tbuckley/cabot-search huggingface dataset:
Update: Noncongenital Zika Virus Disease Cases — 50 U.S. States and the District of Columbia, 2016
Authors: Victoria Hall, William L. Walker, Nicole P. Lindsey, Jennifer A. Lehman, Jonathan Kolsin, Kimberly Landry, Ingrid B. Rabe, Susan L. Hills, Marc Fischer, J. Erin Staples, Carolyn V. Gould, Stacey W. Martin
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Zika virus is a flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections also have been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-3). Most Zika virus infections are asymptomatic or result in mild clinical illness, characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis; Guillain-Barré syndrome, meningoencephalitis, and severe thrombocytopenia rarely have been associated with Zika virus infection (1). However, congenital Zika virus infection can result in fetal loss, microcephaly, and other birth defects (1,2). In 2016, a total of 5,168 noncongenital Zika virus disease cases were reported from U.S. states and the District of Columbia. Most cases (4,897, 95%) were in travelers returning from Zika virus-affected areas. A total of 224 (4%) cases were acquired through presumed local mosquitoborne transmission, and 47 (1%) were acquired by other routes. It is important that providers in the United States continue to test symptomatic patients who live in or recently traveled to areas with ongoing Zika virus transmission or had unprotected sex with someone who lives in or traveled to those areas. All pregnant women and their partners should take measures to prevent Zika virus infection during pregnancy. A list of affected areas and specific recommendations on how to prevent Zika virus infection during pregnancy are available at https://www.cdc.gov/pregnancy/zika/protect-yourself.html.
THE ROLE OF MITRAL REGURGITATION, LEFT ATRIAL DYNAMICS, AND RIGHT VENTRICULAR TO PULMONARY CIRCULATION COUPLING DURING EXERCISE ON CARDIOPULMONARY EXERCISE PERFORMANCE IN LEFT HEART DISEASE
Authors: Tadafumi Sugimoto, Francesco Bandera, Greta Generati, Eleonora Alfonzetti, Vincenzo Tufaro, Marco Guazzi
Journal: Journal of the American College of Cardiology (2018)
Antibiotic use and outcomes with systemic therapy in metastatic renal cell carcinoma (mRCC).
Authors: Aly-Khan A. Lalani, Wanling Xie, Xun Lin, John A. Steinharter, Dylan J. Martini, Audrey Duquette, Dominick Bosse, Rana R. McKay, Ronit Simantov, Xiao X. Wei, Bradley A McGregor, Lauren Christine Harshman, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2018)

607 Background: Antibiotic (Abx) use is shown to alter commensal gut microbiota, a key regulator of immune homeostasis. We conducted the largest investigation to date on the impact of Abx use on outcomes in mRCC patients treated with systemic agents. Methods: Two cohorts were analyzed: an institutional cohort (DFCI, n = 146) of patients receiving PD-1/PD-L1-based immune checkpoint inhibitors (ICI), and an external cohort from pooled phase II/III clinical trials (Pfizer, n = 4144) of patients treated with interferon (IFN, n = 510), mTOR inhibitors (n = 660), and VEGF inhibitors (n = 2974). Abx use was defined as Abx treatment at any time between 8-weeks pre- and 4-weeks post the start of systemic therapy. We examined the associations of Abx use and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using Cox/logistic regression models, adjusted for prognostic factors including risk groups. Results: In the DFCI cohort, 15% had non-clear cell histology, 43% had first-line ICI, 45% had combotherapy. Baseline characteristics were balanced between Abx users (n = 31, 21%) and non-users (p &gt; 0.15). Abx users had a lower ORR (12.9 vs 34.8%, p = 0.026) and shorter PFS compared to non-users (Table). In the external cohort, Abx users (n = 709) had lower ORR (19.3 vs 24.2%, p = 0.005). IFN treated patients (current or prior cytokines) had worse OS if they received Abx compared to those who did not. However, there was no OS difference by Abx use in mTOR or VEGF treated patients without prior cytokines. Conclusions: Abx use was independently associated with worse outcomes in mRCC patients receiving contemporary ICI or historic cytokine immunotherapy. We hypothesize that concurrent use of Abx may reduce the efficacy of ICI due to a complex interplay with the host microbiome. [Table: see text]
GPs in Northern Ireland to receive 1% pay uplift under contract agreement
Authors: Abi Rimmer
Journal: BMJ (2014)

Changes to the GP contract in Northern Ireland have been agreed for 2014-15, including a 1% pay uplift and the removal of 263 points from the Quality and Outcomes Framework (QOF).

