bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between Metabolite of Prostaglandin E2 and the incidence of colorectal adenomas
Authors: Jiang Jia , Li Anjie , Lai Xiaolian , Zhang Hanqun , Wang Chonghong , Wang Huimin , Li Libo , Liu Yuncong , Xie Lu , Yang Can , Zhang Cui , Lu Shuoyan , Li Yong
Published: February 2023

Colorectal cancer is a common malignancy, and the incidence and mortality rates continue to rise. An important factor in the emergence of inflammation-induced colorectal carcinogenesis is elevated cyclooxygenase-2. Prostaglandin E2 (PGE2) over-production is frequently equated with cyclooxygenase-2 gene over-expression. PGE2 can be assessed by measuring the level of prostaglandin’s main metabolite, PGE-M, in urine. Colorectal adenoma is a precancerous lesion that can lead to colorectal cancer. We conducted research to evaluate the association between urinary levels of the PGE-M and the risk of colorectal adenomas. In a western Chinese population, we identified 152 cases of adenoma and 152 controls patients without polyps. Adenoma cases were categorized into control, low-risk and high-risk groups. There was no significant change in PGE-M levels, between the control group and the low-risk adenoma group. In the high-risk group, the PGE-M levels were 23% higher than the control group. When compared to people with the lowest urine PGE-M levels (first quartile), people with greater urinary PGE-M levels had a higher chance of developing high-risk colorectal adenomas, with an adjusted odds ratio (95% CI) of 1.65 (0.76-3.57) in the fourth quartile group, (p= 0.013). We conclude urinary PGE-M is associated with the risk of developing high-risk adenomas. Urinary PGE-M level may be used as a non-invasive indicator for estimating cancer risk.
PARP inhibitor-related haemorrhages: What does the real-world study say?
Authors: Wang Shiyan , Guo Mengran , Zhang Xiang , Fan Ping , Jin Zhaohui
Published: February 2023

Background

PARP inhibitors (PARPis) are novel molecular targeted therapeutics for inhibition of DNA repair in tumor cells, which are commonly used in ovarian cancer. Recent case reports have indicated that haemorrhages-related adverse events may be associated with PARPis. However, little is known about the characteristics and signal strength factors of this kind of adverse event.

Methods

A pharmacovigilance study from January 2004 to March 2022 based on the FDA adverse event reporting system (FAERS) database was conducted by adopting the proportional imbalance method based on the four algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural networks (BCPNN) and multi-item gamma Poisson shrinker (MGPS).

Results

725 cases of PARPi-haemorrhages-related adverse events were identified with a fatality rate of 4.72% (30/725) and a median age of 67 years. About 88% of the adverse events occurred within 6 months, and the median duration (IQR) was 68 days. Most adverse events (n=477, 75.11%) were related to the treatment of niraparib. Importantly, niraparib exposure was associated with a significant increase in haemorrhages-related adverse events (ROR (95% CI), 1.13(1.03,1.23), PRR (χ2), 1.12(7.32), IC (IC 025), 0.17(0.15). In addition, petechiae, gingival bleeding, bloody urine, as well as rectal haemorrhage should be monitored when using niraparib.

Conclusion

Recognition and management of PARPi-haemorrhages-related adverse events is of significance to clinical practice. In this study, we provided a safety signal that haemorrhage-related adverse events should be monitored for when using niraparib. However, larger and more robust post-market safety studies are needed to improve the quality of this evidence.
JAG1 is correlated to suppressive immune microenvironment and predicts immunotherapy resistance in lung adenocarcinoma
Authors: He Jing , Li Lu , Lv Lulu , Chen Xiaoyan , Ge Minghui , Ren Yong , Tang Xinyu , Liu Ping , Gao Wen
Published: February 2023

Background

The current exploration of the tumor immune microenvironment is enthusiastic, but few studies explored the impact of angiogenesis on the immune microenvironment. Immunotherapy combined with anti-angiogenesis therapy has become one of the first-line treatment for lung adenocarcinoma. Our study aimed to explore the reasons for resistance of immunotherapy, and explore markers for immunotherapy combined with anti-angiogenesis therapy.

Methods

First, by unsupervised clustering of 36 angiogenesis-related genes in lung adenocarcinoma patients from TCGA database, AGS1 and AGS2 groups were distinguished with significantly different clinical outcomes. Secondly, the immune microenvironment and metabolic characteristics were analyzed. Next, we used the GDSC and GEO database to analyze therapeutic responses. Then, through multivariate Cox regression, the hub gene: JAG1, significantly related to prognosis was selected, and further verified by multi-omics data. Finally, we validated that patient with high JAG1 expression had a low immune-infiltrating tumor microenvironment through single-cell transcriptomic data.

Results

Compared with the AGS1 group, AGS2 showed an immune “cold” phenotype with lower lymphocyte infiltration, and was associated with worse prognoses. At the same time, the immunosuppressive TGF-β response was significantly higher in AGS2. Furthermore, the glycolysis ability of the AGS2 was stronger than AGS1. The expression of JAG1 was significantly higher in the AGS2, and was significantly negatively correlated with the degree of immune infiltration, accompanying with higher glycolytic capacity. The above results indicate that patients with high expression of JAG1 may lead to immunosuppressive phenotype due to its strong glycolytic capacity, thus making immunotherapy resistance.

