tbuckley/cabot-search huggingface dataset:
Longitudinal relationship between inflammatory markers and patient-reported symptom severity during induction therapy for multiple myeloma.
Authors: Mary H Sailors, Xin Shelley Wang, Ping Liu, Valen E. Johnson, James M. Reuben, Evan N. Cohen, Loretta A. Williams, Tito R. Mendoza, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2012)

9083 Background: Multiple myeloma (MM) patients undergoing induction therapy experience both disease- and therapy-related symptoms. We investigated the association between the trajectory of symptom severity and changes in levels of inflammatory markers. Methods: MM patients (N=62) rated symptoms via the M. D. Anderson Symptom Inventory (MDASI) twice a week during induction therapy. Patients contributed serum samples before the start of every chemotherapy cycle. A panel of pro- and anti-inflammatory cytokines and markers was evaluated by Luminex. Ordinal regression analyses were used to describe the relationship between cytokines and symptom outcomes across time. These analyses were adjusted for patient and clinical factors (age, sex, diabetes diagnosis, anemia, BMI, comorbidity, staging, ECOG PS, prior treatment status, tumor response, opioid use, and chemo regimen). Results: Bortezomib-based induction therapy was received by 89% of the sample. Fatigue was persistently the most severe symptom during induction therapy, followed by disturbed sleep, muscle weakness, pain, drowsiness, and bone aches. Numbness, which is representative of chemotherapy-induced peripheral neuropathy, significantly worsened from baseline (p=0.01). We observed significant longitudinal associations between sIL-1R1 and distress and sadness (both p=0.02); between sIL-6R and disturbed sleep (p=0.001), poor appetite (p=0.04), and sore mouth (p=0.006). IL-6 was significantly associated with pain, fatigue, nausea, and sore mouth (all p&lt;.05). A negative association between sTNF-RII and pain, sleep, distress, remembering, poor appetite, and nausea (all p&lt;0.05) was also observed. MCP-1 was positively associated with numbness (p=0.04); while MIP-1α was negatively associated with sleep, numbness, constipation, poor attention (all p&lt;0.01), and bone aches (p=0.0006). IL-10 was negatively associated with mood interference (p=0.04). Conclusions: Frequent assessment can document the longitudinal course of multiple symptoms during induction and provides opportunity to evaluate systemic inflammation as a potential source of symptom burden during induction therapy for MM.
Drug discovery technologies: <i>Caenorhabditis elegans</i> as a model for anthelmintic therapeutics
Authors: Daniel Sepúlveda‐Crespo, Rosa M. Reguera, Francisco Rojo‐Vázquez, Rafael Balaña‐Fouce, María Martínez‐Valladares
Journal: Medicinal Research Reviews (2020)

Abstract Helminthiasis is one of the gravest problems worldwide. There is a growing concern on less available anthelmintics and the emergence of resistance creating a major threat to human and livestock health resources. Novel and broad‐spectrum anthelmintics are urgently needed. The free‐living nematode Caenorhabditis elegans could address this issue through automated high‐throughput technologies for the screening of large chemical libraries. This review discusses the strong advantages and limitations for using C elegans as a screening method for anthelmintic drug discovery. C elegans is the best model available for the validation of novel effective drugs in treating most, if not all, helminth infections, and for the elucidation the mode of action of anthelmintic candidates. This review also focuses on available technologies in the discovery of anthelmintics published over the last 15 years with particular attention to high‐throughput technologies over conventional screens. On the other hand, this review highlights how combinatorial and nanomedicine strategies could prolong the use of anthelmintics and control resistance problems.
Recommendations for the Prescription of Opioids at Discharge After Abdominopelvic Surgery
Authors: David D. Q. Zhang, Fahima Dossa, Anuj Arora, Maria C. Cusimano, Brittany Speller, Tari Little, Karim Ladha, Savtaj Brar, David R. Urbach, Andrea C. Tricco, Duminda N. Wijeysundera, Hance A. Clarke, Nancy N. Baxter
Journal: JAMA Surgery (2020)

