Miracle-dz/UniFAR-FTUs huggingface dataset:
Rhabdomyolysis in DOMS

Summary A 26-year-old man with a previous history of external twin bursitis was remitted to our Department for a bone scintigraphy. Before the study, the patient performed an elevated number of intense sprints. Bone scintigraphy showed a bilaterally increased activity in both anterior rectum muscles suggesting rhabdomyolysis. Biochemical studies and MRT confirmed the diagnosis.
Survivin Splice Variants in Arsenic Trioxide (As2O3)-Induced Deactivation of PI3K and MAPK Cell Signalling Pathways in MCF-7 Cells

Several pathways are deregulated during carcinogenesis but most notably, tumour cells can lose cell cycle control and acquire resistance to apoptosis by expressing a number of anti-apoptotic proteins such as the Inhibitors of Apoptosis Protein (IAP) family of proteins that include survivin, which is implicated in cancer development. There is no study which had proven that arsenic trioxide (As2O3) has any effect on the splicing machinery of survivin and its splice variants, hence this study was aimed at determining the cytotoxic effect of As2O3 and its effect on the expression pattern of survivin splice variants in MCF-7 cells. As2O3 inhibited the growth of the MCF-7 cells in a concentration-dependent manner. The Muse® Cell Analyser showed that As2O3-induced G2/M cell cycle arrest, promoted caspase-dependent apoptosis without causing any damage to the mitochondrial membrane of MCF-7 cells. As2O3 also deactivated two survival pathways, Mitogen-Activated Protein Kinase (MAPK) and Phosphoinositide 3-Kinase (PI3K) signalling pathways in MCF-7 cells. Deactivation of the two pathways was accompanied by the upregulation of survivin 3α during As2O3-induced G2/M cell cycle arrest and apoptosis. Survivin 2B was found to be upregulated only during As2O3-induced G2/M cell cycle arrest but downregulated during As2O3-induced apoptosis. Survivin wild-type was highly expressed in the untreated MCF-7 cells, the expression was upregulated during As2O3-induced G2/M cell cycle arrest and it was downregulated during As2O3-induced apoptosis. Survivin variant ΔEx3 was undetected in both untreated and treated MCF-7 cells. Survivin proteins were localised in both the nucleus and cytoplasm in MCF-7 cells and highly upregulated during the As2O3-induced G2/M cell cycle arrest, which can be attributed to the upregulation of survivin-2B. This study has provided the first evidence showing that the novel survivin 2B splice variant may be involved in the regulation of As2O3-induced G2/M cell cycle arrest only. This splice variant can therefore, be targeted for therapeutic purposes against Luminal A breast cancer cells.
Mirabegron induces relaxant effects via cAMP signaling‐dependent and ‐independent pathways in detrusor smooth muscle

We previously found that mirabegron exerts a relaxant effect in the presence of the β3‐adrenoceptor antagonist SR58894A during carbachol‐induced contraction in human and pig detrusor. The aim of this study was to explore the possible mechanism underlying the relaxant effects of mirabegron using detrusor smooth muscle.
The Effect of Whey and Soy Protein Isolates on Cognitive Function in Older Australians with Low Vitamin B12: A Randomised Controlled Crossover Trial

Whey protein isolate (WPI) is high in vitamin B12 and folate. These and other related markers (holotranscobalamin, methylmalonic acid and homocysteine) have been linked with cognitive health. This study explored the efficacy of WPI for improving cognitive function via delivery of vitamin B12. Moderately vitamin B12-deficient participants aged between 45 and 75 years (n = 56) were recruited into this randomised controlled crossover trial. Participants (55% female) consumed 50 g whey (WPI; active) or soy protein isolate (SPI; control) for eight weeks. Following a 16-week washout phase, they consumed the alternative supplement. Consumption of WPI significantly improved active B12 and folate status but did not result in direct improvements in cognitive function. However, there was evidence of improvement in reaction time (p = 0.02) and reasoning speed (p = 0.04) in the SPI condition for females. Additional analyses showed that changes in active B12, HcY and folate measures during WPI treatment correlated with improvements in cognitive function (all p < 0.05). Results indicate that WPI itself did not result in improved cognitive function but some evidence of benefit of SPI for females was found. However, consistent with previous research, we present further evidence of a role for active B12, HcY and folate in supporting cognitive improvement in adults with low B vitamin status.
Treatment Patterns and Clinical Outcomes in Advanced Lung Neuroendocrine Tumors in Real-World Settings: A Multicenter Retrospective Chart Review Study.

