tbuckley/cabot-search huggingface dataset:
Abstract PO-055: Phase II clinical trial of subtype directed neoadjuvant therapy in patients with localized pancreatic cancer
Authors: Susan Tsai, Erkut Borazanci, Margaret Gulley, Naim Rashid, Jason Merker, Abdul H. Khan, Phillip Chisholm, Bryan Hunt, Tamara Giorgadze, William Hall, Mandana Kamgar, Douglas B. Evans, Jen Jen Yeh
Journal: Cancer Research (2021)

Abstract Background: Preoperative (neoadjuvant) therapy has become the preferred treatment sequencing strategy for patients with localized pancreatic cancer. During neoadjuvant therapy, approximately 30% of patients will experience metastatic disease progression while on treatment. Therefore, tools to aid clinicians to select efficacious first-line chemotherapeutic regimens is a critical unmet need. The most common neoadjuvant chemotherapy regimens used are 5-fluorouracil/irinotecan/oxaliplatin (mFOLFIRINOX) and gemcitabine/nab-paclitaxel (GnP). There is growing data to suggest an association of pancreatic cancer subtype (classical versus basal-like) with treatment response to therapy. Recently, the translation of tumor subtyping to the clinic has been successfully achieved using the Purity Independent Subtyping of Tumors (PurIST) single sample classifier. We aim to assess the clinical response to pancreatic cancer subtype-directed therapy in patients with localized pancreatic cancer. Methods: This is a phase II, multicenter, single-arm clinical trial for previously untreated patients with localized (resectable or borderline resectable) pancreatic cancer. Patients will undergo endoscopic ultrasound guided biopsy of the primary tumor and PurIST classifier to determine classical versus basal-like subtype. Patients with classical subtype will be assigned to mFOLFIRINOX and patients with basal-like tumors will be assigned to GnP. Following two months of therapy, patients will be restaged with a computed tomography scan, carbohydrate antigen (CA19-9) levels, performance status assessment, and a repeat endoscopic ultrasound guided biopsy for research. The primary endpoint is composite clinical response as measured by radiographic response, CA19-9 decline, and performance status following two months of treatment. Correlative endpoints include blood-based biomarkers for association with clinical response and stroma-specific response to therapy. The study has enrolled 4 of the anticipated 41 patients at the time of submission. Clinical Trial information: NCT 04683315. Citation Format: Susan Tsai, Erkut Borazanci, Margaret Gulley, Naim Rashid, Jason Merker, Abdul H. Khan, Phillip Chisholm, Bryan Hunt, Tamara Giorgadze, William Hall, Mandana Kamgar, Douglas B. Evans, Jen Jen Yeh. Phase II clinical trial of subtype directed neoadjuvant therapy in patients with localized pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-055.
Could High-Sensitivity Cardiac Troponin Testing Rule Out Acute Myocardial Infarction in the Prehospital Setting?
Authors: Jamie G. Cooper, James Ferguson, Lorna A. Donaldson, Kim M.M. Black, Judith L. Horrill, Elaine M. Davidson, Neil W. Scott, Takeshi Fujisawa, Andrew R. Chapman, Nicholas L. Mills
Journal: Journal of the American College of Cardiology (2021)
Gabarap Loss Mediates Immune Escape in High Risk Multiple Myeloma
Authors: Annamaria Gulla, Eugenio Morelli, Mehmet K. Samur, Cirino Botta, Megan Johnstone, Giada Bianchi, Mariateresa Fulciniti, Leona Yamamoto, Rao Prabhala, Kenneth Wen, Paul G. Richardson, Yu-Tzu Tai, Dharminder Chauhan, Teru Hideshima, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2021)
Abstract 9379: Ferroptosis Inhibitor Exerts Greater Efficacy Than Apoptosis and Necroptosis Inhibitors on Improving Cardiac Function via Restoring Cardiac Mitochondrial Function and Attenuating Cardiomyocyte Death in Rats With Iron-Overloaded Cardiomyopathy
Authors: Sirinart Kumfu, Jirapas Sripetchwandee, Natthaphat Siri-angkul, Natticha Sumneang, Chayodom Maneechote, Busarin Arunsak, Titikorn Chunchai, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Circulation (2021)

