tbuckley/cabot-search huggingface dataset:
Endoscopic removal of an eroded magnetic sphincter augmentation device
Authors: Baldwin Yeung, Grant Fullarton
Journal: Endoscopy (2017)

Magnetic sphincter augmentation with the LINX device (Torax Medical, Shoreview, Minnesota, USA) is an effective treatment for gastroesophageal reflux disease (GERD). It is associated with shorter operating time and lower rate of gas bloat [1]. Erosion is estimated to range from 0.1 % to 1.2 %; it may be higher with the smaller device. The most common method for device removal involves a combined endoscopic-laparoscopic approach [2] [3]. Endoscopic removal using a bipolar grasping device has also been reported [4]. We report the first case of LINX erosion in the United Kingdom and its endoscopic removal using Olympus loop cutters.
Irinotecan in combination with platinum in refractory or relapsed small cell lung cancer.
Authors: Shufei Yu, Yan Wang
Journal: Journal of Clinical Oncology (2013)

e18504 Background: To evaluate the efficacy and safety of irinotecan in combination with platinum against refractory or relapsed small cell lung cancer. Methods: In this retrospective study, we analyzed the data of 1,140 patients who diagnosed small cell lung cancer at our hospital between 2009 and 2012. Of all the patients, 34 were treated with irinotecan and nedaplatin (irinotecan 60mg/m 2 on days 1,8 nedaplatin 85mg/m 2 day 1,every 3 weeks), and 20 patients were treated with irinotecan and cisplatin (irinotecan 60mg/m 2 on days 1,8 cisplatin 75mg/m 2 day 1,every 3 weeks ) as the second line treatment. Prognostic factors of overall survival (OS) were estimated by Kaplan-Meier and Cox's Regression-proportional hazards model. Results: Of 54 eligible patients, median progression free survival (PFS) was 21weeks, and median OS was 58 weeks. Median PFS was 23 weeks for irinotecan plus nedaplatin and 19 weeks for irinotecan plus cisplatin (P=0.410). Median OS was 62 weeks and 58 weeks, respectively (P=0.714).The response rate (RR) was 29% and 33.3%, respectively (HR 0.818,95%CI 0.234to2.855; P=0.753). In multivariate analysis, younger age, extensive stage while diagnosed, brain metastasis, treated with 3 cycles of irinotecan in combination with platinum or less, and PS≥1 were all associated with a statistically significant increase in the mortality harzard. Toxicity profile was slightly different for each of the arms: hematologic toxicity was higher with nedaplatin, and diarrhea was higher with cisplatin. Conclusions: Irinotecan plus platinum is effective and tolerable for refractory and relapsed small cell lung cancer. [Table: see text]
Insects: an underrepresented resource for the discovery of biologically active natural products
Authors: Lauren Seabrooks, Longqin Hu
Journal: Acta Pharmaceutica Sinica B (2017)

Nature has been the source of life-changing and -saving medications for centuries. Aspirin, penicillin and morphine are prime examples of Nature׳s gifts to medicine. These discoveries catalyzed the field of natural product drug discovery which has mostly focused on plants. However, insects have more than twice the number of species and entomotherapy has been in practice for as long as and often in conjunction with medicinal plants and is an important alternative to modern medicine in many parts of the world. Herein, an overview of current traditional medicinal applications of insects and characterization of isolated biologically active molecules starting from approximately 2010 is presented. Insect natural products reviewed were isolated from ants, bees, wasps, beetles, cockroaches, termites, flies, true bugs, moths and more. Biological activities of these natural products from insects include antimicrobial, antifungal, antiviral, anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.
Gesture or sign? A categorization problem
Authors: Corrine Occhino, Sherman Wilcox
Journal: Behavioral and Brain Sciences (2017)

Abstract Goldin-Meadow &amp; Brentari (G-M&amp;B) rely on a formalist approach to language, leading them to seek objective criteria by which to distinguish language and gesture. This results in the assumption that gradient aspects of signs are gesture. Usage-based theories challenge this view, maintaining that all linguistic units exhibit gradience. Instead, we propose that the distinction between language and gesture is a categorization problem.
Simon Albert Philip Jenkins
Authors: Deborah Joseph
Journal: BMJ (2017)

Simon Albert Philip Jenkins was born in Ellesmere, Shropshire. He qualified from Birmingham University in 1960 with distinction in social medicine. His preregistration jobs were at North Staffordshire Royal Infirmary, followed by a senior house officer post in medicine and rheumatology at Manchester Royal Infirmary in 1961. He became an assistant in general practice in Heywood, Lancashire, in 1962 and then joined a small, busy urban practice in Bury, Lancashire, in 1963. He was instrumental in organising five separate partnerships into a single effective group practice to form the Minden Medical Centre in the centre of Bury in 1969. He was a strong advocate of personal lists, which his practice still adhered to for 40 years.

