Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer.

The aim of this study was to investigate the role of specific cytotoxic T lymphocytes (CTLs) activated by dendritic cells (DCs) presenting cationic nanoparticles with the K-ras (12-Val) mutant peptide in the killing of different pancreatic cancer cell lines in vivo and in vitro. Peripheral blood DCs were induced by rhGM-CSF and IL-4 and cultured. DCs were sensitized by whole antigen of PANC-1 with expression of K-ras mutant, K-ras mutant peptide (K-ras+peptide) and cationic nanoparticles with K-ras mutant peptide (K-ras+peptide-CNP), respectively. Cell surface markers were measured by flow cytometry. Lymphocyte proliferation was detected by the 3H-TdR test, and IL-12 and IFN‑γ secretion was detected by ELISA. 125I-UdR was used to measure the killing effect of CTLs. The antitumor activity of CTLs in tumor-bearing nude mouse models prepared with PANC-1 and SW1990 cells was evaluated. Results showed that, compared with K-ras+peptide, low concentrations of K-ras+peptide-CNP were effectively presented by DCs (P<0.05). CTLs induced by DCs pulsed with whole tumor antigen had a significantly greater killing effect (P<0.05) on PANC-1 and SW1990 pancreatic cancer cells compared with K-ras+peptide- and K-ras+peptide-CNP-induced CTLs. CTLs induced by DCs pulsed with K-ras+peptide and K-ras+peptide- CNP had a specific killing effect (P<0.05) on PANC-1 cells and no effect (P>0.05) on SW1990 cells. In conclusion, cationic nanoparticles with the K-ras (12-Val) mutant peptide can be effectively presented by DCs at a low concentration. CTLs induced by K-ras+peptide-CNP had specific killing activity for the pancreatic cancer cell line with the K-ras mutant and significantly inhibited tumor growth and increased the survival time of tumor-bearing nude mice. Although this study confirmed that whole cell antigen induced a good antitumor immune response, the possibility of immune tolerance and autoimmunity which has been previously proven contribute to the difficulty in the application of this DC vaccine.
Association of Chronic Rhinosinusitis With Depression and Anxiety in a Nationwide Insurance Population

Importance Chronic rhinosinusitis (CRS) is associated with a decreased quality of life, affecting physical and emotional aspects of daily function, the latter of which could manifest as depression and anxiety. Objective To evaluate the risk of depression and anxiety in CRS, depending on the CRS phenotype (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]). Design, Setting, and Participants This retrospective nationwide cohort study used population-based insurance data (consisting of data from approximately 1 million patients). The study population included 16 224 patients with CRS and 32 448 individuals without CRS, with propensity score matching between groups according to sociodemographic factors and enrollment year. Data were collected from January 1, 2002, through December 31, 2013, and analyzed from July 1 through November 15, 2018. Main Outcomes and Measures Survival analysis, the log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of depression and anxiety for each group. Results Among the 48 672 individuals included in the study population (58.8% female), the overall incidence of depression during the 11-year follow-up was 1.51-fold higher in the CRS group than in the non-CRS group (24.2 vs 16.0 per 1000 person-years; adjusted HR, 1.54; 95% CI, 1.48-1.61). The incidence of anxiety was also higher in the CRS group than in the comparison group (42.2 vs 27.8 per 1000 person-years; adjusted HR, 1.57; 95% CI, 1.52-1.62). Moreover, the adjusted HRs of developing depression (CRSsNP, 1.61 [95% CI, 1.54-1.69]; CRSwNP, 1.41 [95% CI, 1.32-1.50]) and anxiety (CRSsNP, 1.63 [95% CI, 1.57-1.69]; CRSwNP, 1.45 [95% CI, 1.38-1.52]) were greater in patients with CRSsNP than in those with CRSwNP. Conclusions and Relevance This observational study suggests that CRS is associated with an increased incidence of depression and anxiety. Specifically, findings from this study found that patients without nasal polyps showed a higher risk of developing depression and anxiety than those with nasal polyps.
The validity of the EMG and MMG techniques to examine muscle hypertrophy

