tbuckley/cabot-search huggingface dataset:
A comprehensive systematic review of the impact of dietary factors during pregnancy on childhood atopic outcomes
Authors: Carina Venter, Hasan Arshad, Kate Maslin, Rosan Meyer, Marion Groetch, Michaela Palumbo, Lauren Vanderlinden, Miriam BenAbdallah, Matthew Greenhawt, David Fleischer
Journal: Journal of Allergy and Clinical Immunology (2020)
The public health effects of interventions similar to basic income: a scoping review
Authors: Marcia Gibson, Wendy Hearty, Peter Craig
Journal: The Lancet Public Health (2020)

Universal, unconditional basic income is attracting increasing policy and academic interest. Income is a key health determinant, and a basic income could affect health through its effect on other determinants, such as employment. However, there is little evidence of its potential effects on public health, because no studies of interventions which meet the definition of basic income have been done. However, there is evidence from studies of interventions with similarities to basic income. Therefore, we aimed to identify these studies and to consider what can be learned from them about the potential effects of such interventions on health and socioeconomic outcomes. We did a systematic scoping review of basic income-like interventions, searching eight bibliographic and eight specialist databases from inception to July, 2019, with extensive hand searching. We included publications in English of quantitative and qualitative studies done in upper-middle-income or high-income countries, of universal, permanent, or subsistence-level interventions providing unconditional payments to individuals or families. We sought to identify the range of outcomes reported by relevant studies, and report health, education, employment, and social outcomes. We extracted and tabulated relevant data and narratively reported effects by intervention and outcome. We identified 27 studies of nine heterogeneous interventions, some universal and permanent, and many evaluated using randomised controlled trials or robust quasi-experimental methods. Evidence on health effects was mixed, with strong positive effects on some outcomes, such as birthweight and mental health, but no effect on others. Employment effects were inconsistent, although mostly small for men and larger for women with young children. There was evidence of spill-over effects in studies measuring effects on large populations. In conclusion, little evidence exists of large reductions in employment, and some evidence suggests positive effects on some other outcomes, including health outcomes. Evidence for macro-level effects is scarce. Quasi-experimental and dynamic modelling approaches are well placed to investigate such effects.
Assisted dying: RCGP continues to oppose change in law after polling members
Authors: Abi Rimmer
Journal: BMJ (2020)

The Royal College of General Practitioners (RCGP) will continue to oppose a change in the law on assisted dying, having conducted a survey of its members.

The decision was ratified by the college’s governing council on 21 February. The RCGP said that 6674 members responded to its survey on assisted dying, a 13.47% response rate.

Of those who responded, 47% (3144) said that the RCGP should oppose a change in the law on assisted dying. A further 40% of respondents (2684) said that the RCGP should support a change in the law on assisted dying provided a regulatory framework and appropriate safeguarding processes are in place, 11% (701) said that the college should have a neutral position, and 2% (145) abstained.

The RCGP Council agreed that the survey results did not support a change in …
Predicting toxicity-related docetaxel discontinuation and survival in metastatic castration-resistant prostate cancer (mCRPC) using open phase III trial data.
Authors: Anish B. Parikh, Alberto Martini, John Sfakianos, Matt D. Galsky, William K. Oh, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2020)

