tbuckley/cabot-search huggingface dataset:
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Authors: Sunil R. Hingorani, Emanuel F. Petricoin, Anirban Maitra, Vinodh Rajapakse, Catrina King, Michael A. Jacobetz, Sally Ross, Thomas P. Conrads, Timothy D. Veenstra, Ben A. Hitt, Yoshiya Kawaguchi, Don Johann, Lance A. Liotta, Howard C. Crawford, Mary E. Putt, Tyler Jacks, Christopher V.E. Wright, Ralph H. Hruban, Andrew M. Lowy, David A. Tuveson
Journal: Cancer Cell (2004)
TCTAP A-134 Novel Interventional Therapeutic Approach for Patients with Peripheral Pulmonary Artery Stenosis in Adulthood
Authors: Hiroto Shimokawahara, Mitsutaka Nakashima, Takanori Naito, Masataka Shigetoshi, Aiko Ogawa, Mitsuru Munemasa, Hiromi Matsubara
Journal: Journal of the American College of Cardiology (2017)
A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors
Authors: Birgit Geoerger, Franck Bourdeaut, Steven G. DuBois, Matthias Fischer, James I. Geller, Nicholas G. Gottardo, Aurélien Marabelle, Andrew D.J. Pearson, Shakeel Modak, Thomas Cash, Giles W. Robinson, Marlyane Motta, Alessandro Matano, Suraj G. Bhansali, Jason R. Dobson, Sudha Parasuraman, Susan N. Chi
Journal: Clinical Cancer Research (2017)

Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off). Dose escalation was guided by a Bayesian logistic regression model with overdose control and real-time PK.Results: Thirty-two patients (median age, 5.5 years) received ribociclib 280, 350, or 470 mg/m2 Three patients had dose-limiting toxicities of grade 3 fatigue (280 mg/m2; n = 1) or grade 4 thrombocytopenia (470 mg/m2; n = 2). Most common treatment-related adverse events (AE) were hematologic: neutropenia (72% all-grade/63% grade 3/4), leukopenia (63%/38%), anemia (44%/3%), thrombocytopenia (44%/28%), and lymphopenia (38%/19%), followed by vomiting (38%/0%), fatigue (25%/3%), nausea (25%/0%), and QTc prolongation (22%/0%). Ribociclib exposure was dose-dependent at 350 and 470 mg/m2 [equivalent to 600 (RP2D)-900 mg in adults], with high interpatient variability. Best overall response was stable disease (SD) in nine patients (seven with neuroblastoma, two with primary CNS MRT); five patients achieved SD for more than 6, 6, 8, 12, and 13 cycles, respectively.Conclusions: Ribociclib demonstrated acceptable safety and PK in pediatric patients. MTD (470 mg/m2) and RP2D (350 mg/m2) were equivalent to those in adults. Observations of prolonged SD support further investigation of ribociclib combined with other agents in neuroblastoma and MRT. Clin Cancer Res; 23(10); 2433-41. ©2017 AACR.
Erratum. Diabetic Retinopathy: A Position Statement by the American Diabetes Association. Diabetes Care 2017;40:412–418
Authors: Sharon D. Solomon, Emily Chew, Elia J. Duh, Lucia Sobrin, Jennifer K. Sun, Brian L. VanderBeek, Charles C. Wykoff, Thomas W. Gardner
Journal: Diabetes Care (2017)

In the print version of the above-mentioned article, the following paragraph on page 413 was corrected and two additional references (51 and 52) were added:

