bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of cachexia on bone turnover in cancer patients: a case-control study
Authors: Zwickl Hannes , Zwickl-Traxler Elisabeth , Haushofer Alexander , Seier Josef , Podar Klaus , Weber Michael , Hackner Klaus , Jacobi Nico , Pecherstorfer Martin , Vallet Sonia 
Published: June 2021

Abstract
Background
Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients.

Methods
In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio.

Results
Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 μg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis.

Conclusions
CTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer.
Identification of a novel heterozygous SPTB mutation by whole genome sequencing in a Chinese patient with hereditary spherocytosis and atrial septal defect: a case report
Authors: Du Zhanhui , Luo Gang , Wang Kuiliang , Bing Zhen , Pan Silin 
Published: June 2021

Abstract
Background
Hereditary spherocytosis (HS) is a common inherited red blood cell membrane disorder characterized by an abnormal increase of spherocytes in peripheral blood. SPTB gene mutation is one of the most common causes of HS; however, few cases of HS resulting from SPTB mutation in the Chinese population have been reported so far.

Case presentation
A 3-year-old Chinese girl presented to Qingdao Women and Children’s Hospital, Qingdao University, with atrial septal defect (ASD). Meanwhile, she was clinically diagnosed with HS. Whole genome sequencing (WGS) was performed for the proband and her parents for genetic molecular analysis. A novel SPTB mutation (c.1756delG) was detected by WGS and confirmed by Sanger sequencing in the proband. This mutation results in a frameshift with a premature termination codon in exon 12, leading to a nonsense mutation (p.Ala586Profs*7). Her parents had no similar symptoms, and blood routine and serum biochemical tests showed no significant abnormalities. The patient’s mother did not know of any relatives with HS-like symptoms. Percutaneous transcatheter closure was successfully performed for treating the ASD.

Conclusion
In this study, we identified a novel SPTB frameshift mutation in a Chinese girl with HS. This finding would expand the spectrum of SPTB mutations, provide a valuable insight into the genotyping of HS in the Chinese population, and contribute to the clinical management and genetic counseling in HS.
Assessing the perceived changes in neighborhood physical and social environments and how they are associated with Chinese internal migrants’ mental health
Authors: Yang Min , Hagenauer Julian , Dijst Martin , Helbich Marco 
Published: June 2021

Abstract
Background
Migrants experience substantial changes in their neighborhood physical and social environments along their migration journeys, but little is known about how perceived changes in their neighborhood environment pre- and post-migration correlate with their mental health. Our aim was to examine the associations between recalled changes in the perceived neighborhood physical and social environments and migrants’ mental health in the host city.

Methods
We used cross-sectional data on 591 migrants in Shenzhen, China. We assessed their risk of mental illness using the General Health Questionnaire (GHQ). Neighborhood perceptions were collected retrospectively pre- and post-migration. We used random forests to analyze possibly non-linear associations between GHQ scores and changes in the neighborhood environment, variable importance, and for exploratory analysis of variable interactions.

Results
Perceived changes in neighborhood aesthetics, safety, and green space were non-linearly associated with migrants’ mental health: A decline in these characteristics was associated with poor mental health, while improvements in them were unrelated to mental health benefits. Variable importance showed that change in safety was the most influential neighborhood characteristic, although individual-level characteristics—such as self-reported physical health, personal income, and hukou (i.e., the Chinese household registration system)—appeared to be more important to explain GHQ scores and also strongly interacted with other variables. For physical health, we found different associations between changes in the neighborhood provoked by migration and mental health.

Conclusion
Our findings suggest that perceived degradations in the physical environment are related to poorer post-migration mental health. In addition, it seems that perceived changes in the neighborhood environment play a minor role compared to individual-level characteristics, in particular migrants’ physical health condition. Replication of our findings in longitudinal settings is needed to exclude reverse causality.
Clinical research: low-level laser therapy in accelerating orthodontic tooth movement
Authors: Zheng Junyi , Yang Kai 
Published: June 2021

Abstract
Background
The present study aimed to investigate the effects of low-level laser therapy (LLLT) on orthodontic tooth movement and its correlation with the levels of interleukin-1β (IL-1β), receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in gingival crevicular fluid (GCF).

Methods
This split-mouth design study included 12 patients scheduled for the extraction of both upper first premolars. Patients were randomly selected for experimental group that received left- or right-side radiation with a diode laser (810 nm wavelength, 100 mW power output, 6.29 J/cm2 energy density). Laser treatment was applied on days 0, 7, 14, and 21, after loading the canine retraction forces. GCF concentrations of IL-1β, RANKL, and OPG were analyzed. The upper arch of each patient was scanned with an intraoral scanner to assess tooth movement.

Results
The cumulative tooth movement over 28 days was significantly higher in the laser group than in the control group. We observed significant reductions in OPG levels and increases in IL-1β and RANKL levels in GCF samples on the experimental sides.