75 Background: Docetaxel (D) is widely used in mCRPC, however its optimal use remains unclear in the current treatment (tx) landscape. Biomarkers to predict D toxicity may help inform tx selection. Methods: Through Project Data Sphere, we pooled patient (pt) data from the control arms of three frontline mCRPC trials: ASCENT2, VENICE, and MAINSAIL. Tx in each control arm consisted of D 75mg/m2 every 21 days + prednisone 5mg twice/day. The primary outcome was occurrence of toxicity-related D discontinuation (TRDD). Reasons for D discontinuation were recorded and demographic/clinical data were considered in a competing risks regression (CRR) to develop a model to predict TRDD. Cumulative incidence (CI) of TRDD was estimated after accounting for the occurrence of competing events (death or progression). This model was used to build a risk calculator to predict TRDD, the output of which was used in a classification and regression tree (CART) to identify 3 risk groups. Overall survival (OS) for the pooled cohort and for each risk group was assessed via the Kaplan-Meier (KM) method. Results: 1568/1600 pts had complete data and were studied. 41.4% died from any cause during the trials; median follow-up for survivors was 12.1 months (mos). Median OS for the entire cohort was 21 mos. CRR yielded the following significant factors that were included in the predictive model and risk calculator: age, ECOG performance status, AST, bilirubin, use of analgesics, and diagnoses of diabetes and chronic kidney disease. Pooled CI of TRDD was 19% after accounting for competing events (death, 474 pts; progression, 59 pts) within 12 mos of starting tx. CART analysis defined the risk groups as low (model-derived TRDD risk ≤24%), intermediate (25-64%), and high (≥65%). In each risk group, probability of TRDD during tx was 14%, 58%, and 79%, and median OS was 24 mos, 20 mos, and 13 mos, respectively (p&lt;0.001). Conclusions: Tx selection in mCRPC remains a challenge. Our model can help clinicians balance D toxicity and efficacy in order to make better-informed decisions.
Hyperactive PI3Kδ predisposes naive T cells to activation via aerobic glycolysis programs
Authors: Yanjun Jia, Qiuyun Yang, Yanping Wang, Wenyan Li, Xuemei Chen, Tao Xu, Zhirui Tian, Minxuan Feng, Liang Zhang, Wenjing Tang, Na Tian, Lina Zhou, Wenxia Song, Xiaodong Zhao
Journal: Cellular and Molecular Immunology (2020)
INTREPId (INTermediate Risk Erection PreservatIon Trial): A randomized trial of radiation therapy and darolutamide for prostate cancer.
Authors: Martin T. King, David R. Wise, Lawrence M. Scala, Neil M. Mariados, Amanda Whitbeck, Mark Pomerantz, Sharon Bober, Elai Davicioni, Glenn Bubley, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2020)

TPS384 Background: Men with intermediate risk prostate cancer are often recommended external beam radiation therapy (EBRT) with or without 4-6 months of androgen deprivation therapy (ADT). However, ADT can be associated with prolonged erectile dysfunction due to delayed testosterone recovery. Darolutamide is a second-generation androgen receptor with low blood-brain barrier penetration. We hypothesize that men who receive Darolutamide with RT rather than ADT with RT are able to achieve surrogate PSA endpoints indicative of long-term disease control while preserving erectile function. Methods: This is an open label, phase 2B, multi-center, randomized controlled trial. Eligibility criteria include intermediate risk prostate cancer, good erectile quality per the EPIC-26 questionnaire, and archival tissue suitable for submission to Decipher Biosciences (San Diego, CA). Men will be stratified by Decipher score (low/intermediate vs high), RT modality (EBRT vs Brachytherapy/stereotactic body radiation therapy/combination RT), and age (&gt;65 vs &lt;65). Men with a Decipher high score will be strongly encouraged to undergo extreme RT dose-escalation. The primary endpoint is PSA nadir ≤ 0.5 within 6 months from end of treatment (EOT). The hierarchical endpoint is maintenance of good erectile quality at 3 months from EOT. The key secondary endpoint is interval to PSA failure at 3 years from EOT. Endpoints will be analyzed in a fixed-sequence hierarchical method. 220 patients will be accrued over 3 years. Non-inferiority margins for the primary and key secondary endpoints are 9% (90% power) and 4.9% (80% power), respectively. Men will be randomized to 6 months of GnRH agonist plus bicalutamide 50 mg daily with RT or 6 months of darolutamide 600 mg twice daily with RT. Assessments will occur at baseline, during treatment, EOT, and at regularly scheduled intervals up to 36 months from EOT. Correlative endpoints include discovering transcriptomic and radiomic predictors of response. Clinical trial information: NCT04025372.
Proteome Instability Is a Therapeutic Vulnerability in Mismatch Repair-Deficient Cancer
Authors: Daniel J. McGrail, Jeannine Garnett, Jun Yin, Hui Dai, David J.H. Shih, Truong Nguyen Anh Lam, Yang Li, Chaoyang Sun, Yongsheng Li, Rosemarie Schmandt, Ji Yuan Wu, Limei Hu, Yulong Liang, Guang Peng, Eric Jonasch, David Menter, Melinda S. Yates, Scott Kopetz, Karen H. Lu, Russell Broaddus, Gordon B. Mills, Nidhi Sahni, Shiaw-Yih Lin
Journal: Cancer Cell (2020)
NAD(P)H: Quinone oxidoreductase (NQO1) and catalase expression in nonseminomatous germ cell tumors.
Authors: Neda Hashemi-Sadraei, Nabil Adra, Kenneth A. Kessler, Muhammad T. Idrees, Lawrence Einhorn, David A. Boothman
Journal: Journal of Clinical Oncology (2020)