Introduction: Iron overload cardiomyopathy (IOC) is a common cause of death in iron overload patients. Previous studies reported that iron overload led to cardiac mitochondrial dysfunction and cardiomyocyte death through multiple pathways including apoptosis, necroptosis and ferroptosis. However, the dominant cell death pathway in the iron-overloaded heart remains to be clarified. Hypothesis: We tested the hypothesis that apoptosis, necroptosis and ferroptosis play equally important roles in IOC; and inhibitors of the three cell death pathways have equal beneficial effect on improving cardiac function in iron-overloaded rats. Methods: Male Wistar rats received intraperitoneal injection of iron dextran, 5 days/week for 4 weeks. Then, the rats were divided into 5 groups (n=4/group) being treated with vehicle, apoptosis inhibitor (z-VAD-FMK), necroptosis inhibitor (necrostatin-1), ferroptosis inhibitor (ferrostatin-1) and iron chelator (deferoxamine) for 2 weeks. Cardiac function, mitochondrial function, mitophagy, apoptosis, necroptosis and ferroptosis were determined. Results: Iron-overloaded rats showed impaired cardiac and mitochondrial function associated with excessive mitophagy and increased expression of apoptosis- and ferroptosis-related proteins. All cell death inhibitors could decrease cardiac mitophagy, apoptosis and ferroptosis in iron overloaded rats. Ferrostatin-1 was more effective than the other drugs in diminishing mitochondrial depolarization and bax/bcl-2 ratio (Figure A). Therefore, ferrostatin-1 and deferoxamine reversed iron overload-induced cardiac dysfunction as indicated by the restored left ventricular ejection fraction (Figure B), whereas z-VAD-FMK and necrostatin-1 only partially improved this parameter. Conclusions: Ferroptosis might be the dominant type of cardiomyocyte death in IOC, and inhibition of ferroptosis is a potential therapeutic strategy against this condition.
Antifibrotic factor KLF4 is repressed by the miR-10/TFAP2A/TBX5 axis in dermal fibroblasts: insights from twins discordant for systemic sclerosis
Authors: Maya Malaab, Ludivine Renaud, Naoko Takamura, Kip D Zimmerman, Willian A da Silveira, Paula S Ramos, Sandra Haddad, Marc Peters-Golden, Loka R Penke, Bethany Wolf, Gary Hardiman, Carl D Langefeld, Thomas A Medsger, Carol A Feghali-Bostwick
Journal: Annals of the Rheumatic Diseases (2021)

Systemic sclerosis (SSc) is a complex disease of unknown aetiology in which inflammation and fibrosis lead to multiple organ damage. There is currently no effective therapy that can halt the progression of fibrosis or reverse it, thus studies that provide novel insights into disease pathogenesis and identify novel potential therapeutic targets are critically needed.We used global gene expression and genome-wide DNA methylation analyses of dermal fibroblasts (dFBs) from a unique cohort of twins discordant for SSc to identify molecular features of this pathology. We validated the findings using in vitro, ex vivo and in vivo models.Our results revealed distinct differentially expressed and methylated genes, including several transcription factors involved in stem cell differentiation and developmental programmes (KLF4, TBX5, TFAP2A and homeobox genes) and the microRNAs miR-10a and miR-10b which target several of these deregulated genes. We show that KLF4 expression is reduced in SSc dFBs and its expression is repressed by TBX5 and TFAP2A. We also show that KLF4 is antifibrotic, and its conditional knockout in fibroblasts promotes a fibrotic phenotype.Our data support a role for epigenetic dysregulation in mediating SSc susceptibility in dFBs, illustrating the intricate interplay between CpG methylation, miRNAs and transcription factors in SSc pathogenesis, and highlighting the potential for future use of epigenetic modifiers as therapies.
Measuring the Toll of the COVID-19 Pandemic in Rural Bangladesh
Authors: Thomas Beaney, Jonathan Clarke, Vageesh Jain
Journal: JAMA Network Open (2021)

Prabhat Barnwal, PhD; Yuling Yao, PhD; Yiqian Wang, MA; Nishat Akter Juy, BS; Shabib Raihan, MBA; Mohammad Ashraful Haque, MS; Alexander van Geen, PhD
Peptide ligands targeting FGF receptors promote recovery from dorsal root crush injury via AKT/mTOR signaling
Authors: Ying Zhao, Qiang Wang, Chen Xie, Yuling Cai, Xue Chen, Yuhui Hou, Liu He, Jianping Li, Min Yao, Shuangxi Chen, Wutian Wu, Xiaojia Chen, An Hong
Journal: Theranostics (2021)

