bluuebunny/crossref_metadata_2025 huggingface dataset:
Epileptic seizure prediction based on EEG using pseudo-three-dimensional CNN
Authors: Liu Xin , Li Chunyang , Lou Xicheng , Kong Haohuan , Li Xinwei , Li Zhangyong , Zhong Lisha
Published: March 2024

Epileptic seizures are characterized by their sudden and unpredictable nature, posing significant risks to a patient’s daily life. Accurate and reliable seizure prediction systems can provide alerts before a seizure occurs, as well as give the patient and caregivers provider enough time to take appropriate measure. This study presents an effective seizure prediction method based on deep learning that combine with handcrafted features. The handcrafted features were selected by Max-Relevance and Min-Redundancy (mRMR) to obtain the optimal set of features. To extract the epileptic features from the fused multidimensional structure, we designed a P3D-BiConvLstm3D model, which is a combination of pseudo-3D convolutional neural network (P3DCNN) and bidirectional convolutional long short-term memory 3D (BiConvLstm3D). We also converted EEG signals into a multidimensional structure that fused spatial, manual features, and temporal information. The multidimensional structure is then fed into a P3DCNN to extract spatial and manual features and feature-to-feature dependencies, followed by a BiConvLstm3D input to explore temporal dependencies while preserving the spatial features, and finally, a channel attention mechanism is implemented to emphasize the more representative information in the multichannel output. The proposed has an average accuracy of 98.13%, an average sensitivity of 98.03%, an average precision of 98.30% and an average specificity of 98.23% for the CHB-MIT scalp EEG database. A comparison of the proposed model with other baseline methods was done to confirm the better performance of features through time–space nonlinear feature fusion. The results show that the proposed P3DCNN-BiConvLstm3D-Attention3D method for epilepsy prediction by time–space nonlinear feature fusion is effective.
Self-esteem mediates the relationship between the parahippocampal gyrus and decisional procrastination at resting state
Authors: Ling Weili , Yang Fan , Huang Taicheng , Li Xueting
Published: March 2024

When faced with a conflict or dilemma, we tend to postpone or even avoid making a decision. This phenomenon is known as decisional procrastination. Here, we investigated the neural correlates of this phenomenon, in particular the parahippocampal gyrus (PHG) that has previously been identified in procrastination studies. In this study, we applied an individual difference approach to evaluate participants’ spontaneous neural activity in the PHG and their decisional procrastination levels, assessed outside the fMRI scanner. We discovered that the fractional amplitude of low-frequency fluctuations (fALFF) in the caudal PHG (cPHG) could predict participants’ level of decisional procrastination, as measured by the avoidant decision-making style. Importantly, participants’ self-esteem mediated the relationship between the cPHG and decisional procrastination, suggesting that individuals with higher levels of spontaneous activity in the cPHG are likely to have higher levels of self-esteem and thus be more likely to make decisions on time. In short, our study broadens the PHG’s known role in procrastination by demonstrating its link with decisional procrastination and the mediating influence of self-esteem, underscoring the need for further exploration of this mediation mechanism.
The correlation between iodine and metabolism: a review
Authors: Zhang Le , Shang Fangjian , Liu Cong , Zhai Xiaodan
Published: March 2024

Iodine is involved in the synthesis of thyroid hormones and plays a crucial role in human life. Both iodine deficiency and excess are common issues in certain populations. Iodine also has extrathyroidal effects on organs that can uptake it independently of thyroid hormones. Recently, multiple clinical studies have shown a connection between iodine intake and metabolic disorders, such as metabolic syndrome, obesity, diabetes, hypertension, and dyslipidemia. However, the results of these studies have been inconsistent, and the mechanisms behind these associations are still not well understood. Therefore, in this review, we aim to examine the recent research progress regarding the relationship between iodine and metabolic disorders, along with the relevant mechanisms.
The association between diverse serum folate with MAFLD and liver fibrosis based on NHANES 2017–2020
Authors: Cai Jiacheng , Chen Dahua , Luo Wenjing , Xu Feng , Feng Xiaofeng , Zhang Liangshun , Liu Huiwei , Shen Jianwei , Ye Hua
Published: March 2024

Background

Metabolically Associated Fatty Liver Disease (MAFLD) marks a progression from the previous paradigm of Non-Alcoholic Fatty Liver Disease (NAFLD), presenting a redefined diagnostic framework that accentuates metabolic factors while recognizing non-alcoholic contributors. In our investigation, our principal aim was to scrutinize the conceivable correlation between diverse serum folate levels and the prevalence of MAFLD and liver fibrosis.

Methods

In our investigation, we conducted an extensive analysis utilizing data derived from the National Health and Nutrition Examination Survey (NHANES) across the years 2017–2020. We aimed to investigate the association between different serum folate concentrations and the prevalence of MAFLD and liver fibrosis by comprehensive multivariate analysis. This analytical approach considered various variables, encompassing sociodemographic characteristics, lifestyle factors, hypertension, and diabetes. By including these potential confounders in our analysis, we aimed to ensure the stability of the findings regarding the association between different serum folate concentrations and the development of MAFLD and liver fibrosis.

