tbuckley/cabot-search huggingface dataset:
The psychological impact of early prostate cancer: A prospective evaluation.
Authors: Hadas Dresler, Daniel Keizman, David Sarid, Debi Oren
Journal: Journal of Clinical Oncology (2020)

210 Background: Early prostate cancer is often considered as being associated with a good prognosis and quality of life. However, early prostate cancer research mainly focus on its medical aspects, rarely considering its psychological impact. We aimed to prospectively analyze the correlation between illness perception, quality of life (QOL) and psychological distress among prostate cancer patients, in comparison to healthy controls. Methods: Early prostate cancer patients and healthy controls were prospectively recruited through convenience sampling. Participants filled questionnaires of demographic, illness perception (IPQ-R), QOL (MOS SF-36) and anxiety and depression (HADS). We compared the illness perception, QOL and psychological distress between patients and healthy controls. Results: 51 early prostate cancer patients and 65 healthy men controls were included. Median age was 69. Patients and healthy participants differed in illness perception ['consequences' (p&lt;.001), 'emotional representations' (p&lt;.001)] and psychological distress (p&lt;.01). There was a correlation between the patient illness perception and QOL (p&lt;.05) and psychological distress (p&lt;.05). Among patients, the correlation between psychological distress and QOL was mediated by illness perception (p&lt;.05), while it was not among controls. Conclusions: Diagnosis of early prostate cancer may have a psychological impact. Among early prostate cancer patients, a correlation may exist between illness perception, and quality of life (QOL) and psychological distress. Our results emphasize the need to identify patient distress and to implement therapeutic interventions also in a disease which usually is associated with a good prognosis.
Theodore Michael Strouthidis
Authors: Stuart Bruce, James Dennison
Journal: BMJ (2020)

Theodore Michael Strouthidis’s first post after house jobs in Alexandria was as a medical officer on American oil rigs in Libya. He moved to the UK in 1965 and met his future wife, Vicky, during his first week as a house physician at St Helier Hospital. He applied for the post of cardiology registrar …
Comparative efficacy of local versus systemic salvage therapies for recurrent prostate cancer after primary radiotherapy.
Authors: Glenn Bauman, Keyue Ding, Joseph Chin, Alessandra Iaboni, Laurence Klotz, David P. Dearnaley, Eric M. Horwitz, Juanita M. Crook, Christopher J. O'Callaghan
Journal: Journal of Clinical Oncology (2020)

