bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viewing education differently: A novel educational approach using virtual tumor board cases.
Authors: Ogden John R , Agarwal Mohit Shiv , Chiec Lauren , Shonkwiler Erin , Chaby Michael , Dempsey Naomi , Pishvaian Michael J. , Klempner Samuel J , Benson Al Bowen , Lieu Christopher Hanyoung , Jahanzeb Mohammad 
Published: January 2022

653 Background: Caring for patients with cancer requires the expertise of specialists from pathology, radiology, surgical, radiation and medical oncology. Cancer centers discuss complicated cases at multidisciplinary tumor boards, where these experts collaborate on the optimal management strategies. Tumor boards present an opportunity for oncology providers to learn current guidelines and manage complex cases. Unfortunately, these opportunities occur infrequently and are limited to individual cancer centers. Virtual tumor board case scenarios could provide a valuable educational resource for professionals in all areas of oncology looking to enhance their knowledge and understanding of complex patient management. Methods: Well-renowned gastrointestinal oncology faculty conducted virtual tumor board panels via an online platform to discuss challenging cases submitted by community oncology providers and trainees. The panel consisted of specialists from radiology, medical, surgical, and radiation oncology. The case discussions were then formatted into individual scenario videos with case-based questions asked at the beginning and end of the discussions. These videos were viewed by trainees and practitioners in various fields of oncology. A survey was conducted to assess the educational value of these videos. Results: 10 unique gastrointestinal scenario videos were created from expert panel case discussions. These were viewed by 12 unique viewers, who were surveyed on their experience. Responders included Fellows/Residents (83%) and advanced practice providers (APPs) (17%). These included trainees/APPs from medical oncology (50%), radiation oncology (42%) and radiology (8%). All 12 responders felt the videos were a valuable educational resource that they would continue to use in the future. Of the responders, 7/12 (58%) felt these virtual scenarios were more educational than their own institutional tumor boards, while the remaining 5/12 (42%) felt they were equally educational. Responders to the survey indicated they would use these videos for a variety of purposes, as indicated below. Conclusions: Scenario videos created from virtual tumor boards conducted by expert panelists can provide a novel and valuable educational resource for trainees across all fields of oncology. It is a convenient way for viewers to stay up to date on current guidelines and apply the knowledge gained to their own practice. Additionally, it allows viewers a unique opportunity to hear from renowned experts in various oncology fields. Expansion and continued production of these scenario videos could enhance the education and practice of professionals in the field of oncology. Further assessment and evaluation of the impacts of these videos will be necessary.[Table: see text]
Clinical features and outcomes of tumor lysis syndrome in patients with gastrointestinal cancers.
Authors: Kelkar Neil , Wang Jue 
Published: January 2022

655 Background: In recent years, tumor lysis syndrome (TLS), an oncologic emergency typically associated with cytotoxic therapies, has been increasingly reported across a spectrum of cancer types including GI cancers. The objective of this study was to investigate the clinical characteristics and outcomes of TLS in GI cancers. Methods: Systematic review of the literature and pooled analysis of published cases of TLS in solid tumors. Two additional cases treated in our intuition are also included. Results: A total of 246 patients with TLS in solid tumors were included in this study. The median age was 56 years (7 months -94 years). The male: female ratio was 1.3. The most common sites were gastrointestinal (29%), followed by genitourinary (24%), lung (12%), melanoma (10%), breast cancer (8.1%), and GYN tumors (7.8%). Liver metastasis was documented in 70% of patients. TLS occurred after various cancer-directed therapies in 69% of subjects, and spontaneously in 31% of subjects. Older age and liver metastasis predict high mortality. The clinical features, treatment, and outcomes of TLS in 74 cases of GI cancers including HCC (n = 27), colorectal (n = 22), gastric (n = 8), cholangiocarcinoma (n = 6), pancreatic cancer (n = 4), GIST (n = 3), and PNET (n = 2) were compared. The mortality rate of TLS in this cohort was 100% in pancreases and cholangiocarcinoma, 66.7% in GIST, 57.7% in HCC, 54.5% in CRC, 50% in Gastric cancer. Conclusions: Documented across different sites consistently, TLS in GI cancers is associated with very high mortality. The development of a wider range of novel therapies and the application of more intensive therapy for the treatment of GI cancers likely contributed to the increased risk of TLS.[Table: see text]
BREAKWATER: Randomized phase 3 study of encorafenib (enco) + cetuximab (cet) ± chemotherapy for first-line treatment (tx) of BRAF V600E-mutant (BRAFV600) metastatic colorectal cancer (mCRC).
Authors: Kopetz Scott , Grothey Axel , Yaeger Rona , Ciardiello Fortunato , Desai Jayesh , Kim Tae Won , Maughan Tim , Van Cutsem Eric , Wasan Harpreet Singh , Yoshino Takayuki , Edwards Michelle L. , Golden Adele , Gollerkeri Ashwin , Tabernero Josep 
Published: January 2022

