tbuckley/cabot-search huggingface dataset:
Active surveillance of postradical prostatectomy biochemical recurrence: Long-term assessment of outcomes.
Authors: Tom Edward Ahlering, Erica Huang, Linda My Huynh, Huang Wei Su
Journal: Journal of Clinical Oncology (2021)

5081 Background: Biochemical recurrence (BCR) following radical prostatectomy (RP) is an unreliable predictor of distant metastatic progression/prostate cancer death, resulting in potential complications &amp; expenses of overtreatment. Little has been published on management decisions &amp; outcomes of active surveillance (AS). We characterize our long term experience with AS following post-RP BCR without radiation/androgen deprivation therapy. Methods: From June 2002 - September 2019, 1865 men underwent RP. 406 experienced BCR; of these, 138 (34%) were observed without treatment intervention. BCR defined as PSA&gt;0.2 ng/dl, x2. PSAs checked every 1-3 months and entered into a PSADT graph. Men were considered to be formally AS after 3+ years of increasing DT following RP. Men with decreasing DT were treated and censored. Results: The table depicts demographics of the AS patients; median follow-up was 7.3 years (IQR: 4.6-10.6) post-RP. Of patients on AS, average age was 63.7 +/- 7.2 years and 86%, 48%, 40%, 51% and 14% were GG 1 through 5, respectively. Current DT of AS patients averages 20 months, with 0% PCSM. Only 10% of patients with decreasing DT began treatment after average 4 years following BCR. Conclusions: Of 406 patients experiencing post-RP BCR, 34% of patients are effectively managed with AS, with 0% PCSM across all GG. Presently 69 (50%) AS men have been under observation for 7.3 to 18 years. This suggests that significant portion of patients display benign recurrence, characterized by increasing DT following BCR and can be managed safely with observation alone.[Table: see text]
Symptom-level modelling unravels the shared genetic architecture of anxiety and depression
Authors: Jackson G. Thorp, Adrian I. Campos, Andrew D. Grotzinger, Zachary F. Gerring, Jiyuan An, Jue-Sheng Ong, Wei Wang, Suyash Shringarpure, Enda M. Byrne, Stuart MacGregor, Nicholas G. Martin, Sarah E. Medland, Christel M. Middeldorp, Eske M. Derks
Journal: Nature Human Behaviour (2021)
Improving financial disclosures in oncology.
Authors: Joseph Heng, Blase N. Polite
Journal: Journal of Clinical Oncology (2021)

e18642 Background: The Physician Payments Sunshine Act, as part of the Affordable Care Act, was enacted in 2010 to improve transparency of payments from drug and medical device manufacturers to physicians, which are easily accessible in a public database (OpenPayments CMS). However, in a review conducted of clinical drug trials in oncology, one-third of oncologist authors did not disclose their industry payments. Failure to disclose financial conflicts of interest can lead to a loss of public trust and in some cases may lead to legal liability. The American Society for Clinical Oncology and our institutional polices require all faculty to fully report financial conflicts of interest (COI). This pilot project aims to evaluate the accuracy of financial COI disclosures among our oncologists at the University of Chicago, and improve subsequent disclosures. Methods: This project was approved through the institutional quality improvement process. In May 2020, we crossmatched COI disclosures on journal publications for 37 practicing clinical hematologists/oncologists in our institution with 2017 and 2018 records on OpenPayments. We then conducted a department-wide Grand Rounds to review omissions, and to remind faculty of ASCO and University COI policies. In addition, we privately contacted individual oncologists to review any COI omissions. We reminded faculty that at the end of 2020 we would again review the accuracy of their disclosures. Results: We examined a total of 37 practicing hematologists/oncologists’ disclosure forms. At initial review, 6/37 (16.2%) of oncologists had incomplete or missing disclosures. A total of $569,182.95 in payments was not disclosed in 2018. 2 of these 6 oncologists did not disclose relevant payments from pharmaceutical companies whose drugs were referred to in publications. Several disclosure errors appeared to be inadvertent omissions as they were disclosed in other publications. Reasons given for disclosure omissions were: “oversight”, “did not believe to be relevant to publication”, “confusion over journal COI policies”, “unnecessary due to low payment amount”, "too many journals to update disclosures in". At the final review, only 2 of the 6 oncologists with disclosure omissions had updated disclosures at the end of the year despite education provided at multiple grand rounds and private communications. Conclusions: This pilot project demonstrated that education sessions and individual feedback improved adherence to COI disclosure policies, but not fully. Additional feedback and enforcement mechanisms may be required for full compliance. In addition, a centralized disclosure form (such as ASCO’s disclosure form) that journals can easily access may improve disclosure adherence.
Organic iodine-based preparation inhibits growth of B16/F10 melanoma in C57BL6 mice with thyroid disorders.
Authors: Irina V. Kaplieva, Elena M. Frantsiyants, Valeria A. Bandovkina, Ekaterina I. Surikova, Irina V. Neskubina, Lidia K. Trepitaki, Natalia D. Cheryarina, Ludmila A. Nemashkalova, Viktoria V. Pozdnyakova, Yuriy V. Przhedetskiy, Viktoria Yu. Przhedetskaya, Natalia A. Maksimova, Maria G. Ilchenko, Olga Khokhlova, Natalia A. Zakharova, Oleg I. Kit, Marina A. Engibaryan, Astanda K. Gvaramiya
Journal: Journal of Clinical Oncology (2021)

