tbuckley/cabot-search huggingface dataset:
Partnership in Cancer Survivorship Optimization (PICASSO) project: An Indian Cancer Society (ICS) initiative for cancer survivorship program in India.
Authors: Purna Arun Kurkure, Vandana Salil Dhamankar, Shreya Joshi, Shekhar Jha, Sheila Nair, Savita Goswami
Journal: Journal of Clinical Oncology (2018)

46 Background: Ugam is a support group of childhood cancer survivors from After Completion of Treatment (ACT) clinic at Tata Memorial Hospital (TMH), functioning under umbrella of Indian Cancer Society (ICS), not for profit organisation. Ugam’s mission is empowerment of survivors and advocacy. ACT-Ugam has provided role model for holistic care to cancer survivors.Project PICASSO (Partnership in Cancer Survivorship Optimization) is developed by ICS to promote &amp; facilitate paediatric cancer unit (PCU) based ACT clinic &amp; provide psychosocial support for holistic care of cancer survivors across the country. Methods: A survey was conducted for identifying the survivorship practices in pediatric cancer units (PCU) in Mumbai based hospitals to identify the partners who will setup PCU based ACT clinic. ICS will provide professional and technical assistance to ACT Clinic survivors to enable them to live a productive life. This will include identifying survivor’s need, psycho social counseling, career counseling / aptitude tests, registering them as Ugam members, funding for education if required, soft skills development programme for job readiness, facilitating job placements, survivorship care plan &amp; information material. Ugam database was reviewed for its experience in the field so far to extrapolate the services to partner institutes under PICASSO. Results: Project PICASSO was launched by ICS in May 2016. Among five Mumbai based PCUs who participated in survey, only one (TMH) has organized survivorship program. Communication is ongoing for launch of the project with other units. Total Ugam members- 280 ( 2009 to date), male:female 195:85. Career guidance and aptitude testing provided to &gt; 50 survivors, job placements 9, educational &amp; vocational scholarships through ICS and by referring to other sources &gt; 100. International scholarships to present at conferences: 5. Conclusions: Existing model of Ugam is marching towards fulfillment of its mission of empowerment and advocacy. Expansion of Ugam activities to include more survivors from other partnering units will lead to development of a national care model for cancer survivors.
Neurocognitive Outcomes and Interventions in Long-Term Survivors of Childhood Cancer
Authors: Kevin R. Krull, Kristina K. Hardy, Lisa S. Kahalley, Ilse Schuitema, Shelli R. Kesler
Journal: Journal of Clinical Oncology (2018)

Recent research has demonstrated that survivors of childhood cancer are at risk for a myriad of late effects that affect physical and mental quality of life. We discuss the patterns and prevalence of neurocognitive problems commonly experienced by survivors of CNS tumors and acute lymphoblastic leukemia, the two most commonly researched cancer diagnoses. Research documenting the direct effects of tumor location and treatment type and intensity is presented, and patient characteristics that moderate outcomes (eg, age at diagnosis and sex) are discussed. Potential biologic mechanisms of neurotoxic treatment exposures, such as cranial irradiation and intrathecal and high-dose antimetabolite chemotherapy, are reviewed. Genetic, brain imaging, and neurochemical biomarkers of neurocognitive impairment are discussed. Long-term survivors of childhood cancer are also at risk for physical morbidity (eg, cardiac, pulmonary, endocrine) and problems with health behaviors (eg, sleep); research is reviewed that demonstrates these health problems contribute to neurocognitive impairment in survivors with or without exposure to neurotoxic therapies. We conclude this review with a discussion of literature supporting specific interventions that may be beneficial in the treatment of survivors who already experience neurocognitive impairment, as well as in the prevention of impairment manifestation.
Montelukast for persistent asthma [3] (multiple letters)
Authors: Brian J. Lipworth, Stephen Fowler, Graeme Currie, Alyn H. Morice, Douglas Robinson, Debbie A. Campbell, Peter J. Barnes, Andrew Szczeklik, Lucyna Mastalerz, Ewa Nizankowska, Marek Sanak
Journal: The Lancet (2001)
Real-world analysis of treatment patterns and persistence of octreotide LAR and other agents in patients with advanced gastrointestinal neuroendocrine tumors (GI NET): A multicenter study.
Authors: Matthew H. Kulke, Al Bowen Benson, A. Dasari, Lynn Huynh, Beilei Cai, Todor Totev, Nina Roesner, Mei Sheng Duh, Maureen Neary, Emily K. Bergsland
Journal: Journal of Clinical Oncology (2018)

