tbuckley/cabot-search huggingface dataset:
Reliability of Quantitative 18F-FDG PET/CT Imaging Biomarkers for Classifying Early Response to Chemoradiotherapy in Patients With Locally Advanced Non–Small Cell Lung Cancer
Authors: Kevin P. Horn, Hannah M.T. Thomas, Hubert J. Vesselle, Paul E. Kinahan, Robert S. Miyaoka, Ramesh Rengan, Jing Zeng, Stephen R. Bowen
Journal: Clinical Nuclear Medicine (2021)

Purpose of the Report We evaluated the reliability of 18 F-FDG PET imaging biomarkers to classify early response status across observers, scanners, and reconstruction algorithms in support of biologically adaptive radiation therapy for locally advanced non–small cell lung cancer. Patients and Methods Thirty-one patients with unresectable locally advanced non–small cell lung cancer were prospectively enrolled on a phase 2 trial (NCT02773238) and underwent 18 F-FDG PET on GE Discovery STE (DSTE) or GE Discovery MI (DMI) PET/CT systems at baseline and during the third week external beam radiation therapy regimens. All PET scans were reconstructed using OSEM; GE-DMI scans were also reconstructed with BSREM-TOF (block sequential regularized expectation maximization reconstruction algorithm incorporating time of flight). Primary tumors were contoured by 3 observers using semiautomatic gradient-based segmentation. SUV max , SUV mean , SUV peak , MTV (metabolic tumor volume), and total lesion glycolysis were correlated with midtherapy multidisciplinary clinical response assessment. Dice similarity of contours and response classification areas under the curve were evaluated across observers, scanners, and reconstruction algorithms. LASSO logistic regression models were trained on DSTE PET patient data and independently tested on DMI PET patient data. Results Interobserver variability of PET contours was low for both OSEM and BSREM-TOF reconstructions; intraobserver variability between reconstructions was slightly higher. ΔSUV peak was the most robust response predictor across observers and image reconstructions. LASSO models consistently selected ΔSUV peak and ΔMTV as response predictors. Response classification models achieved high cross-validated performance on the DSTE cohort and more variable testing performance on the DMI cohort. Conclusions The variability FDG PET lesion contours and imaging biomarkers was relatively low across observers, scanners, and reconstructions. Objective midtreatment PET response assessment may lead to improved precision of biologically adaptive radiation therapy.
Sequential Cellular Niche Plays a Crucial Role in the Generation of Enucleated Erythrocytes from Human Pluripotent Stem Cells
Authors: Jun Shen, Ziceng Feng, Cuicui Lyu, Dixie Hoyle, Guangzhen Ji, Wei Wen, Jing Xu, Lu Zhang, Jianping Zhang, Xiaobing Zhang, Tao Cheng, Zack Wang
Journal: Blood (2017)
Abstract 123: Adenoviral RhoA Regulation of Dynamin-related Protein 1 and Cardiac Mitochondrial Fission
Authors: Cameron S Brand, Valerie P Tan-Sah, Joan Heller Brown, Shigeki Miyamoto
Journal: Circulation Research (2016)

