Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of an interprofessional pain service on nonmalignant pain control.

PURPOSE The primary objective of this project is to evaluate an existing interprofessional, nonmalignant pain service by measuring the difference in patient pain scores (numeric rating scale-11) before and after a pharmacist-led pain education class and medication therapy management (MTM) visit. Secondary objectives include determining the percentage of pharmacist recommendations approved, patient satisfaction, and difference in immediate release (IR) and extended release (ER) opioid use before and after enrollment. METHODS Baseline data was obtained from a retrospective chart review. Enrolled patients attended an educational pain class with the pharmacist. At the MTM visit with the pharmacist 3-14 days after the initial education class, the patient's pain score was assessed along with his/her medication use and a care plan was developed and forwarded to the referring provider for implementation. Three months after the pain class and participation in the MTM visit, patients were contacted via phone to complete a survey. The survey questions assess patient satisfaction with the pain education program, their current pain score, and their knowledge of information covered during the pain class. RESULTS Patients reported an average pre-enrollment pain score of 8.3/10 (n = 39) and a post-survey pain score of 5.6/10 (n = 39). The IR opioid use averaged 19.7 morphine equivalent daily dose (MEDD) at enrollment and decreased by 40% to 11.8 MEDD. The provider approval rate of the pharmacist recommended interventions ranges from 80%-92% depending on the pre designated disease state category. CONCLUSION An interprofessional, nonmalignant pain service including a pharmacist-led class resulted in a decrease in average pain scores and MEDD in an underserved population.
New concepts in regenerative medicine approaches to the treatment of female stress urinary incontinence.

PURPOSE OF REVIEW Update on recent regenerative medicine approaches to the treatment of stress urinary incontinence (SUI) caused by intrinsic sphincter deficiency (ISD). RECENT FINDINGS In the treatment of female SUI/ISD, results using different types of cellular therapy have been disappointing, and new approaches are desirable. To advance our regenerative medicine approaches to SUI/ISD, it is critical to utilize animal models that best parallel the pathophysiology of this disease in women. Many current animal models mimic acute SUI/ISD. However, SUI/ISD in women is usually a chronic condition resulting from previous muscle and nerve sphincter damage during parturition or muscle loss during aging. Similar to women, a nonhuman primate (NHP) model of chronic SUI/ISD has demonstrated only modest response to cell therapy. However, treatment with stromal cell-derived factor 1 (SDF1), also known as C-X-C motif chemokine 12 (CXCL12) restored continence in this model. SUMMARY As a potential therapeutic approach, the use of a well characterized chemokine, such as CXCL12, may by-pass the lengthy and expensive process of cell isolation, expansion, and injection. Recent findings in this new NHP model of chronic SUI/ISD may open up the field for noncell-based treatments.
Electrospun Core-Shell Nanofibrous Membranes with Nanocellulose-Stabilized Carbon Nanotubes for Use as High-Performance Flexible Supercapacitor Electrodes with Enhanced Water Resistance, Thermal Stability and Mechanical Toughness.

A high-performance flexible supercapacitor electrode with a core-shell structure is successfully developed from cellulose nanocrystal (CNC) stabilized carbon nanotubes (CNTs). By incorporating polyvinyl alcohol (PVA) and polyacrylic acid (PAA), a crosslinked nanofibrous membrane (CNT-CNC/PVA-PAA) is prepared as the core material via directional electrospinning followed by a thermal treatment. The flexible supercapacitor electrodes are eventually fabricated via the in situ polymerization of polyaniline (PANI), which was used as the coating shell material, on the aligned electrospun nanofibers. By taking advantage of the thermally-induced esterification crosslinking that occurs among PVA, PAA and the CNT-CNC nanohybrids, the membranes present with enhanced water resistance, mechanical strength and thermal stability. After the surface coating of the PANI shell, the optimized PANI@CNT-CNC/PVA-PAA nanofibrous membranes exhibit a large porosity, an enhanced specific surface area, a superior tensile strength of ~54.8 MPa and a favorable electroconductivity of ~0.44 S m-1. As expected, the nanofibrous electrodes with a specific capacitance of 164.6 F g-1 can maintain 91% of the original capacitance after 2000 cycles. The symmetrical solid-state supercapacitor assembled by the nanofibrous electrodes shows an excellent capacitance of 155.5 F g-1 and a remarkable capacitance retention of 92%, 90% and 89% after 2000 cycles under flat, bending and twisting deformations, respectively.
Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression

Aerobic glycolysis is a hallmark of metabolic reprogramming in tumor progression. However, the mechanisms regulating glycolytic gene expression remain elusive in neuroblastoma (NB), the most common extracranial malignancy in childhood. Herein, we identify that CUT‐like homeobox 1 (CUX1) and CUX1‐generated circular RNA (circ‐CUX1) contribute to aerobic glycolysis and NB progression. Mechanistically, p110 CUX1, a transcription factor generated by proteolytic processing of p200 CUX1, promotes the expression of enolase 1, glucose‐6‐phosphate isomerase, and phosphoglycerate kinase 1, while circ‐CUX1 binds to EWS RNA‐binding protein 1 (EWSR1) to facilitate its interaction with MYC‐associated zinc finger protein (MAZ), resulting in transactivation of MAZ and transcriptional alteration of CUX1 and other genes associated with tumor progression. Administration of an inhibitory peptide blocking circ‐CUX1‐EWSR1 interaction or lentivirus mediating circ‐CUX1 knockdown suppresses aerobic glycolysis, growth, and aggressiveness of NB cells. In clinical NB cases, CUX1 is an independent prognostic factor for unfavorable outcome, and patients with high circ‐CUX1 expression have lower survival probability. These results indicate circ‐CUX1/EWSR1/MAZ axis as a therapeutic target for aerobic glycolysis and NB progression.
A Quasi-Experimental Study Examining the Impact and Challenges of Implementing a Fitness-Based Health Risk Assessment and a Physical Activity Counseling Intervention in the Workplace Setting

Objectives: Few adults participate in enough physical activity for health benefits. The workplace provides a unique environment to deliver heath interventions and can be beneficial to the employee and the employer. The purpose of the study was to explore the use of a physical activity counseling (PAC) program and a fitness-based health risk assessment (fHRA) in the hospital workplace. Methods: A workplace-based intervention was developed utilizing a PAC program and an fHRA to improve physical activity levels of employees. Hospital employees were enrolled in a 4-month PAC program and given the option to also enroll in an fHRA program (PAC + fHRA). Physical activity was assessed by accelerometry and measured at baseline, 2 months, and 4 months. Changes in musculoskeletal fitness for those in the fHRA program were assessed at baseline and 2 months. Results: For both groups (PAC n = 22; PAC + fHRA n = 16), total and moderate to vigorous physical activity in bouts of 10 minutes or more increased significantly by 18.8 (P = .004) and 10.2 (P = .048) minutes per week at each data collection point, respectively. Only participants with gym memberships demonstrated increases in light physical activity over time. Those in the fHRA group significantly increased their overall musculoskeletal fitness levels from baseline levels (18.2 vs 21.7, P < .001). There was no difference in the change in physical activity levels between the groups. Conclusions: A PAC program in the workplace may increase physical activity levels within 4 months. The addition of an fHRA does not appear to further increase physical activity levels; however, it may improve overall employee musculoskeletal fitness levels.
Quantitation of neonicotinoid insecticides, plus qualitative screening for other xenobiotics, in small-mass avian tissue samples using UHPLC high-resolution mass spectrometry

We developed and validated a liquid chromatography–high-resolution mass spectrometry (LC-HRMS) analytical method for quantitatively measuring pesticide concentrations in small-body avian tissue samples using homogenized 1–2-d-old chicken carcasses as the test matrix. We quantified the following key insecticides: sulfoxaflor (sulfoximine class) and the neonicotinoids dinotefuran, nitenpyram, thiamethoxam, acetamiprid, thiacloprid, clothianidin, and imidacloprid. We used fortified chick carcass samples to validate method accuracy (80–125% recoveries), precision (<20% relative standard deviation), and sensitivity (≤1.2 ppb) for these targeted analytes. This method also uses full-scan, high-resolution MS to screen for the presence of a wide variety of other xenobiotics in bird carcasses. The utility of our screening process was demonstrated by the detection of carbaryl in some samples. This sensitive LC-HRMS analytical method for insecticide detection in a matrix of homogenized carcass is ideal for evaluating small birds for insecticide exposure. This novel whole-carcass method may allow for research studies of small-bodied, free-ranging avian species, and could provide insight regarding their exposure to multiple classes of environmental contaminants.
Aberrant ER Stress Induced Neuronal-IFNβ Elicits White Matter Injury Due to Microglial Activation and T-Cell Infiltration after TBI

