tbuckley/cabot-search huggingface dataset:
Twenty Year Follow-Up of Reflux Oesophagitis: Long Term Consequences and Complications
Authors: N McDougall, H Lawther, J Collins
Journal: Endoscopy (2004)

Introduction: Reflux oesophagitis is the most common abnormal finding at OGD yet the long term outcome of the condition is unknown. This study assessed the level of reflux symptoms, drug consumption and complications in patients 20 years after diagnosis of oesophagitis.
Abstract 234: Mitofilin Directly Interacts With Cyclophilin D in the Inner Membrane of Heart Mitochondria
Authors: Jean C. Bopassa
Journal: Circulation Research (2015)

Introduction: We recently found that acute estrogen treatment delays the mitochondrial permeability transition pore (mPTP) opening and reduces ROS production after ischemia/reperfusion, suggesting that estrogen promotes mitochondrial integrity. As mitochondrial inner membrane protein (mitofilin) has been found to control mitochondrial cristae morphology and function, and cyclophylin-D is a mitochondrial peptidyl-prolyl isomerase known to modulate the opening of the mPTP, we investigated whether a direct interaction between these two proteins exist in the inner membrane of mitochondria. Methods: Western blot analysis and immunoprecipitation were performed in isolated heart mitochondrial fractions from male WT (C57BL/6NCrL) mice using mitofilin and cyclophilin-D monoclonal antibodies of. Mitofilin and cyclophylin-D distribution in isolated cardiomyocytes as well as in single mitochondria was also visualized using high resolution microscopy. Results: Western blot analysis shows that both mitofilin and cyclophilin-D proteins were abundantly expressed in the heart mitochondria. Immunoprecipitation with mitofilin antibody pulled down cyclophilin-D, which was detected by Western blot analysis. Co-immunoprecipitation with cyclophylin-D antibody confirms its direct association with mitofilin as mitofilin was detected by Western analysis in the immunoprecipitated product. High resolution microscopy revealed a higher degree of colocalization between mitofilin and cyclophylin-D in both cardiomyocytes and mitochondrial fractions. Conclusion: Together, these data indicate that mitofilin directly interacts with cyclophylin-D in the inner membrane of heart mitochondria. As mitofilin plays an important role in controlling mitochondrial cristae morphology and cyclophylin-D, known to modulate the opening of the mPTP, this interaction between mitofilin-cyclophilin-D may have an impact in the opening of the mPT pore.
Role of Platelet-Derived Tgfβ1 in the Progression of Ovarian Cancer
Authors: Qianghua Hu, Takeshi Hisamatsu, Monika Haemmerle, Min Soon Cho, Sunila Pradeep, Rajesha Rupaimoole, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Stephen T.C. Wong, Anil K. Sood, Vahid Afshar-Kharghan
Journal: Clinical Cancer Research (2017)

Purpose: Transforming growth factor β1 (Tgfβ1) plays an important role in cancer. Most of Tgfβ1 in plasma is from platelets; thus, we studied whether platelet Tgfβ1 has any role in the progression of ovarian cancer, and whether this role is limited to metastasis or also involves the growth of primary tumors.Experimental Design: We compared the growth of murine ovarian cancer cell-induced tumors in platelet-specific Tgfβ1-deficient mice and wild-type mice. Using resected tumor nodules, we studied the effect of platelet Tgfβ1 on neoangiogenesis and on platelet extravasation into tumors. To investigate the effect of Tgfβ1 at different stages of ovarian cancer, we reduced expression of Tgfβ1 receptor (its TgfβR1 component) in tumors at different time points after injection of cancer cells, and compared the final tumor size.Results: Lack of platelet Tgfβ1 in mice reduced tumor growth, neoangiogenesis, and platelet extravasation. Ovarian cancer tumors in platelet-specific Tgfβ1-deficient mice reached less than half of their size in wild-type littermates. Knockdown of TgfβR1 on cancer cells in the first 2 weeks after their injection reduced tumor growth, but was less effective if initiated after 3 weeks.Conclusions: We showed that platelet Tgfβ1 increased the growth of primary tumors in murine models of ovarian cancer. We also showed that inhibition of TgfβR1 is more effective in reducing the growth of ovarian cancer if initiated earlier. Our results supported a therapeutic benefit in preventing platelet activation, degranulation, and release of Tgfβ1 in ovarian cancer. Clin Cancer Res; 23(18); 5611-21. ©2017 AACR.
NHS pay cap is barrier to recruitment and retention, unions warn
Authors: Abi Rimmer
Journal: BMJ (2017)

The public sector pay cap is preventing the best people from being recruited and retained by the NHS, health unions have warned.

