tbuckley/cabot-search huggingface dataset:
SPAG5 upregulation contributes to enhanced c-MYC transcriptional activity via interaction with c-MYC binding protein in triple-negative breast cancer
Authors: Ming Li, Anqi Li, Shuling Zhou, Hong Lv, Wentao Yang
Journal: Journal of Hematology & Oncology (2019)

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks effective therapeutic targets. Sperm-associated antigen 5 (SPAG5) is a mitotic spindle-associated protein that is involved in various biological processes in cervical cancer and bladder urothelial carcinoma. However, the role of SPAG5 in TNBC remains undefined. The expression of SPAG5 was examined in TNBC patients via quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry (IHC). The biological functions of SPAG5 in TNBC and the underlying mechanisms were investigated in vitro and in vivo. SPAG5 expression was significantly upregulated in TNBC tissues compared with that in paired adjacent noncancerous tissues (ANTs). High SPAG5 expression was associated with increased lymph node metastasis and high risk of local recurrence. SPAG5 protein expression was significantly associated with poor disease-free survival in TNBC. Gene set enrichment analysis of TNBC data from The Cancer Genome Atlas (TCGA) indicated that high SPAG5 expression was significantly associated with cell cycle and the ATR-BRCA pathway. Functional assays demonstrated that SPAG5 expression promoted tumor growth in vitro and in vivo. In addition, SPAG5-silenced cells were more sensitive to the PARP inhibitor (PARPi) olaparib. Mechanistically, SPAG5 interacted with c-MYC binding protein (MYCBP), thereby increasing MYCBP protein levels and leading to increased c-MYC transcriptional activity, which promoted the expression of the c-MYC target genes: CDC20, CDC25C, BRCA1, BRCA2, and RAD51.Knockdown of MYCBP or c-MYC abolished the SPAG5-induced cell-cycle progression and cell proliferation of TNBC. Collectively, our results indict that SPAG5 is an efficient prognostic factor in TNBC, and that SPAG5 knockdown increases the sensitivity of TNBC to the PARPi olaparib. SPAG5 promotes tumor growth and DNA repair by increasing c-MYC transcriptional activity via interaction with MYCBP. The SPAG5/MYCBP/c-MYC axis may represent a potential therapeutic target for TNBC treatment.
Correlation between time to PSA progression (TTPP), radiographic progression-free survival (rPFS) and overall survival (OS) in first-line abiraterone/enzalutamide (Abi/Enza) and docetaxel (Doc) treated patients in a prospective cohort study.
Authors: David Lorente, Elena Castro, Rebeca Lozano, Javier Puente, Nuria Romero-Laorden, Rafael Morales-Barrera, Alejo Rodriguez Vida, M Isabel Sáez, Maria Jose Mendez-Vidal, Eva Fernandez, Elena Almagro, Amaia Hernandez, Susana Hernando Polo, Begoña Pérez-Valderrama, Fernando López-Campos, Casilda Llacer Perez, A. Montesa, Nuria Lainez, Josep M. Piulats, David Olmos
Journal: Journal of Clinical Oncology (2019)

267 Background: Abiraterone, enzalutamide and docetaxel represent first-line (1L) treatment options in mCRPC. A significant correlation between rPFS and OS has been reported for patients treated with 1L abi and enza in mCRPC. It is however unclear whether TTPP or rPFS present a similar magnitude of correlation with OS in Doc-treated pts. Methods: We evaluated the association of TTPP and rPFS with OS in pts treated with 1L Abi/Enza or Doc in a prospective multicenter observational cohort study. TTPP and rPFS were defined as per PCWG2. Correlation between TTPP and rPFS with OS was evaluated with Spearman rho coefficients (r), and by calculating the concordance index (c-index) in Cox-regression models. Results: 406 out of 419 pts received 1L Abi/Enza or Doc. After a median follow-up of 40 months (m), 253 mCRPC-related deaths were observed, with a median OS of 31.3 m (95% CI: 27.6-35). Median rPFS and TTPP were 10.8 m (95% CI:9.7-11.9) and 7.2 m (95% CI:6.7-7.7), respectively. Significant correlations between rPFS/TTPP and OS were observed in all pts treated at 1L, as well as in Abi/Enza and Doc treated pts (Table). R and c-index were consistently higher in Abi/Enza treated pts than in Doc treated pts, with a higher difference in predictive accuracy of the Cox regression model observed when comparing the association between TTPP and OS (c-index 0.788 in Abi/Enza treated pts vs 0.627 in Doc treated pts). Conclusions: Differences in r and c-index were observed when evaluating the association between TTPP/rPFS and OS in Abi/Enza and Doc treated pts, suggesting rPFS and TTPP may better predict OS in Abi/Enza than in Doc-treated pts. Indirect comparisons of TTPP in Abi/Enza vs Doc pts may therefore not reflect their true impact on OS. Further insight on the exact significance of TTPP is needed. Clinical trial information: NCT03075735. [Table: see text]
Cost-effectiveness of metastasis-directed therapy in the setting of oligometastatic hormone-sensitive prostate cancer.
