202 afterwards, indicating an 222.0% post-PSA increase. Contrastingly, non-NPS drug-related death case reporting increased by only 8.0%. Synthetic cannabinoid, anxiolytic/sedative and stimulant NPS were detected in the largest proportions of deaths pre-PSA; post-PSA stimulant NPS detections reduced whilst synthetic cannabinoid and anxiolytic/sedative detections increased. Post-PSA, average decedent age increased significantly (mean age pre-PSA 34.4 ± 10.8 vs post-PSA 38.3 ± 9.4), and they were significantly more likely to have been living in deprived areas (pre-PSA 50.0% vs post-PSA 65.9%). Conclusions: Reporting of deaths following NPS use has risen despite introduction of the PSA. Whilst deaths amongst younger individuals and those living in more affluent areas has reduced, additional approaches to prohibition are needed to curb their persistence in deprived demographics.
CTCF as a regulator of alternative splicing: new tricks for an old player

Abstract Three decades of research have established the CCCTC-binding factor (CTCF) as a ubiquitously expressed chromatin organizing factor and master regulator of gene expression. A new role for CTCF as a regulator of alternative splicing (AS) has now emerged. CTCF has been directly and indirectly linked to the modulation of AS at the individual transcript and at the transcriptome-wide level. The emerging role of CTCF-mediated regulation of AS involves diverse mechanisms; including transcriptional elongation, DNA methylation, chromatin architecture, histone modifications, and regulation of splicing factor expression and assembly. CTCF thereby appears to not only co-ordinate gene expression regulation but contributes to the modulation of transcriptomic complexity. In this review, we highlight previous discoveries regarding the role of CTCF in AS. In addition, we summarize detailed mechanisms by which CTCF mediates AS regulation. We propose opportunities for further research designed to examine the possible fate of CTCF-mediated alternatively spliced genes and associated biological consequences. CTCF has been widely acknowledged as the ‘master weaver of the genome’. Given its multiple connections, further characterization of CTCF’s emerging role in splicing regulation might extend its functional repertoire towards a ‘conductor of the splicing orchestra’.
Anti-seizure Drug Levels in Children Aged 2-12 Years Presenting With Breakthrough Seizures: A Single Center Cross-sectional Study.

OBJECTIVE To study the anti-seizure drug levels and associated factors in children with breakthrough seizures. METHODS This cross-sectional study was conducted at a public hospital between November 2017 to April 2019, included 145 children with epilepsy aged 2 to 12 years presenting with breakthrough seizure. Anti-seizure drug levels were measured, and the levels were categorized as within, below, and above the reference range. RESULTS Children with epilepsy receiving sodium valproate, phenytoin and carbamazepine were 111 (73%), 31 (20.4%) and 10 (6.6%), respectively, of which 7 were receiving multiple anti-seizure drugs. Drug levels below the reference range were found in 64 (44.1%), within the reference range in 70 (48.3%), and the above reference range in 11 (7.6%) children. CONCLUSION Nearly half the children with breakthrough seizures had sub-therapeutic levels, especially those on phenytoin therapy. Drug levels in below therapeutic range do not predict the occurrence of breakthrough seizures.
Quality and Accuracy of Cervical Radiculopathy-specific Information on the Internet

We evaluated the quality and accuracy of the content surrounding cervical radiculopathy available on the internet. The majority of internet sites currently offering cervical radiculopathy information to patients are physician driven. Despite the wide number of sources available, the quality, accuracy, pertinence and intelligibility of the information remains highly variable. Study Design. Cross-sectional analysis. Objective. This study aimed to evaluate the quality and accuracy of the content surrounding cervical radiculopathy available on the internet. Summary of Background Data. Those experiencing cervical radiculopathy and their families are increasingly browsing the worldwide web for medical information. As the information offered is likely to influence their health care choices, spine care providers must understand the quality and accuracy of that information. Methods. Independent searches were conducted on the three most commonly accessed search engines (Google, Yahoo, and Bing) using the keyword “cervical radiculopathy. ” The searches were performed on June 28th, 2019. The top 50 sites from each search engines were reviewed. The websites were evaluated using quality, accuracy and usability markers. Results. Seventy-seven unique websites were analyzed; 54.5% were physician or medical group professional sites, 20.8% as non-physician, 10.4% as unidentified, 7.8% as academics, and 6.5% were commercial. Accuracy ranged from <25% to >75% were recorded with a mean accuracy of 3.5 signifying 50% to 75% agreement. Overall, website categories had a significant effect on Journal of American Medical Association (JAMA) score, content quality, accuracy, total summary scores, distraction index, reading ease, and grade level (P < 0.05). Academic sites had the highest mean quality content, accuracy and total summary scores. Four of the top five websites with the highest total summary scores were physician driven. On average, Health on the Net code (HONcode) certified websites had lower grade level readability with greater reading ease and higher DISCERN and JAMA scores than uncertified sites (P < 0.05). Conclusion. Despite the wide number of sources available, the quality, accuracy, pertinence, and intelligibility of the information remains highly variable. Clinicians treating patients with cervical radiculopathy should direct them to verifiable sites with regulated information and, where possible, contribute high- quality information to those sites. Level of Evidence: 4
Masculinity's association with the interpersonal theory of suicide among military personnel.