In a letter sent to prime minister Theresa May on 19 June, 16 organisations representing NHS and public sector staff warned that the pay cap had forced professionals out of their jobs.1 “Those who stay are overstretched and under pressure to do ever more with less,” the letter said.

The news comes after England’s health secretary Jeremy Hunt said that he had “sympathy” for calls to increase NHS pay and that he would put the case for lifting the …
The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis
Authors: Lei Xu, Xueying Mao, Tianyu Guo, Pui Ying Chan, Greg Shaw, John Hines, Elzbieta Stankiewicz, Yuqin Wang, R. Tim D. Oliver, Amar Sabri Ahmad, Daniel Berney, Jonathan Shamash, Yong-Jie Lu
Journal: Clinical Cancer Research (2017)

Purpose: To develop an approach for the investigation of different subtypes of circulating tumor cells (CTC) and other cells to evaluate their potential prognostic value of prostate cancer.Experimental Design: Malignancy of CTCs undergoing epithelial-to-mesenchymal transition (EMT) was confirmed by repeated FISH. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters. AUC analysis was applied to compare the performance for metastasis prediction between serum PSA level alone and a combined risk score using both PSA and EMTing CTC count. Circulating megakaryocytes and cancer patient survival association was performed using Cox model.Results: The majority of vimentin (VIM)+/CD45- cells were malignant, with genomic alterations in several genomic regions. The number of cytokeratin (CK)-/VIM+/CD45- CTCs correlated with disease burden, tumor aggressiveness, and poorer survival. Meanwhile, CK+/VIM+/CD45- CTCs were associated with metastases better than other subtypes of CTCs in these limited samples. Combination of PSA level and the number of CK+/VIM+/CD45- CTCs enhanced the prediction of cancer metastases [AUC, 0.921; 95% confidence interval (CI), 0.858-0.985]. The number of circulating megakaryocytes was potentially associated with good patient survival in advanced prostate cancer (HR, 0.849; 95% CI, 0.628-1.146, per cell increase), and the difference between the number of mesenchymal CTCs and megakaryocytes strongly correlated to poor survival (HR, 10.17; 95% CI, 2.164-47.789, if score ≥2.0).Conclusions: This CTC analysis approach and the potential association of megakaryocytes with cancer prognosis may greatly enhance our ability to investigate the cancer metastasis process and to predict/monitor cancer progression. Clin Cancer Res; 23(17); 5112-22. ©2017 AACR.
Interferon-Stimulated Gene Expression in Peripheral Blood Mononuclear Cell Subpopulations
Authors: S Behan, V Leroy, J Hegarty, C O'Farrelly
Journal: Endoscopy (2004)

Aim: Our aim was to assess expression of a panel of IFN-stimulated genes (ISGs) with direct anti-viral properties in cell lines representing peripheral blood cell subpopulations.
How are young women 18-24 counseled on hereditary breast and ovarian cancer (HBOC) testing?
Authors: Amy Abramowitz, Julia Rachel Trosman, Christine B. Weldon, Julian C. Schink, Melissa A Simon
Journal: Journal of Clinical Oncology (2014)