Authors: Neil Rohit Parikh, Nicholas George Nickols, Matthew Rettig, Christopher R. King, Ann C. Raldow, Michael L. Steinberg, Phuoc T. Tran, Amar Upadhyaya Kishan
Journal: Journal of Clinical Oncology (2019)

147 Background: Androgen deprivation therapy (ADT) has historically been used as the backbone of treatment in patients with newly-diagnosed hormone-sensitive metastatic prostate cancer. However, recent literature has suggested the potential utility of metastasis-directed therapy (MDT) in a subset of patients with oligometastatic prostate cancer (OPC), potentially allowing for ADT-free survival. Methods: A cost-effectiveness analysis was performed comparing (1) ADT upfront versus (2) MDT followed by salvage ADT in patients with asymptomatic hormone-sensitive OPC. MDT was delivered via stereotactic body radiation therapy (SBRT) over 3 fractions. ADT consisted of Lupron injections every 3 months. Costs were calculated from a payor’s perspective based on Medicare CPT codes, CLAB fee schedule, and ASP drug prices. ADT-free survival was modeled based on results from STOMP trial; costs of retreatment were not considered in the MDT arm. Based on prior literature, health utility was assumed to be 0.9 without ADT, and 0.82 with ADT. Given paucity of long-term data on survival effect of MDT with delayed ADT, both arms were assumed to have identical long-term disease transition state probabilities. Results: Total cost of ADT upfront vs. MDT + salvage ADT was $3,430 vs. $9,434 at 1 year, and $10,289 vs. $13,806 at 3 years. Compared to ADT alone, MDT + salvage ADT showed improvements in quality-adjusted life years (QALYs) of 0.07 and 0.15 at 1 and 3 years respectively, translating to incremental cost-effectiveness ratio (ICER) of $85,385/QALY at 1 year and $24,118/QALY at 3 years. Conclusions: Using a willingness-to-pay ICER threshold of $100,000/QALY, MDT with SBRT is shown to be a cost-effective option compared to ADT alone in patients with OPC, particularly when utilizing a longer follow-up time period.
