Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Thiopurine Metabolite Monitoring on the Durability of Thiopurine Monotherapy in Pediatric IBD.

Background Thiopurine metabolite monitoring to proactively dose optimize to achieve therapeutic levels has not been used consistently, and it is unclear if this would lead to better outcomes. We aimed to compare 6-month outcomes between standard and optimized dosing strategies and define long-term predictors of thiopurine durability. Methods Two hundred sixteen pediatric IBD patients with at least 2 6-thioguanine nucleotide (6-TGN) levels were grouped for analysis by start dose: >2.5 mg/kg/day AZA (group 1) or <2.5 mg/kg/day (group 2) and further subgrouped depending on whether dosing was optimized to achieve 6-TGN >235 pmol/8 × 108 RBC. The metabolites, 6TGN and 6MMP, were univariate and multivariate analyses tested associations among metabolite levels, laboratory data, and the primary outcome of 6-month steroid-free clinical remission (SFR) (HBI ≤4 for CD; partial Mayo Score [pMS] ≤2 for UC). Thiopurine durability was measured using Kaplan Maier survival analysis. Results 6-MP, azathioprine, pediatrics, therapeutic drug monitoring, pediatrics were measured a median 59 (43-76) days after initiation of thiopurine. Both dosing strategies led to similar initial 6-TGN levels (group 1 = median 209 [IQR: 155-272] with 25% of patients >235; group 2 = 196 [139-274] with 29% >235). Steroid-free clinical remission was achieved in 74% of the 180 still on thiopurines at 6 months. Start dose was not associated with 6-month SFR-73% in group 1 and 77% in group 2 within those on thiopurines at 6 months (P = 0.61). Fixed- and optimized-dosing subgroups had similar 6-month 6-TGN levels, SFR rate, and percentage 6-TGN > 235. Only 6-TGN level >235 at 6 months predicted thiopurine durability (3 years [1.7-7.7] vs 2.5 years [0.83-5]; log-rank P < 0.001), and this did not retain significant in a multivariate model. Initial dosing strategy, first 6-TGN level, 6-month SFR, 6MMP:6TGN ratio, and delta-MCV did not predict durability. The rate of adverse events was 22%. Conclusions Steroid-free clinical remission and 6-TGN levels at 6 months were no different between a standardized, fixed dosing strategy and a metabolite-driven, optimized dosing strategy.
Higher Longitudinal Milk Intakes Are Associated with Increased Height in a Birth Cohort Followed for 17 Years.

Background Height is an indicator of nutritional status; linear growth faltering has recognized consequences for cognitive, emotional, and chronic disease risk. Although height is routinely studied in developing countries, less attention is given to height in the United States. Objective The objective of this study was to identify longitudinal associations between childhood and adolescent beverage intakes, nutrient adequacy, or energy intake and height in a birth cohort. Methods Data for participants through ages 2-17 y (n = 717; 353 males, 364 females) recruited at birth for the longitudinal Iowa Fluoride Study (IFS) were used in the current cohort analyses. Beverage intakes (n = 708) were collected by beverage-frequency questionnaires at 3- to 6-mo intervals, whereas nutrient data (n = 652) were obtained from 3-d food diaries completed at 3- to 6-mo intervals through age 8.5 y and from Block Kids' food-frequency questionnaires at 2-y intervals after age 8.5 y. Nutrient adequacy ratios were calculated with the use of age- and sex-specific Estimated Average Requirements. Height was measured at clinic visits when the participants were approximately ages 5, 9, 11, 13, 15, and 17 y. Linear mixed models were used to identify longitudinal associations between dietary variables and height. A baseline model that adjusted for changing growth patterns during adolescence was established. Dietary and potential confounding variables were added to this baseline model. Results Milk intake adjusted for mean adequacy ratio, energy intake, and baseline socioeconomic status was associated with height; for each additional 8 ounces (236 mL) of milk consumed per day throughout childhood and adolescence, height increased, on average, by 0.39 cm (95% CI: 0.18, 0.60 cm; P < 0.001). Conclusions IFS participants' height increased by 0.39 cm for each additional 8 ounces (236 mL) of milk consumed throughout childhood and adolescence. The clinical implications of the mild linear growth faltering observed in healthy youth are unknown. This trial was registered at www.clinicaltrials. gov as 199112665.
CONSORT-epidural dexmedetomidine improves gastrointestinal motility after laparoscopic colonic resection compared with morphine