The prescription of opioids at discharge after abdominopelvic surgery is variable and often excessive. A lack of guidance for abdominopelvic surgeons may explain the suboptimal nature of current prescribing practices.To systematically review existing recommendations on the prescription of opioids at discharge, the appropriate disposal of opioids, and the prevention of chronic postsurgical opioid use after abdominopelvic surgery.This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. From January 2010 to December 2018, a search of MEDLINE, PsycINFO, HealthSTAR, Embase, and the difficult to locate and unpublished (ie, gray) literature was performed using a peer-reviewed strategy with variations of the terms opioid, surgery, and guideline to identify English-language documents that contained recommendations published by professional societies or health care institutions. The quality of clinical practice guidelines was assessed using the Appraisal of Guidelines Research and Evaluation II (AGREE II) tool. A descriptive synthesis of results was performed.Of 5530 citations screened, 41 full-text documents were included in the systematic review. Fifteen clinical practice guidelines were identified. AGREE II domain scores varied substantially. Identified among the 41 included documents were 98 recommended interventions for the prescription of opioids at discharge, 8 interventions for the disposal of opioids, and 8 interventions for the prevention of chronic postsurgical opioid use. Only 13 of 114 interventions (11.4%) were supported by an assessment of strength or level of evidence, and the amount of opioid recommended after specific abdominopelvic surgical procedures varied widely between guidance documents, even for the same procedure.Current guidance for the prescription of opioids at discharge after abdominopelvic surgery is heterogeneous and rarely supported by evidence. More research is needed on this topic to guide the development of future recommendations.
MITRAL REGURGITATION AND IMPACT ON OUTCOMES IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION: A TOPCAT ANALYSIS
Authors: Ginger Jiang, Kevin Kennedy, Jordan B. Strom, Pablo Quintero Pinzon, Lisa Fleming, Michael C. Gavin, Arthur Garan, Marwa A. Sabe
Journal: Journal of the American College of Cardiology (2020)
TRANSCATHETER AORTIC VALVE REPLACEMENT OUTCOMES IN RADIATION-ASSOCIATED AORTIC STENOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Abdul Haseeb, Najam Saqib, Raza Mian, Muhammad Bilal, Hamza Hafeez, Mirza Mujadil Ahmad, Sharath Rajagopalan, Muhammad Siddique Pir, Noman Lateef, Samir B. Pancholy
Journal: Journal of the American College of Cardiology (2020)
IFCT0401-bio trial: Pathological and EGF-r molecular analysis of tumor-biopsy samples from patients with non-resectable, pneumonic-type adenocarcinoma (P-ADC) treated by gefinitib. Preliminary results from surgical specimens
Authors: J. Cadranel, M. Wislez, F. Coulet, V. Poulot, J. F. Morã, P. Debove, M. Perol, P. J. Souquet, F. Soubrier, M. Antoine
Journal: Journal of Clinical Oncology (2006)

7185 Background: P-ADC is often a bronchioloalveolar carcinoma (BAC) variant in the 2004 WHO pathological classification. A French prospective multicentric phase II trial (IFCT0401) evaluated gefitinib as first line treatment in non-resectable P-ADC. Tissue samples were collected for central pathological review and molecular analysis in attempt to determine if an association existed between disease control (DC) by gefitinib and biological markers. Methods: Histologic types were classified according to the 2004 WHO classification as BAC variants and ADC, other types and as non-mucinous or mucinous/mixed. Immunohistochemistry were performed using antibodies against the following proteins: TTF1, Ki67, phosphorylated AKT, erbB2, and EGFR. Polysomy/amplification was examined for erbB2 and EGFR. EGFR 18–21 and K-ras 1 exons were amplified and sequenced. Results: A tissue specimen was collected from 67 of the 88 eligible participants, among which 35 were from surgical resection. This subgroup did not differ from the overall trial population in terms of sex ratio (0.51 vs 0.56), proportion of non-smokers (34 vs 55%) and DC rate (34 vs 29%). Results described herein were obtained in 22 of the 35 surgical specimens collected. Sixteen were BAC variants (73%) and 6 ADC other types. Of the 22, 14 were non-mucinous and 8 mucinous. TTF1, Ki67, P-AKT, erbB2 as well as EGFR expression did not differ between BAC variants and ADC other types. TTF1 and EGFR scores of expression were higher in non-mucinous than in mucinous P-ADC. DC on gefitinib was significantly associated with non-mucinous subtype (p = 0.006), higher TTF1 (p = 0.06) and EGFR (p = 0.07) scores of expression, but not with other markers. K-ras exon-1 codon 12 mutation was found in 6 tumors of which 5 progressed on gefitinib. Polysomy of EGFR was seen in 2 tumors, 1 of which also contained EGFR mutation (exon-19 deletion); both were controlled by gefitinib. Conclusions: Among patients with P-ADC who received gefitinib, non-mucinous subtype, high TTF1 or EGFR score of expression, and EGFR polysomy and/or mutation may have improved DC, while K-ras mutation seems associated with disease progression. [Table: see text]
The evolutionary foundations of resource-rational analysis
Authors: Armin W. Schulz
Journal: Behavioral and Brain Sciences (2020)

