tbuckley/cabot-search huggingface dataset:
18F-FDG PET/CT Finding of Primary Cardiac Lymphoma
Authors: Hayato Kaida, Takahiro Kumode, Masatomo Kimura, Kazunari Ishii
Journal: Clinical Nuclear Medicine (2020)

Abstract An 80-year-old woman experienced dyspnea. Cardiac enlargement was detected by chest radiography at a local hospital. She was admitted to our hospital, and echocardiography and CT revealed pericardial effusion and multiple tumor lesions in right atrium. 18 F-FDG PET/CT demonstrated multiple nodular accumulations in these tumors (SUV max , 14.5). Cytologic analysis of the pericardial fluid revealed a diffuse large B-cell lymphoma. Primary cardiac lymphoma (PCL) is rare, and there are few reports about the 18 F-FDG PET/CT imaging features of PCLs. In high 18 F-FDG uptake in multiple tumors in the right atrium and large pericardial effusion, a PCL should be considered.
Cxcr6-Based Mesenchymal Stem Cell Gene Therapy Potentiates Skin Regeneration in Murine Diabetic Wounds
Authors: Neha R. Dhoke, Komal Kaushik, Amitava Das
Journal: Molecular Therapy (2020)

Mesenchymal stem cell (MSC) therapies for wound healing are often compromised due to low recruitment and engraftment of transplanted cells, as well as delayed differentiation into cell lineages for skin regeneration. An increased expression of chemokine ligand CXCL16 in wound bed and its cognate receptor, CXCR6, on murine bone-marrow-derived MSCs suggested a putative therapeutic relevance of exogenous MSC transplantation therapy. Induction of the CXCL16-CXCR6 axis led to activation of focal adhesion kinase (FAK), Src, and extracellular signal-regulated kinases 1/2 (ERK1/2)-mediated matrix metalloproteinases (MMP)-2 promoter regulation and expression, the migratory signaling pathways in MSC. CXCL16 induction also increased the transdifferentiation of MSCs into endothelial-like cells and keratinocytes. Intravenous transplantation of allogenic stable MSCs with Cxcr6 gene therapy potentiated skin tissue regeneration by increasing recruitment and engraftment as well as neovascularization and re-epithelialization at the wound site in excisional splinting wounds of type I and II diabetic mice. This study suggests that activation of the CXCL16-CXCR6 axis in bioengineered MSCs with Cxcr6 overexpression provides a promising therapeutic approach for the treatment of diabetic wounds.
Reply to de Steenhuijsen Piters and Bogaert: Bacterial DNA in Fetal Lung Samples May Be Explained by Sample Contamination
Authors: Denise Al Alam, Soula Danopoulos, Brendan Grubbs, Nur A’tikah Binte Mohamed Ali, Micheál Mac Aogáin, Sanjay H. Chotirmall, David Warburton, Amit Gaggar, Namasivayam Ambalavanan, Charitharth Vivek Lal
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

In addition, the lack of information about the indications for the D&C or D&E procedures makes us question whether pregnancy complications, such as miscarriage, which is likely accompanied by local inflammation (5), bacterial translocation, and infection, might be at the basis of their findings.All of the above information is essential to assess the potential biological origin of the observed bacterial DNA in fetal samples.In conclusion, although we do not dispute the possibility of the existence of a fetal lung microbiome signature, the study lacked robust controls during both sample collection and laboratory processes, giving rise to speculation about the validity of the reported findings.Therefore, we believe that the presented data insufficiently support the authors' conclusion that the human fetal lung harbors a microbiome signature.We do agree, however, that the road on which they have embarked-studying fetal tissues at early stages of pregnancy-is an interesting and important one, and therefore warrants more research.
Effect of a conditional cash transfer programme on leprosy treatment adherence and cure in patients from the nationwide 100 Million Brazilian Cohort: a quasi-experimental study
Authors: Julia M Pescarini, Elizabeth Williamson, Joilda S Nery, Anna Ramond, Maria Yury Ichihara, Rosemeire L Fiaccone, Maria Lucia F Penna, Liam Smeeth, Laura C Rodrigues, Gerson O Penna, Elizabeth B Brickley, Mauricio L Barreto
Journal: The Lancet Infectious Diseases (2020)

