bluuebunny/crossref_metadata_2025 huggingface dataset:
Inverse association between low-density lipoprotein cholesterol and bone mineral density in young- and middle-aged people: The NHANES 2011–2018
Authors: Xiao Fangjun , Peng Peng , Gao Shihua , Lin Tianye , Fang Weihua , He Wei
Published: August 2022

Objectives

Low-density lipoprotein cholesterol (LDL-C) plays an essential part in bone metabolism. However, the correlation between LDL-C levels and bone mineral density (BMD) is still controversial. This study aimed to explore the relationship between LDL-C levels and lumbar BMD in young- and middle-aged people.

Methods

We conducted a cross-sectional study comprising 4,441 participants aged 20–59 from the National Health and Nutrition Examination Survey (NHANES). LDL-C levels and lumbar BMD were used as independent and dependent variables, respectively. We evaluated the correlation between LDL-C levels and lumbar BMD through a weighted multivariate linear regression model. We performed a subgroup analysis of the relationship between LDL-C levels and lumbar BMD based on age, gender, and body mass index (BMI).

Results

After adjusting for confounding factors, LDL-C levels were negatively correlated with lumbar BMD. In subgroup analyses stratified by gender, this negative association was statistically significant in men and women. In the subgroup analysis stratified by age, a negative connection existed in people aged 30–49 years. In the subgroup analysis divided by BMI, there was an inverse correlation in overweight people (25 ≤ BMI < 30).

Conclusions

Our research observed an inverse association between LDL-C levels and lumbar BMD in young- and middle-aged people, especially in people aged 30–49 years and who are overweight. Close monitoring of BMD and early intervention may be required for these people.
Tracing and regulating redox homeostasis of model benthic ecosystems for sustainable aquaculture in coastal environments
Authors: Shono Nobuaki , Ito Mana , Umezawa Akio , Sakata Kenji , Li Ailong , Kikuchi Jun , Ito Katsutoshi , Nakamura Ryuhei
Published: August 2022

Aquaculture in coastal environments has an increasingly important role in the world’s food supply; however, the accumulation of organic compounds on seafloors due to overfeeding adversely affects benthic ecosystems. To assess the ecological resilience of aquafarms to nutrient influx, we investigated the redox homeostasis of benthic ecosystems using a marine oligochaete as a model benthic organism in aquaculture fields. Real-time monitoring of the redox potential of a model benthic ecosystem constructed in an electrochemical reactor allowed evaluation of the homeostatic response of the system to nutrient addition. Although the detrimental effects of overfeeding were confirmed by irreversible potential changes in the sediment, redox homeostasis was reinforced through a cooperative relationship between oligochaetes and sediment microorganisms. Specifically, the oligochaetes exhibited reversible changes in metabolism and body position in response to dynamic changes in the sediment potential between −300 and 500 mV, thereby promoting the decomposition of organic compounds. The potential-dependent changes in metabolism and body position were reproduced by artificially manipulating the sediment potential in electrochemical reactors. Given the importance of benthic animals in sustaining coastal ecosystems, the electrochemical monitoring and physiologic regulation of marine oligochaetes could offer an intriguing approach toward sustainable aquaculture.
Microbiota differences of skin and pharyngeal microbiota between patients with plaque and guttate psoriasis in China
Authors: Hu Jingjin , Lu Wenhua , Li Xingyu , Yang Jing , Tan Minjia , Hu Kun , Wang Qiaolin , Deng Sichun , Liu Yijie , Chen Junchen , Zhu Wu , Kuang Yehong
Published: August 2022

Psoriasis can be provoked or exacerbated by environmental exposures such as certain microbiomes. The distinction between plaque psoriasis (PP) and guttate psoriasis (GP) in the skin or pharyngeal microbiota is not yet clear. High-throughput sequencing using Illumina MiSeq was used in this study to characterize skin and pharyngeal microbial composition in patients with PP [large PP (LPP, n = 62), small PP (SPP, n = 41)] and GP (n = 14). The alpha- and beta-diversity of skin microbiota LPP was similar to that of the SPP group, but different from the GP group. There were no differences in pharyngeal microbiota among the groups. According to linear discriminant analysis effect size (LEfSe) analysis, Staphylococcus, Stenotrophomonas, Enhydrobacter, Brevundimonas, and Allorhizobium–Neorhizobium–Pararhizobium–Rhizobium were the dominant genera of skin microbiota in PP. Diversity of skin microbiota correlated with Psoriasis Area and Severity Index (PASI). Moderate-to-severe psoriasis and mild psoriasis have different microbiota compositions. The skin microbiota may be related to the pharyngeal microbiota. Furthermore, two microbiota-based models could distinguish psoriasis subtypes with area under the receiver-operating characteristic curve (AUC-ROC) of 0.935 and 0.836, respectively. In conclusion, the skin microbiota in patients with LPP is similar to that in patients with SPP, but displays variations compared to that of GP, no differences are noted between subtypes in pharyngeal microbiota. Skin microbiota diversity correlated with PASI.
Effective mechanisms of water purification for nitrogen-modified attapulgite, volcanic rock, and combined exogenous microorganisms
Authors: Zheng Yao , Wang Yuqin , Yang Xiaoxi , Gao Jiancao , Xu Gangchun , Yuan Julin
Published: August 2022

