tbuckley/cabot-search huggingface dataset:
Exploring cancer clinical trialparticipation in the new normal ofCOVID-19: The patient perspective
Authors: M. A. Raymond, M. A. Simonetta
Journal: Journal of Clinical Oncology (2021)

Background: The impact of coronavirus (COVID-19) has significantly affected cancer patientsseeking to enroll in a clinical trial  The pandemichas led to an unprecedented disruption across the cancer research community pausing trial operations  Data from the National Institute of Health and the National Library of Medicine indicates 988 cancer clinical trials were suspended from March September 1 2020, with 60% of institutions enrolling patients at a lower rate  Our research underscores the patient perspective of clinical trial participation amid COVID-19  Methods: July September 2020 Nationwide eight-week online survey and interviews  Research goals: gain a better understanding of barriers and cultural attitudes of ethnically diverse communities regarding trial participation;learn the enhanced safety measures needed for patients to feel comfortable returning to the clinic;better understand the importance of effective patientclinician communication  Results: 511 patient participants reported the following insights: 86% reported their healthcare team had not discussed trial participation;99% reported being comfortable with telehealth visits for prescreening and monitoring;82% receive care at community-based hospitals  Barriers to enrollment and additional safety considerations include gaps in outreach and education services for ethnically diverse communities;absence of cultural sensitivity and disregard of historical perspective;financial insecurity and travel;and the need for increased COVID-19 testing, enhanced safety protocols and a proven vaccine  Participants identified their ethnicity as 38% Caucasian;24% Black/African American;19% Hispanic/Latino;16% Asian;2% Native American/Pacific Islander  Conclusions: Clinical trials provide patients access to the newest treatments, and yet only 2%-3% of adult cancer patients enroll in a trial  Common barriers to trial participation have been widely researched, but now amongst the coronavirus pandemic, additional barriers are evident  Based on our research, our call to action is clear: work with key opinion leaders in ethnically diverse populations to help build trust and mutual respect when discussing research studies;andengage patients and clinicians to openly discuss clinical trial enrollment working toward patientcentered communication  The coronavirus pandemic is a devastating public health threat, and it will take a collective effort from the entire cancer community to minimize the effect of COVID-19 on cancer clinical trial participation
QIM21-093: Guideline and Standard Development for Medically Integrated Dispensing Pharmacies for Oral Anticancer Medication: ASCO/NCODA Standards
Authors: Josh Nubla, Ginger Blackmon, Austin Starkey
Journal: Journal of the National Comprehensive Cancer Network (2021)

"QIM21-093: Guideline and Standard Development for Medically Integrated Dispensing Pharmacies for Oral Anticancer Medication: ASCO/NCODA Standards" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Kinomic profile in patient-derived glioma cells during hypoxia reveals c-MET-PI3K dependency for adaptation
Authors: Hong Sheng Cheng, Charlie Marvalim, Pengcheng Zhu, Cheng Lui Daniel Law, Zhi Yan Jeremy Low, Yuk Kien Chong, Beng Ti Ang, Carol Tang, Nguan Soon Tan
Journal: Theranostics (2021)

