bluuebunny/crossref_metadata_2025_split huggingface dataset:
KDM6A promotes hepatocellular carcinoma progression and dictates lenvatinib efficacy by upregulating FGFR4 expression
Authors: Guo Wenyun , Li Songling , Qian Yifei , Li Linfeng , Wang Fan , Tong Yu , Li Qianyu , Zhu Zijun , Gao Wei‐Qiang , Liu Yanfeng 
Published: October 2023

AbstractBackgroundHepatocellular carcinoma (HCC) is one of the major causes of death from cancer and has a very poor prognosis with few effective therapeutic options. Despite the approval of lenvatinib for the treatment of patients suffering from advanced HCC, only a small number of patients can benefit from this targeted therapy.MethodsDiethylnitrosamine (DEN)‐CCL4 mouse liver tumour and the xenograft tumour models were used to evaluate the function of KDM6A in HCC progression. The xenograft tumour model and HCC cell lines were used to evaluate the role of KDM6A in HCC drug sensitivity to lenvatinib. RNA‐seq and ChIP assays were conducted for mechanical investigation.ResultsWe revealed that KDM6A exhibited a significant upregulation in HCC tissues and was associated with an unfavourable prognosis. We further demonstrated that KDM6A knockdown remarkably suppressed HCC cell proliferation and migration in vitro. Moreover, hepatic Kdm6a loss also inhibited liver tumourigenesis in a mouse liver tumour model. Mechanistically, KDM6A loss downregulated the FGFR4 expression to suppress the PI3K–AKT–mTOR signalling pathway, leading to a glucose and lipid metabolism re‐programming in HCC. KDM6A and FGFR4 levels were positively correlated in HCC specimens and mouse liver tumour tissues. Notably, KDM6A knockdown significantly inhibited the efficacy of lenvatinib therapy in HCC cells in vitro and in vivo.ConclusionsOur findings revealed that KDM6A promoted HCC progression by activating FGFR4 expression and may be an essential molecule for influencing the efficacy of lenvatinib in HCC therapy.
Identification of an APOE ε4–specific blood‐based molecular pathway for Alzheimer's disease risk
Authors: Tao Qiushan , Zhang Chao , Mercier Gustavo , Lunetta Kathryn , Ang Ting Fang Alvin , Akhter‐Khan Samia , Zhang Zhengrong , Taylor Andrew , Killiany Ronald J. , Alosco Michael , Mez Jesse , Au Rhoda , Zhang Xiaoling , Farrer Lindsay A. , Qiu Wendy Wei Qiao ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: October 2023

AbstractINTRODUCTIONThe precise apolipoprotein E (APOE) ε4‐specific molecular pathway(s) for Alzheimer's disease (AD) risk are unclear.METHODSPlasma protein modules/cascades were analyzed using weighted gene co‐expression network analysis (WGCNA) in the Alzheimer's Disease Neuroimaging Initiative study. Multivariable regression analyses were used to examine the associations among protein modules, AD diagnoses, cerebrospinal fluid (CSF) phosphorylated tau (p‐tau), and brain glucose metabolism, stratified by APOE genotype.RESULTSThe Green Module was associated with AD diagnosis in APOE ε4 homozygotes. Three proteins from this module, C‐reactive protein (CRP), complement C3, and complement factor H (CFH), had dose‐dependent associations with CSF p‐tau and cognitive impairment only in APOE ε4 homozygotes. The link among these three proteins and glucose hypometabolism was observed in brain regions of the default mode network (DMN) in APOE ε4 homozygotes. A Framingham Heart Study validation study supported the findings for AD.DISCUSSIONThe study identifies the APOE ε4–specific CRP–C3–CFH inflammation pathway for AD, suggesting potential drug targets for the disease.Highlights
Identification of an APOE ε4 specific molecular pathway involving blood CRP, C3, and CFH for the risk of AD.
CRP, C3, and CFH had dose‐dependent associations with CSF p‐Tau and brain glucose hypometabolism as well as with cognitive impairment only in APOE ε4 homozygotes.
Targeting CRP, C3, and CFH may be protective and therapeutic for AD onset in APOE ε4 carriers.
Day‐flying lepidoptera larvae have a poorer ability to thermoregulate than adults
Authors: Ashe‐Jepson Esme , Hayes Matthew P. , Hitchcock Gwen E. , Wingader Keira , Turner Edgar C. , Bladon Andrew J. 
Published: October 2023