After duration of diabetes, hyperglycemia has been the most consistently associated risk factor for retinopathy. A large and consistent set of observational studies and clinical trials document the association of poor glucose control …
Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape
Authors: Ross A. Pollack, R. Brad Jones, Mihaela Pertea, Katherine M. Bruner, Alyssa R. Martin, Allison S. Thomas, Adam A. Capoferri, Subul A. Beg, Szu-Han Huang, Sara Karandish, Haiping Hao, Eitan Halper-Stromberg, Patrick C. Yong, Colin Kovacs, Erika Benko, Robert F. Siliciano, Ya-Chi Ho
Journal: Cell Host & Microbe (2017)
TCTAP A-145 Altered Cut Off Value of Instantaneous Wave Free Ratio (iFR) for Detecting Myocardial Ischemia Defined by Fraction Flow Reserve (FFR) in Hemodialysis Patients Compared with Non-hemodialysis Patients
Authors: Tairo Kurita, Akihiro Takasaki, Kaoru Dohi, Shuusuke Fukuoka, Tomoyuki Nakata, Naoki Fujimoto, Masuda Jun, Kozo Hoshino, Takashi Tanigawa, Masaaki Ito
Journal: Journal of the American College of Cardiology (2017)
Botulism From Drinking Prison-Made Illicit Alcohol — Arizona, 2012
Authors: Graham Briggs, Shoana Anderson, Kenneth Komatsu, Joli Weiss, Evan Henke, Clarisse A. Tsang, Muhammad Vasiq, Agam K. Rao, Rajal K. Mody, Carolina Luquez, Janet K. Dykes, Jamae F. Morris, Tara C. Anderson, Laura E. Adams, Seema Yasmin
Journal: MMWR Morbidity and Mortality Weekly Report (2013)
Risk of Ocular Hypertension in Adults with Noninfectious Uveitis
Authors: Ebenezer Daniel, Maxwell Pistilli, Srishti Kothari, Naira Khachatryan, R. Oktay Kaçmaz, Sapna S. Gangaputra, H. Nida Sen, Eric B. Suhler, Jennifer E. Thorne, C. Stephen Foster, Douglas A. Jabs, Robert B. Nussenblatt, James T. Rosenbaum, Grace A. Levy-Clarke, Nirali P. Bhatt, John H. Kempen
Journal: Ophthalmology (2017)
Differential intratumoral distributions of CD8 and CD163 immune cells as prognostic biomarkers in breast cancer
Authors: Sotirios P. Fortis, Michael Sofopoulos, Nectaria N. Sotiriadou, Christoforos Haritos, Christoforos K. Vaxevanis, Eleftheria A. Anastasopoulou, Nicole Janssen, Niki Arnogiannaki, Alexandros Ardavanis, Graham Pawelec, Sonia A. Perez, Constantin N. Baxevanis
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Tumor immune cell infiltrates are essential in hindering cancer progression and may complement the TNM classification. CD8+ and CD163+ cells have prognostic impact in breast cancer but their spatial heterogeneity has not been extensively explored in this type of cancer. Here, their potential as prognostic biomarkers was evaluated, depending on their combined densities in the tumor center (TC) and the tumor invasive margin (IM). <h3>Methods</h3> CD8+ and CD163+ cells were quantified by immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from a cohort totaling 162 patients with histologically-confirmed primary invasive non-metastatic ductal breast cancer diagnosed between 2000 and 2015. Clinical follow-up (median 6.9&nbsp;years) was available for 97 of these patients. <h3>Results</h3> Differential densities of CD8+ and CD163+ cells in the combined TC and IM compartments (i.e., high(H)/low(L), respectively for CD8+ cells and the reverse L/H combination for CD163+ cells) were found to have significant prognostic value for survival, and allowed better patient stratification than TNM stage, tumor size, lymph node invasion and histological grade. The combined evaluation of CD8+ and CD163+ cell densities jointly in TC and IM further improves prediction of clinical outcomes based on disease-free and overall survival. Patients having the favorable immune signatures had favorable clinical outcomes despite poor clinicopathological parameters. <h3>Conclusions</h3> Given the important roles of CD8+ and CD163+ cells in regulating opposing immune circuits, adding an assessment of their differential densities to the prognostic biomarker armamentarium in breast cancer would be valuable. Larger validation studies are necessary to confirm these findings. <h3>Trial registrations</h3> Study code: IRB-ID 6079/448/10-6-13 Date of approval: 10/06/2013 Retrospective study (2000–2010) First patient prospectively enrolled 14/2/2014
Comparison of open esophagectomy with minimally invasive esophagectomy: An observational nationwide study in Japan.
Authors: HIROYA TAKEUCHI, Hiroaki Miyata, Soji Ozawa, Harushi Udagawa, Harushi Osugi, Hisahiro Matsubara, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2015)

