tbuckley/cabot-search huggingface dataset:
PET With 11C-Methyl-l-Methionine as a Predictor of Consequential Outcomes at the Time of Discontinuing Temozolomide-Adjuvant Chemotherapy in Patients With Residual IDH-Mutant Lower-Grade Glioma
Authors: Takaaki Beppu, Takeshi Iwaya, Yuichi Sato, Jun-Ichi Nomura, Kazunori Terasaki, Toshiaki Sasaki, Noriyuki Yamada, Shunrou Fujiwara, Tamotsu Sugai, Kuniaki Ogasawara
Journal: Clinical Nuclear Medicine (2022)

The aim of this study was to clarify whether PET with 11C-methyl-l-methionine (11C-met PET) can predict consequential outcomes at the time of discontinuing temozolomide (TMZ)-adjuvant chemotherapy in patients with residual isocitrate dehydrogenase gene (IDH)-mutant lower-grade glioma.Among 30 patients showing residual lesions of IDH-mutant lower-grade glioma, we compared the tumor-to-normal brain tissue ratio of standardized uptake values (SUVT/N) from 11C-met PET at the time of discontinuing TMZ-adjuvant chemotherapy with putative predictive factors including age, Karnofsky Performance Scale, number of courses of adjuvant therapy, residual tumor size, and promotor methylation status of O6-methylguanine-DNA methyl-transferase gene (MGMT). For each factor, progression-free survival (PFS) was compared between groups divided by cutoff values, determined to predict tumor relapse using receiver operating characteristic curves for each factor. Univariate and multivariate analyses were conducted using log-rank testing and Cox regression analysis, respectively. In addition, PFS was compared between patients grouped by combined findings from multiple predictors identified from univariate and multivariate analyses.Univariate and multivariate analyses identified SUVT/N from 11C-met PET and MGMT methylation status as independent predictors of outcomes after TMZ discontinuation. When comparing 3 groups assigned by the combination of MGMT and SUVT/N findings, PFS differed significantly among groups.The present study suggested that 11C-met PET at the time of discontinuing TMZ-adjuvant chemotherapy allows prediction of outcomes at least comparable to MGMT methylation status in patients with residual IDH-mutant lower-grade glioma. Further, 11C-met PET allows more precise prediction of outcomes by assessment in combination with MGMT findings.
Determination of Brain Death
Authors: David M. Greer
Journal: New England Journal of Medicine (2021)

The determination of brain death is typically made on the basis of clinical assessment (shown in a video) and requires demonstration of the permanent loss of all brain function, including brainstem function, in the absence of factors that may confound the assessment. If these factors cannot be eliminated, or if the examination cannot be safely or fully performed, ancillary testing is conducted.
Abstract P044: A Novel Digital Therapeutic Program Is Feasible For Patients With Peripheral Artery Disease
Authors: Saemundur Oddsson, Carl Wahlgren, Joakim Nordanstig, Anders Gottsäter, Thrudur Gunnarsdottir, Hildigunnur Ulfsdottir, Elias Gudmundsson, Agusta Bjornsdottir, Tryggvi Thorgeirsson
Journal: Circulation (2022)

