bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-extracellular RNA promotes pro-inflammatory response of astrocytes to exogenous and endogenous danger signals
Authors: Fischer Silvia , Nasyrov Emil , Brosien Monika , Preissner Klaus T. , Marti Hugo H. , Kunze Reiner 
Published: November 2021

Abstract
Objective
Astrocytes participate in the local innate immune response of the central nervous system. In response to stress such as ischemia, activated cells release endogenous factors known as damage-associated molecular patterns (DAMPs). Self-extracellular RNA (eRNA) is such a ubiquitous alarm signal. However, it is unclear whether eRNA is involved in the early acute phase of cerebral ischemia and is sufficient to sensitize astrocytes towards a DAMP or PAMP (pathogen-associated molecular pattern) reaction.

Methods
Pro-inflammatory activation upon eRNA stimulation was characterized in primary murine astrocyte cultures. In vivo, an experimental stroke model was used to localize and quantify eRNA in murine brain sections. Using primary cortical neurons and the mouse hippocampal neuronal cell line HT-22, neuronal RNA release upon stress conditions related to cerebral hypoxia/ischemia was analyzed.

Results
While low-dose eRNA alone did not promote pro-inflammatory activation of astrocytes in culture, it strongly enhanced the expression of pro-inflammatory cytokines in the presence of either Pam2CSK4, a synthetic PAMP molecule that mimics bacterial infection, or high mobility group box 1 (HMGB1), a prominent DAMP. Synergism of eRNA/Pam2CSK4 and eRNA/HMGB1 was prevented by blockage of the astroglial toll-like receptor (TLR)-2. Inhibition of NF-κB- and mitogen-activated protein kinase-dependent signaling pathways hampered eRNA/Pam2CSK4-mediated pro-inflammatory activation of astrocytes. In vivo, the amount of non-nuclear, presumably extracellular ribosomal RNA in close proximity to neurons significantly accumulated across the infarct core and peri-infarct areas that was accompanied by transcriptional up-regulation of various pro-inflammatory factors. Accordingly, the exposure of neurons to hypoxic/ischemic stress in vitro resulted in the release of eRNA, partly mediated by active cellular processes dependent on the cytosolic calcium level.

Conclusion
The DAMP signal eRNA can sensitize astrocytes as active players in cerebral innate immunity towards exogenous and endogenous activators of inflammation (PAMPs and DAMPs) in a synergistic manner via TLR2-NF-κB-dependent signaling mechanisms. These findings provide new insights into the pathogenesis of ischemic stroke and other inflammatory neurological disorders. Further studies will clarify whether administration of RNase in vivo may serve as an effective treatment for inflammatory brain pathologies.
Regulation of the p75 neurotrophin receptor attenuates neuroinflammation and stimulates hippocampal neurogenesis in experimental Streptococcus pneumoniae meningitis
Authors: Zhang Dandan , Zhao Shengnan , Zhang Zhijie , Xu Danfeng , Lian Di , Wu Jing , He Dake , Sun Kun , Li Ling 
Published: November 2021

Abstract
Background
Streptococcus pneumoniae meningitis is a destructive central nervous system (CNS) infection with acute and long-term neurological disorders. Previous studies suggest that p75NTR signaling influences cell survival, apoptosis, and proliferation in brain-injured conditions. However, the role of p75NTR signaling in regulating pneumococcal meningitis (PM)-induced neuroinflammation and altered neurogenesis remains largely to be elucidated.

Methods
p75NTR signaling activation in the pathological process of PM was assessed. During acute PM, a small-molecule p75NTR modulator LM11A-31 or vehicle was intranasally administered for 3 days prior to S. pneumoniae exposure. At 24 h post-infection, clinical severity, histopathology, astrocytes/microglia activation, neuronal apoptosis and necrosis, inflammation-related transcription factors and proinflammatory cytokines/mediators were evaluated. Additionally, p75NTR was knocked down by the adenovirus-mediated short-hairpin RNA (shRNA) to ascertain the role of p75NTR in PM. During long-term PM, the intranasal administration of LM11A-31 or vehicle was continued for 7 days after successfully establishing the PM model. Dynamic changes in inflammation and hippocampal neurogenesis were assessed.