Results

In our investigation, we utilized multiple linear regression models to thoroughly analyze the data, revealing noteworthy insights. Evidently, elevated levels of both total folate and 5-MTHF exhibited a distinct negative correlation with CAP, while 5-MTHF demonstrated a notable negative correlation with LSM. Furthermore, multiple logistic regression models were employed for an in-depth examination of the data. As the concentrations of total folate and 5-MTHF in the serum increased, a substantial decrease in the likelihood of MAFLD and liver fibrosis occurrence was observed.

Conclusion

The findings of this investigation robustly suggest the prevalence of MAFLD and liver fibrosis decreased significantly with the increase of serum concentrations of total folate and 5-MTHF.
Parental knowledge and attitude of postoperative paediatric pain: stepwise linear regression analysis
Authors: Desalegn Mitiku , Shitemaw Tewoderos , Getahun Genanew Kassie , Lemma Lire
Published: March 2024

Background

Despite the fact that mothers care for their children's pain in most cases, it has been noted that mothers have limited knowledge and attitude about paediatric pain. This study aims to assess parental knowledge and attitude of postoperative paediatric pain (POPP).

Method

This is institutional based cross sectional study conducted with 102 parents at Nigist Eleni Mohamed Memorial Comprehensive Specialized Hospital (NEMMCSH). A convenience sampling technique was used to select parents. This study has used a questionnaire (Parental Pain Expression Perception (PPEM), examine parents' attitudes and knowledge about how their children exhibit their pain and Medication Attitude Questioner (MAQs), focuses on how parents feel about giving their child analgesic medication to alleviate post-operative pain). Descriptive statistics were utilized to analyse the parent's response and presented with frequency and percentage. Factor analysis to analyze factor structure and stepwise linear regression analysis to examine the impact of socio-demographic factors in predicting parental knowledge and attitude about POPP were done. The statistical tests were performed at 95% confidence interval and 5% significance level.

Result

A total of 102 parents fulfilling the inclusion criteria were included. About 78% of parents agreed that children always express pain by crying or whining. The majority of parents (75.6%) believe children who are playing are not in pain. Regarding parental attitudes about pain medications, majority of parents (61%) believe that children should be given pain medication as little as possible because of its side effects. According to about 26.8% of parents, giving children pain medication for pain might teach them to use drugs for other issues. On the other hand, 63.4% of parents say that giving children pain medication as little as possible is the most effective way to manage their pain. Parents of younger children and parents from rural area are more likely to score higher in attention seeking sub-score of PPEP while parents from urban residence and those parents who are employed are more likely to perceive about the side effects of pain medications (Side effects factors).

Conclusion

The overall knowledge and attitude of parents about postoperative pain and pain medications were poor.
Sex differences in normal fetal regional brain apparent diffusion coefficient changes assessed by in utero DWI
Authors: Ren Jing-Ya , Zhu Ming , Dong Su-Zhen
Published: March 2024

Objective

There are differences in the vulnerability of male and female fetal brains to adverse intrauterine exposure, preterm birth, and associated perinatal brain injury. The main objective of this study was to identify any statistically significant difference in the change of apparent diffusion coefficient (ADC) in the intracranial regions of male and female fetuses in the second and third trimesters.

Methods

Diffusion-weighted imaging (DWI) was performed in 200 fetuses between 20 and 37 gestational ages (GA) with normal results or suspicious results on sonography followed by structural MRI. Pairwise ADC values of the regions of interest (ROIs) were manually delineated on either side of the cerebral white matter: frontal white matter (FWM), parietal white matter (PWM), occipital white matter (OWM), temporal white matter (TWM), basal ganglia (BG), thalamus (THA), cerebellar hemisphere (CBM), and a single measurement in the pons. The changes in these values were studied over the gestational range, along with potential sex differences and asymmetries of the cerebral hemispheres.

Results

During the third trimester, ADC values in OWM, TWM, and CBM were significantly higher in male fetuses than those in female fetuses (p < 0.05). After the correction of false-discovery rates (FDR), the difference in CBM was the only statistically significant (p = 0.0032). However, the decreased rate of ADC values in male fetuses in CWM (except for FWM), BG, THA, CBM, and pons was higher than that in female fetuses during the second and third trimesters.

Conclusions

We have shown some differences in the intracranial regional ADC changes between male and female fetuses using in utero DWI during the second and third trimesters.
Whole-transcriptome profiling and identification of cold tolerance-related ceRNA networks in japonica rice varieties
Authors: Wang Hao , Jia Yan , Bai Xu , Wang Jin , Liu Ge , Wang Haixing , Wu Yulong , Xin Junying , Ma Huimiao , Liu Zhenyu , Zou Detang , Zhao Hongwei
Published: March 2024

Introduction

Low-temperature stress negatively impacts rice yield, posing a significant risk to food security. While previous studies have explored the physiological and linear gene expression alterations in rice under low-temperature conditions, the changes in competing endogenous RNA (ceRNA) networks remain largely unexamined.

Methods

We conducted RNA sequencing on two japonica rice varieties with differing cold-tolerance capabilities to establish ceRNA networks. This enabled us to investigate the transcriptional regulatory network and molecular mechanisms that rice employs in response to low-temperature stress.

