Takshan/R1 huggingface dataset:
Multiple mini-interview as a predictor of performance in the objective structured clinical examination among Physician Associates in the United Kingdom: a cohort study.

Introduction: Patient satisfaction and health care outcomes are directly linked to useful communication skills. Therefore, excellent interpersonal skills are imperative for health care professionals. Multiple mini-interview (MMI) is designed as a selection tool to assess the communication skills of applicants in medical schools during the admission process. However, objective structured clinical examination (OSCE) assesses students' communication and clinical skills at the end of their academic terms. Recently, Anglia Ruskin University, Chelmsford, UK, adopted MMI in the selection process for the first cohort of MSc Physician Associate trainees for the academic year 2015-2016. This study aimed to determine the likelihood of MMI as a predictor of future performance of communication skills in the OSCE. Materials and methods: The anonymous data of the average scores of communication skills attained in MMI and OSCE at the end of year 1 were collected for 30 students from the Physician Associate program team. Subsequently, Pearson's correlation was computed to determine the relationship between the average scores of communication skills attained in MMI, and OSCE during trimester 2 and trimester 3 by the Physician Associate trainees. Results: The study showed positive correlation between the scores of communication skills attained in MMI and OSCE during trimester 2 (r=0.956, n=30, p<0.001) and trimester 3 (r=0.966, n=30, p<0.001). Conclusion: The study provides empirical evidence for the validity of MMI as a predictor of future performance of Physician Associate trainees' communication skills during subsequent OSCEs.
Glutathione-S-transferases and Chemotherapy Resistance of Hodgkin's Lymphoma Cell Lines.

BACKGROUND: Glutathione-S-transferases (GSTs) are associated with multidrug resistance of tumor cells and are involved in drug detoxification and control of apoptosis. We analyzed the impact of GSTs on apoptosis of Hodgkin's lymphoma (HL) cells. MATERIALS AND METHODS: Expression of GST isoforms in HL cell lines was assessed by analysis of DNA microarray data and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The impact of the GST inhibitor ethacrynic acid (EA) on HL cell survival was analyzed in vitro. RESULTS: DNA microarray analysis and qRT-PCR analysis demonstrated higher expression of GST isoforms in chemoresistant HL cells. Therefore, GSTs may contribute to chemoresistance of HL cells. Incubation of GST-expressing chemoresistant L-1236 HL cells with EA significantly enhanced the activity of cisplatin against these cells. CONCLUSION: Our data suggest that the combined treatment with chemotherapy and GST inhibitors such as EA might be an interesting option for patients with chemoresistant HL.
Development of "Core Syllabus" for Facial Anatomy Teaching to Aesthetic Physicians: A Delphi Consensus.

Background: A detailed understanding of facial anatomy, specifically the vascular framework, is crucial for delivering safe nonsurgical aesthetic procedures. To date, there is no core document based on consensus for the teaching of facial anatomy to aesthetic physicians exists. The aim of this study was to ascertain the most critical anatomical structures for avoiding disastrous complications during nonsurgical aesthetic procedures. Methods: After a detailed literature review, Delphi questionnaire was developed listing 154 anatomical structures of the face and neck for consensus review. Thirty-five international experts in surgical and nonsurgical facial aesthetics were invited to complete an online survey designed to rank the relevance of each anatomical element on a Likert scale from 1 (not at all important) to 4 (very important) or 5 (no opinion). Consensus for items included in the core syllabus was predefined as achieving a Cronbach's α ≥ 0.90 and an agreement score of ≥ 80%. Results: Thirty-four international experts (97.14%) completed the iterative online Delphi survey. The consensus among the specialists polled was achieved after 1 round of the survey (Cronbach's α = 0.94). The expert panel reached an agreement score of ≥ 80% on 137 of the 154 anatomical structures listed. Conclusion: The outcome of this Delphi study represents an essential first step in systematizing an evidence-based facial anatomy "Core Syllabus" for the teaching of aesthetic physicians and practitioners. This "Core Syllabus" will act as a blueprint for the educators while crafting a program.
A novel neuregulin - jagged1 paracrine loop in breast cancer transendothelial migration.

