bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecologic Analysis of Correlates of Cervical Cancer Morbidity and Mortality in Sub-Saharan Africa
Authors: Gapare Claire Ruvimbo , El-Zein Mariam , Patel Harshita , Tope Parker , Franco Eduardo L. 
Published: June 2022

Abstract

Background:
Cervical cancer is the fourth leading cause of death among women worldwide, with 85% of the burden falling on low- to middle- income countries. We studied the correlates of cervical cancer incidence and mortality, and case-fatality in Sub-Saharan Africa.

Methods:
Country-level data on 16 putative cervical cancer correlates for 37 Sub-Saharan African countries were collected from publicly available data sources. We performed univariate and multiple (stepwise) linear regression analyses to identify correlates of cervical cancer incidence and mortality, and case-fatality.

Results:
In univariate analyses, incidence and mortality rates were significantly correlated with contraceptive use, penile cancer incidence, and human immunodeficiency virus prevalence. Incidence rates were also correlated with literacy rates, whereas mortality rates were correlated with the proportion of rural population and screening coverage. Multiple regression analyses showed contraceptive use (P = 0.009) and penile cancer incidence (P = 0.004) as associated with cervical cancer incidence. Penile cancer incidence (P = 9.77 × 10–5) and number of medical doctors (P = 0.0433) were associated with mortality. The goodness of fit of the incidence and mortality models was moderate at best, explaining 49% and 37% of variability in the data, respectively. However, the case-fatality model had the best fit explaining most of the variation (adjusted R2 = 0.948; P = 6.822 × 10–16).

Conclusions:
To reduce the burden of cervical cancer in Sub-Saharan Africa, it would be important to design multimodal interventions that not only target screening and HPV vaccination, but also focus on cervical cancer correlates.

Impact:
Identifying contextual factors associated with cervical cancer in this region could inform targeted interventions.
Genome-Wide Association Study of Pregnancy in Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study
Authors: Rotz Seth J. , Worley Sarah , Hu Bo , Bazeley Peter , Baedke Jessica L. , Hudson Melissa M. , Kuo Dennis J. , Oeffinger Kevin C. , Robison Leslie L. , Sahoo Debashis , Wang Fan , Yasui Yutaka , Armstrong Gregory T. , Bhatia Smita 
Published: June 2022

Abstract

Background:
Gonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported.

Methods:
Leveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of SNPs on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. We calculated sex-stratified hazard ratios, using Cox proportional hazards modeling, adjusting for birth cohort (before 1965 vs. 1965 or later) and doses of relevant chemotherapies; replication was attempted in the independent St. Jude Lifetime Cohort study (SJLIFE).

Results:
In the CCSS cohort, nine SNPs were found to be suggestive (P &lt; 10–7) or statistically significantly (P &lt; 5 × 10–8) associated with pregnancy, however, none of the SNPs were replicated in SJLIFE. Cohorts differed based on the overall pregnancy rate, frequency of sterilizing procedures, and birth cohort.

Conclusions:
We were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors.

Impact:
Future attempts at replication should be considered in cohorts treated in a comparable era. In addition, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.
First-In-Human Phase I Study of the OX40 Agonist MOXR0916 in Patients with Advanced Solid Tumors
Authors: Kim Tae Won , Burris Howard A. , de Miguel Luken Maria J. , Pishvaian Michael J. , Bang Yung-Jue , Gordon Michael , Awada Ahmad , Camidge D. Ross , Hodi F. Stephen , McArthur Grant A. , Miller Wilson H. , Cervantes Andres , Chow Laura Q. , Lesokhin Alexander M. , Rutten Annemie , Sznol Mario , Rishipathak Deepali , Chen Shang-Chiung , Stefanich Eric , Pourmohamad Tony , Anderson Maria , Kim Jeong , Huseni Mahrukh , Rhee Ina , Siu Lillian L. 
Published: June 2022

Abstract

Purpose:
OX40, a receptor transiently expressed by T cells upon antigen recognition, is associated with costimulation of effector T cells and impairment of regulatory T-cell function. This first-in-human study evaluated MOXR0916, a humanized effector-competent agonist IgG1 monoclonal anti-OX40 antibody.

