tbuckley/cabot-search huggingface dataset:
Correlation of clinical characteristics and immunologic profile of stage III NSCLC patients.
Authors: Nattanit Suriyaphan, Pimpin Incharoen, Songporn Oranratnachai, Pimtip Sanvarinda, Narumol Trachu, Dittapol Muntham, Phichai Chansriwong, Thanyanan Reungwetwattana
Journal: Journal of Clinical Oncology (2021)

e20552 Background: Recently, immunotherapy has significantly increased mPFS and mOS in unresectable stage III NSCLC whom completed concurrent chemoradiation (CCRT). Predictive biomarker for immunotherapy in this setting has not been established yet. Methods: This is a retrospective study in stage III NSCLC patients in Ramathibodi hospital between year of 2013 and 2019. Clinical data of 176 patients were retrieved from electronic medical record. Only 64 patients had adequate tissue for tissue array for immunohistochemistry (IHC) staining of protein expression in CD3, CD4, CD8, FOXP3, PDL-1, CD163, CD 138, CD20 in stroma and tumor cells. We also performed IHC staining for Microsatellite Instability (MSI). Optimum cut point for each protein expression was performed by C-statistic. Survival analysis was performed. All statistical analysis was performed by Stata version 15. Results: Of 176 patients, majority of patient were male (63.6%), age ≥65 years (63.6%), never-smoker (40.9%), stage IIIB (44.9%) and adenocarcinoma (67.6%). EGFR-positive patients were 47.7%. Most of the patients underwent CCRT (32.4%), only 11.9% underwent trimodality treatment. Doublet-carboplatin based chemotherapy was the most common regimen (61.5%). The mOS was 2.9 years and mPFS was 1.6 years. Multivariable analysis showed stage IIIB patients, patients whom received only systemic treatment or best palliative care had significantly shorter OS. Trimodality treatment showed significantly longer OS compared to bimodality (CCRT) (HR = 0.18, P= 0.02), as well as cisplatin-based chemotherapy had significantly longer OS compared to carboplatin-based regimen (HR = 0.47, P= 0.005). Of 64 patients whom had tissue testing in our study, majority of patients had of MSI-low (81.25%), PD-L1 negative (78.13%). Regarding tumor microenvironment, patients with high protein expression of CD3, CD4, CD8 and CD20 in stromal cells showed significantly longer OS, whereas MSI and PD-L1 were not significantly associated with survival outcomes. Conclusions: OS in stage III NSCLC in our population (2.9 years) is comparable with other studies (2.4 years). Trimodalities treatment significantly increased OS compared to CCRT. High protein expression of CD3, CD4, CD8 and CD20 in stroma probably potential prognostic and predictive biomarkers for immunotherapy in stage III NSCLC. Larger cohort is needed to explore.
Dual mechanistic TRAIL nanocarrier based on PEGylated heparin taurocholate and protamine which exerts both pro-apoptotic and anti-angiogenic effects
Authors: Jeong Uk Choi, Ji-young Kim, Seung Woo Chung, Na Kyeong Lee, Jooho Park, Seho Kweon, Young Seok Cho, Ha Rin Kim, Sung Mook Lim, Jin Woo Park, Kang Choon Lee, Youngro Byun
Journal: Journal of Controlled Release (2021)

