bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Authors: Sheth Sangini S. , Oh Ji Eun , Bellone Stefania , Siegel Eric R. , Greenman Michelle , Mutlu Levent , McNamara Blair , Pathy Shefali , Clark Mitchell , Azodi Masoud , Altwerger Gary , Andikyan Vaagn , Huang Gloria , Ratner Elena , Kim Daniel J. , Iwasaki Akiko , Levi Angelique W. , Buza Natalia , Hui Pei , Flaherty Sean , Schwartz Peter E. , Santin Alessandro D. 
Published: April 2024

Abstract

Purpose:
We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients.

Patients and Methods:
We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less. Secondary outcomes were HPV clearance and tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and posttreatment by flow cytometry among study arms.

Results:
Of the 114 evaluable patients 77% and 23% harbored CIN2 and CIN3, respectively. Regression to CIN1 or less was observed in 95% of patients in the imiquimod group (Arm B) compared with 79% in the control/surveillance (Arm A); P = 0.043 and 84% in the imiquimod+9vHPV group (Arm C; P = 0.384 vs. Arm A). Neither of the treatment-arm differences from Arm A reached the prespecified α = 0.025 significance level. No significant differences were noted in the secondary outcome of rate of HPV clearance. The number of tissue-resident memory CD4/CD8 T cells in cytobrush samples demonstrated a &gt;5-fold increase in Arm B/imiquimod when compared with Arm A/surveillance (P &lt; 0.01). In contrast, there was no significant difference in T-cell responses among participants in Arm C when compared with Arm A. Imiquimod treatment was well tolerated.

Conclusions:
Although imiquimod induced a higher regression to CIN1 or less and significant increases in CD4/CD8 T cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.
Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice
Authors: Trotter Timothy N. , Wilson Andrea , McBane Jason , Dagotto Carina E. , Yang Xiao-Yi , Wei Jun-Ping , Lei Gangjun , Thrash Hannah , Snyder Joshua C. , Lyerly Herbert Kim , Hartman Zachary C. 
Published: April 2024

Abstract

The ability to temporally regulate gene expression and track labeled cells makes animal models powerful biomedical tools. However, sudden expression of xenobiotic genes [e.g., GFP, luciferase (Luc), or rtTA3] can trigger inadvertent immunity that suppresses foreign protein expression or results in complete rejection of transplanted cells. Germline exposure to foreign antigens somewhat addresses these challenges; however, native fluorescence and bioluminescence abrogates the utility of reporter proteins and highly spatiotemporally restricted expression can lead to suboptimal xenoantigen tolerance. To overcome these unwanted immune responses and enable reliable cell tracking/gene regulation, we developed a novel mouse model that selectively expresses antigen-intact but nonfunctional forms of GFP and Luc, as well as rtTA3, after CRE-mediated recombination. Using tissue-specific CREs, we observed model and sex-based differences in immune tolerance to the encoded xenoantigens, illustrating the obstacles of tolerizing animals to foreign genes and validating the utility of these “NoGlow” mice to dissect mechanisms of central and peripheral tolerance. Critically, tissue unrestricted NoGlow mice possess no detectable background fluorescence or luminescence and exhibit limited adaptive immunity against encoded transgenic xenoantigens after vaccination. Moreover, we demonstrate that NoGlow mice allow tracking and tetracycline-inducible gene regulation of triple-transgenic cells expressing GFP/Luc/rtTA3, in contrast to transgene-negative immune-competent mice that eliminate these cells or prohibit metastatic seeding. Notably, this model enables de novo metastasis from orthotopically implanted, triple-transgenic tumor cells, despite high xenoantigen expression. Altogether, the NoGlow model provides a critical resource for in vivo studies across disciplines, including oncology, developmental biology, infectious disease, autoimmunity, and transplantation.

