tbuckley/cabot-search huggingface dataset:
Mortality Implications of Prediabetes and Diabetes in Older Adults
Authors: Olive Tang, Kunihiro Matsushita, Josef Coresh, A. Richey Sharrett, John W. McEvoy, B. Gwen Windham, Christie M. Ballantyne, Elizabeth Selvin
Journal: Diabetes Care (2019)

OBJECTIVE Diabetes in older age is heterogeneous, and the treatment approach varies by patient characteristics. We characterized the short-term all-cause and cardiovascular mortality risk associated with hyperglycemia in older age. RESEARCH DESIGN AND METHODS We included 5,791 older adults in the Atherosclerosis Risk in Communities Study who attended visit 5 (2011–2013; ages 66–90 years). We compared prediabetes (HbA1c 5.7% to &amp;lt;6.5%), newly diagnosed diabetes (HbA1c ≥6.5%, prior diagnosis &amp;lt;1 year, or taking antihyperglycemic medications &amp;lt;1 year), short-duration diabetes (duration ≥1 year but &amp;lt;10 years [median]), and long-standing diabetes (duration ≥10 years). Outcomes were all-cause and cardiovascular mortality (median follow-up of 5.6 years). RESULTS Participants were 58% female, and 24% had prevalent cardiovascular disease. All-cause mortality rates, per 1,000 person-years, were 21.2 (95% CI 18.7, 24.1) among those without diabetes, 23.7 (95% CI 20.8, 27.1) for those with prediabetes, 33.8 (95% CI 25.2, 45.5) among those with recently diagnosed diabetes, 29.6 (95% CI 25.0, 35.1) for those with diabetes of short duration, and 48.6 (95% CI 42.4, 55.7) for those with long-standing diabetes. Cardiovascular mortality rates, per 1,000 person-years, were 5.8 (95% CI 4.6, 7.4) among those without diabetes, 6.6 (95% CI 5.2, 8.5) for those with prediabetes, 11.5 (95% CI 7.0, 19.1) among those with recently diagnosed diabetes, 8.2 (95% CI 5.9, 11.3) for those with diabetes of short duration, and 17.3 (95% CI 13.8, 21.7) for those with long-standing diabetes. After adjustment for other cardiovascular risk factors, prediabetes and newly diagnosed diabetes were not significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.03 [95% CI 0.85, 1.23] and HR 1.31 [95% CI 0.94, 1.82], respectively) or cardiovascular mortality (HR 1.00 [95% CI 0.70, 1.43] and HR 1.35 [95% CI 0.74, 2.49], respectively). Excess mortality risk was primarily concentrated among those with long-standing diabetes (all-cause: HR 1.71 [95% CI 1.40, 2.10]; cardiovascular: HR 1.72 [95% CI 1.18, 2.51]). CONCLUSIONS In older adults, long-standing diabetes has a substantial and independent effect on short-term mortality. Older individuals with prediabetes remained at low mortality risk over a median 5.6 years of follow-up.
Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Pajukanta P, Lilja HE, Sinsheimer JS, Cantor RM, Lusis AJ, Gentile M, Duan XJ, Soro-Paavonen A, Naukkarinen J, Saarela J, Laakso M, Ehnholm C, Taskinen MR, Peltonen L. Nat Genet 2004; 36:371-6.
Authors: Janna Saija Saarela
Journal: Nature Genetics (2004)
Tudor Domain-Focused CRISPR Dropout Screen Identifies SGF29 As a Novel Essential Gene in MLL-Rearranged Leukemias
Authors: Anthony K. N. Chan, Christopher D. Delaney, Lu Yang, Wen-Han Chang, Kazuya Miyashita, Qiao Liu, Sheela Pangeni Pokharel, Scott A. Armstrong, Chun-Wei David Chen
Journal: Blood (2019)
Accrual and retention trends among diverse patients in a supportive cancer care trial.
Authors: Grace A. Hanvey, Adaixa Padron, Elizabeth L. Kacel, Chantel Ulfig, Deidre B. Pereira
Journal: Journal of Clinical Oncology (2019)

