Miracle-dz/UniFAR-FTUs huggingface dataset:
Value of global metabolomics in association with diagnosis and clinicopathological factors of renal cell carcinoma

Renal cell carcinoma (RCC) is a malignant tumor that currently lacks clinically useful biomarkers indicative of early diagnosis or disease status. RCC has commonly been diagnosed based on imaging results. Metabolomics offers a potential technology for discovering biomarkers and therapeutic targets by comprehensive screening of metabolites from patients with various cancers. We aimed to identify metabolites associated with early diagnosis and clinicopathological factors in RCC using global metabolomics (G‐Met). Tumor and nontumor tissues were sampled from 20 cases of surgically resected clear cell RCC. G‐Met was performed by liquid chromatography mass spectrometry and important metabolites specific to RCC were analyzed by multivariate statistical analysis for cancer diagnostic ability based on area under the curve (AUC) and clinicopathological factors (tumor volume, pathological T stage, Fuhrman grade, presence of coagulation necrosis and distant metastasis). We identified 58 metabolites showing significantly increased levels in tumor tissues, 34 of which showed potential early diagnostic ability (AUC >0.8), but 24 did not discriminate between tumor and nontumor tissues (AUC ≤0.8). We recognized 6 pathways from 9 metabolites with AUC >0.8 and 7 pathways from 10 metabolites with AUC ≤0.8 about malignant status. Clinicopathological factors involving malignant status correlated significantly with metabolites showing AUC ≤0.8 (p = 0.0279). The tricarboxylic acid cycle (TCA) cycle, TCA cycle intermediates, nucleotide sugar pathway and inositol pathway were characteristic pathways for the malignant status of RCC. In conclusion, our study found that metabolites and their pathways allowed discrimination between early diagnosis and malignant status in RCC according to our G‐Met protocol.
An assessment of early functional rehabilitation and hospital discharge in conventional versus robotic‐arm assisted unicompartmental knee arthroplasty: A PROSPECTIVE COHORT STUDY

Aims The objectives of this study were to compare postoperative pain, analgesia requirements, inpatient functional rehabilitation, time to hospital discharge, and complications in patients undergoing conventional jig‐based unicompartmental knee arthroplasty (UKA) versus robotic‐arm assisted UKA. Patients and Methods This prospective cohort study included 146 patients with symptomatic medial compartment knee osteoarthritis undergoing primary UKA performed by a single surgeon. This included 73 consecutive patients undergoing conventional jig‐based mobile bearing UKA, followed by 73 consecutive patients receiving robotic‐arm assisted fixed bearing UKA. All surgical procedures were performed using the standard medial parapatellar approach for UKA, and all patients underwent the same postoperative rehabilitation programme. Postoperative pain scores on the numerical rating scale and opiate analgesia consumption were recorded until discharge. Time to attainment of predefined functional rehabilitation outcomes, hospital discharge, and postoperative complications were recorded by independent observers. Results Robotic‐arm assisted UKA was associated with reduced postoperative pain (p < 0.001), decreased opiate analgesia requirements (p < 0.001), shorter time to straight leg raise (p < 0.001), decreased number of physiotherapy sessions (p < 0.001), and increased maximum knee flexion at discharge (p < 0.001) compared with conventional jig‐based UKA. Mean time to hospital discharge was reduced in robotic UKA compared with conventional UKA (42.5 hours (sd 5.9) vs 71.1 hours (sd 14.6), respectively; p < 0.001). There was no difference in postoperative complications between the two groups within 90 days' follow‐up. Conclusion Robotic‐arm assisted UKA was associated with decreased postoperative pain, reduced opiate analgesia requirements, improved early functional rehabilitation, and shorter time to hospital discharge compared with conventional jig‐based UKA.
Emergence and the spread of the F200Y benzimidazole resistance mutation in Haemonchus contortus and Haemonchus placei from buffalo and cattle

