tbuckley/cabot-search huggingface dataset:
Abstract 719: Effectiveness of Therapeutic RNA Interference is Dependent on Genomic Target Selection and Emergence of Escape Mutants: Implications for Enteroviral Heart Disease
Authors: Sabine Merl, Cornelia Michaelis, Rainer Wessely
Journal: Circulation (2006)

Background: We have shown previously that therapeutic RNA interference with short interfering RNA (siRNA) may limit coxsackieviral (CVB) heart disease ( Circulation 2005 ; 111 : 1583 –92 ). Aim of this study was the identification of major factors that limit early efficacy of antiviral siRNA therapy. Methods and results: To assess therapeutic efficacy of siRNA depending on genomic target selection, siRNA were designed against distinct regions representing the entire CVB genome (5′UTR, VP1, VP2, 2A, 3C, 3D) and examined for their antiviral effectiveness in permissive human HeLa cells (Fig.A ). siRNA targeting the 3CD region were particularly protective for cell survival and inhibition of viral replication. Early effectiveness of single siRNA application was hampered by the emergence of viral escape mutants. Sequencing of siRNA resistant viral genomes revealed the occurrence of 1 or 2 point mutations at the siRNA binding site. Yet, mutated viruses remained fully susceptible to siRNA targeting different genomic regions. Thus, simultaneous administration of dual siRNA decreased the emergence of viral escape mutants. Delivery of a siRNA cocktail with 3 different siRNA almost completely suppressed the emergence of viral escape and further improved therapeutic effectiveness (Fig.B ). Conclusion: The early effect of antiviral RNA interference is highly dependent on genomic target selection and impeded by the occurrence of viral escape mutations containing single or dual mutations at the siRNA binding site. Administration of at least three siRNA molecules targeting different regions is sufficient to significantly suppress viral escape, thus leading to improved outcome.
One-step primary endoscopic ultrasound-guided choledochoduodenostomy without lumen-apposing metal stent using a Franseen needle and an ultra-stiff high-sliding guidewire
Authors: Tadahisa Inoue, Rena Kitano, Mayu Ibusuki, Tomoya Kitada, Kazumasa Sakamoto, Jun Arai, Kiyoaki Ito
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) using a lumen-apposing metal stent (LAMS) can be used as a primary treatment for malignant distal biliary obstruction because of its higher technical success rates and shorter procedure times than conventional transpapillary metal stent placement [1] [2]. However, it is unsuitable for minimally dilated common bile ducts (CBDs) and thin 6-mm-diameter LAMSs are commonly used owing to large flanges. Other disadvantages include high costs, early stent dysfunction, and adverse events caused by biliary wall compression, duodenobiliary reflux, and cautery puncture [3]. Conversely, EUS-CDS with conventional metal stents requires a fistula dilation step that is time-consuming, leading to biliary peritonitis and a high risk of stent migration. Therefore, we propose a novel one-step EUS-CDS method without a LAMS using a Franseen needle and an ultra-stiff, high-sliding guidewire.
Multiple pancreaticobiliary fistulas combined with acute necrotizing pancreatitis: a rare complication of pancreatic extracorporeal shock wave lithotripsy
Authors: Guangchao Li, Peng Wang, Limei Wang, Zhen Li, Rui Ji, Hongbo Ren, Ning Zhong
Journal: Endoscopy (2024)