Results

We identified 364 differentially expressed circular RNAs (circRNAs), 224 differentially expressed microRNAs (miRNAs), and 12,183 differentially expressed messenger RNAs (mRNAs). WRKY family was the most prominent transcription factor family involved in cold tolerance. Based on the expression patterns and targeted relationships of these differentially expressed RNAs, we discerned five potential ceRNA networks related to low-temperature stress in rice: osa-miR166j-5p from the miR166 family was associated with cold tolerance; osa-miR528-3p and osa-miR156j-3p were linked to stress response; and osa-miR156j-3p was involved in the antioxidant system. In addition, Os03g0152000 in the antioxidant system, as well as Os12g0491800 and Os05g0381400, correlated with the corresponding stress response and circRNAs in the network. A gene sequence difference analysis and phenotypic validation of Os11g0685700 (OsWRKY61) within the WRKY family suggested its potential role in regulating cold tolerance in rice.

Discussion and conclusion

We identified Os11g0685700 (OsWRKY61) as a promising candidate gene for enhancing cold tolerance in japonica rice. The candidate miRNAs, mRNAs, and circRNAs uncovered in this study are valuable targets for researchers and breeders. Our findings will facilitate the development of cold-tolerant rice varieties from multiple angles and provide critical directions for future research into the functions of cold-tolerance-related miRNAs, mRNAs, and circRNAs in rice.
Calcium signaling facilitates chilling- and GA- induced dormancy release in tree peony
Authors: Gai Weiling , Liu Chunying , Yang Mengjie , Li Feng , Xin Hua , Gai Shupeng
Published: March 2024

Calcium plays a crucial role in plant growth and development, yet little is known about its function in endodormancy regulation. Tree peony (Paeonia suffruticosa), characterized by compound buds and large flowers, is well-known for its ornamental and medicinal value. To break bud dormancy release is a prerequisite of flowering and forcing culture, particularly during the Spring Festival. In this study, the Ca2+ chelator EGTA and Ca2+ channel blocker LaCl3 were applied, resulting in a significant delay in budburst during both chilling- and gibberellin (GA)- induced dormancy release in a dosage-dependent manner. As expected, the retardation of bud break was recovered by the supplementation of 30 mM CaCl2, indicating a facilitating role of calcium in dormancy release. Accordingly, several calcium-sensor-encoding genes including Calmodulin (CaM) and Ca2+-dependent protein kinases (CDPKs) were significantly up-regulated by prolonged chilling and exogenous GAs. Ultrastructure observations revealed a decline in starch grains and the reopening of transport corridors following prolonged chilling. Calcium deposits were abundant in the cell walls and intercellular spaces at the early dormant stage but were enriched in the cytosol and nucleus before dormancy release. Additionally, several genes associated with dormancy release, including EBB1, EBB3, SVP, GA20ox, RGL1, BG6, and BG9, were differentially expressed after calcium blocking and recovery treatments, indicating that calcium might partially modulate dormancy release through GA and ABA pathways. Our findings provide novel insights into the mechanism of dormancy release and offer potential benefits for improving and perfecting forcing culture technology in tree peonies.
Urban professionals’ restorative tourism: exploring the role of perceived environmental restorativeness, push and pull motivations and destination attributes on tourism expectations
Authors: Ding Xianyao , Xu Jiajun
Published: March 2024

Introduction

Urban professionals often seek respite from their daily routines through restorative tourism, driven by a complex interplay of motivations that include both internal “push” factors and external “pull” factors. This study investigates the intricate relationship between the perceived environmental restorativeness of tourist destinations and the expectations of urban professionals engaging in restorative tourism. Furthermore, it examines how push and pull motivations mediate this relationship while also considering the moderating effect of destination attributes.

Methods

The multiple regression analyses on the survey data collected from 221 urban professionals with restorative tourism experiences provided quantitative evidence regarding the hypothesized relationships among perceived environmental restorativeness, push and pull motivations, destination attributes, and tourism expectations.

Results

The results showed that perceived environmental restorativeness has a positive effect on urban professionals’ tourism expectations; urban professionals’ pull motivation and push motivation each play a mediating role between perceived environmental restorativeness and tourist expectations; and restorative tourism destination attributes have a moderating effect between perceived environmental restorativeness and push motivation, as well as the relationship between perceived environmental restorativeness and pull motivation.

Discussion

This study provides essential theoretical contributions to restorative tourism and practical implications when designing restorative tourism destinations that target urban professionals.
How work stress influence turnover intention among Chinese local undergraduate university teachers: the mediating effect of job burnout and the moderating effect of self-efficacy
Authors: Pei Shuimei , Wang Shichao , Jiang Ruixuan , Guo Jianpeng , Ni Jianchao
Published: March 2024

Background

Turnover intention is one of the common disturbances that affect the career development and management of university teachers. With an aim to solve this thorny issue, the study examined the associations between turnover intention and work stress among local undergraduate university teachers in China.

Methods

A questionnaire survey was carried out on 7,565 local university teachers. Initially, confirmatory factor analysis was employed to validate the reliability and validity of the scale. Subsequently, descriptive statistics and correlation analyses were conducted. Following this, a latent moderated structural equation (LMS) was used to explore the relationship among work stress, job burnout, self-efficacy, and turnover intention. Moreover, the bias-corrected Bootstrap method was applied to further examine the mediating effects, moderating effects, and moderated mediating effects in the model.

