Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effectiveness of Target Low-Density Lipoprotein Cholesterol Achieved with Strict Management in Secondary Prevention of Long-Term Coronary Events in Japanese Patients.

Background In the secondary prevention of long-term coronary events, a target value of low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL is recommended as standard management in Japanese guidelines. However, the effectiveness of strict management on lowering LDL-C remains unclear. Objectives To clarify whether strict management of LDL-C < 70 mg/dL is more effective in preventing long-term coronary event recurrence than standard management. Methods We retrospectively investigated 344 patients with previous percutaneous coronary interventions who underwent late coronary angiography to examine recurrence of cardiac ischemia beyond the early restenosis period from January 2007 to August 2019. Patients were stratified into three groups according to achieved LDL-C value; LDL-C < 70 mg/dL (n = 53), 70 to < 100 mg/dL (n = 130), and ≥ 100 mg/dL (n = 161). Endpoints were acute coronary syndrome (recurrent-ACS) and late coronary revascularization. Results After follow-up (median 6.0 years), 200 patients (58%) underwent late coronary revascularization, including 94 recurrent-ACS. The incidence of recurrent-ACS was significantly lower in the patients who achieved LDL-C < 70 mg/dL than in those with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.009 and p = 0.001, respectively). There was no significant difference between the patients with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.140). There was also no significant difference in late revascularization between the patients with LDL-C < 70 mg/dL and LDL-C 70 to < 100 mg/dL. In patients with LDL-C < 100 mg/dL (n = 183), LDL-C [hazard ratio (HR) 1.035, p = 0.007] and HbA1c (HR 1.338, p = 0.001) were independently associated with recurrent-ACS. Conclusions In Japanese patients, LDL-C was a residual risk for recurrent-ACS even after recommended standard LDL-C lowering management target values had been achieved.
Establishment of primary chicken embryo myoblast cell culture, antigenic epitopes prediction and production of anti activin receptor type IIB polyclonal antibody in chicken

Abstract The detection of activin receptor typeIIB (ACTRIIB) protein, a prominent negative muscle growth regulator has paramount value in augmenting growth traits through molecular breeding schemes in chicken. The study was formulated to establish primary chicken embryo myoblast culture (CEM) using 9th and 18th day chick embryos and to develop antibodies for immunodetection of ACTRIIB protein. The physicochemical and structural attributes of the ACTRIIB sequence were evaluated to identify substantial antigenic regions. The ACTRIIB sequence was transfected into CEM and expressed protein was injected subcutaneously into rats to produce hyperimmune serum. The average propensity of protein sequence for beta turns, surface accessibility, chain flexibility, antigenicity, hydrophilicity and linear epitopes was 0.978, 1.000, 0.991, 1.038, 1.258 and 0.512, respectively. The 9th day CEM exhibited confluency (80–90%) earlier than the 18th day. The expression of myogenic regulatory factors in 9th day myoblasts was higher than the 18th day by 7.28, 5.16, 6.28 and 6.93 folds for MYF5, MRF4, MYOG and MYOD, respectively. The ACTRIIB mRNA was downregulated by 2.54 folds on the 9th day compared to the 18th day myoblasts and protein varied significantly between 9th and 18th day myoblasts. The CEM culture can be harnessed unequivocally to investigate molecular mechanisms underlying muscle growth besides raising antibodies.
Glucometabolic consequences of acute and prolonged inhibition of fatty acid oxidation[S]