Background: Fibroblast growth factor receptors (FGFRs) are key targets for nerve regeneration and repair. The therapeutic effect of exogenous recombinant FGFs in vivo is limited due to their high molecular weight. Small peptides with low molecular weight, easy diffusion, low immunogenicity, and nontoxic metabolite formation are potential candidates. The present study aimed to develop a novel low-molecular-weight peptide agonist of FGFR to promote nerve injury repair. Methods: Phage display technology was employed to screen peptide ligands targeting FGFR2. The peptide ligand affinity for FGFRs was detected by isothermal titration calorimetry. Structural biology-based computer virtual analysis was used to characterize the interaction between the peptide ligand and FGFR2. The peptide ligand effect on axon growth, regeneration, and behavioral recovery of sensory neurons was determined in the primary culture of sensory neurons and dorsal root ganglia (DRG) explants in vitro and a rat spinal dorsal root injury (DRI) model in vivo. The peptide ligand binding to other membrane receptors was characterized by surface plasmon resonance (SPR) and liquid chromatography-mass spectrometry (LC-MS)/MS. Intracellular signaling pathways primarily affected by the peptide ligand were characterized by phosphoproteomics, and related pathways were verified using specific inhibitors. Results: We identified a novel FGFR-targeting small peptide, CH02, with seven amino acid residues. CH02 activated FGFR signaling through high-affinity binding with the extracellular segment of FGFRs and also had an affinity for several receptor tyrosine kinase (RTK) family members, including VEGFR2. In sensory neurons cultured in vitro, CH02 maintained the survival of neurons and promoted axon growth. Simultaneously, CH02 robustly enhanced nerve regeneration and sensory-motor behavioral recovery after DRI in rats. CH02-induced activation of FGFR signaling promoted nerve regeneration primarily via AKT and ERK signaling downstream of FGFRs. Activation of mTOR downstream of AKT signaling augmented axon growth potential in response to CH02. Conclusion: Our study revealed the significant therapeutic effect of CH02 on strengthening nerve regeneration and suggested a strategy for treating peripheral and central nervous system injuries.
Responding to the UK government’s replacement of “health inequalities”
Authors: Andrew Moscrop
Journal: BMJ (2021)

Scally’s observations on the disappearance of the term “health inequalities” in UK government communications and its replacement with “health disparities” are an important commentary.1