Patients and Methods:
Eligible patients with locally advanced or metastatic refractory solid tumors were treated with MOXR0916 intravenously once every 3 weeks (Q3W). A 3+3 dose-escalation stage (0.2–1,200 mg; n = 34) was followed by expansion cohorts at 300 mg (n = 138) for patients with melanoma, renal cell carcinoma, non–small cell lung carcinoma, urothelial carcinoma, and triple-negative breast cancer.

Results:
MOXR0916 was well tolerated with no dose-limiting toxicities observed. An MTD was not reached. Most patients (95%) experienced at least one adverse event (AE); 56% of AEs, mostly grade 1–2, were related to MOXR0916. Most common treatment-related AEs included fatigue (17%), diarrhea (8%), myalgia (7%), nausea (6%), decreased appetite (6%), and infusion-related reaction (5%). Pharmacokinetic (PK) parameters were dose proportional between 80 and 1,200 mg and supported Q3W administration. The recommended expansion dose based on PK and OX40 receptor saturation was 300 mg Q3W. Immune activation and upregulation of PD-L1 was observed in a subset of paired tumor biopsies. One renal cell carcinoma patient experienced a confirmed partial response. Overall, 33% of patients achieved stable disease.

Conclusions:
Although objective responses were rarely observed with MOXR0916 monotherapy, the favorable safety profile and evidence of tumor immune activation in a subset of patients support further investigation in combination with complementary agents such as PD-1/PD-L1 antagonists.
Protective Effects of MicroRNA‐200b‐3p Encapsulated by Mesenchymal Stem Cells–Secreted Extracellular Vesicles in Myocardial Infarction Via Regulating BCL2L11
Authors: Wan Jun , Lin Shaoyan , Yu Zhuo , Song Zhengkun , Lin Xuefeng , Xu Rongning , Du Songlin 
Published: June 2022

Background
Extracellular vesicles (EVs) are a popular treatment candidate for myocardial injury. This work investigated the effects of mesenchymal stem cells (MSCs)–secreted EVs–derived miR‐200b‐3p on cardiomyocyte apoptosis and inflammatory response after myocardial infarction (MI) through targeting BCL2L11 (Bcl‐2–like protein 11) .

Methods and Results
EVs from MSCs were isolated and identified. EVs from MSCs with transfection of miR‐200b‐3p for overexpression were injected into MI mice. The effect of miR‐200b‐3p on cardiac function, infarction area, myocardial fibrosis, cardiomyocyte apoptosis, and inflammatory response was determined in MI mice. The targeting relationship between miR‐200b‐3p and BCL2L11 was verified, and the interaction between BCL2L11 and NLR family pyrin domain containing 1 (NLRP1) was also verified. MI mice were injected with an overexpressing BCL2L11 lentiviral vector to clarify whether BCL2L11 can regulate the effect of miR‐200b‐3p on MI mice. EVs from MSCs were successfully extracted. MSCs‐EVs improved cardiac function and reduced infarction area, apoptosis of cardiomyocytes, myocardial fibrosis, and inflammation in MI mice. Upregulation of miR‐200b‐3p further enhanced the effects of MSCs‐EVs on the myocardial injury of MI mice. BCL2L11 was targeted by miR‐200b‐3p and bound to NLRP1. Upregulation of BCL2L11 negated the role of miR‐200b‐3p–modified MSCs‐EVs in MI mice.

Conclusions
A summary was obtained that miR‐200b‐3p–encapsulated MSCs‐EVs protect against MI‐induced apoptosis of cardiomyocytes and inflammation via suppressing BCL2L11.
Correlation Between Cardiac Images, Biomarkers, and Amyloid Load in Wild‐Type Transthyretin Amyloid Cardiomyopathy
Authors: Morioka Mami , Takashio Seiji , Nakashima Naoya , Nishi Masato , Fujiyama Akira , Hirakawa Kyoko , Hanatani Shinsuke , Usuku Hiroki , Yamamoto Eiichiro , Kidoh Masafumi , Oda Seitaro , Matsushita Kenichi , Ueda Mitsuharu , Tsujita Kenichi 
Published: June 2022

Background

Several imaging parameters and biomarkers provide diagnostic and prognostic information for wild‐type transthyretin amyloid cardiomyopathy. However, the relevance of these parameters and their association with cardiac amyloid load requires further substantiation. We aimed to elucidate the association of imaging parameters obtained using
99m
Tc‐labeled pyrophosphate scintigraphy, cardiovascular magnetic resonance imaging, global longitudinal strain (GLS), and cardiac biomarkers with cardiac amyloid load in patients with wild‐type transthyretin amyloid cardiomyopathy.