Conclusion

Patients with high expression of JAG1 enhanced glycolytic capacity was likely to cause suppressed immune microenvironment. JAG1 may be a marker for resistance of immunotherapy. Combining anti-angiogenesis therapy could be considered to improve the prognosis of those patients.
Hepatectomy versus transcatheter arterial chemoembolization for resectable BCLC stage A/B hepatocellular carcinoma beyond Milan criteria: A randomized clinical trial
Authors: Fang Chongkai , Luo Rui , Zhang Ying , Wang Jinan , Feng Kunliang , Liu Silin , Chen Chuyao , Yao Ruiwei , Shi Hanqian , Zhong Chong
Published: February 2023

Background

Hepatectomy is the recommended option for radical treatment of BCLC stage A/B hepatocellular carcinoma (HCC) that has progressed beyond the Milan criteria. This study evaluated the efficacy and safety of preoperative neoadjuvant transcatheter arterial chemoembolization (TACE) for these patients.

Methods

In this prospective, randomized, open-label clinical study, BCLC stage A/B HCC patients beyond the Milan criteria were randomly assigned (1:1) to receive either neoadjuvant TACE prior to hepatectomy (NT group) or hepatectomy alone (OP group). The primary outcome was overall survival (OS), while the secondary outcomes were progression-free survival (PFS) and adverse events (AEs).

Results

Of 249 patients screened, 164 meeting the inclusion criteria were randomly assigned to either the NT group (n = 82) or OP group (n = 82) and completed follow-up requirements. Overall survival was significantly greater in the NT group compared to the OP group at 1 year (97.2% vs. 82.4%), two years (88.4% vs. 60.4%), and three years (71.6% vs. 45.7%) (p = 0.0011) post-treatment. Similarly, PFS was significantly longer in the NT group than the OP group at 1 year (60.1% vs. 39.9%), 2 years (53.4% vs. 24.5%), and 3 years (42.2% vs. 24.5%) (p = 0.0003). No patients reported adverse events of grade 3 or above in either group.

Conclusions

Neoadjuvant TACE prolongs the survival of BCLC stage A/B HCC patients beyond the Milan criteria without increasing severe adverse events frequency.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR2200055618.
Chimeric antigen receptor-T cells are effective against CEACAM5 expressing non-small cell lung cancer cells resistant to antibody-drug conjugates
Authors: Kim Ye-Jin , Li Wei , Zhelev Doncho V. , Mellors John W. , Dimitrov Dimiter S. , Baek Du-San
Published: February 2023

Chimeric antigen receptor-T (CAR-T) cells and antibody-drug conjugates (ADCs) are promising therapeutic strategies in oncology. The carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is overexpressed in tumors including non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC), and is an attractive target for therapies based on CAR-T cell or/and ADCs. We previously developed a highly specific antibody-based CAR-T cells targeting CEACAM5 and the tumoricidal effect of CAR-T cells was proved against neuro-endocrine prostate cancer (NEPC) cells expressing CEACAM5. Here, we compare the anti-tumor efficacy of our CAR-T cells with that of an anti-CEACAM5 ADC being clinically evaluated against NSCLC. Our anti-CEACAM5 CAR-T cells showed cytotoxicity in a CEACAM5 surface concentration dependent manner and reduced tumor growth in both ADC-responsive and -non-responsive CEACAM5-expressing NSCLC cells in vitro and in vivo. In contrast, the ADC exhibited cytotoxicity independent on the CEACAM5 cell surface concentration. Even though clinical translation of CEACAM5 targeting CAR-T cell therapies is still in preclinical stage, our CAR-T cell approach could provide a potential therapeutic strategy for CEACAM5-positive cancer patients with resistance to ADCs.
miR-92a and integrin expression in fibrovascular membranes in proliferative diabetic retinopathy
Authors: Luo Qianyi , Hajrasouliha Amir R. , Bhatwadekar Ashay D.
Published: February 2023

Diabetic retinopathy (DR) is a leading cause of vision impairment. The proliferative form of DR (PDR) involves fibrovascular membrane (FVM) formation at the vitreoretinal interface. MicroRNAs (miRNAs) are a class of non-coding RNA molecules that play an important role in gene regulation; a single miRNA could regulate multiple genes. We previously reported that miR-92a, a suppressor of integrins α5 and αv, was downregulated in DR. Considering the integrin’s role in FVM pathology and the potential involvement of miR-92a in DR, we asked a question whether miR-92a could play a critical role in FVM pathology. We collected the FVM and epiretinal membranes of individuals with PDR and macular pucker (control) undergoing pars plana vitrectomy. The frozen sections of membranes were stained for α5 and αvβ3 integrins. The miR-92a levels were assessed using real-time quantitative PCR. The FVMs of individuals with PDR stained brighter for integrin subunits α5 and αvβ3 compared to the epiretinal membranes of subjects with macular pucker. miR-92a levels were decreased in FVM subjects. In conclusion, our studies demonstrate that miR-92a decrease is associated with an increase in integrins α5 and αvβ3, thus contributing to the inflammatory milieu in PDR.
Comparison of oxygen supplementation in very preterm infants: Variations of oxygen saturation features and their application to hypoxemic episode based risk stratification
Authors: Ramanand Pravitha , Indic Premananda , Travers Colm P. , Ambalavanan Namasivayam
Published: February 2023

