bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hierarchical opportunistic screening model for osteoporosis using machine learning applied to clinical data and CT images
Authors: Liu Liyu , Si Meng , Ma Hecheng , Cong Menglin , Xu Quanzheng , Sun Qinghua , Wu Weiming , Wang Cong , Fagan Michael J. , Mur Luis A. J. , Yang Qing , Ji Bing 
Published: February 2022

Abstract
Background
Osteoporosis is a common metabolic skeletal disease and usually lacks obvious symptoms. Many individuals are not diagnosed until osteoporotic fractures occur. Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for osteoporosis detection. However, only a limited percentage of people with osteoporosis risks undergo the DXA test. As a result, it is vital to develop methods to identify individuals at-risk based on methods other than DXA.

Results
We proposed a hierarchical model with three layers to detect osteoporosis using clinical data (including demographic characteristics and routine laboratory tests data) and CT images covering lumbar vertebral bodies rather than DXA data via machine learning. 2210 individuals over age 40 were collected retrospectively, among which 246 individuals’ clinical data and CT images are both available. Irrelevant and redundant features were removed via statistical analysis. Consequently, 28 features, including 16 clinical data and 12 texture features demonstrated statistically significant differences (p < 0.05) between osteoporosis and normal groups. Six machine learning algorithms including logistic regression (LR), support vector machine with radial-basis function kernel, artificial neural network, random forests, eXtreme Gradient Boosting and Stacking that combined the above five classifiers were employed as classifiers to assess the performances of the model. Furthermore, to diminish the influence of data partitioning, the dataset was randomly split into training and test set with stratified sampling repeated five times. The results demonstrated that the hierarchical model based on LR showed better performances with an area under the receiver operating characteristic curve of 0.818, 0.838, and 0.962 for three layers, respectively in distinguishing individuals with osteoporosis and normal BMD.

Conclusions
The proposed model showed great potential in opportunistic screening for osteoporosis without additional expense. It is hoped that this model could serve to detect osteoporosis as early as possible and thereby prevent serious complications of osteoporosis, such as osteoporosis fractures.
Cellular diversity and gene expression profiles in the male and female brain of Aedes aegypti
Authors: Cui Yingjun , Behura Susanta K. , Franz Alexander W. E. 
Published: February 2022

Abstract
Background
Aedes aegypti is a medically-important mosquito vector that transmits arboviruses including yellow fever, dengue, chikungunya, and Zika viruses to humans. The mosquito exhibits typical sexually dimorphic behaviors such as courtship, mating, host seeking, bloodfeeding, and oviposition. All these behaviors are mainly regulated by the brain; however, little is known about the function and neuron composition of the mosquito brain. In this study, we generated an initial atlas of the adult male and female brain of Ae. aegypti using 10xGenomics based single-nucleus RNA sequencing.

Results
We identified 35 brain cell clusters in male and female brains, and 15 of those clusters were assigned to known cell types. Identified cell types include glia (astrocytes), Kenyon cells, (ventral) projection neurons, monoaminergic neurons, medulla neurons, and proximal medulla neurons. In addition, the cell type compositions of male and female brains were compared to each other showing that they were quantitatively distinct, as 17 out of 35 cell clusters varied significantly in their cell type proportions. Overall, the transcriptomes from each cell cluster looked very similar between the male and female brain as only up to 25 genes were differentially expressed in these clusters. The sex determination factor Nix was highly expressed in neurons and glia of the male brain, whereas doublesex (dsx) was expressed in all neuron and glia cell clusters of the male and female brain.

