bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients
Authors: Mahmood Syed S , Riedell Peter A , Feldman Stephanie , George Gina , Sansoterra Stephen A , Althaus Thomas , Rehman Mahin , Mead Elena , Liu Jennifer E , Devereux Richard B , Weinsaft Jonathan W , Kim Jiwon , Balkan Lauren , Barbar Tarek , Lee Chuy Katherine , Harchandani Bhisham , Perales Miguel-Angel , Geyer Mark B , Park Jae H , Palomba M Lia , Shouval Roni , Tomas Ana A , Shah Gunjan L , Yang Eric H , Gaut Daria L , Rothberg Michael V , Horn Evelyn M , Leonard John P , Van Besien Koen , Frigault Matthew J , Chen Zhengming , Mehrotra Bhoomi , Neilan Tomas G , Steingart Richard M 
Published: March 2023

Abstract

Aims
Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient’s immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality.

Methods and results
From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104–647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan–Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6–4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4–8.8) after adjusting for cancer burden.

Conclusion
Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin.
Incidence of clinical atrial fibrillation and related complications using a screening algorithm at a nationwide level
Authors: Roger Antoine , Cottin Yves , Bentounes Sid Ahmed , Bisson Arnaud , Bodin Alexandre , Herbert Julien , Maille Baptiste , Zeller Marianne , Deharo Jean Claude , Lip Gregory Y H , Fauchier Laurent 
Published: March 2023

Abstract

Aims
In a recent position paper, the European Heart Rhythm Association (EHRA) proposed an algorithm for the screening and management of arrhythmias using digital devices. In patients with prior stroke, a systematic screening approach for atrial fibrillation (AF) should always be implemented, preferably immediately after the event. Patients with increasing age and with specific cardiovascular or non-cardiovascular comorbidities are also deemed to be at higher risk. From a large nationwide database, the aim was to analyse AF incidence rates derived from this new EHRA algorithm.

Methods and results
Using the French administrative hospital discharge database, all patients hospitalized in 2012 without a history of AF, and with at least a 5-year follow-up (FU) (or if they died earlier), were included. The yearly incidence of AF was calculated in each subgroup defined by the algorithm proposed by EHRA based on a history of previous stroke, increasing age, and eight comorbidities identified via International Classification of Diseases 10th Revision codes. Out of the 4526 104 patients included (mean age 58.9 ± 18.9 years, 64.5% women), 1% had a history of stroke. Among those with no history of stroke, 18% were aged 65–74 years and 21% were ≥75 years. During FU, 327 012 patients had an incidence of AF (yearly incidence 1.86% in the overall population). Implementation of the EHRA algorithm divided the population into six risk groups: patients with a history of stroke (group 1); patients &gt; 75 years (group 2); patients aged 65–74 years with or without comorbidity (groups 3a and 3b); and patients &lt; 65 years with or without comorbidity (groups 4a and 4b). The yearly incidences of AF were 4.58% per year (group 2), 6.21% per year (group 2), 3.50% per year (group 3a), 2.01% per year (group 3b), 1.23% per year (group 4a), and 0.35% per year (group 4b). In patients aged &lt; 65 years, the annual incidence of AF increased progressively according to the number of comorbidities from 0.35% (no comorbidities) to 9.08% (eight comorbidities). For those aged 65–75 years, the same trend was observed, i.e. increasing from 2.01% (no comorbidities) to 11.47% (eight comorbidities).