Indirect financial costs and barriers to health-care access might contribute to leprosy treatment non-adherence. We estimated the association of the Brazilian conditional cash transfer programme, the Programa Bolsa Família (PBF), on leprosy treatment adherence and cure in patients in Brazil.
Schizophrenia-Associated MicroRNA–Gene Interactions in the Dorsolateral Prefrontal Cortex
Authors: Danielle M. Santarelli, Adam P. Carroll, Heath M. Cairns, Paul A. Tooney, Murray J. Cairns
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Schizophrenia-associated anomalies in gene expression in postmortem brain can be attributed to a combination of genetic and environmental influences. Given the small effect size of common variants, it is likely that we may only see the combined impact of some of these at the pathway level in small postmortem studies. At the gene level, however, there may be more impact from common environmental exposures mediated by influential epigenomic modifiers, such as microRNA (miRNA). We hypothesise that dysregulation of miRNAs and their alteration of gene expression have significant implications in the pathophysiology of schizophrenia. In this study, we integrate changes in cortical gene and miRNA expression to identify regulatory interactions and networks associated with the disorder. Gene expression analysis in post-mortem prefrontal dorsolateral cortex (BA 46) (n = 74 matched pairs of schizophrenia, schizoaffective, and control samples) was integrated with miRNA expression in the same cohort to identify gene–miRNA regulatory networks. A significant gene–miRNA interaction network was identified, including miR-92a, miR-495, and miR-134, which converged with differentially expressed genes in pathways involved in neurodevelopment and oligodendrocyte function. The capacity for miRNA to directly regulate gene expression through respective binding sites in BCL11A, PLP1, and SYT11 was also confirmed to support the biological relevance of this integrated network model. The observations in this study support the hypothesis that miRNA dysregulation is an important factor in the complex pathophysiology of schizophrenia.
Comparison of C3d immunohistochemical staining to enzyme-linked immunosorbent assay and immunofluorescence for diagnosis of bullous pemphigoid
Authors: Leo L. Wang, Ata S. Moshiri, Roberto Novoa, Cory L. Simpson, Junko Takeshita, Aimee S. Payne, Emily Y. Chu
Journal: Journal of the American Academy of Dermatology (2020)
Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial
Authors: Antoine Italiano, Olivier Mir, Simone Mathoulin-Pelissier, Nicolas Penel, Sophie Piperno-Neumann, Emmanuelle Bompas, Christine Chevreau, Florence Duffaud, Natacha Entz-Werlé, Esma Saada, Isabelle Ray-Coquard, Cyril Lervat, Nathalie Gaspar, Perrine Marec-Berard, Hélène Pacquement, John Wright, Maud Toulmonde, Alban Bessede, Amandine Crombe, Michèle Kind, Carine Bellera, Jean-Yves Blay
Journal: The Lancet Oncology (2020)
In type 2 diabetes, SGLT-2 inhibitors reduce risk for major kidney outcomes
Authors: Sarah Yoon Ai Ng, Doreen Zhu, William G. Herrington
Journal: Annals of Internal Medicine (2020)

Source Citation Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7:845-54. 31495651
Expression and prognostic significance of directed therapy targets and mutational analysis of the EGFR pathway in malignant salivary gland tumors.
Authors: Jerome F Cros, Helene Blons, Emilie Sbidian, Eric Tartour, Stephane Hans, Daniel Brasnu, Pierre Laurent-Puig, Patrick Bruneval, Cecile Badoual
Journal: Journal of Clinical Oncology (2012)

