tbuckley/cabot-search huggingface dataset:
Immune escape mechanisms associated with tumor recurrence after adoptive cell transfer immunotherapy.
Authors: Marco Donia, Rikke Andersen, Katja Harbst, Manja Idorn, Shamaila Munir, Eva Ellebaek, Anja Mueller, Paolo Fagone, Ferdinando Nicoletti, Salvatore Travali, Sine Reker Hadrup, Mads Hald Andersen, Barbara Seliger, Goran Jonsson, Per thor Straten, Inge Marie Svane
Journal: Journal of Clinical Oncology (2014)

3054 Background: Adoptive cell transfer immunotherapy (ACT) with tumor infiltrating lymphocytes (TILs) results in unprecedented rates of durable clinical responses but some patients initially responding achieve only a temporary disease remission before tumor recurrence. Methods: Disease relapse in a case of metastatic melanoma experiencing tumor recurrence after complete response to treatment with TILs was characterized at the cellular and molecular level using primary tumor cell lines and tumor infiltrating lymphocytes derived from metastatic lesions resected at different time points. Results: Multiple mechanisms linked to tumor-intrinsic evolutional phenomena associated with tumor re-growth despite durable persistence of peripheral antitumor responses were identified. Tumor-cell intrinsic alterations led to both impaired immune sensitivity and universally reduced immune recognition associated with multiple defects in antigen processing machinery, but not to antigen loss or increased expression of immune suppressive molecules such as PD-L1. In addition, cell lines from tumor recurrence were characterized by increased in vivo malignancy independent of immune response sensitivity, in the absence of new known melanoma driver mutations. Conclusions: Data from this study brings direct evidence that tumor cell evolutionary mechanisms responsible for immune escape, and associated with disease recurrence in human metastatic tumors after effective immunotherapies targeting multiple antigens, are extraordinarily complex and multifactorial. Future strategies to extend duration of responses to immunotherapy should consider targeting this complexity
Safety analysis of a phase III randomized trial of chemotherapy with or without bevacizumab (B) in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Authors: Athanassios Argiris, Shuli Li, Panayiotis Savvides, Arlene A. Forastiere, Barbara Burtness
Journal: Journal of Clinical Oncology (2015)

6022 Background: The addition of B, an anti-VEGF monoclonal antibody, to chemotherapy has improved outcomes in several solid tumors. Pemetrexed plus B in R/M SCCHN showed promising efficacy but significant incidence (15%) of grade 3-5 bleeding (Argiris et al. JCO 2011). Methods: Patients (pts) with performance status (PS) 0-1, adequate laboratory parameters, no history of bleeding, not receiving anticoagulation or having blood vessel invasion were randomized to: A) one of 4 regimens (investigator’s choice): A1, cisplatin (C) 100 mg/m2, 5-FU 1000 mg/m2/day x 4 days; A2, carboplatin (Cb) AUC 6, 5-FU 1000 mg/m2/day x 4 days; A3, C 75 mg/m2, docetaxel (D) 75 mg/m2; A4, Cb AUC 6, D 75 mg/m2, every 3 weeks, or B) the same regimen (B1, B2, B3, B4) plus B 15 mg/Kg IV, every 3 weeks, until progression. All pts received prophylactic antibiotics. Chemotherapy could be stopped after 6 cycles after maximum response. The primary endpoint was overall survival with a planned sample size of 400. Results: We report safety results from a total of 357 pts, 183 in Arm A (A1 = 15; A2 = 10; A3 = 88; A4 = 68) and 174 in Arm B (B1 = 12; B2 = 8; B3 = 85; B4 = 66). PS 1, 55%; female, 14%; age ≥ 65, 25%. Grade (G) 5 treatment-related adverse events (AEs), 5% in arm A vs 8% in arm B (p = 0.23), causes (%): febrile neutropenia, 1 vs 0; cardiac arrest, 0 vs 1; gastric hemorrhage, 0 vs 1; tracheal/tracheostomy hemorrhage, 0 vs 2; laryngeal/pharyngeal/bronchial hemorrhage, 0 vs 3; lung infection 1 vs 0; sepsis, 0 vs 1; nervous system/other 0 vs 2. G 5 bleeding AEs, all reported, 1% vs 4% (p = 0.06); treatment-related, 0 vs 3.6 (p = 0.007); G 3-5 bleeding AEs, all reported, 3.6 vs 7.8 (p = 0.08); treatment-related, 0.5 vs 7.3 (p = 0.0004). G 3/4 treatment-related AEs in arm A vs B (%): febrile neutropenia, 7/2 vs 9/6; fatigue, 9/0 vs 17/0; diarrhea, 1/0 vs 5/0; mucositis, 4/0 vs 15/1; vomiting 4/0 vs 6/1; neutropenia, 1/25 vs 7/32; thrombocytopenia, 1/5 vs 5/3; hypertension, 0/0 vs 5/0; thromboembolic, 0/0 vs 4/1. Female gender, age ≥ 65 and PS 1 were risk factors for G 3-5 bleeding with B. Conclusions: The incidence of G 5 toxicities was similar to previous phase III ECOG trials. B increased grade 3-5 bleeding but not overall G 5 AEs. Clinical trial information: NCT00588770.
Abstract P334: Comparative Effectiveness of Left Ventricular Assist Devices as a Bridge to Heart Transplantation
Authors: Robert S Higgins, Sherri Wissman, Kelly MacBriar, Erin Bumgardner, Emily Burke, Pallavi Solanki, Ayehsa Hasan, Juan Crestanello, Chittoor Sai-Sudhakar, Gary Haas, William Abraham, Carl Leier
Journal: Circulation Research (2011)