AbstractChanges to ambient temperatures under climate change may detrimentally impact small ectotherms that rely on their environment for thermoregulation; however, there is currently a limited understanding of insect larval thermoregulation. As holometabolous insects, Lepidoptera differ in morphology, ecology and behaviour across the life cycle, and so it is likely that adults and larvae differ in their capacity to thermoregulate. In this study, we investigated the thermoregulatory capacity (buffering ability) of 14 species of day‐flying Lepidoptera, whether this is influenced by body length or gregariousness, and whether it differs between adult and larval life stages. We also investigated what thermoregulation mechanisms are used: microclimate selection (choosing locations with a particular temperature) or behavioural thermoregulation (controlling temperature through other means, such as basking). We found that Lepidoptera larvae differ in their buffering ability between species and body lengths, but gregariousness did not influence buffering ability. Larvae are worse at buffering themselves against changes in air temperature than adults. Therefore Lepidoptera may be more vulnerable to adverse temperature conditions during their larval life stage. Adults and larvae rely on different thermoregulatory mechanisms; adults primarily use behavioural thermoregulation, whereas larvae use microclimate selection. This implies that larvae are highly dependent on the area around their foodplant for effective thermoregulation. These findings have implications for the management of land and species, for example, highlighting the importance of creating and preserving microclimates and vegetation complexity surrounding Lepidoptera foodplants for larval thermoregulation under future climate change.
Policy feedback and the enforcement of international wildlife treaties in Germany
Authors: Gabehart Kayla M. , Fullerton Allegra H. , Stefes Christoph H. 
Published: October 2023

AbstractLaws are only as good as their enforcement. International treaties are no exception. We investigate how Germany implements international wildlife protection treaties, namely the International Trade in Endangered Species of Wild Fauna and Flora and the Bern Convention. We find that Germany's federal system allows for uneven enforcement of national legislation across the 16 federal states. We utilize Policy Feedback Theory as a theoretical lens to examine how federalism (re‐)produces different enforcement regimes. We rely on qualitative analysis of interviews of German street‐level bureaucrats, government officials, and NGO representatives. We find that macrolevel context impacts how institutions enforce wildlife protection policies. Particularly, Germany's federal structure permits either centralized, decentralized, or cooperative arrangements that result in differences in resources, affecting the ways bureaucrats view their roles and responsibilities. These resource and interpretive effects further feedback into the contextual structure of the federal enforcement system.
Potentilla thuringiaca Bernh. ex Link in Germany—A polyploid enigma
Authors: Gregor Thomas , Korsch Heiko , Paule Juraj 
Published: October 2023

AbstractPlants in German states Thuringia and Bavaria previously thought to belong to Potentilla thuringiaca belong to at least three different taxa. Most populations in Thuringia and Bavaria are rather uniform and have a ploidy of 2n = 10x. These populations belong to P. thuringiaca as originally described. A lectotype and an epitype are designated for P. thuringiaca. In an isolated range in Eastern Thuringia, we found octoploids (2n = 8x), which are characterized mainly by a higher number of flowering stems. These populations are described as Potentilla saalae T. Gregor & Korsch. Decaploid (2n = 10x) plants from a very small range in the Bavarian Rhoen with more rounded central leaves are probably of independent origin. The relationship of German P. thuringiaca populations to those in the Alps, the Balkans, the Carpathians, and Eastern Europe is unresolved.
Superior component compositions and antioxidant activity of Volvariella volvacea oil compared to those of Agrocybe cylindracea and two Lentinula edodes oils
Authors: Kang Jingjing , Yue Yue , Wei Shaofeng , Chen Huifang , Luo Peng 
Published: October 2023