The study tested the water purification mechanism of the combination of microorganisms and purification materials via characteristic, enzymatic, and metagenomics methods. At 48 h, the removal rates of total nitrogen, total phosphorous, and Mn chemical oxygen demand in the combination group were 46.91, 50.93, and 65.08%, respectively. The alkaline phosphatase (AKP) activity increased during all times tested in the volcanic rock, Al@TCAP, and exogenous microorganism groups, while the organophosphorus hydrolase (OPH), dehydrogenase (DHO), and microbial nitrite reductase (NAR) activities increased at 36-48, 6-24, and 36-48 h, respectively. However, the tested activities only increased in the combination groups at 48 h. Al@TCAP exhibits a weak microbial loading capacity, and the Al@TCAP removal is primarily attributed to adsorption. The volcanic rock has a sufficient ability to load microorganisms, and the organisms primarily perform the removal for improved water quality. The predominant genera Pirellulaceae and Polynucleobacter served as the sensitive biomarkers for the treatment at 24, 36-48 h. Al@TCAP increased the expression of Planctomycetes and Actinobacteria, while volcanic rock increased and decreased the expression of Planctomycetes and Proteobacteria. The growth of Planctomycetes and the denitrification reaction were promoted by Al@TCAP and the exogenous microorganisms. The purification material addition group decreased the expression of Hyaloraphidium, Chytridiomycetes (especially Hyaloraphidium), and Monoblepharidomycetes and increased at 36-48 h, respectively. Ascomycota, Basidiomycota, and Kickxellomycota increased in group E, which enhanced the nitrogen cycle through microbial enzyme activities, and the growth of the genus Aspergillus enhanced the phosphorous purification effect.
Genomic and virologic characterization of samples from a shipboard outbreak of COVID-19 reveals distinct variants within limited temporospatial parameters
Authors: Cer Regina Z. , Voegtly Logan J. , Adhikari Bishwo N. , Pike Brian L. , Lueder Matthew R. , Glang Lindsay A. , Malagon Francisco , Ana Ernesto Santa , Regeimbal James M. , Potts-Szoke Maria F. , Schully Kevin L. , Smith Darci R. , Bishop-Lilly Kimberly A.
Published: August 2022

Early in the pandemic, in March of 2020, an outbreak of COVID-19 occurred aboard the aircraft carrier USS Theodore Roosevelt (CVN-71), during deployment in the Western Pacific. Out of the crew of 4,779 personnel, 1,331 service members were suspected or confirmed to be infected with SARS-CoV-2. The demographic, epidemiologic, and laboratory findings of service members from subsequent investigations have characterized the outbreak as widespread transmission of virus with relatively mild symptoms and asymptomatic infection among mostly young healthy adults. At the time, there was no available vaccination against COVID-19 and there was very limited knowledge regarding SARS-CoV-2 mutation, dispersal, and transmission patterns among service members in a shipboard environment. Since that time, other shipboard outbreaks from which data can be extracted have occurred, but these later shipboard outbreaks have occurred largely in settings where the majority of the crew were vaccinated, thereby limiting spread of the virus, shortening duration of the outbreaks, and minimizing evolution of the virus within those close quarters settings. On the other hand, since the outbreak on the CVN-71 occurred prior to widespread vaccination, it continued over the course of roughly two months, infecting more than 25% of the crew. In order to better understand genetic variability and potential transmission dynamics of COVID-19 in a shipboard environment of immunologically naïve, healthy individuals, we performed whole-genome sequencing and virus culture from eighteen COVID-19-positive swabs collected over the course of one week. Using the unique variants identified in those genomes, we detected seven discrete groups of individuals within the population aboard CVN-71 infected with viruses of distinct genomic signature. This is in stark contrast to a recent outbreak aboard another U.S. Navy ship with >98% vaccinated crew after a port visit in Reykjavik, Iceland, where the outbreak lasted only approximately 2 weeks and the virus was clonal. Taken together, these results demonstrate the utility of sequencing from complex clinical samples for molecular epidemiology and they also suggest that a high rate of vaccination among a population in close communities may greatly reduce spread, thereby restricting evolution of the virus.
Bedside interpretation of cerebral energy metabolism utilizing microdialysis in neurosurgical and general intensive care
Authors: Nordström Carl-Henrik , Forsse Axel , Jakobsen Rasmus Peter , Mölström Simon , Nielsen Troels Halfeldt , Toft Palle , Ungerstedt Urban
Published: August 2022