Objective: The purpose of this investigation was to examine the ability of the electromyographic (EMG) and mechanomyographic (MMG) amplitude versus torque relationships to track group and individual changes in muscle hypertrophy as a result of resistance training. Approach: Twelve women performed four weeks of forearm flexion blood flow restriction (BFR) resistance training at a frequency of three times per week. The training was performed at an isokinetic velocity of 120° · s−1 with a training load that corresponded to 30% of concentric peak torque. Muscle hypertrophy was determined using ultrasound-based assessments of muscle cross-sectional area from the biceps brachii. Training-induced changes in the slope coefficients of the EMG amplitude and MMG amplitude versus torque relationships were determined from the biceps brachii during incremental (10%–100% of maximum) isometric muscle actions. Main results: There was a significant (p < 0.001; d = 2.15) mean training-induced increase in muscle cross-sectional area from 0 week (mean ± SD = 5.86 ± 0.65 cm2) to 4 weeks (7.42 ± 0.80 cm2), a significant (p = 0.023; d = 0.36) decrease in the EMG amplitude versus torque relationship (50.70 ± 20.41 to 43.82 ± 17.76 µV · Nm−1), but no significant (p = 0.192; d = 0.17) change in the MMG amplitude versus torque relationship (0.018 ± 0.009 to 0.020 ± 0.009 m · s−2 · Nm−1). There was, however, great variability for the individual responses for the EMG and MMG amplitude versus torque relationships. Significance: The results of the present study indicated that the EMG amplitude, but not the MMG amplitude versus torque relationship was sensitive to mean changes in muscle cross-sectional area during the early-phase of resistance training. There was, however, great variability for the individual EMG amplitude versus torque relationships that limits its application for identifying individual changes in muscle hypertrophy as a result of BFR.
Lithium and the Woozle effect

Lithium is the oldest and most‐studied treatment for bipolar depression. Many treatment guidelines place lithium as a top treatment recommendation for bipolar depression; yet some guidelines do not recommend lithium at all. These discrepancies were explored by examining the following errors: the Woozle effect (evidence by citation), reference inflation (overreporting the findings of cited studies) and belief perseverance (maintaining a belief despite new contradictory evidence) as possible causes for these discrepancies.
Depressive symptoms and impaired physical function after acute lung injury: a 2-year longitudinal study.

RATIONALE Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. OBJECTIVES To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. METHODS This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 ("depressive symptoms") in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living ("impaired physical function") in patients without baseline impairment. MEASUREMENTS AND MAIN RESULTS During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. CONCLUSIONS Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors' long-term outcomes.
The Association of Functional Status with Mortality and Dialysis Modality Change: Results from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS)

Background: Little is known about the prevalence of functional impairment in peritoneal dialysis (PD) patients, its variation by country, and its association with mortality or transfer to hemodialysis. Methods: A prospective cohort study was conducted in PD patients from 7 countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) (2014 – 2017). Functional status (FS) was assessed by combining self-reports of 8 instrumental and 5 basic activities of daily living, using the Lawton-Brody and the Katz questionnaires. Summary FS scores, ranging from 1.25 (most dependent) to 13 (independent), were based on the patient's ability to perform each activity with or without assistance. Logistic regression was used to estimate the odds ratio (OR; 95% confidence interval [CI]) of a FS score < 11 comparing each country with the United States (US). Cox regression was used to estimate the hazard ratio (HR; 95% CI) for the effect of a low FS score on mortality and transfer to hemodialysis, adjusting for case mix. Results: Of 2,593 patients with complete data on FS, 48% were fully independent (FS = 13), 32% had a FS score 11 to < 13, 14% had a FS score 8 to < 11, and 6% had a FS score < 8. Relative to the US, low FS scores (< 11; more dependent) were more frequent in Thailand (OR = 10.48, 5.90 – 18.60) and the United Kingdom (UK) (OR = 3.29, 1.77 – 6.08), but similar in other PDOPPS countries. The FS score was inversely and monotonically associated with mortality but not with transfer to hemodialysis; the HR, comparing a FS score < 8 vs 13, was 4.01 (2.44 – 6.61) for mortality and 0.91 (0.58 – 1.43) for transfer to hemodialysis. Conclusion: Regional differences in FS scores observed across PDOPPS countries may have been partly due to differences in regional patient selection for PD. Functional impairment was associated with mortality but not with permanent transfer to hemodialysis.
Points of Contact: Using First-Person Narratives to Help Foster Empathy in Psychiatric Residents

ObjectivesThe authors aimed to determine if writing narratives in psychiatric training can foster empathy for severely and persistently mentally ill patients.MethodsOne resident wrote first-person narrative pieces about three different patients at a community mental health clinic. She reviewed these pieces with a writing supervisor weekly. The supervisor and resident examined the style of writing, choice of words, and story line to help the resident learn about her feelings about the patient.ResultsIn each narrative, different choices were made that provided clues about that particular resident-patient relationship. These writing exercises helped the resident become more connected to her patients, develop interviewing skills, and engage in more self-reflection.ConclusionNarrative writing effectively fostered empathy in a PGY-1 psychiatric resident working with severely and persistently mentally ill patients. This exercise also fostered understanding of countertransference and improved psychiatric history-taking skills. Psychiatry training programs may want to consider incorporating narrative writing exercises into their curriculum.
The association between the severity of chronic kidney disease and medical costs among patients with type 2 diabetes

