bluuebunny/crossref_metadata_2025 huggingface dataset:
Don’t overthink it: The paradoxical nature of expertise for the detection of errors in conceptual business process models
Authors: Boutin Karl-David , Davis Christopher , Hevner Alan , Léger Pierre-Majorique , Labonte-LeMoyne Elise
Published: November 2022

Business process models are widely used artifacts in design activities to facilitate communication about business domains and processes. Despite being an extensively researched topic, some aspects of conceptual business modeling are yet to be fully explored and understood by academicians and practitioners alike. We study the attentional characteristics specific to experts and novices in a semantic and syntactic error detection task across 75 Business Process Model and Notation (BPMN) models. We find several intriguing results. Experts correctly identify more error-free models than novices, but also tend to find more false positive defects. Syntactic errors are diagnosed faster than semantic errors by both groups. Both groups spend more time on error-free models. Our findings regarding the ambiguous differences between experts and novices highlight the paradoxical nature of expertise and the need to further study how best to train business analysts to design and evaluate conceptual models.
White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology
Authors: Jindachomthong Kantiya , Yang Chengran , Huang Yuegao , Coman Daniel , Rapanelli Maximiliano , Hyder Fahmeed , Dougherty Joseph , Frick Luciana , Pittenger Christopher
Published: November 2022

Introduction

An inactivating mutation in the histidine decarboxylase gene (Hdc) has been identified as a rare but high-penetrance genetic cause of Tourette syndrome (TS). TS is a neurodevelopmental syndrome characterized by recurrent motor and vocal tics; it is accompanied by structural and functional abnormalities in the cortico-basal ganglia circuitry. Hdc, which is expressed both in the posterior hypothalamus and peripherally, encodes an enzyme required for the biosynthesis of histamine. Hdc knockout mice (Hdc-KO) functionally recapitulate this mutation and exhibit behavioral and neurochemical abnormalities that parallel those seen in patients with TS.

Materials and methods

We performed exploratory RNA-seq to identify pathological alterations in several brain regions in Hdc-KO mice. Findings were corroborated with RNA and protein quantification, immunohistochemistry, and ex vivo brain imaging using MRI.

Results

Exploratory RNA-Seq analysis revealed, unexpectedly, that genes associated with oligodendrocytes and with myelin production are upregulated in the dorsal striatum of these mice. This was confirmed by qPCR, immunostaining, and immunoblotting. These results suggest an abnormality in myelination in the striatum. To test this in an intact mouse brain, we performed whole-brain ex vivo diffusion tensor imaging (DTI), which revealed reduced fractional anisotropy (FA) in the dorsal striatum.

Discussion

While the DTI literature in individuals with TS is sparse, these results are consistent with findings of disrupted descending cortical projections in patients with tics. The Hdc-KO model may represent a powerful system in which to examine the developmental mechanisms underlying this abnormality.
Function and development of interneurons involved in brain tissue oxygen regulation
Authors: Aksenov Daniil P. , Gascoigne David A. , Duan Jubao , Drobyshevsky Alexander
Published: November 2022

The regulation of oxygen in brain tissue is one of the most important fundamental questions in neuroscience and medicine. The brain is a metabolically demanding organ, and its health directly depends on maintaining oxygen concentrations within a relatively narrow range that is both sufficiently high to prevent hypoxia, and low enough to restrict the overproduction of oxygen species. Neurovascular interactions, which are responsible for oxygen delivery, consist of neuronal and glial components. GABAergic interneurons play a particularly important role in neurovascular interactions. The involvement of interneurons extends beyond the perspective of inhibition, which prevents excessive neuronal activity and oxygen consumption, and includes direct modulation of the microvasculature depending upon their sub-type. Namely, nitric oxide synthase-expressing (NOS), vasoactive intestinal peptide-expressing (VIP), and somatostatin-expressing (SST) interneurons have shown modulatory effects on microvessels. VIP interneurons are known to elicit vasodilation, SST interneurons typically cause vasoconstriction, and NOS interneurons have to propensity to induce both effects. Given the importance and heterogeneity of interneurons in regulating local brain tissue oxygen concentrations, we review their differing functions and developmental trajectories. Importantly, VIP and SST interneurons display key developmental milestones in adolescence, while NOS interneurons mature much earlier. The implications of these findings point to different periods of critical development of the interneuron-mediated oxygen regulatory systems. Such that interference with normal maturation processes early in development may effect NOS interneuron neurovascular interactions to a greater degree, while insults later in development may be more targeted toward VIP- and SST-mediated mechanisms of oxygen regulation.
Altered expression of glycobiology-related genes in Parkinson’s disease brain
Authors: Schneider Jay S. , Singh Garima
Published: November 2022

