bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dikkopf-1 promotes matrix mineralization of osteoblasts by regulating Ca+-CAMK2A-CREB
Authors: Park Hyosun , Jo Sungsin , Jang Mi-Ae , Choi Sung Hoon , Kim Tae-Hwan 
Published: June 2022

Abstract
Dickkopf-1 (DKK1) is a secreted protein that acts as an antagonist of the canonical WNT/β-catenin pathway, which regulates osteoblast differentiation. However, the role of DKK1 on osteoblast differentiation has not yet been fully clarified. Here, we investigate the functional role of DKK1 on osteoblast differentiation. Primary osteoprogenitor cells were isolated from human spinal bone tissues. To examine the role of DKK1 in osteoblast differentiation, we manipulated the expression of DKK1, and the cells were differentiated into mature osteoblasts. DKK1 overexpression in osteoprogenitor cells promoted matrix mineralization of osteoblast differentiation but did not promote matrix maturation. DKK1 increased Ca+ influx and activation of the Ca+/calmodulin-dependent protein kinase II Alpha (CAMK2A)-cAMP response element-binding protein (CREB) and increased translocation of p-CREB into the nucleus. In contrast, stable DKK1 knockdown in SaOS2 cells exhibited reduced nuclear translocation of p-CREB and matrix mineralization. Overall, we suggest that manipulating DKK1 regulates the matrix mineralization of osteoblasts by Ca+-CAMK2A-CREB, and DKK1 is a crucial gene for bone mineralization of osteoblasts.
Comparative analysis of the bacterial community in the cuttlefish Sepia pharaonis with different statuses
Authors: 许 丽婷 , Ruan Yilong , Jiang Maowang , Peng Ruibing , Jiang Xiamin , Zhang Weiwei , Han Qingxi 
Published: June 2022

Abstract
The cuttlefish Sepia pharaonis is rich in nutritional value, and thus has been cultured in large-scale artificial culture. During its culture process in 2021 and 2022, a contagious disease with a mortality as high as 90% occurred when the dorsal mantle length of the cuttlefish was approximately 2.5 cm, which presented as obvious symptoms of small white spots on their dorsal mantle surface. To address the cause of the disease outbreak from a microbiome perspective, the bacterial communities in the healthy, infected, and dead cuttlefish S. pharaonis were assessed using bacterial culturing and 16S rRNA sequencing technology. Cultivable bacteria showed that there was an antagonistic phenomenon in the healthy S. pharaonis, and the highest diversity of bacteria was found in the dead individuals. The bacterial community was distinctly different among the three groups of samples, characterized by decreased alpha diversity and alteration of the dominant bacteria and bacterial community structures as the disease progressed. In addition, bacterial genera can be used as biomarkers for this disease, including Photobacterium, Bacillus, and Halarcobacter. In conclusion, the balance of the microbiome is necessary for S. pharaonis to remain healthy, and biomarker bacteria can aid in the early detection of occurrences of disease.
Sodium butyrate alleviates chronic alcoholic neuroinflammation by regulating microgila polarization through GPR109A / PPAR-γ / NF-κB signaling pathway
Authors: Wei Huiling , Ren Yi , Yu Chunyang , Zhang Chun , Guo Li , Wang Ting , Chen Feifei , Zhang Xiaoxia , Wang Hao , Liu Juan 
Published: June 2022

Abstract
Background
Alcohol can cause neuroinflammation, leading to neuron damage and further memory and cognitive impairment. Recent animal studies have shown that the exposure to chronic alcohol consumption induces robust inflammatory microglial activation in the brain. However, as a novel anti-inflammation approach, the impact of sodium butyrate on chronic alcohol-induced neuroinflammation still remains unclear.
Methods
Sixty female C57BL/6J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. Mice were subjected to different behavioral tests to assess aberrant behaviours (deficits in cognitive functions, depression and anxiety). Pathological changes were further investigated by Hematoxylin and eosin staining (HE) and Nissl staining. The microglial activation and microglial polarization were observed by immunohistochemistry (IHC), immunofluorescence (IF) and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of inflammatory factors. G-protein coupled receptor 109A (GPR109A), peroxisome proliferator-activated receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) mRNA and protein levels were evaluated by reverse transcription‑quantitative (RT‑q) PCR and western blot (WB).
Results
As indicated by the behavioural tests, inflammatory indicators, microglial activation (M1/M2 microglia polarization) and brain morphology, sodium butyrate administration ameliorated aberrant behaviours (locomotor hypoactivity, anxiety disorders and depressive behaviours, impaired learning and spatial recognition memory), effectively reduced neuroinflammation and neuronal damage. The effectiveness of sodium butyrate may attribute to the GPR109A receptor in microglia by up-regulating the expression of PPAR-γ and inhibiting the activation of NF-κB.
Conclusion
Sodium butyrate ameliorates neuroinflammation induced by chronic alcohol exposure and improves memory and cognitive functions in mice via modulating microglia-mediated GPR109A / PPAR-γ / NF-κB signaling pathway.
Evaluation and mapping of the social values for ecosystem services in the urban river landscape. Case study: Zamora and Malacatos rivers in Loja - Ecuador
Authors: Alvarado-Arias Natalia , Cabrera-Torres Francisco , Moya-Almeida Vinicio 
Published: June 2022

