bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidating the Early SARS-CoV-2 Dynamics and Concomitant Immune Responses in Unvaccinated Participants of an Intensely Sampled Longitudinal Surveillance Study
Authors: Gunawardana Manjula , Webster Simon , Rivera Sofia , Cortez John , Breslin Jessica , Pinales Cristian , Buser Christopher , Ibarrondo Javier , Yang Otto , Bobardt Michael , Gallay Philippe , Adler Amy , Ramirez Christina , Anton Peter , Baum Marc
Published: April 2022

A comprehensive understanding of the SARS-CoV-2 infection dynamics and the ensuing host immune responses is needed to explain the pathogenesis as it relates to viral transmission. Here, we report results from an ongoing, longitudinal, workplace clinical surveillance study that address knowledge gaps surrounding SARS-CoV-2 in vivo kinetics, particularly in the earliest stages after exposure. Nine study participants who developed COVID-19 between November, 2020 and March, 2021 were monitored at high temporal resolution for three months in terms of viral loads as well as associated inflammatory biomarker and antibody responses. Analysis of the resulting datasets, supported by Bayesian modeling, allowed the underlying kinetic processes to be described, yielding a number of unexpected findings. Early viral replication is more rapid (median doubling time, 3.1 hours) than previously thought, shrinking the window between exposure and viral shedding. Results from our small study give a rare insight into the life-cycle of COVID-19 infection and hold a number of important biological, clinical, and public health implications.
Heme oxygenase-1 alleviates ischemia-reperfusion injury by inhibiting hepatocyte pyroptosis after liver transplantation in rats
Authors: Wang Tao , Fang Yuan , Zhang XiaoLi , Yang Yang , Jin Li , Li ZhiTao , Tang WeiQiang , Zhao Dan , Miao YingLei , Zeng Zhong , Huang HanFei
Published: April 2022

Background:Heme oxygenase-1 (HO-1) is recognized as a key cytoprotective mechanism for inflammation during ischemia-reperfusion injury (IRI). Accumulating evidence suggests that pyroptosis plays an important role in inflammation of IRI. However, the mechanism between HO-1 and pyroptosis in IRI requires further investigation.Methods:The "two-cuff" method was performed to establish a model of liver transplantation (LT) from donors after circulatory death. The HO-1 overexpression and shRNA recombinant adeno-associated virus (AAV) were constructed and transfected into rats. Flow cytometry was used to detect the expression of ROS in cells to evaluate the degree of oxidative stress. An automatic biochemical analyzer was performed to detect serum ALT and AST levels and evaluate liver function. Paraffin sections were stained with HE to observe the degree of pathological damage to the tissues. ELISA was applied to detect the levels of IL-1β and IL-18 in the liver tissues. The tissues were analyzed for the expression of HO-1, pro-caspase-1, p22, full-GSDMD, and cleaved-N-GSDMD by western blot. Immunohistochemistry was used to detect the expression of NLRP3. Results.The model was successfully constructed, and the difference in survival time obtained was statistically significant after HO-1 overexpression and shRNA recombinant AAV transfected into the donor. The expression of HO-1 was time-dependent with IRI. HE and Suzuki score showed that the short-term groups' tissue necrosis was severer than the control. ROS, ALT, and AST expression in the short-term after IRI was significantly higher than control. The expression of pro-caspase-1, p22, full-GSDMD, and cleaved-N-GSDMD trend was consistent with HO-1, increased significantly in short-term while decreasing in long-term. The expression level of NLRP3 was the lowest in the recent six hours. At six hours after IRI, compared with HO-1-shRNA groups, the ROS, IL-1β, IL-18, ALT, and AST in the HO-1 overexpression were significantly reduced, as well as p22 and cleaved-N-GSDMD, were significantly inhibited. Immunohistochemical revealed that the expression of NLRP3 had a higher level in HO-1 overexpression groups.Conclusion.HO-1 improved the survival rate of rats after LT. And HO-1 promoted the recovery of IRI after LT. This study demonstrated that HO-1 could inhibit hepatocyte pyroptosis, thereby reducing IRI after LT.
Cross-modal facilitation of memory through actions
Authors: Gasser Camille , Davachi Lila
Published: April 2022

Throughout our lives, the actions we produce can be highly familiar and repetitive (e.g., commuting to work); yet layered upon these routine actions are unique, one-shot, episodic experiences. Substantial research has shown that prior knowledge can facilitate learning of conceptually-related new information. However, despite the central role our behavior plays in ongoing experience, little is known about how engagement in a familiar sequence of actions might influence memory for unrelated, non-motor information coincident with those actions. To this end, participants encoded novel items while simultaneously following a sequence of actions (button presses) that was either predictable/well-learned or random. Across three experiments, we find that temporal order memory, but not item or source memory, is significantly enhanced for novel items encoded while participants executed predictable versus random action sequences. Such results suggest that the execution of predictable behaviors during novel learning scaffolds within-event temporal memory, an essential feature of episodic experiences.
Bristol Rabbit Pain Scale (BRPS): Clinical utility, validity and reliability
Authors: Benato L. , Murrell J. , Rooney N.
Published: April 2022

