tbuckley/cabot-search huggingface dataset:
Metabolomic analysis of dynamic response and drug resistance of gastric cancer cells to 5-fluorouracil.
Authors: Shinsuke Sasada, Yoshihiro Miyata, Yasuhiro Tsutani, Jun Hihara, Morihito Okada
Journal: Journal of Clinical Oncology (2013)

e22053 Background: Metabolomics has developed as an important new tool in cancer research. It is expected to lead to the discovery of biomarker candidates for cancer diagnosis and treatment. The current study aimed to perform a comprehensive metabolomic analysis of the intracellular dynamic responses of human gastric cancer cells to 5-fluorouracil (5-FU), referencing the mechanism of drug action and drug resistance. Methods: Small metabolites in gastric cancer cells and 5-FU–resistant cells were measured by liquid chromatography-mass spectrometry. Candidates for drug targets were selected according to the presence or absence of resistance, before and after 5-FU treatment. In addition, the gene expression of each candidate was assessed by reverse transcription-polymerase chain reaction. Results: The number of metabolites in cancer cells dramatically changed during short-term treatment with 5-FU. Particularly, proline was reduced to one-third of its original level and glutamate was increased by a factor of 3 after 3 h of treatment. The metabolic production of glutamate from proline proceeds by proline dehydrogenase (PRODH), producing superoxide. After 5-FU treatment, PRODH mRNA expression was upregulated 2-fold and production of superoxide was increased by a factor of 3. In 5-FU–resistant cells, proline and glutamate levels were less affected than in non-resistant cells, and PRODH mRNA expression and superoxide generation were not increased following treatment. Conclusions: The authors identified a candidate biomarker, PRODH, for drug effects using the metabolomic approach, a result that was confirmed by conventional methods. In the future, metabolomics will play an important role in the field of cancer research.
Patient-physician communication about code status preferences: A randomized controlled trial.
Authors: Wadih Rhondali, Pedro Emilio Perez-Cruz, David Hui, Gary B. Chisholm, Shalini Dalal, Walter F. Baile, Eva Chittenden, Marilène Filbet, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

9049 Background: Code status discussions are important in cancer care. The best modality for such discussions has not been established. Our objective was to determine the impact of a physician ending a code status discussion with a question (autonomy approach) versus a recommendation (beneficence approach) on patients’ do-not-resuscitate (DNR) preference. Methods: Patients in a supportive care clinic watched two videos showing a physician-patient discussion regarding code status. Both videos were identical except for the ending: one ended with the physician asking for the patient’s code status preference and the other with the physician recommending DNR. Patients were randomly assigned to watch the videos in different sequences. The main outcome was the proportion of patients choosing DNR for the video patient. Results: 78 patients completed the study. 74% chose DNR after the question video, 73% after the recommendation video (p=NS). Median physician compassion score was very high and not different for both videos (p=0.73). 30/30 patients who had chosen DNR for themselves and 30/48 patients who had not chosen DNR for themselves chose DNR for the video patient (100% v/s 62%, p&lt;0.001). Age (OR=1.1/year, p=0.01) and white ethnicity (OR=9.43, p=0.004) predicted DNR choice for the video patient. Conclusions: Ending DNR discussions with a question or a recommendation did not impact DNR choice or perception of physician compassion. Therefore, both approaches are clinically appropriate. All patients who chose DNR for themselves and most patients who did not choose DNR for themselves chose DNR for the video patient. Age and race predicted DNR choice.
Association of puberty timing with type 2 diabetes: A systematic review and meta-analysis
Authors: Tuck Seng Cheng, Felix R. Day, Rajalakshmi Lakshman, Ken K. Ong
Journal: PLoS Medicine (2020)