413 Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme which detoxifies quinones and reduces oxidative stress. NQO1 is expressed in multiple tumor types at levels up to 200-fold above normal tissue, including in breast, pancreatic, and non-small cell lung cancers. NQO1 bioactivatable drugs have the potential to deliver tumor-selective DNA damage and cell death by exploiting the elevation of NQO1. Alterations in catalase expression can cause marked cytoprotection. The ratio of NQO1:catalase activities is presumed to be a predictive marker for therapeutic activity of NQO1 bioactivatable drugs. There is no data available on NQO1 and catalase expression in germ cell tumors. Methods: Patients with germ cell tumor who underwent orchiectomy/tumor resection between January 2016 and December 2018 were identified from the Indiana University Melvin and Bren Simon Cancer Center database. Patients with non-seminomatous germ cell tumor of testis or primary mediastinal non-seminomatous germ cell tumor were selected. Immunohistochemistry staining for NQO1 and catalase was performed on tumor tissue. Results: NQO1 and catalase expression were assessed in 16 patients. Fifteen of 16 tumors stained positive for NQO1, 13 of which were moderately to strongly positive. Conversely, the majority of tumors were catalase deficient or only mildly positive for catalase. The details of the Immunostaining is summarized in the table below. Conclusions: Non-seminomatous germ cell tumors appear to have overexpression of NQO1 and deficiency of catalase. NQO1 bioactivatable agents could be beneficial in treating patients with refractory non-seminomatous germ cell tumors.[Table: see text]
Anti–PD-1 treatment impairs opioid antinociception in rodents and nonhuman primates
Authors: Zilong Wang, Changyu Jiang, Qianru He, Megumi Matsuda, Qingjian Han, Kaiyuan Wang, Sangsu Bang, Huiping Ding, Mei-Chuan Ko, Ru-Rong Ji
Journal: Science Translational Medicine (2020)

PD-1 regulates opioid signaling in primary sensory and spinal cord neurons and plays a critical role in opioid antinociception.
Genetic Association between CYSLTR2 Polymorphisms and Nonsteroidal Anti-inflammatory Drugs-induced urticaria/angioedema
Authors: Raquel Jurado Escobar, Melanie Pareja-MartÃn, Inmaculada Doña, Natalia Perez-Sanchez, James Perkins, Gador Bogas Herrera, Joan Bartra, Maria ISIDORO GARCÍA, Jose Laguna, Cristobalina Mayorga, Maria Torres Jaen, Jose Cornejo-Garcia
Journal: Journal of Allergy and Clinical Immunology (2020)
Atezolizumab (atezo) therapy for upper tract (UT) urothelial carcinoma (UC): Subgroup analysis of the single-arm international SAUL study in pretreated locally advanced/metastatic urinary tract carcinoma.
Authors: Cora N. Sternberg, Yohann Loriot, Rosa Tambaro, Consuelo Buttigliero, Franco Morelli, Zsuzsanna Papai, Margitta Retz, Andrea Necchi, Michiel Simon Van Der Heijden, Guy Faust, Andres Felipe Cardona Zorrilla, Nuria Lainez, Stefano Panni, Olatz Etxaniz, Laurence Krieger, Maria Jose José Mendez Vidal, Maartje Los, Sabine de Ducla, Simon Fear, Axel Stuart Merseburger
Journal: Journal of Clinical Oncology (2020)

488 Background: UTUC is rarer than bladder UC and typically responds poorly to standard chemotherapy. Analysis of 220 biomarker-evaluable atezo-treated patients (pts) in phase II/III trials suggested worse outcomes in UT vs lower tract UC [Galsky, ESMO 2018]. We explored clinical outcomes in pts with UTUC (renal pelvis or ureter) treated with atezo in the SAUL study. Methods: The single-arm SAUL study (NCT02928406) [Sternberg, Eur Urol 2019] enrolled a broader pt population, including pts with poor clinical characteristics and/or immune-mediated conditions, more representative of real-world practice than typically enrolled in randomized phase III immunotherapy trials. Pts with urinary tract carcinoma received atezo 1200 mg q3w until disease progression/unacceptable toxicity. Baseline characteristics, safety and efficacy were analyzed in subgroups of pts with UTUC (subdivided into renal pelvis or ureter UC) vs bladder UC. Results: Baseline characteristics in the 4 subgroups were generally similar, except for a numerically lower proportion of pts with 0 prior lines of therapy for metastatic disease in the UTUC vs bladder UC subgroup (30% vs 41%). Treatment exposure, safety and efficacy are shown below. Conclusions: These exploratory analyses of SAUL showed very similar efficacy and safety in UT vs bladder UC. This provides reassurance that atezo is active and has an acceptable safety profile in pts with UTUC, who are generally expected to have worse outcomes than bladder UC pts. Clinical trial information: NCT02928406 . [Table: see text]
Association of myeloid suppressor cells with resistance to checkpoint blockade immunotherapy in urothelial carcinoma.
Authors: Debasish Sundi, Megan Christina Duggan, Himanshu Savardekar, Hyunwoo Kwon, Steven Sun, Brooke Benner, Mallory DiVincenzo, Cheryl T. Lee, Robert S. Svatek, William Edgar Carson
Journal: Journal of Clinical Oncology (2020)

