tbuckley/cabot-search huggingface dataset:
Abstract P2-01-15: Inflammatory breast cancer cells are characterized by attenuated SMAD dependent TGFβ signaling leading to impaired cell motility responses
Authors: C Rypens, C Van Berckelaer, C Billet, J Hauspy, F Bertucci, V Peter, L Dirix, S Van Laere
Journal: Cancer Research (2019)

Abstract Introduction.Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer with elevated metastatic potential, characterized by the frequent presence of tumor emboli in dermal and parenchymal lymph vessels. In the past, evidence was provided that TGFβ signaling is part of the molecular biology of this disease. In this study, this relation was further examined. Materials and methods. TGFβ1 induced cell motility (i.e. XCELLigence, wound healing assays), gene expression (RNA-sequencing) and peptide phosphorylation (i.e. PAMGene technology) patterns were investigated in a panel of 3 IBC and 3 subtype-matched nIBC cell lines. In addition, a series of tissue samples from 75 and 135patients with and without IBC was investigated for nuclear expression of total SMAD2, SMAD3 and SMAD4 using immunohistochemistry. Finally, SMAD protein expression data were related to gene expression data from patients with available Affymetrix HGU133plus2 profiles. Results. The cell motility inducing capacity of TGFβ1 was strongly abrogated in all IBC cells independent of their molecular subtype (P=0.003). Genes differentially expressed between IBC and nIBC cells post 4 hours of TGFβ1 revealed attenuated expression of SMAD3 transcriptional regulators with concomitant overexpression of MYC target genes in IBC. Assessment of SMAD expression in patient samples demonstrated a near absence of nuclear SMAD3 expression in the primary tumors from patients with IBC (P&amp;lt;0.001) and a further reduction of SMAD3 staining intensity was observed in tumor emboli (P=0.019). Integrated analysis of gene and protein expression data revealed that a substantial fraction of the IBC signature genes correlated with SMAD3 and these genes (i.e. 21/24; P&amp;lt;0.001) carry evidence in favor of attenuated SMAD3 signaling in IBC. Discussion. It is demonstrated that IBC cells are characterized by attenuated SMAD3 protein expression and transcriptional activity that obliterates the cell motility inducing capacity of TGFβ1. Recent studies revealed that SMAD3 is essential for TGFβ1 induced cell motility through induction of epithelial to mesenchymal transition (EMT). In the absence of SMAD3 expression, a partial EMT is induced leading to collectively invading cancer cells that are gifted with a high metastatic potential and favor lymphatic dissemination, thereby providing an intriguing explanatory model of the biology of tumor emboli in IBC. Citation Format: Rypens C, Van Berckelaer C, Billet C, Hauspy J, Bertucci F, Peter V, Dirix L, Van Laere S. Inflammatory breast cancer cells are characterized by attenuated SMAD dependent TGFβ signaling leading to impaired cell motility responses [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-15.
Rethinking T Cells in Pancreas Cancer
Authors: Benjamin D. Medina, George Miller
Journal: Clinical Cancer Research (2019)

Patients with pancreatic ductal adenocarcinoma do not benefit from checkpoint blockade. However, human tumors harbor evidence of adaptive immunity in clonally expanded T-cell populations. Immune intact modeling of human tumors identifies stromal sequestration as a mechanism of immune escape. Targeting the stroma combined with checkpoint blockade unleashes antitumor immunity.See related article by Seo et al., p. 3934.
Prophylactic Hypothermia for Severe Traumatic Brain Injury
Authors: Nicolas Engrand, Alexandre Pharaboz, Vera Dinkelacker
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract P5-16-17: Titanium-coated polypropylene mesh for immediate implant-based breast reconstruction – Our initial experience
Authors: A Munir, S Holt, A Huws, S Khan, Y Shariaha, S Khawaja
Journal: Cancer Research (2019)

Abstract Background: The use of titanium-coated polypropylene mesh (TCPM) is an alternative to a-cellular dermal matrix for the implant based breast reconstruction by providing extra implant coverage especially in the lower half. The aim of our study was to analyze short-term outcomes of TCPM based implant breast reconstruction and compare the patient- and procedure-related factors to implant loss and surgical complications. Methods: Between 2013and 2016, implant breast reconstructions after conservative mastectomies using TCMP was performed in 50 patients (with 58 reconstructions). Complications were divided into major (need for additional surgery), minor (conservative treatment), and implant loss. Univariate analyses were performed to determine the influence of the patient- and procedure-related factors on postoperative complications and implant loss. Results: Fifty patients had therapeutic mastectomies with 8 of them also had contra lateral risk reducing mastectomies. With median follow-up of 17.5 months, four of 50 patients had implant loss. Reasons for implant loss were skin necrosis in 2 cases, infection in 1 case and necrosis with infection in another case. One of these patients had a revised reconstruction one year later. One additional patient required implant replacement because of capsule contracture. No risk factors were observed for patient-associated complications. Univariate analysis revealed an increased risk for implant loss in patients with skin necrosis (p &amp;lt; 0.01). Conclusions: This titanium-coated polypropylene mesh shows acceptable complication rates and its use in immediate implant breast reconstruction is safe and effective. Citation Format: Munir A, Holt S, Huws A, Khan S, Shariaha Y, Khawaja S. Titanium-coated polypropylene mesh for immediate implant-based breast reconstruction – Our initial experience [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-16-17.
Abstract ES1-3: Advanced HER2-positive breast cancer: Overcoming treatment resistance
Authors: M Rimawi
Journal: Cancer Research (2019)

