tbuckley/cabot-search huggingface dataset:
Left Atrial Appendage Closure after Ablation for Atrial Fibrillation
Authors: Oussama M. Wazni, Walid I. Saliba, Devi G. Nair, Eloi Marijon, Boris Schmidt, Troy Hounshell, Henning Ebelt, Carsten Skurk, Saumil Oza, Chinmay Patel, Arvindh Kanagasundram, Ashish Sadhu, Sri Sundaram, Jose Osorio, George Mark, Madhukar Gupta, David B. DeLurgio, Jeffrey Olson, Jens Erik Nielsen-Kudsk, Lucas V.A. Boersma, Jeff S. Healey, Karen P. Phillips, Federico M. Asch, Katherine Wolski, Kristine Roy, Thomas Christen, Brad S. Sutton, Kenneth M. Stein, Vivek Y. Reddy
Journal: New England Journal of Medicine (2024)

Oral anticoagulation is recommended after ablation for atrial fibrillation among patients at high risk for stroke. Left atrial appendage closure is a mechanical alternative to anticoagulation, but data regarding its use after atrial fibrillation ablation are lacking.
Accurate Inference of the Polyploid Continuum using Forward-time Simulations
Authors: Tamsen Dunn, Arun Sethuraman
Journal: Molecular Biology and Evolution (2024)

Abstract Multiple rounds of whole-genome duplication (WGD) followed by diploidization have occurred throughout the evolutionary history of angiosperms. Much work has been done to model the genomic consequences and evolutionary significance of WGD. While researchers have historically modeled polyploids as either allopolyploids or autopolyploids, the variety of natural polyploids span a continuum of differentiation across multiple parameters, such as the extent of polysomic vs. disomic inheritance, and the degree of genetic differentiation between the ancestral lineages. Here we present a forward-time polyploid genome evolution simulator called SpecKS. SpecKS models polyploid speciation as originating from a 2D continuum, whose dimensions account for both the level of genetic differentiation between the ancestral parental genomes, as well the time lag between ancestral speciation and their subsequent reunion in the derived polyploid. Using extensive simulations, we demonstrate that changes in initial conditions along either dimension of the 2D continuum deterministically affect the shape of the Ks histogram. Our findings indicate that the error in the common method of estimating WGD time from the Ks histogram peak scales with the degree of allopolyploidy, and we present an alternative, accurate estimation method that is independent of the degree of allopolyploidy. Lastly, we use SpecKS to derive tests that infer both the lag time between parental divergence and WGD time, and the diversity of the ancestral species, from an input Ks histogram. We apply the latter test to transcriptomic data from over 200 species across the plant kingdom, the results of which are concordant with the prevailing theory that the majority of angiosperm lineages are derived from diverse parental genomes and may be of allopolyploid origin.
Effective therapy of simvastatin compound ointment in LSS variants-induced palmoplantar keratoderma
Authors: Yumeng Wang, Anqi Zhao, Haisheng Huang, Yujuan Zhai, Yeqiang Liu, Yifan Yang, Chaolan Pan, Qiaoyu Cao, Wei He, Qin Zeng, Qin Yan, Min Li, Ming Li
Journal: British Journal of Dermatology (2024)

In this study, palmoplantar keratosis in four patients with variants in the LSS gene showed various degrees of improvement after 4–16 weeks of therapy using simvastatin and cholesterol ointment, while keratosis in a patient with MBTPS2 variant displayed poor response.
Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia
Authors: John L Sapp, Anthony S L Tang, Ratika Parkash, William G Stevenson, Jeff S Healey, Lorne J Gula, Girish M Nair, Vidal Essebag, Lena Rivard, Jean-Francois Roux, Pablo B Nery, Jean-Francois Sarrazin, Guy Amit, Jean-Marc Raymond, Marc Deyell, Chris Lane, Frederic Sacher, Christian de Chillou, Vikas Kuriachan, Amir AbdelWahab, Isabelle Nault, Katia Dyrda, Stephen Wilton, Umjeet Jolly, Arvindh Kanagasundram, George A Wells
Journal: New England Journal of Medicine (2024)