Abstract Aims: Examine healthcare costs across chronic kidney disease (CKD) stages for US patients with type 2 diabetes (T2D). Materials and methods: IQVIA Real World Data Adjudicated Claims linked electronic medical records and insurance claims from January 1, 2012 through March 31, 2017 were used for this retrospective study. Adults diagnosed with T2D and comorbid CKD were included. General linear models incorporating splines were constructed, and information from these regressions were used to inform the relationship between medical costs and CKD. Multivariable analyses controlled for patient characteristics, vital signs, general health, prior medication use, prior visit to specialists, index A1c, and year of index date. Results: There were 6,645 individuals who met the study criteria. Results generally indicate sharp increases in annual total medical costs and non-drug medical costs in the 1 year post-period for patients with Stage 4 or 5 CKD (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73 m2) with each 1 point reduction in eGFR from 30 associated with an increase of $1,870 in all-cause total medical costs (p < 0.0001) and $1,805 of all-cause non-drug medical costs (p < 0.0001). Similarly, each point decline below 30 mL/min was associated annual cost increases of $1,701 for CKD-related total medical costs, $1,695 for CKD-related non-drug medical costs, $173 for diabetes-related medical costs, and $187 for diabetes-related non-drug medical costs (all p < 0.0001). Limitations: The investigation included only patients with medical insurance and laboratory test results, and results may not be generalizable to all T2D patients with CKD. The methodology allowed us to determine associations, not causation, and potential confounders, such as duration of diabetes, diet, exercise, or social support, could not be assessed. Conclusions: Results indicate there are sharp and significant increases in medical costs among T2D patients with Stage 4 and 5 CKD compared to those with earlier stages of CKD.
High value-added compounds from fruit and vegetable by-products – Characterization, bioactivities, and application in the development of novel food products

Abstract Fruit and vegetable processing industry is one of the relevant generators of food by-products, which display limited commercial exploitation entailing economic and environmental problems. However, these by-products present a considerable amount of dietary fiber as well as bioactive compounds with important biological activities such as antioxidant and antimicrobial properties. Therefore, the international scientific community has considered the incorporation of their extracts or powders to preserve or fortify food products an area of interest, mainly because nowadays consumers demand the production of safer and health-promoting foods. In the present review, several statistical and other relevant data concerning the increasing generation of fruit and vegetable by-products (FVB) are critically analyzed and presented. Next, a special focus is given to the chemical characterization and bioactivities (namely antioxidant and antimicrobial properties) of several FVB. Lastly, an in-depth review with recent studies (briefly compiled) about the incorporation of fruit and vegetable processing wastes in animal, dairy, beverages, and bakery products, among others is provided.
Role of Type 1 IFNs in Antiglioma Immunosurveillance—Using Mouse Studies to Guide Examination of Novel Prognostic Markers in Humans

Purpose: We hypothesized that the type 1 IFNs would play a pivotal role in antiglioma immunosurveillance through promotion of type 1 adaptive immunity and suppression of immunoregulatory cells. Experimental Design: We induced de novo gliomas in Ifnar1−/− (deficient for type 1 IFN receptors) or wild-type mice by intracerebroventricuar transfection of NRas and a short hairpin RNA against P53 using the Sleeping Beauty transposon system. We analyzed the survival of 587 glioma patients for single nucleotide polymorphisms (SNP) in type 1 IFN–related genes. Results: Ifnar1−/− mice exhibited accelerated tumor growth and death. Analyses of brain tumor–infiltrating lymphocytes in Ifnar1−/− mice revealed an increase of cells positive for CD11b+Ly6G+ and CD4+FoxP3+, which represent myeloid-derived suppressor cells and regulatory T cells, respectively, but a decrease of CD8+ cytotoxic T lymphocytes (CTLs) compared with wild-type mice. Ifnar1−/− mouse–derived glioma tissues exhibited a decrease in mRNA for the CTL-attracting chemokine Cxcl10, but an increase of Ccl2 and Ccl22, both of which are known to attract immunoregulatory cell populations. Dendritic cells generated from the bone marrow of Ifnar1−/− mice failed to function as effective antigen-presenting cells. Moreover, depletion of Ly6G+ cells prolonged the survival of mice with developing gliomas. Human epidemiologic studies revealed that SNPs in IFNAR1 and IFNA8 are associated with significantly altered overall survival of patients with WHO grade 2 to 3 gliomas. Conclusions: The novel Sleeping Beauty–induced murine glioma model led us to discover a pivotal role for the type 1 IFN pathway in antiglioma immunosurveillance and relevant human SNPs that may represent novel prognostic markers. Clin Cancer Res; 16(13); 3409–19. ©2010 AACR.
Vitamin D Supplementation and Physical Activity of Young Soccer Players during High-Intensity Training