BACKGROUND: The interaction of breast cancer cells with other cells in the tumor microenvironment plays an important role in metastasis. Invasion and intravasation, two critical steps in the metastatic process, are influenced by these interactions. Macrophages are of particular interest when it comes to studying tumor cell invasiveness. Previous studies have shown that there is paracrine loop signaling between breast cancer cells and macrophages involving colony stimulating factor 1 (CSF-1) produced by tumor cells and epidermal growth factor (EGF) production by macrophages. In this paper, we identify a novel paracrine loop between tumor cells and macrophages involving neuregulin (NRG1) and notch signaling. METHODS: The aim of this study was to determine the role of NRG1, a ligand of the ErbB3 receptor, in macrophage stimulation of tumor cell transendothelial migration and intravasation. We used fluorescence-activated cell sorting (FACS) and western blot to determine ErbB3 and NRG1 expression, respectively. An in vitro transendothelial migration (iTEM) assay was used to examine the effects of short hairpin (sh)RNA targeting NRG1 in tumor cells and clustered regularly interspaced short palindromic repeats (CRISPR) knockout of jagged 1 (JAG1) in macrophages. Orthotopic xenograft injections in mice were used to confirm results in vivo. RESULTS: In our system, macrophages were the primary cells showing expression of ErbB3, and a blocking antibody against ErbB3 resulted in a significant decrease in macrophage-induced transendothelial migration of breast cancer cells. Stimulation of macrophages with NRG1 upregulated mRNA and protein expression of JAG1, a ligand of the Notch receptor, and JAG1 production by macrophages was important for transendothelial migration of tumor cells. CONCLUSIONS: This study demonstrates that stimulation of macrophages by tumor cell NRG1 can enhance transendothelial migration and intravasation. We also demonstrate that this effect is due to induction of macrophage JAG1, an important ligand of the Notch signaling pathway.
The contributions of diseases to disability burden among the elderly population in China.

OBJECTIVE: To assess the contributions of diseases to disability burden among older persons in China. METHOD: Based on the 2006 China Disability Survey (n = 354,859), we used the attribution method and Sullivan method to obtain disability prevalence and life expectancy with disability (LED) by disease, respectively. RESULTS: At disease group level, ear, eye, circulatory and musculoskeletal diseases, injury, and poisoning were the five leading causes of disability burden in terms of their contributions to disability prevalence and LED. At individual disease level, presbycusis, cataracts, cerebrovascular disease, osteoarthritis, and unclassified injuries were the five leading conditions, which accounted for 64% of disabilities and caused males and females aged 60 to have 3.04 and 3.76 years of LED, respectively. DISCUSSION: Along with the epidemiologic transition, chronic conditions have become the predominant contributor to disability burden among elderly persons in China. And, presbycusis, cataracts, cerebrovascular disease, osteoarthritis, and unclassified injuries should be the priorities in ameliorating disability.
African Swine Fever Virus Georgia 2007 with a Deletion of Virulence-Associated Gene 9GL (B119L), when Administered at Low Doses, Leads to Virus Attenuation in Swine and Induces an Effective Protection against Homologous Challenge.

UNLABELLED: African swine fever virus (ASFV) is the etiological agent of an often lethal disease of domestic pigs. Disease control strategies have been hampered by the unavailability of vaccines against ASFV. Since its introduction in the Republic of Georgia, a highly virulent virus, ASFV Georgia 2007 (ASFV-G), has caused an epizootic that spread rapidly into Eastern European countries. Currently no vaccines are available or under development to control ASFV-G. In the past, genetically modified ASFVs harboring deletions of virulence-associated genes have proven attenuated in swine, inducing protective immunity against challenge with homologous parental viruses. Deletion of the gene 9GL (open reading frame [ORF] B119L) in highly virulent ASFV Malawi-Lil-20/1 produced an attenuated phenotype even when administered to pigs at 10(6) 50% hemadsorption doses (HAD50). Here we report the construction of a genetically modified ASFV-G strain (ASFV-G-Δ9GLv) harboring a deletion of the 9GL (B119L) gene. Like Malawi-Lil-20/1-Δ9GL, ASFV-G-Δ9GL showed limited replication in primary swine macrophages. However, intramuscular inoculation of swine with 10(4) HAD50 of ASFV-G-Δ9GL produced a virulent phenotype that, unlike Malawi-Lil-20/1-Δ9GL, induced a lethal disease in swine like parental ASFV-G. Interestingly, lower doses (10(2) to 10(3) HAD50) of ASFV-G-Δ9GL did not induce a virulent phenotype in swine and when challenged protected pigs against disease. A dose of 10(2) HAD50 of ASFV-G-Δ9GLv conferred partial protection when pigs were challenged at either 21 or 28 days postinfection (dpi). An ASFV-G-Δ9GL HAD50 of 10(3) conferred partial and complete protection at 21 and 28 dpi, respectively. The information provided here adds to our recent report on the first attempts toward experimental vaccines against ASFV-G. IMPORTANCE: The main problem for controlling ASF is the lack of vaccines. Studies on ASFV virulence lead to the production of genetically modified attenuated viruses that induce protection in pigs but only against homologous virus challenges. Here we produced a recombinant ASFV lacking virulence-associated gene 9GL in an attempt to produce a vaccine against virulent ASFV-G, a highly virulent virus isolate detected in the Caucasus region in 2007 and now spreading though the Caucasus region and Eastern Europe. Deletion of 9GL, unlike with other ASFV isolates, did not attenuate completely ASFV-G. However, when delivered once at low dosages, recombinant ASFV-G-Δ9GL induces protection in swine against parental ASFV-G. The protection against ASFV-G is highly effective after 28 days postvaccination, whereas at 21 days postvaccination, animals survived the lethal challenge but showed signs of ASF. Here we report the design and development of an experimental vaccine that induces protection against virulent ASFV-G.
Preferentially Expressed Antigen in Melanoma (PRAME) and the PRAME family of Leucine-Rich Repeat Proteins".