Conclusion
With the parameter settings used in this study, LLLT could, to some extent, lead to changes in bone metabolism, which could accelerate orthodontic tooth movement.
Trial registration: Chinese Clinical Trial Registry, ChiCTR2000039594. Registered 2 November 2020—Retrospectively registered, www.chictr.org.cn/edit.aspx?pid=62465&htm=4.
Self-referral and associated factors among patients attending adult outpatient departments in Debre tabor general hospital, North West Ethiopia
Authors: Abere Tigist Misganaw , Atnafu Desta Debalkie , Mulu Yaread 
Published: June 2021

Abstract
Background
Self-referral leads to diminished quality of health care service; increase resource depletion and poorer patient outcomes. However, a significant number of patients referred themselves to the higher health care facilities without having referral sheets globally including Ethiopia. Even though the problem is much exacerbated in Ethiopia, there is limited evidence regarding self-referral patients in Ethiopia in particular in the study area.

Objective
To assess the magnitude and associated factors of self-referral among patients at the adult outpatient department in Debre Tabor general hospital, North West Ethiopia.

Method
Institution-based cross-sectional study was conducted from March 11–April 9, 2020 among 693 patients who attended adult outpatient departments. A systematic sampling technique was employed. Structured and pretested interviewer-administered questionnaire was used for data collection. Data were coded, cleaned and entered into Epi Info version 7.1 and exported to SPSS version 23 for further analysis. Binary logistic regression analysis was employed. In bivariable analysis p-value, less than 0.25 was used to select candidate variables for multivariable analysis. P-values less than 0.05 and 95% confidence intervals were used to select significant variables on the outcome of interest.

Result
The proportion of self-referral was 443(63.9%) with 95% CI (60.5; 67.5). Formally educated, (AOR = 1.83; (95% CI: 1.12, 3.01)), enrolled to Community Based Health Insurance (AOR = 1.57; (95% CI: 1.03, 2.39)), poor knowledge about referral system (AOR = 2.07; 95% CI: (1.28, 3.39)), not and partially available medication in the nearby Primary Health Care facilities (AOR = 2.12; (95% CI: 1.82, 6.15)) & (AOR = 3.24; (95% CI: 1.75, 5.97)) respectively and history of visiting general hospital (AOR = 1.52; (95%CI: 1.03, 2.25)) were factors statistically associated with self-referral.

Conclusion and recommendation
The proportion of self-referral was low compared to the Ethiopian health sector transformation plan 2015/16–20. Socio-demographic and institutional factors were associated with self-referral. Therefore, regional health bureau better to work to fulfill the availability of medications in the primary health care facilities. In addition, Community Based Health Insurance (CBHI) agency should work to implement the law of out-of-pocket expenditure which states to pay 50% for self-referred patients who claim utilization of healthcare.
CircRNA_100290 promotes GC cell proliferation and invasion via the miR-29b-3p/ITGA11 axis and is regulated by EIF4A3
Authors: Wang Gang , Sun Dan , Li Wenhui , Xin Yan 
Published: June 2021

Abstract
Background
Circular RNAs (circRNAs) have been reported to be important regulators of the development and progression of various carcinomas. However, the role of circRNA_100290 in gastric cancer (GC) is still unclear. This study aimed to investigate the role of circRNA_100290 in GC invasion and metastasis and the possible underlying mechanism.

Methods
The expression of circRNA_100290 in GC cells and tissues was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The role of circRNA_100290 in cell proliferation, migration, and invasion was evaluated in the AGS and HGC-27 cell lines in vitro. Bioinformatics tools, dual-luciferase reporter assays, Western blot assays and qRT-PCR were used to explore the pathways downstream of circRNA_100290. The mechanism underlying the regulation of circRNA_100290 expression was explored using RNA immunoprecipitation, qRT-PCR, and Western blot assays.

Results
The expression of circRNA_100290 was significantly upregulated in GC cells and 102 GC tissues, and high circRNA_100290 expression in GC was closely related to Borrmann’s type, lymph node metastasis and tumour-node-metastasis stage. In vitro, knockdown of circRNA_100290 in AGS and HGC-27 cells significantly inhibited cell proliferation, migration, and invasion. Mechanistically, a dual-luciferase reporter assay confirmed the direct interaction between circRNA_100290 and miR-29b-3p, which targets ITGA11, an oncogene that is closely related to epithelial–mesenchymal transition (EMT). In addition, EIF4A3, an RNA-binding protein (RBP), could inhibit the formation of circRNA_100290 by binding to the flanking sites of circRNA_100290. Low EIF4A3 expression in GC was related to a poor prognosis.

Conclusions
Elevated circRNA_100290 expression in GC promotes cell proliferation, invasion and EMT via the miR-29b-3p/ITGA11 axis and might be regulated by EIF4A3. CircRNA_100290 might be a promising biomarker and target for GC therapy.