Background The Bristol Rabbit Pain Scale (BRPS) was developed using a unique combination of methods, focus groups and behavioural observation, that led to a composite pain scale of six categories (Demeanour, Posture, Locomotion, Ears, Eyes and Grooming) with four intensities of pain (0, 1, 2, and 3), and a total score of 0-18. The aim of this study was to assess the clinical utility, validity and reliability of the BRPS. Materials and methodsThe clinical utility of the BRPS was tested using a questionnaire composed of ten questions each on a five-point Likert scale ranging from one (strongly disagree) to five (strongly agree). The questionnaire asked questions such as whether the BRPS was easy and quick to use and whether it provided information that was clinically useful. The questionnaire was tested for internal reliability using the Cronbach’s alpha reliability coefficient. The construct validity (how well the tool measures the concept it was designed for) was measured by observers blindly rating 20 rabbits pre- and post-surgery whilst the criterion validity (the degree to which the tool correlates with a gold standard) was assessed by correlating the BRPS with a numerical rating scale (NRS) with a total score of 0-10. Inter-rater reliability was tested by quantifying the agreement in the pain scores given by nine participants when assessing the same 40 video clips. The intra-rater reliability was measured by testing how consistent the participants were when rating the same clips one month later. Results The median score of the ten questions of the clinical utility test was 4 (range 2-5). The Cronbach’s alpha reliability coefficient of the clinical utility test was good (α=0.811) demonstrating good internal consistency. The median (range) pain score of the BRPS and the NRS were 3 (0-14) and 0 (0-8) before surgery and 12 (1-18) and 7 (0-10) after surgery respectively. The BRPS demonstrated high construct validity (Z= -11.452; p ≤ 0.001) and there was a strong correlation between the BRPS and the NRS (Rho=0.851; p ≤ 0.001) indicating high criterion validity. The inter-rater and the intra-rater agreements were α =0.8633 and α =0.8610 respectively, which is considered good. ConclusionsThis study showed that the BRPS is a suitable tool for quantifying pain in rabbits in a clinically useful, valid and reliable way.
Nicotinamide mononucleotide enhances the efficacy and persistence of CD19 CAR-T cells via NAD + –Sirt1 axis
Authors: Yu Zhen , Tong Shuai , Zhang Can , Bai Yue , An Zhijing , Xu Chang , Wang Fang , Hu Yi , Zhuang Qinghui , Zhong Xiaosong
Published: April 2022

Chimeric antigen receptor (CAR)-modified T cells targeting antigens expressed on tumor cells have exhibited significant antitumor effects on several types of hematological malignancies, including acute myeloid leukemia, lymphoma, B cell maturation antigen, and CD19-positive acute lymphoblastic leukemia. However, several drawbacks, particularly the poor persistence, limit the use of CAR-T cell-based therapy. Nicotinamide mononucleotide (NMN), the precursor of nicotinamide adenine dinucleotide (NAD+), has been shown to reverse age-related complications and slow the aging rate by enhancing NAD+ levels in the body. However, whether NMN treatment could enhance the longevity and persistence of CAR-T cells and improve their antitumor efficacy is still unclear. In this study, we observed that NMN treatment limited differentiation and significantly increased stem cell–like memory (Tscm) and stem cell–like memory (Tcm) in CD19 CAR-T cells. In addition, both telomerase length and proliferation ability were increased, whereas apoptosis was reduced after NMN treatment of CD19 CAR-T cells. High-throughput sequencing data indicated that NMN treatment upregulated Sirt1 expression in CD19 CAR-T cells and downregulated genes downstream of Sirt1, such as NF-κB, TP53, and Bax. Animal experiments showed that NMN treated CAR-T cells exerted great antitumor efficacy in human xenografted mouse models. In conclusion, NMN enhances the efficacy and longevity of CD19 CAR-T cells via the NAD+–Sirt1 axis.
Early alterations of CD24hiCD38hi regulatory B cells (Bregs) in patients with sepsis
Authors: Bai Jianwen , Wang Chunmei Chunmei , Xu Huihui , Leng Fengying , Huo Fangjie , Li Yinzhen , Liu Siting , Xu Mingzheng
Published: April 2022

Background: Sepsis still remains a major challenge in intensive care medicine with unacceptably high mortality in patients with septic shock. Due to the current limitations of human CD20+CD24+CD38+ Breg (Breg) cells studies among sepsis, here, we tried to evaluate the early alterations of Breg cells and its severity and prognostic value in patients with sepsis.Methods: Peripheral blood from 58 patients with sepsis and 22 healthy controls was analyzed using flow cytometry to evaluate the frequency and numbers of Breg cells. All cases were divided into the sepsis group and septic shock group according to sepsis 3.0 criteria and were grouped according to whether they non-survived (dead group) or survived (alive group) followed up until death or 28 days after enrollment and were compared the differences of Breg cells frequency and numbers, separately. Interleukin (IL)-10 serum levels were measured by ELISA. Spearman's correlation analysis was performed on the Breg cell frequency and clinical indices. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to assess the sensitivity and specificity of Breg cells for the prognosis of sepsis. Survival curve analysis and binary logistic regression were performed to estimate the value of Breg cells in prognosis among cases with sepsis. Results: Compared to controls, sepsis patients had decreased proportions and numbers of Breg cells in their peripheral blood and increased serum levels of IL-10. The sepsis patients with low frequency of Breg cells were associated with an increased risk of septic shock. Breg cells frequency is inversely associated with lactate, SOFA and APACHE II and positively correlated with Treg frequency. Low levels of Breg cells were associated with an increased risk of death in patients with sepsis. The patients with lower Breg cells frequency and numbers showed a shorter overall survival. Numbers of Breg cells were prediction factors for poor prognosis.Conclusions: For sepsis patients, the frequency and numbers of Breg cells were decreased, and low frequency and numbers of Breg cells revealed poor prognosis. Breg cells may be used as a reliable resource in the determination of sepsis severity and prognosis.
Impact of different unconditional monetary incentives on survey response rates in men with prostate cancer: a 2-arm SWAT
Authors: McIntosh Megan , Opozda Melissa J , O’Callaghan Michael , Vincent Andrew D , Galvão Daniel A. , Short Camille E
Published: April 2022

