tbuckley/cabot-search huggingface dataset:
Impact of Low-Dose Computed Tomography Screening for Primary Lung Cancer on Subsequent Risk of Brain Metastasis
Authors: Chloe C. Su, Julie T. Wu, Joel W. Neal, Rita A. Popat, Allison W. Kurian, Leah M. Backhus, Seema Nagpal, Ann N. Leung, Heather A. Wakelee, Summer S. Han
Journal: Journal of Thoracic Oncology (2021)

Brain metastasis (BM) is one of the most common metastases from primary lung cancer (PLC). Recently, the National Lung Screening Trial revealed the efficacy of low-dose computed tomography (LDCT) screening on LC mortality reduction. Nevertheless, it remains unknown if early detection of PLC through LDCT may be potentially beneficial in reducing the risk of subsequent metastases. Our study aimed to investigate the impact of LDCT screening for PLC on the risk of developing BM after PLC diagnosis.We used the National Lung Screening Trial data to identify 1502 participants who were diagnosed with PLC in 2002 to 2009 and have follow-up data for BM. Cause-specific competing risk regression was applied to evaluate an association between BM risk and the mode of PLC detection-that is, LDCT screen-detected versus non-LDCT screen-detected. Subgroup analyses were conducted in patients with early stage PLC and those who underwent surgery for PLC.Of 1502 participants, 41.4% had PLC detected through LDCT screening versus 58.6% detected through other methods, for example, chest radiograph or incidental detection. Patients whose PLC was detected with LDCT screening had a significantly lower 3-year incidence of BM (6.5%) versus those without (11.9%), with a cause-specific hazard ratio (HR) of 0.53 (p = 0.001), adjusting for age at PLC diagnosis, PLC stage, PLC histology, and smoking status. This significant reduction in BM risk among PLCs detected through LDCT screening persisted in subgroups of participants with early stage PLC (HR = 0.47, p = 0.002) and those who underwent surgery (HR = 0.37, p = 0.001).Early detection of PLC using LDCT screening is associated with lower risk of BM after PLC diagnosis on the basis of a large population-based study.
Abstract 16930: Asymmetric Chromatid Segregation Identifies Human Cardiac Stem Cells that Regenerate Extensively the Infarcted Myocardium
Authors: Yingnan Bai, Donato Cappetta, Junghyun Kim, Christian Arranto, Fumihiro Sanada, Domenico D'Amario, Alex Matsuda, Maria Virginia Caballero, Silvana Bardelli, Barbara Ogòrek, Ada Pesapane, Chiara Mangiaracina, Weining Bian, Giorgia Palano, Toru Hosoda, Annarosa Leri, Marcello Rota, Joseph Loscalzo, Jan Kajstura, Piero Anversa
Journal: Circulation (2012)

According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old DNA template, opposing accumulation of replication errors and attenuating tel...
Assessment of chemotherapy-induced cognitive impairment: A prospective study of the biochemical and metabolic effects of platinum/taxane-based chemotherapy in gynecologic cancer patients.
Authors: Megan Leigh Gleason Hutchcraft, Amelia J Anderson-Mooney, Emily Van Meter Dressler, D. Allan Butterfield, Daret St. Clair, David K. Powell, Lisa Koehl, Frederick A. Schmitt, Brent Shelton, Justin W. Gorski, Lauren Ashley Baldwin, Christopher Philip DeSimone, Holly H. Gallion, Fredrick R. Ueland, Rachel W. Miller
Journal: Journal of Clinical Oncology (2021)

