tbuckley/cabot-search huggingface dataset:
Feasibility study of a simple reaction test for immediate sideline-analysis â€“ preliminary results$
Authors: Axel Gnsslen, Werner Krutsch
Journal: British Journal of Sports Medicine (2017)

Objective Reaction testing is an integral part of sideline testing in sport-related concussion. Present established tools include time-demanding computer-based tools and analysis of the clinical reaction time with a special apparatus. The present tool is a mobile phone program using a simple reaction time equivalent. Design Case control study. Setting Professional German Hockey League Players and regional youth players. Participants 20 professional ice-hockey players. Interventions (or Assessment of risk factors) Analysis of a simple dual task reaction time (sRT; one of two symbols) and a complex one of four symbol reaction time (cRT). Outcome measures Analysis of average baseline times, fastest and slowest 10% values, overall application time and comparison to 4 players sustaining concussions. Main results Mean sRT was 0,354s (95% confidence intervals (0,330;0,377) with fastest 10% 0,294s and slowest time 0,539s. The overall procedure needed 65,4s. Mean cRT was 0,43s (95% confidence intervals (0,423;0,437) with fastest 10% 0,34s and slowest time 0,592s. The overall procedure needed 117,364. The 4 patients with sustained concussion had immediately a sRT and a cRT of 0,518s and 0,677s, respectively. A value of 0,5s is probably an expected cut-off. Conclusions This simple web- and mobile-phone-based program allows safe analysis of prolonged reaction times in concussed athletes. Competing interests None.
Using CRISPR-Cas9 to Generate Gene-Corrected Autologous iPSCs for the Treatment of Inherited Retinal Degeneration
Authors: Erin R. Burnight, Manav Gupta, Luke A. Wiley, Kristin R. Anfinson, Audrey Tran, Robinson Triboulet, Jeremy M. Hoffmann, Darcey L. Klaahsen, Jeaneen L. Andorf, Chunhua Jiao, Elliott H. Sohn, Malavika K. Adur, Jason W. Ross, Robert F. Mullins, George Q. Daley, Thorsten M. Schlaeger, Edwin M. Stone, Budd A. Tucker
Journal: Molecular Therapy (2017)

Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function. We developed a homology-directed repair strategy targeting a homozygous Alu insertion in exon 9 of male germ cell-associated kinase (MAK) and demonstrated restoration of the retinal transcript and protein in patient cells. We generated a CRISPR-Cas9-mediated non-homologous end joining (NHEJ) approach to excise a major contributor to Leber congenital amaurosis, the IVS26 cryptic-splice mutation in CEP290, and demonstrated correction of the transcript and protein in patient iPSCs. Lastly, we designed allele-specific CRISPR guides that selectively target the mutant Pro23His rhodopsin (RHO) allele, which, following delivery to both patient iPSCs in vitro and pig retina in vivo, created a frameshift and premature stop that would prevent transcription of the disease-causing variant. The strategies developed in this study will prove useful for correcting a wide range of genetic variants in genes that cause inherited retinal degeneration.
DIPG-12. OPTIMIZATION OF OSMOTIC PUMP IMPLANTATION FOR DELIVERY OF THERAPEUTICS VIA CONVECTION ENHANCED DELIVERY IN PRECLINICAL MODELS OF DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Kathleen Knudson, Sridevi Yadavilli, Roger Packer, Javad Nazarian
Journal: Neuro-Oncology (2017)