OBJECTIVE Given that the majority of those who die by suicide are male, masculine traits have been examined as a potential link to the development of capability for suicide. However, research has not examined if such traits influence suicidal desire (i.e., thwarted belongingness, perceived burdensomeness). This study examined the influence of stereotypically masculine traits of stoicism, sensation seeking, physical aggression, verbal aggression, and self-reliance on all three components of the Interpersonal Theory of Suicide within a sample of male and female service members. METHODS A total of 953 service members were recruited as part of a larger study. RESULTS Sensation seeking and stoicism were positively associated with capability for suicide. With regard to suicidal desire, self-reliance and verbal aggression were positively associated with both perceived burdensomeness and thwarted belongingness. Stoicism was positively associated with thwarted belongingness. CONCLUSIONS Findings suggest that different masculine traits are associated with the three components of the Interpersonal Theory of Suicide in various ways. Stoicism may be an especially important masculine trait that influences a component of suicidal desire and capability for suicide.
Ecofriendly dyeing of silk with extract of yerba mate (Ilex paraguariensis)

Silk fabric was dyed with extract of roasted yerba mate (Ilex paraguariensis). Dyeing experiments were carried out at varying dyestuff concentration, temperature and pH. The influence of mordants, such as potassium alum and tannin, was investigated. The best results in dyeing were produced with 20 g L–1 of dyestuff concentration, pH 3 and temperature of 90℃. Mordants showed negligible influence. The kinetic study showed that the pseudo-second-order equation better represented experimental data, which is related to the chemisorption process as the rate-controlling step. The equilibrium data were easily adjusted by the Langmuir–Freundlich model, indicating the significant contribution of the chemisorption process in a monolayer followed by a multilayer physisorption. The thermodynamic study indicated that dye adsorption was spontaneous and endothermic.
Deconvolution of distinct lithology chemistry through oversampling with the Mars Science Laboratory Alpha Particle X-Ray Spectrometer

The Alpha Particle X-Ray Spectrometer (APXS) determines the chemical composition of Martian rocks and soils on-board both active National Aeronautics and Space Administration (NASA) rovers using X-ray emission spectroscopy through complementary particle-induced X-ray emission (PIXE) and X-ray fluorescence (XRF) excitation methods. A single APXS spectrum represents the sum of the signals from within the instrument's field of view (FOV). In the past, features smaller than the FOV have been investigated through repeated measurements with stepwise lateral offsets. These lateral offsets allow for empirically extracting, through elemental correlations, distinct compositions of different features. Here, we present a novel analytical method for deconvolving the endmember chemistry of visually distinct components through oversampling and the integrated analysis of the elemental data and supporting images. We discuss specifically the method's application to three targets investigated by the Mars Science Laboratory rover Curiosity during its traverse, as well as the added information that can be gained from this method in the future. Copyright © 2016 John Wiley & Sons, Ltd.
Quantifying Heterogeneity of Testicular Histopathology in Men with Nonobstructive Azoospermia

Purpose: We sought to determine if testicular histopathological heterogeneity is associated with sperm retrieval rates (SRRs) in men with nonobstructive azoospermia (NOA) who are undergoing microdissection testicular sperm extraction (mTESE). Materials and Methods: All patients undergoing mTESE by a single, high-volume surgeon at a tertiary infertility referral center between 2010 and 2020 were evaluated. Pathology reports from testis biopsy at the time of mTESE reported by fellowship-trained genitourinary pathologists were reviewed. Testicular heterogeneity was correlated to absolute SRRs. Logistic regression was used to determine if heterogeneity was associated with sperm retrieval. Results: A total of 918 men with mTESE were included. Of these, 391 men (43%) had 1 pathology, 388 men (42%) had 2, 108 (12%) had 3, and 31 (3.4%) had 4. Overall, the most common histopathology was Sertoli-cell only, followed by maturation arrest. The overall SRR was 42% with a clinical intrauterine gestation rate of 30%. Increasing histopathological variety was associated with higher SRRs (p <0.01); a SRR of 33% was observed when one histopathological subtype was present vs 94% with 4 subtypes. Furthermore, men with any foci of spermatogenesis had higher SRRs. Conclusions: In men with NOA, increasing testicular histopathological heterogeneity is correlated with higher SRRs driven by the identification of focal areas of spermatogenesis. This is an important, although predictable, observation. While diagnostic biopsy is not routinely required, these findings emphasize the value of having histology to perhaps predict the chance of sperm retrieval for future mTESE procedures.
Comprehensive characterization of naturally occurring antioxidants from the twigs of mulberry ( Morus alba ) using on‐line high‐performance liquid chromatography coupled with chemical detection and high‐resolution mass spectrometry

