tbuckley/cabot-search huggingface dataset:
Healthcare resource utilization, quality metrics, and costs of bladder cancer within the oncology care model.
Authors: L. Johnetta Blakely, Zsolt Hepp, Rupali Fuldeore, Samantha Tomicki, Jared Hirsch, Gabriela Dieguez, Heidi Wirtz
Journal: Journal of Clinical Oncology (2021)

54 Background: The Oncology Care Model (OCM) incentivizes practices to provide higher quality, lower cost care for Medicare beneficiaries through payment arrangements that include financial and performance accountability for 6-month care episodes. We sought to describe the existing experience with bladder cancer (BC) for OCM practices, in the context of all OCM cancer types, given the dynamic treatment landscape in which new and emerging therapies will impact spending and patient care in this payment model. Objective: To estimate healthcare resource utilization (HRU), OCM quality metrics, and costs for OCM episodes among Medicare beneficiaries with BC. Methods: OCM episodes triggered by receipt of cancer therapy (index event) were identified among Medicare beneficiaries (100% Research Identifiable Files) from 2016-18. Other inclusion criteria were enrollment in Parts A &amp; B for the entire OCM episode (6 months or until death) and 6 months pre-index date, Medicare as primary payer, and ≥1 qualifying Evaluation &amp; Management visit during the episode. A cancer type was assigned to each episode. BC episodes were stratified as low- (defined by receipt of BCG and/or mitomycin without other systemic therapy) or high-risk (receipt of systemic therapy other than BCG or mitomycin) based on OCM definitions. Results: Of the 2.2 million OCM cancer episodes identified among 1 million beneficiaries, 60,099 (̃3%) were BC episodes. Our analytic cohort consisted of 43,621 BC episodes (69% low-risk and 31% high-risk) among 33,497 beneficiaries. Across BC episodes, average patient age was 76.6 years and 77% were male. Relative to low-risk episodes, high-risk episodes included higher metastatic cases (40 vs 2%), and more comorbidity burden (7.4 vs 4.3 Charlson comorbidity score). High-risk episodes had more hospital admissions (0.7 vs 0.2) and intensive care unit use (17 vs 5%), longer length of stay (5.9 vs 4.9 days), and higher rates of surgery (7 vs 1%) and mortality (17 vs 2%). Among OCM quality metrics, high-risk episodes had higher inpatient admissions (42 vs 15%) and emergency department visits (37 vs 20%) relative to low-risk episodes. Average spending per high-risk BC episode was ̃$38,000 (vs $9,204 for low-risk), with ̃$11,000 spent on systemic therapies and ̃$7,000 on inpatient services. Conclusions: High-risk OCM episodes of BC, which included 40% metastatic BC, had higher HRU and costs, and lower quality performance, than low-risk episodes. Novel therapies offer a significant opportunity to optimize BC management and improve quality of care, particularly for high-risk episodes. Further, as &lt; 3% of OCM episodes were attributed to BC, and only one-third of BC episodes were classified as high-risk, controlling expenditure on novel therapies in BC episodes is unlikely to impact overall performance for practices participating in OCM.
Histone deacetylase inhibitors improve the antitumor effect of conditionally replicating adenovirus by increasing CAR expression
Authors: Mi-Young Park, Yoon-Jin Lee, Sung-Youn Kwon, Ho-Il Yoon, Jae-Ho Lee, Yung-Jue Bang, Choon-Taek Lee
Journal: Cancer Research (2007)

3300  The efficacy of adenoviral gene therapy was partly influenced by the infectivity of adenovirus which was determined by CAR expression on cancer cells. The expression levels of CAR in cancer cells were extremely variable. In general, cancer cells in human tumor tissue showed lower level of CAR expression compared with corresponding cancer cell lines. We previously reported that sodium butyrate, histone deacetylase inhibitor(HDAC inhibitor), could increase the CAR expression in CAR deficient bladder cancer lines and made them vulnerable to adenovirus-p16 (Lee CT et al. Clin Cancer Res 2001). In this study, we used new HDAC inhibitor (SK-7041, -7068) and conditionally replicating adenovirus(CRAD: ad-Δ24) for the oncolytic adenoviral gene therapy in several CAR deficient cancer cell lines. Pretreatment of SK-7041 and SK-7068: Park JH et al. Clin Cancer Res 2004) increased the CAR expression in two human bladder cancer cell lines(J82, HT1376) and two human lung cancer cell lines (NCI H460 and NCI H2122). The luciferase expression from ad-Δ24-luc was markedly increased by pretreatment of SK-7041 and SK7068. Cell cytolysis due to ad-Δ24 was markedly increased by SK-7041 and SK-7068 in J82, HT1376, NCI H460 and NCI H2122. This finding suggests the value of combination therapy with HDAC inhibitor and CRAD. Further study will focus on the animal tumor models with different cell lines.