AbstractThe biological activity of an oil not only depends on its fatty acid composition but also the lipid composition and trace components. In this paper, to select the optimal mushroom oil, the component compositions (fatty acids, lipids, polyphenols, flavones, tocopherols, and unsaponifiable matters) and antioxidant activities in vitro of four mushroom oils (Agrocybe cylindracea, two Lentinula edodes, and Volvariella volvacea) were investigated and compared. The results showed that the four tested oils had the same fatty acid composition in different amounts, but the lipid component, minor components, and free radical scavenging activity in the tested oils varied widely depending on the type of mushroom. Overall, Volvariella volvacea oil was considered superior to the other three tested oils, as it had the largest contents of polar lipids, diglycerides, polyunsaturated fatty acids (74.38%), unsaponifiable matter (319.09 mg/kg), total phenols (124.08 mg/100 g), tocopherols (139.86 mg/100 g), as well as the highest ABTS and FRAP values (349.45 and 3801.70 μmol Trolox/100 g). This finding suggests that Volvariella volvacea oil is a promising resource that should be further researched.
Enhancement of nutritional quality and shelf life of fish products (powder & chapatti) via fortifying with orange‐fleshed sweet potato
Authors: Mekonnen Habtamu Birhanu , Aychiluhm Tewodros Birhanu 
Published: October 2023

AbstractDespite its high protein, fat, and mineral contents, fish contains trace amounts of carbohydrates and vitamins, notably vitamin A. The perishable nature of fresh fish makes it challenging to store for a prolonged time, necessitating the use of additives to enhance its shelf life, nutritional, and other quality aspects. Sweet potatoes are the preferred option to blend with fish due to their cost and abundance. This study aims to prepare fortified fish powder and make food products (chapatti) using it. Fish powder and sweet potato powder were prepared by drying them in an oven at 60°C and 45°C, respectively. The two dried samples were then ground and mixed in various ratios, followed by analyzing their nutritional and other parameters using standard methods. Vitamin A and beta‐carotene levels were analyzed using HPLC and UV–Vis spectroscopy techniques, respectively. The findings indicated that the outcomes displayed enhanced nutrition and extended storage capacity. The amount of beta‐carotene (876.12 ± 14.76 to 3182.4 ± 123.1 μg/100 g) and carbohydrates (4.49 ± 1.02 to 52.31 ± 0.21) increased. The packed fortified flour is safe for human consumption for up to 90 days, as per the International Commission for Microbiological Specifications for Foods. The chapatti made from fortified flour was also deemed acceptable by the panelists.
Transcriptomic and morphological maturation of human astrocytes in cerebral organoids
Authors: Verkerke Marloes , Berdenis van Berlekom Amber , Donega Vanessa , Vonk Daniëlle , Sluijs Jacqueline A. , Butt Nayab F. , Kistemaker Lois , de Witte Lot D. , Pasterkamp R. Jeroen , Middeldorp Jinte , Hol Elly M. 
Published: October 2023

AbstractCerebral organoids (CerOrgs) derived from human induced pluripotent stem cells (iPSCs) are a valuable tool to study human astrocytes and their interaction with neurons and microglia. The timeline of astrocyte development and maturation in this model is currently unknown and this limits the value and applicability of the model. Therefore, we generated CerOrgs from three healthy individuals and assessed astrocyte maturation after 5, 11, 19, and 37 weeks in culture. At these four time points, the astrocyte lineage was isolated based on the expression of integrin subunit alpha 6 (ITGA6). Based on the transcriptome of the isolated ITGA6‐positive cells, astrocyte development started between 5 and 11 weeks in culture and astrocyte maturation commenced after 11 weeks in culture. After 19 weeks in culture, the ITGA6‐positive astrocytes had the highest expression of human mature astrocyte genes, and the predicted functional properties were related to brain homeostasis. After 37 weeks in culture, a subpopulation of ITGA6‐negative astrocytes appeared, highlighting the heterogeneity within the astrocytes. The morphology shifted from an elongated progenitor‐like morphology to the typical bushy astrocyte morphology. Based on the morphological properties, predicted functional properties, and the similarities with the human mature astrocyte transcriptome, we concluded that ITGA6‐positive astrocytes have developed optimally in 19‐week‐old CerOrgs.
Choices of medical institutions and associated factors in older patients with multimorbidity in stabilization period in China: A study based on logistic regression and decision tree model
Authors: Wang Xiaoran , Zhang Dan 
Published: October 2023