Conclusion
These findings at a nationwide scale confirm the relevance of the subgroups in the EHRA algorithm for identifying a higher risk of AF incidence, showing that older patients (&gt;75 years, regardless of comorbidities) have a higher incidence of AF than those with prior ischaemic stroke. Further studies are needed to evaluate the usefulness of algorithm-based risk stratification strategies for AF screening and the impact of screening on major cardiovascular event rates.
The R-wave amplitude in V1 on baseline electrocardiogram correlates with the occurrence of high-degree atrioventricular block following left bundle branch block after transcatheter aortic valve replacement
Authors: Yagel Oren , Belhassen Bernard , Planer David , Amir Offer , Elbaz-Greener Gabby 
Published: March 2023

AbstractAimsSeveral procedural and electrocardiogram (ECG) parameters have been associated with the occurrence of high-degree atrioventricular block (AVB) requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR). We hereunder sought to assess if the baseline R-wave amplitude in V1 ECG lead of patients with normal QRS duration undergoing TAVR is associated with a higher patient’s risk for developing high-degree AVB following left bundle branch block (LBBB).Methods and resultsIn this retrospective single-centre study in 720 consecutive patients who underwent TAVR, 141 (19.6%) patients with normal QRS duration developed a new LBBB after TAVR. The 24 (17%) patients who underwent PPI for reasons other than high-degree AVB were excluded from further analysis. In the remaining 117 study patients, 14 (12%) developed high-degree AVB requiring PPI (Group 1) while the remaining 103 (88%) patients did not (Group 2). There were no significant differences in baseline demographic or procedural characteristics nor in PR interval, QRS duration, and QRS axis between these two groups. The incidence of left anterior hemiblock was higher in Group 1 (3 of 14, 21.4%) than that in Group 2 (9 of 103, 8.7%), but the difference was not statistically significant (P = 0.156). The R-wave amplitude in V1 was smaller in Group 1 than that in Group 2 (0.029 ± 0.04 mV vs. 0.11 ± 0.14 mV, P = 0.0316). In the receiver-operating characteristics analysis, the cutoff for R-wave amplitude pre-TAVR was 0.03 mV, area under the curve = 0.7219 (P = 0.0002).ConclusionThe R-wave amplitude in lead V1 during baseline ECG in patients with normal QRS duration may predict the occurrence of high-degree AVB following new LBBB after TAVR.
New insertable cardiac monitors show high diagnostic yield and good safety profile in real-world clinical practice: results from the international prospective observational SMART Registry
Authors: Quartieri Fabio , Harish Manyam , Calò Leonardo , Ebrahim Iftikhar , Fusco Antonio , Mester Stephen , Cauti Filippo , Park Seung-Jung , Francia Pietro , Giovagnoni Marco , Adragao Pedro , Vezi Brian , Lin Wenjiao , Hutson Chananit Sintuu , Grammatico Andrea 
Published: March 2023

Abstract

Aims
Insertable cardiac monitors (ICMs) are indicated for long-term monitoring of unexplained syncope or palpitations, and for detection of bradycardia, ventricular tachycardia, and/or atrial fibrillation (AF). The aim of our study was to evaluate the safety and clinical value associated with a new generation ICM (Confirm Rx™, Abbott, Illinois, USA), featuring a new remote monitoring system based on smartphone patient applications.

Methods and results
The SMART Registry is an international prospective observational study. The main endpoints were ICM safety (incidence of serious adverse device and procedure-related events (SADEs) at 1 month), ICM clinical value (incidence of device-detected true arrhythmias and of clinical diagnoses and interventions), and patient-reported experience measurements (PREMs). A total of 1400 subjects were enrolled. ICM indications included syncope (49.1%), AF (18.8%), unexplained palpitations (13.6%), risk of ventricular arrhythmia (6.6%), and cryptogenic stroke (6.0%). Freedom from SADEs at 1 month was 99.4% (95% Confidence Interval: 98.8–99.7%). In the 6-month monitoring period, the ICM detected true cardiac arrhythmias in 45.7% of patients and led to clinical interventions in a relevant proportion of patients; in particular, a pacemaker implant was performed after bradycardia detection in 8.9% of subjects who received an ICM for syncope and oral anticoagulation therapy was indicated after AF detection in 15.7% of subjects with cryptogenic stroke. PREMs showed that 78.2% of subjects were satisfied with the remote monitoring patient app.

