tbuckley/cabot-search huggingface dataset:
Two-step endoscopic ultrasound-guided rendezvous technique combined with antegrade electrohydraulic lithotripsy for a huge pancreatic duct stone
Authors: Takeshi Ogura, Nobu Nishioka, Masanori Yamada, Kazuya Ueshima, Kazuhide Higuchi
Journal: Endoscopy (2019)

The endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a useful procedure for difficult cannulation of not only the bile duct, but also the pancreatic duct [1] [2] [3] [4]. In addition, if guidewire passage from the papilla across the obstructed site is challenging, antegrade guidewire insertion under EUS guidance is one of several possible methods. Herein, we describe a two-step EUS-RV technique combined with antegrade electrohydraulic lithotripsy (EHL) for a huge pancreatic duct stone.
Self care interventions could advance sexual and reproductive health in humanitarian settings
Authors: Carmen H Logie, Kaveh Khoshnood, Moses Okumu, Sabina Faiz Rashid, Fidan Senova, Hamza Meghari, Claire Uwase Kipenda
Journal: BMJ (2019)

Forcibly displaced people often lack access to adequate sexual and reproductive health services. <b>Carmen Logie and colleagues</b> examine the role of self care interventions in filling the gap
Response: Still puzzling about a clear definition of pulmonary arterial hypertension in newborns
Authors: Erika B. Rosenzweig, Steven H. Abman, Rolf M.F. Berger
Journal: European Respiratory Journal (2019)

We appreciate the comments by G. Calcaterra and co-workers regarding the recent summary of the Paediatric Task Force from the 6th World Symposium on Pulmonary Hypertension (WSPH; Nice, 2018) [1]. While many messages endure, including the ongoing emphasis in 2018 on the distinct needs and approach to children with pulmonary hypertension (PH), we have learned much since the last symposium in 2013. Even in the absence of a dramatic change in the therapeutic landscape for children with PH, we examined new and important paediatric data from the past five years that informed our contemporary approach and defined ongoing needs and knowledge gaps for the future. Insights into defining paediatric pulmonary hypertension <http://ow.ly/Qdkn30nDcIx>
NHS to roll out blood tests for pre-eclampsia after positive study results
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Placental growth factor blood tests for pre-eclampsia are to be made more widely available to pregnant women in England after a trial found that the test can hasten accurate diagnosis.

Pre-eclampsia is suspected in around 10% of pregnancies in the UK and affects around 80 000 women each year. Placental growth factor testing indicates whether a woman is at high, medium, or low risk.

Researchers from King’s College London found that by measuring the concentration of placental growth factor in a woman’s blood doctors could diagnose pre-eclampsia on average two days sooner. The study, published in the Lancet , found that quicker …
Therapeutic Targeting of High-Mobility Group Box-1 in Pulmonary Arterial Hypertension
Authors: Neil M. Goldenberg, Yijie Hu, Xudong Hu, Allen Volchuk, Yidan D. Zhao, Mariya M. Kucherenko, Christoph Knosalla, Marc de Perrot, Kevin J. Tracey, Yousef Al-Abed, Benjamin E. Steinberg, Wolfgang M. Kuebler
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

