bluuebunny/crossref_metadata_2025_split huggingface dataset:
A functional SNP in miR-625-5p binding site of AKT2 3'UTR is associated with noise-induced hearing loss susceptibility in the Chinese population
Authors: Miao Long , Wang Boshen , Zhang Juan , Yin Lihong , Pu Yuepu 
Published: February 2021

Abstract
This study aimed to explore the association of several single nucleotide polymorphisms (SNPs) within the AKT2 gene and noise-induced hearing loss (NIHL) susceptibility and explore the potential mechanism underlying NIHL. Three SNPs (rs2304186, rs41275750 and rs76524493) were genotyped in a Chinese population which consists of 690 NIHL patients and 650 normal hearing controls. Bioinformatic analysis was conducted to predict the potential miRNA-binding site of SNPs. Cell transfection and dual-luciferase reporter assay were performed to investigate the potential molecular mechanism of SNPs involved in NIHL. The results revealed rs2304186 GT genotype (OR = 1.41; 95% CI = 1.09–1.83) and TT genotype (OR = 1.51; 95% CI = 1.08–2.10) imparted increased risk of NIHL, and the increased risk could also be found in a dominant model (OR = 1.44; 95% CI = 1.12–1.84). The stratification analysis showed that rs2304186 GT/TT conferred a higher risk for NIHL, especially in subgroups of male, age (35–45 and > 45 years), noise exposure time (> 16 years), and noise exposure level (≤ 85 and ≥ 92 dB), compared with GG genotype. In addition, the haplotype TCCTACT (rs2304186-rs41275750-rs76524493) was associated with NIHL risk (OR = 1.19; 95% CI = 1.02–1.40). Rs2304186 G allele combined with hsa-miR-625-5p mimics could significantly decrease the luciferase activity compared with T allele, indicating rs2304186 altered the binding affinity of hsa-miR-625-5p to SNP rs2304186 mutation region, thus directly targeting AKT2. In conclusion, our study provides evidence for the first time that SNP rs2304186 of AKT2 3′UTR affects NIHL susceptibility by affecting the binding affinity of has-miR-625-5p in an allele-specific manner and it may act as a potential biomarker of NIHL susceptibility.
Multi-institutional Survey of Thymic Carcinoma Patients in Hokushin Region
Authors: Uramoto Hidetaka , Takiguchi Tomoya , Koizumi Tomonobu , Tanimoto Azusa , Hayashi Ryuji , Nakazawa Yozo , Ito Ken-ichi , Nakada Mitsutoshi , Hirono Yasuo , Nishino Yoshikazu , Yano Seiji 
Published: February 2021

Abstract
Background: The purpose of this study was to validate the clinical and epidemiological factors, diagnosis and initial treatment among thymic carcinoma patients.Methods: We surveyed retrospective data from 152,921 cancer patients in 22 principal hospitals.Results: A total of 88 thymic carcinoma cases were newly diagnosed. These patients consisted of 49 men and 38 women, with a median age of 66 years old. Eight patients were discovered in cancer screening, 9 in a voluntary setting, 14 at health checkups, 25 at follow-up of other diseases, and 32 cases by introduction from another hospital. Only 14 cases had been diagnosed with localized disease, but 5 cases were accompanied by regional lymph node metastasis. Furthermore, 12 cases showed infiltration into adjacent organs, and 24 cases had distant metastasis. Eighty-three cases were diagnosed by a pathological diagnosis. A surgical approach, chemotherapy, and radiotherapy were performed for 29, 35 patients, and 31 patients, respectively, while 17 patients received best supportive care.Conclusion: The diagnosis of thymic carcinoma is still difficult, and this disease has a tragically rapid progression if when discovered during follow-up of other diseases. An innovative modality for the early detection of thymic carcinoma is needed in modern medical society.
Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection
Authors: Zhou Zhuo , Zhang Xinyi , Lei Xiaobo , Xiao Xia , Jiao Tao , Ma Ruiyi , Dong Xiaojing , Jiang Qi , Wang Wenjing , Shi Yujin , Zheng Tian , Tan Yuting , Xiang Zichun , Ren Lili , Deng Tao , Jiang Zhengfan , Dou Zhixun , Wei Wensheng , Wang Jianwei 
Published: February 2021

