bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phthalates and Phenols, Leukocyte Telomere Length, and Breast Cancer Risk and Mortality in the Long Island Breast Cancer Study Project
Authors: Zhang Xueying , Wolff Mary S. , Shen Jing , Parada Humberto , Santella Regina M. , Neugut Alfred I. , Chen Jia , Teitelbaum Susan L. 
Published: October 2021

Abstract

Background:
Phthalates and phenols from the environment have been inconsistently associated with breast cancer risk or mortality. Studies on the potential modifying role of leukocyte telomere length (LTL), a biomarker of biological aging, on these associations are lacking.

Methods:
We included 1,268 women from the Long Island Breast Cancer Study Project with available data on phthalate and phenol analytes and LTL measurements. Twenty-two phthalate and phenol analytes were measured in spot urines and LTL was measured in blood. The modifying effect of LTL on the associations of individual analyte with breast cancer risk as well as mortalities was estimated using interaction terms between LTL and urinary concentrations of analyte in logistic regression and Cox regression models, respectively. ORs, HRs, and corresponding 95% confidence intervals for a one-unit (ln μg/g creatinine) increase of urinary phthalate/phenol level were estimated at 10th, 50th, and 90th percentiles of LTL.

Results:
LTL significantly (P &lt; 0.05) modified associations between 11 of 22 of urinary phthalate/phenols analytes and breast cancer risk. An inverse association between phthalate/phenols analytes and breast cancer risk at shorter LTL and a positive association at longer LTL was generally suggested. No modifying effect was found for LTL on the association between these phthalate/phenols analytes and breast cancer mortalities.

Conclusions:
LTL may modify the associations between phthalate and phenol exposures and breast cancer risk.

Impact:
This study is the first study that determined the modifying effect of biological aging in the association between environmental chemical exposure and breast cancer risk.
Schlaf‘, Kindlein, schlaf‘: Schlafverhalten von Säuglingen unter Propranolol-Therapie
Authors: Hamm Henning 
Published: October 2021

Sleep problems are frequently reported in infants treated with propranolol for infantile hemangiomas, possibly serving as a marker for a negative impact on central nervous system function. In this cohort study, we objectively investigate the sleep behavior of infants with infantile hemangiomas on propranolol compared to a healthy, untreated control group. Sleep of propranolol-treated infants and controls was investigated using ankle actigraphy and a 24-h diary for 7–10 days at ages 3 and 6 months. The main outcome measures were the Number of Nighttime Awakenings and Sleep Efficiency. The main secondary outcome measures included 24-hour Total Sleep, daytime sleep behavior, and parent-rated infant sleep quality and behavioral development based on the Brief Infant Sleep Questionnaire (BISQ) and the age-appropriate Ages-and-Stages Questionnaire (ASQ), respectively. Fifty-four term-born infants were included in each cohort. No group difference in any investigated parameter was seen at age 3 months. At age 6 months, the propranolol group exhibited a decrease in Sleep Efficiency and a trend towards an increased Number of Nighttime Awakenings compared to the control group. Treated infants at 6 months also had shorter daytime waking periods. 24-hour Total Sleep was unaffected by propranolol. No negative impact of propranolol on subjective sleep quality and behavioral development was noted. <b>Conclusion:</b> Propranolol exerts a measurable yet mild impact on objectively assessed infants’ sleep measures. Behavioral developmental scores were unaffected. Our results support propranolol as first-line therapy for complicated infantile hemangiomas. <b>What is Known:</b> •Sleep disorders are frequently reported in infants with infantile hemangiomas treated with propranolol and often lead to treatment discontinuation. •	Investigations of the sleep pattern in this patient group using objective measures are lacking. <b>What is New:</b> •	The sleep pattern of propranolol-treated infants is assessed using actigraphy and a 24-h sleep diary and compared to healthy, untreated controls. •	Propranolol leads to a decreased sleep efficiency at night and an increased demand of daytime sleep, yet effects are mild overall.
Cardiovascular Progerin Suppression and Lamin A Restoration Rescue Hutchinson-Gilford Progeria Syndrome
Authors: Sánchez-López Amanda , Espinós-Estévez Carla , González-Gómez Cristina , Gonzalo Pilar , Andrés-Manzano María J. , Fanjul Víctor , Riquelme-Borja Raquel , Hamczyk Magda R. , Macías Álvaro , del Campo Lara , Camafeita Emilio , Vázquez Jesús , Barkaway Anna , Rolas Loïc , Nourshargh Sussan , Dorado Beatriz , Benedicto Ignacio , Andrés Vicente 
Published: October 2021