As part of the changes, agreed by the British Medical Association’s Northern Ireland General Practitioners Committee and the Northern Ireland government, the QOF was reduced to a total of 649 points. The removal of 263 points equates to approximately £13m that will be transferred into the …
Diploma in Mountain Medicine (DMM)
Authors: Mike Brookes
Journal: BMJ (2005)

Any doctor interested in mountains, whether it be high altitude research, expedition medicine, mountain rescue, pre-hospital care in a hazardous environment, or just plain mountaineering.

2004 as a GP trainee.

I am interested in pre-hospital medicine and wilderness medicine; I am a doctor for a mountain rescue team and have participated in several expeditions to remote areas as a services doctor and mountain leader. Having experienced at first hand several altitude related illnesses I thought it appropriate to learn about the pathophysiology, prevention, and treatment strategies to …
Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide
Authors: Adam Vandergriff, Ke Huang, Deliang Shen, Shiqi Hu, Michael Taylor Hensley, Thomas G. Caranasos, Li Qian, Ke Cheng
Journal: Theranostics (2018)

Rationale: Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies. Recent studies have used intramyocardial injection in order to concentrate exosomes in the infarct. Though effective in a research setting, this method is not clinically appealing due to its invasive nature. We propose the use of a targeting peptide, cardiac homing peptide (CHP), to target intravenously-infused exosomes to the infarcted heart. Methods: Exosomes were conjugated with CHP through a DOPE-NHS linker. Ex vivo targeting was analyzed by incubating organ sections with the CHP exosomes and analyzing with fluorescence microscopy. In vitro assays were performed on neonatal rat cardiomyocytes and H9C2 cells. For the animal study, we utilized an ischemia/reperfusion rat model. Animals were treated with either saline, scramble peptide exosomes, or CHP exosomes 24 h after surgery. Echocardiography was performed 4 h after surgery and 21 d after surgery. At 21 d, animals were sacrificed, and organs were collected for analysis. Results: By conjugating the exosomes with CHP, we demonstrate increased retention of the exosomes within heart sections ex vivo and in vitro with neonatal rat cardiomyocytes. In vitro studies showed improved viability, reduced apoptosis and increased exosome uptake when using CHP-XOs. Using an animal model of ischemia/reperfusion injury, we measured the heart function, infarct size, cellular proliferation, and angiogenesis, with improved outcomes with the CHP exosomes. Conclusions: Our results demonstrate a novel method for increasing delivery of for treatment of myocardial infarction. By targeting exosomes to the infarcted heart, there was a significant improvement in outcomes with reduced fibrosis and scar size, and increased cellular proliferation and angiogenesis.
Identification of HLA-A0201 restricted epitope of novel cancer/testis antigens VCX/Y and generation of antigen-specific T-cell receptor engineered T cells for treatment of solid tumor malignancies.
Authors: Ke Pan, Cassian Yee
Journal: Journal of Clinical Oncology (2018)

160 Background: To identify HLA-A0201 restricted epitope of novel cancer/testis antigen VCX/Y, generate antigen specific T cells and T-cell receptor (TCR) engineered T cells for adoptive cell therapy (ACT) of solid cancer patients. Methods: Reverse-immunology method was used to identify HLA-A0201 restricted epitope of VCX/Y. The high binding score peptide or whole length of VCX3A mRNA were pulsed or transfected to mature dendritic cells (mDC) from HLA-A0201+ donor and then stimulated autologous naïve T cells. Tetramer guided sorting were performed to purify the epitope specific T cells and CTL clones were generated with limiting dilution. TCR were cloned out from high activity CTL clone and the recombinant of retrovirus vector were constructed to introduce the TCR to allogeneic PBMC to generate the TCR engineered T cells. Results: One peptide which its sequence was shared with all VCX/Y members was identified. Interesting, only CTL clone generated from simulation of VCX3A mRNA transfected DC can recognize naturally processed VCX/Y presented by HLA-A0201+ tumor cells. Cold target inhibition detection confirmed that this VCX/Y peptide was naturally processed and recognized by HLA-A0201+ CTL clone. After infection of retrovirus containing the TCR from high activity of CTL clone, the TCR engineered T cells can recognize HLA-A2+ tumor cells but not normal lung cells. Moreover, these TCR engineered T cells specifically secreted IFN-γ in response to T2 cells pulsed with peptide, as well as HLA-A0201+ and VCX/Y overexpressed tumor cells. Conclusions: VCX/Y peptide we identified is a novel candidate peptide antigen for vaccine or for endogenous adoptive T cell therapy. The correlated high activity TCR gene can generate TCR engineered T cells from patients with anti-tumor activity and offer an alternative adoptive T cell treatment for patients with VCX/Y expressing solid tumor malignancies.
Protease/protease inhibitor balance in blood plasma to predict postoperative complications in operated patients with pancreatic head cancer.
Authors: Oleg Ivanovich Kit, Elena Frantsiyants, Larisa S. Kozlova, Valeria A. Bandovkina, Evgeniy N. Kolesnikov, Mikhail Anatolievich Kozhushko, Tanzila Beksultanovna Kazieva, Michail Averkin, Vladimir Trifanov
Journal: Journal of Clinical Oncology (2018)