Left ventricular assist devices (LVAD) have evolved to be more frequently utilized in patients with advanced congestive heart failure as a bridge to heart transplantation. In the era of limited healthcare resources and diminishing funding for innovative technologies, there is little data to evaluate the comparative effectiveness of LVADs in comparison to more conventional heart failure therapies leading to heart transplantation without mechanical circulatory support. Objective . To evaluate the clinical outcomes, complications, length of stay, financial impact and satisfaction of patients with advanced heart failure undergoing heart transplantation as part of a comprehensive heart failure program with or without LVAD as a bridge to transplant (BTT). Methods We retrospectively reviewed 25 patients undergoing heart transplantation from 2009–2010 (12 patients without LVAD, 13 with LVAD as BTT). Inpatient hospital, financial and clinic records were reviewed to evaluate length of stay, morbidity, mortality, DRG assignment, insurance status, charges and cost, reimbursement and patient satisfaction. All patients received surveys assessing their satisfaction with the mechanical circulatory support and transplant program. Results There were 14 males and 11 females (avg age 54 ).In the non- LVAD group, 9 patients fell into DRG 1 ,3 were in DRG 2;in the LVAD group, 10 patients fell in DRG 1, 3 patients were in DRG 2.Complications occurring in the LVAD patients included pneumonia (2),CVA, depression, rejection and bowel perforation ;in the non-LVAD patients pneumonia, pulmonary embolus, aspergillosis, peri-rectal abscess and failure to thrive; Mortality at 1 year occurred in 2 patients after LVAD; 1 patient after transplant without LVAD. All patients responded that they were very satisfied with the advanced heart failure program whether they received LVAD prior to transplant or not Conclusions Transplant recipients with advanced heart failure have comparable clinical outcomes after transplant whether they required LVAD implantation prior to transplant. Perioperative care algorithms focused on reduction of common post-operative complications resulting in significant financial impact (ie pulmonary), should be developed to address these issues.
A novel role for CRTC2 in hepatic cholesterol synthesis through SREBP‐2
Authors: Yujie Li, Yongfeng Song, Meng Zhao, Yanjing Guo, Chunxiao Yu, Wenbin Chen, Shanshan Shao, Chao Xu, Xinli Zhou, Lifang Zhao, Zhenhai Zhang, Tao Bo, Yu Xia, Christopher G. Proud, Xuemin Wang, Li Wang, Jiajun Zhao, Ling Gao
Journal: Hepatology (2017)

