tbuckley/cabot-search huggingface dataset:
A phase II trial of low-dose nab-paclitaxel for patients with previously treated or recurrent advanced gastric cancer (OGSG1302).
Authors: Masashi Hirota, Shigeyuki Tamura, Hirokazu Taniguchi, Atsushi Takeno, Hiroshi Imamura, Junya Fujita, Jin Matsuyama, Yutaka Kimura, Junji Kawada, Motohiro Hirao, Kazuhiro Nishikawa, Kazumasa Fujitani, Yukinori Kurokawa, Daisuke Sakai, Hisato Kawakami, Toshio Shimokawa, Taroh Satoh
Journal: Journal of Clinical Oncology (2020)

350 Background: Paclitaxel is a key drug in second-line chemotherapy for advanced or recurrent gastric cancer (AGC) and nanoparticle albumin-bound paclitaxel (nab-PTX) is also widely used in Japan. A previous phase II trial in Japan showed the effectiveness of nab-PTX (260 mg/m2) administered every 3 weeks (q3w) in patients with AGC with a response rate (RR) of 27.8%; however, toxicity was major concern with grade ≥3 neutropenia (49.1%) and peripheral neuropathy (23.6%). To solve this problem, we investigated the efficacy and safety of low-dose q3w nab-PTX regimen in AGC. Methods: Eligibility requirements included: aged ≥20 years, HER2-negative, histologically confirmed, unresectable or recurrent gastric adenocarcinoma, one or more prior chemotherapy containing fluoropyrimidine regimens, presence of measurable lesion(s) according to RECIST ver. 1.1, ECOG PS of 0–2, and adequate organ function. Nab-PTX was administered at a dose of 220 mg/m 2 every 3 weeks. The primary endpoint was the RR. Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease-control rate (DCR), incidence of adverse events, relative dose intensity and proportion of patients who received subsequent chemotherapy. Results: Thirty-three patients were enrolled from 10 institutions in Japan. Of the 32 patients treated with protocol therapy, RR (CR, PR) was 3.1% (95% CI, 0–16.2%), which was not reached the protocol-specified threshold (p = 0.966). DCR (CR, PR, SD) was 37.5% (95% CI, 21.1–56.3%), median OS and PFS were 6.3 months (95% CI, 4.4–14.2) and 2.2 months (95% CI, 1.8-3.1). Relative dose intensity was 97.8% (215 mg/m 2 ). 62.5% of patients received subsequent chemotherapy. Most common grade ≥3 adverse events were neutropenia (38%), anemia (13%), fatigue (19%), anorexia (16%), and peripheral neuropathy (13%). Conclusions: Low-dose regimen of q3w nab-PTX was slightly less toxic, although it did not demonstrate the same effect as the original regimen in response rate. Therefore, it is not recommended for AGC in second or later line setting. Clinical trial information: UMIN 000012701.
Post-tuberculosis mortality and morbidity: valuing the hidden epidemic
Authors: Matthew Quaife, Rein M G J Houben, Brian Allwood, Ted Cohen, Anna K Coussens, Anthony D Harries, Sanne van Kampen, Florian M Marx, Sedona Sweeney, Robert S Wallis, Nicolas A Menzies
Journal: The Lancet Respiratory Medicine (2020)
Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC
Authors: Shugeng Gao, Ning Li, Shunyu Gao, Qi Xue, Jianming Ying, Shuhang Wang, Xiuli Tao, Jun Zhao, Yousheng Mao, Bing Wang, Kang Shao, Wendong Lei, Dali Wang, Fang Lv, Liang Zhao, Fan Zhang, Ziran Zhao, Kai Su, Fengwei Tan, Yibo Gao, Nan Sun, Dawei Wu, Yue Yu, Yun Ling, Zhijie Wang, Chunjian Duan, Wei Tang, Lei Zhang, Shun He, Ning Wu, Jie Wang, Jie He
Journal: Journal of Thoracic Oncology (2020)

