bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of dopamine receptor D1 promotes osteogenic differentiation and reduces glucocorticoid-induced bone loss by upregulating the ERK1/2 signaling pathway
Authors: Zhu Jie , Feng Chengcheng , Zhang Weicheng , Wang Zhidong , Zhong Mengdan , Tang Wenkai , Wang Zhifang , Shi Haiwei , Yin Zhengyu , Shi Jiandong , Huang Yu , Xiao Long , Geng Dechun , Wang Zhirong 
Published: February 2022

Abstract
Background
The inhibition of osteogenic differentiation is a major factor in glucocorticoid-induced bone loss, but there is currently no effective treatment. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of the neuroendocrine system in bone metabolism has emerged, the precise effects of dopamine receptor signaling on osteoblastogenesis remain unknown.

Methods
In vitro, western blotting and immunofluorescence staining were used to observe the expression of dopamine receptors in MC3T3-E1 and BMSCs cells treated with dexamethasone (Dex). In addition, Alizarin red S (ARS) and alkaline phosphatase (ALP) staining and western blotting were used to evaluate the effect of D1R activation on osteogenic differentiation in Dex-induced MC3T3-E1 cells via the ERK1/2 signaling pathway. In vivo, micro-CT and hematoxylin and eosin (H&E), toluidine blue and immunohistochemical staining were used to determine the effect of D1R activation on Dex-induced bone loss.

Results
We demonstrated that the trend in D1R but not D2-5R was consistent with that of osteogenic markers in the presence of Dex. We also demonstrated that the activation of D1R promoted Dex-induced osteogenic differentiation by activating the ERK1/2 pathway in vitro. We further demonstrated that a D1R agonist could reduce Dex-induced bone loss, while pretreatment with a D1R inhibitor blocked the effect of a D1R agonist in vivo.

Conclusions
Activation of D1R promotes osteogenic differentiation and reduces Dex-induced bone loss by activating the ERK1/2 pathway. Hence, D1R could serve as a potential therapeutic target for glucocorticoid-induced osteoporosis.
Early response to eptinezumab indicates high likelihood of continued response in patients with chronic migraine
Authors: Buse Dawn C. , Winner Paul K. , Charleston Larry , Hirman Joe , Cady Roger , Brevig Thomas 
Published: February 2022

AbstractBackgroundA clinical ability to describe the response trajectory of patients receiving preventive migraine treatment could expedite and improve therapeutic management decisions. This post hoc analysis of the PROMISE-2 study evaluated the consistency and predictive power of Month 1 treatment response on later response in patients with chronic migraine.MethodsPROMISE-2 was a double-blind, placebo-controlled trial that randomized adults with chronic migraine to eptinezumab 100 mg, 300 mg, or placebo administered IV every 12 weeks for up to 24 weeks (2 infusions over 6 study months). Migraine responder rates (MRRs) were calculated from monthly migraine days over 4-week intervals compared with baseline. Patients were grouped by MRR during Month 1 (< 25%, 25–< 50%, 50–< 75%, and ≥ 75%), with the number of subsequent study months (Months 2–6) with ≥50% and ≥ 75% MRR calculated in each subgroup. A similar analysis was conducted using Patient Global Impression of Change (PGIC) rating to define Month 1 subgroups (very much improved, much improved, minimally improved, and no change/worse) and rates of very much improved or much improved PGIC during Months 2–6.ResultsIn the eptinezumab 100 mg, 300 mg, and placebo groups, respectively, 194/356 (54.5%), 212/350 (60.6%), and 132/366 (36.1%) patients were ≥ 50% migraine responders during Month 1. More eptinezumab-treated patients were ≥ 75% migraine responders (100 mg, 110/356 [30.9%]; 300 mg, 129/350 [36.9%]; placebo, 57/366 [15.6%]) and more placebo-treated patients were < 25% migraine responders (eptinezumab 100 mg, 103/356 [28.9%]; 300 mg, 80/350 [22.9%]; placebo, 153/366 [41.8%]). Among patients who achieved ≥75% migraine response in Month 1, more than one-third attained ≥75% migraine response for all 5 subsequent study months and more than two-thirds achieved ≥75% migraine response for ≥3 months. More than two-thirds of those in the very much improved (PGIC) subgroup at Month 1 were much or very much improved for all 5 subsequent months.ConclusionsIn this post hoc analysis of data from PROMISE-2, more eptinezumab-treated than placebo-treated patients were early (Month 1) responders, and most early responders went on to achieve a high level of response for at least half of the 24-week treatment period. Potential for later response in early non-responders was also observed.Trial registrationClinicalTrials.govidentifier:NCT02974153; registered November 23, 2016.
Identification of a novel m6A-related lncRNA pair signature for predicting the prognosis of gastric cancer patients
Authors: Wang Jun-Mei , Li Xuan , Yang Peng , Geng Wen-Bin , Wang Xiao-Yong 
Published: February 2022