Conclusions
An initial cell atlas of the brain of the mosquito Ae. aegypti has been generated showing that the cellular compositions of the male and female brains of this hematophagous insect differ significantly from each other. Although some of the rare brain cell types have not been detected in our single biological replicate, this study provides an important basis for the further development of a complete brain cell atlas as well as a better understanding of the neurobiology of the brains of male and female mosquitoes and their sexually dimorphic behaviors.
Self-reported health and the well-being paradox among community-dwelling older adults: a cross-sectional study using baseline data from the Canadian Longitudinal Study on Aging (CLSA)
Authors: Whitmore Carly , Markle-Reid Maureen , McAiney Carrie , Ploeg Jenny , Griffith Lauren E. , Phillips Susan P. , Wister Andrew , Fisher Kathryn 
Published: February 2022

Abstract
Background
Self-reported health is a widely used epidemiologic measure, however, the factors that predict self-reported health among community-dwelling older adults (≥65 years), especially those with multimorbidity (≥2 chronic conditions), are poorly understood. Further, it is not known why some older adults self-report their health positively despite the presence of high levels of multimorbidity, a phenomenon known as the well-being paradox. The objectives of this study were to: 1) examine the factors that moderate or mediate the relationship between multimorbidity and self-reported health; 2) identify the factors that predict high self-reported health; and 3) determine whether these same factors predict high self-reported health among those with high levels of multimorbidity to better understand the well-being paradox.

Methods
A cross-sectional analysis of baseline data from the Canadian Longitudinal Study on Aging was completed (n = 21,503). Bivariate stratified analyses were used to explore whether each factor moderated or mediated the relationship between multimorbidity and self-reported health. Logistic regression was used to determine the factors that predict high self-reported health in the general population of community-dwelling older adults and those displaying the well-being paradox.

Results
None of the factors explored in this study moderated or mediated the relationship between multimorbidity and self-reported health, yet all were independently associated with self-reported health. The ‘top five’ factors predicting high self-reported health in the general older adult population were: lower level of multimorbidity (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.74-0.76), female sex (OR 0.62, CI 0.57-0.68), higher Life Space Index score (OR 1.01, CI 1.01-1.01), higher functional resilience (OR 1.16, CI 1.14-1.19), and higher psychological resilience (OR 1.26, CI 1.23-1.29). These same ‘top five’ factors predicted high self-reported health among the subset of this population with the well-being paradox.

Conclusions
The factors that predict high self-reported health in the general population of older adults are the same for the subset of this population with the well-being paradox. A number of these factors are potentially modifiable and can be the target of future interventions to improve the self-reported health of this population.
Simultaneous bilateral fallopian tubal pregnancy of a laparoscopic definite spontaneous unilateral ovulation: a case report
Authors: Wang Zhen-zhen , Xu Lian-wei , Zhao Li , Chen Yi-jia , Liu Hui-cong , Yu Er-kai 
Published: February 2022

Abstract
Background
Bilateral simultaneous fallopian tubal pregnancy is one of the rarest forms of ectopic pregnancy. Due to the lack of unique features and clinical presentation to distinguish bilateral from unilateral ectopic pregnancy, challenges the diagnosis.

Case report
A 27-year-old Asian woman presented with pelvic pain and vaginal bleeding. Pelvic transvaginal ultrasound showed fluid in Douglas Pouch and posterior fornix puncture revealed unclotted blood. Laparoscopic examination unveiled bilateral ectopic pregnancy with two corpus luteum visible in the right ovary, suggesting a double spontaneous unilateral ovulation. Bilateral fallopian tube fenestration and embryo extraction were performed to preserve fertility.

Conclusion
Diagnosis of bilateral tubal pregnancy is difficult during preoperative ultrasound examination and careful examination during laparoscopic inspection of the whole pelvic cavity to avoid missed diagnosis.
Genome-wide association study of serum tumor markers in Southern Chinese Han population
Authors: Li Xiukuan , Bai Fenghua , Wei Xingwei , Jin Tianbo , Li Chen , Zhang Yutian , Lin Mei , Zhou Xiaoli , Xie Yufei , He Chanyi , Lin Qi , He Ping , Chu Shuyuan , Ding Yipeng 
Published: February 2022

Abstract
Background
Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers.