559 Background: Myeloid immune cells such as myeloid derived suppressor cells (MDSC) and tumor associated macrophages (TAM) have been hypothesized to cause resistance to immune checkpoint blockade (ICB). This is a pressing clinical problem for patients with bladder cancer. Here we determined if we could identify immune cells associated with resistance to ICB in the BBN963 mouse model, and if we could identify therapeutic strategies to target those same suppressor immune cells from patients with bladder cancer. Methods: BBN963 subcutaneous allografts were established in C57BL6/J mice. Response to anti-PD-L1 ICB was classified as partial or complete response according to RECIST criteria. Immune cell subsets with the tumors was evaluated by gene expression profiling and flow cytometry. Peripheral blood from patients with bladder cancer was collected under an IRB-approved protocol. MDSC were purified by flow sorting (CD11b + CD33 + HLA-DR low/neg ) and screened for viability (Annexin-V staining) after 24 hours of exposure to a panel potential MDSC inhibitors. Results: 16/22 (72%) subjects met criteria for partial or complete response, while 6/22 (28%) were classified as anti-PD-L1 non-responders. Mice in the control group had a 0/10 (0%) response to isotype control (IgG) treatment. Monocytic MDSC (CD11b + Ly6C + ) were much more frequent among the intratumoral CD45 + cells of non-responding subjects as compared to control mice. Nanostring immune panel gene expression profiling revealed that combination treatment of tumor bearing mice with anti-PD-L1 plus ibrutinib (a putative MDSC inhibitor) decreased mRNA biomarkers of tumor-infiltrating macrophages. In vitro screening of patient-derived peripheral blood mononuclear cells showed that an inhibitor of the bromodomain and extraterminal domain (BET) family BRD4 specifically decreased MDSC viability. Conclusions: Monocytic MDSC appear to be associated with resistance to anti-PD-L1 ICB in a new murine model. Analysis of MDSC from patients with bladder cancer suggests that these myeloid suppressor cells can be specifically targeted.
TMPRSS2: ERG expression in prostate cancer—Imaging and clinicopathological correlations.
Authors: Vittorio Fasulo, Massimo Lazzeri, Marinella Corbetta, Marco Paciotti, Davide Maffei, Giulia Soldà, Luigi Domanico, Nicola Frego, Federica Regis, Pietro Diana, Rosanna Asselta, Nicolo' Buffi, Paolo Casale, Alberto Saita, Chiara Chiereghin, Giovanni Lughezzani, Monica Zuradelli, Rodolfo Hurle, Stefano Duga, Giorgio Ferruccio Guazzoni
Journal: Journal of Clinical Oncology (2020)