221 Background: We sought to compare two common salvage strategies for radio-recurrent prostate cancer: androgen deprivation therapy (ADT: PR7 RCT NCT00003653) or local salvage ablation using cryotherapy (CRYO: single institution study Williams, Eur Urol. 2011;60(3):405). Methods: Pre-salvage therapy prognostic variables common to the two datasets (Gleason score at initial treatment, time from original RT, use of ADT at time of original RT, PSA at time of salvage, patient age) were used for propensity matching between patients from previously published ADT (1) and CRYO (2) datasets. Progression free survival (PFS, defined as time from initial treatment to development of castrate resistance or death); Disease Specific Survival (DSS, defined as time from salvage to prostate cancer related death) and Overall Survival (OS, defined as time from salvage to death from any cause) were compared between the propensity matched cohorts using Log-Rank and Cox PH regression statistics. Raw linear propensity scores included in the PH model to account for residual variability. A planned subset analysis examined the effect of neoadjuvant ADT among the CRYO cohort (no CRYO patients had adjuvant ADT). Results: Overall, 1119/1386 (ADT) and 172/187 (CRYO) patients were included in the propensity matched analysis. Median follow up was 6.7 yrs (ADT) and 18.7 yrs (CRYO). Median PFS (95% CI) was 10.7 yrs (9.5, 12.3) for CRYO vs. 7.0 yrs (6.1, 10.0) for ADT (HR 0.63 (0.44, 0.89), p = 0.009). Median OS was also longer for CRYO vs. ADT: 12.3 (11.0, 13.8) vs. 10.2 (9.4, not reached) yrs (HR 0.69; p = 0.02). 10 year DSS event rate was 16.5% CRYO vs. 18.5% ADT but was not statistically different. Neoadjuvant ADT did not affect outcomes in CRYO. Conclusions: A 3-year PFS and 2-year OS benefit was noted for the CRYO vs. ADT cohorts while no difference was noted in DSS. Potential explanations include residual bias not corrected for in the propensity scoring, variable follow-up duration, adverse effects from differing cumulative exposure to ADT or a combination of these factors. Prospective comparisons are required to control for these potential biases and compare other important outcomes such as side effects and quality of life.
Lymphocyte Transformation Test Effectivity based on the Antigen presenting Cells Employed in Immediate Allergic Reactions to Betalactams
Authors: Tahia Fernandez, Ruben Fernández-Santamaría, Gador Bogas Herrera, MarÃa Salas, Alba Rodriguez-Nogales, Maria Francisca Palomares Jerez, Maria Rodriguez-Sanchez, Ana Molina Bueno, Maria Vega, Cristobalina Mayorga, Maria Torres Jaen
Journal: Journal of Allergy and Clinical Immunology (2020)
Author Correction: Human somatic cell mutagenesis creates genetically tractable sarcomas
Authors: Sam D. Molyneux, Paul D. Waterhouse, Dawne Shelton, Yang W. Shao, Christopher M. Watling, Qing-Lian Tang, Isaac S. Harris, Brendan C. Dickson, Pirashaanthy Tharmapalan, Geir K. Sandve, Xiaoyang Zhang, Swneke D. Bailey, Hal Berman, Jay S. Wunder, Zsuzsanna Izsvák, Mathieu Lupien, Tak W. Mak, Rama Khokha
Journal: Nature Genetics (2020)
Patterns of sensitization to inhalant allergens, Ole e 1 and Ole e 7 in children and adolescents born in the same area with different origin.
Authors: Maria Somoza Alvarez, Laura Victorio Puche, Natalia Blanca-Lopez, Francisco Javier Ruano Pérez, Maria Vázquez de La Torre Gaspar, Isabel Torres Rojas, Jose Damian Lopez Sanchez, Maria Garrido-Arandia, Laura Martín-Pedraza, Araceli Diaz Perales, M Teresa Villalba, Gabriela Canto Díez, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2020)
Is body mass index (BMI) associated with favorable outcomes in metastatic renal cell carcinoma (mRCC) treated with nivolumab? An ancillary study of the NIVOREN-GETUG AFU-26 trial.
Authors: Emeline Colomba, Cécile Dalban, Aude Flechon, Christine Chevreau, Gwenaelle Gravis, Constance Thibault, Brigitte Laguerre, Philippe Barthelemy, Delphine Borchiellini, Marine Gross Goupil, Lionnel Geoffrois, Frederic Rolland, Antoine Thiery-Vuillemin, Florence Joly, Sylvain Ladoire, Florence Tantot, Bernard Escudier, Laurence Albiges
Journal: Journal of Clinical Oncology (2020)