G protein coupled receptors can signal downstream through various pathways, including activation of the small G protein RhoA. In cardiomyocytes, RhoA signaling is protective against ischemia/reperfusion injury. We have previously shown that this is mediated through downstream activation of Protein Kinase D (PKD), increased phosphorylation of cofilin, and diminished translocation of pro-apoptotic proteins to the mitochondria (Xiang et al, Sci. Signaling 2013). Mitophagy, a process that removes damaged mitochondria and limits mitochondrial death signaling, has also been suggested to be a cardioprotective response to oxidative stress. A step considered to be preliminary to clearance of damaged mitochondria via mitophagy is mitochondrial fission, and we hypothesized that RhoA signaling increases mitochondrial fission in cardiomyocytes. Constitutively active RhoA expressed in neonatal rat ventricular myocytes (NRVMs) was found to accumulate at the mitochondria. This was associated with an increase in small, fragmented mitochondria as observed by fluorescent confocal microscopy and electron microscopy, indicative of increased mitochondrial fission. The main protein involved in mitochondrial fission, dynamin-related protein 1 (Drp1), translocates from the cytosol to the mitochondria when activated. We used a tagged adenoviral Drp1 construct to determine whether expression of active RhoA changes Drp1 levels at the mitochondria. Mitochondrial Drp1 increased within 12 hours of adenoviral expression of active RhoA. Adenoviral RhoA expression also increased phosphorylation of Drp1 at serine-616 in NRVMs. In summary, we show that in cardiomyocytes, RhoA associates with mitochondria, can increase Drp1 phosphorylation and Drp1 mitochondrial localization, and can induce mitochondrial fission. The relationship between these mitochondrial signaling events and the protein kinases that are involved are currently under investigation. We suggest that G protein coupled receptors that stimulate RhoA can induce Drp1 accumulation and mitochondrial fission, which contributes to their cardioprotective effect.
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study
Authors: Jesus G Berdeja, Deepu Madduri, Saad Z Usmani, Andrzej Jakubowiak, Mounzer Agha, Adam D Cohen, A Keith Stewart, Parameswaran Hari, Myo Htut, Alexander Lesokhin, Abhinav Deol, Nikhil C Munshi, Elizabeth O'Donnell, David Avigan, Indrajeet Singh, Enrique Zudaire, Tzu-Min Yeh, Alicia J Allred, Yunsi Olyslager, Arnob Banerjee, Carolyn C Jackson, Jenna D Goldberg, Jordan M Schecter, William Deraedt, Sen Hong Zhuang, Jeffrey Infante, Dong Geng, Xiaoling Wu, Marlene J Carrasco-Alfonso, Muhammad Akram, Farah Hossain, Syed Rizvi, Frank Fan, Yi Lin, Thomas Martin, Sundar Jagannath
Journal: The Lancet (2021)
Early reduction in circulating monocyte count predicts maintenance of remission in patients with rheumatoid arthritis treated with anti-TNF therapy
Authors: Muhammad Ruhul Amin Shipa, Raj Amarnani, Su-Ann Yeoh, M D Mainuddin, Michael R Ehrenstein
Journal: Annals of the Rheumatic Diseases (2021)

Maintenance of remission once achieved is becoming a critical goal for patients with rheumatoid arthritis (RA) as outcomes improve and advances in therapies continue.1 2 Identification of biomarkers to facilitate tailoring of treatment is often linked to modest response criteria, but less frequently to the more stringent target of sustained remission. We have previously implicated monocytes as potential predictor of response to anti-tumour necrosis factor (TNF) through modulation of regulatory T cells, which may promote maintenance of remission through re-establishment of immune tolerance.3 Circulating monocyte numbers are increased in RA but fall in patients who respond to TNF blockade.4 Whether changes in monocyte numbers can also predict loss of remission, once achieved, to anti-TNF therapy is unknown. We therefore addressed whether the change in monocyte counts in the first year from initiation of anti-TNF therapy (baseline) would predict loss of remission (LOR) in patients who achieved sustained remission.

We extracted data (June 2020) from two independent cohorts of adult biologic-naive patients with RA who attained sustained remission while treated with anti-TNF between January 2008 and December 2019 (online supplemental table 1). In this retrospective study, Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate ≤2.6 on at least two occasions (3–6 months apart) after initiation of anti-TNF therapy was used as the definition of remission, as this index was routinely calculated at the treating hospitals. A more stringent definition of remission based on the Clinical Disease Activity Index (CDAI ≤2.8) …
The changing role of Sport &amp; Exercise Medicine in the post COVID-19 world
Authors: Polly Baker, Robin Chatterjee
Journal: British Journal of Sports Medicine (2021)

The original research studies, ‘Injury patterns differ with age in male youth football: A four season prospective study of 1111 time loss injuries in an elite national academy’ (see page 794) and ‘Injury prevention knowledge beliefs and strategies in elite female footballers at the FIFA Women’s World Cup France 2019’ (see page 801) , serve as a reminder that the physical and mental health issues that existed before the pandemic still remain. For the elite athlete, training during lockdown, having to live in bubbles and isolation from family and friends have added to the mental pressures, stresses and strains that already existed, such as those captured in the editorial ‘Batting against mental health in elite cricket’ (see page 765) . [...]as the problems of our patients evolve with the changing times, while we will also change our educational focus, we will still maintain the highest standards of research and provide you with the tutelage you need to navigate the new normal.
Finally, Effective Inhibitors of Mutant KRAS
Authors: Neal Rosen
Journal: New England Journal of Medicine (2021)

