tbuckley/cabot-search huggingface dataset:
Implementation of an electronic patient reported outcome system in a prostate cancer urology clinic.
Authors: Maria Spillane, Phil Pollock, Lindsay Hedden, Eugenia Wu, Larry Goldenberg, Jennifer M. Jones, Andrew Matthew, Tran Truong, Yuliya Gavrylyuk, Celestia S. Higano
Journal: Journal of Clinical Oncology (2018)

143 Background: The Prostate Clinic at Vancouver General Hospital recently implemented electronic Patient Reported Outcomes (ePRO) collection from prostate cancer patients (pts). The ePRO system was adopted from the University Health Network, Toronto. Our objective was to review the successes and challenges related to the implementation of the system during its first 6 months of use. Methods: All newly diagnosed pts, those going for a prostate biopsy, and pts booking surgery are asked to complete ePRO on iPads at their clinic appointment. The ePRO includes the EPIC-26, EQ-5D-5L, WHODAS 2.0 questionnaires and the Distress Thermometer. It takes about 4-5 minutes to complete the questions, and consent to be contacted about future prostate cancer research is also requested. Afterwards, pts complete ePROs at each clinic appointment. They receive a report summarizing that day’s responses in the context of previous responses. Results: Between 4-1-17 and 10-16-17, 360 pts were eligible to complete the ePRO. 311/360 pts (86.4%) filled out the ePRO at least once. Of the 49 who didn’t, 24 were missed by the coordinator and 21 were not referred by clinic staff. Only 4 pts (8.2%) refused to answer the ePRO. 18 of the 311 pts only partially answered the ePRO, most often due to the length of the questionnaires. 396 instances of ePRO were completed by 311 pts. WiFi connectivity issues were encountered 30/396 times, which prolonged ePRO completion time, and on 3 occasions resulted in patients refusing to complete ePRO. Conclusions: Implementation of the ePRO system into our urology clinic is a success based on a high completion and low refusal rate, and was organized mainly by a single individual. Challenges include training clinic staff to refer pts to complete ePROs at appropriate times, technical difficulties with WiFi connectivity, and the need to interact with each pt individually, which can be time consuming and result in lost data. Eventually, all pts will be trained to pick up an iPad and complete ePROs prior to each appointment. We found the system straightforward to use, and have updated our iPads with additional questionnaires. It is clear that systems collecting ePROs will become standard practice as technology improves and costs go down.
Bone Regeneration: Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration (Adv. Healthcare Mater. 10/2018)
Authors: Lin Weng, Sunil Kumar Boda, Hongjun Wang, Matthew J. Teusink, Franklin D. Shuler, Jingwei Xie
Journal: Advanced Healthcare Materials (2018)

In article 1701415, Jingwei Xie and co-workers report the fabrication of novel three-dimensional (3D) hybrid nanofiber aerogels composed of electrospun PLGA-collagen-gelatin (PCG) and Sr-Cu co-doped bioactive glass (BG) fiber segments, with incorporation of heptaglutamate E7 domain specific BMP-2 peptides, through calcium binding. Their potential applications in healing a critical-sized cranial bone defect is reported.
Thrombocytopenia in hematologic malignancy and solid tumors in the United States.
Authors: Dimitri Bennett, Nittaya Suppapanya, Kelly Grotzinger
Journal: Journal of Clinical Oncology (2012)

