bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Ozone Exposures with the risk of thyroid nodules in Hunan Province: a population-based cohort study
Authors: He Qiao , Wu Min , Shi Qiman , Tan Hailong , Wei Bo , Tang Neng , Chen Jianjun , Liu Mian , Duan Saili , Chang Shi , Huang Peng 
Published: July 2022

Abstract
Background
Increasing evidence associates air pollution with thyroid dysfunction, whereas the potential relationship between exposure to ozone (O3) and Thyroid Nodules (TNs) is unclear.

Methods
This retrospective cohort study investigated the association between O3 exposure and TNs in Hunan province, enrolling 191,357 Chinese adults who lived in Hunan province from January 2009 to December 2019 and received voluntary medical examinations. Individual exposure levels to O3 from 2010 to 2019 were measured on account of participants’ residential addresses at the district level. Associations of O3 exposure with the risk of incidental TNs were assessed by restricted cubic splines and surveyed as odds ratios after adjusting for demographic factors.

Results
In total, 81,900 adults were newly diagnosed with TNs during the study period. Age-standardized TNs detection rate in Hunan province increased from 25.9 to 46.3% between 2010 and 2019, with the greatest annual percent change being 8.1 [95% CI, 7.3–8.8]. A similar trend has been found in all tumor sizes, ages, and both sexes. O3 exposure presented a statistically significant dose-dependent positive correlation (greater than 0.036 ppm) with TNs. Similarly, long-term exposure to high levels of O3 (1-year average O3 concentrations exceeding 0.0417 ppm) was found positively associated with increased TSH levels.

Conclusions
High-level O3 exposure in the long term was associated with an increase in TSH. Consequently, increased TSH was related to the increased risk of TNs. Being exposed to high-level O3 in the long term was related to the increased detection rates of TNs in Hunan province, which could be mediated by TSH.
Can prenatal diagnosis of parachute mitral valve be achieved? A case report of fetal parachute mitral valve
Authors: Dai Xiaohui , Chen Jiao , Liu Hanmin , Wu Lin , Zhao Fumin 
Published: July 2022

AbstractParachute mitral valve (PMV) is a common form of congenital mitral stenosis and is difficult to diagnose prenatally. This report describes a fetal case of PMV with coarctation of the aorta that was diagnosed at 25 weeks’ gestation by echocardiography and confirmed at autopsy. We describe the ultrasonographic features in this case and present a useful sign for making a prenatal diagnosis of PMV.
How successful was the use of a community of practice for the implementation of evidence-based practices for heart failure within the United States Department of Veterans Affairs: Insights from a formative evaluation
Authors: Sahay Anju , Mittman Brian S. , Gholami Parisa , Lin Shoutzu , Heidenreich Paul A. 
Published: July 2022

Abstract
Background
Communities of Practice (CoPs) are a promising approach to facilitate the implementation of evidence-based practices (EBPs) to improve care for chronic conditions like heart failure (HF). CoPs involve a complex process of acquiring and converting both explicit and tacit knowledge into clinical activities. This study describes the conceptualization, creation, capacity-building and dissemination of a CoP sustained over 9 years, and evaluates its value and impact on EBP.

Methods
In July 2006, a CoP called the Heart Failure Provider Network (HF Network) was established within the United States Department of Veterans Affairs (VA) with the overarching goal of improving the quality of care for HF patients. We assessed (formative) the HF Network in terms of its various activities (inputs) and proximal impacts (mediators) at the individual level, and its distal impacts (outcomes) at the site level including implementation of new/improved EBPs at the systemwide level.

Results
The HF Network membership grew steadily over the 9 years. The CoP has involved a total of 1341 multidisciplinary and multilevel members at all 144 VA Health Care Systems (sites). Most members were practising clinicians (n = 891, 66.4%), followed by administrators (n = 342, 25.5%), researchers (n = 70, 5.2%) and others (n = 38, 2.8%). Participation was assessed to be “active” for 70.6% versus “passive” for 29.4% of members. The distribution of active members (clinicians 64.7%, administrators 21.6%) was similar to the distribution of overall membership.

Conclusions
Survey respondents perceived the HF Network as useful in terms of its varied activities and resources relevant for patient care. Strong evidence shows that these members, particularly those who considered themselves influential in improving quality of care, noted multiple benefits of membership, which included confirmation of their own clinical practices, evidence-based changes to their practice and help in understanding facilitators and barriers in setting up or running HF clinics and other programmes. Such CoPs have strong impacts on the quality of care being delivered for both mandated and non-mandated initiatives.
Determinants of pre-eclampsia among women attending delivery services in public health institutions of Debre Tabor Town: a case–control study
Authors: Ayele Alemu Degu , Tilahun Zemenu Alemu 
Published: July 2022

Abstract
Background
The burden of pre-eclampsia has been continued as a public health importance in both developed and developing countries. However, the consequence of the disease is significantly high in developing countries, where treatment may be unsuccessful due to unclear etiology and late presentation of cases. The determinants of pre-eclampsia are not well known in the Ethiopian population specifically in the study area. Therefore, this study was aimed to identify the determinant factors of pre-eclampsia among women attending delivery services in public health institutions of Debre Tabor Town.