Diffuse intrinsic pontine gliomas (DIPG) are fatal, high-grade gliomas arising in pons of children. Due to the blood brain barrier (BBB), it is difficult to effectively deliver chemotherapy agents into the tumor. Convection-enhanced delivery (CED) has been shown to deliver agents into tissues via a continuous hydrostatic pressure gradient. An effective long-term continuous administration of chemotherapeutic agents directly into the pons, bypassing the BBB, can be achieved via CED by implanting a cannula attached to an osmotic pump. Our objective is to optimize the technique for placement of the CED cannula carrying an osmotic pump into the pons of a murine DIPG mouse model. An osmotic pump with a capacity to infuse 100ul over 4 weeks was used. Two cohort of mice were selected. The first cohort was to test feasibility, and the cannula was placed into the pons of non-tumor bearing mice. The second cohort was stereotactically injected with human primary DIPG cells into the pons. Afterward, a cannula was stereotactically implanted and the osmotic pump loaded with Evans blue dye or DII was placed subcutaneously. Evans blue dye and DII facilitate ex vivo and in vivo visualization of the implantation site, respectively. We first show that osmotic pump installation into pons itself does not affect the overall survival of the mouse. We further track the exact placement of cannula and delivery of the dye into the pontine tumor by comparing the tumor location in haematoxylin and eosin stained sections with DII fluorescent signal/Evans blue dye at infusion site. The next step is to study the delivery of therapeutics by this technique to determine tumor growth and survival in DIPG xenografts. We conclude that surgical implantation of a cannula in the mouse brainstem is feasible and provides an opportunity for drug testing by direct delivery to tumor.
Apatinib in Chinese patients with advanced hepatocellular carcinoma: A phase II randomized, open-label trial.
Authors: Shukui Qin
Journal: Journal of Clinical Oncology (2014)

4019 Background: Advanced hepatocellular carcinoma (HCC) is the third most common cause of cancer death in worldwide. Apatinib is a novel oral multi-kinase inhibitor of the vascular endothelial growth factor receptor-2 . Here report the results of phase II clinical study of apatinib as first- line treatment in chinese patients with advanced HCC. Methods: This was a multicenter, randomized, open-label, dose-finding, phase II trial. Treatment naive Patients with advanced HCC had Child-Pugh liver function class A were randomized to receive apatinib 850 mg/qd or 750 mg/qd. The efficacy was assessed at the end of each 8 weeks period. Primary endpoint was time to progression (TTP). Secondary endpoint included overall survival (OS), objective response rate (ORR), disease control rate (DCR), the level of α-fetoprotein (AFP) and safety. According to oncology clinical trial Simon two-stage design, thirty-six patients were enrolled into stage 1 and 85 patients were enrolled into stage 2 (extension phase) of the trial. The trial was registered with ClinicalTrial.gov, NO. NCT01192971. Results: From 2010.07-2012.03 Total 121 patients were enrolled. The patient baseline characteristics of two treatment groups were similar with regards to disease status, ECOG scores, number of metastatic sites, pathological grading and prior therapy (P>0.05). For efficacy, median time to progression of the 850 mg group and the 750 mg group was 4.2 months and 3.3 months respectively. The median overall survival of the two groups was 9.7 months and 9.8 months respectively. The DCR was 48.57% for 850 mg qd group and 37.25% for 750 mg qd, respectively. Apatinib has been well tolerable in patients, most of the adverse event could be managed by dose interruptions or reductions. There was no significant favorable safety profile between two groups, above 2% of patients were elevated aminotransferase, thrombocytopenia, elevated bilirubin, hypertension, leukocytopenia, hand-and-foot syndrome, fatigue. Conclusions: Results of this uncontrolled phase II study indicated that apatinib has potential survival benefit in patients with advance HCC. 850 mg/qd or 750 mg/qd was recommended dose for further clinical study. Clinical trial information: NCT01192971.
Data from the First CD20-Targeted Immunotoxin, MT-3724, in a Phase I/Ib Study in Relapsed/Refractory (R/R) Non-Hodgkin's B-Cell Lymphoma (NHL)
Authors: Paul A Hamlin, Michelle A. Fanale, Steven I. Park, David J. Valacer, Jack Higgins, Anas Younes
Journal: Blood (2016)
Erratum: Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients (American Journal of Respiratory and Critical Care Medicine (2014) 189 (1383-1394))
Authors: N. W. Lonardo, M. C. Mone, R. Nirula, E. J. Kimball, K. Ludwig, X. Zhou, B. C. Sauer, K. Nechodom, C. Teng, R. G. Barton
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Circulating Tumor DNA: Measurement and Clinical Utility
Authors: Joshua Donaldson, Ben Ho Park
Journal: Annual Review of Medicine (2017)

