tbuckley/cabot-search huggingface dataset:
Differences in presentation and management patterns in patients with hepatocellular carcinoma (HCC): Data from HCC registry in Asia.
Authors: Pierce K. H. Chow, Lequn Li, Jiangtao Li, Fan Jia, Hee-Jee Wang, Kiyoshi Hasegawa, Jin-Mo Yang, Poh-Seng Tan, Shukui Qin, Kwang-Hyub Han, Brian Goh, Ho Seong Han, Junji Furuse, Xu Zhu, Joanna Zhi Jie Ling, Mihir Gandhi
Journal: Journal of Clinical Oncology (2019)

229 Background: HCC is the 6th most common cancer worldwide with &gt; 70% of cases in Asia. There is limited real-world data on the diagnosis, treatment modalities, outcomes and treatment costs in HCC. Methods: The HCC Registry in Asia (AHCC08) is a multi-country longitudinal cohort study of HCC patients diagnosed between 2013 and 2019. Target sample size is 2500 from 9 geographies: China, Singapore, South Korea, Japan, Taiwan, Australia, New Zealand, Hong Kong, and Thailand. We present initial data on diagnosis, etiology, stage at presentation, and treatment modalities of HCC from China [CN] (5 centers), Singapore [SG] (3 centers), South Korea [SK] (4 centers), and Japan [JP] (2 centers). Results: 657 patients (436 CN; 102 SG; 85 SK; 34 JP) were evaluated in August 2018. Patients from China were diagnosed at a younger age, while patients from Japan were diagnosed at an older age (mean age 51 years CN; 67 years SG; 58 years SK; 68 years JP). The highest proportion of regular alcohol drinkers were from Japan (16% CN; 21% SG; 24% SK; 50% JP) and occasional drinkers from China (20% CN; 17% SG; 12% SK; 15% JP). 77% had Hepatitis B across the 5 geographies, with the highest incidence in China (93%), followed by South Korea (68%). 27% were diagnosed using AASLD/APASL imaging criteria, with the highest utilization in Singapore (66% AASLD; 80% APASL) and South Korea (64% AASLD; 20% APASL). Later-stage patients (according to Barcelona Clinic Liver Cancer staging guidelines) were more predominant in Japan (Stage C: 28% CN, 16% SG, 8% SK, 41% JP; Stage D: 0.5% CN, 0% SG, 1% SK, 3% JP). Relatively few radiofrequency ablations were carried out as the first-line therapy across the 5 geographies (2% CN; 5% SG; 2% SK; 0% JP). In China, liver resection was preferred in first-line HCC treatment (65% CN vs 28% SG, SK, and JP aggregated), followed by loco-regional (27% CN vs 7% SG, SK, and JP aggregated) and systemic therapy (2% CN vs 10% SG, SK, and JP aggregated). Conclusions: There is considerable variation in presentation and management patterns between the 5 geographies. These data will benefit policymakers, companies and clinicians in improving policies and developing treatment strategies for HCC. (ClinicalTrials.gov: NCT03233360).
Nuclear Entry of CRTC1 as Druggable Target of Acquired Pigmentary Disorder
Authors: Cheong-Yong Yun, Seung Deok Hong, Young Hee Lee, Jiyeon Lee, Da-Eun Jung, Ga Hyun Kim, Song-Hee Kim, Jae-Kyung Jung, Ki Ho Kim, Heesoon Lee, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Journal: Theranostics (2019)