Methods and Results

Eighty‐eight patients with wild‐type transthyretin amyloid cardiomyopathy who underwent
99m
Tc‐labeled pyrophosphate scintigraphy and cardiovascular magnetic resonance were retrospectively evaluated. Quantitative cardiac amyloid load was obtained from 61 patients after myocardial biopsy. Correlations were assessed using Pearson’s correlation coefficient applied to medical record data. The mean heart to contralateral ratio, native T1, extracellular volume, and GLS were 1.91±0.36, 1419.4±56.4 ms, 56.5±13.6%, and −9.4±2.5%, respectively. Median high‐sensitivity cardiac troponin T (hs‐cTnT) and BNP (B‐type natriuretic peptide) levels were 0.0478 (0.0334‐0.0691) ng/mL and 213.8 (125.8–392.7) pg/mL, respectively. The mean cardiac amyloid load was 22.9±15.0%. The heart to contralateral ratio correlated significantly with native T1 (
r
=0.397), extracellular volume (
r
=0.477), GLS (
r
=0.363), cardiac amyloid load (
r
=0.379), and Ln (hs‐cTnT) (
r
=0.247). Further, cardiac amyloid load correlated significantly with native T1 (
r
=0.509), extracellular volume (
r
=0.310), GLS (
r
=0.446), and Ln (hs‐cTnT) (
r
=0.354). Compared with BNP, hs‐cTnT levels better correlated with several imaging parameters and cardiac amyloid load.

Conclusions

Increased cardiac amyloid load correlated with increased
99m
Tc‐labeled pyrophosphate positivity, native T1, extracellular volume, and hs‐cTnT levels, and an impaired GLS, suggesting that imaging parameters and cardiac biomarkers may reflect histological and functional changes attributable to amyloid deposition in the myocardium.
Corin Missense Variants, Blood Pressure, and Hypertension in 11 322 Black Individuals: Insights From REGARDS and the Jackson Heart Study
Authors: Parcha Vibhu , Irvin Marguerite R. , Lange Leslie A. , Armstrong Nicole D. , Pampana Akhil , Meyer Mariah , Judd Suzanne E. , Arora Garima , Arora Pankaj 
Published: June 2022

Background
Corin enzyme contributes to the processing of inactive natriuretic peptides to bioactive hormones. In Black individuals, Corin gene variants (rs111253292 [Q568P] and rs75770792 [T555I]) have been previously reported to have a modest association with blood pressure (BP) and hypertension.

Methods and Results

We evaluated the association of Corin genotype with BP traits, prevalent hypertension, and incident hypertension among self‐identified 11 322 Black Americans in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study and the JHS (Jackson Heart Study) using multivariable‐adjusted regression modeling. Multivariable‐adjusted genotype‐stratified differences in NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and BNP (B‐type natriuretic peptide) levels were assessed. Genotype‐stratified
NPPA
and
NPPB
expression differences in healthy organ donor left atrial and left ventricular heart tissue (N=15) were also examined. The rs111253292 genotype was not associated with systolic BP (β±SE, 0.42±0.58; −1.24±0.82), diastolic BP (0.51±0.33; −0.41±0.46), mean arterial pressure (0.48±0.38; −0.68±0.51), and prevalent hypertension (odds ratio [OR], 0.93 [95% CI, 0.80–1.09]; OR, 0.79 [95% CI, 0.61–1.01]) in both REGARDS and JHS, respectively. The rs75770792 genotype was not associated with systolic BP (0.48±0.58; −1.26±0.81), diastolic BP (0.52±0.33; −0.33±0.45), mean arterial pressure (0.50±0.38; −0.63±0.50), and prevalent hypertension (OR, 1.02 [95% CI, 0.84–1.23]; OR, 0.87 [95% CI, 0.67–1.13]) in both cohorts, respectively. The Corin genotype was also not associated with incident hypertension (OR, 1.35 [95% CI, 0.94–1.93]; OR, 0.95 [95% CI, 0.64–1.39]) in the study cohorts. The NT‐proBNP levels in REGARDS and BNP levels in JHS were similar between the Corin genotype groups. In heart tissue, the
NPPA
and
NPPB
expression was similar between the genotype groups.