Hypoxic microenvironment is a hallmark of solid tumors, especially glioblastoma.The strong reliance of glioma-propagating cells (GPCs) on hypoxia-induced survival advantages is potentially exploitable for drug development.Methods: To identify key signaling pathways for hypoxia adaptation by patient-derived GPCs, we performed a kinase inhibitor profiling by screening 188 small molecule inhibitors against 130 different kinases in normoxia and hypoxia.Potential kinase candidates were prioritized for in vitro and in vivo investigations using a ranking algorithm that integrated information from the kinome connectivity network and estimated patients' survival based on expression status.Results: Hypoxic drug screen highlighted extensive modifications of kinomic landscape and a crucial functionality of c-MET-PI3K.c-MET inhibitors diminished phosphorylation of c-MET and PI3K in GPCs subjected to hypoxia, suggesting its role in the hypoxic adaptation of GPCs.Mechanistically, the inhibition of c-MET and PI3K impaired antioxidant defense, leading to oxidative catastrophe and apoptosis.Repurposed c-MET inhibitors PF04217903 and tivantinib exhibited hypoxic-dependent drug synergism with temozolomide, resulting in reduced tumor load and growth of GPC xenografts.Detailed analysis of bulk and single-cell glioblastoma transcriptomes associates the cellular subpopulation over-expressing c-MET with inflamed, hypoxic, metastatic, and stem-like phenotypes.Conclusions: Thus, our "bench to bedside (the use of patient-derived GPCs and xenografts for basic research) and back (validation with independent glioblastoma transcriptome databases)" analysis unravels the novel therapeutic indications of c-MET and PI3K/Akt inhibitors for the treatment of glioblastoma, and potentially other cancers, in the hypoxic tumor microenvironment.
A Blood-Based Prognostic Liver Secretome Signature Predicts Long-term Risk of Hepatic Decompensation in Cirrhosis
Authors: Naoto Fujiwara, Austin J Fobar, Indu Raman, Quan-Zhen Li, Jorge A Marrero, Neehar D Parikh, Amit G Singal, Yujin Hoshida
Journal: Clinical Gastroenterology and Hepatology (2021)
Ion Channel Degeneracy, Variability, and Covariation in Neuron and Circuit Resilience
Authors: Jean-Marc Goaillard, Eve Marder
Journal: Annual Review of Neuroscience (2021)

The large number of ion channels found in all nervous systems poses fundamental questions concerning how the characteristic intrinsic properties of single neurons are determined by the specific subsets of channels they express. All neurons display many different ion channels with overlapping voltage- and time-dependent properties. We speculate that these overlapping properties promote resilience in neuronal function. Individual neurons of the same cell type show variability in ion channel conductance densities even though they can generate reliable and similar behavior. This complicates a simple assignment of function to any conductance and is associated with variable responses of neurons of the same cell type to perturbations, deletions, and pharmacological manipulation. Ion channel genes often show strong positively correlated expression, which may result from the molecular and developmental rules that determine which ion channels are expressed in a given cell type.
CLO21-027: Defining Optimal Lymph Node Dissection and Clinical Impact of Number of Harvested Lymph Nodes During Esophageal Resection for Early Stage Esophageal Cancer
Authors: Anupam Rishi, Jordan McDonald, Sabrina Saeed, Rutika Mehta, David Pointer, Jessica Frakes, Sarah Hoffe, Jacques Fontaine, Jose Pimiento
Journal: Journal of the National Comprehensive Cancer Network (2021)

"CLO21-027: Defining Optimal Lymph Node Dissection and Clinical Impact of Number of Harvested Lymph Nodes During Esophageal Resection for Early Stage Esophageal Cancer" published on 17 Mar 2021 by National Comprehensive Cancer Network.
<i>Ciliary Rootlet Coiled-Coil 2 (crocc2)</i> Is Associated with Evolutionary Divergence and Plasticity of Cichlid Jaw Shape
Authors: Michelle C Gilbert, Emily Tetrault, Mary Packard, Dina Navon, R Craig Albertson
Journal: Molecular Biology and Evolution (2021)