Rationale: SOX10 (SRY-related HMG-box 10) and MITF-M (microphthalmia-associated transcription factor M) restrict the expression of melanogenic genes, such as TYR (tyrosinase), in melanocytes.DACE (diacetylcaffeic acid cyclohexyl ester) inhibits melanin production in α-MSH (α-melanocyte stimulating hormone)-activated B16-F0 melanoma cells.In this study, we evaluated the antimelanogenic activity of DACE in vivo and elucidated the molecular basis of its action.Methods: We employed melanocyte cultures and hyperpigmented skin samples for pigmentation assays, and applied chromatin immunoprecipitation, immunoblotting, RT-PCR or siRNA-based knockdown for mechanistic analyses.Results: Topical treatment with DACE mitigated UV-B-induced hyperpigmentation in the skin with attenuated expression of MITF-M and TYR.DACE also inhibited melanin production in α-MSHor ET-1 (endothelin 1)-activated melanocyte cultures.As a mechanism, DACE blocked the nuclear import of CRTC1 (CREB-regulated co-activator 1) in melanocytes.DACE resultantly inhibited SOX10 induction, and suppressed the transcriptional abilities of CREB/CRTC1 heterodimer and SOX10 at MITF-M promoter, thereby ameliorating facultative melanogenesis.Furthermore, this study unveiled new issues in melanocyte biology that i) KPNA1 (Impα5) escorted CRTC1 as a cargo across the nuclear envelope, ii) SOX10 was inducible in the melanogenic process, and iii) CRTC1 could direct SOX10 induction at the transcription level. Conclusion:We propose the targeting of CRTC1 as a unique strategy in the treatment of acquired pigmentary disorders.
Abstract 19294: A Physical Activity Intervention Improves 400-Meter Walking Velocity as Compared to a Successful Aging Intervention in Patients with Peripheral Artery Disease: The LIFE Study Randomized Trial
Authors: Mary McDermott, Denise Bonds, Thomas Buford, Tim Church, John Dodson, Roger Fielding, Jack Guralnik, Steve Kritchevsky, Laura Lovato, Marco Pahor, Randall Stafford, Anne Newman
Journal: Circulation (2014)

Background: The LIFE Study was a multi-centered randomized trial that compared the ability of a structured physical activity (PA) intervention vs. a successful aging intervention (SA) to prevent mo...
Abstract 18238: Beneficial Effects of Omega-3 Polyunsaturated Fatty Acids in Myocardial Performance, Left Ventricle Strain, Fibrosis and Endothelial Function of Ischemic Heart Failure Patients
Authors: Evangelos Oikonomou, Georgia Vogiatzi, Dimitrios Karlis, Theodoros Zografos, Gerasimos Siasos, Christina Chrysohoou, Stella Brili, Georgios Lazaros, Alexios Antonopoulos, Georgios Georgiopoulos, Sotirios Tsalamandris, Konstantinos Mourouzis, Dimitrios Tousoulis
Journal: Circulation (2017)

Introduction: Polyunsaturated fatty acids (PUFAs) exert favorable effect in HF patients. However, the effects of omega-3 PUFAs on cardiac function and remodeling have not been adequately assessed. Hypothesis: Omega-3 PUFAs may affect endothelial function, myocardial fibrosis and left ventricular (LV) performance in patients with systolic HF. Methods: We enrolled 31 stable ischemic HF patients with reduced LVEF, separated in two arms (omega-3 PUFAs-2gr/day- or placebo for 8 weeks), in a cross-over double blind design. All subjects were evaluated at baseline (BS) and after completion of each treatment arm. Endothelial function was assessed using FMD of the brachial artery. LV function before and after treatment was assessed using LVEF, determined by the biplane modified Simpson method, and LV global longitudinal strain (LVGLS). Soluble ST2 levels were measured as a biomarker of myocardial fibrosis. Results: At BS there was no difference in the examined parameters between the 2 arms of the study. Compared to...
Abstract 18568: Leveraging Parent Participation in Real-World Weight Management Programs to Improve Children’s Health: Preliminary Data
Authors: MinKyoung Song, Christopher S Lee, Karen S Lyons, Kerri Winters-Stone
Journal: Circulation (2017)

Introduction: Research shows that parents’ participation in weight management interventions can help reduce obesity in their children. However, no studies have examined if those findings from highly controlled settings can be replicated in real-world settings. The current study uses an existing real-world resource - in the form of, a widely available commercial adult weight-management program - as a delivery vehicle for intervention. Results provide insight into translating clinical findings into innovative, low-cost, community-based interventions. Purpose: Examine the impact from overweight/obese parents’ participation in an 8-week Weight Watchers’ program on health behaviors and outcomes in their overweight/obese children. Methods: We used data from 20 parents and their children aged 6 to 12 years collected at baseline and 8-weeks follow-up visits. Physical activity and sedentary time data were collected using accelerometers during two, seven-day cycles. Dietary behavior data were collected using the Bl...
Image Gallery: Spoon‐shaped nails in an 11‐year‐old boy
Authors: A. Calleja‐Algarra, R. Aragón‐Miguel, J.J. Andrés‐Lencina, M. Prieto Barrios, C. Vico Alonso, V. Velasco‐Tamariz, S.I. Palencia Pérez
Journal: British Journal of Dermatology (2019)
Abstract 14701: Future Risk of Cardiovascular Disease in Adults with Prolonged Exposure to High Blood Pressure
Authors: Ann M Navar-Boggan, Eric D Peterson, Ralph B D’Agostino, Benjamin Neely, Allan D Sniderman, Michael J Pencina
Journal: Circulation (2014)