Conclusions

Corin
gene variants observed more commonly in Black individuals are not associated with differences in NP expression, circulating NP levels, and BP or hypertension as previously reported in candidate gene studies. Understanding the genetic determinants of complex cardiovascular traits in underrepresented populations requires further evaluation.
Histone Deacetylase 6 Inhibitor JS28 Prevents Pathological Gene Expression in Cardiac Myocytes
Authors: Ngo Vivien , Fleischmann Bernd K. , Jung Manfred , Hein Lutz , Lother Achim 
Published: June 2022

Background
Epigenetic modulators have been proposed as promising new drug targets to treat adverse remodeling in heart failure. Here, we evaluated the potential of 4 epigenetic drugs, including the recently developed histone deacetylase 6 (HDAC6) inhibitor JS28, to prevent endothelin‐1 induced pathological gene expression in cardiac myocytes and analyzed the chromatin binding profile of the respective inhibitor targets.

Methods and Results
Cardiac myocytes were differentiated and puromycin‐selected from mouse embryonic stem cells and treated with endothelin‐1 to induce pathological gene expression (938 differentially expressed genes, q<0.05). Dysregulation of gene expression was at least in part prevented by epigenetic inhibitors, including the pan‐BRD (bromodomain‐containing protein) inhibitor bromosporine (290/938 genes), the BET (bromodomain and extraterminal) inhibitor JQ1 (288/938), the broad‐spectrum HDAC inhibitor suberoylanilide hydroxamic acid (227/938), and the HDAC6 inhibitor JS28 (210/938). Although the 4 compounds were similarly effective toward pathological gene expression, JS28 demonstrated the least adverse effects on physiological gene expression. Genome‐wide chromatin binding profiles revealed that HDAC6 binding sites were preferentially associated with promoters of genes involved in RNA processing. In contrast, BRD4 binding was associated with genes involved in core cardiac myocyte functions, for example, myocyte contractility, and showed enrichment at enhancers and intronic regions. These distinct chromatin binding profiles of HDAC6 and BRD4 might explain the different effects of their inhibitors on pathological versus physiological gene expression.

Conclusions
In summary, we demonstrated, that the HDAC6 inhibitor JS28 effectively prevented the adverse effects of endothelin‐1 on gene expression with minor impact on physiological gene expression in cardiac myocytes. Selective HDAC6 inhibition by JS28 appears to be a promising strategy for future evaluation in vivo and potential translation into clinical application.
TAGE Score for Symptomatic Intracranial Hemorrhage Prediction After Successful Endovascular Treatment in Acute Ischemic Stroke
Authors: Janvier Paul , Kerleroux Basile , Turc Guillaume , Pasi Marco , Farhat Wassim , Bricout Nicolas , Benzakoun Joseph , Legrand Laurence , Clarençon Frédéric , Bracard Serge , Oppenheim Catherine , Boulouis Grégoire , Henon Hilde , Naggara Olivier , Ben Hassen Wagih 
Published: June 2022

Background:
Determine if early venous filling (EVF) after complete successful recanalization with mechanical thrombectomy in acute ischemic stroke is an independent predictor of symptomatic intracranial hemorrhage (sICH) and integrate EVF into a risk score for sICH prediction.

Methods:
Consecutive patients with anterior acute ischemic stroke treated by mechanical thrombectomy issued from patients enrolled in the THRACE trial (Thrombectomie des Artères Cérébrales) and from 2 prospective registries were included and divided into a derivation (Center I; n=402) and validation cohorts (THRACE and center 2; n=507). EVF was evaluated by 2 blinded readers. sICH was defined according to the modified European cooperative acute stroke study II. Clinical and radiological data were analyzed in the derivation cohort (C1) to identify independent predictors of sICH and construct a predictive score test on the validation cohort (THRACE + C2).