AbstractBackgroundAs China's population ages, its disease spectrum is changing, and the coexistence of multiple chronic diseases has become the norm with respect to the health status of its elderly population. However, the health institution choices of older patients with multimorbidity in stabilization period remains underresearched. This study investigate the factors influencing the choices of older patients with multimorbidity to provide references for the rational allocation of healthcare resources.MethodsA multistage, stratified, whole‐group random‐sampling method was used to select eligible older patients from September to December of 2022 who attended the Community Health Service Center of Guangdong Province. We adopted a self‐designed questionnaire to collect patients' general, disease‐related, social‐support information, their intention to choose a healthcare provider. A binary logistic regression and decision tree model based on the Chi‐squared automatic interaction detector algorithm were implemented to analyze the associated factors involved.ResultsA total of 998 patients in stabilization period were included in the study, of which 593 (59.42%) chose hospital and 405 (40.58%) chose primary care. Our binary logistic regression results revealed that age, sex, individual average annual income, educational level, self‐reported health status, activities of daily living, alcohol consumption, family doctor contracting, and family supervision of medication or exercise were the principal factors influencing the choice of medical institutions for older patients with multimorbidity (p < 0.05). The decision‐tree model reflected three levels and 11 nodes, and we screened a total of four influencing factors: activities of daily living, age, a family doctor contract, and patient sex. The data showed that the logistic regression model possessed an accuracy of 72.9% and that the decision tree model exhibited an accuracy of 68.7%. Prediction using the binary logistic regression was thus statistically superior to the categorical decision‐tree model based on the Chi‐squared automatic interaction detector algorithm (Z = 3.238, p = 0.001).ConclusionMore than half of older patients with multimorbidity in stabilization period chose hospitals for healthcare. Efforts should be made to improve the quality of healthcare services and increase the medical contracting rate and recognition of family doctors so as to attract older patients with multimorbidity to primary medical institutions.
Cost‐effectiveness analysis of tislelizumab in combination with chemotherapy for the first‐line treatment of patients with metastatic or recurrent nasopharyngeal carcinoma in China
Authors: Tang Yu‐kai , Xu Zhe , Ye Zhuo‐miao , Li Shi‐ran , Zhou Qin 
Published: October 2023

AbstractBackgroundThe combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first‐line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost‐effective in China. The purpose of this study is to evaluate the cost‐effectiveness of tislelizumab plus GP for the first‐line treatment of R/M NPC from the perspective of the Chinese healthcare system.MethodsA partitioned survival model with three discrete health states was constructed to evaluate the cost‐effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE‐309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality‐adjusted life years (QALYs), total cost, and incremental cost–benefit ratio (ICER).ResultsThe tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost‐effective at the willingness‐to‐pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD‐L1 expression had little impact on the ICER of this regimen.ConclusionIn patients with R/M NPC, the regimen of tislelizumab plus GP, as the first‐line treatment, is more cost‐effective than the GP regimen in China.
Appraising Nigeria’s approach to combating antimicrobial resistance
Authors: Onah Solomon Inalegwu , Umar Hadiza Joy 
Published: October 2023