Kirsten rat sarcoma viral oncogene homologue (KRAS) is one of the most highly mutated oncogenes in human cancer, occurring in 95% of pancreatic, 50% of colorectal, and 32% of lung adenocarcinomas and other tumors as well.1 KRAS and two family members, NRAS and HRAS, function as transducers of the signals induced by activated growth factor receptors. RAS is a member of the family of guanine nucleotide–binding proteins. When bound to guanosine diphosphate (GDP), these proteins are inactive. Receptor activation leads to the activation of a family of guanine nucleotide exchange factors (GEFs), which cause GDP to be replaced by guanosine . . .
Impact of Optimal Medical Therapy on 10-Year Mortality After Coronary Revascularization
Authors: Hideyuki Kawashima, Patrick W Serruys, Masafumi Ono, Hironori Hara, Neil O'Leary, Michael J Mack, David R Holmes, Marie-Claude Morice, Stuart J Head, Arie Pieter Kappetein, Daniel J F M Thuijs, Milan Milojevic, Thilo Noack, Friedrich-Wilhelm Mohr, Piroze M Davierwala, Faisal Sharif, John W McEvoy, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2021)
Contemporary Lung Cancer Screening and the Promise of Blood-Based Biomarkers
Authors: Mitchell S. von Itzstein, David E. Gerber, John D. Minna
Journal: Cancer Research (2021)

Abstract In this issue, the study by Dagnino and colleagues represents an important addition to the maturing field of blood-based biomarkers for lung cancer screening. Their comprehensive approach to analyzing circulating inflammatory proteins identified CDCP1 as a potential biomarker for distinguishing patients with or without lung cancer, a finding that was confirmed in a validation cohort. CDCP1 blood levels, when combined with smoking history, gave an AUC receiver operator characteristic of 0.75. Analysis of transcripts in peripheral blood cells suggested a Wnt/β-catenin signaling–based mechanism for CDCP1 in tumorigenesis providing biologic plausibility. CDCP1 now joins the ranks of other potential blood-based lung cancer screening biomarkers (including epithelial tumor marker proteins, tumor-associated miRNA, antitumor antibodies, and tumor-specific DNA methylation) that need validation in future clinical trials. Further exploration of how CDCP1 levels might be integrated into current lung cancer screening programs, including both detection of lung cancer, and evaluation of the need for invasive biopsies, as well as how CDCP1 performs in different racial populations, is warranted. See related article by Dagnino et al., p. 3738
Hedgehog Pathway Mutations Drive Oncogenic Transformation in High-Risk T-Cell Acute Lymphoblastic Leukemia
Authors: Melissa A. Burns, Zi Wei Liao, Gayle P. Pouliot, Kristen E. Stevenson, Donna S. Neuberg, Aaron R. Thorner, Matthew D. Ducar, Emily A. Silverman, Stephen P. Hunger, Mignon L. Loh, Stuart S. Winter, Kimberly P. Dunsmore, Brent Wood, Meenakshi Devidas, Marian H. Harris, Lewis B. Silverman, Stephen E. Sallan, Alejandro Gutierrez
Journal: Blood (2017)
ピオグリタゾンは2型糖尿病患者におけるLDLよりも代謝性疾患の定量的及び定性的マーカー,mall dense LDLを低下させる
Authors: Takata Yasunori, Funada Junichi, Morioka Norikatsu, Hashida Hidetoshi, Iwata Takeru, Okayama Hideki, Osawa Haruhiko
Journal: Circulation (2010)
Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia
Authors: Ari Polachek, Victoria Furer, Mirna Zureik, Sharon Nevo, Liran Mendel, David Levartovsky, Jonathan Wollman, Valerie Aloush, Reut Tzemach, Ofir Elalouf, Marina Anouk, Mark Berman, Ilana Kaufman, Or Carmi, Yael Lahat, Tali Eviatar, Hagit Padova, Hagit Sarbagil-Maman, Sara Borok, Adi Broyde, Lihi Eder, Daphna Paran, Ori Elkayam
Journal: Annals of the Rheumatic Diseases (2021)

To investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS).The study population included 156 consecutive PsA patients who were recruited prospectively and fulfilled the ClASsification criteria for Psoriatic ARthritis criteria. The patients underwent complete clinical evaluation including assessment of fulfilment of the 2016 fibromyalgia classification criteria. All of the patients underwent US evaluation including 52 joints, 40 tendons and 14 entheses. The US score was based on the summation of a semiquantitative score (including synovitis, tenosynovitis and enthesitis). Scoring was performed by a sonographer blinded to the clinical data. Spearman's correlation coefficient and multivariate linear regression models were used to examine the association of FMS with clinical and the US scores.Forty-two patients (26.9%) with coexisting PsA and FMS were compared with 114 (73.1%) PsA patients without FMS. Patients with PsA and FMS had significantly increased scores for clinical composite indices, including non-Minimal Disease Activity, Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS) (p<0.001). In contrast, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with CPDAI, DAPSA and PASDAS (p<0.001) in the PsA without FMS but not in the PsA with FMS group. FMS was significantly associated with higher clinical scores (p<0.001) but not with the US score (multivariable linear regression models).US has significantly greater value than composite clinical scores in the assessment of disease activity in PsA patients with FMS.
Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia
Authors: Yang-Yang Ding, Hannah Kim, Kellyn Madden, Joseph P. Loftus, Gregory M. Chen, David Hottman Allen, Ruitao Zhang, Jason Xu, Chia-Hui Chen, Yuxuan Hu, Sarah K. Tasian, Kai Tan
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Systems biology approaches can identify critical targets in complex cancer signaling networks to inform new therapy combinations that may overcome conventional treatment resistance. Experimental Design: We performed integrated analysis of 1,046 childhood B-ALL cases and developed a data-driven network controllability-based approach to identify synergistic key regulator targets in Philadelphia chromosome–like B-acute lymphoblastic leukemia (Ph-like B-ALL), a common high-risk leukemia subtype associated with hyperactive signal transduction and chemoresistance. Results: We identified 14 dysregulated network nodes in Ph-like ALL involved in aberrant JAK/STAT, Ras/MAPK, and apoptosis pathways and other critical processes. Genetic cotargeting of the synergistic key regulator pair STAT5B and BCL2-associated athanogene 1 (BAG1) significantly reduced leukemia cell viability in vitro. Pharmacologic inhibition with dual small molecule inhibitor therapy targeting this pair of key nodes further demonstrated enhanced antileukemia efficacy of combining the BCL-2 inhibitor venetoclax with the tyrosine kinase inhibitors ruxolitinib or dasatinib in vitro in human Ph-like ALL cell lines and in vivo in multiple childhood Ph-like ALL patient-derived xenograft models. Consistent with network controllability theory, co-inhibitor treatment also shifted the transcriptomic state of Ph-like ALL cells to become less like kinase-activated BCR-ABL1–rearranged (Ph+) B-ALL and more similar to prognostically favorable childhood B-ALL subtypes. Conclusions: Our study represents a powerful conceptual framework for combinatorial drug discovery based on systematic interrogation of synergistic vulnerability pathways with pharmacologic inhibitor validation in preclinical human leukemia models.
Abstract LB082: Prostate cancer incidence and mortality in the United States, 2000-2016
Authors: Michael Rutalira Koko, Rasaki Aranmolate, Raza Z. Shah, Glodi Mutamba
Journal: Cancer Research (2021)

Abstract Background/Purpose Prostate cancer (PC) is the second most common and deadly cancer among men in the United States. In general, incidence rate of prostate cancer has declined while mortality rate has increased over the past 15 years. The purpose of this study is to assess the incidence and mortality rates of this cancer according to race/ethnicity from 2000-2016. Methods We obtained data from the Surveillance, Epidemiology and End Results (SEER) 18 program to calculate incidence and mortality rates by race/ethnicity from 2000 to 2016. The Annual Percent Change (APC) was also obtained for incidence and mortality rates by race/ethnicity. Results From 2000-2016, the overall incidence rate has decreased significantly from 77.4 to 49.1 per 100,000 (APC = -3.1). Asian and Pacific Islander had the highest decline in incidence rate from 44.4 to 23.4 per 100,000 whereas African-American had the lowest decline from 113.3 to 72.4 per 100,000 (APC -4.4 vs -2.9 respectively). Conversely, the death rate has increased substantially, particularly among White and Black (APC = 8.6 vs 6.6). However, African-Americans still have a disproportionate mortality rate compared to White (46.5 vs 28.8 per 100,000). Conclusion African-Americans are still suffering disproportionately from the PC. There is a need to implement public health interventions to improve PC screening among African-Americans, and examine additional factors that may contribute to the burden of this cancer among African-Americans. Citation Format: Michael Rutalira Koko, Rasaki Aranmolate, Raza Z. Shah, Glodi Mutamba. Prostate cancer incidence and mortality in the United States, 2000-2016 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB082.
Causal manipulation of self-other mergence in the dorsomedial prefrontal cortex
Authors: Marco K. Wittmann, Nadescha Trudel, Hailey A. Trier, Miriam C. Klein-Flügge, Alejandra Sel, Lennart Verhagen, Matthew F.S. Rushworth
Journal: Neuron (2021)

