Miracle-dz/UniFAR-FTUs huggingface dataset:
The Evaluation of APTT Reagents in Reference Plasma, Recombinant FVIII Products; Kovaltry® and Jivi® Using CWA, Including sTF/7FIX Assay

The FVIII activity in patients treated with several extended half-life FVIII (EHL-FVIII) agents different when various activated partial thromboplastin time (APTT) reagents were used. The present study examined the difference in clot waveform analysis (CWA) findings and FVIII activity when various APTT reagents and CWA were used. The CWA including FVIII activity was measured using 12 APTT reagents, and the FIX activation based on a small amount of tissue factor assay (sTF/FIX) were examined in reference plasma (RP), EHL-FVIII (Jivi®) and Kovaltry®. The 3 APTT reagents were associated with high variation in the peak time and height in the CWA when analyzing low concentrations of FVIII. The peak time and height could not be measured with one APTT reagent, and there were marked differences in the CWA findings between Jivi® and Kovaltry® among APTT reagents. Several APTT reagents showed a markedly lower FVIII activity with Jivi® than with Kovaltry®. In the FVIII assay, the peak time measured with sTF/FIX did not differ markedly between Jivi® and Kovaltry®; however, the FVIII activity in Jivi® (as measured by the peak height) tended to be higher than in Kovaltry®. The CWA findings for monitoring Jivi® varied for monitoring Jivi® depending on the APTT reagents used, and sTF/FIX assay may be able to measure the EHL-FVIII.
Prevalence and predictors of potentially inappropriate prescribing in middle-aged adults: a repeated cross-sectional study

Background Potentially inappropriate prescribing (PIP) is common in older adults and known to be associated with polypharmacy and multimorbidity. Less is known about the prevalence and causes of PIP in middle-aged adults. Aim To determine the prevalence and predictors of PIP in middle-aged adults. Design and setting A repeated cross-sectional study was conducted using primary care data in London. Method PIP was defined using the PRescribing Optimally in Middle-aged People’s Treatments (PROMPT) criteria. Prescribing and demographic data were extracted from Lambeth DataNet (LDN), a pseudonymised database of all patients registered at general practices in Lambeth, for those aged 45–64 years prescribed ≥1 medicines in each year from 2014–2019 (n = 46 633–52 582). Prevalence and trends over 6 years were investigated, including the association of PIP with polypharmacy, multimorbidity, deprivation, sex, and age. Results The prevalence of PIP decreased from 20% in 2014 to 18% in 2019. The most prevalent PROMPT criteria in 2019 were the use of ≥2 drugs from the same pharmacological class (7.6%), use of non-steroidal anti-inflammatory drugs for >3 months (7.1%) and use of proton pump inhibitors above recommended maintenance dosages for >8 weeks (3.1%). Over the study period, the prevalence of multimorbidity increased (47–52%) and polypharmacy remained stable (27%). Polypharmacy, multimorbidity, deprivation, and age were independently associated with PIP. Sex was the only variable not associated with PIP. Conclusion Almost one-fifth of middle-aged adults prescribed medicines are exposed to PIP, as defined by the PROMPT criteria. This is likely to be linked with exposure to avoidable adverse drug events. The PROMPT criteria may provide a useful aid in interventions to optimise prescribing.
IL-21/IL-21R Signaling Aggravated Respiratory Inflammation Induced by Intracellular Bacteria through Regulation of CD4+ T Cell Subset Responses