Methods
We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci.

Results
The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037.

Conclusion
MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China.
Cannabidiol and refractory epilepsy: parental and caregiver perspectives of participation in a compassionate access scheme
Authors: Harte S. , Singh Y. , Malone S. , Heussler H. , Wallace G. 
Published: February 2022

Abstract
Background
The Compassionate Access Scheme (CAS) being delivered through the Queensland Children’s Hospital is designed to allow access to an investigational purified Cannabidiol oral solution to paediatric patients with severe refractory epilepsy. The objectives of this study were to conduct semi-structured interviews to:
1. Understand families’ expectations and attitudes about the use of an investigational cannabinoid product for their child’s seizures;
2. Understand families’ perceptions of Cannabidiol’s efficacy for their child’s seizures; and other aspects of their child’s behaviour, quality of life and/or cognition.

Methods
Children aged 2-18 years had been enrolled in, or were enrolled in a compassionate access scheme for Cannabidiol at the time of the study. Semi-structured interviews (n = 19) with parents or caregivers (n = 23) of children diagnosed with refractory epilepsy were voice-recorded, transcribed and analysed to generate common themes.

Results
Key themes emerged relating to seizure activity, family and school engagement, drug safety and legal access, efficacy, clinical support, social acceptance of the medication and program delivery. The use of Cannabidiol was perceived to have benefits in relation to reducing the severity and frequency of seizure activity for almost a third of patients experiencing refractory epilepsy. Participants described other benefits including improved social engagement, wakefulness and a reduction of side effects related to a reduction of conventional medication dosage.

Conclusion
This study provided unique perspectives of families’ experiences managing untreatable epilepsy, their experiences with conventional and experimental pharmacological treatments and health services. Whilst families’ perceptions showed the use of Cannabidiol did not provide a therapeutic reduction in the seizure activity for all patients diagnosed with refractory epilepsy, it’s use as an additional pharmacological agent was perceived to provide other benefits by some patient families.
Evaluation and optimisation of a footwear assessment tool for use within a clinical environment
Authors: Ellis Stephen , Branthwaite Helen , Chockalingam Nachiappan 
Published: February 2022

AbstractFootwear has been documented as a significant factor in the aetiology of foot pain in the general population. Assessing footwear in a clinical setting continues to be practitioner specific and there is limited guidance to direct advice. Health professionals must have access to clinically appropriate and reliable footwear assessment tools to educate patients on healthier footwear choices. The primary aim of this study was to critique what elements should be in a footwear assessment tool with a secondary aim of testing the agreed tool for validity.A combined Nominal Group Technique and then a Delphi technique from purposively sampled experts of foot health professions were employed to critique elements of footwear assessment. The agreed tool was then tested by practising podiatrists on 5 different shoes to assess the validity and reliability of the measures.Twelve test evaluation criteria were identified receiving significant ratings to form the final footwear assessment tool consisting of five footwear themes. Application of the tool in a clinical setting validated the themes of footwear characteristics, footwear structure, motion control and wear patterns. However, the assessment of footwear fit was not reliable.The footwear tool was refined based on the collective consensus achieved from the rounds creating a more clinically appropriate tool. The validity of this tool was assessed as high in some of the themes but for those that were lower, a training need was identified.
Effectiveness of wearable devices as a support strategy for maintaining physical activity after a structured exercise intervention for employees with metabolic syndrome: a randomized controlled trial
Authors: Bayerle Pauline , Kerling Arno , Kück Momme , Rolff Simone , Boeck Hedwig Theda , Sundermeier Thorben , Ensslen Ralf , Tegtbur Uwe , Lauenstein Dirk , Böthig Dietmar , Bara Christoph , Hanke Alexander , Terkamp Christoph , Haverich Axel , Stiesch Meike , de Zwaan Martina , Haufe Sven , Nachbar Lars 
Published: February 2022

