tbuckley/cabot-search huggingface dataset:
Chest pain
Authors: M. Jelinek, K. Barraclough
Journal: BMJ (2009)

<h3>Summary</h3> Early life stress, prenatal exposure to glucocorticoids (GCs), confers a higher risk of psychiatric and neurodevelopmental disorders in children. Increasingly, the importance of microglia in these disorders has been recognised. Studies on GCs exposure during microglial development have been limited, and there are few, if any, human studies. We established an <i>in vitro</i> model of ELS by continuous pre-expoure of human iPS-microglia to GCs during primitive haematopoiesis (the critical stage of iPS-microglial differentiation) and then examined how this exposure affected the microglial phenotype as they differentiated and matured to microglia. The iPS-microglia predominately expressed glucocorticoid receptors over mineralocorticoid receptors, and the GR-α splice variant. Chronic GCs exposure during primitive haematopoiesis was able to recapitulate <i>in vivo</i> ELS effects. Thus pre-exposure to prolonged GCs resulted in increased type I interferon signalling, the presence of Cyclic GMP-AMP synthase-positive (cGAS) micronuclei, and cellular senescence in the matured iPS-microglia. The findings from this <i>in vitro</i> ELS model have ramifications for the responses of microglia in the pathogenesis of GC-mediated ELS- associated disorders such as schizophrenia, attention-deficit hyperactivity disorder and autistic spectrum disorder. <h3>Highlights</h3> Human iPS-derived-microglia predominantly express glucocorticoid receptor NR3C1 compared with mineralocorticoid receptor NR3C2, and a predominant splice variant of the NR3C1 of GR-α. GC expression shows a differentiation-linked increment from iPSC to iPS-microglia. An early-life stress model was established by exposing iPSC to glucocorticoids during primitive haematopoiesis. RNA-seq analysis revealed that this early glucocorticoid exposure led to enhanced type I interferon inducible gene expression in the subsequent iPS-microglia. Furthermore, micronuclei formation and cellular senescence markers were upregulated in the iPSC-microglia, indicating genomic instability due to early chronic GC exposure. These findings have ramifications for the microglial responses in ELS linked neurodevelopmental disorders such as schizophrenia, attention-deficit hyperactivity disorder and autistic spectrum disorder. <h3>Graphical abstract</h3>
Soundings: Death in the parlour
Authors: Kevin Barraclough
Journal: BMJ (2001)

One of the unavoidable features of rural general practice is the proximity of suffering. At times it seems as though a miasma of pain and premature death hangs in little pockets around the valley, affecting patients, neighbours, and friends. As one stays longer in practice, the picturesque villages become shrouded with recollections not apparent to the casual visitor.

As a trainee I was told that this was a privilege, a claim I viewed then, and now, with some ambivalence. There is certainly an edge to observing suffering on the mattress in the front room that, personally, I did not experience on the hospital ward. I remember a friend, an experienced surgical trainee, vomiting at the sight of blood at the scene of a car crash. The juxtaposition of blood with tar and grit forms an altogether different texture from that of blood with vinyl and steel. Equally, the texture of pain seems different when projected against the vignette of a sideboard pregnant with memorabilia.

Inevitably, in unguarded moments, you start to wonder how you will react when you are no longer an observer, but are a more active participant in pain. It is clear that there is an art to suffering with dignity. Those who manage it seem to achieve a certain detachment—a sense of irony which, while it does not necessarily soften the experience, at least seems to makes it endurable. But you also see those who suffer sharply, determined to wound as well as be wounded.

Personally, I think I'll opt for the grouchy, difficult old curmudgeon performance—a role my family tells me I have been perfecting over the years. I'll grumble about youth, explicit sex on television, and the government (so no change there, then). But I hope I won't complain about my lot—that way lies real pain.

