Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging angiogenesis inhibitors for non-small cell lung cancer

ABSTRACT Introduction: Angiogenesis represents a complex process crucial during embryo development, wound healing, and collateral formation for improved organ perfusion. Numerous stimulatory and inhibitory pathways through their balance regulate angiogenesis and vascular homeostasis. Targeting the pathways implicated in the regulation of angiogenesis and neo-angiogenesis plays an important role in cancer research, treatment, and patients’ outcome. Antiangiogenic strategies, including monoclonal antibodies binding vascular endothelial growth factor (VEGF) or the corresponding receptor and small molecules which inhibit the function of different angio–related tyrosine kinase, produced interesting results in cancer treatments including non-small-cell lung cancer (NSCLC). Areas covered: The current state-of-the-art of anti-angiogenesis treatment in the management of NSCLC patients is reviewed and discussed. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken in order to discuss about emerging angiogenesis inhibitors in NSCLC. Expert opinion: Targeting angiogenesis remains an important therapeutic strategy in the management of NSCLC. Moreover, VEGF has been recognized having also an immunosuppressive action leading to investigate the potential activity of angiogenic inhibitors in restoring the antitumor immunity by targeting VEGF/VEGF-Receptor. Furthermore, new anti-angiogenic drugs for which there is also the availability of predictive biomarkers are welcome.
Experiences, Attitudes, and Behaviors of the Unemployed: The Role of Motivation and Psychological Needs

Alleviating the psychological burden of unemployment and preventing the unemployed from withdrawing from the labor market remains a priority for unemployment researchers and practitioners alike. Job search motivation and the differential relationships with experienced psychological need satisfaction (and need frustration) potentially induce different well-being (i.e., experiences), attitudinal outcomes (i.e., employment commitment), and behavioral outcomes (i.e., job search intensity) in unemployment. This study examined if job search motivation relates to the experiences, attitudes, and behavior of the unemployed over time through basic need satisfaction and frustration. In a two-wave study (nT1 = 461; nT2 = 244), the results demonstrated that job search motivation has no relationship with the affective experiences, attitudes toward employment, and job search behavior over time. It also showed that only controlled motivation and amotivation were significantly related to need frustration. Finally, only psychological need satisfaction, and not the frustration of their needs, was significantly related to affective experiences over time. The implications for unemployment and self-determination theory research are discussed, and recommendations for practitioners are made.
Poly Lactic-co-Glycolic Acid Nanoparticles Containing Human Gastric Tumor Lysates as Antigen Delivery Vehicles for Dendritic Cell-Based Antitumor Immunotherapy

ABSTRACT Stimulating antitumor T cells using dendritic cells (DCs) is a novel and promising method in cancer therapy. Poly lactic-co-glycolic acid is one of the best-known polymers used for encapsulating antigen to protect them against proteolytic enzymes. In this study, poly lactic-co-glycolic acid nanoparticles (NPs) were used as DC antigen delivery vehicles in a preclinical model of immunotherapy of gastric cancer. The DCs were generated from peripheral blood monocytes by conventional in vitro differentiation and loaded with either soluble tumor lysate or lysate encapsulated in NPs using a double emulsion/solvent evaporation technique. Morphology of NPs was determined by scanning electron microscopy. Tumor lysate, either in the soluble form or encapsulated in NPs, was loaded into DC and stimulatory capacity was compared using patient-derived autologous CD3+ T cells as responders. The amount of relevant cytokines produced by Ag-loaded DC and in DC/T cell cocultures was evaluated as a measure of initial DC stimulation and T-cell responses, respectively. Significance increases in expression of DC surface molecules (i.e., CD80, CD83, CD86, and Human Leukocyte Antigen–DR (HLA-DR)) and cytokine production by both DC and DC/T cell cocultures (i.e., interleukin (IL)-12:IL-10 and interferon [IFN]-γ:IL-4 ratios) was observed following loading with lysate NP versus controls. The results suggest that NP-encapsulated antigen can shift antitumor T-cell responses toward a Th1 bias, which potentially increases DC vaccine potency in clinical settings.
Caecocolic intussusception associated with a caecal polyp and concurrent hepatocellular carcinoma in a cat