AbstractBackgroundMetabolic syndrome (MetS) is associated with an increased risk for cardiovascular events and high socioeconomic costs. Despite lifestyle interventions focusing on exercise are effective strategies to improve parameters of the above aspects, many programs fail to show sustained effects in the long-term.MethodsAt visit 2 (V2) 129 company employees with diagnosed MetS, who previously participated in a 6-month telemonitoring-supported exercise intervention, were randomized into three subgroups for a 6-month maintenance treatment phase. A wearable activity device was provided to subgroup A and B to assess and to track physical activity. Further subgroup A attended personal consultations with individual instructions for exercise activities. Subgroup C received neither technical nor personal support. 6 months later at visit (V3), changes in exercise capacity, MetS severity, work ability, health-related quality of life and anxiety and depression were compared between the subgroups with an analysis of variance with repeated measurements.ResultsThe total physical activity (in MET*h/week) declined between visit 2 and visit 3 (subgroup A: V2: 48.0 ± 33.6, V3: 37.1 ± 23.0; subgroup B: V2: 52.6 ± 35.7, V3: 43.8 ± 40.7, subgroup C: V2: 51.5 ± 29.7, V3: 36.9 ± 22.8, for all p = 0.00) with no between-subgroup differences over time (p = 0.68). In all three subgroups the initial improvements in relative exercise capacity and MetS severity were maintained. Work ability declined significantly in subgroup C (V2: 40.3 ± 5.0, V3: 39.1 ± 5.7; p < 0.05), but remained stable in the other subgroups with no between-subgroup differences over time (p = 0.38). Health-related quality of life and anxiety and depression severity also showed no significant differences over time.ConclusionsDespite the maintenance of physical activity could not be achieved, most of the health related outcomes remained stable and above baseline value, with no difference regarding the support strategy during the maintenance treatment phase.Trial registrationThe study was completed as a cooperation project between the Volkswagen AG and the Hannover Medical School (ClinicalTrials.gov Identifier: NCT02029131).
Spontaneous tumor lysis syndrome in adrenal adenocarcinoma: a case report and review of the literature
Authors: Shafie Mahan , Teymouri Alireza , Parsa Samaneh , Sadeghian Ali , Zarei Jalalabadi Narjes 
Published: February 2022

Abstract
Background
Tumor lysis syndrome is an oncologic emergency that classically occurs following cancer therapy, although spontaneous tumor lysis syndrome can also occur in malignancies, albeit rarely. Spontaneous tumor lysis syndrome has previously been reported in some hematologic malignancies, but it rarely happens in solid tumors and seems to be associated with a higher mortality rate. This is the first case of adrenal adenocarcinoma that developed spontaneous tumor lysis syndrome.

Case presentation
We present a rare case of spontaneous tumor lysis syndrome occurring in a patient previously diagnosed with adrenal adenocarcinoma. The patient was a 64-year-old Persian man with abdominal pain, hypersomnia, and fatigue who was previously diagnosed with right adrenocortical carcinoma and had undergone right adrenalectomy with regional lymph nodes resection 5 months previously. On physical examination, the patient had abdominal distension and mild tenderness at the right upper quadrant. Pitting edema was detected bilaterally in the lower extremities. Initial imaging revealed multiple and large lesions suggestive of liver metastases. The laboratory data showed hyperkalemia, hyperuricemia, hyperphosphatemia, and elevated serum creatinine level indicative of spontaneous tumor lysis syndrome in the patient. Despite immediate and intensive care with antibiotics, hydration, treatment with a hypouricemic agent, and renal replacement therapy, the patient ultimately died from multiorgan failure.