5554 Background: Malignant salivary gland tumors are rare and pleomorphic entities (24 sub types, WHO 2005). Curative treatment relies on surgery sometimes completed by radiotherapy. Management of non-surgical, locally advanced or metastatic tumors is difficult as conventional chemotherapies are ineffective. Directed therapies may provide important benefits for these patients. The aim of this work was to assess the expression and prognostic value of directed therapy targets on salivary gland tumors and search for mutations within the key players of the EGFR pathway. Methods: Immunochemistry on formalin fixed paraffin embedded (FFPE) samples from 124 patients for c-KIT, EGFR, c-ERBB2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was performed and related to progression free interval and survival. DNA was extracted from FFPE samples and conditional for treatment mutations of EGFR/KRAS/BRAF were assessed. An additional high throughput screening for mutations of key oncogenic genes was performed. Results: EGFR was the most expressed marker, found across almost all histotypes. Expression of the other markers was heterogeneous but some potential therapy leads were suggested by high levels of C-ERBB2 and androgen receptors in salivary duct carcinomas or C-KIT over expression in myoepithetial carcinomas. Tumor grade and a high proliferation index (Ki67&gt;20%) were associated with progression free interval and survival. None of the other marker was. No mutation was found in EGFR/KRAS/BRAF. 7% (7/104) of the tumors harbored a mutation at the codon 61 of HRAS. In epithelial and epithelial-myoépithélial carcinoma, the mutation rate reached 33%. Mutations of PI3K and p53 were the most frequently found in the broader screen. Conclusions: Several tumor subtypes expressed frequently some targets of directed therapies suggesting potential therapy leads. The EGFR/MAPK pathway seems intact suggesting a low efficacy of small kinase inhibitors such as erlotinib or gefitinib. The mutation of H-RAS, known to be important but not sufficient to trigger urothelial carcinoma, could be a key oncogenic event in tumors with a myoepithelial component.
Abstract P3-06-14: Inhibition of PRKCQ enhances chemosensitivity of triple negative breast cancer by regulating EMT and Bim
Authors: Hanna Yoko Irie, Jessica H. Byerly, Elisa R. Port
Journal: Cancer Research (2020)

Abstract Background/Rationale: While some patients with triple negative breast cancer (TNBC) achieve long-term remission with standard-of-care chemotherapy, many have cancers that are chemotherapy resistant, putting them at risk for metastatic recurrence. There is also a lack of targeted therapies for TNBC, highlighting the need for novel therapeutic strategies for this subtype. PRKCQ, a member of the novel protein kinase C family, is preferentially expressed in TNBC compared to other breast cancer subtypes and we previously reported that PRKCQ expression is sufficient to promote oncogenic activities (growth-factor independent growth, anoikis resistance and migration). In addition, PRKCQ suppression inhibits growth of TNBC tumor xenografts. We sought to determine if PRKCQ expression modulation impacts sensitivity of triple negative breast cancer cells to standard of care chemotherapy and whether PRKCQ inhibition could be a strategy to enhance chemosensitivity of drug-resistant TNBC. Methods: We determined the effects of modulating PRKCQ expression, using PRKCQ cDNA or shRNA vectors, on sensitivity of TNBC cells to the apoptotic effects of standard-of-care chemotherapy, including those cancers that are relatively chemotherapy resistant at baseline. We also determined the mechanisms by which PRKCQ regulates sensitivity to chemotherapy. Results: Increased PRKCQ expression in non-transformed MCF-10A breast epithelial cells promotes resistance to the apoptosis-inducing effects of Doxorubicin or Paclitaxel treatment. These effects are dependent on PRKCQ kinase activity as a catalytically inactive PRKCQ failed to promote resistance. Downregulation of PRKCQ or inhibition of its kinase activity enhanced sensitivity of TNBC cells to chemotherapy. PRKCQ impacts chemotherapy sensitivity of TNBC by regulating epithelial-mesenchymal transition (EMT) and expression of Bim, a pro-apoptotic Bcl2 family protein. Conclusions. PRKCQ promotes resistance of TNBC to standard of care chemotherapies by promoting EMT and suppressing pro-apoptotic Bim. Inhibiting PRKCQ expression or activity sensitizes TNBC cells to chemotherapy and could be an effective strategy to overcome chemotherapy resistance of a subset of triple negative breast cancers, thereby improving patient outcomes. Citation Format: Hanna Yoko Irie, Jessica H. Byerly, Elisa R. Port. Inhibition of PRKCQ enhances chemosensitivity of triple negative breast cancer by regulating EMT and Bim [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-06-14.
Young-Onset Colon Cancer and Recurrence Risk by Gene Expression
Authors: George J Chang, Y Nancy Y You, Christy A Russell, Marni B Tierno, Michelle Turner, John P Bennett, Anna Lau, Howard S Hochster
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract The incidence and mortality from colorectal cancer in younger adults (younger than 55 years) is increasing. We reviewed the complete database of a gene-expression test, Oncotype DX Colon Recurrence Score test, to determine age-related differences in recurrence score (RS) and single-gene results (7 cancer-related of the 12-gene assay). We included 20 478 stage II and III A and B colon cancer patients submitted to Genomic Health. RS results were grouped by low-, intermediate-, and high-risk groups. Single-gene scores were described using median and interquartile range. Of all patients 72.5% and 72.6% of those younger than 40 years had low-risk RS. Comparing older with younger patients, RS or single-gene expression did not differ by age group or stage. Young-onset colon cancer does not differ by expression of the RS component genes. Most patients with stage II and III colon cancer have low-risk disease as measured by the 12-gene assay, regardless of age.
Association of High Traditional Masculinity and Risk of Suicide Death
Authors: Daniel Coleman, William Feigelman, Zohn Rosen
Journal: JAMA Psychiatry (2020)