630 Background: Adipose tissue might affect response to immune checkpoint inhibitors (CPI) in cancer patients (pts). Higher BMI is associated with improved outcomes in mRCC under VEGFR TKI but BMI impact under CPI remains unclear. Methods: We analysed BMI in the NIVOREN GETUG AFU 26 study, a prospective study that evaluated the safety and efficacy of nivolumab in mRCC after failure of prior VEGFR inhibitors. We investigated the association between BMI, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). BMI (weight/height 2) was classified according to the World Health Organization (WHO) categories: underweight as BMI &lt; 18.5; normal weight as 18.5 ≤ BMI ≤ 24.9; overweight as 25 ≤ BMI ≤ 29.9 and obesity as BMI ≥ 30. Survival distributions were compared using a Log-Rank test, supported by uni- and multivariate Cox regressions to estimate the Hazard Ratio (HR) and its 95% CIs. Median follow-up (FU) and the 95% CI were calculated using the reverse Kaplan–Meier method. Results: Overall, 708 pts were included in the BMI analysis: 20 pts (2.8%) were underweight, 322(45.5%) had normal weight, 255(36.0%) were overweight and 111(15.7%) obese. Median age was 64 years, 77.3% were male, performance status was ≥ 80% in 81.2%, and IMDC risk group was good, intermediate and poor in respectively 18.2%, 56.4%, 25.4%. Outcomes according to BMI is detailed in table, median FU was 23.9 months (95%CI 23.0-24.5). BMI adjusted to known prognostic factors was not significant in the multivariate analysis. Conclusions: Higher BMI patients seems to have better outcomes with nivolumab in mRCC. Further characterisation is on-going to explore the relation of BMI with established risk factor in pts under CPI in mRCC.[Table: see text]
Ribociclib (RIBO) + letrozole (LET) in male patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) and no prior endocrine therapy (ET) for ABC: Preliminary subgroup results from the phase IIIb CompLEEment-1 trial
Authors: C. Zamagni, M. Campone, I. Kudryavcev, U. Brown-Glaberman, P.H. Cottu, A. Ring, J. Lu, M. Martín, M. De Laurentiis, K. Zhou, J. Wu, L. Menon, H.A. Azim
Journal: Annals of Oncology (2018)
Intraesophageal administration of oxazolone to skin-sensitized mice results in experimental eosinophilic esophagitis‏ ‏resembling human disease
Authors: Shmuel Avlas, Michal Itan, Avishay Dolitzky, Chen Varol, Marc Rothenberg, Ariel Munitz
Journal: Journal of Allergy and Clinical Immunology (2020)
Abstract 20051: S-nitrosoglutathione Improves Post-resuscitation Cerebral Perfusion and Inhibits Neuronal Apoptosis via Reciprocating eNOS-NO Signaling
Authors: Wei-Tien Chang, Woan-Yi Wang, Min-Hsuan Hsu, Chih-Hung Wang, Min-Shan Tsai, Hsiao-Ju Cheng, Chien-Hua Huang, Wen-Jone Chen
Journal: Circulation (2017)

Introduction: Cerebral vasoconstriction is usually encountered in the post-resuscitation phase, which adversely affects neurological prognosis. Nitric oxide (NO) is an important signaling molecule ...
Associations of fat and carbohydrate intake with cardiovascular disease and mortality: prospective cohort study of UK Biobank participants
Authors: Frederick K Ho, Stuart R Gray, Paul Welsh, Fanny Petermann-Rocha, Hamish Foster, Heather Waddell, Jana Anderson, Donald Lyall, Naveed Sattar, Jason M R Gill, John C Mathers, Jill P Pell, Carlos Celis-Morales
Journal: BMJ (2020)

