Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1.

IMPORTANCE Immune checkpoint inhibitor therapy has shown benefit in various cancers, but their potential in endometrial cancer (EC) is unknown. OBSERVATIONS Prediction of neoantigen load was performed using sequencing data from the Cancer Genome Atlas data set. Evaluation of tumor-infiltrating lymphocytes (TILs) and PD-1 and PD-L1 expression was performed in 63 patients with EC referred to our institution. The predicted median (range) neoantigen load (predicted neoepitopes per sample) was proportional to the mutational load: highest in ultramutated polymerase e (POLE) tumors (8342 [628-20 440]), less in hypermutated MSI (541 [146-8063]; P < .001), and lowest in microsatellite-stable tumors (70.5 [7-1877]; P < .001). The POLE and MSI ECs exhibited higher numbers of CD3+ (44.5 vs 21.8; P = .001) and CD8+ (32.8 vs 13.5; P < .001) TILs compared with microsatellite-stable tumors. PD-1 was overexpressed in TILs (81% vs 28%; P < .001) and peritumoral lymphocytes (90% vs 28%; P < .001) of POLE and MSI tumors. PD-L1 expression was infrequently noted in tumor cells but was common in intraepithelial immune cells and more frequent in POLE and MSI tumors (39% vs 13%; P = .02). CONCLUSIONS AND RELEVANCE Polymerase e-mutated and MSI ECs are associated with high neoantigen loads and number of TILs, which is counterbalanced by overexpression of PD-1 and PD-L1. Polymerase e-mutated and MSI EC tumors may be excellent candidates for PD-1-targeted immunotherapies.
The Effect of Testosterone Propionate on Mammary Tumors in Mice of the C3H Strain

A rela t ionship be tween estrogenic activity and the product ion of tumors of the m a m m a r y g land has been clearly demons t r a t ed in various strains of mice. In v iew of the inh ib i tory action of testosterone on estrus, lactation, and the vaginal response to estrone in mice (4, 5), t he possibility of affecting spontaneous t u m o r format ion by inhib i t ion of estrogenic activity seemed wor thy of fu r the r invest igat ion. In 1936 , Lacassagne (2) reported that injections of testosterone had not al tered the inc idence of spontaneous m a m m a r y cancer in females of a h igh cancer strain, but the a m o u n t of h o r m o n e used was small. This report presents the end results of long-cont inued adminis t ra t ion of testosterone propionate on the developmen t of spontaneous m a m m a r y carc inoma in female mice of a h igh cancer strain (a ) w h e n injections were begun by the 5th week of life, and (b ) w h e n injections were given to older females wi th a history of n o r m a l breeding. It also includes observations on the fai lure of testosterone to affect the g r o w t h rate of m a m m a r y carc inoma in mice w h e n admin i s te red after the t u m o r is of palpable size. T h e exper iments were started in the spring of 1938 and extended over 2 years. T h e y were well unde r way w h e n the repor t of N a t h a n s o n and A n d e r v o n t (3) was published, bu t since our exper iments differed in some respects f rom theirs, it was decided to con t inue them.
Estimating mean change in population salt intake using spot urine samples.

Background Spot urine samples are easier to collect than 24-h urine samples and have been used with estimating equations to derive the mean daily salt intake of a population. Whether equations using data from spot urine samples can also be used to estimate change in mean daily population salt intake over time is unknown. We compared estimates of change in mean daily population salt intake based upon 24-h urine collections with estimates derived using equations based on spot urine samples. Methods Paired and unpaired 24-h urine samples and spot urine samples were collected from individuals in two Australian populations, in 2011 and 2014. Estimates of change in daily mean population salt intake between 2011 and 2014 were obtained directly from the 24-h urine samples and by applying established estimating equations (Kawasaki, Tanaka, Mage, Toft, INTERSALT) to the data from spot urine samples. Differences between 2011 and 2014 were calculated using mixed models. Results A total of 1000 participants provided a 24-h urine sample and a spot urine sample in 2011, and 1012 did so in 2014 (paired samples n = 870; unpaired samples n = 1142). The participants were community-dwelling individuals living in the State of Victoria or the town of Lithgow in the State of New South Wales, Australia, with a mean age of 55 years in 2011. The mean (95% confidence interval) difference in population salt intake between 2011 and 2014 determined from the 24-h urine samples was -0.48g/day (-0.74 to -0.21; P < 0.001). The corresponding result estimated from the spot urine samples was -0.24 g/day (-0.42 to -0.06; P = 0.01) using the Tanaka equation, -0.42 g/day (-0.70 to -0.13; p = 0.004) using the Kawasaki equation, -0.51 g/day (-1.00 to -0.01; P = 0.046) using the Mage equation, -0.26 g/day (-0.42 to -0.10; P = 0.001) using the Toft equation, -0.20 g/day (-0.32 to -0.09; P = 0.001) using the INTERSALT equation and -0.27 g/day (-0.39 to -0.15; P < 0.001) using the INTERSALT equation with potassium. There was no evidence that the changes detected by the 24-h collections and estimating equations were different (all P > 0.058). Separate analysis of the unpaired and paired data showed that detection of change by the estimating equations was observed only in the paired data. Conclusions All the estimating equations based upon spot urine samples identified a similar change in daily salt intake to that detected by the 24-h urine samples. Methods based upon spot urine samples may provide an approach to measuring change in mean population salt intake, although further investigation in larger and more diverse population groups is required.
The Japanese Housewife Overseas