Excessive circulating FAs have been proposed to promote insulin resistance (IR) of glucose metabolism by increasing the oxidation of FAs over glucose. Therefore, inhibition of FA oxidation (FAOX) has been suggested to ameliorate IR. However, prolonged inhibition of FAOX would presumably cause lipid accumulation and thereby promote lipotoxicity. To understand the glycemic consequences of acute and prolonged FAOX inhibition, we treated mice with the carnitine palmitoyltransferase 1 (CPT-1) inhibitor, etomoxir (eto), in combination with short-term 45% high fat diet feeding to increase FA availability. Eto acutely increased glucose oxidation and peripheral glucose disposal, and lowered circulating glucose, but this was associated with increased circulating FAs and triacylglycerol accumulation in the liver and heart within hours. Several days of FAOX inhibition by daily eto administration induced hepatic steatosis and glucose intolerance, specific to CPT-1 inhibition by eto. Lower whole-body insulin sensitivity was accompanied by reduction in brown adipose tissue (BAT) uncoupling protein 1 (UCP1) protein content, diminished BAT glucose clearance, and increased hepatic glucose production. Collectively, these data suggest that pharmacological inhibition of FAOX is not a viable strategy to treat IR, and that sufficient rates of FAOX are required for maintaining liver and BAT metabolic function.
Determination of the secondary structures of proteins by circular dichroism spectra. Calculation of the protein basic circular dichroism spectra for antiparallel and parallel β-structures and β-bends

New “reference” circular dichroism spectra of α helix, β-structure (both parallel and antiparallel), β-bends, and the unordered form are obtained from circular dichroism spectra and x-ray data for six proteins (myoglobin, lysozyme, lactate dehydrogenase, papain, ribonuclease, and subtilisin BPN′). Circular dichroism spectra for α-helix and antiparallel β-structure are similar to those for poly(Llysine). The circular dichroism spectrum of the parallel β-structure is qualitatively similar to that theoretically calculated by Madison and Schellman. The circular dichroism spectrum of β-bends is qualitatively similar to that theoretically calculated by Woody. The spectrum of the unordered form is close to that of the denaturated proteins. These “reference” circular dichroism spectra used for the analysis of the secondary structure of ten globular proteins (besides the six reference proteins D-glyceraldehyde 3-phosphate dehydrogenase, concanavalin A, cytochrome c, and insulin).
Lidocaine-loaded reduced graphene oxide hydrogel for prolongation of effects of local anesthesia: In vitro and in vivo analyses

Abstract Lidocaine is widely used as a local anesthetic for alleviation of post-operative pain and for management of acute and chronic painful conditions. Although several approaches are currently used to prolong the duration of action, an effective strategy to achieve neural blockage for several hours remains to be identified. In this study, a lidocaine-loaded Pluronic® F68-reduced graphene oxide hydrogel was developed to achieve sustained release of lidocaine. Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the synthesis of Pluronic® F68-reduced graphene oxide. Transmission electron microscopy showed wrinkled, flat nanosheets with micelles attached. The developed hydrogel showed desirable pH, viscosity, adhesiveness, hardness, and cohesiveness for topical application. The ex vivo release study demonstrated the ability of the Pluronic® F68-reduced graphene oxide hydrogel to prolong release up to 10 h, owing to the strong π–π interactions between the graphene oxide and the lidocaine. In comparison with a commercial lidocaine ointment, the developed graphene oxide hydrogel showed sustained anesthetic effect in the radiant heat tail flick test and sciatic nerve block model. Thus, this study demonstrates the potential of using Pluronic® F68-reduced graphene oxide nanocarriers to realize prolonged effects of local anesthesia for effective pain management.
Syntheses, Structures and Magnetic Properties of Dinuclear Copper(II)–Lanthanide(III) Complexes Bridged by 2‐Hydroxymethyl‐1‐methylimidazole

Three discrete dinuclear copper(II)–lanthanide(III) complexes, namely, [CuLn(mmi)2(NO3)3(H2O)2] [Ln = La (1), Sm (2)] and [CuGd(mmi)2(NO3)2(H2O)3][NO3] (3) (Hmmi = 2-hydroxymethyl-1-methylimidazole) were synthesized and structurally characterized by X-ray diffraction analysis. In these complexes, dinuclear cores of CuII and LnIII are consolidated by a pair of μ-1,1-O bridges from mmi at a distance of 3.36–3.46 A. The temperature dependence of the magnetic susceptibility and the field dependence of the magnetization indicate that 1, 2 and 3 exhibit paramagnetic, antiferromagnetic and ferromagnetic behaviours, respectively. The value of the JCu–Gd coupling constant of 3 [8.7(1) cm–1] is fairly large, which is probably related to the small dihedral angles, α (5.0°), between the two planes of O–Cu–O and O–Gd–O in the CuO2Gd core. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Impact of functionalized linkers on the energy landscape of ZIFs