424 Background: Limited data are available to document recent treatment paradigms that span NET disease course. This study aims to report long-term, real-world treatment patterns of advanced GI NET patients (pts) based on data from four tertiary cancer centers (Dana-Farber, MD Anderson, UCSF and Northwestern). Methods: Retrospective chart review was conducted in pts diagnosed with advanced, well differentiated GI NET at age ≥18 years and treated with somatostatin analogs (SSAs), targeted therapy (TT), cytotoxic chemotherapy (CC), peptide receptor radiotherapy, liver-directed therapy (LDT) or interferon from 7/2011-12/2014. Eligible pts were followed from advanced NET diagnosis date (earliest recorded diagnosis: 3/1987) to end of follow-up/death (latest recorded date: 5/2017). Analyses of treatment and dosing patterns were performed and persistence of therapy was estimated using Kaplan-Meir analysis. Results: 273 pts were included with mean age of 59 years at advanced NET diagnosis; 64% had functional NET; 57% had ileum as primary tumor site; and 63% had carcinoid syndrome (CS). Most common CS symptoms were diarrhea (87%) and flushing (73%). Majority of pts received octreotide alone (88%) or in combination (2%) with LDT, TT or CC as first-line. Of the 161 pts on second-line, 88% received octreotide alone or in combination; 5 pts (3%) received lanreotide. Most common dose at initiation for octreotide was 30mg/4 weeks (51%) and 20mg/4 weeks (32%); 68% of pts never received &gt; 30mg/4 weeks over the entire treatment course. Median time to treatment discontinuation was 145 months (mos) for octreotide (functional NET: 145; non-functional NET: 117), 13 mos for TT and 6 mos for CC. Conclusions: This study showed that octreotide is the mainstay of treatment for advanced GI NET, as 90% of pts received octreotide alone or in combination with other treatment modalities agents as first-line therapy. 74% continued octreotide alone or in combination with other treatment modalities in the second-line. Most commonly prescribed dose was 30 mg/4 weeks. Pts remained on octreotide long term, with median treatment duration of 12 years.
Are anthracyclines needed for the neoadjuvant treatment of patients with HER2-positive early breast cancer?
Authors: Agnieszka Irena Jagiello-Gruszfeld, Katarzyna Pogoda, Anna Niwinska, Izabela Lemanska, Ewa Szombara, Anna Gorniak, Beata Jagielska, Zbigniew Nowecki
Journal: Journal of Clinical Oncology (2018)

e12599 Background: Trastuzumab sc with standard chemotherapy is approved for use in the neoadjuvant setting for HER2 -positive breast cancer patients. A retrospective analysis was performed in group of patients (pts) treated with docetaxel, trastuzumab and carboplatin (TCH) in the neoadjuvant setting in patients with early breast cancer. Methods: From 01.07.2016 to 31.12.2017 in our Clinic 58 pts with early, HER2-positive breast cancer (tumor size < 50 mm and > 10 mm and cN0 or cN1) were treated with chemotherapy carboplatin (AUC6), docetaxel 75 mg/m2 and trastuzumab 600 mg sc, x 6 cycles every 21 days. Trastuzumab was continued after surgery to 18 cycles. Data on patient demographics, stage of breast cancer, pathology reports, surgical data, and information on systemic therapy were collected. The pCR was defined as ypT0 ypN0. Results: Median age was 51 (range 23 to 76 years). 37 (64%) of patients was HR-positive. The most common adverse events were neutropenia (grade 3-4, n = 16 pts), diarrhea (grade 3, n = 4) and febrile neutropenia (n = 5). The 42 pts (72%) received peg-GCSF as primary prophylaxis of FN, and 1 (2%) darbopoetin due to anemia grade 2. There was no symptomatic heart failure, but 6 pts (10%) had > 10% asymptomatic decrease in LVEF. In 2 pts (4%) allergic reaction grade 3 after trastuzumab injection (sc) was observed. Chemotherapy induced polyneuropathy (grade 1-2) was observed in 17 (29%) of pts. All patients were evaluable for pCR. Higher rates of pCR were achieved in the HER2+/HR- cohort (66%, n = 14). In HER2+/HR+ tumors, the pCR rate was 48% (n = 18). Conclusions: In HER2+ early breast cancer, a trastuzumab sc together with carboplatin and docetaxel neoadjuvant chemotherapy achieved high rates of pCR ( 55%). This is the optimal and safety treatment option in countries where there is no access to a dual HER2 blockade (pertuzumab plus trastuzumab) in neoadjuvant setting.
Prevalence of advanced colorectal neoplasia according to risk categories at screening colonoscopy in a tertiary referral center.
Authors: Eduardo Negrete Carballo, Fidel David Huitzil Melendez
Journal: Journal of Clinical Oncology (2018)