Background Emerging studies have investigated the association between puberty timing, particularly age at menarche (AAM), and type 2 diabetes. However, whether this association is independent of adiposity is unclear. We aimed to systematically review published evidence on the association between puberty timing and type 2 diabetes (T2D) or impaired glucose tolerance (IGT), with and without adjustment for adiposity, and to estimate the potential contribution of puberty timing to the burden of T2D in the United Kingdom (UK). Methods and findings We searched PubMed, Medline, and Embase databases for publications until February 2019 on the timing of any secondary sexual characteristic in boys or girls in relation to T2D/IGT. Inverse-variance-weighted random-effects meta-analysis was used to pool reported estimates, and meta-regression was used to explore sources of heterogeneity. Twenty-eight observational studies were identified. All assessed AAM in women (combined N = 1,228,306); only 1 study additionally included men. In models without adjustment for adult adiposity, T2D/IGT risk was lower per year later AAM (relative risk [RR] = 0.91, 95% CI 0.89–0.93, p < 0.001, 11 estimates, n = 833,529, I2 = 85.4%) and higher for early versus later menarche (RR = 1.39, 95% CI 1.25–1.55, p < 0.001, 23 estimates, n = 1,185,444, I2 = 87.8%). Associations were weaker but still evident in models adjusted for adiposity (AAM: RR = 0.97 per year, 95% CI 0.95–0.98, p < 0.001, 12 estimates, n = 852,268, I2 = 51.8%; early menarche: RR = 1.19, 95% CI 1.11–1.28, p < 0.001, 21 estimates, n = 890,583, I2 = 68.1%). Associations were stronger among white than Asian women, and in populations with earlier average AAM. The estimated population attributable risk of T2D in white UK women due to early menarche unadjusted and adjusted for adiposity was 12.6% (95% CI 11.0–14.3) and 5.1% (95% CI 3.6–6.7), respectively. Findings in this study are limited by residual and unmeasured confounding, and self-reported AAM. Conclusions Earlier AAM is consistently associated with higher T2D/IGT risk, independent of adiposity. More importantly, this research has identified that a substantial proportion of T2D in women is related to early menarche, which would be expected to increase in light of global secular trends towards earlier puberty timing. These findings highlight the need to identify the underlying mechanisms linking early menarche to T2D/IGT risk.
Final results following exclusive chemotherapy for selected patients with squamous cell carcinoma of the laryngopharynx
Authors: C. Holsinger, V. Bassot, D. Brasnu, O. Laccourreye
Journal: Journal of Clinical Oncology (2007)

6039 Purpose: To determine the long-term oncologic outcomes for patients with squamous cell carcinoma (SCC) of the laryngopharynx treated with exclusive chemotherapy after complete clinical response to induction chemotherapy. Materials and Methods: After platin-based induction chemotherapy, selected patients with a complete clinical and histologic response were treated exclusively with additional chemotherapy and observed closely. The rates of overall survival, disease control, and organ preservation were calculated. Results: Survival at 1- and 5-years was 94.5% and 60.2%, respectively. Main causes of death were metachronous second primaries (27) and intercurrent disease (23) than local recurrence (10), distant metastasis, (9) and nodal recurrence (4). The 1-, 3- and 5- year Kaplan-Meier local control estimates were 73.5%, 53.3%, and 50.3%, respectively. No variable was associated with local recurrence using a multivariate analysis. Salvage treatment resulted in an observed final 85.6% local control rate and varied from 96% in patients with glottic cancer to 71% in patients with tumor originating from other locations. Overall, this treatment approach was well-tolerated: 30 patients (20%) experienced grade 3 toxicity; two patients (1.4%) had grade 4 toxicity events. Overall, chemotherapy allowed for successful modulation of local therapy in 66% of patients (96/146). Conclusions: For selected patients, exclusive chemotherapy does not significantly impact survival and maintains function in a majority of patients. Most remarkable, platin-based chemotherapy permitted us to modulate and to diminish the extent of local therapy. Future work should be directed to identify markers of response and resistance to identify which patients are best suited for this approach. No significant financial relationships to disclose.
Soluble SLAMF7 promotes the growth of myeloma cells via homophilic interaction with surface SLAMF7
Authors: Jiro Kikuchi, Mitsuo Hori, Hidekatsu Iha, Noriko Toyama-Sorimachi, Shotaro Hagiwara, Yoshiaki Kuroda, Daisuke Koyama, Tohru Izumi, Hiroshi Yasui, Atsushi Suzuki, Yusuke Furukawa
Journal: Leukemia (2019)
Trends in research participant categories and descriptions in abstracts from the International BCI Meeting series, 1999 to 2016
Authors: Brandon S. Eddy, Sean C. Garrett, Sneha Rajen, Betts Peters, Jack Wiedrick, Deirdre McLaughlin, Abigail O’Connor, Ashley Renda, Jane E. Huggins, Melanie Fried-Oken
Journal: Brain-Computer Interfaces (2019)