In the United States, men die by suicide at 3.5 times the rate of women. 1 One driver of this gender disparity may be high traditional masculinity (HTM), a set of norms that includes competitiveness, emotional restriction, and aggression. 2 Quantitative studies of HTM are interrelated with discourse on hegemonic masculinity. 3Using norm-and trait-based measures, HTM men were found to have higher suicidal ideation (SI), 2,4 but to our knowledge, the association with suicide death has not been tested with a credible measure of HTM.Add Health is a nationally representative study of adolescents into adulthood.Feigelman and colleagues 5 found 9 Add Health variables associated with suicide (Figure , A andB) and weak nonsignificant effects for depression and gun access.This study hypothesizes that HTM is associated with suicide, depression, gun access, and the 9 variables previously noted.No prediction was made for HTM regarding SI or suicide attempts.Methods | Add Health began with 20 745 adolescents in 1995 and in 2014 was matched with death records using the National Death Index.The details of the methods of Add Health can be found at http://www.cpc.unc.edu/addhealth.The Add Health study was reviewed and approved for human participant issues at the University of North Carolina Chapel Hill.Under that protocol, written informed consent was elicited from all participants.The secondary analysis of this data was approved by the institutional review board at Fordham University.Death by suicide was defined by National Death Index procedures.Through the use of a method novel to suicide research, an established procedure was replicated for scoring gender-typed attitudes and behaviors in which a single latent probability variable of identifying as male was generated from 16 gender-discriminating variables (including not crying, physically fit, not moody, not emotional, liking yourself, fighting, and risk taking). 6Participants scoring 73% probability or higher of identifying as male (>1 SD above the mean) were coded as HTM.Details of additional variables can be found in Feigelman et al. 5 Because of the small number of suicides, the analysis was limited to bivariate tests and effect sizes: χ 2 and odds ratios (ORs) and t tests and Cohen d.Stata, version 14 (StataCorp), was used for all data analyses and the criterion P value was set at P< .05.Results | Of the 22 suicide deaths, 21 were men (OR, 21.7; 95% CI; 2.9-161; χ 2 = 18.8;P < .001).All subsequent analyses include men only.High-traditional masculinity men were 2.
Abstract P2-16-11: Impact of progesterone receptor status on response to neoadjuvant chemotherapy in oestrogen receptor positive breast cancer patients
Authors: Michael R Boland, Eanna J Ryan, Timothy Nugent, Darina Gilroy, John Kennedy, Dhaffir Alazawi, Terence J Boyle, Elizabeth M Connolly
Journal: Cancer Research (2020)