40 Background: Despite reporting similar levels of willingness to participate in clinical trials, minority cancer patients remain underrepresented in research interventions. The purpose of this analysis was to examine participant age, race, and ethnicity as predictors of study interest, eligibility, enrollment decision, and attrition in an intervention providing supportive care for women with cancer. Methods: Patients from the UF&amp;Shands Gynecologic Oncology Service (N = 568) were approached for recruitment to either a six-week cognitive-behavioral intervention for insomnia and pain or a psychoeducational control condition. These women were queried about their willingness to participate in the study, interest level, and reasons for declining participation if they did not wish to enroll in the trial. Among enrolled patients (N = 64), predictors of attrition were explored. Results: Of approached patients, 57.2% were older than age 60, 14.7% were non-White, and 3.2% were Hispanic. Chi-square analyses indicated that there were no significant differences in interest level by age [χ 2 (2,441) = 2.732, p = .255], race [χ 2 (2,439) = 2.019, p = .364], or ethnicity [χ 2 (2,431) = 3.242, p = .198]. Eligible minority patients were significantly more likely to enroll than were non-Hispanic Whites [χ 2 (1,364) = 4.125, p = .042], with Hispanic recruitment driving this difference (p = .011). Survival analyses demonstrated no differences in attrition hazard based on age (B = -.088, p = .825), race (B = .583, p = .275), or ethnicity (B = -19.518, p = .999) among enrolled patients. Conclusions: In our supportive cancer clinical trial (CCT), there were no significant differences in trial interest across racial and ethnic minority groups. In fact, Hispanics were more likely to enroll than non-Hispanics. Furthermore, neither race nor ethnicity was a significant predictor of trial attrition. Future investigation is needed to better understand racial and ethnic disparities in cancer research enrollment, motivators and barriers to participation in supportive cancer care trials, potential inconsistencies in accrual patterns among minority cancer patients, and best practices for enrolling and retaining diverse participants for supportive CCTs. Clinical trial information: NCT02609880.
Oxidative Stress Regulates T Cell Pathogenicity in Gvhd
Authors: Mohammed Hanief Sofi, Yongxia Wu, Min Dai, Steven Douglas Schutt, Anusara Daenthanasanmak, Jessica Lauren Heinrichs, Hung D Nguyen, David Bastian, Supinya Iamsawat, Mengmeng Zhang, Shikhar Mehrotra, Xue-Zhong Yu
Journal: Blood (2017)
A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity
Authors: Sajid Khan, Xuan Zhang, Dongwen Lv, Qi Zhang, Yonghan He, Peiyi Zhang, Xingui Liu, Dinesh Thummuri, Yaxia Yuan, Janet S. Wiegand, Jing Pei, Weizhou Zhang, Abhisheak Sharma, Christopher R. McCurdy, Vinitha M. Kuruvilla, Natalia Baran, Adolfo A. Ferrando, Yong-mi Kim, Anna Rogojina, Peter J. Houghton, Guangcun Huang, Robert Hromas, Marina Konopleva, Guangrong Zheng, Daohong Zhou
Journal: Nature Medicine (2019)
Impact of mortality reviews on supportive care utilization, end-of-life care, and inpatient mortality.
Authors: Yasmin Karimi, Vasu Divi, Sandy Srinivas, Andrea Segura Smith, Jennifer Hansen, Irina Tokareva, Zeynep Tulu, Haley Hedlin, Joshua Fronk, Eben Lloyd Rosenthal, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2019)