Abstract
Background
Accumulating studies have demonstrated that lncRNAs play vital roles in the prognosis of gastric cancer (GC); however, the prognostic value of N6-methyladenosine-related lncRNAs has not been fully reported in GC. This study aimed to construct and validate an m6A-related lncRNA pair signature (m6A-LPS) for predicting the prognosis of GC patients.

Methods
GC cohort primary data were downloaded from The Cancer Genome Atlas. We analysed the coexpression of m6A regulators and lncRNAs to identify m6A-related lncRNAs. Based on cyclical single pairing along with a 0-or-1 matrix and least absolute shrinkage and selection operator-penalized regression analyses, we constructed a novel prognostic signature of m6A-related lncRNA pairs with no dependence upon specific lncRNA expression levels. All patients were divided into high-risk and low-risk group based on the median risk score. The predictive reliability was evaluated in the testing dataset and whole dataset with receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis was used to identify potential pathways.

Results
Fourteen m6A-related lncRNA pairs consisting of 25 unique lncRNAs were used to construct the m6A-LPS. Kaplan–Meier analysis showed that the high-risk group had poor prognosis. The area under the curve for 5-year overall survival was 0.906, 0.827, and 0.882 in the training dataset, testing dataset, and whole dataset, respectively, meaning that the m6A-LPS was highly accurate in predicting GC patient prognosis. The m6A-LPS served as an independent prognostic factor for GC patients after adjusting for other clinical factors (p < 0.05). The m6A-LPS had more accuracy and a higher ROC value than other prognostic models for GC. Functional analysis revealed that high-risk group samples mainly showed enrichment of extracellular matrix receptor interactions and focal adhesion. Moreover, N-cadherin and vimentin, known biomarkers of epithelial–mesenchymal transition, were highly expressed in high-risk group samples. The immune infiltration analysis showed that resting dendritic cells, monocytes, and resting memory CD4 T cells were significantly positively related to the risk score. Thus, m6A-LPS reflected the infiltration of several types of immune cells.

Conclusions
The signature established by pairing m6A-related lncRNAs regardless of expression levels showed high and independent clinical prediction value in GC patients.
Prevalence of HIV infection among non-elderly individuals with hepatitis C in Japan: a population-based cohort study using a health insurance claim data
Authors: Ikeuchi Kazuhiko , Okushin Kazuya , Saito Makoto , Adachi Eisuke , Tsutsumi Takeya , Takura Tomoyuki , Yotsuyanagi Hiroshi 
Published: February 2022

AbstractBackgroundHepatitis C virus (HCV) has been mainly transmitted through injection drug use, but recently, sexual transmission among men who have sex with men (MSM), which is also a major route of HIV transmission, is increasing. However, the prevalence of HIV and the incidence of other sexually transmitted infections (STIs) among HCV patients have been rarely reported.MethodsUsing a healthcare insurance claim data of employees and their dependents covering seven-million people in Japan, we evaluated HIV prevalence among HCV patients aged 20–59 years. Hemophilia patients were excluded. HIV and HCV were defined by registered diagnoses and receiving viral RNA testing. The time course of HCV and HIV infections was analyzed. Incidences of syphilis, amebiasis, chlamydia, gonorrhea, hepatitis A, and hepatitis B were assessed.ResultsFrom April 2012 to August 2018, 6,422 HCV patients were identified. HIV prevalence was 0.48% (31/6422, 95% CI [confidence interval]: 0.33–0.68%). HIV was diagnosed after HCV in 3.2% (1/31), before HCV in 58.1% (18/31), and concurrently in 38.7% (12/31). Compared with HCV patients without HIV infection, HCV/HIV co-infected patients were younger (median age, 37 vs 51 years,p < 0.001), more likely to be male (30/31 [96.8%] vs 3059/6391 [47.9%],p < 0.001), more likely to have other STIs (38.7% [12/31] vs 0.9% [56/6391],p < 0.001), and live in Tokyo, the most populous capital city in Japan (67.7% [21/31] vs 11.6% [742/6391],p < 0.001). In Tokyo, the HIV prevalence among 20–30 s male with HCV was 18.6% (13/70; 95% CI, 10.3–29.7%).ConclusionsHIV prevalence among young male HCV patients was very high in Tokyo. HCV/HIV co-infected patients were more likely to acquire HIV before HCV, which is a known feature of MSM. They also had a higher incidence of STIs. These findings suggest that HCV might be prevalent as an STI among MSM particularly in Tokyo.
Severe maternal morbidity: admission shift from intensive care unit to obstetric high-dependency unit
Authors: Gu Ning , Zheng Yaning , Dai Yimin 
Published: February 2022

