Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Multiple Antigens Recognized by Tumor-Infiltrating Lymphocytes From a Single Patient: Tumor Escape by Antigen Loss and Loss of MHC Expression

Abstract: The authors describe a patient who experienced recurrence of metastatic melanoma after an initial dramatic response to immunotherapy using peptides derived from gp100, MART-1, and tyrosinase emulsified in incomplete Freund’s adjuvant, and present data to support the hypothesis that the progression of disease in this patient was due to in vivo immunoselection for immunoresistant tumor variants. The authors previously demonstrated the existence of T-cell clones in this patient’s peripheral blood and tumor-infiltrating lymphocytes (TILs) reactive against multiple antigens, including gp100, the tyrosinase-related protein (TRP)-2, a novel TRP-2 isoform-TRP-2-6b, SOX10, and the melanoma antigen NY-ESO-1. In addition to the multiple HLA-A2 restricted T-cell clones, the authors have now identified additional HLA-B/C-restricted as well as class II (HLA-DP)-restricted anti-melanoma antigen T-cell clones from this patient’s TIL. One recurrent tumor showed loss of expression of multiple tumor antigens but retention of HLA class I expression. The other recurrent lesion showed total loss of HLA class I expression even though the tumor cells still expressed many melanoma antigens. This paper thus provides evidence for both the effectiveness of the immune destruction of cancer as well as problems associated with antigen-loss tumor escape mechanisms.
Urinary excretion of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide in pregnant women receiving buprenorphine maintenance treatment.

BACKGROUND Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum. METHODS We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum. Specimens were analyzed using a fully validated liquid chromatography-mass spectrometry method with limits of quantification of 5 microg/L for BUP and BUP-Gluc and 25 microg/L for NBUP and its conjugated metabolite. We examined ratios of metabolites across trimesters and postpartum to identify possible changes in metabolism during pregnancy. RESULTS NBUP-Gluc was the primary metabolite identified in urine and exceeded BUP-Gluc concentrations in 99% of specimens. Whereas BUP-Gluc was identified in more specimens than NBUP, NBUP exceeded BUP-Gluc concentrations in 77.9% of specimens that contained both analytes. Among all participants, the mean BUP-Gluc:NBUP-Gluc ratio was significantly higher in the second trimester compared to the third trimester, and there were significant intrasubject differences between trimesters in 71% of participants. In 3 women, the percent daily dose excreted was higher during pregnancy than postpregnancy, consistent with other data indicating increased renal elimination of drugs during pregnancy. CONCLUSIONS These data are the first to evaluate urinary disposition of BUP and metabolites in a cohort of pregnant women. Variable BUP excretion during pregnancy may indicate metabolic changes requiring dose adjustment during later stages of gestation.
Lessons in cross-cultural measurement of depressive symptoms: findings from a mixed-methods study in Ghana

ABSTRACT As the public health importance of depression grows in low-income countries, development of culturally relevant and valid measurement tools is increasingly necessary to inform effective interventions. This research was embedded within the Family Health and Wealth Study, an ongoing multi-country cohort study. We use mixed methods to assess the reliability and various aspects of validity, including cultural relevance, of a 10-item version of the Center for Epidemiologic Studies Depression (CES-D 10) Scale among men and women of reproductive age in Kumasi, Ghana. The scale demonstrated adequate internal consistency reliability, and factor analysis supported a one-factor model for both men and women in the study setting. However, qualitative findings highlighted several additional relevant symptom groups in the study population that were not included in the scale: loss of concentration, loss of appetite, suicidal ideation and becoming quiet or withdrawn. Although quantitative analyses indicated that the CES-D 10 scale demonstrated adequate reliability and validity as a measure of depressive symptoms, qualitative analyses revealed that this scale failed to fully capture depression as it is conceptualized in the study community. Our results underline the importance of integrating culturally-specific information on mental health when developing and adapting measurement tools in new settings.
An exploration of the prevalence and predictors of work-related well-being among psychosocial oncology professionals: An application of the job demands–resources model