Introduction: Patients with peripheral artery disease (PAD) are at increased risk for adverse cardiovascular and limb events and impaired quality of life. Lifestyle factors, such as patient physical activity levels and dietary habits, are known risk factors. Limited data is available on the feasibility and efficacy of tailored PAD digital therapeutic programs, focused on improving lifestyle (e.g. physical activity levels, dietary habits, sleep, stress, energy levels) and medication adherence. Hypothesis: We assessed the hypothesis that a digital therapeutic program is feasible among elderly patients with PAD. Methods: Patients were recruited from two vascular surgery specialty clinics in Sweden. Fourteen patients signed informed consent forms and started a four-week intervention based on the first weeks of the SK-111 digital program (Sidekick Health). Questionnaires were administered at baseline and at the end of the intervention. Data on in-app activity was collected throughout the intervention. Results: Out of the 14 patients (8 men, 6 women) who started the intervention, 11 stayed active within the platform from week 1 through 4. The 11 active participants performed a median of 7.1 activities in the app/day (IQR=3.4-12.9) and logged a median number of 4500 steps/day (IQR=2700-6455). The amount of physical activity logged/day went up from a mean of 21 (SD=39) min/day to 33 (SD=54) min/day from week 1 to week 4 (p=0.201). Seven participants (median age=72, IQR=69-73 years) answered both pre and post questionnaires. No changes were observed from pre to post intervention for either the walking distance domain of the Walking Impairment Questionnaire: 22.7 (SD=0.1) and 24.3 (SD=0.1), (p=0.499) or the Vascular Quality of Life Questionnaire sum score: 15.4 (SD=3.2) and 15.6 (SD=3.4), (p=0.864). For the pre-post medication adherence question (“During the last week, did you ever forget to take your PAD medication?” Rated from 0-10), ratings went down from 2.0 (SD=3.6) before to 0.1 (SD=0.4) after intervention (p=0.048). A post-program question asking whether using the platform helped them remember to take their medication, 5/7 (71%) patients considered it helpful. When asked how likely patients would be to recommend the PSP to others, the average score was 83/100. Conclusions: The findings from this feasibility study indicate that a PAD digital therapeutic program is feasible for elderly patients with PAD. A multicenter RCT is currently ongoing, where the clinical effectiveness of the full SK-111 will be further explored in this patient group.
Abstract 11438: Texture Analysis Identifies Differences in Cardiac Magnetic Resonance T1 Maps of Pediatric Heart Transplant Patients with Rejection
Authors: Devika Patel, Jason Mandell, Russell Cross, Karin Hamann, Christopher Rossi, Joshua Kanter, John T Berger, Laura Olivieri, Ashish Doshi
Journal: Circulation (2021)

Introduction: Graft rejection is a significant contributor to morbidity and mortality in pediatric heart transplant recipients, despite surveillance by endomyocardial biopsy (EMB). Cardiac Magnetic Resonance (CMR) T1 mapping has shown potential for noninvasive diagnosis of rejection. However, variability in normative T1 values across field strengths, vendors, and individual scanners limits the utility of absolute T1 values to diagnose rejection across institutions. Texture analysis is an emerging method for quantifying spatial distribution of relative voxel intensities rather than using the absolute voxel intensities themselves and may serve as an additional method for evaluating T1 maps. Hypothesis: We hypothesized that T1 maps from patients with rejection would exhibit differences in texture features from patients without rejection. Methods: This study included 19 cases from 17 pediatric transplant patients (mean age 11.8 ± 5 year, graft age 5.9 ± 4.7 years, 41% female) who underwent CMR imaging and EMB. 8 short axis slices of breath-held T1 mapping using Modified Look-Locker Inversion (MOLLI) recovery on 1.5T Siemens scanner were obtained. Left ventricular myocardium was semiautomatically segmented from T1 maps, excluding the blood pool and epicardial myocardium. Image texture analysis was performed on a single mid-ventricular slice from each case. Rejection was defined as acute cellular rejection (biopsy grade 1R or higher) or negative biopsy with decreased function requiring treatment. T-test analysis was performed to compare differences in texture analysis between patients with and without rejection. Results: Analysis of T1 maps showed differences (p-value ≤ 0.10) between patients with and without rejection in texture features of energy (0.062 ± 0.012 vs 0.091 ± 0.051), entropy (4.59 ± 0.23 vs 4.23 ± 0.60), and variance (0.031 ± 0.005 vs 0.025 ± 0.009). Discussion: In this small pilot study, texture analysis identified differences in tissue character between patients with and without graft rejection. Evaluation of tissue character via texture analysis may provide an additional method for diagnosis of rejection, given the variability in normative T1 values across institutions.
12P A phase II study of atezolizumab in combination with bevacizumab, carboplatin or cisplatin, and pemetrexed for EGFR-mutant metastatic NSCLC patients after failure of EGFR TKIs
Authors: S-G. Wu, C-C. Ho, J.C. Yang, B-C. Liao, C-Y. Yang, Y-T. Lin, C-J. Yu, W-Y. Liao, J-Y. Shih
Journal: Annals of Oncology (2022)
Abstract 071: Gaps In Statin Initiation And Target Lipid Reduction Arise Early After Diabetes Diagnosis
Authors: Alexander Heilman, Theodore Warsavage, Wenhui Liu, Sridharan Raghavan
Journal: Circulation (2022)