Abstract
Background
To study temporal trends of intensive care unit (ICU) admission in obstetric population after the introduction of obstetric high-dependency unit (HDU).

Methods
This is a retrospective study of consecutive obstetric patients admitted to the ICU/HDU in a provincial referral center in China from January 2014 to December 2019. The collected information included maternal demographic characteristics, indications for ICU and HDU admission, the length of ICU stay, the total length of in-hospital stay and APACHE II score. Chi-square and ANOVA tests were used to determine statistical significance. The temporal changes were assessed with chi-square test for linear trend.

Results
A total of 40,412 women delivered and 447 (1.11%) women were admitted to ICU in this 6-year period. The rate of ICU admission peaked at 1.59% in 2016 and then dropped to 0.67% in 2019 with the introduction of obstetric HDU. The average APACHE II score increased significantly from 6.8 to 12.3 (P < 0.001) and the average length of ICU stay increased from 1.7 to 7.1 days (P < 0.001). The main indications for maternal ICU admissions were hypertensive disorders in pregnancy (39.8%), cardiac diseases (24.8%), and other medical disorders (21.5%); while the most common reasons for referring to HDU were hypertensive disorders of pregnancy (46.5%) and obstetric hemorrhage (43.0%). The establishment of HDU led to 20% reduction in ICU admission, which was mainly related to obstetric indications.

Conclusions
The introduction of HDU helps to reduce ICU utilization in obstetric population.
Developing a 5-gene prognostic signature for cervical cancer by integrating mRNA and copy number variations
Authors: Liu Wenxin , Jiang Qiuying , Sun Chao , Liu ShiHao , Zhao Zhikun , Wu Dongfang 
Published: February 2022

Abstract
Background
Cervical cancer is frequently detected gynecological cancer all over the world. This study was designed to develop a prognostic signature for an effective prediction of cervical cancer prognosis.

Methods
Differentially expressed genes (DEGs) were identified based on copy number variation (CNV) data and expression profiles from different databases. A prognostic model was constructed and further optimized by stepwise Akaike information criterion (stepAIC). The model was then evaluated in three groups (training group, test group and validation group). Functional analysis and immune analysis were used to assess the difference between high-risk and low-risk groups.

Results
The study developed a 5-gene prognostic model that could accurately classify cervical cancer samples into high-risk and low-risk groups with distinctly different prognosis. Low-risk group exhibited more favorable prognosis and higher immune infiltration than high-risk group. Both univariate and multivariate Cox regression analysis showed that the risk score was an independent risk factor for cervical cancer.

Conclusions
The 5-gene prognostic signature could serve as a predictor for identifying high-risk cervical cancer patients, and provided potential direction for studying the mechanism or drug targets of cervical cancer. The integrated analysis of CNV and mRNA expanded a new perspective for exploring prognostic signatures in cervical cancer.
Fetal cardiac parameters for predicting postnatal operation type of fetuses with tetralogy of Fallot
Authors: Park Suyeon , Won Hye-Sung , Kim Rina , Kim Mijin , Yu Jeong Jin , Park Chun Soo , Yun Tae-Jin , Jung Yewon , Al Harbi Usamah , Lee Mi-Young 
Published: February 2022