Not long ago the unfairness of our unequal health outcomes was insufferable, it was said. In 2016, in her first statement as prime minister, Theresa May vowed to fight “against the burning injustice …
Higher metastasis and death rates in cutaneous squamous cell carcinomas with lymphovascular invasion
Authors: Kylee J.B. Kus, Fadi Murad, Timothy D. Smile, Michael Chang, Sepideh Ashrafzadeh, Guohai Zhou, Evelyn O. Ilori, Shlomo A. Koyfman, Allison T. Vidimos, Chrysalyne D. Schmults, Emily S. Ruiz
Journal: Journal of the American Academy of Dermatology (2021)
Clinical Trials of BCMA-Targeted CAR-T Cells Utilizing a Novel Non-Viral Transposon System
Authors: Caitlin Costello, Ben A Derman, Mehmet Hakan Kocoglu, Abhinav Deol, Abbas Abbas Ali, Tara Gregory, Bhagirathbhai Dholaria, Jesus G Berdeja, Adam D Cohen, Krina K. Patel, David S. Siegel, Rajneesh Nath, Katherine McArthur, Joanne McCaigue, Christopher E Martin, Majid Ghoddusi, Hamid Namini, Eric M. Ostertag, Matthew A. Spear, Rajesh Belani, Nina Shah
Journal: Blood (2021)
Acute Myelopathy in a Man With Cutaneous Papules
Authors: Shermyn Neo, Chee Seng Sim, Chia Chun Ang
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
A Woman in Her 60s With an Unusual Recurrent High Fever and Chills
Authors: Jiehua Li, Hao He, Chang Shu
Journal: JAMA Cardiology (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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Cardiology journal
Characterization of Bruton Tyrosine Kinase Inhibitor (BTKi)-Related Adverse Events in a Head-to-Head Trial of Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia (CLL)
Authors: John F. Seymour, John C. Byrd, Peter Hillmen, Paolo Ghia, Arnon P. Kater, Asher Chanan-Khan, Richard Furman, Susan M. O'Brien, Jennifer R Brown, Anthony R. Mato, Stephan Stilgenbauer, Nataliya Kuptsova-Clarkson, Paulo Miranda, Dennis Wagner, Kara Higgins, Sophia Sohoni, Wojciech Jurczak
Journal: Blood (2021)
High Rates of Remission with the Initial Treatment of Oral Azacitidine Plus CHOP for Peripheral T-Cell Lymphoma (PTCL): Clinical Outcomes and Biomarker Analysis of a Multi-Center Phase II Study
Authors: Jia Ruan, Alison J. Moskowitz, Neha Mehta-Shah, Lubomir Sokol, Zhengming Chen, Riyaad Rahim, Wei Song, Nikita Kotlov, Grigorii Nos, Vladislav Maksimov, Maria Victoria Revuelta, Andrea Sboner, Michael Sigouros, Koen van Besien, Steven M. Horwitz, Sarah C. Rutherford, Erin C. Mulvey, Morton Coleman, Ari Melnick, Olivier Elemento, Giorgio Inghirami, John P. Leonard, Peter Martin, Leandro Cerchietti
Journal: Blood (2021)
Relationship of Hydroxyurea Adherence to Depression and Fatigue Among Children and Adolescents with Sickle Cell Disease: A Longitudinal Cohort Study
Authors: Sherif M. Badawy, Kathryn King, Olivia E. Atherton, Daniel Mroczek, Alexis A. Thompson, David Cella, Tonya M. Palermo, Jane L. Holl, Robert I. Liem
Journal: Blood (2021)
A Myelodepletive Phenotype Is Associated with Distinctive Molecular Features and Adverse Outcomes in Patients with Myelofibrosis
Authors: Giacomo Coltro, Francesco Mannelli, Giuseppe Gaetano Loscocco, Carmela Mannarelli, Giada Rotunno, Chiara Maccari, Fabiana Pancani, Alessandro Atanasio, Ayalew Tefferi, Alessandro Vannucchi, Paola Guglielmelli
Journal: Blood (2021)
Loss of Lamin B1 in Myeloid Neoplasms with 5q Deletion Causes Myeloid-Biased Hematopoiesis and Pelger-Huet Nuclear Anomaly
Authors: Andreea Reilly, J. Philip Creamer, Massiel Chavez Stolla, Yuchuan Wang, Jing Du, Rachel Wellington, Stephanie Busch, Elihu H. Estey, Pamela S. Becker, Min Fang, Sioban B. Keel, Janis L. Abkowitz, Lorinda A. Soma, Jian Ma, Zhijun Duan, Sergei Doulatov
Journal: Blood (2021)
Circulating Metabolomics Suggest Neutropenic Fever As a Metabolic Derangement Related to Intestinal Tissue Damage and Gut Dysbiosis
Authors: Armin Rashidi, Maryam Ebadi, Tauseef Ur Rehman, Heba Elhusseini, Harika Nalluri, Thomas Kaiser, Sivapriya Ramamoorthy, Shernan G Holtan, Alexander Khoruts, Daniel J. Weisdorf, Christopher Staley
Journal: Blood (2021)
HLA-B Leader Dimorphism Impacts on Outcomes of HLA-Matched Related/Unrelated Transplantation: Analysis of the Japanese Society for Transplantation and Cellular Therapy
Authors: Minoru Kanaya, Yasuo Morishima, Nobuyoshi Arima, Masahiro Hirayama, Souichi Shiratori, Noriko Doki, Yukiyasu Ozawa, Takahiro Fukuda, Masatsugu Tanaka, Masashi Sawa, Satoru Takada, Shuichi Ota, Toshiro Kawakita, Junya Kanda, Tatsuo Ichinohe, Yoshiko Atsuta, Satoko Morishima
Journal: Blood (2021)
Effect of Daratumumab-Containing Induction on CD34+ Hematopoietic Stem Cells before Autologous Stem Cell Transplantation in Multiple Myeloma
Authors: Ondrej Venglar, Tereza Sevcikova, Anjana Anilkumar Sithara, Veronika Kapustova, Jan Vrana, David Zihala, Ludmila Muronova, Lucie Huvarova, Lucie Broskevicova, Michal Simicek, Zdenek Koristek, Roman Hajek, Tomas Jelinek
Journal: Blood (2021)
Abstract 10236: Prospective Assessment of ECG-Image-based Real-Time Individual Virtual-Heart Automatic Localization (RIVAL) for Scar-Related Ventricular Tachycardia (VT)
Authors: Shijie Zhou, Eric Sung, Amir AbdelWahab, John L Sapp, Konstantinos Aronis, B. M Horacek, Ronald D Berger, Harikrishna S Tandri, Jonathan Chrispin, Natalia Trayanova
Journal: Circulation (2021)