ABSTRACT Objective: Burnout is reportedly high among oncology healthcare workers. Psychosocial oncologists may be particularly vulnerable to burnout. However, their work engagement may also be high, counteracting stress in the workplace. This study aimed to document the prevalence of both burnout and work engagement, and the predictors of both, utilizing the job demands–resources (JD–R) model, within a sample of psychosocial oncologists. Method: Psychosocial-oncologist (N = 417) clinicians, recruited through 10 international and national psychosocial-oncology societies, completed an online questionnaire. Measures included demographic and work characteristics, burnout (the MBI–HSS Emotional Exhaustion (EE) and Depersonalization (DP) subscales), the Utrecht Work Engagement Scale, and measures of job demands and resources. Results: High EE and DP was reported by 20.2 and 6.6% of participants, respectively, while 95.3% reported average to high work engagement. Lower levels of job resources and higher levels of job demands predicted greater burnout, as predicted by the JD–R model, but the predicted interaction between these characteristics and burnout was not significant. Higher levels of job resources predicted higher levels of work engagement. Significance of results: Burnout was surprisingly low and work engagement high in this sample. Nonetheless, one in five psychosocial oncologists have high EE. Our results suggest that both the positive (resources) and negative (demands) aspects of this work environment have an on impact burnout and engagement, offering opportunities for intervention. Theories such as the JD–R model can be useful in guiding research in this area.
Insulin-Like Growth Factor (IGF) System in Liver Diseases

Hepatocyte differentiation, proliferation, and apoptosis are affected by growth factors produced in liver. Insulin-like growth factor 1 and 2 (IGF1 and IGF2) act in response to growth hormone (GH). Other IGF family components include at least six binding proteins (IGFBP1 to 6), manifested by both IGFs develop due to interaction through the type 1 receptor (IGF1R). The data based on animal models and/or in vitro studies suggest the role of IGF system components in cellular aspects of hepatocarcinogenesis (cell cycle progression, uncontrolled proliferation, cell survival, migration, inhibition of apoptosis, protein synthesis and cell growth), and show that systemic IGF1 administration can reduce fibrosis and ameliorate general liver function. In epidemiologic and clinicopathological studies on chronic liver disease (CLD), lowered serum levels, decreased tissue expression of IGF1, elevated production of IGF1R and variable IGF2 expression has been noted, from the start of preneoplastic alterations up to the developed hepatocellular carcinoma (HCC) stage. These changes result in well-known clinical symptoms of IGF1 deficiency. This review summarized the current data of the complex role of IGF system components in the most common CLD (nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma). Better recognition and understanding of this system can contribute to discovery of new and improved versions of current preventive and therapeutic actions in CLD.
Proton pump inhibitor-responsive esophageal eosinophilia: still a valid diagnosis?

Purpose of review To update rapidly evolving concepts regarding the controversial entity of ‘proton pump inhibitor (PPI)-responsive esophageal eosinophilia,’ referring to patients with clinical, endoscopic and histologic features of eosinophilic esophagitis (EoE) who achieve remission on PPI therapy. Recent findings Up to half of pediatric and adult patients with typical EoE symptoms and histology achieve clinico-pathologic remission on PPI therapy, irrespective of whether esophageal pH monitoring demonstrates abnormal acid reflux. In patients with clinical and histologic features of EoE, genotypic and phenotypic features of PPI responders and nonresponders are virtually indistinguishable, and different from those of patients with gastroesophageal reflux disease. In PPI responders, PPIs effects on esophageal Th2 inflammation and gene expression are similar to those of topical steroids in PPI nonresponders. These therapies, along with diets, recently have been shown to be potentially interchangeable in two small series. Summary Proton pump inhibitor-responsive esophageal eosinophilia is an inappropriate disease descriptor, arbitrarily based on a response to a single drug, and should be abandoned. Patients who have esophageal eosinophilia and esophageal symptoms that resolve with PPI therapy have phenotypic, molecular, mechanistic, and therapeutic features indistinguishable from similar patients who do not respond to PPIs. These patients with PPI responsiveness should be considered within the spectrum of EoE.
Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004.

BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver disease in children and adolescents. The majority of studies of NAFLD in children have been in select populations of the clinically obese. Study aims were to estimate the prevalence of elevated alanine aminotransferase (ALT, as a marker of NAFLD) in a general contemporary adolescent population and to identify leading risk factors for ALT elevation (>30 U/L). METHODS We analyzed data of adolescent participants (aged 12-19 years; N = 5586) in the National Health and Nutrition Examination Survey 1999-2004, a representative sample of the civilian noninstitutionalized US population. RESULTS The prevalence of elevated ALT levels (>30 U/L) was 7.4% among white adolescents, 11.5% among Mexican American adolescents, and 6.0% among black adolescents. Elevated ALT levels were prevalent in 12.4% of male subjects compared with 3.5% of female subjects. Multivariable associations with elevated ALT levels were found for sex (odds ratio [OR] male vs female, 7.7; 95% confidence interval [CI], 3.9-15.1), ethnicity (OR black vs white, 0.6; 95% CI, 0.3-1.3; OR Mexican American vs white, 1.6; 95% CI, 1.0-2.6), waist circumference (OR per 1 SD, 1.4; 95% CI, 1.0-2.0), and fasting insulin level (OR per 1 SD, 1.6; 95% CI, 1.2-2.1). Age, C-reactive protein levels, and triglyceride levels were also positively and socioeconomic position inversely associated with elevated ALT levels. The magnitude of associations were similar across ethnic groups. CONCLUSIONS ALT level is associated with waist circumference and insulin resistance even in a young population. These characteristics could be utilized to identify adolescents who may benefit from screening for NAFLD, offering an opportunity to prevent disease progression at an early age.
A hermeneutic phenomenological study on the perception of second language acquisition and personality type by adult second language learners in a formal learning environment

The purpose of this hermeneutic phenomenological study was to describe the perceived experience of second language acquisition for adult second language learners in a formal learning environment at the Community College of Virginia (a pseudonym) and to describe how these learners perceived that their personality type either enhanced or inhibited their experience of second language acquisition. All students who were enrolled in an introductory-level Spanish course at the Community College of Virginia were invited to complete a preliminary questionnaire to determine their initial eligibility for the study. Prospective participants who met the initial eligibility requirements of the study took the Myers-Briggs Type Indicator Complete questionnaire to determine their personality type. A purposeful sampling procedure was used to secure six participants, each with different personality types, for an in-depth study of their perceived experience of second language acquisition. The data were collected through semistructured interviews, open-ended journal entries, and semi-structured focus groups, and were analyzed using phenomenological reflection. The adult second language learners at the Community College of Virginia defined second language acquisition as the ability to comprehend and to produce comprehensibly in a variety of formats. These learners were apprehensive about their experience acquiring a second language, but they perceived that using their second language outside of the classroom had enhanced their experience. They also perceived that being outgoing, sociable, adaptable, and open had enhanced their experience.
Attitudes Toward Medical Cannabis Legalization Among Serbian Medical Students

ABSTRACT Background: Currently, medical cannabis polices are experiencing rapid changes, and an increasing number of nations around the world legalize medical cannabis for certain groups of patients, including those in Serbia. Objectives: To determine medical students' attitudes toward medical cannabis legalization and to examine the factors influencing their attitudes. Methods: Fourth-year medical students at the Faculty of Medicine, University of Belgrade, had participated in a cross-sectional study. Data were collected by an anonymous questionnaire. Results: Overall, 63.4% students supported medical cannabis legalization, and only 20.8% supported its legalization for recreational use. Students who previously used marijuana (p <.001) and alcohol (p =.004) were significantly more in favor of medical cannabis legalization compared with students who never used them. Support for marijuana recreational use was also related to prior marijuana (p <.001) and alcohol consumption (p =.006). Only cancer (90.4%) and chronic pain (74.2%) were correctly reported approved medical indications by more than half the students. Students who supported medical cannabis legalization showed better knowledge about indications, in contrast to opponents for legalization who showed better knowledge about side effects. Beliefs that using medical cannabis is safe and has health benefits were correlated with support for legalization, and previous marijuana and alcohol use, while beliefs that medical cannabis poses health risks correlated most strongly with previous marijuana use. Conclusions/Importance: The medical students' attitudes toward medical cannabis legalization were significantly correlated with previous use of marijuana and alcohol, knowledge about medical indications and side effects, and their beliefs regarding medical cannabis health benefits and risks.
Features versus Feelings: Dissociable Representations of the Acoustic Features and Valence of Aversive Sounds