AbstractBackgroundTo assess fetal cardiac parameters predictive of postnatal operation type in fetuses with tetralogy of Fallot (TOF).MethodsEchocardiographic data obtained in the second and third trimesters were retrospectively reviewed for fetuses diagnosed with TOF between 2014 and 2018 at Asan Medical Center. The following fetal cardiac parameters were analyzed: 1) pulmonary valve annulus (PVA) z-score, 2) right pulmonary artery (RPA) z-score, 3) aortic valve annulus (AVA) z-score, 4) pulmonary valve peak systolic velocity (PV-PSV), 5) PVA/AVA ratio, and 6) RPA/descending aorta (DAo) ratio. These cardiac parameters were compared between a primary corrective surgery group and a palliative shunt operation followed by complete repair group.ResultsA total of 100 fetuses with TOF were included. Only one neonatal death occurred. Ninety patients underwent primary corrective surgery and 10 neonates underwent a multistage surgery. The PVA z-score, RPA z-score, and RPA/DAo ratio measured in the second trimester and the PVA z-score, RPA z-score, and PVA/AVA raio measured in the third trimester were significantly lower in the multistage surgery group, while the PV-PSV as measured in both trimesters were significantly higher in the multistage surgery group.ConclusionFetal cardiac parameters are useful for predicting the operation type necessary for neonates with TOF.
Regulation of genetically engineered (GE) mosquitoes as a public health tool: a public health ethics analysis
Authors: Meghani Zahra 
Published: February 2022

Abstract
Background
In recent years, genetically engineered (GE) mosquitoes have been proposed as a public health measure against the high incidence of mosquito-borne diseases among the poor in regions of the global South. While uncertainties as well as risks for humans and ecosystems are entailed by the open-release of GE mosquitoes, a powerful global health governance non-state organization is funding the development of and advocating the use of those bio-technologies as public health tools.
In August 2016, the US Food and Drug Agency (FDA) approved the uncaged field trial of a GE Aedes aegypti mosquito in Key Haven, Florida. The FDA’s decision was based on its assessment of the risks of the proposed experimental public health research project. The FDA is considered a global regulatory standard setter. So, its approval of the uncaged field trial could be used by proponents of GE mosquitoes to urge countries in the global South to permit the use of those bio-technologies.

Method
From a public health ethics perspective, this paper evaluates the FDA’s 2016 risk assessment of the proposed uncaged field trial of the GE mosquito to determine whether it qualified as a realistic risk evaluation.

Results
The FDA’s risk assessment of the proposed uncaged field trial did not proximate the conditions under which the GE mosquitoes would be used in regions of the global South where there is a high prevalence of mosquito-borne diseases.

Conclusion
Given that health and disease have political-economic determinants, whether a risk assessment of a product is realistic or not particularly matters with respect to interventions meant for public health problems that disproportionately impact socio-economically marginalized populations. If ineffective public health interventions are adopted based on risk evaluations that do not closely mirror the conditions under which those products would actually be used, there could be public health and ethical costs for those populations.
Improvement of polydopamine-loaded salidroside on osseointegration of titanium implants
Authors: Yi Qingqing , Liang Pengchen , Liang Dongyu , Cao Liou , Sha Shuang , Jiang Xinquan , Chang Qing 
Published: February 2022

Abstract
Background
Microarc oxidation (MAO) on the surface of medical pure titanium can improve its histocompatibility, and loading drugs on the surface can resist excessive intimal hyperplasia.

Methods
In this study, salidroside (SAL) was loaded on the surface of porous titanium (Ti) with polydopamine (PDA) carrier. The effects of SAL on the osteogenesis and angiogenesis of Ti implants were studied by phalloidin staining, alizarin red staining, ALP staining, wound-healing assay, cell transwell assay, matrigel tube formation, and osteogenic and angiogenic genes and proteins expression detected by PCR and western blot in vitro. The bone defect model experiments in rats was established in vivo including X-ray, micro CT, hematoxylin and eosin staining (HE), immunohistochemistry (IHC), Goldner's trichrome analysis, Safranin O-fast green staining and determination of contents of TNF-α and IL-6 in serum.

Results
EDS and EDS mapping showed that SAL could be loaded on the surface of the MAO coating by PDA. A drug release experiment showed that SAL loaded on the Ti coating could release slowly and stably without sudden release risk. In vitro cell experiments showed that the SAL coating could promote the proliferation, morphology, calcification and alkaline phosphate activity of MC3T3-E1 cells. At the same time, it promoted the migration and tube formation of HUVEC cells. The SAL coating promoted osteogenesis and angiogenesis by promoting the expression of genes and proteins related to. In vivo experiments, HE and IHC showed that SAL significantly promoted the expression of COL-1 and CD31. Goldner's trichrome and Safranin O-fast green staining showed that SAL coating could increase the new bone tissue around the implantation site. The SAL coating had anti-inflammatory activity by reducing the levels of TNF-α and IL-6 in vivo.

