bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between glucocorticoids and viral load during the Omicron wave in mainland China
Authors: Bai Guangxu , Li Yan , Liu Yang , Wang Xinming , Yu Xuezhong , Ren Lili , Xu Jun 
Published: November 2023

Abstract
Background
Coronavirus disease 19 (COVID-19) is a major public health problem that cannot be ignored. As a widely used drug in the treatment of COVID-19, whether glucocorticoids may accelerate the clearance of COVID-19 is still not clear, and the glucocorticoids may improve the prognosis of patients is also controversial. Therefore, to explore the relationship between COVID-19 viral load and the use of glucocorticoids we designed this study.

Methods
Patients with COVID-19 infection who were admitted to the emergency department of Peking Union Medical College Hospital from the end of 2022 to early 2023 were enrolled in this study. Characteristics of baseline, clinical and laboratory evaluation especially immunological indicator and daily viral load were carefully collected. Kolmogorov–Smirnov test, Student’s t test, Mann–Whitney U test and proportional-hazards model (Cox model) were chosen as appropriate for comparison of variables.

Results
By comparing the daily COVID-19 viral load and prognosis of patients with and without glucocorticoid therapy, we found that glucocorticoids did not statistically enhance the clearance or replication of COVID-19, nor did it change the 28-days and in-hospital mortality. However, glucocorticoid therapy may be a favorable factor for COVID-19 negative conversion in Cox model. The inflammatory factors in patients with glucocorticoid therapy were significantly decreased.

Conclusions
We believe that the real effect of glucocorticoids may be to improve the destruction of host immune system caused by inflammatory storm through host immune regulation and then achieve the improvement of clinical symptoms.
Long non-coding RNA GAS5 promotes cisplatin-chemosensitivity of osteosarcoma cells via microRNA-26b-5p/TP53INP1 axis
Authors: Li Guowei , Yan Xue 
Published: November 2023

AbstractOsteosarcoma is a common malignant bone tumor. Cisplatin (DDP) achieves a high response rate in osteosarcoma. Here we aim to study the dysregulation of long non-coding RNA the growth arrest-specific transcript 5 (GAS5), and its roles in DDP-resistance of osteosarcoma. The expression of mRNA and microRNA in osteosarcoma tissues and osteosarcoma cell lines were detected by quantitative reverse-transcription polymerase chain reaction, and protein expression levels were measured by western blotting assay. Cell Counting Kit-8 and 5-Ethynyl-2′-deoxyuridine were used to measure cell proliferation. Flow cytometer assay was used to evaluate cell apoptosis. The interactions between miR-26b-5p and GAS5 or tumor protein p53-induced nuclear protein 1 (TP53INP1) were verified by dual luciferase reporter along with biotin RNA pull-down assays. GAS5 was identified to be significantly lowly expressed in osteosarcoma samples especially in cisplatin-resistant (DDP-resistant) tissues. GAS5 was also downregulated in DDP-resistant cells. Over-expressed GAS5 prominently increased the sensitivity of osteosarcoma cells to DDP in vitro. Furthermore, over-expression of GAS5 suppressed cell proliferation and facilitated apoptosis of DDP-resistant cells. Mechanistically, GAS5 sponged miR-26b-5p, over-expression of which reversed the effects of GAS5 on cell proliferation and apoptosis of DDP-resistant cells. In addition, miR-26b-5p targeted TP53INP1. TP53INP1 abrogated the functions of miR-26b-5p on cell proliferation and apoptosis in DDP-resistant cells. Taken together, GAS5 enhanced the sensitivity of osteosarcoma cells to DDP via GAS5/miR-26b-5p/TP53INP1 axis. Therefore, GAS5 may be a potential indicator for the management of osteosarcoma.
Transcriptomic profiles reveal the characteristics of oocytes and cumulus cells at GV, MI, and MII in follicles before ovulation
Authors: Hu Yena , Zhang Ran , Zhang Shuoping , Ji Yaxing , Zhou Qinwei , Leng Lizhi , Meng Fei , Gong Fei , Lu Guangxiu , Lin Ge , Hu Liang 
Published: November 2023

Abstract
Background
The oocyte and its surrounding cumulus cells (CCs) exist as an inseparable entity. The maturation of the oocyte relies on communication between the oocyte and the surrounding CCs. However, oocyte evaluation is primarily based on morphological parameters currently, which offer limited insight into the quality and competence of the oocyte. Here, we conducted transcriptomic profiling of oocytes and their CCs from 47 patients undergoing preimplantation genetic testing for aneuploidy (PGT-A). We aimed to investigate the molecular events occurring between oocytes and CCs at different stages of oocyte maturation (germinal vesicle [GV], metaphase I [MI], and metaphase II [MII]). Our goal is to provide new insights into in vitro oocyte maturation (IVM).