Background

Oxygen supplementation is commonly used to maintain oxygen saturation (SpO2) levels in preterm infants within target ranges to reduce intermittent hypoxemic (IH) events, which are associated with short- and long-term morbidities. There is not much information available about differences in oxygenation patterns in infants undergoing such supplementations nor their relation to observed IH events. This study aimed to describe oxygenation characteristics during two types of supplementation by studying SpO2 signal features and assess their performance in hypoxemia risk screening during NICU monitoring.

Subjects and methods

SpO2 data from 25 infants with gestational age <32 weeks and birthweight <2,000 g who underwent a cross over trial of low-flow nasal cannula (NC) and digitally-set servo-controlled oxygen environment (OE) supplementations was considered in this secondary analysis. Features pertaining to signal distribution, variability and complexity were estimated and analyzed for differences between the supplementations. Univariate and regularized multivariate logistic regression was applied to identify relevant features and develop screening models for infants likely to experience a critically high number of IH per day of observation. Their performance was assessed using area under receiver operating curves (AUROC), accuracy, sensitivity, specificity and F1 scores.

Results

While most SpO2 measures remained comparable during both supplementations, signal irregularity and complexity were elevated while on OE, pointing to more volatility in oxygen saturation during this supplementation mode. In addition, SpO2 variability measures exhibited early prognostic value in discriminating infants at higher risk of critically many IH events. Poincare plot variability at lag 1 had AUROC of 0.82, 0.86, 0.89 compared to 0.63, 0.75, 0.81 for the IH number, a clinical parameter at observation times of 30 min, 1 and 2 h, respectively. Multivariate models with two features exhibited validation AUROC > 0.80, F1 score > 0.60 and specificity >0.85 at observation times ≥ 1 h. Finally, we proposed a framework for risk stratification of infants using a cumulative risk score for continuous monitoring.

Conclusion

Analysis of oxygen saturation signal routinely collected in the NICU, may have extensive applications in inferring subtle changes to cardiorespiratory dynamics under various conditions as well as in informing clinical decisions about infant care.
Vestibular anomalies and dysfunctions in children with inner ear malformations: A narrative review
Authors: Brotto Davide , Ariano Marzia , Sozzi Mosè , Cenedese Roberta , Muraro Eva , Sorrentino Flavia , Trevisi Patrizia
Published: February 2023

About 20% of children with congenital hearing loss present malformations of the inner ear. In the past few years much has been understood about the morphology and function of the anterior part of the labyrinth, since hearing loss may have a dramatic effect on the overall development of a child. Nowadays, for most of them, a chance for hearing rehabilitation is available, making hearing loss a treatable condition. The anomalies range from the lack of development of the whole inner ear to specific anomalies of isolated structures. Despite the frequent concomitant involvement of the posterior part of the labyrinth, this part of the inner ear is frequently neglected while discussing its morphology and dysfunction. Even though vestibular and balance function/dysfunction may have a significant impact on the global development of children, very little is known about these specific disorders in patients with inner ear malformations. The aim of this review is to summarize the available literature about vestibular anomalies and dysfunctions in children with inner ear malformations, discussing what is currently known about the topic.
Therapeutic touch and therapeutic alliance in pediatric care and neonatology: An active inference framework
Authors: McParlin Zoe , Cerritelli Francesco , Manzotti Andrea , Friston Karl J , Esteves Jorge E
Published: February 2023

Therapeutic affective touch has been recognized as essential for survival, nurturing supportive interpersonal interactions, accelerating recovery—including reducing hospitalisations, and promoting overall health and building robust therapeutic alliances. Through the lens of active inference, we present an integrative model, combining therapeutic touch and communication, to achieve biobehavioural synchrony. This model speaks to how the brain develops a generative model required for recovery, developing successful therapeutic alliances, and regulating allostasis within paediatric manual therapy. We apply active inference to explain the neurophysiological and behavioural mechanisms that underwrite the development and maintenance of synchronous relationships through touch. This paper foregrounds the crucial role of therapeutic touch in developing a solid therapeutic alliance, the clinical effectiveness of paediatric care, and triadic synchrony between health care practitioner, caregiver, and infant in a variety of clinical situations. We start by providing a brief overview of the significance and clinical role of touch in the development of social interactions in infants; facilitating a positive therapeutic alliance and restoring homeostasis through touch to allow a more efficient process of allostatic regulation. Moreover, we explain the role of CT tactile afferents in achieving positive clinical outcomes and updating prior beliefs. We then discuss how touch is implemented in treatment sessions to promote cooperative interactions in the clinic and facilitate theory of mind. This underwrites biobehavioural synchrony, epistemic trust, empathy, and the resolution of uncertainty. The ensuing framework is underpinned by a critical application of the active inference framework to the fields of pediatrics and neonatology.
The industrially important genus Kaempferia: An ethnopharmacological review
Authors: Singh Arpit , Singh Nitesh , Singh Sanchita , Srivastava Ravi Prakash , Singh Lav , Verma Praveen C. , Devkota Hari P. , Rahman Laiq ur , Kumar Rajak Bikash , Singh Amrita , Saxena Gauri
Published: February 2023