Abstract
Context:
The progressive degradation of urban rivers has serious socio-ecological impacts, compromising the provision of ecosystem services (ES), thus affecting the quality of life of the inhabitants, however, few are integrated into the social perspective together with the diagnosis of the immaterial and non-monetary benefits as complementary knowledge to traditional approaches.
Objective
This work sought to add complexity to the diagnosis of the ES, through the identification and mapping of the positive and negative landscape preferences of the local community concerning the urban fluvial landscape of the Zamora and Malacatos rivers in the urban-periurban environment of the city of Loja in Ecuador.
Methods
This work is resolved with the dissemination of a virtual geo-form, processed with the SolVES model, a participatory mapping tool (PPGIS) that integrates social and biophysical variables.
Results
The value points obtained revealed different spatial patterns for each social value group. The positives exhibited more dispersed patterns, clustering in peripheral areas. The negatives were concentrated in the centre of the city. Of the ten social values studied, the most relevant were: Learning, Aesthetic, Therapeutic and Disgust, Poor and Inaccessible Infrastructure, and Flood Threat. The environmental variable with the greatest contribution was the Horizontal Distance to Green Areas.
Conclusions
The results help to identify possible places of conflict as well as attractive locations based on place-based knowledge, which enables a better understanding of the value of the benefits of urban rivers, further, it stimulates the inclusion of the local community in the development of more participatory management and governance and sensitive to the landscape.
A resampling-based empirical Bayes method for precise false discovery rate estimation under dependence
Authors: Hawinkel Stijn , Bijnens Luc , Thas Olivier 
Published: June 2022

Abstract
Many methods exist for controlling or estimating the false discovery rate (FDR), which is the mean of the false discovery proportion (FDP). However, in the presence of correlation between the test statistics, the FDP may show considerable variation between repeated experiments. Here we first provide an intuitive explanation for this phenomenon by demonstrating an increased sampling variability of the test statistics when tests are dependent. Next, we propose an empirical Bayes solution based on resampling techniques that is applicable to many types of test statistics, and allows to estimate the null distribution more precisely. This reduces the variability of the FDP and even yields an increase in sensitivity. Furthermore the implicit assumptions made by empirical Bayes approaches to false discovery rate estimation are explored. We demonstrate our approach on the differential expression problem in RNA-sequencing, and on a data integration problem of microbiome sequence count and flow cytometry data, where the test statistics are correlated by design. Our algorithm is available as the R-package reconsi.
Pan-cancer analysis reveals nucleolar and spindle-associated protein 1 as a predictive marker for human cancer
Authors: Zheng Jiehua , Chen Yaokun , Wu Jinyao , Zheng Daitian , Liu Yiyuan , Cai Jiehui , Chen Lingzhi , Ji Zeqi , Tian Huiting , Yang Qiuping , Chen Yexi , Li Zhiyang 
Published: June 2022

Abstract
Understanding the driving factors and the common and unique mechanisms of human tumorigenesis is essential for the development of effective treatments. As a potential oncogene, nucleolar and spindle-associated protein 1 (NUSAP1) participates in the regulation of a variety of tumor cells (e.g. hepatocellular carcinoma), lung cancer proliferation, metastasis, and drug resistance. However, a systematic pan-cancer analysis has not yet been carried out. Using The Cancer Genome Atlas and Gene Expression Omnibus datasets, the Human Protein Atlas, and several bioinformatics tools, we investigated the expression and potential carcinogenic effects of NUSAP1 in 33 tumors. We found that NUSAP1 overexpression usually indicated poor overall survival in patients with tumors with high NUSAP1 expression, such as lung cancer, breast cancer, and hepatocellular carcinoma. We also analyzed the NUSAP1 mutation burden in cancers and NUSAP1-related survival in patients with tumors, compared NUSAP1 phosphorylation in normal and primary tumor tissues, and explored possible functional mechanisms of NUSAP1-mediated tumorigenesis. The current pan-cancer analysis provides a relatively comprehensive overview of the carcinogenic effects of NUSAP1 in a variety of human cancers, which may stimulate new ideas for treating several tumors.
Effective Localization of Energy Harvesting Empowered UWSNS Using Krill Herd Optimization and Support Value
Authors: Vankdothu Ramdas , Abdul Hameed Mohd , Banothu Balaji 
Published: June 2022