The precise mechanisms initiating and perpetuating the cellular degeneration in Parkinson’s disease (PD) remain unclear. There is decreased expression of the main brain gangliosides, and GM1 ganglioside in particular, in the PD brain along with decreased expression of the genes coding for the glycosyltranferase and the sialyltransferase responsible for the synthesis of these brain gangliosides. However, potentially important pathogenic mechanisms contributing to the neurodegeneration in PD may also include altered levels of expression of genes involved in glycosylation, sialylation and sphingolipid synthesis and metabolism. Although various studies have described pathological lipid and glycolipid changes in PD brain, there have been limited studies of expression of glycobiology-related genes in PD brain. The current study was performed as an initial attempt to gain new information regarding potential changes in glycoprotein and glycolipid-related genes in PD by investigating the gene expression status for select glycosyltransferases, sialyltransferases, sialidases, sphingosine kinases, and lysosomal enzymes in the substantia nigra and putamen from patients with PD and neurologically normal controls. Results showed altered expression of glycosyltransferase genes (B3GALT2 and B4GALT1) potentially involved in microglial activation and neuroinflammation, sphingosine-1-phosphate (S1P) modulators (SPHK1, SPHK2, and SGPL1) involved in sphingolipid synthesis and metabolism, polysialyltransferase genes (ST8SIA2 and ST8SIA4) that encode enzymes responsible for polysialic acid (polySia) biosynthesis, and the sialidase NEU4, expression of which has been linked to the clearance of storage materials from lysosomes. The data presented here underscore the complexity of the glycolipid/sphingolipid dysregulation in the PD brain and continued and expanded study of these processes may not only provide a greater understanding of the complex roles of aberrant glycosylation sialylation, and sphingolipid synthesis/metabolism in the pathophysiology of PD but may identify potential druggable targets for PD therapeutics.
Serum triglycerides level is independently associated with renal outcomes in patients with non-dialysis chronic kidney disease: Results from KNOW-CKD study
Authors: Suh Sang Heon , Oh Tae Ryom , Choi Hong Sang , Kim Chang Seong , Bae Eun Hui , Oh Kook-Hwan , Han Seung Hyeok , Ma Seong Kwon , Kim Soo Wan
Published: November 2022

To investigate whether high serum triglycerides (TG) level is associated with adverse renal outcomes in patients with non-dialysis chronic kidney disease (CKD), a total of 2,158 subjects from a prospective cohort study (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were divided into the quartile by serum TG level. The primary outcomes were composite renal events, which is defined as a composite of decline of kidney function (the first occurrence of > 50% decline of estimated glomerular filtration rate or doubling of serum creatinine from the baseline) or onset of end-stage renal disease (initiation of dialysis or kidney transplantation). During the median follow-up of 6.940 years, the cumulative incidence of composite renal event was significantly differed by serum TG level in Kaplan–Meier curve analysis (P < 0.001, by Log-rank test). Cox regression analysis demonstrated that, compared to that of the 1st quartile, the risk of composite renal event was significantly higher in the 4th quartile (adjusted hazard ratio 1.433, 95% confidence interval 1.046 to 1.964). The association between high serum TG level and adverse renal outcome remained consistent in the cause-specific hazard model. Subgroup analyses revealed that the association is modified by age, estimated glomerular filtration rate, and spot urine albumin-to-creatinine ratio. In conclusion, high serum TG level is independently associated with adverse renal outcomes in patients with non-dialysis CKD. Interventional studies are warranted to determine whether lowering serum TG levels may alter the natural course of CKD.
Angiotensin-converting enzyme inhibitory peptides and isoflavonoids from soybean [Glycine max (L.) Merr.]
Authors: Ramlal Ayyagari , Nautiyal Aparna , Baweja Pooja , Kumar Vikash , Mehta Sahil , Mahto Rohit Kumar , Tripathi Shikha , Shanmugam Aravindam , Pujari Mallikarjuna Bingi , Raman Pushpa , Lal S. K. , Raju Dhandapani , Rajendran Ambika
Published: November 2022

Angiotensin-converting enzyme I (ACE I) is a zinc-containing metallopeptidase involved in the renin-angiotensin system (RAAS) that helps in the regulation of hypertension and maintains fluid balance otherwise, which results in cardiovascular diseases (CVDs). One of the leading reasons of global deaths is due to CVDs. RAAS also plays a central role in maintaining homeostasis of the CV system. The commercial drugs available to treat CVDs possess several fatal side effects. Hence, phytochemicals like peptides having plant-based origin should be explored and utilized as alternative therapies. Soybean is an important leguminous crop that simultaneously possesses medicinal properties. Soybean extracts are used in many drug formulations for treating diabetes and other disorders and ailments. Soy proteins and its edible products such as tofu have shown potential inhibitory activity against ACE. Thus, this review briefly describes various soy proteins and products that can be used to inhibit ACE thereby providing new scope for the identification of potential candidates that can help in the design of safer and natural treatments for CVDs.
Impact of aging on food consumption in rural China: Implications for dietary upgrading and health improvement
Authors: Gao Ming , Wu Bi , Jin Wencheng , Wei Jiashuo , Wang Jiwen , Li Jinkai
Published: November 2022

Background

The issue of population aging in rural China is getting profound; nevertheless, its impact on food consumption has not been well evaluated. This study aims to examine the relationship between rural aging and family food consumption in rural China.

Materials and methods

Using the statistical yearbook data and the nationally representative household-level data from the China Rural Fixed Observation Points, this study compares the evolution of food consumption between rural and urban residents from 1985 to 2020 and analyzes the structure of food consumption expenditure of rural residents. Next, this study further investigates the impact of aging on food consumption in rural households with ordinary least squares.

Results

(1) The principal foods consumed by rural residents in 2020 are meat and meat products (36.8%), grain (24.5%), and vegetables (10.9%). (2) An increase in older adults has decreased the absolute consumption of all foods, while it increased relative consumption of meat and meat products, aquatic products, edible oil and fats, poultry, eggs, and sugar. (3) Due to differences in the structure of young adults’ food consumption, older adults would increase their consumption of fruits and vegetables if they lived with younger adults.