Case summary A 17-year-old female neutered domestic shorthair cat presented for several days of reduced faecal volume and a rectal prolapse. Physical examination revealed a 2 cm rectal prolapse, hepatomegaly and a low body condition score of 3/9. Haematology and biochemistry revealed a mild non-regenerative anaemia (haematocrit 24.5%; reference interval [RI] 30.3–52.3%), a mild mature neutrophilia (16.21 × 109/l; RI 1.48–10.29 × 109/l) and a mild increase in alanine aminotransferase activity (222 IU/l; RI 12–130 IU/l). Abdominal radiographs identified hepatomegaly. The rectal prolapse was reduced under general anaesthesia. Abdominal ultrasound identified a caecocolic intussusception and a large hepatic mass. Thoracic radiographs were unremarkable. Hepatic fine-needle aspirate cytology revealed well-differentiated hepatocytes. A typhlectomy was performed and the quadrate liver lobe, with mass, was resected. Gross examination of the caecum identified a focal polyp; histopathology showed moderate plasmacytic–lymphocytic typhlitis and reactive mucosal-associated lymphoid tissue. The hepatic mass was diagnosed as a well-differentiated hepatocellular carcinoma. Six weeks postoperatively the cat had gained 0.5 kg, had an improved body condition score of 5/9 and resolution of clinical signs. The cat died acutely 1 year later from an unknown cause. Relevance and novel information Caecocolic intussusception is rare in cats and uncommon in dogs. This is the third report in a cat and the first associated with a caecal polyp. As reported in dogs, the outcome following surgery was good. Hepatocellular carcinoma is a rarely reported feline neoplasm, which may have a good prognosis with surgical resection.
Identification of prognostic molecular biomarkers in 157 HPV‐positive and HPV‐negative squamous cell carcinomas of the oropharynx

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing due to high‐risk HPV infection. We explored the significance of genetic alterations in HPV‐positive (HPV‐P) and HPV‐negative (HPV‐N) OPSCC patients on long‐term outcome. A total of 157 cases of primary resected OPSCC diagnosed from 1978 to 2005 were subjected to a targeted exome sequencing by MSK‐IMPACT™ interrogating somatic mutations in 410 cancer‐related genes. Mutational profiles were correlated to recurrence and survival outcomes. OPSCC included 47% HPV‐positive (HPV‐P) and 53% HPV‐negative (HPV‐N) tumors arising in the base of tongue (BOT, 43%), palatine tonsil (30%) and soft palate (SP, 27%). HPV negative status, SP location and smoking were associated with poorer outcome. Poorer overall survival was found in NOTCH1‐mutated HPV‐P (p = 0.039), and in SOX2‐amplified HPV‐N cases (p = 0.036). Chromosomal arm gains in 8p and 8q, and 16q loss were more common in HPV‐P (p = 0.005, 0.04 and 0.01, respectively), while 9p, 18q and 21q losses were more frequent in HPV‐N OPSCC (p = 0.006, 0.002 and 0.01, respectively). Novel, potentially functional JAK3, MYC and EP300 intragenic deletions were found in HPV‐P, and FOXP1, CDKN2A, CCND1 and RUNX1 intragenic deletions and one FGFR3 inversion were detected in HPV‐N tumors. HPV‐N/TP53‐wild‐type OPSCC harbored recurrent mutations in NOTCH1/3/4 (39%), PIK3CA, FAT1 and TERT. In comparison to their oral and laryngeal counterparts, HPV‐N OPSCC were genetically distinct. In OPSCC, HPV status, tumor subsite and smoking determine outcome. Risk‐stratification can be further refined based on the mutational signature, namely, NOTCH1 and SOX2 mutation status.
Anal Sex Role Segregation and Versatility Among Men Who Have Sex With Men: EXPLORE Study