Abstract Objective To investigate the association of macronutrient intake with all cause mortality and cardiovascular disease (CVD), and the implications for dietary advice. Design Prospective population based study. Setting UK Biobank. Participants 195 658 of the 502 536 participants in UK Biobank completed at least one dietary questionnaire and were included in the analyses. Diet was assessed using Oxford WebQ, a web based 24 hour recall questionnaire, and nutrient intakes were estimated using standard methodology. Cox proportional models with penalised cubic splines were used to study non-linear associations. Main outcome measures All cause mortality and incidence of CVD. Results 4780 (2.4%) participants died over a mean 10.6 (range 9.4-13.9) years of follow-up, and 948 (0.5%) and 9776 (5.0%) experienced fatal and non-fatal CVD events, respectively, over a mean 9.7 (range 8.5-13.0) years of follow-up. Non-linear associations were found for many macronutrients. Carbohydrate intake showed a non-linear association with mortality; no association at 20-50% of total energy intake but a positive association at 50-70% of energy intake (3.14 v 2.75 per 1000 person years, average hazard ratio 1.14, 95% confidence interval 1.03 to 1.28 (60-70% v 50% of energy)). A similar pattern was observed for sugar but not for starch or fibre. A higher intake of monounsaturated fat (2.94 v 3.50 per 1000 person years, average hazard ratio 0.58, 0.51 to 0.66 (20-25% v 5% of energy)) and lower intake of polyunsaturated fat (2.66 v 3.04 per 1000 person years, 0.78, 0.75 to 0.81 (5-7% v 12% of energy)) and saturated fat (2.66 v 3.59 per 1000 person years, 0.67, 0.62 to 0.73 (5-10% v 20% of energy)) were associated with a lower risk of mortality. A dietary risk matrix was developed to illustrate how dietary advice can be given based on current intake. Conclusion Many associations between macronutrient intake and health outcomes are non-linear. Thus dietary advice could be tailored to current intake. Dietary guidelines on macronutrients (eg, carbohydrate) should also take account of differential associations of its components (eg, sugar and starch).
Harmonization and Standardization of Panel-Based Tumor Mutational Burden Measurement: Real-World Results and Recommendations of the Quality in Pathology Study
Authors: Albrecht Stenzinger, Volker Endris, Jan Budczies, Sabine Merkelbach-Bruse, Daniel Kazdal, Wolfgang Dietmaier, Nicole Pfarr, Udo Siebolts, Michael Hummel, Sylvia Herold, Johanna Andreas, Martin Zoche, Lars Tögel, Eugen Rempel, Jörg Maas, Diana Merino, Mark Stewart, Karim Zaoui, Matthias Schlesner, Hanno Glimm, Stefan Fröhling, Jeff Allen, David Horst, Gustavo Baretton, Claudia Wickenhauser, Markus Tiemann, Matthias Evert, Holger Moch, Thomas Kirchner, Reinhard Büttner, Peter Schirmacher, Andreas Jung, Florian Haller, Wilko Weichert, Manfred Dietel
Journal: Journal of Thoracic Oncology (2020)
BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers
Authors: Florence Coussy, Rania El-Botty, Sophie Château-Joubert, Ahmed Dahmani, Elodie Montaudon, Sophie Leboucher, Ludivine Morisset, Pierre Painsec, Laura Sourd, Léa Huguet, Fariba Nemati, Jean-Luc Servely, Thibaut Larcher, Sophie Vacher, Adrien Briaux, Cécile Reyes, Philippe La Rosa, Georges Lucotte, Tatiana Popova, Pierre Foidart, Nor Eddine Sounni, Agnès Noel, Didier Decaudin, Laetitia Fuhrmann, Anne Salomon, Fabien Reyal, Christopher Mueller, Petra Ter Brugge, Jos Jonkers, Marie-France Poupon, Marc-Henri Stern, Ivan Bièche, Yves Pommier, Elisabetta Marangoni
Journal: Science Translational Medicine (2020)

Triple-negative breast cancer xenografts with BRCAness, high expression of SLFN11, and RB1 loss are highly sensitive to topoisomerase I inhibitors.
Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods
Authors: Canrong Wu, Yang Liu, Yueying Yang, Peng Zhang, Wu Zhong, Yali Wang, Qiqi Wang, Yang Xu, Mingxue Li, Xingzhou Li, Mengzhu Zheng, Lixia Chen, Hua Li
Journal: Acta Pharmaceutica Sinica B (2020)

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.
Prevention of Falls in Community-Dwelling Older Adults
Authors: David A. Ganz, Nancy K. Latham
Journal: New England Journal of Medicine (2020)

Patients should be asked annually about falls in the past year to identify those at high risk for future falls. The risk of falling can be reduced by exercise programs focused on balance and strength training and, among persons at high risk, by assessing a standard set of risk factors for falls and addressing modifiable ones.
Analysis of single nucleotide polymorphisms in coding and non-coding regions of human BRCA1 and BRCA2 genes
Authors: Silvia Casadei, Ian Seymour, Simonetta Rosato, Elena Lucchi, Fabio Falcini, Dino Amadori, Daniele Calistri
Journal: Cancer Research (2004)