Abstract
The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain to be determined. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells’ self-nucleic acids can be employed as a “danger signal” to alarm the immune system.
Residual Efficacy of Fludora® Fusion Against Anopheles Arabiensis in Simple Huts in Ethiopia
Authors: Animut Abebe , Horstmann Sebastian 
Published: February 2021

Abstract
Emergence and spread of malaria vectors resistant to the available insecticides required a new and efficacious insecticide. Residual efficacy of Fludora® Fusion was evaluated against insecticide susceptible Anopheles arabiensis in ten circular huts similar to the residential huts. Fludora® Fusion WP-SB 562.5, FICAM WP80 and Clothianidin WG70 were sprayed, by experienced technician, on interior wall surfaces: paint, dung, smooth mud, and rough mud. WHO cone bioassays were carried out a month after spraying and thereafter on monthly intervals for 12 months. Knockdown was recorded at 60 minutes and mortality at 24 hours, 48 hours and 72 hours holding time post-exposure. Fludora Fusion induced 100% An. arabiensis mortality during the first four months post-treated on all surface types at 24 hours holding time post-exposure. Its activity remained over 80% from the fifth to the twelfth month post-treated on the surfaces with the exception of two assessment points, at seventh month and eleventh month, on paint and smooth mud surfaces. FICAM induced 100% mortality rate during the first 4 months and 92% mortality during the fifth month post-treatment on painted surfaces. Its activity was over 96% mortality 1-month post-treatment on smooth mud and rough mud surfaces and 92% mortality 2-month post-treatment on dung surfaces. Clothianidin caused 89% and 86% mortality 1-month post-treatment on smooth mud and rough mud surfaces. Fludora Fusion can be used as alternative indoor residual insecticide spraying against An. arabiensis in Ethiopia. However, the insecticide shall also be tested in residential houses prior to employing at a larger scale.
Investigation of Gama Ray Shielding Properties of the (Al:Si) and (Al+Na):Si doped International Simple Glasses (ISG) using Phy-X/PSD and SRIM Software’s
Authors: KAMIŞLIOĞLU Miraç 
Published: February 2021

Abstract
In this investigation, the gamma photon shielding properties for the (Al:Si) and (Al + Na):Si dopped ISG glasses were investigated by using Photon Shielding and Dosimetry (Phy-X / PSD) software for the selected energy range. The obtained results showed that the highest MAC value belong to ISG-A00N glass. It was seen that the MAC values which were examined at all energies changed in harmony with WinXCom. Substituting an atomic fraction of (Al:Si) with (Al + Na):Si resulted in a reduction of the total atomic cross-section of the glass, which lowered the mass attenuation coefficient (MAC). In this study, computations were made for glasses with SiO2, Al2O3, B2O3, Na2O, CaO and ZrO2 content given with ISG-C, ISG-A00, ISG-A12, ISG-A22, ISG-A00N, ISG-A11N, ISG-A18N and ISG-A23N codes. MAC, LAC, HVL, TVL, Zeff, Neff, Ceff Zeq, EBF, EABF and FNRCS calculations were applied to assess the radiation protection parameters by using Phy-X/PSD software. In addition, MSP and PR values were calculated by using the SRIM code. In fact, each obtained parameter provides us very important information on radiation protection, and these methods are frequently used in the literature. ISG-A00N glasses were observed to have the highest attenuation coefficient. Thus, the MAC value gradually decreased as the Al, Na and Si contents increased. Likewise, the HVL, TVL and MFP values changed coherent with this. Moreover, Zeff and Neff values were seen in the ISG-A00N sample to take the maximum values to each other inversely. The most effective glass sample was seen as ISG-A00N glass at the mean free path penetration power of MSP and PR values. When all the results were evaluated, ISG-A00N glass which has the highest Si and Ca contents and density was found to be the glass with the best radiation shielding feature. It is also noteworthy that this glass does not contain any Al component. As the results of the investigation, it was found out that a very small doped of the Si increases the radiation shielding feature on the glass. It was seen that the ISG-A23N had the lowest ∑R value. The obtained results revealed that the ISG-A00N > ISG-A00 > ISG-C > ISG-A12 > ISG-A11N > ISG-A22 > ISG-A18N > ISG-A23N samples, in ascending order that attenuators for low energy radiations.
Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer
Authors: Kurouzmi Sasagu , Kaira Kyoichi , Matsumoto Hiroshi , Kurosumi Masafumi , Yokobori Takehiko , Kanai Yoshikatsu , Sekine Chikako , Honda Chikako , Katayama Ayaka , Furuya Mio , Shiino Sho , Makiguchi Takaya , Mongan Nigel , Rakha Emad , Oyama Tetsunari , Fujii Takaaki , Shirabe Ken , Horiguchi Jun 
Published: February 2021