45 Background: 22% of US patients with cancer die in a hospital setting. As part of an effort to reduce unexpected inpatient (inpt) mortality, we reviewed records of all inpt cancer deaths at Stanford Hospital and reported findings to the treatment teams. Methods: Deaths with a cancer related ICD 9/10 code between 5/2017 and 6/2019 were reviewed by a multidisciplinary team. Findings and potential opportunities for improvement were communicated to the pt’s primary outpt oncologist, inpt oncologists and other involved providers. Observed to expected (O:E) mortality for the year prior to the intervention (5/2016–4/2017), Year 1 (5/2017–4/2018) and Year 2 (5/2018–4/2019) of the intervention were compared with two sided t test, α=0.05 (Vizient Inc, Irving TX). Changes in supportive care utilization and end of life care between cases reviewed in Year 1 and Year 2 were compared with chi square analysis. Results: There were 236 inpatient deaths reviewed. The median age was 64 years; 76% had solid tumors; 68% had metastatic disease; 33% had a previous inpt admission; 34% received chemotherapy in the last 2 weeks of life. Median length of stay was 7 days and 37% were admitted to the intensive care unit (ICU). The O:E mortality ratio significantly decreased between the year prior to intervention and Year 2 (0.95 vs. 0.69; p = .019), and Years 1 and 2 (0.90 vs. 0.69; p = .003). There was no noted difference in number of palliative care consults or resuscitation status at the time of death between Years 1 and 2. There was an increased frequency of advance care plan documentation on admission in Year 2 (p = .007). Conclusions: Cancer pts who die in the hospital have high rates of recent hospitalizations, chemotherapy/radiation use in the last 2 weeks of life and ICU admissions. Decrease in O:E is likely multifactorial. Potential factors are improved documentation of comorbidities, increased access to palliative care services, and facilitation of hospice referrals which were partially driven by results of our reviews and resulting awareness around end of life care. Work is ongoing to standardize documentation of goals of care conversations in the electronic medical record and employ lay health workers for earlier end of life discussions.
Pneumonia mortality, comorbidities matter?
Authors: Venceslau Hespanhol, Cristina Bárbara
Journal: Pulmonology (2019)

Pneumonia remains one of the most important causes of mortality. In Portugal, it is the first cause of respiratory death, excluding lung cancer. This is a retrospective cohort study designed to seek for explanations, identifying the characteristics of patients and measure the impact of each one of them on the risk of dying from pneumonia. We analyzed demographic and clinical data of all patients (pts) with 18 years or older with pneumonia requiring hospitalization registered on the national health service registry of mainland Portugal over 2015. A total of 36366 patients corresponding to 40696 pneumonia hospital admissions in 2015 were analyzed. Most of the patients were very old (median age 80 years). Hospital mortality for pneumonia was higher among older (30,3% pts > 75 years). Pneumococcus is the more frequent bacterial isolate, reaching 41.2% of the isolates of total pneumonia cases. The frequency of pneumococcus decreases with aging; conversely, gram-negative bacteria and staphylococcus increase. Pneumococcus is more frequently identified in the winter, closely related to influenza outbreaks. Gram-negative bacteria are more prevalent during the summer months. Diabetes, obesity, COPD, and tobacco smoking are not associated with an increased risk of dying from pneumonia. Patients older than 75 years; living in a senior house; or with chronic renal disease, lung cancer, metastatic disease, mobility impairment, cachexia, dementia, cerebrovascular disease, and ischemic heart disease are at greater risk of dying from pneumonia. Comorbidities contribute decisively to the risk of dying from pneumonia in the hospital, regardless of their type or origin.
Transcription Factors Involved in Tumorigenesis Are Over-Represented in Mutated Active DNA-Binding Sites in Neuroblastoma
Authors: Mario Capasso, Vito Alessandro Lasorsa, Flora Cimmino, Marianna Avitabile, Sueva Cantalupo, Annalaura Montella, Biagio De Angelis, Martina Morini, Carmen de Torres, Aurora Castellano, Franco Locatelli, Achille Iolascon
Journal: Cancer Research (2019)