578 Background: Colorectal cancer (CRC) is the third most common cancer in the world. There is strong evidence that screening for colorectal cancer improves survival in conutries with high incidence. Although Mexico is considered a country with a low incidence of CRC, 4694 potentially preventable deaths occur every year. There is no established CRC screening program in our country, risk stratification of the target populations to be screened may bring potential advantages, making the strategy more cost-effective. The Asia-Pacific Colorectal Screening (APCS) score, is a validated risk-stratification tool that helps identify individuals at risk for advanced colorectal neoplasm amongst the asymptomatic population. Methods: We performed a retrospective, cross-sectional analysis of database records from 1172 patients who underwent screening colonoscopy betwen january 2013 and november 2014. Results: The prevalence of advanced colorectal neoplasia was 2.9%. Applying the APCS stratification, 91 subjects (7.8%) were in the average risk tier, 849 subjects (72.4%) in the moderate risk tier and 232 (19.8%) subjects in the high risk tier. The prevalence of advanced neoplasia in the average risk, moderate risk and high risk groups was 0%, 2.6% and 5.1%, respectively. The subjects in the high risk tier had 2.21-fold (p = 0.021) increased prevalence of advanced neoplasia than those in the average-moderate tier. Conclusions: The APCS score is a simple risk stratification index for colorectal advanced neoplasm that uses elementary clinical information on age, gender, family history and smoking to stratify the risk of colorectal advanced neoplasm in asymptomatic subjects for priority of colorectal screening.
A major locus controls local adaptation and adaptive life history variation in a perennial plant
Authors: Jing Wang, Jihua Ding, Biyue Tan, Kathryn M. Robinson, Ingrid H. Michelson, Anna Johansson, Björn Nystedt, Douglas G. Scofield, Ove Nilsson, Stefan Jansson, Nathaniel R. Street, Pär K. Ingvarsson
Journal: Genome biology (2018)

The initiation of growth cessation and dormancy represent critical life-history trade-offs between survival and growth and have important fitness effects in perennial plants. Such adaptive life-history traits often show strong local adaptation along environmental gradients but, despite their importance, the genetic architecture of these traits remains poorly understood. We integrate whole genome re-sequencing with environmental and phenotypic data from common garden experiments to investigate the genomic basis of local adaptation across a latitudinal gradient in European aspen (Populus tremula). A single genomic region containing the PtFT2 gene mediates local adaptation in the timing of bud set and explains 65% of the observed genetic variation in bud set. This locus is the likely target of a recent selective sweep that originated right before or during colonization of northern Scandinavia following the last glaciation. Field and greenhouse experiments confirm that variation in PtFT2 gene expression affects the phenotypic variation in bud set that we observe in wild natural populations. Our results reveal a major effect locus that determines the timing of bud set and that has facilitated rapid adaptation to shorter growing seasons and colder climates in European aspen. The discovery of a single locus explaining a substantial fraction of the variation in a key life-history trait is remarkable, given that such traits are generally considered to be highly polygenic. These findings provide a dramatic illustration of how loci of large-effect for adaptive traits can arise and be maintained over large geographical scales in natural populations.
Injectable OPF/graphene oxide hydrogels provide mechanical support and enhance cell electrical signaling after implantation into myocardial infarct
Authors: Jin Zhou, Xiaoning Yang, Wei Liu, Chunlan Wang, Yuan Shen, Fengzhi Zhang, Huimin Zhu, Hongji Sun, Jiayun Chen, Johnny Lam, Antonios G Mikos, Changyong Wang
Journal: Theranostics (2018)