Results
Our results revealed that both 24 h (acute) and 7, 14, 28 day (long-term) groups of infected rats showed increased p75NTR expression in the brain. During acute PM, modulation of p75NTR through pretreatment of PM model with LM11A-31 significantly alleviated S. pneumoniae-induced clinical severity, histopathological injury and the activation of astrocytes and microglia. LM11A-31 pretreatment also significantly ameliorated neuronal apoptosis and necrosis. Moreover, we found that blocking p75NTR with LM11A-31 decreased the expression of inflammation-related transcription factors (NF-κBp65, C/EBPβ) and proinflammatory cytokines/mediators (IL-1β, TNF-α, IL-6 and iNOS). Furthermore, p75NTR knockdown induced significant changes in histopathology and inflammation-related transcription factors expression. Importantly, long-term LM11A-31 treatment accelerated the resolution of PM-induced inflammation and significantly improved hippocampal neurogenesis.

Conclusion
Our findings suggest that the p75NTR signaling plays an essential role in the pathogenesis of PM. Targeting p75NTR has beneficial effects on PM rats by alleviating neuroinflammation and promoting hippocampal neurogenesis. Thus, the p75NTR signaling may be a potential therapeutic target to improve the outcome of PM.
Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma
Authors: Liu Yang , Zhang Zhiling , Liu Ruiqi , Wei Wensu , Zhang Zitong , Mai Lixin , Guo Shengjie , Han Hui , Zhou Fangjian , He Liru , Dong Pei 
Published: November 2021

Abstract
Background
Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC).

Methods
We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting. Survival outcomes were calculated from the anti-PD-1 treatment using the Kaplan–Meier method. Univariate and multivariate analyses were performed by Cox proportional hazards models.

Results
Thirty-two (43.2%) patients received anti-PD-1/TA therapy alone (anti-PD-1/TA alone group), and 42 (56.8%) received SBRT in addition (anti-PD-1/TA + SBRT group). The median duration of first-line therapy was 8.6 months. Patients in the anti-PD-1/TA + SBRT group had significantly longer overall survival (OS) (38.5 vs 15.4 months; P = 0.022). On multivariate analysis, oligometastasis, ECOG performance status 0–1, anti-PD-1/TA + SBRT, and duration of first-line therapy ≥ 8.6 months were predictors for OS. The addition of SBRT was associated with improved OS in patients with clear-cell type (HR 0.19; 95% CI 0.07–0.55; P = 0.002) and duration of first-line therapy ≥ 8.6 months (HR 0.22; 95% CI 0.06–0.88; P = 0.032). Grade ≥ 3 toxicities occurred in 23 patients (54.8%) in the anti-PD-1/TA + SBRT group, and in 21 patients (65.6%) in the anti-PD-1/TA alone group.

Conclusions
Incorporating SBRT into anti-PD-1/TA therapy is safe and tolerable. Further investigation is needed, particularly in patients with clear-cell histology and a longer duration of response to first-line antiangiogenic therapy.
Massive QTL analysis identifies pleiotropic genetic determinants for stress resistance, aroma formation, and ethanol, glycerol and isobutanol production in Saccharomyces cerevisiae
Authors: Ho Ping-Wei , Piampongsant Supinya , Gallone Brigida , Del Cortona Andrea , Peeters Pieter-Jan , Reijbroek Frank , Verbaet Jules , Herrera Beatriz , Cortebeeck Jeroen , Nolmans Robbe , Saels Veerle , Steensels Jan , Jarosz Daniel F. , Verstrepen Kevin J. 
Published: November 2021

Abstract
Background
The brewer’s yeast Saccharomyces cerevisiae is exploited in several industrial processes, ranging from food and beverage fermentation to the production of biofuels, pharmaceuticals and complex chemicals. The large genetic and phenotypic diversity within this species offers a formidable natural resource to obtain superior strains, hybrids, and variants. However, most industrially relevant traits in S. cerevisiae strains are controlled by multiple genetic loci. Over the past years, several studies have identified some of these QTLs. However, because these studies only focus on a limited set of traits and often use different techniques and starting strains, a global view of industrially relevant QTLs is still missing.

