bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the association between birthweight and breast cancer using summary statistics from a perspective of genetic correlation, mediation, and causality
Authors: Zhang Meng , Qiao Jiahao , Zhang Shuo , Zeng Ping 
Published: May 2022

AbstractBackgroundPrevious studies demonstrated a positive relationship between birthweight and breast cancer; however, inconsistent, sometimes even controversial, observations also emerged, and the nature of such relationship remains unknown.MethodsUsing summary statistics of birthweight and breast cancer, we assessed the fetal/maternal-specific genetic correlation between them via LDSC and prioritized fetal/maternal-specific pleiotropic genes through MAIUP. Relying on summary statistics we conducted Mendelian randomization (MR) to evaluate the fetal/maternal-specific origin of causal relationship between birthweight, age of menarche, age at menopause and breast cancer.ResultsWith summary statistics we identified a positive genetic correlation between fetal-specific birthweight and breast cancer (rg = 0.123 andP = 0.013) as well as a negative but insignificant correlation between maternal-specific birthweight and breast cancer (rg = − 0.068,P = 0.206); and detected 84 pleiotropic genes shared by fetal-specific birthweight and breast cancer, 49 shared by maternal-specific birthweight and breast cancer. We also revealed fetal-specific birthweight indirectly influenced breast cancer risk in adulthood via the path of age of menarche or age at menopause in terms of MR-based mediation analysis.ConclusionThis study reveals that shared genetic foundation and causal mediation commonly drive the connection between the two traits, and that fetal/maternal-specific birthweight plays substantially distinct roles in such relationship. However, our work offers little supportive evidence for the fetal origins hypothesis of breast cancer originating in utero.
Epigenetic regulation of innate immune memory in microglia
Authors: Zhang Xiaoming , Kracht Laura , Lerario Antonio M. , Dubbelaar Marissa L. , Brouwer Nieske , Wesseling Evelyn M. , Boddeke Erik W. G. M. , Eggen Bart J. L. , Kooistra Susanne M. 
Published: May 2022

AbstractBackgroundMicroglia are the tissue-resident macrophages of the CNS. They originate in the yolk sac, colonize the CNS during embryonic development and form a self-sustaining population with limited turnover. A consequence of their relative slow turnover is that microglia can serve as a long-term memory for inflammatory or neurodegenerative events.MethodsUsing ATAC-, ChIP- and RNA-sequencing, we characterized the epigenomes and transcriptomes of FACS-purified microglia from mice exposed to different stimuli. A repeated endotoxin challenge (LPS) was used to induce tolerance in microglia, while genotoxic stress (DNA repair deficiency-induced accelerated aging through Ercc1 deficiency) resulted in primed (hypersensitive) microglia.ResultsWhereas the enrichment of permissive epigenetic marks at enhancer regions could explain training (hyper-responsiveness) of primed microglia to an LPS challenge, the tolerized response of microglia seems to be regulated by loss of permissive epigenetic marks. We identify that inflammatory stimuli and accelerated aging as a result of genotoxic stress activate distinct gene networks. These gene networks and associated biological processes are partially overlapping, which is likely driven by specific transcription factor networks, resulting in altered epigenetic signatures and distinct functional (desensitized vs. primed) microglia phenotypes.ConclusionThis study provides insight into epigenetic profiles and transcription factor networks associated with transcriptional signatures of tolerized and trained microglia in vivo, leading to a better understanding of innate immune memory of microglia.
Epidemiologic analysis of 8000 acute vertebral fractures: evolution of treatment and complications at 10-year follow-up
Authors: Bigdon Sebastian F. , Saldarriaga Yannis , Oswald Katharina A. C. , Müller Martin , Deml Moritz C. , Benneker Lorin M. , M. Ecker Timo , Albers Christoph E. 
Published: May 2022