Zeolitic imidazolate frameworks (ZIFs) are well-known for their thermal and chemical stability, as well as for their structural diversity reminiscent of those found in the realm of zeolites. Linker–linker interactions were recognized as essential in the discovery of new topologies through the choice of substituted imidazolates. However, the impact of the linker through modification of the imidazolate's substituents on the energy landscape of ZIFs remains to be rationalized. In this work, LiB-based ZIFs serve as model crystal structures to explore the impact of linker–linker interactions, varying the number and position of methyl groups. The study focuses on the characteristics of experimental and hypothetical structures studied by first principle DFT-D calculations, and further interpreted through QSPR and Non covalent interaction (NCI) analysis. We provide an empirical QSPR model accounting for linker and topology effects on the stability of the frameworks. Both the position and number of substituents on the imidazolate linkers have a profound impact on the energy landscape of ZIFs, reshuffling the ranking of stabilized versus less stable topologies that were otherwise almost isoenergetic with unsubstituted imidazolate. NCI analysis revealed that methyl substituents induce repulsive interactions within the boron-centred cluster that are compensated by attractive non-bonded interactions at the larger scale of the solid. Besides the kinetic factors at play in ZIF synthesis which are difficult to consider from a modelling perspective, our calculations show that thermodynamic considerations are at work, explaining the intractability of certain topologies with certain linkers. Our calculations provide insight into the magnitude of the thermodynamic penalties that must be overcome in order to form particular topologies and the energy scale that needs to be overcome to generate lower density materials – a target for many experimental groups. The identified dominant linker–linker interactions could be exploited to overcome the limitations of current synthesis techniques.
Prognostic Value of Antithrombin Levels in COVID-19 Patients and Impact of Fresh Frozen Plasma Treatment: A Retrospective Study

Objective: The defective interplay between coagulation and inflammation may be the leading cause of intravascular coagulation and organ dysfunction in coronavirus disease-19 (COVID-19) patients. Abnormal coagulation profiles were reported to be associated with poor outcomes. In this study, we assessed the prognostic values of antithrombin (AT) activity levels and the impact of fresh frozen plasma (FFP) treatment on outcome. Materials and Methods: Conventional coagulation parameters as well as AT activity levels and outcomes of 104 consecutive critically ill acute respiratory distress syndrome (ARDS) patients with laboratory-confirmed COVID-19 disease were retrospectively analyzed. Patients with AT activity below 75% were treated with FFP. Maximum AT activity levels achieved in those patients were recorded. Results: AT activity levels at admission were significantly lower in nonsurvivors than survivors (73% vs. 81%). The cutoff level for admission AT activity was 79% and 58% was the lowest AT for survival. The outcome in those patients who had AT activity levels above 75% after FFP treatment was better than that of the nonresponding group. As well as AT, admission values of D-dimer, C-reactive protein, and procalcitonin were coagulation and inflammatory parameters among the mortality risk factors. Conclusion: AT activity could be used as a prognostic marker for survival and organ failure in COVID-19-associated ARDS patients. AT supplementation therapy with FFP in patients with COVID-19-induced hypercoagulopathy may improve thrombosis prophylaxis and thus have an impact on survival.
A multiple sclerosis disease progression measure based on cumulative disability