Abstract For two decades, HER2 has been an attractive therapeutic target. Anti-HER2 agents have transformed the care of HER2+ breast cancer and greatly improved its outcomes. However, treatment resistance remains a considerable clinical problem, and some patients still recur and progress despite optimal treatment. A particular challenge in advanced HER2+ breast cancer remains to be CNS metastasis. Special attention needs to be given to this devastating event given its serious sequelae, and its prevalence among patients battling this disease. As more agents are being approved in the early setting, improving outcomes in this setting, patients who suffer a recurrence may have more limited options and more resistant disease. The good news is that there is a number of anti-HER2 agents being explore in the advanced setting of HER2+ breast cancer. They fit into three major categories: new or optimized monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors. There is also great interest in studying other classes of agents in combination with anti-HER2 treatment, like immune-oncology agents, in this space. The plethora of agents being developed in this setting highlights the importance to understand more about potential mechanisms of resistance. This will help guide development strategies, deliver tailored treatment approaches, and design more effective agents and regimen. Resistance may be the end result of many possible molecular changes that mediate its emergence, and a variety of strategies are needed to elucidate them. That includes comprehensive in depth molecular profiling, as well as functional validation of detected alterations. Moreover, each tumor may have many underlying molecular changes in different cell sub-populations. It is therefore mandatory that development strategies for new agents and combinations should rely on clinical and biologic factors to help improve outcomes for patients with advanced HER2+ breast cancer. Citation Format: Rimawi M. Advanced HER2-positive breast cancer: Overcoming treatment resistance [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES1-3.
Practice Patterns of United States Military Ophthalmologists in Iraq and Afghanistan: 2002–2018
Authors: Jordan W. Winegar, Grant A. Justin, Matthew C. Caldwell, Christopher J. Calvano, John B. Cason, Elizabeth M. Hofmeister, Travis C. Frazier, Robert A. Mazzoli, Marcus H. Colyer, Brett W. Davies
Journal: Ophthalmology (2019)
The case for a national examination
Authors: Andrew Nanapragasam
Journal: BMJ (2013)

Medical education should, at least in theory, be of an equal standard across medical schools. In the United Kingdom, it falls to the General Medical Council to maintain this standard. Maintaining a similar level of knowledge at the 32 medical schools is a challenging task. It is achieved through annual self assessment carried out by the university and impromptu inspections by the GMC.1 The GMC’s Tomorrow’s Doctors outlines the core knowledge that any medical school must provide; it ensures that all junior doctors meet the criteria needed for qualification.

These guidelines, however, stop short of being too prescriptive. This encourages diversity among medical schools, permitting some universities to take a more traditional approach with a lecture based format, while others incorporate more modern problem based learning …
Зміни реологічних властивостей жовчі у пацієнтів з неалкогольною жировою хворобою печінки в поєднанні з гіперурикемією
Authors: A.S. Svintsitsky, N.P. Kozak, O.V. Barabanchyk
Journal: GASTROENTEROLOGY (2014)

Під час роботи проаналізовано результати дослідження колоїдних властивостей жовчі, біохімічні показники у пацієнтів з неалкогольною жировою хворобою печінки в поєднанні з гіперурикемією. Під час дослідження було виявлено, що на фоні підвищеного вмісту сечової кислоти відмічається порушення спектра жовчних кислот, зростання холевої та дезоксихолевої кислоти, зниження тауринової кислоти. Дисбаланс між цими показниками та закислення жовчі призводить до підвищення літогенних властивостей жовчі, що, у свою чергу, сприяє утворенню жовчних каменів. Застосування урсодезоксихолевої кислоти, розувастатину та алопуринолу у зазначених в дослідженні дозуваннях у хворих на неалкогольну жирову хворобу печінки в поєднанні з гіперурикемією сприяє покращенню клінічної симптоматики, нормалізації біохімічних показників, а також нормалізує спектр жовчних кислот.
Abstract PD1-07: Withdrawn
Authors: SJ Howell, S Waters, C Twelves, J Joffe, S Moon, C Bale, R Venkitaraman, P Bezecny, A Casbard, C Wilhelm-Benartzi, M Carucci, R Butler, F Alchami, R Jones
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Howell SJ, Waters S, Twelves C, Joffe J, Moon S, Bale C, Venkitaraman R, Bezecny P, Casbard A, Wilhelm-Benartzi C, Carucci M, Butler R, Alchami F, Jones R. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD1-07.
Limits to Compensatory Mutations: Insights from Temperature-Sensitive Alleles
Authors: Katarzyna Tomala, Piotr Zrebiec, Daniel L Hartl
Journal: Molecular Biology and Evolution (2019)

