tbuckley/cabot-search huggingface dataset:
Flagellum and toxin phase variation impacts intestinal colonization and disease development in a mouse model of <i>Clostridioides difficile</i> infection
Authors: Dominika Trzilova, Mercedes A. H. Warren, Nicole C. Gadda, Caitlin L. Williams, Rita Tamayo
Journal: Gut Microbes (2022)

Clostridioides difficile is a major nosocomial pathogen that can cause severe, toxin-mediated diarrhea and pseudomembranous colitis. Recent work has shown that C. difficile exhibits heterogeneity in swimming motility and toxin production in vitro through phase variation by site-specific DNA recombination. The recombinase RecV reversibly inverts the flagellar switch sequence upstream of the flgB operon, leading to the ON/OFF expression of flagellum and toxin genes. How this phenomenon impacts C. difficile virulence in vivo remains unknown. We identified mutations in the right inverted repeat that reduced or prevented flagellar switch inversion by RecV. We introduced these mutations into C. difficile R20291 to create strains with the flagellar switch "locked" in either the ON or OFF orientation. These mutants exhibited a loss of flagellum and toxin phase variation during growth in vitro, yielding precisely modified mutants suitable for assessing virulence in vivo. In a hamster model of acute C. difficile infection, the phase-locked ON mutant caused greater toxin accumulation than the phase-locked OFF mutant but did not differ significantly in the ability to cause acute disease symptoms. In contrast, in a mouse model, preventing flagellum and toxin phase variation affected the ability of C. difficile to colonize the intestinal tract and to elicit weight loss, which is attributable to differences in toxin production during infection. These results show that the ability of C. difficile to phase vary flagella and toxins influences colonization and disease development and suggest that the phenotypic variants generated by flagellar switch inversion have distinct capacities for causing disease.
Endoscopic full-thickness resection of a duodenal gastrointestinal stromal tumor with extraluminal component: the usefulness of traction and sutures
Authors: Hugo Uchima, Elisenda Garsot, Juan Colán-Hernández, Marta Viciano, Arantxa Clavell, Ingrid Marín, Vicente Moreno
Journal: Endoscopy (2022)

Gastrointestinal stromal tumors (GISTs) are the most common sarcomas of the gastrointestinal tract. Those that are < 5 cm with ≤ 5 mitoses per 50 high power fields (HPFs) are considered low risk for metastasis and may be treated by local resection. Duodenal GISTs account for 4 %–5 % of all GISTs, they are usually retroperitoneal, which can make a surgical approach more challenging [1] [2] [3] [4]. Herein, we present a case of a duodenal GIST treated by full-thickness resection via natural orifice transluminal endoscopic surgery (NOTES).
Increased mortality risk in multiple-myeloma patients with subsequent malignancies: a population-based study in the Netherlands
Authors: Mirian Brink, Monique C. Minnema, Otto Visser, Mark-David Levin, Eduardus F. M. Ward Posthuma, Annemiek Broijl, Pieter Sonneveld, Marjolein van der Klift, Wilfried W. H. Roeloffzen, Matthijs Westerman, Cleo R. van Rooijen, Paul A. F. Geerts, Sonja Zweegman, Niels W. C. J. van de Donk, Avinash G. Dinmohamed
Journal: Blood Cancer Journal (2022)
PULMONARY ARTERY CANNULATION TO ENHANCE VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION THERAPY IN A PATIENT WITH MULTIPLE INTRACARDIAC THROMBI
Authors: Prapaipan Putthapiban, Natthapon Angsubhakorn, Reza Salabat, Jason Hoff, Ahmed Seliem
Journal: Journal of the American College of Cardiology (2022)
Targeting E2 ubiquitin-conjugating enzyme UbcH5c by small molecule inhibitor suppresses pancreatic cancer growth and metastasis
Authors: Simin Qi, Xiaoqing Guan, Jia Zhang, Dehua Yu, Xuefei Yu, Qinglin Li, Wenjuan Yin, Xiang-Dong Cheng, Weidong Zhang, Jiang-Jiang Qin
Journal: Molecular Cancer (2022)