e12001 Background: Thrombocytopenia (TCP) frequently occurs in patients with hematologic or solid malignancies resulting from the underlying disease processes or a complication of cancer treatments. Severe TCP may both increase the risk of bleeding, interrupt or reduce optimal dosing with therapies. Epidemiological data on these patients are limited. Therefore, to increase our knowledge, we identified patients with hematologic &amp; solid malignancies &amp; assessed the frequency of primary, secondary &amp; TCP not otherwise classified, following diagnosis &amp; through treatment using a large US claims database. Methods: Hematologic &amp; solid malignancy adult cases were identified during the calendar year 2008 in the Integrated Healthcare Information Service, a medical &amp; prescription claims database comprised of ~101.7 million members from 46 health plans in the US. Malignancies were defined using ICD-9 diagnosis codes; 2 codes were required to confirm cancer. TCP was defined as the presence of at least 2 claims with ICD-9 codes 287.3 or 287.4 or 287.5 within 365 days of the first malignancy diagnosis in 2008. All grades of TCP thus might be reflected as platelet counts were not used to verify diagnostic coding. Adults on active cancer therapy as well as those for whom cancer therapy was not yet initiated &amp; those who have completed their therapeutic regimen are included in the analyses. Results: The frequency of TCP was higher among patients with hematologic malignancies compared to those with solid tumors. Among hematologic cancers, TCP was more common among patients diagnosed with acute myeloid leukemia 33.4% &amp; acute lymphoblastic leukemia 19.1%, followed by aplastic anemia 13.6%, MDS 12.6%, multiple myeloma 9.4%, chronic lymphocytic leukemia 6.9%, chronic myelogenous leukemia 5.9% &amp; non-Hodgkin’s lymphoma 5.1%. Of all patients with solid tumors, the greatest proportion with TCP were observed among those with small cell lung cancer 9.4%; TCP was relatively rare among patients with cancers of the ovary 3.1%, non-small cell lung cancer 2.9%, cervical cancer 2.3%, bladder 1.6%, uterus 1.1%, &amp; breast cancer 0.7%. Conclusions: Overall, TCP occurrence varies widely by cancer type but is commonly higher among patients with hematological malignancies than solid tumors.
Sleep Apnea and Cardiovascular Disease
Authors: John S. Floras
Journal: Circulation Research (2018)

Synchronization of molecular, metabolic, and cardiovascular circadian oscillations is fundamental to human health. Sleep-disordered breathing, which disrupts such temporal congruence, elicits hemodynamic, autonomic, chemical, and inflammatory disturbances with acute and long-term consequences for heart, brain, and circulatory and metabolic function. Sleep apnea afflicts a substantial proportion of adult men and women but is more prevalent in those with established cardiovascular diseases and especially fluid-retaining states. Despite the experimental, epidemiological, observational, and interventional evidence assembled in support of these concepts, this substantial body of work has had relatively modest pragmatic impact, thus far, on the discipline of cardiology. Contemporary estimates of cardiovascular risk still are derived typically from data acquired during wakefulness. The impact of sleep-related breathing disorders rarely is entered into such calculations or integrated into diagnostic disease-specific algorithms or therapeutic recommendations. Reasons for this include absence of apnea-related symptoms in most with cardiovascular disease, impediments to efficient diagnosis at the population level, debate as to target, suboptimal therapies, difficulties mounting large randomized trials of sleep-specific interventions, and the challenging results of those few prospective cardiovascular outcome trials that have been completed and reported. The objectives of this review are to delineate the bidirectional interrelationship between sleep-disordered breathing and cardiovascular disease, consider the findings and implications of observational and randomized trials of treatment, frame the current state of clinical equipoise, identify principal current controversies and potential paths to their resolution, and anticipate future directions.
Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology
Authors: Maria G. Crespo‐Leiro, Marco Metra, Lars H. Lund, Davor Milicic, Maria Rosa Costanzo, Gerasimos Filippatos, Finn Gustafsson, Steven Tsui, Eduardo Barge‐Caballero, Nicolaas De Jonge, Maria Frigerio, Righab Hamdan, Tal Hasin, Martin Hülsmann, Sanem Nalbantgil, Luciano Potena, Johann Bauersachs, Aggeliki Gkouziouta, Arjang Ruhparwar, Arsen D. Ristic, Ewa Straburzynska‐Migaj, Theresa McDonagh, Petar Seferovic, Frank Ruschitzka
Journal: European Journal of Heart Failure (2018)
Coronary Atherosclerotic Precursors of Acute Coronary Syndromes
Authors: Hyuk-Jae Chang, Fay Y. Lin, Sang-Eun Lee, Daniele Andreini, Jeroen Bax, Filippo Cademartiri, Kavitha Chinnaiyan, Benjamin J.W. Chow, Edoardo Conte, Ricardo C. Cury, Gudrun Feuchtner, Martin Hadamitzky, Yong-Jin Kim, Jonathon Leipsic, Erica Maffei, Hugo Marques, Fabian Plank, Gianluca Pontone, Gilbert L. Raff, Alexander R. van Rosendael, Todd C. Villines, Harald G. Weirich, Subhi J. Al’Aref, Lohendran Baskaran, Iksung Cho, Ibrahim Danad, Donghee Han, Ran Heo, Ji Hyun Lee, Asim Rivzi, Wijnand J. Stuijfzand, Heidi Gransar, Yao Lu, Ji Min Sung, Hyung-Bok Park, Daniel S. Berman, Matthew J. Budoff, Habib Samady, Leslee J. Shaw, Peter H. Stone, Renu Virmani, Jagat Narula, James K. Min
Journal: Journal of the American College of Cardiology (2018)
Androgen receptor polyglutamine expansion drives age-dependent quality control defects and muscle dysfunction
Authors: Samir R. Nath, Zhigang Yu, Theresa A. Gipson, Gregory B. Marsh, Eriko Yoshidome, Diane M. Robins, Sokol V. Todi, David E. Housman, Andrew P. Lieberman
Journal: Journal of Clinical Investigation (2018)