Action-based organization of a cerebellar module specialized for predictive control of multiple body parts
Authors: Shane A Heiney, Gregory J Wojaczynski, Javier F Medina
Journal: Neuron (2021)

The role of the cerebellum in predictive motor control and coordination has been thoroughly studied during movements of a single body part. In the real world, however, actions are often more complex. Here, we show that a small area in the rostral anterior interpositus nucleus (rAIN) of the mouse cerebellum is responsible for generating a predictive motor synergy that serves to protect the eye by precisely coordinating muscles of the eyelid, neck, and forelimb. Within the rAIN region, we discovered a new functional category of neurons with unique properties specialized for control of motor synergies. These neurons integrated inhibitory cutaneous inputs from multiple parts of the body, and their activity was correlated with the vigor of the defensive motor synergy on a trial-by-trial basis. We propose that some regions of the cerebellum are organized in poly-somatotopic "action maps" to reduce dimensionality and simplify motor control during ethologically relevant behaviors.
Hidden Historical Habitat-Linked Population Divergence and Contemporary Gene Flow of a Deep-Sea Patellogastropod Limpet
Authors: Ting Xu, Yan Wang, Jin Sun, Chong Chen, Hiromi Kayama Watanabe, Junlin Chen, Pei-Yuan Qian, Jian-Wen Qiu
Journal: Molecular Biology and Evolution (2021)

Hydrothermal vents and hydrocarbon seeps in the deep ocean are rare oases fueled by chemosynthesis. Biological communities inhabiting these ecosystems are often distributed in widely separated habitats, raising intriguing questions on how these organisms achieve connectivity and whether habitat types facilitate intraspecific divergence. The deep-sea patellogastropod limpet Bathyacmaea nipponica that colonizes both vents and seeps across ∼2,400 km in the Northwest Pacific is a feasible model to answer these questions. We analyzed 123 individuals from four vents and three seeps using a comprehensive method incorporating population genomics and physical ocean modeling. Genome survey sequencing and genotyping-by-sequencing resulted in 9,838 single-nucleotide polymorphisms for population genomic analyses. Genetic divergence and demographic analyses revealed four habitat-linked (i.e., three seep and one vent) genetic groups, with the vent genetic group established via the opportunistic invasion of a few limpet larvae from a nearby seep genetic group. TreeMix analysis uncovered three historical seep-to-vent migration events. ADMIXTURE and divMigrate analyses elucidated weak contemporary gene flow from a seep genetic group to the vent genetic group. Physical ocean modeling underlined the potential roles of seafloor topography and ocean currents in shaping the genetic connectivity, contemporary migration, and local hybridization of these deep-sea limpets. Our study highlighted the power of integrating genomic and oceanographic approaches in deciphering the demography and diversification of deep-sea organisms. Given the increasing anthropogenic activities (e.g., mining and gas hydrate extraction) affecting the deep ocean, our results have implications for the conservation of deep-sea biodiversity and establishment of marine protected areas.
