tbuckley/cabot-search huggingface dataset:
Contrast-induced nephropathy: Basic concepts, pathophysiological implications and prevention strategies
Authors: Charalampos Mamoulakis, Konstantinos Tsarouhas, Irini Fragkiadoulaki, Ioannis Heretis, Martin F. Wilks, Demetrios A. Spandidos, Christina Tsitsimpikou, Aristides Tsatsakis
Journal: Pharmacology & Therapeutics (2017)
An unexplored brain-gut microbiota axis in stroke
Authors: Shu Wen Wen, Connie H. Y. Wong
Journal: Gut Microbes (2017)

Microbiota research, in particular that of the gut, has recently gained much attention in medical research owing to technological advances in metagenomics and metabolomics. Despite this, much of the research direction has focused on long-term or chronic effects of microbiota manipulation on health and disease. In this addendum, we reflect on our recent publication that reported findings addressing a rather unconventional hypothesis. Bacterial pneumonia is highly prevalent and is one of the leading contributors to stroke morbidity and mortality worldwide. However, microbiological cultures of samples taken from stroke patient with a suspected case of pneumonia often return with a negative result. Therefore, we proposed that post-stroke infection may be due to the presence of anaerobic bacteria, possibly those originated from the host gut microbiota. Supporting this, we showed that stroke promotes intestinal barrier breakdown and robust microbiota changes, and the subsequent translocation of selective bacterial strain from the host gut microbiota to peripheral tissues (i.e. lung) induces post-stroke infections. Our findings were further supported by various elegant studies published in the past 12 months. Here, we discuss and provide an overview of our key findings, supporting studies, and the implications for future advances in stroke research.
Radiofrequency ablation for early-stage breast cancer: results from 5 years of follow-up in a prospective multicenter study.
Authors: Takayuki Kinoshita, Naohito Yamamoto, Tomomi Fujisawa, Masato Takahashi, Kenjiro Aogi, Takashi Hojo, Hitoshi Tsuda, Masayuki Yoshida
Journal: Journal of Clinical Oncology (2017)

e12098 Background: Given the increasing number of early-stage breast cancers detected by screening mammography, we aim to establish RFA as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase 1 study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Building on these results, we designed a Phase 2 clinical trial to investigate the efficacy of a non-surgical RFA procedure. Methods: From Nov. 2009 to Nov. 2012, 58 patients with early-stage breast cancer received non-surgical RFA therapy. Patients had localized solitary N0 tumors with a maximum diameter of 1 cm. They underwent RFA and sentinel lymph node biopsy under general anesthesia and adjuvant therapy and breast irradiation. Follow-up evaluation for residual tumor at 3, 6, and 12 months after RFA included clinical breast examination, diagnostic imagings (ultrasound, magnetic resonance, and mammography), and vacuum-assisted biopsy. Surgical resection was recommended for patients with suspected residual disease or incomplete ablation. The primary endpoint was the frequency of adverse events. Secondary endpoints included the complete ablation rate and ipsilateral breast relapse-free rate. The diagnostic performance of the follow-up examinations and cosmetic outcomes were evaluated for exploratory purposes. Results: The follow-up period ranged from 450 to 2552 days (median, 1832 days). The 57 patients completed the non-surgical RFA procedure and underwent diagnostic imaging and needle biopsy after 3 months. Seven patients with suspected incomplete ablation underwent surgical resection; incomplete ablation was confirmed in 5 (8.6%, 2 with invasive and 3 with non-invasive ductal carcinoma). During subsequent follow-up, 1 patient each was diagnosed with contralateral breast cancer and brain tumor. No ipsilateral breast tumor relapse or distant recurrence was documented. Cosmetic results were excellent in 94% of patients. Conclusions: RFA is a promising alternative to surgery for treating localized, early-stage breast cancers. Clinical trial information: UMIN000008675.
Traitement endoscopique des sténoses anastomotiques cholédoco-cholédociennes post transplantation hépatique (TH) par prothèse métallique extirpable
Authors: H Audin-Mamlouk, P Bauret, M Bismuth, JP Carabalona, P Puche, E Jacquet, F Navarro, GP Pageaux
Journal: Endoscopy (2009)

Introduction: Les complications biliaires post TH sont fréquentes avec une prévalence de 8 à 30%. Les sténoses de l'anastomose cholédoco-cholédocienne (SACC) représentent la majorité de ces complications. Leur traitement n'est pas codifié et la place de la cholangiografie rétrograde reste encore débattue. Actuellement un des traitements reconnus consiste en la pose d'une ou plusieurs prothèses plastiques avec une période de calibrage en moyenne de 6 mois. Objectif: Evaluer la faisabilité et l'efficacité de la mise en place et de l'extraction endoscopiques de prothèses métalliques expansives couvertes dans les SACC.
Les prothèses oesophagiennes métalliques expansives dans le traitement palliatif du cancer de l'oesophage: comparaison des résultats et des complications chez 56 malades ayant reçu une radio-chimiothérapie vs. 60 malades non traités antérieurement
Authors: S Lecleire, F Di Fiore, M Antonietti, P Ducrotte, B Paillot, P Michel, E Lerebours, E Ben Soussan
Journal: Endoscopy (2005)