TPS211 Background: Approximately 10% of patients (pts) with mCRC have BRAF mutations (mostly V600E). First-line tx options for BRAFV600E mCRC are limited to cytotoxic chemotherapy ± anti-VEGF or anti-EGFR; or immune checkpoint inhibitors in pts with MSI-H tumors. In Europe, Japan, and USA, the combination of BRAF inhibitor enco + EGFR inhibitor cet is approved for tx of BRAFV600E mCRC after prior therapy. In BEACON CRC, enco + cet resulted in a median overall survival (OS) of 9.3 months (95% confidence interval [CI]: 8.0–11.3) and an objective response rate (ORR) of 19.5% (95% CI: 14.5%–25.4%) in previously treated pts with BRAFV600E mCRC (median follow-up: 12.8 months); 57.4% of pts had grade 3/4 adverse events (AEs), and 9% discontinued due to AEs. Given the poor prognosis of pts with BRAFV600E mCRC and based on the efficacy and tolerability of enco + cet from BEACON CRC, the BREAKWATER study will evaluate the efficacy and safety of enco + cet ± chemotherapy in tx-naive pts with BRAFV600E mCRC. Methods: BREAKWATER is an open-label, global, multicenter, randomized, phase 3 study with a safety lead-in (SLI). Approximately 60 and 870 pts will be enrolled in the SLI and phase 3 parts of the study, respectively. Pts must have mCRC with BRAF V600E-mutation (determined using tumor tissue or blood); ECOG performance status 0/1; and adequate bone marrow, hepatic, and renal function. Pts in the SLI must have evaluable disease (RECIST v1.1) and have received ≤ 1 prior tx regimen; those previously treated with a BRAF or EGFR inhibitor, or both oxaliplatin and irinotecan, will be excluded. Pts in the phase 3 study must have measurable disease and be tx naive for metastatic disease. Study tx and endpoints are shown in the table. Enrollment began on 06-Jan-2021. Clinical trial information: NCT04607421. [Table: see text]
NRG-GI004/SWOG-S1610: Colorectal cancer metastatic dMMR immuno-therapy (COMMIT) study—A randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC).
Authors: Rocha Lima Caio Max Sao Pedro , Yothers Greg , Jacobs Samuel A. , Sanoff Hanna Kelly , Cohen Deirdre Jill , Guthrie Katherine A , Henry Norah Lynn , Ganz Patricia A. , Kopetz Scott , Lucas Peter C. , Blanke Charles David , Wolmark Norman , Hochster Howard S. , George Thomas J. , Overman Michael J. 
Published: January 2022