To the Editor:The importance of the immune system in pulmonary arterial hypertension (PAH) pathogenesis is increasingly recognized by clinicians and scientists (1).Immune cells are recruited to the lungs of patients with PAH (2), and preclinical studies have demonstrated their requirement for disease progression (3).The importance of the human immune system in PAH pathogenesis is underscored by our recent finding that mice, which do not develop robust experimental pulmonary hypertension, are rendered susceptible to severe disease when reconstituted with human immune tissue (4).Consequently, several clinical trials are investigating immunomodulation as PAH treatment (1).The ubiquitously expressed damage-associated molecular pattern HMGB1 (high-mobility group box-1) is gaining recognition as a mediator of PAH.HMGB1 can be secreted from immune cells in response to stress, and it mediates many paracrine and autocrine effects in inflammatory conditions (5).HMGB1, by binding TLR4 (Toll-like receptor 4), activates macrophages and lymphocytes; induces TNF (tumor necrosis factor), IL-6, and IL-1b; and triggers autoimmunity (5).All of these factors are hallmarks of PAH (1).Expression of both HMGB1 and TLR4 is elevated in lungs of patients with PAH (6), and HMGB1 is secreted in response to hypoxia (7).Conversely, mice treated with neutralizing antibodies against HMGB1 (6) or deficient in TLR4 are protected from hypoxia-induced pulmonary hypertension (8).Although targeting HMGB1/TLR4 signaling may be a promising new treatment for PAH, this strategy can be expected to come at a cost, given the multiple roles of these molecules in infection and immunity.In this study, we first consolidated the critical role of HMGB1 in PAH in human samples and animal models.Next, we tested the therapeutic efficacy of a novel peptide, P5779, which specifically targets extracellular HMGB1 in its disulfide form, disrupting its interaction with the TLR4 adaptor MD-2 (9).Hence, P5779 does not affect the epigenetic functions of intracellular HMGB1 or non-HMGB1-mediated TLR4 signaling, thus minimizing potential off-target effects of anti-HMGB1 therapies for PAH.Some of these results were previously reported in abstract form (10).
Antitumour activity and tolerability of an EphA2-targeted nanotherapeutic in multiple mouse models
Authors: Walid S. Kamoun, Dmitri B. Kirpotin, Zhaohua Richard Huang, Suresh K. Tipparaju, Charles O. Noble, Mark E. Hayes, Lia Luus, Alexander Koshkaryev, Jaeyeon Kim, Ken Olivier, Tad Kornaga, Shinji Oyama, Vasileios Askoxylakis, Christine Pien, Geoffrey Kuesters, Nancy Dumont, Alexey A. Lugovskoy, Sarah A. Schihl, John H. Wilton, Melissa L. Geddie, James Suchy, Stephanie Grabow, Neeraj Kohli, C. Patrick Reynolds, Rachel Blaydes, Yu Zhou, Andrew J. Sawyer, James D. Marks, Daryl C. Drummond
Journal: Nature Biomedical Engineering (2019)
Combined Tumor Sequencing and Case-Control Analyses of RAD51C in Breast Cancer
Authors: Na Li, Simone McInerny, Magnus Zethoven, Dane Cheasley, Belle W X Lim, Simone M Rowley, Lisa Devereux, Norah Grewal, Somayeh Ahmadloo, David Byrne, Jue Er Amanda Lee, Jason Li, Stephen B Fox, Thomas John, Yoland Antill, Kylie L Gorringe, Paul A James, Ian G Campbell
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Loss-of-function variants in RAD51C are associated with familial ovarian cancer, but its role in hereditary breast cancer remains unclear. The aim of this study was to couple breast tumor sequencing with case-control data to clarify the contribution of RAD51C to hereditary breast cancer. Methods RAD51C was sequenced in 3080 breast cancer index cases that were negative in BRCA1/2 clinical tests and 4840 population-matched cancer-free controls. Pedigree and pathology data were analyzed. Nine breast cancers and one ovarian cancer from RAD51C variant carriers were sequenced to identify biallelic inactivation of RAD51C, copy number variation, mutational signatures, and the spectrum of somatic mutations in breast cancer driver genes. The promoter of RAD51C was analyzed for DNA methylation. Results A statistically significant excess of loss-of-function variants was identified in 3080 cases (0.4%) compared with 2 among 4840 controls (0.04%; odds ratio = 8.67, 95% confidence interval = 1.89 to 80.52, P&amp;lt; .001), with more than half of the carriers having no personal or family history of ovarian cancer. In addition, the association was highly statistically significant among cases with estrogen-negative (P &amp;lt;. 001) or triple-negative cancer (P &amp;lt; .001), but not in estrogen-positive cases. Tumor sequencing from carriers confirmed bi-allelic inactivation in all the triple-negative cases and was associated with high homologous recombination deficiency scores and mutational signature 3 indicating homologous recombination repair deficiency. Conclusions This study provides evidence that germline loss-of-function variants of RAD51C are associated with hereditary breast cancer, particularly triple-negative type. RAD51C-null breast cancers possess similar genomic and clinical features to BRCA1-null cancers and may also be vulnerable to DNA double-strand break inducing chemotherapies and poly ADP-ribose polymerase inhibitors.
Propentdyopents as Heme Degradation Intermediates Constrict Mouse Cerebral Arterioles and Are Present in the Cerebrospinal Fluid of Patients With Subarachnoid Hemorrhage
Authors: Alexander Joerk, Marcel Ritter, Niklas Langguth, Raphael Andreas Seidel, Diana Freitag, Karl-Heinz Herrmann, Anna Schaefgen, Marvin Ritter, Milena Günther, Charline Sommer, Dirk Braemer, Jan Walter, Christian Ewald, Rolf Kalff, Jürgen Rainer Reichenbach, Matthias Westerhausen, Georg Pohnert, Otto Wilhelm Witte, Knut Holthoff
Journal: Circulation Research (2019)