Les prothèses œsophagiennes métalliques expansives (POME) sont employées en première intention dans le traitement palliatif de la dysphagie du cancer de l'œsophage. Cependant, l'insertion de POME peut être suivie de complications potentiellement graves. Leur survenue plus fréquente chez des malades ayant été traités antérieurement par radiothérapie et chimiothérapie (RT-CT) reste encore incertaine. Le but de l'étude était d'analyser rétrospectivement d'une part l'efficacité symptomatique d'un traitement par POME chez des malades atteints de cancer de l'œsophage, et d'autre part de comparer la fréquence des complications survenant après insertion de POME, selon la réalisation antérieure d'un traitement par RT-CT ou l'absence de traitement antérieur.
Evaluation of utility of pharmacokinetic studies in phase I combination trials.
Authors: Kehua Wu, Larry House, Jacqueline Ramirez, Mark J. Ratain
Journal: Journal of Clinical Oncology (2012)

2611 Background: There are many phase I clinical combination trials including drug-drug interaction (DDI) studies, but very few of them report positive results. We hypothesized that the utility of DDI studies is low in the absence of a mechanistic hypothesis. Methods: We retrospectively reviewed 119 phase I (2 drug) combination studies published in 2007-2011. Results: Only 23 (19%) studies had a positive rationale, either inhibition/induction of a drug metabolizing enzyme or transporter, co-substrates for the same enzyme or transporter, potential for end-organ toxicity, or protein- binding. Only 9 (8%) studies demonstrated a statistically significant effect DDI, based on AUC of parent drug or active metabolite. There was a strong association between lack of rationale and a lack of interaction, as only 2% of studies without a rationale demonstrated a DDI, compared to 30% of studies with a rationale (Fisher’s exact test, p=0.0004) (Table). Conclusions: DDI studies should not be routinely performed as part of phase I clinical trials. [Table: see text]
Human erythrocyte protein 4.2 deficiency associated with hemolytic anemia and a homozygous 40glutamic acid--&gt;lysine substitution in the cytoplasmic domain of band 3 (band 3Montefiore)
Authors: AC Rybicki, JJ Qiu, S Musto, NL Rosen, RL Nagel, RS Schwartz
Journal: Blood (1993)
Germinal-center development of memory B cells driven by IL-9 from follicular helper T cells
Authors: Yifeng Wang, Jingwen Shi, Jiacong Yan, Zhengtao Xiao, Xiaoxiao Hou, Peiwen Lu, Shiyue Hou, Tianyang Mao, Wanli Liu, Yuanwu Ma, Lianfeng Zhang, Xuerui Yang, Hai Qi
Journal: Nature Immunology (2017)
Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: A retrospective case series.
Authors: Marc C. Chamberlain, Bryan T. Kim
Journal: Journal of Clinical Oncology (2017)

e13538 Objective: A single institution retrospective evaluation of nivolumab following disease progression on bevacizumab in adults with recurrent glioblastoma (GBM) with an objective of determining progression free survival (PFS). Background: There is no accepted therapy for recurrent GBM after failure of bevacizumab. Methods: 16 adults, ages 52-72 years (median 62), with recurrent GBM were treated. All patients had previously been treated with surgery, concurrent radiotherapy and temozolomide, and post-radiotherapy temozolomide. Bevacizumab (with or without lomustine) was administered to all patients at first recurrence. Patients were treated with nivolumab only (3mg/kg) once every 2 weeks at second recurrence. One cycle of nivolumab was defined as 2 treatments. Neurological evaluation was performed bi-weekly and neuroradiographic assessment every 4 weeks. Results: A total of 37 treatment cycles (median 2) were administered of nivolumab in which there were 14 Grade 2 adverse events (AEs) and Grade 3 AEs in 2 patients. No Grade 4 or 5 AEs were seen. Following 1 month of nivolumab, 7 patients’ demonstrated progressive disease and discontinued therapy. No patient demonstrated a response though 9 patients demonstrated neuroradiographic stable response. Survival in the entire cohort ranged from 2 - 6 months with a median of 3.5 months (CI: 2.8, 4.2). Median and 6-month PFS at 6 months was 2.0 months (range 1-5 months; CI: 1.3, 2.7) and 0% respectively. Conclusions: Nivolumab salvage therapy demonstrated no survival advantage in patients with recurrent bevacizumab refractory GBM emphasizing a continued unmet need in neuro-oncology.
Psychiatric disorders with systemic retinoids: a systematic review of case reports
Authors: M. Le Moigne, J.-P. Fournier, S. Bulteau, M. Grall-Bronnec, A. Khammari, C. Victorri-Vigneau, B. Dreno
Journal: British Journal of Dermatology (2017)