Abstract Cichlid fishes exhibit rapid, extensive, and replicative adaptive radiation in feeding morphology. Plasticity of the cichlid jaw has also been well documented, and this combination of iterative evolution and developmental plasticity has led to the proposition that the cichlid feeding apparatus represents a morphological “flexible stem.” Under this scenario, the fixation of environmentally sensitive genetic variation drives evolutionary divergence along a phenotypic axis established by the initial plastic response. Thus, if plasticity is predictable then so too should be the evolutionary response. We set out to explore these ideas at the molecular level by identifying genes that underlie both the evolution and plasticity of the cichlid jaw. As a first step, we fine-mapped an environment-specific quantitative trait loci for lower jaw shape in cichlids, and identified a nonsynonymous mutation in the ciliary rootlet coiled-coil 2 (crocc2), which encodes a major structural component of the primary cilium. Given that primary cilia play key roles in skeletal mechanosensing, we reasoned that this gene may confer its effects by regulating the sensitivity of bone to respond to mechanical input. Using both cichlids and zebrafish, we confirmed this prediction through a series of experiments targeting multiple levels of biological organization. Taken together, our results implicate crocc2 as a novel mediator of bone formation, plasticity, and evolution.
Childhood antecedents of adolescent personality disorders
Authors: D P Bernstein, P Cohen, A Skodol, S Bezirganian, J S Brook
Journal: American Journal of Psychiatry (1996)

The purpose of this study was to investigate the childhood antecedents of personality disorders that are diagnosed in adolescence.A randomly selected community sample of 641 youths was assessed initially in childhood and followed longitudinally over 10 years. Childhood behavior ratings were based on maternal report; diagnoses of adolescent personality disorders were based on data obtained from both maternal and youth informants. Four composite measures of childhood behavior problems were used: conduct problems, depressive symptoms, anxiety/fear, and immaturity. Adolescent personality disorders were considered present only if the disorders persisted over a 2-year period. For all analyses, personality disorders were grouped into the three clusters (A, B, and C) of DSM-III-R.Logistic regression analyses indicated that all four of the putative childhood antecedents were associated with greater odds of an adolescent personality disorder 10 years later. Childhood conduct problems remained an independent predictor of personality disorders in all three clusters, even when other childhood problems were included in the same regression model. Additionally, depressive symptoms emerged as an independent predictor of cluster A personality disorders in boys, while immaturity was an independent predictor of cluster B personality disorders in girls. No moderating effects of age at time of childhood assessment were found.These results support the view that personality disorders can be traced to childhood emotional and behavioral disturbances and suggest that these problems have both general and specific relationships to adolescent personality functioning.
Weight and Metabolic Changes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living With HIV
Authors: Bernard Surial, Catrina Mugglin, Alexandra Calmy, Matthias Cavassini, Huldrych F. Günthard, Marcel Stöckle, Enos Bernasconi, Patrick Schmid, Philip E. Tarr, Hansjakob Furrer, Bruno Ledergerber, Gilles Wandeler, Andri Rauch
Journal: Annals of Internal Medicine (2021)

Background: Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain. Objective: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF. Design: Cohort study. Setting: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland. Participants: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer. Measurements: Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions Z tests. Results: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months. Limitation: Short follow-up, small subgroup analyses, and potential residual confounding. Conclusion: Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels. Primary Funding Source: Swiss National Science Foundation.
Low SARS-CoV-2 Transmission in Elementary Schools — Salt Lake County, Utah, December 3, 2020–January 31, 2021
Authors: Rebecca B. Hershow, Karen Wu, Nathaniel M. Lewis, Alison T. Milne, Dustin Currie, Amanda R. Smith, Spencer Lloyd, Brian Orleans, Erin L. Young, Brandi Freeman, Noah Schwartz, Bobbi Bryant, Catherine Espinosa, Yoshinori Nakazawa, Elizabeth Garza, Olivia Almendares, Winston E. Abara, Daniel C. Ehlman, Keith Waters, Mary Hill, Ilene Risk, Kelly Oakeson, Jacqueline E. Tate, Hannah L. Kirking, Angela Dunn, Snigdha Vallabhaneni, Adam L. Hersh, Victoria T. Chu
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