Preferentially expressed antigen in melanoma (PRAME) is the best characterized member of the PRAME family of leucine-rich repeat (LRR) proteins. Mammalian genomes contain multiple members of the PRAME family whereas in other vertebrate genomes only one PRAME-like LRR protein was identified. PRAME is a cancer/testis antigen that is expressed at very low levels in normal adult tissues except testis but at high levels in a variety of cancer cells. In contrast to most other cancer/testis antigens, PRAME is expressed not only in solid tumors but also in leukemia cells. Expression of PRAME and other members of the PRAME family is regulated epigenetically. PRAME interacts with varying pathways that might be directly involved in the malignant phenotype of cancer cells. For instance, PRAME is able to dominantly repress retinoic acid signaling in these cells. On the other hand, PRAME-derived peptides can be recognized as epitopes by cytotoxic T cells and PRAME represents an attractive target for immunological treatment strategies.
Chair based exercise in community settings: a cluster randomised feasibility study.

BACKGROUND: Some older people who find standard exercise programmes too strenuous may be encouraged to exercise while remaining seated - chair based exercises (CBE). We previously developed a consensus CBE programme (CCBE) following a modified Delphi process. We firstly needed to test the feasibility and acceptability of this treatment approach and explore how best to evaluate it before undertaking a definitive trial. METHODS: A feasibility study with a cluster randomised controlled trial component was undertaken to 1. Examine the acceptability, feasibility and tolerability of the intervention and 2. Assess the feasibility of running a trial across 12 community settings (4 day centres, 4 care homes, 4 community groups). Centres were randomised to either CCBE, group reminiscence or usual care. Outcomes were collected to assess the feasibility of the trial parameters: level of recruitment interest and eligibility, randomisation, adverse events, retention, completion of health outcomes, missing data and delivery of the CCBE. Semi- structured interviews were conducted with participants and care staff following the intervention to explore acceptability. RESULTS: 48% (89 out of 184 contacted) of eligible centres were interested in participating with 12 recruited purposively. 73% (94) of the 128 older people screened consented to take part with 83 older people then randomised following mobility testing. Recruitment required greater staffing levels and resources due to 49% of participants requiring a consultee declaration. There was a high dropout rate (40%) primarily due to participants no longer attending the centres. The CCBE intervention was delivered once a week in day centres and community groups and twice a week in care homes. Older people and care staff found the CCBE intervention largely acceptable. CONCLUSION: There was a good level of interest from centres and older people and the CCBE intervention was largely welcomed. The trial design and governance procedures would need to be revised to maximise recruitment and retention. If the motivation for a future trial is physical health then this study has identified that further work to develop the CCBE delivery model is warranted to ensure it can be delivered at a frequency to elicit physiological change. If the motivation for a future trial is psychological outcomes then this study has identified that the current delivery model is feasible. TRIAL REGISTRATION: ISRCTN27271501 . Date registered: 30/01/2018.
Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

BACKGROUND: While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. METHODS: A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. RESULTS: No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and higher overall burden of mutations in all cancer genes. CONCLUSIONS: We identified several pathogenic variants that likely predispose to at least one of the tumours in patients with multiple cancers. We additionally present evidence that there may be a higher burden of variants of unknown significance in 'cancer genes' in patients with multiple cancer types. Further screens of this nature need to be carried out to build evidence to show if the cancers observed in these patients form part of a cancer spectrum associated with single germline variants in these genes, whether multiple layers of susceptibility exist (oligogenic or polygenic), or if the occurrence of multiple different cancers is due to random chance.
Predictors of exclusive breastfeeding knowledge and intention to or practice of exclusive breastfeeding among antenatal and postnatal women receiving routine care: a cross-sectional study.