Background: Fewer than 60% of US adults with diabetes achieve low-density lipoprotein cholesterol (LDL) targets for atherosclerotic cardiovascular disease (ASCVD) prevention. Examining initiation of ASCVD primary prevention measures after diabetes diagnosis may reveal actionable gaps in diabetes care. Methods: We studied individuals in the VA Health Care System with newly diagnosed diabetes based on diagnosis codes and medications without known ASCVD and without a prior statin prescription at the time of diabetes diagnosis. We categorized 10-year ASCVD risk using the AHA/ACC pooled cohort equation (PCE) as &lt;7.5%, 7.5-20%, or ≥20% at the time of diabetes diagnosis. We compared statin initiation, LDL trajectories, and achieving target LDL (defined as two consecutive values &lt;100 mg/dL) within the first 5 years after diabetes diagnosis across ASCVD risk categories using multivariable Cox proportional hazards regression adjusted for baseline HbA1c, body mass index, and glomerular filtration rate. Results: Among 72,757 individuals who were statin-naïve at the time of diabetes diagnosis, 41,763 (57.4%) were prescribed a statin within 5 years. Relative to those in the lowest ASCVD risk category, the cumulative incidence of 5-year statin initiation increased in those with intermediate (hazard ratio [HR] 1.11 [1.08, 1.1], p&lt;0.001) and high risk (HR 1.19 [1.15, 1.22], p&lt;0.001) (Figure). LDL levels declined after diabetes diagnosis in all individuals with steeper declines in those at intermediate and high ASCVD risk (Figure). Among 55,844 individuals without LDL at goal at the time of diabetes diagnosis, 32,674 (58.5%) achieved target LDL within 5 years. Achievement of 5-year target LDL increased across ASCVD risk categories: HR 1.22 [1.18, 1.28] (p&lt;0.001) and HR 1.27 [1.22, 1.31] (p&lt;0.001) in those with 10-year risk 7.5-20% and ≥20%, respectively, relative to those with &lt;7.5% risk (Figure). Conclusion: Gaps in ASCVD primary prevention through statin therapy and LDL reduction arise early after diabetes diagnosis.
Why is knowledge faster than (true) belief?
Authors: Evan Westra
Journal: Behavioral and Brain Sciences (2021)

Abstract Phillips and colleagues convincingly argue that knowledge attribution is a faster, more automatic form of mindreading than belief attribution. However, they do not explain what it is about knowledge attribution that lends it this cognitive advantage. I suggest an explanation of the knowledge-attribution advantage that would also help to distinguish it from belief-based and minimalist alternatives.
Thoracic Oncology: Current Standard Therapy and Future Developments
Authors: Thomas E. Stinchcombe, Jeffrey D. Bradley
Journal: Journal of Clinical Oncology (2022)

Article Tools OVERVIEWS Special Series: Thoracic Oncology: Current and Future Therapy Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.21.02396 Journal of Clinical Oncology - published online before print January 5, 2022 PMID: 34985922 Thoracic Oncology: Current Standard Therapy and Future Developments Thomas E. Stinchcombe , MD1xThomas E. StinchcombeSearch for articles by this author and Jeffrey D. Bradley , MD2xJeffrey D. BradleySearch for articles by this author Show More 1Duke Cancer Institute, Durham, NC2Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA https://doi.org/10.1200/JCO.21.02396 First Page Full Text PDF Figures and Tables © 2022 by American Society of Clinical OncologyAUTHOR CONTRIBUTIONSConception and design: All authorsCollection and assembly of data: All authorsData analysis and interpretation: All authorsManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTThoracic Oncology: Current Standard Therapy and Future DevelopmentsThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Thomas E. StinchcombeThis author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Genentech/Roche, Foundation Medicine, EMD Serono, Novartis, Daiichi Sankyo, Lilly, Medtronic, Puma Biotechnology, Janssen Oncology, Regeneron, Turning Point Therapeutics, Sanofi/Aventis, GlaxoSmithKlineResearch Funding: AstraZeneca (Inst), Takeda (Inst), Advaxis (Inst), Regeneron (Inst), Seattle Genetics (Inst), Mirati Therapeutics (Inst)Jeffrey BradleyHonoraria: AstraZeneca/MedImmune, Mevion Medical SystemsConsulting or Advisory Role: Varian Medical Systems, GenentechNo other potential conflicts of interest were reported.
Abstract 028: Microbiota Composition And Diversity Is Associated With Trunk Fat: Findings From Baltimore Longitudinal Study Of Aging
Authors: Curtis Tilves, Toshiko Tanaka, Moira K Differding, Adam P Spira, Luigi Ferrucci, Noel T Mueller
Journal: Circulation (2022)