Abstract:Anal sex role patterns and correlates during unprotected anal sex were examined longitudinally among HIV-negative men who have sex with men. Nearly 9.6% were exclusively receptive, 16.7% exclusively insertive, and 63.0% versatile. Versatility was more likely with primary and HIV-negative/unknown status partners and among younger men and substance users but less likely among Blacks and with higher number of partners. Exclusively receptive role was more likely with HIV-negative/unknown status partners and among younger men and substance users but less likely with higher number of partners. Examining anal sex role patterns helps understand the factors that drive the epidemic among men who have sex with men.
Paroxetine in the treatment of depressed patients with haematological malignancy: an open‐label study

The efficacy and tolerability of paroxetine in the treatment of depressive disorders is well known, however, its efficacy and safety for the treatment of depression in patients with cancer has been poorly studied. Therefore this study was aimed at evaluating the efficacy and tolerability of paroxetine in the treatment of depressed patients with haematological malignancy (HM).
The Effects of Blood Flow Restriction on Muscle Activation and Hypoxia in Individuals with Chronic Ankle Instability.

CONTEXT Muscle dysfunction is common in patients with chronic ankle instability (CAI). Blood flow restriction (BFR) may enhance muscle responses during exercise and provide an opportunity to enhance muscle adaptations to ankle rehabilitation exercises; however, there is no evidence examining the effect of BFR on muscle function in CAI patients. OBJECTIVE Examine the effects of BFR on muscle activation and oxygen saturation during submaximal ankle eversion and dorsiflexion exercises in individuals with CAI. DESIGN Crossover study design. SETTING Laboratory setting. PATIENTS (OR OTHER PARTICIPANTS) Nineteen (n=19) young adults with a history of CAI. INTERVENTIONS Participants performed four sets (30, 15, 15, 15) of eversion and dorsiflexion resistance exercises at 30% of maximum voluntary isometric contraction (MVIC) during two conditions, BFR and control. For BFR, a cuff was applied above the knee at 80% of blood flow occlusion. For control, the cuff was not inflated. MAIN OUTCOME MEASURES Fibularis longus and tibialis anterior electromyography (EMG) muscle activation, lower-leg muscle oxygen saturation (SmO2), and ratings of perceived exertion (RPE) were recorded during exercises. RESULTS Average grand mean muscle activation was 5.6% greater during eversion (P=.03) and 7.7% greater during dorsiflexion (P=.01) resistance exercises with BFR compared to control; however, the magnitudes of the effects of BFR were only clinically important during the dorsiflexion exercises. Lower-leg muscle oxygen saturation was 31-44% lower (P<.001) during BFR exercises. RPE were significantly higher during BFR exercises (P<.001). CONCLUSIONS Greater muscle activation and hypoxia were present during submaximal resistance exercise with BFR in participants with CAI. Greater muscle activation and hypoxia during BFR exercises may be important acute responses mediating the training-related muscle adaptations that have been observed with BFR. The presence of these acute responses in CAI patients supports further research examining BFR as a potential ankle rehabilitation tool.
Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964–2014

Objectives To examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years. Design Swedish nationwide register-based cohort study 1964–2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873. Results During 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn’s disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002–2014 had 2.3 years shorter mean estimated life span than matched comparators. Conclusions Adult-onset and elderly-onset patients with UC, Crohn’s disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.
The semantic network supports approximate computation.

