tbuckley/cabot-search huggingface dataset:
A novel t-stage classification system for adrenocortical carcinoma: Proposal from the U.S. Adrenocortical Carcinoma Study Group.
Authors: Caroline Elizabeth Poorman, Cecilia Grace Ethun, Lauren McLendon Postlewait, Thuy Tran, Timothy M. Pawlik, Tracy S Wang, Ioannis Hatzaras, John E Phay, Ryan C Fields, Sharon M. Weber, Jason K. Sicklick, Adam Charles Yopp, Jason David Prescott, Quan-Yang Duh, Carmen C. Solorzano, Konstantinos Ioannis Votanopoulos, George A. Poultsides, Shishir Kumar Maithel
Journal: Journal of Clinical Oncology (2017)

266 Background: The 7th AJCC T-stage classification system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. Methods: Patients undergoing curative-intent resections for ACC from 1993-2014 at 13 institutions comprising the US ACC Study Group were included. Primary outcome was disease-specific survival (DSS). Results: Of 265 patients with ACC, 149 had complete data for analysis. The current T-stage system failed to differentiate patients with T2 vs T3 disease ( p= 0.10). Presence of LVI was associated with worse DSS compared to no LVI (36 vs. 168mos; p= 0.001). After accounting for the individual components of the current T-stage system (size and extra-adrenal invasion), LVI persisted as a poor prognostic factor on multivariable analysis (HR 2.14, 95% CI 1.05-4.38, p= 0.04). LVI positivity further stratified patients with T2 and T3 disease, (T2: 37mos vs median not reached; T3: 36 vs 96mos; p =0.03), but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: &lt; 5cm, (-)local invasion, (+/-)LVI; T2: &gt; 5cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: &gt; 5cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167mos; T2: 96mos; T3: 37mos; T4: 15mos; p&lt; 0.001). Conclusions: The current AJCC T-stage system for ACC does not adequately stratify patients by survival, particularly for T2 and T3 disease. The proposed T-stage classification system, which incorporates lymphovascular invasion, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this novel T-stage classification should be considered for future AJCC staging systems.
Aberrant Activation of NF-κB and Hypoxia Enhances Glycolytic Enzyme Hexokinase II Expression in B-Cell Lymphoma through Activation of HIF-1
Authors: Kei Nakajima, Keita Kirito, Ichiro Kawashima, Megumi Koshiishi, Takuma Kumagai, Toru Mitsumori
Journal: Blood (2017)
PTU-018 Endoscopy: the effect of hospital anxiety and depression scale on patient experience
Authors: SA Raju, L Marks, H-L Ching, ME McAlindon
Journal: Gut (2017)

Introduction  The effect a patients baseline anxiety and depression has on their experience of oesophagogastroduodenoscopy (OGD) is unclear, as is how this affects their view of the service. We present a questionnaire study of patients undergoing OGD in our endoscopy department.  Method  A closed ended questionnaire was given to adult patients attending outpatient OGD between November 2016 and January 2017. The patients hospital anxiety and depression scale (HADS), sedation requirement, expectations, experience of OGD and service evaluation were assessed in the questionnaire. Patients were asked to rank questions focused on unpleasant sensations (gagging, vomiting, choking and bloating), discomfort and pain. All patients were offered sedation with fentanyl and midazolam.  Results  Questionnaires were completed by 100 patients: 46 female (med: 62 years±13.5 years), 54 male (med: 57±13 years). There was a significant difference in anxiety score (AS) between females and males (med: 7±3.15 vs 4.5±3.5 respectively p=0.001) and depression score (DS) (med: 5±3.5 vs 2±2.75 respectively p=0.026). Patients with a high AS or DS had statistically significantly greater concerns and expectations prior to OGD but no statistically significant difference in their experiences of unpleasant sensations or discomfort (Table 1). Patients with a higher AS and DS experienced statistically significantly more pain than those with lower scores. Sedated patients experienced less unpleasant sensations and discomfort.  Conclusion  Patients with higher AS or DS have greater concerns prior to OGD. However, their actual experiences are no different to those with lower scores with regards to unpleasant sensations and discomfort. Sedated patients reported a better experience suggesting a beneficial role of sedation in reducing awareness of unpleasant sensations and discomfort.  Disclosure of Interest  None Declared
Abstract 19166: Race/Ethnicity and Socioeconomic Factors are Associated With Bystander CPR in Pediatric Out of Hospital Cardiac Arrest: A Study From the Cardiac Arrest Registry to Enhance Survival (CARES)
Authors: Maryam Y Naim, Heather M Griffis, Rita V Burke, Bryan F McNally, Lihai Song, Robert A Berg, Vinay M Nadkarni, Kimberly Vellano, Richard N Bradley, David Markenson, Joseph W Rossano
Journal: Circulation (2017)