Conclusion

The findings of this study suggest that rural older adults may increase their consumption of fruits and vegetables by advocating intergenerational cohabitation while maintaining their intake of protein to achieve a balanced dietary structure and improve their health condition.
Gamma-glutamyl-leucine levels are causally associated with elevated cardio-metabolic risks
Authors: Wu Qiong , Li Jiankang , Zhu Jinghan , Sun Xiaohui , He Di , Li Jun , Cheng Zongxue , Zhang Xuhui , Xu Yuying , Chen Qing , Zhu Yimin , Lai Maode
Published: November 2022

Objective

Gamma-glutamyl dipeptides are bioactive peptides involved in inflammation, oxidative stress, and glucose regulation. Gamma-glutamyl-leucine (Gamma-Glu-Leu) has been extensively reported to be associated with the risk of cardio-metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes. However, the causality remains to be uncovered. The aim of this study was to explore the causal-effect relationships between Gamma-Glu-Leu and metabolic risk.

Materials and methods

In this study, 1,289 subjects were included from a cross-sectional survey on metabolic syndrome (MetS) in eastern China. Serum Gamma-Glu-Leu levels were measured by untargeted metabolomics. Using linear regressions, a two-stage genome-wide association study (GWAS) for Gamma-Glu-Leu was conducted to seek its instrumental single nucleotide polymorphisms (SNPs). One-sample Mendelian randomization (MR) analyses were performed to evaluate the causality between Gamma-Glu-Leu and the metabolic risk.

Results

Four SNPs are associated with serum Gamma-Glu-Leu levels, including rs12476238, rs56146133, rs2479714, and rs12229654. Out of them, rs12476238 exhibits the strongest association (Beta = −0.38, S.E. = 0.07 in discovery stage, Beta = −0.29, S.E. = 0.14 in validation stage, combined P-value = 1.04 × 10–8). Each of the four SNPs has a nominal association with at least one metabolic risk factor. Both rs12229654 and rs56146133 are associated with body mass index, waist circumference (WC), the ratio of WC to hip circumference, blood pressure, and triglyceride (5 × 10–5 < P < 0.05). rs56146133 also has nominal associations with fasting insulin, glucose, and insulin resistance index (5 × 10–5 < P < 0.05). Using the four SNPs serving as the instrumental SNPs of Gamma-Glu-Leu, the MR analyses revealed that higher Gamma-Glu-Leu levels are causally associated with elevated risks of multiple cardio-metabolic factors except for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (P > 0.05).

Conclusion

Four SNPs (rs12476238, rs56146133, rs2479714, and rs12229654) may regulate the levels of serum Gamma-Glu-Leu. Higher Gamma-Glu-Leu levels are causally linked to cardio-metabolic risks. Future prospective studies on Gamma-Glu-Leu are required to explain its role in metabolic disorders.
Early lean mass sparing effect of high-protein diet with excess leucine during long-term bed rest in women
Authors: Vinci Pierandrea , Di Girolamo Filippo Giorgio , Mangogna Alessandro , Mearelli Filippo , Nunnari Alessio , Fiotti Nicola , Giordano Mauro , Bareille Marie-Pierre , Biolo Gianni
Published: November 2022

Muscle inactivity leads to muscle atrophy. Leucine is known to inhibit protein degradation and to promote protein synthesis in skeletal muscle. We tested the ability of a high-protein diet enriched with branched-chain amino acids (BCAAs) to prevent muscle atrophy during long-term bed rest (BR). We determined body composition (using dual energy x-ray absorptiometry) at baseline and every 2-weeks during 60 days of BR in 16 healthy young women. Nitrogen (N) balance was assessed daily as the difference between N intake and N urinary excretion. The subjects were randomized into two groups: one received a conventional diet (1.1 ± 0.03 g protein/kg, 4.9 ± 0.3 g leucine per day) and the other a high protein, BCAA-enriched regimen (1.6 ± 0.03 g protein-amino acid/kg, 11.4 ± 0.6 g leucine per day). There were significant BR and BR × diet interaction effects on changes in lean body mass (LBM) and N balance throughout the experimental period (repeated measures ANCOVA). During the first 15 days of BR, lean mass decreased by 4.1 ± 0.9 and 2.4 ± 2.1% (p < 0.05) in the conventional and high protein-BCAA diet groups, respectively, while at the end of the 60-day BR, LBM decreased similarly in the two groups by 7.4 ± 0.7 and 6.8 ± 2.4%. During the first 15 days of BR, mean N balance was 2.5 times greater (p < 0.05) in subjects on the high protein-BCAA diet than in those on the conventional diet, while we did not find significant differences during the following time intervals. In conclusion, during 60 days of BR in females, a high protein-BCAA diet was associated with an early protein-LBM sparing effect, which ceased in the medium and long term.
Visualising spatial heterogeneity in glioblastoma using imaging habitats
Authors: Waqar Mueez , Van Houdt Petra J. , Hessen Eline , Li Ka-Loh , Zhu Xiaoping , Jackson Alan , Iqbal Mudassar , O’Connor James , Djoukhadar Ibrahim , van der Heide Uulke A. , Coope David J. , Borst Gerben R.
Published: November 2022

