tbuckley/cabot-search huggingface dataset:
Which is the best procedure for the treatment of gastric cancer in the upper stomach?
Authors: Reo Sato, Masanori Tokunaga, Masahiro Watanabe, Shizuki Sugita, Akiko Tonouchi, Yuri Tanaka, Eigo Akimoto, Takeshi Ono, Akira Kameyama, Akio Kaito, Takahiro Kinoshita
Journal: Journal of Clinical Oncology (2019)

159 Background: The incidence of upper-third early gastric cancer (EGC) has been increasing in East Asia. Although total gastrectomy (TG) has been a standard treatment for upper-third EGC, proximal gastrectomy (PG) or distal gastrectomy (DG) can be indicated for some selected patients. Theoretically, the more we preserve stomach volume, the better postoperative quality of life will be. However, this issue is not fully investigated. The aim of this study was to clarify the most suitable procedure for upper-third EGC. Methods: This study included 187 patients who underwent TG (n = 20), PG (n = 138), or DG (n = 29) for cT1N0 upper-third gastric cancer between 2009 and August 2017. Surgical outcomes, including bodyweight change one year after the surgery, were retrospectively compared among surgical procedures. DG was generally selected if the distance between the esophagogastric junction (EGJ) and proximal margin of the tumor was more than 20 mm. PG was chosen if at least the distal half of the stomach could be preserved. Otherwise, TG was performed. Results: Background characteristics and proportion of laparoscopic approach were not different among the groups. The duration of surgery was not significantly different, but intraoperative blood losswas significantly less in DG than PG (19 vs. 39 g, p = 0.02). The incidence of Clavien-Dindo classification grade IIIa or more anastomosis-related complications was less frequent in DG (3.4%) than in PG (15.9%, p = 0.13) or TG (10%, p = 0.56), although the differences were not statistically significant. Albumin and hemoglobin levels one year after surgery were not significantly different among the groups. Bodyweight loss one year after surgery was less in DG (11.1%) than in PG (14.6%, p = 0.03) or TG (16.6%, p &lt; 0.01). Conclusions: DG was a safe procedure with less bodyweight loss, and thus preservation of the EGJ should be considered for all patients with tumors at least 2 cm apart from the EGJ. If the distance between EGJ and tumor is less than 2 cm, PG or TG will be indicated. However, surgical outcomes between PG and TG in this study were not different, and therefore, further investigations including long term quality of life are necessary.
Patients with severe eosinophilic asthma treated with Mepolizumab: Results from our clinical practice
Authors: Irene Hernandez-Martin, Pilar Barranco, Marta Sanchez-Jareño, Paola Palao-Ocharan, Javier Dominguez-Ortega, David Romero-Ribate, Juan Alberto Luna-Porta, Santiago Quirce
Journal: Journal of Allergy and Clinical Immunology (2019)
Toward Minimum Standards Guidelines for the Delivery of Neurological Care in Complex Humanitarian Settings
Authors: Farrah J. Mateen
Journal: JAMA Neurology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Mitogenomes Uncover Extinct Penguin Taxa and Reveal Island Formation as a Key Driver of Speciation
Authors: Theresa L Cole, Daniel T Ksepka, Kieren J Mitchell, Alan J D Tennyson, Daniel B Thomas, Hailin Pan, Guojie Zhang, Nicolas J Rawlence, Jamie R Wood, Pere Bover, Juan L Bouzat, Alan Cooper, Steven R Fiddaman, Tom Hart, Gary Miller, Peter G Ryan, Lara D Shepherd, Janet M Wilmshurst, Jonathan M Waters
Journal: Molecular Biology and Evolution (2019)