Abstract Background Pancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet. Methods Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR. Results UbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models. Conclusions These results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent.
LONG-TERM MORTALITY RISK ASSOCIATED TO CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP) IN PATIENTS WITH SEVERE AORTIC VALVE STENOSIS UNDERGOING TAVR
Authors: Silvia Mas-Peiro, Khalil Abou-El-Ardat, Graziella Pergola, Alexander Berkowitsch, Manja Meggendorfer, Michael Rieger, Mariuca Vasa-Nicotera, Stefanie Dimmeler, Andreas Zeiher
Journal: Journal of the American College of Cardiology (2022)
A critique of the marketisation of long-term residential and nursing home care
Authors: Christine Corlet Walker, Angela Druckman, Tim Jackson
Journal: The Lancet Healthy Longevity (2022)

Long-term care systems across countries within the Organisation for Economic Co-operation and Development have undergone a progressive marketisation and financialisation in recent decades, characterised by the embedding of neoliberal market values such as competition, consumer choice, and the profit motive. In this Personal View, we argue that these make poor guiding principles for the care sector, identifying the dysfunctional dynamics that arise as a result, and reflecting on the clinical implications of each, with a focus on facility-based care. We outline why providers can scarcely respond to competitive forces without compromising care quality. We explain why the promotion of consumer choice cannot effectively motivate improvements to quality of care. And we explore how privatisation opens the door to predatory financial practices. We conclude by considering how far proposals for reform can take us, ultimately arguing for a rejection of neoliberal market ideology, and calling for sector-wide discussions about what principles would be more fitting for a caring economy.
Privacy and Health Practices in the Digital Age
Authors: Monique Pyrrho, Leonardo Cambraia, Viviane Ferreira de Vasconcelos
Journal: The American Journal of Bioethics (2022)

Increasing privacy concerns are arising from expanding use of aggregated personal information in health practices. Conversely, in light of the promising benefits of data driven healthcare, privacy is being frequently dismissed as outdated, costly and ultimately egotistical. This paper aims to review the theoretical framework on privacy in order to overcome the often simplistic debate between the primacy of individual or collective interests. As a result, it is argued that although privacy can be understood as freedom of personal choice in matters of sharing intimacy, it is foundational to both community belonging and to social and political organizations at large. Ethical decisions on the use of data analytics technologies in health practices should also take into account the social effects of violating privacy.
Relationship between asthma and severe COVID-19: a national cohort study
Authors: Ted Dolby, Vahe Nafilyan, Ann Morgan, Constantinos Kallis, Aziz Sheikh, Jennifer K Quint
Journal: Thorax (2022)