Recommendations for Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy
Authors: Benjamin A. Derman, Andrew M. Davis
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
PL03.3.A Development and characterization of CD317-specific CAR T cells as an innovative immunotherapeutic strategy against glioblastoma
Authors: L Hänsch, M Peipp, R Myburgh, M Silginer, T Weiss, D Gramatzki, F Vasella, M Manz, M Weller, P Roth
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Due to the limited success of existing therapies for gliomas, innovative therapeutic options are urgently needed. Chimeric antigen receptor (CAR) T cell therapy has been successful in patients with hematological malignancies. However, using this treatment against solid tumors such as glioblastomas is more challenging. Here, we generated CAR T cells targeting the transmembrane protein CD317 (BST-2, HM1.24) which is overexpressed in glioma cells and may therefore serve as a novel target antigen for CAR T cell-based immunotherapy. MATERIAL AND METHODS CAR T cells targeting CD317 were generated by lentiviral transduction of human T cells from healthy donors. The anti-glioma activity of CD317-CAR T cells was determined in lysis assays using different glioma target cell lines with varying CD317 expression levels. The efficiency of CD317-CAR T cells to control tumor growth in vivo was evaluated in clinically relevant orthotopic xenograft glioma mouse models. RESULTS We created a second-generation CAR construct targeting CD317 and observed strong anti-glioma activity of CD317-CAR T cells in vitro. Glioma cells with a CRISPR/Cas9-mediated CD317 knockout were resistant to CD317-specific CAR T cells, demonstrating their target antigen-specificity. Since CD317 is also expressed by T cells, transduction with a CD317-directed CAR resulted in fratricide of the transduced T cells. Silencing of CD317 in CAR T cells by integrating a specific shRNA into the CAR vector significantly increased the viability, proliferation and cytotoxic function of the CAR T cells. Importantly, intratumoral treatment with CD317-CAR T cells prolonged the survival and cured a significant fraction of glioma-bearing nude mice. CONCLUSION We demonstrate strong CD317-specific anti-tumor activity of CD317-CAR T cells against various glioma cell lines in vitro and in xenograft glioma models in vivo. These data lay a scientific basis for the subsequent evaluation of this therapeutic strategy in clinical neuro-oncology.
Shared decision-making to foster same-day discharge for patients with breast cancer undergoing mastectomy with or without immediate implant-based reconstruction.
Authors: Melissa Shelby, Stephanie Byrum, Julie A Billar, Michelle Carnes, Maryam Khan, Amber Decker, Gale Walthall
Journal: Journal of Clinical Oncology (2021)

65 Background: In 2020, over 324,500 cases of invasive and non-invasive breast cancer were diagnosed, of which 36% underwent mastectomies. The post-operative period for these breast cancer patients can be an especially taxing time, not just because of the physical recovery involved, but the associated financial toxicity a patient may face. Consideration of these factors, and a desire to optimize shared decision-making between providers, nursing staff and patients, prompted the breast team at Banner MD Anderson Cancer Center (BMDACC) to coordinate a system change in post-operative planning for mastectomy patients. Methods: Implementing same day discharge (SDD) as a quality improvement process change for breast cancer patients undergoing mastectomy with or without immediate implant-based reconstruction began in December 2018. A collaborative effort to reduce length of stay while maintaining quality and safety was the goal of the process change. Shared decision making was utilized as the methodology for the quality initiative. Open communication and honest expectations of the postoperative management allowed the patient to be actively involved and helped to remove any preconceived notions about the necessity of post-operative hospitalization. A chart review comprised of retrospective data from 2017-2018 and prospective data from 2019-2020 was performed on SDD and admitted (ADM) patients who underwent mastectomy with or without immediate implant-based reconstruction. The SDD group was contacted to