Abstract
In this paper, using support value-based adaptive fuzzy c-means clustering and krill herd optimization, we demonstrate how to effectively localise energy harvesting enabled underwater wireless sensor networks. Replacement or recharge of a sensor node's battery is challenging in an aquatic environment. As a result, building an energy harvester that is both efficient and dependable is essential to ensure the continued operation of an underwater wireless sensor network (UWSN). We presented a technique that is capable of harvesting energy from a variety of sources and distributing it to the sensor nodes. The proposed work gathers energy from sensor nodes with insufficient batteries and begins communicating once they have sufficient energy storage. The RSS (received signal strength) and TOA (time of arrival) of active nodes are used to determine the network's location. This is based on the characteristics of the channels used in underwater optical communication. Following that, the RSS and TOA measures' support values are determined. Then, using support value-based adaptive fuzzy c-means clustering, support kernel matrices are created. The proposed support kernel matrices significantly reduce path error during data transmission. To increase sensor node localisation, the obtained support kernel matrices are further improved using a krill herd optimization approach. The proposed method outperforms existing techniques in the laboratory.
Isolation Enhancement in UWB-MIMO Antenna Using Decoupling Structure
Authors: Srinivasa Pasumarthi , Ramya Vinukonda Venkata Sesha , Sireesha Vadlamudi 
Published: June 2022

Abstract
This article presents a compact UWB MIMO antenna. The proposed MIMO antenna covers bandwidth of 3.9–13.4 GHz. The proposed MIMO antenna gives good isolation between two elements from 8-13.4 GHz. In order to reduce mutual coupling over entire operating band a novel decoupling is inserted between them. It provides minimum of -18 dB isolation over entire operating band. The performance of the MIMO antenna is further evaluated in terms of gain, ECC, radiation pattern, and diversity gain.
Deep Learning Artificial Intelligence Evaluation of Optical Coherence Tomography Scans in a Non-infectious Pan-uveitis Cohort
Authors: Barbosa Joshua , Zlojutro Paul , Gardner Peter , Le Kim , Lin Xihui 
Published: June 2022

Abstract
BACKGROUND: To evaluate Deep Learning (DL) Artificial Intelligence (AI) application to optical coherence tomography scans of non-infectious pan-uveitis patients. METHODS: Consecutive patients with non-infectious pan-uveitis were included in the study if they had an OCT scan (Zeiss, Germany) of the macula. Inflammation was graded on the Nussenblatt scoring system by a uveitis specialist. A DL AI system developed using Python 3.9 and open source TensorFlow software was then trained to classify inflammation as high, low, or none. Performance was assessed by AUC scores. Training to cross-validation used an 80:20 split with 2000 iterations in all evaluations.RESULTS: 154 scans of 52 patients were analyzed. 38 (70.4%) of patients were female and the mean age of participants was 50.3 ± 15.5 years. 58 (37.7%) of OCT scans were graded as no inflammation, 61 (39.6%) scans as mild inflammation, and 35 (22.7%) scans as high inflammation. The AUC for OCT images was 0.830 (CI95: 0.784 to 0.876).CONCLUSION: Deep Learning AI can be applied in the grading of non-infectious pan-uveitis OCT scans in a precise manner.
Activation of HCN channels caused by elevated cAMP levels in periaqueductal gray promotes bone cancer pain
Authors: Lei Xiaolu , Yan Yan , Zeng Junwei , Wang Rong , Li Song , Xiao Zhi , Liu Xiaohong 
Published: June 2022