Conclusion
The evaluated ICM is associated with an excellent safety profile and high diagnostic yield. Patients reported positive experiences associated with the use of their smartphone for the device remote monitoring.
Acute Severe Ulcerative Colitis Is Associated With an Increased Risk of Acute Pouchitis
Authors: Kayal Maia , Posner Hannah , Milwidsky Hadar Meringer , Plietz Michael , Khaitov Sergey , Sylla Patricia , Greenstein Alexander , Dubinsky Marla C , Mehandru Saurabh , Colombel Jean Frederic 
Published: March 2023

Abstract

Background
Pouchitis occurs in up to 80% of patients after total proctocolectomy (TPC) with ileal pouch–anal anastomosis (IPAA) and has been associated with microbial and host-related immunological factors. We hypothesized that a more robust immune response at the time of colectomy, manifested by acute severe ulcerative colitis (ASUC), may be associated with subsequent acute pouchitis.

Methods
This was a retrospective cohort analysis of all patients with UC or indeterminate colitis complicated by medically refractory disease or dysplasia who underwent TPC with IPAA at Mount Sinai Hospital between 2008 and 2017 and at least 1 subsequent pouchoscopy. Acute pouchitis was defined according to the Pouchitis Disease Activity Index. Cox regression was used to assess unadjusted relationships between hypothesized risk factors and acute pouchitis.

Results
A total of 416 patients met inclusion criteria. Of the 165 (39.7%) patients who underwent urgent colectomy, 77 (46.7%) were admitted with ASUC. Acute pouchitis occurred in 228 (54.8%) patients a median of 1.3 (interquartile range, 0.6-3.1) years after the final surgical stage. On multivariable analysis, ASUC (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.04-2.17) and a greater number of biologics precolectomy (HR, 1.57; 95% CI, 1.06-2.31) were associated with an increased probability of acute pouchitis, while older age at colectomy (HR, 0.98; 95% CI, 0.97-0.99) was associated with a decreased probability. Time to pouchitis was significantly less in patients admitted with ASUC compared with those not (P = .002).

Conclusion
A severe UC disease phenotype at the time of colectomy was associated with an increased probability of acute pouchitis.
Monitoring the Monitor? Selective Responses to Human Rights Transgressions
Authors: Attia Hana , Grauvogel Julia 
Published: March 2023

AbstractSanctions are among the most frequently used foreign policy tools to address human rights violations, but they can be highly politicized. Since the early 2000s, human rights sanctions have been increasingly triggered by standardized rankings of states’ performances. While research on economic statecraft suggests that coercive measures based on cross-national assessments may be less influenced by strategic considerations, scholarship on rankings highlights how standardized performance indicators can also be political. This paper investigates whether sanctions based on standardized human rights assessments are also influenced by senders’ strategic political and economic interests. Empirically, we examine the case of United States human trafficking sanctions that combines universal rankings in the first stage and country-specific sanctions waivers in the second. The analysis leverages novel data on all Trafficking in Persons (TIP) rankings by the US State Department and presidential sanctions waivers from 2003 to 2018. Despite the TIP report's reputation as a reliable indicator, we find that both stages in the process of imposing human trafficking sanctions are driven by strategic attempts to minimize the economic and political costs of sanctions for the US. These findings have broader implications for the reputation and effectiveness of other human rights rankings by the US.
Repurposing antifungals: population pharmacokinetics of itraconazole and hydroxy-itraconazole following administration of a nanocrystal formulation
Authors: Jansen Anouk M E , Ter Heine Rob , Donnelly J P , Blijlevens Nicole , Brüggemann Roger J M 
Published: March 2023

Abstract

Objectives
To describe itraconazole and hydroxy-itraconazole pharmacokinetics following intravenous (IV) administration of a previously developed nanocrystal formulation (NCF) in haematopoietic cell transplant (HCT) recipients for prophylaxis of invasive fungal disease.