Environmental risk factors for cleft lip and palate in low-resource settings: a case-control study
Authors: Allyn Auslander, Roberta Mckean-Cowdin, Frederick Brindopke, Kathy Magee, Melissa DiBona, William Magee
Journal: The Lancet Global Health (2019)

BackgroundCleft lip with or without palate is the most common birth defect with a global prevalence of 1 in 700 births. Although there is a clear algorithm of care in developed countries, the lack of access to surgery in low-income and middle-income countries (LMICs) means that millions of people live with this easily treated condition. Although smoke exposure from unsafe cooking practices no longer occurs in the developed world and is not routinely studied, exposure to smoke from cooking remains an important challenge to health in LMICs. We aimed to understand whether exposure to cooking smoke is associated with cleft lip and palate in these low-resource settings.MethodsWe conducted a case–control study of mothers of a child with cleft lip with or without palate (cases) and population-matched mothers of children who do not have the condition (controls) in partnership with Operation Smile. Participants were from Vietnam, the Philippines, Honduras, Nicaragua, Morocco, Democratic Republic of the Congo, and Madagascar. Participants provided written consent and the University of Southern California gave ethical approval for the study. The primary exposure of interest was smoke inhalation in the form of smoking before or during pregnancy, paternal (ie, the father of the child) smoking, living with any smoker, or cooking indoors over a fire. We used logistic regression with multiple adjustment models to assess these smoke exposures as possible risk factors for cleft lip and palate.FindingsWe included data from 2168 cases and 2080 controls, recruited between 2011 and 2017. We found that <1% of the mothers in our study smoked cigarettes, but 59·3% (n=1234) cases and 39·1% (n=848) controls cooked over a fire inside their home. We did not find a significant effect of household smoking, smoking 3 months before or during pregnancy, or paternal smoking in our data. Case mothers were 1·47 (95% CI 1·2–1·8) times more likely to cook over a fire indoors than were controls, after mutual adjustment for all other smoke exposure, confounders, and urban versus rural place of dwelling.InterpretationExposure to smoke while cooking is a well-established health risk in LMICs for a wide variety of diseases, but has never been studied with respect to cleft lip and palate. We have shown that it may play a role in the risk of cleft lip and palate, and that it may be a larger risk factor than active or passive tobacco smoke exposure. Exposures specific to low-resource settings must be taken into account when we study preventable risk factors in order to develop strategies that will address the populations at the highest risk of having to live with this condition.FundingNone.
Favorable Inductive Remission Rate of Decitabine Combined Chemotherapy on &lt; 60-Years of Age MDS-like AML in the First Course
Authors: Fengqi Liu, Xiuzhen Tong, Zhenhai Zhou, Dong Zheng, Hehua Wang, Junru Liu, Beihui Huang, Chang Su, Waiyi Zou, Duorong Xu, Juan Li
Journal: Blood (2018)
Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy
Authors: Youqiong Ye, Qingsong Hu, Hu Chen, Ke Liang, Yuan Yuan, Yu Xiang, Hang Ruan, Zhao Zhang, Anren Song, Huiwen Zhang, Lingxiang Liu, Lixia Diao, Yanyan Lou, Bingying Zhou, Li Wang, Shengtao Zhou, Jianjun Gao, Eric Jonasch, Steven H. Lin, Yang Xia, Chunru Lin, Liuqing Yang, Gordon B. Mills, Han Liang, Leng Han
Journal: Nature Metabolism (2019)
Abstract 14669: Prehospital Blood Pressure Measurement in Major Traumatic Brain Injury: Concordance Between EMS Provider Documentation and Non-Invasive Monitor Data Tracking
Authors: Octavio Perez, Eric Helfenbein, Bruce J Barnhart, Saeed Babaeizadeh, Dawn B Jorgenson, Chengcheng Hu, Vatsal Chikani, Joshua B Gaither, Samuel M Keim, Duane Sherrill, Daniel W Spaite
Journal: Circulation (2017)

Background: Recent studies have shown that the lowest prehospital systolic blood pressure (SBP) is strongly associated with mortality across a remarkably wide range (far above 90 mmHg) in traumatic...