Key Points IL-21/IL-21R can aggravate C. muridarum lung infection. IL-21/IL-21R can suppress Th1/Th17 cell responses in C. muridarum lung infection. The IL-21/IL-21R interaction plays an important role in a variety of immune diseases; however, the roles and mechanisms in intracellular bacterial infection are not fully understood. In this study, we explored the effect of IL-21/IL-21R on chlamydial respiratory tract infection using a chlamydial respiratory infection model. The results showed that the mRNA expression of IL-21 and IL-21R was increased in Chlamydia muridarum–infected mice, which suggested that IL-21 and IL-21R were involved in host defense against C. muridarum lung infection. IL-21R−/− mice exhibited less body weight loss, a lower bacterial burden, and milder pathological changes in the lungs than wild-type (WT) mice during C. muridarum lung infection. The absolute number and activity of CD4+ T cells and the strength of Th1/Th17 responses in IL-21R−/− mice were significantly higher than those in WT mice after C. muridarum lung infection, but the Th2 response was weaker. Consistently, IL-21R−/− mice showed higher mRNA expression of Th1 transcription factors (T-bet/STAT4), IL-12p40, a Th17 transcription factor (STAT3), and IL-23. The mRNA expression of Th2 transcription factors (GATA3/STAT6), IL-4, IL-10, and TGF-β in IL-21R−/− mice was significantly lower than that in WT mice. Furthermore, the administration of recombinant mouse IL-21 aggravated chlamydial lung infection in C57BL/6 mice and reduced Th1 and Th17 responses following C. muridarum lung infection. These findings demonstrate that IL-21/IL-21R may aggravate chlamydial lung infection by inhibiting Th1 and Th17 responses.
A comparative whole genome sequencing analysis identified a candidate locus for lack of operculum in cultivated gilthead seabream (Sparus aurata).

The gilthead seabream (Sparus aurata, Sparidae family) is commonly used for aquaculture. Despite its great economic value, several problems in its cultivation remain. One of the major concerns is the high frequency of morphological abnormalities occurring during the early developmental stages. Partial and/or total lack of operculum is the most frequent anomaly affecting the fish cranial region. The existence of genetic factors that can at least partially determine this defect has been hypothesized. In this work, two DNA pools of highly related fry, one composed of normal-looking (control) fish and the other lacking an operculum (case), were constructed and whole-genome resequencing data produced from the two were compared. The analysis revealed a 1 Mb region on chromosome 2 with higher heterozygosity in the lack of operculum DNA pool than in the control DNA pool, consistent with the enrichment, in the first DNA pool, of one or more haplotypes causing or predisposing to the defect together with other normal haplotypes. A window-based FST analysis between the two DNA pools indicated that the same region had the highest divergence score. This region contained 2921 SNVs, 10 of which, with predicted high impacts (three splice donor and seven stop-gained variants), were detected in novel genes that are homologous to calcium-sensing receptor-like genes, probably involved in bone development. Other studies are needed to clarify the genetic mechanisms involved in predisposing fry to this deformity and then to identify associated markers that could be used in breeding programs to reduce the frequency of this defect in the broodstock.
Documentation of extensive genetic diversity in the Ovar-DRB1 gene in native Turkish sheep

Abstract Indigenous breeds have a high level of genetic diversity that might contribute to develop animal breeds with desired traits such as disease resistance and high productivity. Major histocompatibility complex (MHC) is a key component of adaptive immune system and consists of highly polymorphic genes that take part in adaptive immune response and disease resistance. Exploring and understanding the effect of polymorphisms in MHC could be beneficial to future animal breeding strategies. In this study, we sequenced the highly polymorphic Exon2 of the ovine DRB1 gene using Sanger sequencing to explore the diversity of this gene in six indigenous Turkish sheep breeds and two crossbreeds. In total, 894 haplotypes from 447 sheep were investigated, and 69 different haplotypes including 27 novel ones were identified. Among the identified haplotypes there were common and breed specific haplotypes. There was a relatively high diversity of the alleles within indigenous breeds. Allelic diversity patterns were mostly associated with geographical differences. The results of this study highlight the genetic variation within indigenous breeds which has important implications for biodiversity and the adaptability of breeds to specific environments. There is value to further studies which include other genomic regions and traits, and these could guide breeding strategies.
Cost-effectiveness of Community-Based Depression Interventions for Rural and Urban Adults With Type 2 Diabetes: Projections From Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II