The microdialysis technique was initially developed for monitoring neurotransmitters in animals. In 1995 the technique was adopted to clinical use and bedside enzymatic analysis of glucose, pyruvate, lactate, glutamate and glycerol. Under clinical conditions microdialysis has also been used for studying cytokines, protein biomarkers, multiplex proteomic and metabolomic analyses as well as for pharmacokinetic studies and evaluation of blood-brain barrier function. This review focuses on the variables directly related to cerebral energy metabolism and the possibilities and limitations of microdialysis during routine neurosurgical and general intensive care. Our knowledge of cerebral energy metabolism is to a large extent based on animal experiments performed more than 40 years ago. However, the different biochemical information obtained from various techniques should be recognized. The basic animal studies analyzed brain tissue homogenates while the microdialysis technique reflects the variables in a narrow zone of interstitial fluid surrounding the probe. Besides the difference of the volume investigated, the levels of the biochemical variables differ in different compartments. During bedside microdialysis cerebral energy metabolism is primarily reflected in measured levels of glucose, lactate and pyruvate and the lactate to pyruvate (LP) ratio. The LP ratio reflects cytoplasmatic redox-state which increases instantaneously during insufficient aerobic energy metabolism. Cerebral ischemia is characterized by a marked increase in intracerebral LP ratio at simultaneous decreases in intracerebral levels of pyruvate and glucose. Mitochondrial dysfunction is characterized by a moderate increase in LP ratio at a very marked increase in cerebral lactate and normal or elevated levels of pyruvate and glucose. The patterns are of importance in particular for interpretations in transient cerebral ischemia. A new technique for evaluating global cerebral energy metabolism by microdialysis of the draining cerebral venous blood is discussed. In experimental studies it has been shown that pronounced global cerebral ischemia is reflected in venous cerebral blood. Jugular bulb microdialysis has been investigated in patients suffering from subarachnoid hemorrhage, during cardiopulmonary bypass and resuscitation after out of hospital cardiac arrest. Preliminary results indicate that the new technique may give valuable information of cerebral energy metabolism in clinical conditions when insertion of an intracerebral catheter is contraindicated.
EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic review
Authors: Wood Oliver W. G. , Yeung Jason H. Y. , Faull Richard L. M. , Kwakowsky Andrea
Published: August 2022

Glutamate is the main excitatory neurotransmitter in the human central nervous system, responsible for a wide variety of normal physiological processes. Glutamatergic metabolism and its sequestration are tightly regulated in the normal human brain, and it has been demonstrated that dysregulation of the glutamatergic system can have wide-ranging effects both in acute brain injury and neurodegenerative diseases. The excitatory amino acid transporter 2 (EAAT2) is the dominant glutamatergic transporter in the human brain, responsible for efficient removal of glutamate from the synaptic cleft for recycling within glial cells. As such, it has a key role in maintaining excitatory-inhibitory homeostasis. Animal studies have demonstrated dysregulation or alterations of EAAT2 expression can have implications in neurodegenerative disorders. Despite extensive research into glutamatergic alterations in AD mouse models, there is a lack of studies examining the expression of EAAT2 within the AD human brain. In this systematic review, 29 articles were identified that either analyzed EAAT2 expression in the AD human brain or used a human-derived cell culture. Studies were inconclusive as to whether EAAT2 was upregulated or downregulated in AD. However, changes in localization and correlation between EAAT2 expression and symptomatology was noted. These findings implicate EAAT2 alterations as a key process in AD progression and highlight the need for further research into the characterization of EAAT2 processes in normal physiology and disease in human tissue and to identify compounds that can act as EAAT2 neuromodulators.
Brain laterality evaluated by F-18 fluorodeoxyglucose positron emission computed tomography in autism spectrum disorders
Authors: Keeratitanont Keattichai , Theerakulpisut Daris , Auvichayapat Narong , Suphakunpinyo Chanyut , Patjanasoontorn Niramol , Tiamkao Somsak , Tepmongkol Supatporn , Khiewvan Benjapa , Raruenrom Yutapong , Srisuruk Piyawan , Paholpak Suchat , Auvichayapat Paradee
Published: August 2022

Background and rationale

Autism spectrum disorder (ASD) is a neuropsychiatric disorder that has no curative treatment. Little is known about the brain laterality in patients with ASD. F-18 fluorodeoxyglucose positron emission computed tomography (F-18 FDG PET/CT) is a neuroimaging technique that is suitable for ASD owing to its ability to detect whole brain functional abnormalities in a short time and is feasible in ASD patients. The purpose of this study was to evaluate brain laterality using F-18 FDG PET/CT in patients with high-functioning ASD.

Materials and methods

This case-control study recruited eight ASD patients who met the DSM-5 criteria, the recorded data of eight controls matched for age, sex, and handedness were also enrolled. The resting state of brain glucose metabolism in the regions of interest (ROIs) was analyzed using the Q.Brain software. Brain glucose metabolism and laterality index in each ROI of ASD patients were compared with those of the controls. The pattern of brain metabolism was analyzed using visual analysis and is reported in the data description.

Results

The ASD group’s overall brain glucose metabolism was lower than that of the control group in both the left and right hemispheres, with mean differences of 1.54 and 1.21, respectively. We found statistically lower mean glucose metabolism for ASD patients than controls in the left prefrontal lateral (Z = 1.96, p = 0.049). The left laterality index was found in nine ROIs for ASD and 11 ROIs for the control. The left laterality index in the ASD group was significantly lower than that in the control group in the prefrontal lateral (Z = 2.52, p = 0.012), precuneus (Z = 2.10, p = 0.036), and parietal inferior (Z = 1.96, p = 0.049) regions.