Significance:
Multitolerant NoGlow mice enable tracking and gene manipulation of transplanted tumor cells without immune-mediated rejection, thus providing a platform to investigate novel mechanisms of adaptive immunity related to metastasis, immunotherapy, and tolerance.
Artificial Intelligence–Assisted Cancer Status Detection in Radiology Reports
Authors: Arya Ankur , Niederhausern Andrew , Bahadur Nadia , Shah Neil J. , Nichols Chelsea , Chatterjee Avijit , Philip John 
Published: April 2024

Abstract

Cancer research is dependent on accurate and relevant information of patient's medical journey. Data in radiology reports are of extreme value but lack consistent structure for direct use in analytics. At Memorial Sloan Kettering Cancer Center (MSKCC), the radiology reports are curated using gold-standard approach of using human annotators. However, the manual process of curating large volume of retrospective data slows the pace of cancer research. Manual curation process is sensitive to volume of reports, number of data elements and nature of reports and demand appropriate skillset. In this work, we explore state of the art methods in artificial intelligence (AI) and implement end-to-end pipeline for fast and accurate annotation of radiology reports. Language models (LM) are trained using curated data by approaching curation as multiclass or multilabel classification problem. The classification tasks are to predict multiple imaging scan sites, presence of cancer and cancer status from the reports. The trained natural language processing (NLP) model classifiers achieve high weighted F1 score and accuracy. We propose and demonstrate the use of these models to assist in the manual curation process which results in higher accuracy and F1 score with lesser time and cost, thus improving efforts of cancer research.

Significance:
Extraction of structured data in radiology for cancer research with manual process is laborious. Using AI for extraction of data elements is achieved using NLP models’ assistance is faster and more accurate.
Tradução de La Araucana por Dom Pedro II Itinerários do Processo Criativo
Authors: Sackl Ana Maria B. C. 
Published: April 2024

Dom Pedro II criou um acervo de traduções em várias línguas, algumas do espanhol para o português principalmente de obras clássicas da literatura espanhola, este artigo foca na tradução do poema épico La Araucana e os modos de circulação do processo de criação. “La Araucana” de Ercilla, narra a Guerra de Arauco acontecida na atual Patagônia chilena no século XVI entre espanhóis e Araucanos, na qual o autor Don Alonso de Ercilla (1554)[1] participou. Descrevem-se nesta pesquisa as instituições onde os documentos de referência foram achados e analisam-se os modos de circulação dos mesmos no processos de criação, o dossiê genético está constituído por: manuscritos pesquisados no Instituto Histórico Geográfico Brasileiro (IGHB) do Rio de Janeiro, uma página do manuscrito tradutório inédito de Pedro de Alcântara; uma ata póstuma em honra ao imperador da mesma Instituição; um exemplar do livro La Araucana publicada em Anveres em 1597 propriedade da Biblioteca Nacional do RJ; excertos dos Diários de d. Pedro II do Arquivo Histórico de Petrópolis e dados mencionados pelo imperador sobre a importância de La Araucana, na sua tradução de Prometheo Acorrentado (1907.p.174)[2]de Eschylo pertencente à Biblioteca Imperial. Utiliza-se o embasamento teórico da Crítica Genética[1] ERCILLA. La Araucana. Primera, Segvnda, y Tercera Partes de la Aravcana, En Anvers, En casa de Pedro Bellero. (1597)[2] ALCÂNTARA, Pedro de (1907). Prometheu Acorrentado. Original de Eschylo vertido Litteralmente para o Portuguez por Dom Pedro II. 2º edição.Trasladação Poética do texto Barão de Parapiacaba. Rio de Janeiro. Imprensa Nacional. Biblioteca do Museu Imperial. Petrópolis RJ.
Long‐Term Safety and Efficacy of Mavacamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results of the PIONEER‐OLE Study
Authors: Masri Ahmad , Lester Steven J. , Stendahl John C. , Hegde Sheila M. , Sehnert Amy J. , Balaratnam Ganesh , Shah Ashish , Fox Shawna , Wang Andrew 
Published: April 2024

Background
The phase 2 PIONEER‐HCM (Phase 2 Open‐label Pilot Study Evaluating Mavacamten in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction) study showed that mavacamten improved left ventricular outflow tract gradients, exercise capacity, and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), but the results of longer‐term treatment are less well described. We report interim results from the PIONEER‐OLE (PIONEER Open‐Label Extension) study, the longest‐term study of mavacamten in patients with symptomatic obstructive HCM.

