bluuebunny/crossref_metadata_2025_split huggingface dataset:
The overexpression of TDP-43 in astrocytes causes neurodegeneration via a PTP1B-mediated inflammatory response
Authors: Lee Shinrye , Kim Seyeon , Kang Ha-Young , Lim Hye Ryeong , Kwon Younghwi , Jo Myungjin , Jeon Yu-Mi , Kim Sang Ryong , Kim Kiyoung , Ha Chang Man , Lee Seongsoo , Kim Hyung-Jun 
Published: October 2020

Abstract
Background
Cytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown.

Methods
To investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP-43-Gfp. The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absence of a Ptp61f RNAi transgene.

Results
PTP1B inhibition suppressed TDP-43-induced secretion of inflammatory cytokines (interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)) in primary astrocytes. Using a neuron-astrocyte coculture system and astrocyte-conditioned media treatment, we demonstrated that PTP1B inhibition attenuated neuronal death and mitochondrial dysfunction caused by overexpression of TDP-43 in astrocytes. In addition, neuromuscular junction (NMJ) defects, a shortened lifespan, inflammation and climbing defects caused by pan-glial overexpression of TDP-43 were significantly rescued by downregulation of ptp61f (the Drosophila homologue of PTP1B) in flies.

Conclusions
These results indicate that PTP1B inhibition mitigates the neuronal toxicity caused by TDP-43-induced inflammation in mammalian astrocytes and Drosophila glial cells.
Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro
Authors: Ding Bo , Lin Chengheng , Liu Qian , He Yingying , Ruganzu John Bosco , Jin Hui , Peng Xiaoqian , Ji Shengfeng , Ma Yanbing , Yang Weina 
Published: October 2020

AbstractBackgroundGlial activation and neuroinflammation play a crucial role in the pathogenesis and development of Alzheimer’s disease (AD). The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to amyloid beta (Aβ)-induced neuroinflammation. This study aimed to investigate the neuroprotective effects of tanshinone IIA (tan IIA), a natural product isolated from traditional Chinese herbalSalvia miltiorrhizaBunge, against Aβ-induced neuroinflammation, cognitive impairment, and neurotoxicity as well as the underlying mechanisms in vivo and in vitro.MethodsOpen-field test, Y-maze test, and Morris water maze test were conducted to assess the cognitive function in APP/PS1 mice. Immunohistochemistry, immunofluorescence, thioflavin S (Th-S) staining, enzyme-linked immunosorbent assay (ELISA), real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting were performed to explore Aβ deposition, synaptic and neuronal loss, microglial and astrocytic activation, RAGE-dependent signaling, and the production of pro-inflammatory cytokines in APP/PS1 mice and cultured BV2 and U87 cells.ResultsTan IIA treatment prevented spatial learning and memory deficits in APP/PS1 mice. Additionally, tan IIA attenuated Aβ accumulation, synapse-associated proteins (Syn and PSD-95) and neuronal loss, as well as peri-plaque microgliosis and astrocytosis in the cortex and hippocampus of APP/PS1 mice. Furthermore, tan IIA significantly suppressed RAGE/nuclear factor-κB (NF-κB) signaling pathway and the production of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in APP/PS1 mice and cultured BV2 and U87 cells.ConclusionsTaken together, the present results indicated that tan IIA improves cognitive decline and neuroinflammation partly via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro. Thus, tan IIA might be a promising therapeutic drug for halting and preventing AD progression.
Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma
Authors: Lee Hong Kyu , Kwon Mi Jung , Ra Yong Joon , Lee Hee Sung , Kim Hyoung Soo , Nam Eun Sook , Cho Seong Jin , Park Hye-Rim , Min Soo Kee , Seo Jinwon , Choe Ji-Young , Min Kyueng-Whan , Kang So Young 
Published: October 2020

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC.

Methods
We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers.

Results
PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002).

Conclusions
PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.
Ethnobotanical study on plants used for traditional beekeeping by Dulong people in Yunnan, China
Authors: Cheng Zhuo , Luo Binsheng , Fang Qiong , Long Chunlin 
Published: October 2020

Abstract
Background
The Dulong (Drung) people have used plant materials in traditional beekeeping for many decades. However, there are few studies on the plants used in traditional beekeeping. Furthermore, traditional ecological knowledge (TEK) associated with beekeeping is still poorly understood. TEK and plants associated with beekeeping play an important role in the conservation of native bees and the development of beekeeping. It is therefore very urgent to investigate, record, and study the plants and TEK of Dulong beekeeping.