He held clinical assistant posts in accident and emergency medicine in the 1960s and anaesthetics in the 70s.

Simon was very active in medicopolitics and became a fellow of the BMA in 1990. He was a member of the association’s General Medical Services Committee for many years, becoming chairman of the computing subcommittee from 1985 to 1993 and chairman of the joint computing group of the GMSC/RCGP from 1992 to 1994.

He was head of the UK delegation to the UEMO (the medicopolitical organisation of European GPs) in 1982-86 and 1991-97. He represented his profession at conferences in Berlin (1988), Rhodes (1995), and Athens (1996).

As a BMA representative he was involved in Europe-wide negotiations with EPIC (Ex Prisoners Interpretative Centre) Northern Ireland in 1993, and AIM (Advanced Informatics in Medicine) in 1994.

Simon saw one of his main …
The SLC22 Transporter Family: A Paradigm for the Impact of Drug Transporters on Metabolic Pathways, Signaling, and Disease
Authors: Sanjay K. Nigam
Journal: The Annual Review of Pharmacology and Toxicology (2018)

The SLC22 transporter family consists of more than two dozen members, which are expressed in the kidney, the liver, and other tissues. Evolutionary analysis indicates that SLC22 transporters fall into at least six subfamilies: OAT (organic anion transporter), OAT-like, OAT-related, OCT (organic cation transporter), OCTN (organic cation/carnitine transporter), and OCT/OCTN-related. Some-including OAT1 [SLC22A6 or NKT (novel kidney transporter)] and OAT3 (SLC22A8), as well as OCT1 (SLC22A1) and OCT2 (SLC22A2)-are widely studied drug transporters. Nevertheless, analyses of knockout mice and other data indicate that SLC22 transporters regulate key metabolic pathways and levels of signaling molecules (e.g., gut microbiome products, bile acids, tricarboxylic acid cycle intermediates, dietary flavonoids and other nutrients, prostaglandins, vitamins, short-chain fatty acids, urate, and ergothioneine), as well as uremic toxins associated with chronic kidney disease. Certain SLC22 transporters-such as URAT1 (SLC22A12) and OCTN2 (SLC22A5)-are mutated in inherited metabolic diseases. A new systems biology view of transporters is emerging. As proposed in the remote sensing and signaling hypothesis, SLC22 transporters, together with other SLC and ABC transporters, have key roles in interorgan and interorganism small-molecule communication and, together with the neuroendocrine, growth factor-cytokine, and other homeostatic systems, regulate local and whole-body homeostasis.
Recommendations for Surveillance for Children with Leukemia-Predisposing Conditions
Authors: Christopher C. Porter, Todd E. Druley, Ayelet Erez, Roland P. Kuiper, Kenan Onel, Joshua D. Schiffman, Kami Wolfe Schneider, Sarah R. Scollon, Hamish S. Scott, Louise C. Strong, Michael F. Walsh, Kim E. Nichols
Journal: Clinical Cancer Research (2017)

Abstract Leukemia, the most common childhood cancer, has long been recognized to occasionally run in families. The first clues about the genetic mechanisms underlying familial leukemia emerged in 1990 when Li-Fraumeni syndrome was linked to TP53 mutations. Since this discovery, many other genes associated with hereditary predisposition to leukemia have been identified. Although several of these disorders also predispose individuals to solid tumors, certain conditions exist in which individuals are specifically at increased risk to develop myelodysplastic syndrome (MDS) and/or acute leukemia. The increasing identification of affected individuals and families has raised questions around the efficacy, timing, and optimal methods of surveillance. As part of the AACR Childhood Cancer Predisposition Workshop, an expert panel met to review the spectrum of leukemia-predisposing conditions, with the aim to develop consensus recommendations for surveillance for pediatric patients. The panel recognized that for several conditions, routine monitoring with complete blood counts and bone marrow evaluations is essential to identify disease evolution and enable early intervention with allogeneic hematopoietic stem cell transplantation. However, for others, less intensive surveillance may be considered. Because few reports describing the efficacy of surveillance exist, the recommendations derived by this panel are based on opinion, and local experience and will need to be revised over time. The development of registries and clinical trials is urgently needed to enhance understanding of the natural history of the leukemia-predisposing conditions, such that these surveillance recommendations can be optimized to further enhance long-term outcomes. Clin Cancer Res; 23(11); e14–e22. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.
Life expectancy difference and life expectancy ratio: two measures of treatment effects in randomised trials with non-proportional hazards
Authors: Hakim-Moulay Dehbi, Patrick Royston, Allan Hackshaw
Journal: BMJ (2017)