e21580 Background: The thyroid gland is the most important regulator of the body's response to stressful influences, including malignant growth. Iodine is a constituent of thyroid hormones, and it plays an important role in anti-tumor protection. The purpose of the study was to analyze the levels of thyroid hormones in the thyroid gland of male and female mice with B16/F10 melanoma, as well as the effect of an organic iodine-based preparation on the survival of animals with transplanted melanoma. Methods: Levels of total (T3, T4) and free (FT3, FT4) thyroid hormones were measured by RIA in the thyroid of male and female С57ВL/6 mice (n = 80) with transplantable B16/F10 melanoma. The effect of an organic iodine-based preparation on the dynamics of the melanoma growth was studied in the main group of animals (n = 42) receiving per os 1,3-diethylbenzimidazolium triiodide in a single dose of 0.4 mg/kg throughout the experiment; the control group (n = 20) received distilled water. The tumor volume and survival of mice were measured. Results: The lowT3/lowT4 syndrome developed in females with transplantable B16/F10 melanoma starting from week 2 of the experiment, diagnosed by decreasing levels of FТ3 and FТ4 by 3 times and lower and normal levels of T3 and T4. In males, melanoma growth caused the thyroid hypofunction expressed in a decrease in the levels of T3 and T4 by 2 times, and FT3 and FT4 by 1.5 times. The latent period prior to the tumor onset was 10-12 days in females and 5-7 days in males. The survival of females was 5-6 weeks, males – 3-4 weeks. The administration of the organic iodine-based preparation extended the latent period in females up to 14-18 days, in males up to 10-14 days; the survival of females increased by 1.8 times, males by 1.5 times. 9% of females in the main group showed complete tumor resorption without relapses throughout their lives. Conclusions: The growth of transplantable B16/F10 melanoma in male and female С57ВL/6 mice was accompanied by suppression of the thyroid function with the development of uncontrolled hypothyroidism in males and the lowT3/lowT4 syndrome in females, which correlates with the survival of animals.
Characteristics of patients with psoriasis with Psoriasis Area and Severity Index &lt; 10 treated with biological agents: results from the French PsoBioTeq cohort
Authors: M. Beylot‐Barry, J. Seneschal, D. Tran, H. Bachelez, N. Beneton, A. Dupuy, P. Joly, D. Jullien, E. Mahé, C. Paul, M.‐A. Richard, E. Sbidian, M. Viguier, O. Chosidow, F. Tubach
Journal: British Journal of Dermatology (2021)

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Abstract 15161: Stretchable Electronic Wearable" Sensors Allow Quantitative Assessment of CPR
Authors: Maxwell Li, Yonatan E Weiner, Ahmed Harhash, Kaitlyn R Ammann, Rebecca Slepian, Karl B Kern, Marvin J Slepian
Journal: Circulation (2018)