Kaempferia, a genus of the family Zingiberaceae, is widely distributed with more than 50 species which are mostly found throughout Southeast Asia. These plants have important ethnobotanical significance as many species are used in Ayurvedic and other traditional medicine preparations. This genus has received a lot of scholarly attention recently as a result of the numerous health advantages it possesses. In this review, we have compiled the scientific information regarding the relevance, distribution, industrial applications, phytochemistry, ethnopharmacology, tissue culture and conservation initiative of the Kaempferia genus along with the commercial realities and limitations of the research as well as missing industrial linkages followed by an exploration of some of the likely future promising clinical potential. The current review provides a richer and deeper understanding of Kaempferia, which can be applied in areas like phytopharmacology, molecular research, and industrial biology. The knowledge from this study can be further implemented for the establishment of new conservation strategies.
Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease
Authors: Jiang Zebin , Wu Zemin , Liu Ruixue , Du Qin , Fu Xian , Li Min , Kuang Yongjun , Lin Shen , Wu Jiaxuan , Xie Weiji , Shi Ganggang , Peng Yanqiang , Zheng Fuchun
Published: February 2023

Dyslipidemia due to renal insufficiency is a common complication in patients with chronic kidney diseases (CKD), and a major risk factor for the development of cardiovascular events. Atorvastatin (AT) is mainly used in the treatment of dyslipidemia in patients with CKD. However, response to the atorvastatin varies inter-individually in clinical applications. We examined the association between polymorphisms in genes involved in drug metabolism and transport, and plasma concentrations of atorvastatin and its metabolites (2-hydroxy atorvastatin (2-AT), 2-hydroxy atorvastatin lactone (2-ATL), 4-hydroxy atorvastatin (4-AT), 4-hydroxy atorvastatin lactone (4-ATL), atorvastatin lactone (ATL)) in kidney diseases patients. Genotypes were determined using TaqMan real time PCR in 212 CKD patients, treated with 20 mg of atorvastatin daily for 6 weeks. The steady state plasma concentrations of atorvastatin and its metabolites were quantified using ultraperformance liquid chromatography in combination with triple quadrupole mass spectrometry (UPLC−MS/MS). Univariate and multivariate analyses showed the variant in ABCC4 (rs3742106) was associated with decreased concentrations of AT and its metabolites (2-AT+2-ATL: β = -0.162, p = 0.028 in the dominant model; AT+2-AT+4-AT: β = -0.212, p = 0.028 in the genotype model), while patients carrying the variant allele ABCC4-rs868853 (β = 0.177, p = 0.011) or NR1I2-rs6785049 (β = 0.123, p = 0.044) had higher concentrations of 2-AT+2-ATL in plasma compared with homozygous wildtype carriers. Luciferase activity was enhanced in HepG2 cells harboring a construct expressing the rs3742106-T allele or the rs868853-G allele (p < 0.05 for each) compared with a construct expressing the rs3742106G or the rs868853-A allele. These findings suggest that two functional polymorphisms in the ABCC4 gene may affect transcriptional activity, thereby directly or indirectly affecting release of AT and its metabolites from hepatocytes into the circulation.
Efficacy of herbal medicine treatment based on syndrome differentiation for Parkinson’s disease: A systematic review and meta-analysis of randomized placebo-controlled clinical trials
Authors: Jun Purumea , Zhao HuiYan , Jung In Chul , Kwon Ojin , Han Chang-Hyun , Won Jiyoon , Jang Jung-Hee
Published: February 2023

Background: Parkinson’s disease (PD), the second most common progressive neurodegenerative disease, causes heterogeneous clinical symptoms. Patients experience a range of motor and non-motor symptoms, and personalized diagnosis and treatment are needed. In traditional East Asian medicine, syndrome differentiation (SD) is a diagnostic approach for customized therapy that uses a comprehensive analysis and varies for the same disease. We aimed to evaluate the efficacy of herbal medicine (HM) prescribed according to the SD of PD.

Methods: Ten electronic databases were searched from inception to August 2021 without language limitations. All randomized controlled trials (RCTs) involving HM for SD of PD were included. Assessment of Cochrane's risk of bias and meta-analysis and Grading of Recommendations Assessment, Development, and Evaluation was also performed. Effect measurement was summarized using the mean difference (MD) with 95% confidence interval, through a meta-analysis.