4052 Background: To date, there has been a very limited number of prospective multicenter trials to verify the benefits of minimally invasive esophagectomy (MIE) such as thoracoscopic esophagectomy for esophageal cancer. In this study, we focused on the comparison of MIE and open esophagectomy (OE) using a Japanese nationwide database. Methods: Patient registration for the National Clinical Database (NCD) commenced in January 2011. It is a nationwide project that is linked to the surgical board certification system in Japan. Propensity score matching was performed to compare the MIE with the OE by use of the 2011-2012 NCD database. Results: Esophagectomy for 9584 patients with thoracic esophageal cancer were categorized into MIE (n = 3589) with OE (n = 5995) in the NCD 2011-2012 database. Propensity score matching created a matched cohort of 3515 pairs of patients with MIE and with OE. The operative time was significantly longer in the MIE group than in the OE group (P < 0.001), whereas blood loss was markedly lesser in the MIE group than in the OE group (P < 0.001). There was no significant differences in overall morbidity between the MIE (42.0%) and OE groups (43.1%). In particular, the incidence of the patients who needed prolonged respiratory ventilation more than 48 hours after surgery was significantly less in the MIE group than the OE group ((8.9% vs 10.9%, P = 0.006). Moreover, the incidence of superficial surgical site infection was significantly less in the MIE group compared with the OE group (6.7% vs 8.1%, P = 0.037). However, the reoperation rate within 30 days was significantly higher in the MIE group than in the OE group (7.0% vs 5.3%, P = 0.004). There were no significant differences in 30-day or operative mortality rates between the MIE and OE groups (30-day mortality: MIE 0.9% vs OE 1.1%, operative mortality: MIE 2.5% vs OE 2.8%). Conclusions: Our results suggest that MIE is comparable with conventional OE in terms of short-term outcome after surgery and is regarded as a desirable surgical option for patients with esophageal cancer although MIE was associated with higher reoperation rates and there were no marked benefits in operative mortality.
2D VIDEO FEEDBACK IMPROVES LANDING TECHNIQUE IN ELITE FEMALE HANDBALL PLAYERS
Authors: Anne Benjaminse, Ina Janssen, Wytze Postma, Bert Otten
Journal: British Journal of Sports Medicine (2017)

Background In handball an anterior cruciate ligament injury often occurs during a jump shot landing. Video feedback is effective to improve landing although little is known about its influence in sport-specific movements. Objective Test effectiveness of video overlay feedback on landing technique. Design Randomized controlled trial. Setting Controlled laboratory with elite athletes. Participants Sixteen female handball players were randomly assigned to a Control (CG) or Video (VG) Group. Interventions Both groups performed jump shots in pre-test (5 trials), two training sessions (TR1 &amp; TR2, 2x10 trials) and post-test (5 trials). In TR1 and TR2, the VG received self-controlled video feedback of an expert model with an overlay of their own jump shots. Main Outcome Measurements Knee and hip flexion angles (initial contact (IC), maximum (MAX) and range of motion (ROM)). Landing Error Scoring System (LESS) score. Shot accuracy, jump height and distance to assess performance. Results From pre- to post-test, knee (pre-test IC: −12.4°±3.9, post-test IC: −17.3°±2.4, pre-test MAX: −70.4°±2.8, post-test MAX: −99.6°±11.3, pre-test ROM: −58.1°±5.3, post-test ROM: −82.3°±10.5) and hip (pre-test IC: 29.7°±4.4, post-test IC: 38.7°±6.4, pre-test MAX: 58.9°±11.4, post-test MAX: 97.8°±17.6, pre-test ROM: 31.6°±12.5, post-test ROM: 63.9°±11.7) flexion improved in the VG (p&lt;0.05). The VG reduced their LESS score (pre-test 8.1, post-test 4.0; p&lt;0.05). CG did not show significant changes, resulting in group*time interaction effects for mentioned variables (p&lt;0.05). No differences were found in shot accuracy and jump height, whilst jump distance increased at post-test in the VG. Conclusions Overlay visual feedback is effective to improve landing technique during a jump shot whilst maintaining performance. For enhancing injury prevention, it is imperative to determine long-term effects and transfer to training and game situations.
Increase in the Incidence of Diabetes and Its Implications
Authors: Julie R. Ingelfinger, John A. Jarcho
Journal: New England Journal of Medicine (2017)

Diabetes mellitus is among the most prevalent and morbid chronic diseases, affecting the health of millions of persons worldwide. According to the Global Burden of Disease (GBD) report for 2015, the prevalence of diabetes rose from approximately 333 million persons in 2005 to approximately 435 million persons in 2015, an increase of 30.6%.1 During the same interval, the annual number of deaths from diabetes rose from 1.2 million to 1.5 million.2 This increase is attributed in the GBD report to population growth and aging, with small decreases in age-specific and cause-specific mortality over the same period.Although the GBD analyses . . .
Toxicity profile of temozolomide in the treatment of 300 malignant glioma patients in Korea.
Authors: Chae-yong Kim, So Hyun Bae, Min-Jung Park, Min Mi Lee, Tae Min Kim, Young-Hoon Kim, Yu Jung Kim, Chul-Kee Park
Journal: Journal of Clinical Oncology (2012)