Introduction: A critical determinant of cardiopulmonary resuscitation (CPR) efficacy is administration of compressions of adequate frequency and depth. Current attempts at assessing CPR compression...
Abstract TMIM-078: USING A DYNAMIC, LOW-SHEAR ENVIRONMENT TO MIMIC PHYSIOLOGICAL FLUID SHEAR STRESS IN OVARIAN CANCER <i>IN VITRO</i> MODELING
Authors: Timothy J. Masiello, L.P. Madhubhani Hemachandra, James Castracane
Journal: Clinical Cancer Research (2019)

Abstract Ovarian cancer is the most lethal gynecological cancer with a five-year survival rate as low as 30%. Early diagnosis could offer high chances of survival as most ovarian cancer cases are diagnosed only after metastasis has taken place. Some of the challenges in diagnosis and treatment are due to ovarian cancer's preference for the transcoelomic metastatic pathway over the more well-known hematogenic pathway, where spheroids suspended in the peritoneal cavity invade through the mesothelial layer that lines it. Spheroids for in vitro experiments have been generated for decades using common methods such as hanging drops and liquid overlay, but these models typically do not account for the fluid shear stress present in vivo, especially following the formation of ascites. One method to mimic this in vitro is to use dynamic cell culture to generate shear stress. Fluid movement parameters (rotation, shaking, etc.) can be tuned to achieve physiologically-relevant shear stress while facilitating the formation of spheroids. Dynamic culture improves the roundness and size consistency of spheroids, facilitating functional assays such as spheroid migration and mesothelial clearance. The addition of shear stress is expected to increase the metastatic behavior of spheroids as it better recreates the in vivo environment. This model also provides a platform for incorporating other in vivo elements such as co-culture, use of ascites samples, etc. This work is ultimately aimed at improving our fundamental understanding of peritoneal metastasis with new insights for determining optimal therapeutic approaches. Citation Format: Timothy J. Masiello, L.P. Madhubhani Hemachandra, and James Castracane. USING A DYNAMIC, LOW-SHEAR ENVIRONMENT TO MIMIC PHYSIOLOGICAL FLUID SHEAR STRESS IN OVARIAN CANCER IN VITRO MODELING [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr TMIM-078.
Comparison of Health-Related Quality of Life (HRQL) in Asian Patients with Chronic Hepatitis C Treated with Interferon (IFN)-free Ribavirin (RBV)-Containing Regimens vs Interferon-free and Ribavirin-free Regimens
Authors: Zobair M. Younossi, Maria Stepanova, Kwang-Hyub Han, Wan-Long Chuang, Henry Lik-Yuen Chan, Young-Suk Lim, Rong-Nan Chien, Sang Hoon Ahn, Sook-Hyang Jeong, Ting-Tsung Chang, Seung Woon Paik, Cheng-Yuan Peng, Chi-Jen Chu, Youn-Jae Lee, Ching-Lung Lai, Jia-Horng Kao, Sharon Hunt
Journal: Hepatology (2016)
NHS to trial “artificial pancreas” for patients with type 1 diabetes
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Up to 1000 patients with type 1 diabetes will be fitted with an “artificial pancreas” in a landmark trial, NHS England has announced.

The “closed loop” technology automatically balances blood sugar levels by constantly measuring glucose levels and delivering insulin directly to the bloodstream, when needed, through a pump. It is designed to offer better glucose control, reduce the risk of hypoglycaemia, and remove the need for finger prick tests.

Announcing the trial at the NHS Confederation’s virtual conference on 15 April, NHS England’s chief executive Simon Stevens said the technology marked a new …
Usefulness of cell-penetrating peptides and penetration accelerating sequence for nose-to-brain delivery of glucagon-like peptide-2
Authors: Tomomi Akita, Ryosuke Kimura, Saki Akaguma, Mio Nagai, Yusuke Nakao, Mamiko Tsugane, Hiroaki Suzuki, Jun-ichiro Oka, Chikamasa Yamashita
Journal: Journal of Controlled Release (2021)
Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease
Authors: Mari Aksnes, Hans Christian D. Aass, Ann Tiiman, Trine Holt Edwin, Lars Terenius, Nenad Bogdanović, Vladana Vukojević, Anne-Brita Knapskog
Journal: Translational Neurodegeneration (2021)