Methods
Unmatched case–control study was conducted from December 1, 2020, to January 15, 2021, among 264 mothers (88 cases and 176 controls). A case–control incidence density sampling technique was applied and data were collected using an interviewer-administered pre-tested questionnaire. Data were entered using Epi-data version 4.2 and analyzed by statistical package for social science (SPSS) version 23. Bivariate and multivariable logistic regression analyses were conducted. Finally, a significant association was declared at a p-value of ≤ 0.05 with 95% CI.

Results
Young age at menarche (10–15 years) (AOR: 7.69; 95% CI: 3.10–25.29), status of the current pregnancy (AOR: 5.88; 95% CI:2.93–22.42), new partner (AOR: 4.16; 95% CI: 3.49–17.03), family history of pre-eclampsia (AOR: 1.52; 95% CI: 1.40–4.18), and alcohol drinking (AOR: 2.18; 95% CI: 2.04–11.79) were found to be significantly associated with pre-eclampsia.

Conclusions
The current study identified that young age at menarche, the status of current pregnancy, new partner, family history of pre-eclampsia, and alcohol drinking were some of the determinant factors of pre-eclampsia. We suggested that health care providers should use these identified factors as a screening means for prediction, early diagnoses, and timely interventions of pre-eclampsia. Health care professionals should also deliver information regarding the risk of alcohol drinking during pregnancy in the preconception period and at early antenatal care services.
Development of a multi-route physiologically based pharmacokinetic (PBPK) model for nanomaterials: a comparison between a traditional versus a new route-specific approach using gold nanoparticles in rats
Authors: Chou Wei-Chun , Cheng Yi-Hsien , Riviere Jim E. , Monteiro-Riviere Nancy A. , Kreyling Wolfgang G. , Lin Zhoumeng 
Published: July 2022

AbstractBackgroundPhysiologically based pharmacokinetic (PBPK) modeling is an important tool in predicting target organ dosimetry and risk assessment of nanoparticles (NPs). The methodology of building a multi-route PBPK model for NPs has not been established, nor systematically evaluated. In this study, we hypothesized that the traditional route-to-route extrapolation approach of PBPK modeling that is typically used for small molecules may not be appropriate for NPs. To test this hypothesis, the objective of this study was to develop a multi-route PBPK model for different sizes (1.4–200 nm) of gold nanoparticles (AuNPs) in adult rats following different routes of administration (i.e., intravenous (IV), oral gavage, intratracheal instillation, and endotracheal inhalation) using two approaches: a traditional route-to-route extrapolation approach for small molecules and a new approach that is based on route-specific data that we propose to be applied generally to NPs.ResultsWe found that the PBPK model using this new approach had superior performance than the traditional approach. The final PBPK model was optimized rigorously using a Bayesian hierarchical approach with Markov chain Monte Carlo simulations, and then converted to a web-based interface using R Shiny. In addition, quantitative structure–activity relationships (QSAR) based multivariate linear regressions were established to predict the route-specific key biodistribution parameters (e.g., maximum uptake rate) based on the physicochemical properties of AuNPs (e.g., size, surface area, dose, Zeta potential, and NP numbers). These results showed the size and surface area of AuNPs were the main determinants for endocytic/phagocytic uptake rates regardless of the route of administration, while Zeta potential was an important parameter for the estimation of the exocytic release rates following IV administration.ConclusionsThis study suggests that traditional route-to-route extrapolation approaches for PBPK modeling of small molecules are not applicable to NPs. Therefore, multi-route PBPK models for NPs should be developed using route-specific data. This novel PBPK-based web interface serves as a foundation for extrapolating to other NPs and to humans to facilitate biodistribution estimation, safety, and risk assessment of NPs.
Acute mitral valve regurgitation secondary to papillary muscle rupture due to infective endocarditis
Authors: Amirkhosravi Farshad , Al Abri Qasim , Lu Alexander J. , El Nihum Lamees I. , Eng Renee K. , von Ballmoos Moritz C. Wyler , Ramchandani Mahesh K. 
Published: July 2022

Abstract
Background
Papillary muscle rupture due to infective endocarditis is a rare event and proper management of this condition has not been described in the literature. Our case aims to shed light on treatment strategies for these patients using the current guidelines.

Case presentation
This case presents a 58-year-old male with acute heart failure secondary to papillary muscle rupture. He underwent an en bloc resection of his mitral valve with a bioprosthetic valve replacement. Specimen pathology later showed necrotic papillary muscle due to infective endocarditis. The patient was further treated with antibiotic therapy. He recovered well post-operatively and continued to do well after discharge.