Persistent endoplasmic reticulum (ER) stress in neurons is associated with activation of inflammatory cells and subsequent neuroinflammation following traumatic brain injury (TBI); however, the underlying mechanism remains elusive. We found that induction of neuronal-ER stress, which was mostly characterized by an increase in phosphorylation of a protein kinase R-like ER kinase (PERK) leads to release of excess interferon (IFN)β due to atypical activation of the neuronal-STING signaling pathway. IFNβ enforced activation and polarization of the primary microglial cells to inflammatory M1 phenotype with the secretion of a proinflammatory chemokine CXCL10 due to activation of STAT1 signaling. The secreted CXCL10, in turn, stimulated the T-cell infiltration by serving as the ligand and chemoattractant for CXCR3+ T-helper 1 (Th1) cells. The activation of microglial cells and infiltration of Th1 cells resulted in white matter injury, characterized by impaired myelin basic protein and neurofilament NF200, the reduced thickness of corpus callosum and external capsule, and decline of mature oligodendrocytes and oligodendrocyte precursor cells. Intranasal delivery of CXCL10 siRNA blocked Th1 infiltration but did not fully rescue microglial activation and white matter injury after TBI. However, impeding PERK-phosphorylation through the administration of GSK2656157 abrogated neuronal induction of IFNβ, switched microglial polarization to M2 phenotype, prevented Th1 infiltration, and increased Th2 and Treg levels. These events ultimately attenuated the white matter injury and improved anxiety and depressive-like behavior following TBI. SIGNIFICANCE STATEMENT A recent clinical study showed that human brain trauma patients had enhanced expression of type-1 IFN; suggests that type-1 IFN signaling may potentially influence clinical outcome in TBI patients. However, it was not understood how TBI leads to an increase in IFNβ and whether induction of IFNβ has any influence on neuroinflammation, which is the primary reason for morbidity and mortality in TBI. Our study suggests that induction of PERK phosphorylation, a characteristic feature of ER stress is responsible for an increase in neuronal IFNβ, which, in turn, activates microglial cells and subsequently manifests the infiltration of T cells to induce neuroinflammation and subsequently white matter injury. Blocking PERK phosphorylation using GSK2656157 (or PERK knockdown) the whole cascade of neuroinflammation was attenuated and improved cognitive function after TBI.
Detecting Hypoglycemia Incidents Reported in Patients’ Secure Messages: Using Cost-Sensitive Learning and Oversampling to Reduce Data Imbalance

Background Improper dosing of medications such as insulin can cause hypoglycemic episodes, which may lead to severe morbidity or even death. Although secure messaging was designed for exchanging nonurgent messages, patients sometimes report hypoglycemia events through secure messaging. Detecting these patient-reported adverse events may help alert clinical teams and enable early corrective actions to improve patient safety. Objective We aimed to develop a natural language processing system, called HypoDetect (Hypoglycemia Detector), to automatically identify hypoglycemia incidents reported in patients’ secure messages. Methods An expert in public health annotated 3000 secure message threads between patients with diabetes and US Department of Veterans Affairs clinical teams as containing patient-reported hypoglycemia incidents or not. A physician independently annotated 100 threads randomly selected from this dataset to determine interannotator agreement. We used this dataset to develop and evaluate HypoDetect. HypoDetect incorporates 3 machine learning algorithms widely used for text classification: linear support vector machines, random forest, and logistic regression. We explored different learning features, including new knowledge-driven features. Because only 114 (3.80%) messages were annotated as positive, we investigated cost-sensitive learning and oversampling methods to mitigate the challenge of imbalanced data. Results The interannotator agreement was Cohen kappa=. 976. Using cross-validation, logistic regression with cost-sensitive learning achieved the best performance (area under the receiver operating characteristic curve=0.954, sensitivity=0.693, specificity 0.974, F1 score=0.590). Cost-sensitive learning and the ensembled synthetic minority oversampling technique improved the sensitivity of the baseline systems substantially (by 0.123 to 0.728 absolute gains). Our results show that a variety of features contributed to the best performance of HypoDetect. Conclusions Despite the challenge of data imbalance, HypoDetect achieved promising results for the task of detecting hypoglycemia incidents from secure messages. The system has a great potential to facilitate early detection and treatment of hypoglycemia.
Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis

Cytomegalovirus (CMV) has been implicated in glioblastoma (GBM); however, a mechanistic connection in vivo has not been established. The purpose of this study is to characterize the effects of murine CMV (MCMV) on GBM growth in murine models. Syngeneic GBM models were established in mice perinatally infected with MCMV. We found that tumor growth was markedly enhanced in MCMV+ mice, with a significant reduction in overall survival compared with that of controls (P < 0.001). We observed increased angiogenesis and tumor blood flow in MCMV+ mice. MCMV reactivation was observed in intratumoral perivascular pericytes and tumor cells in mouse and human GBM specimens, and pericyte coverage of tumor vasculature was strikingly augmented in MCMV+ mice. We identified PDGF-D as a CMV-induced factor essential for pericyte recruitment, angiogenesis, and tumor growth. The antiviral drug cidofovir improved survival in MCMV+ mice, inhibiting MCMV reactivation, PDGF-D expression, pericyte recruitment, and tumor angiogenesis. These data show that MCMV potentiates GBM growth in vivo by increased pericyte recruitment and angiogenesis due to alterations in the secretome of CMV-infected cells. Our model provides evidence for a role of CMV in GBM growth and supports the application of antiviral approaches for GBM therapy.
New‐Onset Diabetes Mellitus in Peritoneal Dialysis and Hemodialysis Patients: Frequency, Risk Factors, and Prognosis—A Review

New‐onset diabetes mellitus (NODM) is observed in both hemodialysis (HD) and peritoneal dialysis (PD) patients. The prevalence of NODM in dialysis patients is slightly higher compared to subjects of the general population. Based on currently published data there is no convincing evidence that the risk of NODM is different between HD and PD patients. Data on the effect of glucose load on risk of NODM in dialysis patients remain controversial. PD modality (automated or continuous ambulatory PD) has no significant influence on NODM incidence. Chronic inflammation is associated with NODM in dialysis patients. Reported differences in NODM between PD and HD patients are possibly also influenced by differences in demographic factors between these patient groups. Mortality in NODM patients is lower than mortality in patients with preexisting DM. This may be partly explained by the younger age and lower number of comorbidities in patients with NODM.
Diagnostic value of high b-value (2000 s/mm2) DWI for thyroid micronodules

Abstract The aim of the study was to assess the diagnostic value of high b-value (2000 s/mm2) diffusion-weighted imaging (DWI) in differentiating malignant from benign thyroid micronodules. Consecutive patients with thyroid micronodules scheduled for Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) or surgery were underwent high b-value DWI with 3 b-values: 0, 800, and 2000 s/mm2. Signal intensity ratios (SIRs) of thyroid micronodules to adjacent normal thyroid tissue on DWI were measured as SIRb0, SIRb800 and SIRb2000. Apparent diffusion coefficients (ADCs) according to the three different b-values were acquired as: ADCb0–800, ADCb0–2000 and ADCb0–800–2000. The 6 diagnostic indicators were evaluated by receiver operating characteristic (ROC) and diagnostic ability was compared between the high b-value DWI and US. Sixty-two malignant thyroid micronodules (48 patients, 13 men and 35 women, aged 44.8 ± 11.7 years) and 57 benign thyroid micronodules (40 patients, 6 men and 34 women, aged 49.6 ± 12.5 years) were enrolled into the final statistical analysis. Among the alone diagnostic indicators, SIRb2000 had the highest diagnostic ability in differentiating malignant from benign thyroid micronodules with area under curve (AUC) of 0.975, sensitivity of 90.32% and specificity of 96.49%. Compared to US, SIRb2000 had a significantly better diagnostic ability US for thyroid micronodules (P < .001) with dramatically raised positive predict value (96.6% vs 78.9%) and reduced false-positive rate (3.51% vs 26.32%). High b-value (2000 s/mm2) DWI can contribute to differentiating malignant from benign thyroid micronodules.
Social Studies Content Knowledge Interventions for Students With Emotional and Behavioral Disorders: A Meta-Analysis