The selective cytotoxicity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) to cancer cells but not to normal cells makes it an attractive candidate for cancer therapeutics. However, the disadvantages of TRAIL such as physicochemical instability and short half-life limit its further clinical applications. In this study, TRAIL was encapsulated into a novel anti-angiogenic nanocomplex for both improved drug distribution at the tumor site and enhanced anti-tumor efficacy. A nanocomplex was prepared firstly by entrapping TRAIL into PEG-low molecular weight heparin-taurocholate conjugate (LHT7), which is previously known as a potent angiogenesis inhibitor. Then, protamine was added to make a stable form of nanocomplex (PEG-LHT7/TRAIL/Protamine) by exerting electrostatic interactions. We found that entrapping TRAIL into the nanocomplex significantly improved both pharmacokinetic properties and tumor accumulation rate without affecting the tumor selective cytotoxicity of TRAIL. Furthermore, the anti-tumor efficacy of nanocomplex was highly augmented (73.77±4.86%) compared to treating with only TRAIL (18.49 ± 19.75%), PEG-LHT7/Protamine (47.84 ± 14.20%) and co-injection of TRAIL and PEG-LHT7/Protamine (56.26 ± 9.98%). Histological analysis revealed that treatment with the nanocomplex showed both anti-angiogenic efficacy and homogenously induced cancer cell apoptosis, which suggests that accumulated TRAIL and LHT7 in tumor tissue exerted their anti-tumor effects synergistically. Based on this study, we suggest that PEG-LHT7/Protamine complex is an effective nanocarrier of TRAIL for enhancing drug distribution as well as improving anti-tumor efficacy by exploiting the synergistic mechanism of anti-angiogenesis.
Identification and characterization of de novo TP53 mutation carriers in Li-Fraumeni syndrome families: A single institution experience.
Authors: Carlos Christian Vera Recio, Jessica Corredor, Elissa Dodd-Eaton, Angelica M. Gutierrez-Barrera, Najat C. Daw, Banu Arun, Wenyi Wang
Journal: Journal of Clinical Oncology (2021)

10538 Background: Li-Fraumeni syndrome (LFS) is an inherited cancer syndrome mainly caused by a deleterious mutation in TP53. An estimated 48% of LFS patients present due to a deleterious de novo mutation (DNM) in TP53. The knowledge of DNM status, DNM or familial mutation (FM), of an LFS patient requires genetic testing of both parents which is often inaccessible, making de novo LFS patients an understudied population. Famdenovo.TP53 is a Mendelian Risk prediction model used to predict DNM status of TP53 mutation carriers based on the cancer-family history and several input genetic parameters, including disease-gene penetrance. The good predictive performance of Famdenovo.TP53 was demonstrated using data collected from four historical US cohorts. We hypothesize that by incorporating penetrance estimates that are specific for different types of cancers diagnosed in family members, we can develop a model with further improved calibration, accuracy and prediction. Methods: We present Famdenovo.CS, which uses cancer-specific penetrance estimates that were derived previously using a Bayesian semi-parametric competing risk model, to calculate the DNM probability. We use our model to analyze 101 families recently collected from the Clinical Cancer Genetic program at MD Anderson Cancer Center (CCG-TP53) that includes 20 families with known DNM status and 81 families with unknown DNM status. We used the concordance index (AUC), observed:expected ratios (OE) and Brier score (BS) to measure our model’s discrimination, calibration and accuracy, respectively. We estimate the proportion of probands that present a DNM and compare DNM to FM carriers in several areas including: cancer types diagnosed, age at diagnosis, number of primary cancers diagnosed, sex, amino acid change caused by mutation in TP53. Results: Famdenovo.CS showed equally good discrimination and calibration performance to Famdenovo.TP53, while improving the overall accuracy, demonstrated by a decrease in the Brier score of -0.09 (95% CI: [-0.02, -0.19]). Of the 101 probands in the CCG-TP53 cohort, we predict 39 to be DNMs and 62 to be FMs. The cancer types and ages of diagnosis observed in FMs and DNMs are similarly distributed. Conclusions: Famdenovo.CS shows improved model accuracy in the CCG cohort. DNMs in TP53 are a prevalent cause of LFS and we did not find differences in the clinical characteristics of DNM and FM carriers. Our model allows for a systematic identification and characterization of TP53 DNM carriers.
30-day readmission after TAVR (Transcatheter Aortic Valve Replacement (TAVR) in patients with malignancy.
Authors: Shristi Upadhyay Upadhyay Banskota, Miguel Salazar, Estefania Gauto, Hugo Macchi, Prajwal Shrestha, Nabin Khanal
Journal: Journal of Clinical Oncology (2021)