Methods
Fieldwork was conducted in the Dulong community of Gongshan County, Yunnan Province, China. Six Dulong villages were investigated. Ethnobotanical methods such as free listing, semi-structured interviews, participatory observation, and key informant interviews were used to collect data. A total of 42 Dulong respondents provided information about plants used in traditional beekeeping. TEK related to traditional beekeeping plants was documented. Citation frequency, abundance, and preference ranking of log beehive plant species were used to identify plant resources that are “easier to obtain” and “more preferred.”

Results
There are two general methods of traditional Dulong beekeeping: living tree beekeeping and log beehive beekeeping. The investigation revealed that 38 species (in 19 families), including 30 tree species, 5 bamboo species, 2 herbaceous species, and 1 liana species, are used in traditional Dulong beekeeping. Different plant parts are used for different purposes. Twenty-seven tree species are used to make log beehives. Species from the family Pinaceae and Fagaceae are the most frequently represented. Seven of the most commonly reported species used to build log beehives were scored by ten beekeepers. Based on this scoring, the beekeepers’ most preferred species for making log beehives are Alnus nepalensis, Pinus yunnanensis, and Juglans regia.

Conclusion
The Dulong people have used various plants for traditional beekeeping and have accumulated rich TEK associated with apiculture. Future research will include a nutritive components analysis of honey from traditional Dulong beekeeping and an ethnobotanical investigation of melliferous species used in traditional Dulong apicultural systems. The application of plants and TEK associated with beekeeping is important for improving livelihoods in local communities, conserving biocultural diversity, and protecting the eco-environment of the Dulongjiang area.
Informing urban climate planning with high resolution data: the Hestia fossil fuel CO2 emissions for Baltimore, Maryland
Authors: Roest Geoffrey S. , Gurney K. R. , Miller S. M. , Liang J. 
Published: October 2020

AbstractBackgroundCities contribute more than 70% of global anthropogenic carbon dioxide (CO2) emissions and are leading the effort to reduce greenhouse gas (GHG) emissions through sustainable planning and development. However, urban greenhouse gas mitigation often relies on self-reported emissions estimates that may be incomplete and unverifiable via atmospheric monitoring of GHGs. We present the Hestia Scope 1 fossil fuel CO2(FFCO2) emissions for the city of Baltimore, Maryland—a gridded annual and hourly emissions data product for 2010 through 2015 (Hestia-Baltimore v1.6). We also compare the Hestia-Baltimore emissions to overlapping Scope 1 FFCO2emissions in Baltimore’s self-reported inventory for 2014.ResultsThe Hestia-Baltimore emissions in 2014 totaled 1487.3 kt C (95% confidence interval of 1158.9–1944.9 kt C), with the largest emissions coming from onroad (34.2% of total city emissions), commercial (19.9%), residential (19.0%), and industrial (11.8%) sectors. Scope 1 electricity production and marine shipping were each generally less than 10% of the city’s total emissions. Baltimore’s self-reported Scope 1 FFCO2emissions included onroad, natural gas consumption in buildings, and some electricity generating facilities within city limits. The self-reported Scope 1 FFCO2total of 1182.6 kt C was similar to the sum of matching emission sectors and fuels in Hestia-Baltimore v1.6. However, 20.5% of Hestia-Baltimore’s emissions were in sectors and fuels that were not included in the self-reported inventory. Petroleum use in buildings were omitted and all Scope 1 emissions from industrial point sources, marine shipping, nonroad vehicles, rail, and aircraft were categorically excluded.ConclusionsThe omission of petroleum combustion in buildings and categorical exclusions of several sectors resulted in an underestimate of total Scope 1 FFCO2emissions in Baltimore’s self-reported inventory. Accurate Scope 1 FFCO2emissions, along with Scope 2 and 3 emissions, are needed to inform effective urban policymaking for system-wide GHG mitigation. We emphasize the need for comprehensive Scope 1 emissions estimates for emissions verification and measuring progress towards Scope 1 GHG mitigation goals using atmospheric monitoring.
Design and feasibility of a novel program of cervical screening in Nigeria: self-sampled HPV testing paired with visual triage
Authors: Desai Kanan T. , Ajenifuja Kayode O. , Banjo Adekunbiola , Adepiti Clement A. , Novetsky Akiva , Sebag Cathy , Einstein Mark H. , Oyinloye Temitope , Litwin Tamara R. , Horning Matt , Olanrewaju Fatai Olatunde , Oripelaye Mufutau Muphy , Afolabi Esther , Odujoko Oluwole O. , Castle Philip E. , Antani Sameer , Wilson Ben , Hu Liming , Mehanian Courosh , Demarco Maria , Gage Julia C. , Xue Zhiyun , Long Leonard R. , Cheung Li , Egemen Didem , Wentzensen Nicolas , Schiffman Mark 
Published: October 2020

Abstract
Background
Accelerated global control of cervical cancer would require primary prevention with human papillomavirus (HPV) vaccination in addition to novel screening program strategies that are simple, inexpensive, and effective. We present the feasibility and outcome of a community-based HPV self-sampled screening program.