Conclusion

Individuals with ASD have lower brain glucose metabolism than control. In addition, the number of ROIs for left laterality index in the ASD group was lower than control. Left laterality defects may be one of the causes of ASD. This knowledge can be useful in the treatment of ASD by increasing the left-brain metabolism. This trial was registered in the Thai Clinical Trials Registry (TCTR20210705005).
OCT4 induces EMT and promotes ovarian cancer progression by regulating the PI3K/AKT/mTOR pathway
Authors: Xie Weiwei , Yu Jun , Yin Yujia , Zhang Xiaoqian , Zheng Xiaocui , Wang Xipeng
Published: August 2022

Background

Octamer-binding transcription factor 4 (OCT4) is a key stem cell transcription factor involved in the development of various cancers. The role of OCT4 in ovarian cancer (OC) progression and its molecular mechanism are not fully understood.

Methods

First, immunohistochemistry (IHC) assays of ovarian benign cyst tissues, OC tissues, and omental metastatic tissues were performed to reveal OCT4 expression profiles. We knocked down OCT4 in two OC cell lines (SKOV3 and A2780) using a lentiviral vector and performed in vitro and in vivo experiments. OCT4 was knocked down to assess the proliferation, migration, and invasion of OC cells using CCK-8, colony formation, wound healing, and Transwell assays. In addition, the nude tumor mouse model was used for in vivo study. Mechanistically, we demonstrated that OCT4 influenced protein expression in the phosphoinositol 3-kinase (PI3K)/AKT/mTOR pathway and epithelial-mesenchymal transition (EMT)-related proteins by Western blotting and immunofluorescence (IF) assays. The interaction between OCT4 and p-AKT was further confirmed by coimmunoprecipitation (CoIP) assays. Importantly, AKT activation by its activator SC79 reversed the biological functions of OCT4 knockdown.

Results

OCT4 expression was significantly upregulated in OC samples and metastatic tissues. OCT4 knockdown notably inhibited the proliferation, migration, and invasion of OC cells in vitro and in vivo. Moreover, the expression of p-PI3K, p-AKT, and p-mTOR was downregulated after OCT4 knockdown. An AKT agonist reversed the effect of OCT4 knockdown on OC cells. EMT in OC samples was enhanced by OCT4.

Conclusions

Our study shows that OCT4 promotes the proliferation, migration, and invasion of OC cells by participating in the PI3K/AKT/mTOR signaling axis, suggesting that it could serve as a potential therapeutic target for OC patients.
A novel signature based on necroptosis-related long non-coding RNAs for predicting prognosis of patients with glioma
Authors: Xia Pengfei , Huang Yimin , Chen Gang
Published: August 2022

Necroptosis is closely related to the occurrence and development of tumors, including glioma. A growing number of studies indicate that targeting necroptosis could be an effective treatment strategy against cancer. Long non-coding RNA (lncRNA) is also believed to play a pivotal role in tumor epigenetics. Therefore, it is necessary to identify the functions of necroptosis-related lncRNAs in glioma. In this study, the transcriptome and clinical characteristic data of glioma patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were collected, and the differentially expressed necroptosis-related lncRNAs in TCGA that have an impact on overall survival (OS) were screened out to construct risk score (RS) formula, which was verified in CGGA. A nomogram was constructed to predict the prognosis of glioma patients based on clinical characteristics and RS. In addition, Gene Set Enrichment Analysis (GSEA) was used to analyze the main enrichment functions of these necroptosis-related lncRNAs and the immune microenvironment. A total of nine necroptosis-related lncRNAs have been identified to construct the RS formula, and the Kaplan–Meier (K-M) survival analysis showed significantly poorer outcomes in the high RS group in both TCGA and CGGA databases. Moreover, the receiver operating characteristic (ROC) curve shows that our prediction RS model has good predictability. Regarding the analysis of the immune microenvironment, significant differences were observed in immune function and immune checkpoint between the high RS group and the low RS group. In conclusion, we constructed a necroptosis-related lncRNA RS model that can effectively predict the prognosis of glioma patients and provided the theoretical basis and the potential therapeutic targets for immunotherapy against gliomas.
Long non-coding RNA LINC00152 in cancer: Roles, mechanisms, and chemotherapy and radiotherapy resistance
Authors: Li Shuang , Yao Weiping , Liu Ruiqi , Gao Liang , Lu Yanwei , Zhang Haibo , Liang Xiaodong
Published: August 2022

Long non-coding RNA LINC00152 (cytoskeleton regulator, or LINC00152) is an 828-bp lncRNA located on chromosome 2p11.2. LINC00152 was originally discovered during research on hepatocarcinogenesis and has since been regarded as a crucial oncogene that regulates gene expression in many cancer types. LINC00152 is aberrantly expressed in various cancers, including gastric, breast, ovarian, colorectal, hepatocellular, and lung cancer, and glioma. Several studies have indicated that LINC00152 is correlated with cell proliferation, apoptosis, migration, invasion, cell cycle, epithelial-mesenchymal transition (EMT), chemotherapy and radiotherapy resistance, and tumor growth and metastasis. High LINC00152 expression in most tumors is significantly associated with poor patient prognosis. Mechanistic analysis has demonstrated that LINC00152 can serve as a competing endogenous RNA (ceRNA) by sponging miRNA, regulating the abundance of the protein encoded by a particular gene, or modulating gene expression at the epigenetic level. LINC00152 can serve as a diagnostic or prognostic biomarker, as well as a therapeutic target for most cancer types. In the present review, we discuss the roles and mechanisms of LINC00152 in human cancer, focusing on its functions in chemotherapy and radiotherapy resistance.
N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A Comprehensive Review
Authors: Licata Anna , Minissale Maria Giovanna , Stankevičiūtė Simona , Sanabria-Cabrera Judith , Lucena Maria Isabel , Andrade Raul J , Almasio Piero Luigi
Published: August 2022

Aims: N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment.