OBJECTIVE We estimated the cost-effectiveness of the Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II community-based exercise (EXER), cognitive behavioral therapy (CBT), and EXER+CBT interventions in adults with type 2 diabetes and depression relative to usual care (UC) and each other. RESEARCH DESIGN AND METHODS Data were integrated into the Michigan Model for Diabetes to estimate cost and health outcomes over a 10-year simulation time horizon from the health care sector and societal perspectives, discounting costs and benefits at 3% annually. Primary outcome was cost per quality-adjusted life-year (QALY) gained. RESULTS From the health care sector perspective, the EXER intervention strategy saved $313 (USD) per patient and produced 0.38 more QALY (cost saving), the CBT intervention strategy cost $596 more and gained 0.29 more QALY ($2,058/QALY), and the EXER+CBT intervention strategy cost $403 more and gained 0.69 more QALY ($585/QALY) compared with UC. Both EXER and EXER+CBT interventions dominated the CBT intervention. Compared with EXER, the EXER+CBT intervention strategy cost $716 more and gained 0.31 more QALY ($2,323/QALY). From the societal perspective, compared with UC, the EXER intervention strategy saved $126 (cost saving), the CBT intervention strategy cost $2,838/QALY, and the EXER+CBT intervention strategy cost $1,167/QALY. Both EXER and EXER+CBT interventions still dominated the CBT intervention. In comparison with EXER, the EXER+CBT intervention strategy cost $3,021/QALY. Results were robust in sensitivity analyses. CONCLUSIONS All three Program ACTIVE II interventions represented a good value for money compared with UC. The EXER+CBT intervention was highly cost-effective or cost saving compared with the CBT or EXER interventions.
Comparison of the effects of different pretreatments on the structure and enzymatic hydrolysis of Miscanthus

Miscanthus is regarded as a desired bioenergy crop with enormous lignocellulose residues for biofuels and other chemical products. In this study, the effect of different pretreatments (including microwave, NaOH, CaO, and microwave + NaOH/CaO) on sugar yields was investigated, leading to largely varied hexose yields at 4.0–73.4% (% cellulose) released from enzymatic hydrolysis of pretreated Miscanthus residues. Among them, the highest yield of 73.4% for hexoses was obtained from 12% NaOH (w/v) solution pretreatment, whereas 1% CaO (w/w) and microwave pretreatment resulted in a lower hexose yield than the control (without pretreatment). The sugar yield from microwave followed with 1% NaOH pretreatment was 4.3 times higher than that of microwave followed with 1% CaO. However, the enzymatic hydrolysis efficiencies of the sample were 15.2% and 58.5% under microwave pretreatment followed by 12% NaOH or 12.5% CaO, respectively, which were lower than those of the same concentration of alkali (NaOH and CaO) pretreatments. To investigate the mechanism of varied enzymatic saccharification under different pretreatments, the changes in the surface structure and porosity of the Miscanthus‐pretreated lignocelluses were studied by means of Fourier transform infrared, Congo red staining, and scanning electron microscopy analysis. The results show that the different pretreatments destroy the cell wall cladding structure and reduce the bonding force between cellulose, hemicellulose, and lignin to different degrees, therefore increasing the accessibility of cellulose and enhancing cellulose digestion.
Visualization of endogenous gut bacteria in Drosophila melanogaster using fluorescence in situ hybridization

All metazoans are colonized by a complex and diverse set of microorganisms. The microbes colonize all parts of the body and are especially abundant in the gastrointestinal tract, where they constitute the gut microbiome. The fruit fly Drosophila melanogaster turned out to be an exquisite model organism to functionally test the importance of an intact gut microbiome. Still, however, fundamental questions remain unanswered. For example, it is unknown whether a fine-tuned regionalization of the gut microbiome exists and how such a spatial organization could be established. In order to pave the way for answering this question, we generated an optimized and adapted fluorescence in situ hybridization (FISH) protocol. We focused on the detection of the two major Drosophila gut microbiome constituting bacteria genera: Acetobacter and Lactobacillus. FISH allows to detect the bacteria in situ and thus to investigate their spatial localization in respect to the host as well as to other microbiome members. We demonstrate the applicability of the protocol using a diverse set of sample types.
Weighted Error Entropy-Based Information Theoretic Learning for Robust Subspace Representation