Background: We developed a novel RIVAL system that consists of a CT-based computational simulation to identify VT circuits and an ECG-based automated approach to localize VT exit sites. Objective: Prospectively assess the ability of the RIVAL system to localize VT circuits and exits. Methods: Patients presenting for VT ablation were enrolled into the study. Pre-procedural cardiac CT was performed and used to conduct heart simulations for predicting VT circuits. The patient’s CT geometry with the predicted VT circuits was registered to the electroanatomic shell created during the procedure and imported into the RIVAL program. During the procedure, exit sites of induced VTs are localized in real-time using the 12-lead ECG onto the patient-specific CT surface. Predicted ablation regions obtained by combining RIVAL-predicted VT circuits with exit sites were analyzed offline to assess localization accuracy to the invasive VT ablation procedure. Results: Four patients with ischemic cardiomyopathy undergoing VT ablation had preprocedural cardiac CT. In P1, two VTs were induced during the procedure. The RIVAL predicted 2 VT circuits and achieved a mean localization error of 7.0mm for VT exit site prediction (Fig1). There was a spatial concordance between the predicted ablation areas and the clinical ablation regions. For P2, three VTs were induced during the VT ablation. A large area of scar was associated with 6 RIVAL-predicted VT circuits. The exit site localization accuracy could not be precisely quantitated because the VTs terminated with ablation at a mid-diastolic site. For P3, no VTs were inducible, however substrate modification (SM) was performed in the anterior-apical LV. The RIVAL predicted only one VT circuit located in the area where SM was performed. No VT was induced for P4 and the RIVAL did not predict any VT circuits. Conclusions: The RIVAL predicts the VT circuit and exit accurately, which may improve the precision of ablation therapies and procedure outcomes.
Transgender-specific COVID-19-related stressors and their association with depressive symptoms among transgender adults: A nationwide cross-sectional survey in South Korea
Authors: Hyemin Lee, Arjee J. Restar, Don Operario, Sungsub Choo, Carl G. Streed Jr, Horim Yi, Ranyeong Kim, Yun-Jung Eom, Seung-Sup Kim
Journal: International Journal of Transgender Health (2021)

Introduction COVID-19 has disproportionately impacted marginalized groups, including transgender populations, reproducing and exacerbating inequalities and vulnerabilities that existed in those groups prior to the pandemic. This study aimed to assess the prevalence of transgender-specific COVID-19-related stressors and their association with depressive symptoms among South Korean transgender adults.Methods We conducted a nationwide cross-sectional study of 564 South Korean transgender adults (trans women, trans men, and nonbinary people) from October 7 to October 31, 2020. We measured four transgender-specific COVID-19-related stressors as follows: (A) had difficulty receiving gender-affirming healthcare due to economic hardship related to COVID-19, (B) had difficulty receiving gender-affirming healthcare due to limited access to hospitals under the COVID-19 situation, (C) had difficulty purchasing a public face mask due to gender information on an identification card, and (D) avoided getting a COVID-19 test in fear of unfair treatment and dirty looks due to gender identity, despite having COVID-19 symptoms. Past-week depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale.Results Of the total participants, 30.7% experienced any of the four transgender-specific COVID-19-related stressors, and 70.2% were classified as having depressive symptoms during the past week. We found statistically significant associations with depressive symptoms among participants who reported that they had difficulty receiving gender-affirming healthcare due to either economic hardship (adjusted prevalence ratio [aPR] = 1.20, 95% Confidence Interval [CI] = 1.05–1.37) or limited access to hospitals (aPR = 1.15, 95% CI = 1.00–1.32), respectively. Furthermore, those who had two or more of the four transgender-specific COVID-19-related stressors were 1.21 times (95% CI = 1.05–1.40) more likely to report depressive symptoms, compared to those who did not report any stressor.Conclusion Transgender-specific COVID-19-related stressors may negatively influence depressive symptoms among South Korean transgender adults. Given these findings, transgender-inclusive interventions should be implemented at the policy level during the COVID-19 pandemic in South Korea.
Incidence of Breakthrough Fungal Infections in Acute Myeloid Leukemia Patients Receiving Low Intensity Therapy in the Upfront and Relapsed/Refractory Setting
Authors: Kaci Shuman, Rebecca Garcia Hunt, Maho Hibino, Tyler Stone, Sarah Dralle, Megan Manuel, Susan Lyerly, Leslie Renee Ellis, Rupali Bhave, Timothy S. Pardee, Bayard L. Powell, Daniel R. Reed
Journal: Blood (2021)