Circulating tumor DNA (ctDNA) is a component of the "naked" DNA found in blood. It can be isolated from plasma and represents combined genetic material from the primary tumor and metastases. Quantitative and qualitative information about a cancer, including mutations, can be derived using digital polymerase chain reaction and other technologies. This "liquid biopsy" is quicker and more easily repeated than tissue biopsy, yields real-time information about the cancer, and may suggest therapeutic options. All stages of cancer therapy have the ability to benefit from ctDNA, starting with screening for cancer before it is clinically apparent. During treatment of metastatic disease, it is useful to predict response and monitor disease progression. Currently, ctDNA is used in the clinic to select patients who may benefit from epidermal growth factor receptor-targeted therapy in non-small cell lung cancer. In the future, ctDNA technology promises useful applications in every part of clinical oncology care.
Abstract 13097: Flow and Cardiac Output Redistribution in the Fetus With {S,D,D} Transposition of the Great Arteries and Intact Ventricular Septum: Insights Into the Pathophysiology
Authors: Max E Godfrey, Kevin G Friedman, Monika Drogosz, Abraham M Rudolph, Wayne Tworetzky
Journal: Circulation (2016)

Introduction: Although the postnatal physiology of {S,D,D} transposition of the great arteries with intact ventricular septum (TGA) is well established, little is known about fetal TGA. In the normal fetus, the pulmonary valve (PV) is larger than the aortic valve (AoV), there is exclusive right to left flow at the foramen ovale (FO) and ductus arteriosus (DA), and the left ventricle (LV) ejects 40% of combined cardiac output (CCO) through the aorta, primarily to the brain. In TGA, the LV ejects O 2 -rich blood to the pulmonary artery, theoretically leading to pulmonary vasodilation, increased branch pulmonary arterial flow and resultant reduced DA flow. We tested the hypothesis that TGA anatomy results in altered distribution of CCO, FO and DA flow, and valve size. Methods: We analyzed valve size, color flow and pulse Doppler on echocardiograms of 74 fetuses with TGA (2003-2015). Findings were compared with our institutional normal fetal data, n=222. Results: The LV component of CCO was higher in TGA than in controls (50.7% vs 40.2%, p&lt;0.001) with no difference in total CCO. Flow was bidirectional at the FO in 56 (75.7%) fetuses and at the DA in 24 (32.4%). Only 21.6% had normal exclusive right to left flow at both shunts. Bidirectional shunting was more common in the 3 rd trimester than the 2 nd (p&lt;0.03). In contrast to normal, TGA AoV and PV sizes were nearly identical, hence the AoV z-score was higher than the PV z-score (1.13 vs -0.65, p&lt;0.001). Conclusion: In TGA there is loss of normal right sided dominance, as each ventricle provides half of the CCO. The AoV is relatively large as it carries 50% of CCO rather than the normal 40%. The PV is relatively small as it carries 50% rather than the normal 60% of CCO. There is increased LV component of CCO (to the pulmonary arteries) and frequently bidirectional FO and DA flow. This may support the theory that high pulmonary arterial O 2 content lowers pulmonary vascular resistance, thereby increasing branch pulmonary arterial flow and venous return, increasing LV preload and output. Pulmonary sensitivity to O 2 is thought to increase later in gestation, which may explain the increased bidirectional shunting. Consequences of these flow alterations include increased aortic and likely brain flow, perhaps compensating for substrate deficiency in TGA.
Clinical outcomes of IMRT versus 3D-CRT in preoperative chemoradiotherapy for locally advanced rectal cancer (LARC) treated in a community setting.
Authors: Gustavo Ferraris, Maria Fernanda Diaz Vazquez, Jorge Palazzo, Sharon Salenius, Steven E. Finkelstein, Eduardo Fernandez
Journal: Journal of Clinical Oncology (2015)