e18620 Background: Hospital readmissions after cardiac procedures are increasingly the major focus of quality improvement efforts. Although some reflect appropriate care, others are potentially preventable readmissions (PPRs). We aim to describe the burden, timing, and factors associated with readmissions after transcatheter aortic valve replacement (TAVR) in patients with malignancy. Methods: We performed a retrospective study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for TAVR with a concomitant diagnosis of malignancy. We aimed to identify 30-day readmission rate, mortality, healthcare related utilization of resources and other independent predictors of readmission. Results: A total of 2,213 patients with malignancy underwent TAVR. The 30-days readmission rate was 16% (n=355). Main causes of readmissions were found to be heart failure, sepsis, acute hypercapnic respiratory failure, coronary artery disease with angina, and AKI with ATN. Readmitted patients were more likely to come from small metropolitan areas (43.1% vs 33.6, p≤0.01), micropolitan areas (1.4% vs 0.35%, p≤0.01), rural hospital (20.3% vs 8.8%, p≤0.01), non-teaching hospital (23.5% vs 9.1%, p≤0.01), and small sized hospitals (11.5% vs 4%, p≤0.01). Patients re-admitted were more likely to have malnutrition (8% vs 3.2%, p≤0.01), new VTEs (3.8% vs 0.6, p≤0.01), AKI (26% vs 13.6%, p≤0.01) and deaths (4.6% vs 1.7%, p≤0.01). The total health care in-hospital economic burden of readmission was $5.9 million in total charges and $25 million in total costs. Independent predictors of readmission were disposition to short-term skilled nursing facilities, home-health care, and sepsis. Conclusions: We concluded that readmissions after TAVR in patients with malignancy are associated with higher in-hospital mortality rate and pose a higher health care burden. We also identified risk factors that can be targeted to decrease readmissions after TAVR, health care burden, and patient mortality.[Table: see text]
Recurrent Glioma
Authors: Amarnath Jena, Sangeeta Taneja, Anna Ara Khan, Shanti K. Sogani
Journal: Clinical Nuclear Medicine (2021)

Neuroimaging modalities such as contrast-enhanced MRI and PET provide significant insight in the evaluation of gliomas. However, their reliability in successfully differentiating the tumor recurrence with treatment-related changes is still technologically challenging. The current study aims to qualitatively investigate the potential of the hybrid PET/multiparametric MRI modality to noninvasively distinguish between these 2 outcomes of brain tumor diagnostics for optimum and early patient management.A cohort of 26 suspected recurrent glioma cases proved on histology and/or clinicoradiological outcome forms the part of this study. A 3-point visual analytical scale was used to qualify lesions as recurrent or posttreatment radiation effects on PET, conventional MRI, dynamic susceptibility contrast-perfusion-weighted imaging, apparent diffusion coefficient, and the MR spectroscopy according to their level of suspicion.Of the 26 patients, 21 patients were classified as recurrence and 5 as radiation necrosis. Advanced MRI parameters (perfusion, diffusion, and spectroscopy) integrated with 18F-DOPA PET imaging resulted in superior diagnostic performance obtained on visual assessment with an accuracy of 95%, sensitivity of 96%, and specificity approaching up to 100% over individual modalities.The combination of multiple MR parameters evaluated together with 18F-DOPA PET offers an attractive approach to noninvasively distinguish true recurrence from radiation necrosis. However, further prospective studies with larger cohorts are warranted with additional neuropathological validations.
Effects of Evolution, Ecology, and Economy on Human Diet: Insights from Hunter-Gatherers and Other Small-Scale Societies
Authors: Herman Pontzer, Brian M. Wood
Journal: Annual Review of Nutrition (2021)

We review the evolutionary origins of the human diet and the effects of ecology economy on the dietary proportion of plants and animals. Humans eat more meat than other apes, a consequence of hunting and gathering, which arose ∼2.5 Mya with the genus Homo. Paleolithic diets likely included a balance of plant and animal foods and would have been remarkably variable across time and space. A plant/animal food balance of 50/50% prevails among contemporary warm-climate hunter-gatherers, but these proportions vary widely. Societies in cold climates, and those that depend more on fishing or pastoralism, tend to eat more meat. Warm-climate foragers, and groups that engage in some farming, tend to eat more plants. We present a case study of the wild food diet of the Hadza, a community of hunter-gatherers in northern Tanzania, whose diet is high in fiber, adequate in protein, and remarkably variable over monthly timescales.
Pancreatic cancer outcomes in Nova Scotia: Searching for small windows of opportunity.
Authors: Peiran Sun, Ravi Ramjeesingh
Journal: Journal of Clinical Oncology (2021)