[Based on research over a six-year period into three age groups of women, this important new study offers in depth analysis for the first time of the experience of expatriate Japanese wives living temporarily in the United Kingdom. It focuses on the roles of the ‘housewife’ in the context of the changing status of women in contemporary Japan. , Based on research over a six-year period into three age groups of women, this important new study offers in depth analysis for the first time of the experience of expatriate Japanese wives living temporarily in the United Kingdom. It focuses on the roles of the ‘housewife’ in the context of the changing status of women in contemporary Japan. ]
From the hospital organisation to the childbirth practice: Italian women’s experiences

Objective: To compare the hospital management of childbirth with respect to women’s perception and satisfaction. Method: Semi-structured interviews were conducted with 20 first-time Italian mothers, who were recruited in the obstetrics and gynaecology operative unit of a large public hospital in Northern Italy during the 3 days following the births of their children. Data were electronically coded with ATLAS.ti software and a qualitative analysis was conducted. Women’s childbirth narrations were compared with the formal procedures stated in the corporate documents of the hospital. Results: Expectations, control-medicalisation, and the relationship with the caregivers were the main themes that emerged from the interviews. The women’s expectations were related to the hospital’s reputation, which centred on medical specialisation and humanisation. Their actual experiences were characterised by their trust for hospital staff and willingness to give up internal control in order to accept medical interventions. These factors were related to the external control that the women accepted in order to preserve their child’s and their own safety. Although the hospital organisational model was centred on the humanisation of care and patient-centred service, these directives did not correspond to the women’s actual experiences. Conclusions: Health services should take into account the consumers’ perspective and address personal agency in order to increase satisfaction and guarantee a more respectful childbirth care.
Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small-Cell Lung Cancer.

IMPORTANCE Early-phase trials with monoclonal antibodies targeting PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death 1 ligand 1) have demonstrated durable clinical responses in patients with non-small-cell lung cancer (NSCLC). However, current assays for the prognostic and/or predictive role of tumor PD-L1 expression are not standardized with respect to either quantity or distribution of expression. OBJECTIVE To demonstrate PD-L1 protein distribution in NSCLC tumors using both conventional immunohistochemistry (IHC) and quantitative immunofluorescence (QIF) and compare results obtained using 2 different PD-L1 antibodies. DESIGN, SETTING, AND PARTICIPANTS PD-L1 was measured using E1L3N and SP142, 2 rabbit monoclonal antibodies, in 49 NSCLC whole-tissue sections and a corresponding tissue microarray with the same 49 cases. Non-small-cell lung cancer biopsy specimens from 2011 to 2012 were collected retrospectively from the Yale Thoracic Oncology Program Tissue Bank. Human melanoma Mel 624 cells stably transfected with PD-L1 as well as Mel 624 parental cells, and human term placenta whole tissue sections were used as controls and for antibody validation. PD-L1 protein expression in tumor and stroma was assessed using chromogenic IHC and the AQUA (Automated Quantitative Analysis) method of QIF. Tumor-infiltrating lymphocytes (TILs) were scored in hematoxylin-eosin slides using current consensus guidelines. The association between PD-L1 protein expression, TILs, and clinicopathological features were determined. MAIN OUTCOMES AND MEASURES PD-L1 expression discordance or heterogeneity using the diaminobenzidine chromogen and QIF was the main outcome measure selected prior to performing the study. RESULTS Using chromogenic IHC, both antibodies showed fair to poor concordance. The PD-L1 antibodies showed poor concordance (Cohen κ range, 0.124-0.340) using conventional chromogenic IHC and showed intra-assay heterogeneity (E1L3N coefficient of variation [CV], 6.75%-75.24%; SP142 CV, 12.17%-109.61%) and significant interassay discordance using QIF (26.6%). Quantitative immunofluorescence showed that PD-L1 expression using both PD-L1 antibodies was heterogeneous. Using QIF, the scores obtained with E1L3N and SP142 for each tumor were significantly different according to nonparametric paired test (P < .001). Assessment of 588 serial section fields of view from whole tissue showed discordant expression at a frequency of 25%. Expression of PD-L1 was correlated with high TILs using both E1L3N (P = .007) and SP142 (P = .02). CONCLUSIONS AND RELEVANCE Objective determination of PD-L1 protein levels in NSCLC reveals heterogeneity within tumors and prominent interassay variability or discordance. This could be due to different antibody affinities, limited specificity, or distinct target epitopes. Efforts to determine the clinical value of these observations are under way.
Cardiovascular biomarkers in patients with psoriasis