e17756 Background: To compare the potential advantages of IMRT and 3DCRT in locoregional control and toxicity in patients with LARC. Methods: This is a retrospective analysis of a cohort of 235 consecutively treated patients with T2/T4 and N0/N1 rectal adenocarcinoma who underwent 5-FU based neoadjuvant chemo-RT between 2/2006 and 8/2012. All of them were preoperatively assessed by a surgeon. Radiation modality was correlated with clinical outcome (local and distant control) and rates of acute and late toxicity were compared for hematological, GU, GI and skin. The Chi-Squared test was used to compare the patient characteristic and radiation parameters between the two arms and univariate and multivariate Cox regression analyses were also performed. Results: 140 patients (59,6%) received IMRT, and 95 patients (40,4%) received 3DCRT to a median total dose of 5040 cGy and the median age was 64,5 years. Median follow-up time was 24 months. Rates of local recurrence were similar between IMRT group and 3DCRT group and rates of distant metastases after completion of therapy were not significantly between arms. Statistically significant differences in locoregional control and survival were not found between IMRT and 3DCRT (p = 0,56 and p = 0,24 respectively), nor in colostomy free for low-lying tumors (p = 0.44) Patients who received IMRT had a high significant reduction in all grade ≥ 3 acute toxicities versus grade ≤ 2 toxicities with respect to skin (P < 0,001), hematological (p < 0,001),urinary (P = 0,017), and GI symptoms (p = 0,0006), and late GI toxicity (p < .001) as compared to those treated with 3DCRT. The incidence of grade ≥ 3 diarrhea was 16 % among 3DCRT compared to 5 % among IMRT patients. In univariate analysis, clinical T stage, age, KPS, and adjuvant chemotherapy given were associated with better overall survival (all p < 0,05) and total radiation dose was associated with better DFS (p = 0,0065) The rates of pathological complete response were similar in the 3DCRT versus IMRT (15%) Conclusions: IMRT for rectal cancer reduces all grade ≥ 2 acute and late toxicities compared to 3DCRT, reducing treatment-related morbidity associated with chemo-radiation therapy.
Retrospective comparison of response rates and survival with neoadjuvant docetaxel versus anthracycline-based chemotherapy for locally advanced breast cancer patients
Authors: D. Gupta, V. Raina, N. K. Shukla, G. K. Rath, B. K. Mohanti, D. N. Sharma
Journal: Journal of Clinical Oncology (2009)

e11564 Background: LABC is a major problem in our country comprising of ≥ 20% of all breast cancer patients. Neoadjuvant chemotherapy is now standard treatment for LABC but randomized trials have failed to show survival advantage. Methods: We retrospectively analyzed locally advanced breast cancer (stage III) patients who received neoadjuvant chemotherapy (NACT) from January 2000 to December 2008. Out of 3000 case records screened, 570 (19%) were LABC and 110/570 (19%) treatment-naïve patients started on NACT were analyzed. Ninety one (37 docetaxel [D], 54 anthracycline [A]) patients were eligible for response and survival analysis. Pathological CR (pCR) was defined as no evidence of malignancy in both breast and axilla. Survival curves generated using Kaplan-Meier method and survivals compared using log-rank test. Results: Median age of whole cohort was 45 years (range 25–68 years). Premenopausal were 42% and ER+ 49.5%. Most (90%) were T4 tumors and 70% were stage IIIB. Median number of preoperative cycles was 3 and 6 in D and A group. Overall clinical response rates for breast primary were 74.3% (CR 28.6%) and 53.7% (CR 16.7%, p=0.58) while for axilla ORR were 75.7% (51.4% CR) vs 54.8% (40.4% CR, p=0.77) respectively for D and A. Corresponding pCR rates were 19% vs 13% respectively. There was no significant difference in disease free (3 year 56.84% vs 61.16%, p=0.80) and overall survival (3 year 70% vs 78.5%, p=0.86) between two groups. Those who achieved pCR in both groups also had no survival advantage (p=0.34) over non achievers. There was no difference in pCR rates for ER+ vs ER- patients but ER+ patients had significantly higher DFS than ER- patients (p=0.05). Conclusions: Although pCR rates were higher with docetaxel based NACT, it did not translate into superior DFS/OS compared to anthracycline based chemotherapies. Achievement of pCR too, was not associated with any survival advantage. No significant financial relationships to disclose.
Gesture and language: Distinct subsystem of an integrated whole
Authors: Susan Goldin-Meadow, Diane Brentari
Journal: Behavioral and Brain Sciences (2017)