BackgroundPatients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain.MethodsIn an international trial, we randomly assigned in a 1:1 ratio patients with previous myocardial infarction and clinically significant ventricular tachycardia (defined as ventricular tachycardia storm, receipt of appropriate implantable cardioverter–defibrillator [ICD] shock or antitachycardia pacing, or sustained ventricular tachycardia terminated by emergency treatment) to receive antiarrhythmic drug therapy or to undergo catheter ablation. All the patients had an ICD. Catheter ablation was performed within 14 days after randomization; sotalol or amiodarone was administered as antiarrhythmic drug therapy according to prespecified criteria. The primary end point was a composite of death from any cause during follow-up or, more than 14 days after randomization, ventricular tachycardia storm, appropriate ICD shock, or sustained ventricular tachycardia treated by medical intervention.ResultsA total of 416 patients were followed for a median of 4.3 years. A primary end-point event occurred in 103 of 203 patients (50.7%) assigned to catheter ablation and in 129 of 213 (60.6%) assigned to drug therapy (hazard ratio, 0.75; 95% confidence interval, 0.58 to 0.97; P=0.03). Among patients in the catheter ablation group, adverse events within 30 days after the procedure included death in 2 patients (1.0%) and nonfatal adverse events in 23 patients (11.3%). Among the patients assigned to drug therapy, adverse events that were attributed to antiarrhythmic drug treatment included death from pulmonary toxic effects in 1 patient (0.5%) and nonfatal adverse events in 46 patients (21.6%).ConclusionsAmong patients with ischemic cardiomyopathy and ventricular tachycardia, an initial strategy of catheter ablation led to a lower risk of a composite primary end-point event than antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH2 ClinicalTrials.gov number, NCT02830360.)
Preclinical development of lyophilized self-replicating RNA vaccines for COVID-19 and malaria with improved long-term thermostability
Authors: Gaurav K Gulati, Adrian C Simpson, Zachary MacMillen, Kyle Krieger, Shibbu Sharma, Jesse H Erasmus, Steven G Reed, James W Davie, Marion Avril, Amit P Khandhar
Journal: Journal of Controlled Release (2024)
Clinical and Genetic Markers of Vascular Toxicity in Glioblastoma Patients: Insights from NRG Oncology RTOG-0825
Authors: Joshua D Strauss, Mark R Gilbert, Minesh Mehta, Ang Li, Renke Zhou, Melissa L Bondy, Erik P Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera, Merideth M Wendland, Volker W Stieber, Vinay K Puduvalli, Serah Choi, Nina L Martinez, H Ian Robins, Grant K Hunter, Chi-Fan Lin, Vivian A Guedes, Melissa A Richard, Stephanie L Pugh, Terri S Armstrong, Michael E Scheurer
Journal: Neuro-Oncology (2024)

Abstract Background Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment. Methods In total, 591 non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N = 367) by occurrence of thrombosis or hypertension (grade ≥ 2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the clinical model as a single nucleotide polymorphism (SNP)-dose-effect variable to produce the final genetic models. Results Thrombosis and hypertension were experienced by 62 (11%) and 59 (10%) patients, respectively. Patients who experienced hypertension displayed improved survival over those without hypertension (median overall survival: 25.72 vs. 15.47 months, p = 0.002). The genetic model of thrombosis included corticosteroid use (odds ratio [OR]: 7.13, p = 0.02), absolute neutrophil count (OR: 1.008, p = 0.19), body surface area (OR: 18.87, p = 0.0008), and SNP-dose effect (3 variants; OR: 3.79, p &amp;lt; 0.0001). The genetic model of hypertension included bevacizumab use (OR: 0.97, p = 0.95) and the SNP-dose effect (6 variants; OR: 4.44, p &amp;lt; 0.0001). Conclusions In this study, germline variants were superior in predicting hypertension than clinical variables alone. Additionally, corticosteroid use was a considerable risk factor for thrombosis. Future investigations should confirm the hazard of corticosteroid use on thrombosis and the impact of bevacizumab in other malignancies after accounting for the genetic risk of hypertension.
A Multi‐Channel Handheld Diagnostic Device Based on Green Biomimetic Material for Point‐of‐Care Testing of Vitamin C in Human Fluids
Authors: Donglei Fu, Yueyan Dong, Junping Yin, Bowen Zhang, Shuaibo Zhang, Junjie Deng, Hua Shui, Xinghai Liu
Journal: Advanced Healthcare Materials (2024)