The hazard ratio (HR) is the most common measure of treatment effect in clinical trials that use time-to-event outcomes such as survival. When survival curves cross over or separate only after a considerable time, the proportional hazards assumption of the Cox model is violated, and HR can be misleading. We present two measures of treatment effects for situations where the HR changes over time: the life expectancy difference (LED) and life expectancy ratio (LER). LED is the difference between mean survival times in the intervention and control arms. LER is the ratio of these two times. LED and LER can be calculated for at least two time intervals during the trial, allowing for curves where the treatment effect changes over time. The two measures are readily interpretable as absolute and relative gains or losses in life expectancy.
Recruitment of a Lineage-Specific Virulence Regulatory Pathway Promotes Intracellular Infection by a Plant Pathogen Experimentally Evolved into a Legume Symbiont
Authors: Delphine Capela, Marta Marchetti, Camille Clérissi, Anthony Perrier, Dorian Guetta, Carine Gris, Marc Valls, Alain Jauneau, Stéphane Cruveiller, Eduardo P.C. Rocha, Catherine Masson-Boivin
Journal: Molecular Biology and Evolution (2017)

Ecological transitions between different lifestyles, such as pathogenicity, mutualism and saprophytism, have been very frequent in the course of microbial evolution, and often driven by horizontal gene transfer. Yet, how genomes achieve the ecological transition initiated by the transfer of complex biological traits remains poorly known. Here, we used experimental evolution, genomics, transcriptomics and high-resolution phenotyping to analyze the evolution of the plant pathogen Ralstonia solanacearum into legume symbionts, following the transfer of a natural plasmid encoding the essential mutualistic genes. We show that a regulatory pathway of the recipient R. solanacearum genome involved in extracellular infection of natural hosts was reused to improve intracellular symbiosis with the Mimosa pudica legume. Optimization of intracellular infection capacity was gained through mutations affecting two components of a new regulatory pathway, the transcriptional regulator efpR and a region upstream from the RSc0965–0967 genes of unknown functions. Adaptive mutations caused the downregulation of efpR and the over-expression of a downstream regulatory module, the three unknown genes RSc3146–3148, two of which encoding proteins likely associated to the membrane. This over-expression led to important metabolic and transcriptomic changes and a drastic qualitative and quantitative improvement of nodule intracellular infection. In addition, these adaptive mutations decreased the virulence of the original pathogen. The complete efpR/RSc3146–3148 pathway could only be identified in the genomes of the pathogenic R. solanacearum species complex. Our findings illustrate how the rewiring of a genetic network regulating virulence allows a radically different type of symbiotic interaction and contributes to ecological transitions and trade-offs.
3D Bioprinting Human Induced Pluripotent Stem Cell Constructs for In Situ Cell Proliferation and Successive Multilineage Differentiation
Authors: Qi Gu, Eva Tomaskovic‐Crook, Gordon G. Wallace, Jeremy M. Crook
Journal: Advanced Healthcare Materials (2017)

The ability to create 3D tissues from induced pluripotent stem cells (iPSCs) is poised to revolutionize stem cell research and regenerative medicine, including individualized, patient‐specific stem cell‐based treatments. There are, however, few examples of tissue engineering using iPSCs. Their culture and differentiation is predominantly planar for monolayer cell support or induction of self‐organizing embryoids (EBs) and organoids. Bioprinting iPSCs with advanced biomaterials promises to augment efforts to develop 3D tissues, ideally comprising direct‐write printing of cells for encapsulation, proliferation, and differentiation. Here, such a method, employing a clinically amenable polysaccharide‐based bioink, is described as the first example of bioprinting human iPSCs for in situ expansion and sequential differentiation. Specifically, we have extrusion printed the bioink including iPSCs, alginate (Al; 5% weight/volume [w/v]), carboxymethyl‐chitosan (5% w/v), and agarose (Ag; 1.5% w/v), crosslinked the bioink in calcium chloride for a stable and porous construct, proliferated the iPSCs within the construct and differentiated the same iPSCs into either EBs comprising cells of three germ lineages—endoderm, ectoderm, and mesoderm, or more homogeneous neural tissues containing functional migrating neurons and neuroglia. This defined, scalable, and versatile platform is envisaged being useful in iPSC research and translation for pharmaceuticals development and regenerative medicine.
Endoscopic tattoo: the importance and need for standardised guidelines and protocol
Authors: Mei Yang, Daniel Pepe, Christopher M Schlachta, Nawar A Alkhamesi
Journal: Journal of the Royal Society of Medicine (2017)