The emergence of islands has been linked to spectacular radiations of diverse organisms. Although penguins spend much of their lives at sea, they rely on land for nesting, and a high proportion of extant species are endemic to geologically young islands. Islands may thus have been crucial to the evolutionary diversification of penguins. We test this hypothesis using a fossil-calibrated phylogeny of mitochondrial genomes (mitogenomes) from all extant and recently extinct penguin taxa. Our temporal analysis demonstrates that numerous recent island-endemic penguin taxa diverged following the formation of their islands during the Plio-Pleistocene, including the Galápagos (Galápagos Islands), northern rockhopper (Gough Island), erect-crested (Antipodes Islands), Snares crested (Snares) and royal (Macquarie Island) penguins. Our analysis also reveals two new recently extinct island-endemic penguin taxa from New Zealand's Chatham Islands: Eudyptes warhami sp. nov. and a dwarf subspecies of the yellow-eyed penguin, Megadyptes antipodes richdalei ssp. nov. Eudyptes warhami diverged from the Antipodes Islands erect-crested penguin between 1.1 and 2.5 Ma, shortly after the emergence of the Chatham Islands (∼3 Ma). This new finding of recently evolved taxa on this young archipelago provides further evidence that the radiation of penguins over the last 5 Ma has been linked to island emergence. Mitogenomic analyses of all penguin species, and the discovery of two new extinct penguin taxa, highlight the importance of island formation in the diversification of penguins, as well as the extent to which anthropogenic extinctions have affected island-endemic taxa across the Southern Hemisphere's isolated archipelagos.
Down-Regulation of CD25 Antigen in Hairy Cell Leukemia Patients after Treatment
Authors: Mirela Anghelina, Narendranath Epperla, Kerry A. Rogers, Ling Guo, Qiuhong Zhao, James S. Blachly, David M. Lucas, Christopher C. Oakes, Gerard Lozanski, Michael R. Grever, Leslie A. Andritsos
Journal: Blood (2018)
Randomized phase II trial of the carboxylesterase (CES)-converted novel drug EDO-S7.1 in patients (pts) with advanced biliary tract cancers (BTC).
Authors: Ulrich-Frank Pape, Stefan Kasper, Johannes Meiler, Marianne Sinn, Arndt Vogel, Lothar Mueller, Oswald Burkhard, Karel Caca, Steffen Heeg, Victor Rodriguez Laval, Anya A Kühl, Ruza Arsenic, Holger Jansen, Nalan Utku
Journal: Journal of Clinical Oncology (2019)

264 Background: The novel drug EDO-S7.1 (CAP7.1) is converted to active etoposide by CES allowing administration of higher doses, reducing resistance, and permitting treatment of advanced tumors. Methods: The primary objective was to compare disease control rate (DCR) in 22 pts with unresectable BTC randomized 1:1 to 3-week cycles of EDO-S7.1 (200 or 150mg/m 2 ; iv) given on days (d) 1–5, or best supportive care (BSC) until progression (assessed every 4 weeks). Secondary objectives were progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. BSC pts could crossover to EDO-S7.1 upon progression. Results: DCR favored EDO-S7.1 (55.6% [CI 21.2, 86.3] vs BSC (20.0% [2.5, 55.6]; treatment difference –12.80, 72.39). More EDO-S7.1 treated pts achieved sustainable stable disease (SD) or partial response (PR) vs BSC. Progressive disease occurred in 40% EDO-S7.1 vs 70% BSC pts. Three pts (30%) who progressed on BSC achieved SD following crossover to EDO-S7.1, and one pt (10%) PR (total: 40.0% [12.2, 73.8]) vs two pts with SD following BSC (20.0% [2.5, 55.6]; treatment difference –0.17, 0.57; p=0.0786). Median PFS was 103d with EDO-S7.1 vs 39d with BSC (p=0.006), and median TTF 92d vs 39d, respectively (p=0.006). Median OS was 227d with EDO-S7.1 vs 162d with BSC (p=0.088), and estimated 1-year OS 44% vs 11.3%, respectively. EDO-S7.1 had significant efficacy in pts with metastatic disease (p=0.029) or without prior surgery (p=0.032). Seven pts were eligible for exploratory analysis of tumor CES via immunohistochemistry. 4/7 pts had CES+ tumors and longer median PFS (195d [163, 233]) and OS (302d [214, 838]) vs pts with CES– tumors (46d [46, 83] and 83d [43, 319], respectively). The most common drug-related adverse events (G3–4) (%) were leukopenia 65 (26.1), neutropenia 78.3 (56.5), thrombocytopenia 56.5 (17.4), anemia 52.2 (17.4), alopecia 34.4 (0), fatigue 26.1 (0), and abdominal pain 30.4 (0). Conclusions: EDO-S7.1 demonstrated efficacy in pts with advanced BTC and may provide a new biomarker-guided therapeutic option with stratification by intra-tumor CES assessment. These findings will be explored in a larger patient cohort. Clinical trial information: NCT02094560.
Micro-CT of tracheal stenosis in trisomy 21
Authors: Susan C Shelmerdine, Michael T Ashworth, Alistair D Calder, Nagarajan Muthialu, Owen J Arthurs
Journal: Thorax (2019)

A male infant with trisomy 21, born at 36 weeks' gestation, had care withdrawn at 2 months of age and was referred for postmortem investigations. The child had been ventilator dependent since the first week of life following surgery for intestinal perforation from necrotising enterocolitis. A CT thorax at 1 month of age demonstrated a tight tracheal stenosis, inferior to the tip of the endotracheal tube, with a luminal diameter of 1.2 mm over a length of 1 cm (figure 1). There were no associated cardiovascular or bronchial tree anomalies. Despite efforts to optimise the child’s condition for tracheal reconstruction, he was subsequently found to have an underlying immune deficit disorder with profound lymphopenia and continued to require iontropic support for haemodynamic compromise. After a further month of expectant clinical management without improvement, care was withdrawn.