Introduction: Bystander CPR (BCPR) is associated with improved survival following pediatric out of hospital cardiac arrest (OHCA). It is unknown if race/ethnicity and socioeconomic factors are asso...
Targeting PIWIL2-like (PL2L) proteins by a monoclonal antibody for immunotherapy of both solid and hematopoietic cancers.
Authors: Jian-Xin Gao, Hong-Min Lu, Yu-Jie Fu, Meng-Yao Liu, Wu-Yan Xia, Ning Liu, Hai-Yan Chen, Hailong Wu, Lin-Feng Li
Journal: Journal of Clinical Oncology (2016)

e14001 Background: Broad spectrum immunotherapeutic target is critical but has encountered a bottle-neck for immunotherapy to cure cancers. We have previously reported that the PIWIL2-like (PL2L) protein 60, a product of alienation-activated PIWIL2 gene, is widely expressed in various types of hematopoietic and solid tumors and mediates tumorigenesis. However, it is unknown whether PL2L60 is an efficient broad spectrum target for cancer immunotherapy. Methods: PL2L-specific monoclonal antibody (mAb: KAO3) was used to pretreat various types of tumor cell lines from human or mouse before inoculation or treat the established tumors from the same lines, including lymphoma, melanoma, breast cancer, lung cancer and cervical cancer. The machanisms underlying mAb KAO3 inhibiting tumorigenesis were explored using the parameters of cell cycle, cell proliferation, apoptosis and complement-dependent cytotoxicity. The KAO3+ tumor cells were isolated to compare KAO3- cells in tumorigenesis of various tumor cell types of human and mouse. Results: we show that a monoclonal antibody (mAb; clone KAO3) specific for PIWIL2 and PL2L proteins including PL2L60 of both human and mouse can efficiently suppress the development of various types of tumors. Pretreatment of various types of human or mouse cancer cells with the mAb KAO3 before inoculation efficiently inhibits their tumorigenesis in the severe combined immunodeficiency (SCID) mice. Moreover, injection of the mAb into the established tumors such as lymphoma, breast cancer, lung cancer and cervical cancer significantly inhibits tumor growth, and prolongs overall survival of the tumor-bearing SCID mice. The inhibitory efficiency of the mAb KAO3 is associated with the level of KAO3-specific antigen expressed on tumor cell surface. The mAb KAO3 induces apoptosis of tumor cell lines through arresting the cell cycle at G2/M phase and activation of complements. The KAO3+ tumor cells either from mouse or human are more tumorigenic than the KAO3-ones. Conclusions: we have identified a broad spectrum target for immunotherapy of both solid and hematopoietic cancers, and the mAb KAO3 is a potential new agent used for the tumor immunotherapy.
Active Sampling State Dynamically Enhances Olfactory Bulb Odor Representation
Authors: Rebecca Jordan, Izumi Fukunaga, Mihaly Kollo, Andreas T. Schaefer
Journal: Neuron (2018)