1315  Breast cancer susceptibility is mainly due to inactivating mutations in the highly predisposing BRCA1 and BRCA2 genes, but several common low penetrance alleles may account for the residual non-BRCA1/BRCA2 familial aggregation. We aimed to investigate the association of some polymorphisms in BRCA1 and BRCA2 genes and the presence of or the predisposition to breast cancer. The prevalence of 9 BRCA1 and 11 BRCA2 sequence variants located in coding and non-coding regions of both genes was analyzed in 4 subgroups of healthy women and patients belonging to high and low risk families. The presence of individual polymorphisms varied from a complete absence to more than 70% in the different subgroups. We identified two BRCA2 polymorphisms, BRCA2 N372H and IVS21-66T>C, which significantly correlate with the presence of familial breast cancer. In fact, within the high risk families, the frequency of the N372H polymorphism was significantly higher in affected (53.5%) than in unaffected women (35%) (Χ2=4.089; P C polymorphism was more frequent in patients (75%) than in healthy women (56.7%) (Χ2=4.089; P C were alternately present on at least nine different BRCA2 haplotypes and were thus not dependent on a specific haplotype. In fact, due to the high variability within the BRCA2 gene sequence, several minor haplotypes never exceeded 20% allelic frequency within each subgroup. Our data are in agreement with previous results on British and Australian case series which demonstrated that the N372H polymorphism of BRCA2 is responsible for an increased risk of breast cancer in the general population. Our results represent the first report on the association between the amino acid substitution-generating polymorphism N372H and the intronic variant polymorphism IVS21-66T>C, and the increased risk in women with a strong family history of breast cancer in the Italian population. In conclusion, our data seem to indicate that common polymorphisms could represent low penetrance alleles and play a role, in addition to mutations, in the predisposition to and development of breast cancer, thus refining the definition of at risk individuals and increasing the efficacy of mutation analysis.
Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1
Authors: Xiaohong Hong, Na Liu, Yelin Liang, Qingmei He, Xiaojing Yang, Yuan Lei, Panpan Zhang, Yin Zhao, Shiwei He, Yaqin Wang, Junyan Li, Qian Li, Jun Ma, Yingqin Li
Journal: Molecular Cancer (2020)

Abstract Background Circular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods Here, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity. Results We identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients. Conclusions Our findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients.
PRINT: Prostate cancer intensive, non-cross reactive therapy for CRPC—Early observations of efficacy.
Authors: Bobby Chi-Hung Liaw, Che-Kai Tsao, Matt D. Galsky, Richard Lorne Bakst, Robert Stewart, Richard Stock, William K. Oh
Journal: Journal of Clinical Oncology (2020)

e17575 Background: Optimal sequencing of therapeutic agents in mCRPC remains debated, but the standard approach is to treat with one agent until resistance is met before switching. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat intrinsic heterogeneity, delay or prevent drug resistance, and minimize treatment toxicity. Methods: Patients received treatment with 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 50 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month regimen, patients are followed on ADT alone. Primary endpoint for the study is PSA or radiographic time to progression (TTP). Results: From 3/2017 to 1/2020, 38 of 40 planned men with mCRPC were enrolled, 28 patients have completed the 9-month study regimen and evaluable for TTP analysis. With median follow up of 54+ weeks, median time to PSA progression after therapy completion is 14.7+ weeks (95%CI; 5.5-23.9+ weeks). PSA response rates showed successive improvements with each sequential treatment module (Table). Eight patients (21.1%) continue on post-study surveillance with ADT alone, two of which have remained off any mCRPC agents for over a year (82+ weeks, 79+ weeks). In patients needing to restart therapy, experience with efficacy and tolerability of each agent while on the study, has helped inform subsequent mCRPC drug selection. The study regimen is well-tolerated, with few grade 3/4 AE’s: hyperglycemia (15.8%), diarrhea (5.3%), anemia (2.6%), fatigue (2.6%), neutropenia (2.6%), and thrombocytopenia (2.6%). Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen demonstrates significant antitumor benefits, with potential for long-term suppression of disease. Further longitudinal follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160 . [Table: see text]
Points based immigration system risks pushing social care sector “over the edge”
Authors: Abi Rimmer
Journal: BMJ (2020)

Changes to the immigration system could prevent some NHS and social care staff from being able to work in the UK, experts have warned.

The government has announced a points based immigration system that will take effect in the UK from 1 January 2021, although the Migration Advisory Committee (MAC) advises against such a system.1

The government said that the new system would end free movement and assign points for specific skills, qualifications, and salaries or professions and that visas will be awarded only to people who gain enough points.

All applicants will be required to have a job offer, and the minimum salary …