Figure 1 
Antemortem CT thorax obtained 1 month prior to death. (A) A coronal 5 mm minimum intensity projection (miniP) image, viewed on lung windows, demonstrates the tight tracheal stenosis immediately distal to the endotracheal tube (red square bracket). Axial CT sections obtained (B) above, (C) at the …
Early detection of pancreatic ductal adenocarcinoma using abnormal urinary fragmentation ratio of a liver-originated protein.
Authors: Motoyasu Kan, Shuichi Mitsunaga, Masafumi Ikeda, Izumi Ohno, Hironobu Tsubouchi, Shigehisa Yanagi, Nobuhiro Matsumoto, Nobuaki Okumura, Toshifumi Takao, Masamitsu Nakazato
Journal: Journal of Clinical Oncology (2019)

214 Background: Non PDAC tissue-originated proteins are cleaved by proteases derived from PDAC, which can result in abnormal cleavage patterns in the urine of PDAC patients. Urinary proteomic analysis for quantifying the ratios of the abnormal protein fragments to the non-fragmented protein levels in the urine may be useful to distinguish early PDAC from healthy controls. This proof-of-concept study was planned to determine the usefulness of measuring the protein fragments from non PDAC tissue-originated proteins in the urine using the multiple-reaction-monitoring technique (MRM) for discriminating resectable PDAC from healthy controls. Methods: Urinary proteins were digested with trypsin, and resultant peptides were measured by MRM analysis and the ratio of the level of each fragment to the non-fragmented protein level (fragmentation ratio) was calculated. Fragments for which the fragmentation ratios were higher in the PDAC group than those in the healthy group were defined as abnormal protein fragments. The diagnostic capability of each abnormal protein fragment for discriminating cases of PDAC from healthy controls was evaluated by receiver operating characteristic (ROC) curve analysis. Results: A total of 21 patients with resectable PDAC and 30 healthy control subjects were enrolled in this study. All the PDAC patients were treated by pancreatic resection. Urine samples for this study were collected prior to the surgery from the PDAC patients. The non PDAC tissue-originated protein was determined as a liver-originated protein. The fragmentation ratios for six fragments were found to be higher in the PDAC group as compared to those in the healthy control group, and these fragments were determined as abnormal protein fragments. ROC curve analysis was performed for each of the abnormal fragments to determine the areas under the curve (AUCs) for discriminating cases of PDAC from healthy controls. The best AUC was 0.81 (95% CI, 0.68-0.91). Conclusions: The urinary fragmentation ratios showed the ability to discriminate cases of resectable PDAC from a healthy control group; abnormal fragmentation ratios may be promising, noninvasively measurable biomarkers of early PDAC.
High Prevalence of PPM1D Mutations in Therapy-Related AML/MDS Is Due to Context-Specific Clonal Hematopoiesis
Authors: Joanne Hsu, Tajhal Dayaram, Ayala Tovy, Etienne De Braekeleer, Mira Jeong, Jason H. Rogers, Feng Wang, Jianhua Zhang, Guillermo Garcia-Manero, Hagop M. Kantarjian, George S. Vassiliou, Andrew Futreal, Lawrence Donehower, Koichi Takahashi, Margaret Goodell
Journal: Blood (2018)
MDH1 and MPP7 Regulate Autophagy in Pancreatic Ductal Adenocarcinoma
Authors: Maria New, Tim Van Acker, Jun-Ichi Sakamaki, Ming Jiang, Rebecca E. Saunders, Jaclyn Long, Victoria M.-Y. Wang, Axel Behrens, Joana Cerveira, Padhmanand Sudhakar, Tamas Korcsmaros, Harold B.J. Jefferies, Kevin M. Ryan, Michael Howell, Sharon A. Tooze
Journal: Cancer Research (2019)