Glioblastoma is a high-grade aggressive neoplasm characterised by significant intra-tumoral spatial heterogeneity. Personalising therapy for this tumour requires non-invasive tools to visualise its heterogeneity to monitor treatment response on a regional level. To date, efforts to characterise glioblastoma’s imaging features and heterogeneity have focussed on individual imaging biomarkers, or high-throughput radiomic approaches that consider a vast number of imaging variables across the tumour as a whole. Habitat imaging is a novel approach to cancer imaging that identifies tumour regions or ‘habitats’ based on shared imaging characteristics, usually defined using multiple imaging biomarkers. Habitat imaging reflects the evolution of imaging biomarkers and offers spatially preserved assessment of tumour physiological processes such perfusion and cellularity. This allows for regional assessment of treatment response to facilitate personalised therapy. In this review, we explore different methodologies to derive imaging habitats in glioblastoma, strategies to overcome its technical challenges, contrast experiences to other cancers, and describe potential clinical applications.
Multi-omics approach to identifying isoform variants as therapeutic targets in cancer patients
Authors: Shaw Timothy I. , Zhao Bi , Li Yuxin , Wang Hong , Wang Liang , Manley Brandon , Stewart Paul A. , Karolak Aleksandra
Published: November 2022

Cancer-specific alternatively spliced events (ASE) play a role in cancer pathogenesis and can be targeted by immunotherapy, oligonucleotide therapy, and small molecule inhibition. However, identifying actionable ASE targets remains challenging due to the uncertainty of its protein product, structure impact, and proteoform (protein isoform) function. Here we argue that an integrated multi-omics profiling strategy can overcome these challenges, allowing us to mine this untapped source of targets for therapeutic development. In this review, we will provide an overview of current multi-omics strategies in characterizing ASEs by utilizing the transcriptome, proteome, and state-of-art algorithms for protein structure prediction. We will discuss limitations and knowledge gaps associated with each technology and informatics analytics. Finally, we will discuss future directions that will enable the full integration of multi-omics data for ASE target discovery.
Efficacy and safety of Shenfu injection for the treatment of post-acute myocardial infarction heart failure: A systematic review and meta-analysis
Authors: Wu Yanhua , Li Shuang , Li Zunjiang , Mo Zhaofan , Luo Ziqing , Li Dongli , Wang Dawei , Zhu Wei , Ding Banghan
Published: November 2022

Objective: This systematic review and meta-analysis aimed to investigate the adjuvant effect and safety of Shenfu injection (SFI) on the treatment of post-acute myocardial infarction heart failure (PAMIHF).

Methods: Seven databases were searched to identify randomized controlled trials (RCTs) associated with SFI and PAMIHF treatment from May 1990 to May 2022. Primary outcomes included NT-proBNP and left ventricular ejection fraction (LVEF), and secondary outcomes included total effective rate, BNP, heart rate (HR), cardiac output (CO), and adverse event (AE). The risk of bias evaluation was assessed by the ROB2 tool, meta-analysis, subgroup analysis, sensitivity analysis, and publication bias were conducted by RevMan5.3 software, and the Grade of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to evaluate the quality of evidence of meta results.

Results: A total of 36 studies with 3231 PAMIHF patients were included. The meta results suggested that adjuvant SFI therapy was superior to conventional medical therapy alone. It improved the total effective rate [RR = 1.33; 95% CI (1.25.1.40); p < 0.00001], increased LVEF [SMD = 0.98; 95% CI (0.71, 1.24); p < 0.00001], and decreased HR [SMD = −1.14; 95% CI (−1.28, −0.99); p < 0.00001]. In addition, adjuvant SFI therapy (9.73%, 66/678) had a rate of AE lower than that of conventional medical therapy alone (21.7%, 147/677) when regarding safety [RR = 0.45; 95% CI (0.35, 0.57); p < 0.00001]. The quality of the evidence for the outcomes was rated from “very low” to “moderate.”

Conclusion: Adjuvant SFI therapy was safer to improve the total effective rate and the heart function of PAMIHF patients. However, well-designed RCTs were needed to confirm the efficacy and safety of adjuvant SFI therapy in PAMIHF treatment due to the low quality of the evidence for the outcomes caused by a small sample size and unclear risk of bias existed in included studies.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=151856), identifier CRD42020151856.
Nitidine chloride, a benzophenanthridine alkaloid from Zanthoxylum nitidum (Roxb.) DC., exerts multiple beneficial properties, especially in tumors and inflammation-related diseases
Authors: Lu Qiang , Luo Shuang , Shi Zhongfeng , Yu Mingzhen , Guo Weifeng , Li Cailan
Published: November 2022