AbstractStudy designThis is a retrospective cohort study.ObjectivesThis study aims to determine the proportional incidence, clinical characteristics, treatment patterns with complications and changes in treatment of vertebral fractures over 10 years at a Swiss university hospital.MethodsA retrospective cohort study was performed. All patients with an acute vertebral fracture were included in this study. The extracted anonymized data from the medical records were manually assessed. Demographic data, exact location, etiology, type of treatment and complications related to the treatment were obtained.ResultsOf 330,225 treated patients, 4772 presented with at least one vertebral fracture. In total 8307 vertebral fractures were identified, leading to a proportional incidence of 25 vertebral fractures in 1000 patients. Fractures were equally distributed between genders. Male patients were significantly younger and more likely to sustain a traumatic fracture, while female patients more commonly presented with osteoporotic fractures. The thoracolumbar junction (Th11-L2) was the most frequent fracture site in all etiologies. More than two-thirds of vertebral fractures were treated surgically (68.6%). Out of 4622 performed surgeries, we found 290 complications (6.3%). The odds for surgical treatment in osteoporotic fractures were two times higher before 2010 compared to 2010 and after (odds ratio: 2.1, 95% CI 1.5–2.9,p < 0.001).ConclusionTwenty-five out of 1000 patients presented with a vertebral fracture. More than 4000 patients with over 8307 vertebral body fractures were treated in 10 years. Over two-thirds of all fractures were treated surgically with 6.3% complications. There was a substantial decrease in surgeries for osteoporotic fractures after 2009.
Association between obesity and bone mineral density in middle-aged adults
Authors: Li Yue 
Published: May 2022

Abstract
Background
The relationship between obesity and bone mineral density (BMD) varies in different studies. Our aim in this study was to explore the association between obesity (body mass index ≥ 30) and BMD among adults 40–59 years of age.

Methods
This study was conducted on a sample of 2218 participants (986 men and 1232 women) aged 40 to 59 years from the National Health and Nutrition Examination Survey 2011–2018. The independent variable was body mass index (BMI). The outcome variable was lumbar BMD. The associations of BMI with lumbar BMD were examined using multivariable linear regression models.

Results
BMI was positively associated with lumbar BMD after adjusting for other covariates [β 0.006; 95% confidence interval (CI) 0.003–0.008]. An inverted U-shaped association between BMI and lumbar BMD was further identified, with the point of infection at approximately 50 kg/m2. In the subgroup analyses, the relationship between BMI and lumbar BMD in women and blacks was an inverted U-shape.

Conclusion
Based on the results, it may be beneficial to appropriately increase BMI to promote BMD. However, considering the inverted U-shaped association, excessive BMI may be harmful to bone health in women and blacks.
A positive feedback loop between gastric cancer cells and tumor-associated macrophage induces malignancy progression
Authors: Piao Haiyan , Fu Lingfeng , Wang Yuxin , Liu Yang , Wang Yue , Meng Xiangyu , Yang Dong , Xiao Xiang , Zhang Jun 
Published: May 2022

Abstract
Background
Hypoxia and inflammation tumor microenvironment (TME) play a crucial role in tumor development and progression. Although increased understanding of TME contributed to gastric cancer (GC) progression and prognosis, the direct interaction between macrophage and GC cells was not fully understood.

Methods
Hypoxia and normoxia macrophage microarrays of GEO database was analyzed. The peripheral blood mononuclear cell acquired from the healthy volunteers. The expression of C-X-C Motif Chemokine Ligand 8 (CXCL8) in GC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR), western-blot, Elisa and immunofluorescence. Cell proliferation, migration, and invasion were evaluated by cell counting kit 8 (CCK8), colony formation, real-time imaging of cell migration and transwell. Flow Cytometers was applied to identify the source of cytokines. Luciferase reporter assays and chromatin immunoprecipitation were used to identify the interaction between transcription factor and target gene. Especially, a series of truncated and mutation reporter genes were applied to identify precise binding sites. The corresponding functions were verified in the complementation test and in vivo animal experiment.

Results
Our results revealed that hypoxia triggered macrophage secreted CXCL8, which induced GC invasion and proliferation. This macrophage-induced GC progression was CXCL8 activated C-X-C Motif Chemokine Receptor 1/2 (CXCR1/2) on the GC cell membrane subsequently hyperactivated Janus kinase 1/ Signal transducer and activator of transcription 1 (JAK/STAT1) signaling pathway. Then, the transcription factor STAT1 directly led to the overexpression and secretion of Interleukin 10 (IL-10). Correspondingly, IL-10 induced the M2-type polarization of macrophages and continued to increase the expression and secretion of CXCL8. It suggested a positive feedback loop between macrophage and GC. In clinical GC samples, increased CXCL8 predicted a patient’s pessimistic outcome.