Results: Thirteen RCTs involving 843 participants were included. The overall risk of bias was either low or unclear. Compared with the placebo, a combined therapy of HM and Western medicine (WM) significantly improved the total Unified Parkinson’s Disease Rating Scale (UPDRS) (MD = −8.03, [−10.27, −5.79], p < 0.00001; I2 = 0%) and was more beneficial, as assessed using the UPDRS (I–III), the Parkinson’s Disease Questionnaire-39, and the Non-Motor Symptoms Scale. Adverse events did not differ between the groups.

Conclusion: The findings suggest that the combined treatment of WM and HM based on SD diagnosis has additional benefits in PD treatment. However, the methodological quality of the included RCTs was suboptimal. Nevertheless, this systematic review is the first to investigate the efficacy of HM treatment according to the SD diagnosis in PD. The clinically meaningful improvement in HM according to SD in PD needs to be tested in further studies with rigorous designs and longer follow-up periods.

Systematic Review Registration: [https://inplasy.com/inplasy-2021-10-0020/], identifier [INPLASY2021100020].
Practice of CYP450 genotyping and phenotyping in children in a real-life setting
Authors: Rodieux Frédérique , Daali Youssef , Rollason Victoria , Samer Caroline F. , Ing Lorenzini Kuntheavy
Published: February 2023

Pharmacokinetics varies widely between children. Many factors play an important role in this variability, such as ontogeny, pharmacogenetics, gender, comorbidities, and drug-drug interactions. Significant work has already been done in adults to understand the impact of genetic polymorphisms on drug-metabolizing enzyme activity and drug response. Data remain poor in children due to ontogeny that impacts genotyping-phenotyping correlation and the difficulty enrolling children in prospective studies. Our study aimed to describe the use of cytochromes P450 (CYP) phenotyping and/or genotyping tests in children in a real-life setting and assess the correlation between the genotype and the phenotype. We reviewed the results of tests performed between January 2005 and December 2020. Fifty-two children were genotyped and/or phenotyped. Four patients were excluded from the present analysis as they only underwent ABCB1 genotyping, without CYP testing. Of the remainder, 18 underwent simultaneous CYP genotyping and phenotyping, while 17 underwent CYP genotyping only, and 13 underwent CYP phenotyping only. In all cases, investigations were performed after the following situations: insufficient clinical response to treatment, low plasma concentrations, and adverse drug reactions (ADR). The vast majority of cases were related to immunosuppressive or antipsychotic therapy. Genotyping and/or phenotyping explained or contributed to the aforementioned clinical events in 56% of cases. The correlation between the genotype and the phenotype showed variability depending on the assessed cytochrome. In several cases, the phenotype did not correspond to the genotype because of comedications. In conclusion, there is clearly value in guiding drug based on CYP activity in children.
Amplifying the efficacy of ALA-based prodrugs for photodynamic therapy using nanotechnology
Authors: Lou Liang , Zhou Shizhe , Tan Sijia , Xiang Menghua , Wang Wei , Yuan Chuang , Gao Liqian , Xiao Qicai
Published: February 2023

5-aminolevulinic acid (ALA) is a clinically approved prodrug involved in intracellular Heme biosynthesis to produce the natural photosensitizer (PS) Protoporphyrin IX (PpIX). ALA based photodynamic therapy (PDT) has been used to treat various malignant and non-malignant diseases. However, natural ALA has disadvantages such as weak lipophilicity, low stability and poor bioavailability, greatly reducing its clinical performance. The emerging nanotechnology is expected to address these limitations and thus improve the therapeutic outcomes. Herein, we summarized important recent advances in the design of ALA-based prodrugs using nanotechnology to improve the efficacy of PDT. The potential limitations and future perspectives of ALA-based nanomedicines are also briefly presented and discussed.
SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock
Authors: Bunch Connor M. , Chang Eric , Moore Ernest E. , Moore Hunter B. , Kwaan Hau C. , Miller Joseph B. , Al-Fadhl Mahmoud D. , Thomas Anthony V. , Zackariya Nuha , Patel Shivani S. , Zackariya Sufyan , Haidar Saadeddine , Patel Bhavesh , McCurdy Michael T. , Thomas Scott G. , Zimmer Donald , Fulkerson Daniel , Kim Paul Y. , Walsh Matthew R. , Hake Daniel , Kedar Archana , Aboukhaled Michael , Walsh Mark M.
Published: February 2023

Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function—including fibrinolysis—to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.
GC-MS and UHPLC-QTOFMS-assisted identification of the differential metabolites and metabolic pathways in key tissues of Pogostemon cablin
Authors: Wang Xiaobing , Zhong Liting , Zou Xuan , Gong Lizhen , Zhuang Jiexuan , Zhang Danhua , Zheng Hai , Wang Xiaomin , Wu Daidi , Zhan Ruoting , Chen Likai
Published: February 2023