Background:
Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder characterized by premature aging and death mainly because of myocardial infarction, stroke, or heart failure. The disease is provoked by progerin, a variant of lamin A expressed in most differentiated cells. Patients look healthy at birth, and symptoms typically emerge in the first or second year of life. Assessing the reversibility of progerin-induced damage and the relative contribution of specific cell types is critical to determining the potential benefits of late treatment and to developing new therapies.

Methods:

We used CRISPR-Cas9 technology to generate
Lmna

HGPSrev/HGPSrev

(
HGPSrev
) mice engineered to ubiquitously express progerin while lacking lamin A and allowing progerin suppression and lamin A restoration in a time- and cell type–specific manner on Cre recombinase activation. We characterized the phenotype of
HGPSrev
mice and crossed them with Cre transgenic lines to assess the effects of suppressing progerin and restoring lamin A ubiquitously at different disease stages as well as specifically in vascular smooth muscle cells and cardiomyocytes.

Results:

Like patients with HGPS,
HGPSrev
mice appear healthy at birth and progressively develop HGPS symptoms, including failure to thrive, lipodystrophy, vascular smooth muscle cell loss, vascular fibrosis, electrocardiographic anomalies, and precocious death (median lifespan of 15 months versus 26 months in wild-type controls,
P
<0.0001). Ubiquitous progerin suppression and lamin A restoration significantly extended lifespan when induced in 6-month-old mildly symptomatic mice and even in severely ill animals aged 13 months, although the benefit was much more pronounced on early intervention (84.5% lifespan extension in mildly symptomatic mice,
P
<0.0001, and 6.7% in severely ill mice,
P
<0.01). It is remarkable that major vascular alterations were prevented and lifespan normalized in
HGPSrev
mice when progerin suppression and lamin A restoration were restricted to vascular smooth muscle cells and cardiomyocytes.

Conclusions:

HGPSrev
mice constitute a new experimental model for advancing knowledge of HGPS. Our findings suggest that it is never too late to treat HGPS, although benefit is much more pronounced when progerin is targeted in mice with mild symptoms. Despite the broad expression pattern of progerin and its deleterious effects in many organs, restricting its suppression to vascular smooth muscle cells and cardiomyocytes is sufficient to prevent vascular disease and normalize lifespan.
Using Well-Understood Single-Objective Functions in Multiobjective Black-Box Optimization Test Suites
Authors: Brockhoff Dimo , Auger Anne , Hansen Nikolaus , Tušar Tea 
Published: October 2021

Abstract
Several test function suites are being used for numerical benchmarking of multiobjective optimization algorithms. While they have some desirable properties, such as well-understood Pareto sets and Pareto fronts of various shapes, most of the currently used functions possess characteristics that are arguably underrepresented in real-world problems such as separability, optima located exactly at the boundary constraints, and the existence of variables that solely control the distance between a solution and the Pareto front. Via the alternative construction of combining existing single-objective problems from the literature, we describe the bbob-biobj test suite with 55 bi-objective functions in continuous domain, and its extended version with 92 bi-objective functions (bbob-biobj-ext). Both test suites have been implemented in the COCO platform for black-box optimization benchmarking and various visualizations of the test functions are shown to reveal their properties. Besides providing details on the construction of these problems and presenting their (known) properties, this article also aims at giving the rationale behind our approach in terms of groups of functions with similar properties, objective space normalization, and problem instances. The latter allows us to easily compare the performance of deterministic and stochastic solvers, which is an often overlooked issue in benchmarking.
Systemic lupus erythematosus and pregnancy: A retrospective single-center study of 215 pregnancies from Portugal
Authors: Braga António , Barros Tânia , Faria Raquel , Marinho António , Carvalheira Graziela , Rocha Guilherme , Farinha Fátima , Neves Esmeralda , Vasconcelos Carlos , Braga Jorge 
Published: October 2021