Preoperative endoscopic tattoo is becoming more important with the advent of minimally invasive surgery. Current practices are variable and are operator-dependent. There are no evidence-based guidelines to aid endoscopists in clinical practice. Furthermore, there are still a number of issues with endoscopic tattoo including poor intraoperative visualisation, complications from tattooing and inaccurate documentation leading to the need for intraoperative endoscopy, prolonged operative time and reoperation due to lack of oncologic resection. This review aims to collate and summarise evidence for the best practice of endoscopic tattoo for colorectal lesions in order to provide guidance for endoscopists.
Can cognitive recovery time be estimated by clinical recovery time in concussion suffered by soccer athletes?
Authors: Moacir Silva Neto, Paulo Teixeira, Michael Collins
Journal: British Journal of Sports Medicine (2017)

Objective Determine if there is a correlation between the Clinical Recovery Time (CRT) and the Time from CRT to Cognitive Recovery (CGRT). Design A non-concurrent cohort study. Setting Chart review of Soccer Athletes who suffered concussion and were followed in the Concussion Management Program of the University of Pittsburgh Medical Centre. Participants 92 charts were reviewed. Average Age was 16.2 (SD=2.7), 62% were females. Both CRT and CGRT were retrieved for 42 athletes. Outcome measures CRT was determined by the days that were necessary for a list of rated concussion symptoms to be considered normal. Cognitive Recovery Time (CGRT) was determined when the computerised cognitive test used on follow-ups was considered to be back to normal by trained neuropsychologists. Main results CRT: Median time=23 days. Mean time=42 (SD=53) days (Minimum=1 day and Maximum 231 days). Time from CRT to CGRT: Median time=10 days. Mean time=17.7 (SD=27) days (Minimum=−7 days and Maximum of 157 days). Bivariate correlation of CRT to Time from CRT to CGRT was 0.195 (p=0.216). Conclusions Both CRT ad CGRT vary a lot among soccer players who suffer concussion. Time from CRT to CGRT didn’t correlate with CRT and can’t be estimated based on CRT. Both CRT and CGRT should be evaluated independently during rehabilitation of concussed soccer athletes. Competing interests None. Share holder of ImPACT Applications, Inc.
Association of obesity with breast cancer clinical and pathological factors: Analysis of Turkish National Breast Cancer Registry.
Authors: Ugur Coskun, Kadri Altundag, Mehmet Aliustaoglu, Dogan Uncu, Metin Ozkan, Irfan Cicin, Aydin Ciltas, Tamer Elkiran, Murat Kocer, Abdurrahman Isikdogan, Aziz Karaoglu, Salim Basol Tekin, Nilufer Avci, Arife Ulas, Berna Oksuzoglu, Feyyaz Ozdemir, Esra Dumanli, Alper Sevinc, Saadettin Kilickap, Mustafa Benekli
Journal: Journal of Clinical Oncology (2015)