Abstract Resource-rational analysis would profit from being integrated more explicitly with an evolutionary psychological perspective. In particular, by taking more strongly into consideration the fact that efficiency considerations are a key driver of the evolution of human and animal minds, it becomes clearer: (1) why it is reasonable to assume that cognitive mechanisms trade-off accuracy against effort, (2) how this trade-off occurs, and (3) how to overcome some of the challenges of resource-rational analysis.
GLOBAL LONGITUDINAL STRAIN AS A THERAPEUTIC GUIDE FOR MYOCARDIAL DYSFUNCTION DURING TRASTUZUMAB TREATMENT: A RANDOMIZED SINGLE-CENTER STUDY
Authors: Lafayete W.F. Ramos, Marcos Vinícius F. Ramos, Eliane Elly, Cristiano S. Freitas, Pedro Amoedo
Journal: Journal of the American College of Cardiology (2020)
TRIGLYCERIDE-RICH LIPOPROTEINS-CHOLESTEROL IS STRONGLY ASSOCIATED WITH COGNITIVE PERFORMANCE WHILE TRIGLYCERIDES NOT: A CROSS-SECTIONAL ANALYSIS
Authors: Giuliano Generoso, Claudia K. Suemoto, Isabela Bensenor, Raul Santos, Steven R. Jones, Krishnaji Kulkarni, Michael Blaha, Peter Toth, Paulo Lotufo, Marcio Bittencourt
Journal: Journal of the American College of Cardiology (2020)
HSR20-114: Impact of Social Determinants of Health on Unplanned Acute Care Service Utilization for Patients With Hematologic Malignancies
Authors: Joyce LaMori, Kai Zu, Kristina L. Greenwood, Besa Smith, Tyler Smith, Alaina Lee
Journal: Journal of the National Comprehensive Cancer Network (2020)

"HSR20-114: Impact of Social Determinants of Health on Unplanned Acute Care Service Utilization for Patients With Hematologic Malignancies" published on 20 Mar 2020 by National Comprehensive Cancer Network.
Advancing rational analysis to the algorithmic level
Authors: Falk Lieder, Thomas L Griffiths
Journal: Behavioral and Brain Sciences (2020)

Abstract The commentaries raised questions about normativity, human rationality, cognitive architectures, cognitive constraints, and the scope or resource rational analysis (RRA). We respond to these questions and clarify that RRA is a methodological advance that extends the scope of rational modeling to understanding cognitive processes, why they differ between people, why they change over time, and how they could be improved.
Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, and breast cancer risk: observational and Mendelian randomization analyses with ∼430 000 women
Authors: N. Murphy, A. Knuppel, N. Papadimitriou, R.M. Martin, K.K. Tsilidis, K. Smith-Byrne, G. Fensom, A. Perez-Cornago, R.C. Travis, T.J. Key, M.J. Gunter
Journal: Annals of Oncology (2020)