The commentaries have led us to entertain expansions of our paradigm to include new theoretical questions, new criteria for what counts as a gesture, and new data and populations to study. The expansions further reinforce the approach we took in the target article: namely, that linguistic and gestural components are two distinct yet integral sides of communication, which need to be studied together.
運動を通した換気指数としてのVE対VCO2勾配と最小VE/VCO2(Min.VE/VCO2)間の臨床的意味における差異
Authors: Ebi Yoshiko, Maeda Tomoko, Nagayama Masatoshi, Hamamoto Hiromu, Sumiyoshi Tetsuya, Itoh Haruki
Journal: Circulation (2009)
Development and Validation of an Ultradeep Next-Generation Sequencing Assay for Testing of Plasma Cell-Free DNA from Patients with Advanced Cancer
Authors: Filip Janku, Shile Zhang, Jill Waters, Li Liu, Helen J. Huang, Vivek Subbiah, David S. Hong, Daniel D. Karp, Siqing Fu, Xuyu Cai, Nishma M. Ramzanali, Kiran Madwani, Goran Cabrilo, Debra L. Andrews, Yue Zhao, Milind Javle, E. Scott Kopetz, Rajyalakshmi Luthra, Hyunsung J. Kim, Sante Gnerre, Ravi Vijaya Satya, Han-Yu Chuang, Kristina M. Kruglyak, Jonathan Toung, Chen Zhao, Richard Shen, John V. Heymach, Funda Meric-Bernstam, Gordon B. Mills, Jian-Bing Fan, Neeraj S. Salathia
Journal: Clinical Cancer Research (2017)

Purpose: Tumor-derived cell-free DNA (cfDNA) in plasma can be used for molecular testing and provide an attractive alternative to tumor tissue. Commonly used PCR-based technologies can test for limited number of alterations at the time. Therefore, novel ultrasensitive technologies capable of testing for a broad spectrum of molecular alterations are needed to further personalized cancer therapy.Experimental Design: We developed a highly sensitive ultradeep next-generation sequencing (NGS) assay using reagents from TruSeqNano library preparation and NexteraRapid Capture target enrichment kits to generate plasma cfDNA sequencing libraries for mutational analysis in 61 cancer-related genes using common bioinformatics tools. The results were retrospectively compared with molecular testing of archival primary or metastatic tumor tissue obtained at different points of clinical care.Results: In a study of 55 patients with advanced cancer, the ultradeep NGS assay detected 82% (complete detection) to 87% (complete and partial detection) of the aberrations identified in discordantly collected corresponding archival tumor tissue. Patients with a low variant allele frequency (VAF) of mutant cfDNA survived longer than those with a high VAF did (P = 0.018). In patients undergoing systemic therapy, radiological response was positively associated with changes in cfDNA VAF (P = 0.02), and compared with unchanged/increased mutant cfDNA VAF, decreased cfDNA VAF was associated with longer time to treatment failure (TTF; P = 0.03).Conclusions: Ultradeep NGS assay has good sensitivity compared with conventional clinical mutation testing of archival specimens. A high VAF in mutant cfDNA corresponded with shorter survival. Changes in VAF of mutated cfDNA were associated with TTF. Clin Cancer Res; 23(18); 5648-56. ©2017 AACR.
Those pernicious items
Authors: Ruth Rosenholtz
Journal: Behavioral and Brain Sciences (2017)