Results

The hypothesized moderated mediation model was verified significant. Work stress directly and positively predicted job burnout and turnover intention, with job burnout serving a partial mediating role between work stress and turnover intention. Additionally, self-efficacy negatively moderated the direct impact of work stress on job burnout, as well as the mediating effect of job burnout. As the self-efficacy of university teachers increased, the direct effect of work stress on job burnout and the mediating effect of job burnout decreased.

Conclusion

This study expanded the research on the antecedent variables of university teachers’ turnover intention and revealed the individual contingency mechanism by which work stress affected turnover intention: the negative moderating effect of self-efficacy. Work stress induced university teachers’ turnover intention, and this phenomenon was more obvious for faculties with low self-efficacy. Administrators of local undergraduate universities need to rationalize the allocation of teachers’ job responsibilities and pay attention to the negative consequences of work stress in order to reduce turnover intentions. Particular attention should be paid to enhance teachers’ self-efficacy. The findings of this study can provide in-depth recommendations for university faculty management and policy making, which can help shape a working atmosphere more conducive to teaching and research, thus enhancing the overall quality and competitiveness of faculty members within universities.
Trends in pediatric firearm-related injuries and disparities in acute outcomes
Authors: Mulugeta Makda G. , Bailey Gabrielle , Parsons Kendall , Gillespie Scott , Johnson Laura M. , Doh Kiesha Fraser , Reisner Andrew , Blackwell Laura S.
Published: March 2024

Background

Firearm-related injuries (FRI) are an increasing cause of death and injury in children. The etiology for this rise is multifactorial and includes socioeconomic factors. Despite its prevalence and documented increase over COVID-19, there is a paucity of research on disparities and the influence of social determinants of health (SDH) in pediatric FRI. This study aims to explore the epidemiology of this vulnerable population in Atlanta, trends over time and relevant dates such as COVID-19 and a state firearm law, and disparities in clinical outcomes.

Methods

Retrospective cohort of patients with FRI (0–20 years-old, x̄=9.8, Median = 11) presenting to our hospital EDs from January 2014 to April 2023 (N = 701) and eligible for the Trauma Registry. This period includes two major events, namely the COVID-19 pandemic (March 2020), and passage of state law Constitutional Carry Act (SB 319) (April 2022), allowing for permit-less concealed firearm carry. Single series interrupted time series (ITS) models were run and clinical outcome differences between race and insurance groups were calculated unadjusted and adjusted for confounders using inverse propensity treatment weights (IPTW). The primary outcome was mortality; secondary are admission and discharge.

Results

Majority of FRI involved patients who were male (76.7%), Black (74.9%), publicly insured (82.6%), ≤12 years-old (61.8%), and injured by unintentional shootings (45.6%) or assault (43.7%). During COVID-19, there was a sustained increase in FRI rate by 0.42 patients per 1,000 trauma visits per month (95% CI 0.02–0.82, p = 0.042); post-SB 319 it was 2.3 patients per 1,000 trauma visits per month (95% CI 0.23–4.31, p = 0.029). Publicly insured patients had 58% lower odds of mortality than privately insured patients (OR 0.42, 95% CI 0.18–0.99, p = 0.047). When controlled for race and mechanism of injury, among other confounding factors, this association was not significant (p = 0.652).

Conclusion

Pediatric FRI are increasing over time, with disproportionate burdens on Black patients, at our hospitals. Disparities in mortality based on insurance necessitate further study. As social and economic repercussions of COVID-19 are still present, and state firearm law SB 319 is still in effect, assessment of ongoing trends is warranted to inform preventative strategies.
Heritage and hesitancy: how preference for traditional Chinese medicine influences vaccine attitudes
Authors: Lan Yaxin , Jin Lei
Published: March 2024

Introduction

Vaccine hesitancy, amplified by the COVID-19 pandemic, is a pressing public health challenge. This study investigates the association between Traditional Chinese Medicine (TCM) preference and COVID-19 vaccine hesitancy within China.

Methods

The study uses data from the 2021 Chinese General Social Survey (CGSS) (N = 2,690). Logistic regressions and Karlson-Holm-Breen (KHB) method are employed to analyzed the relationship between TCM preference and vaccine hesitancy.

Results

The study reaffirms prior findings by revealing a robust and stable association between TCM preference and vaccine hesitancy, which remains unaffected by socioeconomic and demographic confounders, as well as institutional trust dynamics of healthcare system. Contrary to expectations, TCM enthusiasts do not exhibit vaccine hesitancy based on divergent epistemological views concerning vaccine risks and immunity acquisition compared to biomedicine.