Background: Gut microbes have been associated with overall obesity in humans, including in monozygotic twins discordant on obesity, and they are sufficient to cause weight gain in mice. Trunk fat mass (TFM) is a stronger predictor of cardiometabolic diseases than overall obesity, but there is a dearth of human studies that have examined the association between gut microbiota and TFM using high-resolution shotgun metagenomic. Objective: To examine the association of gut microbiota diversity and composition with TFM. Methods: Baltimore Longitudinal Study of Aging is a racially diverse longitudinal cohort of adults ages ≥20. From 2013 to 2017, a subset of N=829 participants with DEXA scans for body composition also provided fecal samples for shotgun sequencing. We examined associations of microbiota alpha and beta diversity with TFM using ANCOVA and PERMANOVA, respectively. We tested for differential abundance of bacterial species across quartiles of TFM using ANCOM-BC. We then examined species significantly associated with TFM using splines and linear regression. All statistical models were adjusted for age, sex, and race. Results: Our analytic sample had a mean age of 70.5 years and BMI of 27.4 kg/m 2 , was 55.4% female, and 65.9% identified as White. TFM was associated with beta diversity (Weighted UniFrac p&lt;0.001), but not alpha diversity (Shannon p=0.93). A doubling in the Bacteroidetes : Firmicutes ( B / F ) ratio—a metric associated with obesity in prior studies—was associated with -0.55 kg (95%CI: -0.78, -0.31) lower TFM. After FDR-correction, four bacterial species ( R. gnavus, Clostridium, Blautia, Dorea spp. ) were associated with higher TFM, and in a monotonic fashion ( Figure ). These four species, but not the B / F ratio, remained significant after adjustment for BMI. Conclusion: In a large multiracial sample of US adults, four bacterial species were uniquely associated with abdominal fat independent of BMI. Future directions include verifying these associations in longitudinal models adjusting for lifestyle factors.
On the Twentieth Anniversary of Dendritic Cell Vaccines – Riding the Next Wave
Authors: Gerald P. Linette, Beatriz M. Carreno
Journal: Cancer Research (2022)

In the mid 1990's, a convergence of discoveries in dendritic cell (DC) biology and tumor antigen identification led investigators to study DCs as adjuvants for cancer vaccines. On the twentieth anniversary of a seminal clinical study by Jacques Banchereau and colleagues, we revisit the key events that prompted the initial wave of DC vaccine clinical studies and lessons learned that, in our opinion, helped forge the path for the field that we now call immuno-oncology. It is essential to recall that prior to the discovery of immune checkpoint therapy and chimeric antigen receptor (CAR) T-cell therapy, skepticism prevailed regarding the potential therapeutic benefit of immunotherapies. In hindsight, we can now appreciate how the early DC cancer vaccine trials helped investigators sustain their attention on adaptive immunity specific for malignant cells. These vaccines demonstrated clear evidence for induction of antigen-specific T cells and were well tolerated despite low rates of objective clinical response. In the context of the current era some 20 years later, harnessing DC vaccines has been shown to increase the breadth and diversity of tumor-specific T cells, and by trafficking to sites of metastases promote an inflamed tumor microenvironment. See related article by Banchereau and colleagues, Cancer Res 2001; 61:6451–8
Mechanisms and Models of Kidney Tubular Necrosis and Nephron Loss
Authors: Francesca Maremonti, Claudia Meyer, Andreas Linkermann
Journal: Journal of the American Society of Nephrology (2022)

Understanding nephron loss is a primary strategy for preventing CKD progression. Death of renal tubular cells may occur by apoptosis during developmental and regenerative processes. However, during AKI, the transition of AKI to CKD, sepsis-associated AKI, and kidney transplantation ferroptosis and necroptosis, two pathways associated with the loss of plasma membrane integrity, kill renal cells. This necrotic type of cell death is associated with an inflammatory response, which is referred to as necroinflammation. Importantly, the necroinflammatory response to cells that die by necroptosis may be fundamentally different from the tissue response to ferroptosis. Although mechanisms of ferroptosis and necroptosis have recently been investigated in detail, the cell death propagation during tubular necrosis, although described morphologically, remains incompletely understood. Here, we argue that a molecular switch downstream of tubular necrosis determines nephron regeneration versus nephron loss. Unraveling the details of this "switch" must include the inflammatory response to tubular necrosis and regenerative signals potentially controlled by inflammatory cells, including the stimulation of myofibroblasts as the origin of fibrosis. Understanding in detail the molecular switch and the inflammatory responses to tubular necrosis can inform the discussion of therapeutic options.
Cancer-Associated Hypercalcemia
Authors: Theresa A. Guise, John J. Wysolmerski
Journal: New England Journal of Medicine (2022)