In the era of "Great Health", maintaining an appropriate level of vitamin C is crucial for human health as it directly impacts the proper functioning of the immune system. In this study, a handheld nonenzymatic electrochemical sensor based on biomimetic material prussian blue functionalized polydopamine is proposed for point-of-care testing (POCT) of vitamin C in human fluids. Particularly, Prussian blue, known as a bio-antidote, and polydopamine, a main component of cuttlefish ink, ensure the safety and reliability of home testing. The experimental results quantitatively demonstrate that this electrochemical POCT sensor enables rapid and accurate determination of vitamin C with a wide linear detection range from 0.2 to 200 µm, a low limit of detection at 0.03 µm, and high sensitivity at 0.33 µA µm-1 cm-2. More importantly, the performance evaluation using human urine and saliva samples confirms satisfactory accuracy and recovery rates for vitamin C determination by this electrochemical POCT sensor. Thus, the proposed handheld electrochemical POCT sensor holds potential utility as an affordable tool for VC determination and home-based healthcare.
Clinical significance of complete remission and measurable residual disease in relapsed/refractory multiple myeloma patients treated with T‐cell redirecting immunotherapy
Authors: Aintzane Zabaleta, Noemi Puig, Maria‐Teresa Cedena, Aina Oliver‐Caldes, José J. Perez, Cristina Moreno, Luis‐Esteban Tamariz‐Amador, Paula Rodriguez‐Otero, Felipe Prosper, Veronica Gonzalez‐Calle, Lucía López‐Corral, Beatriz Rey‐Búa, Borja Puertas, Fátima Mirás, José María Sánchez‐Pina, Nieves López‐Muñoz, Manel Juan, E. Azucena González‐Navarro, Álvaro Urbano, Carlos Fernández de Larrea, Joan Blade, Juan‐José Lahuerta, Joaquín Martinez‐Lopez, Maria‐Victoria Mateos, Jesús F. San Miguel, Bruno Paiva
Journal: American Journal of Hematology (2024)

Abstract The impact of measurable residual disease (MRD) in relapse/refractory multiple myeloma (RRMM) patients treated with T‐cell redirecting immunotherapy is uncertain. We analyzed MRD dynamics using next‐generation flow in 201 patients treated in clinical trials with chimeric antigen receptor (CAR) T cells and T‐cell engagers (TCE). Achieving MRD negativity at 10 −6 was associated with 89% reduction in the risk of progression and/or death. Survival outcomes were improved in patients with sustained versus transient MRD negativity and were dismal in those who remained MRD positive. The intent‐to‐treat MRD negative rates were higher in patients treated with CAR T cells versus TCE. However, among patients achieving MRD negativity, there were no differences in survival outcomes when stratified according to treatment with CAR T cells versus TCE. In multivariate analysis including the number of prior lines of treatment, International Staging System, cytogenetic risk, extramedullary disease and type of T‐cell redirecting immunotherapy, only the complete remission (CR) and MRD statuses showed independent prognostic value for progression‐free and overall survival. In conclusion, our study shows that deep and sustained MRD negative CR is the most relevant prognostic factor and should be considered as the treatment endpoint in RRMM patients treated with CAR T cells and TCE.
Efficacy and safety of intranasal medications for allergic rhinitis: Network meta‐analysis
Authors: Bernardo Sousa‐Pinto, Rafael José Vieira, Antonio Bognanni, Sara Gil‐Mata, Renato Ferreira‐da‐Silva, André Ferreira, António Cardoso‐Fernandes, Henrique Ferreira‐Cardoso, Manuel Marques‐Cruz, Vítor Henrique Duarte, João Castro‐Teles, Miguel Campos‐Lopes, Ana Teixeira‐Ferreira, Nuno Lourenço‐Silva, Ivan Chérrez‐Ojeda, Anna Bedbrook, Ludger Klimek, Juan Jose Yepes Nuñez, Torsten Zuberbier, João A. Fonseca, Holger J. Schünemann, Jean Bousquet
Journal: Allergy (2024)