Skeletal muscle has emerged as a critical, disease-relevant target tissue in spinal and bulbar muscular atrophy, a degenerative disorder of the neuromuscular system caused by a CAG/polyglutamine (polyQ) expansion in the androgen receptor (AR) gene. Here, we used RNA-sequencing (RNA-Seq) to identify pathways that are disrupted in diseased muscle using AR113Q knockin mice. This analysis unexpectedly identified substantially diminished expression of numerous ubiquitin/proteasome pathway genes in AR113Q muscle, encoding approximately 30% of proteasome subunits and 20% of E2 ubiquitin conjugases. These changes were age, hormone, and glutamine length dependent and arose due to a toxic gain of function conferred by the mutation. Moreover, altered gene expression was associated with decreased levels of the proteasome transcription factor NRF1 and its activator DDI2 and resulted in diminished proteasome activity. Ubiquitinated ADRM1 was detected in AR113Q muscle, indicating the occurrence of stalled proteasomes in mutant mice. Finally, diminished expression of Drosophila orthologues of NRF1 or ADRM1 promoted the accumulation of polyQ AR protein and increased toxicity. Collectively, these data indicate that AR113Q muscle develops progressive proteasome dysfunction that leads to the impairment of quality control and the accumulation of polyQ AR protein, key features that contribute to the age-dependent onset and progression of this disorder.
Establishing a research agenda for early-onset colorectal cancer
Authors: Caitlin C. Murphy, Amit G. Singal
Journal: PLoS Medicine (2018)