Cholesterol synthesis is regulated by the transcription factor sterol regulatory element binding protein 2 (SREBP-2) and its target gene 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), which is the rate-limiting enzyme in cholesterol synthesis. Cyclic adenosine monophosphate-responsive element (CRE) binding protein-regulated transcription coactivator (CRTC) 2 is the master regulator of glucose metabolism. However, the effect of CRTC2 on cholesterol and its potential molecular mechanism remain unclear. Here, we demonstrated that CRTC2 expression and liver cholesterol content were increased in patients with high serum cholesterol levels who underwent resection of liver hemangiomas, as well as in mice fed a 4% cholesterol diet. Mice with adenovirus-mediated CRTC2 overexpression also showed elevated lipid levels in both serum and liver tissues. Intriguingly, hepatic de novo cholesterol synthesis was markedly increased under these conditions. In contrast, CRTC2 ablation in mice fed a 4% cholesterol diet (18 weeks) showed decreased lipid levels in serum and liver tissues compared with those in littermate wild-type mice. The expression of lipogenic genes (SREBP-2 and HMGCR) was consistent with hepatic CRTC2 levels. In vivo imaging showed enhanced adenovirus-mediated HMGCR-luciferase activity in adenovirus-mediated CRTC2 mouse livers; however, the activity was attenuated after mutation of CRE or sterol regulatory element sequences in the HMGCR reporter construct. The effect of CRTC2 on HMGCR in mouse livers was alleviated upon SREBP-2 knockdown. CRTC2 modulated SREBP-2 transcription by CRE binding protein, which recognizes the half-site CRE sequence in the SREBP-2 promoter. CRTC2 reduced the nuclear protein expression of forkhead box O1 and subsequently increased SREBP-2 transcription by binding insulin response element 1, rather than insulin response element 2, in the SREBP-2 promoter.
IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in gastric carcinogenesis
Authors: Yuhang Zhou, Tingting Huang, Ho Lam Siu, Chi Chun Wong, Yujuan Dong, Feng Wu, Bin Zhang, William K. K. Wu, Alfred S. L. Cheng, Jun Yu, Ka Fai To, Wei Kang
Journal: Molecular Cancer (2017)

Gastric cancer (GC) is one of the frequent causes of cancer-related death in eastern Asian population. IGF2BP2 lists in the top rank up-regulated genes in GC, but its functional role is unclear.The expression of IGF2BP3 in GC cell lines and primary samples was examined by qRT-PCR and Western blot. The biological role of IGF2BP3 was revealed by a series of functional in vitro studies. Its regulation by microRNAs (miRNAs) was predicted by TargetScan and confirmed by luciferase assays and rescue experiments.IGF2BP3 ranked the No.1 of the up-regulated genes by expression microarray analysis in GC cell lines. The expression level of IGF2BP3 was observed in GC tissues comparing with non-tumorous gastric epitheliums. The up-regulated IGF2BP3 expression was associated with poor disease specific survival. IGF2BP3 knockdown significantly inhibited cell proliferation and invasion. Apart from copy number gain, IGF2BP3 has been confirmed to be negatively regulated by tumor-suppressive miRNA, namely miR-34a. The expression of miR-34a showed negative correlation with IGF2BP3 mRNA expression in primary GC samples and more importantly, re-overexpression of IGF2BP3 rescued the inhibitory effect of miR-34a.We compressively revealed the oncogenic role of IGF2BP3 in gastric tumorigenesis and confirmed its activation is partly due to the silence of miR-34a. Our findings identified useful prognostic biomarker and provided clinical translational potential.
Early adverse events and long-term outcomes of endoscopic sphincterotomy in a pediatric population: a single-center experience
Authors: Jin Cho, In Jeong, Hyun Kim, Seak Oh, Kyung Kim
Journal: Endoscopy (2017)

<b>Background and aims:</b> The use of endoscopic sphincterotomy (EST) in the management of pancreaticobiliary disease in children is increasing. However, studies of long-term outcomes are limited in pediatric patients. Therefore, this study evaluated the early adverse events and long-term outcomes following EST in pediatric patients. <b>Patients and methods:</b> We retrospectively analyzed data from 198 pediatric patients who underwent ESTs at Asan Medical Center Children's Hospital between 1994 and 2013. The median age was 8.7 years (range 18 months to17 years). We evaluated the indications, success rates, early adverse events, and long-term outcomes. <b>Results:</b> Long-term information was available in 198 patients with a median follow-up duration of 42 months (range, 1.8 – 232.1 months). Early adverse events (< 30 days) following 294 ESTs among 198 patients included pancreatitis in 17 (5.7 %), hemorrhages in 6 (2.0 %), sepsis in 3 (1.0 %), and perforations in 2 (0.7 %). Long-term complications ( > 30 days) developed in 12 patients (6.1 %), including cholangitis with or without bile duct stone (n = 7), and minor papilla restenosis (n = 5). The cumulative incidence rates of long-term complications were 3.1 %, 6.1 %, 9.3 %, and 9.3 %, at 1, 5, 10, and 15 years. There were no procedure-related pancreaticobiliary malignancies or deaths. All adverse events and long-term complications improved with appropriate management. <b>Conclusions:</b> In pediatric patients with pancreaticobiliary disease, EST has a high level of technical success. In addition, pediatric EST showed low rates of early adverse events and long-term complications, which could be managed safely. Our results suggest that EST is a safe method for treating pancreaticobiliary disease, even in the pediatric population.
SENP1 activity sustains cancer stem cell in hypoxic HCC
Authors: Alice Conigliaro, Marco Tripodi, Maurizio Parola
Journal: Gut (2017)