Background: Men are often viewed as a difficult group to recruit for psychological research, including in psycho-oncology. Whilst research has demonstrated the effectiveness of monetary incentives for encouraging research participation, little research has examined different large unconditional incentive amounts. Larger unconditional incentives may result in increased participation of men in psychological research. This randomised study within a case-control trial of men diagnosed with early-stage prostate cancer aimed to investigate whether (a) response rates to a 30-minute questionnaire completed via mail, online, or phone would vary with different unconditional incentive amounts, and (b) demographics would vary in those who responded within the different incentive groups. Methods: We conducted this randomised study within a case-control cross-sectional study aiming to identify the social-ecological factors influcing treatment discontinuation in prostate cancer patients. A total of 238 participants from the cross-sectional study were randomised to receive one of two unconditional incentives (n=121 received AUD$10, n=117 received AUD$20) with the study materials (consent form and survey). Results: Overall, 113 (47%) responded; n=61/121 (50.4%) in the AUD$10 group, and n=52/117 (44.4%) in the AUD$20 group. No difference was found in response rates by incentive group (odds ratio 1.27, 95% CI=0.76-2.12, p=0.36). Additionally, there were no differences in the demographics of the responders vs. non-responders within each incentive group (all p>0.05). Conclusions: Unlike previous research, we were unable to show that higher monetary incentives were more effective for increasing response rates. An AUD$20 unconditional incentive may be no more effective than a lesser amount for encouraging prostate cancer survivors to participate in research involving long questionnaires. Future research should consider the cost-benefits of providing large unconditional incentives, as non-responses will result in lost resources perhaps better utilised in other engagement strategies.
Ethylene and polyamines interact in rice spikelet degeneration in response to water stress during meiosis
Authors: Chu Guang , Chen Song , Xu Chunmei , Liu Yuanhui , Zhang Xiufu , Wang Danying
Published: April 2022

This study aimed to investigate whether an interaction existed between ethylene and polyamines (PAs), which mediated the effects of water stress (WS) during meiosis on rice (Oryza sativa L.) spikelet degeneration. Two indica hybrid rice cultivars, HY113 (a drought-resistant rice cultivar) and ZZY8 (a drought-susceptible rice cultivar), were used in the present study, which were exposed to two soil moisture treatments: well water (WW) and WS. The spikelet degeneration rate (SDR) in WS plants increased by 12.1% for HY113 and 29.5% for ZZY8 compared with WW plants. The concentration of free spermidine (Spd) and free spermine (Spm) and the activities of S-adenosyl-l-methionine decarboxylase and Spd synthase were all significantly reduced in young panicles by the WS, with more reduction for ZZY8 than for HY113. The ethylene evolution rate, the concentrations of putrescine (Put), 1-aminocylopropane-1-car-boxylic acid (ACC), and H2O2, and the activities of ACC synthase and ACC oxidase in young panicles significantly increased for both cultivars under WS treatment, with more increase for ZZY8 than for HY113. Furthermore, when Spd or aminoethoxyvinylglycine (an inhibitor of ethylene synthesis) was applied to the young panicles of WS plants in the pollen mother cell meiosis prophase, the SDR significantly reduced. An opposite effect was observed when ACC or methylglyoxal-bis(guanylhydrazone) (an inhibitor of Spd and Spm synthesis) was applied to young panicles of WS plants. The results of the present study suggested the existence of an antagonistic interaction between ethylene and PA biosynthesis, which likely mediated the effect of WS during meiosis on rice spikelet degeneration.
KIT-c-Jun Signaling Up-regulated HMGCS1 to Promote Colorectal Cancer Development
Authors: Abbas Muhammad Khawar , Yang Liu , Sun Haimei , Sun Tingyi , Wu Bo , Ma Jian , Liu Xiaohui , Chen Hong , Yang Shu , Zhou Deshan
Published: April 2022