Disordered Eating Behaviors in Youth and Young Adults With Type 1 or Type 2 Diabetes Receiving Insulin Therapy: The SEARCH for Diabetes in Youth Study
Authors: Angel S.Y. Nip, Beth A. Reboussin, Dana Dabelea, Anna Bellatorre, Elizabeth J. Mayer-Davis, Anna R. Kahkoska, Jean M. Lawrence, Claire M. Peterson, Lawrence Dolan, Catherine Pihoker
Journal: Diabetes Care (2019)

OBJECTIVE This study examines the prevalence of disordered eating behaviors (DEB) and its associations with glycemic control, insulin sensitivity (IS), and psychosocial functioning in a large, diverse cohort of youth and young adults with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS In the SEARCH for Diabetes in Youth study, 2,156 youth and young adults with type 1 diabetes (mean ± SD age 17.7 ± 4.3 years; 50.0% female) and 149 youth and young adults with type 2 diabetes (age 21.8 years ± 3.5; 64.4% female) who were receiving insulin therapy completed the Diabetes Eating Problem Survey–Revised (DEPS-R), a self-reported measure for identifying disordered eating. DEB were defined as a DEPS-R score ≥20. Demographic characteristics, clinical measures, and health behaviors of participants with DEB and those without DEB were compared by using t tests. RESULTS DEB were observed in 21.2% of participants with type 1 diabetes and 50.3% of participants with type 2 diabetes. Participants encountered challenges in maintaining a healthy weight while controlling their diabetes. For both types of diabetes, individuals with DEB had a significantly higher BMI z score, lower insulin sensitivity, more depressive symptoms, and poorer quality of life than those without DEB. Diabetic ketoacidosis episodes occurred more frequently in youth with type 1 diabetes with DEB compared to those without DEB. CONCLUSIONS These findings highlight that DEB are prevalent among youth and young adults with type 1 and type 2 diabetes and who are receiving insulin therapy, and DEB are associated with poorer clinical outcomes and psychosocial well-being. Heightened awareness and early interventions are needed to address DEB for this at-risk population, as are longitudinal studies evaluating the course of DEB and diabetes outcomes.
Performance of creatinine- or cystatin C–based equations to estimate glomerular filtration rate in sub-Saharan African populations
Authors: Justine B. Bukabau, Eric Yayo, Appolinaire Gnionsahé, Dagui Monnet, Hans Pottel, Etienne Cavalier, Aliocha Nkodila, Jean Robert R. Makulo, Vieux M. Mokoli, François B. Lepira, Nazaire M. Nseka, Jean-Marie Krzesinski, Ernest K. Sumaili, Pierre Delanaye
Journal: Kidney International (2019)
Correlation between PSA kinetics and detection rate of PSMA-PET in the setting of biochemical recurrent prostate cancer: A systematic review and meta-analysis.
Authors: Ricardo Pereira Mestre, Giorgio Treglia, Matteo Ferrari, Mariarosa Pascale, Calogero Mazzara, Ngwa C Azinwi, Anna Llado, Anastasios Stathis, Luca Giovanella, Enrico Roggero
Journal: Journal of Clinical Oncology (2019)

71 Background: Serum prostate-specific antigen (PSA) may predict the risk of positive positron emission tomography/computed tomography with radiolabeled prostate-specific membrane antigen (PSMA-PET/CT) in patients with biochemical recurrent prostate cancer (BRPCa). However, to date, there are no clear data regarding the correlation between PSA kinetics and PSMA-PET findings. We performed a systematic review and meta-analysis to provide evidence-based data in this setting. Methods: A comprehensive literature search of studies published through October 2018 in PubMed/MEDLINE, EMBASE and Cochrane library databases was performed. A meta-analysis to establish the detection rate (DR) of PSMA-PET using different cut-off values of PSA doubling time (PSAdt) and a pooled analysis to establish whether shorter PSAdt may predict positive PSMA-PET results was performed in patients with BRPCa. Results: Twelve articles were included in the systematic review and eight articles (including 1398 patients) were selected for the meta-analysis. The pooled DR including 95% confidence intervals (95% CI) of PSMA-PET in restaging prostate cancer (PCa) patients was 72% (95% CI: 60-82%), increasing to 83% (95% CI: 75-90%) when PSAdt was ≤ 6 months and decreasing to 60% (95% CI: 37-80%) when PSAdt was &gt; 6 months. PSAdt ≤ 6 months may predict the positive result of PSMA-PET (pooled odds ratio: 3.22; 95% CI: 1.17-8.88). Statistical heterogeneity among the included studies was found. Conclusions: PSA kinetics, and in particular shorter PSAdt, may be predictor of PSMA-PET positivity in patients with BRPCa. Further larger studies in this setting are warranted.
