tbuckley/cabot-search huggingface dataset:
Exosomes Derived from Cancer Associated Fibroblasts Elicit Survival and Drug Resistance of Primary Lymphoma Cells
Authors: Shunsuke Kunou, Kazuyuki Shimada, Tomoya Hikita, Tomohiro Aoki, Akihiko Sakamoto, Fumihiko Hayakawa, Chitose Oneyama, Hitoshi Kiyoi
Journal: Blood (2018)
Clinical Course of Primary Immune Thrombocytopenia with Positive Antiphospholipid Antibodies
Authors: Ana Clara Cruz, Sabrina Saraiva, Marina Pereira Colella, Gabriela G Yamaguti Hayakawa, Erich Vinicius De Paula, Joyce Maria Annichino Bizzacchi, Fernanda Andrade Orsi
Journal: Blood (2018)
Analysis of survival and objective response (OR) in patients with hepatocellular carcinoma in a phase III study of lenvatinib (REFLECT).
Authors: Masatoshi Kudo, Richard S. Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Ann-Lii Cheng, Fabio Piscaglia, Kazuomi Ueshima, Hiroshi Aikata, Arndt Vogel, Carlos Lopez, Marc Pracht, Zhiqiang Meng, Bruno Daniele, Joong-Won Park, Daniel H. Palmer, Corina E. Dutcus, Toshiyuki Tamai, Kenichi Saito, Riccardo Lencioni
Journal: Journal of Clinical Oncology (2019)

186 Background: In REFLECT, Lenvatinib (LEN) demonstrated treatment effect on overall survival (OS) by statistical confirmation of noninferiority to sorafenib (SOR). OR rates for LEN versus SOR were: 24% versus 9% by investigator review and 41% versus 12% by independent review (Kudo et al 2018). Since the relationship between OR and OS in phase III HCC studies is unclear, we explored the relationship between OR and OS in REFLECT. Methods: OR assessed by investigators per mRECIST were used to analyze the association between OR and OS of pts treated with LEN or SOR. The median OS of responders (CR or PR) was compared to that of nonresponders (SD, PD, or UNK/NE) irrespective of treatment. Landmark analyses were performed by OR status at several fixed time points as sensitivity analyses, and the effect on OS was evaluated by Cox regression with OR as a time-dependent covariate, with other prognostic factors. Results: Median OS was 22.4 months for responders and 11.4 months for nonresponders. Hazard ratios (HR) of landmark analyses at 2, 4, and 6 months were 0.75 (95% CI, 0.57–0.98), 0.72 (95% CI, 0.56–0.92), and 0.73 (95% CI, 0.57–0.93). Independent predictors of OS based on unstratified Cox regression are in the table. Conclusions: In REFLECT, OR was an independent predictor of OS in pts with HCC regardless of treatment. The results indicate this correlation is worth further investigation. Clinical trial information: NCT01761266. [Table: see text]
A Large‐Scale Multicenter Study Validates Aldo‐Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma
Authors: Xu Ye, Cunyan Li, Xuyu Zu, Minglin Lin, Qiang Liu, Jianghua Liu, Guoguo Xu, Zhiyong Chen, Yongliang Xu, Long Liu, Diteng Luo, Zhe Cao, Guiyuan Shi, Zirui Feng, Hongyu Deng, Qianjin Liao, Chuan Cai, Duan‐Fang Liao, Jing Wang, Junfei Jin, Deliang Cao
Journal: Hepatology (2019)