Purpose
Colorectal cancer (CRC) ranks 2nd in morbidity and 3rd in mortality among all cancers worldwide. 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is ubiquitously expressed in humans. Remarkably, the mevalonate pathway is often dysregulated in many cancers, suggesting tumor dependency on this classic metabolic pathway. In addition to altered substrates in the mevalonate pathway, it was recently found that HMGCS1 was highly expressed in prostate, melanoma and breast cancers. The transmembrane glycoprotein KIT is critical for the survival and development of various cells through activating downstream pathways and targets. Our previous research has proved that KIT is hyper-expressed in CRC and promotes CRC progression. However, whether HMGCS1 mediates the tumor-promoting effect of KIT signaling has not been unclosed.
Material and Methods
We investigated the regulatory mechanism of KIT signaling on HMGCS1 expression and the role of increased HMGCS1 in CRC development by the use of gene over-expression and knock-down techniques in CRC cells, biological function tests, protein-DNA binding detection, bioinformatics, database analysis and c-kit loss-of-function mutant mice (Wadsm/m).
Results
HMGCS1 was up-regulated by KIT-JNK-c-Jun signaling in CRC cells and could be a biomarker for CRC. Highly expressed HMCGS1 promoted CRC cell proliferation and invasion while inhibiting apoptosis. Our results provided evidence for the role of HMGCS1 in CRC progression and suggested that blocking KIT-JNK-c-Jun-HMGCS1 might be a new strategy for treating CRC patients.
Conclusion
Our results indicated that KIT signaling could up-regulate HMGCS1 in CRC mediated by Ap-1/c-Jun. Hyper-expressed HMGCS1 promotes CRC cell proliferation and invasion while inhibiting apoptosis.
Knowledge, Impact and Ethical Issues of Cancer Genomics among Oncologists
Authors: Sharawy Iman , Yassin Mohamed , Kelany Mohamed , Mostafa Ahmad , Orabi Mohamed El , Wasly Nancy El
Published: April 2022

Rapid advances in cancer genomic technologies not only affected testing and treatment but also have resulted in innumerable possibilities for research. This study was conducted to assess current knowledge of clinical cancer genomics, research, related ethical issues, and future impact among oncologists to help direct tailored competency-based curriculum development. A web-based survey was developed and organized into four sections: demographic information, cancer genomics knowledge, oncologists' perception of cancer genomics' future impact; and related ethical issues. Ninety percent of respondents were Egyptians, 83% knew what cancer genomics is and 66% knew its basic areas. Eighty-three % thought that cancer genomics will have an impact in the next 5 years. Nearly half (46%) of the respondents thought that there is a clear boundary between cancer genomics research and clinical care. Most oncologists refused using genetic data sharing (80%) or data transfer (79%) to third parties without consent. The core competencies of the proposed curriculum were then developed. There were 20 core competencies organized in two main domains: knowledge and skills (12 on knowledge and 8 on skills) for cancer genomics and associated ethics. Our findings could benchmark standards for postgraduate curriculum development of cancer genomics and its related ethics issues.
Molecular Identification of Pseudallescheria and Scedosporium Species complex from Soil in Sudan
Authors: Mhmoud Najwa A¹
Published: April 2022

Background: Species of the genus Scedosporium is a complex of ubiquitous filamentous fungal species that distributed varies according to geographic region. Several Pseudallescheria and Scedosporium species are indicator organisms of pollution in soil and water. In addition, the fungi may cause life-threatening infections in both immunocompromised and immunocompetent patients. This work aimed to investigate the environmental fungal occurrence of Pseudallescheria and Scedosporium species by using morphological characters and molecular sequencing. Results: Our results demonstrate that the most frequently recovered species of Scedosporium from environmental samples belonged to the Scedosporium apiospermum species complex in soil and water collected from 18 Sudanese states. These strains were identified according to their microscopic morphology and further confirmed by BT2 gene (98-100%sequence similarity) Scedosporium apiospermum was the microorganism most commonly recovered with 1662 isolates, followed by Scedosporium. boydii with 1168 , Scedosporium aurantiacum with 192 isolates, Scedosporium dehoogii with 22 isolates and Scedosporium angustum with 15 isolates .Conclusion: In conclusion, the data herein presented suggest that the presence of high numbers of Scedosporium apiospermum and Scedosporium boydii isolates in Sudanese environment may be relevant to their relative prevalence as causative agents of infection. Further surveys targeted at the environments of particular at risk groups patients, are indicated as are studies examining the genetic relatedness of environmental and clinical isolates using molecular-based tools.
Bee venom induced the interaction of phosphorylated histone variant, γH2AX, and intracellular location of beta actin in cancer cells
Authors: tetikoğlu sinan , uzuner Selcen çelik
Published: April 2022

Bee venom is a natural compound and candidate anti-cancer agent with selective cytotoxic effect on some cancer cells. However, the cellular mechanisms of how bee venom selectively targets cancer cells remain elusive. The aim of this study was to reveal the genotoxic effect of bee venom in concordance with the location of β-actin protein throughout nucleus or/and cytoplasm. For this aim, the level of H2AX phosphorylation (γH2AX) and intracellular location of β-actin were assessed by immunofluorescence in liver (HEPG2) and metastatic breast (MDA-MB-231) cancer cell lines compared to normal fibroblasts (NIH3T3) after bee venom. Co-localisation of γH2AX and β-actin were also analysed. The results showed that the levels of γH2AX staining decreased in normal cells but increased in cancer cells. Majority of β-actin was localised within the cytoplasm of normal cells after bee venom, but it was mostly accumulated within the nucleus in cancer cells. Co-localisation of β-actin and γH2AX both in nucleus and cytoplasm was induced in each cell by different patterns. The results showed that normal and cancerous cells had different responses against bee venom, and suggested that bee venom induced a cellular response by the interaction between γH2AX and β-actin.
Remote influence on intraseasonal variability of rainfall over Vietnam. Part 1: Observed composites
Authors: Le Hong Hanh , Hall Nicholas M.J. , Ngo-Duc Thanh
Published: April 2022