Abstract Hulleman &amp; Olivers (H&amp;O) identify a number of problems with item-based thinking and its impact on our understanding of visual search. I detail ways in which item-thought is worse than the authors suggest. I concur with the broad strokes of the theory they set out, and also clarify the relationship between their view and our recent theory of visual search.
TRTH-22. DEVELOPING RISK-BASED SELECTION CRITERIA FOR THE NEXT SIOP TRIAL OF “SIGHT-SAVING THERAPY” FOR CHILDREN WITH NF1-ASSOCIATED VISUAL PATHWAY GLIOMA (NF1-VPG) – A QUALITATIVE ANALYSIS OF A CONSENSUS SURVEY
Authors: David Walker, Chiara Pilotto, Ismail Beshlawi, Enrico Opocher, Amedeo Aziz, Astrid Sehested, Michael J Fisher, Tim Jaspan, Ian Simmons, Rosalie Ferner, Jacques Grill, Rory Deasy, Darren Hargrave, Pablo Hernaiz Driever, Jo-Fen Liu
Journal: Neuro-Oncology (2017)

INTRODUCTION: A consensus survey involving 98 multi-disciplinary specialists for the first survey (10 cases) and 46 for the second survey (15 cases) in SIOP-E brain tumour group, European NF1 society and the Optic Pathway Glioma Working Group in North America were asked to identify case-based criteria for primary observation, treatment or randomisation in 25 representative, newly diagnosed, NF1-VPG childhood cases which had been the subject of a consensus workshop as part of the SIOP-LGG 2004 trial. Respondents provided justifying statements for their selection of preferred strategy which are the focus for this report. METHODS: Qualitative analysis following grounded theory, using the comparative method categorized 808 comments to: 173 for primary observation, 426 for primary treatment and 209 for primary randomization. These were grouped into 8 themes by two reviewers and compared with the kappa statistic. The themes were: 1) risk of progression, 2) visual function, 3) age and sex, 4) site/dimension of tumour, 5) other symptoms, 6) inconclusive comments, 7) equipoise and 8) parental consent. The themes were analysed by strategy selected for each case. RESULT: Good agreement was achieved for theme allocation between reviewers (k: 0.762). Comments selected for observation were supported by responses categorised as: unknown risk of progression (32%), good vision function (25%); for treatment as poor vision and intention to preserve-improve vision (38%); for randomization as unknown risk of progression (15%), tumour site/dimension (13%) and stable vision (12%). CONCLUSION: This survey and its qualitative analysis identified sufficient uncertainty to propose a randomised trial design for observation versus treatment in a subgroup of newly diagnosed NF1-VPG. A pilot cohort with vision assessment date, site of tumour and age is needed to conduct a power calculation to design a future international randomised trial to study risk of progression and response to new treatments. Collaborations would be welcome. This abstract submitted on behalf of the SIOP-e OPG Nottingham Workshop 2014 (Participating centres: Berlin, Copenhagen, GOS, Hamburg, Leeds, Nottingham, Padua, Paris, Vienna).
Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography
Authors: J. Wartiovaara
Journal: Journal of Clinical Investigation (2004)

The definition of "totipotent" was incorrectly identified as "Cell committed to a specific lineage that is capable of giving rise to all types of differentiated cells and tissues, including extraembryonic tissues."The correct definition is "Cell not committed to a specific lineage that is capable of giving rise to all types of differentiated cells and tissues, including extraembryonic tissues."