Background: Existing severity measurements in multiple sclerosis (MS) are often cross-sectional, making longitudinal comparisons of disease course between individuals difficult. Objective: The objective of this study is to create a severity metric that can reliably summarize a patient’s disease course. Methods: We developed the nARMSS – normalized ARMSS (age-related MS severity score) over follow-up, using the deviation of individual ARMSS scores from the expected value and integrated over the corresponding time period. The nARMSS scales from −5 to +5; a positive value indicates a more severe disease course for a patient when compared to other patients with similar disease timings. Results: Using Swedish MS registry data, the nARMSS was tested using data at 2 and 4 years of follow-up to predict the most severe quartile during the subsequent period up to 10 years total follow-up. The metric used was area under the curve of the receiver operating characteristic (AUC-ROC). This resulted in measurements of 0.929 and 0.941. In an external Canadian validation cohort, the equivalent AUC-ROCs were 0.901 and 0.908. Conclusion: The nARMSS provides a reliable, generalizable and easily measurable metric which makes longitudinal comparison of disease course between individuals feasible.
Enhanced expression of queuine tRNA-ribosyltransferase 1 (QTRT1) predicts poor prognosis in lung adenocarcinoma

Background Lung adenocarcinoma (LUAD) is the most frequently diagnosed type of lung cancer with high percentage of tumor relapse and metastasis. The correlation between queuine tRNA-ribosyltransferase 1 (QTRT1) expression and LUAD remains largely unknown. In this study, we aim to investigate the potential role of QTRT1 expression in the prognosis of LUAD. Methods We abstracted data from The Cancer Genome Atlas (TCGA) and four independent Gene Expression Omnibus (GEO) datasets. In total, 1,012 LUAD samples and 112 normal tissue samples were selected. The relationship between QTRT1 expression, methylation, and clinical features in LUAD were determined, and bioinformatics analyses were also performed. Results The expression of QTRT1 was higher in LUAD patients. A marked downregulation in QTRT1 methylation in LUAD was also found. Low QTRT1 expression was associated with longer overall survival across the GEO and TCGA datasets (P=0.0033, 0.0022, respectively). Furthermore, QTRT1 expression was significantly correlated with ‘axoneme assembly’, ‘androgen response’, and ‘epithelial mesenchymal transition’, as determined by Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) term enrichment analysis. Conclusions QTRT1 was highly expressed in LUAD, and enhanced expression of QTRT1 might therefore serve as a biomarker for poor prognosis in LUAD. The result of bioinformatic analyses might present a new insight for investigating the pathogenesis of LUAD.
Prediction of Specialty Coffee Flavors Based on Near-Infrared Spectra Using Machine and Deep Learning Methods.

BACKGROUND Specialty coffee fascinates people with its bountiful flavors. Currently, flavor descriptions of specialty coffee beans are only offered by certified coffee cuppers. However, such professionals are rare, and the market demand is tremendous. The hypothesis of this study was to investigate the feasibility to train machine learning (ML) and deep learning (DL) models for predicting the flavors of specialty coffee using near-infrared spectra of ground coffee as the input. Successful model development would provide a new and objective framework to predict complex flavors in food and beverage products. RESULTS In predicting seven categories of coffee flavors, the developed models using the ML method (i.e., support vector machine) and the deep convolutional neural network (DCNN) achieved similar performance with the recall and accuracy of 70-73% and 75-77%, respectively. Through the proposed visualization method - a focusing plot, the potential correlation among the highly-weighted spectral region of the DCNN model, the predicted flavor categories, and the corresponding chemical composition was presented. CONCLUSION This study has proven the feasibility to apply ML and DL methods on the near-infrared spectra of ground coffee to predict specialty coffee flavors. The effective models provided moderate prediction for seven flavor categories based on 266 samples. The results of classification and visualization indicate that the developed DCNN model is a promising and explainable method for coffee flavor prediction. This article is protected by copyright. All rights reserved.
Inter-rater Reliability of the Modified Japanese Orthopedic Association Score in Degenerative Cervical Myelopathy