Remote influences on anomalous rainfall over North, Central and South Vietnam during extended summer (May-October) are explored using a 38-year (1979-2016) global dataset. Composites of wet and dry events with lags of up to two weeks are assembled for rainfall indices over these three subregions. The moisture budget and the large-scale dynamics associated with these events are described.
The moisture budget for composite precipitation events is examined using vertically integrated moisture flux convergence, vertically integrated tendency and evaporation. Variations are mainly explained by the flux convergence, which is seen to serve as a reasonable proxy for intraseasonal variability in rainfall.
Rainfall extremes of opposing signs show markedly asymmetrical large-scale precursors and different pathways of influence. Wet and dry events in North and Central Vietnam are seen to originate from Europe and propagate at high latitudes. The exact nature of the precursors is sensitive to the definition of the composite index. There is also a pathway of influence along the Asian jet, which impacts South Vietnam, especially for wet events which often coincide with dry events in the north. South and Central Vietnam are also influenced by tropical divergent precursors, which are again asymmetric between wet and dry events.
Assessment of Prenatal Developmental Toxicity Study of Bitter Melon Seed Extract from Supercritical Carbon Dioxide (scCO2) Extraction in Wistar Rats
Authors: Chung Wan-Yu , Nath Hritika , Hsu Pang-Kuei , Kuan Chen-Meng
Published: April 2022

Bitter melon (Momordica charantia) seed extracts exert hypoglycemic effects on animals and humans, but their safety and toxicological effects are still controversial in pregnant women. This study aims to assess the prenatal developmental toxicity of a bitter melon seed extract prepared from supercritical carbon dioxide (scCO2) extraction in Wistar rats based on the Organization for Economic Cooperation and Development (OECD) guideline No. 414. The extract was administered orally from gestation day (GD) 5 to 19, through gavage, to 25 mated female rats per group at the dose levels of 0, 250, 500, and 1000 mg/kg body weight (BW)/day, and all rats were sacrificed on GD 20. There were no mortality, morbidity, and obvious clinical signs of toxicity observed in the control and treatment groups. The results of body weight, weight gain, reproductive parameters (e.g., live/dead foetuses, sex ratio, anogenital distance), fetal examination (i.e., external and visceral observations), organ weight, and thyroid hormone analysis (i.e., tri-iodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH)) in all treatment groups were comparable with those of the control group. The changes in the mean body weight at GD 20, carcass weight in the middle and high groups, and the number of unossified xiphisternum in the high group were considered treatment related but non-adverse. Moreover, gross pathological examination did not find any abnormal lesions in vital organs and thyroid gland. Accordingly, the no observed adverse effect level (NOAEL) of the bitter melon seed extract for maternal and developmental toxicity was determined to be 1000 mg/kg BW.
Effect of Fluid Shear Stress on Apoptosis and Osteogenesis of Mesenchymal Stem Cells
Authors: Jiao Fei , Zhang Xiao , Ye Chongyang , Sun Qing , Gao Yan , Liu Chenglin , Huo Bo
Published: April 2022

Mechanical cues, including fluid shear stress (FSS) of interstitial flow within bone cavities, induce osteogenic differentiation of mesenchymal stem cells (MSCs). However, whether FSS leads to the apoptosis of MSCs and its relation with osteogenic differentiation are still unclear. In this study, the effect of FSS on apoptosis and osteogenesis of MSCs is investigated. FSS is applied intermittently to MSCs through a cone-plate flow chamber system for 3 d. And results show that FSS inhibits the apoptosis of MSCs. Compared with static culture group, FSS promotes osteogenesis, as shown by the expression of three osteogenic differentiation markers, namely, alkaline phosphatase (ALP), osteocalcin (OCN), and collagen I (COL I). Double staining of individual cells shows that the relationship of apoptosis and osteogenic differentiation of MSCs is mutually exclusive. YAP may mediate the FSS-inhibiting apoptosis of MSCs. The results will further elucidate the mechanism of mechanical stimulation-induced bone remodeling.
Expression of breast cancer resistant protein and P-glycoprotein in cultured primary bovine mammary epithelial cells isolated from tissue and milk
Authors: Roux-Pullen Lerica Le , de Laarschot Vienna Van , Doelen Marjolein Oosterveer-van der , Gehring Ronette
Published: April 2022

