tbuckley/cabot-search huggingface dataset:
Conclusions of study of short term use of oral corticosteroids and related harms seem wrongheaded
Authors: Fergus W Hamilton
Journal: BMJ (2017)

Waljee and colleagues studied the short term use of oral corticosteroids and related harms among adults in the United States,1 but their conclusions seem wrongheaded.

Firstly, the underlying indication for the steroids cannot be accounted for, so there will be clear confounding by indication. Despite the apparent matching, patients prescribed steroids for upper respiratory tract infections …
A history of multiple concussions does not alter the transcranial doppler-based assessment of the neurovascular coupling response
Authors: Jonathan D Smirl, Alexander D Wright, Kevin Bouilane, Kelsey Bryk, Paul van Donkelaar
Journal: British Journal of Sports Medicine (2017)

Objective To determine how a history of 3+ concussions alters elevations in cerebral blood velocity (CBV) in the posterior cerebral artery (PCA) during visual tasks. Design Retrospective Cohort. Setting Laboratory. Participants 136 male contact-sport athletes (19.1±1.4 years, 66 football, 70 hockey) were recruited; 39 presented with 0 previous concussions, 16 with 3+ previous concussions; exclusion criteria included history of concussion within 6 months. Intervention Transcranial Doppler ultrasound indexed PCA-CBV during a series of visual tasks. Participants closed their eyes (20-seconds) and, when prompted, opened their eyes to complete a visual task (40-seconds). Testing occurred prior to the start of their athletic season. The visual trial raw traces were averaged together to enhance the signal-to-noise ratio of outcome measurements. The independent variable tested was concussion history. Outcomes Eyes-closed CBV (cm/s), peak elevation in CBV after eyes-open (cm/s), relative change in CBV (%), and total activation during the first 30 seconds of the task (indexed via area under the curve-AUC) Main results Independent samples T-Tests indicated there were no effects of concussion history on any outcome: Eyes-closed CBV (p=0.950), peak CBV (p=0.903), % CBV elevation (p=0.593), and AUC (p=0.718). Conclusions A history of multiple concussions does not alter the cerebrovasculature’s ability to maintain nutrient delivery required for visual challenges in cortical areas supplied by the PCA. This is an important finding; despite the long-term neurocognitive deficits associated with a history of concussions, the transcranial Doppler assessment of neurovascular coupling appears intact for this population of younger adult contact-sport athletes. Competing interests None.
Cell Adhesion: Dynamic Cellular Interactions with Extracellular Matrix Triggered by Biomechanical Tuning of Low‐Rigidity, Supported Lipid Membranes (Adv. Healthcare Mater. 10/2017)
Authors: Setareh Vafaei, Seyed R. Tabaei, Kabir H. Biswas, Jay T. Groves, Nam‐Joon Cho
Journal: Advanced Healthcare Materials (2017)

In article number 1700243, Naam-Joon Cho and co-workers develop a mechanically tunable substrate for cell adhesion studies. Single cell adhesion on extracellular matrix protein functionalized lipid bilayer is depicted to introduce a new method to evaluate cell-substrate interaction on low rigidity substrates, which closely mimic the physiological environment. In this particular case, a unique reorganization of the ECM protein is characterized with cell adhesion on the experimental platform.
DIPG-31. CLINICO-PATHOLOGICAL REVIEW OF 26 CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Keita Terashima, Kaoru Yoshida, Chikako Kiyotani, Yoko Shioda, Tomoo Osumi, Motohiro Kato, Daisuke Tomizawa, Kenichi Usami, Hideki Ogiwara, Yoshiyuki Tsutsumi, Hiroshi Fuji, Takako Yoshioka, Hideto Iwafuchi, Yoshiko Nakano, Koichi Ichimura, Kimikazu Matsumoto
Journal: Neuro-Oncology (2017)