284 Background: The TMPRSS2:ERG gene fusion (T:E) is found in up to 70% of prostate cancers (PCa) and results in androgen dependent overexpression of ERG, promoting tumor growth. The early identification of T:E may be helpful even in low-risk PCa. Although T:E can be non-invasively detected in urine, its correlation with new imaging tools (MRI and high-frequency ultrasound) and clinical outcome remains vague.This study investigates T:E expression in patients scheduled for random/software-assisted MRI or micro-ultrasound (29Mhz) fusion biopsy. Methods: This is a prospective cohort study in patients with suspected PCa enrolled between 2016 and 2019, approved by local authorities with Prot. N. 336/19, 14/05/2019. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they had ³1 suspicious lesion (PI-RADS V.2 &gt;2) at mpMRI or PRIMUS &gt;2 at MICRO-US. For each patient, 1 prostatic core from the highest PI-RADS or PRIMUS lesion was collected for T:E analysis (a core from the right lobe in negative patients). Histological analyses were performed by experienced genitourinary pathologists. RNA was extracted from a dedicated fresh biopsy and RT-PCR was performed with different primer couples to detect the most frequent T:E fusions. All amplified products were checked by sequencing. Results: The cohort consists of 92 patients (median PSA 7.13 ng/ml, IQR 5.25-11.04 - average age 65ys), 81 with a diagnosis of PCa after biopsy. mpMRI was performed on 63 (68.5%) patients and was positive in 58 (92%), who underwent fusion biopsy. T:E fusion transcripts were detected in 23.5% of individuals with a diagnosis of PCa. Among patients positive for T:E, those analyzed by MRI were 100% positive (73% PI-RADS ≥4), those analyzed by MICRO-US were 83% positive. Sensitivity of the T:E assay for any PCa was 23.5%, specificity 100%, with negative and positive predicting values of 15% and 100%. There was no correlation between T:E and family history, PSA, PIRADS, PRI-MUS and Gleason score. Conclusions: Our finding showed a 100% of specificity making T:E an attractive tool for early cancer detection. In the future, identification of T:E in semen could represent a screening test for clinical stratification of patients with suspected PCa.
The role of kidney transplantation as a component of integrated care for chronic kidney disease
Authors: Philip J. O'Connell, Mark Brown, Tak Mao Chan, Rolando Claure-Del Granado, Simon J. Davies, Somchai Eiam-Ong, Mohamed H. Hassan, Kamyar Kalantar-Zadeh, Adeera Levin, Dominique E. Martin, Elmi Muller, Shahrzad Ossareh, Irma Tchokhonelidze, Michele Trask, Ahmed Twahir, Anthony J.O. Were, Chih-Wei Yang, Alexander Zemchenkov, Paul N. Harden
Journal: Kidney International Supplements (2020)
Assessment of Expert-Level Automated Detection of <i>Plasmodium falciparum</i> in Digitized Thin Blood Smear Images
Authors: Po-Chen Kuo, Hao-Yuan Cheng, Pi-Fang Chen, Yu-Lun Liu, Martin Kang, Min-Chu Kuo, Shih-Fen Hsu, Hsin-Jung Lu, Stefan Hong, Chan-Hung Su, Ding-Ping Liu, Yi-Chin Tu, Jen-Hsiang Chuang
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Decades of effort have been devoted to establishing an automated microscopic diagnosis of malaria, but there are challenges in achieving expert-level performance in real-world clinical settings because publicly available annotated data for benchmark and validation are required. <h3>Objective</h3> To assess an expert-level malaria detection algorithm using a publicly available benchmark image data set. <h3>Design, Setting, and Participants</h3> In this diagnostic study, clinically validated malaria image data sets, the Taiwan Images for Malaria Eradication (TIME), were created by digitizing thin blood smears acquired from patients with malaria selected from the biobank of the Taiwan Centers for Disease Control from January 1, 2003, to December 31, 2018. These smear images were annotated by 4 clinical laboratory scientists who worked in medical centers in Taiwan and trained for malaria microscopic diagnosis at the national reference laboratory of the Taiwan Centers for Disease Control. With TIME, a convolutional neural network–based object detection algorithm was developed for identification of malaria-infected red blood cells. A diagnostic challenge using another independent data set within TIME was performed to compare the algorithm performance against that of human experts as clinical validation. <h3>Main Outcomes and Measures</h3> Performance on detecting<i>Plasmodium falciparum</i>–infected blood cells was measured by average precision, and performance on detecting<i>P falciparum</i>infection at the image level was measured using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). <h3>Results</h3> The TIME data sets contained 8145 images of 36 blood smears from patients with suspected malaria (30<i>P falciparum</i>–positive and 6<i>P falciparum</i>–negative smears) that had reliable annotations. For clinical validation, the average precision was 0.885 for detecting<i>P falciparum</i>–infected blood cells and 0.838 for ring form. For detecting<i>P falciparum</i>infection on blood smear images, the algorithm had expert-level performance (sensitivity, 0.995; specificity, 0.900; AUC, 0.997 [95% CI, 0.993-0.999]), especially in detecting ring form (sensitivity, 0.968; specificity, 0.960; AUC, 0.995 [95% CI, 0.990-0.998]) compared with experienced microscopists (mean sensitivity, 0.995 [95% CI, 0.993-0.998]; mean specificity, 0.955 [95% CI, 0.885-1.000]). <h3>Conclusions and Relevance</h3> The findings suggest that a clinically validated expert-level malaria detection algorithm can be developed by using reliable data sets.