Results
Here, we combined the power of 1125 fully sequenced inbred segregants with high-throughput phenotyping methods to identify as many as 678 QTLs across 18 different traits relevant to industrial fermentation processes, including production of ethanol, glycerol, isobutanol, acetic acid, sulfur dioxide, flavor-active esters, as well as resistance to ethanol, acetic acid, sulfite and high osmolarity. We identified and confirmed several variants that are associated with multiple different traits, indicating that many QTLs are pleiotropic. Moreover, we show that both rare and common variants, as well as variants located in coding and non-coding regions all contribute to the phenotypic variation.

Conclusions
Our findings represent an important step in our understanding of the genetic underpinnings of industrially relevant yeast traits and open new routes to study complex genetics and genetic interactions as well as to engineer novel, superior industrial yeasts. Moreover, the major role of rare variants suggests that there is a plethora of different combinations of mutations that can be explored in genome editing.
Global stakeholder perspectives of home birth: a systematic scoping review
Authors: Brunton Ginny , Wahab Samira , Sheikh Hassan , Davis Beth Murray 
Published: November 2021

AbstractHome birth is experienced by people very differently worldwide. These experiences likely differ by the type of stakeholder involved (women, their support persons, birth attendants, policy-makers), the experience itself (low-risk birth, transfer to hospital, previous deliveries), and by the health system within which home birth occurs (e.g., high-resource versus low- and middle-resource countries). Research evidence of stakeholders’ perspectives of home birth could usefully inform personal and policy decisions about choosing and providing home birth, but the current literature is fragmented and its breadth is not fully understood.We conducted a systematic scoping review to understand how the research literature on stakeholders’ perspectives of home birth is characterized in terms of populations, settings and identified issues, and what potential gaps exist in the research evidence. A range of electronic, web-based and key informant sources of evidence were searched. Located references were assessed, data extracted, and descriptively analyzed using robust methods.Our analysis included 460 full reports. Findings from 210 reports of studies in high-resource countries suggested that research with fathers and same-sex partners, midwives, and vulnerable populations and perspectives of freebirth and transfer to hospital could be synthesized. Gaps in primary research exist with respect to family members, policy makers, and those living in rural and remote locations. A further 250 reports of studies in low- and middle-resource countries suggested evidence for syntheses related to fathers and other family members, policy makers, and other health care providers and examination of issues related to emergency transfer to hospital, rural and remote home birth, and those who birth out of hospital, often at home, despite receiving antenatal care intended to increase healthcare-seeking behavior. Gaps in primary research suggest an examination is needed of perspectives in countries with higher maternal mortality and among first-time mothers and young mothers.Our scoping review identified a considerable body of research evidence on stakeholder perspectives of home birth. These could inform the complex factors influencing personal decisions and health system planning around home birth in both high- and low- and middle-resource countries. Future primary research is warranted on specific stakeholders worldwide and with vulnerable populations in areas of high maternal mortality.
Dynamic changes of genomic methylation profiles at different growth stages in Chinese Tan sheep
Authors: Liu Yufang , Xu Qiao , Kang Xiaolong , Wang Kejun , Wang Jve , Feng Dengzhen , Bai Ying , Fang Meiying 
Published: November 2021

Abstract
Background
Tan sheep, an important local sheep breed in China, is famous for their fur quality. One-month-old Tan sheep have white, curly hair with beautiful flower spikes, commonly known as “nine bends”, which has high economic value. However, the “nine bends” characteristic gradually disappears with age; consequently, the economic value of the Tan sheep decreases. Age-related changes in DNA methylation have been reported and may be responsible for age-induced changes in gene expression. Until now, no genome-wide surveys have been conducted to identify potential DNA methylation sites involved in different sheep growth stages. In this study we investigated the dynamic changes of genome-wide DNA methylation profiles in Tan sheep using DNA from skin and deep whole-genome bisulfite sequencing, and compared the DNA methylation levels at three different growth stages: 1, 24, and 48 months old (mon1, mon24, and mon48, respectively).