METHODS: Twenty-six patients with diffuse intrinsic pontine glioma (DIPG) were retrospectively analyzed at National Center for Child Health and Development, one of the largest pediatric brain tumor centers in Japan. The following information was collected from the electric medical record: clinical characteristics, surgery / pathology reports, treatments and outcomes. RESULTS: Between June, 2002 and April, 2016, 26 patients were diagnosed as DIPG and treated. Median age was 6 years (2–12). There were 19 boys and 7 girls. Common presenting symptoms included, cranial nerve palsies, ataxia, long-tract signs, vomiting, and altered consciousness. 20 patients (77%) were diagnosed within 40 days from symptom onset. 13 patients (50%) underwent biopsy. Patients who underwent biopsy tend to have atypical imaging and clinical features. Interval from diagnosis to radiation therapy was significantly longer in biopsy group than non-biopsy group (29 days and 8 days respectively, p=0.04). Histopathlogy diagnoses were: glioblastoma 4, anaplastic astrocytoma 5 and other glioma 4. H3 K27M mutations were detected in 5 patients among 8 patients tested (63%). CMV protein was not detected in all 4 patients tested. All but one patient underwent focal radiation therapy (RT) of 54Gy/30 fractions and one patient presented with dissemination underwent craniospinal RT. Fourteen patients (54%) did not receive any chemotherapy as an upfront treatment. Seven patients (27%) received temozolomide (TMZ)-based chemotherapy and the rest (19%) received other chemotherapy regimen. Mean overall survival (OS) of all 26 patients was 313 days. Mean progression-free survival (PFS) was 201 days. Biopsy, TMZ, any chemotherapy or H3 K27M mutation was not associated with survival outcomes. CONCLUSIONS: DIPG continues to be an incurable disease. Biopsy in DIPG is safe and feasible. H3 K27M mutation is a frequent event in DIPG. Chemotherapy is not a standard upfront treatment for DIPG.
The effect of a novel molecular targeting compound as K-samII/KGFR phosphorylation inhibitor, Ki23057, on biliary tract cancer
Authors: Nobuya Yamada, Ryosuke Amano, Masakazu Yashiro, Katsunobu Sakurai, Koichi Yasuda, Masaichi Ohira, Atsushi Miwa, Kosei Hirakawa
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5613 

Background: Biliary tract cancer is difficult to be diagnosed in the early stage, and the prognosis is very poor. Biliary tract cancer is histologically similar to scirrhous gastric cancer and proliferates in association with fibrosis. We previously reported that keratinocyte growth factor (KGF) played an important role in the growth of scirrhous gastric cancer and Ki23057, KGF receptor inhibitor, inhibited the cancer growth. The aim of the current study is to clarify the possibility of KGF receptor-targeted molecular therapy for treating biliary tract cancer.

Materials and Methods: Two human biliary tract cancer cell lines were used in this study. OCUCh-LM1 was derived from extrahepatic bile duct carcinoma, and OCUG-1 from gallbladder carcinoma. Ki23057, a newly developed small molecule acting K-samII/KGFR autophosphorylation inhibitor, is a tyrosine kinase inhibitor that competes with ATP for the binding site. The expression of KGFR mRNA in these cell lines was determined by RT-PCR. The effect of several growth factors on proliferation of these cell lines was measured by calculating the number of cancer cells. The inhibitory effect of Ki23057 on the viability of these cell lines was measured by MTT assay. The effect of Ki23057 on the growth of xenografts in nude mice was investigated.

Results: RT-PCR showed that both cell lines expressed KGFR mRNA. The proliferation of OCUCh-LM1 and OCUG-1 cells were increased significantly by adding KGF. Cell viability assay showed that Ki23057 inhibited proliferation of OCUCh-LM1 and OCUG-1. A marked inhibitory effect of Ki23057 on the growth of xenografts of OCUCh-LM1 was found in Ki23057-treated mice. Apoptotic index in xenografted tumor was significantly increased following Ki23057 treatment, compared to the control.

Conclusion: Our results suggest that a novel K-samII/KGFR phosphorylation inhibitor, Ki23057, has a high potential for use as a clinical agent for the treatment of biliary tract cancer.
The association between psychological distress and concussion history in college athletes
Authors: Patricia R Combs, Erin B Wasserman, Corey J Rodrigo, Kevin G Guskiewicz, Jason P Mihalik
Journal: British Journal of Sports Medicine (2017)