Conclusion
Our work identified a positive feedback loop governing cancer cells and macrophage in GC that contributed to tumor progression and patient outcome.
Beta 2 adrenergic receptor and mu opioid receptor interact to potentiate the aggressiveness of human breast cancer cell by activating the glycogen synthase kinase 3 signaling
Authors: Rousseau Bénédicte , Murugan Sengottuvelan , Palagani Ajay , Sarkar Dipak K. 
Published: May 2022

Abstract
Background
Opioid and beta-adrenergic receptors are recently shown to cross talk via formation of receptor heterodimers to control the growth and proliferation of breast cancer cells. However, the underlying cell signaling mechanism remained unclear.

Methods
To determine the effect of the interaction of the two systems in breast cancer, we employed triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468, CRISPR or chemical inhibition or activation of beta-adrenergic receptors (B2AR) and mu-opioid receptors (MOR) gene, and PCR array technology and studied aggressive tumor phenotype and signaling cascades.

Results
We show here that in triple-negative breast cancer cells, the reduction in expression B2AR and MOR by genetic and pharmacological tools leads to a less aggressive phenotype of triple-negative breast cancer cells in vitro and in animal xenografts. Genomic analysis indicates the glycogen synthase kinase 3 (GSK3) pathway as a possible candidate messenger system involved in B2AR and MOR cross talk. GSK3 inactivation in MDA-MB-231 and MDA-MB-468 cells induced similar phenotypic changes as the inhibition of B2AR and/or MOR, while a GSK3 activation by wortmannin reversed the effects of B2AR and/or MOR knockdown on these cells. GSK3 inactivation also prevents B2AR agonist norepinephrine or MOR agonist DAMGO from affecting MDA-MB-231 and MDA-MB-468 cell proliferation.

Conclusions
These data confirm a role of B2AR and MOR interaction in the control of breast cancer cell growth and identify a possible role of the GSK3 signaling system in mediation of these two receptors’ cross talk. Screening for ligands targeting B2AR and MOR interaction and/or the GSK3 system may help to identify novel drugs for the prevention of triple-negative breast cancer cell growth and metastasis.
Analgesic effect of auricular point acupressure for acute pain in patients with dementia: study protocol for a randomized controlled trial
Authors: Chai Xiao-Min , Shi Hong-Yan , Zhang Jun-Jun , Wang Lei , Gao Hai-Xiang , Dai Ya-Liang , Gao Lu-Lu , Yu Jian-Qiang , Li Yu-Xiang , Wang Carol Chunfeng 
Published: May 2022

Abstract
Background
Common and frequent as acute pain is, it is often underestimated and undertreated in older people with dementia in nursing homes and inadequate pain management remains an issue.

Methods
The study is designed to be a randomized, sham-controlled trial and is underway in nursing homes located in China. A total of 206 dementia patients are being recruited from nursing homes in Yinchuan, China. They are randomly allocated to an intervention or a controlled group in a 1:1 ratio. The intervention group will be treated with true APP therapy, while the other group will receive APP at sham point stimulation therapy. The patients will be assessed at baseline (T0), at 5 min during performing the intervention (T1), and at 5 min after completion of the intervention (T2). The primary outcome is the level of pain relief at T1 and T2. Physiological parameters, side effects and additional use of analgesics during the procedure, satisfaction from caregivers, and acceptance of patients are evaluated as secondary outcomes.

Discussion
The results of this study are expected to verify the analgesic effect of APP for acute pain in patients with mild dementia in nursing homes. It has the potential to prompt APP therapy to be implemented widely in dementia patients with acute pain in nursing homes.

Trial registration
Chinese Clinical Trial Registry ChiCTR2100047932. Registered on 27 June 2021. Currently, patient recruitment is ongoing. Recruitment is expected to take place from December 2020 to December 2021.
Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies
Authors: Álvaro-Alonso Elena Alba , Lorenzo Mª Paz , Escobar-Rodríguez Ismael , Aguilar-Ros Antonio 
Published: May 2022

Abstract
Purpose
The Pharmacy Service of the Infanta Leonor University Hospital acquires, compounds, distributes and dispenses more than 3000 L of methadone oral solution to Drug Addiction Patients Centers per year. Our purpose is to develop and validate an improved high performance liquid chromatography (HPLC) method to quantify methadone hydrochloride in a new oral solution with methylhydroxybenzoate (methylparaben) and propylhydroxybenzoate (propylparaben) to be implemented in physicochemical stability studies that allow to provide more information and even to increase the beyond-use date.