Pulsed Dye Laser Treatment of Port-Wine Stains in Infancy Without the Need for General Anesthesia
Authors: Hana Jeon, Leonard J. Bernstein, Daniel A. Belkin, Sabrina Ghalili, Roy G. Geronemus
Journal: JAMA Dermatology (2019)

Recent concerns regarding repetitive use of general anesthesia in children younger than 3 years have placed greater importance on the controversy surrounding the timing of the initiation of port-wine stain (PWS) laser treatment.To evaluate the use of PWS treatments at the age of 1 year or younger in the office setting without general anesthesia.Retrospective cohort study based on medical record reviews at a single, high-volume laser center for children who started pulsed dye laser treatment at the age of 1 year or younger for their PWS between 2000 and 2017. The data cutoff was at 1 year after the initial treatment to have comparable data points.The primary outcome was improvement of PWSs using before and after photographs, which were reviewed by 4 physicians independently and graded using the following 5-point visual analog scale (VAS): poor (grade 1: 0%-25% improvement), fair (grade 2: 26%-50% improvement), good (grade 3: 51%-75% improvement), excellent (grade 4: 76%-99% improvement), and complete (grade 5: 100% improvement) clearance.Of the 197 patients (73 [37.1%] boys; 124 [62.9%] girls), most (149 [75.6%]) had facial lesions. The mean age at the time of first treatment was 3.38 months (range, 5-355 days) and the mean number of treatments was 9.8 (range, 2-23; median, 10). Per the mean physician VAS grading of 197 patients, 51 patients (25.9%) showed 100% clearance (mean [range] VAS score of 4.78 [4.5 - 5]); 81 patients (41.1%) showed 76 to 99% improvement (mean [range] VAS score of 3.91 [3.5 to <4.5]); 44 patients (22.3%) showed 51% to 75% improvement (mean [range] VAS score of 2.86 [2.5 to <3.5]); 13 patients (6.6%) showed 26% to 50% improvement (mean [range] VAS score of 2.12 [1.5 to <2.5]); and 8 patients (4.1%) showed 0 to 25% improvement (mean [range] VAS score of 0.78 [0 to <1.5]). The presence of a V1 (first branch of the trigeminal nerve [ophthalmic nerve]) lesion was associated with a statistically significantly higher clearance rate by a VAS grade of 0.55 (95% CI, 0.25-0.84; P < .001). The mean (SD) VAS grade for all patients was 3.65 (1.26), corresponding to excellent clearance. None of the patients experienced scarring or permanent pigmentary change.In this study, treatment of PWSs in infancy was both safe and effective. Early intervention allows for treatment without general anesthesia, maximizing the chance to achieve clearance before school age and thereby minimizing the negative outcome of PWSs for both the patient and the family.
Interpreting survival outcomes for African-American (AA) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T (SIP-T) with number needed to treat to benefit (NNTB).