voluntarily answer a survey on their outpatient surgical experience using the Consumer Assessment of Healthcare Providers and Systems Outpatient and Ambulatory Surgery Survey (OAS CAHPS) .Results: The utilization of shared decision-making revealed an increase in SDD with no increase in readmission or adverse events (Table). The OAS CAHPS survey was completed by78% SDD; findings revealed 95% of patients responded positively to all questions. Conclusions: For patients undergoing mastectomy, with or without immediate implant-based reconstruction, SDD is a safe and value-based initiative that has been adopted as standard of care at BMDACC. [Table: see text]
Self-reported Practices of Frontline Cannabis Dispensary Workers and the Implications for Clinicians
Authors: Theresa E. Matson, Katharine A. Bradley, Gwen T. Lapham
Journal: JAMA Network Open (2021)

Jessica S. Merlin, MD, PhD, MBA; Andrew Althouse, PhD; Robert Feldman, MS; Julia H. Arnsten, MD, MPH; Hailey W. Bulls, PhD; Jane M. Liebschutz, MD, MPH; Shannon M. Nugent, PhD; Steven R. Orris, BS; Rebecca Rohac, BS; Joanna L. Starrels, MD, MSCE; Benjamin J. Morasco, PhD; Devan Kansagara, MD, MCR
A Missense Variant in the IL-6 Receptor and Protection From Peripheral Artery Disease
Authors: Michael G. Levin, Derek Klarin, Marios K. Georgakis, Julie Lynch, Katherine P. Liao, Benjamin F. Voight, Christopher J. O’Donnell, Kyong-Mi Chang, Themistocles L. Assimes, Philip S. Tsao, Scott M. Damrauer
Journal: Circulation Research (2021)
Covid-19 infection in patients with hematological diseases in Brazil: Clinical characteristics and prognostic factors
Authors: K. T. Maio, L. B. De Oliveira Alves, B. Del Guerra De Carvalho Moraes, M. Bellesso, A. Brandao, G. H. H. Fonseca, A. Duran, J. Pereira, L. Mariano, E. M. Rego, H. Higashino, S. Chevret, S. F. Costa, V. Rocha
Journal: HemaSphere (2021)

Background: The COVID-19 pandemic had a high burden in Brazil. To date, data on mortality and prognostic factors of COVID-19 infection in Brazilian patients with hematological disorders are scarce. Aims: To describe the characteristics and outcomes of patients with hematological disorders admitted to the hematological COVID care unit of a reference center in Brazil;to analyze the impact of prognostic factors on in-hospital mortality. Methods: This prospective, single-center study,included 118 patients who have been admitted to the hematological COVID care unit of the Hospital das Clinicas da Faculdade de Medicina da USP, S.o Paulo, Brazil, from March to September 2020.All patients had >18 years,an underlying hematological disease and a moderate or severe COVID- 19 infection.For analyses, patients were grouped in:(1)benign or no oncological treatment(n=43),(2) intensive chemotherapy,including induction protocols for acute leukemia and stem cell transplantation conditioning(n=44) or(3) intermediate chemotherapy,including lymphoma regimens,myeloma triple treatment or continuous treatment( n=31).The primary outcome was in-hospital mortality;secondary outcome was overall survival after admission in the COVID-19 unit.Univariate analysis(UVA) used odds ratio(OR) for baseline characteristics and ROC curve analysis for laboratory tests collected at admission.Multivariate analyses(MVA) were adjusted by age and hematological disease status group.The median follow-up and survival time after COVID-19-unit admission were estimated by Kaplan- Meier method.All statistical tests were two-sided;p-values 440 U/L(OR=16.8,95%CI 4.9-71.8),C-reactive protein(CRP)>100 mg/L(OR=4.1,95%CI 1.4-13.6) or platelet count<150x10e9/L(OR=3.7,95%CI 1.3-11.7), regardless of age(OR=1.2,95%CI 1.0-1.5).79% of in-hospital deaths were from COVID-19;others were mainly due to hematological disease.The overall median survival time after admission was 92 days(95% CI 34-NA) and the 75-day survival probability was 51%(95%CI 41-60).25% of patients had hospital readmission,mostly due to other infections. Summary/Conclusion: In line with other reports,patients with hematological diseases are at higher risk of mortality from COVID-19 infection, particularly in low and middle income countries.In our cohort, prognostic factors were status of disease,platelets count,LDH and CRP. These findings might help risk stratification and prioritization of vaccines in this setting.