1546 Background: Women often learn about their HBOC risk before the age of 25 (Bradbury 2009), and women 18-24 are often interested in genetic testing (Werner-Lin 2012). While guidelines do not preclude this, they do not provide specific guidance on genetic counseling or testing for women 18-24 (18-24s). We aim to identify how genetic counselors (GCs) counsel these women, what challenges they experience, and how these challenges may be addressed. Methods: IRB approved interviews with GCs at NCCN centers. The framework approach of qualitative research and simple frequencies were used for analyses. Results: Phone interviews were conducted with GCs from 11 NCCN centers. Although 73% of GCs use age and life stage considerations in counseling, only 45% routinely recommend testing for 18-24s. Those who test 18-24s routinely, cite the following reasons: studies show these women handle testing with maturity; women need genetic information for family / health planning; some 18-24s are diagnosed with cancer; and women consider recommendation to wait until 25 paternalistic. GCs who do not routinely recommend testing to 18-24s (55%) cite these barriers: lack of screening guidelines for 18-24s beyond self-exams; concern that families coerce 18-24s into testing; and perceived lack of understanding of available options by 18-24s. However, 80% of those who do not routinely test 18-24s, may do so on exception: very young HBOC family history, patient requests testing multiple times and demonstrates understanding of implications, or a woman needs the information for family planning. GCs provided recommendations for improving the genetic services for 18-24s: formal training and standardized approach to counseling (55%), frequent and long term follow-up using a “medical home” model (45%), involvement of psychosocial and fertility specialists (27%), and access to 18-24 peer support (27%). Conclusions: Lack of guidelines on genetic counseling and testing of women 18-24 result in variability of HBOC counseling and testing practices and potentially sub-optimal care for these women. Counselors and patients would benefit from formalized guidelines and training on genetic assessment for women 18-24.
Mitochondrial DNA depletion induces innate immune dysfunction rescued by IFN-γ
Authors: John D. Widdrington, Aurora Gomez-Duran, Jannetta S. Steyn, Angela Pyle, Marie-Helene Ruchaud-Sparagano, Jonathan Scott, Simon V. Baudouin, Anthony J. Rostron, John Simpson, Patrick F. Chinnery
Journal: Journal of Allergy and Clinical Immunology (2017)

Sepsis is a clinical syndrome with increasing incidence and mortality in which a systemic inflammatory response is triggered by infection. The clinical outcome of sepsis is primarily determined by the host response; in particular, monocyte deactivation plays a key role in sepsis-induced immune suppression and contributes to mortality.1,2 While the underlying mechanisms of monocyte deactivation are not understood, there is increasing evidence that mitochondrial dysfunction contributes to the pathogenesis of sepsis.
IMpower132: A phase III clinical program—1L atezolizumab plus platinum-based chemotherapy in chemo-naive advanced non-squamous NSCLC.
Authors: Howard Jack West, Makoto Nishio, Manuel Cobo Dols, Haruhiro Saito, Michael Howland, Tien Hoang, Takashi Asakawa, Alan Sandler, Mark A. Socinski
Journal: Journal of Clinical Oncology (2017)

TPS9101 Background: Platinum-based chemotherapy (chemo) is the current standard of care for patients (pts) with newly diagnosed advanced non-squamous NSCLC. The combination of platinum-based chemo and pemetrexed (pem) provides comparable benefit to pts as other standard platinum doublets commonly used and has a favorable toxicity profile. However, the survival benefit conferred by this combination leaves considerable room for improvement. The anti–PD-L1 mAb atezolizumab (atezo) inhibits the interaction of PD-L1 with its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. In the OAK trial, pts with 2L/3L advanced NSCLC had improved mOS in the atezo arm (13.8 mo) vs the docetaxel arm (9.6 mo), with a survival benefit observed across PD-L1 expression levels. The potential for chemo to further augment responses to atezo, with tolerable safety, has also been demonstrated. A global, Phase III, randomized, open-label trial, IMpower132 (NCT02657434), is being conducted to evaluate 1L atezo + platinum-based chemo + pem in chemo-naive pts with stage IV NSCLC. Methods: Eligibility criteria include stage IV NSCLC, measurable disease (RECIST v1.1), no prior chemo and ECOG PS 0-1. Exclusion criteria include tumors known to harbor EGFR or ALK driver mutations, untreated CNS metastases, autoimmune disease and prior exposure to immunotherapy. Pts will be enrolled regardless of PD-L1 expression status and randomized to the treatment arms. Pts will be stratified by sex, ECOG PS, type of chemo (carboplatin [carbo] vs cisplatin [cis]) and smoking status. Pts will receive four or six 21-day cycles of either atezo + carbo/cis + pem or carbo/cis + pem. Following the induction phase, pts will receive maintenance atezo + pem or pem alone, depending on their allocated treatment regimen. Pts receiving atezo may continue until loss of clinical benefit.Co-primary endpoints are investigator-assessed PFS and OS. Secondary endpoints include IRF-assessed PFS, investigator-assessed ORR and safety. Predictive biomarkers associated with efficacy will be evaluated. Approximately 568 pts will be enrolled. Clinical trial information: NCT02657434.
Fludarabine/Treosulfan/Thiotepa/ATG Conditioning for Related Transplantation in β Thalassaemia Major Leads to Early and Sustained Engraftment with Low Incidence of VOD and GvHD
Authors: Farah O'Boyle, Leena Karnik, Anne Bradshaw, Richard M Szydlo, Josu de la Fuente
Journal: Blood (2016)
PN but not PT Determined by MRI May Accurately Stage Rectal Cancers after Neoadjuvant Radiochemotherapy
Authors: FM Smith, E Carton, RB Stephens, M Keoghan, C Brodie, C Stewart, E Gaffney, MJ Kennedy, JV Reynolds
Journal: Endoscopy (2004)