In most of the existing representation learning frameworks, the noise contaminating the data points is often assumed to be independent and identically distributed (i.i.d.), where the Gaussian distribution is often imposed. This assumption, though greatly simplifies the resulting representation problems, may not hold in many practical scenarios. For example, the noise in face representation is usually attributable to local variation, random occlusion, and unconstrained illumination, which is essentially structural, and hence, does not satisfy the i.i.d. property or the Gaussianity. In this article, we devise a generic noise model, referred to as independent and piecewise identically distributed (i.p.i.d.) model for robust presentation learning, where the statistical behavior of the underlying noise is characterized using a union of distributions. We demonstrate that our proposed i.p.i.d. model can better describe the complex noise encountered in practical scenarios and accommodate the traditional i.i.d. one as a special case. Assisted by the proposed noise model, we then develop a new information-theoretic learning framework for robust subspace representation through a novel minimum weighted error entropy criterion. Thanks to the superior modeling capability of the i.p.i.d. model, our proposed learning method achieves superior robustness against various types of noise. When applying our scheme to the subspace clustering and image recognition problems, we observe significant performance gains over the existing approaches.
Clinical characterization and identification of rare genetic variants in atypical hemolytic uremic syndrome: A Swedish retrospective observational study

Complement‐mediated atypical hemolytic uremic syndrome (aHUS) is an ultra‐rare renal disease primarily caused by genetic alterations in complement proteins. The genetic work‐up required for confirmation of diagnosis is complicated and not always logistically accessible. The aim of the present study was to apply a diagnostic scheme compliant with the American College of Medical Genetics and Genomics guidelines to investigate the prevalence of complement‐mediated aHUS among subjects formerly included in a retrospective cohort of clinically suspected aHUS. Clinical outcomes and genetic correlations to complement analyses were assessed. Subjects were investigated with medical record reviewing, inquiries, and laboratory analyses composed of whole genome sequencing; enzyme‐linked immunosorbent assays for factor I, factor H, and factor H‐specific antibodies; nephelometry for complement components three of four; flow cytometry for CD46 surface expression and immunoblotting for the presence of factor H‐related protein 1. In total, 45% (n = 60/134) of the subjects were deceased at the time of study. Twenty of the eligible subjects consented to study participation. Based on genetic sequencing and clinical characteristics, six were categorized as definite/highly suspected complement‐mediated aHUS, 10 as non‐complement‐mediated aHUS and four as having an HUS‐like phenotype. In the complement‐mediated aHUS group, two subjects had not received an aHUS diagnosis during the routine clinical management. Disease‐contributing/likely disease‐contributing genetic variants were identified in five subjects, including a novel missense variant in the complement factor H gene (c.3450A>G, p.I1150M). This study illustrates the risk for misdiagnosis in the management of patients with complement‐mediated aHUS and the importance of a comprehensive assessment of both phenotype and genotype to reach a diagnosis.
aser A blation versus R adiofrequency A blation for thyroid nodules: Twelve-month results of a randomized trial (LARA II study)

Context : Radiofrequency ablation (RFA) seems to achieve a significantly larger nodule volume reduction rate (VRR) than laser ablation (LA) in benign non-functioning thyroid nodules (BNTNs) Objective : To compare the efficacy and safety of both treatments at 12-month follow-up in patients with solid or predominantly solid BNTN. Design: Single-center, 12-month, randomized, superiority, open-label, parallel-group trial Setting : Outpatient clinic. Conclusion : RFA achieved a significantly larger nodule volume reduction at 12 months; however, the technical success rate was similar in the RFA and LA groups. The study design was described previously (11). The LA versus RFA (LARA) study is a single-center, 12-month, randomized, superiority, open-label, parallel-group trial performed at Santa Maria Goretti Hospital (Lazio, Italy). The trial was conducted in compliance with the principles of the Declaration of Helsinki, the trial protocol was approved by the Institutional Review Board and Ethics Committee (Ethics Committee Lazio 2, approval number: CE 93321), and the participants provided written informed consent before commencing trial-related activities. This trial was registered with ClinicalTrials.gov (NCT02714946). The inclusion criteria were as follows: (a) age >18 years; (b) solitary thyroid nodules or dominating nodules that are well-defined in multinodular goiter; (c) nodule volume ≥5 mL; (d) solid or predominantly solid nodule (solid portion >80%); (e) compression symptoms or cosmetic concerns for which the patients specifically requested treatment, or >20% increase in nodule volume in 1 year, regardless of symptoms; (f) confirmation of benign thyroid nodules in a single fine-needle aspiration and thyroid core-needle biopsy; and (g) normal serum levels of thyroid hormones, thyrotropin, and calcitonin, with the absence of anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies. The exclusion criteria included the following: (a) nodules showing ultrasonographic features suggestive of malignancy; (b) earlier treatment for thyroid nodules; (c) pregnancy; and (d) hyperfunctioning lesions, evaluated biochemically and/or with [ 99m Tc]-pertechnetate scintigraphy.
Pre‐exposure of voglibose exerts cerebroprotective effects through attenuating activation of the polyol pathway and inflammation