Methods: Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs).

Results: In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The mortality rate across different studies ranged from 0 to 52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100–150 mg/kg) and oral (70–140 mg/kg), and length of treatment varied—12, 24, or 48 h for I.V. regimen and 72 h for oral administration. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality; if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one.

Conclusion: NAC improves hepatotoxicity and reduces mortality. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients.
Effects of GLP-1 Receptor Agonists on Biological Behavior of Colorectal Cancer Cells by Regulating PI3K/AKT/mTOR Signaling Pathway
Authors: Tong Guoxiang , Peng Tianhao , Chen Ya , Sha Lijuan , Dai Huikang , Xiang Yidong , Zou Zhiqi , He Heli , Wang Sha
Published: August 2022

Colorectal cancer (CRC) has become one of the top ten malignant tumors with a high incidence rate and mortality. Due to the lack of a good CRC screening program, most of the CRC patients are being transferred at the time of treatment. The conventional treatment cannot effectively improve the prognosis of CRC patients, and the target drugs can significantly prolong the overall survival of patients in the advanced stage. However, the use of single drug may lead to acquired drug resistance and various serious complications. Therefore, combined targeted drug therapy is the main alternative treatment with poor effect of single targeted drug therapy, which has important research significance for the treatment of CRC. Therefore, this study intends to culture CRC cell linesin vitroat the cell level and intervene with the GLP-1 receptor agonist liraglutide. The effects of liraglutide on the PI3K/Akt/mTOR signal pathway and CRC cell proliferation, cycle, migration, invasion, and apoptosis are explored by detecting cell proliferation, cycle, migration, invasion, and apoptosis and the expression of related mRNA and protein. The results showed that liraglutide, a GLP-1 receptor agonist, could block the CRC cell cycle, reduce cell proliferation, migration, and invasion and promote apoptosis by inhibiting the PI3K/Akt/mTOR signal pathway.
National trends in the use of oral chemotherapy over 13 years
Authors: Moreira A. , Bernardo C. , Ramos C. , Aguiar P. , Alves da Costa F.
Published: August 2022

Background: Systemic cancer therapy has traditionally been administered using an intravenous (IV) route, implying patients’ frequent visits to hospitals to access to their therapy. If we consider the actual pipeline in oncology, oral chemotherapy will be the main component of cancer treatment in the next few years. This shift in the administration route requires different care models in order to guarantee treatment efficacy and safety.

Objective: To analyze time trends in oral chemotherapy consumption in Portugal.

Method: Oral chemotherapy consumption over a 13-year period (2008–2020) was analyzed, considering dispensed units by the administration route with respective costs, resorting to the drug regulatory agency (INFARMED I.P.) database. Oral consumption patterns were further explored using common daily doses (CDD) for three conditions, including chronic myeloid leukemia (CML), non-small-cell lung cancer (NSCLC), and breast cancer (BC), to adjust for the effect of varying doses. Data were analyzed descriptively resorting to Microsoft Office Excel 2010.

Results: Overall chemotherapy consumption increased +Δ54.7%, with the highest contribution in units observed in oral forms (+Δ58.8%). The total expenditure increased +Δ96.5%, and despite the increase in oral forms (+Δ221.6%), intravenous forms continued to be the major cost driver, with an important contribution from immunotherapy. Much of the increase was led by the approval of 40 new IV and 48 new oral cancer medications with higher costs introduced in the market. Using CDD as an alternative metric to units had varying impacts by indication. The observed increases seemed to focus on specific cancer sites with varying effect; in CML, there was a 2.39-fold increase, compared to 4.41 for NSCLC and 1.86 for BC. However, for BC, two distinct sub-patterns were observed for hormone therapy (increasing 1.83) and for the novel tyrosine kinase inhibitors (increasing 40.8).

Conclusion: The growing use of oral chemotherapy is obvious and calls for investments in supporting patients in managing medication adherence and adverse events. The shifts in the healthcare system are complex and need to be prioritized. Our data suggest that priority could be attributed to cancer sites driving innovation, namely, advanced breast cancer.
Efficacy and safety of combined immunotherapy and antiangiogenesis with or without chemotherapy for advanced non-small-cell lung cancer: A systematic review and pooled analysis from 23 prospective studies
Authors: Gao Ruo-Lin , Song Jun , Sun Li , Wu Zhi-Xuan , Yi Xiao-Fang , Zhang Shu-Ling , Huang Le-Tian , Ma Jie-Tao , Han Cheng-Bo
Published: August 2022

Purpose: Immune checkpoint and antiangiogenic inhibitors have a potentially synergistic antitumor effect. We aimed to assess the efficacy and safety of immunotherapy in combination with antiangiogenesis therapy with or without chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).