Plant-derived alkaloids are a kind of very important natural organic compounds. Nitidine chloride is one of the main active ingredients in Zanthoxylum nitidum (Roxb.) DC. which is a frequently-used Chinese herbal medicine. Z. nitidum has many kinds of efficacy, such as activating blood circulation and removing stasis, promoting qi circulation and relieving pain, and detoxication and detumescence. In China, Z. nitidum is usually used for the treatment of gastrointestinal diseases, toothache, and traumatic injury. At present, there are numerous studies of nitidine chloride with regard to its pharmacology, pharmacokinetics, toxicology, etc. However, a systematic, cutting-edge review of nitidine-related studies is extremely lacking. The present paper aimed at comprehensively summarizing the information on the extraction, separation and purification, pharmacology, pharmacokinetics, toxicology and formulation of nitidine chloride. The knowledge included in the present study were searched from the following academic databases involving Web of Science, PubMed, Google scholar, Elsevier, CNKI and Wanfang Data, till July 2022. In terms of nitidine chloride extraction, enzymatic method and ultrasonic method are recommended. Resin adsorption and chromatography were usually used for the separation and purification of nitidine chloride. Nitidine chloride possesses diversified therapeutical effects, such as anti-tumor, anti-inflammation, anti-colitis, anti-malaria, anti-osteoporosis, anti-rheumatoid and so on. According to pharmacokinetics, the intestinal absorption of nitidine chloride is passive diffusion, and it is rarely excreted with urine and feces in the form of prototype drug. Nitidine chloride has a moderate binding to plasma protein, which is independent of the drug concentration. As to toxicology, nitidine chloride showed certain toxicity on liver, kidney and heart. Certain new formulations, such as nanoparticle, microsphere and nano-micelle, could increase the therapeutic effect and decrease the toxicity of nitidine chloride. Despite limitations such as poor solubility, low bioavailability and certain toxicity, nitidine chloride is still a promising natural alkaloid for drug candidates. Extensive and intensive exploration on nitidine chloride is essential to promote the usage of nitidine-based drugs in the clinic practice.
Medication non-adherence and associated factors among older adult stroke survivors in China
Authors: Cao Wenjing , Kadir Azidah Abdul , Wang Juan , Hu Lin , Wen Linlan , Yu Mei , Peng Liqun , Chen Lanying , Luo Na , Hassan Intan Idiana
Published: November 2022

Aim: Medication non-adherence has remained a common and costly global health issue of growing importance among older adults. This study aims to determine the prevalence and associated factors related to medication non-adherence among older adult stroke survivors in China.

Methods and results: In this cross-sectional study, a total of 402 older adult stroke survivors were recruited from three tertiary hospitals in China. The results of the survey showed that 61.4% exhibited medication non-adherence. The chances of medication non-adherence among older adult stroke survivors who had primary school or less educational levels were higher than those who had senior secondary and junior college educational levels [OR (95% CI) = 0.440(0.249, 0.778)] as well as those who had a bachelor’s degree or above educational levels [OR (95%CI) = 0.367(0.202, 0.667)]. Moreover, the probability of medication non-adherence with 4–5 and ≥6 types of total prescription medications per day increased by 1.993 times [OR (95% CI) = 1.993(1.190, 3.339))] and 2.233 times [OR (95%CI) = 2.233(1.159, 4.300)], respectively, as compared to when there were ≤3 types. Furthermore, medication non-adherence decreased with the increase in health literacy scores (β = −0.641 (95% CI; (0.913, 0.965)) and BMQ specific-necessity scores (β = −0.131 (95% CI; 0.806, 0.995)). On the other hand, when the BMQ specific-concerns score increased by one unit, medication non-adherence increased by 11.1% [OR (95% CI) = 1.111(1.044, 1.182)].

Conclusion: The present study found that patient medication adherence among older adult stroke survivors in China is problematic and associated with educational levels, total prescribed drugs per day, beliefs about medication, and health literacy scores. This indicates that measures should be taken to enhance medication adherence among such higher-risk populations.
Molecular mechanisms of ferroptosis and the potential therapeutic targets of ferroptosis signaling pathways for glioblastoma
Authors: Zhang Meng , Lei Qian , Huang Xiaobo , Wang Yi
Published: November 2022

Ferroptosis is a newly identified form of cell death that differs from autophagy, apoptosis and necrosis, and its molecular characteristics include iron-dependent lipid reactive oxygen species accumulation, mitochondrial morphology changes, and membrane permeability damage. These characteristics are closely related to various human diseases, especially tumors of the nervous system. Glioblastoma is the most common primary malignant tumor of the adult central nervous system, and the 5-year survival rate is only 4%–5%. This study reviewed the role and mechanism of ferroptosis in glioblastoma and the research status and progress on ferroptosis as a potential therapeutic target. The mechanism of ferroptosis is related to the intracellular iron metabolism level, lipid peroxide content and glutathione peroxidase 4 activity. It is worth exploring how ferroptosis can be applied in disease treatment; however, the relation between ferroptosis and other apoptosis methods is poorly understood and methods of applying ferroptosis to drug-resistant tumors are insufficient. Ferroptosis is a promising therapeutic target for glioblastoma. In-depth studies of its mechanism of action in glioblastoma and applications for clinical treatment are expected to provide insights for glioblastoma patients.
Cardiovascular and renal outcomes with sodium glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus: A system review and network meta-analysis
Authors: Tian Lei , Ai Sinan , zheng Huijuan , Yang Hanwen , Zhou Mengqi , Tang Jingyi , Liu Weijing , Zhao Wenjing , Wang Yaoxian
Published: November 2022