Much brain-computer interface (BCI) research is intended to benefit people with disabilities (PWD), though they are rarely included as study participants. When included, a range of clinical and non-clinical descriptions are used leading to difficulty interpreting and replicating results. We examined trends in inclusion and description of study participants with disabilities across six International BCI Meetings from 1999 to 2016. Meeting abstracts were analyzed by trained independent reviewers. Results suggested declines in participation by PWD across Meetings until the 2016 Meeting. Fifty-eight percent of abstracts identified PWD as end-users, though only twenty-two percent included participants with disabilities, suggesting evidence of a persistent translational gap. Increased diagnostic specificity was noted at the 2013 and 2016 Meetings. Studies often identified physical and/or communication impairments in participants with disabilities versus impairments in other areas. Implementing participatory action research principles and user-centered design strategies within BCI research is critical to bridge the translational gap.
SNPs talk to genes using landlines: long-range chromatin interactions link genetic risk with epigenetic patterns in Takayasu arteritis
Authors: Christian M Hedrich, George Tsokos
Journal: Annals of the Rheumatic Diseases (2019)

Systemic autoimmune/inflammatory conditions are complex both at the clinical and pathomechanistic level. While a number of rare conditions are caused by mutations in single genes, most autoimmune/inflammatory diseases are underlined by multiple genetic variants which, through poorly characterised or unknown processes, confer so-called ‘genetic susceptibility’. The influence of environmental factors necessary for the expression of a clinical entity is usually mandated in the form of epigenetic changes.1–3 

Over the last decade, genome-wide association studies (GWAS) have identified a wealth of associations between genetic variants and autoimmune/inflammatory conditions. Studies have provided compelling evidence for germline polymorphisms and/or copy-number variants contributing to the risk for the development of disease. In most cases, genetic variants only increased the risk of developing disease, while the underlying disease-causing mechanisms remained unclear. Furthermore, healthy individuals may also carry risk alleles for inflammatory conditions while never developing symptoms.4 Understanding the contribution of genetic variants to disease expression is complex because most disease-associated gene variants are located in intergenic or intronic (non-coding) regions, limiting our understanding of their exact impact on genes, their influence on gene expression and underlying molecular events. The fact that a significant proportion of disease-associated polymorphisms are located distant from genes, perhaps not even affecting neighbouring gene expression, led to the hypothesis that genetic variants may interfere with the regulation of distant genes on the same or even other chromosomes.