Conclusion
In patients who present with papillary muscle rupture secondary to infective endocarditis, clinical symptoms should drive the treatment strategy. Despite the etiology, early mitral valve surgery remains treatment of choice for patients who have papillary muscle rupture leading to acute heart failure. Culture-guided prolonged antibiotic treatment is vital in this category of patients, especially those who have a prosthetic valve implanted.
The long-term effect of mTOR inhibition on lipid and glucose metabolism in tuberous sclerosis complex: data from the Dutch TSC registry
Authors: Mulder Femke V. M. , Peeters Evelien F. H. I. , Westerink Jan , Zwartkruis Fried J. T. , de Ranitz-Greven Wendela L. 
Published: July 2022

Abstract
Background
MTOR inhibition is an effective treatment for many manifestations of tuberous sclerosis complex. Because mTOR inhibition is a disease modifying therapy, lifelong use will most likely be necessary. This study addresses the long-term effects of mTOR inhibitors on lipid and glucose metabolism and aims to provide better insight in the incidence and time course of these metabolic adverse effects in treated TSC patients.

Methods
All patients who gave informed consent for the nationwide TSC Registry and were ever treated with mTOR inhibitors (sirolimus and/or everolimus) were included. Lipid profiles, HbA1c and medication were analysed in all patients before and during mTOR inhibitor treatment.

Results
We included 141 patients, the median age was 36 years, median use of mTOR inhibitors 5.1 years (aimed serum levels 3.0–5.0 µg/l). Total cholesterol, LDL- and HDL-cholesterol levels at baseline were similar to healthy reference data. After start of mTOR inhibition therapy, total cholesterol, LDL-cholesterol and triglycerides increased significantly and were higher compared to healthy reference population. Mean total cholesterol levels increased by 1.0 mmol/L after 3–6 months of mTOR inhibition therapy but did not increase further during follow-up. In this study, 2.5% (3/118) of patients developed diabetes (defined as an HbA1c ≥ 48 mmol/mol) during a median follow-up of 5 years.

Conclusions
Hypercholesterolemia is a frequent side effect of mTOR inhibition in TSC patients, and predominantly occurs within the first year of treatment. Although hyperglycemia is a frequent side effect in other indications for mTOR inhibition, incidence of diabetes mellitus in TSC patients was only 2.5%. This may reflect the difference of mTOR inhibition in patients with normal mTOR complex pathway function versus patients with overactive mTOR complex signaling due to a genetic defect (TSC patients).
Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants
Authors: Wang Wenli , Lu Fengying , Zhang Bin , Zhou Qin , Chen Yingping , Yu Bin 
Published: July 2022

AbstractObjectiveThis study explores and discusses the possible factors affecting the positive predictive value (PPV) of non-invasive prenatal screening (NIPS) for the detection of fetal copy number variants (CNVs) in pregnant women.MethodsNIPS was performed for 50,972 pregnant women and 212 cases were suspected as fetal CNVs. Post additional genetic counseling for these women, 96 underwent invasive prenatal diagnosis (amniocentesis), following which they received chromosomal microarray analysis (CMA). We analyzed the PPV of NIPS for the detection of fetal CNVs and the possible interference factors that could affect the PPV.ResultsAmong the 96 pregnant women that received prenatal diagnosis by CMA, 37 cases were confirmed to be true positive for fetal CNVs with a PPV of 38.5%. There was no significant difference between the women with different NIPS indications. Five cases were reported as the false positive and false negative of fetal CNVs and the differences were mainly reflected in the inconsistency of chromosome fragments. Depending on the sizes of the CNVs, the PPVs were 48.7% for CNVs < 3 Mb, 41.4% for CNVs falling within 3 ~ 5 Mb, 42.9% for the CNVs falling within 5 ~ 10 Mb, and 14.3% for CNVs > 10 Mb. Based on the chromosomal locations of CNVs, the PPV(4.8%) of the chromosomes of group C(including chromosomes 6 ~ 12), was lower than that of the other groups (41.2% ~ 66.7%) (p = 0.021). However, there were no significant differences in the CNV characteristics, fetal fractions, unique reads, and the Z-scores between these groups.ConclusionNIPS with a low-coverage sequencing depth has a certain effect on detection of fetal CNVs with the PPV of 38.5%. Chromosomal locations of CNVs may be the main factor that influences its effect. This study can contribute to an increased accuracy in genetic counseling and in predicting NIPS results that are positive for fetal CNVs.
Effects of a smartphone app-augmented treatment for children with oppositional defiant disorder / conduct disorder and peer-related aggressive behavior – a pilot study
Authors: Görtz-Dorten Anja , Frank Marlin , Fessel Anja , Hofmann Leonie , Döpfner Manfred 
Published: July 2022