Results
In this study, 11 skin samples from three growth stages (four for mon1, four for mon24, and three for mon48) were used for DNA methylation analysis and gene expression profiling. There were 52, 288 and 236 differentially methylated genes (DMGs) identified between mon1 and mon24, mon1 and mon48, and mon24 and mon48, respectively. Of the differentially methylated regions, 1.11%, 7.61%, and 7.65% were in the promoter in mon1 vs. mon24, mon24 vs. mon48, and mon1 vs. mon48, respectively. DMGs were enriched in the MAPK and WNT signaling pathways, which are related to age growth and hair follicle morphogenesis processes. There were 51 DMGs associated with age growth and curly fleece formation. Four DMGs between mon1 and mon48 (KRT71, CD44, ROR2 and ZDHHC13) were further validated by bisulfite sequencing.

Conclusions
This study revealed dynamic changes in the genomic methylation profiles of mon1, mon24, and mon48 sheep, and the percentages of methylated cytosines were 3.38%, 2.85% and 4.17%, respectively. Of the DMGs, KRT71 and CD44 were highly methylated in mon1, and ROR2 and ZDHHC13 were highly methylated in mon48. These findings provide foundational information that may be used to develop strategies for potentially retaining the lamb fur and thus improving the economic value of Tan sheep.
Exploration of the investment patterns of potential retail banking customers using two-stage cluster analysis
Authors: Kovács Tibor , Ko Andrea , Asemi Asefeh 
Published: November 2021

AbstractIdentifying investment patterns as part of customer segmentation is one of the most important tasks in retail banking. Clustering customers effectively is an important element of improving marketing policy and strategic planning. There are several methods for identifying similar groups of customers and describing their characteristics to offer them appropriate products. However, using machine learning methods is rare, and the application is limited for certain types of data. The aim of this study is to investigate the benefits of using a two-stage clustering method using neural-network-based Kohonen self-organizing maps followed by hierarchical clustering for identifying the investment patterns of potential retail banking customers. The unique benefit of this method is the ability to use both categorical and numerical variables at the same time. This research examined 1,542 responses received for an online investment survey, focusing on the questions that are related to the respondents’ investment preferences and their current financial assets. The research utilizes descriptive statistics and multiple correspondence analysis (MCA) to understand the variables and Kohonen self-organizing maps (SOMs), in combination with hierarchical clustering, to identify customer groups and describe the characteristics of these clusters. The analysis was able to identify clusters of potential customers with similar preferences and gained insights into their investment patterns related to their investment portfolio and investment behavior, including their savings profile, attitude to risk-taking, and preferences for investment advice. These findings were supported by additional insights through the application of multiple correspondence analysis (MCA) describing patterns of financial instruments and portfolios. The main contribution of the research is the combined application of the machine learning methods Kohonen SOM, hierarchical clustering, and MCA for investment pattern analysis in the retail banking business.
Cancer nanotechnology: current status and perspectives
Authors: Kemp Jessica A. , Kwon Young Jik 
Published: November 2021

AbstractModern medicine has been waging a war on cancer for nearly a century with no tangible end in sight. Cancer treatments have significantly progressed, but the need to increase specificity and decrease systemic toxicities remains. Early diagnosis holds a key to improving prognostic outlook and patient quality of life, and diagnostic tools are on the cusp of a technological revolution. Nanotechnology has steadily expanded into the reaches of cancer chemotherapy, radiotherapy, diagnostics, and imaging, demonstrating the capacity to augment each and advance patient care. Nanomaterials provide an abundance of versatility, functionality, and applications to engineer specifically targeted cancer medicine, accurate early-detection devices, robust imaging modalities, and enhanced radiotherapy adjuvants. This review provides insights into the current clinical and pre-clinical nanotechnological applications for cancer drug therapy, diagnostics, imaging, and radiation therapy.
River discharge prediction for ungauged mountainous river basins during heavy rain events based on seismic noise data
Authors: P.C. Shakti , Sawazaki Kaoru 
Published: November 2021