The olfactory bulb (OB) is the first site of synaptic odor information processing, yet a wealth of contextual and learned information has been described in its activity. To investigate the mechanistic basis of contextual modulation, we use whole-cell recordings to measure odor responses across rapid learning episodes in identified mitral/tufted cells (MTCs). Across these learning episodes, diverse response changes occur already during the first sniff cycle. Motivated mice develop active sniffing strategies across learning that robustly correspond to the odor response changes, resulting in enhanced odor representation. Evoking fast sniffing in different behavioral states demonstrates that response changes during active sampling exceed those predicted from feedforward input alone. Finally, response changes are highly correlated in tufted cells, but not mitral cells, indicating there are cell-type-specific effects on odor representation during active sampling. Altogether, we show that active sampling is strongly associated with enhanced OB responsiveness on rapid timescales.
Book: The Woman in the Surgeon's Body
Authors: S. Creighton
Journal: BMJ (1998)

Harvard University Press 21$.95, pp 267 ISBN 0 674 95467 X Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> “Anybody but the girl! Give me a trained monkey—I'drather have anybody but the girl!” So raged a male senior surgeon intheatres when scheduled to have a female trainee assisting him. Thisis just one episode illustrating this riveting study on women surgeons in the United States. “What's an anthropologist doingstudying surgeons?” the author was asked while conducting a study on21male surgeons; she replied (perhaps jokingly), “Well, there were no other primitives left.” She now turns her attention to women surgeons, and clearly the term primitives was not a misrepresentationof many of their male colleagues. The author studied 33 women surgeons of differing ages practising in eastern andmid-western United States. There was a wide representation of career stages and surgical … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
The Bloodwise TAP Calibre Feasibility Study to Assess the Mechanism of Action of Idelalisib in B-Cell Receptor Pathway (BCR) Inhibition in Chronic Lymphocytic Leukaemia (CLL)
Authors: Talha Munir, Peter Hillmen, Andy Rawstron, Kristian Brock, Samuel Munoz-Vicente, Francesca Yates, Surita Dalal, Ruth M de Tute, Chris P Fox, Donald Macdonald, Christopher Fegan, Adrian Bloor, Anna Schuh, Gina Doody
Journal: Blood (2017)
Macrophage-Derived Granulin Drives Resistance to Immune Checkpoint Inhibition in Metastatic Pancreatic Cancer
Authors: Valeria Quaranta, Carolyn Rainer, Sebastian R. Nielsen, Meirion L. Raymant, Muhammad S. Ahmed, Dannielle D. Engle, Arthur Taylor, Trish Murray, Fiona Campbell, Daniel H. Palmer, David A. Tuveson, Ainhoa Mielgo, Michael C. Schmid
Journal: Cancer Research (2018)

Abstract The ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumor microenvironment that suppresses and excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immunoprotective role of the metastatic tumor microenvironment in pancreatic cancer is not completely understood. In this study, we find that macrophage-derived granulin contributes to cytotoxic CD8+ T-cell exclusion in metastatic livers. Granulin expression by macrophages was induced in response to colony-stimulating factor 1. Genetic depletion of granulin reduced the formation of a fibrotic stroma, thereby allowing T-cell entry at the metastatic site. Although metastatic PDAC tumors are largely resistant to anti–PD-1 therapy, blockade of PD-1 in granulin-depleted tumors restored the antitumor immune defense and dramatically decreased metastatic tumor burden. These findings suggest that targeting granulin may serve as a potential therapeutic strategy to restore CD8+ T-cell infiltration in metastatic PDAC, thereby converting PDAC metastatic tumors, which are refractory to immune checkpoint inhibitors, into tumors that respond to immune checkpoint inhibition therapies. Significance: These findings uncover a mechanism by which metastatic PDAC tumors evade the immune response and provide the rationale for targeting granulin in combination with immune checkpoint inhibitors for the treatment of metastatic PDAC. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4253/F1.large.jpg. Cancer Res; 78(15); 4253–69. ©2018 AACR.
Efficacy and Safety of Mepolizumab in Uncontrolled Patients with Severe Eosinophilic Asthma Following a Switch from Omalizumab (OSMO Study): Exacerbation and Safety Outcomes
Authors: Dmitry Galkin, Mark C. Liu, Bradley E. Chipps, Kenneth R. Chapman, Xavier Muñoz, Miguel Angel Bergna, Jay Azmi, Dalal Mouneimne, Sandra Joksaite, Frank C. Albers
Journal: Journal of Allergy and Clinical Immunology (2018)
Popliteal artery entrapment syndrome: an approach to diagnosis and management
Authors: Maira Hameed, Alexander Coupland, Alun H Davies
Journal: British Journal of Sports Medicine (2018)