After myocardial infarction (MI), the scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive hydrogel could not only provide mechanical support to the infarcted region, but also synchronize contraction and restore ventricular function by electrically connecting isolated cardiomyocytes to intact tissue. Methods: We created a conductive hydrogel by introducing graphene oxide (GO) nanoparticles into oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels. The hydrogels were characterized by AFM and electrochemistry workstation. A rat model of myocardial infarction was used to investigate the ability of OPF/GO to improve cardiac electrical propagation in the injured heart in vivo. Echocardiography (ECHO) was used to evaluate heart function 4 weeks after MI. Ca2+ imaging was used to visualize beating cardiomyocytes (CMs). Immunofluorescence staining was used to visualize the expression of cardiac-specific markers. Results: OPF/GO hydrogels had semiconductive properties that were lacking in pure OPF. In addition, the incorporation of GO into OPF hydrogels could improve cell attachment in vitro. Injection of OPF/GO 4 weeks after myocardial infarction in rats enhanced the Ca2+ signal conduction of cardiomyocytes in the infarcted region in comparison with PBS or OPF alone. Moreover, the injection of OPF/GO hydrogel into the infarct region enhanced the generation of cytoskeletal structure and intercalated disc assembly. Echocardiography analysis showed improvement in load-dependent ejection fraction/fractional shortening of heart function 4 weeks after injection. Conclusions: We prepared a conductive hydrogel (OPF/GO) that provide mechanical support and biological conduction in vitro and in vivo. We found that injected OPF/GO hydrogels can provide mechanical support and electric connection between healthy myocardium and the cardiomyocytes in the scar via activating the canonical Wnt signal pathway, thus upregulating the generation of Cx43 and gap junction associated proteins. Injection of OPF/GO hydrogel maintained better heart function after myocardial infarction than the injection of a nonconductive polymer.
Association of vitamin D with incidence risk of breast cancer.
Authors: Veenoo Agarwal, Byron Manning, Caroline Wong, Andrew Davidson, Andrew D. Redfern
Journal: Journal of Clinical Oncology (2018)

e12540 Background: Low serum vitamin D (Vit-D) is associated with an increased risk of breast cancer (BC). Patients with adequate levels of Vit-D/replacement have lower rates of BC incidence. Aims: A prospective study to profile the extent of Vit-D deficiency in the Western Australian BC population, the association between Vit-D level and BC biology, and to determination of outcomes of supplementation with Vit-D post-diagnosis in Vit-D deficient patients. Methods: The study consists of 411 adult, non-pregnant women, with invasive unilateral BC of any stage, diagnosed between 2000 and 2013. Mean follow up was 77 months. Intervention: Vit-D supplementation for patients with low serum levels and lifestyle changes for patients with low-normal serum levels to achieve target serum concentrations. Main outcome measures: Correlates of tumour biology and Vit-D serum level. Time to progression and overall survival Results: In this WA cohort of BC patients 64% were either Vit-D deplete (n = 118, 29%) or Vit-D deficient (n = 145, 35%). Serum Vit-D levels were significantly inversely correlated with tumour grade (p = 0.032), lymph node status (p = 0.048), and composite measure of aggressiveness of tumour biology (r = -0.172, P = 0.002) (modified Nottingham Prognostication Index to include HER2/Neu). Simple supplementation resulted in correction of Vit-D levels to within the normal range in 92% of patients. Advice on increased Vit-D consumption in diet or greater sun exposure was significantly less successful with 38% of levels correcting. Hazard ratios between initially deficient, deplete or replete groups Vit-D level groups did not show a significant difference in relapse or BC specific mortality over the duration of follow up. Conclusions: A significant correlation between decreasing serum Vit-D levels and an increasing index of aggressive tumour biology was found. Supplementation advice frequently resulted in correction of deficiency. Survival data suggests efficacy of our simple supplementation strategy in removing the detriment of Vit-D deficiency for BC survivors. Further randomised supplementation studies are required.
Racial/ethnic variation in incidence rates for anal cancer in New Mexico.
Authors: Diaa Osman, Bridget N. Fahy, Jessica Belmonte, Angela W. Meisner, Charles Wiggins
Journal: Journal of Clinical Oncology (2018)