258 Background: Our purpose was to study the protease/protease inhibitor (P/PI) balance in the blood plasma of patients with cancer of the head of the pancreas before and after pancreatoduodenal resection (PDR) with postoperative complications. Methods: The study was performed using clinical observation, biochemical examinations and statistical analysis in Microsoft Office Excel 2010. The blood plasma of 92 patients with pancreatic head cancer (53 men and 39 women aged 45-76 years, Т 2-4 N 0 M 0 ) was studied before the surgery (b/s) and on days 1, 7, 14 and 17 after PDR. The patients were divided into two groups: g1 – 69 patients without postoperative (p/o) complications and g2 – 23 patients with p/o complications: generalization – 7, thrombosis - 8, acute postoperative pancreatitis - 2, gastrostasis - 2, anastomotic leakage - 4 patients. Kinetics of trypsin-like proteases (TLP) and α-1-proteinase inhibitor (α1PI) was studied by spectrophotometry. The data were compared with the blood plasma of 39 healthy donors (N). Results: TLP activity b/s exceeded N in g1 and g2 by 4.1 and 10.6 times; TLP in g2 was 2.6 times higher than in g1. The α1PI activity b/s was higher than N by 1.2 times (p &lt; 0.05) in g1 and lower than N by 2.0 times in g2; α1PI in g2 was 2.4 times lower than in g1. After PDR, activity of TLP increased in all patients on day 1 but decreased on days 7-14 in g1 remaining 2.7 times higher than N by the discharge. The TLP activity in g2 by the discharge was similar to levels b/s and exceeded g1 by 4.4 and N by 12.1 times. The α1PI activity after PDR increased in all patients on days 1-17, but in g1 by the discharge it was similar to N and in g2 it was 1.5 times lower than N. The TLP/α1PI ratio was higher in g2 than in g1 at all times. Conclusions: A high TLP activity and a low α1PI activity, compared to N, were maintained in the blood plasma of all patients with p/o complications, despite their types. The P/PI balance in g2 was shifted to the left being 5.5-9.0 times higher than in g1 at all times which allowed the prognosis of postoperative complications before the surgery, perioperatively or on day 1 after the surgery.
Direct‐acting antiviral sustained virologic response: Impact on mortality in patients without advanced liver disease
Authors: Lisa I. Backus, Pamela S. Belperio, Troy A. Shahoumian, Larry A. Mole
Journal: Hepatology (2018)

The impact of sustained virologic response (SVR) on mortality after direct-acting antiviral (DAA) treatment is not well documented in patients without advanced liver disease and affects access to treatment. This study evaluated the impact of SVR achieved with interferon-free DAA treatment on all-cause mortality in hepatitis C virus-infected patients without advanced liver disease. This observational cohort analysis was comprised of 103,346 genotype 1, 2, and 3, hepatitis C virus-monoinfected patients without advanced liver disease, defined by FIB-4 ≤3.25 and no diagnosis of cirrhosis, hepatic decompensation, or hepatocellular carcinoma or history of liver transplantation, identified from the Veterans Affairs Hepatitis C Clinical Case Registry. Among 40,664 patients treated with interferon-free DAA regimens, 39,374 (96.8%) achieved SVR and 1,290 (3.2%) patients were No SVR; 62,682 patients constituted the untreated cohort. The mortality rate for SVR patients of 1.18 deaths/100 patient-years was significantly lower than the rates for both No SVR patients (2.84 deaths/100 patient-years; P < 0.001) and untreated patients (3.84 deaths/100 patient-years; P < 0.001). SVR patients with FIB-4 <1.45 and 1.45-3.25 had a 46.0% (P = 0.036) and 63.2% (P < 0.001) reduction in mortality rates, respectively, compared to No SVR patients and 66.7% (P < 0.001) and 70.6% (P < 0.001) reduction in mortality rates, respectively, compared to untreated patients. In multivariate Cox proportional hazard models controlling for baseline demographics, clinical characteristics, and comorbidities, SVR was independently associated with reduced risk of death compared to No SVR (hazard ratio, 0.44; 95% confidence interval, 0.32-0.59; P < 0.001) and compared to untreated patients (hazard ratio, 0.32; 95% confidence interval, 0.29-0.36; P < 0.001).Successfully treating hepatitis C virus with DAAs in patients without clinically apparent advanced liver disease translates into a significant mortality benefit. (Hepatology 2018).
I am an A level student wanting a career in medical research. Would a degree in medicine or one in an academic discipline, such as physiology, be more useful? If I were to opt for medicine, would it be a problem that I have little intention of becoming a doctor and therefore little evidence that I am interested in the field?
Authors: Howard Clark
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
I wish to become a hepatologist. Is there training in the United Kingdom for this alone or must I also study luminal gastroenterology and internal medicine?
Authors: Alan R Watson
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
The president of the Royal College of Surgeons of England
Authors: Leyla Sanai
Journal: BMJ (2006)