Abstract
PURPOSE: L-type amino acid transporter 1 (LAT1), also referred to as SLC7A5, is believed to regulate tumor metabolism and be associated with tumor proliferation. In invasive breast cancer, we clinicopathologically investigated the utility of LAT1 expression. METHODS: LAT1 expression was evaluated via immunohistochemistry analyses in 250 breast cancer patients undergoing long-term follow-up. We assessed the relationship between LAT1 expression and the patients’ outcomes and clinicopathological factors. Breast cancer-specific survival stratified by LAT1 expression was assessed.RESULTS: High LAT1 expression was significantly correlated with estrogen receptor (ER) negativity, progesterone receptor negativity, high histological grade, increased tumor-infiltrating lymphocytes, and programmed death ligand 1 positivity. Among the ER-positive and human epidermal growth factor 2-negative type cases, high LAT1 was an independent indicator of poor outcomes (hazard ratio (HR) = 2.97; 95% confidence interval (CI), 1.16–7.62; p = 0.023). Moreover, high LAT1 expression was an independent poor prognostic factor in luminal B-like breast cancer with aggressive features (HR = 3.39; 95% CI, 1.35–8.52; p = 0.0094).CONCLUSIONS: High LAT1 expression identified a subgroup of invasive breast cancer characterized by aggressive behavior and high tumor immunoreaction. Our findings suggest that LAT1 might be a candidate therapeutic target for breast cancer patients, particularly those with luminal B-like type breast cancer.
Botulinum toxin type A relieve neuropathic pain by suppressing the expression of CXCL13/CXCR5 and GAT-1 in chronic constriction injury rats
Authors: Bu Huilian , Bu Huilian , Jiao Pengfei , Jiao Pengfei , Fan Xiaochong , Fan Xiaochong , Gao Yan , Gao Yan , Zhang Lirong , Zhang Lirong , Guo Haiming , Ma Minyu , Ma Minyu 
Published: February 2021

Abstract
Botulinum toxin type A (BTX-A) was widely used to treat neuropathic pain in clinic. The underlying analgesic mechanism of BTX-A involves in axonal transport. The chemokine (C-X-C motif) ligand 13 (CXCL13) and GABA transporter 1 (GAT-1) played important roles in chronic pain. We established a chronic constriction injury (CCI) model. The pain behaviors of rats were measured by testing paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs). The level of proteins was measured by western blots. In our results, the CCI rats showed decrease of PWTs and PWLs, which were relieved by BTX-A. BTX-A reversed the over-expression of CXCL13 and GAT-1 in spinal cord, DRG, sciatic nerve and plantar in CCI rats and characterized in dose-dependent manner. The inhibition of BTX-A on proteins we examined didn’t show significant trend among time points. The analgesic effect of BTX-A disappeared after the axon transport of sciatic nerve blocked by the colchicine. But the PWTs of the colchicine treated CCI rats were higher than non- colchicine-treated CCI rats. Colchicine decreased the levels of CXCL13 and GAT-1 in CCI rats. What’s more, the proteins we examined peaked at the sciatic nerve in the non-colchicine group, but the phenomenon disappeared in the colchicine group. In conclusion, the BTX-A and colchicine relieve neuropathic pain and suppress the increase of CXCL13 and GAT-1. Colchicine prevents the analgesic effect of BTX-A by blocking axon transport. The axon transport may play roles in the peripheral mechanisms of neuropathic pain.
Estimating Age-Specific Mean Sojourn Time of Breast Cancer and Sensitivity of Mammographic Screening by Breast Density among Korean Women
Authors: Choi Eunji , Suh Mina , Jung So-Youn , Jung Kyu-Won , Park Sohee , Jun Jae Kwan , Choi Kui Son 
Published: February 2021