So what about that old chestnut about an omnipotent good god and the existence of suffering in the world? (“Don't ask me that question,” says God in the BBC Radio 4 comedy Old Harry's Game. “It really pisses me off.”) Well, the answer, as usual, was discovered by the eminent metaphysical philosopher Woody Allen. He was asked in an interview whether he felt the presence of so much suffering in the world meant that, if God exists, He must be evil. Not actually evil, Allen mused. The worst that can be said about Him is that He's an underachiever.
The dexamethasone suppression test and response to methylphenidate in depression
Authors: H Sternbach, H Gwirtsman, R H Gerner
Journal: American Journal of Psychiatry (1981)

The authors studied 19 inpatients with major depressive episode or schizoaffective disorder, depressed type, and compared their response to the dexamethasone suppression test (DST) with their response to the methylphenidate stimulation test. They found a significant negative correlation between responses to DST and to methylphenidate.
A Liver Score that Combines Direct Markers of Extracellular Matrix Formation with Platelet Count, INR and Age Accurately Diagnose Liver Fibrosis and Cirrhosis in Patients with Alcohol Overuse
Authors: M. Thiele, B.S. Madsen, M. Nielsen, J. Hansen, L. Møller, S. Detlefsen, D. Leeming, O.S. de Muckadell, M. Karsdal, A. Krag
Journal: Journal of Hepatology (2016)
Measles outbreak in Gibraltar, August–October 2008 – a preliminary report
Authors: V Kumar
Journal: Eurosurveillance (2008)

To date, 276 clinical diagnosed cases of measles have been notified in Gibraltar. The outbreak, which has been ongoing since August 2008 and affected almost 1% of the local population, unmasked errors in vaccination uptake assumptions and highlighted the need for improved data recording and research on disease transmission rates in small crowded populations.
Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma
Authors: Saad Z. Usmani, Brendan M. Weiss, Torben Plesner, Nizar J. Bahlis, Andrew Belch, Sagar Lonial, Henk M. Lokhorst, Peter M. Voorhees, Paul G. Richardson, Ajai Chari, A. Kate Sasser, Amy Axel, Huaibao Feng, Clarissa M. Uhlar, Jianping Wang, Imran Khan, Tahamtan Ahmadi, Hareth Nahi
Journal: Blood (2016)
Sexual Harassment and Discrimination Experiences of Academic Medical Faculty
Authors: Reshma Jagsi, Kent A. Griffith, Rochelle Jones, Chithra R. Perumalswami, Peter Ubel, Abigail Stewart
Journal: JAMA (2016)

This survey study of recent National Institutes of Health career development (K) award recipients assessed the proportion who reported gender bias and advantage and sexual harrassment in their professional careers.
Laboratory support during and after the Ebola virus endgame: towards a sustained laboratory infrastructure
Authors: I Goodfellow, C Reusken, M Koopmans
Journal: Eurosurveillance (2015)

The Ebola virus epidemic in West Africa is on the brink of entering a second phase in which the (inter)national efforts to slow down virus transmission will be engaged to end the epidemic. The response community must consider the longevity of their current laboratory support, as it is essential that diagnostic capacity in the affected countries be supported beyond the end of the epidemic. The emergency laboratory response should be used to support building structural diagnostic and outbreak surveillance capacity.
Abstract B2-03: Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers
Authors: Eunjee Lee, Koichi Ito, Eric E. Schadt, Hanna Y. Irie, Jun Zhu
Journal: Cancer Research (2015)