Pogostemon cablin is an important aromatic medicinal herb widely used in the pharmaceutical and perfume industries. However, our understanding of the phytochemical compounds and metabolites within P. cablin remains limited. To our knowledge, no integrated studies have hitherto been conducted on the metabolites of the aerial parts of P. cablin. In this study, twenty-three volatile compounds from the aerial parts of P. cablin were identified by GC-MS, predominantly sesquiterpenes. Quantitative analysis showed the highest level of patchouli alcohol in leaves (24.89 mg/g), which was 9.12 and 6.69-fold higher than in stems and flowers. UHPLC-QTOFMS was used to analyze the non-volatile compounds of leaf, stem and flower tissues. The differences in metabolites between flower and leaf tissues were the largest. Based on 112, 77 and 83 differential metabolites between flower-leaf, flower-stem and leaf-stem, three tissue-specific biomarkers of metabolites were identified, and the differential metabolites were enriched in several KEGG pathways. Furthermore, labeling differential metabolites in the primary and secondary metabolic pathways showed that flowers accumulated more lipids and amino acids, including proline, lysine and tryptophan; the leaves accumulated higher levels of terpenoids, vitamins and flavonoids, and stems contained higher levels of carbohydrate compounds. Based on the role of acetyl coenzyme A, the distribution and possible exchange mechanism of metabolites in leaves, stems and flowers of P. cablin were mapped for the first time, laying the groundwork for future research on the metabolites in P. cablin and their regulatory role.
The long noncoding RNA LINC15957 regulates anthocyanin accumulation in radish
Authors: Tan Huping , Luo Xiaobo , Lu Jinbiao , Wu Linjun , Li Yadong , Jin Yueyue , Peng Xiao , Xu Xiuhong , Li Jingwei , Zhang Wanping
Published: February 2023

Radish (Raphanus sativus L.) is an important root vegetable crop belonging to the Brassicaceae family. Anthocyanin rich radish varieties are popular among consumers because of their bright color and high nutritional value. However, the underlying molecular mechanism responsible for skin and flesh induce anthocyanin biosynthesis in transient overexpression, gene silencing and transcriptome sequencing were used to verify its function in radish anthocyanin accumulation, radish remains unclear. Here, we identified a long noncoding RNA LINC15957, overexpression of LINC15957 was significantly increased anthocyanin accumulation in radish leaves, and the expression levels of structural genes related to anthocyanin biosynthesis were also significantly increased. Anthocyanin accumulation and expression levels of anthocyanin biosynthesis genes were significantly reduced in silenced LINC15957 flesh when compared with control. By the transcriptome sequencing of the overexpressed LINC15957 plants and the control, 5,772 differentially expressed genes were identified. A total of 3,849 differentially expressed transcription factors were identified, of which MYB, bHLH, WD40, bZIP, ERF, WRKY and MATE were detected and differentially expressed in the overexpressed LINC15957 plants. KEGG enrichment analysis revealed the genes were significant enriched in tyrosine, L-Phenylalanine, tryptophan, phenylpropanol, and flavonoid biosynthesis. RT-qPCR analysis showed that 8 differentially expressed genes (DEGs) were differentially expressed in LINC15957-overexpressed plants. These results suggested that LINC15957 involved in regulate anthocyanin accumulation and provide abundant data to investigate the genes regulate anthocyanin biosynthesis in radish.
Teaching the Turkish language to foreigners at higher education level in Northern Cyprus: An evaluation based on self-perceived dominant intelligence types, twenty-first-century skills and learning technologies
Authors: Karakaş Kurt Esra , Güneyli Ahmet
Published: February 2023

Introduction

There are many foreign students in higher education in Northern Cyprus. Both the academic and life skills of these students depend on attaching the necessary importance to their Turkish language teaching. The goal of this study is to examine how university students employ learning technology, twenty-first-century abilities, and perceived categories of intelligence in the process of learning a foreign language.

Methods

In line with the quantitative research design, this study utilized a descriptive approach. Purposeful and convenience sampling methods were used to create the study sample. As a result, the institution in Northern Cyprus with the largest international student body was chosen. At this university, one of the authors of this study has been employed, and Turkish is the language of teaching. The study sample consisted of 431 university students who took Turkish as a foreign language in the 2021–2022 academic year at the selected university.

Results

The results of the study revealed a weak yet statistically significant correlation between twenty-first-century skills and usage of foreign language-learning technologies. Additionally, students' twenty-first-century skill scores differed significantly, whereas their foreign language-learning technology scale scores did not match their self-perceived intelligence types.