Previous experiments with temperature-sensitive mutants of the yeast enzyme orotidine 5'-phosphate decarboxylase (encoded in gene URA3) yielded the unexpected result that reversion occurs only through exact reversal of the original mutation (Jakubowska A, Korona R. 2009. Lack of evolutionary conservation at positions important for thermal stability in the yeast ODCase protein. Mol Biol Evol. 26(7):1431-1434.). We recreated a set of these mutations in which the codon had two nucleotide substitutions, making exact reversion much less likely. We screened these double mutants for reversion and obtained a number of compensatory mutations occurring at alternative sites in the molecule. None of these compensatory mutations fully restored protein performance. The mechanism of partial compensation is consistent with a model in which protein stabilization is additive, as the same secondary mutations can compensate different primary alternations. The distance between primary and compensatory residues precludes direct interaction between the sites. Instead, most of the compensatory mutants were clustered in proximity to the catalytic center. All of the second-site compensatory substitutions occurred at relatively conserved sites, and the amino acid replacements were to residues found at these sites in a multispecies alignment of the protein. Based on the estimated distribution of changes in Gibbs free energy among a large number of amino acid replacements, we estimate that, for most proteins, the probability that a second-site mutation would have a sufficiently large stabilizing effect to offset a temperature-sensitive mutation in the order of 10-4 or less. Hence compensation is likely to take place only for slightly destabilizing mutations because highly stabilizing mutations are exceeding rare.
Testicular torsion: acute testicular pain in a teenage boy
Authors: Paul Cullis, Justin Gould, Marc Cendron
Journal: BMJ (2010)

Test your knowledge with our picture quiz A 14 year old boy presented to the emergency department with a three hour history of left sided testicular pain. The pain had woken him and had worsened over time. He said that ibuprofen helped to alleviate the pain slightly. He described the pain as severe, aching in character, and non-radiating. He denied experiencing other symptoms, prior episodes of testicular discomfort, or recent trauma. He was otherwise healthy except for anxiety, for which he took a regular anxiolytic. On physical examination the left testis and epididymis were enlarged and tender, with a normal axis. Also, the cremasteric reflex was apparent on the right side but could not be elicited on the left. He subsequently had a scrotal ultrasound scan.
British medical students killed on elective in Borneo
Authors: Poonam Jani
Journal: BMJ (2014)

Two medical students studying at Newcastle University have been stabbed to death while on elective in Kuching, Borneo.

Fourth years Aidan Brungar, aged 22, and Neil Dalton, 23, who were on a six week placement at Sarawak General Hospital, were attacked after an altercation with four local men as they returned to their hostel after a night out.

Malaysian police said the students were killed on Wednesday 6 August at 04:15 local time after an earlier argument at a local bar in the Jalan Padungan region, the Guardian …
An atypical pneumonia
Authors: Sabina Patel, Laura Byrne, Simon Limb
Journal: BMJ (2011)

A 47 year old Zimbabwean woman presented with gradual onset shortness of breath of two months’ duration. She was breathless at rest, with a non-productive cough, and had had a fever for one week. She had no history of haemoptysis or night sweats but had lost 5 kg in weight over two months. No cardiac symptoms were elicited. She had no previous medical problems, history of smoking, or recent foreign travel.

On examination, she had a regular pulse of 122 beats per minute and a respiratory rate of 22 breaths per minute. Her temperature was 39°C and she had an oxygen saturation of 91% on air. There was no palpable lymphadenopathy. Her chest was resonant to percussion, with vesicular breath sounds and no added sounds. Examination of all other systems was normal. A chest radiograph was taken. 

(1) Describe the chest radiograph findings.

(2) What is the differential diagnosis and most likely diagnosis?