The question of the association between isotretinoin and the development of psychiatric disorders has been debated for the past 20 years. Some authors have argued that similar psychiatric symptoms or disorders could also be induced by other systemic retinoids1. However, few reports have included a formal assessment of the causal link between systemic retinoids and psychiatric disorders.

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The Nationwide Cancer Genome Screening Project in Japan SCRUM-Japan GI-SCREEN: Efficient identification of cancer genome alterations in advanced non-colorectal (Non-CRC) gastrointestinal cancer.
Authors: Atsuo Takashima, Wataru Okamoto, Shuichi Hironaka, Takeshi Kato, Yoshito Komatsu, Takeshi Kajiwara, Naoki Izawa, Taito Esaki, Hiroki Hara, Ryota Nakanishi, Yoshiyuki Yamamoto, Hiromichi Ebi, Shigenori Kadowaki, Takeshi Kuwata, Satoshi Fujii, Toshihiko Doi, Atsushi Ohtsu, Kohei Shitara, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2016)

4058 Background: We conduct the nationwide cancer genome screening project in Japan since 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), called as SCRUM-Japan GI-SCREEN 2015-01-Non CRC. The objective is to evaluate the frequency of cancer genome alterations in aNon-CRC and to identify patients (pts) who are candidate for clinical trial for corresponding targeting agents. Methods: Pts with aNon-CRC including esophageal cancer (EC), gastric cancer (GC), and other types of aNon-CRC. Twenty ng of DNA and 10 ng of RNA were extracted from FFPE tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutation, copy number variant (CNV) and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to whether genetic driver of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. Results: As of October 31st in 2015, a total of 243 GC and 85 EC pts were enrolled and 235 GC and 83 EC samples were available. A total of 231 GC and 79 EC samples were analyzed and four GC and EC samples each are currently under analysis. The sequence with the OCP was successfully performed in 174 GC (75.3%) and 52 EC (65.8%). The most frequently detected mutations were TP53 (48.3%), PIK3CA (6.9%), KRAS, and SMAD4 (5.7%) in GC and were TP53 (76.9%), NFE2L2 (25.0%), CDKN2A, and PIK3CA (9.6%) in EC. Those of CNVs were ERBB2 (8.6%), CCNE1 (5.2%), FGFR2, and KRAS (4.0%) in GC and were CCND1 (44.2%), EGFR (13.5%), and SOX2 (9.6%) in EC. WIPF2-ERBB2 fusion and EGFR vIII were detected in GC and FGFR3-TACC3 fusion was detected in EC. Pts with PIK3CA or AKT1 mutation, MET or FGFR2 amplification and FGFR3-TACC3 fusion were enrolled in early clinical trials. Conclusions: This nationwide screening system is efficient to detect rare mutations in GI cancer. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial information: UMIN000016344.
Erratum: Corrigendum: Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum
Authors: Juliane Najm, Denise Horn, Isabella Wimplinger, Jeffrey A Golden, Victor V Chizhikov, Jyotsna Sudi, Susan L Christian, Reinhard Ullmann, Alma Kuechler, Carola A Haas, Armin Flubacher, Lawrence R Charnas, Gökhan Uyanik, Ulrich Frank, Eva Klopocki, William B Dobyns, Kerstin Kutsche
Journal: Nature Genetics (2008)
Continued monoclonal protein response beyond day 100 after auto-transplantation for multiple myeloma.
Authors: Wilson I. Gonsalves, Morie Gertz, Yi Lin, Martha Lacy, Angela Dispenzieri, Suzanne R. Hayman, Francis Buadi, David Dingli, Prashant Kapoor, Arleigh Robertson McCurdy, Preet Paul Singh, Vinay Gupta, Shaji Kumar
Journal: Journal of Clinical Oncology (2013)