Benzimidazoles have been intensively used in the livestock sector, particularly in small ruminants for over 40 years. This has been led to the widespread emergence of resistance in a number of small ruminant parasite species, in particular Haemonchus contortus. In many counties benzimidazole resistance in the small ruminants H. contortus has become severely compromising its control; but there is a little information on benzimidazole resistance in H. contortus infecting buffalo and cattle. Resistance to benzimidazoles have also been reported in the large ruminant parasite, Haemonchus placei, but again there is relatively little information on its prevalence. Hence it is extremely important to understand how resistance-conferring mutations emerge and spread in both parasites in the buffalo and cattle host in order to develop the approaches for the recognition of the problem at an early stage of its development. The present study suggests that the F200Y (TAC) mutation is common in H. contortus, being detected in 5/7 populations at frequencies between 7 to 57%. Furthermore, 6/10 H. placei populations contained the F200Y (TAC) mutation, albeit at low frequencies of between 0.4 to 5%. The phylogenetic analysis suggests that the F200Y (TAC) mutation in H. contortus has emerged on multiple occasions in the region, with at least three independent emergence of resistance alleles across the populations. In contrast, the F200Y (TAC) resistance-conferring mutation in H. placei is only seen on a single haplotype. A high level of haplotype frequency of the susceptible alleles in the region, suggests that the unique resistance conferring-mutation has spread from a single emergence; likely by anthropogenic animal movement. Overall, these results provide the first clear genetic evidence for the spread of benzimidazoles resistance-conferring mutations to multiple different locations from a single emergence in H. placei; while supporting previous small ruminant-based observations of multiple emergence of resistance mutations in H. contortus.
Biomimetic Designer Scaffolds Made of D,L-Lactide-ɛ-Caprolactone Polymers by 2-Photon Polymerization

Traditionally tissue engineering (TE) strategy relies on three components: cells, signaling systems (e.g., growth factors), and extracellular matrix (ECM). Nowadays the combination of cells, signaling systems, an artificial ECM, and appropriate bioreactor systems has recently been defined as the “Tissue Engineering Quadriad”1 taking into consideration the fundamental role of the dynamic physiological environment. Not surprisingly, the establishment of an artificial ECM with the necessary flexibility seems to be a mission impossible without advanced materials and fabrication techniques. This claim applies to therapeutic (regeneration) as well as diagnostic (disease-modeling) approaches. To meet the challenge to mimic the hierarchical structured and complex milieu of the natural ECM it was tried in this study to combine a flexible photosensitive polymer platform based on (D,L)-lactide-ɛ-caprolactone methacrylate (LCM) with a nanoscale rapid prototyping technique based on two-photon polymerization (2-PP). Polyesters, such as poly-ɛ-caprolactone or poly-(D, L)-lactide, are very popular candidates for mimicking the ECM, because of their adjustable biophysical and biochemical properties. 2-PP represents a versatile lithographic method for the generation of scaffolds with defined size and shape, due to a spatial resolution <100 nm. This unique performance enables the fabrication of mathematically defined structures (scaffolds) based on triply periodic minimal surfaces with a tailor-made stiffness, permeability, and degradation behavior. Especially the Schwarz P minimal surface, which divides the interior of a scaffold into two intertwining labyrinths, plays an important role in generating custom-made or designer scaffolds. This review gives an overview of materials, techniques, and appropriate geometries to establish a conceptual framework to engineer such scaffolds. Furthermore, selected application scenarios in bone and tumor TE were introduced in the sense of a first proof of principle to show the high potential of this concept in therapeutic (regeneration) and diagnostic (disease-modeling) approaches. Impact Statement In tissue engineering (TE), the establishment of cell targeting materials, which mimic the conditions of the physiological extracellular matrix (ECM), seems to be a mission impossible without advanced materials and fabrication techniques. With this in mind we established a toolbox based on (D,L)-lactide-ɛ-caprolactone methacrylate (LCM) copolymers in combination with a nano–micromaskless lithography technique, the two-photon polymerization (2-PP) to mimic the hierarchical structured and complex milieu of the natural ECM. To demonstrate the versatility of this toolbox, we choose two completely different application scenarios in bone and tumor TE to show the high potential of this concept in therapeutic and diagnostic application.
Adjunct faculty perspectives regarding the use of technology in the traditional classroom

This qualitative study examines the perspectives of adjunct faculty regarding the use of technology in the traditional (brick and mortar) classroom. Thirty-two semi-structured interviews were utilized to gain the perspective of the adjunct faculty members from a two year and a four year institution. Over the last thirty years the number of adjunct faculty members hired by institutions of higher education has dramatically increased. However, within the literature few have explored issues from the adjunct faculty‘s perspective. The use of technology in higher education is an expensive and ever growing trend. Today‘s traditional classrooms contain types of learning technology, but there is a lack of research that examines the use of technology in the traditional classroom. The increase in adjunct faculty numbers equates into more adjunct faculty teaching in traditional classrooms. Therefore to examine the use of technology in the traditional classroom the perspectives of the adjunct faculty are a necessary component. This study was guided by higher education and technological theory as well as concepts. Findings demonstrate that simply viewing technology as useful is not sufficient to encourage the use of technology, but instead a positive attitude toward the technology must be fostered. This study found that the main factors that foster a positive attitude in the adjunct faculty are convenience, flexibility, student need, and student learning. If the adjunct faculty members view the use of technology as aiding one or more of these factors the technology will be utilized in the classroom. The main barriers to the adjunct faculty members use of technology are also related to these factors. The lack of skill, lack of
Self-Efficacy, Self-Regulation, Social Support, and Outcomes Expectations for Daily Physical Activity in Adults with Chronic Stroke: A Descriptive, Exploratory Study