Abstract Background Intranasal antihistamines (INAH), corticosteroids (INCS), and their fixed combinations (INAH+INCS) are one of the cornerstones of the treatment of allergic rhinitis (AR). We performed a systematic review and network‐meta‐analysis comparing the efficacy and safety of INAH, INCS, and INAH+INCS in patients with AR. Methods We searched four electronic bibliographic databases and three clinical trial databases for randomised controlled trials assessing the use of INAH, INCS, and INAH+INCS in adults with seasonal or perennial AR. We performed a network meta‐analysis on the Total Nasal Symptom Score, Total Ocular Symptom Score, Rhinoconjunctivitis Quality‐of‐Life Questionnaire, development of adverse events, and withdrawals due to adverse events. Certainty of evidence was assessed using GRADE‐NMA. Results We included 167 primary studies, most of which assessed patients with seasonal AR. Among individual medications, azelastine‐fluticasone, and fluticasone furoate were the most frequently highest‐ranked interventions for efficacy outcomes, being regularly associated with clinically meaningful larger improvements when compared to other active treatments. Considering drug classes, INAH+INCS were the highest‐ranked interventions for all outcomes in which they were assessed, followed in most cases by INCS. In 105 out of 184 comparisons in seasonal AR, and 28 out of 97 comparisons in perennial AR, certainty of evidence was considered “high” or “moderate”. Conclusion Intranasal medications for AR display clinically relevant differences in their efficacy, but all show a good safety profile. To our knowledge, this is the first network meta‐analysis comparing INAH, INCS, and INAH+INCS in AR, providing relevant evidence for guideline developers and practising physicians on the most efficacious treatments.
Periodontal and orthodontic management of impacted canines
Authors: Mohammad Qali, Chenshuang Li, Chun‐Hsi Chung, Nipul Tanna
Journal: Periodontology 2000 (2024)

Abstract The maxillary and mandibular canines are described by many clinicians as the “cornerstone” of the arch. When in their optimal position, they play a critical role in providing a well‐balanced occlusal scheme that contributes toward functional as well as neuromuscular stability, harmony, esthetics, and dentofacial balance. When an aberration is noted with the normal eruptive and development process, early diagnosis with strategic intervention is critical and may often require a multidisciplinary approach. A proper diagnosis, risk assessment, and management of the soft tissues, hard tissues, and adjacent structures are vital for a successful outcome. This review highlights the diagnostic and treatment modalities that require consideration for the orthodontic as well as the periodontal management of impacted canines. The reader is guided through the etiology, diagnosis, prevention, and intervention of clinical cases that were managed with different approaches.
A prophylactic tyrosine kinase inhibitor strategy based on measurable residual disease pre‐transplantation for Ph<sup>+</sup> acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation: A prospective multicenter cohort study
Authors: Hui Liu, Hui Xu, Peiru Chi, Zinan Feng, Xiaojun Xu, Danian Nie, Xudong Li, Xinquan Liang, Zhiping Fan, Na Xu, Fen Huang, Ren Lin, Zhixiang Wang, Hua Jin, Hongsheng Zhou, Xutao Guo, Dongjun Lin, Jing Sun, Qifa Liu, Li Xuan
Journal: American Journal of Hematology (2024)