e24051 Background: Chemotherapy-induced cognitive impairment (CICI) is a common side effect of cancer therapy, affecting up to 75% of cancer patients. Oxidative stress is thought to play a key role in CICI and patients who have been treated with chemotherapy have demonstrated biochemical brain changes on magnetic resonance spectroscopy (MRS). Methods: Following institutional review board approval, chemotherapy-naïve gynecologic cancer patients scheduled to receive intravenous platinum/taxane-based chemotherapy were identified. The primary objective of this study was identification of chemotherapy-induced cognitive function changes using the Montreal Cognitive Assessment (MoCA) tool. This exploratory analysis evaluates correlations between changes in MoCA scores, oxidative analytes TNF-a, protein carbonyls (PC), and 4-hydroxynonenal (HNE) protein adducts, and MRS metabolic signals. Testing was performed at baseline and three weeks post-treatment. Simple linear regression was performed to evaluate the correlation between changes in MoCA scores and oxidative metabolites. Results: Fourteen patients were enrolled. Six patients had complete pre/post oxidative stress data, and four patients had complete pre/post MRS data. Five of six had decreased PC values (mean net change -15.17%, SD 0.15), half had increased HNE levels (mean net change +16.38%, SD 0.38), and four of six had decreased TNF-a values (mean net change -15.10%, SD 0.27) (Table). MoCA scores were positively correlated with serum PC levels ( r = 0.86, p = 0.03) and not significantly correlated with TNF-a or HNE levels. Of those with complete pre/post MRS data, all patients had a decrease in glycerophosphocholine + phosphocholine/creatinine ratio signals. MoCA raw score prior to and after completion of chemotherapy. A higher score indicates improved test performance. Positive percentage of oxidative stress markers (PC, HNE, TNF-a) indicates increased post-therapy levels compared to pre-therapy. Conclusions: In this study, we evaluated candidate oxidative stress serum markers and changes in MRS metabolite signals for CICI. Serum PC levels correlate with cognitive screening scores. For patients undergoing brain imaging, MRS evaluation for individual choline components, glycerophosphocholine and phosphocholine, may serve as an additional marker of oxidative damage. This pilot study highlights the potential value of serum PC levels and dedicated brain imaging for signs of oxidative stress, including MRS, to guide future CICI identification studies. Clinical trial information: NCT03324945. [Table: see text]
Effectiveness of a killed whole-cell oral cholera vaccine in Bangladesh: further follow-up of a cluster-randomised trial
Authors: Mohammad Ali, Firdausi Qadri, Deok Ryun Kim, Md Taufiqul Islam, Justin Im, Faisal Ahmmed, Ashraful Islam Khan, K Zaman, Florian Marks, Jerome H Kim, John D Clemens
Journal: The Lancet Infectious Diseases (2021)

BackgroundKilled whole-cell oral cholera vaccines (OCVs) are widely used for prevention of cholera in developing countries. However, few studies have evaluated the protection conferred by internationally recommended OCVs for durations beyond 2 years of follow-up.MethodsIn this study, we followed up the participants of a cluster-randomised controlled trial for 2 years after the end of the original trial. Originally, we had randomised 90 geographical clusters in Dhaka slums in Bangladesh in equal numbers (1:1:1) to a two-dose regimen of OCV alone (targeted to people aged 1 year or older), a two-dose regimen of OCV plus a water–sanitation–hygiene (WASH) intervention, or no intervention. There was no masking of group assignment. The WASH intervention conferred little additional protection to OCV and was discontinued at 2 years of follow-up. Surveillance for severe cholera was continued for 4 years. Because of the short duration and effect of the WASH intervention, we combined the two OCV intervention groups. The primary outcomes were OCV overall protection (protection of all members of the intervention clusters) and total protection (protection of individuals who got vaccinated in the intervention clusters) against severe cholera, which we assessed by multivariable survival models appropriate for cluster-randomised trials. This trial is registered on ClinicalTrials.gov, NCT01339845.FindingsThe study was done between April 17, 2011, and Nov 1, 2015. 268 896 participants were present at the time of the first dose, with 188 206 in the intervention group and 80 690 in the control group. OCV coverage of the two groups receiving OCV was 66% (123 659 of 187 214 participants). During 4 years of follow-up, 441 first episodes of severe cholera were detected (243 episodes in the vaccinated groups and as 198 episodes in the unvaccinated group). Overall OCV protection was 36% (95% CI 19 to 49%) and total OCV protection was 46% (95% CI 32 to 58). Cumulative total vaccine protection was notably lower for people vaccinated before the age of 5 years (24%; −30 to 56) than for people vaccinated at age 5 years or older (49%; 35 to 60), although the differences in protection for the two age groups were not significant (p=0·3308). Total vaccine protection dropped notably (p=0·0115) after 3 years in children vaccinated at 1–4 years of age.InterpretationThese findings provide further evidence of long-term effectiveness of killed whole-cell OCV, and therefore further support for the use of killed whole-cell OCVs to control endemic cholera, but indicate that protection is shorter-lived in children vaccinated before the age of 5 years than in people vaccinated at the age of 5 years or older.FundingBill & Melinda Gates Foundation.TranslationFor the Bengali translation of the abstract see Supplementary Materials section.
The effect of neoadjuvant chemotherapy on quality of life for patients with muscle invasive bladder cancer (MIBC) undergoing cystectomy.
Authors: Christina Sossenheimer, Amy Cizik, Sara Lenherr, Brock O Neil, Christopher B. Dechet, Alejandro Sanchez, Jonathan David Tward
Journal: Journal of Clinical Oncology (2021)