Popliteal artery entrapment syndrome (PAES) is an anomaly resulting in symptomatic extrinsic compression of the popliteal artery by the surrounding musculotendinous structures; most frequently the medial head of the gastrocnemius muscle. This may be congenital or acquired through muscular hypertrophy. PAES can be further classified by anatomical type (I–VI, table 1). It may exist alone or in combination with popliteal vein and/or tibial nerve compression as part of popliteal entrapment syndrome.

View this table:

Table 1 
Popliteal entrapment syndrome classification (Popliteal Vascular Entrapment Forum)6 



PAES is a frequent cause of intermittent claudication in an otherwise healthy, often athletic cohort, with potentially severe adverse sequelae and can represent a diagnostic challenge.

A 38-year-old female competitive ‘ironman triathlete’ athlete with no medical history presented with exertional left calf pain. On examination, the patient had a full complement of lower-limb pulses.

A lower-limb arterial duplex scan detected bilateral popliteal artery occlusion on forced plantar flexion. As there were unilateral symptoms, a CT angiogram was performed which detected no abnormality. A bilateral lower-limb angiogram initially demonstrated normal arterial anatomy. However, on forced plantar flexion, complete occlusion of both popliteal arteries was evident (figure 1).



Figure 1 
Lower-limb arterial angiogram at rest (left) and during forced plantar flexion demonstrating bilateral popliteal artery occlusion (right).



The patient was diagnosed with bilateral PAES and underwent staged popliteal artery releases. At 1 year …
Global overview of health systems oversight and financing for kidney care
Authors: Aminu K. Bello, Mona Alrukhaimi, Gloria E. Ashuntantang, Ezequiel Bellorin-Font, Mohammed Benghanem Gharbi, Branko Braam, John Feehally, David C. Harris, Vivekanand Jha, Kailash Jindal, David W. Johnson, Kamyar Kalantar-Zadeh, Rumeyza Kazancioglu, Peter G. Kerr, Meaghan Lunney, Timothy Olusegun Olanrewaju, Mohamed A. Osman, Jeffrey Perl, Harun Ur Rashid, Ahmed Rateb, Eric Rondeau, Aminu Muhammad Sakajiki, Arian Samimi, Laura Sola, Irma Tchokhonelidze, Natasha Wiebe, Chih-Wei Yang, Feng Ye, Alexander Zemchenkov, Ming-hui Zhao, Adeera Levin
Journal: Kidney International Supplements (2018)
Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus <sup>131</sup>I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016
Authors: Mazyar Shadman, Hongli Li, Lisa Rimsza, John P. Leonard, Mark S. Kaminski, Rita M. Braziel, Catherine M. Spier, Ajay K. Gopal, David G. Maloney, Bruce D. Cheson, Shaker Dakhil, Michael LeBlanc, Sonali M. Smith, Richard I. Fisher, Jonathan W. Friedberg, Oliver W. Press
Journal: Journal of Clinical Oncology (2018)

Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133-tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.
Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease
Authors: Laetitia Dou, Stéphane Poitevin, Marion Sallée, Tawfik Addi, Bertrand Gondouin, Nathalie McKay, Michael S. Denison, Noémie Jourde-Chiche, Ariane Duval-Sabatier, Claire Cerini, Philippe Brunet, Françoise Dignat-George, Stéphane Burtey
Journal: Kidney International (2018)
Клінічний досвід комплексного застосування противірусної терапії, природних та преформованих фізичних чинників у хворих на хронічний вірусний гепатит С
Authors: N.V. Dragomiretska, G.M. Izha, I.B. Zabolotna, M.V. Kalinichenko, N.O. Shevchenko
Journal: GASTROENTEROLOGY (2013)