Aldo‐keto reductase family 1 member B10 (AKR1B10) is a secretory protein overexpressed in hepatocellular carcinoma (HCC). We aimed to evaluate AKR1B10 as a serum marker for detection of HCC. Herein, we conducted a cohort study that consecutively enrolled 1,244 participants from three independent hospitals, including HCC, healthy controls (HCs), benign liver tumors (BLTs), chronic hepatitis B (CHB), and liver cirrhosis (LC). Serum AKR1B10 was tested by time‐resolved fluorescent assays. Data were plotted for receiver operating characteristic (ROC) curve analyses. Alpha‐fetoprotein (AFP) was analyzed for comparison. An exploratory discovery cohort demonstrated that serum AKR1B10 increased in patients with HCC (1,567.3 ± 292.6 pg/mL; n = 69) compared with HCs (85.7 ± 10.9 pg/mL; n = 66; P &lt; 0.0001). A training cohort of 519 participants yielded an optimal diagnostic cutoff of serum AKR1B10 at 267.9 pg/mL. When ROC curve was plotted for HCC versus all controls (HC + BLT + CHB + LC), serum AKR1B10 had diagnostic parameters of the area under the curve (AUC) 0.896, sensitivity 72.7%, and specificity 95.7%, which were better than AFP with AUC 0.816, sensitivity 65.1%, and specificity 88.9%. Impressively, AKR1B10 showed promising diagnostic potential in early‐stage HCC and AFP‐negative HCC. Combination of AKR1B10 with AFP increased diagnostic accuracy for HCC compared with AKR1B10 or AFP alone. A validation cohort of 522 participants confirmed these findings. An independent cohort of 68 patients with HCC who were followed up showed that serum AKR1B10 dramatically decreased 1 day after operation and was nearly back to normal 3 days after operation. Conclusion : AKR1B10 is a potent serum marker for detection of HCC and early‐stage HCC, with better diagnostic performance than AFP.
Neonatal sepsis in South Asia: huge burden and spiralling antimicrobial resistance
Authors: Suman Chaurasia, Sindhu Sivanandan, Ramesh Agarwal, Sally Ellis, Mike Sharland, M Jeeva Sankar
Journal: BMJ (2019)

<b>M Jeeva Sankar and colleagues</b> call for urgent action to improve quality of care at birth and implement antimicrobial stewardship in health facilities in South Asia to reduce neonatal deaths from sepsis
Prevalence of <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> gene mutations in metastatic colorectal cancer patients: A systematic literature review and meta-analysis.
Authors: Kimberly Lowe, Lauren C Bylsma, Elizabeth D Levin-Sparenberg, Laura Sangaré, Jon Fryzek, Dominik D Alexander
Journal: Journal of Clinical Oncology (2019)

523 Background: A systematic literature review and meta-analysis was conducted to summarize the prevalence of KRAS, NRAS, and BRAF mutations in mCRC patients. These mutations have substantial implications for treatment decisions among mCRC patients. Methods: Multiple databases were searched to identify observational studies and clinical trials (standard of care arms only) that reported mutation status among mCRC patients. Random effects meta-analysis models were used to estimate summary prevalence estimates for each of the mutations. Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity in mutation prevalence. Results: The meta-analyses included 275 studies comprising over 77,000 mCRC patients. The summary prevalence estimate was 35.9% for KRAS mutations, 7.1% for BRAF mutations, and 4.1% for NRAS mutations. Female patients had significantly more KRAS and BRAF mutations than males ( KRAS: 42.2% vs. 37.3%, p = 0.011; BRAF: 11.0% vs. 7.9%, p = 0.018), and significant variation by study location was observed for both KRAS (p = 0.025) and BRAF (p = 0.002) mutation prevalence. Conclusions: The prevalence of KRAS, BRAF, or NRAS mutations in mCRC patients varies significantly by gender and study location. compared to patients with wild-type tumors. The results of these analyses are informative for clinicians, patients, and researchers.
Epidemiological trends of HPV-related anal cancers amongst males globally: A systematic literature review.
Authors: Anuj Walia, Xuan Wang, Martha Nicholson, Lucy Sun, Jessica R. Wong, Jennifer Eriksson, Smita Kothari, Edith Morais
Journal: Journal of Clinical Oncology (2019)

492 Background: Anal cancer is associated with human papillomavirus (HPV), a sexually transmitted infection, which can be prevented by the HPV vaccination. Few countries do recommend vaccination for the male population, but all males are at risk of contracting HPV. This study aimed to identify the latest evidence on the incidence of anal cancer and pre-cancer related to HPV in males globally and to analyze the epidemiological trends. Methods: A systematic literature search was performed using Medline and EMBASE. Studies containing original anal cancer incidence data in males published between January 1, 2008 and March 23, 2018 in English were included. Results: The global incidence of anal cancers and pre-cancers among the general male population was identified in 25 studies with observations ranging between 1968 and 2014. Incidence over time was reported in Australia and Europe. In an Australian national study, anal cancer incidence increased from 0.77 to 1.3 per 100,000 persons from 1982-2005, and in the UK from 0.79 to 1.06 per 100,000 persons from 1962-2002. In Denmark, the anal cancer range increased from 0.20-0.41 to 0.69-1.3 per 100,000 person-years (PYs) from pre-2000 to post-2000, and in France from 0.2 to 0.5 per 100,000 PYs from 1982-2012. In two national US studies, the mean incidence of pre-cancers was 1.5 in the period 1997-2009, and 0.41 from 1978-2007 per 100,000 PYs. The burden of anal cancers and pre-cancers increased the most among high-risk males reported in US studies. For HIV-positive males, mean incidence of cancer increased from 10.5 during 1980-1989 to 42.3 in 1996-2004 per 100,000 PYs, and for HIV-positive MSM, incidence increased from 47 to 270 per 100,000 PYs between 1984 and 2013. The mean pre-cancer incidence among HIV-positive males increased from 1.7 during 1980-1989 to 29.5 in 1996-2004 per 100,000 PYs. Conclusions: This systematic literature review demonstrates the increase in anal cancer and pre-cancer incidences over time in men, especially in high-risk male populations. The burden of anal cancers and pre-cancers increase over time in all male populations highlights the unmet medical need and the importance of preventative interventions such as HPV gender-neutral vaccinations.
Effectiveness of laparoscopic surgery in patients with large gastric GIST (diameter &gt; 5cm).
Authors: Fei Li, Chongchong Gao
Journal: Journal of Clinical Oncology (2019)