Abstract The contribution of coding mutations to oncogenesis has been largely clarified, whereas little is known about somatic mutations in noncoding DNA and their role in driving tumors remains controversial. Here, we used an alternative approach to interpret the functional significance of noncoding somatic mutations in promoting tumorigenesis. Noncoding somatic mutations of 151 neuroblastomas were integrated with ENCODE data to locate somatic mutations in regulatory elements specifically active in neuroblastoma cells, nonspecifically active in neuroblastoma cells, and nonactive. Within these types of elements, transcription factors (TF) were identified whose binding sites were enriched or depleted in mutations. For these TFs, a gene expression signature was built to assess their implication in neuroblastoma. DNA- and RNA-sequencing data were integrated to assess the effects of those mutations on mRNA levels. The pathogenicity of mutations was significantly higher in transcription factor binding site (TFBS) of regulatory elements specifically active in neuroblastoma cells, as compared with the others. Within these elements, there were 18 over-represented TFs involved mainly in cell-cycle phase transitions and 15 under-represented TFs primarily regulating cell differentiation. A gene expression signature based on over-represented TFs correlated with poor survival and unfavorable prognostic markers. Moreover, recurrent mutations in TFBS of over-represented TFs such as EZH2 affected MCF2L and ADP-ribosylhydrolase like 1 expression, among the others. We propose a novel approach to study the involvement of regulatory variants in neuroblastoma that could be extended to other cancers and provide further evidence that alterations of gene expression may have relevant effects in neuroblastoma development. Significance: These findings propose a novel approach to study regulatory variants in neuroblastoma and suggest that noncoding somatic mutations have relevant implications in neuroblastoma development.
EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications
Authors: Boheng Li, Wee-Joo Chng
Journal: Journal of Hematology & Oncology (2019)

Abstract EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which along with other PRC2 components mediates gene expression suppression via the methylation of Histone H3 at lysine 27. Recent studies have revealed a dichotomous role of EZH2 in physiology and in the pathogenesis of cancer. While it plays an essential role in the development of the lymphoid system, its deregulation, whether due to genetic or non-genetic causes, promotes B cell- and T cell-related lymphoma or leukemia. These findings triggered a boom in the development of therapeutic EZH2 inhibitors in recent years. Here, we discuss physiologic and pathogenic function of EZH2 in lymphoid context, various internal causes of EZH2 aberrance and how EZH2 modulates lymphomagenesis through epigenetic silencing, post-translational modifications (PTMs), orchestrating with surrounding tumor micro-environment and associating with RNA or viral partners. We also summarize different strategies to directly inhibit PRC2-EZH2 or to intervene EZH2 upstream signaling.
Utilizing the Cholecystagogue, Ensure Plus, Results in Similar Hepatobiliary Scintigraphy Study Results and Patient Outcomes Status Post Cholecystectomy, in Comparison With Sincalide
Authors: Justin G. Peacock, Jared M. Katchen, Chad T. Christensen, Kevin P. Banks
Journal: Clinical Nuclear Medicine (2019)

To determine if use of the oral cholecystagogue, Ensure Plus (EP), in hepatobiliary scintigraphy (HBS) leads to a similar distribution of normal and abnormal gallbladder ejection fractions (GBEFs) versus other historical secondary findings of chronic biliary disease in a similar patient population compared with the conventional cholecystokinin analog, sincalide. The HBS findings analyzed included the GBEF, small bowel transit time, gallbladder fill time, and reversal of the normal gallbladder versus small bowel transit. The secondary objectives were to determine whether patient outcomes were significantly different for EP and sincalide HBS study patients following cholecystectomy, namely, the surgical pathology and patient-reported biliary-type pain.We reviewed all HBS examinations over a retrospective 34-month period. Data from 446 patients who underwent sincalide or EP HBS with GBEF determination for evaluation of chronic symptoms concerning for biliary etiology met the inclusion criteria. The aforementioned HBS findings and postsurgical patient outcomes were obtained for each patient group.Comparing HBS examinations performed with sincalide or EP, no significant differences were noted in the major HBS findings of similar patient populations. Outcomes for the sincalide and EP groups status post cholecystectomy were assessed to determine their sensitivity, specificity, positive predictive value, and negative predictive value. The outcomes assessed were the histopathology and patient-reported amelioration of biliary-type pain. No significant differences were noted.The sincalide and EP cholecystagogues did not lead to significantly different HBS findings for similar patient populations or postcholecystectomy outcomes.
Apolipoprotein E–related glomerular disorders
Authors: Takao Saito, Akira Matsunaga, Megumu Fukunaga, Kiyotaka Nagahama, Shigeo Hara, Eri Muso
Journal: Kidney International (2019)