Results:

Symptomatic ICH rate was similar between the two cohorts (9.9% and 8.9% respectively,
P
=0.9). Time from onset-to-successful recanalization >270 minutes (odds ratio [OR], 7.8 [95% CI, 2.5–24]), Alberta Stroke Program Early CT Score (≤5 [OR, 2.49 (95% CI, 1.8–8.1) or 6–7 [OR, 1.15 (95% CI, 1.03–4.46)]), glucose blood level >7 mmol/L (OR, 2.92 [95% CI, 1.26–6.7]), and EVF presence (OR, 11.9 [95% CI, 3.8–37.5]) were independent predictors of sICH and constituted the Time–Alberta Stroke Program Early CT–Glycemia–EVF score. Time–Alberta Stroke Program Early CT–Glycemia–EVF score was associated with an increased risk of sICH in the derivation cohort (OR increase per unit, 1.99 [95% CI, 1.53–2.59];
P
<0.001) with area under the curve, 0.832 [95% CI, 0.767–0.898]. The score had good performance in the validation cohort (area under the curve, 0.801 [95% CI, 0.69–0.91]).

Conclusions:
Time–Alberta Stroke Program Early CT–Glycemia–EVF score is a simple tool with readily available clinical variables with good performances for sICH prediction after mechanical thrombectomy.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01062698.
Clinical application of dexmedetomidine combined with dezocine in local anesthesia for endoscopic dacryocystorhinostomy
Authors: Zhao Lu , Sun Zuojun , Shen Wenting , Zeng Yongheng 
Published: June 2022

ObjectiveTo investigate the clinical effect of dexmedetomidine combined with dezocine in local anesthesia for endoscopic dacryocystorhinostomy (DCR).MethodsNinety patients undergoing elective endoscopic DCR were randomly divided into two groups, local anesthesia group (LA group n = 45) and general anesthesia group (GA group, n = 45). These subjects were all American Society of Anesthesiologists (ASA)-Physical Status I-II patients. The changes of mean arterial pressure (MAP) and heart rate (HR) were observed and recorded before anesthesia (T0), after anesthesia (T1), at the beginning of surgery (T2), and at the end of surgery (T3). The visual analogue scale (VAS) score was observed and recorded immediately after awakening from anesthesia and at 1, 2, 6, and 12 h after surgery. Additionally, the occurrence of adverse reactions after surgery and the sedation-agitation scale (SAS) score after awakening were recorded.ResultsCompared with the LA group, the MAP and HR of the GA group were significantly lower at T1 and T2, but significantly higher at T3. Local anesthesia was associated with lower VAS score immediately after awakening and at 1, 2, 6, and 12 h after surgery. Also, local anesthesia caused a lower incidence of postoperative agitation, nausea, and vomiting. The SAS score in the LA group was markedly higher than that in the GA group.ConclusionLocal anesthesia with dexmedetomidine and dezocine as adjuvants in endoscopic DCR has more stable hemodynamics and reduces the stress response during perioperative period. Also, this anesthesia achieves better postoperative sedation and analgesia effects, reduces postoperative complications, and improves the quality of awakening from anesthesia. Collectively, local anesthesia is a comfortable and safe option for patients with high risks of general anesthesia and those unwilling to receive general anesthesia.
Fluorescence-guided surgery for osteoradionecrosis of the jaw: a retrospective study
Authors: Aljohani Suad , Fliefel Riham , Brunner Teresa Franziska , Chronopoulos Aristeidis , Binmadi Nada , Otto Sven 
Published: June 2022

Objective Osteoradionecrosis of the jaw (ORNJ) is one of the most severe head and neck complications in patients treated with radiotherapy. The goal of treatment is to suppress ORNJ progression. Currently, surgical removal of necrotic bone is an effective management approach for advanced stages. In this study, we present our experience in managing ORNJ using fluorescence-guided surgery. Methods Nineteen ORNJ lesions in 15 hospitalized patients were treated with fluorescence-guided surgery. We retrospectively reviewed patients’ demographic data, comorbidities, local preceding event, location, ORNJ stage, and treatment outcomes with a median follow-up of 12 months. Results Twelve lesions (63%) were treated surgically under tetracycline fluorescence, and seven lesions (37%) were surgically treated under auto-fluorescence. Overall, four lesions (21%) achieved complete mucosal healing, eight lesions (42%) showed partial mucosal healing with bone exposure and no signs or symptoms of inflammation, and seven lesions (37%) were progressive. The results showed that either healing or ORNJ stabilization was achieved in 63% of lesions (n = 12). Conclusion Fluorescence-guided surgery can be beneficial in curing or stabilizing ORNJ. However, randomized clinical trials are needed to confirm these findings.