Results
Our findings indicate that oocyte maturation is a complex and dynamic process and that MI oocytes can be further classified into two distinct subtypes: GV-like-MI oocytes and MII-like-MI oocytes. Human oocytes and cumulus cells at three different stages of maturation were analyzed using RNA-seq, which revealed unique transcriptional machinery, stage-specific genes and pathways, and transcription factor networks that displayed developmental stage-specific expression patterns. We have also identified that both lipid and cholesterol metabolism in cumulus cells is active during the late stage of oocyte maturation. Lipids may serve as a more efficient energy source for oocytes and even embryogenesis.

Conclusions
Overall, our study provides a relatively comprehensive overview of the transcriptional characteristics and potential interactions between human oocytes and cumulus cells at various stages of maturation before ovulation. This study may offer novel perspectives on IVM and provide a reliable reference data set for understanding the transcriptional regulation of follicular maturation.
Logic-based modeling and drug repurposing for the prediction of novel therapeutic targets and combination regimens against E2F1-driven melanoma progression
Authors: Singh Nivedita , Khan Faiz M , Bala Lakshmi , Vera Julio , Wolkenhauer Olaf , Pützer Brigitte , Logotheti Stella , Gupta Shailendra K. 
Published: November 2023

AbstractMelanoma presents increasing prevalence and poor outcomes. Progression to aggressive stages is characterized by overexpression of the transcription factor E2F1 and activation of downstream prometastatic gene regulatory networks (GRNs). Appropriate therapeutic manipulation of the E2F1-governed GRNs holds the potential to prevent metastasis however, these networks entail complex feedback and feedforward regulatory motifs among various regulatory layers, which make it difficult to identify druggable components. To this end, computational approaches such as mathematical modeling and virtual screening are important tools to unveil the dynamics of these signaling networks and identify critical components that could be further explored as therapeutic targets. Herein, we integrated a well-established E2F1-mediated epithelial-mesenchymal transition (EMT) map with transcriptomics data from E2F1-expressing melanoma cells to reconstruct a core regulatory network underlying aggressive melanoma. Using logic-based in silico perturbation experiments of a core regulatory network, we identified that simultaneous perturbation of Protein kinase B (AKT1) and oncoprotein murine double minute 2 (MDM2) drastically reduces EMT in melanoma. Using the structures of the two protein signatures, virtual screening strategies were performed with the FDA-approved drug library. Furthermore, by combining drug repurposing and computer-aided drug design techniques, followed by molecular dynamics simulation analysis, we identified two potent drugs (Tadalafil and Finasteride) that can efficiently inhibit AKT1 and MDM2 proteins. We propose that these two drugs could be considered for the development of therapeutic strategies for the management of aggressive melanoma.
Graphical abstract
Trichinella spiralis cathepsin L induces macrophage M1 polarization via the NF-κB pathway and enhances the ADCC killing of newborn larvae
Authors: Liu Ruo Dan , Meng Xiang Yu , Le Li Chen , Xu Qiu Yi , Lin Xin Zhi , Dong Bo Rang , Ye Chu Yan , Miao Tian Tian , Si Xin Yi , Long Shao Rong , Cui Jing , Wang Zhong Quan 
Published: November 2023

Abstract
Background
During the early stages of Trichinella spiralis infection, macrophages predominantly undergo polarization to the M1-like phenotype, causing the host’s inflammatory response and resistance against T. spiralis infection. As the disease progresses, the number of M2-type macrophages gradually increases, contributing to tissue repair processes within the host. While cysteine protease overexpression is typically associated with inflammation, the specific role of T. spiralis cathepsin L (TsCatL) in mediating macrophage polarization remains unknown. The aim of this study was to assess the killing effect of macrophage polarization mediated by recombinant T. spiralis cathepsin L domains (rTsCatL2) on newborn larvae (NBL).