Authors: Kelvin A. Moses, Scott C. Flanders, Matthew Harmon, Nancy N. Chang, Walter Rayford, David I. Quinn, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2019)

222 Background: AA men often present with more aggressive prostate cancer and are less likely to receive treatment, negatively affecting quality-of-life and overall survival (OS). Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic or minimally symptomatic mCRPC. Data from the PROCEED registry showed that OS for AA pts treated with SIP-T was 9.3 mo longer than OS for Caucasian pts. In a prior subgroup analysis of Phase III data, AA pts realized a 30.7-mo difference in OS with SIP-T vs. placebo (PBO). We calculated the NNTB to further interpret the OS benefit in AA pts. Methods: Data were pooled from 3 Phase III mCRPC SIP-T trials (D9901, D9902A, and IMPACT). The absolute risk reduction (ARR) is calculated from Kaplan-Meier estimates at 12-, 24-, and 36-mo for all SIP-T subjects, and an AA cohort, receiving ≥1 infusion. NNTB, the inverse of the ARR, represents the number of pts needed to be treated with SIP-T to prevent 1 additional death compared to PBO. All NNTB values are rounded up. Results: Of the 737 pooled mCRPC pts enrolled, 488 men were randomized to SIP-T (n=33 AA), and 249 to PBO. Baseline clinical characteristics between the SIP-T and PBO groups were well balanced; however, compared to overall SIP-T and PBO, AA SIP-T pts were more likely to have received prior chemotherapy, lower hemoglobin, and better performance status. The NNTB at 12-mo was the same (13) for both the pooled SIP-T and AA treated cohort. At 24-mo, the NNTB values were 10 for pooled and 5 for AA. At 36-mo, an NNTB of 8 (pooled) and 3 (AA) SIP-T treatments prevented 1 additional death (Table). Conclusions: This NNTB analysis shows a favorable survival benefit for AA men treated with SIP-T and all treated SIP-T subjects. NNTB values declined over 3-years, suggesting durability of clinical benefit with SIP-T, and that it may address a known survival disparity in AA with prostate cancer. Studies with larger sample sizes may confirm if AA pts derive a greater OS benefit from SIP-T. Clinical trial information: NCT00065442. [Table: see text]
Association of Weight Fluctuation With Mortality in Japanese Adults
Authors: John Cologne, Ikuno Takahashi, Benjamin French, Akiko Nanri, Munechika Misumi, Atsuko Sadakane, Harry M. Cullings, Yuko Araki, Tetsuya Mizoue
Journal: JAMA Network Open (2019)

Weight cycling is associated with the risk of mortality from heart disease, but many studies have not distinguished between simple nonlinear (monotone) weight changes and more complex changes that reflect fluctuations.To assess whether extreme body weight variation is associated with mortality after controlling for nonlinear weight changes.In this prospective clinical cohort study, 4796 Japanese atomic bomb survivors were examined in the clinic as part of a biennial health examination and research program. The study consisted of a 20-year longitudinal baseline period (July 1, 1958, to June 30, 1978) and subsequent mortality follow-up of 27 years (July 1, 1978, to June 30, 2005) Participants were initially between the ages of 20 and 49 years during the baseline period and, throughout the baseline period, had no diagnoses of cardiovascular disease (CVD) or cancer and attended at least 7 of 10 scheduled examinations. Data analysis was performed from October 16, 2015, to May 13, 2016.Residual variability in body mass index (BMI) during the baseline period.Outcomes were mortality from ischemic heart disease, cerebrovascular disease, other CVDs combined, other causes (except cancer), and cancer. Root mean squared error was calculated to capture individual residual variation in BMI after adjustment for baseline BMI trends, and the association of magnitude of residual variation with mortality was calculated as relative risk.In total, 4796 persons (mean [SD] age, 35.0 [7.3] years at first baseline examination; 3252 [67.8%] female; mean [SD] BMI, 21.2 [2.8] at first baseline visit [20.6 (2.4) among men and 21.5 (2.9) among women]) participated in the study. During follow-up, 1550 participants died: 82 (5.3% of all deaths) of ischemic heart disease, 181 (11.7%) of cerebrovascular disease, 186 (12.0%) of other CVDs, 615 (39.7%) of cancer, and 486 (31.3%) of other causes. Magnitude of residual variation in weight was associated with all-cause mortality (relative risk, 1.25 for 1 U of additional variation; 95% CI, 1.06-1.47) and ischemic heart disease mortality (relative risk, 2.49; 95% CI, 1.41-4.38).The findings suggest that an association exists between weight variation and heart disease mortality and that weight loss interventions, if deemed to be necessary, should be considered carefully.