Indeed, interactions between genes and/or regulatory regions through DNA folding (allowing for physical contact between otherwise distant regions) and/or interactions between chromosomes mediating regulatory events has been suggested. Several genes linked to the immune response are regulated by long-distance chromatin interactions, including (but not limited to) cytokine genes in the Th2 cluster ( IL4, IL5 and IL13 on chromosome …
Abstract 14348: Retention of CPR Skills in High School Students Following a 45-minute Instructor-led Course With Hands-on Practice: A Cross-sectional Analysis
Authors: Lorrel E Brown, Travis Carroll, Avnish Tripath, Carlos Lynes, William C Dillon
Journal: Circulation (2016)

Introduction: Currently, 32 states require CPR training for high school students; it is unknown whether real-world training leads to skill retention. The purpose of this study was to evaluate longi...
Population and the Environment — Time for Another Contraception Revolution
Authors: Deborah J. Anderson
Journal: New England Journal of Medicine (2019)

Interview with Dr. Deborah Anderson on the potential for new contraceptive methods to ease problems associated with population growth. (06:00)Download As the world population continues to grow, pressures on the environment will become more critical. The time seems ripe for another contraception revolution to provide options for the diverse populations that are not currently being served by modern contraception.
Dietary Cholesterol or Egg Consumption and Cardiovascular Outcomes—Reply
Authors: Victor W. Zhong, Linda Van Horn, Norrina B. Allen
Journal: JAMA (2019)

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Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide Using As Conditioning Fludarabine Melphalan Plus 200-400cGy of Total Body Irradiation. Very Good Balance Between Tolerance and Anti Leukemic Activity
Authors: Amado J Karduss-Urueta, Rosendo Perez, Gloria Suarez, Alejo Jimenez, Giovanni Ruiz, Angela Maria Trujillo, Monica Ramirez, Jose Betancur, Pedro Reyes, Luis Rodolfo Gomez, Angelica Cardona
Journal: Blood (2016)
Practice patterns in the treatment of locally advanced resectable esophageal carcinoma: A national survey of Canadian thoracic surgeons.
Authors: Gordon Buduhan
Journal: Journal of Clinical Oncology (2012)

e14695 Background: Many institutions have adopted a multimodality strategy for treating locally advanced resectable esophageal cancer including surgery, chemotherapy and radiation. While many neoadjuvant protocols have been studied, there is no well defined standard treatment. In order to determine current practices and clinician opinions regarding treatment of esophageal cancer, a survey study of practicing Canadian thoracic surgeons was performed. Methods: Members of the Canadian Association of Thoracic Surgeons were contacted by email; those who currently treat esophageal cancer were asked to complete an online survey. Three separate emails were sent to maximize participation. Results: The response rate was 54% (56 /104). Of the respondents, 85% exclusively practiced general thoracic surgery, 87% worked at a University-affiliated hospital. We presented a hypothetical patient with bulky, resectable distal esophageal adenocarcinoma with enlarged paraesophageal lymph nodes (T3N1M0). 54% stated that neoadjuvant chemoradiation followed by surgery was their institution’s treatment of choice, while 33% used neoadjuvant chemotherapy plus surgery. When asked to choose the best treatment for this patient based on available evidence, 33% chose neoadjuvant chemoradiation, 33% favored neoadjuvant chemotherapy, 31% were undecided. Regarding neoadjuvant chemotherapy vs. chemoradiation, 63% strongly agreed or agreed there was insufficient evidence to decide whether or not one treatment was superior to the other. 73% strongly agreed or agreed to support a future randomized trial of preoperative chemotherapy vs. preoperative chemoradiation for esophageal cancer patients. Conclusions: Most Canadian thoracic surgeons use either neoadjuvant chemotherapy or chemoradiation followed by surgery for locally advanced resectable esophageal cancer. There is wide variation in practice patterns with no clear standard approach. 63% feel there is insufficient evidence to decide whether or not one treatment is superior to the other, and the majority support a future trial of neoadjuvant chemotherapy vs. chemoradiation. A pilot study is being planned to determine feasibility.
C-reactive protein as adverse prognostic marker for men with castration-resistant prostate cancer (CRPC): Confirmatory results
Authors: R. Prins, B. L. Rademacher, S. Mongoue-Tchokote, K. M. Eilers, T. M. Beer
Journal: Journal of Clinical Oncology (2009)