IntroductionProgrammed death receptor-1 (PD-1) inhibitors have shown efficacy in first-line treatment of NSCLC; however, evidence of PD-1 inhibitor as neoadjuvant treatment is limited. This is a phase 1b study to evaluate the safety and outcome of PD-1 inhibitor in neoadjuvant setting.MethodsTreatment-naive patients with resectable NSCLC (stage IA–IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 out of 22). Operation was performed between day 29 and 43. Positron emission tomography–computed tomography scans were obtained at baseline and before the operation. The primary end point was safety. Efficacy end points included rate of major pathologic response (MPR) and objective response rate. Expression of programmed cell death ligand 1 was also evaluated (registration number: ChiCTR-OIC-17013726).ResultsA total of 40 patients enrolled, all of whom received two doses of sintilimab and 37 underwent radical resection. A total of 21 patients (52.5%) experienced neoadjuvant treatment-related adverse events (TRAEs). Four patients (10.0%) experienced grade 3 or higher neoadjuvant TRAEs, and one patient had grade 5 TRAE. Eight patients achieved radiological partial response, resulting in an objective response rate of 20.0%. Among 37 patients, 15 (40.5%) achieved MPR, including six (16.2%) with a pathologic complete response in primary tumor and three (8.1%) in lymph nodes as well. Squamous cell NSCLC exhibited superior response compared with adenocarcinoma (MPR: 48.4% versus 0%). Decrease of maximum standardized uptake values after sintilimab treatment correlated with pathologic remission (p < 0.00001). Baseline programmed cell death ligand 1 expression of stromal cells instead of tumor cells was correlated with pathologic regression (p = 0.0471).ConclusionsNeoadjuvant sintilimab was tolerable for patients with NSCLC, and 40.5% MPR rate is encouraging. The decrease of maximum standardized uptake values after sintilimab might predict pathologic response.
Letter to the Editor: Appraisal of Cardiac Ejection Fraction With Liver Disease Severity
Authors: Won Ho Kim, Seong‐Mi Yang, Kook Hyun Lee
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. To the Editor: With interest, we read the study by Kwon et al.,1 which analyzed a large cohort of liver transplantation recipients. They suggested preoperative left ventricular ejection fraction (LVEF) <60% as a cutoff in patients with Model for End‐Stage Liver Disease (MELD) score ≥ 20 to predict posttransplant all‐cause mortality or graft failure. We have several points to discuss about their analysis. Firstly, although the authors adjusted pulmonary hypertension as a covariate in the multivariable Cox regression analysis, more rigorous adjustment for right heart–associated parameters is required. It is unclear how pulmonary hypertension was defined in their analysis, and the severity of pulmonary hypertension is unknown. Given the contribution of portopulmonary hypertension, pulmonary vascular resistance, and right ventricular end‐diastolic volume to posttransplant graft and patient survival or patient morbidity,2 more right heart–associated variables should be adjusted in their analysis. Secondly, the etiology of patient mortality was not evaluated. All‐cause mortality and graft failure may result from noncardiovascular etiology, including recurrence of hepatocellular or other carcinoma, or renal failure. Although the end‐diastolic elastance with low end‐diastolic volume in nonsurvivors could explain the contribution of low LVEF to death, the clinical etiology of the patient mortality should be evaluated whether this low LVEF was actually associated with cardiovascular death. Thirdly, they determined the cutoff of LVEF and MELD score by using a minimal P‐value approach for the conditional inference tree model and log‐rank test between survivors and nonsurvivors. As the adequate cutoff of LVEF is the mainstay of their analysis, other methods of establishing a cutoff, such as Youden’s Index where the sum of sensitivity and specificity is maximal, could validate their cutoff as a sensitivity analysis.5 Fourthly, the power of Cox regression analysis should be considered to determine whether the patient number was sufficient to present the current hazard ratios. According to our calculation, the power to detect the observed hazard ratios for 90‐day all‐cause mortality and graft failure in patients with MELD score ≥ 20 with the available patient number of 883 patients was 63.9% and 77.6%, respectively. This suggests that the study power could be insufficient and that more patients with MELD score ≥ 20 are required to support their conclusion.
Determination of quality of care for patients with hepatocellular carcinoma in Nova Scotia.
Authors: Cathie Ouellet, Ravi Ramjeesingh
Journal: Journal of Clinical Oncology (2020)