2041 Background: Toxicity of temozolomide itself has been rarely reported in the field of neuro-oncology. In an attempt to explore the toxicity profiles of temozolomide we investigated the records of 300 glioma patients in two institutions in Korea. Methods: We reviewed the records of 300 glioma patients who were treated with temozolomide between Jan 2004 and May 2010 at two hospitals of our university at two medical centers in Seoul National University, Korea. The age range of patients was 17 ~ 84 years old with its median of 49 years old. Their pathologies were glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, gliomastosis cerebri, gliosarcoma and others. Temozolomide was used as only concurrent manner with radiotherapy in 46 patients, as both concurrent and adjuvant manner in 93 patients, and as only adjuvant or palliative manner in 161 patients. We classified the side effects by Common Terminology Criteria for Adverse Events version 3.0(CTCAE). Results: We found 603 events of side effects of temozolomide. Nonhematolgic toxicities were most common (n=482). Especially, nausea(n=135), vomiting(n=110), and anorexia(n=40) were common among all kinds of toxicities. Hematologic adverse events(n=121), for example, thrombocytopenia(n=43), anemia(n=33), and neutropenia(n=20) were the second common toxicities. Some patients suffered from fatigue(n=31). None of our patient presented fatal Pneumocystis jiroveci pneumonitis. In our series, 512 cases(84.9%) of toxicity were grade 1 or 2, and 91 cases(15.1%) were grade 3 or 4. Grade 3 or 4 toxicity were 140 cases(15.1%). Only 27 cases(2.9%) presented grade 4 toxicity. There was no mortality due to temozolomide. Only 4 patients (1.3%) presented leukopenia, which is different pattern compared with the incidence reported in prior studies from western countries. Conclusions: Temozolomide had many kinds of toxicities. However, most of the toxicity was tolerable. This profile could be used to prevent toxic reactions more effectively and improve the patient’s quality of life. Furthermore, we could use these lessons for education of patients during the treatment with temozolomide.
Optic nerve astrocyte reactivity protects function in experimental glaucoma and other nerve injuries
Authors: Daniel Sun, Sara Moore, Tatjana C. Jakobs
Journal: The Journal of Experimental Medicine (2017)

Reactive remodeling of optic nerve head astrocytes is consistently observed in glaucoma and other optic nerve injuries. However, it is unknown whether this reactivity is beneficial or harmful for visual function. In this study, we used the Cre recombinase (Cre)–loxP system under regulation of the mouse glial fibrillary acidic protein promoter to knock out the transcription factor signal transducer and activator of transcription 3 (STAT3) from astrocytes and test the effect this has on reactive remodeling, ganglion cell survival, and visual function after experimental glaucoma and nerve crush. After injury, STAT3 knockout mice displayed attenuated astrocyte hypertrophy and reactive remodeling; astrocytes largely maintained their honeycomb organization and glial tubes. These changes were associated with increased loss of ganglion cells and visual function over a 30-day period. Thus, reactive astrocytes play a protective role, preserving visual function. STAT3 signaling is an important mediator of various aspects of the reactive phenotype within optic nerve astrocytes.
Obstructive sleep apnoea as a risk factor for osteopenia and osteoporosis in the male population: further data and comments
Authors: Claudio Liguori, Eleonora Piccirilli, Francesca Izzi, Nicola Biagio Mercuri, Umberto Tarantino, Fabio Placidi
Journal: European Respiratory Journal (2017)

We have recently read some criticisms raised from Sforza et al . [1] in Sleep Medicine about our paper entitled "Obstructive sleep apnoea as a risk factor for osteopenia and osteoporosis in the male population" published in the European Respiratory Journal last March [2]. In the latter, we reported the significant reduction of the bone mineral density in a large population of male severe obstructive sleep apnoea (OSA) patients (apnoea–hypopnoea index >30 events per h) compared to a population of age- and body mass index (BMI)-matched controls [2]. Since we published our report as a research letter we could not provide the full data, neither in the manuscript nor in the form of supplementary material [2]. For this reason we write this correspondence in order to specify our results and to respond to the criticisms from Sforza et al . [1], and thank the Editor for giving us this opportunity. We would specify that in the previous study of our group we included consecutive male OSA patients admitted to our outpatient clinic, who underwent polygraphic cardiorespiratory monitoring according to the American Academy of Sleep Medicine criteria [3]. Since the aim of our study was to evaluate the possible influence of severe OSA on bone mineral density in the male population, we ruled out possible confounding factors that might have reduced the reliability of our results by excluding all the patients who presented one or more conditions with known influence on bone health (see exclusion criteria of the previous paper) [2]. Therefore, we excluded 148 out of 240 male OSA patients since: 67 were affected by diabetes, 31 had chronic obstructive pulmonary disease, four showed thyroid dysfunction, three reported use of corticosteroids in the 4 weeks preceding the inclusion in the study, 29 reported diuretic treatments, nine reported vitamin supplements consumption and five had history of fractures. Moreover, we compared the group of 92 male OSA patients to a group of 50 male subjects who were age- and BMI-matched with OSA patients not showing OSA syndrome (OSAS) at the polygraphic recording. OSAS has been defined according to the recent International Classification of Sleep Disorder, 3rd edition (ICSD3) (table 1) [4]. Obstructive sleep apnoea as a risk factor for osteopenia and osteoporosis in males: further data and comments <http://ow.ly/RNCJ309KtPp>
Initial Experience With Simultaneous 18F-FDG PET/MRI in the Evaluation of Cardiac Sarcoidosis and Myocarditis
Authors: Kate Hanneman, Michael Kadoch, Henry H. Guo, Mehran Jamali, Andrew Quon, Andrei Iagaru, Robert Herfkens
Journal: Clinical Nuclear Medicine (2017)