Bernie Ribeiro qualified in medicine at the University of London in 1967, and after house jobs in the Middlesex Hospital and St Alban9s he trained as a surgical registrar at Orsett General Hospital in Essex. He was elected as president of the Royal College of Surgeons in May 2005 and took office in July 2005. He retains clinical commitments as consultant general surgeon at Basildon and Thurrock General Hospital
Postoperative chemotherapy in patients who are pN+ following neoadjuvant chemoradiation for locally advanced esophageal cancer.
Authors: Samual Francis, Christopher Duane Nevala-Plagemann, Courtney Christine Cavalieri, Shane Lloyd, Ignacio Garrido-Laguna
Journal: Journal of Clinical Oncology (2018)

97 Background: Esophageal cancer survival rates have improved since the widespread adoption of neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy for patients who present with locally advanced disease. Unfortunately, overall prognosis for these patients remains poor. In this study, we sought to assess the effect of additional adjuvant chemotherapy in patients who have positive lymph nodes (pN+) following surgery. Methods: Using the National Cancer Database we retrospectively identified all patients with locally advanced esophageal cancer who received neoadjuvant CRT from 2004 to 2014. We then identified patients within this dataset who were found to be pN+ following neoadjuvant chemoradiation and esophagectomy and categorized them as having received adjuvant chemotherapy versus no additional chemotherapy. Survival analysis was performed using Kaplan-Meier estimation and propensity score matching. Results: 2,045 patients were identified as being pN+ following neoadjuvant CRT. Within this group, 14% received adjuvant chemotherapy. The 1, 5, and 8 year overall survival (OS) of patients receiving adjuvant therapy was 87%, 30%, and 21% compared to 76%, 23%, and 16% in those receiving neoadjuvant therapy alone, respectively (p = 0.0017). After a propensity score matched analysis, median OS was found to be significantly longer in the those receiving neoadjuvant CRT plus adjuvant chemotherapy compared to neoadjuvant CRT alone (27.8 months vs 22.2 months; HR 0.78; 95% CI, 0.62 to 0.97; p = 0.032). Conclusions: While not currently the standard of care, our data suggests that adjuvant chemotherapy may improve survival in patients with locally advanced esophageal cancer who are found to be pN+ following surgery. Additional prospective studies are needed to confirm this finding.
Protein targeting chimeric molecules specific for bromodomain and extra-terminal motif family proteins are active against pre-clinical models of multiple myeloma
Authors: Xiaohui Zhang, Hans C. Lee, Fazal Shirazi, Veerabhadran Baladandayuthapani, Heather Lin, Isere Kuiatse, Hua Wang, Richard J. Jones, Zuzana Berkova, Ram Kumar Singh, Jing Lu, Yimin Qian, Kanak Raina, Kevin G. Coleman, Craig M. Crews, Bingzong Li, Huihan Wang, Yared Hailemichael, Sheeba K. Thomas, Zhiqiang Wang, R. Eric Davis, Robert Z. Orlowski
Journal: Leukemia (2018)
Expression of Adipocyte/Macrophage Fatty Acid–Binding Protein in Tumor-Associated Macrophages Promotes Breast Cancer Progression
Authors: Jiaqing Hao, Fei Yan, Yuwen Zhang, Ashley Triplett, Ying Zhang, Debra A. Schultz, Yanwen Sun, Jun Zeng, Kevin A.T. Silverstein, Qi Zheng, David A. Bernlohr, Margot P. Cleary, Nejat K. Egilmez, Edward Sauter, Shujun Liu, Jill Suttles, Bing Li
Journal: Cancer Research (2018)