Methods
In a prospective Phase II study, 10 HCT recipients received itraconazole NCF administered in 2-hour infusions of 200 mg twice daily for 2 days, followed by 200 mg once daily until Day 14. Full pharmacokinetic curves were obtained on Days 7 and 14. Additional samples were collected pre- and post-infusion until Day 6, pre-infusion on Days 10 and 12, and during washout on Days 16, 17, 18, 19 and 28. Itraconazole and hydroxy-itraconazole pharmacokinetics were analysed by non-linear mixed-effects population pharmacokinetic modelling.

Results
Four-hundred and seventy-one itraconazole and 471 paired hydroxy-itraconazole concentrations from 10 patients were included for analysis. Data were best described by a semi-mechanistic model with central and peripheral itraconazole compartments and a hydroxy-itraconazole compartment with dissolution of itraconazole drug particles from nanocrystals and first-order distribution and elimination. The final model included interindividual variability on itraconazole clearance and hydroxy-itraconazole clearance.

Conclusions
This study provides information on the pharmacokinetic properties of the itraconazole NCF useful for development of this formulation. Our results suggest that itraconazole NCF is a suitable formulation and may warrant renewal in the setting of repurposing. Our findings may be useful for the reformulation of other highly lipophilic compounds as well.
Neutrophil defect and lung pathogen selection in cystic fibrosis
Authors: Jennings Scott , Hu Yawen , Wellems Dianne , Luo Meng , Scull Callie , Taylor Christopher M , Nauseef William M , Wang Guoshun 
Published: March 2023

AbstractCystic fibrosis is a life-threatening genetic disorder caused by mutations in the CFTR chloride channel. Clinically, over 90% of patients with cystic fibrosis succumb to pulmonary complications precipitated by chronic bacterial infections, predominantly by Pseudomonas aeruginosa and Staphylococcus aureus. Despite the well-characterized gene defect and clearly defined clinical sequelae of cystic fibrosis, the critical link between the chloride channel defect and the host defense failure against these specific pathogens has not been established. Previous research from us and others has uncovered that neutrophils from patients with cystic fibrosis are defective in phagosomal production of hypochlorous acid, a potent microbicidal oxidant. Here we report our studies to investigate if this defect in hypochlorous acid production provides P. aeruginosa and S. aureus with a selective advantage in cystic fibrosis lungs. A polymicrobial mixture of cystic fibrosis pathogens (P. aeruginosa and S. aureus) and non–cystic fibrosis pathogens (Streptococcus pneumoniae, Klebsiella pneumoniae, and Escherichia coli) was exposed to varied concentrations of hypochlorous acid. The cystic fibrosis pathogens withstood higher concentrations of hypochlorous acid than did the non–cystic fibrosis pathogens. Neutrophils derived from F508del-CFTR HL-60 cells killed P. aeruginosa less efficiently than did the wild-type counterparts in the polymicrobial setting. After intratracheal challenge in wild-type and cystic fibrosis mice, the cystic fibrosis pathogens outcompeted the non–cystic fibrosis pathogens and exhibited greater survival in the cystic fibrosis lungs. Taken together, these data indicate that reduced hypochlorous acid production due to the absence of CFTR function creates an environment in cystic fibrosis neutrophils that provides a survival advantage to specific microbes—namely, S. aureus and P. aeruginosa—in the cystic fibrosis lungs.
Research progress on pharmacological effects of isoalantolactone
Authors: Xu Lu , Sun Yanan , Cai Qihan , Wang Mengmeng , Wang Xinliang , Wang Siming , Ni Zhiyu 
Published: March 2023

Abstract

Objectives
To review the pharmacokinetics, pharmacological action and mechanism of isoalantolactone (IAL). Explore the therapeutic potential of isoalantolactone.
Keywords including isoalantolactone, pharmacological effects, pharmacokinetic and toxicity were used for literature search in PubMed, Excerpta Medica Database (EMBASE) and Web of Science, to identify articles published from 1992 to 2022.