Background: We have previously shown that epidural dexmedetomidine, when used as an adjunct to levobupivacaine for control of postoperative pain after open colonic resection, improves recovery of gastrointestinal motility compared with morphine. Methods: Sixty patients undergoing laparoscopic colonic resection were enrolled and allocated randomly to treatment with dexmedetomidine (group D) or morphine (group M). Group D received an epidural loading dose of dexmedetomidine (5 mL, 0.5 &mgr;g/kg), followed by continuous epidural administration of dexmedetomidine (80 &mgr;g) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Group M received an epidural loading dose of morphine (5 mL, 0.03 mg/kg) followed by continuous epidural administration of morphine (4.5 mg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Verbal rating score (VRS) of pain, postoperative analgesic requirements, side effects related to analgesia, and time to postoperative first flatus (FFL) and first feces (FFE) were recorded. Results: VRS and postoperative analgesic requirements were not significantly different between the treatment groups. In contrast, FFL and FFE were significant delayed in group M compared with group D (P < .05). Patients in group M also had a significantly higher incidence of nausea, vomiting, and pruritus (P < .05). No neurological deficits were observed in either group. Conclusions: Compared with morphine, epidural dexmedetomidine is a better adjunct to levobupivacaine for control of postoperative pain after laparoscopic colonic resection.
Combining Word Feature Vector Method with the Convolutional Neural Network for Slot Filling in Spoken Language Understanding

Slot filling is an important problem in Spoken Language Understanding (SLU) and Natural Language Processing (NLP), which involves identifying a user's intent and assigning a semantic concept to each word in a sentence. This paper presents a word feature vector method and combines it into the convolutional neural network (CNN). We consider 18 word features and each word feature is constructed by merging similar word labels. By introducing the concept of external library, we propose a feature set approach that is beneficial for building the relationship between a word from the training dataset and the feature. Computational results are reported using the ATIS dataset and comparisons with traditional CNN as well as bi-directional sequential CNN are also presented.
An Integrative Volatile Terpenoid Profiling and Transcriptomics Analysis for Gene Mining and Functional Characterization of AvBPPS and AvPS Involved in the Monoterpenoid Biosynthesis in Amomum villosum

Amomum villosum, also known as Fructus Amomi, has been used to treat digestive diseases such as abdominal pain, vomiting, and dysentery. Volatile terpenoids are the active metabolites in the essential oil of Fructus Amomi. Nevertheless, downstream genes responsible for activating metabolites biosynthesis in A. villosum still remain unclear. Here, we report the use of an integrative volatile terpenoid profiling and transcriptomics analysis for mining the corresponding genes involved in volatile terpenoid biosynthesis. Ten terpene synthase (TPS) genes were discovered, and two of them were cloned and functionally characterized. AvTPS1 (AvPS: pinene synthase) catalyzed GPP to form α-pinene and β-pinene; AvTPS3 (AvBPPS: bornyl diphosphate synthase) produced bornyl diphosphate as major product and the other three monoterpenoids as minor products. Metabolite accumulation and gene expression pattern combined with AvPS biochemical characterization suggested that AvPS might play a role in biotic defense. On the other hand, the most active ingredient, bornyl acetate, was highly accumulated in seeds and was consistent with the high expression of AvBPPS, which further indicated that AvBPPS is responsible for the biosynthesis of bornyl acetate, the final metabolite of bornyl diphosphate in A. villosum. This study can be used to improve the quality of A. villosum through metabolic engineering, and for the sustainable production of bornyl acetate in heterologous hosts.
A NOTE ON SIMULATION FOR ESTIMATING THE VARIANCE OF THROUGHPUT IN FLOW LINES WITH FINITE BUFFERS