Methods
A HPLC-Agilent® 1100 equipment, comprising a quaternary pump and an ultraviolet diode-array-detector (DAD) was used. An analytical method development and validation was completed. The curve was constructed from methadone working concentrations of 75–125% (7.5, 9.0, 10.0, 11.0 and 12.5 mg/mL) to assess the linear relationship between the concentration of the analyte and the obtained areas. Precision and accuracy were calculated. Detection and quantification limit (LD, LQ) were estimated using the EURACHEM method. Forced-degradation studies were also performed.

Results
Chromatographic conditions were: flow rate 1.6 mL/min; mobile phase 55% acetonitrile and 45% sodium phosphate 25 mM (pH = 10); injection volume was 5 µL. The column was a Waters-XTerra™ RP18, maintained at 40 °C. DAD was λ = 254 nm. Retention times for methadone, methylparaben and propylparaben were 4.34, 0.70 and 0.88 min respectively.
The method was linear (y = 284.3x − 97.8, r = 0.996). Instrumental precision was 0.33% for standards (n = 10); intra-assay precision 0.53% (n = 6) and inter-assay precision 1.95% (n = 12). The relative standard deviation percentage for accuracy was 1.28%. The recovery percentage was 101.5 ± 1.5%. LQ and LD were 2.18 µg/mL and 2.0 µg/mL respectively. The most destabilizing conditions were oxidizing and alkaline. The chromatograms confirmed no interference with the methadone signal.

Conclusions
The HPLC method has proved to be valid and reproducible for methadone quantification in a new oral solution with methylparaben and propylparaben. This assay is a rapid, simple and reliable technique that can be used in daily analysis and physicochemical stability studies.
Inhibitory effect of lignin on the hydrolysis of xylan by thermophilic and thermolabile GH11 xylanases
Authors: Kellock Miriam , Rahikainen Jenni , Borisova Anna S. , Voutilainen Sanni , Koivula Anu , Kruus Kristiina , Marjamaa Kaisa 
Published: May 2022

Abstract
Background
Enzymatic hydrolysis of lignocellulosic biomass into platform sugars can be enhanced by the addition of accessory enzymes, such as xylanases. Lignin from steam pretreated biomasses is known to inhibit enzymes by non-productively binding enzymes and limiting access to cellulose. The effect of enzymatically isolated lignin on the hydrolysis of xylan by four glycoside hydrolase (GH) family 11 xylanases was studied. Two xylanases from the mesophilic Trichoderma reesei, TrXyn1, TrXyn2, and two forms of a thermostable metagenomic xylanase Xyl40 were compared.

Results
Lignin isolated from steam pretreated spruce decreased the hydrolysis yields of xylan for all the xylanases at 40 and 50 °C. At elevated hydrolysis temperature of 50 °C, the least thermostable xylanase TrXyn1 was most inhibited by lignin and the most thermostable xylanase, the catalytic domain (CD) of Xyl40, was least inhibited by lignin. Enzyme activity and binding to lignin were studied after incubation of the xylanases with lignin for up to 24 h at 40 °C. All the studied xylanases bound to lignin, but the thermostable xylanases retained 22–39% of activity on the lignin surface for 24 h, whereas the mesophilic T. reesei xylanases become inactive. Removing of N-glycans from the catalytic domain of Xyl40 increased lignin inhibition in hydrolysis of xylan when compared to the glycosylated form. By comparing the 3D structures of these xylanases, features contributing to the increased thermal stability of Xyl40 were identified.

Conclusions
High thermal stability of xylanases Xyl40 and Xyl40-CD enabled the enzymes to remain partially active on the lignin surface. N-glycosylation of the catalytic domain of Xyl40 increased the lignin tolerance of the enzyme. Thermostability of Xyl40 was most likely contributed by a disulphide bond and salt bridge in the N-terminal and α-helix regions.