Abstract Background The aggregation of amyloid β (Aβ) is central in the pathogenesis of Alzheimer’s disease (AD). Recently it has been shown that specifically, larger, Thioflavin T-binding Aβ aggregates are associated with increased neuroinflammation and cytokine release. This study was aimed to quantify fibrillary amyloid aggregates, so-called nanoplaques, and investigate their relationship with cytokines in the cerebrospinal fluid (CSF). Methods CSF was collected from 111 patients assessed for cognitive complaints at the Oslo University Hospital Memory Clinic. The patients were grouped based on their amyloid status. The CSF nanoplaque concentration was quantified with the Thioflavin T-fluorescence correlation spectroscopy (ThT-FCS) assay. The levels of nine cytokines (eotaxin-1, granulocyte stimulating factor, interleukin [IL]-6, IL-7, IL-8, monocyte chemoattractant protein-1, gamma-induced protein 10, macrophage inflammatory protein [MIP]-1α, and MIP-1β) were quantified with a magnetic bead-based multiplex assay and read on a Luminex IS 200 instrument. Results There were 49 amyloid-negative and 62 amyloid-positive patients in the cohort; none of the cytokines differed significantly between the amyloid groups. The increased nanoplaque levels were associated with levels of MIP-1β below the lower limit of quantification, and with decreased levels of MIP-1α and IL-8. The associations remained significant when adjusted for age, sex, cognitive function, apolipoprotein ε4 status and CSF core biomarker levels. Conclusion The cytokine levels were not associated with amyloid status in this cohort. The nanoplaque levels were negatively associated with MIP-1β, MIP-1α and IL-8, which is in line with recent findings suggesting that the upregulation of some cytokine markers has a protective role and is negatively associated with AD progression.
Corrigendum for: “Protein S protects against allergic bronchial asthma by modulating Th1/Th2 balance. Allergy 2020 Sept; 75 (9) 2267‐2278”
Authors: Kentaro Asayama, Tetsu Kobayashi, Corina N. D'Alessandro‐Gabazza, Masaaki Toda, Taro Yasuma, Hajime Fujimoto, Tomohito Okano, Haruko Saiki, Atsuro Takeshita, Kentaro Fujiwara, Valeria Fridman D'Alessandro, Kota Nishihama, Toshiaki Totoki, Ryo Inoue, Yoshiyuki Takei, Esteban C. Gabazza
Journal: Allergy (2021)

In Fig. 6C of the original version of this article, due to an inadvertent mistake, an incorrect histogram was placed in the panel describing the IFNγ-positive cells in the presence of human protein S under Th2 condition. The error has been corrected, as described below. This correction has not changed the description, results, interpretation, or the original conclusion of the manuscript.
A phase II trial combining tumor-targeting <i>TP53</i> gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer.
Authors: Chris Poki Leung, Minal A. Barve, Ming-Shiang Wu, Kathleen F. Pirollo, James F. Strauss, Wei-Chih Liao, Shih-Hung Yang, Robert Alan Nunan, Jana Adams, Joe B. Harford, Esther H. Chang
Journal: Journal of Clinical Oncology (2021)

4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m 2 /wk and 125 mg/m 2 /wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]
Improved lymph node metastasis prediction from preoperative esophageal squamous cell cancer CT by graph attention convolutional neural network (GACNN).
Authors: Mingjun Ding, Hui Cui, Butuo Li, Bing Zou, Yiyue Xu, Bingjie Fan, Wanlong Li, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2021)