Objective Systemic lupus erythematosus (SLE) is a life-threatening disorder that affects women at reproductive age. We evaluate the clinical impact of pregnancy in a cohort of Portuguese SLE patients and the risk factors associated with maternal and fetal adverse outcomes. Methods A retrospective observational study that included all pregnant women with SLE managed at a Portuguese tertiary hospital, between January 1993 and December 2019. Baseline maternal information was collected, and maternal–fetal and neonatal outcomes were evaluated. Disease activity before and during pregnancy was assessed. Results We included 215 pregnancies from 143 patients. Lupus nephritis was present in 20.0% and antiphospholipid syndrome (APS) in 21.9% of the cases. Preconception consultation was performed in 86.9% of the pregnancies, and 92.5% of the patients had no or low disease activity at conception. During gestation, 79.6% of the patients were under treatment, and hydroxychloroquine (HCQ) was the most commonly used drug (63.7%). Low-dose acetylsalicylic acid (ASA) was prescribed at conception in 87.9% of the patients. The live birth rate was 84.2%. An adverse pregnancy outcome (APO) occurred in 41.4% of the pregnancies. A miscarriage rate of 15.3% and a preterm delivery rate of 15.4% were found. Preeclampsia and fetal growth restriction complicated 13.1% and 14.0% of the gestations, respectively. Neonatal lupus occurred in 7.1% of the newborns, and there were 2 cases of congenital heart block. Significant risk factors for the development of AOP were disease activity at conception, lupus flare, hypocomplementemia, positivity for lupus anticoagulant, and APS. The use of ASA was significantly associated with a reduced incidence of miscarriage. An SLE flare was diagnosed in 16.3% of the cases. We identified as risk factors for lupus flares the presence of active disease at conception, a previous history of lupus nephritis, and the use of chronic medication. HCQ use during pregnancy was associated with a significant reduction of flare incidence during pregnancy and postpartum. Conclusions Pregnancy in an SLE patient is associated with an increased incidence of adverse obstetric outcomes. Good disease control before pregnancy and adequate treatment, especially with HCQ, is crucial to achieving the best obstetric results.
Aneurysmal Bone Cysts of the Craniofacial Origin: A Systematic Review
Authors: Rehman Rafey , Dekhou Antonio , Osto Muhammad , Agemy Jacob , Chaaban Amneah , Yuhan Brian , Thorpe Eric 
Published: October 2021

ObjectiveAneurysmal bone cysts (ABCs) are blood‐filled, locally destructive, benign bone tumors. Our objective was to conduct a systematic review outlining patient demographics, clinical characteristics, management, and outcomes of those with ABCs of the craniofacial bones.Data SourcesUsing PubMed, Cochrane, and Embase databases, 116 studies were included.Review MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines, a systematic review was conducted. Data including patient demographics, clinical characteristics, treatment strategies, and patient outcomes were collected.ResultsA total of 127 patients from 116 studies were identified. Age ranged from 8 months to 90 years, with a mean age of 19.0 years. The most commonly affected craniofacial locations were the mandible (n = 31, 24.4%), temporal bone (n = 21, 16.5%), and occipital bone (n = 14, 11.0%). The most common presenting symptoms included a nontender mass (n = 51, 40.2%), a tender mass (n = 31, 24.4%), and generalized headache (n = 30, 23.6%). Imaging modalities included computed tomography (CT) and magnetic resonance imaging (MRI) (n = 77, 60.6%), CT alone (n = 31, 24.4%), and MRI alone (n = 8, 6.2%). All patients underwent surgical resection, with 1 patient requiring adjuvant radiation in addition to surgery. In total, 121 patients were disease‐free and symptom‐free without evidence of recurrence (17.4‐month mean follow‐up, 5.4 months average time to first recurrence).ConclusionThe current literature’s characterization of ABCs in craniofacial bones is limited to case reports and case series. Given the rarity of these tumors, head and neck surgeons may rely on systematic reviews such as the present analysis to guide management.
Cost‐effective Analysis of Subcutaneous vs Sublingual Immunotherapy From the Payor’s Perspective
Authors: Hardin Frances Mei , Eskander Peter N. , Franzese Christine 
Published: October 2021