Abstract Introduction The mulberry tree ( Morus alba L.) is a prolific source of biologically active compounds. There is considerable growing interest in probing M. alba twigs as a source of disruptive antioxidant lead candidates for cosmetic skin care product development. Objective An integrated approach using high‐performance liquid chromatography (HPLC) coupled with either chemical detection (CD) or high‐resolution mass spectrometry (HRMS) was applied to the hydroalcoholic extract of M. alba to detect and identify lead antioxidant compounds, respectively. Material and methods The twigs were weighed, powdered and homogenized using a mill and the extract was prepared using 70% aqueous ethanol. The antioxidant metabolites were detected with HPLC coupled with CD (based on the ORAC assay) and their structural identification was carried out using a Q‐Exactive Orbitrap MS instrument. Results Using this approach, 13 peaks were detected as overall contributors to the antioxidant activity of M. alba , i.e. mulberrosides (A & E), oxyresveratrol & its derivatives, moracin & its derivatives and a dihydroxy‐octadecadienoic acid, which together accounted for >90% of the antioxidant activity, highlighting the effectiveness of the integrated approach based on HPLC‐CD and HPLC‐HRMS. Additionally, a (3,4‐dimethoxyphenyl‐1‐O‐β‐D‐apiofuranosyl‐(1″ → 6′)‐O‐β‐D‐glucopyranoside was also discovered for the first time from the twig extract and is presented here. Conclusion To our knowledge, this is the first report from M. alba twigs using HPLC‐CD and HPLC‐HRMS that identifies key compounds responsible for the antioxidant property of this native Chinese medicinal plant.
Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population: a cross-sectional study of risk factors and bacterial genomic diversity

ABSTRACT Antibiotic resistant Klebsiella pneumoniae is a leading public health threat and gastrointestinal carriage is an established risk factor for subsequent infections during hospitalization. Our study contributes new knowledge of risk factors for gastrointestinal carriage and the genomic population structure of K. pneumoniae colonizing humans in a representative sample of a general population in a community setting. Altogether, 2,975 participants (54% women) >40 y in the population-based Tromsø Study: Tromsø7, Norway (2015–2016) were included. Fecal samples were screened for K. pneumoniae, which were characterized using whole-genome sequencing. Risk factors for carriage were analyzed using multivariable logistic regression on data from questionnaires and the Norwegian Prescription Database. Prevalence of K. pneumoniae gastrointestinal carriage was 16.3% (95% CI 15.0–17.7, no gender difference). Risk factors associated with carriage included age ≥60 y, travel to Greece or Asia past 12 months (adjusted odds ratio 1.49, 95% CI 1.11–2.00), Crohn’s disease/ulcerative colitis (2.26, 1.20–4.27), use of proton pump inhibitors (1.62, 1.18–2.22) and non-steroidal anti-inflammatory drugs past 6 months (1.38, 1.04–1.84), and antibiotic use the last month (1.73, 1.05–2.86). Prevalence was higher among those having used combinations of drug classes and decreased over time with respect to preceding antibiotic use. The K. pneumoniae population was diverse with 300 sequence types among 484 isolates distributed across four phylogroups. Only 5.2% of isolates harbored acquired resistance and 11.6% had virulence factors. Identification of risk factors for gastrointestinal carriage allows for identification of individuals that may have higher risk of extraintestinal infection during hospitalization. The findings that specific diseases and drugs used were associated with carriage show an impact of these possibly through modulating the human gut microbiota promoting colonization. The diverse population structure of carriage isolates reflects the ecologically adaptive capacity of the bacterium and challenges for vaccine prospects and the identification of reservoirs as a potential source for human colonization.
Under-5 mortality and morbidity outcomes of fertility postponement in Turkey: explanations by observed and unobserved characteristics

ABSTRACT This paper investigates the association between advanced maternal age and under-5 mortality and morbidity in Turkey, and is the first such study in the country to use a sibling comparison model to analyze this phenomenon. The study is based on data obtained from the 2013 Turkey Demographic and Health Survey, and analyzes the association of advanced maternal age with: (1) under-five mortality, using Cox proportional hazard models and their stratified versions to compare sibling groups born to the same mother in the 1978–2013 period, and (2) under-five morbidity; specifically, being born with low birth weight, stunting, underweight, and wasting based on between- and within-sibling groups models for the 2008–2013 period. Overall, our findings suggest that the hazard of under-5 mortality increases as maternal age increases. We conclude that period effects have failed to reverse the impeding effects of advanced maternal age on child mortality. Between-sibling group models indicate a positive but close to null association between advanced maternal age and child morbidity in general, although these positive associations vanish once we apply within-sibling group models. This result can be partially attributed to our controlling for unobserved characteristics specific to sibling groups, in addition to other methodological differences.
CroSR391, an ortholog of the λ Cro repressor, plays a major role in suppressing polVR391‐dependent mutagenesis