506 Background: Hepatocellular carcinoma (HCC) is the most common primary malignancy found in the liver. Little is known about the outcomes of HCC patients in the province of Nova Scotia (NS). There is suggestion that closer proximity to tertiary cancer center provides better outcomes for HCC patients. We postulate that cancer care for HCC patients differs based on a patient’s accessibility to an academic cancer care center. Methods: A retrospective chart review of HCC patients diagnosed from 2015 to 2017, looking at referrals patterns, treatments and wait time was undertaken. Patients who live within the urban area of Halifax, NS (N = 97), where the academic cancer center is, was compared to patients who live outside Halifax (rural, N = 70). Results: 167 patients were identified with a diagnosis of HCC, which included 139 males and 28 females with median age of 68 years old at HCC diagnosis. During that period, only 35.3% of patients diagnosed with HCC had a tissue diagnosis and 67.7% had a baseline AFP (16% had an AFP &gt; 400). Just over 76% were diagnosed based on clinical features. Surgical intervention occurred in 15.6% and local treatments including radiation and TACE occurred in 35.3% of patients .Referral rate to Medical Oncology (MO) was 37.7%, of which 34.1% of patients had seen a MO at the time of data cut off (09-15-2019). 22 patients were eligible for systemic therapy but only 14 patients received systemic treatment (sorafenib n = 14). Conclusions: Initial data suggests patients who live in Halifax appear to have better outcomes than those outside. Further analysis is required to identify what differs between the urban and rural centers accounting for the seen difference in survival. [Table: see text]
Sociodemographic characteristics as predictors of outcomes in hepatocellular carcinoma: A retrospective cohort study.
Authors: Bryce David Beutler, Mark Bilinyi Ulanja, Vijay Aluru, Nageshwara Gullapalli
Journal: Journal of Clinical Oncology (2020)

503 Background: It has been established that race, insurance status, and socioeconomic class play an important role in predicting health care outcomes. However, the impact of these factors has yet to be investigated in the setting of hepatocellular carcinoma (HCC). Methods: We designed a retrospective cohort study utilizing data from the SEER program (2007-2015) to identify patients with resectable HCC (N = 28518). Exposures of interest were race (Asian [AS], Black [BL], Native American/Alaska Native [NA/AN], or White [WH]), insurance status (Medicare/Private Insurance [ME/PI], Medicaid [MAID], or No Insurance [NI]), and median household income. Endpoints included: (1) likelihood of surgical recommendation and (2) overall survival. Multinomial logistic regression for relative risk ratio (RRR) and Cox models were used to identify pertinent associations. Results: Race, insurance status, and socioeconomic class had statistically significant effects on the likelihood of surgical recommendation and overall survival. AS were more likely to receive a recommendation for hepatic resection (RRR = 1.60; 95% CI: 1.42 – 1.80; Reference Race: BL) and exhibited prolonged overall survival (HR = 0.77; 95% CI: 0.73 – 0.82) as compared to members of other ethnic groups; there was no difference in these endpoints between BL, NA/AN, or WH individuals. Patients who had ME/PI were more likely than those with MAID or NI to receive a surgical recommendation. ME/PI was also associated with superior overall survival. Individuals with a household income in the highest quintile were less likely to receive a surgical recommendation than those in the lower quintiles, but nevertheless demonstrated prolonged survival. Conclusions: Race, insurance status, and socioeconomic class have measurable effects on HCC management and outcomes. The underlying causes of these disparities warrant further investigation. [Table: see text]
抗カルバミル化タンパク質(anti-CarP)抗体は関節リウマチの発症に先行する | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Shi Jing, Van De Stadt Lotte A, Levarht E W Nivine, Huizinga Tom W J, Hamann Doerte, Van Schaardenburg Dirkjan, Toes Rene E M, Trouw Leendert A
Journal: Annals of the Rheumatic Diseases (2014)
Does aberrant hepatic arterial anatomy impact the complication rate or survival following resection of pancreatic adenocarcinoma?
Authors: Nicketti M Handy, Angelena Crown, Kimberly A. Bertens, Jesse Clanton, Adnan Alseidi, Thomas Biehl, William Scott Helton, Flavio G. Rocha
Journal: Journal of Clinical Oncology (2020)