Graphical abstract
Machine learning classification of texture features of MRI breast tumor and peri-tumor of combined pre- and early treatment predicts pathologic complete response
Authors: Hussain Lal , Huang Pauline , Nguyen Tony , Lone Kashif J. , Ali Amjad , Khan Muhammad Salman , Li Haifang , Suh Doug Young , Duong Tim Q. 
Published: June 2021

AbstractPurposeThis study used machine learning classification of texture features from MRI of breast tumor and peri-tumor at multiple treatment time points in conjunction with molecular subtypes to predict eventual pathological complete response (PCR) to neoadjuvant chemotherapy.Materials and methodThis study employed a subset of patients (N = 166) with PCR data from the I-SPY-1 TRIAL (2002–2006). This cohort consisted of patients with stage 2 or 3 breast cancer that underwent anthracycline–cyclophosphamide and taxane treatment. Magnetic resonance imaging (MRI) was acquired pre-neoadjuvant chemotherapy, early, and mid-treatment. Texture features were extracted from post-contrast-enhanced MRI, pre- and post-contrast subtraction images, and with morphological dilation to include peri-tumoral tissue. Molecular subtypes and Ki67 were also included in the prediction model. Performance of classification models used the receiver operating characteristics curve analysis including area under the curve (AUC). Statistical analysis was done using unpaired two-tailedt-tests.ResultsMolecular subtypes alone yielded moderate prediction performance of PCR (AUC = 0.82,p = 0.07). Pre-, early, and mid-treatment data alone yielded moderate performance (AUC = 0.88, 0.72, and 0.78,p = 0.03, 0.13, 0.44, respectively). The combined pre- and early treatment data markedly improved performance (AUC = 0.96,p = 0.0003). Addition of molecular subtypes improved performance slightly for individual time points but substantially for the combined pre- and early treatment (AUC = 0.98,p = 0.0003). The optimal morphological dilation was 3–5 pixels. Subtraction of post- and pre-contrast MRI further improved performance (AUC = 0.98,p = 0.00003). Finally, among the machine-learning algorithms evaluated, the RUSBoosted Tree machine-learning method yielded the highest performance.ConclusionAI-classification of texture features from MRI of breast tumor at multiple treatment time points accurately predicts eventual PCR. Longitudinal changes in texture features and peri-tumoral features further improve PCR prediction performance. Accurate assessment of treatment efficacy early on could minimize unnecessary toxic chemotherapy and enable mid-treatment modification for patients to achieve better clinical outcomes.
Understanding the impact of more realistic low-dose, prolonged engineered nanomaterial exposure on genotoxicity using 3D models of the human liver
Authors: Llewellyn Samantha V. , Conway Gillian E. , Zanoni Ilaria , Jørgensen Amalie Kofoed , Shah Ume-Kulsoom , Seleci Didem Ag , Keller Johannes G. , Kim Jeong Won , Wohlleben Wendel , Jensen Keld Alstrup , Costa Anna , Jenkins Gareth J. S. , Clift Martin J. D. , Doak Shareen H. 
Published: June 2021

Abstract
Background
With the continued integration of engineered nanomaterials (ENMs) into everyday applications, it is important to understand their potential for inducing adverse human health effects. However, standard in vitro hazard characterisation approaches suffer limitations for evaluating ENM and so it is imperative to determine these potential hazards under more physiologically relevant and realistic exposure scenarios in target organ systems, to minimise the necessity for in vivo testing. The aim of this study was to determine if acute (24 h) and prolonged (120 h) exposures to five ENMs (TiO2, ZnO, Ag, BaSO4 and CeO2) would have a significantly different toxicological outcome (cytotoxicity, (pro-)inflammatory and genotoxic response) upon 3D human HepG2 liver spheroids. In addition, this study evaluated whether a more realistic, prolonged fractionated and repeated ENM dosing regime induces a significantly different toxicity outcome in liver spheroids as compared to a single, bolus prolonged exposure.

Results
Whilst it was found that the five ENMs did not impede liver functionality (e.g. albumin and urea production), induce cytotoxicity or an IL-8 (pro-)inflammatory response, all were found to cause significant genotoxicity following acute exposure. Most statistically significant genotoxic responses were not dose-dependent, with the exception of TiO2. Interestingly, the DNA damage effects observed following acute exposures, were not mirrored in the prolonged exposures, where only 0.2–5.0 µg/mL of ZnO ENMs were found to elicit significant (p ≤ 0.05) genotoxicity. When fractionated, repeated exposure regimes were performed with the test ENMs, no significant (p ≥ 0.05) difference was observed when compared to the single, bolus exposure regime. There was < 5.0% cytotoxicity observed across all exposures, and the mean difference in IL-8 cytokine release and genotoxicity between exposure regimes was 3.425 pg/mL and 0.181%, respectively.