e18614 Background: To examine the relationship between neoadjuvant chemotherapy (NAC) clinical risk factors, and patient reported quality of life in patients with MIBC undergoing cystectomy. Methods: cT2-T4, N0, M0 MIBC patients who underwent radical cystectomy were identified from a prospectively maintained institutional outcomes database. PROMIS-Ca surveys (physical function (PF), pain interference, fatigue, depression, and anxiety domains) were administered at consultation and follow-up as part of routine clinical care. Patients were stratified as receiving NAC vs. none and surveys were anchored to date of cystectomy. Non-parametric kernel regressions with variance-covariance matrix bootstrapping were used to estimate the mean effect of covariates on each domain T-score with 95% confidence intervals. Covariates were: body mass index, smoking history, age, Charlson comorbidity score, pT and pN stage, urinary diversion-type, and survey time relative to the cystectomy date. T-score changes over time were modeled by including univariable parameters with a P&lt;=0.1 in a multivariable model (MVA) for each domain and predicting the marginal means at date of cystectomy, 6 and 12 months postop. Results: The median age was 68 (IQR 60-73) years. NAC was received by 69/134 patients (40 Gem/Cis, 24 MVAC, 5 unknown). On univariate analyses NAC significantly reduces PF (mean change in t-score, 95%CI; -2.4, -3.7 to -0.8, p=0.001), trends toward more pain (0.94, -0.20 to 1.78, p=0.074), but does not influence fatigue, depression or anxiety. Other covariates with p&lt;0.05 reducing PF were BMI (-0.31, -0.53 to -0.03), pT4 vs pT1-2 (-0.31, -0.53 to -0.03), Charlson 1 vs 0 (-0.31, -0.53 to -0.03), age (-0.31, -0.53 to -0.03), and days from surgery (-0.31, -0.53 to -0.03). Table shows how t-scores predicted from the MVA change over time. Conclusions: MIBC patients have mild to moderate impairment in physical function, fatigue, and pain before and after cystectomy, suggesting a need for increased focus on rehabilitation and wellness programs. Although the univariable analysis implies there may be differences in PF and Pain for those receiving NAC vs none, future studies with increased power are needed to properly adjust for the interplay of other significant covariates.[Table: see text]
Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study
Authors: Eric Pujade-Lauraine, Keiichi Fujiwara, Jonathan A Ledermann, Amit M Oza, Rebecca Kristeleit, Isabelle-Laure Ray-Coquard, Gary E Richardson, Cristiana Sessa, Kan Yonemori, Susana Banerjee, Alexandra Leary, Anna V Tinker, Kyung Hae Jung, Radoslaw Madry, Sang-Yoon Park, Charles K Anderson, Fabian Zohren, Ross A Stewart, Caimiao Wei, Samuel S Dychter, Bradley J Monk
Journal: The Lancet Oncology (2021)
Clinical performance of methylation-based liquid biopsy test COLVERA after optimization of test interpretation rules.
Authors: Zivjena Vucetic, Naima Loayza, Susanne Kartin Pedersen, Missy Tuck, Lawrence Charles LaPointe
Journal: Journal of Clinical Oncology (2021)