Abstract Introduction Breast cancer patients respond differently to neoadjuvant chemotherapy (NAC) based on hormone receptor subtype. Oestrogen receptor positive/Her-2 receptor negative (ER+HER-) patients respond poorest but the effect of progesterone receptor (PR) status on response within this group has not been elucidated. The aim of this study was to assess the impact of PR status on response to NAC in ER+HER- breast cancer patients. Methods All patients receiving NAC over a seven-year period (2011-2017) were retrospectively identified from a prospectively maintained database within a specialised breast referral unit. Clinicopathological details were collated for all patients found to be ER+HER-. Primary outcomes including breast complete pathological response (PCR) rate and axillary PCR rate were compared between patients found to be progesterone receptor positive and negative. Secondary outcomes including grade and presence of lymphovascular invasion were also assessed. Results 206 patients were identified (151 in the ER+PR+HER- group and 55 in the ER+PR-HER- group). When compared with the PR+ group, patients found to be PR negative were more likely to achieve a breast PCR (3.3% vs 25.4%; Chi Square test; p=0.001), which was confirmed on multivariate analysis (p=0.001).In patients who were initially node positive, PR negativity was associated with a higher rate of axillary nodal PCR compared to those found to be PR positive(12.2% vs 25.5%; Chi Square test; p=0.04). ER+PR-HER- patients were more likely to have higher grade tumours but not LVI. Conclusion Over a quarter of ER+HER- patients who are PR negative will have a complete pathological response to NAC in the breast and axilla. Such patients should be considered for NAC at diagnosis. Citation Format: Michael R Boland, Eanna J Ryan, Timothy Nugent, Darina Gilroy, John Kennedy, Dhaffir Alazawi, Terence J Boyle, Elizabeth M Connolly. Impact of progesterone receptor status on response to neoadjuvant chemotherapy in oestrogen receptor positive breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-11.
ATRX/EZH2 complex epigenetically regulates FADD/PARP1 axis, contributing to TMZ resistance in glioma
Authors: Bo Han, Xiangqi Meng, Pengfei Wu, Ziwei Li, Siyi Li, Yangong Zhang, Caijun Zha, Qile Ye, Chuanlu Jiang, Jinquan Cai, Tao Jiang
Journal: Theranostics (2020)

Rationale: Glioma is the most common primary malignant brain tumor in adults. Chemoresistance of temozolomide (TMZ), the first-line chemotherapeutic agent, is a major issue in the management of patients with glioma. Alterations of alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene constitute one of the most prevalent genetic abnormalities in gliomas. Therefore, elucidation of the role of ATRX contributing to TMZ resistance in glioma is urgently needed. Methods: We performed the bioinformatics analysis of gene expression, and DNA methylation profiling, as well as RNA and ChIP-seq data sets. CRISPR-Cas9 gene editing system was used to achieve the ATRX knockout in TMZ resistant cells. In vitro and in vivo experiments were carried out to investigate the role of ATRX contributing to TMZ resistance in glioma. Results: We found that ATRX expression was upregulated via DNA demethylation mediated by STAT5b/TET2 complex and strengthened DNA damage repair by stabilizing PARP1 protein in TMZ resistant cells. ATRX elicited PARP1 stabilization by the down-regulating of FADD expression via the H3K27me3 enrichment, which was dependent on ATRX/EZH2 complex in TMZ resistant cells. Magnetic resonance imaging (MRI) revealed that the PARP inhibitor together with TMZ inhibited glioma growth in ATRX wild type TMZ resistant intracranial xenograft models. Conclusions: The present study further illustrated the novel mechanism of the ATRX/PARP1 axis contributing to TMZ resistance. Our results provided substantial new evidence that PARP inhibitor might be a potential adjuvant agent in overcoming ATRX mediated TMZ resistance in glioma.
Long-Term Changes in Gut Microbial Metabolite Trimethylamine N-Oxide and Coronary Heart Disease Risk
Authors: Yoriko Heianza, Wenjie Ma, Joseph A. DiDonato, Qi Sun, Eric B. Rimm, Frank B. Hu, Kathryn M. Rexrode, JoAnn E. Manson, Lu Qi
Journal: Journal of the American College of Cardiology (2020)
Increasing Spending on Primary Care to Reduce Health Care Costs—Reply
Authors: Suhas Gondi, Zirui Song
Journal: JAMA (2020)

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Rammya Mathew: Racism in medicine—migrant doctors aren’t here just to “fill a gap”
Authors: Rammya Mathew
Journal: BMJ (2020)

Even at its inception, it was clear that the NHS could not be fully staffed by “homegrown” doctors.1 Because of this, doctors and other healthcare workers historically bypassed immigration laws, and the 1960s and ’70s saw a surge in the number of doctors migrating from the Indian subcontinent to work in the NHS. This included my parents.

Working abroad was revered, and the NHS in particular was a beacon of opportunity. Nevertheless, my parents’ decision to relocate to the UK was riddled with risk and uncertainty. Neither of them came from an affluent family, so they had just one chance to make it. While jumping through the hoops required for General Medical Council registration, …