School closures affected more than 55 million students across the United States when implemented as a strategy to prevent the transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Reopening schools requires balancing the risks for SARS-CoV-2 infection to students and staff members against the benefits of in-person learning (2). During December 3, 2020-January 31, 2021, CDC investigated SARS-CoV-2 transmission in 20 elementary schools (kindergarten through grade 6) that had reopened in Salt Lake County, Utah. The 7-day cumulative number of new COVID-19 cases in Salt Lake County during this time ranged from 290 to 670 cases per 100,000 persons.† Susceptible§ school contacts¶ (students and staff members exposed to SARS-CoV-2 in school) of 51 index patients** (40 students and 11 staff members) were offered SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing. Among 1,041 susceptible school contacts, 735 (70.6%) were tested, and five of 12 cases identified were classified as school-associated; the secondary attack rate among tested susceptible school contacts was 0.7%. Mask use among students was high (86%), and the median distance between students' seats in classrooms was 3 ft. Despite high community incidence and an inability to maintain ≥6 ft of distance between students at all times, SARS-CoV-2 transmission was low in these elementary schools. The results from this investigation add to the increasing evidence that in-person learning can be achieved with minimal SARS-CoV-2 transmission risk when multiple measures to prevent transmission are implemented (3,4).
Results of Pivotal Phase 2 Trial of SL-401 in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Naveen Pemmaraju, Kendra L. Sweet, Andrew A. Lane, Anthony S. Stein, Sumithira Vasu, William Blum, David A. Rizzieri, Eunice S. Wang, Madeleine Duvic, Phyu Aung, Danielle Shubert, Sharon Spence, Shay Shemesh, Janice Chen, Christopher Brooks, Ivan Bergstein, Peter McDonald, Trishna Goswami, John Mark Sloan, Jeffrey E. Lancet, Hagop M. Kantarjian, Marina Konopleva
Journal: Blood (2017)
Abstract 15225: Atrial Conduction Delay Following Premature Stimulation Implies High Risk for Developing Postoperative Atrial Fibrillation in Cardiac Surgery Patients
Authors: Muhammad S Khan, Kennosuke Yamashita, Vikas Sharma, Ravi Ranjan, Craig Selzman, Derek J Dosdall
Journal: Circulation (2019)

Introduction: Following cardiac surgery, 20-50% of patients experience postoperative atrial fibrillation (POAF) during the first week. This adds an estimated $1 billion in the US healthcare economy...
Envisioning the Veterans Affairs Health Care System of the Future
Authors: Baligh R. Yehia, Stephan D. Fihn
Journal: JAMA (2021)

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P23.02 Clinicopathological and Prognostic Features of 67 Cases With Pulmonary Sarcomatoid Carcinoma: An 18-Year Single Center Experience
Authors: F. Ferhatoğlu, F. Amirov, B. Özkan, M. Kara, S.A. Toker, N. Ak, E. Aydın, E.D. Yılmazbayhan, A. Aydıner
Journal: Journal of Thoracic Oncology (2021)
MA10.03 The FITNESS Study: An Innovative Approach to Assessing Disability in Older Adults with Lung Cancer
Authors: N. Arrato, M. Grogan, J. Benedict, S. Janse, M. Naughton, B. Andersen, D. Carbone, E. Paskett, A. Rosko, C. Presley
Journal: Journal of Thoracic Oncology (2021)
Glioma cell heparan sulfate proteoglycans have an enhanced co-stimulator activity in FGF-2 signaling
Authors: Gui Su, Karianna Decker, Dianhua Qiao, Andreas Friedl
Journal: Cancer Research (2004)