BACKGROUND Using data from four tertiary referral centers in the U.S., we assessed real-world treatment patterns and clinical outcomes of patients with advanced lung neuroendocrine tumors (NETs). SUBJECTS, MATERIALS, AND METHODS We performed a retrospective chart review of adult patients with locally advanced/metastatic (typical/atypical) lung NETs treated between July 2011 and December 2014. Index date was histologically confirmed typical/atypical carcinoid tumor diagnosis date. Data included baseline characteristics, treatment patterns, progression, death, and lung NET-related health care resource use from index date through last contact/death. Time to treatment discontinuation and first progression, time from first to second progression, and overall survival (OS) were estimated using Kaplan-Meier analysis. RESULTS We identified 83 patients; 19 (23%) had functional NET. First-line treatments included somatostatin analogs (SSAs) alone (56%) or in combination with other therapies (6%), cytotoxic chemotherapy (20%), external beam radiation therapy (EBRT) (9%), liver-directed therapy (LDT) (4%), and everolimus/other (5%). Sixty patients had second-line therapy including SSA alone (18%) or in combination (40%), cytotoxic chemotherapy (17%), everolimus (12%), LDT (7%), EBRT (3%), and other treatments (3%). Median time (months) to first-line discontinuation were as follows: SSAs, 43.3; cytotoxic chemotherapy, 3.6. Overall median time (months) to investigator-assessed progression following treatment initiation was 12.4. Median OS (months) following treatment initiation was 66.4 for all patients and 81.5 for patients receiving SSAs. CONCLUSION SSAs, alone and in combination, are common treatments for advanced lung NETs. Patients have additional treatment options and relatively long survival compared with patients with other advanced cancers. Treatment pattern assessment following approval of newer treatments is needed. IMPLICATIONS FOR PRACTICE Somatostatin analogs (SSAs), cytotoxic chemotherapy, EBRT, liver-directed therapy, and targeted therapies are common treatments for locally advanced/metastatic (typical/atypical) lung neuroendocrine tumors (NETs). SSAs alone or in combination with other treatment modalities were the most common first- and second-line therapy, followed by cytotoxic chemotherapy. Patients continued treatment with SSAs long-term with median treatment duration of 43 months. Median overall survival was 66 months following initiation of first-line therapy for all patients. Treatment pattern assessment beyond the time period of this study is needed given recent U.S. Food and Drug Administration approvals for additional treatments for lung NETs that will likely be incorporated in the treatment landscape.
Quantitative Radiographic Evaluation of Elbow Incongruity in Labrador and Golden Retrievers with Confirmed Medial Coronoid Disease

Abstract Objectives The purpose of this study was to objectively estimate humeroradial (HR), humeroulnar (HU) and radioulnar (RU) congruity on mediolateral elbow radiographs of Labrador and Golden Retrievers without and with medial coronoid disease (MCD), and to determine the correlation between traditional and modified RU-step assessment techniques. Materials and Methods Extended mediolateral elbow radiographs of Labrador and Golden Retrievers without MCD (control group) and with confirmed MCD (diseased group) were investigated. Absolute and average HR and HU distances were determined and standardized by the radius of the corresponding humeral condyle. Traditional RU-step was measured, and a modified procedure of RU-step assessment was generated. The correlation between the two RU-step assessment procedures was tested. Results A total of 131 (197 elbows) Labrador and Golden Retrievers met the criteria for inclusion in the control and diseased groups. The normalized HR and HU distances increased significantly (p ≤ 0.002) in dogs with MCD. There was a significant increase (p < 0.0001) in the traditional and modified RU-step in dogs with MCD. A significant correlation (r s = 0.74, p < 0.0001) was identified between traditional and modified RU-step calculated for control and diseased elbows. Clinical Relevance Dogs with confirmed MCD had quantitative radiographic evidences of elbow incongruity. Modified RU-step procedure may be an alternative to the traditional technique and can be utilized during routine quantification of HR and HU congruity. Validation of the reported measurements is, however, warranted.
Large but Nonstenotic Carotid Artery Plaque in Patients With a History of Embolic Stroke of Undetermined Source