e16093 Background: Lymph node (LN) metastasis is the most important factor for decision making in esophageal squamous cell carcinoma (ESCC). A more accurate prediction model for LN metastatic status in ESCC patients is needed. Methods: In this retrospective study, 397 ESCC patients who took Contrast-Enhanced CT (CECT) within 15 days before surgery between October 2013 and November 2018 were collected. There are 924 (798 negative and 126 positive) LNs with pathologically confirmed status after surgery. All LNs were randomly divided into a training set (n = 663) and validation set (n = 185). Data augmentation including shifting and rotation was performed in the training set, resulting in 1326 negative and 1140 positive LN samples. The GACNN model was trained over CT volumetric patches centred at manually segmented LN samples. GACNN was composed of a 3D UNet encoder to extract deep features, and a graph attention layer to integrate morphological features extracted from segmented LN. The model was validated using the validation set (135 negative and 50 positive) and measured by area under ROC curve (auc), sensitivity (sen), and specificity (spe). Results: GACNN achieved better auc, sen, and spe of 0.802, 0.765, and 0.826, when compared to 3 other models including CT radiomics model (auc 0.733, sen 0.689, spe 0.765), 3D UNet encoder (auc 0.778, sen 0.722, spe 0.767), and our model without morphological features (auc 0.796, sen 0.754, spe 0.803). The improvement was statistically significant (p &lt; 0.001). Conclusions: Our prediction model improved the prediction of LN metastasis, which has the potential to assist LN metastasis risk evaluation and personalized treatment planning in ESCC patients for surgery or radiotherapy.
Real-world survival outcomes associated with completion of adjuvant chemotherapy for stage III colon cancer.
Authors: Jemma Megan Boyle, Angela Kuryba, Thomas E Cowling, Jan van der Meulen, Nicola S Fearnhead, Kate Walker, Michael Braun, Ajay Aggarwal
Journal: Journal of Clinical Oncology (2021)

3596 Background: The optimal duration of adjuvant combination chemotherapy administered to patients with stage III colon cancer is debated. Our study assessed the effect of completed chemotherapy cycles on 3-year colon cancer-specific mortality, as well as the effect of dose reduction and early discontinuation of oxaliplatin in patients with 100% completion, within a real-world population. Methods: 4,147 patients undergoing major resection between 01 June 2014 and 30 April 2017 with pathological stage III colon cancer in the English National Health Service were identified. Chemotherapy data were obtained from linked administrative hospital records and a national chemotherapy dataset. Patients were stratified according to completion of &lt; 50% ( &lt; 6 FOLFOX cycles or &lt; 4 CAPOX cycles), 50-92% (6-11 FOLFOX cycles or 4-7 CAPOX cycles) or 100% of cycles (12 FOLFOX cycles or 8 CAPOX cycles). Competing-risk regression analysis for 3-year colon cancer-specific death was performed with adjustment for patient, tumour and hospital-level characteristics to estimate subdistribution hazard ratios (sHR) as a measure of relative risk. Results: Patients included within our study were less fit and had increased rates of high-risk disease (T4 and/or N2 pathological staging) compared to the IDEA study. For FOLFOX, the 3-year cumulative incidence of colon cancer-specific death in patients completing 100% of cycles was 15.1% (95% CI, 12.8% to 17.6%), 18.2% (95% CI, 15.3% to 21.3%) for 50-92% of cycles and 26.4% (95% CI, 20.6% to 32.5%) for &lt; 50% of cycles. For CAPOX, this was 12.0% (95% CI, 10.2% to 14.0%) for 100% completion of cycles, 18.2% (95% CI, 15.6% to 21.0%) for 50-92% of cycles, and 19.8% (95% CI, 15.8% to 24.1%) for &lt; 50% cycles. Compared to 100% completion of FOLFOX cycles, colon cancer-specific death was higher in patients recorded as completing &lt; 50% (sHR 2.17; 95% CI, 1.56 to 3.03; P = &lt; 0.001) and 50-92% of FOLFOX cycles (sHR 1.40; 95% CI, 1.09 to 1.78; P = 0.007). Compared to 100% completion of CAPOX cycles, colon cancer-specific death was higher in patients recorded as completing &lt; 50% (sHR 2.02; 95% CI 1.53 to 2.67; P&lt; 0.001) and 50-92% of CAPOX cycles (sHR 1.63; 95% CI 1.27 to 2.10; P&lt; 0.001). Dose reduction and early discontinuation of oxaliplatin did not have a statistically significant effect on mortality. Conclusions: Patients within the real world setting were more likely to have poor prognostic factors. Those who completed adjuvant chemotherapy for stage III colon cancer had improved survival rates regardless of dose reduction or early discontinuation of oxaliplatin.