<h3>Background</h3> Epidemiological evidence supports a positive association between circulating insulin-like growth factor-1 (IGF-1) concentrations and breast cancer risk, but both the magnitude and causality of this relationship are uncertain. We conducted observational analyses with adjustment for regression dilution bias, and Mendelian randomization (MR) analyses allowed for causal inference. <h3>Patients and methods</h3> We investigated the associations between circulating IGF-1 concentrations and incident breast cancer risk in 206 263 women in the UK Biobank. Multivariable hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. HRs were corrected for regression dilution using repeat IGF-1 measures available in a subsample of 6711 women. For the MR analyses, genetic variants associated with circulating IGF-1 and IGF-binding protein-3 (IGFBP-3) levels were identified and their association with breast cancer was examined with two-sample MR methods using genome-wide data from 122 977 cases and 105 974 controls. <h3>Results</h3> In the UK Biobank, after a median follow-up of 7.1 years, 4360 incident breast cancer cases occurred. In the multivariable-adjusted models corrected for regression dilution, higher IGF-1 concentrations were associated with a greater risk of breast cancer (HR per 5 nmol/l increment of IGF-1 = 1.11, 95% CI = 1.07–1.16). Similar positive associations were found by follow-up time, menopausal status, body mass index, and other risk factors. In the MR analyses, a 5 nmol/l increment in genetically-predicted IGF-1 concentration was associated with a greater breast cancer risk (odds ratio = 1.05, 95% CI = 1.01–1.10; <i>P</i> = 0.02), with a similar effect estimate for estrogen-positive (ER<sup>+</sup>) tumours, but no effect found for estrogen-negative (ER<sup>−</sup>) tumours. Genetically-predicted IGFBP-3 concentrations were not associated with breast cancer risk (odds ratio per 1-standard deviation increment = 1.00, 95% CI = 0.97–1.04; <i>P</i> = 0.98). <h3>Conclusion</h3> Our results support a probable causal relationship between circulating IGF-1 concentrations and breast cancer, suggesting that interventions targeting the IGF pathway may be beneficial in preventing breast tumorigenesis.
Abstract 14306: Patients With Stable Systolic Heart Failure and Renal Insufficiency: The Effects of Furosemide Dose Reduction on Renal Function and Clinical Status
Authors: Paul McKie, Lynn K Harstad, Sherry L Benike, John A Schirger, Alessandro Cataliotti, Horng C Chen
Journal: Circulation (2013)

Background: Furosemide (F) and other loop diuretics are mainstays in heart failure (HF) management. While essential in achieving euvolemia, increasing data suggests that excessive F may impair rena...
Abstract 18236: Perilipin 5 Links Lipid Droplets with Mitochondria
Authors: Hong Wong, Da-Wei Gong, Urrmila Sreenivasan, Andrew Saladino, Brian M Polster, William C Stanley, Carole Sztalryd
Journal: Circulation (2011)

Maintaining cellular lipid homeostasis is crucial to heart function, and is compromised in obesity-induced cardiomyopathy. Lipid droplets (LDs) play a central role in lipid homeostasis by mediating fatty acids (FA) storage in the form of triglyceride (TAG), lowering intracellular lipid levels that mediate cellular lipotoxicity. LD and mitochondrial function are intimately related but mechanisms of interaction have not been uncovered. Perilipin 5 (Plin5) is the newest perilipin protein coating LD surfaces and is highly expressed in heart. We investigated Plin5's role in interactions between mitochondria and LDs using a combination of cell culture and transgenic model studies. We have studied cardiomyocytes using live confocal imaging and electron microscopy analysis and found that Plin5 expression recruits mitochondria to the LD surface thru a C-terminal region. At the molecular level, Plin5 interacts with the key lipolytic proteins adipocyte triglyceride lipase and its co-lipase CGI-58, as determined by FRET and co-immunoprecipitation studies. At the metabolic level, we found that Plin5 regulates LD hydrolysis by limiting basal lipolysis but not after protein kinase a (pka) activation and that plin5 is a phoshorylated protein and a putative pka downstream target. Compared to control cells, plin5 expressing cells show (p&lt;0.05) decreased palmitate (PA) β-oxidation detected by cell respirometry and increased PA incorporation into TAG. These in vitro results suggest that Plin5 regulates cardiac LD hydrolysis and controls local FA flux to protect mitochondria against FA surge in physiological conditions. To investigate plin5 function in vivo, we obtained transgenic mice with heart-specific plin5 over-expression (αMHC-plin5). Preliminary results suggest that these mice have a strong cardiac lipid droplet phenotype. Hearts from αMHC-plin5 mice expressed at least 20-fold higher levels of plin5 and exhibit a 3.5- fold increase in TAG content versus non-transgenic littermate. These studies support a conclusion that Plin5 is a promising key gene in the pathways that efficiently couple the LD storage compartment to the mitochondria FA utilization compartment and will help unravel the underpinnings of cardiac cellular lipid homeostasis.
Effect of short course, high-dose valproic acid on proliferation in breast adenocarcinomas.
Authors: Adam Louis Cohen, Rachel Factor, Matthias Schabel, Andrea Bild, Theresa Louise Werner
Journal: Journal of Clinical Oncology (2013)