e16219 Background: While pancreatic cancer (PC) globally has poor outcomes, there are still regional variation in PC outcomes in Canada. Nova Scotia (NS) has been documented to have some of the worst outcomes in PC but the details and barriers to the care of PC in NS have never been analyzed. Methods: A retrospective chart review was performed on PC patients (pts) diagnosed in NS from 2013 to 2017 for patient characteristics, referral pattern, treatments and wait times. Cox proportional hazards methods were used to analyze overall survival (OS) with Age, Stage, Eastern Cooperative Oncology Group Performance Status (PS), Charleston Comorbidity Index (CCI), receiving ERCP and receiving chemotherapy as covariates in the multivariate analysis. Results: 667 consecutive pts were identified, which included 357 males and 310 females with a median age of 71 at diagnosis. 42 (6.25%) lived beyond 2 years, while 163 (24.4%) survived for under 30 days and 260 (39%) survived for under 60 days. Patients with a limited survival (under 30 days) when compared to pts who survived &gt; 60 days are older (mean 75 vs 71, P &lt; 0.05), had a higher proportion of ECOG &gt; 2 (81.6% vs 20.3%, P &lt; 0.01), and a higher proportion of stage 4 disease (73.9% vs 41.2%, P &lt; 0.01). There was no significant difference in any measure of wait times. Pts with limited survival were less likely to be seen by Medical Oncology (MO) (20.9% vs 70.9%, P &lt; 0.001), and less likely to receive chemotherapy (1.2% vs 45%, P &lt; 0.001) or ERCP (27% vs 53.8%, P &lt; 0.01). Multivariate analysis showed that receiving ERCP (P = 0.027) and chemotherapy(P &lt; 0.001) are independent predictors of survival, even when accounting for PS, CCI, stage, and age. Conclusions: Analysis of PC outcomes in NS demonstrates a large proportion of pts dying within 30 days of diagnosis. Those pts are older and present with higher stage and worse PS but did not have any significant difference in diagnostic and referral wait times. Those pts receive fewer referrals to Oncology services, fewer potentially life prolonging treatments and we uniquely discovered ERCP as an independent predictor of survival in our population. While further work is needed, this study characterized some of the unique challenges of PC care in NS as a province with a higher proportional of older adults and highlights potential opportunities to improve early healthcare delivery in older adults with limited windows for care.
Хірургічна корекція структурно-функціональних порушень печінки у хворих на хронічний калькульозний холецистит та її віддалені результати
Authors: N.V. Prolom
Journal: GASTROENTEROLOGY (2013)

Під час оперативного втручання з приводу хронічного калькульозного холециститу 52 хворим після морфологічного підтвердження стеатозу печінки виконана хірургічна корекція структурно-функціональних змін печінки точковим електродом апарату хірургічної діатермії в шаховому порядку по передній поверхні правої і лівої частки печінки в кожній зоні із зниженим електричним потенціалом. У післяопераційному періоді хворим проводили комплекс реабілітаційних заходів.Віддалені результати показують, що застосування медикаментозної та хірургічної корекції структурно-функціональних порушень печінки під час холецистектомії забезпечує покращання стану печінки, що проявляється зниженням на 76,9 % її морфологічних змін та функціонального стану.Підсумком роботи стала розробка шляхів поліпшення результатів хірургічного лікування хворих на холецистит, що дозволило зменшити частоту післяопераційних ускладнень і поліпшити якість життя у 92,3 % пацієнтів.
A phase 3, multicenter, randomized study evaluating the efficacy of TAR-200 in combination with cetrelimab versus concurrent chemoradiotherapy in participants with muscle-invasive urothelial carcinoma of the bladder.
Authors: Stephen B. Williams, Christopher Cutie, Kirk A Keegan, Bradley Raybold, Milin Acharya, Wei Zhu, Xiang Li, Lang A O'Dondi, Neil Beeharry, Daniel Eidelberg Spratt
Journal: Journal of Clinical Oncology (2021)