Objective To examine how baseline measures of psychological distress, including depression, anxiety, and somatization, in college athletes are affected by concussion history. Design Cross-sectional study. Setting A National Collegiate Athletic Association Division I university. Subjects Division I college athletes (age=20.6±1.4 years) with a self-reported history of 1 or more concussions (n=128; 52 (41%) females; 76 (59%) males) and with no self-reported concussion history (n=286; 100 (35%) females; 186 (65%) males). An additional 67 student-athletes were excluded due to incomplete demographic information. Intervention Athletes self-reported concussion history on a questionnaire completed during pre-season baseline testing. Outcome measures All participants completed the Brief Symptom Inventory18 (BSI-18) during the same pre-season baseline assessment. Results There were no significant differences in total BSI-18 scores ( P =0.47) between participants with a concussion history (median BSI-18 score=0, IQR=0–2) and those with no concussion history (median BSI-18 score=0, IQR=0–3). Additionally, there were no significant differences found between groups for any BSI-18 subset score (Depression: P =0.99; Anxiety: P =0.53, Somatization: P =0.07). Conclusions A history of 1 or more concussions does not influence baseline psychological distress measures in college athletes. While associations between concussion history and increased risk of clinical depression in retired professional athletes have been reported, our data do not support this association at the college level. Our results may underscore the need to develop more sensitive questionnaires to assess psychological distress among otherwise young healthy emerging adults. Future research should explore more diverse samples, and explore the utility of psychological distress measures during post-injury recovery. Competing interests None.
Somatic Mutations Drive Distinct Imaging Phenotypes in Lung Cancer
Authors: Emmanuel Rios Velazquez, Chintan Parmar, Ying Liu, Thibaud P. Coroller, Gisele Cruz, Olya Stringfield, Zhaoxiang Ye, Mike Makrigiorgos, Fiona Fennessy, Raymond H. Mak, Robert Gillies, John Quackenbush, Hugo J.W.L. Aerts
Journal: Cancer Research (2017)

Tumors are characterized by somatic mutations that drive biological processes ultimately reflected in tumor phenotype. With regard to radiographic phenotypes, generally unconnected through present understanding to the presence of specific mutations, artificial intelligence methods can automatically quantify phenotypic characters by using predefined, engineered algorithms or automatic deep-learning methods, a process also known as radiomics. Here we demonstrate how imaging phenotypes can be connected to somatic mutations through an integrated analysis of independent datasets of 763 lung adenocarcinoma patients with somatic mutation testing and engineered CT image analytics. We developed radiomic signatures capable of distinguishing between tumor genotypes in a discovery cohort (n = 353) and verified them in an independent validation cohort (n = 352). All radiomic signatures significantly outperformed conventional radiographic predictors (tumor volume and maximum diameter). We found a radiomic signature related to radiographic heterogeneity that successfully discriminated between EGFR+ and EGFR- cases (AUC = 0.69). Combining this signature with a clinical model of EGFR status (AUC = 0.70) significantly improved prediction accuracy (AUC = 0.75). The highest performing signature was capable of distinguishing between EGFR+ and KRAS+ tumors (AUC = 0.80) and, when combined with a clinical model (AUC = 0.81), substantially improved its performance (AUC = 0.86). A KRAS+/KRAS- radiomic signature also showed significant albeit lower performance (AUC = 0.63) and did not improve the accuracy of a clinical predictor of KRAS status. Our results argue that somatic mutations drive distinct radiographic phenotypes that can be predicted by radiomics. This work has implications for the use of imaging-based biomarkers in the clinic, as applied noninvasively, repeatedly, and at low cost. Cancer Res; 77(14); 3922-30. ©2017 AACR.
Combination of paclitaxel, bevacizumab and MEK162 in second line treatment in platinum-relapsing patient derived ovarian cancer xenografts
Authors: Francesca Ricci, Federica Guffanti, Giovanna Damia, Massimo Broggini
Journal: Molecular Cancer (2017)

Advanced ovarian cancer is very responsive to first line platinum therapy, however almost invariably it relapses with a resistant disease. We have reported that patient derived ovarian xenografts (PDXs), independently from the degree of the initial response to cisplatin (DDP), show a significantly lower response to a second DDP cycle. We here report the effect of new combination regimens containing a MEK inhibitor (MEK), bevacizumab (BEV) and paclitaxel (PTX) as second line therapy in platinum-relapsing PDXs. We selected three DDP-relapsing PDX models based on the presence of activation of the RAS/RAF/MEK/ERK axis, mutated p53, lack of PTEN expression and activation of the PI3K pathway. In all the selected xenograft models, the antitumor efficacy of the doublets can be summarized as PTX/BEV > BEV/MEK > PTX/MEK and the antitumor activity of the triple combination was higher than any double combination. All the different combinations were well tolerated. The present data corroborate the activity of bevacizumab in combination with chemotherapy for the treatment of relapsing ovarian tumors and suggest that the addition of another targeted agents (MEK inhibitor) can further increase the antitumor activity without any increase in toxicity. PDX models represent a useful model to test second line therapy after failure of DDP first line.
LDH Levels Predict Progression-Free Survival in Treatment-NaÏVe Patients with Trisomy 12 Chronic Lymphocytic Leukemia
Authors: Francesco Autore, Paolo Strati, Idanna Innocenti, Francesco Corrente, Livio Trentin, Agostino Cortelezzi, Marta Coscia, Alessandro Gozzetti, Massimo Gentile, Fortunato Morabito, Giovanni D'Arena, Roberta Murru, Donatella Iolanda Vincelli, Gianluigi Reda, Candida Vitale, Alessandra Ferrajoli, Luca Laurenti
Journal: Blood (2016)
ATRT-10. EARLY POST RADIATION CHANGES AND EFFICACY IN CHILDREN WITH ATRT TREATED ON COG ACNS 0333: A COMPARISON OF PROTON VS PHOTON THERAPY
Authors: Anita Mahajan, Doug Strother, Ian Pollack, Tom Merchant, Chris Williams-Hughes, Allen Buxton, Tianni Zhou, Mark Krailo, Alyssa Reddy
Journal: Neuro-Oncology (2017)