Introduction: High blood pressure (HBP) in early and mid-adulthood has been associated with increased future risk of cardiovascular disease (CVD). Hypothesis: In addition to prevalent disease, the ...
Strong Dose-response On Immunoglobulin Makers During a Phase II Allergen Immunotherapy Study With Subcutaneously Administered Tyrosine Adsorbed Modified Grass Allergen + MPL
Authors: Sabine Lassmann, Denise Lee, Stefan Zielen, Werner Aberer, Anette Wade, Karolin Kluehr, Jennifer Raab, Rachel Ballard, Chris Jones, Kulasari Gunawardena, Matthias Kramer, Murray A. Skinner
Journal: Journal of Allergy and Clinical Immunology (2019)
The influence of renal function on gemcitabine-based chemotherapy for advanced biliary tract cancer: An exploratory subgroup analysis of JCOG1113.
Authors: Makoto Ueno, Chigusa Morizane, Takuji Okusaka, Gakuto Ogawa, Yuya Sato, Masafumi Ikeda, Masato Ozaka, Kazuya Sugimori, Akira Fukutomi, Hiroki Hara, Nobumasa Mizuno, Hiroaki Yanagimoto, Keiji Sano, Kazutoshi Tobimatsu, Kei Yane, Shoji Nakamori, Naohiro Sata, Tomohiro Nishina, Hiroshi Ishii, Junji Furuse
Journal: Journal of Clinical Oncology (2019)

368 Background: JCOG1113 is a randomized phase III trial to evaluate gemcitabine (GEM) plus S-1 (GS) versus GEM plus cisplatin (GC) regarding overall survival (OS) for advanced biliary tract cancer (BTC) (UMIN000001685) and the non-inferiority of GS was demonstrated. It is necessary to consider renal function using cisplatin or S-1 because cisplatin has renal toxicity, and the toxicity of S-1 is affected by renal function. Therefore, we evaluated the influence of renal function on the efficacy and safety of GC and GS in JCOG1113. Methods: All enrolled patients (pts) in JCOG1113 (n = 354) were analyzed. Eligibility criteria included chemotherapy-naïve pts with recurrent or unresectable biliary tract adenocarcinoma, ECOG-PS of 0–1, CCr &gt; 50 ml/min, and adequate organ function. Renal function was classified into two groups by creatinine clearance (CCr) as calculated by the Cockcroft-Gault formula; high CCr (CCr ≥ 80 ml/min) or low CCr (80 &gt; CCr ≥ 50 ml/min). The impact of renal function on OS and progression-free survival (PFS) were compared using the Cox regression model. The adverse events (AEs) were compared using Fisher’s exact test. Results: Eighty-eight pts on GC and 88 pts on GS were included in the high CCr group, and 87 pts on GC and 91 pts on GS were included in the low CCr group. There were no differences between the groups regarding, sex, PS, primary site, biliary drainage, operation, or recurrence, except for age. The hazard ratio (HR) of GS to GC for OS was 1.12 (95% CI 0.81–1.56) in the high CCr group and 0.80 (95% CI 0.58–1.11) in the low CCr group. The HR of GS to GC for PFS was 1.06 (95% CI 0.78–1.44) in the high CCr group and 0.69 (95% CI 0.50–0.94) in the low CCr group. Grade 3-4 AEs of white blood cell count decreased (35.3%/23.6%), anemia (29.4%/7.9%) and platelet count decreased (18.8%/10.1%) were more common in GC than GS in the low CCr group. In contrast, the incidence of all grade 3-4 non-hematological AEs was higher (36.0%/11.8%) in GS than GC in the low CCr group ( p = 0.0002). Conclusions: GS was better in terms of OS, PFS, and hematological toxicities than GC in the low CCr group. GS might be recommended for the population with lower renal function in the treatment for advanced BTC.
Factors associated with biopsy diagnosis of hepatocellular carcinoma.
Authors: Young soo Rho, Jared David Acoba
Journal: Journal of Clinical Oncology (2019)