Discussion

This research enriches understandings of the intricate relations between healthcare paradigms and vaccine attitudes, inviting further inquiry into the role of CAM in shaping vaccination behaviors across different cultures and contexts. The insights bear significant public health implications for enhancing vaccine acceptance and coverage, particularly among populations where CAM practices wield substantial influence.
Decoupling the role of verbal and non-verbal audience behavior on public speaking anxiety in virtual reality using behavioral and psychological measures
Authors: Girondini Matteo , Frigione Ivana , Marra Mariapia , Stefanova Milena , Pillan Margherita , Maravita Angelo , Gallace Alberto
Published: March 2024

Public speaking is a communication ability that is expressed in social contexts. Public speaking anxiety consists of the fear of giving a speech or a presentation and the perception of being badly judged by others. Such feelings can impair the performance and physiological activation of the presenter. In this study, eighty participants, most naive in Virtual Reality experience, underwent one of four virtual reality public speaking scenarios. Four different conditions were tested in a between-group design, where the audience could express positive or negative non-verbal behavior (in terms of body gesture and facial expression), together with positive or adverse questions raised during a question-and-answer session (Q&A). The primary outcomes concerned the virtual audience behavior’s effect on perceived anxiety and physiological arousal. In general, perceived anxiety seemed to be unaffected neither by the verbal nor non-verbal behavior of the audience. Nevertheless, experimental manipulation showed a higher susceptibility to public speaking anxiety in those participants who scored higher on the Social Interaction Anxiety Scale (SIAS) than those with lower Social Interaction Anxiety Scale scores. Specifically, in the case where the verbal attitude was negative, high SIAS trait participants reported a higher level of anxiety. Participants’ physiological arousal was also affected by the proposed scenarios. Participants dealing with an approving audience and encouraging Q&A reported increased skin conductance response. The lack of correlation between reported anxiety and skin conductance response might suggest a physiological engagement in an interactive exchange with the virtual audience rather than a form of discomfort during the task.
Local food system and household responses to external shocks: the case of sustainable coffee farmers and their cooperatives in Western Honduras during COVID-19
Authors: Rodriguez-Camayo Fernando , Lundy Mark , Borgemeister Christian , Ramirez-Villegas Julian , Beuchelt Tina
Published: March 2024

Introduction

The COVID-19 pandemic lockdowns (people confined to home, with movement restrictions) presented an external shock to livelihoods and food systems worldwide, most severely affecting vulnerable households in low-income countries. While evidence is available regarding how COVID-19 generally affected low-income countries, the specific dynamics of local food-system responses and sustainably-certified coffee farm households has not been examined, despite them being usually deemed to be more resilient to shocks. This research examines how local food systems in Honduras changed during lockdowns, how certified coffee households coped with the shock, especially food insecurity, and the potential role of coffee cooperatives in increasing households’ resilience under future shocks and stressors.

Methods

We applied a mixed-methods approach that combined a structured household survey with semi-structured qualitative interviews with 91 households, 6 cooperative representatives, and 18 food-system representatives.

Results

We found that coffee-income-dependent households experienced greater food insecurity during lockdown than coffee households with diversified incomes. Before lockdown the local food system was highly dependent on external fresh food from outside the state. Food suppliers changed altered fresh-food procurement strategies, mostly to maintain fresh-food availability at the beginning of the pandemic. However, more than half the interviewed households lacked confidence regarding food security, amid rising food prices and local shortages. Certified coffee cooperatives supported their members by providing food assistance, cash transfers, and credit.

Discussion

Some of these strategies are difficult to maintain where crises are recurrent and that may render households more vulnerable to future extreme events. Rather, coffee cooperatives could diversify and support their members in growing and marketing additional food crops. This could be a key approach for boosting local food security and strengthening the local food system.
Application of extracorporeal membrane oxygenation in the remote transport of a patient with a ruptured sinus of Valsalva aneurysm: a case report
Authors: Liao Xiaozu , Zhong Shi , Huang Weizhao , Li Binfei
Published: March 2024

Background

A ruptured sinus of Valsalva aneurysm can lead to rapid heart failure and sudden cardiac death. Management of patients who develop severe heart failure and need to be transferred to a specialized hospital for surgical treatment can be challenging. In patients with severe shock due to a ruptured sinus of Valsalva aneurysm into the right atrium, extracorporeal membrane oxygenation (ECMO) transport is an effective means to ensure patient safety, but increases the right cardiac load. We report the experience of veno-arterial (VA) ECMO transport in the treatment of acute cardiogenic shock caused by rupture of a congenital sinus of Valsalva aneurysm.

Case presentation

We describe the case of an 18-year-old male who began having acute episodes of chest pain, shortness of breath, palpitations, and dizziness 18 h before presenting to the emergency department. An echocardiogram revealed an acute ruptured sinus of Valsalva aneurysm and a shunt to the right atrium. The patient presented with severe shock. VA-ECMO was administered to ensure safe transport to the cardiac center. The outcome of emergency surgical repair was good. The patient was on ECMO for 8 h. He returned to the general ward after 7 days and was successfully discharged after 40 days. He had good exercise tolerance 2 years after surgery and no evidence of heart failure.