35 Background: Recently, the application of laparoscopic or DaVinci surgery in relatively small gastrointestinal stromal tumors (GIST) has been increasingly recognized. However, the use in large stromal tumors, especially with a diameter greater than 5 cm, remains controversial for fear of tumor rupture. The aim of our study is to observe the effectiveness of laparoscopic approach in treatment of large gastric GIST. Methods: Patients who were diagnosed with gastric GIST (diameter &gt; 5cm) at Xuanwu Hospital, China and underwent laparoscopic surgery from May 2011 to May 2018 were assessed. We set intraoperative tumor rupture as primary outcome. Secondly outcomes were conversion rate, operating time, estimated blood loss, length of postoperative hospital stay and recurrence rate at the end of the follow-up. Results: Fourty patients were included in our study with tumor size (7.54 ty-tw) cm (range, 5.0~13.8 cm). There was no intraoperative tumor rupture occurred. The median duration of operation was (76.3±29.9) minutes with estimated blood loss (28.7±15.2) mL. The median time for length of postoperative hospital stay was (5.8±4.1) days. The follow-up period for all the patients was 23.1 months (range, 2.4~51months). No local or distant recurrence was observed. Conclusions: Laparoscopic resection for large gastric GIST is feasible and effective. Laparoscopic surgery can substitute for open surgery as standard approach for gastric stromal tumors.
Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response
Authors: J.E. Stein, A. Soni, L. Danilova, T.R. Cottrell, T.F. Gajewski, F.S. Hodi, S. Bhatia, W.J. Urba, W.H. Sharfman, M. Wind-Rotolo, R. Edwards, E.J. Lipson, J.M. Taube
Journal: Annals of Oncology (2019)

With increasing anti-PD-1 therapy use in patients with melanoma and other tumor types, there is interest in developing early on-treatment biomarkers that correlate with long-term patient outcome. An understanding of the pathologic features of immune-mediated tumor regression is key in this endeavor.
Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency
Authors: Laura-Jayne Gardiner, Luzie U. Wingen, Paul Bailey, Ryan Joynson, Thomas Brabbs, Jonathan Wright, James D. Higgins, Neil Hall, Simon Griffiths, Bernardo J. Clavijo, Anthony Hall
Journal: Genome biology (2019)