Although analytical approaches and exact solution methods are best for manufacturing system design, it is not easy when the systems become complex. Thus, approximation methods are required and the accuracies of the methods are analyzed by simulation. However, unlike the first order measures such as the mean of throughput, the second order measures such as the variance rate of throughput is difficult to be converged using simulation study. This paper introduces various phenomena empirically when the variance rate of throughput is estimated by simulation in flow lines.
The impact of environmental and behavioural cofactors on the development of cervical disorders in HR-HPV-infected women in Serbia

Abstract Persistent infection with one or more highly oncogenic human papillomaviruses (HPVs) or high-risk-HPV (HR-HPV) is necessary but not a sufficient aetiological agent for the development of cervical neoplasia. A number of viral, host, environmental and behavioural factors are suggested to be associated with the progression of cervical disorder. This study aimed to evaluate the impact of environmental and behavioural cofactors on the development of cervical disorders in HR-HPV-infected women in Serbia. A total of 541 women have been tested by PCR for the presence of HPV on the cervix. HPV genotypes were determined by direct DNA sequencing. Women identified as HR-HPV-positive were further classified into four subgroups according to their cytological status. All relevant information about demographical and behavioural factors was obtained by interviewer-based questionnaire. A number of analytical and descriptive statistical methods were used for processing the data. The cofactors found to be of significance for the progression of cervical disease were older age, body mass index >25, lower educational level, long-term smoking, previous genital infections and cervical interventions. On the other hand, condom use was found to have a protective role. Information about these cofactors might be very important for the development of more efficient cancer prevention programmes and promotion of anti-HPV vaccination.
Immediate improvement of left ventricular mechanics following transcatheter aortic valve replacement.

BACKGROUND Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become a widespread technique for patients with severe AS considered inoperable or high risk for traditional open-surgery. This procedure could have a positive impact in LV mechanics. The aim of this study was to evaluate the immediate effect of TAVR on LV function recovery, as assessed by myocardial deformation parameters. METHODS One-hundred twelve consecutive patients (81.4 ± 6.4 years, 50% female) from 10 centres in Europe with severe AS who successfully underwent TAVR with either a self-expanding CoreValve (Medtronic, Minneapolis, MN) or a mechanically expanded Lotus valve (Boston Scientific, Natick, MA) were enrolled in a prospective multi-center study. A complete echocardiographic examination was performed at baseline and immediately before discharge, including the assessment of LV strain using standard two-dimensional images. RESULTS Echocardiographic examination with global longitudinal strain (GLS) quantification could be obtained in 92 patients, because of echocardiographic and logistic reasons. Between examinations, a modest statistically significant improvement in GLS could be seen (GLS% -15.00 ± 4.80 at baseline;-16.15 ± 4.97 at discharge, p = 0.028). In a stratified analysis, only women showed a significant improvement in GLS and a trend towards greater improvement in GLS according to severity of systolic dysfunction as measured by LV ejection fraction could be noted. CONCLUSIONS Immediate improvement in GLS was appreciated after TAVR procedure. Whether this finding continues to be noted in a more prolonged follow-up and its clinical implications need to be assessed in further studies.
Chromatin That Guides Dosage Compensation Is Modulated by the siRNA Pathway in Drosophila melanogaster