Abstract Interventions are needed to increase physical activity throughout the day in adults with chronic stroke, but mechanisms of action for doing so have not been identified. In this descriptive, exploratory study of 36 ambulatory, community-dwelling adults with chronic stroke, participants completed questionnaires investigating self-efficacy, self-regulation, social support, and outcomes expectations for daily physical activity. In the absence of any intervention, participants consistently reported high self-efficacy and outcomes expectations but low use of self-regulation and social support strategies. Discussion of how these results can inform the development of interventions to facilitate daily physical activity in adults with chronic stroke is provided.
HES1 Protein Modulates Human Papillomavirus–Mediated Carcinoma of the Uterine Cervix

PURPOSE Cervical cancer (CC) is the most common cancer affecting women worldwide. Human papillomavirus (HPV) infection is a major contributing factor for the development of CC. The development of CC occurs progressively from precancer stages to cancerous stages (ie, invasive squamous cell carcinoma [ISCC] and adenocarcinoma [ADC]). ADC is a rare form of CC that develops from the mucinous endocervical epithelium. It is believed that the downstream targets of Notch signaling contribute to the etiology of CC. One such target is HES1, whose role in the modulation of ADC is unknown. The purpose of this study is to determine the role of HES1 protein in HPV-associated ADC subtype of CC and also to compare its expression in histologic subtypes of precancer and ISCC. PATIENTS AND METHODS A total of 148 patients (30 with precancers, 98 with ISCC, and 20 with ADC) and 40 normal control participants were analyzed for the expression of HES1 via immunohistochemistry, with results validated by immunoblotting. RESULTS The comparison between HPV-16 and HES1 expression was significant in precancer (cervical intraepithelial neoplasia grades 1 to 3; P = .013), ISCC (International Federation of Gynecology and Obstetrics stages I to IV; P = .001), and ADC (P = .007). An overall significant mean difference was observed between HES1, JAG1, and Notch-3 proteins in precancer (P = .001), ISCC (P = .001), and ADC (P = .001). Pairwise comparisons between HES1 and JAG1 and HES1 and Notch-3 were also found to be significant. CONCLUSION This study showed that among all HPV-16–positive precancers, the major HES1 positivity signal arises from cervical intraepithelial neoplasia grades 2 and 3 that develops into ISCC. Moreover, HPV-16–positive ADC also showed an association with HES1. The HES1, JAG1, and Notch-3 proteins showed their synergistic role in modulating HPV associated ADC along with histologic subtypes of precancer and ISCC of CC.
The Validity of Risk Assessment Instruments for Transition-Age Youth

Objective: There is increasing recognition in the justice system that transition-age youth (TAY) are in a unique developmental period that may require tailored policies and practices. This study investigated the differential predictive validity and potential for disparate impact of both juvenile (the Structured Assessment of Violence Risk for Youth and Youth Level of Service/Case Management Inventory) and adult risk assessment instruments (the Historical-Clinical-Risk Management–20 [HCR-20] and the Violence Risk Appraisal Guide [VRAG]) with this age group (ages 16–24), relative to adolescents (ages 12–15) or older adults (ages 25–40). Method: The authors obtained secondary data sets for the 4 instruments totaling 3,353 cases. The final samples for each instrument after exclusions ranged from 1,181 cases for the VRAG to 290 cases for the HCR-20. Results: Age group generally did not moderate the prediction of any recidivism or of violent recidivism. The only exception was on the HCR-20, which significantly predicted recidivism regardless of age but operated better for TAY than adults. The VRAG was the only instrument with significant mean age–related differences in risk scores. Conclusions: The potential for an unfair impact of risk assessments on TAY is minimal regardless of whether they are processed in the juvenile or adult justice systems. This preliminary evidence suggests well-validated instruments used in either system should accurately quantify the likelihood of recidivism for TAY; however, this does not necessarily translate into effective risk management for this developmental period. More research using study designs developed specifically for examining age-related differences is needed.
Optimal Time to Administer Once-Daily Oral Cardiovascular Agents: Evidence Based on Randomized Clinical Trials in the Last Ten Years