235 Background: Hepatocellular carcinoma (HCC) is one of the few cancers that can be diagnosed based on imaging findings. Although not always mandatory for diagnosis, biopsy (Bx) can confirm HCC and its histologic subtype. We have demonstrated that Bx is associated with worse survival compared to imaging diagnosis in a multivariate analysis. In turn, factors associated with undergoing a Bx diagnosis were examined. Methods: We obtained demographic, diagnostic, and treatment data of 171,013 patients diagnosed with HCC between 2004–2015 from the National Cancer Database. Binary logistic regression examined factors associated with Bx. Variables analyzed included race, sex, age, comorbidity, facility type, insurance, tumor size, presence of metastatic disease, alpha fetoprotein, total bilirubin, year of diagnosis and administration of therapy. Analysis was performed using SPSS v25. Results: We included 160,517 patients for the final analysis. The median age was 62 (18–90), 73.9% were male and 74.1% were white. 11.5% of tumors were 2 cm or smaller and 13.7% of HCC were metastatic. 78,485 (47.7%) underwent Bx. In a multivariate model, black patients (OR 1.093; 95% CI: 1.061-1.126), older patients (OR 1.579; 95% CI 1.537–1.622), larger tumor size (OR 3.208; 95% CI: 3.085–3.335), private (OR 1.129; 95% CI 1.094-1.164) or Medicare insurance (OR 1.056; 95% CI 1.021–1.093), and metastasis at time of diagnosis (OR 1.318; 95% CI 1.275–1.361) were associated with Bx diagnosis. Factors associated with an imaging diagnosis were female (OR 0.964; 95% CI 0.941–0.987), Asian/Pacific Islanders (OR 0.686; 95% CI 0.657–0.717), more comorbidities (OR 0.578; 95% CI 0.559–0.597), treatment at an academic center (OR 0.447; 95% CI 0.436–0.458), hyperbilirubinemia (OR 0.807; 95% CI 0.784-0.831) or elevated AFP (OR 0.571; 95% CI 0.549-0.594). Over the examined study period 2004-2015, imaging diagnosis was increasingly used. Conclusions: Although imaging alone can be adequate to diagnose many cases of HCC, nearly half of the cohort underwent a Bx. Even though diagnosis by imaging was more frequently used in recent years, there were still racial and institutional differences in pattern of care.
Silica cloaking of adenovirus enhances gene delivery while reducing immunogenicity
Authors: Ajay A. Sapre, Gen Yong, Ya-san Yeh, Laura E. Ruff, Justin S. Plaut, Zeynep Sayar, Anupriya Agarwal, Jacqueline Martinez, Theresa N. Nguyen, Yu-Tsueng Liu, Bradley T. Messmer, Sadik C. Esener, Jared M. Fischer
Journal: Journal of Controlled Release (2019)
Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate‐to‐severe atopic dermatitis
Authors: G. Yosipovitch, M. Reaney, V. Mastey, L. Eckert, A. Abbé, L. Nelson, M. Clark, N. Williams, Z. Chen, M. Ardeleanu, B. Akinlade, N.M.H. Graham, G. Pirozzi, H. Staudinger, S. Plaum, A. Radin, A. Gadkari
Journal: British Journal of Dermatology (2019)