Cancer-associated hypercalcemia often occurs late in the course of solid-tumor development and is associated with a poor prognosis. Treatment includes intravenous hydration followed by antiresorptive agents, typically intravenous bisphosphonates. Successful management ultimately depends on effective treatment of the underlying cancer.
Mitochondrial Telomerase Reverse Transcriptase Protects From Myocardial Ischemia/Reperfusion Injury by Improving Complex I Composition and Function
Authors: Niloofar Ale-Agha, Philipp Jakobs, Christine Goy, Mark Zurek, Julia Rosen, Nadine Dyballa-Rukes, Sabine Metzger, Jan Greulich, Florian von Ameln, Olaf Eckermann, Klaus Unfried, Fedor Brack, Maria Grandoch, Matthias Thielmann, Markus Kamler, Nilgün Gedik, Petra Kleinbongard, Andre Heinen, Gerd Heusch, Axel Gödecke, Joachim Altschmied, Judith Haendeler
Journal: Circulation (2021)

Background: The catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), has protective functions in the cardiovascular system. TERT is not only present in the nucleus but also in mitochondria. However, it is unclear whether nuclear or mitochondrial TERT is responsible for the observed protection, and the appropriate tools are missing to dissect this. Methods: We generated new mouse models containing TERT exclusively in the mitochondria (mitoTERT mice) or the nucleus (nucTERT mice) to finally distinguish between the functions of nuclear and mitochondrial TERT. Outcome after ischemia/reperfusion, mitochondrial respiration in the heart, and cellular functions of cardiomyocytes, fibroblasts, and endothelial cells, as well, were determined. Results: All mice were phenotypically normal. Although respiration was reduced in cardiac mitochondria from TERT-deficient and nucTERT mice, it was increased in mitoTERT animals. The latter also had smaller infarcts than wild-type mice, whereas nucTERT animals had larger infarcts. The decrease in ejection fraction after 1, 2, and 4 weeks of reperfusion was attenuated in mitoTERT mice. Scar size was also reduced and vascularization increased. Mitochondrial TERT protected a cardiomyocyte cell line from apoptosis. Myofibroblast differentiation, which depends on complex I activity, was abrogated in TERT-deficient and nucTERT cardiac fibroblasts and completely restored in mitoTERT cells. In endothelial cells, mitochondrial TERT enhanced migratory capacity and activation of endothelial nitric oxide synthase. Mechanistically, mitochondrial TERT improved the ratio between complex I matrix arm and membrane subunits, explaining the enhanced complex I activity. In human right atrial appendages, TERT was localized in mitochondria and there increased by remote ischemic preconditioning. The telomerase activator TA-65 evoked a similar effect in endothelial cells, thereby increasing their migratory capacity, and enhanced myofibroblast differentiation. Conclusions: Mitochondrial, but not nuclear TERT, is critical for mitochondrial respiration and during ischemia/reperfusion injury. Mitochondrial TERT improves complex I subunit composition. TERT is present in human heart mitochondria, and remote ischemic preconditioning increases its level in those organelles. TA-65 has comparable effects ex vivo and improves the migratory capacity of endothelial cells and myofibroblast differentiation. We conclude that mitochondrial TERT is responsible for cardioprotection, and its increase could serve as a therapeutic strategy.
Undetected COVID-19 cases in Africa
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2021)

A new analysis by WHO has concluded that the vast majority of cases of COVID-19 in Africa are not being detected. At time of the analysis, Oct 10, 2021, Africa had recorded around 8·4 million SARS-CoV-2 infections, and 217 000 deaths (the continent has since reported another 200 000 or so infections and 2000 deaths). WHO calculated that the true number of infections was seven times higher than the reported figure. The same analysis showed that two in three deaths from COVID-19 are not being registered in Africa.