3546 Background: Clinical guidelines recommend surveillance for patients who complete primary treatment for colorectal cancer (CRC) with the aim of detecting recurrence when amenable to curative intent treatment. Currently recommended surveillance protocols, including imaging and CEA have limitations both in sensitivity and specificity, thus novel methods that detect circulating tumor DNA (ctDNA) have been introduced into clinical practice. COLVERA is a laboratory-developed, real-time PCR test that detects DNA methylation of BCAT1 and IKZF1 genes. These two genes are hypermethylated in 95% of CRC tissue and COLVERA showed improved sensitivity for detection of recurrent disease in comparison to CEA in several clinical populations. The current study evaluated the impact of optimizing the assay’s qualitative reporting method on actionability and clinical performance for recurrence detection in CRC surveillance setting. Methods: Two previously described cohorts of CRC patients (N=322 and N=144) who completed primary treatment and were undergoing surveillance were evaluated. Imaging and blood collections were performed at, or adjacent to, a standard of care visit. cfDNA was extracted from whole blood, bisulphite-treated and assayed in triplicates for BCAT1/IKZF methylation. Previously, any positive replicate of either target gene was reported as COLVERA “detected”. In the current study, COLVERA is “detected” when at least one replicate of IKZF1 or multiple replicates of either IKZF1 and/or BCAT1 are present. Sensitivity, specificity, and diagnostic odds ratio (DOR) for CRC recurrence detection from a single time-point blood sample was determined using radiological imaging as clinical reference standard. Results: In the first cohort (N=322), overall COLVERA test positivity was 6.5% (21/322) with a sensitivity of 59.3% (95% CI: 38.8 - 77.6) and specificity of 98.3% (96.1 - 99.5) for detecting recurrence at a time-point adjacent to imaging, representing improved specificity, from 91.5% (87.7 - 94.4%), with minimal decrease in sensitivity, from 63.0% (42.4 – 80.6). Similarly, in the second cohort (N=144) sensitivity was 62% (47.2 -75.4), compared to 66.0% (57.1 – 69.3) under the prior interpretation method, while specificity was 92.6% (85.3-97), compared to 90.4% (84.7 - 94.7). A high DOR of 84 (26 - 272) (previously 18 (7.6 – 44.4)) indicates that the revised COLVERA interpretation method is clinically more informative and differentiates with greater accuracy patients with and without the disease. Conclusions: This change in the COLVERA interpretation rule resulted in optimized clinical specificity with minimal impact on sensitivity. For an assay intended to aid in surveillance and early recurrence detection, improved accuracy allows the physician to have increased confidence in making actionable decisions based on test result, including further imaging or treatment.
Family members’ attitudes towards disclosure of cancer diagnosis to patients in China.
Authors: Xi Rao, Yongshen Zhang, Feng-Ming Spring Kong
Journal: Journal of Clinical Oncology (2021)

12131 Background: Informed consent is very important aspect of treatment, in western countries, a diagnosis of malignancy should be delivered the paient directly. It was the decision of the patient for further disclosure. However, in China, people are always family centered decision making, a diagnosis of cancer is traditionally delivered to the family members, with a protective assumption. We used anonymized questionnaire to investigate the attitude of Chinese people towards to cancer diagnosis disclosure and correlated factors. Methods: This is a survey study conducted by a web system named “Wenjuan Xing”. The study questionnaires were designed in dual English and Chinese. answered by the same person. The regarding questions that answered by the same person are as following: “If your close family member is diagnosed with a malignant tumor, would you like to tell him the truth?”, “If yes/no, what’s your reason?”. Demographic information include gender, age, economic status, education level, health condition, residential region, occupation, nationality and major reasons. The survey link was placed on Wechat contact of these investigators, social media and also distributed in Oncology Center of a general hospital in Mainland China. The answers of the questions were captured directly online, data can also be exported into excel format for compiled analysis. Results: A total of 1470 people completed the survey questions from January to July 2020. The potential factors which influence disclosing diagnosis were registered, 1041 (70.8%) family members are in favor of informing the diagnosis to patients, 429 (29.2%) are not. The main reasons for disclosure diagnosis are ‘it is his or her life, he/she has to be in control’ (N=832) and she or he can plan his/her remaining life and leave the world with no regret (N=588). The famliy member who hide the diagnosis worry that paitents could not handle the stress would have poor quality of life (N=295) and die faster(N=323). 1425(96.9%) people want to know the diagnosis if they have a malignanti tumor, while 45 (3.1%) don’t want to know.The univariate analysis revealed educational level, health condition and residential region are correlated to disclosing diagnosis. The logistic regression anaylsis show a significant effort to disclosing diagnosis(OR= 1.9, 95% CI (1.4, 2.7) P&lt;0.001).Interaction and stratified analyses were conducted according to education level and redidential region (P interaction= 0.0406). In the high education level group, people who live in other countries(America, Europe) (P=0.009 OR=29.7 CI 2.3-375.7) more likely to disclose the diagnosis compared to mainland in China. Conclusions: The majority of Chinese people want to know the diagnosis. People who have higher education level and live in western countries more likely prefer disclosure of diagnosis to patients.
STAT6 polymorphism was correlated with gefitinib-induced diarrhea in patients with non-small cell lung cancer.
Authors: Shaoxing Guan, Xi Chen, Youhao Chen, Min Huang, Li Zhang, Xueding Wang
Journal: Journal of Clinical Oncology (2021)