Abstract
Background: High breast cancer incidence among women in forties are specific to Asian, implicating dense breast. This study examined the natural history of breast cancer progression among Korean women according to the levels of breast density.Methods: We applied a three-state Markov model to fit the natural history of breast cancer to data in the Korean National Cancer Screening Program. Diagnosis of breast cancer was ascertained by linkage to the Korean Central Cancer Registry. Disease progression rates (i.e., transition rates from healthy to preclinical state, and from preclinical to clinical state) were estimated across levels of breast density determined by the Breast Imaging, Reporting and Data System (BI-RADS). Preclinical incidence of breast cancer, mean sojourn time (MST) and mammographic screening sensitivity were simultaneously generated in the model.Results: Overall prevalence of dense breast among Korean women was 53.9%, which declined with age. Transition rate from healthy to preclinical state, indicating the preclinical incidence of breast cancer, was estimated to be higher among women aged 40-49 years (0.0019, 95% CI; 0.0017-0.0021) and women aged 50-59 years (0.0020, 95% CI; 0.0017-0.0022), than older women aged 60-69 years (0.0014, 95% CI; 0.0012-0.0017). Transition rate from preclinical to clinical state was also fastest among younger age groups, which directly translated to the shortest MSTs, estimated as 1.98 (95% CI; 1.67-2.33), 2.49 (95% CI; 1.92-3.22) and 3.07 (95% CI; 2.11-4.46) years for women in forties, fifties and sixties, respectively. The sensitivity of the mammographic screening was higher among older women (0.70, 95% CI; 0.62-0.77) than women in fifties (0.65, 95% CI; 0.62-0.77) and women in forties (0.61, 95% CI; 0.54-0.61). Having dense breasts increased the likelihood of the preclinical cancer risk (1.96 to 2.35 times) and decreased the duration of MST (1.53 to 2.02 times).Conclusions: Korean women showed 1.5 to 2 times higher prevalence of dense breast tissues, compared to Western women. This study estimated Korean-specific parameters for the natural history of breast cancer that would be utilized for establishing optimal screening strategies in countries with higher dense breast prevalence.
Efficacy of Mesenchymal Stromal Cells in Preclinical Models of Necrotizing Enterocolitis: a Systematic Review Protocol
Authors: Maltais-Bilodeau Camille , Henckel Ewa , Cobey Kelly D. , Ahmadzai Nadera , Skidmore Becky , Ferretti Emanuela , Thébaud Bernard 
Published: February 2021

Abstract
BackgroundNecrotizing enterocolitis is an acute inflammatory disease of the intestine that can lead to necrosis and bowel perforation. It is a severe complication of preterm birth with a prevalence of 7% in infants with a birth weight less than 1500 grams. It’s mortality rate is up to 30% and survival after necrotizing enterocolitis leads to long-term gastrointestinal and neurocognitive consequences. The current treatment is supportive and includes bowel rest and decompression and antibiotics. Thus, new treatments are necessary to reduce mortality and morbidity. Mesenchymal stromal cells are known to have anti-inflammatory properties and might be a promising option for treatment. Here we present a protocol for a systematic review with the aim to explore the efficacy of cell therapies with mesenchymal stromal cells in animal models of necrotizing enterocolitis. The primary outcome is histological signs of necrotizing enterocolitis. Additional outcomes include survival, bowel perforation, gut permeability, gut motility, levels of inflammatory markers, cytokine levels and adverse events.MethodsWe will conduct a systematic search of MEDLINE, Embase, and Web of Science databases. The retrieved records will be screened individually by two investigators. We will include all preclinical in vivo animal models of experimentally induced NEC that evaluate the efficacy of mesenchymal stromal cells or other cell therapy treatments. Outcome data will be extracted from each article and risk of bias assessment performed. Funnel plots and SYRCLE’s risk of bias tool for animal studies will be used. Data will be reported as ratios, divided in predefined subgroups where relevant. DiscussionThis systematic review aims to examine the efficacy of mesenchymal stromal cells in preclinical models of necrotizing enterocolitis and whether there is sufficient evidence to support a clinical trial of efficacy and safety of the treatment with mesenchymal stromal cells in infants with necrotizing enterocolitis.Systematic review registrationThis protocol has been registered on Open Science framework: osf.io/5rc6t
A Multifunctional Biodegradable Prussian blue Analogue for Synergetic Photothermal/Photodynamic/Chemodynamic therapy and Intrinsic Tumor Metastasis Inhibition
Authors: Hao Yuting , Mao Lianzhi , Zhang Rongjun , Liao Xiaoshan , Yuan Miaomiao , Liao Wenzhen 
Published: February 2021