Conclusion

Although ECMO transport can increase right cardiac load, it is an effective and safe method to move patients with severe shock caused by a ruptured sinus of Valsalva aneurysm into the right atrium. Methods to decrease right cardiac load, such as decreasing ECMO flow combined with cardiotonic drugs, should be adopted. Successful treatment involves rapid establishment of cardiopulmonary bypass and urgent repair of the ruptured sinus of Valsalva aneurysm.
The MoLfa1 Protein Regulates Fungal Development and Septin Ring Formation in Magnaporthe oryzae
Authors: Wu Jia-Qi , Zhu Xue-Ming , Bao Jian-Dong , Wang Jiao-Yu , Yu Xiao-Ping , Lin Fu-Cheng , Li Lin
Published: March 2024

Septins play a key regulatory role in cell division, cytokinesis, and cell polar growth of the rice blast fungus (Magnaporthe oryzae). We found that the organization of the septin ring, which is essential for appressorium-mediated infection in M. oryzae, requires long-chain fatty acids (LCFAs), which act as mediators of septin organization at membrane interfaces. However, it is unclear how septin ring formation and LCFAs regulate the pathogenicity of the rice blast fungus. In this study, a novel protein was named MoLfa1 because of its role in LCFAs utilization. MoLfa1 affects the utilization of LCFAs, lipid metabolism, and the formation of the septin ring by binding with phosphatidylinositol phosphates (PIPs), thereby participating in the construction of penetration pegs of M. oryzae. In addition, MoLfa1 is localized in the endoplasmic reticulum (ER) and interacts with the ER-related protein MoMip11 to affect the phosphorylation level of Mps1. (Mps1 is the core protein in the MPS1-MAPK pathway.) In conclusion, MoLfa1 affects conidia morphology, appressorium formation, lipid metabolism, LCFAs utilization, septin ring formation, and the Mps1-MAPK pathway of M. oryzae, influencing pathogenicity.
Local Production of Acute Phase Proteins: A Defense Reaction of Cancer Cells to Injury with Focus on Fibrinogen
Authors: Hamar Péter
Published: March 2024

This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys. In both models, production of FN chains was predominant among the locally produced acute phase proteins. The production and extracellular release of FN into the tumor microenvironment is a known method of self-defense in tumor cells. We propose that the lAPR is a new, novel cellular defense mechanism like the heat shock response (HSR). In this review, we demonstrate a potential synergism between FN inhibition and mEHT in cancer treatment, suggesting that the effectiveness of mEHT and chemotherapy can be enhanced by inhibiting the HSR and/or the lAPR. Non-anticoagulant inhibition of FN offers potential new therapeutic options for cancer treatment.
Atlas of Tumor and Tumor Microenvironment Cells of Lymphovascular Space Invasion (LVSI) in High-Grade Serous Endometrial Adenocarcinoma: A Case Study
Authors: Sulaiman Raed , Dale Adam , Lin Xiaoqian , Aske Jennifer C. , Gaster Kris , Starks David , Espaillat Luis Rojas , De Pradip , Dey Nandini
Published: March 2024

Lymphovascular invasion (LVSI) is defined as the presence of tumor cells within a definite endothelial-lined space (lymphatics or blood vessels) in the organ surrounding invasive carcinoma. The presence of LVI is associated with an increased risk of lymph nodes and distant metastases. Lymphovascular invasion is described as cancer within blood or lymph vessels and is an independent risk factor for metastasis, recurrence, and mortality. This study aims to present the marker-based immunohistological characterization of cells around LVSI in a high-grade adenocarcinoma of the endometrium to build a cellular atlas of cells of LVSI. A cellular characterization of the cells around lymphovascular space invasion in a 67-year-old female patient with invasive high-grade serous endometrial adenocarcinomas is presented. Resected tumor tissue from a consented patient with invasive high-grade serous endometrial adenocarcinoma was obtained within an hour of surgery. The expressions of the epithelial markers (CK8, 18, and EpCAM), LCA (leukocyte common antigen) marker (CD45), proliferation marker (Ki67), apoptosis markers (cleaved PARP and cleaved caspase3), immune cell markers (CD3, CD4, CD8, CD56, CD68, CD163, FoxP3, PD-1, PD-L1), pro-inflammatory marker (IL-12-RB2), and fibroblast/mesenchyme markers (S100A7, SMA, and TE-7) of the resected tissue on the IHC stains were evaluated and scored by a pathologist. Acknowledging the deterministic role of LVSI in a high-grade adenocarcinoma of the endometrium, our study presents the first marker-based immunohistological atlas of the tumor and TME compartments in the context of epithelial cell markers, proliferation markers, apoptosis markers, macrophage markers, and fibroblast markers. Our study demonstrates that an aggressive disease like a high-grade adenocarcinoma of the endometrium inflicts the pro-metastatic event of LVSI by involving the immune landscape of both tumor and TME. This study demonstrates, for the first time, that the tumor cells within LVSI are positive for IL-12R-B2 and S100A4.
Calcium Induces the Cleavage of NopA and Regulates the Expression of Nodulation Genes and Secretion of T3SS Effectors in Sinorhizobium fredii NGR234
Authors: Kim Wonseok , Acosta-Jurado Sebastián , Kim Sunhyung , Krishnan Hari B.
Published: March 2024