Background We aimed to determine whether children and adults with poorly controlled or more severe asthma have greater risk of hospitalisation and/or death from COVID-19. Methods We used individual-level data from the Office for National Statistics Public Health Data Asset, based on the 2011 census in England, and the General Practice Extraction Service data for pandemic planning and research linked to death registration records and Hospital Episode Statistics admission data. Adults were followed from 1 January 2020 to 30 September 2021 for hospitalisation or death from COVID-19. For children, only hospitalisation was included. Results Our cohort comprised 35 202 533 adults and 2 996 503 children aged 12–17 years. After controlling for sociodemographic factors, pre-existing health conditions and vaccine status, the risk of death involving COVID-19 for adults with asthma prescribed low dose inhaled corticosteroids (ICS) was not significantly different from those without asthma. Adults with asthma prescribed medium and high dosage ICS had an elevated risk of COVID-19 death; HRs 1.18 (95% CI 1.14 to 1.23) and 1.36 (95% CI 1.28 to 1.44), respectively. A similar pattern was observed for COVID-19 hospitalisation; fully adjusted HRs 1.53 (95% CI 1.50 to 1.56) and 1.52 (95% CI 1.46 to 1.56) for adults with asthma prescribed medium and high-dosage ICS, respectively. Risk of hospitalisation was greater for children with asthma prescribed one (2.58 (95% CI 1.82 to 3.66)) or two or more (3.80 (95% CI 2.41 to 5.95)) courses of oral corticosteroids in the year prior to the pandemic. Discussion People with mild and/or well-controlled asthma are neither at significantly increased risk of hospitalisation with nor more likely to die from COVID-19 than adults without asthma.
TIME TO RELAPSE AFTER WEANING IMMUNE SUPPRESSIVE THERAPY IN CARDIAC SARCOIDOSIS: A SINGLE-CENTER EXPERIENCE
Authors: Kelly Arps, Jayanth Doss, Kelly V. Geiger, Adam DeVore, Ravi Karra, Han W. Kim, Jonathan P. Piccini, Sean Pokorney, Albert Y. Sun
Journal: Journal of the American College of Cardiology (2022)
SARCOMERE MUTATIONS DO NOT AGGRAVATE THE PROGNOSIS OF HYPERTROPHIC CARDIOMYOPATHY PATIENTS UNDERGOING SEPTAL MYECTOMY
Authors: Jian Zhang, Changpeng Song, Changsheng Zhu, Kunlun Yin, Changrong Nie, Yang Zhang, Manyun Huang, Xinxin Zheng, Jie Lu, Zhou Zhou, Shuiyun Wang, Xiaohong Huang
Journal: Journal of the American College of Cardiology (2022)
5-Year Outcomes of PCI Guided by Measurement of Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve
Authors: Matthias Götberg, Karolina Berntorp, Rebecca Rylance, Evald H. Christiansen, Troels Yndigegn, Ingibjörg J. Gudmundsdottir, Sasha Koul, Lennart Sandhall, Mikael Danielewicz, Lars Jakobsen, Sven-Erik Olsson, Hans Olsson, Elmir Omerovic, Fredrik Calais, Pontus Lindroos, Michael Maeng, Dimitrios Venetsanos, Stefan K. James, Amra Kåregren, Jörg Carlsson, Jens Jensen, Ann-Charlotte Karlsson, David Erlinge, Ole Fröbert
Journal: Journal of the American College of Cardiology (2022)
THE IMPACT OF ACUTE MYOCARDIAL INFARCTION ON THE INCIDENCE AND MORTALITY OF VENTRICULAR ARRHYTHMIAS IN HOSPITALIZED PATIENTS WITH CARDIOGENIC SHOCK UNDERGOING MECHANICAL CIRCULATORY SUPPORT
Authors: Jose S. Aguilar-Gallardo, Marta Lorente Ros, Francisco Romeo, Kevin Rabii, Johanna Paola Contreras, Mount Sinai Morningside
Journal: Journal of the American College of Cardiology (2022)
YIA22-004: The Feasibility of a Digitized Peer-To-Peer Patient Support System for Patients With Locally Advanced Head and Neck Cancer Undergoing Chemoradiation
Authors: Kedar Kirtane, Jameel Muzaffar, Julie Kish, Laura B Oswald, Brian D Gonzalez, Taylor Welniak, Yvelise Rodriguez, Christine H Chung
Journal: Journal of the National Comprehensive Cancer Network (2022)

"YIA22-004: The Feasibility of a Digitized Peer-To-Peer Patient Support System for Patients With Locally Advanced Head and Neck Cancer Undergoing Chemoradiation" published on 31 Mar 2022 by National Comprehensive Cancer Network.
NOT ALL ST ELEVATION MYOCARDIAL INFARCTIONS ARE PLAQUE RUPTURE: IVUS AS A TOOL TO DIAGNOSE AORTIC DISSECTION
Authors: Kiersten Frenchu, Anil Jonnalagadda, Aadil Lodhi, Hitesh Raheja, Madison Tanis, Gengo Sunagawa, Yoshiya Toyoda, Ted M. Parris, David Fiss, Aswin Mathew, Marinos Charalambous, Brian O'Murchu, Riyaz Bashir, Vladimir Lakhter
Journal: Journal of the American College of Cardiology (2022)
Abstract P1-05-08: Targeting tumor heterogeneity and breast cancer metastasis through the metastatic microenvironment mediated epigenetic reprogramming
Authors: Li Yang, Jae Young So, Nicolas Skrypek, Anand Merchant, George Nelson, Howard Yang, Maxwell Lee
Journal: Cancer Research (2022)