TPS232 Background: Despite the superiority in progression-free survival (PFS) of inhibition of programmed cell death-1 (PD-1) pathway in dMMR/MSI-H as compared to chemotherapy with either anti-vascular endothelial growth factor receptor (VEGFr) or anti-epithelial growth factor receptor (EGFr) antibodies in mCRC, more pts had progressive disease as the best response in the anti-PD1 monotherapy arm (29.4% vs. 12.3%) with mean PFS of 13.7 months ( N Engl J Med 2020; 383:2207). We hypothesize that the dMMR/MSI-H mCRC pts may be more effectively treated by the combination of PD-1 pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-1 therapy (atezo) alone. Preclinical work demonstrated synergistic effects between anti-PD-1/anti-VEGF and between oxaliplatin/anti-PD-1 in murine CRC models and phase II data showed activity of anti-PD-1/anti-VEGF in chemotherapy refractory colon cancer. Additionally, in other solid tumor malignancies, anti-PD1 plus anti-VEGFr (i.e., HCC and RCC) as well as anti-PD1 plus chemotherapy (i.e., gastric and esophageal cancers) combinations are standard first-line treatments. Methods: The redesigned COMMIT study was reactivated on 1/29/2021 as a two-arm prospective phase III open-label trial randomizing (1:1) mCRC dMMR/MSI-H (211 pts) to atezo monotherapy versus mFOLFOX6/bev+atezo combination. Assuming our control arm, atezo monotherapy, 48% PFS at 24 months, as assessed by site investigator, we have 80% power to detect a hazard ratio of 0.6 (equivalent to 64.4% PFS at 24 months) with alpha 0.025 one-sided. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and centrally-reviewed PFS. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2) or MSI-H by local CLIA-certified PCR or NGS panel; and measurable disease per RECIST. Enrollment actively continues to the target accrual of 211 patients randomized between the two immunotherapy arms. Support: U10CA180868, -180822, -180888, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.
AdvanTIG-203: A randomized phase 2 study comparing anti-TIGIT ociperlimab plus tislelizumab versus tislelizumab plus placebo as second-line treatment in patients with advanced or recurrent esophageal squamous cell carcinoma (ESCC) expressing programmed death-ligand 1 (PD-L1).
Authors: Xu Rui-hua , Kim Sung-Bae , Tougeron David , Zuo Yunxia , Yang Haiyuan , Zhang Juan , Shi Jingwen , Van Cutsem Eric 
Published: January 2022

TPS370 Background: The programmed death-1 (PD-1)/PD-L1 pathway plays an important role in tumor induced immunosuppression. PD-L1 overexpression is observed in approximately 30–60% of esophageal cancers and is associated with poor prognosis. Anti-PD-1 agents demonstrate moderate efficacy in PD-L1-positive esophageal cancer in terms of response rate and overall survival, however, long-term outcomes remain poor due to primary and secondary resistance driven by tumor immune escape. The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is upregulated on T-cells and natural killer cells in multiple solid tumors, which can inhibit anticancer immune responses. Ociperlimab (BGB-A1217) is a novel, humanized, monoclonal antibody that binds TIGIT with high specificity and affinity, blocking the interaction with its ligands on tumor cells. Preclinical and clinical studies suggest that dual targeting with anti-TIGIT and anti-PD-1 antibodies produces synergistic immune cell activation and enhanced antitumor activity. Methods: AdvanTIG-203 is a Phase 2, global, randomized, double-blind, placebo-controlled study (NCT04732494) of patients with unresectable, locally advanced, recurrent or metastatic ESCC, who progressed on or after 1st line systemic therapy and whose tumors express PD-L1 (visually-estimated combined positive score ≥ 10%). After stratification by Eastern Cooperative Oncology Group performance status (0 or 1), number of metastatic sites (≤ 1 or ≥ 2) and region (Asian or non-Asian), 280 patients will be randomized (1:1) to either ociperlimab 900 mg intravenous (IV) plus tislelizumab 200 mg IV every 3 weeks (Q3W), or tislelizumab plus placebo Q3W, until disease progression (per RECIST v1.1), unacceptable toxicity, death or withdrawal of consent. Co-primary endpoints are investigator-assessed overall response rate (ORR) and overall survival (OS) in the intention-to-treat population. A sample size of 280 patients was estimated to provide approximately 94.8% power to detect a 20% difference in ORR at a one-sided significance level of 0.025. With 198 deaths, the study was estimated to provide approximately 86% power to detect a hazard ratio of 0.65 for OS. Secondary endpoints are ORR by independent review, progression-free survival, duration of response, disease control rate, and clinical benefit rate per investigator and independent assessment, cancer-specific health-related quality of life (HRQoL), and safety. Exploratory endpoints include but are not limited to expression of TIGIT, CD226, CD155, CD112, and PD-L1, pharmacokinetics, immunogenicity, and generic HRQoL measures. Clinical trial information: NCT04732494.
Optimizing pancreatic cancer management with next generation imaging and liquid biopsy (CHANGE-PDAC).
Authors: Tsang Erica S , Collisson Eric Andrew , Wang Zhen J. , Piawah Sorbarikor , Sanchez Taylor , Tempero Margaret A. , Ko Andrew H. 
Published: January 2022