Conclusion
In conclusion, whilst there was no difference between a single, bolus or fractionated, repeated ENM prolonged exposure regimes upon the toxicological output of 3D HepG2 liver spheroids, there was a difference between acute and prolonged exposures. This study highlights the importance of evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner.
Predictive value of computed tomography with coronal reconstruction in right hemicolectomy with complete mesocolic excision for right colon cancers: a retrospective study
Authors: Yu Hui , Zhuang Yong , Jian Jinliang , Yang Chunkang 
Published: June 2021

Abstract
Background
Understanding the vascular anatomy is critical for performing central vascular ligation (CVL) in right hemicolectomy with complete mesocolic excision (CME). This study aimed to investigate the predictive value of multi-slice spiral computed tomography (MSCT) with coronal reconstruction in right hemicolectomy with CME.

Methods
This is a retrospective descriptive study. Eighty patients with right colon cancer who underwent right hemicolectomy from December 2015 to January 2020 were included. The intraoperative reports (including imaging data) and MSCT images with coronal reconstruction were analysed and compared. The detection rates of the ileocolic vein (ICV) and ileocolic artery (ICA) roots and the accuracy in predicting their anatomical relationship were analysed. The detection rate and accuracy in predicting the location of the gastrocolic trunk of Henle (GTH), middle colic artery (MCA) and middle colic vein (MCV) were analysed. The distance from the ICV root to the GTH root (ICV-GTH distance) was measured and analysed. The maximum distance from the left side of the superior mesenteric artery (SMA) to the right side of the superior mesenteric vein (SMV), named the ‘lsSMA-rsSMV distance’, was also measured and analysed.

Results
In seventy-four (92.5%) patients, both the ICV and ICA roots were located; their anatomical relationship was determined by MSCT, and the accuracy of the prediction was 97.2% (72/74). The GTH was located by MSCT in 75 (93.7%) patients, and the accuracy of the prediction was 97.33% (73/75). The MCA was located by MSCT in 47 (58.75%) patients, and the accuracy was 78.72% (37/47). The MCV was located by MSCT in 51 (63.75%) patients, and the accuracy of the prediction was 84.31% (43/51). The ICV-GTH distance was measured in 73 (91.2%) patients, and the mean distance was 4.28 ± 2.5 cm. The lsSMA-rsSMV distance was measured in 76 (95%) patients, and the mean distance was 2.21 ± 0.6 cm.

Conclusions
With its satisfactory accuracy in predicting and visualising the information of key anatomical sites, MSCT with coronary reconstruction has some predictive value in CME with CVL in right hemicolectomy.
Thymosin β4 reverses phenotypic polarization of glial cells and cognitive impairment via negative regulation of NF-κB signaling axis in APP/PS1 mice
Authors: Wang Meng , Feng Li-Rong , Li Zi-Long , Ma Kai-Ge , Chang Ke-Wei , Chen Xin-Lin , Yang Peng-Bo , Ji Sheng-Feng , Ma Yan-Bing , Han Hua , Ruganzua John Bosco , Yang Wei-Na , Qian Yi-Hua 
Published: June 2021

Abstract
Background
Thymosin β4 (Tβ4) is the most abundant member of the β-thymosins and plays an important role in the control of actin polymerization in eukaryotic cells. While its effects in multiple organs and diseases are being widely investigated, the safety profile has been established in animals and humans, currently, little is known about its influence on Alzheimer’s disease (AD) and the possible mechanisms. Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.

Methods
Behavior tests were conducted to assess the learning and memory, anxiety and depression in APP/PS1 mice. Thioflavin S staining, Nissl staining, immunohistochemistry/immunofluorescence, ELISA, qRT-PCR, and immunoblotting were performed to explore Aβ accumulation, phenotypic polarization of glial cells, neuronal loss and function, and TLR4/NF-κB axis in APP/PS1 mice.

Results
We demonstrated that Tβ4 protein level elevated in all APP/PS1 mice. Over-expression of Tβ4 alone alleviated AD-like phenotypes of APP/PS1 mice, showed less brain Aβ accumulation and more Insulin-degrading enzyme (IDE), reversed phenotypic polarization of microglia and astrocyte to a healthy state, improved neuronal function and cognitive behavior performance, and accidentally displayed antidepressant-like effect. Besides, Tβ4 could downregulate both TLR4/MyD88/NF-κB p65 and p52-dependent inflammatory pathways in the APP/PS1 mice. While combination drug of TLR4 antagonist TAK242 or NF-κB p65 inhibitor PDTC exerted no further effects.

Conclusions
These results suggest that Tβ4 may exert its function by regulating both classical and non-canonical NF-κB signaling and is restoring its function as a potential therapeutic target against AD.