A 54-year-old woman with a history of chronic pancreatitis and cholecystectomy 4 years prior presented with intermittent abdominal pain. Computed tomography (CT) revealed large pancreatic calcifications, main pancreatic duct (MPD) dilation, and pneumatosis in the bile and pancreatic ducts ([Fig. 1]). She underwent pancreatic extracorporeal shock wave lithotripsy (ESWL) first, during which small stone fragments were expelled ([Fig. 2]). However, her abdominal pain worsened, with low grade fever post-procedure. Laboratory tests and CT revealed acute necrotizing pancreatitis, extensive exudation and peripancreatic fluid collection, and impacted stones in the pancreatic head ([Fig. 3]). Abdominal pain control proved difficult without analgesics. Enhanced CT suspected a connection between the MPD and the common bile duct (CBD) ([Fig. 3], arrow). Further endoscopic retrograde cholangiopancreatography found two fistula openings near the major papilla, which proved to be bile and pancreatic duodenal fistulas. Pancreatography confirmed the presence of a pancreaticobiliary fistula, linking the distal CBD to the MPD ([Fig. 4], [Video 1]). After clearing fragments, a 7-Fr × 9-cm single-pigtail plastic stent was placed and significantly improved her symptoms.
Percutaneous transhepatic cholangioscopy combined with endoscopic retrograde cholangiopancreatography for bilateral biliary bridge drainage for malignant biliary obstruction
Authors: Gang Tang, Jingyi Zhang, Rui Chen, Jie Zhang, Rongxing Zhou
Journal: Endoscopy (2024)

Biliary drainage in advanced malignant hilar biliary obstruction (MHBO) is challenging, especially with Bismuth-Corlette III–IV [1]. By placing a bridge stent between the left and right hepatic ducts, the non-communication system in MHBO can be drained, which is potentially a very promising biliary drainage strategy for MHBO [2]. However, due to the complexity of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) technology, reports on EUS-HGS bridge drainage are still limited. We report a novel approach to bridge bilateral hepatic duct drainage using ultrasound-guided percutaneous transhepatic cholangioscopy (PTCS) combined with endoscopic retrograde cholangiopancreatography (ERCP) in MHBO.
Intake of sugar sweetened beverages among children and adolescents in 185 countries between 1990 and 2018: population based study
Authors: Laura Lara-Castor, Renata Micha, Frederick Cudhea, Victoria Miller, Peilin Shi, Jianyi Zhang, Julia R Sharib, Josh Erndt-Marino, Sean B Cash, Simon Barquera, Dariush Mozaffarian
Journal: BMJ (2024)

Abstract Objective To quantify global intakes of sugar sweetened beverages (SSBs) and trends over time among children and adolescents. Design Population based study. Setting Global Dietary Database. Population Children and adolescents aged 3-19 years in 185 countries between 1990 and 2018, jointly stratified at subnational level by age, sex, parental education, and rural or urban residence. Results In 2018, mean global SSB intake was 3.6 (standardized serving=248 g (8 oz)) servings/week (1.3 (95% uncertainly interval 1.0 to 1.9) in south Asia to 9.1 (8.3 to 10.1) in Latin America and the Caribbean). SSB intakes were higher in older versus younger children and adolescents, those resident in urban versus rural areas, and those of parents with higher versus lower education. Between 1990 and 2018, mean global SSB intakes increased by 0.68 servings/week (22.9%), with the largest increases in sub-Saharan Africa (2.17 servings/week; 106%). Of 185 countries included in the analysis, 56 (30.3%) had a mean SSB intake of ≥7 servings/week, representing 238 million children and adolescents, or 10.4% of the global population of young people. Conclusion This study found that intakes of SSBs among children and adolescents aged 3-19 years in 185 countries increased by 23% from 1990 to 2018, parallel to the rise in prevalence of obesity among this population globally. SSB intakes showed large heterogeneity among children and adolescents worldwide and by age, parental level of education, and urbanicity. This research should help to inform policies to reduce SSB intake among young people, particularly those with larger intakes across all education levels in urban and rural areas in Latin America and the Caribbean, and the growing problem of SSBs for public health in sub-Saharan Africa.
2024 ACC Expert Consensus Decision Pathway on Clinical Assessment, Management, and Trajectory of Patients Hospitalized With Heart Failure Focused Update
Authors: Steven M. Hollenberg, Lynne Warner Stevenson, Tariq Ahmad, Biykem Bozkurt, Javed Butler, Leslie L. Davis, Mark H. Drazner, James N. Kirkpatrick, Alanna A. Morris, Robert Lee Page, Hasan Khalid Siddiqi, Alan B. Storrow, John R. Teerlink
Journal: Journal of the American College of Cardiology (2024)
2024 Update to the 2020 ACC/AHA Clinical Performance and Quality Measures for Adults With Heart Failure
Authors: Michelle M. Kittleson, Khadijah Breathett, Boback Ziaeian, David Aguilar, Vanessa Blumer, Biykem Bozkurt, Rebecca L. Diekemper, Michael P. Dorsch, Paul A. Heidenreich, Corrine Y. Jurgens, Prateeti Khazanie, George Augustine Koromia, Harriette G.C. Van Spall
Journal: Journal of the American College of Cardiology (2024)
Interferon regulatory factor 8-driven reprogramming of the immune microenvironment enhances antitumor adaptive immunity and reduces immunosuppression in murine glioblastoma
Authors: Megan Montoya, Sara A Collins, Pavlina Chuntova, Trishna S Patel, Takahide Nejo, Akane Yamamichi, Noriyuki Kasahara, Hideho Okada
Journal: Neuro-Oncology (2024)