The type III secretion system (T3SS) is a key factor for the symbiosis between rhizobia and legumes. In this study, we investigated the effect of calcium on the expression and secretion of T3SS effectors (T3Es) in Sinorhizobium fredii NGR234, a broad host range rhizobial strain. We performed RNA-Seq analysis of NGR234 grown in the presence of apigenin, calcium, and apigenin plus calcium and compared it with NGR234 grown in the absence of calcium and apigenin. Calcium treatment resulted in a differential expression of 65 genes, most of which are involved in the transport or metabolism of amino acids and carbohydrates. Calcium had a pronounced effect on the transcription of a gene (NGR_b22780) that encodes a putative transmembrane protein, exhibiting a 17-fold change when compared to NGR234 cells grown in the absence of calcium. Calcium upregulated the expression of several sugar transporters, permeases, aminotransferases, and oxidoreductases. Interestingly, calcium downregulated the expression of nodABC, genes that are required for the synthesis of nod factors. A gene encoding a putative outer membrane protein (OmpW) implicated in antibiotic resistance and membrane integrity was also repressed by calcium. We also observed that calcium reduced the production of nodulation outer proteins (T3Es), especially NopA, the main subunit of the T3SS pilus. Additionally, calcium mediated the cleavage of NopA into two smaller isoforms, which might affect the secretion of other T3Es and the symbiotic establishment. Our findings suggest that calcium regulates the T3SS at a post-transcriptional level and provides new insights into the role of calcium in rhizobia–legume interactions.
Integrative Kinase Activity Profiling and Phosphoproteomics of rd10 Mouse Retina during cGMP-Dependent Retinal Degeneration
Authors: Roy Akanksha , Zhou Jiaming , Nolet Merijn , Welinder Charlotte , Zhu Yu , Paquet-Durand François , Groten John , Tomar Tushar , Ekström Per
Published: March 2024

Inherited retinal degenerative diseases (IRDs) are a group of rare diseases that lead to a progressive loss of photoreceptor cells and, ultimately, blindness. The overactivation of cGMP-dependent protein kinase G (PKG), one of the key effectors of cGMP-signaling, was previously found to be involved in photoreceptor cell death and was studied in murine IRD models to elucidate the pathophysiology of retinal degeneration. However, PKG is a serine/threonine kinase (STK) with several hundred potential phosphorylation targets and, so far, little is known about the specificity of the target interaction and downstream effects of PKG activation. Here, we carried out both the kinome activity and phosphoproteomic profiling of organotypic retinal explant cultures derived from the rd10 mouse model for IRD. After treating the explants with the PKG inhibitor CN03, an overall decrease in peptide phosphorylation was observed, with the most significant decrease occurring in seven peptides, including those from the known PKG substrate cyclic-AMP-response-element-binding CREB, but also Ca2+/calmodulin-dependent kinase (CaMK) peptides and TOP2A. The phosphoproteomic data, in turn, revealed proteins with decreased phosphorylation, as well as proteins with increased phosphorylation. The integration of both datasets identified common biological networks altered by PKG inhibition, which included kinases predominantly from the so-called AGC and CaMK families of kinases (e.g., PKG1, PKG2, PKA, CaMKs, RSKs, and AKTs). A pathway analysis confirmed the role of CREB, Calmodulin, mitogen-activated protein kinase (MAPK) and CREB modulation. Among the peptides and pathways that showed reduced phosphorylation activity, the substrates CREB, CaMK2, and CaMK4 were validated for their retinal localization and activity, using immunostaining and immunoblotting in the rd10 retina. In summary, the integrative analysis of the kinome activity and phosphoproteomic data revealed both known and novel PKG substrates in a murine IRD model. This data establishes a basis for an improved understanding of the biological pathways involved in cGMP-mediated photoreceptor degeneration. Moreover, validated PKG targets like CREB and CaMKs merit exploration as novel (surrogate) biomarkers to determine the effects of a clinical PKG-targeted treatment for IRDs.
Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes
Authors: Fernández-Coto Diana Lashidua , Gil Jeovanis , Ayala Guadalupe , Encarnación-Guevara Sergio
Published: March 2024

Glioblastoma, a type of cancer affecting the central nervous system, is characterized by its poor prognosis and the dynamic alteration of its metabolic phenotype to fuel development and progression. Critical to cellular metabolism, mitochondria play a pivotal role, where the acetylation of lysine residues on mitochondrial enzymes emerges as a crucial regulatory mechanism of protein function. This post-translational modification, which negatively impacts the mitochondrial proteome’s functionality, is modulated by the enzyme sirtuin 3 (SIRT3). Aiming to elucidate the regulatory role of SIRT3 in mitochondrial metabolism within glioblastoma, we employed high-resolution mass spectrometry to analyze the proteome and acetylome of two glioblastoma cell lines, each exhibiting distinct metabolic behaviors, following the chemical inhibition of SIRT3. Our findings reveal that the protein synthesis machinery, regulated by lysine acetylation, significantly influences the metabolic phenotype of these cells. Moreover, we have shed light on potential novel SIRT3 targets, thereby unveiling new avenues for future investigations. This research highlights the critical function of SIRT3 in mitochondrial metabolism and its broader implications for cellular energetics. It also provides a comparative analysis of the proteome and acetylome across glioblastoma cell lines with opposing metabolic phenotypes.
Effective Targeting of Melanoma Cells by Combination of Mcl-1 and Bcl-2/Bcl-xL/Bcl-w Inhibitors
Authors: Peng Zhe , Gillissen Bernhard , Richter Antje , Sinnberg Tobias , Schlaak Max S. , Eberle Jürgen
Published: March 2024