BACKGROUND/OBJECTIVES: COG ACNS0333 is a prospective study evaluating surgery, intensive chemotherapy and radiation therapy (RT) in the management of ATRT. The therapy sequence was based on patient age, disease location and extent. Both proton RT (PRT) and photon RT (XRT) modalities were permitted. In this study the early post-RT changes and efficacy of PRT and XRT were compared. METHODS: All RT plans were reviewed centrally. Pre-operative, post-operative, pre-RT and first post-RT MRI scans were available and reviewed. Patient characteristics, treatment sequence, RT plan, tumor volume, brain and brainstem dosimetric parameters were evaluated. RESULTS: 41 of 65 evaluable patients on protocol received RT between 5/2009 and 11/2013 (14 PRT, 27 XRT). Median age at RT was 1.7y (range 0.6 – 13.9y). 6/41 patients received craniospinal RT. Median tumor dose was 50.4Gy (range 45-54Gy). All patients had >1 post-RT MRI scans available. At a median post-diagnosis follow up of 9 months, tumor control was equivalent after PRT and XRT (p=0.83). At a median post-RT follow up of 5 months (range 1.4–36.1) 10/42 patients had in-field MRI changes of varying severity (3 PRT, 7 XRT) in the absence of clear tumor progression. These MRI changes were noted between 2–6 months post-RT. Patients with post-RT MRI changes tended to have larger tumors with larger pre-operative tumor volume (median 137 cc vs 57 cc) and larger CTV’s (median 257cc vs 125 cc); however, the difference was not statistically different (p=0.21). CONCLUSION: In this early analysis of COGACNS 0333 there were no detectable differences in tumor control between the patients treated with PRT vs XRT. Reactive changes were seen with both modalities but were not excessive with either.
Abstract 205: Mlip is a New Integrator of Physiological Stress Required For Proper Cardiac Adaptation
Authors: Marie-Elodie Cattin, Jessica Wang, Cassandra Roeske, Esther Mak, Stephanie L Thorn, Jean N DaSilva, Yibin Wang, Aldon J Lusis, Patrick G Burgon
Journal: Circulation Research (2015)

Aging and diseases are generally a result of the inability of tissues to properly adapt to stress. The heart is particularly vulnerable to disequilibrium in homeostasis as its regenerative capacities are limited. Many molecular players have been identified as cardiac gate-keepers and integrators of stress, all essential to preserve cardiac function. However, the molecular basis of the relationship between aging and the pathogenesis of cardiac dysfunction remains poorly understood. Muscle enriched A-type lamin interacting protein (MLIP) is a unique mammalian protein of unknown function that was recently identified through its interaction with A-type lamins in the heart and as a modulator of cardiac hypertrophy in vitro. Here we report that young Mlip deficient mice develop dilated cardiomyopathy, manifested by an increase in heart mass with reduced cardiac function. Through global gene expression profiling of the Mlip deficient hearts, we identified a deregulation in mTOR signalling, a key stress sensing canonical pathway. Analysis of mTOR regulatory proteins (AMPK and AKT) revealed hyperactivation of the mTOR pathway and a deregulated integration of these two stress/nutrient sensors. These data support the notion that Mlip deficient hearts have impaired cardiac adaptation due to deregulated mTOR activity resulting in maladaptive remodeling, and the development of dilated cardiomyopathy. These results are further supported by a genetic association between Mlip and early response to pro-hypertrophic stimulus. Collectively, these results demonstrate that Mlip is required for normal integration of physiological stress (postnatal cardiac growth, isoproterenol-induced hypertrophy) through the regulation of the AMPK/Akt/mTOR pathway to maintain cardiac homeostasis in the adult heart.
Factors predicting the instant effect of motor function after subthalamic nucleus deep brain stimulation in Parkinson’s disease
Authors: Xin-Ling Su, Xiao-Guang Luo, Hong Lv, Jun Wang, Yan Ren, Zhi-Yi He
Journal: Translational Neurodegeneration (2017)