Rationale: Delayed ischemic neurological deficit is the most common cause of neurological impairment and unfavorable prognosis in patients with subarachnoid hemorrhage (SAH). Despite the existence of neuroimaging modalities that depict the onset of the accompanying cerebral vasospasm, preventive and therapeutic options are limited and fail to improve outcome owing to an insufficient pathomechanistic understanding of the delayed perfusion deficit. Previous studies have suggested that BOXes (bilirubin oxidation end products), originating from released heme surrounding ruptured blood vessels, are involved in arterial vasoconstriction. Recently, isolated intermediates of oxidative bilirubin degradation, known as PDPs (propentdyopents), have been considered as potential additional effectors in the development of arterial vasoconstriction. Objective: To investigate whether PDPs and BOXes are present in hemorrhagic cerebrospinal fluid and involved in the vasoconstriction of cerebral arterioles. Methods and Results: Via liquid chromatography/mass spectrometry, we measured increased PDP and BOX concentrations in cerebrospinal fluid of SAH patients compared with control subjects. Using differential interference contrast microscopy, we analyzed the vasoactivity of PDP isomers in vitro by monitoring the arteriolar diameter in mouse acute brain slices. We found an arteriolar constriction on application of PDPs in the concentration range that occurs in the cerebrospinal fluid of patients with SAH. By imaging arteriolar diameter changes using 2-photon microscopy in vivo, we demonstrated a short-onset vasoconstriction after intrathecal injection of either PDPs or BOXes. Using magnetic resonance imaging, we observed a long-term PDP-induced delay in cerebral perfusion. For all conditions, the arteriolar narrowing was dependent on functional big conductance potassium channels and was absent in big conductance potassium channels knockout mice. Conclusions: For the first time, we have quantified significantly higher concentrations of PDP and BOX isomers in the cerebrospinal fluid of patients with SAH compared to controls. The vasoconstrictive effect caused by PDPs in vitro and in vivo suggests a hitherto unrecognized pathway contributing to the pathogenesis of delayed ischemic deficit in patients with SAH.
Automated quantitative tumour response assessment of MRI in neuro-oncology with artificial neural networks: a multicentre, retrospective study
Authors: Philipp Kickingereder, Fabian Isensee, Irada Tursunova, Jens Petersen, Ulf Neuberger, David Bonekamp, Gianluca Brugnara, Marianne Schell, Tobias Kessler, Martha Foltyn, Inga Harting, Felix Sahm, Marcel Prager, Martha Nowosielski, Antje Wick, Marco Nolden, Alexander Radbruch, Jürgen Debus, Heinz-Peter Schlemmer, Sabine Heiland, Michael Platten, Andreas von Deimling, Martin J van den Bent, Thierry Gorlia, Wolfgang Wick, Martin Bendszus, Klaus H Maier-Hein
Journal: The Lancet Oncology (2019)
Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial
Authors: Andrew Davies, Thomas E Cummin, Sharon Barrans, Tom Maishman, Christoph Mamot, Urban Novak, Josh Caddy, Louise Stanton, Shamim Kazmi-Stokes, Andrew McMillan, Paul Fields, Christopher Pocock, Graham P Collins, Richard Stephens, Francesco Cucco, Alexandra Clipson, Chulin Sha, Reuben Tooze, Matthew A Care, Gareth Griffiths, Ming-Qing Du, David R Westhead, Catherine Burton, Peter W M Johnson
Journal: The Lancet Oncology (2019)

Biologically distinct subtypes of diffuse large B-cell lymphoma can be identified using gene-expression analysis to determine their cell of origin, corresponding to germinal centre or activated B cell. We aimed to investigate whether adding bortezomib to standard therapy could improve outcomes in patients with these subtypes.
Beware of False-Positive FDG PET/CT Interpretations for Presacral Recurrent Rectal Cancer
Authors: Jan P. Pennings, Robbert J. de Haas, Koert P. de Jong, Rudi A.J.O. Dierckx, Thomas C. Kwee
Journal: Clinical Nuclear Medicine (2019)