Cardiovascular and renal impairment are the most common complications of type 2 diabetes mellitus (T2DM). As an emerging class of glucose-lowing agents sodium glucose co-transporter 2 (SGLT2), possesses beneficial effects on cardiovascular and renal outcomes in patients with T2DM. The aim of this study is to assess the efficacy of different SGLT2 inhibitors for cardiovascular and renal outcomes for patients with T2DM when compared with placebo. We performed a systematic search of PubMed, Embase, and the Cochrane library from inception through November 2021. Randomized clinical trials enrolling participants with T2DM were included, in which SGLT2 inhibitors were compared with each other or placebo. The primary outcomes including all-caused mortality, Cardiovascular outcomes (cardiovascular mortality, hospitalization for heart failure), and the renal composite outcomes (worsening persistent microalbuminuria or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death). The data for the outcomes were pooled and recorded as Hazard rations (HRs) with 95% confidence intervals (CLs). Two researcher independently screened the trials and drawn the data. Ten trials enrolling 68,723 patients were included. Compared with placebo groups, Canagliflozin [HR, 0.85 (95%CI, 0.75–0.98)], ertugliflozin [HR, 0.93 (95%CI, 0.78–1.11)], and sotagliflozin [HR, 0.94 (95%CI, 0.79–1.12)] were associated with a reduction in all-cause mortality. Canagliflozin [HR, 0.84 (95%CI, 0.72–0.97)], dapagliflozin [HR, 0.88 (95%CI, 0.79–0.99)], empagliflozin [HR, 0.62 (95%CI, 0.49–0.78)], ertugliflozin [HR, 0.92 (95%CI, 0.77–1.10)], and sotagliflozin [HR, 0.88 (95%CI, 0.73–1.06)] were associated with a reduction in cardiovascular mortality; Canagliflozin [HR, 0.64 (95%CI, 0.53–0.77)], dapagliflozin [HR, 0.71 (95%CI, 0.63–0.81)], empagliflozin [HR, 0.65 (95%CI, 0.50–0.85)], ertugliflozin [HR, 0.70 (95%CI, 0.54–0.90)], and sotagliflozin [HR, 0.66 (95%CI, 0.56–0.77)] were associated with a reduction in hospitalization for heart failure. Dapagliflozin [HR, 0.55 (95%CI, 0.47–0.63)], Empagliflozin [HR, 0.54 (95%CI, 0.39–0.74)], canagliflozin [HR, 0.64 (95%CI, 0.54–0.75)], sotagliflozin [HR, 0.71 (95%CI, 0.46–1.09)], and ertugliflozin [HR, 0.81 (95%CI, 0.63–1.04)] were associated with a reduction in the renal composite outcome. All SGLT2 inhibitors showed a reduction in cardiovascular mortality, hospitalization for heart failure, renal composite outcomes and all-cause mortality. Canagliflozin and empagliflozin seemed to have the same efficacy in reducing hospitalization for heart failure, but empagliflozin had advantage in reducing cardiovascular mortality, whereas dapagliflozin most likely showed the best renal composite outcomes.
Adenosine reduces sinoatrial node cell action potential firing rate by uncoupling its membrane and calcium clocks
Authors: Wirth Ashley N. , Tsutsui Kenta , Maltsev Victor A. , Lakatta Edward G.
Published: November 2022

The spontaneous action potential (AP) firing rate of sinoatrial nodal cells (SANC) is regulated by a system of intracellular Ca2+ and membrane ion current clocks driven by Ca2+-calmodulin-activated adenylyl cyclase-protein kinase-A signaling. The mean AP-cycle length (APCL) and APCL variability inform on the effectiveness of clock coupling. Endogenous ATP metabolite adenosine binds to adenosine receptors (A1, A3) that couple to Gi protein-coupled receptors, reducing spontaneous AP firing rate via Gβγ signaling that activates IKAch,Ado. Adenosine also inhibits adenylyl cyclase activity via Gαi signaling, impacting cAMP-mediated protein kinase-A-dependent protein phosphorylation. We hypothesize that in addition to IKAch,Ado activation, adenosine impacts also Ca2+via Gαi signaling and that both effects reduce AP firing rate by reducing the effectiveness of the Ca2+ and membrane clock coupling. To this end, we measured Ca2+ and membrane potential characteristics in enzymatically isolated single rabbit SANC. 10 µM adenosine substantially increased both the mean APCL (on average by 43%, n = 10) and AP beat-to-beat variability from 5.1 ± 1.7% to 7.2 ± 2.0% (n = 10) measured via membrane potential and 5.0 ± 2.2% to 10.6 ± 5.9% (n = 40) measured via Ca2+ (assessed as the coefficient of variability = SD/mean). These effects were mediated by hyperpolarization of the maximum diastolic membrane potential (membrane clock effect) and suppression of diastolic local Ca2+releases (LCRs) (Ca2+-clock effect): as LCR size distributions shifted to smaller values, the time of LCR occurrence during diastolic depolarization (LCR period) became prolonged, and the ensemble LCR signal became reduced. The tight linear relationship of coupling between LCR period to the APCL in the presence of adenosine “drifted” upward and leftward, i.e. for a given LCR period, APCL was prolonged, becoming non-linear indicating clock uncoupling. An extreme case of uncoupling occurred at higher adenosine concentrations (>100 µM): small stochastic LCRs failed to self-organize and synchronize to the membrane clock, thus creating a failed attempt to generate an AP resulting in arrhythmia and cessation of AP firing. Thus, the effects of adenosine to activate Gβγ and IKACh,Ado and to activate Gαi, suppressing adenylyl cyclase activity, both contribute to the adenosine-induced increase in the mean APCL and APCL variability by reducing the fidelity of clock coupling and AP firing rate.
Salicylic acid improves Nasturtium officinale phytoremediation capability for cadmium-contaminated paddy soils
Authors: Zheng Yangxia , Zhang Ran , Zhu Ying , Ao Qiaoman , Liu Han , Li Aihui , Lin Lijin , Wang Li
Published: November 2022

Introduction

Cadmium (Cd) contamination is a severe problem in paddy soils that has affected crops’ safety. The present study aimed at remediating Cd-contaminated paddy soil by improving the phytoremediation capability of aquatic accumulator plants.