A tight monolayer of mammary epithelial cells, in which the transporter expression is well characterised, could be a useful in vitro model for studying how chemicals cross the blood-milk-barrier (BMB) and accumulate in milk. The efflux transporter breast cancer resistance protein (BCRP) is the predominant efflux transporter in the BMB. In order for an in vitro cell culture model to mimic the in vivo BMB, the expression of BCRP should be higher than that of the efflux transporter p-glycoprotein (P-gp). The aim of the study reported in this communication was to determine the relationship between the transcription of ABCG2 and ABCB1 (encoding for BCRP and P-gp respectively) in primary bovine mammary epithelial cells in culture. Cells were sourced from both lactating udder tissue after routine slaughter of the donor, and then cryopreserved until use, as well as from fresh, raw milk of healthy cows in mid-lactation. In this study a total of 18 RNA samples from 18 individual trypsinisations, originating from 6 individual isolations (3 milk isolations and 3 udder tissue isolations) were analysed by rt-PCR. In all eighteen samples analysed, the mRNA detected for P-gp was higher per sample than the mRNA detected for BCRP. In six samples no mRNA for BCRP was detected at 40 amplification cycles. Our study showed that when pbMEC is cultured in the proliferation medium as described, P-gp mRNA expression is consistently higher than BCRP mRNA expression. This relationship is the inverse of the relationship between BCRP and P-gp in the BMB in vivo.
The mechanism of a humid climate on the joints of normal rats and collagen- induced arthritis rats: mutual effects on faecal metabolism and microbial diversity
Authors: Wang Dingnan , Zheng Zhili , Yu Han , Dou Dou , Gao Yining , Xu Shuang , Li Zhiming , Sun Lili , Qiu Xudong , Zhong Xianggen
Published: April 2022

BackgroundStudies have shown that high humidity is a condition that aggravates the pain of rheumatoid arthritis (RA), but the relevant mechanism is controversial. Currently, there is a lack of animal experimental studies on high humidity as an adverse factor related to the pathogenesis of RA.MethodsWe used healthy SD rats and collagen-induced arthritis (CIA) rats to investigate the effects of high humidity on arthritis in healthy rats and CIA rats. Integrated metabolomics analyses of faeces and 16S rRNA sequencing of the faecal microbiota were performed to comprehensively analyse the results and diversity of the faecal microbiota and metabolites in healthy rats and CIA rats.ResultsIn this study, high humidity aggravated arthritis in CIA rats, including articular cartilage lesions, arthritis scores, and proinflammatory cytokines. High humidity had a certain effect on articular cartilage extent, arthritis score and proinflammatory cytokines of healthy rats. Furthermore, high humidity caused significant changes in faecal microbes and faecal metabolites in healthy and CIA rats. Sequencing of the 16S rRNA unit in faecal samples showed that high humidity aggravated inflammation-related bacteria in healthy and CIA rats. Faecal metabolomics results showed that high humidity significantly altered faecal metabolites in healthy rats and CIA rats, and the changes in biological functions were mainly related to the inflammatory response and oxidative stress. Combined analysis showed that there was a strong correlation between the faecal microbiota and faecal metabolites.ConclusionHigh humidity is an adverse factor for the onset and development of RA, and its mechanism is related to the inflammatory response and oxidative stress. However, how high humidity leads to the pathogenesis of RA needs to be further determined.
Transcriptome Dysregulation in Hepatoblastoma: The Pivotal Role of Noncoding Rnas and Changes in Lipid Metabolism
Authors: Rivas Maria Prates , Aguiar Talita Ferreira Marques , de Andrade Edson Mario , Pires Sara Ferreira , Defelicibus Alexandre , Barros Bruna , Novak Estela , Cristofani Lilian Maria , Odone Vicente , Cypriano Monica , de Toledo Silvia Regina Caminada , Cunha Isabela Werneck da , Costa Cecilia Maria Lima da , Carraro Dirce Maria , Tojal Israel , Mendes Tiago Antônio de Oliveira , Krepischi Ana Cristina Victorino
Published: April 2022

Hepatoblastoma, the most common liver tumor in children and exhibited the lowest mutational burden among solid cancers, pointing to chromosomal and epigenetic changes as the main drivers of tumorigenesis. Previous studies explored hepatoblastoma transcriptomes focusing on risk stratification, but no consensual molecular signature emerged. We performed whole-transcriptome analysis with total RNA sequencing using 14 hepatoblastomas compared with control liver samples. A set of 1,492 differentially expressed genes (DEGs) was detected, 1,031 upregulated and 461 downregulated, comprising 920 protein-coding genes (62%). A strong dysregulation of non-coding RNA genes (ncRNAs) was revealed, mostly upregulated. Among the top 50 genes with the highest expression, 42% of them were ncRNAs, and three (MAGED4, SNO144-16, and RP11-431J24.2) were exclusively expressed by hepatoblastomas. Upregulated biological processes were linked to cell differentiation, communication and signaling pathways, as well as embryonic and developmental processes. Enriched biological processes in downregulated genes included mainly negative regulation of oxidation and metabolism inhibition, affecting amine, nicotinamide, and lipids. An integrative analysis between miRNA-mRNA and protein-protein interaction networks highlighted major biological processes associated with metabolism and oxidation reactions of lipids and carbohydrates, methylation-dependent chromatin silencing, and DNA methylation. Four upregulated miRNAs (miR-186, miR-214, miR-377, and miR-494) were disclosed, potentially targeting more than 10 protein-coding transcripts, which suggested a possible role in their negative regulation. In conclusion, the RNASeq analysis revealed the disruption of metabolic pathways, including lipids, amines, and nicotinamides, and disclosed a robust ncRNA transcriptome perturbation, highlighting a new epigenetic player in the control of hepatoblastoma gene expression, along with DNA methylation.
Acid-base balance, osmoregulation and hematological changes in tilapia (Oreochromis niloticus) after sublethal cadmium exposure
Authors: Soegianto Agoes , Yulianto Bambang , Payus Carolyn Melissa , Affandi Moch , Mukholladun Wildanun , Indriyasari Khudrotul Nisa , Marchellina Ary , Rahmatin Nailul Muthiati
Published: April 2022