Abstract
Background

To date, various Prussian blue analogues (PBA) have been prepared for biomedical applications due to their unique structural advantages. However, the safety and effectiveness of tumor treatment still need further exploration.
Results

This contribution reports a facile synthesis of novel PBA with superior tumor synergetic therapy effects and a detailed mechanistic evaluation of their intrinsic tumor metastasis inhibition activity. The as-synthesized PBA have a uniform cube structure with a diameter of approximately 220 nm and showed high near infrared light (NIR) photoreactivity, photothermal conversion efficiency (41.44%) and photodynamic effect. Additionally, PBA could lead to chemodynamic effect which caused by Fenton reaction and ferroptosis. The combined therapy strategy of PBA exhibit notable tumor ablation properties due to photothermal therapy (PTT)/photodynamic therapy (PDT)/ chemodynamic therapy (CDT) effect without obvious toxicity in vivo. The PBA also demonstrate potential as a contrast agent for magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. More importantly, careful investigations reveal that PBA displays excellent biodegradation and anti-metastasis properties. Further exploration of this PBA implies that its underlying mechanism of intrinsic tumor metastasis inhibition activity can be attributed to modulation of epithelial mesenchymal transition (EMT) expression.
Conclusions

The considerable potential exhibits by as-synthesized PBA make it an ideal candidate as a synergetic therapeutic agent for tumor treatment.
Nerve Transfer Surgery in Spinal Cord Injury: Online Information Sharing
Authors: Moltaji Syena , Novak Christine B , Dengler Jana 
Published: February 2021

Abstract
BackgroundNerve transfer to improve upper extremity function in persons with cervical spinal cord injury (SCI) is a new reconstructive option, and has led to more people seeking and sharing surgical information and experiences. This study evaluated the role of social media in information-sharing on nerve transfer surgery within the SCI community.MethodsData were collected from Facebook, which is the favored information-sharing platform among individuals seeking medical information. Searched terms included ‘spinal cord injury’ and ‘SCI’ and excluded groups with: less than two members (n = 7); closed groups (n = 2); not pertaining to SCI (n = 13); restricted access (n = 36); and non-English (n = 2). Within public and private accessed groups, searches were conducted for ‘nerve’, ‘transfer’, ‘nerve transfer’, and ‘nerve surgery’. Each post about nerve transfer, responses to posts, and comments about nerve transfer in response to unrelated posts were tabulated. Thematic content analyses were performed and data were categorized as seeking information, sharing information, sharing support, and sharing appreciation.ResultsThe search yielded 99 groups; 35 met the inclusion criteria (average size = 2,007, largest = 12,277). Nerve transfer was discussed in nine groups, with 577 total mentions. In the seeking information axis, posts were related to personal experience (54%), objective information (31%), surgeon/center performing the procedure (9%), and second opinion (4%). At least 13% of posts were from individuals learning about nerve transfers for the first time. In the sharing information axis, the posts: shared personal experience (52%); shared objective information (13%); described alternative treatment (3%); tagged someone to share information (11%); linked to outside resources (12%); and recommended a specific surgeon/center (9%).ConclusionSocial media is an important source of information and support for people with SCI. There is a paucity of information on nerve transfers. These study findings will inform implementation of future education strategies.