P04.07 The molecular evolution of oligodendrogliomas
Authors: M Padovan, W Vallentgoed, I de Heer, G Lombardi, M van den Bent, P French
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Oligodendroglioma (OD) is defined by the presence of both IDH1/2 mutation and 1p/19q codeletion. Although prognosis of OD patients is relatively favorable, tumours usually relapse and often evolve to a higher malignancy grade, with some acquiring the treatment induced hypermutated phenotype. To better understand how these tumours evolve in time, we examined the molecular differences between matched primary and recurrent ODs. MATERIAL AND METHODS We identified 21 patients who underwent surgery at least twice [male: 11, female: 10, median age: 44 years (31–66)]. Clinical data were available for 14/21 patients: 5/14 received a treatment between resections [4 radiotherapy, 1 radiotherapy followed by PCV chemotherapy]; median time from the first to the second surgery was 71.5 months (12–158). Whole genome DNA-methylation analysis was performed using Illumina’s MethylationEPIC ‘850K’ BeadChip. Results were evaluated using the Molecularneuropathology.org platform (version 3.1.5) and in R. RESULTS Most samples were WHO grade 2 ODs [14, 10 and 1 tumours in first, second and third resection group, respectively]; WHO grade 3 was found in 6, 10 and 3 tumours in first, second and third resection, respectively; in 4 patients the tumour showed malignant progression from grade 2 to 3. Most ODs exhibited an IDH1 R132H mutation [17/21 patients]; in no cases was IDH1/2 mutation lost during progression. DNA methylation analysis was successfully performed in 41/45 cases [primary OD: 17, recurrent OD: 24] for a total of 18 matched pairs. 37 samples were assigned to the “IDH mutant glioma, subclass 1p/19q codeleted OD”; the remaining 4 were assigned to various other methylation classes but CNV (copy number variation) analysis confirmed the 1p19q codeletion in all samples. Recurrent tumours exhibited de novo loss of chromosome 4 in 3/24 cases (12.5%) and loss of chromosome 13 in 3/24 cases (12.5%). In unsupervised analysis of the 1000 most variable CpG sites, samples from the same patient clustered together. This indicates that the inter-tumour variability is greater than the intra-, temporal- or grading variability between tumours. There were no overt differences in DNA methylation levels between the primary and matched recurrent OD. However, lower genome wide DNA methylation levels were observed in tumours that dedifferentiated to grade 3 ODs compared to those of grade 2, indicating that DNA demethylation is associated to higher malignancy grade. CONCLUSION DNA methylation analysis in a cohort of primary and recurrent oligodendrogliomas highlights the genomic and epi-genetic changes that are acquired at tumour progression. We are currently expanding the cohort and collecting/integrating the clinical data to better explore the evolution of recurrent ODs.
Urinary L-FABP is a promising prognostic biomarker of ACLF and mortality in patients with decompensated cirrhosis
Authors: Adrià Juanola, Isabel Graupera, Chiara Elia, Salvatore Piano, Cristina Solé, Marta Carol, Martina Pérez-Guasch, Octavi Bassegoda, Laia Escudé, Ana-Belén Rubio, Marta Cervera, Laura Napoleone, Emma Avitabile, Ann T. Ma, Núria Fabrellas, Elisa Pose, Manuel Morales-Ruiz, Wladimiro Jiménez, Ferran Torres, Gonzalo Crespo, Elsa Solà, Pere Ginès
Journal: Journal of Hepatology (2021)
Rapid and Label‐Free Detection of 5‐Hydroxymethylcytosine in Genomic DNA Using an Au/ZnO Nanorods Hybrid Nanostructure‐Based Electrochemical Sensor
Authors: Kiesar Sideeq Bhat, Hyejin Kim, Asrar Alam, Myunggon Ko, Jungeun An, Sooman Lim
Journal: Advanced Healthcare Materials (2021)

Abstract Ten‐eleven‐translocation (TET) proteins modify DNA methylation by oxidizing 5‐methylcytosine (5mC) to 5‐hydroxymethylcytosine (5hmC). Loss of 5hmC, a widely accepted epigenetic hallmark of cancers, is proposed as a biomarker for early cancer diagnosis and prognosis. Thus, precise quantification of 5hmC holds great potential for diverse clinical applications. DNAs containing 5mC or 5hmC display different adsorption affinity toward the gold surface, thus producing different electrochemical responses. Here a novel, label‐free electrochemical sensor based on gold nanoparticles (Au NPs)/zinc oxide nanorods (ZnO NRs) nanostructure for the facile and real‐time detection of 5hmC‐enriched DNAs is reported. The hybrid structure is fabricated by the vertical hydrothermal growth of ZnO NRs onto indium tin oxide glass substrate, followed by the decoration of ZnO NRs with Au NPs via sputtering. Successful fabrication is confirmed by analyzing the morphology and chemical composition of the sensor. By coupling the fabricated sensor with cyclic voltammetry, its functionality in distinguishing genomic DNAs containing different levels of 5hmC is validated. Notably, the sensor device successfully and consistently detects 5hmC loss in primary hepatocellular carcinoma, compared to the normal tissues. Thus, the novel sensing strategy to assess DNA hydroxymethylation will likely find broad applications in early cancer diagnosis and prognosis evaluation.