Abstract MicroRNAs (miRNAs) play a key role in regulating tumor progression and metastasis. However, miRNA's activity can't be measured by its expression level. We developed a computational approach, ActMiR, for identifying active miRNAs and miRNA-mediated regulatory mechanisms. Applying ActMiR to four cancer datasets in The Cancer Genome Atlas (TCGA), we showed that (1) miRNA activity was tumor subtype specific; (2) genes correlated with inferred miRNA activities were more likely to enrich for miRNA binding motifs; (3) expression levels of these genes and inferred miRNA activities were more likely to be negatively correlated. For the four cancer types in TCGA we identified 64~203 key miRNAs for each cancer subtype and annotated their biological functions. For ER-/HER2- breast cancers we identified activities of key miRNAs let-7d and miR-18a as potential prognostic markers and validated them in two independent ER-/HER2- breast cancer data sets. We experimentally validated their causal relationships with their target genes. Similarly, we showed that key miRNA activities but no miRNA expression level were consistently associated with clinical outcomes for other cancer types. Taken together, the inferred activity of key miRNA provided a functional link to its mediated regulatory network, and can be used to robustly predict patient's survival. Citation Format: Eunjee Lee, Koichi Ito, Eric E. Schadt, Hanna Y. Irie, Jun Zhu. Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-03.
Induction of Lung Cancers in Preselected, Localized Sites in the Dog<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: Rao R. Paladugu, Edwin C. Shore, Arthur H. Cohen, Kimito Matsumura, John R. Benfield
 8
Journal: JNCI Journal of the National Cancer Institute (1980)

Cancers were induced in 10 dogs in preselected sites within the lung. These 10 animals were among 89 dogs enrolled in 10 protocols with different carcinogens, doses, and techniques over 6 years. The 10 dogs that developed cancers were included in five of these protocols; 4 of the cancers were included in one of the protocols. The administered carcinogens included the aromatic hydrocarbons benzo[a]pyre ne (BP), N-methyl-N-nitrosourea (MNU), 7,12-dimethylbenz[a]anthracene (DMBA), 3-methylcholanthrene (MCA), and yttrium-91 (91Y) beta radiation. The techniques of application included intrabronchial and intrapulmonary sustained-release implants of DMBA and91Y, serial intrabronchial submucosal injections of BP, DMBA, and MCA, or topical application of MNU. The intervals from the first application of a carcinogen to the diagnosis of malignant disease ranged from 8 to 56 months. Of the tumors induced, 9 were centrally located squamous cell carcinomas and 1 was a peripherally located carcinosarcoma. Four of the dogs were killed or died with stage 3 disease. The remaining 6 dogs are alive and are being evaluated serially; all 6 are in stage 1.
ITPKA Gene Body Methylation Regulates Gene Expression and Serves as an Early Diagnostic Marker in Lung and Other Cancers
Authors: Yi-Wei Wang, Xiaotu Ma, Yu-An Zhang, Mei-Jung Wang, Yasushi Yatabe, Stephen Lam, Luc Girard, Jeou-Yuan Chen, Adi F. Gazdar
Journal: Journal of Thoracic Oncology (2016)

Despite recent advances in cancer therapy, the overall 5-year survival rate of patients with lung cancer remains low. The aim of our study was to search for novel markers for early diagnosis in patients with lung cancer. Complementary DNA microarray analysis was performed in primary lung adenocarcinomas and cell lines to search for differentially expressed genes, followed by in vivo and in vitro tumorigenic assays to characterize the oncogenic potential of the candidate genes. Gene body methylation was analyzed by 450K methylation array, bisulfite sequencing, and quantitative methylation-specific polymerase chain reaction assays. In silico analysis of The Cancer Genome Atlas data set was also performed. Inositol-trisphosphate 3-kinase A gene (ITPKA), a kinase with limited tissue distribution, was identified as a potential oncogene. We showed that ITPKA expression is up-regulated in many forms of cancers, including lung and breast cancers, and that overexpressed ITPKA contributes to tumorigenesis. We also demonstrated that ITPKA expression is regulated by epigenetic DNA methylation of ITPKA gene body through modulation of the binding of SP1 transcription factor to the ITPKA promoter. ITPKA gene body displayed low or absent levels of methylation in most normal tissue but was significantly methylated in malignant tumors. In lung cancer, ITPKA gene body methylation first appeared at the in situ carcinoma stage and progressively increased after invasion. ITPKA is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis. ITPKA gene body methylation regulates its expression and thus serves as a novel and potential biomarker for early cancer detection.
Internal Biliary Fistula
Authors: Mario A. Calonje
Journal: JAMA (1962)