TPS640 Background: Pancreatic ductal adenocarcinoma (PDAC) is anticipated to become the second-leading cause of cancer-related deaths by 2030. Systemic therapy remains the mainstay of treatment for those with unresectable/metastatic disease. There is an urgent need for biomarkers to rapidly assess treatment response to spare patients from the significant toxicities and costs of an ineffective regimen, and to guide decision-making for a therapeutic switch with a higher chance of efficacy. Circulating tumor (ct)DNA and PET/MRI represent promising emerging biomarkers for early response prediction. This is a prospective non-randomized study examining the role of ctDNA and PET/MRI in adjudicating early treatment response among patients with unresectable locally advanced or metastatic PDAC receiving systemic therapy. Methods: Approximately 158 patients with advanced PDAC will be recruited at the time of initiation of a new line of treatment in either the first or later-line setting. Patients receiving both standard of care and/or experimental therapies are permitted to enroll. Research blood samples will be collected at pre-treatment, 48 hours, two weeks, one month, and two months after treatment start for analysis of mutant ctDNA (using the FoundationOne/Natera platform). PET/MRI will be performed at pre-treatment and 4 weeks post treatment. All patients must have an ECOG performance status of 0-2 and have radiographically measurable disease. Clinical data will be collected prospectively, including demographics, ECOG performance status, CA 19-9 levels, chemotherapy type and dose intensity, and clinical and radiographic assessment of treatment response using RECIST 1.1 criteria. Enrollment began in August 2021. The primary endpoint is the correlation between change in tumor-derived ctDNA with radiographic progression, as measured by the change in tumor size. The Wilcoxon rank sum test will be used to compare the change in ctDNA with treatment between response vs. resistance. Cox proportional hazard regression modelling will be used to correlate the change in ctDNA with progression-free survival and overall survival. Secondary endpoints include defining thresholds for early chemotherapy switch using dynamic and quantitative changes in ctDNA and PET/MRI biomarkers for use in future prospective trials, establishing the relationship between early changes in PET/MRI and treatment response/resistance, and developing a multivariable model combining ctDNA and PET/MRI biomarkers to predict treatment response/resistance.
Finite size effect on the Fermi arc surface states in Weyl semimetal
Authors: Chang Mingqi , Sheng Li 
Published: January 2022

Abstract
A hallmark of the Weyl semimetal is the presence of two gapless Fermi arc surface states between two Weyl nodes. The Fermi arc surface states give rise to quantum anomalous Hall effect. Through analytically solving a finite size Weyl semimetal slab, we find that the two surface states can couple together producing a gap in the spectrum of Fermi arc surface states. Due to the finite size effect, the quantum anomalous Hall effect of Fermi arc states will be modified. This effect is anticipated to be measurable in experiment.
Marketing Opioids to Veterans and Older Adults: A Content Analysis of Internal Industry Documents Released from State of Oklahoma v. Purdue Pharma LP, et al.
Authors: Yakubi Hanna , Gac Brian , Apollonio Dorie E. 
Published: January 2022