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies, however there were different conclusions about that through long- and short-term follow-ups. We aimed to investigate the factors which influence the predictive value of levodopa responsiveness, and discover more predictive factors of surgical outcomes. Twenty-three PD patients underwent bilateral STN-DBS and completed our follow-up. Clinical evaluations were performed 1 week before and 3 months after surgery. STN-DBS significantly improved motor function of PD patients after 3 months; preoperative levodopa responsiveness and disease subtype predicted the effect of DBS on motor function; gender, disease duration and duration of motor fluctuations modified the predictive effect of levodopa responsiveness on motor improvement; the duration of motor fluctuations and severity of preoperative motor symptoms modified the predictive effect of disease subtype on motor improvement. The intensity of levodopa responsiveness served as a predictor of motor improvement more accurately in female patients, patients with shorter disease duration or shorter motor fluctuations; PD patients with dominant axial symptoms benefit less from STN-DBS compared to those with limb-predominant symptoms, especially in their later disease stage.
Physical activity and concussion risk in male youth ice hockey players
Authors: Tracy A Blake, Willem H Meeuwisse, Patricia K Doyle-Baker, Brian L Brooks, Luz Palacios-Derflingher, Carolyn A Emery
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate the association between self-reported physical activity (PA) and concussion incidence in male youth ice hockey players. Design pooled data from three prospective cohort studies. Setting Community ice hockey rinks and sport medicine clinics. Participants PeeWee (ages 11–12), Bantam (ages 13–14), and Midget (ages 15–17) male youth ice hockey players (n=1208). Assesment of risk factors Participants reported six-week physical education and extra-curricular sport participation history upon study entry. Concussion incidence rate ratios [IRRs (95% CI)] associated with 1). total six-week PA volume, and 2). meeting the Canadian PA recommendations of one hour of daily PA (≥42 hours/six weeks) were calculated using multivariable Poisson regression (covariates: age, competition level, concussion history). Models were adjusted for hockey exposure, and cluster by team, study year and city (α&lt;0.05). Outcome measure Medically-diagnosed concussions during the study period. Main results Total PA volume did not affect concussion incidence in male youth ice hockey players [IRR: 0.996 (95% CI: 0.990–1.003]. Concussion incidence was higher in male ice hockey players who did not meet the PA recommendations versus those who met the PA recommendations amongst PeeWee [IRR: 2.94 (95% CI: 1.29–6.66)] and Bantam [IRR: 2.18 (95% CI: 1.12–3.94)] participants, but not amongst Midget participants [IRR: 1.37 (95% CI: 0.72–2.59)]. There was no evidence of confounding or modification by competition level or concussion history. Conclusions While total PA volume was not associated with concussion risk, PeeWee and Bantam male youth ice hockey players whose six-week PA history was below the PA recommendations were at greater risk of concussion. This research will inform future studies examining the mechanism of this association. Competing interests None.
Clinical Predictors of Venous Thromboembolism during Therapy for Childhood Acute Lymphoblastic Leukemia
Authors: Marion K Mateos, Toby N. Trahair, Chelsea Mayoh, Pasquale M Barbaro, Rosemary Sutton, Tamas Revesz, Draga Barbaric, Jodie Giles, Frank Alvaro, Francoise Mechinaud, Daniel Catchpoole, Rishi S Kotecha, Luciano Dalla-Pozza, Glenn M Marshall
Journal: Blood (2016)
Cardiovascular Reactivity Among Surgeons: Not Music to Everyone's Ears
Authors: William H. Edwards
Journal: JAMA (1995)

To the Editor.  —The most memorable and anxiolytic effect on a patient from music in the operating room was related to us after she awoke in the recovery room. She said she was certainly glad she had survived and was alive because the last thing she remembered prior to her anesthesia was Amazing Grace, which was playing in the operating room. She felt she must surely be in heaven.  It is gratifying to see confirmation that music does indeed have a psychophysiological effect on us as surgeons. 1