AbstractSeveral mountainous river basins in Japan do not have a consistent hydrological record due to their complex environment and remoteness, as discharge measurements are not economically feasible. However, understanding the flow rate of rivers during extreme events is essential for preventing flood disasters around river basins. In this study, we used the high-sensitivity seismograph network (Hi-net) of Japan to identify the time and peak discharge of heavy rain events. Hi-net seismograph stations are distributed almost uniformly at distance intervals of approximately 20 km, while being available even in mountainous regions. The Mogami River Basin in Northeastern Japan was selected as a target area to compare the seismic noise data of two Hi-net stations with the hydrological response of a nearby river. These stations are not located near hydrological stations; therefore, direct comparison of seismic noise and observed discharge was not possible. Therefore, discharge data simulated using a hydrological model were first validated with gauging station data for two previous rain events (10–23 July 2004 and 7–16 September 2015). Then, the simulated river discharge was compared with Hi-net seismic noise data for three recent events (10–23 July 2004, 7–16 September 2015, and 10–15 October 2019). The seismic noise data exhibited a similar trend to the time series of simulated discharge in a frequency range of 1–2 Hz for the selected events. Discharge values predicted from the noise data effectively replicate the simulated discharge values in many cases, especially the timing and amount of peak discharge.Simulated and predicted discharge near NIED Hi-net seismic stations in the Mogami River Basin for the event of October 2019 (Typhoon Hagibis).
Birds and plastic pollution: recent advances
Authors: Wang Limin , Nabi Ghulam , Yin Liyun , Wang Yanqin , Li Shuxin , Hao Zhuang , Li Dongming 
Published: November 2021

AbstractPlastic waste and debris have caused substantial environmental pollution globally in the past decades, and they have been accumulated in hundreds of terrestrial and aquatic avian species. Birds are susceptible and vulnerable to external environments; therefore, they could be used to estimate the negative effects of environmental pollution. In this review, we summarize the effects of macroplastics, microplastics, and plastic-derived additives and plastic-absorbed chemicals on birds. First, macroplastics and microplastics accumulate in different tissues of various aquatic and terrestrial birds, suggesting that birds could suffer from the macroplastics and microplastics-associated contaminants in the aquatic and terrestrial environments. Second, the detrimental effects of macroplastics and microplastics, and their derived additives and absorbed chemicals on the individual survival, growth and development, reproductive output, and physiology, are summarized in different birds, as well as the known toxicological mechanisms of plastics in laboratory model mammals. Finally, we identify that human commensal birds, long-life-span birds, and model bird species could be utilized to different research objectives to evaluate plastic pollution burden and toxicological effects of chronic plastic exposure.
Plastering mud around the entrance hole affects the estimation of threat levels from nest predators in Eurasian Nuthatches
Authors: Yu Jiangping , Zhang Li , Yi Guodong , Zhang Keqin , Yao Jiyuan , Fang Jian , Shen Chao , Wang Haitao 
Published: November 2021

AbstractBackgroundFor cavity-nesting birds, the nest entrance plays an important role in preventing predators from accessing nests. Several species of nuthatches use mud to narrow the entrance of cavities. In theory, the smaller the entrance hole size, the more effective it is against predators; however, few studies have tested whether narrowing the entrance hole size can affect the estimation of threat levels from nest predators in cavity-nesting birds.MethodsUsing dummy experiments, we tested whether Eurasian Nuthatches (Sitta europaea, narrow the entrance hole of cavities) and Cinereous Tits (Parus cinereus, do not narrow the entrance hole, as a control) perform different nest defence behaviours against Common Chipmunks (Tamias sibiricus, small nest predator) and Red Squirrels (Sciurus vulgaris, larger nest predator).ResultsBoth nuthatches and tits exhibited stronger response behaviours (high dummy response scores) against chipmunks than against squirrels. Compared with tits, nuthatches exhibited more aggressive behaviours to chipmunks, but their responses to squirrels were similar.ConclusionsNest defence behaviours of nuthatches to chipmunks differed from tits, and the results suggested that nuthatches might estimate threat levels of nest predators according to their narrowed entrance-hole size.