Abstract
Context: From 1999 to 2018 the opioid epidemic claimed more than 500,000 lives in the United States. Military veterans and older adults were particularly affected; veterans' deaths attributed to opioid use increased by 65% from 2010 to 2016, while opioid prescriptions for older adults increased ninefold between 1995 and 2010.
Methods: We reviewed internal pharmaceutical industry documents released in legal discovery to determine how companies targeted these groups to increase prescribing and sales. This review included an analysis of corporate goals and plans identified through internal emails, sales pitches, and presentations.
Findings: These policy and advertising campaigns focused on (a) lobbying policy makers, (b) undertaking unbranded campaigns promoting opioid use, and (c) promoting opioid use in research and the popular media. Opioid manufacturers claimed that opioids could resolve preexisting concerns identified among military veterans and older adults and that the use of opioids would improve quality of life. These campaigns were positioned as public health initiatives and efforts to increase disease awareness.
Conclusions: The findings suggest a need for regulatory reform and transparency related to lobbying, advocacy group relationships with industry, and pharmaceutical advertising.
Brain Stimulation Using Responsive Neurostimulation Improves Verbal Memory: A Crossover Case–Control Study
Authors: Haneef Zulfi , Gavvala Jay R. , Combs Hannah L. , Han Albert , Ali Irfan , Sheth Sameer A. , Stinson Jennifer M. 
Published: January 2022

BACKGROUND:
The effects of brain stimulation on memory formation in humans have shown conflicting results in previous studies. We hypothesized that direct cortical stimulation using an implanted responsive neurostimulation (RNS) system will improve memory.

OBJECTIVE:
To evaluate whether direct cortical stimulation using RNS improves memory as measured with recall scores of a list-learning task.

METHODS:
During outpatient visits, a list-learning task (Hopkins Verbal Learning Test-Revised) was administered to 17 patients with RNS implants. Patients were read a list of 12 semantically related words and asked to recall the list after 3 different learning trials. True or sham stimulations were performed for every third word presented for immediate recall. Most patients had frontotemporal network stimulation—one patient each had insular and parietal stimulations. After a 20-min delay, they were asked to recall the list again, first freely and then through a “yes/no” recognition paradigm. A crossover design was used in which half the patients had true stimulation during the initial visit and half had sham stimulation—followed by crossover to the other group at the next visit.

RESULTS:
The Hopkins Verbal Learning Test–Revised delayed recall raw score was higher for the stimulation condition compared with the nonstimulation condition (paired t-test, P = .04, effect size d = 0.627).

CONCLUSION:
Verbal memory improves by direct cortical stimulation during a list-learning task. The RNS system can be effectively used in memory research using direct cortical stimulation. This study has implications in the development of neurostimulation devices for cognitive enhancement in conditions such as epilepsy, dementia, and traumatic brain injury.
Aberrant RET expression affects normal mammary gland post-lactation transition, enhancing cancer potential
Authors: Vallone Sabrina A. , García Solá Martín , Schere-Levy Carolina , Meiss Roberto P. , Hermida Gladys N. , Chodosh Lewis A. , Kordon Edith C. , Hynes Nancy E. , Gattelli Albana 
Published: January 2022

ABSTRACT
RET is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors with oncogenic activity in the breast are known to participate in specific developmental stages. We found that RET is differentially expressed during mouse mammary gland development: RET is present in lactation and its expression dramatically decreases in involution, the period during which the lactating gland returns to a quiescent state after weaning. Based on epidemiological and pre-clinical findings, involution has been described as tumor promoting. Using the Ret/MTB doxycycline-inducible mouse transgenic system, we show that sustained expression of RET in the mammary epithelium during the post-lactation transition to involution is accompanied by alterations in tissue remodeling and an enhancement of cancer potential. Following constitutive Ret expression, we observed a significant increase in neoplastic lesions in the post-involuting versus the virgin mammary gland. Furthermore, we show that abnormal RET overexpression during lactation promotes factors that prime involution, including premature activation of Stat3 signaling and, using RNA sequencing, an acute-phase inflammatory signature. Our results demonstrate that RET overexpression negatively affects the normal post-lactation transition.