Background: Sporadic studies have investigated the influence of administration time (morning versus evening) on the efficacy and safety of once-daily medications. It is necessary to let clinicians know the developments during the last ten years. Methods: Focusing on chronotherapeutic topic, a literature search on randomized controlled trials (RCTs) of oral oncedaily cardiovascular agents was conducted using PubMed, Cochrane Library, Scopus and Web of Science from Jan 01, 2008 to Sept 30, 2018. Results: Forty-seven RCTs investigated cardiovascular agents. Thirty-five RCTs showed the advantages of evening or bedtime dosing, only one RCT showed the superiority of morning dosing (perindopril for patients with obstructive sleep apnoea and hypertension), and 11 RCTs showed no relationship between dosing time and therapeutic outcomes. Two RCTs reported the difference in occurrence of actual side effects following morning versus evening administration (significantly lower incidence of edema following bedtime dosing of nifedipine rather than morning dosing, significantly lower rate of CKD event following bedtime dosing of ≥ 1 hypertension medications rather than therapy with all medications upon awakening). Rivaroxaban and amlodipine were cases of exhibiting chronopharmacokinetic feature. Factors determining whether to exhibit administration timedependent effects may include disease characteristics, gender, drug combination, treatment course, types of medications, dose, pharmaceutical dosage forms, and outcome measures. Conclusion: Chronotherapy intervention may be considered to improve medication therapy management before attempting to increase dose or add more drugs. Clinicians should educate patients about optimal administration time to take oral oncedaily medications. More RCTs are needed to explore the possibility of optimal dosing time because relevant descriptions are unavailable in prescribing information for many once-daily oral cardiovascular medications.
Using Intervention Mapping to develop and implement a home-based sedentary behavior change intervention after stroke.

Prolonged sedentary behavior is a problem immediately following a stroke and it persists from the acute to chronic phases of recovery. Frequently interrupting sedentary time might help to mitigate the associated detrimental health consequences. The purpose of this article was to describe the process followed in the systematic development and implementation of a theory- and home-based sedentary behavior change intervention for people with stroke. The Intervention Mapping protocol was used to design, develop and implement a STand Up Frequently From Stroke (STUFFS) program aimed at reducing prolonged sedentary behavior after stroke. A qualitative inquiry with people with stroke (n = 13) informed the development of the intervention. The systematic approach followed in the development process including the theoretical basis, content development, and evaluation planning were described. Program reception was assessed using thematic content analysis of exit-interview data (n = 25). The 8-weeks STUFFS intervention is a home-based sedentary behavior change program that provides education about the risks of prolonged sedentary behavior and facilitates behavior change, including the use of motivational tools to empower people with stroke to reduce sedentary behavior. The program was well-received and acceptable to people with stroke (89% satisfaction). This article provides information that furthers knowledge about theory-based strategies to reduce sedentary behavior in the home environment after stroke and facilitates implementation of this type of intervention.Trial registration: This study is registered at www.clinicaltrials. gov (No. NCT02980744).
A New Structural Modification Approach for Seismic Protection Based on Adaptive Negative Stiffness Device: Conceptual Analysis

Column forces, displacements and accelerations experienced by the structure during strong ground motions can be reduced by weakening and (or) softening the structure and adding a supplemental damper. Although this approach proved to be promising analytically, the concept of “structural strength reduction” leads to inelastic behavior and large permanent deformations in the main structural system. In this paper a new concept is developed to emulate weakening in a structural system by adding an “adaptive negative stiffness device” (NSD) and shifting the “yielding” away from the main structural system; leading, to the new idea of “apparent weakening” with reduced inelastic excursions in the main structural system. This is achieved through an adaptive negative stiffness system (ANSS), which is a combination of NSD and a damper. Engaging the NSD at an appropriate displacement (simulated yield displacement), that is well below the actual yield displacement of the structural system, will result in a composite structure-device assembly that behaves like a yielding structure. The NSD has a re-centering mechanism thereby avoiding permanent deformation in the composite structuredevice assembly unless, the main structure itself yields. Essentially, a yieldingstructure is “mimicked” without any, or with minimum yielding and permanent deformation in the main structure. In summary, the main structural system undergoes less acceleration, less displacements and less base shear, while the ANSS “absorbs” them. This paper presents the working principle and details on development and study of the ANSS/NSD. Through numerical simulations, the effectiveness and the superior performance of the ANSS/NSD as compared to a structural system with supplemental passive dampers is presented.
Comparative Genomic Screen in Two Yeasts Reveals Conserved Pathways in the Response Network to Phenol Stress

Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.