Sequence exchange between homologous chromosomes through crossing over and gene conversion is highly conserved among eukaryotes, contributing to genome stability and genetic diversity. A lack of recombination limits breeding efforts in crops; therefore, increasing recombination rates can reduce linkage drag and generate new genetic combinations.We use computational analysis of 13 recombinant inbred mapping populations to assess crossover and gene conversion frequency in the hexaploid genome of wheat (Triticum aestivum). We observe that high-frequency crossover sites are shared between populations and that closely related parents lead to populations with more similar crossover patterns. We demonstrate that gene conversion is more prevalent and covers more of the genome in wheat than in other plants, making it a critical process in the generation of new haplotypes, particularly in centromeric regions where crossovers are rare. We identify quantitative trait loci for altered gene conversion and crossover frequency and confirm functionality for a novel RecQ helicase gene that belongs to an ancient clade that is missing in some plant lineages including Arabidopsis.This is the first gene to be demonstrated to be involved in gene conversion in wheat. Harnessing the RecQ helicase has the potential to break linkage drag utilizing widespread gene conversions.
Triple Intrathecal Therapy (Methotrexate/Hydrocortisone/Cytarabine) Does Not Improve Disease-Free Survival Versus Intrathecal Methotrexate Alone in Children with High Risk B-Lymphoblastic Leukemia: Results of Children's Oncology Group Study AALL1131
Authors: Wanda L. Salzer, Michael J. Burke, Meenakshi Devidas, Lia Gore, Joanne M. Hilden, Eric Larsen, Karen R. Rabin, Patrick A. Zweidler-McKay, Michael J. Borowitz, Brent Wood, Nyla A. Heerema, Andrew J. Carroll, Naomi Winick, William L. Carroll, Elizabeth A. Raetz, Mignon L. Loh, Stephen P. Hunger
Journal: Blood (2018)
Prevalence, Underlying Causes, and Preventability of Sepsis-Associated Mortality in US Acute Care Hospitals
Authors: Chanu Rhee, Travis M. Jones, Yasir Hamad, Anupam Pande, Jack Varon, Cara O’Brien, Deverick J. Anderson, David K. Warren, Raymund B. Dantes, Lauren Epstein, Michael Klompas
Journal: JAMA Network Open (2019)

Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown.To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals.Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, 2017, to March 31, 2018.Clinicians reviewed cases for sepsis during hospitalization using Sepsis-3 criteria, hospice-qualifying criteria on admission, immediate and underlying causes of death, and suboptimal sepsis-related care such as inappropriate or delayed antibiotics, inadequate source control, or other medical errors. The preventability of each sepsis-associated death was rated on a 6-point Likert scale.The study cohort included 568 patients (289 [50.9%] men; mean [SD] age, 70.5 [16.1] years) who died in the hospital or were discharged to hospice. Sepsis was present in 300 hospitalizations (52.8%; 95% CI, 48.6%-57.0%) and was the immediate cause of death in 198 cases (34.9%; 95% CI, 30.9%-38.9%). The next most common immediate causes of death were progressive cancer (92 [16.2%]) and heart failure (39 [6.9%]). The most common underlying causes of death in patients with sepsis were solid cancer (63 of 300 [21.0%]), chronic heart disease (46 of 300 [15.3%]), hematologic cancer (31 of 300 [10.3%]), dementia (29 of 300 [9.7%]), and chronic lung disease (27 of 300 [9.0%]). Hospice-qualifying conditions were present on admission in 121 of 300 sepsis-associated deaths (40.3%; 95% CI 34.7%-46.1%), most commonly end-stage cancer. Suboptimal care, most commonly delays in antibiotics, was identified in 68 of 300 sepsis-associated deaths (22.7%). However, only 11 sepsis-associated deaths (3.7%) were judged definitely or moderately likely preventable; another 25 sepsis-associated deaths (8.3%) were considered possibly preventable.In this cohort from 6 US hospitals, sepsis was the most common immediate cause of death. However, most underlying causes of death were related to severe chronic comorbidities and most sepsis-associated deaths were unlikely to be preventable through better hospital-based care. Further innovations in the prevention and care of underlying conditions may be necessary before a major reduction in sepsis-associated deaths can be achieved.
The Erythro-Myeloblastic Island (EMBI): A Hematopoietic Niche Balancing Erythropoiesis and Myelopoiesis
Authors: Katie Giger Seu, Laurel Romano, Julien Papoin, Edward David Muench, Diamantis Konstantinidis, André Olsson, Kashish Chetal, Joel Anne Chasis, Mohandas Narla, Nathan Salomonis, H Leighton Grimes, Lionel Blanc, Theodosia A. Kalfa
Journal: Blood (2018)
On the road again: Travel patterns and outcomes in rectal cancer.
Authors: Mary Kledzik, Anthony Joseph Scholer, Adam Khader, Juan Santamaria-Barria, Trevan D Fischer, Melanie Goldfarb
Journal: Journal of Clinical Oncology (2019)