5168 Background: We previously reported that higher serum concentrations of C-reactive protein (CRP) are associated with shorter survival in men with metastatic CRPC treated with docetaxel-containing chemotherapy. We sought to confirm these hypothesis-generating findings in an independent data set. Methods: Baseline samples were stored (-80ºC) from 119 CRPC patients enrolled in 6 phase I or II clinical trials of chemotherapy as well as non-cytotoxic agents conducted at OHSU. 91% of patients had metastases and 9% had PSA-only disease. 16% had prior chemotherapy exposure. Median follow-up is 19.7 months (0.9–98.5 months) and 89% have died. In addition to CRP, we examined alkaline phosphatase, hemoglobin, age, ECOG PS, and PSA collected at study entry. After examining the form of the risk function using the generalized additive model method, univariate and multivariate Cox proportional hazard models were used to assess associations between baseline individual categorical and continuous variables. Results: Quartiles of CRP were: 1: 0–1.0, 1.1–4.9, 5.0–17.0, and 17.1 to 311 mg/L, somewhat lower than in our previous study. In a Cox multivariate model, log 2 (CRP) (HR 1.09 p = 0.036) as well as hemoglobin and log 2 (Alk Phos) were independently associated with survival. Thus, the risk of death increased 8.7% for every doubling of CRP. Conclusions: In an independent data set from patients with CRPC, we confirmed that higher baseline CRP is associated with shorter survival. This readily measurable biomarker has the potential to improve prognostic models and should be validated in a prospective clinical trial. This finding also suggests that inflammation may play an important role in the natural history of advanced prostate cancer. Additional studies of the mechanisms that may explain the inverse relationship between CRP and survival are under way. No significant financial relationships to disclose.
Circulating myeloid-derived suppressor cells (MDSC) and correlation to poor prognosis, Th2-polarization, inflammation, and nutritional damages in patients with gastric cancer.
Authors: Kenji Gonda, Masahiko Shibata, Yasuyuki Kanke, Takashi Yazawa, Tomoyuki Monma, Satoshi Suzuki, Izumi Nakamura, Shinji Ohki, Tatsuo Shimura, Hitoshi Ohto, Seiichi Takenoshita
Journal: Journal of Clinical Oncology (2013)

3063 Background: Recent studies have shown that myeloid-derived suppressor cells (MDSC), which have been identified in most patients, are potent suppressors of T cell activation. MDSC have been reported to be correlated with tumorigenesis and the progression of tumors. We have previously reported significant correlations of MDSC with nutritional damage and inflammation in many types of cancer. In this study the quantitative detection of MDSC in peripheral blood was analyzed in the prognosis in patients with gastric cancer. Methods: We tested PBMCs from 29 preoperative patients with gastric cancer and 18 healthy volunteers using flow cytometric analysis (CD14 - CD11b + CD33 + ). Markers for nutritional status (serum levels of total protein), inflammation (NLR: neurphil/lymphocyte ratio, serum levels of vascular endothelial growth factor: VEGF) and Th2-polarization (PBMC’s production of IL-6 and IL-10) were measured in this study. The prognosis of the patients was assessed by Kaplan-Meier tests for correlation with levels of MDSC. Results: MDSC levels in 29 preoperative patients with gastric cancer were significantly higher than in normal volunteers. These levels were not associated with pathological characteristics. However they were significantly correlated with the production of IL-6 and IL-10, VEGF levels and NLR. A significant inverse correlation with levels of total protein was obtained. MDSCs were increased in stage IV patients compared with healthy volunteer and 2-year survival rate of the patients with higher levels of MDSC (&gt; 1.104%PBMC) was significantly poorer (median OS, 498 vs 473 days; p = 0.048), while there was no significant difference in patients with stages I, II, and III. Conclusions: These data suggest that increased MDSC is an effective biomarker for immunosuppression due to Th2-polarization, nutritional impairment, systemic inflammation and poor prognosis in advanced patients with gastric cancer.