Graphical Abstract
Recycling industrial food wastes for lipid production by oleaginous yeasts Rhodosporidiobolus azoricus and Cutaneotrichosporon oleaginosum
Authors: Donzella Silvia , Serra Immacolata , Fumagalli Andrea , Pellegrino Luisa , Mosconi Giacomo , Lo Scalzo Roberto , Compagno Concetta 
Published: May 2022

Abstract
Background
Microbial lipids have been emerging as a sustainable alternative to vegetable oils and animal fat to produce biodiesel and industrial relevant chemicals. The use of wastes for microbial processes can represent a way for upgrading low value feedstock to high value products, addressing one of the main goals of circular economy, the reduction of wastes by recycling. Two oleaginous yeasts, Rhodosporidiobolus azoricus and Cutaneotrichosporon oleaginosum, were used in this study to demonstrate the feasibility of the proposed approach.

Results
In this study wastes from industrial food processing, as pumpkin peels and syrup from candied fruits manufacture, were used for yeast cultivation and for lipids production. Evaluation of growth and sugar consumption revealed marked differences between the yeasts in capacity to utilize the main sugars present in the feedstock. In particular, we observed an unexpected limitation in glucose metabolism on mineral defined media by R. azoricus. Both species showed ability to grow and accumulate lipids on media exclusively composed by undiluted pumpkin peel hydrolysate, and R. azoricus was the best performing. By a two-stage process carried out in bioreactor, this species reached a biomass concentration of 45 g/L (dry weight) containing 55% of lipids, corresponding to a lipid concentration of 24 g/L, with a productivity of 0.26 g/L/h and yield of 0.24 g lipids per g of utilized sugar.

Conclusions
Wastes from industrial food processing were sufficient to completely support yeast growth and to induce lipid accumulation. This study provides strong evidence that the concept of valorisation through the production of lipids from the metabolism of nutrients present in agro-industrial wastes by oleaginous yeasts is promising for implementation of biotechnological processes in a circular economy contest.
Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
Authors: de Castro Rodrigo O. , Carbajal Agustin , Previato de Almeida Luciana , Goitea Victor , Griffin Courtney T. , Pezza Roberto J. 
Published: May 2022

AbstractTestis development and sustained germ cell production in adults rely on the establishment and maintenance of spermatogonia stem cells and their proper differentiation into spermatocytes. Chromatin remodeling complexes regulate critical processes during gamete development by restricting or promoting accessibility of DNA repair and gene expression machineries to the chromatin. Here, we investigated the role of Chd4 and Chd3 catalytic subunits of the NURD complex during spermatogenesis. Germ cell-specific deletion of chd4 early in gametogenesis, but not chd3, resulted in arrested early gamete development due to failed cell survival of neonate undifferentiated spermatogonia stem cell population. Candidate assessment revealed that Chd4 controls expression of dmrt1 and its downstream target plzf, both described as prominent regulators of spermatogonia stem cell maintenance. Our results show the requirement of Chd4 in mammalian gametogenesis pointing to functions in gene expression early in the process.
Mobile health apps for systemic lupus erythematosus and lupus nephritis: a critical appraisal
Authors: Ramasamy Akshara , Dugyala Poojitha , Mohan Chandra 
Published: May 2022

Abstract
Objectives
To critically assess the quality and functionality of the available mobile apps for systemic lupus erythematosus and lupus nephritis patients.

Methods
Two reviewers independently searched the App Store and Google Play Store for eligible mobile health (mHealth) apps. Two separate searches were done: one for systemic lupus erythematosus (SLE) and the other for lupus nephritis (LN). The Mobile App Rating Scale (MARS) was used to rate the quality of all selected apps.

Results
From the systemic lupus erythematosus screening, our search yielded 841 apps. Within these 841 apps, 17 of them were ultimately included. From the lupus nephritis screening, our search returned 1152 apps. Of the 1152 apps, 2 were ultimately included. Our search strategy included apps specifically designed for patients with SLE and LN. The MARS average of all the systemic lupus erythematosus apps was 2.7 out of 5. The MARS average of the two lupus nephritis apps was 2.6 out of 5.

Conclusion
Mobile health apps can serve as an effective tool for telehealth, engaging patients in self-care and for increasing the quality of life of lupus patients. While several mobile health technologies exist for patients with SLE and LN, there is still a significant need for app quality improvement and expanding the comprehensiveness of offered functions.