FDG PET/CT is considered an accurate method for the detection of recurrent rectal cancer in the pelvis. Excess presacral soft tissue is found in up to half of patients after (chemo)radiation and surgery for rectal cancer, and usually represents fibrosis that is metabolically inactive. However, presacral soft tissue that is FDG avid is generally considered suspicious for recurrent cancer. Nevertheless, FDG avidity in the presacral space not uncommonly proves to be due to benign inflammatory changes, and additional MRI may be diagnostically useful, as demonstrated in the presented 2 cases.
Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data
Authors: Charles M. Rudin, John T. Poirier, Lauren Averett Byers, Caroline Dive, Afshin Dowlati, Julie George, John V. Heymach, Jane E. Johnson, Jonathan M. Lehman, David MacPherson, Pierre P. Massion, John D. Minna, Trudy G. Oliver, Vito Quaranta, Julien Sage, Roman K. Thomas, Christopher R. Vakoc, Adi F. Gazdar
Journal: Nature reviews. Cancer (2019)
18F–Prostate-Specific Membrane Antigen 1007 and 18F-FCH PET/CT in Local Recurrence of Prostate Cancer
Authors: Ewa Witkowska-Patena, Agnieszka Giżewska, Jolanta Miśko, Mirosław Dziuk
Journal: Clinical Nuclear Medicine (2019)

Abstract 18 F–prostate-specific membrane antigen (PSMA) 1007 is one of the most promising radiotracers for PET imaging of relapsing prostate cancer. Minimal urinary clearance seems to be its most valuable and outstanding feature. We present images of biochemically relapsed prostate cancer where 18 F-PSMA-1007 PET/CT (performed to verify an ambiguous finding adjacent to the urinary bladder found in 18 F-FCH PET/CT) proved superior to radiocholine and precisely visualized site of local recurrence.
Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice
Authors: Aris A. Polyzos, Do Yup Lee, Rupsa Datta, Meghan Hauser, Helen Budworth, Amy Holt, Stephanie Mihalik, Pike Goldschmidt, Ken Frankel, Kelly Trego, Michael J. Bennett, Jerry Vockley, Ke Xu, Enrico Gratton, Cynthia T. McMurray
Journal: Cell Metabolism (2019)
局部 PDT 不良作用的管理
Authors: S.H. Ibbotson, T.H. Wong, C.A. Morton, N.J. Collier, A. Haylett, K.E. McKenna, R. Mallipeddi, H. Moseley, L.E. Rhodes, D.C. Seukeran, K.A. Ward, M.F. Mohd Mustapa, L.S. Exton
Journal: British Journal of Dermatology (2019)

光动力治疗 (PDT) 常用于治疗某些类型的低危非黑色素瘤皮肤癌和癌前晒伤,在很多皮肤科服务机构中都有提供。本次回顾的目的是调查关于这种形式治疗的副作用的医学文献中已发表的证据,以及防和及治疗这些副作用的方法。这是回顾和更新 PDT 使用及其在皮肤科执业中定位指导原则更大工作的一部分,该指导原则另行在《英国皮肤病杂志》中刊出(Wong et al., Br J Dermatol 2018 https://doi.org/10.1111/bjd.16838)。本文回顾了所有与 PDT 副作用相关的已发表证据,并基于在皮肤科诊所中积极进行 PDT 治疗的作者的广泛经验对其进行具体分析。作者们发现,PDT 治疗期间的不适和疼痛是仅有的值得关注的主要副作用,但这可通过使用改良的低强度治疗方案显著减轻,因此通常不会限制治疗或其结局。罕见副作用包括对 PDT 所用药物过敏,这在大面积接受多次治疗的患者中最可能发生。没有其他值得注意的副作用,得出了以下整体结论,此治疗耐受良好,PDT 在皮肤科执业中具有重要地位。这巩固了 PDT 作为某些皮肤病安全有效治疗的地位和重要性,尤其是表皮非黑色素瘤皮肤癌和癌前晒伤。
Abstract 19549: Impact of Body Mass Index and Indexation Method on High Left Ventricular Mass
Authors: Saadia Qazi, Philimon Gona, Carol J Salton, Jane J Lee, Lu Zhang, Christopher J O'Donnell, Warren J Manning, Michael L Chuang
Journal: Circulation (2017)

Introduction: High left ventricular mass (LVM) is associated with excess cardiovascular morbidity and mortality. To account for differences in body size LVM is often indexed to height (HT), a power...
Activation of hedgehog signaling associates with early disease progression in chronic lymphocytic leukemia
Authors: Emanuela M. Ghia, Laura Z. Rassenti, Donna S. Neuberg, Alejandro Blanco, Fouad Yousif, Erin N. Smith, John D. McPherson, Thomas J. Hudson, Olivier Harismendy, Kelly A. Frazer, Thomas J. Kipps
Journal: Blood (2019)
Anthony James Jones
Authors: Stephen Orife, Umo Esen
Journal: BMJ (2019)