Aims: To assess the accuracy of MRI staging in patients who underwent neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer
Нервная анорексия: обзор и клинический случай
Authors: L.V. Demeshkina, O.N. Serdiuchenko, D.A. Ptushkina, O.P. Petishko
Journal: GASTROENTEROLOGY (2020)

Статья посвящена актуальной проблеме — нервной анорексии. Авторы рассматривают эту проблему с учетом современных знаний и рекомендаций относительно нервной анорексии. В статье приводятся данные о распространенности, критериях диагностики, стадиях, клинических проявлениях и современных подходах к лечению нервной анорексии. Детально проанализирован клинический случай выявления и лечения нервной анорексии в условиях стационара у больной Г.
Use of Adjuvant Chemotherapy After Surgery in Patients With Colon Cancer
Authors: Alain J. Gelibter, Claudia Mosillo, Grazia Sirgiovanni
Journal: JAMA Surgery (2017)

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Safety of pregnancy in patients (pts) with history of estrogen receptor positive (ER+) breast cancer (BC): Long-term follow-up analysis from a multicenter study.
Authors: Matteo Lambertini, Niels Kroman, Lieveke Ameye, Octavi Cordoba, Alvaro Pinto, Giovanni Benedetti, Maj-Britt Jensen, Shari I. Gelber, Maria Del Grande, Michail Ignatiadis, Evandro De Azambuja, Marianne Paesmans, Fedro Peccatori, Hatem A. Azim Jr.
Journal: Journal of Clinical Oncology (2017)

LBA10066 Background: Physicians and pts remain concerned on the safety of pregnancy following BC, particularly in women with history of ER+ disease. Previously, we showed no detrimental effect of pregnancy on BC outcome within the first 5 years following conception (Azim et al. JCO 2013). Here, we report long-term follow-up data. Methods: In this multicenter retrospective study, pts with pregnancy after BC (pregnant cohort) were matched (1:3) according to tumor and treatment characteristics with pts without subsequent pregnancy (non-pregnant cohort). To adjust for guaranteed time bias, each non-pregnant pt should have been disease free for a minimum time not inferior to the time elapsing between BC diagnosis and conception in the matched pregnant one. Primary endpoint was disease-free survival (DFS) in pts with ER+ BC. Secondary endpoints were DFS and overall survival (OS) in ER-negative and all pts irrespective of ER status. We also evaluated the impact of induced abortion on BC outcome. Results: The study included 1,207 pts, 333 pregnant and 874 non-pregnant. A total of 57% of pts had ER+ BC. After 12.5 years from conception, no DFS difference was observed between pregnant and non-pregnant pts with ER+ BC (hazard ratio [HR] 0.94; 95% confidence intervals [CI] 0.70-1.26; p = 0.68), ER- BC (HR 0.75; 95% CI 0.53-1.06; p = 0.10), and all pts (HR 0.85; 95% CI 0.68-1.06; p = 0.15). There was no OS difference between the 2 cohorts in pts with ER+ BC (HR 0.84; 95% CI 0.60-1.18; p = 0.32), but a significant improved OS was observed in the pregnant cohort for ER- pts (HR 0.57; 95% CI 0.36-0.90; p = 0.01) yielding a significant overall estimate (HR 0.72; 95% CI 0.55-0.94; p = 0.02). Abortion did not have any impact on outcome (HR 0.80; 95% CI 0.56-1.13; p = 0.20), irrespective of ER status. Conclusions: This is the largest study addressing the safety of pregnancy in pts with history of ER+ BC. Long-term follow-up confirms that pregnancy is safe and should not be discouraged irrespective of ER status. Our results further strengthen the rationale of the ongoing IBCSG-BIG-NABCG POSITIVE trial (NCT02308085) addressing the role of temporary interruption of adjuvant endocrine therapy to allow pregnancy.
Abstract 337: Alternative Angiogenic Pathway Driven by Stimulus-Dependent Phosphorylation of Profilin-1
Authors: Yi Fan, Paul L Fox
Journal: Circulation Research (2012)