Methods
rTsCatL2 was expressed in Escherichia coli strain BL21. Polarization of the rTsCatL2-induced RAW264.7 cells was analyzed by enzyme-linked immunosorbent assay (ELISA), quantitative PCR (qPCR), western blot, immunofluorescence and flow cytometry. The effect of JSH-23, an inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), on rTsCatL2-induced M1 polarization investigated. Cytotoxic effects of polarized macrophages on NBL were observed using in vitro killing assays.

Results
Following the co-incubation of rTsCatL2 with RAW264.7 murine macrophage cells, qPCR and ELISA revealed increased transcription and secretion levels of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, IL-1β and tumor necrosis factor alpha (TNF-α) in macrophages. Western blot analysis showed a significant increase in iNOS protein expression, while the expression level of arginase-1 protein remained unchanged. Flow cytometry revealed a substantial increase in the number of CD86-labeled macrophages. The western blot results also indicated that rTsCatL2 increased the expression levels of phospho-NF-κB and phospho-nuclear factor-κB inhibitor alpha (IκB-α) proteins in a dose-dependent manner, while immunofluorescence revealed that rTsCatL2 induced nuclear translocation of the p65 subunit of NF-κB (NF-κB p65) protein in macrophages. The inhibitory effect of JSH-23 suppressed and abrogated the effect of rTsCatL2 in promoting M1 macrophage polarization. rTsCatL2 mediated polarization of macrophages to the M1-like phenotype and enhanced macrophage adhesion and antibody-dependent cell-mediated cytotoxicity (ADCC) killing of NBL.

Conclusions
The results indicated that rTsCatL2 induces macrophage M1 polarization via the NF-κB pathway and enhances the ADCC killing of NBL. This study provides a further understanding of the interaction mechanism between T. spiralis and the host.

Graphical Abstract
Massive underrepresentation of Arabs in genomic studies of common disease
Authors: Bhattacharya Romit , Chen NingNing , Shim Injeong , Kuwahara Hiroyuki , Gao Xin , Alkuraya Fowzan S. , Fahed Akl C. 
Published: November 2023

AbstractArabs represent 5% of the world population and have a high prevalence of common disease, yet remain greatly underrepresented in genome-wide association studies, where only 1 in 600 individuals are Arab. We highlight the persistent and unaddressed underrepresentation of Arabs in genomic databases and discuss its impact on public health genomics and missed opportunities for biological discovery.
Targeting oncogenic TERT promoter variants by allele-specific epigenome editing
Authors: Kouroukli Alexandra G. , Rajaram Nivethika , Bashtrykov Pavel , Kretzmer Helene , Siebert Reiner , Jeltsch Albert , Bens Susanne 
Published: November 2023

Abstract
Background
Activation of dominant oncogenes by small or structural genomic alterations is a common driver mechanism in many cancers. Silencing of such dominantly activated oncogenic alleles, thus, is a promising strategy to treat cancer. Recently, allele-specific epigenome editing (ASEE) has been described as a means to reduce transcription of genes in an allele-specific manner. In cancer, specificity to an oncogenic allele can be reached by either targeting directly a pathogenic single-nucleotide variant or a polymorphic single-nucleotide variant linked to the oncogenic allele. To investigate the potential of ASEE in cancer, we here explored this approach by targeting variants at the TERT promoter region. The TERT promoter region has been described as one of the most frequently mutated non-coding cancer drivers.

Results
Sequencing of the TERT promoter in cancer cell lines showed 53% (41/77) to contain at least one heterozygous sequence variant allowing allele distinction. We chose the hepatoblastoma cell line Hep-G2 and the lung cancer cell line A-549 for this proof-of-principle study, as they contained two different kinds of variants, namely the activating mutation C228T in the TERT core promoter and the common SNP rs2853669 in the THOR region, respectively. These variants were targeted in an allele-specific manner using sgRNA-guided dCas9-DNMT3A-3L complexes. In both cell lines, we successfully introduced DNA methylation specifically to the on-target allele of the TERT promoter with limited background methylation on the off-target allele or an off-target locus (VEGFA), respectively. We observed a maximum CpG methylation gain of 39% and 76% on the target allele when targeting the activating mutation and the common SNP, respectively. The epigenome editing translated into reduced TERT RNA expression in Hep-G2.