Abstract Targeting tumor heterogeneity and breast cancer metastasis through the metastaticmicroenvironment mediated epigenetic reprogrammingLi Yang and Jae Young So, Nicolas Skrypek, Anand Merchant, George Nelson, Howard H.Yang, Maxwell P. LeeNational Cancer Institute, National Institutes of Health, Bethesda, MD 20892Current cancer treatments are largely based on the genetic characterization of primarytumors and are ineffective for metastatic disease. There is lack of mechanistic understanding ashow cancer cells are selected and evolved to establish distant metastatic colonies. In addition,tumor heterogeneity and biomarker identification remain to be some of the most difficultchallenges in cancer treatment. In the current study, we discovered an increased DNAmethyltransferase 3B (DNMT3B) in metastatic nodules and in tumor cells with epithelia tomesenchymal (EMT) phenotype. Of great interest, high levels of DNMT3B were correlated withpoor clinical outcomes in multiple human breast cancer datasets. Mechanistically, DNMT3Balters multiple pathways including STAT3, NFkappaB, PI3K/Akt, beta-catenin, Notch signalingas well as EMT, which are critical for cancer cell survival, apoptosis, proliferation, invasion, andcolonization. We further identified PGE2 and IL6 as critical inflammatory mediators inDNMT3B induction. Importantly, targeting IL6 or PGE2 production reduced DNMT3Bexpression and improved chemo treatment or PD1 immune therapy. Furthermore, perioperative(surgical removal of primary tumors) targeting DNMT3B in combination with chemotherapymarkedly suppressed tumor recurrence and metastasis in preclinical mouse models for triplenegative breast cancer. Our studies identify DNMT3B as an important mechanism fortranscription regulation in tumor heterogeneity that is critical for tumor invasion and metastasis,thus suggesting a validated target for treating metastatic disease. Citation Format: Li Yang, Jae Young So, Nicolas Skrypek, Anand Merchant, George Nelson, Howard Yang, Maxwell Lee. Targeting tumor heterogeneity and breast cancer metastasis through the metastatic microenvironment mediated epigenetic reprogramming [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-05-08.
IMPACT OF MEDIASTINAL IRRADIATION HISTORY ON CORONARY ARTERY BYPASS GRAFTING SHORT TERM OUTCOMES: INSIGHTS FROM NATIONAL READMISSION DATABASE
Authors: Ahmed Elzanaty, Mahmoud Khalil, Neha Patel, Chandramohan Meenakshisundaram, Salik Nazir, Fnu Zafrullah, Islam Elgendy, Ahmed M. Maraey, Hassan Aboulnour
Journal: Journal of the American College of Cardiology (2022)
HSR22-159: Hip Transposition With the Use of Prophy Ethylene Mesh as a Reconstructive Option After Pelvic Resection of Periacetabular Bone Tumor: A Case Series
Authors: Clariz Salinas Patricio, Dennis Paolo Hondrade Abadilla, Albert Jerome Quintos
Journal: Journal of the National Comprehensive Cancer Network (2022)

"HSR22-159: Hip Transposition With the Use of Prophy Ethylene Mesh as a Reconstructive Option After Pelvic Resection of Periacetabular Bone Tumor: A Case Series" published on 31 Mar 2022 by National Comprehensive Cancer Network.
MECHANISMS AND PROGRESSION OF MITRAL REGURGITATION IN CARDIAC SARCOIDOSIS
Authors: Daniel Sykora, Kathleen Young, John P. Bois, Courtney Arment, Mohamed Elwazir, Panithaya Chareonthaitawee, Nikhil Kolluri, Omar Abou Ezzeddine, Leslie T. Cooper, Andrew Rosenbaum
Journal: Journal of the American College of Cardiology (2022)
Bone marrow clonal hematopoiesis is highly prevalent in blastic plasmacytoid dendritic cell neoplasm and frequently sharing a clonal origin in elderly patients
Authors: Mahsa Khanlari, C. Cameron Yin, Koichi Takahashi, Curtis Lachowiez, Guilin Tang, Sanam Loghavi, Ismael Bah, Wei Wang, Sergej Konoplev, L. Jeffrey Medeiros, Naveen Pemmaraju, Joseph D. Khoury, Sa A. Wang
Journal: Leukemia (2022)
Targeting complement in neurodegeneration: challenges, risks, and strategies
Authors: Wioleta M. Zelek, B. Paul Morgan
Journal: Trends in Pharmacological Sciences (2022)