A family of X-linked repetitive elements enhances dosage compensation of nearby genes in male flies. Here, Deshpande and Meller show that chromatin around these repeats is modified in a siRNA-dependent manner. Proteins that interact with the siRNA effector. Many heterogametic organisms adjust sex chromosome expression to accommodate differences in gene dosage. This requires selective recruitment of regulatory factors to the modulated chromosome. How these factors are localized to a chromosome with requisite accuracy is poorly understood. Drosophila melanogaster males increase expression from their single X chromosome. Identification of this chromosome involves cooperation between different classes of X-identity elements. The chromatin entry sites (CES) recruit a chromatin-modifying complex that spreads into nearby genes and increases expression. In addition, a family of satellite repeats that is enriched on the X chromosome, the 1.688X repeats, promotes recruitment of the complex to nearby genes. The 1.688X repeats and CES are dissimilar, and appear to operate through different mechanisms. Interestingly, the siRNA pathway and siRNA from a 1.688X repeat also promote X recognition. We postulate that siRNA-dependent modification of 1.688X chromatin contributes to recognition of nearby genes. In accord with this, we found enrichment of the siRNA effector Argonaute2 (Ago2) at some 1.688X repeats. Mutations in several proteins that physically interact with Ago2, including the histone methyltransferase Su(var)3-9, enhance the lethality of males with defective X recognition. Su(var)3-9 deposits H3K9me2 on some 1.688X repeats, and this mark is disrupted upon ectopic expression of 1.688X siRNA. Furthermore, integration of 1.688X DNA on an autosome induces local H3K9me2 deposition, but enhances expression of nearby genes in a siRNA-dependent manner. Our findings are consistent with a model in which siRNA-directed modification of 1.688X chromatin contributes to recognition of the male X chromosome for dosage compensation.
Regional structural hypo‐ and hyperconnectivity of frontal–striatal and frontal–thalamic pathways in behavioral variant frontotemporal dementia

Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal–subcortical connections. We aim to characterize the grey and white matter components of frontal–thalamic and frontal–striatal circuits in bvFTD. Twenty‐four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal–striatal–thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p = .032, and 217% in the thalamus, p = .004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p = .002, and 65% in the thalamus, p = .020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal–subcortical networks; however, longitudinal studies are necessary to test this hypothesis.
Integration of prebend optimization in a holistic wind turbine design tool

This paper considers the problem of identifying the optimal combination of blade prebend, rotor cone angle and nacelle uptilt, within an integrated aero-structural design environment. Prebend is designed to reach maximum rotor area at rated conditions, while cone and uptilt are computed together with all other design variables to minimize the cost of energy. Constraints are added to the problem formulation in order to translate various design requirements. The proposed optimization approach is applied to a conceptual 10 MW offshore wind turbine, highlighting the benefits of an optimal combination of blade curvature, cone and uptilt angles.
Hidradenitis suppurativa with SAPHO syndrome maintained effectively with adalimumab, methotrexate, and intralesional corticosteroid injections

Introduction: Hidradenitis suppurativa and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome are chronic, debilitating diseases involving apocrine gland-bearing skin inflammation and bone inflammation, respectively. Although both often present with multiple comorbidities, single patient co-presentation is rare. Methods/Results: This study reports the 8-year treatment course of a 40-year-old man with hidradenitis suppurativa and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome, and reviews relevant literature. Initial oral and topical antibiotics had little effect. Intralesional corticosteroid injections were effective for localized inflammatory lesions but insufficient for hidradenitis suppurativa control. Adalimumab initiation and local excision of a persistent HS lesion led to stabilization. Adalimumab provided dramatic back pain improvement. Synovitis, acne, pustulosis, hyperostosis, osteitis was diagnosed; adalimumab continuation with subsequent methotrexate addition resulted in hidradenitis suppurativa-synovitis, acne, pustulosis, hyperostosis, osteitis control. Conclusions: Literature regarding comorbid hidradenitis suppurativa and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome therapy is scarce but growing. Adalimumab, methotrexate, intralesional corticosteroid, and lifestyle changes successfully maintained a severe hidradenitis suppurativa–synovitis, acne, pustulosis, hyperostosis, osteitis–syndrome case. Further studies beyond a case-based review could yield more definitive treatment plans.
Photobiomodulation in the Postoperative of Bichectomy Surgeries: Case Series.