BackgroundColorectal cancer (CRC) incidence and mortality trends have evolved strikingly in recent decades [1,2].Since the late 1980s, incidence and mortality have declined among older adults (age !50 years) in the United States, with particularly dramatic declines in those over the age of 65 years.These improvements are likely due to a combination of screening [3,4], changes in the prevalence of certain CRC risk and protective factors (e.g., smoking, aspirin use) [5,6], and advances in treatment [7].CRC screening with colonoscopy, sigmoidoscopy, or stool-bases tests facilitates early detection and removal of premalignant lesions (i.e., adenomatous polyps) [8] and is recommended for average-risk persons beginning at age 50 years [9].In contrast to declines in older populations, the incidence of invasive CRC is increasing in younger adults [10,11].Starting around 1990, incidence increased in this age group (20-49 years) from 8.6 per 100,000 to 12.5 per 100,000 [12].The largest absolute increases in incidence have occurred among 40-49-year-olds, from 18.2 per 100,000 in 1992 to 26.5 per 100,000 in 2015.Mortality rates have increased slightly during the same period, ranging from 5.4 to 6.5 per 100,000 among the 40-49-year age group.Similar increases have been reported across the globe [1,13]-from France [14] to Canada [15] to Australia [16,17].These trends have received research and media attention, with intense speculation for why incidence has increased.As a first step, we outline important considerations for establishing a research agenda to advance our understanding of etiological and diagnostic factors contributing to early-onset CRC. Increases in early-onset CRC have been primarily driven by higher rates of rectal cancerEarly-onset CRC has not increased uniformly by anatomic sublocation.While rectal cancer incidence in younger adults increased from 3.0 per 100,000 in 1992 to 4.7 per 100,000 in 2015, there were smaller increases in proximal colon cancer during this period [12].Differences in incidence and distribution of early-onset CRC by sublocation underscore the importance of teasing apart risk factors for colon versus rectal cancer.Generally, risk factors fall into one of three categories: 1) decreased risk of colon cancer but no association with rectal cancer (e.g., dietary intake of folate and calcium); 2) increased risk of colon cancer but no association with rectal cancer (e.g., processed meat, family history); and 3) increased risk of both colon and rectal cancer (e.g., smoking, obesity) [18].Future etiological studies of early-onset CRC should examine risks separately-or how associations may be modified-by sublocation.
Is low level of vitamin D a marker of poor health, or a cause?
Authors: Om P. Kurmi
Journal: European Respiratory Journal (2018)

<b>Vitamin D deficiency is associated with a number of poor health outcomes but the reported findings on incidence of lung cancer and mortality are inconsistent. The current study does not support a causal link between vitamin D and lung cancer.</b>http://ow.ly/NrAd30k94Oq
NS1‐binding protein radiosensitizes esophageal squamous cell carcinoma by transcriptionally suppressing c‐Myc
Authors: Yuwen Wang, Jingjing Cheng, Dan Xie, Xiaofeng Ding, Hailing Hou, Xi Chen, Puchun Er, Furong Zhang, Lujun Zhao, Zhiyong Yuan, Qingsong Pang, Ping Wang, Dong Qian
Journal: Cancer Communications (2018)

Cisplatin-based chemotherapy with concurrent radiotherapy is a standard treatment for advanced esophageal squamous cell carcinoma (ESCC). NS1-binding protein (NS1-BP), a member of the BTB-kelch protein family, has been shown to inhibit the proliferation of Hela cells by suppressing c-Myc. In the present study, we examined the potential function role of NS1-BP expression in ESCC, and particularly, the sensitivity of ESCC to radiotherapy.NS1-BP expression was examined using immunohistochemistry in two cohorts (n = 98 for the training cohort; n = 46 for independent validation cohort) of ESCC patients receiving cisplatin-based chemotherapy and concurrent radiotherapy. Normal esophageal mucosal tissue blocks were used as a control. We also conducted a series of in vitro and in vivo experiments to examine the potential effects of over-expressing NS1-BP on ESCC cells, and particularly their sensitivity to ionizing irradiation.In the training cohort, NS1-BP downregulation was observed in 59% (85/144) of the ESCC specimens. NS1-BP downregulation was associated with chemoradiotherapeutic resistance and shorter disease-specific survival (DSS) in both the training and validation cohorts. Over-expressing NS1-BP in cultured ESCC cells substantially increased the cellular response to irradiation both in vitro and in vivo. NS1-BP also significantly enhanced IR-induced apoptosis, and abrogated IR-induced G2/M cell-cycle arrest and ATM/Chk1 phosphorylation. Immunoprecipitation assays indicated that NS1-BP could interact with c-Myc promoter regions to inhibit its transcription. In ESCC tissues, c-Myc expression was inversely correlated with NS1-BP levels, and was associated with a shorter DSS.Our findings highlight the role and importance of NS1-BP in radiosensitivity of ESCC. Targeting the NS1-BP/c-Myc pathway may provide a novel therapeutic strategy for ESCC.
Tocilizumab discontinuation after attaining remission in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate: results from a prospective randomised controlled study (the second year of the SURPRISE study)
Authors: Yuko Kaneko, Masaru Kato, Yoshiya Tanaka, Masayuki Inoo, Hitomi Kobayashi-Haraoka, Koichi Amano, Masayuki Miyata, Yohko Murakawa, Hidekara Yasuoka, Shintaro Hirata, Eiichi Tanaka, Nobuyuki Miyasaka, Hisashi Yamanaka, Kazuhiko Yamamoto, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2018)