e13522 Background: Our in vitro and in vivo studies showed that single agent valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is effective in a subset of breast cancers. Whether VPA is effective as a single agent and what the optimal dosing would be are unknown. Methods: In an ongoing IRB-approved, window-of-opportunity study testing a genomic predictor of sensitivity to VPA (NCT01007695), we performed biopsies and DCE-MRI on women before and after seven days of escalating doses of VPA on untreated women with breast adenocarcinoma with an intact breast tumor. Within patient dose-escalation was done with a goal dose of 50 mg/kg. Proliferation was assessed with MIB-1 immunohistochemistry. Only correlative secondary endpoints are presented here. Results: Sixteen women have completed treatment and are evaluable. Total and free VPA levels on the last day of treatment averaged 136 µg/ml (range 15-242) and 30 µg/ml (range 1-90), respectively. Proliferation rate by MIB-1 decreased by and average of -7.25% (range +4% to -45%, p=0.04). The change in proliferation did not correlated with VPA levels, although only one of four women with VPA levels less than 100 µg/ml had a decrease in proliferation, compared to five of twelve women with VPA levels greater than 100 µg/ml. Four women had MIB-1 decreases of 10% or greater. Two women have had post-treatment biopsies with fibrosis similar to that seen with chemotherapy treatment effect. DCE-MRI parameters, including ktrans, vp, and kep, did not change significantly with VPA treatment or correlate with VPA levels. Conclusions: VPA as a single agent can reduce proliferation in a subset of women with breast cancers. Higher VPA levels are needed than those achieved at standard dose levels, but VPA levels by themselves do not predict effect. Other monitoring parameters, such as peripheral blood histone acetylation changes, or other predictors of benefit are needed. Clinical trial information: NCT01007695.
Drug safety profiling for assessment of drug combinations in oncology
Authors: S. N. Voss, A. Czarnecki
Journal: Journal of Clinical Oncology (2006)

15037 Background: It is important to understand the safety profile (SP)/toxicity of new drug regimens in oncology. We compared SPs of gemcitabine (Gem) + carboplatin (Carbo) in NSCLC with Gem alone and in different combinations and also tested the methodology of drug safety profiling (DSP). Methods: Spontaneous cases for the period of 1995–2005 were reviewed on the Lilly Safety Database (LSD). DSP was used to evaluate differences in the SPs of several combinations: Gem+Carbo in NSCLC, Gem+Carbo in ovarian cancer, Gem+ cisplatin (Cis) in NSCLC, Gem+Carbo in all indications, and Gem regardless of treatment regimen, for all indications. Frequencies of adverse events (AEs) for all MedDRA System Organ Classes (SOCs) were used for each regimen. In addition, the MedDRA Preferred Terms (PTs) were reviewed to detect potential safety signals. The numbers of AEs in different SOCs were assessed as proportions of the total reports for the Gem combinations in the LSD. Results: With the exception of the Investigations SOC, the proportions of AEs for patients treated for NSCLC with Gem+Carbo were consistent with those for patients treated for NSCLC with Gem+Cis and with Gem for all indications. However, the frequency in the Investigations SOC was consistent with that reported for Gem+Carbo in all indications (14.2% v. 12.0%). A greater frequency of AEs was seen in the Gastrointestinal Disorders SOC for patients treated with Gem+Carbo for ovarian cancer compared to patients treated with Gem+Carbo for NSCLC. The review of individual PTs for Gem+Carbo did not reveal any safety signals. Conclusions: The SP of Gem+Carbo in NSCLC using DSP showed similar patterns to all other Gem combinations with only some differences due to the indication. DSP is a useful tool in assessing the new drug combination treatments in existing or new indications. [Table: see text]
Ten-year improved survival in patients with multi-vessel coronary disease and poor left ventricular function following surgery: A retrospective cohort study
Authors: Ian G. Cummings, Gianluca Lucchese, Sheena Garg, Manish Soni, Akbar F. Majid, Nandor Marczin, Vasileios Panoulas, Shahzad G. Raja
Journal: International Journal of Surgery (2020)