Evidence implicating complement in neuroinflammatory and neurodegenerative diseases (NDDs) has accumulated over the past decade, revealing complement as a driver of pathology across these diverse diseases. Over the same period, there has been an explosion of interest in the development of complement-modulating drugs, first for a few rare complement dysregulation diseases but recently also for more common diseases where complement contributes to the disease process. To date, there has been little attention paid to the potential role of anticomplement drugs in neurodegeneration and the current landscape does not feature drugs that can enter the central nervous system (CNS), a prerequisite in most NDDs. Here we summarise the evidence implicating complement in neurodegeneration, build the case for testing anticomplement drugs, and discuss how drugs may be modified or designed de novo to inhibit complement in neurodegeneration.
Cost-effectiveness of liposomal cytarabine/daunorubicin in patients with newly diagnosed acute myeloid leukemia
Authors: Jan Philipp Bewersdorf, Kishan K. Patel, George Goshua, Rory M. Shallis, Nikolai A. Podoltsev, Scott F. Huntington, Amer M. Zeidan
Journal: Blood (2022)
Mitochondria targeting drugs for neurodegenerative diseases—Design, mechanism and application
Authors: Jiajia Xu, Wei Du, Yunhe Zhao, Kahleong Lim, Li Lu, Chengwu Zhang, Lin Li
Journal: Acta Pharmaceutica Sinica B (2022)

Neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) are a heterogeneous group of disorders characterized by progressive degeneration of neurons. NDDs threaten the lives of millions of people worldwide and regretfully remain incurable. It is well accepted that dysfunction of mitochondria underlies the pathogenesis of NDDs. Dysfunction of mitochondria results in energy depletion, oxidative stress, calcium overloading, caspases activation, which dominates the neuronal death of NDDs. Therefore, mitochondria are the preferred target for intervention of NDDs. So far various mitochondria-targeting drugs have been developed and delightfully some of them demonstrate promising outcome, though there are still some obstacles such as targeting specificity, delivery capacity hindering the drugs development. In present review, we will elaborately address 1) the strategy to design mitochondria targeting drugs, 2) the rescue mechanism of respective mitochondria targeting drugs, 3) how to evaluate the therapeutic effect. Hopefully this review will provide comprehensive knowledge for understanding how to develop more effective drugs for the treatment of NDDs.
Effect of unmanned aerial vehicle (drone) delivery on blood product delivery time and wastage in Rwanda: a retrospective, cross-sectional study and time series analysis
Authors: Marie Paul Nisingizwe, Pacifique Ndishimye, Katare Swaibu, Ladislas Nshimiyimana, Prosper Karame, Valentine Dushimiyimana, Jean Pierre Musabyimana, Clarisse Musanabaganwa, Sabin Nsanzimana, Michael R Law
Journal: The Lancet Global Health (2022)

BackgroundThe accessibility of blood and blood products remains challenging in many countries because of the complex supply chain of short lifetime products, timely access, and demand fluctuation at the hospital level. In an effort to improve availability and delivery times, Rwanda launched the use of drones to deliver blood products to remote health facilities. We evaluated the effect of this intervention on blood product delivery times and wastage.MethodsWe studied data from 20 health facilities between Jan 1, 2015, and Dec 31, 2019, in Rwanda. First, we did a cross-sectional comparison of data on emergency delivery times from the drone operator collected between March 17, 2017, and Dec 31, 2019, with two sources of estimated driving times (Regional Centre for Blood Transfusion estimates and Google Maps). Second, we used interrupted time series analysis and monthly administrative data to assess changes in blood product expirations after the commencement of drone deliveries.FindingsBetween March 17, 2017, and Dec 31, 2019, 12 733 blood product orders were delivered by drones. 5517 (43%) of 12 733 were emergency orders. The mean drone delivery time was 49·6 min (95% CI 49·1 to 50·2), which was 79 min faster than existing road delivery methods based on estimated driving times (p<0·0001) and 98 min faster based on Google Maps estimates (p<0·0001). The decrease in mean delivery time ranged from 3 min to 211 min depending on the distance to the facility and road quality. We also found a decrease of 7·1 blood unit expirations per month after the start of drone delivery (95% CI −11·8 to −2·4), which translated to a 67% reduction at 12 months.InterpretationWe found that drone delivery led to faster delivery times and less blood component wastage in health facilities. Future studies should investigate if these improvements are cost-effective, and whether drone delivery might be effective for other pharmaceutical and health supplies that cannot be easily stored at remote facilities.FundingCanadian Institutes for Health Research.