TPS4586 Background: The standard of care for patients with muscle-invasive bladder cancer (MIBC) consists of neoadjuvant chemotherapy and radical cystectomy (RC) or chemoradiotherapy (CRT). However, RC is associated with potential morbidity or mortality from the procedure. TAR-200 is an intravesical drug-delivery system designed for the local continuous release of gemcitabine within the bladder. Cetrelimab is an investigational immunoglobulin G4 anti–programmed cell death protein-1 antibody. In patients with MIBC, this clinical trial will evaluate whether combination treatment with intravesical TAR-200 and systemic cetrelimab will result in enhanced local and systemic antitumor activity versus concurrent CRT. Methods: SunRISe-2 (NCT04658862) is a prospective, multicenter, open-label, randomized phase 3 study evaluating the efficacy and safety of intravesical TAR-200 plus systemic cetrelimab versus CRT in participants with MIBC. Eligible participants are aged ³18 years with an ECOG performance status of 0, 1, or 2, and histologically proven, cT2-T4a, N0, M0 urothelial carcinoma of the bladder diagnosed within 90 days of the randomization date, and who refuse or are ineligible for RC. Approximately 550 participants will be randomized in a 1:1 ratio and with stratification by 2 factors: transurethral resection of bladder tumor screening results (visibly complete vs incomplete) and screening tumor stage (T0 vs Ta/T1/Tis vs T2-T4a). Participants in Arm 1 will receive intravesical TAR-200 every 3 weeks for the first 18 weeks on study; and, beginning at week 24, every 12 weeks through study year 3. Cetrelimab will be dosed every 3 weeks until month 18. Participants in Arm 2 will receive standard of care CRT (with either cisplatin or gemcitabine, for up to 6 weeks). A primary disease assessment will be performed at week 18 to evaluate treatment response in both arms. Subsequent assessments (axial imaging and cystoscopy) will occur at week 24 and every 12 weeks thereafter through study year 2, and then every 24 weeks through study year 5. The primary endpoint is bladder intact event-free survival. Key secondary endpoints include metastasis-free survival, overall survival, overall response rate (at week 18), and safety and tolerability. Other/exploratory end points include assessments of cancer-specific survival, time to symptomatic progression, pharmacokinetics, immunogenicity, health-related quality of life, healthcare resource utilization, and biomarkers. Participants are being enrolled at approximately 272 study sites worldwide. The study opened for enrollment in December 2020. Clinical trial information: NCT04658862.
Chromosome Fusion Affects Genetic Diversity and Evolutionary Turnover of Functional Loci but Consistently Depends on Chromosome Size
Authors: Francesco Cicconardi, James J Lewis, Simon H Martin, Robert D Reed, Charles G Danko, Stephen H Montgomery
Journal: Molecular Biology and Evolution (2021)

Major changes in chromosome number and structure are linked to a series of evolutionary phenomena, including intrinsic barriers to gene flow or suppression of recombination due to chromosomal rearrangements. However, chromosome rearrangements can also affect the fundamental dynamics of molecular evolution within populations by changing relationships between linked loci and altering rates of recombination. Here, we build chromosome-level assembly Eueides isabella and, together with a recent chromosome-level assembly of Dryas iulia, examine the evolutionary consequences of multiple chromosome fusions in Heliconius butterflies. These assemblies pinpoint fusion points on 10 of the 20 autosomal chromosomes and reveal striking differences in the characteristics of fused and unfused chromosomes. The ten smallest autosomes in D. iulia and E. isabella, which have each fused to a longer chromosome in Heliconius, have higher repeat and GC content, and longer introns than predicted by their chromosome length. When fused, these characteristics change to become more in line with chromosome length. The fusions also led to reduced diversity, which likely reflects increased background selection and selection against introgression between diverging populations, following a reduction in per-base recombination rate. We further show that chromosome size and fusion impact turnover rates of functional loci at a macroevolutionary scale. Together these results provide further evidence that chromosome fusion in Heliconius likely had dramatic effects on population level processes shaping rates of neutral and adaptive divergence. These effects may have impacted patterns of diversification in Heliconius, a classic example of an adaptive radiation.