OBJECTIVE The present study used complex approximate and exact arithmetic computation problems to dissociate the brain networks for strategy-based approximate computation and procedure-based exact computation. METHOD Twenty-eight college students were scanned with MRI while they were solving complex approximate and exact computation problems, including addition, subtraction, multiplication, and division of multidigit integers and fractions. The neuroimaging data were analyzed using whole brain, region of interest, and functional connectivity approaches. RESULTS Results showed that approximate computation relative to exact computation elicited greater activation typically in the bilateral inferior frontal gyrus (orbital), middle temporal gyrus, angular gyrus, and dorsomedial prefrontal cortex. The brain regions overlapped with the general semantic network that also supports mathematical problem solving. In contrast, exact computation elicited greater activations in the left rolandic operculum and bilateral hippocampus. Functional connectivity analysis based on the psychophysiological interaction approach showed that approximate computation had stronger connectivity from the left intraparietal sulcus to the semantic areas. In contrast, exact computation had stronger connectivity from the left intraparietal sulcus to the phonological areas. CONCLUSION The results suggest that the semantic network supports complex approximate computation and the phonological network supports complex exact computation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT Phase 3 study design.

Bemarituzumab is an afucosylated monoclonal antibody against FGFR2b (a FGF receptor) with demonstrated monotherapy clinical activity in patients with late-line gastric cancer whose tumors overexpress FGFR2b (NCT02318329). We describe the rationale and design of the FIGHT trial (NCT03343301), a global, randomized, double-blind, placebo-controlled Phase 3 study evaluating the role of bemarituzumab in patients with previously untreated, FGFR2b-overexpressing advanced gastroesophageal cancer. Patients are randomized in a blinded fashion to the combination of mFOLFOX6 and bemarituzumab or mFOLFOX6 and placebo. Eligible patients are selected based on the presence of either FGFR2b protein overexpression determined by immunohistochemistry or FGFR2 gene amplification determined by circulating tumor DNA. The primary end point is overall survival, and secondary end points include progression-free survival, objective response rate and safety.
Evaluation of a Remote Diagnosis Imaging Model vs Dilated Eye Examination in Referable Macular Degeneration.

Importance In improving clinical outcomes, developing a sustainable, transformative care delivery model is important for accessible, efficient, low-cost, high-quality community-based imaging and diagnosis of retinal diseases. Objective To test the feasibility and accuracy of the remote diagnosis imaging model as a clinical screening tool to facilitate the identification of referable macular degeneration. Design, Setting, and Participants A nonrandomized study of 159 patients was conducted in sites with a relatively high disease prevalence (Duke University Health System endocrinology clinic and 2 Duke University Health System assisted living centers in North Carolina). All patients underwent remote diagnosis imaging, defined as color fundus photography (CFP) and optical coherence tomography (OCT) of nondilated pupils, acquired by nonexpert imagers using a retinal imaging device located at the point of service. The criterion standard examination was defined as a traditional dilated eye examination performed by retinal specialists. Deidentified remote diagnosis images were graded for interpretability and presence of referable macular degeneration, defined as any condition requiring a retinal specialist attention. Data analysis was performed from November 20, 2015, to February 10, 2019. Main Outcomes and Measures Primary outcome was feasibility of the remote retinal imaging. Secondary outcomes were operational characteristics and diagnostic and referral accuracy. Results Of the 159 patients included in the study, the mean (SD) age of enrolled participants was 65 (17) years, with a female to male ratio of 1.3 to 1. Most patients were white (111 [69.8%]), 44 were black patients (27.7%), approximately 1% were Asian patients and Hispanic patients, and 2 patients declined to disclose their race/ethnicity. Thirty-five eyes (22.0%) were determined to require referral to the retinal specialist by criterion standard examination. Remote diagnosis image interpretability was better when OCT was used compared with CFP (241 [96.4%] vs 164 [65.6%]). Remote diagnosis had high diagnostic accuracy in identifying referable macular degeneration: OCT and CFP both had 94% sensitivity (95% CI, 84%-98%), and OCT had specificity higher than for CFP (93% [95% CI, 87%-96% ] vs 63% [95% CI, 53%-71%]). Substantial agreement was found between the criterion standard and OCT (κ = 0.83; 95% CI, 0.76-0.91; P < .001) and between the criterion standard and CFP (κ = 0.76; 95% CI, 0.64-0.87; P < .001). The nonvalidated patient satisfaction survey revealed that 122 participants (76.7%; mean score, 4.16; 95% CI, 3.98-4.35) preferred remote imaging over the standard care examination. Conclusions and Relevance Remote diagnosis imaging and a standard examination by a retinal specialist appeared equivalent in identifying referable macular degeneration in patients with high disease prevalence; these results may assist in delivering timely treatment and seem to warrant future research into additional metrics.
The role of stem cells in liver injury and repair