Methods: PubMed, Embase, the Cochrane library, Google Scholar, Ovid, Scopus, and Web of Science were searched for eligible trials. ClinicalTrials.gov and meeting abstracts were also searched for qualified clinical studies. The inclusion criteria were as follows: prospective studies (including single-arm studies) that evaluated efficacy and/or toxicity of immunotherapy combined with antiangiogenic agents (A + I) with or without chemotherapy (A + I + chemo) in patients with advanced or metastatic NSCLC; and primary outcome of each study reported at least one of these endpoints: progression-free survival (PFS), overall survival, objective response rate (ORR), disease control rate (DCR), or adverse events (AEs).

Results: Twenty three prospective studies comprising 1,856 patients with advanced NSCLC were included. The pooled ORR, median PFS and estimated overall survival were 39%, 6.8 months [95% confidence interval (CI), 5.53–8.13], and 18.6 months in the overall group. Similar ORR and median PFS with A + I + chemo versus A + I were observed in patients treated in first-line setting [59% and 9.47 months (95% CI, 6.45–12.49) versus 52% and 10.9 months (95% CI, 1.81–19.98), respectively]. We also observed improved ORR and mPFS with A + I + chemo versus A + I in subsequent-line setting [56% and 8.1 months (95% CI, 5.00–11.26) versus 22% and 5.1 months (95% CI, 4.01–6.15), respectively]. Efficacy of A + I + chemo therapy was evident across different PD-L1 subgroups, especially in patients with EGFR mutations [ORR: 59%; mPFS: 8.13 months (95% CI: 5.00–11.26)] or baseline liver metastases. The incidence of AEs with a major grade of ≥3 in the overall, A + I, and A + I + chemo groups were 4.1% vs. 5.5% vs. 3.4% for proteinuria, 13.7% vs. 16.2% vs. 9.7% for hypertension, and 1.9% vs. 1.2% vs. 2.8% for rash, respectively. No new safety signals were identified in this pooled analysis.

Conclusion: Immunotherapy combined with antiangiogenic agents with or without chemotherapy showed encouraging antitumor activity and an acceptable toxicity profile in treatment-naïve or pretreated patients with advanced NSCLC. Doublet treatment with immunotherapy and antiangiogenic agents might be a new option for patients with advanced NSCLC, especially those who are treatment-naive or cannot tolerate chemotherapy.
Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo
Authors: Wang Xueni , Luo Xiaowei , Gan Xia , Chen Chunmei , Yang Zaizhun , Wen Jing , Fang Wenxuan , Huang Hailing , Gao Chenghai , Zhou Xuefeng , Feng Xiaotao , Liu Yonghong
Published: August 2022

Advanced prostate cancer has a poor prognosis, and it is urgent to develop new effective drugs. 5′-Epiequisetin is a tetramic acid derivative which was isolated from a marine sponge-derived fungus Fusarium equiseti in our previous study. In this study, 5′-epiequisetin showed cytotoxicity against four prostate cancer cell lines, namely, LNCaP, 22Rv1, DU145, and PC-3 cells, with the lowest IC50 value of 4.43 ± 0.24 μM in PC-3 cells. Further studies showed that it could dramatically regulate the clonal colony formation, apoptosis, and migration of PC-3 cells. In addition, flow cytometry data showed that 5′-epiequisetin could block the cell cycle at the G1 phase. Proteome profiler array and Western blot revealed that 5′-epiequisetin could regulate the expression of proteins responsible for cell proliferation, apoptosis, and migration. 5′-Epiequisetin regulated the expression of PI3K, Akt, phosphorylated Akt, and proteins which control the cell cycle. Meanwhile, 5′-epiequisetin upregulated expression of DR5 and cleave-caspase 3, which play important roles in the process of apoptosis. Moreover, when DR5 was silenced by small interfering RNA, the proportion of apoptotic cells induced by 5′-epiequisetin remarkably declined. In addition, 5′-epiequisetin downregulated the expression of survivin which plays a key role in the process of survival and apoptosis. 5′-Epiequisetin also impacted beta-catenin and cadherins, which were associated with cell migration. In addition, 5′-Epiequisetin significantly inhibited the progression of prostate cancer in mice, accompanied by regulating the protein expression of DR5, caspase 8, survivin, and cadherins in vivo. Taken together, these findings indicated that 5′-epiequisetin showed an anti–prostate cancer effect by inducing apoptosis and inhibiting cell proliferation and migration both in vitro and in vivo, suggesting a promising lead compound for the pharmacotherapy of prostate cancer.
A novel image encryption scheme based on memristive chaotic system and combining bidirectional bit-level cyclic shift and dynamic DNA-level diffusion
Authors: Qian Kun , Feng Wei , Qin Zhentao , Zhang Jing , Luo Xuegang , Zhu Zhengguo
Published: August 2022