Glioblastoma (GBM) has a highly immunosuppressive tumor immune microenvironment (TIME), largely mediated by myeloid-derived suppressor cells (MDSCs). Here, we utilized a retroviral replicating vector (RRV) to deliver Interferon Regulatory Factor 8 (IRF8), a master regulator of type 1 conventional dendritic cell (cDC1) development, in a syngeneic murine GBM model. We hypothesized that RRV-mediated delivery of IRF8 could "reprogram" intratumoral MDSCs into antigen-presenting cells and thereby restore T-cell responses.
Osimertinib-induced DNA resistance mutations in cerebrospinal fluid of EGFR mutated NSCLC patients developing leptomeningeal metastases: ORA-LM study
Authors: J W Tijmen van der Wel, Mirjam C Boelens, Merel Jebbink, Sietske A Smulders, Klaar W Maas, Merel J A Luitse, Annette Compter, Robin P B Boltjes, Nik Sol, Kim Monkhorst, Daan van den Broek, Egbert F Smit, Adrianus J de Langen, Dieta Brandsma
Journal: Neuro-Oncology (2024)

Diagnosis and treatment of leptomeningeal metastases (LM) in epidermal growth factor receptor mutation-positive (EGFRm +) non-small-cell lung carcinoma (NSCLC) is challenging. We aimed to identify resistance mechanisms (RM) to osimertinib in cerebrospinal fluid (CSF) and plasma.
Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy
Authors: Michael H Zaleski, Serena Omo-Lamai, Jia Nong, Liam S Chase, Jacob W Myerson, Patrick M Glassman, Florence Lee, Sahily Reyes-Esteves, Zhicheng Wang, Manthan N Patel, Alina D Peshkova, Hiroaki Komatsu, Paul H Axelsen, Vladimir R Muzykantov, Oscar A Marcos-Contreras, Jacob S Brenner
Journal: Journal of Controlled Release (2024)
Stat Bite: The most frequent five cancers diagnosed worldwide, and the most frequent cancer diagnosed in each of 185 countries among males aged 15-34 years in 2022
Journal: JNCI Journal of the National Cancer Institute (2024)

The most frequent five cancers diagnosed worldwide, and the most frequent cancer diagnosed in each of 185 countries among males aged 15-34 years in 2022Thyroid cancer, with around 40 000 new cases in 2022, has surpassed testicular cancer as the leading cancer diagnosis worldwide among males at young ages (15-34 years) (Figure A).Yet testicular cancer, with around 32 500 new cases, is still the most frequent cancer among males in this age group in 70 countries, largely in populations of European ancestry (Figure B).In contrast, thyroid cancer is the leading cancer among young males in only 4 countries, with China contributing almost three-quarters of incidence burden worldwide, an estimated 29 500 new cases annually.
Ocular blood flow dynamics following sinus rhythm restoration through catheter ablation: laser speckle flowgraphy in patients with persistent atrial fibrillation
Authors: Nobuhiko Yamamoto, Makoto Nakano, Kotaro Nochioka, Masayuki Yasuda, Hiroshi Kunikata, Toru Nakazawa, Satoshi Yasuda
Journal:  (2024)