Twenty-two cases of internal biliary fistula observed between the years 1944 and 1961 are reviewed. Two were artificial fistulas. Of the 20 spontaneous fistulas, only 3 were diagnosed before operation. The signs and symptoms suggest cholecystitis. Recurring colicky pain suddenly relieved or recurrent symptoms of cholecystitis followed by diarrhea, lower abdominal pain, vomiting, and fever should suggest spontaneous internal biliary fistula. The most important roentgenographic finding is air in the biliary tree. This, with intestinal obstruction and a stone shadow in the abdomen, makes the diagnosis certain. Much depends on careful interpretation of roentgenograms and on the alertness of the diagnostician for this particular condition.
Changes in the Con-A-induced redistribution pattern of lymphocytes: a possible aid in the differential diagnosis between malignant lymphoma and other diseases
Authors: H Ben-Bassat, S Penchas, A Polliack, S Mitrani-Rosenbaum, E Naparstek, Y Matzner, A Kedar, D Shouval, A Eldor, M Prokocimer, N Goldblum
Journal: Blood (1980)
Abstract P2-01-07: Neutrophil lymphocyte ratio and breast cancer: A future prognostic indicator for outcome after surgery?
Authors: GJ Williams, AM Huws, SDH Holt, YM Sharaiha
Journal: Cancer Research (2016)

Abstract There is a growing body of literature highlighting the prognostic use of pre-operatively comparing certain white blood cell differentials, namely neutrophils and lymphocytes, with outcomes in many different types of solid tumour cancers. It has been postulated that a raised neutrophil to lymphocyte ratio (NLR) may reflect a greater tumour burden on the patient, and therefore lead to poorer outcomes. There is some evidence that a raised pre-operative NLR may help to predict poorer outcomes following surgery for breast cancer. This observational retrospective proof of concept study aims to assess the association between pre-operative NLR and breast cancer outcomes over a three year period of follow-up from a cohort of 147 patients. The results of this study revealed that the cohort of patients with a raised pre-operative NLR was associated with a clinically significant increased rate of local recurrence of their breast cancer following surgery with curative intent (with or without adjuvant chemotherapy and radiotherapy) compared to those that had a low or normal NLR (20.4% ± 4.9% vs 5.1% ± 4.9% respectively, CI 95%; p=0.004). In relation to intra-operative sentinel lymph node biopsy, the analysis also showed that the incidence of a raised pre-operative NLR was not related to whether there was nodal involvement or not at the time of surgery (33% vs 33%, p=1). This suggests that a raised pre-operative NLR may be an independent prognostic indicator for breast cancer outcomes. This study provides a template for a prospective observational study which is needed to corroborate this result and to account for confounding factors such as concomitant chronic disease. Additionally, a larger cohort sample size with a follow-up of five years is necessary to assess the relationship between pre-operative NLR and mortality due to the latter's relatively low incidence in breast cancer. However, this study further supports that consideration of the pre-operatively calculated NLR may provide an early prognostic indicator for breast cancer outcomes and warrants further investigation. Citation Format: Williams GJ, Huws AM, Holt SDH, Sharaiha YM. Neutrophil lymphocyte ratio and breast cancer: A future prognostic indicator for outcome after surgery?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-01-07.
Abstract P6-17-09: Whole brain radiation therapy (WBRT) with or without concurrent temozolomide for brain metastases in breast cancer patients
Authors: WM El-Sadda, II Abdel-Halim, MM El-Ibrashi, MM Magdi
Journal: Cancer Research (2016)