Hepatocellular carcinoma (HCC) represents the fifth most common cancer and the third leading cause of cancer mortality worldwide, with a minority of patients surviving at 5 years from diagnosis, despite treatment.1 HCC usually develops in conditions of chronic liver disease (CLD), mostly on the background of a cirrhotic liver, with liver transplantation at present being the only treatment strategy to cure both HCC and the specific CLD. All the other therapeutic strategies, because of the underlying liver cirrhosis, have to take into account, and may be limited in their feasibility, by the residual liver function of the individual patient, a critical parameter affecting the patient's prognosis.2 Indeed, even when the surgical intervention is feasible, according to current guidelines, efficient removal of the primary lesions is not often conclusive since intrahepatic recurrence, as well as extrahepatic metastasis, are very frequent and associated with poor prognosis for patients.3 Along these lines, current literature suggests that both the progression of CLD towards HCC development as well as HCC progression and acquisition of resistance to therapy are highly affected by the microenvironment, in which several cells (including tumour-associated macrophages or fibroblasts and cancer stem cells (CSCs)), inflammation, fibrosis as well as hypoxia, oxidative stress and autophagy are believed to play a critical role.4 In particular, hepatic hypoxia (ie, very common in CLD and HCC) and hypoxia-inducible factors (HIFs) are currently believed to be major determinant players that, in agreement with data in other tumours, can contribute to cancer development and progression by promoting and/or modulating transcriptional programmes (metabolic adaptation, …
TCTAP C-256 Aggravating Chronic Limb Ischemia Despite Normal Ankle-brachial Index
Authors: Jeehoon Kang, Chang-Hwan Yoon, Si-Hyuck Kang, JinJu Park, Jung-Won Suh, Young-Seok Cho, Tae-Jin Youn, In-Ho Chae
Journal: Journal of the American College of Cardiology (2017)
Human Factors and Neurophysiological Metrics in Air Traffic Control: A Critical Review
Authors: Pietro Arico, Gianluca Borghini, Gianluca Di Flumeri, Stefano Bonelli, Alessia Golfetti, Ilenia Graziani, Simone Pozzi, Jean-Paul Imbert, Geraud Granger, Railane Benhacene, Dirk Schaefer, Fabio Babiloni
Journal: IEEE Reviews in Biomedical Engineering (2017)

This paper provides a focused and organized review of the research progress on neurophysiological indicators, also called "neurometrics," to show how they can effectively address some of the most important human factors (HFs) needs in the air traffic management (ATM) field. In order to better understand and highlight available opportunities of such neuroscientific applications, state of the art on the most involved HFs and related cognitive processes (e.g., mental workload and cognitive training) are presented together with examples of possible applications in current and future ATM scenarios. Furthermore, this paper will discuss the potential enhancements that further research and development activities could bring to the efficiency and safety of the ATM service.
INJURY INCIDENCE IN CROSS-COUNTRY SKIERS
Authors: Sonya Worth, Duncan Reid, Sharon Henry
Journal: British Journal of Sports Medicine (2017)