Laser speckle flowgraphy (LSFG) is a well-established tool renowned for its non-invasive and reproducible assessment of ocular blood flow. While rhythm control therapies, such as catheter ablation (CA), have shown promise in enhancing cognitive function in atrial fibrillation (AF) patients, the acute impact of CA on microcirculatory changes, particularly in ocular blood flow, remains a topic of limited understanding. The present study aims to delve into the potential of LSFG in detecting microcirculatory alterations following the restoration of sinus rhythm (SR) through CA in patients with AF.
Systemically targeting monocytic myloid-derrived suppressor cells using dendrimers and their cell-level biodistribution kinetics
Authors: Chad A Littrell, Gregory P Takacs, Chenikkayala Siva Sankara, Alexandra Sherman, Kai A Rubach, Julia S Garcia, Coral A Bell, Tejashwini Lnu, Jeffrey K Harrison, Fan Zhang
Journal: Journal of Controlled Release (2024)
A Phase 1b/2 Randomized Clinical Trial of Oleclumab with or without Durvalumab plus Chemotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma
Authors: Andrew L. Coveler, Matthew J. Reilley, Mark Zalupski, Teresa Macarulla, Christos Fountzilas, Mariano Ponz-Sarvisé, Adnan Nagrial, Nataliya V. Uboha, Sophia Frentzas, Michael Overman, Anne Noonan, Wells A. Messersmith, Nick Pavlakis, Niharika B. Mettu, Ina Bisha, Ying Wang, Paul Smith, Elina Murtomaki, Agata A. Bielska, Veronique Bragulat, Zachary A. Cooper, Rakesh Kumar, David R. Spigel
Journal: Clinical Cancer Research (2024)

Pancreatic ductal adenocarcinoma upregulates CD73, potentially contributing to immune surveillance evasion. Combining oleclumab (CD73 inhibitor) and durvalumab with chemotherapy may identify an effective treatment option.
Defective autophagy of pericytes enhances radiation-induced senescence promoting radiation brain injury
Authors: Na Luo, Wenjun Zhu, Xiaoyu Li, Min Fu, Yuanyuan Zhang, Feng Yang, Yiling Zhang, Ziqi Chen, Qiang Zhang, Bi Peng, Qianxia Li, Xin Chen, Yuanhui Liu, Guangyuan Hu, Xiaohong Peng
Journal: Neuro-Oncology (2024)

Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI.
Proposals for Revised International Working Group-European LeukemiaNet Criteria for Anemia Response in Myelofibrosis
Authors: Ayalew Tefferi, Giovanni Barosi, Francesco Passamonti, Juan Carlos Hernandez-Boluda, Prithviraj Bose, Konstanze Döhner, Martin Ellis, Naseema Gangat, Jacqueline S. Garcia, Heinz Gisslinger, Jason Gotlib, Paola Guglielmelli, Vikas Gupta, Claire N. Harrison, Elizabeth O. Hexner, Gabriela S Hobbs, Jean-Jacques Kiladjian, Steffen Koschmieder, Nicolaus Kröger, Andrew T Kuykendall, Giuseppe Gaetano Loscocco, John O. Mascarenhas, Lucia Masarova, Ruben Mesa, Barbara Mora, Olatoyosi Odenike, Stephen T. Oh, Animesh D Pardanani, Anand A Patel, Naveen Pemmaraju, Alessandro Rambaldi, Raajit K. Rampal, Shireen Sirhan, Natasha Szuber, Moshe Talpaz, Pankit Vachhani, Alessandro M. Vannucchi, Tiziano Barbui
Journal: Blood (2024)
To nap or not? Evidence from a meta-analysis of cohort studies of habitual daytime napping and health outcomes
Authors: Ying-Bo Yang, Yong-Bo Zheng, Jie Sun, Lu-Lu Yang, Jiao Li, Yi-Miao Gong, Ming-Zhe Li, Xin Wen, Hao-Yun Zhao, Pei-Pei Shi, Gui-Hua Yu, Zhou-Long Yu, Yu Chen, Kai Yuan, Jia-Hui Deng, Su-Xia Li, Yong-Feng Yang, Zhao-Hui Zhang, Michael V Vitiello, Jie Shi, Yu-Mei Wang, Le Shi, Lin Lu, Yan-Ping Bao
Journal: Sleep Medicine Reviews (2024)
Microsatellite instability at U2AF-binding polypyrimidic tract sites perturbs alternative splicing during colorectal cancer initiation
Authors: Vincent Jonchère, Hugo Montémont, Enora Le Scanf, Aurélie Siret, Quentin Letourneur, Emmanuel Tubacher, Christophe Battail, Assane Fall, Karim Labreche, Victor Renault, Toky Ratovomanana, Olivier Buhard, Ariane Jolly, Philippe Le Rouzic, Cody Feys, Emmanuelle Despras, Habib Zouali, Rémy Nicolle, Pascale Cervera, Magali Svrcek, Pierre Bourgoin, Hélène Blanché, Anne Boland, Jérémie Lefèvre, Yann Parc, Mehdi Touat, Franck Bielle, Danielle Arzur, Gwennina Cueff, Catherine Le Jossic-Corcos, Gaël Quéré, Gwendal Dujardin, Marc Blondel, Cédric Le Maréchal, Romain Cohen, Thierry André, Florence Coulet, Pierre de la Grange, Aurélien de Reyniès, Jean-François Fléjou, Florence Renaud, Agusti Alentorn, Laurent Corcos, Jean-François Deleuze, Ada Collura, Alex Duval
Journal: Genome biology (2024)

Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is common in colorectal cancer (CRC). These cancers are associated with somatic coding events, but the noncoding pathophysiological impact of this genomic instability is yet poorly understood. Here, we perform an analysis of coding and noncoding MSI events at the different steps of colorectal tumorigenesis using whole exome sequencing and search for associated splicing events via RNA sequencing at the bulk-tumor and single-cell levels. Our results demonstrate that MSI leads to hundreds of noncoding DNA mutations, notably at polypyrimidine U2AF RNA-binding sites which are endowed with cis-activity in splicing, while higher frequency of exon skipping events are observed in the mRNAs of MSI compared to non-MSI CRC. At the DNA level, these noncoding MSI mutations occur very early prior to cell transformation in the dMMR colonic crypt, accounting for only a fraction of the exon skipping in MSI CRC. At the RNA level, the aberrant exon skipping signature is likely to impair colonic cell differentiation in MSI CRC affecting the expression of alternative exons encoding protein isoforms governing cell fate, while also targeting constitutive exons, making dMMR cells immunogenic in early stage before the onset of coding mutations. This signature is characterized by its similarity to the oncogenic U2AF1-S34F splicing mutation observed in several other non-MSI cancer. Overall, these findings provide evidence that a very early RNA splicing signature partly driven by MSI impairs cell differentiation and promotes MSI CRC initiation, far before coding mutations which accumulate later during MSI tumorigenesis.
3D-printed aerogels as theranostic implants monitored by fluorescence bioimaging
Authors: Ana Iglesias-Mejuto, Rui Pinto, Pedro Faísca, José Catarino, João Rocha, Luisa Durães, Maria Manuela Gaspar, Catarina Pinto Reis, Carlos A García-González
Journal: Bioactive Materials (2024)