Abstract Background: Breast cancer remains the second leading cause of CNS metastases. HER2 positive and triple negative subtypes are especially and independently at higher risk of developing brain metastases. Although surgical resection and radiosurgery may play a role in the management of selected cases, whole brain radiation therapy remains the standard treatment but with limited efficacy. Temozolomide (TMZ); an oral alkylating agent that cross the blood brain barrier has shown radiosensitizing characteristics as well as synergistic effects of radiation therapy (RT). The aim of the study was to assess the efficacy and safety of WBRT with concomitant TMZ in treatment of brain metastases in breast cancer patients. Patients and methods: A prospective randomized study included 60 patients with newly diagnosed brain metastases (BMs) from breast cancer not candidate for surgical resection or radiosurgery. All patients received WBRT 30 Gy/10 fractions with or without TMZ, administered at a dosage of 75 mg/m2/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment defined as partial response (PR) or complete response (CR) on brain MRI (WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurological symptoms and tolerability. Results: Between October 2011 and October 2013, 60 patients were enrolled in the study, 30 patients received WBRT+TMZ (group A) and 30 patients received WBRT (group B). Median age was 54 years (30-65), median follow up was 10.4 months (3-36). ORR was 80% in the WBRT+TMZ arm versus 50% in the WBRT (p = 0.017). The median PFS were 11.8 versus 5.8 respectively (p = 0.005). The median OS was 13.8 for group A and 10.8 for group B (p = 0.59). WBRT+TMZ was well tolerated with mostly grade 2 non-hematologic toxicity; headache, nausea &amp; vomiting were 6%, 15% &amp; 12% in group A versus 12%, 9% &amp; 6% in group B, respectively. While the most evident hematologic toxicity recorded was lymphopenia grade 2 &amp; 3 (15% &amp; 12% in group A) and (12% &amp; 9% in group B). No grade 4 toxicities were noted. Conclusion: WBRT plus TMZ improve local control and response rate of BMs from breast cancer, which was reflected by improved PFS. Citation Format: El-Sadda WM, Abdel-Halim II, El-Ibrashi MM, Magdi MM. Whole brain radiation therapy (WBRT) with or without concurrent temozolomide for brain metastases in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-09.
Endoscopic ultrasound-guided pancreatic duct drainage: technical approaches to a challenging procedure
Authors: Yen-I Chen, Payal Saxena, Saowanee Ngamruengphong, Yamile Haito-Chavez, Majidah Bukhari, Everson Artifon, Mouen Khashab
Journal: Endoscopy (2016)

Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD) is an effective treatment modality for pancreatic pathologies, including chronic pancreatitis, major or minor papilla inaccessible via endoscopic retrograde cholangiopancreatography, and postsurgical pancreaticoenterostomy stricture [1] [2]. Technically, however, EUS-PDD can be very difficult and is potentially associated with significant complications [3]. The following series of videos aims to improve the understanding and performance of EUS-PDD by describing the three approaches to this challenging procedure ([Video 1]): the transluminal stenting, anterograde drainage, and rendezvous method. To our knowledge, this is the first published video series focused on the different methods and steps of this intricate procedure.
Abstract IA04: Multifaceted functions of the PD-1 pathway
Authors: Arlene H. Sharpe
Journal: Cancer Research (2016)

Abstract The PD-1 co-inhibitory pathway is a key regulator of the critical balance between stimulatory and inhibitory signals needed for effective immune responses to microbes and tumors, as well self-tolerance. This pathway consists of the inhibitory Programmed Death (PD)-1 receptor and its two ligands, PD-L1 (B7-H1; CD274) and PD-L2 (B7-DC; CD273). PD-1 is inducibly expressed on T cells, and its ligands have distinct expression patterns. PD-L1 is broadly expressed on hematopoietic and non-hematopoietic cells, whereas PD-L2 is inducibly expressed primarily on DCs and macrophages. In this talk, mechanisms by which the PD-1:PD-L pathway regulates optimal immune homeostasis and tolerance will be discussed. In addition, the functions of PD-1 pathway in controlling humoral immune responses will be discussed, and compared to the functions of CTLA-4 in regulating humoral immunity. Citation Format: Arlene H. Sharpe. Multifaceted functions of the PD-1 pathway. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA04.