ABSTRACT Introduction: Liver disease is an increasing cause of worldwide mortality, and currently the only curative treatment for end-stage liver disease is whole organ allograft transplantation. Whilst this is an effective treatment, there is a shortage of suitable grafts and consequently some patients die whilst on the waiting list. Cell therapy provides an alternative treatment to increase liver function and potentially ameliorate fibrosis. Areas covered: In this review, we discuss the different cellular sources for therapy investigated to date in humans including mature hepatocytes, hematopoietic stem cells, mesenchymal stromal cells and hepatic progenitor cells. Cells investigated in animals include embryonic stem cells, induced pluripotent stem cells and directly reprogrammed cells. We then appraise the experience and evidence base underlying each cell type. Expert opinion: We discuss how this field may evolve in the years to come focusing on opportunities to enhance the intrinsic regenerative response with therapeutic targets and cell therapies. Growing expertise in tissue engineering will likely lead to increasingly complex bio-reactors and bio-artificial livers, which open a further avenue to restore liver function and delay or prevent the need for transplantation.
Thirty-Day Hospital Readmission After Acute Myocardial Infarction in China.

Background Readmission after acute myocardial infarction in low- and middle-income countries like China is not well characterized. Methods and Results We approached consecutive patients with acute myocardial infarction hospitalized within 24 hours of symptom onset and discharged alive from 53 geographically diverse hospitals in China. We described rates of unplanned 30-day readmission, their timing and admitting diagnoses, and fit Cox proportional hazards models to identify factors associated with readmission. Among 3387 patients, median (interquartile range) age was 61 (52-69) years, and 76.9% were men. The index median length of stay was 11 (8-14) days. Unplanned 30-day readmission occurred in 6.3% of the cohort; most readmissions (77.7%) were for cardiovascular diagnoses. Nearly half (41.9% of all-cause readmissions; 44.3% of cardiovascular readmissions) occurred within 5 days of discharge. Mini-Global Registry of Acute Coronary Events scores at admission (hazard ratio [HR], 1.15 for every 10-point increase; 95% CI, 1.05-1.25), longer length of stay (HR, 1.03; 95% CI, 1.00-1.06 for each extra day), and in-hospital recurrent angina (HR, 1.40; 95% CI, 1.04-1.89) were associated with higher unplanned all-cause readmission. Revascularization during the index hospitalization (70.2% of the cohort) was associated with lower risks of all-cause readmission (HR, 0.27; 95% CI, 0.18-0.42). In addition, left ventricular ejection fraction <0.4 (HR, 1.79; 95% CI, 1.05-3.07) and in-hospital complication (HR, 1.20; 95% CI, 1.03-1.39) were associated with higher risk of unplanned cardiovascular readmission, and ST-segment-elevation myocardial infarction (HR, 0.60; 95% CI, 0.36-0.98) was associated with lower risk of unplanned cardiovascular readmission. Sex, family income, depression, stress level, lower social support, disease-specific health status, and medications were not associated with readmission. Conclusions In China, most readmissions are for cardiovascular events, and almost half occur within 5 days of discharge. Clinical factors identify patients at higher and lower unplanned readmissions. Clinical Trial Registration URL: https://www.clinicaltrials. gov . Unique identifier: NCT01624909.