Conclusion

The research's findings indicate that students in higher education possess twenty-first-century skills. Based on this finding, it is possible to engage students in the courses and accomplish effective foreign language acquisition if foreign language education is carried out in accordance with modern methodologies and based on twenty-first-century abilities. It has been revealed in this study that it is important to include social learning rather than individual and competitive learning in foreign language education classes.
Employee equity incentive, executive psychological capital, and enterprise innovation
Authors: Yu Liping , Hu Jiabin
Published: February 2023

The input and deployment of human resources, such as senior executives and the core employees involved in different innovation processes, is key to developing enterprise innovation activities. Under the same framework, it is crucial to explore how employee equity incentive and senior executives’ psychological capital affect enterprise innovation. This paper’s research sample comprises listed companies that implemented equity incentives in the A-share market from 2010 to 2021, examining the relationship between executive psychological capital, and enterprise innovation. This study found that: (1) Employee equity incentive and executives’ psychological capital can significantly improve the quality of innovation output while promoting enterprises to increase the quantity of innovation outputs; (2) Executive psychological capital contributes to the intermediary effect between employee equity incentive and enterprise innovation; (3) R&D investment has a positive moderating effect on employee equity incentive, senior executives’ psychological capital and enterprise innovation; (4) The innovation incentive effect brought by the implementation of stock options by enterprises is more significant, which also makes the psychological capital of executives maintain a positive role in enterprise innovation; (5) In addition, the positive effects of employee equity incentive and executive psychological capital on enterprise innovation are affected by different property rights. The positive effects of employee equity incentive and executive psychological capital on enterprise innovation in state-owned enterprises are not high.
The relationships between teachers’ emotional labor and display rules, trait emotions, exhaustion, and classroom emotional climate
Authors: Ma Pei , Zhang Lichang , Dong Hui , Yu Jian
Published: February 2023

Introduction

Emotions are an integral part of education, and the way teachers manage their emotions is crucial to educational success. This study focuses on teachers’ emotional labor in secondary school classrooms and examined the relationships between emotional labor strategies and display rules, trait emotions, emotional exhaustion, and classroom emotional climate.

Methods

In the study, 496 secondary school teachers (386 female) aged 21–59 years (mean age = 37.61 ± 8.87 years) completed five self-reported questionnaires. Data were analyzed using structural equation model in AMOS.

Results

The results showed that (1) display rules provide positive situations to deep acting and the expression of naturally felt emotions and mediate teachers’ positive emotions and strategies; (2) positive trait emotions increase the expression of naturally felt emotions and negative trait emotions increase surface acting; (3) surface acting results in emotional exhaustion and has an adverse impact on classroom emotional climate; and (4) deep acting and the expression of naturally felt emotions positively affect classroom emotional climate.

Discussion

These findings revealed that deep acting and the expression of naturally felt emotions are positively related to positive emotions and the classroom setting, whereas surface acting plays a negative role in the emotional states of individuals and the classroom. The study gives the centrality of teacher emotions in the teaching and learning process, clarifies some antecedents and consequences related to emotional labor strategies in a classroom setting, and provides some ideas to optimize educational outcomes. The five variables presented in the study are good examples that can contribute to protecting teachers’ wellbeing and improving the psychosociological environment.
Prevalence of smokeless tobacco use in India and its association with various occupations: A LASI study
Authors: Bharati Bhavna , Sahu Kirti Sundar , Pati Sanghamitra
Published: February 2023

Background

More than two-thirds of deaths in developing countries are due to non-communicable diseases, and tobacco is a leading risk factor. There are numerous different socio-demographic factors that impact on the use of smokeless tobacco, of which occupation is one. The objectives of this study are to find out the overall prevalence of smokeless tobacco use (ever and current use), the pattern of association with various occupations and related variables (current and past workers), and the role of childhood adversity on initiation and use.

Methods

This study used data from the Longitudinal Aging Study in India (LASI) wave 1, a nationally representative cross-sectional study collected in 2017–18. Current and previous users of smokeless tobacco are taken into consideration as the target population. For the data analysis, survey-weighted tools have been applied for descriptive statistics and multivariable logistic regression model. The weighted data analysis has been done using R studio with R version 4.

Results and discussion

From the sample size of 65,561, 38% have used either smoking or smokeless tobacco. Among them, 40% use tobacco in smoke form, 51% use smokeless tobacco, and 9% take both. At the population level, 22.8 and 20.4% are previous and current users of smokeless tobacco, respectively. Type of occupation, type of employer, place of work, kind of business, and workload were found to be significantly associated with smokeless tobacco use. A deaddiction and tobacco quitting policy targeting rural male informal workers should be the focus of the Government.
Changes in vital signs, ventilation mode, and catecholamine use during intensive care aeromedical evacuation flights
Authors: Post Janina , Maeckelburg Marc Christoph , Jagel Vitali , Sammito Stefan
Published: February 2023

Introduction

Especially after (natural) disasters, local health systems are also destroyed or their ability to work is massively restricted. The transport of injured patients is therefore often necessary for further care. Numerous nations keep fixed-wing aircraft with intensive-care capabilities available for secondary transport, but little data on the transport is available to date.

Methods

An analysis of all flights with the German Air Force's intensive care fixed-wing-aircraft carried out in the context of humanitarian aid missions since 2002 with a focus on intubated patients was done.

Results

A total of 38 patients were transported. Two patients had to be intubated on or during transport. There were significant changes in the necessary positive end-expiratory pressure (PEEP) and the fraction of inspired oxygen. Circulatory parameters did not change.