Abstract Relapse is the major cause of treatment failure in Philadelphia chromosome‐positive (Ph + ) acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT). This study aimed to evaluate the effect of a prophylactic tyrosine kinase inhibitor (TKI) strategy on relapse in this population. Patients were assigned to prophylactic or control groups based on measurable residual disease (MRD) pre‐transplantation. The primary endpoint was the cumulative incidence of relapse. A total of 110 patients with Ph + ALL undergoing allo‐HSCT were enrolled in this prospective study. Thirty‐eight patients with positive MRD pre‐transplantation were included in the prophylactic group, and 72 with negative MRD pre‐transplantation were included in the control group. The 4‐year cumulative incidence of relapse was 25.3% (95% CI: 12.1%–41.0%) and 20.3% (11.6%–30.7%; HR = 1.272, 95% CI: 0.551–2.940, p = .549), and non‐relapse mortality was 10.5% (3.3%–22.7%) and 9.7% (4.2%–17.9%; HR = 1.094, 95% CI: 0.320–3.738, p = .928) in the prophylactic and control groups. The 4‐year overall survival was 71.8% (53.2%–84.1%) and 84.1% (72.9%–90.9%; HR = 1.746, 95% CI: 0.741–4.112, p = .196), and leukemia‐free survival was 64.1% (45.8%–77.7%) and 70.0% (57.6%–79.4%; HR = 1.212, 95% CI: 0.607–2.421, p = .585) in the prophylactic and control groups. Our results suggest that prophylactic TKI post‐HSCT in patients with positive MRD pre‐transplantation can produce outcomes comparable to negative MRD pre‐transplantation without TKI post‐HSCT.
Clinical and Immune Effects of Peri‐Transplantation <scp>JAK</scp> Inhibition for Myelofibrosis
Authors: Kristin Rathje, Nico Gagelmann, Anita Badbaran, Claudia Langebrake, Adrin Dadkhah, Johanna Richter, Radwan Massoud, Mathias Schäfersküpper, Franziska E. Marquard, Sofia Oechsler, Evgeny Klyuchnikov, Ina Rudolph, Silke Heidenreich, Christian Niederwieser, Catherina Lueck, Dietlinde Janson, Christine Wolschke, Boris Fehse, Francis Ayuk, Nicolaus Kröger
Journal: American Journal of Hematology (2024)

ABSTRACT Despite the introduction of JAK inhibitors, allogeneic hematopoietic cell transplant remains the only potentially curative treatment for patients with myelofibrosis but has considerable treatment‐related complications. Whether the incorporation of JAK inhibition into the transplant algorithm leads to improved outcomes is still unclear. Here, we analyzed different transplant platforms in myelofibrosis patients undergoing a first transplant, comparing immune profiles and outcomes of (1) 33 patients continuing JAK inhibition at start of conditioning until stable engraftment (PERI‐group), (2) 38 patients receiving JAK inhibition prior to transplant until start of conditioning (PRE‐group), and (3) 38 patients that had never received JAK inhibition (NON‐group). Patients in the PERI‐group showed significantly higher early B‐cell recovery as well as significantly increased late recovery of gamma‐delta T cells and NK cells. We observed excellent neutrophil and platelet engraftment (100% for both) in the PERI‐group and no hematotoxic effects or increased rates of infections following peri‐transplant JAK inhibition. Cumulative incidence of acute graft‐versus‐host disease (GvHD) grade II‐IV at day 100 after transplant was 15% in the PERI‐group versus 29% in the PRE‐group versus 34% in the NON‐group. Cumulative incidence of relapse at 1 year after transplant was 9% in the PERI‐group compared with 16% in the PRE‐group and 18% in the NON‐group. In conclusion, peri‐transplant JAK inhibition was feasible with promising engraftment and acute GvHD rates, though deserves further investigation.
Mastering the Narrative: Precision Reporting of Risk and Outcomes in Liver Transplantation
Authors: Femke H C de Goeij, Chase J Wehrle, Fariba Abassi, Sangeeta Satish, Mingyi Zhang, Rebecca Panconesi, Koji Hashimoto, Charles M Miller, Wojciech G Polak, Pierre-Alain Clavien, Jeroen de Jonge, Andrea Schlegel
Journal: Journal of Hepatology (2024)
The glycosyltransferase ST3GAL4 drives immune evasion in acute myeloid leukemia by synthesizing ligands for the glyco-immune checkpoint receptor Siglec-9
Authors: Vignesh Krishnamoorthy, John Daly, Jimmy Kim, Lidia Piatnitca, Katie A. Yuen, Bhoj Kumar, Mehrnoush Taherzadeh Ghahfarrokhi, Tom Q. T. Bui, Parastoo Azadi, Ly P. Vu, Simon Wisnovsky
Journal: Leukemia (2024)