(3) …
Mucinous colorectal adenocarcinoma: clinical pathology and treatment options
Authors: Cong Luo, Shuyi Cen, Guojun Ding, Wei Wu
Journal: Cancer Communications (2019)

Abstract Mucinous colorectal adenocarcinoma is a distinct subtype of colorectal cancer (CRC) characterized by the presence of abundant extracellular mucin which accounts for at least 50% of the tumor volume. Mucinous colorectal adenocarcinoma is found in 10%–20% of CRC patients and occurs more commonly in female and younger patients. Moreover, mucinous colorectal adenocarcinoma is more frequently located in the proximal colon and diagnosed at an advanced stage. Based on its molecular context, mucinous colorectal adenocarcinoma is associated with the overexpression of mucin 2 (MUC2) and mucin 5AC (MUC5AC) proteins. At the same time, it shows higher mutation rates in the fundamental genes of the RAS/MAPK and PI3K/Akt/mTOR pathways. Mucinous colorectal adenocarcinoma also shows higher rates of microsatellite instability (MSI) than non‐mucinous colorectal adenocarcinoma which might correlate it with Lynch syndrome and the CpG island methylator phenotype. The prognosis of mucinous colorectal adenocarcinoma as to non‐mucinous colorectal adenocarcinoma is debatable. Further, the impaired responses of mucinous colorectal adenocarcinoma to palliative or adjuvant chemotherapy warrant more studies to be performed for a specialized treatment for these patients. In this review, we discuss the molecular background and histopathology of mucinous colorectal adenocarcinoma, and provide an update on its prognosis and therapeutics from recent literatures.
First Situational Judgement Test was a “success,” claims foundation programme
Authors: Chris Thomas
Journal: BMJ (2013)

The first round of Situational Judgement Tests (SJTs) has been declared a “success” by the Foundation Programme Office, the body that administrates the test. The SJT was introduced this year for all applicants to the foundation programme, which allocates first year junior doctor jobs in the UK.

The SJT—which replaces the previous method of assessment, white space questions—requires candidates to read through clinical scenarios and rank a set of given actions in order of preference. The test took place in December 2012 and January 2013, with two main sittings and one contingency sitting. Every UK medical school took part, with most candidates (99.4%) completing the test on the first sitting. Thirteen medical schools reported 100% attendance at the first sitting.

The …
Mitochondria in Sepsis-Induced AKI
Authors: Jian Sun, Jingxiao Zhang, Jiakun Tian, Grazia Maria Virzì, Kumar Digvijay, Laura Cueto, Yongjie Yin, Mitchell H. Rosner, Claudio Ronco
Journal: Journal of the American Society of Nephrology (2019)

AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%–80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI.
Abstract 15783: Reduction in Hepatic Tristetraprolin Increases Oxidative Metabolism and Protects Against High-Fat Diet Induced Diabetes
Authors: Jason S Shapiro, Konrad T Sawicki, Sumeyye Yar, Chunlei Chen, Hossein Ardehali
Journal: Circulation (2015)

Introduction: Type II diabetes mellitus (T2DM) is a growing health problem affecting over 29 million Americans and individuals with T2DM have increased mortality after myocardial infarction and stroke. Thus, it is imperative to find novel treatments for diabetes to offset the increased risk of cardiovascular disease (CVD) related mortality. Tristetraprolin (TTP) is an mRNA binding protein first identified as an insulin responsive gene. It binds to AU-rich elements (AREs) in the 3’ untranslated region (UTR) of certain transcripts and promotes their degradation. Reduced TTP expression has been observed in human patients with obesity and insulin resistance, and computational analysis suggests that TTP may bind to and degrade the mRNA of key enzymes involved in glucose oxidation. Thus, we hypothesized that downregulation of TTP would increase glucose oxidation and protect against T2DM. Results: We found hepatic expression of TTP to be decreased in diabetic mice. Using an in silico analysis to identify mRNAs that are targeted by TTP and play a role in glucose metabolism, we identified the pyruvate dehydrogenase-E2 subunit (PDH-E2) to contain several conserved TTP binding sites in its 3’ UTR. PDH-E2 expression was significantly increased (mRNA &gt; 1.4-fold; protein &gt; 2-fold) in hepatocytes isolated from liver-specific TTP knockout (KO) mice. Furthermore, measurement of PDH-E2 mRNA stability showed that PDH-E2 mRNA is significantly stabilized with TTP deletion, indicating that TTP regulates PDH-E2 mRNA. We then assessed whether the regulation of PDH-E2 by TTP alters glucose metabolism. Using Seahorse, we found a 1.7-fold increase in oxidative metabolism in TTP KO cells fed with glucose and pyruvate. This increase was reversed with siRNA mediated downregulation of PDH-E2. Systemically, liver-specific TTP KO mice fed a high-fat diet had significantly lower blood glucose levels after glucose tolerance tests and insulin tolerance tests. Conclusion: Our results suggest that a decrease in TTP protects against the development of T2DM by increasing PDH-E2 expression and subsequent glucose oxidation in the liver. Together, these data provide a novel, potential therapeutic target for T2DM, a significant modifiable risk factor contributing to CVD mortality.