601 Background: Anal cancer comprises only 2.5% of all digestive system malignancies in the United States; only 8200 new cases are diagnosed annually, nevertheless, an increasing incidence rate has been noted. The goal of this study is to describe the incidence rates of anal cancer in New Mexico. New Mexico is a unique, mainly rural state, with unique demographics consisting of a large mix of patients being primarily Non-Hispanic White, Hispanics or Native Americans. Methods: All incident cases of anal cancer diagnosed among New Mexico residents during the twenty-year period 1995-2014 were identified from the population-based New Mexico Tumor Registry. Average annual age-adjusted incidence rates (US 2000 standard) were calculated by the direct method for non-Hispanic whites, Hispanics and American Indians. Incidence rates for non-Hispanic whites in nine core areas of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program served as the comparison. Results: A total of 556 anal cancers were diagnosed among New Mexico residents during the study period, an average of approximate 28 cancers annually. Anal cancer incidence rates per 100,000 were highest for non-Hispanic whites (1.80, 95% Confidence Interval (CI) 1.62-1.98) in New Mexico, which were similar to rates for non-Hispanic whites (1.70, 95% CI 1.66-1.74) in nine core areas of the SEER Program. Statistically significant lower rates were observed in New Mexico Hispanics (0.92, 95% CI 0.76-1.11) and American Indians (0.75, 95% CI 0.45-1.16). Females had higher rates than males in each of these three racial/ethnic groups. Incidence rates increased from 1995-2004 to 2005-2014 for all race/ethnic groups, with the largest increase observed in Hispanic females. Conclusions: Anal cancer incidence rates vary by race/ethnicity and sex in New Mexico. Further research is needed to characterize time trends in incidence and to identify factors that may account for observed differences in incidence rates by race/ethnicity and sex in New Mexico.
APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types
Authors: Yuan-Ta Lin, Jinsoo Seo, Fan Gao, Heather M. Feldman, Hsin-Lan Wen, Jay Penney, Hugh P. Cam, Elizabeta Gjoneska, Waseem K. Raja, Jemmie Cheng, Richard Rueda, Oleg Kritskiy, Fatema Abdurrob, Zhuyu Peng, Blerta Milo, Chung Jong Yu, Sara Elmsaouri, Dilip Dey, Tak Ko, Bruce A. Yankner, Li-Huei Tsai
Journal: Neuron (2018)
<sup>18</sup>F-Fluoroestradiol (FES) and <sup>18</sup>F-Fluorodeoxyglucose (FDG) PET imaging in lobular breast cancer.
Authors: Poorni Manohar, Lanell Peterson, Vicky Wu, Isaac Jenkins, Alena Novakova-Jiresova, Jennifer M. Specht, Jeanne Link, Kenneth A. Krohn, Paul Kinahan, David A. Mankoff, Hannah M. Linden
Journal: Journal of Clinical Oncology (2018)

1063 Background: The histology and pattern of spread in lobular breast cancer has presented challenges in estimating extent of disease by traditional imaging methods. 18F-FES is an estrogen analogue PET imaging tracer which measures tumor ER expression at multiple tumor sites simultaneously. We compared quantitative FES-PET and clinical FDG-PET SUV uptake between patients with metastatic lobular and ductal carcinoma. Methods: We retrospectively compared FES and FDG SUV uptake between ER+ lobular and ductal metastatic breast cancer patients (199 ductal, 44 lobular) enrolled in various studies at our institution. Up to nine lesions in each patient were evaluated by FES SUVmax and/or FDG SUVmax for a total of 619 lesions in FES images (n = 509 ductal, n = 110 lobular) and 466 lesions in FDG images (n = 378 ductal, n = 88 lobular). Using linear mixed-effects models, we assessed differences between lobular and ductal histologies in both FES SUVmax and FDG SUVmax. Overall survival (OS), from time of FES-PET scan to death, was evaluated between histologies using Kaplan-Meier curves and the Log-Rank test. Results: Among metastatic breast cancer patients with positive FES scans, approximately 10% of patients with ductal histology and 9% with lobular histology had absent FES uptake in at least one lesion. Mean (range) SUVmax in FES and FDG respectively for ductal was 3.48 (0.32, 20.5) and 5.2 (1.1, 26.7) and for lobular was 3.34 (0.61, 9.62) and 4.42 (1.09, 20.0). Difference in FES and FDG SUVmax between histologies was marginal and non-significant. On the natural log scale, lobular carcinomas demonstrated a higher SUVmax (Difference = 0.05, 95%CI = [-0.16, 0.26], p = 0.63) and a lower FDG SUVmax (Difference = -0.53, 95%CI = [-1.61, 0.56], p = 0.34. Following FES-PET imaging, patients with ductal carcinomas had a lower, non-significant median survival time (2.97 vs. 3.03 years, p = 0.81). Conclusions: In the metastatic setting, FES and FDG uptake in multiple lesions in ER+ lobular breast cancer patients did not statistically differ from ductal breast cancer. Metastatic lobular breast cancers have similar FES and FDG avidity to metastatic ductal tumors, suggesting these patients may benefit from similar diagnostic and treatment algorithms.