Psoriasis is a systemic inflammatory disease of the skin with associated comorbidity. Severe forms of psoriasis are associated with increased mortality, which might be due to cardiovascular (CV) comorbidity. In this study, we investigated in 79 patients with psoriasis compared to 80 healthy volunteers different biomarkers that play a role in vascular disease and inflammation, such as C‐reactive protein (CRP), human soluble CD40 ligand (sCD40L), oxidized low‐density lipoprotein (ox‐LDL), human matrix Gla protein (MGP) and fetuin‐A. Our results showed that CRP (P < 0.0001), sCD40L (P < 0.0001) and MGP (P < 0.0001) were increased in the patient cohort. Fetuin‐A showed decreased serum levels in patients with psoriasis (P < 0.0001), whereas ox‐LDL did not show any significant difference. In multivariate analyses controlling for sex, age and BMI, these findings were confirmed. Thus, CV biomarkers are altered in patients with psoriasis. If the decrease in fetuin‐A as well as the increase in sCD40L can be proven in further studies, these biomarkers may help to characterize a subgroup of patients who are at risk to develop CVD and/or monitor the effect of therapeutic antipsoriatic strategies on concomitant diseases. This knowledge may be useful in the management of high‐need patients with psoriasis.
Management of tracheobronchial foreign body aspirations in paediatric age group - A 10 year retrospective analysis

A retrospective analysis of management of tracheobronchial tree in paediatric age group was done over a period of 10 years. These children were aged 0 month to 12 years and male children were predominant. Bronchoscopy performed under general anaesthesia in 316 cases of suspected foreign body inhalation, out of which 206 were positive for the same. There were no post operative complications in any case.
Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders.

IMPORTANCE Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known. OBJECTIVE To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from January 1, 2012, through August 1, 2015. The data analysis was performed on August 24, 2015. EXPOSURE Ipilimumab therapy. MAIN OUTCOMES AND MEASURES Safety, in terms of frequency of autoimmune flares and conventional immune-related adverse events (irAEs), and efficacy, in terms of response rates and overall survival, were evaluated descriptively. RESULTS Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-80] y), 6 had rheumatoid arthritis, 5 had psoriasis, 6 had inflammatory bowel disease, 2 had systemic lupus erythematosus, 2 had multiple sclerosis, 2 had autoimmune thyroiditis, and 7 had other conditions. Thirteen patients (43%) were receiving immunosuppressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or hydroxychloroquine. With ipilimumab treatment, 8 patients (27%) experienced exacerbations of their autoimmune condition necessitating systemic treatment; all were managed with corticosteroids. Conventional grade 3 to 5 irAEs occurred in 10 patients (33%) and were reversible with corticosteroids or with infliximab therapy in 2 cases. One patient with baseline psoriasis died of presumed immune-related colitis after a 1-week delay prior to reporting symptoms. Fifteen patients (50%) had neither autoimmune disease flares nor irAEs. Six patients experienced an objective response (20%), including 1 with a durable complete response. CONCLUSIONS AND RELEVANCE To our knowledge, this is the largest series of patients with preexisting autoimmune disease treated with immune checkpoint inhibitors. Ipilimumab was clinically active and was associated with exacerbations of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable with standard therapies when started in a timely fashion. Ipilimumab therapy may be considered in this setting with vigilant clinical monitoring.
T‐cell receptor gene rearrangement analysis of sequential biopsies in cutaneous T‐cell lymphomas with the Biomed‐2 PCR reveals transient T‐cell clones in addition to the tumor clone

Detection of a dominant T‐cell clone by T‐cell receptor (TCR) gene rearrangement analysis is often essential for the diagnosis of cutaneous T‐cell lymphomas (CTCL). The occurrence of T‐cell clones in addition to the diagnostic T‐cell clone during the course of CTCL has been reported, but the data of these studies have been contradictory. We retrospectively evaluated the data of 114 lesional skin biopsies from 26 patients with Mycosis fungoides and two patients with primary cutaneous anaplastic large cell lymphoma, which were analysed with the standardized Biomed‐2 PCR for the TCRγ and TCRβ locus. A dominant T‐cell clone was repetitively detected in 93% (26/28) of patients. Additional T‐cell clones appeared temporarily in 39% (11/28) of patients. Correlation with the clinical data did not show an association of the presence of additional T‐cell clones with age, number of treatments, progression of disease or survival. Our findings demonstrate that a persistent T‐cell clone, most likely the disease causing tumor clone, is detectable in almost all CTCL patients. In addition, transiently appearing T‐cell clones frequently occur during the course of disease. The biological relevance of these additional clones has still to be determined. However, it is important to take the possibility of additional T‐cell clones into account for diagnostic analyses.
Investigation of the potential of fortified instant matooke flour (ITF) in rehabilitation of malnourished children. Part II: Testing potential of ITF as a vehicle food for malnutrition intervention.