Conclusions
Tumor lysis syndrome in solid tumors has high mortality. Patients susceptible to spontaneous tumor lysis syndrome must receive aggressive treatment immediately, which is crucial for preventing morbidity and mortality. Spontaneous tumor lysis syndrome may be underdiagnosed, and a high degree of clinical suspicion is needed to make the diagnosis and proceed with required interventions. Therefore, clinicians should be aware of this rare phenomenon.
Anti-acne effects of Castanea crenata bur extract and identification of active compound
Authors: You Jiyoung , Ji Hyanggi , Roh Kyung-Baeg , Cho Eunae , Chajra Hanane , Frechet Mathilde , Park Deokhoon , Jung Eunsun 
Published: February 2022

AbstractAcne vulgaris is a common disease of the pilosebaceous unit. Hyperseborrhea, a follicular colonization by Cutibacterium acnes and a complex inflammatory state are pathogenic factors of acne vulgaris. In the present study we investigated the anti-acne efficacy of Castanea crenata bur extract (CBE) in vitro and searched active compound for mitigating hyperseborrhea. In sebocytes, CBE inhibited the sebum synthesis through downregulation of sterol response element-binding protein-1 and peroxisome proliferator-activated receptor γ expression. CBE also inhibited the 5-alpha reductase activity which is associated with androgen-induced sebum production. Moreover, CBE showed anti-inflammatory effect in C. acnes and free fatty acid-induced inflammatory condition through suppressing Toll-like receptor 2 activity. Anti-inflammatory effect was also observed in keratinocytes via inhibition of NF-κB translocation into nuclei. Finally, we identified the ellagic acid as an active compound for inhibiting sebum production in CBE. These findings suggest that CBE have potential to be a multi-target agent for acne vulgaris and a good source of ellagic acid as an anti-sebum compound.
Population pharmacokinetic analysis and dosage recommendations for digoxin in Japanese patients with atrial fibrillation and heart failure using real-world data
Authors: Hirai Toshinori , Kasai Hidefumi , Naganuma Miyoko , Hagiwara Nobuhisa , Shiga Tsuyoshi 
Published: February 2022

Abstract
Background
Digoxin is an important treatment option for reducing the ventricular rate in patients with atrial fibrillation (AF) and heart failure (HF). Digoxin has a narrow therapeutic window and large interindividual variability. A low target blood concentration, especially ≤0.9 ng/mL, is recommended for patients with HF who are taking digoxin. This study aimed to develop a population pharmacokinetic model and to identify clinical factors that affect digoxin exposure and an optimal digoxin dosing regimen in Japanese patients with AF and HF.

Methods
A population pharmacokinetic analysis was performed by using a nonlinear mixed effects model based on 3465 concentration points from 391 patients (>18 years) who were receiving oral digoxin. Using trough serum digoxin concentrations and clinical data, a population pharmacokinetic model was developed for determining covariates of clearance. A 1-compartment model was used to examine the interindividual variability of the oral clearance (CL/F) of digoxin. An appropriate dosage of digoxin was identified using Monte Carlo simulation.

Results
The final model demonstrated that creatinine clearance (CLCR) and the use of amiodarone were factors that contributed to the CL/F of digoxin. Monte Carlo simulation results showed that with a daily maintenance dose of 0.25 mg, the intoxication risk window of a trough serum concentration of ≥0.9 ng/mL could be reached in more than half of patients regardless of renal function category or concurrent use of amiodarone. The appropriate maintenance dosage was 0.125 mg daily for most Japanese patients with AF and HF. However, with a daily dose of 0.125 mg, a trough serum concentration of ≥0.9 ng/mL could be reached in more than half of patients with renal impairments (CLCR 30 mL/min) or concurrent use of amiodarone. A daily maintenance dose of 0.0625 mg was acceptable for these patients.

Conclusions
CLCR and the use of amiodaron were found to contribute to digoxin clearance using a population pharmacokinetic methodology. For Japanese patients with AF and HF, 0.125 mg is an appropriate daily digoxin maintenance dose, but a dose reduction is required for patients with CLCR <30 mL/min or concurrent amiodarone use.