Moderate‐to‐severe atopic dermatitis (AD) is a chronic disease characterized by intense, persistent and debilitating itch, resulting in sleep deprivation, signs of anxiety and depression, impaired quality of life and reduced productivity. The Peak Pruritus Numerical Rating Scale (NRS) was developed and validated as a single‐item, patient‐reported outcome (PRO) of itch severity. To describe the content validity and psychometric assessment (test–retest reliability, construct validity, known‐groups validity, sensitivity to change) of the Peak Pruritus NRS, and to derive empirically a responder definition to identify adults with a meaningful change in itch. Content validity was assessed through in‐depth patient interviews. Psychometric assessments used data from phase IIb and phase III dupilumab clinical trials and included test–retest reliability, construct validity, known‐groups validity and sensitivity to change in patients with moderate‐to‐severe AD. Interview participants indicated that the Peak Pruritus NRS was a relevant, clear and comprehensive assessment of itch severity. Peak Pruritus NRS scores showed large, positive correlations with existing PRO measures of itch, and weak or moderate correlations with clinician‐reported measures assessing objective signs of AD. Peak Pruritus NRS score improvements were highly correlated with improvements in other itch PROs, and moderately correlated with improvements in clinician‐reported measures assessing objective signs of AD. The most appropriate threshold for defining a clinically relevant, within‐person response was ≥ 2–4‐point change in the Peak Pruritus NRS. The Peak Pruritus NRS is a well‐defined, reliable, sensitive and valid scale for evaluating worst itch intensity in adults with moderate‐to‐severe AD.
Role of KDM2B and Non-Canonical PRC1.1 As a Tumor Suppressor in T-ALL
Authors: Yusuke Isshiki, Yaeko Nakajima-Takagi, Motohiko Oshima, Kazumasa Aoyama, Atsunori Saraya, Emiko Sakaida, Chiaki Nakaseko, Koutaro Yokote, Haruhiko Koseki, Atsushi Iwama
Journal: Blood (2018)
C3 glomerulopathy — understanding a rare complement-driven renal disease
Authors: Richard J. H. Smith, Gerald B. Appel, Anna M. Blom, H. Terence Cook, Vivette D D’Agati, Fadi Fakhouri, Véronique Fremeaux-Bacchi, Mihály Józsi, David Kavanagh, John D. Lambris, Marina Noris, Matthew C. Pickering, Giuseppe Remuzzi, Santiago Rodriguez de Córdoba, Sanjeev Sethi, Johan Van der Vlag, Peter F. Zipfel, Carla M. Nester
Journal: Nature Reviews Nephrology (2019)
Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus
Authors: Nan Xu, Jun Li, Yujie Gao, Nuoya Zhou, Qiuying Ma, Min Wu, Yamin Zhang, Xiaoyan Sun, Jun Xie, Guanxin Shen, Ming Yang, Qiming Tu, Xiaowei Xu, Jintao Zhu, Juan Tao
Journal: Biomaterials (2019)
Abstract 1561: Is Aprotinin Really Safe In Thoracic Aortic Surgery? Analysis Of Outcome
Authors: Carlo Banfi, Philippe De Lentdecker, Sylvie Schlumberger, Catherine Klersy, Jean Bachet, Claude Dubois, Bertrand Goudot, Chakir Missaoui, Nabil Hermi, Daniel Guilmet, Gilles Dreyfus, Marc Fischler, Matthieu Debauchez
Journal: Circulation (2007)

Introduction : We aimed at evaluating aprotinin efficacy and renal, cardiac and neurologic safety after thoracic aortic surgery in a single Center. Methods : This retrospective longitudinal study analyses 742 patients (26% female), aged 57 years (SD 15), operated between January 1993 and December 2006. Efficacy and safety were the primary endpoints. Efficacy was defined as perioperative bleeding ≤1200 ml/first 24 h and/or no reintervention for bleeding. Renal adverse events included increased values of creatinine and BUN and/or the initiation of dialysis. Cardiac adverse events included perioperative myocardial infarction, acute LOS, and progression to heart failure. Neurologic adverse events included stroke, transient ischemia and/or clinical neurologic deficits. Results : Aprotinin was given to 525 pts. only. Table 1 shows the outcome according to aprotinin administration. Patients receiving aprotinin had higher bleeding, and renal, neurologic adverse events rate (univariate analysis). Cardiac adverse events and perioperative mortality are similar in both groups. However no evidence of effect was left when accounting for possible confounders (urgent surgery, redo procedure, dissection, antiplatelet medication, NYHA class, deep hypothermia, CPB time). Conclusions : The influence of aprotinin shown at univariable analyis, disappeared when controlling for a series of potential confounders in a multivariable analysis. A randomized control clinical trial would have better answered the question as whether aprotinin has a beneficial therapeutic effect together with a high safety. However, this sample size allowed controlling the effect of the drug for a large series of potential confounders in a multivariate analysis. Thus we were able to elicit a lack of association of aprotinin (ORs close to 1 and narrow 95% CIs) with both efficacy and adverse events. Table 1
Activity Correlations between Direction-Selective Retinal Ganglion Cells Synergistically Enhance Motion Decoding from Complex Visual Scenes
Authors: Norma Krystyna Kühn, Tim Gollisch
Journal: Neuron (2019)