Abstract
Background
Social competence training interventions, especially child-focused ones, have proven to be effective in the treatment of children with conduct disorder. Therapy homework assignments implemented between the therapy sessions are essential for practicing strategies developed during treatment sessions and transferring them to everyday life. However, clinical experience shows that patients’ adherence regarding these assignments is often low, thus diminishing the treatment success. One obstacle in this regard is a lack of motivation. The use of smartphone apps in the context of child and adolescent psychotherapy is relatively new, and may provide novel ways to improve the transfer of coping strategies to daily life between treatment sessions. However, only a small number of high-quality studies have analyzed the systematic use of smartphone apps in therapy. The present study will therefore evaluate patients’ homework assignment adherence when using a smartphone app as compared to a paper-and-pencil method.

Method
The study will be conducted as a randomized controlled trial to evaluate the impact of a smartphone app on the adherence to therapy homework assignments (n = 35) in the treatment of children with aggressive behavior aged 6–12 years compared to paper-and-pencil homework assignments (n = 35).

Discussion
This trial is intended as a pilot study and aims to provide a basis for a subsequent multicenter trial. However, the results may already lead to recommendations for the development and use of mental health-related smartphone apps for children and adolescents with aggressive behavior problems.

Trial registration
Trial registration AUTHARK: German Clinical Trials Register (DRKS) DRKS00015625. Registered on 15th October 2019.
Topical sirolimus solution for lingual microcystic lymphatic malformations in children and adults (TOPGUN): study protocol for a multicenter, randomized, assessor-blinded, controlled, stepped-wedge clinical trial
Authors: Marchand A. , Caille A. , Gissot V. , Giraudeau B. , Lengelle C. , Bourgoin H. , Largeau B. , Leducq S. , Maruani A. 
Published: July 2022

Abstract
Background
Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations presenting as clusters of cysts filled with lymph fluid or blood. Even small well-limited lesions can be responsible for a heavy burden, inducing pain, aesthetic prejudice, or oozing, bleeding, infections. The natural history of LMLMs is progressive worsening punctuated by acute flares. Therapeutic options include surgery, laser excision, and radiofrequency ablation but all are potentially detrimental and expose to local relapse. Therefore, the management frequently relies on a “watchful waiting” approach. In complicated LMLMs, treatment with oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is often used. Topical applications of sirolimus on the buccal mucosae have been reported in other oral diseases with good tolerance and none to slight detectable blood sirolimus concentrations. We aim to evaluate the efficacy and safety of a 1 mg/mL sirolimus solution applied once daily on LMLM of any stage in children and adults after 4, 8, 12, 16, 20, and 24 weeks of treatment compared to usual care (no treatment).

Methods
This is a randomized, multicentric study using an individually randomized stepped-wedge design over 24 weeks to evaluate topical application of a 1 mg/mL sirolimus solution once daily, on LMLM, versus usual care (no treatment), the control condition. Participants begin with an observational period and later switch to the intervention at a randomized time (week 0, 4, 8, or 12). Visits occur every 4 weeks, either in the study center or by teleconsulting. The primary outcome will be the evaluation of global severity of the LMLM on monthly standardized photographs by 3 independent blinded experts using the physical global assessment (PGA) 0 to 5 scale. Secondary outcomes will include lesion size measurement and quality of life assessment, investigator, and patient-assessed global disease and specific symptoms (oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain, and global discomfort) assessment. A biological monitoring will be performed including residual blood sirolimus concentration and usual laboratory parameters.

Discussion
Given the disappointing state of current treatment options in LMLMs, topical sirolimus could become firstline therapy in treating LMLMs if its efficacy and safety were to be demonstrated.

Trial registration
ClinicalTrials.gov NCT04128722. Registered on 24 September 2019.
EudraCT: EUCTR2019-001530-33-FR
Sponsor (University Hospital Center of Tours – CHRU Tours): DR190041-TOPGUN
French regulatory authorities: ID RCB: 2019-001530-33
A randomized, parallel control and multicenter clinical trial of evidence-based traditional Chinese medicine massage treatment VS External Diclofenac Diethylamine Emulgel for the treatment of knee osteoarthritis
Authors: Wen-yue Wang , Ying-peng Xu , Quan-mao Ding , Li-min Xie , De-zhi Wang , Yang Bai , Li-su Wang , Yu-bin Li , Zhi-jun Niu , Yan-xu Ma , Wu-zhong Chen , Li-qun Bai , Yang Liu , Li-kun Jin 
Published: July 2022

Abstract
Background
Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel.

Methods and design
A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3–4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session.

Discussion
This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial.

Trial registration
Chinese Clinical Trial Registry ChiCTR1800014400. Registered on 10 January 2018