Background Prospective, cross-country ski injury incidence data is scarce. Objective To describe injury type and incidence sustained by elite cross-country skiers in north-eastern America. We hypothesized that lower extremity injury incidence would be higher than other body regions. A secondary aim was to determine any factors that correlate with new injury. Design A prospective, longitudinal study that included: demographics (ski and injury history); Movement Competency Screening (MCS); hamstring length measurement; core muscle endurance testing (trunk flexor to extensor ratio). Athletes then completed 12 consecutive, monthly electronic surveys about training, racing, and injury status. Setting Collegiate and professional ski team practices. Patients (or Participants) A convenience sample of 71 cross-country skiers (age 18–27 years, 35 men); 41 participants (18 men) completed the study. Independent variables MCS score; hamstring length; ratio of trunk flexor to extensor endurance; injury history; training activities and hours; training lost to injury. Main Outcome Measurements New injury reports. Results Mean injury incidence was 3.81 new injuries per participant, per 1,000 hours of training. Injury incidences for lower extremity (2.13), and overuse/non-traumatic (2.76) injuries were significantly greater than trunk (0.22), upper extremity (0.46), or acute/traumatic (1.05) injuries (p&lt;0.05). Off-season injury incidence (5.25) was higher than during ski season (2.27), but not significantly (p=0.07). New injury positively correlated with past injury (p=0.04) and also increased as monthly running time increased but not significantly (p=0.08). New injury did not correlate with: MCS score; hamstring length, or; core ratio (p&gt;0.05). Past injuries were a significant predictor of new injuries, when accounting for training time, running time and MCS score (p&lt;0.05). Conclusions This year long, prospective report of injury type and incidence in competitive cross-country skiers demonstrated that lower extremity and overuse/non-traumatic injuries had the highest incidence rates. Previously injured skiers are at greater risk of further injury.
Image Gallery: Nicolau syndrome after misuse of buprenorphine
Authors: O. Espitia, C. Vigneau-Victorri, M.-A. Pistorius
Journal: British Journal of Dermatology (2017)

DEAR EDITOR, A 33-year-old man with drug addiction presented immediately after buprenorphine injection in the left calf vein an intense pain with a purpura, associated with purplish, livedoid skin lesions surrounded by pale skin (a).It evolved within 5 days into a necrotic-centre lesion (b).Nerve ischaemia due to vasospasm caused motor L5-S1 deficiency.Histopathological examination showed capillary thrombotic occlusion and perivascular inflammation (c) with macrophages containing inorganic refringent particles (toluidine blue staining).Under topical corticosteroid and morphine, the pain and livedoid lesions resolved within 3 weeks.However, the resolution of secondary wounds took 4 month.These lesions are known as Nicolau syndrome (NS).NS complicates intramuscular, perinervous or paravascular drug administration, as well as local anaesthesia, nonsteroidal anti-inflammatory drugs, corticosteroids, vaccines and vitamin B complex. 1 The pathogenesis of NS is unknown.Hypothesis are drug-induced vasospasm, mechanical vessel occlusion and inflammation and necrosis of the intima following injection. 2
Use of Video Directly Observed Therapy for Treatment of Latent Tuberculosis Infection — Johnson County, Kansas, 2015
Authors: Elizabeth Lawlor Holzschuh, Stacie Province, Krystle Johnson, Caitlin Walls, Cathy Shemwell, Gary Martin, Amy Showalter, Jennifer Dunlay, Andrew Conyers, Phil Griffin, Nancy Tausz
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis and is spread from person to person through the air. TB can be spread in congregate settings, such as school environments, to varying degrees, based on factors including duration of contact and air ventilation (1); therefore, evaluating potential contacts and exposures can be challenging. In February 2015, a student at a Kansas high school received a diagnosis of active pulmonary TB disease. Screening of 385 (91%) school contacts, four (100%) household contacts, and 19 (90%) social contacts resulted in the identification of 50 persons with latent TB infection. Johnson County Department of Health and Environment (JCDHE) Public Health Emergency Preparedness personnel used their experience with points of distribution logistics to optimize testing clinic layouts and implement the incident command structure. Open communication with students, school staff members, the public, and the media about the investigation from the outset was imperative to reduce rumors and unease that can accompany a large communicable disease investigation. The large number of persons needing treatment for latent TB overwhelmed JCDHE's two TB nurses. As a result, JCDHE developed a policy and procedure to allow persons who met eligibility requirements to complete 12 weekly doses of isoniazid and rifapentine treatment using video directly observed therapy (VDOT) rather than traditional in-person directly observed therapy (DOT). This procedure facilitated treatment compliance and completion; among the eligible 15 persons who chose the 12-week VDOT option, 14 (93%) completed treatment. State and local health departments might consider use of VDOT to monitor treatment of persons with latent TB infection.