Methods and Results
Patients who previously completed PIONEER‐HCM (n=20) were eligible to enroll in PIONEER‐OLE. Patients received oral mavacamten, 5 mg once daily (starting dose), with individualized dose titration at week 6. Evaluations included serial monitoring of safety, echocardiography, Kansas City Cardiomyopathy Questionnaire–Overall Summary Score, and serum NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels. Thirteen patients enrolled and received mavacamten (median study duration at data cutoff, 201 weeks). Most patients (92.3%) received β‐blockers concomitantly. Treatment‐emergent adverse events were predominantly mild/moderate. One patient had an isolated reduction in left ventricular ejection fraction to 47%, which recovered and remained normal with continued treatment at a reduced dose. At week 180, mavacamten was associated with New York Heart Association class improvements from baseline (class II to I, n=9; class III to II, n=1; and unchanged, n=2), sustained reductions in left ventricular outflow tract gradients (mean [SD] change from baseline: resting, −50 [55] mm Hg; Valsalva, −70 [41] mm Hg), and serum NT‐proBNP levels (median [interquartile range] change from baseline: −498 [−2184 to −76] ng/L), and improved Kansas City Cardiomyopathy Questionnaire–Overall Summary Score (mean [SD] change from baseline: +17 [16]).

Conclusions
This long‐term analysis supports the continued safety and effectiveness of mavacamten for >3 years in obstructive HCM.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03496168.
Impact of a Chronic Total Coronary Occlusion on the Incidence of Appropriate Implantable Cardioverter‐Defibrillator Shocks and Mortality: A Substudy of the Dutch Outcome in ICD Therapy (DO‐IT)) Registry
Authors: van Veelen Anna , Verstraelen Tom E. , Somsen Yvemarie B. O. , Elias Joëlle , van Dongen Ivo M. , Delnoy Peter Paul H. M. , Scholten Marcoen F. , Boersma Lucas V. A. , Maass Alexander H. , Strikwerda Sipke , Firouzi Mehran , Allaart Cornelis P. , Vernooy Kevin , Grauss Robert W. , Tukkie Raymond , Knaapen Paul , Zwinderman Aeilko H. , Dijkgraaf Marcel G. W. , Claessen Bimmer E. P. M. , van Barreveld Marit , Wilde Arthur A. M. , Henriques José P. S. , van Gent M. W. F. , Bouwels L. H. R. , van der Voort P. H. , Theuns D. A. M. J. , Bijsterveld N. R. , Abels R. , van Erven L. , Takens L. H. , Kimman G. P. , van der Burg A. E. Borger , Khan M. , Derksen R. , Vet M. W. , Widdershoven J. W. M. G. , Brouwer M. A. , Meine M. , Tuinenburg A. E. , Spierenburg H. A. M. 
Published: April 2024

Background
Chronic total coronary occlusions (CTO) substantially increase the risk for sudden cardiac death. Among patients with chronic ischemic heart disease at risk for sudden cardiac death, an implantable cardioverter defibrillator (ICD) is the favored therapy for primary prevention of sudden cardiac death. This study sought to investigate the impact of CTOs on the risk for appropriate ICD shocks and mortality within a nationwide prospective cohort.

Methods and Results

This is a subanalysis of the nationwide Dutch‐Outcome in ICD Therapy (DO‐IT) registry of primary prevention ICD recipients in The Netherlands between September 2014 and June 2016 (n=1442). We identified patients with chronic ischemic heart disease (n=663) and assessed available coronary angiograms for CTO presence (n=415). Patients with revascularized CTOs were excluded (n=79). The primary end point was the composite of all‐cause mortality and appropriate ICD shocks. Clinical follow‐up was conducted for at least 2 years. A total of 336 patients were included, with an average age of 67±9 years, and 20.5% was female (n=69). An unrevascularized CTO was identified in 110 patients (32.7%). During a median follow‐up period of 27 months (interquartile range, 24–32), the primary end point occurred in 21.1% of patients with CTO (n=23) compared with 11.9% in patients without CTO (n=27;
P
=0.034). Corrected for baseline characteristics including left ventricular ejection fraction, and the presence of a CTO was an independent predictor for the primary end point (hazard ratio, 1.82 [95% CI, 1.03–3.22];
P
=0.038).

Conclusions
Within this nationwide prospective registry of primary prevention ICD recipients, the presence of an unrevascularized CTO was an independent predictor for the composite outcome of all‐cause mortality and appropriate ICD shocks.
Sodium Glucose Transporter 2 Inhibitors Versus Metformin on Cardiovascular and Renal Outcomes in Patients With Diabetes With Low Cardiovascular Risk: A Nationwide Cohort Study
Authors: Chang Hao‐Chih , Chen Yun‐Yu , Kuo Tzu‐Ting , Lin Yenn‐Jiang , Chien Kuo‐Liong , Chang Hung‐Yu , Hung Chung‐Lieh , Chung Fa‐Po 
Published: April 2024

Background
This study investigated whether initial SGLT2 (sodium‐glucose cotransporter 2) inhibitor‐based treatment is superior to metformin‐based regimens as a primary prevention strategy among low‐risk patients with diabetes.