Angiogenesis, the outgrowth of new blood vessels from pre-existing ones, is fundamental to development and post-injury tissue repair. Vascular endothelial growth factor (VEGF)-A guides and enhances directional endothelial cell (EC) migration to initiate angiogenesis, which can be driven by a multistep signaling cascade that directs actin polymerization. Profilin-1 (Pfn-1) is an actin-binding protein that enhances actin filament formation and cell migration, but stimulus-dependent regulation of Pfn-1 has not been observed. Here, we show that VEGF-A-inducible phosphorylation of Pfn-1 at Tyr129 is critical for EC migration and angiogenesis. Chemotactic activation of VEGF receptor kinase-2 (VEGFR2) and its immediate downstream kinase Src directly induce Pfn-1 phosphorylation in the cell leading edge, promoting Pfn-1 binding to actin and actin polymerization. Interestingly, Pfn-1 phosphorylation is robustly and preferentially elevated in blood vessels during tissue repair after myocardial infarction (MI) in humans. Conditional endothelial knock-in of phosphorylation-deficient Y129F Pfn-1 mutant in mice reveals that Pfn-1 phosphorylation is required for VEGF-A-induced EC sprouting migration and critical for angiogenesis in response to wounding and ischemic injury, but not for developmental angiogenesis. Thus, VEGFR2/Src-mediated phosphorylation of Pfn-1 bypasses canonical, multistep intracellular signaling events to initiate EC migration and angiogenesis, and may serve as a selective therapeutic target for angiogenesis-related disorders including ischemic heart disease.
The Evolving Role of Endoscopic Ultrasound Fine Needle Aspiration (EUS FNA) in Pancreatobiliary Disease
Authors: F Gleeson, E Clarke, J Lennon, P MacMathuna
Journal: Endoscopy (2004)

Aim: Endoscopic ultrasound fine needle aspiration (EUS-FNA) may be used to localise, delineate and histologically characterise pancreatic lesions. It has the ability to aspirate more than one site during the same procedure and offers an opportunity to prevent unnecessary surgical intervention. We aim to evaluate the clinical impact of EUS FNA in patients with suspected pancreatobiliary disease.
Stability of and Factors Related to Medical Student Specialty Choice of Psychiatry
Authors: Matthew N. Goldenberg, D. Keith Williams, John J. Spollen
Journal: American Journal of Psychiatry (2017)

Targeted efforts are needed to increase the number of medical students choosing psychiatry, but little is known about when students decide on their specialty or what factors influence their choice. The authors examined the timing and stability of student career choice of psychiatry compared with other specialties and determined what pre- and intra-medical school factors were associated with choosing a career in psychiatry.Using survey data from students who graduated from U.S. allopathic medical schools in 2013 and 2014 (N=29,713), the authors computed rates of psychiatry specialty choice at the beginning and end of medical school and assessed the stability of that choice. A multivariate-adjusted logistic regression and recursive partitioning were used to determine the association of 29 factors with psychiatry specialty choice.Choice of psychiatry increased from 1.6% at the start of medical school to 4.1% at graduation. The stability of psychiatry specialty choice from matriculation to graduation, at just over 50%, was greater than for any other specialty. However, almost 80% of future psychiatrists did not indicate an inclination toward the specialty at matriculation. A rating of "excellent" for the psychiatry clerkship (odds ratio=2.66), a major in psychology in college (odds ratio=2.58), and valuing work-life balance (odds ratio=2.25) were the factors most strongly associated with psychiatry career choice.Students who enter medical school planning to become psychiatrists are likely to do so, but the vast majority of students who choose psychiatry do so during medical school. Increasing the percentage of medical students with undergraduate psychology majors and providing an exemplary psychiatry clerkship are modifiable factors that may increase the rate of psychiatry specialty choice.
ACK1/TNK2 Regulates Histone H4 Tyr88-phosphorylation and AR Gene Expression in Castration-Resistant Prostate Cancer
Authors: Kiran Mahajan, Pavani Malla, Harshani R. Lawrence, Zhihua Chen, Chandan Kumar-Sinha, Rohit Malik, Sudhanshu Shukla, Jongphil Kim, Domenico Coppola, Nicholas J. Lawrence, Nupam P. Mahajan
Journal: Cancer Cell (2017)