Aerogel scaffolds are nanostructured materials with beneficial properties for tissue engineering applications. The tracing of the state of the aerogels after their implantation is challenging due to their variable biodegradation rate and the lack of suitable strategies capable of
AB0436 STRUCTURAL AND INFLAMMATORY IMAGING PARAMETERS IN PSORIATIC ARTHRITIS: A COMPARISON OF DMARD-NAIVE AND DMARD-FAILURE PATIENTS
Authors: N. Ö. Renkli, N. J. Kleinrensink, J. Spierings, S. C. Mastbergen, H. E. Vonkeman, S. C. Mooij, L. G. Schipper, A. Herman, I. Ten Katen, F. Nap, M. Hol, P. De Jong, M. Jansen, W. Foppen
Journal: Annals of the Rheumatic Diseases (2024)
POS0991 THE DEVELOPMENT OF A CLINICAL PREDICTION MODEL FOR TREATMENT RESPONSE IN INDIVIDUAL PSORIATIC ARTHRITIS PATIENTS
Authors: F. T. Perton, J. Spierings, J. N. Pouw, H. E. Vonkeman, S. C. Mooij, L. G. Schipper, A. Herman, S. C. Mastbergen, P. M. J. Welsing
Journal: Annals of the Rheumatic Diseases (2024)
Autochthonous Trichophyton rubrum terbinafine resistance in France: Assessment of antifungal susceptibility tests
Authors: Alicia Moreno-Sabater, Camille Cordier, Anne Cécile Normand, Anne Laure Bidaud, Geneviève Cremer, Jean Philippe Bouchara, Antoine Huguenin, Sébastien Imbert, Isabelle Challende, Cécile Brin, Françoise Foulet, Boualem Sendid, Illan Laloum, Denis Magne, Christophe Hennequin, Michel Monod, Guillaume Desoubeaux, Éric Dannaoui
Journal: Clinical Microbiology and Infection (2024)
Fourth dose bivalent COVID-19 vaccines outperform monovalent boosters in eliciting cross-reactive memory B cells to Omicron subvariants
Authors: Holly A. Fryer, Daryl Geers, Lennert Gommers, Luca M. Zaeck, Ngoc H. Tan, Bernadette Jones-Freeman, Abraham Goorhuis, Douwe F. Postma, Leo G. Visser, P. Mark Hogarth, Marion P.G. Koopmans, Corine H. GeurtsvanKessel, Robyn E. O’Hehir, P. Hugo M. van der Kuy, Rory D. de Vries, Menno C. van Zelm
Journal: Journal of Infection (2024)

Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. Here, we characterized the RBD-specific memory B cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, in direct comparison with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one month after a fourth dose with a monovalent or a BA.1 or BA.5 bivalent vaccine. Serum neutralizing antibodies (NAb) were quantified, as well as RBD-specific Bmem with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. Both bivalent vaccines elicited higher NAb titers against Omicron subvariants compared to the monovalent vaccine. Following either vaccine type, recipients had slightly increased WH1 RBD-specific Bmem numbers. Both bivalent vaccines significantly increased WH1 RBD-specific Bmem binding of all Omicron subvariants tested by flow cytometry, while recognition of Omicron subvariants was not enhanced following monovalent vaccination. IgG1
BCG vaccination of healthcare workers for protection against COVID-19: 12-month outcomes from an international randomised controlled trial
Authors: Nicole L Messina, Laure F Pittet, Ellie McDonald, Cecilia Moore, Simone Barry, Marc Bonten, Anthony Byrne, John Campbell, Julio Croda, Mariana G Croda, Margareth Dalcolmo, Fernando F de Almeida E Val, Roberto D de Oliveira, Glauce Dos Santos, Mark W Douglas, Kaya Gardiner, Amanda Gwee, Bruno A Jardim, Tobias Kollmann, Marcus Vg Lacerda, Michaela Lucas, David J Lynn, Laurens Manning, Helen Marshall, Abby O'Connell, Kirsten P Perrett, Jeffrey J Post, Cristina Prat-Aymerich, Jorge L Rocha, Jesus Rodriguez-Baño, Ushma Wadia, Adilia Warris, Andrew Davidson, Nigel Curtis
Journal: Journal of Infection (2024)