This prospective study in 154 degenerative cervical myelopathy patients found inter-rater reliability of modified Japanese Orthopaedic Association is good (intraclass correlation coefficient = 0.88). However, assessments differed in 75%, and categorization between mild and moderate severity differed in 12% (resulting in conflicting surgical recommendations). Efforts to educate clinicians and standardize administration and may enhance the reliability of this tool. Study Design. Prospective cross-sectional blinded-assessor cohort study. Objective. The aim of this study was to determine the inter-rater reliability of the modified Japanese Orthopaedic Association (mJOA) score in a large cohort of degenerative cervical myelopathy (DCM) patients. Summary of Background Data. The mJOA score is widely accepted as the primary outcome measure in DCM; it has been utilized in clinical practice guidelines and directly influences treatment recommendations, but its reliability has not been established. Methods. A refined version of the mJOA was administered to DCM patients by two or more blinded clinicians. Inter-rater reliability was measured using intraclass correlation coefficient (ICC), agreement, and mean difference for mJOA total score and subscores. Data were also analyzed with analysis of variance for differences by mJOA severity (mild: 15–17, moderate: 12–14, severe: <12), assessor, assessment order, previous surgery, age, and sex. Results. One hundred fifty-four DCM patients underwent 322 mJOA assessments (183 paired assessments). ICC was 0.88 for total mJOA, 0.79 for upper extremity (UE) motor, 0.84 for lower extremity (LE) motor, 0.63 for UE sensation, and 0.78 for urinary function subscores. Paired assessments were identical across all four subscores in 25%. The mean difference in mJOA was 0.93 points between assessors, and this differed by severity (mild: 0.68, moderate: 1.24, severe: 0.87, P = 0.001). Differences of ≥ 2 points occurred in 19%. Disagreement between mild and moderate severity occurred in 12% of patients. Other variables did not demonstrate significant relationships with mJOA scores. Conclusion. The inter-rater reliability of total mJOA and its subscores is good, except for UE sensory function (moderate). However, the vast majority of assessments differed between observers, indicating that this measure should be interpreted carefully, particularly when near the threshold between severity categories, or when a patient is reassessed for deterioration. Further efforts to educate clinicians on administration and to refine the UE sensory subscore may enhance the reliability of this tool. Level of Evidence: 1
Classification algorithm for the ICD-11 chronic pain classification (CAL-CP): development and results from a preliminary pilot evaluation.

ABSTRACT The ICD-11 chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as stand-alone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses.
Targeted Genetic Changes in Candida albicans Using Transient CRISPR‐Cas9 Expression

Candida albicans is an opportunistic fungal pathogen responsible for significant disease and mortality. Absent complete mating and other convenient methods, dissection of its virulence factors relies on robust tools to delete, complement, and otherwise modify genes of interest in this diploid organism. Here we describe the design principles and use of CRISPR associated nuclease 9 (Cas9) and single‐guide RNAs transiently expressed from PCR cassettes to modify genes of interest, generating homozygous mutants in a single transformation step. © 2021 Wiley Periodicals LLC.
Tuning the Dimensions of C60‐Based Needlelike Crystals in Blended Thin Films

A new ordered structure of the C60 derivative PCBM ([6‐6]‐phenyl C61‐butyric acid methyl ester) is obtained in thin films based on the blend PCBM:regioregular P3HT (poly(3‐hexylthiophene)). Rapid formation of needlelike crystalline PCBM structures of a few micrometers up to 100 μm in size is demonstrated by submitting the blended thin films to an appropriate thermal treatment. These structures can grow out to a 2D network of PCBM needles and, in specific cases, to spectacular PCBM fans. Key parameters to tune the dimensions and spatial distribution of the PCBM needles are blend ratio and annealing conditions. The as‐obtained blended films and crystals are probed using atomic force microscopy, transmission electron microscopy, selected area electron diffraction, optical microscopy, and confocal fluorescence microscopy. Based on the analytical results, the growth mechanism of the PCBM structures within the film is described in terms of diffusion of PCBM towards the PCBM crystals, leaving highly crystalline P3HT behind in the surrounding matrix.