Pancreatic ductal adenocarcinoma (PDAC) is driven by metabolic changes in pancreatic cells caused by oncogenic mutations and dysregulation of p53. PDAC cell lines and PDAC-derived xenografts grow as a result of altered metabolic pathways, changes in stroma, and autophagy. Selective targeting and inhibition of one of these may open avenues for the development of new therapeutic strategies. In this study, we performed a genome-wide siRNA screen in a PDAC cell line using endogenous autophagy as a readout and identified several regulators of autophagy that were required for autophagy-dependent PDAC cell survival. Validation of two promising candidates, MPP7 (MAGUK p55 subfamily member 7, a scaffolding protein involved in cell-cell contacts) and MDH1 (cytosolic Malate dehydrogenase 1), revealed their role in early stages of autophagy during autophagosome formation. MPP7 was involved in the activation of YAP1 (a transcriptional coactivator in the Hippo pathway), which in turn promoted autophagy, whereas MDH1 was required for maintenance of the levels of the essential autophagy initiator serine-threonine kinase ULK1, and increased in the activity upon induction of autophagy. Our results provide a possible explanation for how autophagy is regulated by MPP7 and MDH1, which adds to our understanding of autophagy regulation in PDAC. SIGNIFICANCE: This study identifies and characterizes MPP7 and MDH1 as novel regulators of autophagy, which is thought to be responsible for pancreatic cancer cell survival.
Abstract 20078: Low CD3+ and CD73+ Lymphocyte Counts, and High Neutrophil/CD73 Ratio During TTM Are Associated With Poor Outcome After Cardiac Arrest
Authors: Sergey Ryzhov, Sarah Peterson, Richard R Riker, Teresa May, Ivette Emery, John Dziodzio, Angela Leclerc, Edward Jachimowicz, Rutwick Rath, Barbara McCrum, Pauline Boyce, Christine Lord, Deanna Williams, David B Seder
Journal: Circulation (2017)

Introduction: Immune cell activity modulates inflammation and may affect outcomes in post-resuscitation syndrome. We characterized patterns of immune cells circulating in peripheral blood at different time points to establish immune “phenotypes” of patients with good and poor outcomes, and to investigate immune mechanisms of disease after cardiac arrest. Hypothesis: Circulating lymphocyte subpopulations may be associated with outcome after cardiac arrest. Methods: After informed consent, blood samples were collected at 6, 12, 24, 48, 72, and 168 hours after resuscitation. White blood cells were isolated, counted and analyzed for the expression of specific pro-inflammatory antigens using flow cytometry. Cell counts at each time point were correlated with neurological outcomes determined at 3-12 months, and outcomes were classified as good (CPC 1-2) or poor (CPC 3-5) by convention. Results: The 34 research subjects were 55.9±16.6 years old and 23.5% female. Median ischemic time was 17(10-22.5) minutes. Of t...
Phase II Study of Roniciclib in Combination with Cisplatin/Etoposide or Carboplatin/Etoposide as First-Line Therapy in Patients with Extensive-Disease Small Cell Lung Cancer
Authors: Martin Reck, Leora Horn, Silvia Novello, Fabrice Barlesi, István Albert, Erzsébet Juhász, Dariusz Kowalski, Gilles Robinet, Jacques Cadranel, Paolo Bidoli, John Chung, Arno Fritsch, Uta Drews, Andrea Wagner, Ramaswamy Govindan
Journal: Journal of Thoracic Oncology (2019)
Compositional changes to the ileal microbiome precede the onset of spontaneous ileitis in SHIP deficient mice
Authors: Peter Allan Dobranowski, Chris Tang, Jean Philippe Sauvé, Susan Christine Menzies, Laura May Sly
Journal: Gut Microbes (2019)

Inflammatory bowel disease, encompassing both ulcerative colitis and Crohn's disease, is characterized by chronic, relapsing-remitting gastrointestinal inflammation of unknown etiology. SHIP deficient mice develop fully penetrant, spontaneous ileitis at 6 weeks of age, and thus offer a tractable model of Crohn's disease-like inflammation. Since disruptions to the microbiome are implicated in the pathogenesis of Crohn's disease, we conducted a 16S rRNA gene survey of the ileum, cecum, colon, and stool contents of SHIP+/+ and SHIP−/− mice. We predicted that diversity and compositional changes would occur after, and possibly prior to, the onset of overt disease. No differences were found in alpha diversity, but significant changes in beta diversity and specific commensal populations were observed in the ileal compartment of SHIP deficient mice after the onset of overt disease. Specifically, reductions in the Bacteroidales taxa, Muribaculum intestinale, and an expansion in Lactobacillus were most notable. In contrast, expansions to bacterial taxa previously associated with inflammation, including Bacteroides, Parabacteroides, and Prevotella were observed in the ilea of SHIP deficient mice prior to the onset of overt disease. Finally, antibiotic treatment reduced the development of intestinal inflammation in SHIP−/− mice. Thus, our findings indicate that SHIP is involved in maintaining ileal microbial homeostasis. These results have broader implications for humans, since reduced SHIP protein levels have been reported in people with Crohn's disease.
Effects of CDX2 on proliferation and glucose metabolism reprogram by targeting PGAM1 in colorectal cancer.
Authors: Qingguo Li, Shaobo Mo, Xinxiang Li, SanJun Cai
Journal: Journal of Clinical Oncology (2019)