Abstract Tumor-associated macrophages (TAM) play a critical role in cancer development and progression. However, the heterogeneity of TAM presents a major challenge to identify clinically relevant markers for protumor TAM. Here, we report that expression of adipocyte/macrophage fatty acid–binding protein (A-FABP) in TAM promotes breast cancer progression. Although upregulation of A-FABP was inversely associated with breast cancer survival, deficiency of A-FABP significantly reduced mammary tumor growth and metastasis. Furthermore, the protumor effect of A-FABP was mediated by TAM, in particular, in a subset of TAM with a CD11b+F4/80+MHCII−Ly6C− phenotype. A-FABP expression in TAM facilitated protumor IL6/STAT3 signaling through regulation of the NFκB/miR-29b pathway. Collectively, our results suggest A-FABP as a new functional marker for protumor TAM. Significance: These findings identify A-FABP as a functional marker for protumor macrophages, thus offering a new target for tumor immunotherapy. Cancer Res; 78(9); 2343–55. ©2018 AACR.
Oxford Handbook for the Foundation Programme
Authors: Mathi Rasanesan
Journal: BMJ (2005)

S Sanders, J Dawson, S Datta, S Eccles

Oxford University Press, 2005, £19.95, 500 pages.

ISBN 0 19 856789 8

Rating: ⋆⋆⋆⋆/5



It is a common sight to see the new bumbling house officer riffling through The Oxford Handbook of Clinical Medicine ( OHCM ), warmed in their back pocket, searching desperately for the answers to their forever demanding bleep. Taking the long way round to the wards when called to a “low urine output” and wondering how on earth to disclose to the ward sister that they have never written up “bowel prep.” …
INITIATION OF LOOP DIURETIC THERAPY IS ASSOCIATED WITH A LOWER RISK OF 30-DAY ALL-CAUSE READMISSION IN PATIENTS WITH HEART FAILURE NOT RECEIVING DIURETICS PRIOR TO HOSPITALIZATION
Authors: Syed Z. Qamer, Harish Jarrett, Phillip Lam, Helen Sheriff, Cherinne Arundel, Fahad K. Lodhi, Prakash Deedwania, Javed Butler, Gregg C. Fonarow, Ali Ahmed
Journal: Journal of the American College of Cardiology (2018)
JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/β-catenin/CCND1 signaling
Authors: Yaping Zhang, Fangzhen Xia, Xiaoye Liu, Zhuo Yu, Li Xie, Ligen Liu, Chiqi Chen, Haishan Jiang, Xiaoxin Hao, Xiaoxiao He, Feifei Zhang, Hao Gu, Jun Zhu, Haitao Bai, Cheng Cheng Zhang, Guo-Qiang Chen, Junke Zheng
Journal: Journal of Clinical Investigation (2018)

Leukemia-initiating cells (LICs) are responsible for the initiation, development, and relapse of leukemia. The identification of novel therapeutic LIC targets is critical to curing leukemia. In this report, we reveal that junctional adhesion molecule 3 (JAM3) is highly enriched in both mouse and human LICs. Leukemogenesis is almost completely abrogated upon Jam3 deletion during serial transplantations in an MLL-AF9–induced murine acute myeloid leukemia model. In contrast, Jam3 deletion does not affect the functions of mouse hematopoietic stem cells. Moreover, knockdown of JAM3 leads to a dramatic decrease in the proliferation of both human leukemia cell lines and primary LICs. JAM3 directly associates with LRP5 to activate the downstream PDK1/AKT pathway, followed by the downregulation of GSK3β and activation of β-catenin/CCND1 signaling, to maintain the self-renewal ability and cell cycle entry of LICs. Thus, JAM3 may serve as a functional LIC marker and play an important role in the maintenance of LIC stemness through unexpected LRP5/PDK1/AKT/GSK3β/β-catenin/CCND1 signaling pathways but not via its canonical role in cell junctions and migration. JAM3 may be an ideal therapeutic target for the eradication of LICs without influencing normal hematopoiesis.
TEMPORAL RELATIONSHIPS BETWEEN ESOPHAGEAL INJURY TYPE AND PROGRESSION IN PATIENTS UNDERGOING ATRIAL FIBRILLATION ABLATION
Authors: Bharath Yarlagadda, Mohit Turagam, Tawseef Dar, Swathi Paleti, Valay Parikh, Vaishnavi Veerapaneni, Madhu Reddy, Jeremy Ruskin, Douglas Packer, Andrea Russo, Moussa Mansour, Luigi Di Biase, Andrea Natale, Dhanunjaya R. Lakkireddy
Journal: Journal of the American College of Cardiology (2018)