Neurons in sensory systems are often tuned to particular stimulus features. During complex naturalistic stimulation, however, multiple features may simultaneously affect neuronal responses, which complicates the readout of individual features. To investigate feature representation under complex stimulation, we studied how direction-selective ganglion cells in salamander retina respond to texture motion where direction, velocity, and spatial pattern inside the receptive field continuously change. We found that the cells preserve their direction preference under this stimulation, yet their direction encoding becomes ambiguous due to simultaneous activation by luminance changes. The ambiguities can be resolved by considering populations of direction-selective cells with different preferred directions. This gives rise to synergistic motion decoding, yielding more information from the population than the summed information from single-cell responses. Strong positive response correlations between cells with different preferred directions amplify this synergy. Our results show how correlated population activity can enhance feature extraction in complex visual scenes.
Occurrence of irreversible sinusoidal obstruction syndrome during adjuvant chemotherapy for colorectal cancer using oxaliplatin: A multi-center study.
Authors: Takeshi Yamada, Keiji Koda, Hiroshi Yoshida, Kohji Tanakaya, Keiichiro Ishibashi, Kazuhiko Yoshimatsu, Chihiro Kosugi, Soichi Tanaka, Keisuke Hara, Masahiro Tsubaki, Hideo Nakajima, Masatoshi Oya, Hideyuki Ishida
Journal: Journal of Clinical Oncology (2019)

546 Background: Oxaliplatin reduces the recurrence rate after curative surgery for stage III colorectal cancer. However, it can cause hepatic sinusoidal obstruction syndrome (SOS), an adverse effect that creates morbidity after liver resection for recurrence. SOS has conventionally been diagnosed by liver biopsy, which is invasive. We have reported that a 10% increase in splenic volume (SV) indicates SOS (J Surg Oncol 2017). In this multi-center study, we measured SV to evaluate SOS caused by adjuvant chemotherapy. Methods: This multi-center study included the participants of the FACOS study, which included patients with Stage III colon cancer. Participants received 12 cycles of mFOLFOX6 or eight cycles of XELOX as adjuvant chemotherapy. We used multi-detector raw CT to measure SV three times; before surgery, on completion of adjuvant chemotherapy, and 1-year after completing adjuvant chemotherapy. CT images were taken in 5-mm slices. SV was calculated by using a volume calculator SYNAPSE VINCENT v3.0 (Fujifilm, Japan). Results: The FACOS study included 130 patients, 16.9% of whom discontinued treatment. The mean relative dose intensity (RDI) of oxaliplatin was 80.3%. Grade 3 neutropenia, thrombocytopenia, and neuropathy were observed in 28.5%, 6.2%, and 4.6% of patients, respectively. The 3 year DFS was 82.2%. We analyzed data of 75 patients (57.7%) for whom the three CT studies were available. SV on completing chemotherapy (median 181 cm 3 ) and SV 1-year after completing chemotherapy (141 cm 3 ) were significantly higher than that before surgery (128 cm 3 ) (P &lt; 0.001). SV increased by more than 10% after chemotherapy in 72% and was still increased 1 year after chemotherapy in 51% of patients. Conclusions: In our previous single center study, SV had increased in 84% on completing chemotherapy and was still increased in 47% 1 year after completing chemotherapy. Adjuvant chemotherapy without oxaliplatin induced SV increases in only 20% of patients on completing chemotherapy. Thus, these results are reproducible and show the potential of oxaliplatin to induce SOS. Oxaliplatin frequently induces SOS and this SOS persists for over 1 year in half of affected patients. Clinical trial information: UMIN000005427.