Conclusion
Therefore, SAL could improve osteogenesis and angiogenesis in conjunction with the Ti-PDA coating.
The presentation, course and outcome of COVID-19 infection in people with Prader-Willi syndrome: unexpected findings from an international survey
Authors: Whittington J. E. , Holland A. J. , Driscoll D. J. , Hodebeck-Stuntebeck N. , Hoctor A. 
Published: February 2022

Abstract
Background
Prader-Willi syndrome (PWS), is a genetically determined neurodevelopmental disorder, associated with intellectual disabilities and a high incidence of obesity, diabetes mellitus, and respiratory disorders. We hypothesised that COVID-19, a viral infection which more severely affects people with these conditions, would, in people with PWS, present atypically and result in severe outcomes.

Method
A structured on-line questionnaire was piloted with parents and professionals at the International Prader-Willi Syndrome Organization (IPWSO) and promoted internationally through their global network. Family members/other carers were asked to complete if someone they cared for with PWS was strongly suspected or confirmed as having COVID-19.

Results
Over 1 year of the pandemic 72 responses were received, 47 adults, 25 children. The following underlying conditions were present: 16 people with PWS were overweight and 18 obese, five had diabetes mellitus and 18 sleep apnoea. Main presenting symptoms were raised temperature, fatigue/daytime sleepiness, dry cough, headache/pain, and feeling unwell, with illnesses generally lasting less than a week. Length of illness was not significantly related to age, BMI, sex, or genetic subtype. No one was ventilated or in an intensive care unit or died, one person was in hospital for four days needing oxygen.

Conclusions
Contrary to our hypothesis, the PWS cohort had asymptomatic infection or mild illness. A possible explanation, supported by anecdotal evidence from parents and professional carers, is that people with PWS have a degree of innate immunity to viral infections. However, likely selection effects and a relatively low number of responses means that further evidence is needed to test this hypothesis.
circCUL2 induces an inflammatory CAF phenotype in pancreatic ductal adenocarcinoma via the activation of the MyD88-dependent NF-κB signaling pathway
Authors: Zheng Shangyou , Hu Chonghui , Lin Hongcao , Li Guolin , Xia Renpeng , Zhang Xiang , Su Dan , Li Zhihua , Zhou Quanbo , Chen Rufu 
Published: February 2022

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is characterized by clusters of cancer cells surrounded by a dense desmoplastic stroma. However, little is known about stromal cell heterogeneity in the pancreatic tumor microenvironment.

Methods
We conducted circRNA profiling in primary fibroblasts by high-throughput sequencing and detected circCUL2 levels in PDAC tissues by qRT–PCR. We subsequently investigated the effect of circCUL2 on inflammatory cancer-associated fibroblast (iCAF) activation, heterogeneity and protumor activity by ELISA, flow cytometry, colony formation and transwell assays in vitro and by xenograft models in vivo. The regulatory effect of circCUL2 on miR-203a-3p/MyD88/IL6 was examined by RNA pulldown, FISH, and luciferase reporter assays.

Results
We identified that circCUL2 was specifically expressed in cancer-associated fibroblasts (CAFs) but not in cancer cells. Moreover, the enrichment of circCUL2 in tumor tissues was significantly correlated with the poor prognosis of PDAC patients. Upregulation of circCUL2 expression in normal fibroblasts (NFs) induced the iCAF phenotype, and then iCAFs promoted PDAC progression through IL6 secretion in vitro. Furthermore, circCUL2-transduced NFs promoted tumorigenesis and metastasis of PDAC cells in vivo, which was blocked by an anti-IL6 antibody. Mechanistically, circCUL2 functioned as a ceRNA and modulated the miR-203a-3p/MyD88/NF-κB/IL6 axis, thereby further activating the STAT3 signaling pathway in pancreatic cancer cells to induce PDAC progression.

Conclusions
We showed that the circCUL2/miR-203a-5p/MyD88/NF-κB/IL6 axis contributes to the induction of iCAFs and established a distinct fibroblast niche for PDAC progression, which could help the development of strategies that selectively target tumor-promoting CAFs in PDAC.