When subcloned into low‐copy‐number expression vectors, rumAB, encoding polVR391 (RumA′2B), is best characterized as a potent mutator giving rise to high levels of spontaneous mutagenesis in vivo. This is in dramatic contrast to the poorly mutable phenotype when polVR391 is expressed from the native 88.5 kb R391, suggesting that R391 expresses cis‐acting factors that suppress the expression and/or the activity of polVR391. Indeed, we recently discovered that SetRR391, an ortholog of λ cI repressor, is a transcriptional repressor of rumAB. Here, we report that CroSR391, an ortholog of λ Cro, also serves as a potent transcriptional repressor of rumAB. Levels of RumA are dependent upon an interplay between SetRR391 and CroSR391, with the greatest reduction of RumA protein levels observed in the absence of SetRR391 and the presence of CroSR391. Under these conditions, CroSR391 completely abolishes the high levels of mutagenesis promoted by polVR391 expressed from low‐copy‐number plasmids. Furthermore, deletion of croSR391 on the native R391 results in a dramatic increase in mutagenesis, indicating that CroSR391 plays a major role in suppressing polVR391 mutagenesis in vivo. Inactivating mutations in CroSR391 therefore have the distinct possibility of increasing cellular mutagenesis that could lead to the evolution of antibiotic resistance of pathogenic bacteria harboring R391.
Exploiting within‐breed variability in the autochthonous Reggiana breed identified several candidate genes affecting pigmentation‐related traits, stature and udder defects in cattle

Summary Autochthonous cattle breeds constitute important reservoirs of genetic diversity. Reggiana is an Italian local cattle breed reared in the north of Italy for the production of a mono‐breed Parmigiano–Reggiano cheese. Reggiana cattle usually have a classical solid red coat colour and pale muzzle. As part of the strategies designed for the sustainable conservation of this genetic resource, we investigated at the genome‐wise level the within‐breed detected variability of three pigmentation‐related traits (intensity of red coat colour, based on three classes – light/diluted, normal and dark; spotted patterns/piebaldism that sometime emerge in the breed; muzzle colour – pink/pale, grey and black), stature, presence/absence and number of supernumerary teats and teat length. A total of 1776 Reggiana cattle (about two‐thirds of the extant breed population) were genotyped with the GeneSeek GGP Bovine 150k SNP array and single‐marker and haplotype‐based GWASs were carried out. The results indicated that two main groups of genetic factors affect the intensity of red coat colour: darkening genes (including EDN3 and a few other genes) and diluting genes (including PMEL and a few other genes). Muzzle colour was mainly determined by MC1R gene markers. Piebaldism was mainly associated with KIT gene markers. Stature was associated with BTA6 markers upstream of the NCAPG–LCORL genes. Teat defects were associated with TBX3/TBX5, MCC and LGR5 genes. Overall, the identified genomic regions not only can be directly used in selection plans in the Reggiana breed, but also contribute to clarifying the genetic mechanisms involved in determining exterior traits in cattle.
Multidimensional analysis and detection of informative features in human brain white matter

The white matter contains long-range connections between different brain regions and the organization of these connections holds important implications for brain function in health and disease. Tractometry uses diffusion-weighted magnetic resonance imaging (dMRI) to quantify tissue properties along the trajectories of these connections. Statistical inference from tractometry usually either averages these quantities along the length of each fiber bundle or computes regression models separately for each point along every one of the bundles. These approaches are limited in their sensitivity, in the former case, or in their statistical power, in the latter. We developed a method based on the sparse group lasso (SGL) that takes into account tissue properties along all of the bundles and selects informative features by enforcing both global and bundle-level sparsity. We demonstrate the performance of the method in two settings: i) in a classification setting, patients with amyotrophic lateral sclerosis (ALS) are accurately distinguished from matched controls. Furthermore, SGL identifies the corticospinal tract as important for this classification, correctly finding the parts of the white matter known to be affected by the disease. ii) In a regression setting, SGL accurately predicts “brain age. ” In this case, the weights are distributed throughout the white matter indicating that many different regions of the white matter change over the lifespan. Thus, SGL leverages the multivariate relationships between diffusion properties in multiple bundles to make accurate phenotypic predictions while simultaneously discovering the most relevant features of the white matter.