The aim of this study was to confirm that vitamin D supplementation of young soccer players during eight-week high-intensity training would have a significant effect on their motion activity. The subjects were divided into two groups: the experimental one, which was supplemented with vitamin D (SG, n = 20), and the placebo group (PG, n = 16), which was not supplemented with vitamin D. All the players were subjected to the same soccer training, described as High-Intensity Interval Training (HIIT). The data of the vitamin D status, time motion parameters and heart rate were collected just before and after the intervention. A significant increase in 25(OH)D concentration (119%) was observed in the supplemented group, while the non-supplemented group showed a decrease of 8.4%. Based on the obtained results, it was found that physical activity indicators in the players were significantly improved during small-sided games at the last stage of the experiment. However, taking into account the effect of supplementation with vitamin D, there were no statistically significant differences between the placebo and the supplemented groups; thus, the effect size of the conducted experiment was trivial.
Astrocytic cystine/glutamate antiporter is a key regulator of erythropoietin expression in the ischemic retina

Ischemic retinopathies and optic neuropathies are important causes of vision loss. The neuroprotective effect of erythropoietin (EPO) in ischemic neuronal injury and the expression of EPO and its receptor in retinal tissue have been well documented. However, the exact regulatory mechanism of EPO expression in retinal ischemia still remains to be elucidated. In this study, we investigated the role of cystine/glutamate antiporter (system xc−) in the regulation of astrocytic EPO expression by using both in vitro and in vivo models. Under hypoxia, the expression of astrocytic system xc− is up‐regulated both in vitro and in vivo. Inhibition of system xc− resulted in depletion of intracellular glutathione (GSH) and decrement of GSH disulfide ratios in human brain astrocytes (HBAs). In HBAs, hypoxia‐induced stabilization of hypoxia‐inducible factor (Hif)‐2α is nearly completely abolished by inhibition of system xc−. Hypoxia‐induced up‐regulation of astrocytic EPO expression is suppressed by both pharmacological inhibition and siRNA‐mediated knockdown of system xc−. In contrast, basal EPO expression under normoxia is not affected by system xc− modulation. In summary, under hypoxia, increased system xc− acts as the major source of intracellular GSH, which helps in stabilizing Hif‐2α and subsequent up‐regulation of EPO in astrocytes. —Lee, B. J., Jun, H. O. , Kim, J. H. , Kim, J. H. Astrocytic cystine/glutamate antiporter is a key regulator of erythropoietin expression in the ischemic retina. FASEB J. 33, 6045–6054 (2019). www.fasebj. org
Poorly Differentiated Carcinoma of the Thyroid Gland: Current Status and Future Prospects.

BACKGROUND Poorly differentiated thyroid cancer (PDTC) is a rare but clinically highly significant entity because it accounts for most fatalities from non-anaplastic follicular cell-derived thyroid cancer. Due to the relative rarity of the disease and heterogeneous diagnostic criteria, studies on PDTC have been limited. In light of the evolution of ultra-deep next-generation sequencing technologies and through correlation of clinicopathologic and genomic characteristics of PDTC, an improved understanding of the biology of PDTC has been facilitated. Here, the diagnostic criteria, clinicopathologic characteristics, management, and outcomes in PDTC, as well as genomic drivers in PDTC reported in recent next-generation sequencing studies, are reviewed. In addition, future prospects in improving the outcomes in PDTC patients are reviewed. SUMMARY PDTC patients tend to present with adverse clinicopathologic characteristics: older age, male predominance, advanced locoregional disease, and distant metastases. Surgery with clearance of all gross disease can achieve satisfactory locoregional control. However, the majority of PDTC patients die of distant disease. Five-year disease-specific survival for PDTC patients has been reported at 66%. On multivariate analysis, reported predictors of poor survival in PDTC patients have been older age (>45 years), T4a pathological stage, extrathyroidal extension, high mitotic rate, tumor necrosis, and distant metastasis at presentation. BRAFV600E or RAS mutations (27% and 24% of cases, respectively) remain mutually exclusive main drivers in PDTC. TERT promoter mutations represent the most common alteration in PDTC (40%). Mutation in translation initiation factor EIF1AX (11%) and tumor suppressor TP53 (16%) have also been reported in PDTC. High rates of novel mutations (MED12 and RBM10) have been reported in fatal PDTC (15% and 12%, respectively). Chromosome 1q gains represent the most common arm-level alterations in PDTC, and those patients show worse survival rates. Chromosome 22q losses are also found in PDTC and show strong association with RAS mutation. CONCLUSIONS These new insights into the clinicopathologic and molecular characteristics of PDTC, together with further advancement in ultra-deep sequencing technologies, will be conducive in narrowing the focus in order to develop novel targeted therapies and improve the outcomes in PDTC patients.