Objective To evaluate the sustained remission and low disease activity after discontinuation of tocilizumab in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate. Methods The SURPRISE study was a 2-year, open-label randomised controlled study. Among patients who had been randomised to additional tocilizumab (ADD-ON) or switch to tocilizumab (SWITCH) in the first year, those who achieved remission based on the disease activity score for 28 joints (DAS28-ESR&lt;2.6) discontinued tocilizumab at week 52 and were observed for the following 52 weeks. The endpoint of the second year included tocilizumab-free remission and low disease-activity rates, functional outcome, radiological outcomes assessed with the modified total Sharp score (mTSS) and safety. The efficacy of reinstituted tocilizumab/methotrexate was also evaluated. Results A total of 105 patients who achieved remission at week 52 discontinued tocilizumab; 51 in ADD-ON continued methotrexate and 54 in SWITCH received no disease-modifying antirheumatic drugs. Sustained DAS28 low disease-activity rates were significantly higher in ADD-ON than in SWITCH (55%vs27%, p=0.005). Sustained remission rates at week 104 were 24% for ADD-ON and 14% for SWITCH (p=0.29). Radiological progression was comparable between both groups (mTSS; 0.37vs0.64, p=0.36). The restart of tocilizumab induced remission in all except two patients after 36 weeks, irrespective of concomitant methotrexate. Conclusion Sustained low disease activity after tocilizumab discontinuation could be maintained with continued methotrexate in more than half of the patients. Retreatment with tocilizumab led to remission in more than 90% of patients. Trial registration number NCT01120366 ; Results.
Effect of neoadjuvant chemotherapy on the immune microenvironment in non–small cell lung carcinomas as determined by multiplex immunofluorescence and image analysis approaches
Authors: Edwin R. Parra, Pamela Villalobos, Carmen Behrens, Mei Jiang, Apar Pataer, Stephen G. Swisher, William N. William, Jiexin Zhang, Jack Lee, Tina Cascone, John V. Heymach, Marie-Andrée Forget, Cara Haymaker, Chantale Bernatchez, Neda Kalhor, Annikka Weissferdt, Cesar Moran, Jianjun Zhang, Ara Vaporciyan, Don L. Gibbons, Boris Sepesi, Ignacio I. Wistuba
Journal: Journal for ImmunoTherapy of Cancer (2018)