У статті подані результати дослідження ефективності комплексного застосування противірусної терапії, маломінералізованої гідрокарбонатно-сульфатно-хлоридно-натрієвої мінеральної води «Вознесенська», процедур віброакустичної та надзвичайно високочастотної терапії у хворих на хронічний вірусний гепатит С. Розроблений комплекс терапії нейтралізував побічні ефекти антивірусної терапії (лейкоцитопенічний, тромбоцитопенічний і грипоподібний синдроми), сприяв нормалізації функціональних проб печінки й більшості показників імунного статусу, стимулював синтез ендогенного інтерферону α.
Characterizing Disease Burden and Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration
Authors: Usha Chakravarthy, Clare C. Bailey, Robert L. Johnston, Martin McKibbin, Rehna S. Khan, Sajjad Mahmood, Louise Downey, Narendra Dhingra, Christopher Brand, Christopher J. Brittain, Jeffrey R. Willis, Sarah Rabhi, Anushini Muthutantri, Ronald A. Cantrell
Journal: Ophthalmology (2018)

<h3>Purpose</h3> To understand levels of disease burden and progression in a real-world setting among patients from the United Kingdom with bilateral geographic atrophy (GA) secondary to age-related macular degeneration (AMD). <h3>Design</h3> Retrospective cohort analysis of a multicenter electronic medical record (EMR) database. <h3>Participants</h3> Patients who were aged ≥50 years with bilateral GA and no history of choroidal neovascularization (CNV) and who attended 1 of 10 clinical sites using the EMR. <h3>Methods</h3> A deidentified data set was constructed from the records held at the 10 sites. An algorithm was used to extract cases with a GA diagnosis, of which 1901 had bilateral GA and form the basis of this report. A sample of records randomly selected from each center was used to validate disease definitions. <h3>Main Outcome Measures</h3> Progression to blindness (visual acuity [VA] <20 letters or Snellen 3/60 in the better-seeing eye), driving ineligibility (VA ≤70 letters or Snellen 6/12 in the better-seeing eye), progression to CNV, loss of 10 or more letters, and mean change in VA over time. <h3>Results</h3> At first record of GA, 7.1% had a VA in the better-seeing eye equal to or lower than the cutoff for blindness registration and 71.1% had a VA that would have rendered them ineligible to drive. Over time, 16% became legally blind (median time to outcome, 6.2 years) and 66.7% became ineligible to drive (median time to outcome, 1.6 years). In the worse-seeing eye, 40.1% lost ≥10 letters in 2.4 years. Among patients with baseline and 24-month VA measurements, mean VA decline was 6.1 letters in the worse-seeing eye (n = 413) and 12.4 letters in the better-seeing eye (n = 414). The rate of progression to CNV in either eye was 7.4% per patient-year. <h3>Conclusions</h3> At initial diagnosis, based on VA in the better-seeing eye, a high proportion of patients with bilateral GA were ineligible to drive and approximately 7% were eligible for UK blindness registration. The subsequent reduction in VA that occurred in the better-seeing eye would render a further two-thirds ineligible to drive. These findings emphasize the severity of the visual disability associated with GA secondary to AMD.
Miniaturized neural system for chronic, local intracerebral drug delivery
Authors: Canan Dagdeviren, Khalil B. Ramadi, Pauline Joe, Kevin Spencer, Helen N. Schwerdt, Hideki Shimazu, Sebastien Delcasso, Ken-ichi Amemori, Carlos Nunez-Lopez, Ann M. Graybiel, Michael J. Cima, Robert Langer
Journal: Science Translational Medicine (2018)

Recent advances in medications for neurodegenerative disorders are expanding opportunities for improving the debilitating symptoms suffered by patients. Existing pharmacologic treatments, however, often rely on systemic drug administration, which result in broad drug distribution and consequent increased risk for toxicity. Given that many key neural circuitries have sub-cubic millimeter volumes and cell-specific characteristics, small-volume drug administration into affected brain areas with minimal diffusion and leakage is essential. We report the development of an implantable, remotely controllable, miniaturized neural drug delivery system permitting dynamic adjustment of therapy with pinpoint spatial accuracy. We demonstrate that this device can chemically modulate local neuronal activity in small (rodent) and large (nonhuman primate) animal models, while simultaneously allowing the recording of neural activity to enable feedback control.