530 Background: Associations between high volume centers and outcomes have many advocating for centralization of cancer care, which can lead to increased travel, patient burden, and cost. There is, however, some conflicting data regarding outcomes for patients with more advanced disease. This study aims to explore factors associated with travel and the impact on survival for patients receiving surgery for rectal adenocarcinoma. Methods: All patients &gt;18 years of age with rectal adenocarcinoma that had a surgical resection were identified using the National Cancer Database from 2004-2014. Univariate and multivariate (MV) regression analyses determined factors associated with increased travel distance (&lt;50 miles, 50-100 miles, &gt;100 miles) as well as the impact of travel on overall survival (OS). Results: Of 83,933 patients, those that traveled the furthest were more commonly younger, white non-Hispanic, insured, and with less comorbidities (all p&lt;0.05 on MV analysis). Cancer stage, surgical approach, and type of surgery were not associated with travel distance (p=NS). Increased travel distance improved 5-year OS for stage IV disease (10%, p=0.002), and trended toward significance for stage II (4.0%, p=0.06) and stage 1 (4.3%, p=0.09) disease. After controlling for other factors, travel distance did not impact OS for stage II/III disease, but stage I and IV patients traveling 50-100 miles had an increased risk of death (stage I HR 1.16, CI 1.04-1.30; stage IV HR 1.19, CI 1.07-1.32). This was similar in the entire cohort where traveling 50-100 miles had an increased risk of death (HR 1.09; CI 1.03-1.14). Patients treated at non-low volume centers did have improved outcomes across all stages (p&lt;0.01). Patients treated in academic hospitals had improved outcomes in stages I and IV (p=0.02). Conclusions: Younger, white, non-Hispanic patients are most likely to travel longer distances for rectal cancer treatment, regardless of stage. Increased hospital volume improves OS while travel and use of academic centers may impact patients with stage I/IV disease. Educating patients and providers regarding the influence of travel and hospital volume could help reallocate some resources, decrease financial toxicity, and ease the travel burden for patients.
Mediterranean Diet and the Association Between Air Pollution and Cardiovascular Disease Mortality Risk
Authors: Chris C. Lim, Richard B. Hayes, Jiyoung Ahn, Yongzhao Shao, Debra T. Silverman, Rena R. Jones, George D. Thurston
Journal: Circulation (2019)

Background: Recent experimental evidence suggests that nutritional supplementation can blunt adverse cardiopulmonary effects induced by acute air pollution exposure. However, whether usual individual dietary patterns can modify the association between long-term air pollution exposure and health outcomes has not been previously investigated. We assessed, in a large cohort with detailed diet information at the individual level, whether a Mediterranean diet modifies the association between long-term exposure to ambient air pollution and cardiovascular disease mortality risk. Methods: The National Institutes of Health–American Association for Retired Persons Diet and Health Study, a prospective cohort (N=548 845) across 6 states and 2 cities in the United States and with a follow-up period of 17 years (1995–2011), was linked to estimates of annual average exposures to fine particulate matter and nitrogen dioxide at the residential census-tract level. The alternative Mediterranean Diet Index, which uses a 9-point scale to assess conformity with a Mediterranean-style diet, was constructed for each participant from information in cohort baseline dietary questionnaires. We evaluated mortality risks for cardiovascular disease, ischemic heart disease, cerebrovascular disease, or cardiac arrest associated with long-term air pollution exposure. Effect modification of the associations between exposure and the mortality outcomes by alternative Mediterranean Diet Index was examined via interaction terms. Results: For fine particulate matter, we observed elevated and significant associations with cardiovascular disease (hazard ratio [HR] per 10 μg/m 3 , 1.13; 95% CI, 1.08–1.18), ischemic heart disease (HR, 1.16; 95% CI, 1.10–1.23), and cerebrovascular disease (HR, 1.15; 95% CI, 1.03–1.28). For nitrogen dioxide, we found significant associations with cardiovascular disease (HR per 10 ppb, 1.06; 95% CI, 1.04–1.08) and ischemic heart disease (HR, 1.08; 95% CI, 1.05–1.11). Analyses indicated that Mediterranean diet modified these relationships, as those with a higher alternative Mediterranean Diet Index score had significantly lower rates of cardiovascular disease mortality associated with long-term air pollution exposure ( P -interaction&lt;0.05). Conclusions: A Mediterranean diet reduced cardiovascular disease mortality risk related to long-term exposure to air pollutants in a large prospective US cohort. Increased consumption of foods rich in antioxidant compounds may aid in reducing the considerable disease burden associated with ambient air pollution.
EDA Fibronectin-TLR4 Axis Sustains Megakaryocyte Expansion and Inflammation during Bone Marrow Fibrosis Progression
Authors: Alessandro Malara, Cristian Gruppi, Vittorio Abbonante, Daniele Cattaneo, Luigi De Marco, Alessandra Iurlo, Umberto Gianelli, Andrés F Muro, Anil K Chauhan, Vittorio Rosti, Giovanni Barosi, Alessandra Balduini
Journal: Blood (2018)