e21046 Background: Gefitinib-induced diarrhea can be severe, if not properly handled, and can result in severe dose reductions and treatment interruptions or discontinuation. However, the mechanism of gefitinib-induced diarrhea remains unclear. STAT6 promotes disruption of epithelial tight junction integrity, intestinal inflammation and allergic disorders in intestine. Therefore, we explored the correlation between variations in STAT6 and gefitinib-induced diarrhea in advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 160 advanced NSCLC patients carrying EGFR mutations were enrolled. 8 tag single nucleotide polymorphisms (SNP) in STAT6, including rs10876963, rs167769, rs3122929, rs3024975, rs841718, rs324013, rs324015 and rs703817, were selected by Heploview 4.2 and sequenced by Agena MassARRAY System. The associations between tag SNPs of STAT6 and diarrhea were analyzed by Chi square test and multivariate logistic regression. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: 71 patients (44.4%) suffered at least grade 1 gefitinib-induced diarrhea. We found rs167769 was associated with gefitinib- induced diarrhea in NSCLC patients. STAT6 rs167769 TT carriers were all suffering from gefitinib-induced diarrhea (OR = 2.4*10 10 , p = 0.999). Patients with STAT6 rs167769 TT have higher risk of developing severe (grade ≥ 2) diarrhea than those with STAT6 rs167769 CC/CT. Conclusions: STAT6 rs167769 is a predictive biomarker for gefitinib-induced diarrhea and the analysis of polymorphisms of STAT6 rs167769 might be beneficial to optimize gefitinib treatment. Further studies are needed to clarify the underlying mechanisms. Clinical trial information: NCT01994057.
Fluctuating Environments Maintain Genetic Diversity through Neutral Fitness Effects and Balancing Selection
Authors: Farah Abdul-Rahman, Daniel Tranchina, David Gresham
Journal: Molecular Biology and Evolution (2021)

Genetic variation is the raw material upon which selection acts. The majority of environmental conditions change over time and therefore may result in variable selective effects. How temporally fluctuating environments impact the distribution of fitness effects and in turn population diversity is an unresolved question in evolutionary biology. Here, we employed continuous culturing using chemostats to establish environments that switch periodically between different nutrient limitations and compared the dynamics of selection to static conditions. We used the pooled Saccharomyces cerevisiae haploid gene deletion collection as a synthetic model for populations comprising thousands of unique genotypes. Using barcode sequencing, we find that static environments are uniquely characterized by a small number of high-fitness genotypes that rapidly dominate the population leading to dramatic decreases in genetic diversity. By contrast, fluctuating environments are enriched in genotypes with neutral fitness effects and an absence of extreme fitness genotypes contributing to the maintenance of genetic diversity. We also identified a unique class of genotypes whose frequencies oscillate sinusoidally with a period matching the environmental fluctuation. Oscillatory behavior corresponds to large differences in short-term fitness that are not observed across long timescales pointing to the importance of balancing selection in maintaining genetic diversity in fluctuating environments. Our results are consistent with a high degree of environmental specificity in the distribution of fitness effects and the combined effects of reduced and balancing selection in maintaining genetic diversity in the presence of variable selection.
Delgocitinib ointment in pediatric patients with atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and a subsequent open-label, long-term study
Authors: Hidemi Nakagawa, Osamu Nemoto, Atsuyuki Igarashi, Hidehisa Saeki, Kenji Kabashima, Manabu Oda, Takeshi Nagata
Journal: Journal of the American Academy of Dermatology (2021)

Delgocitinib 0.5% ointment, a topical Janus kinase inhibitor, has been approved in Japan for adult patients with atopic dermatitis (AD).To evaluate the efficacy and safety of delgocitinib ointment in pediatric patients with AD.Part 1 of this study was a 4-week double-blind period in which Japanese patients aged 2 through 15 years were randomized in a 1:1 ratio to delgocitinib 0.25% ointment or vehicle ointment. Part 2 was a 52-week extension period. Eligible patients entered part 2 to receive 0.25% or 0.5% delgocitinib ointment.At the initiation of the study, approximately half of the patients had moderate AD. At the end of treatment in part 1, the least-squares mean percent change from baseline in modified Eczema Area and Severity Index score, the primary efficacy endpoint, was significantly greater for delgocitinib ointment than for vehicle (-39.3% vs +10.9%, P < .001). In part 2, improvements in AD were also seen through week 56. Most adverse events were mild and unrelated to delgocitinib across the study periods.Only Japanese patients were included. In part 2, no control group was included and rescue therapy was allowed.Delgocitinib ointment was effective and well tolerated when applied to Japanese pediatric patients with AD for up to 56 weeks.