Methods

We conducted an experiment to investigate the effects of salicylic acid (SA) on the growth and Cd phytoremediation capability of the aquatic accumulator plant Nasturtium officinale.

Results

SA with the concentrations of 100, 150, and 200 mg/L increased the root and shoot biomass of N. officinale, while only 150 mg/L increased the chlorophyll a and b contents. SA increased the activities of peroxidase and catalase of N. officinale to a great extent, but decreased the superoxide dismutase activity and soluble protein content. SA also increased the root Cd content, shoot Cd content, root Cd extraction, and shoot Cd extraction to a large extent. At concentrations of 100, 150, and 200 mg/L, SA increased the shoot Cd extraction by 17.59%, 47.16%, and 43.27%, respectively, compared with the control. Moreover, SA concentration had a quadratic polynomial regression relationship with the root Cd extraction and shoot Cd extraction. The correlation and grey relational analyses revealed that root Cd extraction, shoot biomass, and root biomass were closely associated with shoot Cd extraction of N. officinale.

Conclusion

Thus, our results suggest that SA promoted the growth and improved the phytoremediation (extraction) capability of N. officinale, and 150 mg/L SA was the most suitable concentration.
Chitin amendments eliminate the negative impacts of continuous cropping obstacles on soil properties and microbial assemblage
Authors: Fan Yanli , Liu Junjie , Liu Zhuxiu , Hu Xiaojing , Yu Zhenhua , Li Yansheng , Chen Xueli , Li Lujun , Jin Jian , Wang Guanghua
Published: November 2022

Continuous cropping of soybean leads to soil environment deterioration and soil-borne disease exacerbation, which in turn limits the sustainability of agricultural production. Chitin amendments are considered promising methods for alleviating soybean continuous cropping obstacles; however, the underlying mechanisms of soil sickness reduction remain unclear. In this study, soil amendments with pure and crude chitin at different addition dosages were employed to treat diseased soil induced by continuous cropping of soybean for five years. Chitin amendments, especially crude chitin, remarkably increased soil pH, available phosphorus (AP), potassium (AK) and nitrate nitrogen ( NO3−-N) contents, and improved soybean plant growth and soil microbial activities (FDA). Additionally, chitin application significantly enriched the relative abundances of the potential biocontrol bacteria Sphingomonas, Streptomyces, and Bacillus and the fungi Mortierella, Purpureocillium, and Metarhizium while depleted those of the potential plant pathogens Fusarium, Cylindrocarpon and Paraphoma. Moreover, chitin amendments induced looser pathogenic subnetwork structures and less pathogenic cooperation with other connected microbial taxa in the rhizosphere soils. The structural equation model (SEM) revealed that pure and crude chitin amendments promoted soybean plant growth by indirectly regulating soil pH-mediated soil microbial activities and potentially beneficial microbes, respectively. Therefore, the reduction strategies for continuous cropping obstacles by adding pure and crude chitin were distinct; pure chitin amendments showed general disease suppression, while crude chitin exhibited specific disease suppression. Overall, chitin amendments could suppress potential plant pathogens and improve soil health, thereby promoting soybean growth, which provides new prospects for cultivation practices to control soybean continuous cropping obstacles.
A high-quality genome assembly and annotation of Quercus acutissima Carruth
Authors: Liu Dan , Xie Xiaoman , Tong Boqiang , Zhou Chengcheng , Qu Kai , Guo Haili , Zhao Zhiheng , El-Kassaby Yousry A. , Li Wei , Li Wenqing
Published: November 2022

Introduction

Quercus acutissima is an economic and ecological tree species often used for afforestation of arid and semi-arid lands and is considered as an excellent tree for soil and water conservation.

Methods

Here, we combined PacBio long reads, Hi-C, and Illumina short reads to assemble Q. acutissima genome.

Results

We generated a 957.1 Mb genome with a contig N50 of 1.2 Mb and scaffold N50 of 77.0 Mb. The repetitive sequences constituted 55.63% of the genome, among which long terminal repeats were the majority and accounted for 23.07% of the genome. Ab initio, homology-based and RNA sequence-based gene prediction identified 29,889 protein-coding genes, of which 82.6% could be functionally annotated. Phylogenetic analysis showed that Q. acutissima and Q. variabilis were differentiated around 3.6 million years ago, and showed no evidence of species-specific whole genome duplication.