561 Background: The CDX2 expression is significantly decreased in colorectal cancer (CRC) tissues and lost its expression is associated with poor survival. However, the underline of this activity of CDX2 is not well understood. In the present study, we sought to determine the role of CDX2 in tumorigenesis, and elucidate the possible mechanism. Methods: The effect of CDX2 expression on proliferation of and glycolysis in CRC cells was assessed by altering its expression in vitro and in vivo. Mechanistic investigation was carried out using cell and molecular biological approaches. Human CRC tissues were also used to verify the relationship between CDX2 expression and glycolysis. Results: Forced CDX2 expression in CRC cells inhibited their proliferation and colony formation. In contrast, silencing CDX2 expression had the opposite effect, suggesting that CDX2 is a negative regulator of oncogenesis in CRC. Mechanistically, CDX2 negatively regulated the aerobic glycolysis, a process that contributed to tumor progression by providing energy source and building blocks for macromolecule synthesis. Consistent with this observation, an in vivo subcutaneous xenograft mouse model and in a series of patients (n=71) received PET/CT initial after diagnosed also confirmed the hypothesis that CDX2 is a negative regulator of glycolysis as reflected by the decreased 18 FDG uptake in PET/CT system. Furthermore, increased expression of CDX2 downregulated that of a glycolytic enzyme, phosphoglycerate mutase 1(PGAM1) in vitro. Moreover, there was a negative relationship between CDX2 and PGAM1 expression in human CRC tissues as determined by both RT-PCR and Immunohistochemistry. Luciferase analysis further indicated that CDX2 could inhibited PGAM1 promoter activity at dose dependent. Conclusions: The CDX2 inhibits cell proliferation, reprograms glucose metabolism by targeting PGAM1 expression in CRC, and the CDX2/PGAM1 axis constitutes potential prognostic predictors and therapeutic targets for CRC.
Outcomes of tyrosine kinase inhibitors (TKI) after immunotherapy in unresectable or advanced hepatocellular carcinoma (HCC) patients.
Authors: Thomas Cheung Yau, Vikki Tang, Jess Chan, Gin Wai Kwok, Joanne Chiu, Roland Ching-Yu Leung, Bryan Li, Tan To Cheung
Journal: Journal of Clinical Oncology (2019)

361 Background: The outcomes of tyrosine kinase inhibitor(TKI) treatment after immune checkpoint inhibitors (PD-1i, PD-L1i, CTLA-4i) in unresectable/advanced HCC population is largely unknown. Methods: Retrospective analysis of advanced HCC patients treated with immune checkpoint inhibitors followed by TKI therapy at Queen Mary Hospital, Hong Kong were reviewed for the outcomes. Patients received locoregional therapy immediately after immunotherapy were excluded. Results: From January 2016 to July 2018, 30 HCC patients (83% of HBV, 80% of Child Pugh A, 83% of EHS/ MVI, median AFP=1,353ng/mL) who received TKI (11 lenvatinib, 10 sorafenib, 6 regorafenib, 3 axitinib) after immunotherapy were identified. TKI post-immunotherapy ("index TKI") was administered as third-line or beyond in 70% of patients. At the time of analysis (September 2018), median duration of index TKI was 72 days (IQR 36- 119∗) (∗3 patients were still receiving TKI). AFP declined in 53% of patients and the median change from baseline to nadir was -25% (IQR -65% to +6%). 40% of patients received subsequent systemic therapy. Median OS from index TKI was 602 days (95%CI 124-not reached; death event rate: 47%). 3 patients achieved partial response to TKI and they had at least stable disease with the previous immunotherapy. No unexpected safety issues of TKI and death related to adverse events were noted (table). Conclusions: TKI is active with good tolerabilty following immunotherapy in advanced HCC patients.[Table: see text]