Anthony James Jones (“Tony”) was born in Treorchy, south Wales. He did most of his postgraduate training in obstetrics and gynaecology at East Glamorgan, Bristol, and Leicester hospitals

He was appointed consultant in obstetrics and gynaecology at the South Tyneside District Hospital in South Shields …
Abstract 3525: IMCgp100: A novel bi-specific biologic for the treatment of malignant melanoma
Authors: Namir J. Hassan, Katherine Adams, Giovanna Bossi, Jane Harper, Sandrine Buisson, Samantha Paston, Nathaniel Liddy, Rebecca Ashfield, Jessie Gavarret, Frayne Bianchi, Emma Baston, Debbie Baker, Kristin Ladell, Andrew Sewell, Yi Li, Brian Cameron, Andrew Johnson, Annelise Vuidepot, Penio Todorov, Michael Kalos, Carl June, Giorgos Karakousis, Gerry Linette, David A. Price, Daniel Williams, Yvonne McGrath, Bent K. Jakobsen
Journal: Cancer Research (2012)

Abstract In recent years significant advances in the treatment of metastatic melanoma have emerged. Small molecule drugs provide potent short-term responses for a significant proportion of the patient population; for a minority of patients, immunotherapy has elicited long-term responses with the promise of a cure. Despite these advances, long-term remission for the majority of patients remains elusive and much effort is focussed on combination therapies attempting to bring together the potency of small molecule drugs with the durability of immunotherapy. IMCgp100 is a novel bi-specific immunotherapy comprising a soluble, affinity- enhanced, T cell receptor (TCR) specific for the melanoma-associated antigen gp100, fused to an anti-CD3 specific antibody fragment (scfv). The engineered TCR portion of the drug targets the gp100 peptide 280-288 antigen, which is over- expressed and presented by HLA-A2 on the surface of melanoma cells, thereby effectively coating these cells with CD3-specific antibody fragments. The anti-CD3 scfv portion captures and redirects any T cells in physical contact with the melanoma cell to kill it. In vitro, IMCgp100 potently redirects T cells from the blood of late stage cancer patients to target melanoma cells exhibiting substantial HLA-down regulation, even in the presence of high numbers of regulatory T cells. Target cell killing is observed within hours, and is associated with the release of pro-inflammatory cytokines and dendritic cell cross-presentation of gp100 and other melanoma-specific antigens. Thus, IMCgp100 demonstrates the potential to elicit potent short-term responses and trigger longer-term anti melanoma durability in vivo (ref: paper to be published imminently in Nature Medicine). IMCgp100 is currently under investigation as part of a Phase 1 dose-finding study in patients with unresectable Stage III/Stage IV malignant melanoma. Safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity are assessed after intravenous infusion of IMCgp100, and the maximum tolerated dose (MTD) will be established. We also have a Phase 0 trial open, in which IMCgp100 is injected directly into tumours to assess pharmacodynamic activity in human lesions. Both studies are actively enrolling and preliminary clinical data will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3525. doi:1538-7445.AM2012-3525
Two-Drug Combinations as First-Step Antihypertensive Treatment
Authors: Giuseppe Mancia, Federico Rea, Giovanni Corrao, Guido Grassi
Journal: Circulation Research (2019)

Blood pressure (BP) control in patients with hypertension is variable worldwide, and in general, it results largely unsatisfactory. Factors responsible for this phenomenon include insufficient national cardiovascular healthcare policies for prevention, poor patient compliance with prescribed treatment schedules, and the reluctance of physicians to modify treatment strategies when BP is still elevated, that is, the so-called therapeutic inertia. A further important factor favoring poor BP control is the limited use of combination drug treatment, despite evidence of its superior ability to control BP in patients with difficult-to-treat hypertension. In addition, combination treatment allows to achieve BP control more easily (and more quickly) as compared with monotherapy. This article, after briefly examining the main features of BP control, will review the importance in the treatment of hypertension of the drug combination strategy, based on the recommendations of the 2018 European Society of Cardiology/European Society of Hypertension guidelines. Empahsis will be given to the drug combination treatment as first step of the antihypertensive therapeutic intervention. The potential drawbacks and barriers to combination drug treatment as initial therapeutic strategy will also be briefly discussed.
Balance Between Best Practice and Patient Satisfaction: Antimicrobial Stewardship in Telemedicine
Authors: Kristin Dean, Ian Tong, Rana Hamdy
Journal: JAMA Internal Medicine (2019)

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