775 Background: Patients with aberrant hepatic arterial anatomy (AHAA) are susceptible to tumor invasion and/or ligation during resection of the pancreatic head. The purpose of this study is to determine if AHAA negatively impacts perioperative outcomes or survival. Methods: All patients who underwent either pancreaticoduodenectomy or total pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) between 2005 and 2014 at our center were retrospectively reviewed. Univariate logistic regression was used to compare outcomes between patients with conventional hepatic arterial anatomy to those with AHAA. Survival analysis was performed by Kaplan-Meier method with log rank test. Results: During the study period, 330 patients underwent resection for PDAC, 69 (20.9%) with aberrant hepatic arterial anatomy. The presence of AHAA does not significantly increase operative time (p= 0.110) or length of stay (p=0.518). The overall frequency of complications (49.3% vs 37.9%, p=0.088) was higher in the AHAA group, but not significantly so. Certain postoperative complications are more common in the AHAA group, namely superficial surgical site infection (18.8% vs. 8.8%, p=0.018) and pancreatic fistula (18.8% vs. 10.0%, p=0.042). However, deep SSI, need for blood transfusion, respiratory failure, DGE, bleed from GDA/pseudoaneurysm, biliary fistula, chyle leak, PV thrombus, fascial dehiscence, and reoperation are not statistically different between the two groups. There is a trend for reduced overall survival in the AHAA group that is not statistically significant (p=0.11). Conclusions: Aberrant hepatic arterial anatomy is encountered in greater than 20% of pancreatic surgery patients, and its presence may increase the rate of certain postoperative complications such as superficial surgical site infection and pancreatic fistula.
The origins and significance of O6-carboxymethylguanine as a mispairing lesion in DNA.
Authors: David E. Shuker, Srikanth Ponnada, Philip A. Burns, Yao-Zhong Xu, Sharon A. Moore
Journal: Cancer Research (2006)

5234  Intrroduction: O6-Carboxymethylguanine (O6-CMG) is a modified DNA base derived from nitrosation of glycine (Cupid et al, ChemRes Toxicol 2004, 17, 294-300). As O6-Methylguanine (O6-MeG) is inevitably formed concurrently we have inserted synthesized O6-CMG into defined sites of the p53 cDNA sequence using nucleic acid chemistry and used the modified seqeunces to explore the consequences of mispairing. Methods: O6-CMG was synthesised as a suitably pro\. tected 2’-deoxynucleotide and incorporated into 25- or 26-mers which were then inserted into defined sites on the coding and non-coding strands of the human p53 cDNA sequence iwhich was then ligated into a double-stranded circular plasmid. The p53 seqeunce was amplified using PCR. Single-nucleotide changes that occured in the adduct-containing codons were detected using ARMS-PCR. Unmodified- and O6-MeG-containing sequences were used as negative and positive controls. Results: PCR amplification and the ARMS-PCR assay did not introduce any detectable artefactual mutations in the negative control. O6-MeG resulted in the expected G to T mutations. However, O6-CMG gave not only G to T mutations but also G to A. Conclusions: The pattern of mutations induced by O6-CMG in this system were identical to those produced in a yeast-based functional assay which was in turn similar to the pattern of mutations in p53 from human GI tract cancers. O6-CMG produces a pattern of mutations which is quite distinct from the well-studied O6-MeG. These results underline the possible role of glycine nitrosation in the aetiology of human GI tract cancers. Current studies are aimed at establishing a precursor-product relationship between dietary glycine and O6-CMG in human DNA using stable isotope methodology. We gratefully acknowledge support from the World Cancer Research Fund
Eleven grand challenges in single-cell data science
Authors: David Lähnemann, Johannes Köster, Ewa Szczurek, Davis J. McCarthy, Stephanie C. Hicks, Mark D. Robinson, Catalina A. Vallejos, Kieran R. Campbell, Niko Beerenwinkel, Ahmed Mahfouz, Luca Pinello, Pavel Skums, Alexandros Stamatakis, Camille Stephan-Otto Attolini, Samuel Aparicio, Jasmijn Baaijens, Marleen Balvert, Buys de Barbanson, Antonio Cappuccio, Giacomo Corleone, Bas E. Dutilh, Maria Florescu, Victor Guryev, Rens Holmer, Katharina Jahn, Thamar Jessurun Lobo, Emma M. Keizer, Indu Khatri, Szymon M. Kielbasa, Jan O. Korbel, Alexey M. Kozlov, Tzu-Hao Kuo, Boudewijn P.F. Lelieveldt, Ion I. Mandoiu, John C. Marioni, Tobias Marschall, Felix Mölder, Amir Niknejad, Alicja Rączkowska, Marcel Reinders, Jeroen de Ridder, Antoine-Emmanuel Saliba, Antonios Somarakis, Oliver Stegle, Fabian J. Theis, Huan Yang, Alex Zelikovsky, Alice C. McHardy, Benjamin J. Raphael, Sohrab P. Shah, Alexander Schönhuth
Journal: Genome biology (2020)