In recent years, many researchers have leveraged various memristors to design many novel memristive chaotic systems with complex dynamics. Compared with other chaotic systems, applying these memristive chaotic systems to image encryption is expected to solve some key problems in this field. Therefore, exploiting a recently reported memristive chaotic system, this paper proposes a novel image encryption scheme based on the memristive chaotic system and combining bidirectional bit-level cyclic shift and dynamic DNA-level diffusion (IES-M-BD). First, a discrete memristive chaotic map is employed to generate chaotic sequences. Then, the plaintext image is shifted circularly on bit-level according to chaotic sequences and the hash value of the plaintext image. After that, the shifted matrix is recombined on the bit plane and encoded dynamically by DNA encoding rules. Next, dynamic DNA-level diffusion and DNA-level permutation are carried out in two rounds. Finally, the encrypted image is obtained after dynamic DNA decoding. Simulation tests and performance analyses are also carried out in this paper. The simulation results and the security analyses demonstrate that this encryption scheme has a high security level and can resist various attacks.
Genetic analysis of cryptochrome in insect magnetosensitivity
Authors: Kyriacou Charalambos P. , Rosato Ezio
Published: August 2022

The earth’s magnetic field plays an important role in the spectacular migrations and navigational abilities of many higher animals, particularly birds. However, these organisms are not amenable to genetic analysis, unlike the model fruitfly, Drosophila melanogaster, which can respond to magnetic fields under laboratory conditions. We therefore review the field of insect magnetosensitivity focusing on the role of the Cryptochromes (CRYs) that were first identified in Arabidopsis and Drosophila as key molecular components of circadian photo-entrainment pathways. Physico-chemical studies suggest that photo-activation of flavin adenine dinucleotide (FAD) bound to CRY generates a FADo− Trpo+ radical pair as electrons skip along a chain of specific Trp residues and that the quantum spin chemistry of these radicals is sensitive to magnetic fields. The manipulation of CRY in several insect species has been performed using gene editing, replacement/rescue and knockdown methods. The effects of these various mutations on magnetosensitivity have revealed a number of surprises that are discussed in the light of recent developments from both in vivo and in vitro studies.
Combined de novo transcriptomic and physiological analyses reveal RyALS3-mediated aluminum tolerance in Rhododendron yunnanense Franch
Authors: Xu Yan-Xia , Lei Yun-Sheng , Huang Shan-Xia , Zhang Jing , Wan Zi-Yun , Zhu Xiang-Tao , Jin Song-Heng
Published: August 2022

Rhododendron (Ericaceae) not only has ornamental value, but also has great medicinal and edible values. Many Rhododendron species are native to acid soils where aluminum (Al) toxicity limits plant productivity and species distribution. However, it remains unknown how Rhododendron adapts to acid soils. Here, we investigated the physiological and molecular mechanisms of Al tolerance in Rhododendron yunnanense Franch. We found that the shoots of R. yunnanense Franch did not accumulate Al after exposure of seedlings to 50 μM Al for 7 days but predominantly accumulated in roots, suggesting that root Al immobilization contributes to its high Al tolerance. Whole-genome de novo transcriptome analysis was carried out for R. yunnanense Franch root apex in response to 6 h of 50 μM Al stress. A total of 443,639 unigenes were identified, among which 1,354 and 3,413 were up- and down-regulated, respectively, by 6 h of 50 μM Al treatment. Both Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that genes involved in “ribosome” and “cytoskeleton” are overrepresented. Additionally, we identified Al-tolerance homologous genes including a tonoplast-localized ABC transporter RyALS3; 1. Overexpression of RyALS3; 1 in tobacco plants confers transgenic plants higher Al tolerance. However, root Al content was not different between wild-type plants and transgenic plants, suggesting that RyALS3; 1 is responsible for Al compartmentalization within vacuoles. Taken together, integrative transcriptome, physiological, and molecular analyses revealed that high Al tolerance in R. yunnanense Franch is associated with ALS3; 1-mediated Al immobilization in roots.
Detection of early decayed oranges by structured-illumination reflectance imaging coupling with texture feature classification models
Authors: Cai Zhonglei , Huang Wenqian , Wang Qingyan , Li Jiangbo
Published: August 2022

Citrus fruits are susceptible to fungal infection after harvest. To reduce the economic loss, it is necessary to reject the infected citrus fruit before storage and transportation. However, the infected area in the early stage of decay is almost invisible on the fruit surface, so the detection of early decayed citrus is very challenging. In this study, a structured-illumination reflectance imaging (SIRI) system combined with a visible light-emitting diode (LED) lamp and a monochrome camera was developed to detect early fungal infection in oranges. Under sinusoidal modulation illumination with spatial frequencies of 0.05, 0.15, and 0.25 cycles mm–1, three-phase-shifted images with phase offsets of − 2π/3, 0, and 2π/3 were acquired for each spatial frequency. The direct component (DC) and alternating component (AC) images were then recovered by image demodulation using a three-phase-shifting approach. Compared with the DC image, the decayed area can be clearly identified in the AC image and RT image (AC/DC). The optimal spatial frequency was determined by analyzing the AC image and pixel intensity distribution. Based on the texture features extracted from DC, AC, and RT images, four kinds of classification models including partial least square discriminant analysis (PLS-DA), support vector machine (SVM), least squares-support vector machine (LS-SVM), and k-nearest neighbor (KNN) were established to detect the infected oranges, respectively. Model optimization was also performed by extracting important texture features. Compared to all models, the PLS-DA model developed based on eight texture features of RT images achieved the optimal classification accuracy of 96.4%. This study showed for the first time that the proposed SIRI system combined with appropriate texture features and classification model can realize the early detection of decayed oranges.
Employees Perception of Organizational Crises and Their Reactions to Them – A Norwegian Organizational Case Study
Authors: Sørensen Jarle Løwe , Ranse Jamie , Gray Lesley , Khorram-Manesh Amir , Goniewicz Krzysztof , Hertelendy Attila J.
Published: August 2022