This study addresses the neuronal representation of aversive sounds that are perceived as unpleasant. Functional magnetic resonance imaging in humans demonstrated responses in the amygdala and auditory cortex to aversive sounds. We show that the amygdala encodes both the acoustic features of a stimulus and its valence (perceived unpleasantness). Dynamic causal modeling of this system revealed that evoked responses to sounds are relayed to the amygdala via auditory cortex. While acoustic features modulate effective connectivity from auditory cortex to the amygdala, the valence modulates the effective connectivity from amygdala to the auditory cortex. These results support a complex (recurrent) interaction between the auditory cortex and amygdala based on object-level analysis in the auditory cortex that portends the assignment of emotional valence in amygdala that in turn influences the representation of salient information in auditory cortex.
Histomorphological characteristics of colorectal carcinoma in the young and elderly: Is there a difference?

Introduction: Colorectal carcinoma is among the leading causes of cancer related mortality. There has been an increase in incidence of CRC in the younger age group. Also young patients with CRC reveal different tumor characteristics than average age or older age groups. Aims: This study was undertaken to analyze the differences in Histomorphological characteristics, based on gender, subsite of the tumor, tumor differentiation and disease stage of CRC in young and elderly age group. Materials and Methods: Histopathologically confirmed cases of colorectal cancer from the year 2007-2013 were taken from the Department of Pathology. Sub group analyses of histomorphological features of CRC in patients <40 yrs were compared with > 40 yrs using chi square or Fischer’s exact test. P value of < 0.05 was considered significant. Results: Hundred and three cases of colorectal cancer were included in the study. 20.3% of cases were below the age of 40yrs. In patients less than 40 years, most common site of lesion was the rectum, followed by sigmoid colon and caecum. Mucin secreting/signet ring carcinoma (38.09%) and moderately differentiated carcinoma (28.5%) was more common in young patients, than elderly patients. 16.6% of young patients had Dukes stage A, 66.6% had stage B and 16.6% stage C disease. Conclusion: Colorectal cancer in young patients are associated with aggressive histopathological characteristics and advanced stage at diagnosis. Most of the lesions were seen in rectum followed by sigmoid colon. This emphasizes the development and implementation of effective screening program in young patients. Access this article online Quick Response Code: Website: www.innovativepublication. com
High-Levels of Acquired Drug Resistance in Adult Patients Failing First-Line Antiretroviral Therapy in a Rural HIV Treatment Programme in KwaZulu-Natal, South Africa

Objective To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa. Design Cross-sectional study nested within HIV treatment programme. Methods Adult (≥18 years) HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART) regimen and with evidence of virological failure (one viral load >1000 copies/ml) were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS) for standard second-line regimens were calculated using the Stanford HIVDB 6.0. 5 algorithms. Results A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%); and stavudine, lamivudine and nevirapine (24%). Median duration of ART was 42 months (interquartile range (IQR) 32–53) and median duration of antiretroviral failure was 27 months (IQR 17–40). One hundred and ninety one (86%) had at least one drug resistance mutation. For 34 individuals (15%), the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI) substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR) 5.70, 95% confidence interval (CI) 2.60–12.49). Conclusions There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.
Predictors of early death and survival among children, adolescents and young adults with acute myeloid leukaemia in California, 1988–2011: a population‐based study

A better understanding of factors associated with early death and survival among children, adolescents and young adults with acute myeloid leukaemia (AML) may guide health policy aimed at improving outcomes in these patients. We examined trends in early death and survival among 3935 patients aged 0–39 years with de novo AML in California during 1988–2011 and investigated the associations between sociodemographic and selected clinical factors and outcomes. Early death declined from 9·7% in 1988–1995 to 7·1% in 2004–2011 (P = 0·062), and survival improved substantially over time. However, 5‐year survival was still only 50% (95% confidence interval 47–53%) even in the most recent treatment period (2004–2011). Overall, the main factors associated with poor outcomes were older age at diagnosis, treatment at hospitals not affiliated with National Cancer Institute‐designated cancer centres, and black race/ethnicity. For patients diagnosed during 1996–2011, survival was lower among those who lacked health insurance compared to those with public or private insurance. We conclude that mortality after AML remained strikingly high in California and increased with age. Possible strategies to improve outcomes include wider insurance coverage and treatment at specialized cancer centres.