To navigate social environments, people must simultaneously hold representations about their own and others' abilities. During self-other mergence, people estimate others' abilities not only on the basis of the others' past performance, but the estimates are also influenced by their own performance. For example, if we perform well, we overestimate the abilities of those with whom we are co-operating and underestimate competitors. Self-other mergence is associated with specific activity patterns in the dorsomedial prefrontal cortex (dmPFC). Using a combination of non-invasive brain stimulation, functional magnetic resonance imaging, and computational modeling, we show that dmPFC neurostimulation silences these neural signatures of self-other mergence in relation to estimation of others' abilities. In consequence, self-other mergence behavior increases, and our assessments of our own performance are projected increasingly onto other people. This suggests an inherent tendency to form interdependent social representations and a causal role of the dmPFC in separating self and other representations.
Gel immersion endoscopic submucosal dissection for an anorectal tumor with hemorrhoids close to the dentate line
Authors: Tomoaki Tashima, Yuya Nakano, Ryuhei Jinushi, Kazuya Miyaguchi, Rie Terada, Tomonori Kawasaki, Shomei Ryozawa
Journal: Endoscopy (2021)

Endoscopic submucosal dissection (ESD) of anorectal tumors close to the dentate line poses an increased risk of intraoperative and delayed bleeding due to the development of venous flora, including hemorrhoids, in the rectal submucosa. Moreover, the narrow lumen and proximity of the anal sphincter decrease maneuverability and visibility in the resection field [1] [2]. Recently, during endoscopic hemostasis for gastrointestinal bleeding, the “gel immersion endoscopy” technique, involving injection of clear gel, was used to displace blood and clots to secure good visualization [3] [4]. We report the use of a novel gel product (VISCOCLEAR; Otsuka Pharmaceuticals Factory, Chiyoda, Japan), with a short procedure time, to overcome the difficulty of ESD for anorectal tumors close to the dentate line; this has not been described previously.
Quality indicators for systemic lupus erythematosus based on the 2019 EULAR recommendations: development and initial validation in a cohort of 220 patients
Authors: Katerina Chavatza, Myrto Kostopoulou, Dionysis Nikolopoulos, Ourania Gioti, Konstantina Togia, Laura Andreoli, Martin Aringer, John Boletis, Andrea Doria, Frederic A Houssiau, David Jayne, Marta Mosca, Elisabet Svenungsson, Angela Tincani, George Bertsias, Antonis Fanouriakis, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2021)

Background Quality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations. Methods A total of 44 candidate QIs corresponding to diagnosis, monitoring and treatment, were independently rated for validity and feasibility by 12 experts and analysed by a modified Research and Development Corporation/University of California Los Angeles model. Adherence to the final set of QIs and correlation with disease outcomes (flares, hospitalisations and organ damage) was tested in a cohort of 220 SLE patients with a median monitoring of 2 years (IQR 2–4). Results The panel selected a total of 18 QIs as valid and feasible. On average, SLE patients received 54% (95% CI 52.3% to 56.2%) of recommended care, with adherence ranging from 44.7% (95% CI 40.8% to 48.6%) for diagnosis-related QIs to 84.3% (95% CI 80.6% to 87.5%) for treatment-related QIs. Sustained remission or low disease activity were achieved in 26.8% (95% CI 21.1% to 33.2%). Tapering of prednisone dose to less than 7.5 mg/day was achieved in 93.6% (95% CI 88.2% to 97.0%) while 73.5% (95% CI 66.6% to 79.6%) received the recommended hydroxychloroquine dose. Higher adherence to monitoring-related QIs was associated with reduced risk for a composite adverse outcome (flare, hospitalisation or damage accrual) during the last year of observation (OR 0.97 per 1% adherence rate, 95% CI 0.96 to 0.99). Conclusion We developed QIs for assessing and improving the care of SLE patients. Initial real-life data suggest face validity, but a variable degree of adherence and a need for further improvement.