Tilapia exposed to two different Cd concentrations in freshwater had varying levels of Cd in their gills, with fish exposed to 2 mg/L of Cd having a higher Cd level than fish exposed to 1 mg/L of Cd. The higher Cd level exposure caused considerable metabolic acidosis (lower pH and higher pCO2) and inhibited gill carbonic anhydrase. Fish exposed to higher Cd levels had lower osmolality, levels of plasma Cl− and K+ but constant levels of Na+. All hematological parameters tested in this study, including red blood cells, hemoglobin, hematocrit, and mean cellular hemoglobin concentration hematocrit, decreased as a result of increased Cd exposure. This is consistent with the pO2 measurement, which indicates that fish exposed to greater levels of Cd had a considerable reduction in pO2.
Intelli-NGS: Intelligent NGS, a deep neural network-based artificial intelligence to delineate good and bad variant calls from IonTorrent sequencer data
Authors: Singh Aditya , Bhatia Prateek
Published: April 2022

Ion Torrent is a second-generation sequencing platform with smaller capital costs than Illumina but is also prone to higher machine error than latter (0.5-2% Vs. 0/01 − 0/05%). Limited software tools or pipelines are available for Ion Torrent data filtering and most of them have limitations or take time for analysis. Given to the unexplored possibilities that machine learning could uncover, we explored it to address this issue of solving quality variants from Ion torrent data. The artificial intelligence was developed from scratch in Python 3 using TensorFlow fully connected dense layers. The model takes VCF files as input and solves each variant based on the thirty-five parameters given by the Ion Torrent platform, including the flow-space information which is missed by variant callers other than the default torrent variant caller. The final trained model was able to achieve an accuracy of 93.08% and a ROC-AUC of 0.95 with GIAB validation data. The additional program that was written to run the model annotates each variant using online databases such as dbSNP, ClinVar and others. A probability score for each outcome for each variant is also provided to aid in decision making. The model and running code are available for free at https://www.github.com/aditya-88/intelli-ngs.
The Evaluation of the epigenetics related genes expression (DNMT, HDAC1) in Iranian patients with Systemic Lupus Erythematosus
Authors: Abbasifard Mitra , Mohammadiranjbar Fahimeh , Mohammad-Sadeghipour Maryam , Mahmoodi Mehdi , Hassanshahi Gholamhossein , Swann Jennifer , Hosseiniara Reza , Hajizadeh Mohammad Reza
Published: April 2022

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which the immune system abnormally reacts against cells and tissues leading to inflammation. Epigenetic alterations, including DNA methylation and histone modification, have critical effects on autoimmune disease and SLE pathogenesis via dysregulation of critical genes. Aims: The purpose of this study was to evaluate the epigenetic-related gene expression of DNA methyltransferase (DNMT) and Histone Deacetylase 1 (HDAC1) in Iranian patients with SLE. Methods: This matched case-control study included 16 people with SLE and 16 healthy people who were referred to the Rafsanjan rheumatology clinic, in the southeast of Iran. The expression of DNMT and HDAC1 genes was measured through a Real-time PCR assay of blood samples. Results: DNMT gene expression did not differ significantly between SLE and healthy groups (P=0.21). In contrast, HDAC1 gene expression was enhanced in the SLE group, but this enhancement failed to reach statistical significance (P=0.94). Conclusion: The results of this study suggest that overexpression of HDAC1 could serve as a diagnostic for SLE disease. Additional studies with larger sample sizes are required to confirm our findings. Evaluation of other genes are related to SLE disease is essential and may help to form an accurate diagnosis of the disease.
A 3-Player Game with Bounded Rationality Concerning Ecology Compensation and Environmental Tax Policies
Authors: Chen Xiaozhu , Zhang Jixiang
Published: April 2022

In the face of environmental hazards caused by low nitrogen utilization efficiency, this paper constructed a 3-player game model which contains local governments, peasant households, and polluting enterprises with bounded rationality, all of which take part in the nitrogen cascade in the watersheds. The Nash equilibrium points and local stability of the dynamical systems were investigated. Complex dynamics i.e. bifurcation and chaos arise from the variation of some parameters of the model, including the adjustment speed of decision-making of a boundedly rational player. Numerical simulations were rendered to manifest bifurcation, chaos, maximal Lyapunov exponent, strange attractor, and sensitive dependence on initial conditions. Chaos control of the dynamic systems was discussed using the delayed feedback scheme. Research results indicate that whereas the adjustment speed of players has a destabilizing effect, a proper increment of the ecological compensation or environmental tax rate will restore the local stability of the system. Moreover, while the excessive adjustment speed has caused the system to behave chaotically, an increase of the feedback controller can eliminate chaos and achieve a stable market.
Ribosomal RNA-depletion provides an efficient method for successful dual RNA-Seq expression profiling of a marine sponge holobiont
Authors: Xiang Xueyan , Poli Davide , Degnan Bernard M. , Degnan Sandie M.
Published: April 2022