Recent advances in melanoma therapy have significantly improved the prognosis of metastasized melanoma. However, large therapeutic gaps remain that need to be closed by new strategies. Antiapoptotic Bcl-2 proteins critically contribute to apoptosis deficiency and therapy resistance. They can be targeted by BH3 mimetics, small molecule antagonists that mimic the Bcl-2 homology domain 3 (BH3) of proapoptotic BH3-only proteins. By applying in vitro experiments, we aimed to obtain an overview of the possible suitability of BH3 mimetics for future melanoma therapy. Thus, we investigated the effects of ABT-737 and ABT-263, which target Bcl-2, Bcl-xL and Bcl-w as well as the Bcl-2-selective ABT-199 and the Mcl-1-selective S63845, in a panel of four BRAF-mutated and BRAF-WT melanoma cell lines. None of the inhibitors showed significant effectiveness when used alone; however, combination of S63845 with each one of the three ABTs almost completely abolished melanoma cell survival and induced apoptosis in up to 50–90% of the cells. Special emphasis was placed here on the understanding of the downstream pathways involved, which may allow improved applications of these strategies. Thus, cell death induction was correlated with caspase activation, loss of mitochondrial membrane potential, phosphorylation of histone H2AX, and ROS production. Caspase dependency was demonstrated by a caspase inhibitor, which blocked all effects. Upregulation of Mcl-1, induced by S63845 itself, as reported previously, was blocked by the combinations. Indeed, Mcl-1, as well as XIAP (X-linked inhibitor of apoptosis), were strongly downregulated by combination treatments. These findings demonstrate that melanoma cells can be efficiently targeted by BH3 mimetics, but the right combinations have to be selected. The observed pronounced activation of apoptosis pathways demonstrates the decisive role of apoptosis in the loss of cell viability by BH3 mimetics.
Efficient Assessment of Tumor Vascular Shutdown by Photodynamic Therapy on Orthotopic Pancreatic Cancer Using High-Speed Wide-Field Waterproof Galvanometer Scanner Photoacoustic Microscopy
Authors: Lee Jaeyul , Han Sangyeob , Thapa Magar Til Bahadur , Gurung Pallavi , Lee Junsoo , Seong Daewoon , Park Sungjo , Kim Yong-Wan , Jeon Mansik , Kim Jeehyun
Published: March 2024

To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm2 area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities.
Simultaneous Determination of One-Carbon Folate Metabolites and One-Carbon-Related Amino Acids in Biological Samples Using a UHPLC–MS/MS Method
Authors: Ling Yi , Tan Mei , Wang Xiaoyun , Meng Ziyi , Quan Xiaodong , Ramaswamy Hosahalli , Wang Chao
Published: March 2024

One-carbon folate metabolites and one-carbon-related amino acids play an important role in human physiology, and their detection in biological samples is essential. However, poor stability as well as low concentrations and occurrence in different species in various biological samples make their quantification very challenging. The aim of this study was to develop a simple, fast, and sensitive ultra-high-performance liquid chromatography MS/MS (UHPLC–MS/MS) method for the simultaneous quantification of various one-carbon folate metabolites (folic acid (FA), tetrahydrofolic acid (THF), p-aminobenzoyl-L-glutamic acid (pABG), 5-formyltetrahydrofolic acid (5-CHOTHF), 5-methyltetrahydrofolic acid (5-CH3THF), 10-formylfolic acid (10-CHOFA), 5,10-methenyl-5,6,7,8-tetrahydrofolic acid (5,10-CH+-THF), and 4-α-hydroxy-5-methyltetrahydrofolate (hmTHF)) and one-carbon-related amino acids (homocysteine (Hcy), methionine (Met), S-ade-L-homocysteine (SAH), and S-ade-L-methionine (SAM)). The method was standardized and validated by determining the selectivity, carryover, limits of detection, limits of quantitation, linearity, precision, accuracy, recovery, and matrix effects. The extraction methods were optimized with respect to several factors: protease–amylase treatment on embryos, deconjugation time, methanol precipitation, and proteins’ isoelectric point precipitation on the folate recovery. Ten one-carbon folate metabolites and four one-carbon-related amino acids were detected using the UHPLC–MS/MS technique in various biological samples. The measured values of folate in human plasma, serum, and whole blood (WB) lay within the concentration range for normal donors. The contents of each analyte in mouse plasma were as follows: pABG (864.0 nmol/L), 5-CH3THF (202.2 nmol/L), hmTHF (122.2 nmol/L), Met (8.63 μmol/L), and SAH (0.06 μmol/L). The concentration of each analyte in mouse embryos were as follows: SAM (1.09 μg/g), SAH (0.13 μg/g), Met (16.5 μg/g), 5,10-CH+THF (74.3 ng/g), pABG (20.6 ng/g), and 5-CH3THF (185.4 ng/g). A simple and rapid sample preparation and UHPLC–MS/MS method was developed and validated for the simultaneous determination of the one-carbon-related folate metabolites and one-carbon-related amino acids in different biological samples.