ObjectiveCompare the cost‐effectiveness of subcutaneous immunotherapy (SCIT) and aqueous sublingual immunotherapy (SLIT) as treatment modalities for adult patients with allergic rhinitis and conjunctivitis who undergo testing and qualify for allergen immunotherapy (AIT).MethodsA systematic review was performed to identify key statistics for analysis, including the compliance and efficacy rates for each treatment. The body of literature on this topic is highly heterogeneous, so ranges were obtained and assumptions stated clearly where they were made. Charges were derived from average commercial payor charges from a single hospital institution. A hypothetical 100 patients are examined for the study.ResultsA cost‐effectiveness sensitivity analysis was then performed using a decision tree model to compare the modalities. A sensitivity and threshold analysis was then performed to assess the strength of recommendations after identifying results at baseline.DiscussionAssuming an 80% compliance rate with allergen immunotherapy and an estimated efficacy (assumed to be clinically significant improvement in symptoms) of 70% for SLIT and 80% for SCIT, at the 12‐month mark, the baseline total cost to the payor of SLIT per successful treatment outcome is $1196 while the charge of SCIT per successful treatment outcome is $2691. Our analysis favors SLIT as the more cost‐effective modality per successful outcome.Implications for PracticeWhen compared to SCIT, SLIT is economically favorable and should be considered the financially conscious option for patients with >40% adherence to therapy.
Global connectivity in genome-scale metabolic networks revealed by comprehensive FBA-based pathway analysis
Authors: Gao Yajie , Yuan Qianqian , Mao Zhitao , Liu Hao , Ma Hongwu 
Published: October 2021

Abstract
Background
Graph-based analysis (GBA) of genome-scale metabolic networks has revealed system-level structures such as the bow-tie connectivity that describes the overall mass flow in a network. However, many pathways obtained by GBA are biologically impossible, making it difficult to study how the global structures affect the biological functions of a network. New method that can calculate the biologically relevant pathways is desirable for structural analysis of metabolic networks.

Results
Here, we present a new method to determine the bow-tie connectivity structure by calculating possible pathways between any pairs of metabolites in the metabolic network using a flux balance analysis (FBA) approach to ensure that the obtained pathways are biologically relevant. We tested this method with 15 selected high-quality genome-scale metabolic models from BiGG database. The results confirmed the key roles of central metabolites in network connectivity, locating in the core part of the bow-tie structure, the giant strongly connected component (GSC). However, the sizes of GSCs revealed by GBA are significantly larger than those by FBA approach. A great number of metabolites in the GSC from GBA actually cannot be produced from or converted to other metabolites through a mass balanced pathway and thus should not be in GSC but in other subsets of the bow-tie structure. In contrast, the bow-tie structural classification of metabolites obtained by FBA is more biologically relevant and suitable for the study of the structure-function relationships of genome scale metabolic networks.