Background and Purpose— This study’s objective is to determine if nonstenotic carotid plaque of <50% luminal narrowing predominantly develops ipsilateral rather than contralateral to the stroke site. Methods— This was a cross-sectional observational study. We identified consecutive patients with anterior circulation embolic stroke of undetermined source (ESUS), excluding stroke in multiple vascular territories. Using ultrasonography, we measured the internal carotid plaque size and stenosis for each patient. We dichotomized the plaque size at several predefined thresholds and calculated the frequency of the plaque size and morphology above each threshold ipsilateral versus contralateral to the stroke site. Results— We included 53 patients with unilateral anterior circulation ESUS. Initially, we found that plaque with a thickness ≥1.5 mm was present ipsilateral to the stroke site in 59% of the patients, and present contralateral to the stroke site in 42% of the patients (31/53 versus 22/53 patients; P=0.049). Plaque with low echo likewise had a similar prevalence when present ipsilateral (9%) and contralateral (4%) to the stroke site (5/53 versus 2/53; P=0.25). Conclusions— Internal carotid artery plaque with a thickness ≥1.5 mm but that is nonstenotic (<50%) is considerably more common when ipsilateral to the ESUS site than when contralateral to the ESUS site, especially in plaque with a thickness ≥2.6 mm. Large but nonstenotic carotid artery plaque is associated with anterior circulation ESUS.
Performance of Void-Free Electrospun SPEEK/Cloisite as a Function of Degree of Dispersion State on Nanocomposite Proton Exchange Membrane for Direct Methanol Fuel Cell Application

One of the main problems in direct methanol fuel cell (DMFC) application is methanol crossover. In order to solve the problem, an exfoliated void-free electrospun Sulfonated Poly(Ether Ether Ketone) (SPEEK)/cloisite nanocomposite membrane was developed. The membrane was prepared by immersing electrospun SPEEK/cloisite fiber mats onto incomplete solidified SPEEK polymer matrix. A well dispersed and reduction size of cloisite particles that ranges from 0.29–0.39 µm was observed by using Scanning Electron Microscopy Analysis (SEM) and Atomic Force Microscope (AFM). The effect of the morphology of the composite membrane in terms of degree of dispersion state of the Cloisite on the membrane performance was discussed. SP/e-spunCL15 with fully exfoliated structure exhibited the highest performance as compared to other tested membranes and Nafion® 115 with current density of 1042.2 mAcm−2 and power density of 1.18 mWcm−2. Improved morphological, dimensional change properties, and performance assigned to well-dispersed cloisite15A induced by the electrospinning technique make the membranes more efficient for direct methanol fuel cell applications.
Tailored treatment of patients with hepatocellular carcinoma with portal vein invasion: experience from a multidisciplinary hepatobiliary tumor program within a NCI comprehensive cancer center.

Background Hepatocellular carcinoma (HCC) with portal vein invasion (PVI) has a poor prognosis with limited treatment options. Intra-arterial brachytherapy (IAB) and transarterial chemoembolization (TACE) yield local control but risk accelerating liver dysfunction. The outcomes, survival, and safety of selective liver-directed treatment are reported. Methods Thirty-seven consecutive patients with HCC and PVI treated between 2009 and 2015 were reviewed from a prospectively collected database. Univariate analysis, Kaplan-Meier plots using the log-rank method, and multivariate analyses were performed. Statistical significance was defined as P<0.05. Overall survival was reported in months (median; 95% CI). Results Most patients (59%) had PVI identified at initial HCC diagnosis. The liver-directed therapy group (n=22) demonstrated a survival advantage versus the systemic/supportive care group (n=14) [23.6 (5.8, 30.9) vs. 6.0 (3.5, 8.8) months]. Patients indicated for liver directed therapy had unilateral liver involvement (100% vs. 43%, P<0.0001), lower median alkaline phosphatase (105.5 vs. 208.0, P=0.002), and lower mean Child-Turcotte-Pugh (CTP) score (5.9 vs. 7.2, P=0.04) and tolerated treatment without serious complications. Conclusions In HCC patients presenting with PVI, liver-directed therapy was safely performed in patients with limited venous involvement and preserved liver function. Liver-directed therapy extended survival for these patients indicated for palliative chemotherapy by traditional guidelines.
Childhood Trauma Predicts Cancer Treatment–Related Pain in Breast Cancer Survivors

Background Childhood trauma has been linked to neuropathic pain in noncancer populations, but its relationship with cancer treatment-related neuropathic pain is unknown. Objective This secondary data analysis of a prospective, longitudinal, observational study aimed to explore the relationship of childhood trauma experience with pain severity, pain interference, and neuropathic symptom severity (NSS) 12 months after surgery in women receiving treatment for stage 0 to III breast cancer. Methods Women (N = 44) recruited from a comprehensive cancer center self-reported childhood trauma experience, pain severity, pain interference, NSS, co-occurring symptoms, and pain beliefs via questionnaires. Descriptive statistics were used to describe childhood trauma experience. Linear regression was used to model childhood trauma and other predictors on pain variables 12 months after surgery. Results Childhood trauma predicted pain severity and pain interference 12 months after surgery (P < .05), as did baseline pain severities and helplessness-pain catastrophizing. Age predicted only NSS. Together, the best models predicted 31.6% to 40.9% of the variance in pain severities at 12 months (P < .001). Conclusions Childhood trauma exposure was a significant predictor of pain 12 months after breast cancer surgery and adjuvant treatment. Younger and helplessness-pain catastrophizing women are also at risk. Research is needed to identify preventive neuropathic pain interventions for high-risk women. Implications for Practice Women receiving breast cancer treatment should proactively be assessed for childhood trauma history, possibly by using discreet previsit questionnaires. Childhood trauma survivors may be at high risk for poor pain outcomes and may benefit from tailored pain interventions.
Direct and indirect associations of cognitive reappraisal and suppression with disease biomarkers