BACKGROUND Several photobiomodulation (PBM) protocols with low-power lasers have been reported for pain control and tissue repair in the postoperative period of oral surgeries. However, there are still no reports of a protocol for bichectomy surgeries' postoperative period. OBJECTIVE This article presents six reports of clinical cases in which bichectomy surgery was performed. METHODS In the postoperative period, three patients were submitted to PBM with low-power lasers, while three patients did not receive it. Facial edema was evaluated using a millimeter tape. Pain was determined using the visual analog scale. RESULTS Data of each clinical case were evaluated in a descriptive way and compared. CONCLUSIONS The efficacy of the PBM protocol on the postoperative period of bichectomy surgeries was evidenced by the decrease of edema and pain.
Genomes and Transcriptomes of Duckweeds

Duckweeds (Lemnaceae family) are the smallest flowering plants that adapt to the aquatic environment. They are regarded as the promising sustainable feedstock with the characteristics of high starch storage, fast propagation, and global distribution. The duckweed genome size varies 13-fold ranging from 150 Mb in Spirodela polyrhiza to 1,881 Mb in Wolffia arrhiza. With the development of sequencing technology and bioinformatics, five duckweed genomes from Spirodela and Lemna genera are sequenced and assembled. The genome annotations discover that they share similar protein orthologs, whereas the repeat contents could mainly explain the genome size difference. The gene families responsible for cell growth and expansion, lignin biosynthesis, and flowering are greatly contracted. However, the gene family of glutamate synthase has experienced expansion, indicating their significance in ammonia assimilation and nitrogen transport. The transcriptome is comprehensively sequenced for the genera of Spirodela, Landoltia, and Lemna, including various treatments such as abscisic acid, radiation, heavy metal, and starvation. The analysis of the underlying molecular mechanism and the regulatory network would accelerate their applications in the fields of bioenergy and phytoremediation. The comparative genomics has shown that duckweed genomes contain relatively low gene numbers and more contracted gene families, which may be in parallel with their highly reduced morphology with a simple leaf and primary roots. Still, we are waiting for the advancement of the long read sequencing technology to resolve the complex genomes and transcriptomes for unsequenced Wolffiella and Wolffia due to the large genome sizes and the similarity in their polyploidy.
Pre‐diagnostic plasma concentrations of Fibrinogen, sGPIIb/IIIa, sP‐selectin, sThrombomodulin, Thrombopoietin in relation to cancer risk: Findings from a large prospective study

While enhanced platelet activation may drive cancer progression and metastases, less is known about its role in early cancer development. Thus, we evaluated whether pre‐diagnostic biomarkers of platelet activation and coagulation are related to the risks of common cancers in the prospective EPIC‐Heidelberg Study using a case‐cohort design. Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P‐selectin (sP‐selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n = 2,480) and incident cases of breast (n = 605), prostate (n = 543), and colorectal cancer (n = 249). Multivariable Cox regression models revealed no statistically significant associations between biomarker concentrations and any of the cancer endpoints. Subgroup analyses showed a significant inverse relationship between TPO and colorectal cancer among men, with a hazard ratio (HR, highest vs. lowest quartile) of 0.60 (95% confidence interval: 0.37,0.95), whereas no significant association was observed among women. With regard to fibrinogen levels and breast cancer risk, there was a significant positive association among nulliparous women (HR: 2.53 [95% CI: 1.21, 5.30]), but not among parous women. Overall, our data suggest that enhanced platelet activation and a pro‐coagulative state may not be related to increased risks of common cancers, although studies on other potential biomarkers of platelet activation and further cancer types are needed. Findings from our subgroup analyses require further investigation, as potential underlying mechanisms are not known.