AbstractAimAntibiotic consumption has increased dramatically in recent years, and this increase is predominantly fuelled by low‐ and middle‐income countries. This is a worrying report, as antimicrobial resistance (AMR) is primarily driven by antibiotic consumption. To combat AMR, the Nigerian Ministry of Health established the Antimicrobial Resistance Technical Working Group (AMR‐TWG), which developed and implemented the National Action Plan on Antimicrobial Resistance. This study aims to identify and appraise the current situation in the fight against AMR in Nigeria.MethodsThis study contains a qualitative descriptive assessment of the advancements and the present status of efforts to combat AMR in Nigeria following the execution of the 2017–2022 National Action Plan (NAP) for AMR. The data for this study is soured primarily from the official national policy document on AMR and the responses of the Tracking AMR Country Self‐assessment Survey (TrACSS).ResultsThe results from this study reveal that there have been significant efforts aimed at addressing AMR in Nigeria. These efforts have been focused on improving public awareness of AMR, improving One Health surveillance of AMR, improving infection prevention and control, improving antimicrobial stewardship practices in the country, and investing in research on AMR. However, significant gaps still exist in each of these focus areas that can potentially undermine the attempts that have been made hitherto.ConclusionsNigeria's commitment to the fight against AMR, as exemplified by the 2017–2022 National Action Plan, needs to be sustained and reinforced to safeguard public health and promote responsible antimicrobial use.
Association between transition patterns of sleep problems and suicidal ideation in Chinese female nurses: A prospective study
Authors: Mao Fangxiang , Wan Juan , Sun Yaoyao , Yang Bei , Wang Ying , Cao Fenglin 
Published: October 2023

AbstractObjectiveSuicidal ideation and sleep problems are both common in nurses. However, few longitudinal studies are available to examine the temporal association between sleep and suicidal ideation in nurses.MethodData from the Health Longitudinal Survey of Nurses in Shandong Province was analyzed, involving 623 female nurses who had completed data of concern in 2018 (T1) and 2019 (T2). Sleep problem was assessed by the Pittsburgh Sleep Quality Index, in which the transition patterns for global and specific sleep component and the cumulative number of sleep component problems were defined. Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire. Binary logistic regression was used to explore the association between sleep and suicidal ideation.ResultsChronic and deteriorated global sleep problems is associated with a greater risk of suicidal ideation. For the specific component of sleep, sleep disturbance and short sleep duration are associated with a higher risk of suicidal ideation. The higher number of cumulative sleep component problems is associated with a higher risk of suicidal ideation.ConclusionFindings indicate sleep disturbance and short sleep duration may be pathways to suicidal ideation. Initiatives that target at sleep problems may be important to reduce suicidal ideation in nurses.
Carotenoid characterization, fatty acid profiles, and antioxidant activities of haloarchaeal extracts
Authors: Kesbiç Fevziye Işıl , Gültepe Nejdet 
Published: October 2023

AbstractMicroorganisms that can survive in saline environments, known as halotolerant or halophilic organisms, have a wide range of current and potential uses in biotechnology. In this study, it was aimed to determine the carotenoids of halophilic archaea strains isolated from the brine samples taken from different points of Salt Lake (Turkey) and determine the antioxidant activities of their carotenoids. To identify the halophilic archaea strains, they were cultivated in MAM JCM 168 medium and subjected to antibiotic susceptibility, fatty acid, two‐dimensional and three‐dimensional imaging by scanning electron microscopy and atomic force microscopy, biochemical and phylogenetic assays. The findings show that five different halophilic archaea strains have been identified as Halorubrum lipolyticum, Halorubrum sodomense, Haloarcula salaria, Halorubrum chaoviator, and Haloarcula japonica with 98% and above similarity ratio. The main fatty acids of all haloarchaeal strains were octadecanoic acid (C18:0) and palmitic acid (C16:0). The major carotenoid of the species was determined as all‐trans bacterioruberin, and different carotenoid types such as lycopene, β‐carotene, and 2‐isopentenyl‐3,4‐dehydrorodopin were found as well as bacterioruberin isomers. The antioxidant activities of carotenoids extracted from the species were analyzed by the 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging method and the extracts showed antioxidant activity statistically significantly higher than ascorbic acid and butylated hydroxytoluene as reference products (p < 0.05).