Methods and Results

In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors‐based and metformin‐based regimens were 1:2 matched by propensity score. Study outcomes included all‐cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end‐stage renal disease. Compared with 1928 patients receiving metformin‐based regimens, 964 patients receiving SGLT2 inhibitor‐based regimens had similar all‐cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51–1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25–1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59–1.92]), stroke (HR, 0.78 [95% CI, 0.48–1.27]), and progression to end‐stage renal disease (HR, 0.88 [95% CI, 0.32–2.39]). However, SGLT2 inhibitors were associated with a lower risk of all‐cause mortality (HR, 0.47 [95% CI, 0.23–0.99];
P
for interaction=0.008) and progression to end‐stage renal disease (HR, 0.22 [95% CI, 0.06–0.82];
P
for interaction=0.04) in patients under the age of 65.

Conclusions
In comparison to metformin‐based regimens, SGLT2 inhibitor‐based regimens showed a similar risk of all‐cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first‐line therapy in select low‐risk patients, for example, younger patients with diabetes.
Validation of a Suprasystolic Cuff System for Static and Dynamic Representation of the Central Pressure Waveform
Authors: Tamborini Alessio , Gharib Morteza 
Published: April 2024

Background
Noninvasive pulse waveform analysis is valuable for central cardiovascular assessment, yet controversies persist over its validity in peripheral measurements. Our objective was to compare waveform features from a cuff system with suprasystolic blood pressure hold with an invasive aortic measurement.

Methods and Results

This study analyzed data from 88 subjects undergoing concurrent aortic catheterization and brachial pulse waveform acquisition using a suprasystolic blood pressure cuff system. Oscillometric blood pressure (BP) was compared with invasive aortic systolic BP and diastolic BP. Association between cuff and catheter waveform features was performed on a set of 15 parameters inclusive of magnitudes, time intervals, pressure–time integrals, and slopes of the pulsations. The evaluation covered both static (subject‐averaged values) and dynamic (breathing‐induced fluctuations) behaviors. Peripheral BP values from the cuff device were higher than catheter values (systolic BP–residual, 6.5 mm Hg; diastolic BP–residual, 12.4 mm Hg). Physiological correction for pressure amplification in the arterial system improved systolic BP prediction (
r
2
=0.83). Dynamic calibration generated noninvasive BP fluctuations that reflect those invasively measured (systolic BP Pearson
R
=0.73,
P
<0.001; diastolic BP Pearson
R
=0.53,
P
<0.001). Static and dynamic analyses revealed a set of parameters with strong associations between catheter and cuff (Pearson
R
>0.5,
P
<0.001), encompassing magnitudes, timings, and pressure–time integrals but not slope‐based parameters.

Conclusions
This study demonstrated that the device and methods for peripheral waveform measurements presented here can be used for noninvasive estimation of central BP and a subset of aortic waveform features. These results serve as a benchmark for central cardiovascular assessment using suprasystolic BP cuff‐based devices and contribute to preserving system dynamics in noninvasive measurements.
Food Insecurity and Ideal Cardiovascular Health Risk Factors Among US Adolescents
Authors: Hammad Nour M. , Wolfson Julia A. , de Ferranti Sarah D. , Willett Walter C. , Leung Cindy W. 
Published: April 2024

Background
Food insecurity, a social and economic condition of limited availability of healthy food, is a risk factor for adverse cardiovascular health outcomes among adults; few studies have been conducted in adolescents. This study explores the association between food insecurity and cardiovascular health risk factors among a nationally representative sample of US adolescents, adopting the American Heart Association's Life's Essential 8 metric.

Methods and Results
We analyzed data from 2534 adolescents aged 12 to 19 years from the 2013 to 2018 National Health and Nutrition Examination Surveys. In the sample, 24.8% of adolescents lived in food‐insecure households. After multivariable adjustment, food insecurity was associated with a 3.23‐unit lower total Life's Essential 8 score (95% CI, −6.32, −0.15) and lower scores on diet quality (β=−5.39 [95% CI, −8.91, −1.87]) and nicotine exposure (β=−4.85 [95% CI, −9.24, −0.45]). Regarding diet, food insecurity was associated with 5% lower Healthy Eating Index‐2015 scores [95% CI, −7%, −2%], particularly lower intakes of whole grains and seafood/plant proteins and marginally higher intake of added sugar. Regarding nicotine exposure, food insecurity was associated with ever use of a tobacco product among m (odds ratio, 1.74 [95% CI, 1.20–2.53]). Compared with their food‐secure counterparts, food‐insecure male (odds ratio, 1.98 [95% CI, 1.07–3.65]) and female (odds ratio, 3.22 [95% CI, 1.60–6.45]) adolescents had higher odds of living with a current indoor smoker.