Investigations of host-symbiont interactions can benefit enormously from a complete and reliable holobiont gene expression profiling. The most efficient way to acquire holobiont transcriptomes is to perform RNA-Seq on both host and symbionts simultaneously. However, optimal methods for capturing both host and symbiont mRNAs are still under development, particularly when the host is a eukaryote and the symbionts are bacteria or archaea. Traditionally, poly(A)-enriched libraries have been used to capture eukaryotic mRNA, but the ability of this method to adequately capture bacterial mRNAs is unclear because of the short half-life of the bacterial transcripts. To determine the optimal RNA-Seq approach for animal host–bacterial symbiont analysis, we compared transcriptome bias, depth and coverage achieved by two different mRNA capture and sequencing strategies applied to the marine demosponge Amphimedon queenslandica holobiont, for which genomes of the animal host and three most abundant bacterial symbionts are available. The two strategies were: (i) poly(A) captured mRNA-Seq (Poly(A)-RNA-Seq); and (ii) ribosomal RNA depleted RNA-Seq (rRNA-depleted-RNA-Seq). For the host sponge, we find no significant difference in transcriptomes generated by the two different mRNA capture methods. However, for the symbiont transcriptomes, we confirm the expectation that the rRNA-depleted-RNA-Seq performs much better than the Poly(A)-RNA-Seq. Importantly, the availability of all genomes allowed us to accurately assess the nature of the Poly(A) bias compared to the rRNA-depleted transcriptomes. This comparison demonstrates that RNA-Seq by ribosomal RNA depletion is an effective and reliable method to analyse holobiont transcriptomes.
Clinical Target Volume Automatic Segmentation Based on Lymph Node Stations for Lung Cancer with Bulky Lump Lymph Nodes
Authors: Di Mingyi , Shen Jing , Wang Shaobin , Chen Qi , Chen Yu , Liu Zhikai , Lian Xin , Ma Jiabin , Pang Yantian , Dong Tingting , Wang Bei , Guan Qiu , He Lei , Zhang Yue , Liang Hao , Shen Jie , Zhang Fuquan
Published: April 2022

The lack of standardized delineation of lymph node station in lung cancer radiotherapy leads to nonstandard clinical target volume (CTV) contouring, especially in patients with bulky lump gross target volume lymph nodes (GTVnd). Therefore, this study defines lymph node region boundaries in radiotherapy for lung cancer and automatically contours lymph node stations based on the International Association for the Study of Lung Cancer (IASLC) lymph node map. Computed tomography (CT) scans of 200 patients with small cell lung cancer are collected. The lymph node zone boundaries are defined based on the IASLC lymph node map, with adjustments to meet radiotherapy requirements. Contours of lymph node stations are confirmed by two experienced oncologists. A model (DiUNet) is constructed by incorporating the contours of GTVnd to precisely contour the boundaries. Quantitative evaluation metrics and clinical evaluations are conducted. This is the first study to propose a method that automatically contours lymph node regions station by station based on the IASLC lymph node map with bulky lump GTVnd. Delineation of lymph node stations based on the DiUNet model is a promising strategy to obtain accuracy, consistency, and efficiency for CTV delineation in lung cancer patients, especially for bulky lump GTVnd.
Geochemistry of Neogene Nansatsu volcanic rocks and its implications on the evolution of Au province in South Kyushu
Authors: Ishida Mizuki , Murakami Shunpei , Machida Shiki , Fujinaga Koichiro , Yasukawa Kazutaka , Ishikawa Tsuyoshi , Nagaishi Kazuya , Tajiri Rie , Nakamura Kentaro , Kato Yasuhiro
Published: April 2022

In South Kyushu, Japan, epithermal Au deposits are associated with volcanic rocks younger than 7.5 Ma, whereas Sn and W deposits are associated with middle Miocene (17–12 Ma) Outer Zone granitoids. As magma chemistry often controls the type and size of a mineral deposit, the geochemistry of igneous rocks in this area can provide valuable information about the evolution of metallogenic provinces. In this study, we reported the whole-rock major and trace element and Sr–Nd–Pb isotopic compositions of volcanic rocks from the Nansatsu area in South Kyushu, where several high-sulfidation Au deposits are located. We analyzed samples from the Oldest stage (middle Miocene), Older stage (late Miocene), and Middle stage (early Pliocene) Nansatsu volcanic rocks, which were andesite to dacite in composition, with an island-arc trace element signature. Their elemental compositions largely overlapped with both Outer Zone granitoids and volcanic rocks younger than 7.5 Ma in South Kyushu. Isotopic characteristics suggested that the Oldest stage volcanic rocks had magma sources similar to Outer Zone granitoids, whereas the sources for the Older and Middle stage magmas were similar to those of basalts formed <7.5 Ma in South Kyushu. The Oldest stage rocks (as well as Outer Zone granitoids) incorporated a substantial amount of organic-carbon-rich sedimentary rocks (Shimanto Supergroup), which resulted in reduced magma and consequently, lack of Au mineralization. In contrast, it is likely that the magmas that produced the Older and Middle stage rocks did not contaminate as much Shimanto Supergroup, thus avoiding reduction and early sulfide saturation. Effective transportation of mantle-derived magma, without significant crustal contamination, may have been an important factor for Au mineralization after 7.5 Ma in South Kyushu.