The purpose of this study was to compare combined PET/MRI with PET/CT and cardiac MRI in the evaluation of cardiac sarcoidosis and myocarditis.Ten patients (4 men and 6 women; 56.1 ± 9.6 years old) were prospectively enrolled for evaluation of suspected cardiac sarcoidosis or myocarditis. Written informed consent was obtained. Following administration of 9.9 ± 0.9 mCi F-FDG, patients underwent standard cardiac PET/CT followed by combined PET/MRI using a simultaneous 3-T scanner. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Myocardial involvement was assessed with separate analysis of combined PET/MRI, PET/CT, and cardiac MRI data using dedicated postprocessing software. Estimates of radiation dose were derived from the applied doses of F-FDG and CT protocol parameters.Imaging was acquired with a delay from F-FDG injection of 90.2 ± 27.4 minutes for PET/CT and 207.7 ± 40.3 minutes for PET/MRI. Total scan time for PET/MRI was significantly longer than for PET/CT (81.4 ± 14.8 vs 12.0 minutes, P < 0.001). Total effective radiation dose was significantly lower for PET/MRI compared with PET/CT (6.9 ± 0.6 vs 8.2 ± 1.1 mSv, P = 0.007). There was no significant difference in the number of positive cases identified between combined PET/MRI (n = 10 [100%]), PET/CT (n = 6 [60%]), and cardiac MRI (n = 8 [80%]), P = 0.091.Simultaneous cardiac PET/MRI is feasible in the evaluation of cardiac sarcoidosis and myocarditis achieving diagnostic image quality.
Quantitative proteomic analysis of Parkin substrates in Drosophila neurons
Authors: Aitor Martinez, Benoit Lectez, Juanma Ramirez, Oliver Popp, James D. Sutherland, Sylvie Urbé, Gunnar Dittmar, Michael J. Clague, Ugo Mayor
Journal: Molecular Neurodegeneration (2017)

Parkin (PARK2) is an E3 ubiquitin ligase that is commonly mutated in Familial Parkinson's Disease (PD). In cell culture models, Parkin is recruited to acutely depolarised mitochondria by PINK1. PINK1 activates Parkin activity leading to ubiquitination of multiple proteins, which in turn promotes clearance of mitochondria by mitophagy. Many substrates have been identified using cell culture models in combination with depolarising drugs or proteasome inhibitors, but not in more physiological settings.Here we utilized the recently introduced BioUb strategy to isolate ubiquitinated proteins in flies. Following Parkin Wild-Type (WT) and Parkin Ligase dead (LD) expression we analysed by mass spectrometry and stringent bioinformatics analysis those proteins differentially ubiquitinated to provide the first survey of steady state Parkin substrates using an in vivo model. We further used an in vivo ubiquitination assay to validate one of those substrates in SH-SY5Y cells.We identified 35 proteins that are more prominently ubiquitinated following Parkin over-expression. These include several mitochondrial proteins and a number of endosomal trafficking regulators such as v-ATPase sub-units, Syx5/STX5, ALiX/PDCD6IP and Vps4. We also identified the retromer component, Vps35, another PD-associated gene that has recently been shown to interact genetically with parkin. Importantly, we validated Parkin-dependent ubiquitination of VPS35 in human neuroblastoma cells.Collectively our results provide new leads to the possible physiological functions of Parkin activity that are not overtly biased by acute mitochondrial depolarisation.