Background: Despite consistent evidence showing the importance of exclusive breastfeeding (EBF) for six months, it remains a sub-optimal practice in The Gambia. This study aimed at investigating the determinants of EBF knowledge and intention to or practice of EBF. Methods: A cross-sectional study was conducted among 334 women receiving care at the Edward Francis Small Teaching Hospital (EFSTH) from December 2015 to February 2016. Using a structured interviewer-administered questionnaire, knowledge on EBF was determined and scored. Participants scoring above or equal to the median were determined to have sufficient EBF knowledge. Multivariate logistic regression analyses were used to identify predictors of EBF knowledge and intention to or practice of exclusive breastfeeding. Results: The proportion of women with sufficient exclusive breastfeeding knowledge and intended to or practice EBF were 60.2% and 38.6% respectively, while only 34.4% received EBF counseling. Earning ≥1500 GMD monthly (Adjusted Odds Ratio [aOR] 1.98; 95% Confidence Interval [Cl] 1.24, 3.16), having positive attitude (aOR 2.40; 95% Cl 1.40, 4.10) and partner supporting EBF (aOR 2.18; 95% Cl 1.23, 3.87) predicted sufficient EBF knowledge. Mothers aged 26-34 years (aOR 0.50; 9 5% Cl 0.31, 0.82) and EBF counseling (aOR 2.68; 95% Cl 1.68, 4.29) significantly associated with intention to or practice of exclusive breastfeeding. Conclusion: In conclusion, improving EBF rates will, therefore, require improved access to information on EBF targeting low socio-economically disadvantaged and older mothers. In addition, emphasis on strengthening the ongoing EBF counseling already within the health system is required.
Fecal microbes, short chain fatty acids, and colorectal cancer across racial/ethnic groups.

AIM: To investigate differences in microbes and short chain fatty acid (SCFA) levels in stool samples from Hispanic and non-Hispanic African American, American Indian, and White participants. METHODS: Stool samples from twenty participants were subjected to analysis for relative levels of viable bacteria and for SCFA levels. Additionally, the samples were subjected to 16S rRNA gene pyrosequencing for identification of bacteria present in the stool. We used a metagenome functional prediction technique to analyze genome copy numbers and estimate the abundance of butyrate kinase in all samples. RESULTS: We found that African Americans had significantly lower levels of acetate, butyrate, and total SCFAs than all other racial/ethnic groups. We also found that participant microbial profiles differed by racial/ethnic group. African Americans had significantly more Firmicutes than Whites, with enriched Ruminococcaceae. The Firmicutes/Bacteroidetes ratio was also significantly higher for African Americans than for Whites (P = 0.049). We found Clostridium levels to be significantly and inversely related to total SCFA levels (P = 0.019) and we found Bacteroides to be positively associated (P = 0.027) and Clostridium to be negatively associated (P = 0.012) with levels of butyrate. We also identified a correlation between copy number for a butyrate kinase predicted from 16S rRNA gene abundance and levels of butyrate in stool. CONCLUSION: The identified differences in gut flora and SCFA levels may relate to colorectal cancer mortality differentials and may be useful as targets for future clinical and behavioral interventions.
Maternal anemia is a potential risk factor for anemia in children aged 6-59 months in Southern Africa: a multilevel analysis.

BACKGROUND: The effect of maternal anemia on childhood hemoglobin status has received little attention. Thus, we examined the potential association between maternal anemia and childhood anemia (aged 6-59 months) from selected Southern Africa countries. METHODS: A cross-sectional study using nationally representative samples of children aged 6-59 months from the 2010 Malawi, 2011 Mozambique, 2013 Namibia, and 2010-11 Zimbabwe demographic and health surveys (DHS) was conducted. Generalized linear mixed models (GLMMs) were constructed to test the associations between maternal anemia and childhood anemia, controlling for individual and community sociodemographic covariates. RESULTS: The GLMMs showed that anemic mothers had increased odds of having an anemic child in all four countries; adjusted odds ratio (aOR = 1.69 and 95% confidence interval [CI]:1.37-2.13) in Malawi, (aOR = 1.71; 95% CI: 1.37-2.13) in Mozambique, (aOR = 1.55; 95% CI: 1.08-2.22) in Namibia, and (aOR = 1.52; 95% CI: 1.25-1.84) in Zimbabwe. Furthermore, the odds of having an anemic child was higher in communities with a low percentage of anemic mothers (aOR = 1.52; 95% CI: 1.19-1.94) in Mozambique. CONCLUSIONS: Despite the long-standing efforts to combat childhood anemia, the burden of this condition is still rampant and remains a significant problem in Southern Africa. Thus, public health strategies aimed at reducing childhood anemia should focus more on addressing infections, and micronutrient deficiencies both at individual and community levels in Southern Africa.