Immunotherapy has demonstrated promise as a treatment for acute myeloid leukemia (AML). However, there is still an urgent need to identify new molecules that inhibit the immune response to AML. Most prior research in this area has focused on protein-protein interaction interfaces. While carbohydrates also regulate immune recognition, the role of cell-surface glycans in driving AML immune evasion is comparatively understudied. The Siglecs, for example, are an important family of inhibitory, glycan-binding signaling receptors that have emerged as prime targets for cancer immunotherapy in recent years. In this study, we find that AML cells express ligands for the receptor Siglec-9 at high levels. Integrated CRISPR genomic screening and clinical bioinformatic analysis identified ST3GAL4 as a potential driver of Siglec-9 ligand expression in AML. Depletion of ST3GAL4 by CRISPR-Cas9 knockout (KO) dramatically reduced the expression of Siglec-9 ligands in AML cells. Mass spectrometry analysis of cell-surface glycosylation in ST3GAL4 KO cells revealed that Siglec-9 primarily binds N-linked sialoglycans on these cell types. Finally, we found that ST3GAL4 KO enhanced the sensitivity of AML cells to phagocytosis by Siglec-9-expressing macrophages. This work reveals a novel axis of immune evasion and implicates ST3GAL4 as a possible target for immunotherapy in AML.
Efficacy and safety of antistaphylococcal penicilin or cephazolin-based combinations versus monotherapy for methicillin-susceptible Staphylococcus aureus infective endocarditis. A propensity score analysis of nationwide prospective cohort.
Authors: Jorge Calderón-Parra, Sara Grillo, Patricia Muñoz, Marina Machado-Vilchez, Antonia Delgado-Montero, Arístides De Alarcón-González, Manuel Poyato-Borrego, M A Goenaga-Sánchez, M Carmen Fariñas-Alvarez, José M Miró, Luis Eduardo López-Cortés, Raquel Rodríguez-García, José A Oteo, Antonio Martínez-Ramos
Journal: Journal of Infection (2024)

We aimed to evaluate the usefulness of antistaphylococcal penicillin (ASP) or cephazolin-based combinations versus monotherapy in patients with native-valve infective endocarditis (IE) caused by methicillin-susceptible Staphylococcus aureus (MSSA).
Real-world effectiveness and safety of Azvudine in hospitalized patients with SARS-CoV-2 infection: a multicenter, retrospective cohort study
Authors: Zhigang Ren, Mengzhao Yang, Guanyue Su, Guowu Qian, Yiqiang Yuan, Jia Yu, Silin Li, Changshuang Wang, Mingxia Lu, Hong Luo, Shixi Zhang, Guangming Li, Donghua Zhang, Ling Wang, Guotao Li, Xiaoli Jin, Juan Wang, Mingming Wang, Ming Cheng, Haiyu Wang, Junbiao Chang, Zujiang Yu
Journal: Journal of Infection (2024)

Azvudine has been designated as a priority treatment for patients infected with SARS-CoV-2, however, clinical evidence in hospitalized cases remains insufficient.
Country categorization of diversity in the pathway from medical student to specialist in the Netherlands
Authors: Lianne Mulder, Anouk Wouters, Eddymurphy U Akwiwu, Andries S Koster, Jan Hindrik Ravesloot, Saskia M Peerdeman, Mahdi Salih, Gerda Croiset, Rashmi A Kusurkar
Journal: The Lancet Regional Health - Europe (2024)