Conclusions
We applied an ASEE-mediated approach to silence TERT allele specifically. Our results show that the concept of dominant oncogene inactivation by allele-specific epigenome editing can be successfully translated into cancer models. This new strategy may have important advantages in comparison with existing therapeutic approaches, e.g., targeting telomerase, especially with regard to reducing adverse side effects.
Animal models of primary biliary cholangitis: status and challenges
Authors: Wang Xu , Wei Yi , Yang Yanlei , Yang Yunjiao , Li Haolong , Li Yongzhe , Zhang Fengchun , Wang Li 
Published: November 2023

Abstract
Background
Primary biliary cholangitis (PBC) is an autoimmune liver disease. The aetiology of PBC remains unclear, and its pathogenesis is complex. Animal models are essential to clarify the pathogenesis of PBC and explore the occurrence of early events.

Main body
Herein, we review recent research progress in PBC animal models, including genetically modified, chemically inducible, biologically inducible, and protein-immunised models. Although these animal models exhibit several immunological and pathological features of PBC, they all have limitations that constrain further research and weaken their connection with clinical practice.

Conclusion
The review will benefit efforts to understand and optimise animal models in order to further clarify PBC pathogenesis and molecular targets for therapeutic interventions.
Highly rarefied gas flows in rough channels of finite length
Authors: Shi Zheng , Zhao Yulong , Su Wei , Wu Lei 
Published: November 2023

AbstractHighly rarefied gas flows through a rough channel of finite length with small bumps appended to its surfaces are investigated, by varying the accommodation coefficient $$\alpha$$
α
in Maxwell’s diffuse-specular boundary condition, the characteristic size and position of the bumps, and the channel length. First, we study the influence of the surface bumps and consider the rarefied gas flow in a unit channel with periodic boundary conditions to remove the end effect. It is found that the surface bumps have a significant impact on the flow permeability. When $$\alpha$$
α
is very small (i.e., nearly specular reflection of gas molecules at the channel surface), the apparent gas permeability is dramatically reduced, even in the presence of small bumps, to a value that is almost comparable to the one when fully diffuse gas-surface scattering is assumed. This impact can be taken into account through an effective accommodation coefficient, i.e., the permeability of the rough channel is taken equivalently as that of a smooth channel without bumps but having gas-surface scattering under the effective accommodation coefficient. Second, we study the end effect by connecting a smooth channel of length $$L_0$$

L
0

to two huge gas reservoirs. It is found that (i) the end correction length is large at small $$\alpha$$
α
. Consequently, the mass flow rate barely reduces with increasing $$L_0$$

L
0

rather than scales down by a factor of $$1/L_0$$

1
/

L
0

as predicted by the classical Knudsen diffusion theory; and (ii) the end correction is related to the channel’s aspect ratio. Finally, based on the effective accommodation coefficient and end correction, we explain the exotic flow enhancement in graphene angstrom-scale channels observed by Geim’s research group (Keerthi et al, Nature 558:420–424, 2018).
Ozone micron bubble pretreatment for antibiotic resistance genes reduction in hospital wastewater treatment
Authors: Hsiao Shui-Shu , Hsu Chia-Yu , Ananthakrishnan Balamurugan , Hsu Ming-Hao , Chien Yu-Ting , Wang Li-Pang , Tung Hsin-Hsin 
Published: November 2023