8587 Background: Patients (pts) undergoing an auto-transplant (ASCT) for multiple myeloma (MM) have disease assessment approximately 100 days later. This result may direct decisions of further therapy versus observation. However, some pts continue to experience a decline in their serum or urine monoclonal (M) - protein after day 100 without more therapy. Little is known about the prevalence and significance of this phenomenon. Methods: We identified 903 MM pts who underwent ASCT within 12 months (mos) of diagnosis (Dx) at our institution. Their day 100 post-ASCT M-protein from serum and urine electrophoresis with immunofixation as well as serum free light chains were compared to subsequent values during follow-up. The IMWG criteria were used to evaluate response. Results: Of the pts included, 510 (56%) were male and median age at ASCT was 59 (range 28-76). Median follow up from Dx and ASCT was 82 mos (95% CI; 75 - 86) and 74 mos (95% CI; 70 - 79) respectively. There were 453 (50%) pts seen in follow-up who had not achieved a CR at Day 100 nor initiated on maintenance therapy. Of these pts, 167 (37%) had a further decrease in their M-protein after day 100 at a median of 9.4 mos (95% CI; 8 – 10) post-ASCT. Given the time taken for maximal response, we assessed patients’ clinical response at one year post-ASCT. Compared to patients who did not have further clinical response between day 100 and 1 year, pts experiencing further response had a longer time to next therapy (TTNT) (43 mos vs. 17 mos, P &lt; 0.001) as well as overall survival (OS) (96 mos vs. 62 mos, P &lt; 0.001). Positive predictors for continued response included having an IgG isotype, evolution from a pre-existing MGUS, smoldering myeloma or solitary plasmacytoma and a Day 100 bone marrow plasma cell &lt; 3%. In a multivariate analysis, elevated creatinine at Dx and lack of continued response predicted for shorter TTNT and OS post-ASCT. Older age and high-risk MM by FISH also predicted a shorter OS. Conclusions: In MM pts undergoing ASCT, continued M - protein response was seen in a third of the pts lacking a CR at day 100. This phenomenon appears prognostic and must be considered when interpreting studies evaluating post-ASCT response and the need for further therapy.
Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis
Authors: Robert P. Howlin, Katrina Cathie, Luanne Hall-Stoodley, Victoria Cornelius, Caroline Duignan, Raymond N. Allan, Bernadette O. Fernandez, Nicolas Barraud, Ken D. Bruce, Johanna Jefferies, Michael Kelso, Staffan Kjelleberg, Scott A. Rice, Geraint B. Rogers, Sandra Pink, Caroline Smith, Priya S. Sukhtankar, Rami Salib, Julian Legg, Mary Carroll, Thomas Daniels, Martin Feelisch, Paul Stoodley, Stuart C. Clarke, Gary Connett, Saul N. Faust, Jeremy S. Webb
Journal: Molecular Therapy (2017)
Maternal Obesity and Cerebral Palsy in Offspring—Reply
Authors: Eduardo Villamor, Kristina Tedroff, Sven Cnattingius
Journal: JAMA (2017)

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BMA annual meeting: STPs should be abandoned, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

Sustainability and transformation partnerships (STPs) should be abandoned, the BMA has said.

Delegates at the association’s annual representative meeting in Bournemouth on 26 June voted in favour of a motion that called for the partnerships between local councils and NHS services to be abandoned. It also condemned the “woeful manner in which STPs have been progressed, turning them into vehicles to try to legitimise further cuts to NHS services.”

The debate came as the BMA released figures, obtained through freedom of information requests, which showed that more than 150 jobs with combined annual salaries of at least £8.5m (€9.6m; $10.9m), had …
Intravenously Delivered Mesenchymal Stem Cells
Authors: Dror Luger, Michael J. Lipinski, Peter C. Westman, David K. Glover, Julien Dimastromatteo, Juan C. Frias, M. Teresa Albelda, Sergey Sikora, Alex Kharazi, Grigory Vertelov, Ron Waksman, Stephen E. Epstein
Journal: Circulation Research (2017)

Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm.To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities.Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O2, were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×106) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×106 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were randomized to tail-vein injection of 2×106 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume.Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities.
Chemical Tools for Studying Lipid-Binding Class A G Protein–Coupled Receptors
Authors: Anna Cooper, Sameek Singh, Sarah Hook, Joel D. A. Tyndall, Andrea J. Vernall
Journal: Pharmacological Reviews (2017)

Cannabinoid, free fatty acid, lysophosphatidic acid, sphingosine 1-phosphate, prostanoid, leukotriene, bile acid, and platelet-activating factor receptor families are class A G protein–coupled receptors with endogenous lipid ligands. Pharmacological tools are crucial for studying these receptors and addressing the many unanswered questions surrounding expression of these receptors in normal and diseased tissues. An inherent challenge for developing tools for these lipid receptors is balancing the often lipophilic requirements of the receptor-binding pharmacophore with favorable physicochemical properties to optimize highly specific binding. In this study, we review the radioligands, fluorescent ligands, covalent ligands, and antibodies that have been used to study these lipid-binding receptors. For each tool type, the characteristics and design rationale along with in vitro and in vivo applications are detailed.