Abstract The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands—or even millions—of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems. Here, we outline eleven challenges that will be central to bringing this emerging field of single-cell data science forward. For each challenge, we highlight motivating research questions, review prior work, and formulate open problems. This compendium is for established researchers, newcomers, and students alike, highlighting interesting and rewarding problems for the coming years.
Endoscopic submucosal dissection with double clip and rubber band traction for residual or locally recurrent colonic lesions after previous endoscopic mucosal resection
Authors: Julien Faller, Jérémie Jacques, Borathchakra Oung, Romain Legros, Jérôme Rivory, Fabien Subtil, Jean-Christophe Saurin, Philip Robinson, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2020)

Abstract Background Endoscopic submucosal dissection (ESD) of residual or locally recurrent (RLR) colonic lesions after previous endoscopic mucosal resection (EMR) is an attractive but challenging technique. The present study aimed to evaluate the effectiveness and safety of ESD with double clip and rubber band traction (DCT-ESD) of RLR colonic lesions. Methods We retrospectively analyzed all consecutive DCT-ESD procedures for RLR colonic lesions (rectum excluded) performed in two French centers. The frequency of en bloc and R0 resections, procedure speed, additional surgery, and complications were evaluated. R0 resection was also used to investigate the learning curve. Results Among the 53 resections, 49 (92.5 %) were performed en bloc and 42 (79.2 %) achieved R0. The median procedure speed was 21 mm2/min. There were four (7.5 %) intraoperative perforations and one delayed bleeding; these were successfully treated endoscopically. There was no salvage surgery for complications. The R0 rate increased from 16/26 (61.5 %) for the first 26 procedures to 26/27 (96.3 %, P = 0.002) for the last 27 procedures. Conclusions DCT-ESD appears to be a safe and effective treatment for RLR colonic lesions after EMR.
Concentration of the drug ustekinumab in the blood four weeks after injection, is linked to how well moderate‐to‐severe psoriasis responds to treatment
Authors: N. Van den Berghe, E. De Keyser, R. Soenen, L. Meuleman, S. Lanssens, A. Gils, J. Lambert
Journal: British Journal of Dermatology (2020)

Psoriasis is a chronic inflammatory skin disease causing red, itchy and scaly patches of skin. It affects about 2-3% of the Western population. In moderate-to-severe cases, patients are treated with drugs called biologicals, including ustekinumab. Although these drugs have been shown to improve patients’ symptoms, there are still individuals that do not respond to treatment, meaning they do not see any improvement, or lose response over time, meaning the improvement lessens. One reason for the loss of response is that the drug concentration in the blood of the patient is too low. Therefore, it might be interesting to measure drug concentrations to shed light on what is happening with the drug in the patient. However, measuring drug concentrations is only useful if the drug concentration is associated with what happens to the skin disease. This study, performed in Belgium, aimed to find out if the concentration of the drug ustekinumab was associated with clinical response (whether or not the symptoms improved). Therefore, ustekinumab concentrations were measured in the blood of 49 patients with moderate-to-severe psoriasis, four weeks after ustekinumab injection. The authors found that patients with higher ustekinumab concentrations had a better clinical response than patients with a lower concentration. Moreover, they identified the minimal ustekinumab blood concentration needed at week four to achieve the best response. With this information, the dermatologist can measure drug concentrations to identify patients who do not adequately respond to treatment because of insufficient drug concentrations. In that case, the patient's dose can be adapted to achieve a better response and consequently improve the quality of life. This summary relates to the study: Clinical response correlates with 4-week postinjection ustekinumab concentrations in patients with moderate-to-severe psoriasis
Is Hippocampal Replay a Mechanism for Anxiety and Depression?
Authors: Aaron S. Heller, Rosemary C. Bagot
Journal: JAMA Psychiatry (2020)

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