Of the glomerular disorders that occur due to apolipoprotein E (apoE) mutations, apoE2 homozygote glomerulopathy and lipoprotein glomerulopathy (LPG) have been characterized. ApoE2 homozygote glomerulopathy has been found in individuals expressing homozygous apoE2/2. This was characterized histologically by glomerulosclerosis with marked infiltration of foam cells derived from macrophages, and occasionally with non-lamellated lipoprotein thrombi. Recently, several cases of apoE Toyonaka (Ser197Cys) combined with homozygous apoE2/2 have been reported, in which non-immune membranous nephropathy-like features were observed in glomeruli. Interestingly, in these cases, apoE accumulation was identified by tandem mass spectrometry. Therefore, it is speculated that these findings may arise from apoE molecules without lipids, which result from hinge damage by apoE Toyonaka and may cross the glomerular basement membrane as small molecules. LPG is primarily associated with heterozygous apoE mutations surrounding the low-density lipoprotein-receptor binding site, and it is histologically characterized by lamellated lipoprotein thrombi that lack foam cells. Recent studies have suggested that LPG can be induced by thermodynamic destabilization, hydrophobic surface exposure, and the aggregation of apoE resulting from the incompatibility of apoE mutated residues within helical regions. Additionally, apoE5 may play a supporting role in the development of LPG and in lipid-induced kidney diseases via hyperlipoproteinemia. Thus, it is interesting that many apoE mutations contribute to characteristic glomerular disorders through various mechanisms. In particular, macrophages may uptake lipoproteins into the cytoplasm and contribute to the development of apoE2 homozygote glomerulopathy as foam cells, and their dysfunction may contribute to the accumulation of lipoproteins in the glomerulus, causing lipoprotein thrombi in LPG.
Ribociclib and Endocrine Therapy in Breast Cancer
Authors: Andrea Rocca, Elisabetta Melegari, Michela Palleschi
Journal: New England Journal of Medicine (2019)