The clinical efficacy observed with inhibitors of programed cell death 1/programed cell death ligand 1 (PD-L1/PD-1) in cancer therapy has prompted studies to characterize the immune response in several tumor types, including lung cancer. However, the immunological profile of non-small cell lung carcinoma (NSCLC) treated with neoadjuvant chemotherapy (NCT) is not yet fully characterized, and it may be therapeutically important. The aim of this retrospective study was to characterize and quantify PD-L1/PD-1 expression and tumor-associated immune cells (TAICs) in surgically resected NSCLCs from patients who received NCT or did not receive NCT (non-NCT).We analyzed immune markers in formalin-fixed, paraffin-embedded tumor tissues resected from 112 patients with stage II/III NSCLC, including 61 non-NCT (adenocarcinoma [ADC] = 33; squamous cell carcinoma [SCC] = 28) and 51 NCT (ADC = 31; SCC = 20). We used multiplex immunofluorescence to identify and quantify immune markers grouped into two 6-antibody panels: panel 1 included AE1/AE3, PD-L1, CD3, CD4, CD8, and CD68; panel 2 included AE1/AE3, PD1, granzyme B, FOXP3, CD45RO, and CD57.PD-L1 expression was higher (> overall median) in NCT cases (median, 19.53%) than in non-NCT cases (median, 1.55%; P = 0.022). Overall, density of TAICs was higher in NCT-NSCLCs than in non-NCT-NSCLCs. Densities of CD3+ cells in the tumor epithelial compartment were higher in NCT-ADCs and NCT-SCCs than in non-NCT-ADCs and non-NCT-SCCs (P = 0.043). Compared with non-NCT-SCCs, NCT-SCCs showed significantly higher densities of CD3 + CD4+ (P = 0.019) and PD-1+ (P < 0.001) cells in the tumor epithelial compartment. Density of CD68+ tumor-associated macrophages (TAMs) was higher in NCT-NSCLCs than in non-NCT-NSCLCs and was significantly higher in NCT-SCCs than in non-NCT-SCCs. In NCT-NSCLCs, higher levels of epithelial T lymphocytes (CD3 + CD4+) and epithelial and stromal TAMs (CD68+) were associated with better outcome in univariate and multivariate analyses.NCT-NSCLCs exhibited higher levels of PD-L1 expression and T-cell subset regulation than non-NCT-NSCLCs, suggesting that NCT activates specific immune response mechanisms in lung cancer. These results suggest the need for clinical trials and translational studies of combined chemotherapy and immunotherapy prior to surgical resection of locally advanced NSCLC.
Cancer patient interest and perceptions of health behavior change programs.
Authors: Lawson Eng, Sophia Yijia Liu, Qihuang Zhang, Delaram Farzanfar, Sabrina Yeung, M Catherine Brown, Wei Xu, Doris Howell, David Paul Goldstein, Jennifer M. Jones, Peter Selby, Meredith Elana Giuliani, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

98 Background: Health behavior change including smoking cessation, physical activity (PA) and alcohol moderation are important aspects of cancer survivorship. We assessed cancer pt interest and perceptions of programs for these behaviours. Methods: 501 cancer pts were surveyed on their smoking, PA and alcohol use along with their interest and perceptions for programs for these behaviors. Multivariate logistic regression models identified factors associated with pt interest and perceptions. Results: At diagnosis, 115 pts smoked; 184 were exposed to second hand smoke (SHS); 313 did not meet PA guidelines; 238 were drinking alcohol. At risk pts’ (e.g, smokers for smoking cessation, SHS exposed for household smoking cessation) survey results are shown in the table. Most pts perceived smoking (90%), SHS (83%) and alcohol (56%) to be harmful on quality of life, survival and fatigue while PA (77%) was felt to improve these outcomes. These perceptions were not associated with program interest ( P&gt; 0.05). However, pts perceiving that alcohol worsened and PA improved these outcomes were more to likely believe associated programs are beneficial (alcohol aORs = 2.1-2.2 P&lt; 0.03; PA aORs = 1.9-3.2 P&lt; 0.02) and should be routine care (alcohol aORs = 1.9-3.5 P&lt; 0.03; PA aORs = 1.7-2.4 P&lt; 0.1). Pts with more pack-yrs smoked less likely perceived a benefit in a household smoking cessation program (aOR = 1.02 P&lt; 0.007). Pts preferred discussing programs with doctors ( &gt; 35%) or counsellors ( &gt; 42%). Conclusions: About half of pts feel that health behavior change programs would be beneficial and should be part of routine care. These factors were more important than perception of the behaviors on outcomes in influencing pt interest. Initial discussions with pts should focus on discussing benefits of these programs. [Table: see text]