Abstract Objective: Habitual use of emotion regulation strategies may influence physical health. We examined whether the tendencies to employ cognitive reappraisal and suppression were associated with health biomarkers, and whether stress and sleep quality mediated these associations. Design & main outcome measures: Using data from the Biomarkers substudy (n = 1255) of the national Midlife in the U.S. Study, we tested the hypothesis that there would be indirect, but not direct, associations of cognitive reappraisal and suppression to biomarker indicators of multisystem physiological dysregulation, that is, allostatic load (AL). We computed the proportion of biomarkers in the highest risk quartile within seven biological systems, and summed these scores to compute AL. Associations with the biological systems were also examined separately.Results: Neither reappraisal nor suppression was directly associated with AL or biomarker function in the seven biological systems. Suppression was indirectly associated with higher AL and greater dysregulation in the inflammatory, metabolic, and hypothalamic-pituitary-adrenal systems via its relations to stress and sleep, p < 0.05. Reappraisal was indirectly associated with lower AL and less metabolic and inflammatory dysregulation, ps<0.05. Conclusions: Suppression and reappraisal may have different downstream health effects via stress, sleep, and biomarker expression, suggesting malleable emotion regulation strategies may be an important intervention target.
Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial.

PURPOSE Single-cycle melphalan 200 mg/m2 and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression. PATIENTS AND METHODS Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS. RESULTS The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms. CONCLUSION Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.
Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive, non-small cell lung cancer in China

Abstract Purpose: Pembrolizumab was recently approved in several countries as a first-line treatment for patients with PD-L1 positive, non-small cell lung cancer (NSCLC). However, it is expensive. This study aimed to assess the cost-effectiveness of pembrolizumab in treating advanced NSCLC patients with PD-L1 positive cancer in China. Methods: A Markov model was developed to compare the cost-effectiveness of pembrolizumab with chemotherapy for patients with PD-L1 expression on at least 50% of NSCLC tumor cells. Model inputs for transition probabilities and toxicity were derived from published clinical trial data, while health utilities were estimated from a literature review. Costs for drugs were updated to standard fee data from West China Hospital in 2017. Health outcomes were measured in quality-adjusted life years (QALYs), and cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to test the robustness of the model. Results: Pembrolizumab gained 0.45 QALYs at an incremental cost of $46,362 compared to chemotherapy for an ICER of $103,128 per QALY gained. In most scenarios, the ICER exceeded three times the Chinese Gross Domestic Product per capita. Two-way sensitivity analysis showed that, when the utility of the progression-free status increased to the maximal value of 0.845 and the 1 mg dose price decreased to $10.50, the ICER reduced to $25,216/QALY. Conclusions: Pembrolizumab is not likely to be cost-effective in the treatment of PD-L1 positive, NSCLC for Chinese patients. Less aggressive pricing may increase accessibility for patients in China.
The Influence of Feelings While Driving Regular Cars on the Perception and Acceptance of Self‐Driving Cars

Self‐driving vehicles will affect the future of transportation, but factors that underlie perception and acceptance of self‐driving cars are yet unclear. Research on feelings as information and the affect heuristic has suggested that feelings are an important source of information, especially in situations of complexity and uncertainty. In this study (N = 1,484), we investigated how feelings related to traditional driving affect risk perception, benefit perception, and trust related to self‐driving cars as well as people's acceptance of the technology. Due to limited experiences with and knowledge of self‐driving cars, we expected that feelings related to a similar experience, namely, driving regular cars, would influence judgments of self‐driving cars. Our results support this assumption. While positive feelings of enjoyment predicted higher benefit perception and trust, negative affect predicted higher risk and higher benefit perception of self‐driving cars. Feelings of control were inversely related to risk and benefit perception, which is in line with research on the affect heuristic. Furthermore, negative affect was an important source of information for judgments of use and acceptance. Interest in using a self‐driving car was also predicted by lower risk perception, higher benefit perception, and higher levels of trust in the technology. Although people's individual experiences with advanced vehicle technologies and knowledge were associated with perceptions and acceptance, many simply have never been exposed to the technology and know little about it. In the absence of this experience or knowledge, all that is left is the knowledge, experience, and feelings they have related to regular driving.