Discussion

Overall, there are no clinically relevant deteriorations due to secondary transport with corresponding air transfers. Due to the hypobaric hypoxic conditions on board of all aircrafts, intubation in clinically borderline patients should be performed electively on the ground before flight.
Inter-hemispheric asymmetries in high-latitude electrodynamic forcing and the thermosphere during the October 8–9, 2012, geomagnetic storm: An integrated data–Model investigation
Authors: Hong Yu , Deng Yue , Zhu Qingyu , Maute Astrid , Hairston Marc R. , Waters Colin , Sheng Cheng , Welling Daniel , Lopez Ramon E.
Published: February 2023

Inter-hemispheric asymmetry (IHA) in Earth’s ionosphere–thermosphere (IT) system can be associated with high-latitude forcing that intensifies during storm time, e.g., ion convection, auroral electron precipitation, and energy deposition, but a comprehensive understanding of the pathways that generate IHA in the IT is lacking. Numerical simulations can help address this issue, but accurate specification of high-latitude forcing is needed. In this study, we utilize the Active Magnetosphere and Planetary Electrodynamics Response Experiment-revised fieldaligned currents (FACs) to specify the high-latitude electric potential in the Global Ionosphere and Thermosphere Model (GITM) during the October 8–9, 2012, storm. Our result illustrates the advantages of the FAC-driven technique in capturing high-latitude ion drift, ion convection equatorial boundary, and the storm-time neutral density response observed by satellite. First, it is found that the cross-polar-cap potential, hemispheric power, and ion convection distribution can be highly asymmetric between two hemispheres with a clear By dependence in the convection equatorial boundary. Comparison with simulation based on mirror precipitation suggests that the convection distribution is more sensitive to FAC, while its intensity also depends on the ionospheric conductance-related precipitation. Second, the IHA in the neutral density response closely follows the IHA in the total Joule heating dissipation with a time delay. Stronger Joule heating deposited associated with greater high-latitude electric potential in the southern hemisphere during the focus period generates more neutral density as well, which provides some evidences that the high-latitude forcing could become the dominant factor to IHAs in the thermosphere when near the equinox. Our study improves the understanding of storm-time IHA in high-latitude forcing and the IT system.
Solved and unsolved riddles about low-latitude daytime valley region plasma waves and 150-km echoes
Authors: Chau J. L. , Longley W. J. , Reyes P. M. , Pedatella N. M. , Otsuka Y. , Stolle C. , Liu H. , England S. L. , Vierinen J. P. , Milla M. A. , Hysell D. L. , Oppenheim M. M. , Patra A. , Lehmacher G. , Kudeki E.
Published: February 2023

The Earth’s atmosphere near both the geographic and magnetic equators and at altitudes between 120 and 200 km is called the low-latitude valley region (LLVR) and is among the least understood regions of the ionosphere/thermosphere due to its complex interplay of neutral dynamics, electrodynamics, and photochemistry. Radar studies of the region have revealed puzzling daytime echoes scattered from between 130 and 170 km in altitude. The echoes are quasi-periodic and are observed in solar-zenith-angle dependent layers. Populations with two distinct types of spectral features are observed. A number of radars have shown scattering cross-sections with different seasonal and probing-frequency dependencies. The sources and configurations of the so-called 150-km echoes and the related irregularities have been long-standing riddles for which some solutions are finally starting to emerge as will be described in this review paper. Although the 150-km echoes were discovered in the early 1960s, their practical significance and implications were not broadly recognized until the early 1990s, and no compelling explanations of their generation mechanisms and observed features emerged until about a decade ago. Now, more rapid progress is being made thanks to a multi-disciplinary team effort described here and recent developments in kinetic simulations and theory: 18 of 27 riddles to be described in this paper stand solved (and a few more partially solved) at this point in time. The source of the irregularities is no longer a puzzle as compelling evidence has emerged from simulations and theory, presented since 2016 that they are being caused by photoelectrons driving an upper hybrid plasma instability process. Another resolved riddle concerns the persistent gaps observed between the 150-km scattering layers—we now understand that they are likely to be the result of enhanced thermal Landau damping of the upper hybrid instability process at upper hybrid frequencies matching the harmonics of the electron gyrofrequency. The remaining unsolved riddles, e.g., minute-scale variability, multi-frequency dependence, to name a few, are still being explored observationally and theoretically—they are most likely unidentified consequences of interplay between plasma physics, photochemistry, and lower atmospheric dynamic processes governing the LLVR.
Pathways to greater government accountability for breaches of their obligations in relation to doping in sport: A legal analysis
Authors: Pavot David
Published: February 2023

The State doping scandal in Russia has highlighted a major discrepancy in the fight against doping in sport: on the one hand, the signatories of the Word Anti-Doping Code (federations, NADO's, etc.) are subject to a very strict regime and incur serious sanctions, while on the other hand, States, when they massively violate the rules, do not risk very important consequences in international law. For example, high ranking officials as well as the Russian state apparatus have not been affected with a few exceptions such as the Moscow antidoping laboratory. The aim of this opinion paper is to present a reflection on the different avenues that could be envisaged to make governments more accountable, especially as work is underway on the topic. The development of a true government accountability regime would allow the system to be more balanced.