4345  Fibroblast growth factor 2 (FGF-2) signaling plays an important role in autocrine growth stimulation of gliomas. Heparan sulfate (HS) proteoglycans (HSPGs) regulate FGF-2 signaling by participating in a ternary complex with FGF-2 and FGF receptor 1c (FGFR1c). The goal of this study was to test the hypothesis that altered HSPG profiles contribute to loss of growth control in gliomas. HSPGs were evaluated with a reporter cell assay, which allows analysis of FGF co-stimulator activity in isolation from other cellular factors. In this assay, U251 glioma cell HSPGs had an enhanced ability to activate the FGF-2/FGFR1c complex, compared to normal astrocytes. Binding assays in vitro revealed that this increased activity can be attributed to a dramatically increased binding capacity of glioma cell HS in the ternary complex. In contrast, glioma cell HS affinity in the ternary FGF-2 signaling complex was not significantly different from normal astrocyte HS. This suggests a qualitative difference between glioma and normal astrocyte HS. Specific sulfation patterns and thus protein binding domains within HS are generated by the concerted action of numerous sulfotransferase enzymes. Therefore, we measured the expression profile of these enzymes by quantitative real time RT-PCR. We found that 3-O-sulfotransferase mRNA level was increased, and 2-O-sulfotransferase was decreased in glioma cells compared to normal astrocytes. Next, we examined a possible link between the enhanced activity of glioma HSPGs and specific HSPG core proteins. We found that in a panel of glioma cell lines, expression levels of the GPI-linked cell surface HSPG glypican-1 closely mirrored the activity of glioma HSPGs as FGF-2 co-activators. Furthermore, removal of glypican-1 from U251 HSPGs significantly reduced FGF-2 co-stimulator activity. In summary, our data indicate that altered HSPGs in gliomas contribute to enhanced signaling of FGF-2 via FGFR1c and that glypican-1 plays a specific role in this mitogenic pathway.
Molecular features of untreated breast cancer and initial metastatic event inform clinical decision-making and predict outcome: long-term results of ESOPE, a single-arm prospective multicenter study
Authors: Céline Callens, Keltouma Driouch, Anaïs Boulai, Zakia Tariq, Aurélie Comte, Frédérique Berger, Lisa Belin, Ivan Bièche, Vincent Servois, Patricia Legoix, Virginie Bernard, Sylvain Baulande, Walid Chemlali, François-Clément Bidard, Virginie Fourchotte, Anne Vincent- Salomon, Etienne Brain, Rosette Lidereau, Thomas Bachelot, Mahasti Saghatchian, Mario Campone, Sylvie Giacchetti, Brigitte Sigal Zafrani, Paul Cottu
Journal: Genome Medicine (2021)

Abstract Background Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor. Very few studies have evaluated the impact of metastatic subtyping during the initial metastatic event in a prospective study. The genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting the findings transferability to clinical use. Methods We developed a multicenter, single-arm, prospective clinical trial in order to address these issues. Between November 2010 and September 2013, 123 eligible patients were included. Patients at the first, untreated metastatic event were eligible. All matched primary tumors and metastatic samples were centrally reviewed for pathological typing. Targeted and whole-exome sequencing was applied to matched pairs of frozen tissue. A multivariate overall survival analysis was performed (median follow-up 64 months). Results Per central review in 84 patients (out of 130), we show that luminal A breast tumors are more prone to subtype switching. By combining targeted sequencing of a 91 gene panel ( n = 67) and whole-exome sequencing ( n = 30), a slight excess of mutations is observed in the metastases. Luminal A breast cancer has the most heterogeneous mutational profile and the highest number of mutational signatures, when comparing primary tumor and the matched metastatic tissue. Tumors with a subtype change have more mutations that are private. The metastasis-specific mutation load is significantly higher in late than in de novo metastases. The most frequently mutated genes were TP53 and PIK3CA . The most frequent metastasis-specific druggable genes were PIK3CA , PTEN , KDR , ALK , CDKN2A , NOTCH4 , POLE , SETD2 , SF3B1 , and TSC2 . Long-term outcome is driven by a combination of tumor load and metastasis biology. Conclusions Profiling of the first, untreated, metastatic event of breast cancer reveals a profound heterogeneity mostly in luminal A tumors and in late metastases. Based on this profiling, we can derive information relevant to prognosis and therapeutic intervention, which support current guidelines recommending a biopsy at the first metastatic relapse. Trial registration The trial was registered at ClinicalTrials.gov (NCT01956552).