Organizational sensemaking is crucial for resource planning and crisis management since facing complex strategic problems that exceed their capacity and ability, such as crises, forces organizations to engage in inter-organizational collaboration, which leads to obtaining individual and diverse perspectives to comprehend the issues and find solutions. This online qualitative survey study examines how Norwegian Sea Rescue Society employees perceived the concept of an organizational crisis and how they sensed their co-workers react to it. The scope was the ongoing COVID-19 pandemic, a global event affecting all countries and organizations and responding similarly globally. Data were collected during the Fall of 2020. The instrument of choice was the Internal Crisis Management and Crisis Communication survey (ICMCC). The results showed that the overall sample strongly believed in their organization’s overall resilience level. However, a somewhat vague understanding of roles and responsibilities in a crisis where detected, together with some signs of informal communication, rumor spreading, misunderstanding, frustration, and insecurity. This study contributes to the academic field of organizational research, hence crisis management and sensemaking, and could be valuable to managers and decision-makers across sectors. Increased knowledge about how employees react to a crisis may help optimize internal crisis management planning and utilize robust mitigation and response strategies.
How Does Organizational Unlearning Influence Product Innovation Performance? Moderating Effect of Environmental Dynamism
Authors: Wang Xiaoping , Zheng Chenglin , Mutuc Eugene Burgos , Su Ning , Hu Tianyu , Zhou Haitao , Fan Chuhong , Hu Feng , Wei Shaobin
Published: August 2022

Product innovation integrates technology, knowledge, management practices, and market innovation, making it essential to gain a competitive advantage. Effective management of dynamic knowledge, which is the foundation of and driving force for product innovation, is a powerful tool that allows a firm to successfully innovate, adapt to environmental changes, and improve its competitiveness. In the “nanosecond age,” unlearning and learning in an organization is crucial to a firm’s ability to promptly update its organizational knowledge and maintain innovation vitality. Based on the dynamic knowledge management perspective, this study integrates and constructs a theoretical model with environmental dynamism as the moderating variable, discusses the impact of organizational unlearning on product innovation performance, and empirically analyzes 208 valid questionnaires in the Yangtze River Delta using the multiple regression method. The results show that organizational unlearning shares a positive relationship with dynamic capabilities and product innovation performance. Dynamic capability is positively related to product innovation performance and has a partial mediating effect on the relationship between organizational unlearning and product innovation performance. Environmental dynamism shares a positive moderating effect on the relationship between organizational unlearning and product innovation performance. This study deepens the existing research on the factors that influence product innovation performance, which may help firms improve their dynamic knowledge management and product innovation performance.
The effect of educational gymnastics on postural control of young children
Authors: Anderson Neil , Button Chris , Lamb Peter
Published: August 2022

Fundamental movement skill (FMS) proficiency does not develop solely due to maturation, but also via diverse perceptual-motor experiences across childhood. Practicing gymnastics has been shown to improve postural control. The purpose of the present study was to examine potential changes to postural control of children following a course of educational gymnastics. Two groups of children both completed 20 × 45-min physical education (PE) lessons; one group (n = 43, age = 6.4 ± 0.7, 56% male) completed educational gymnastics lessons in school delivered by a professional coach, the other group completed their typical PE classes (n = 18, age = 6.5 ± 0.3, 33% male). Unipedal balancing performance was assessed by calculating the percentage of successful trials made. Postural sway dynamics were explored by calculating center-of-pressure sample entropy, 95% ellipse sway area and sway velocity. Measurements were taken before the lessons began and immediately after the lessons were completed. The gymnastics group performed better than the typical PE group at unipedal balancing. Females outperformed males in both groups. Males made different changes to postural control (i.e., increased sway regularity and improved stability) compared to females across 3 months. Educational gymnastics enabled children in a critical period of development to make more rapid improvements to postural performance and control. Novel movement experiences, like those offered by educational gymnastics, may have a positive influence on postural control and importantly, physical literacy. Future work should examine how sex effects the development of postural control strategies in young children.
Analysis of distribution characteristics of COVID-19 in America based on space-time scan statistic
Authors: Zhao Yuexu , Liu Qiwei
Published: August 2022

Based on the epidemic data of COVID-19 in 50 states of the United States (the US) from December 2021 to January 2022, the spatial and temporal clustering characteristics of COVID-19 in the US are explored and analyzed. First, the retrospective spatiotemporal analysis is performed by using SaTScan 9.5, and 17 incidence areas are obtained. Second, the reliability of the results is tested by the circular distribution method in the time latitude and the clustering method in the spatial latitude, and it is confirmed that the retrospective spatiotemporal analysis accurately measures in time and reasonably divides regions according to the characteristics in space. Empirical results show that the first-level clustering area of the epidemic has six states with an average relative risk of 1.28 and the second-level clustering area includes 18 states with an average relative risk of 0.86. At present, the epidemic situation in the US continues to expand. It is necessary to do constructive work in epidemic prevention, reduce the impact of epidemic, and effectively control the spread of the epidemic.