in the Supplementary Appendix).We performed this follow-up testing because, in the index case reported by Seikrit et al., 3 the patient had antifactor H antibodies that appeared a few months after diagnosis, concomitant with renal-disease progression and with the disappearance of anti-PLA 2 R antibodies.However, we did not detect anti-factor H antibodies in any patients during follow-up (Fig. 1C).We confirmed the results by means of Western blot assay in selected patients (Fig. S1 and Tables S1 andS2).Taken together, our data do not support the hypothesis that anti-factor H antibodies might contribute to hyperactivation of the alternative pathway and accelerate disease progression in membranous nephropathy.However, the presence of anti-factor H antibodies in very exceptional cases cannot be ruled out.
Effect of cell culture biomaterials for completely xeno-free generation of human induced pluripotent stem cells
Authors: Tzu-Cheng Sung, Hsing-Fen Li, Akon Higuchi, S. Suresh Kumar, Qing-Dong Ling, Yu-Wen Wu, Thierry Burnouf, Michiyo Nasu, Akihiro Umezawa, Kuei-Fang Lee, Han-Chow Wang, Yung Chang, Shih-Tien Hsu
Journal: Biomaterials (2019)
Administration of Third-Party Virus-Specific T-Cells (VST) at the Time of Initial Therapy for Infection after Haemopoietic Stem Cell Transplant Is Safe and Associated with Favourable Clinical Outcomes (the R3ACT-Quickly trial)
Authors: David Gottlieb, Wei Jiang, Selmir Avdic, Leighton Clancy, Gaurav Sutrave, Caroline M Bateman, Elissa Atkins, Adrian Gabriel Selim, Vicki Antonenas, David Collins, Janine Street, Renee Simms, Peter J. Shaw, David Ritchie, Emily Blyth
Journal: Blood (2019)
Health-Related Quality of Life (HRQoL) in Patients with Myelofibrosis Treated with Fedratinib, an Oral, Selective Inhibitor of Janus Kinase 2 (JAK2), in the Randomized, Placebo-Controlled, Phase III JAKARTA Study
Authors: Ruben A Mesa, Nicolaas Schaap, Alessandro M Vannucchi, Jean-Jacques Kiladjian, Francesco Passamonti, Sonja Zweegman, Moshe Talpaz, Srdan Verstovsek, Shelonitda Rose, Derek Tang, Angela Hu, Carrie Brownstein, Shien Guo, Xiaomei Ye, Claire N Harrison
Journal: Blood (2019)
Phase Ib/II study of AVB500 (high affinity inhibitor of GAS6/AXL path) in combination with PAC and PLD in platinum resistant recurrent ovarian cancer
Authors: B.J. Monk, R.L. Coleman, K.N. Moore, K.C. Fuh, L. Bonifacio, G. McIntyre, D. Prohaska, A. Giaccia, M.J. Baker, R. Tabibiazar, M.A. Bookman
Journal: Annals of Oncology (2019)
Nivolumab and AVD for Early-Stage Unfavorable Hodgkin Lymphoma (NIVAHL)
Authors: Paul J Bröckelmann, Helen Goergen, Ulrich Keller, Julia Meissner, Rainer Ordemann, Teresa V Halbsguth, Stephanie Sasse, Martin Sökler, Andrea Kerkhoff, Stephan Mathas, Andreas Hüttmann, Matthias Bormann, Andreas Zimmermann, Michael Fuchs, Bastian von Tresckow, Christian Baues, Andreas Rosenwald, Wolfram Klapper, Carsten Kobe, Peter Borchmann, Andreas Engert
Journal: Blood (2019)
Abstract 15513: Ventricular Arrhythmia Prevalence and Characteristics for HIV+ Persons and Matched, Uninfected Controls
Authors: Alexander J Meyer, Sanjay Dandamudi, Chad J Achenbach, Donald M Lloyd-Jones, Matthew J Feinstein
Journal: Circulation (2017)

Introduction: Sudden cardiac death and myocardial fibrosis are common in HIV. No studies to our knowledge have examined the prevalence and morphology of ventricular ectopy or arrhythmia (VEA) for H...
Building a real-time clinical dashboard to identify and target supportive care interventions in patients with cancer: The Lung Cancer Report Card (LCRC).
Authors: Christian S. Adonizio, Mark Wojtowicz, Jesse Manikowski, Cory Siegrist, Jonathan Hardenstine, Daniel Belletti, Anne Marie Oberle
Journal: Journal of Clinical Oncology (2019)

66 Background: Many studies aiming to improve supportive care of patients with cancer have been single or bundled large population intervention(s). Potential use of unified clinical data architectures has not been realized in oncology, despite large patient-specific data sources generated during routine clinical care (electronic health records). Such systems can systematically apply clinical algorithms and data analytics to identify care gaps in individual patients with specific needs. Methods: Utilizing a design-think paradigm, we developed the LCRC, a near real-time interactive dashboard identifying actionable care gaps in all patients with lung cancer currently followed at Geisinger. Using an iterative process, data analysts served an expanded role in clinical delivery of targeted supportive oncology care, including recommending measures of risk for admission. Results: The table shows aggregate data as of 6/30/2019. Using the LCRC, we were able to identify 174 open care gaps in a population of 1199 active patients. We were also able to identify ‘high-risk’ clinical features in individual patients and the entire patient population. This was completed with analytics alone, without the need for lengthy chart review. Conclusions: By utilizing a population health view, the health system can more accurately estimate resources needed to better address patient needs. The LCRC can be used to directly determine the choice of supportive care interventions for specific patients with lung cancer. [Table: see text]