Chronic hyperglycemia induces activation of the polyol‐sorbitol pathway, which is a major contributor to microvascular complications like stroke. The current study was designed to elucidate the therapeutic role of α‐glucose inhibitor in chronic hyperglycemia‐induced impaired polyol pathway and associated micro‐complications. Male albino‐Wistar rats (200–250 g) were treated with voglibose 10 mg kg−1 day−1/p.o. for 2 weeks before middle cerebral artery occlusion; 72 hr after surgery, neurological score was evaluated and blood was collected for the assessment of various serum biochemical parameters like CRP, CK‐MB, LDH, lipid profile, and blood glucose levels. In the end, brain samples were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+‐K+ ATPase activity oxidative stress‐related parameters, aldose reductase activity, and gene expression studies. Results from the present study indicate that pre‐treatment with voglibose showed significant improvement in lipid parameters but did not impact glucose levels. Voglibose has shown a statistically significant (p < .05) reduction in neurological score and brain infarct volume, and the difference in brain hemisphere weight as compared to the disease control group. Voglibose significantly (p < .05) improve all biochemical parameters and reduced Na+‐K+ ATPase and aldose reductase activity. Moreover, voglibose produced a significant reduction in oxidative stress and down‐regulation of TNF‐α and BCl‐2 gene expression which reduces the risk of factors related to stroke. In conclusion, the pleiotropic effect of voglibose on cerebrovascular complications may be due to inhibition of aldose reductase or anti‐inflammatory pathways.
EEG signatures of cognitive and social development of preschool children–a systematic review

Background Early identification of preschool children who are at risk of faltering in their development is essential to ensuring that all children attain their full potential. Electroencephalography (EEG) has been used to measure neural correlates of cognitive and social development in children for decades. Effective portable and low-cost EEG devices increase the potential of its use to assess neurodevelopment in children at scale and particularly in low-resource settings. We conducted a systematic review aimed to synthesise EEG measures of cognitive and social development in 2-5-year old children. Our secondary aim was to identify how these measures differ across a) the course of development within this age range, b) gender and c) socioeconomic status (SES). Methods and findings A systematic literature search identified 51 studies for inclusion in this review. Data relevant to the primary and secondary aims was extracted from these studies and an assessment for risk of bias was done, which highlighted the need for harmonisation of EEG data collection and analysis methods across research groups and more detailed reporting of participant characteristics. Studies reported on the domains of executive function (n = 22 papers), selective auditory attention (n = 9), learning and memory (n = 5), processing of faces (n = 7) and emotional stimuli (n = 8). For papers investigating executive function and selective auditory attention, the most commonly reported measures were alpha power and the amplitude and latency of positive (P1, P2, P3) and negative (N1, N2) deflections of event related potential (ERPs) components. The N170 and P1 ERP components were the most commonly reported neural responses to face and emotional faces stimuli. A mid-latency negative component and positive slow wave were used to index learning and memory, and late positive potential in response to emotional non-face stimuli. While almost half the studies described changes in EEG measures across age, only eight studies disaggregated results based on gender, and six included children from low income households to assess the impact of SES on neurodevelopment. No studies were conducted in low- and middle-income countries. Conclusion This review has identified power across the EEG spectrum and ERP components to be the measures most commonly reported in studies in which preschool children engage in tasks indexing cognitive and social development. It has also highlighted the need for additional research into their changes across age and based on gender and SES.