Methods
In Ile Ife, Nigeria, 9406 women aged 30–49 years collected vaginal self-samples, which were tested for HPV in the local study laboratory using Hybrid Capture-2 (HC2) (Qiagen). HPV-positive women were referred to the colposcopy clinic. Gynecologist colposcopic impression dictated immediate management; biopsies were taken when definite acetowhitening was present to produce a histopathologic reference standard of precancer (and to determine final clinical management). Retrospective linkage to the medical records identified 442 of 9406 women living with HIV (WLWH).

Results
With self-sampling, it was possible to screen more than 100 women per day per clinic. Following an audio-visual presentation and in-person instructions, overall acceptability of self-sampling was very high (81.2% women preferring self-sampling over clinician collection). HPV positivity was found in 17.3% of women. Intensive follow-up contributed to 85.9% attendance at the colposcopy clinic. Of those referred, 8.2% were initially treated with thermal ablation and 5.6% with large loop excision of transformation zone (LLETZ). Full visibility of the squamocolumnar junction, necessary for optimal visual triage and ablation, declined from 68.5% at age 30 to 35.4% at age 49. CIN2+ and CIN3+ (CIN- Cervical intraepithelial neoplasia), including five cancers, were identified by histology in 5.9 and 3.2% of the HPV-positive women, respectively (0.9 and 0.5% of the total screening population), leading to additional treatment as indicated. The prevalences of HPV infection and CIN2+ were substantially higher (40.5 and 2.5%, respectively) among WLWH. Colposcopic impression led to over- and under-treatment compared to the histopathology reference standard.

Conclusion
A cervical cancer screening program using self-sampled HPV testing, with colposcopic immediate management of women positive for HPV, proved feasible in Nigeria. Based on the collected specimens and images, we are now evaluating the use of a combination of partial HPV typing and automated visual evaluation (AVE) of cervical images to improve the accuracy of the screening program.
Hemophagocytic lymphohistiocytosis in a patient with COVID-19 treated with tocilizumab: a case report
Authors: Tholin Birgitte , Hauge Marit Teigen , Aukrust Pål , Fehrle Lutz , Tvedt Tor Henrik 
Published: October 2020

Abstract
Background
The understanding of coronavirus disease 2019 (COVID-19) is rapidly evolving. Although it is primarily a respiratory illness, other manifestations, such as Guillain-Barré syndrome, immune thrombocytopenia, and immune-mediated thrombotic thrombocytopenic purpura, have been described. We present a case of a patient with hemophagocytic lymphohistiocytosis secondary to COVID-19 treated with tocilizumab with a marked biochemical improvement.

Case presentation
In this case report we present a Caucasian patient with COVID-19 who developed a marked elevation of inflammatory parameters with ferritin 36,023 μg/L, but also elevated C-reactive protein 334 mg/L and lactate dehydrogenase 1074 U/L, 1 week after admission to the intensive care unit. He met five of eight criteria for hemophagocytic lymphohistiocytosis, but he lacked the high fever and cytopenia seen in the majority of cases. He was treated with tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, and over the next days, a rapid decrease in ferritin and C-reactive protein levels was observed. However, his respiratory failure only improved gradually, and he was weaned off the respirator 11 days later.

Conclusion
COVID-19 may induce a hyperinflammatory clinical picture and in some cases develop into hemophagocytic lymphohistiocytosis. In our patient’s case, therapeutic interleukin-6 blockade abrogated signs of hyperinflammation but did not seem to improve pulmonary function. Measurement of ferritin and C-reactive protein, as well as quantification of interleukin-6 on indication, should be performed in patients with severe COVID-19. Specific treatment in such patients must also be contemplated, preferably in randomized controlled trials.
Energy-efficient capture of stochastic events based on on-line scheduling scheme
Authors: Fu Xiao , Cheng Zongmao , Tan Hao 
Published: October 2020