Conclusions
The FBA based pathway calculation improve the biologically relevant classification of metabolites in the bow-tie connectivity structure of the metabolic network, taking us one step further toward understanding how such system-level structures impact the biological functions of an organism.
Circulating adipsin is associated with asymptomatic carotid atherosclerosis in obese adults
Authors: Zhang Jinhua , Teng Fei , Pan Lingling , Guo Dan , Liu Jianfang , Li Kangli , Yuan Youwen , Li Wenyuan , Zhang Huijie 
Published: October 2021

Abstract
Background
Adipsin has been identified as a secreted adipokine that plays a critical pathogenic role in metabolic disorders. However, it is not clear regarding the association of circulating adipsin with cardiovascular disease (CVD). This study will explore the association between circulating adipsin and asymptomatic carotid atherosclerosis in Chinese obese adults.

Methods
A total of 483 obese adult subjects (aged 40 years or older) were enrolled in this study. Serum adipsin concentrations and carotid intima-media thickness (CIMT) were measured to determine these associations.

Results
Individuals with increased CIMT and asymptomatic carotid atherosclerosis had lower levels of circulating adipsin than controls (both p < 0.05). The prevalence of asymptomatic carotid atherosclerosis was significantly higher in subjects with lower levels of serum adipsin than those with higher values (42.5% vs. 36.7%, p < 0.05). Notably, subjects in the lowest quartile of serum adipsin were 1.94 times (p = 0.059) more likely to have increased CIMT and 2.91 times (p = 0.03) more likely to have asymptomatic carotid atherosclerosis than those in the highest quartile in multivariable logistic regression analyses, adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, and HOMA-IR. However, such associations with circulating adipsin were not noted for atherosclerotic plaque.

Conclusions
These findings suggest that circulating adipsin concentrations are a potential marker of risks of increased CIMT and asymptomatic carotid atherosclerosis in obese Chinese adults.
Methodological challenges and solution strategies during implementation of a midwife-led multicenter randomized controlled trial (RCT) in maternity hospitals
Authors: Striebich Sabine , Mattern Elke , Oganowski Theresa , Schäfers Rainhild , Ayerle Gertrud 
Published: October 2021

Abstract
Background
Randomized controlled trials (RCTs), especially multicentric, with complex interventions are methodically challenging. Careful planning under everyday conditions in compliance with the relevant international quality standard (Good Clinical Practice [GCP] guideline) is crucial. Specific challenges exist for RCTs conducted in delivery rooms due to various factors that cannot be planned beforehand. Few published RCTs report challenges and problems in implementing complex interventions in maternity wards. In Germany as well as in other countries, midwives and obstetricians have frequently little experience as investigators in clinical trials.

Methods
The aim is to describe the key methodological and organizational challenges in conducting a multicenter study in maternity wards and the solution strategies applied to them. In particular, project-related and process-oriented challenges for hospital staff are considered. The exemplarily presented randomized controlled trial “BE-UP” investigates the effectiveness of an alternative design of a birthing room on the rate of vaginal births and women-specific outcomes.

Results
The results are presented in five sectors:
1) Selection of and support for cooperating hospitals: they are to be selected according to predefined criteria, and strategies to offer continuous support in trial implementation must be mapped out.
2) Establishing a process of requesting informed consent: a quality-assured process to inform pregnant women early on must be feasible and effective.
3) Individual digital real-time randomization: In addition to instructing maternity teams, appropriate measures for technical failure must be provided.
4) The standardized birthing room: The complex intervention is to be implemented according to the study protocol yet adapted to the prevailing conditions in the delivery rooms.
5) GCP-compliant documentation: midwives and obstetricians will be instructed in high-quality data collection, supported by external monitoring throughout the trial.

Conclusion
Since not all potential challenges can be anticipated in the planning of a trial, study teams need to be flexible and react promptly to any problems that threaten recruitment or the implementation of the complex intervention. Thought should be given to the perspectives of midwives and obstetricians as recruiters and how clinic-intern processes could be adapted to correspond with the trial’s requirements.

Trial registration
The BE-UP study was registered on 07/03/ 2018 in the German Register for Clinical Trials under Reference No. DRKS00012854 and can also be found on the International Clinical Trials Registry Platform (ICTRP) (see https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS0001285).