Conclusions
In this nationally representative sample of adolescents, food insecurity was associated with multiple indicators of cardiovascular health risk. These findings underscore the need for public health interventions and policies to reduce food insecurity and improve cardioprotective behaviors during adolescence, with particular efforts targeting diet quality and nicotine exposure.
Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome
Authors: Stephens Sara B. , Novy Tyler , Spurzem Gabrielle N. , Jacob Benjamin , Beecroft Taylor , Soludczyk Emily , Kozel Beth A. , Weigand Justin , Morris Shaine A. 
Published: April 2024

Background
We aimed to describe the frequency and yield of genetic testing in supravalvar aortic stenosis (SVAS) following negative evaluation for Williams‐Beuren syndrome (WS).

Methods and Results

This retrospective cohort study included patients with SVAS at our institution who had a negative evaluation for WS from May 1991 to September 2021. SVAS was defined as (1) peak supravalvar velocity of ≥2 meters/second, (2) sinotubular junction or ascending aortic
Z
score <−2.0, or (3) sinotubular junction
Z
score <−1.5 with family history of SVAS. Patients with complex congenital heart disease, aortic valve disease as the primary condition, or only postoperative SVAS were excluded. Genetic testing and diagnoses were reported. Of 162 patients who were WS negative meeting inclusion criteria, 61 had genetic testing results available (38%). Chromosomal microarray had been performed in 44 of 61 and was nondiagnostic for non‐WS causes of SVAS. Sequencing of 1 or more genes was performed in 47 of 61. Of these, 39 of 47 underwent
ELN
sequencing, 20 of 39 (51%) of whom had a diagnostic variant. Other diagnoses made by gene sequencing were Noonan syndrome (3
PTPN11
, 1
RIT1)
, Alagille syndrome (3
JAG1
), neurofibromatosis (1
NF1
), and homozygous familial hypercholesterolemia (1
LDLR1
). Overall, sequencing was diagnostic in 29 of 47 (62%).

Conclusions

When WS is excluded, gene sequencing for SVAS is high yield, with the highest yield for the
ELN
gene. Therefore, we recommend gene sequencing using a multigene panel or exome analysis. Hypercholesterolemia can also be considered in individuals bearing the stigmata of this disease.
Shaking Up the People
Authors: Schmitz Tobias 
Published: April 2024

Abstract
This article makes the case that Hos 14:2–3 is the earliest positive call to return (שׁוב) to YHWH in the Hebrew Bible and asks why it is precisely here that repentance is spoken of no longer negatively in reproach but positively in exhortation. First, it argues for a pre-exilic dating of Hos 14:2–5 by referring to Jer 2:35; 3:22; 4:8; 23:20, and 30:24. These passages in Jeremiah quote or allude to Hos 14:5, which speaks of the divine wrath being turned away from Israel. Second, the study argues that it was in the reflection on the fall of the Northern Kingdom that the words of Hosea were collected and expanded upon. In doing so, the scribes sought to make the downfall of the Northern Kingdom understandable as YHWH’s responsibility and to shake up the people: for the divine wrath to disappear, Israel must now return to YHWH.
Subversion through Allusion in Samuel’s Call to Prophecy (1 Sam 3)
Authors: Shapira Hananel 
Published: April 2024

Abstract
The article explores the significance of the strange scene in 1 Sam 3 where Samuel confuses the Lord with Eli and investigates what message the author intended to convey. The article argues that the narrative of Samuel’s call addresses issues that extend beyond his circumstances. Samuel is a representative of the entire prophetic legacy, and the narrator uses the narrative’s peculiarities to validate the essence of prophecy and the prophetic role. The article also explores the similarities and differences between Samuel’s call narrative and Num 12, which claims that only Moses is a trustworthy prophet. The narrator of Samuel’s call narrative uses Num 12 subversively, lending credibility to his own narrative and reinforcing Samuel’s reliability. Ultimately, the method by which the message was conveyed is inconsequential as long as the prophet received and accurately conveyed the divine message.