This study was done to establish potential of instant Tooke (cooking banana) flour (ITF) as a vehicle food for malnutrition intervention. Hypotheses generated were: (1) There is a significant difference in response with respect to weight gain between malnourished subjects rehabilitated using fortified IFT and Mwanamugimu Diatery Regime (MDR); (2) There is a significant difference in response with respect to serum albumin, ferritin and retinol levels between fortified ITF and MDR. To test the hypotheses, 100 malnourished children admitted at Mwanamugimu Nutrition Unit in Uganda, were randomly allocated to a test (IFT diet from part I of study) or control (MDR diet) group. Growth rates and food intake were measured daily, while blood samples were withdrawn during recruitment and before discharge for testing serum albumin, ferritin and retinol levels. Means were compared using SPSS version 11. The test and control diets were adequate in protein but relatively lower for energy against RDA. Protein and energy intake in the test group was significantly (P < 0.05) higher for porridge, while protein intake in the control group was significantly (P < 0.05) higher for kitoobero. Weight gain in the test was significantly (P < 0.05) higher than the control group. However, both groups showed no significant difference in the bio-chemical indicators. The superiority of fortified ITF formulation over the MDR was proved with respect to weight gain but not for the biochemical indicators. Hypothesis one was accepted but two was rejected. Key words: Instant tooke flour (ITF), matooke, malnourished, rehabilitation.
Chronic morbidity and health care seeking behaviour amongst elderly population in rural areas of Uttarakhand.

Background : Ageing is a natural process, always associated with physiological and biological decline. Global population is ageing; the proportion of older persons has been rising steadily, from 7% in 1950 to 11% in 2007, with an expected rise to reach 22 % in 2050. With improving knowledge and awareness the health care seeking behavior has shown an increasingly positive trend. With increasing age, morbidity, especially those arising from chronic diseases also increases. On the contrary, health care delivered at household level has definitely gone down due to financial constraints and increasing cost of living, thus posing a problem for the elderly. Aims & Objective : To find out the prevalence of chronic morbidity and health care seeking behaviour amongst the elderly in rural areas of Uttarakhand. Material and Methods: A cross-sectional study was carried out in rural areas of Uttarakhand to assess the chronic morbidity amongst elderly population. All the persons above the age group of 60 years of the eight villages were interviewed using a pre-defined, pre-tested, semi-structured and indigenously developed questionnaire. Results : The study group suffered from various chronic morbidities like hypertension, diabetes, cardiovascular diseases. Men were greater in number (158, 62.2%). Participants belonging mostly to nuclear families (156, 61.9%). Below the poverty line were (98, 38.9%). Half of the study population had one or the other chronic morbid condition. Majority of the elderly men contacted the health care facility whereas majority of the elderly women chose to use remedies. Conclusion: There is definitely a need of provision of health care services for poor geriatric population. In addition to this government should take up some program for social security of this population along with creating an awareness about the same.
Laser capture microdissection followed by next‐generation sequencing identifies disease‐related microRNAs in psoriatic skin that reflect systemic microRNA changes in psoriasis

Psoriasis is a systemic disease with cutaneous manifestations. MicroRNAs (miRNAs) are small non‐coding RNA molecules that are differentially expressed in psoriatic skin; however, only few cell‐ and region‐specific miRNAs have been identified in psoriatic lesions. We used laser capture microdissection (LCM) and next‐generation sequencing (NGS) to study the specific miRNA expression profiles in the epidermis (Epi) and dermal inflammatory infiltrates (RD) of psoriatic skin (N = 6). We identified 24 deregulated miRNAs in the Epi and 37 deregulated miRNAs in the RD of psoriatic plaque compared with normal psoriatic skin (FCH > 2, FDR < 0.05). Interestingly, 9 of the 37 miRNAs in RD, including miR‐193b and miR‐223, were recently described as deregulated in circulating peripheral blood mononuclear cells (PBMCs) from patients with psoriasis. Using flow cytometry and qRT‐PCR, we found that miR‐193b and miR‐223 were expressed in Th17 cells. In conclusion, we demonstrate that LCM combined with NGS provides a robust approach to explore the global miRNA expression in the epidermal and dermal compartments of psoriatic skin. Furthermore, our results indicate that the altered local miRNA changes seen in the RD are reflected in the circulating immune cells, suggesting that miRNAs may contribute to the pathogenesis of psoriasis.