Abstract
The periaqueductal gray (PAG) is an important relay center for the descending pathways that regulate nociceptive information transduction. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play critical roles in the nerve injury-induced pain hypersensitivity. Previous studies have identified that HCN1 and HCN2 channel protein located in the ventral-lateral periaqueductal gray (vlPAG), a region important for pain regulation. However, it is not clear whether the HCN channel in vlPAG is involved in bone cancer pain (BCP). In this study, we assessed the role of HCN channels in BCP by measuring changes of HCN channel expression and activity in vlPAG neurons in bone cancer rats. In the present study, the BCP model was established by injecting SHZ-88 breast cancer cells into the right tibia bone marrow in rats. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured to evaluate pain behavior in rats. HCN1 and HCN2 channels expression in vlPAG were detected by using Western Blot and immunohistochemistry. In addition, the cAMP level in vlPAG neurons was detected by ELISA, and HCN channel current (Ih) of vlPAG neurons was recorded by whole cell patch-clamp to evaluate HCN channel activity. As a result, decreased MWT and TWL were observed in rats on 7d after SHZ-88 cell inoculation, and the allodynia was sustained until 21d after inoculation. At the same time, HCN1 and HCN2 channels expression and neuronal Ih in vlPAG were significantly increased in BCP rats. In addition, the level of cAMP in vlPAG also increased after SHZ-88 cell inoculation. Furthermore, intravlPAG injection of ZD7288 (HCN channels antagonist) could significantly reduce hyperalgesia and the elevation of cAMP in vlPAG in BCP rats. Our observations suggest that the elevation of cAMP may promote the activation of HCN channels in vlPAG in bone cancer rats, thereby promoting the development of bone cancer pain.
Long-term retrospective study on the incidence of urinary calculi in Wuwei, Gansu Province, China, 1995–2016
Authors: Zhang Shuyuan , Song Shuxuan , Ji Zhaohua , Liu Kun , Ye Yancheng , Zhang Wenhua , Chen Yajun , Shao Zhongjun , Long Yong , Zhang Weilu 
Published: June 2022

Abstract
Objective: This long-term retrospective study explored the cause of increasing urinary calculi in Wuwei, China, from 1995 to 2016.Methods: Joinpoint v10.0, SPSS v22.0, and Excel 2019 were adopted to extract and analyze the medical records of patients with urolithiasis from 12 hospitals in Wuwei city. ArcGIS v10.8 was employed to establish a geographical distribution map and spatial and spatiotemporal analyses were applied to detect epidemic clusters using SaTScan v9.6.Results: Among the 5 497 patients with urolithiasis (mean age 43.07 ± 15.95 years), the majority were male (3 843, 69.9%), resulting in a sex ratio of 2.32:1. The incidence of urolithiasis in males and females showed an overall upward trend, with an annual percentage change (APC) of 15.1% (95% confidence interval (CI): 12.3%–18.1%) and 9.4% (95% CI: 16.4%–22.5%), respectively. From 1995 to 2016, the temporal and spatial distribution of urolithiasis showed an increasing trend in overall incidence and area, and we identified four clusters that allowed for the development and dynamic monitoring of urolithiasis in Wuwei. With the implementation of the new Rural Cooperative Medical Care System (NRCMS), improved insurance reimbursement and coverage for urolithiasis should help reduce the disease burden.Conclusions: In this study, the incidence of urolithiasis showed an upward trend between 1995 and 2016. Regular disease screening and early diagnosis for high-risk populations should be strengthened, which will help improve the prevention and treatment of urolithiasis. This study should provide a reference for local governments to initiate policies for the prevention and treatment of urolithiasis.
Sex differences exist in adult heart group 2 innate lymphoid cells
Authors: Peng Hongyan , Wu Shuting , Wang Shanshan , Yang Qinglan , Wang Lili , Zhang Shuju , Huang Minghui , Li Yana , Xiong Peiwen , Zhang Zhaohui , Cai Yue , Li Liping , Deng Yafei , Deng Youcai 
Published: June 2022