The importance of social studies and civics education is increasing, as evidenced by the growing number of states requiring coursework in this area for graduation and its growing presence in school accountability frameworks. Social studies instruction is critical for all students so that they may understand their roles, rights, and responsibilities as citizens and how their actions can influence their communities. Students who exhibit antisocial behaviors, such as those with emotional and behavioral disorders (EBD), may especially benefit from social studies and civics education as it promotes college and career readiness and provides opportunities to engage in social problem solving and perspective taking. The purpose of this study was to systematically review the social studies and civics intervention research for students with EBD. We sought to describe and evaluate the extant literature, identify promising practices, and suggest areas for future research. A total of 17 intervention studies were identified. Overall, 10 out of the 17 studies met What Works Clearinghouse Design Standards with or without reservations. Eight of the 10 studies were eligible for effect size calculation, resulting in an overall large effect (g = 0.83). Study limitations, implications for school practice, and directions for research are discussed.
Prediction of Cyclic Stress–Strain Property of Steels by Crystal Plasticity Simulations and Machine Learning

In this study, a method for the prediction of cyclic stress–strain properties of ferrite-pearlite steels was proposed. At first, synthetic microstructures were generated based on an anisotropic tessellation from the results of electron backscatter diffraction (EBSD) analyses. Low-cycle fatigue experiments under strain-controlled conditions were conducted in order to calibrate material property parameters for both an anisotropic crystal plasticity and an isotropic J2 model. Numerical finite element simulations were conducted using these synthetic microstructures and material properties based on experimental results, and cyclic stress-strain properties were calculated. Then, two-point correlations of synthetic microstructures were calculated to quantify the microstructures. The microstructure-property dataset was obtained by associating a two-point correlation and calculated cyclic stress-strain property. Machine learning, such as a linear regression model and neural network, was conducted using the dataset. Finally, cyclic stress-strain properties were predicted from the result of EBSD analysis using the obtained machine learning model and were compared with the results of the low-cycle fatigue experiments.
Immune effects of Lactobacillus casei Shirota in treated HIV-infected patients with poor CD4+ T cell recovery: a randomized trial.

BACKGROUND HIV infection leads to depletion of intestinal CD4+ T cells, mucosal barrier dysfunction, increased gut permeability and microbial translocation even among patients on suppressive ART. Previous studies suggest probiotics may help restore intestinal function. METHODS In this double-blind, placebo-controlled pilot study, we enrolled HIV-infected patients on suppressive ART with poor CD4+ recovery to address the effect of daily oral use of Lactobacillus casei Shirota (LcS) on CD4+ T cell count and CD4/CD8 ratio at 6 and 12 weeks after treatment initiation; immune activation and intestinal microbiome composition were addressed as secondary outcomes. RESULTS From Jan/2015 to Jul/2016, 48 patients were randomized (1:1) to active intervention or placebo. Groups had comparable demographic and clinical characteristics; only CD4+ T cell nadir was statistically different between groups. All participants were virologically-suppressed under ART. At week 6, the increment in CD4+ T cell count was 17 cells/mm3 (interquartile range [IQR] -33 to 74) in the active intervention arm and 4 cells/mm3 (IQR -43 to 51) in the placebo arm (p = 0.291); at week 12, the change in CD4+ T cell count was 8 cells/mm3 (IQR -30 to 70) in the active arm and 10 cells/mm3 (IQR -50 to 33) among participants allocated to placebo (p = 0.495). Median change in CD4/CD8 ratio at week 6 compared to baseline was 0 (IQR -0.04 to 0.05) in the active intervention arm and -0.01 in the placebo arm (IQR -0.06 to 0.03; p = 0.671). At week 12, the change in CD4/CD8 ratio was higher in the active product group compared to placebo (respectively 0.07 and 0.01), but this difference failed to reach statistical significance (p = 0.171). We found no significant effects of LcS on immune activation markers, CD4+ and CD8+ subpopulations, sCD14 levels or NK cells at week 12. Finally, we found no statistically significant differences between groups in the change of enteric microbiome at week 12. CONCLUSIONS In this pilot study, we found no statistically significant effect of LcS probiotic on CD4+ T cell counts, CD4/CD8 ratio, immune activation or intestinal microbiome among HIV-infected patients on suppressive ART with poor CD4+ recovery.