AbstractWe improve the off-line scheduling scheme of existing wireless sensor network. Firstly, we introduce Bayesian statistical method in synchronous wireless sensor network. Then, we let duration and interval, the reflection of characteristics of stochastic events, obey exponential distribution. Next, we make Bayes posterior estimation on parameter. Based on Bayesian estimate, we obtain the analytical solution of the capture probability of stochastic events and sensor energy efficiency of capture events. Finally, we propose an on-line scheduling scheme for synchronous wireless sensor networks. This paper compares and analyzes the simulation experiments in on-line scheduling scheme and off-line scheduling scheme, and the results show that compared with off-line scheduling scheme with constant distribution parameter values, on-line scheduling scheme can effectively reduce the probability of missing stochastic events and increase the probability of capturing events, further save energy consumption of wireless sensor network, and extend network lifetime.
Chaos control strategy for a fractional-order financial model
Authors: Xu Changjin , Aouiti Chaouki , Liao Maoxin , Li Peiluan , Liu Zixin 
Published: October 2020

AbstractIn this paper, we propose a new fractional-order financial model which is a generalized version of the financial model reported in the previous publications. By applying a suitable time-delayed feedback controller, we have control for the chaotic behavior of the fractional-order financial model. We investigate the stability and the existence of a Hopf bifurcation of the fractional-order financial model. A new sufficient condition that guarantees the stability and the existence of a Hopf bifurcation for a fractional-order delayed financial model is presented by regarding the delay as bifurcation parameter. The investigation shows that the delay and the fractional order have an important effect on the stability and Hopf bifurcation of involved model. Some simulations justifying the validity of the derived analytical results are given. The obtained results of this article are innovative and are of great significance in handling the financial issues.
Re-expression of DIRAS3 and p53 induces apoptosis and impaired autophagy in head and neck squamous cell carcinoma
Authors: Liu Zhe , Hurst Douglas R. , Qu Xing , Lu Li-Guang , Wu Chen-Zhou , Li Yu-Yu , Li Yi 
Published: October 2020

Abstract
Background
p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors. In this study, we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck squamous cell carcinoma (HNSCC) cell death.

Methods
CAL-27 and SCC-25 cells were treated with Ad-DIRAS3 and rAd-p53 to induce re-expression of DIRAS3 and p53 respectively. The effects of DIRAS3 and p53 re-expression on the growth and apoptosis of HNSCC cells were examined by TUNEL assay, flow cytometric analysis and MTT. The effects of DIRAS3 and p53 re-expression on Akt phosphorylation, oncogene expression, and the interaction of 4E-BP1 with eIF4E were determined by real-time PCR, Western blotting and immunoprecipitation analysis. The ability of DIRAS3 and p53 re-expression to induce autophagy was evaluated by transmission electron microscopy, LC3 fluorescence microscopy and Western blotting. The effects of DIRAS3 and p53 re-expression on HNSCC growth were evaluated by using an orthotopic xenograft mouse model.

Results
TUNEL assay and flow cytometric analysis showed that the concurrent re-expression of DIRAS3 and p53 significantly induced apoptosis (P < 0.001). MTT and flow cytometric analysis revealed that DIRAS3 and p53 re-expression significantly inhibited proliferation and induced cell cycle arrest (P < 0.001). Mechanistically, the concurrent re-expression of DIRAS3 and p53 down-regulated signal transducer and activation of transcription 3 (STAT3) and up-regulated p21WAF1/CIP1 and Bax (P < 0.001). DIRAS3 and p53 re-expression also inhibited Akt phosphorylation, increased the interaction of eIF4E with 4E-BP1, and reduced the expression of c-Myc, cyclin D1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor receptor (EGFR) and Bcl-2 (P < 0.001). Moreover, the concurrent re-expression of DIRAS3 and p53 increased the percentage of cells with GFP-LC3 puncta compared with that in cells treated with control adenovirus (50.00% ± 4.55% vs. 4.67% ± 1.25%, P < 0.001). LC3 fluorescence microscopy and Western blotting further showed that DIRAS3 and p53 re-expression significantly promoted autophagic activity but also inhibited autophagic flux, resulting in overall impaired autophagy. Finally, the concurrent re-expression of DIRAS3 and p53 significantly decreased the tumor volume compared with the control group in a HNSCC xenograft mouse model [(3.12 ± 0.75) mm3 vs. (189.02 ± 17.54) mm3, P < 0.001].

Conclusions
The concurrent re-expression of DIRAS3 and p53 is a more effective approach to HNSCC treatment than current treatment strategies.