Abstract
Background: Group 2 innate lymphoid cells (ILC2s) are the most dominant ILCs in heart tissue, sex-related differences exist in mouse lung ILC2 phenotypes and functions; however, it is still unclear whether there are sex differences in heart ILC2s.Results: Compared with age-matched wild-type (WT) male mice, 8-week-old but not 3 week-old WT female mice harbored an obviously greater percentage and number of heart ILC2s in homeostasis present. However, the percentage of killer-cell lectin-like receptor G1 (Klrg1)- ILC2s were higher but the Klrg1+ ILC2s were lower in female mice than in male mice in both the heart tissue of 3- and 8-week-old mice. Eight-week-old Rag2-/- mice also showed sex differences similar to those of age-matched WT mice. Regarding surface marker expression, compared to age-matched male mice, WT female mice showed higher expression of CD90.2, and lower expression of Klrg1 and Sca-1 in heart total ILC2s. No sex difference in IL-4 and IL-5 secretion by male and female mice heart ILC2s. Increased IL-33 mRNA levels within the heart tissues were also found in female mice compared with male mice.Conclusions: These results have revealed the greater numbers of ILC2s, higher expression of CD90.2, reduced Klrg1 and Sca-1 expression in the heart of female mice than male mice and no sex difference in IL-4 and IL-5 production in male and female mice heart ILC2s. These sex differences of heart ILC2s might be due to the heterogeneity of IL-33 within the heart tissue.
Detailed characterization of PD-1/PD-L1 and CTLA4 expression and tumor-infiltrating lymphocytes in yolk sac tumors
Authors: Xu Hanjie , Zhang Danya , Zhao Can , Qin Lingzhi , Wei Rui , Xi Ling , Li Fei 
Published: June 2022

Abstract
Background: Immune checkpoint blockade (ICB) is considered as a promising approach for cancer treatment. However, the potency of ICB therapy in yolk sac tumors (YSTs) has not been confirmed, and the comprehensive analysis of tumor immune microenvironment and the expression of PD-1/PD-L1 and CTLA4 were also not thoroughly evaluated.Methods: Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tumor specimens from 23 YSTs patients to detect the density and distribution of tumor-infiltrating T cells, tertiary lymphoid structures (TLSs), as well as the expression of PD-1/PD-L1 and CTLA4. Results: Overall, more than half (61%) of all patients exhibited an immune-desert phenotype based on CD3+ T cells. PD-1 expression was identified in five tumor samples (21.7%), and PD-L1 expression exhibited a different positive rate in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) (39.1% and 17.4%). Noteworthily, the rate of positive CTLA4 expression in both TCs and TILs was markedly higher (69.6% and 56.5%) than those of PD-1 and PD-L1 expression. Furthermore, TLSs were observed in 21.74% of all tissues, and samples with TLSs exhibited significantly higher densities of TILs and higher expression of immune checkpoint molecules, particularly PD-1/PD-L1. In addition, tumors located in testes also exhibited a higher density of TILs and higher expression of immune checkpoint molecules.Conclusion: Although a high frequency of CTLA4 expression was found, PD-1/PD-L1 expression, the immune-inflamed phenotype, and TLSs were low frequency in YSTs, suggesting that only a few YSTs patients may be benefit form ICB therapy. Remarkably, patients with tumors located in testes are more likely to benefit from ICB therapy.
The effects of romosozumab combined with active vitamin D 3 on fracture healing in ovariectomized rats
Authors: Takase Ryota , Tsubouchi Yuta , Otsu Takefumi , Kataoka Takashi , Iwasaki Tatsuya , Kataoka Masashi , Tsumura Hiroshi 
Published: June 2022

Abstract
Background: In this study, we investigated the potential acceleration of fracture healing and the bone mineral density-increasing effects of the combination therapy of romosozumab and active vitamin D3 on fractures in ovariectomized rats.Methods: Ovariectomy was performed on forty 24-week-old female Sprague–Dawley rats. After 8 weeks, the rats underwent removal of the periosteum and osteotomy of the femoral shaft followed by osteosynthesis with intramedullary nailing to create fracture models. After surgery, the 40 rats were divided into four groups: the C group (control), the R group (romosozumab, 25 mg/kg, once a month via subcutaneous injection), the VD group (active vitamin D3, 0.2 µg/kg, twice a week via subcutaneous injection), and the R + VD group. A further 10 rats were prepared as the sham group. Ten weeks postintervention, both femurs were removed from all rats, and blood was collected. Soft X‑ray imaging was used to evaluate bone union, and microcomputed tomography (micro-CT) was used for bone morphometric evaluation. Toluidine blue staining of undecalcified specimens was used for histopathological evaluation, and bone turnover marker levels were measured using enzyme-linked immunosorbent assay.Results: Bone morphometry analysis by micro-CT revealed increased mineral density of the trabecular bone in rat femurs from the R + VD group, demonstrating the effectiveness of combination therapy with romosozumab plus active vitamin D3. However, no differences in bone union evaluated using soft X-ray imaging were observed, demonstrating no acceleration of fracture healing.Conclusions: Although combination therapy with romosozumab and active vitamin D3 increased the trabecular bone volume, there was no evidence that it could accelerate fracture healing.