e12657 Background: Obesity is independently associated with breast cancer (BC) recurrence and poor prognosis despite therapy. However there is no data available about the effect of obesity on the natural course of BC in Turkish pts. This analysis focuses on the effect of obesity on the clinicopathological variables of BC. Methods: Pts presenting to medical oncology clinics were prospectively registered after October 2012 in 28 centers. Clinical and pathological characteristics were recorded. Patients were stratified according to body mass index (BMI): non-obese < 30 and obese ≥ 30.The association of BMI with patient demographics and pathologic characteristics were evaluated. Results: BMI of 13749 pts (128 males [0.9%]) were calculated. Obese pts with BMI ≥ 30 were older compared to non-obese pts (mean 51.7±11.7 vs 56.1±10.5 years; p < 0.001). There was no difference in gender in terms of obesity (p = 0.117). Obesity was more prevalent in postmenopausal pts compared to premenopausal women (64% vs 35.5%; p < 0.001). There was no difference in disease stage in obese vs non-obese patients (stage I 15.1% vs 18.5%; stage II 49.2% vs 48.6%; stage III 28% vs 24.6% and stage IV 7.7% vs 8.2%, respectively). Histopathological diagnosis of invasive ductal and lobular cancers were similar (p = 0.965), as well as tumor grades (grade 1: 8.9% vs 8.3%, grade 2: 46.1% vs 45.7%, and grade 3: 30.4% vs 30.3%, respectively) in obese and non-obese pts (p = 0.521). ER and PR status were similar in both groups. However, obese patients had a lower likelihood of Her2 positivity (25.5% vs 29.7%; p < 0.001). Obesity prevalence was not different among patients in BC molecular subgroups of luminal A/B, Her2-enriched and triple-negative (p = 0.186). Conclusions: This was the first large scale study investigating the relationship of obesity with BC clinical and pathological variables in Turkish pts. We showed that Her2 positivity was lower in obese patients. However, there was no association of obesity with ER/PR and BC molecular subtypes. Effect of BMI on patient outcomes will be analyzed separately.
A precision-guided MWNT mediated reawakening the sunk synergy in RAS for anti-angiogenesis lung cancer therapy
Authors: Yujie Su, Yahui Hu, Yu Wang, Xiangting Xu, Yang Yuan, Yunman Li, Zeyuan Wang, Kerong Chen, Fangrong Zhang, Xuefang Ding, Min Li, Jianping Zhou, Yuan Liu, Wei Wang
Journal: Biomaterials (2017)
ACCF/ACR/AIUM/ASE/IAC/SCAI/SCVS/SIR/SVM/SVS/SVU 2013 Appropriate Use Criteria for Peripheral Vascular Ultrasound and Physiological Testing Part II: Testing for Venous Disease and Evaluation of Hemodialysis Access
Authors: Heather L. Gornik, Marie D. Gerhard-Herman, Sanjay Misra, Emile R. Mohler, R. Eugene Zierler, Reza Fazel, Laura Findeiss, Richard Fuchs, John Gillespie, John Gocke, Michael H. Heggeness, Joseph P. Hughes, Michael P. Lilly, Colleen Moore, John S. Pellerito, Michelle L. Robbin, Thom W. Rooke, Melvin Rosenblatt, Fred A. Weaver, Christopher J. White, Michael J. Wolk, Steven R. Bailey, John U. Doherty, Pamela S. Douglas, Z. Jenissa Haidari, Robert C. Hendel, Christopher M. Kramer, James K. Min, Manesh R. Patel, Leslee Shaw, Raymond F. Stainback, Joseph M. Allen
Journal: Journal of the American College of Cardiology (2013)
The Damaging Effect of Passenger Mutations on Cancer Progression
Authors: Christopher D. McFarland, Julia A. Yaglom, Jonathan W. Wojtkowiak, Jacob G. Scott, David L. Morse, Michael Y. Sherman, Leonid A. Mirny
Journal: Cancer Research (2017)

Abstract Genomic instability and high mutation rates cause cancer to acquire numerous mutations and chromosomal alterations during its somatic evolution; most are termed passengers because they do not confer cancer phenotypes. Evolutionary simulations and cancer genomic studies suggest that mildly deleterious passengers accumulate and can collectively slow cancer progression. Clinical data also suggest an association between passenger load and response to therapeutics, yet no causal link between the effects of passengers and cancer progression has been established. To assess this, we introduced increasing passenger loads into human cell lines and immunocompromised mouse models. We found that passengers dramatically reduced proliferative fitness (∼3% per Mb), slowed tumor growth, and reduced metastatic progression. We developed new genomic measures of damaging passenger load that can accurately predict the fitness costs of passengers in cell lines and in human breast cancers. We conclude that genomic instability and an elevated load of DNA alterations in cancer is a double-edged sword: it accelerates the accumulation of adaptive drivers, but incurs a harmful passenger load that can outweigh driver benefit. The effects of passenger alterations on cancer fitness were unrelated to enhanced immunity, as our tests were performed either in cell culture or in immunocompromised animals. Our findings refute traditional paradigms of passengers as neutral events, suggesting that passenger load reduces the fitness of cancer cells and slows or prevents progression of both primary and metastatic disease. The antitumor effects of chemotherapies can in part be due to the induction of genomic instability and increased passenger load. Cancer Res; 77(18); 4763–72. ©2017 AACR.