AbstractOzone micron bubble (OMB) treatment offers a promising approach to effectively eliminate Antibiotic Resistance Genes (ARGs) from infectious medical wastewater and mitigate the threat of drug resistance transmission. This study evaluated the effectiveness of OMB treatment for reducing ARGs from infectious medical wastewater in laboratory and on-site pilot treatment setups. In part, the presence of antibiotic residues in a hospital wastewater treatment plant (WWTP) and the impact of hospital wastewater on the distribution of ARGs in a wastewater collection system were also investigated. The results of wastewater collection system survey revealed a high prevalence of ARGs in the system, particularly mcr-1, largely originating from medical wastewater discharges. Furthermore, analysis of antibiotic residues in the hospital wastewater treatment system showed significant accumulation, particularly of quinolone antibiotics, in the biomass of the biological oxidation tank, suggesting a potential risk of ARG proliferation within the system. Comparison of wastewater samples from domestic and hospital WWTPs revealed a relatively higher abundance of ARGs in the latter, with differences ranging from 2.2 to sixfold between corresponding locations in the treatment plants. Notably, the biological oxidation unit of both WWTPs exhibited a greater proportion of ARGs among all sampled points, indicating the potential proliferation of ARGs within the biomass of the treatment units. ARG degradation experiments showed that OMB treatment resulted in a significantly lower CT value (9.3 mg O3 L−1 min) compared to ozone coarse bubble treatment (102 mg O3 L−1 min) under identical test conditions. Moreover, the use of OMB on site significantly reduced the accumulation of ARGs in hospital wastewater, underscoring its potential as an effective solution for mitigating ARG spread.
Smoking cessation interventions and implementations across multiple settings in Japan: a scoping review and supplemental survey
Authors: Nagasawa Tomomi , Saito Junko , Odawara Miyuki , Kaji Yuki , Yuwaki Keiichi , Imamura Haruhiko , Nogi Kazuya , Nakamura Masakazu , Shimazu Taichi 
Published: November 2023

Abstract
Background
Smoking is the leading risk factor for death worldwide. In Japan, although several evidence-based interventions (EBIs) for smoking cessation have been disseminated or adopted, there is a gap between scientific evidence and the actual implementation. This scoping review aimed to describe the knowledge gaps in local-level smoking cessation interventions in Japan, their implementation outcomes, implementation barriers and facilitators, and the use of implementation strategies.

Methods
This study comprised two approaches: (1) a comprehensive scoping review of primary and grey literature, and (2) a supplemental survey of organizations in the grey literature. For the scoping review, we included original studies or reports on smoking cessation interventions targeting adults aged 18 years and older, or providers of cessation support at various settings (community, workplace, school, and clinical settings) in Japan. The extracted data included basic characteristics, intervention categories, implementation outcomes, factors influencing implementation, and implementation strategies for each intervention. Responses to the supplemental survey were extracted same used for the scoping review. To gain a deeper understanding, semi-structured interviews were conducted with some of the organizations in the survey.

Results
A total of 600 interventions with 691 intervention components, based on EBIs in the 2020 US Surgeon General Report, from 498 articles were included in the data extraction; 32 of the 88 organizations responded to the survey. Regarding the overall knowledge about smoking cessation intervention components, behavioral counseling, and cessation medication in clinical settings were mostly reported (34.7%). Implementation outcomes were measured in 18 articles (3.0%) and penetration was mostly reported. Regarding influential factors, “available resources,” and “knowledge and beliefs about the intervention” for barriers, and “relative priority” for facilitators were mostly reported. Implementation strategies were measured in 29 articles (4.8%), and “Train and educate stakeholders” was mostly reported.

Conclusions
Most EBIs reported in the Japanese literature included smoking cessation treatments in clinical settings. While a few articles focused on the implementation indicators in Japan, significant knowledge and experience were extracted from the grey literature, especially in the workplace and community settings. Future research should focus more on implementation to reduce the knowledge gap regarding smoking cessation interventions.
Belief Updating Beyond the Two-State Setting
Authors: Mohrschladt Hannes , Baars Maren , Langer Thomas 
Published: November 2023

Heuristics and biases in probabilistic belief updating have typically been examined in simple two-state experimental settings. We argue that the two-state setting has probabilistic properties that do not extend to settings with more states. With three states, we find that individuals apply similar heuristics, such as representativeness and anchoring, when providing posterior probability distributions. However, because of the different normative benchmark, the use of these heuristics results in different biases for point estimates. In particular, we demonstrate that the well-known finding of stronger underinference for larger signal sets does not translate from the two-state to the three-state setting. Our findings caution against an indiscriminate transfer of updating biases observed in two-state settings to a broad set of real-world applications. This paper was accepted by Manel Baucells, behavioral economics and decision analysis. Funding: This work was supported by the Fritz Thyssen Stiftung [Grant 20.21.0.023WW]. Supplemental Material: The data and online appendix are available at https://doi.org/10.1287/mnsc.2022.00513 .