Key findings
IAL has a great many obiological activities such as anti-inflammatory, antioxidant, antitumour, neuroprotection, with no obvious toxicity. This review suggests that IAL exerts different pharmacological effects with different mechanisms of action at different doses, and may be a potential drug candidate to treat inflammatory diseases, neurodegenerative diseases and cancer, with medicinal value.

Summary
IAL has various pharmacological activities and medicinal values. However, further research is needed to determine its specific intracellular action sites and targets, so as to fully understand its therapeutic mechanism and provide a reference for the treatment of related diseases.
Multiwavelength monitoring of the nucleus in PBC J2333.9−2343: the giant radio galaxy with a blazar-like core
Authors: Hernández-García L , Panessa F , Bruni G , Bassani L , Arévalo P , Patiño-Alvarez V M , Tramacere A , Lira P , Sánchez-Sáez P , Bauer F E , Chavushyan V , Carraro R , Förster F , Muñoz Arancibia A M , Ubertini P 
Published: March 2023

ABSTRACT
PBC J2333.9−2343 is a giant radio galaxy at z = 0.047 with a bright central core associated to a blazar nucleus. If the nuclear blazar jet is a new phase of the jet activity, then the small orientation angle suggests a dramatic change of the jet direction. We present observations obtained between 2018 September and 2019 January (cadence larger than three days) with Effeslberg, SMARTS-1.3m, ZTF, ATLAS, Swift, and Fermi-LAT, and between 2019 April and 2019 July (daily cadence) with SMARTS-1.3 m and ATLAS. Large (&gt;2 ×) flux increases are observed on time-scales shorter than a month, which are interpreted as flaring events. The cross correlation between the SMARTS-1.3 m monitoring in the NIR and optical shows that these data do not show significant time lag within the measured errors. A comparison of the optical variability properties between non-blazars and blazars AGN shows that PBC J2333.9−2343 has properties more comparable to the latter. The SED of the nucleus shows two peaks, that were fitted with a one-zone leptonic model. Our data and modelling show that the high energy peak is dominated by External Compton from the dusty torus with mild contribution from Inverse Compton from the jet. The derived jet angle of 3 deg is also typical of a blazar. Therefore, we confirm the presence of a blazar-like core in the centre of this giant radio galaxy, likely a Flat Spectrum Radio Quasar with peculiar properties.
BESST: a novel LncRNA knockout strategy with less genome perturbance
Authors: Zhang Shikuan , Chen Yue , Dong Kunzhe , Zhao Yiwan , Wang Yanzhi , Wang Songmao , Qu Chen , Xu Naihan , Xie Weidong , Zeng Chunyu , Lyu Qing Rex , Zhang Yaou 
Published: March 2023

Abstract
Long noncoding RNAs (lncRNAs) are &gt;200 nt RNA transcripts without protein-coding potential. LncRNAs can be categorized into intergenic, intronic, bidirectional, sense, and antisense lncRNAs based on the genomic localization to nearby protein-coding genes. The current CRISPR-based lncRNA knockout strategy works efficiently for lncRNAs distant from the protein-coding gene, whereas it causes genomic perturbance inevitably due to technical limitations. In this study, we introduce a novel lncRNA knockout strategy, BESST, by deleting the genomic DNA fragment from the branch point to the 3′ splicing site in the last intron of the target lncRNA. The BESST knockout exhibited comparable or superior repressive efficiency to RNA silencing or conventional promoter-exon1 deletion. Significantly, the BESST knockout strategy minimized the intervention of adjacent/overlap protein-coding genes by removing an average of ∼130 bp from genomic DNA. Our data also found that the BESST knockout strategy causes lncRNA nuclear retention, resulting in decapping and deadenylation of the lncRNA poly(A) tail. Further study revealed that PABPN1 is essential for the BESST-mediated decay and subsequent poly(A) deadenylation and decapping. Together, the BESST knockout strategy provides a versatile tool for investigating gene function by generating knockout cells or animals with high specificity and efficiency.