Conclusion

The assembled and annotated high-quality Q. acutissima genome not only promises to accelerate the species molecular biology studies and breeding, but also promotes genome level evolutionary studies.
(Un)ready for change? The debate about electronic voting in Portugal and its implementation before and after the pandemic era
Authors: Lisi Marco , Luís Carla
Published: November 2022

The use of electronic voting has been considered an important tool to improve electoral processes in some circumstances, with potential effects in party-voter linkages and participation. However, many countries are skeptical in adopting this digital tool and there are relevant shortcomings in the implementation of electronic voting. Despite favorable conditions for the innovation in voting mechanisms, Portugal is one of the countries still considering the possibility to introduce e-voting. This study argues that we need to consider not only the context in which e-voting takes place, but also the key role of party agents. Drawing on interviews with party officials and experts, primary data collection and media sources, this paper shows that in Portugal e-voting is not regarded as a potential tool to improve the electoral process due to the high level of trust and quality of traditional voting mechanisms, as well as due to the divergent interest of political parties. In addition, party organizations are not familiar with the use of digital tools in terms of grassroot mobilization. Overall, the findings indicate that party barriers are also key for allowing the (non)adoption of e-voting.
The effect of core self-evaluations on career adaptability: The mediating role of protean career attitudes and the moderating role of meritocratic beliefs
Authors: Du Bin , Yu Xuan , Luo Nan , Liu Xuhong
Published: November 2022

Based on the career construction model of adaptation, this study explores the impact of core self-evaluations on career adaptability, with the mediating role of protean career attitudes and moderating role of meritocratic beliefs. The results of the questionnaire survey on 1000 Chinese college students show that: (1) core self-evaluations positively predicted college students’ career adaptability; (2) protean career attitudes mediated the relationship between core self-evaluations and career adaptability; (3) meritocratic beliefs not only moderated the effect protean career attitudes have on career adaptability but also moderated the indirect influence of core self-evaluations on career adaptability through protean career attitudes. These results extend the existing antecedent studies on career adaptability and demonstrate the importance of combining self-mobility beliefs (protean career attitudes) with social mobility beliefs (meritocratic beliefs) in the process of core self-evaluations affecting career adaptability. In conclusion, we hope to further develop the theory of career construction and provide more suggestions for college consultants and students.
Relations between bedtime parenting behaviors and temperament across 14 cultures
Authors: Pham Christie , Desmarais Eric , Jones Victoria , French Brian F. , Wang Zhengyan , Putnam Samuel , Casalin Sara , Linhares Maria Beatriz Martins , Lecannelier Felipe , Tuovinen Soile , Heinonen Kati , Raikkonen Katri , Montirosso Rosario , Giusti Lorenzo , Park Seong-Yeon , Han Sae-Young , Lee Eun Gyoung , Huitron Blanca , de Weerth Carolina , Beijers Roseriet , Majdandžić Mirjana , Gonzalez-Salinas Carmen , Acar Ibrahim , Slobodskaya Helena , Kozlova Elena , Ahmetoglu Emine , Benga Oana , Gartstein Maria A.
Published: November 2022

Objectives

The present study examined parental sleep-supporting practices during toddlerhood in relation to temperament across 14 cultures. We hypothesized that passive sleep-supporting techniques (e.g., talking, cuddling), but not active techniques (e.g., walking, doing an activity together), would be associated with less challenging temperament profiles: higher Surgency (SUR) and Effortful Control (EC) and lower Negative Emotionality (NE), with fine-grained dimensions exhibiting relationships consistent with their overarching factors (e.g., parallel passive sleep-supporting approach effects for dimensions of NE).

Methods

Caregivers (N= 841) across 14 cultures (M = 61 families per site) reported toddler (between 17 and 40 months of age; 52% male) temperament and sleep-supporting activities. Utilizing linear multilevel regression models and group-mean centering procedures, we assessed the role of between- and within-cultural variance in sleep-supporting practices in relation to temperament.

Results

Both within-and between-culture differences in passive sleep-supporting techniques were associated with temperament attributes, (e.g., lower NE at the between-culture level; higher within-culture EC). For active techniques only within-culture effects were significant (e.g., demonstrating a positive association with NE). Adding sleep-supporting behaviors to the regression models accounted for significantly more between-culture temperament variance than child age and gender alone.

Conclusion

Hypotheses were largely supported. Findings suggest parental sleep practices could be potential targets for interventions to mitigate risk posed by challenging temperament profiles (e.g., reducing active techniques that are associated with greater distress proneness and NE).
“I'm too old for this!”: A prospective, multilevel study of job characteristics, age, and turnover intention
Authors: Christensen Jan Olav , Knardahl Stein
Published: November 2022

Introduction

Deciding to leave a job is often foreshadowed by burgeoning job dissatisfaction, which is in turn often attributed to characteristics of the job and work environment. However, while we know that job characteristics influence job satisfaction, health, and motivation, their associations with turnover intention is less clear. Moreover, despite aging workforces, an understanding of how working conditions influence workers across the lifespan is lacking. Therefore, drawing on job design theories and bridging turnover- and aging research, we studied 15 specific job characteristics to determine whether they predicted turnover intentions, and whether the predictive value was modified by age.

Methods

Data were collected from various public and private enterprises in Norway. Moderated multilevel regressions were conducted cross-sectionally (N = 12,485) and prospectively over 2 years (N = 5,504).

Results

Most work factors were associated with turnover intention at both the individual and work unit levels. A social climate of support, trust, and encouragement was most strongly inversely associated with turnover intentions, while role conflict was most strongly positively associated with turnover intentions. Organizational climate, leadership styles, and job control were more important with age while job demands, predictability and role stressors were more important to younger workers. Ten individual level- and four work-unit level factors predicted turnover intentions prospectively, suggesting turnover intentions due to poor working conditions persisted in employees that did not quit.

Discussion

Our results highlight several specific, modifiable job characteristics that are likely to affect turnover intentions, and the impact of certain factors specifically for older workers.