bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension
Authors: Zuo Yifan , Li Boyang , Gao Minglang , Xiong Rui , He Ruyuan , Li Ning , Geng Qing 
Published: March 2024

AbstractInflammation and immune processes underlie pulmonary hypertension progression. Two main different activated phenotypes of macrophages, classically activated M1 macrophages and alternatively activated M2 macrophages, are both involved in inflammatory processes related to pulmonary hypertension. Recent advances suggest that macrophages coordinate interactions among different proinflammatory and anti-inflammatory mediators, and other cellular components such as smooth muscle cells and fibroblasts. In this review, we summarize the current literature on the role of macrophages in the pathogenesis of pulmonary hypertension, including the origin of pulmonary macrophages and their response to triggers of pulmonary hypertension. We then discuss the interactions among macrophages, cytokines, and vascular adventitial fibroblasts in pulmonary hypertension, as well as the potential therapeutic benefits of macrophages in this disease. Identifying the critical role of macrophages in pulmonary hypertension will contribute to a comprehensive understanding of this pathophysiological abnormality, and may provide new perspectives for pulmonary hypertension management.
A novel quinoline with airway relaxant effects and anti-inflammatory properties
Authors: Bergwik Jesper , Liu Jielu , Padra Médea , Bhongir Ravi K. V. , Tanner Lloyd , Xiang Yujiao , Lundblad Mia , Egesten Arne , Adner Mikael 
Published: March 2024

Abstract
Background
In chronic pulmonary diseases characterized by inflammation and airway obstruction, such as asthma and COPD, there are unmet needs for improved treatment. Quinolines is a group of small heterocyclic compounds that have a broad range of pharmacological properties. Here, we investigated the airway relaxant and anti-inflammatory properties of a novel quinoline (RCD405).

Methods
The airway relaxant effect of RCD405 was examined in isolated airways from humans, dogs, rats and mice. Murine models of ovalbumin (OVA)-induced allergic asthma and LPS-induced airway inflammation were used to study the effects in vivo. RCD405 (10 mg/kg) or, for comparisons in selected studies, budesonide (3 mg/kg), were administered intratracheally 1 h prior to each challenge. Airway responsiveness was determined using methacholine provocation. Immune cell recruitment to bronchi was measured using flow cytometry and histological analyses were applied to investigate cell influx and goblet cell hyperplasia of the airways. Furthermore, production of cytokines and chemokines was measured using a multiplex immunoassay. The expression levels of asthma-related genes in murine lung tissue were determined by PCR. The involvement of NF-κB and metabolic activity was measured in the human monocytic cell line THP-1.

Results
RCD405 demonstrated a relaxant effect on carbachol precontracted airways in all four species investigated (potency ranking: human = rat > dog = mouse). The OVA-specific IgE and airway hyperresponsiveness (AHR) were significantly reduced by intratracheal treatment with RCD405, while no significant changes were observed for budesonide. In addition, administration of RCD405 to mice significantly decreased the expression of proinflammatory cytokines and chemokines as well as recruitment of immune cells to the lungs in both OVA- and LPS-induced airway inflammation, with a similar effect as for budesonide (in the OVA-model). However, the effect on gene expression of Il-4, IL-5 and Il-13 was more pronounced for RCD405 as compared to budesonide. Finally, in vitro, RCD405 reduced the LPS-induced NF-κB activation and by itself reduced cellular metabolism.

Conclusions
RCD405 has airway relaxant effects, and it reduces AHR as well as airway inflammation in the models used, suggesting that it could be a clinically relevant compound to treat inflammatory airway diseases. Possible targets of this compound are complexes of mitochondrial oxidative phosphorylation, resulting in decreased metabolic activity of targeted cells as well as through pathways associated to NF-κB. However, further studies are needed to elucidate the mode of action.
Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention
Authors: Chikata Yuichi , Iwata Hiroshi , Miyosawa Katsutoshi , Naito Ryo , Koike Takuma , Moriya Soshi , Yasuda Hidetoshi , Funamizu Takehiro , Doi Shinichiro , Endo Hirohisa , Wada Hideki , Ogita Manabu , Dohi Tomotaka , Kasai Takatoshi , Isoda Kikuo , Okazaki Shinya , Miyauchi Katsumi , Minamino Tohru 
Published: March 2024

Abstract
Background
Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI.

Methods
This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α.

Results
Unadjusted Kaplan–Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28–5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12–5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively).

Conclusion
The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI.
Trial registration: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan—Clinical Trials Registry, UMIN-CTR 000035587).
Risk analysis of the association between different hemoglobin glycation index and poor prognosis in critical patients with coronary heart disease-A study based on the MIMIC-IV database
Authors: Wei Xing , Chen Xinghua , Zhang Zhipeng , Wei Jing , Hu Ben , Long Nv , Feng Jun , Luo Chunmiao 
Published: March 2024

Abstract
Background
The hemoglobin glycation index (HGI) is the difference between the observed and predicted values of glycosylated hemoglobin (HbA1c), which is closely associated with a variety of poor prognoses. However, there are still no studies on the correlation between HGI and poor prognosis in patients with critical coronary artery disease. The purpose of this study was to analyze the correlation between HGI and all-cause mortality in patients with critical coronary artery disease using the MIMIC-IV database.

Methods
The HGI was calculated by constructing a linear regression equation between HbA1c and fasting plasma glucose (FPG). A Kaplan‒Meier survival analysis model was constructed based on the HGI quartiles to clarify the differences in all-cause mortality rates between groups, and the log-rank test was used to assess the differences between groups. The hazard ratio (HR) of HGI as a risk factor for outcome events was assessed using the Cox proportional risk model and restricted cubic spline (RCS), with the Q2 group serving as the reference group.

Results
A total of 5260 patients were included in this study. The 30-day mortality rate of the patients was 4.94% and the mortality rate within 365 days was 13.12%. A low HGI was significantly associated with 30-day mortality (HR, 1.96; 95% CI, (1.38, 2.78); P < 0.001) and 365-day mortality (HR, 1.48; 95% CI, (1.19, 1.85); P < 0.001) in patients with critical coronary artery disease in the completely adjusted Cox proportional risk model. In addition, high levels of HGI were associated with 365-day mortality (HR, 1.31; 95% CI, (1.02, 1.69); P < 0.05). RCS analysis revealed a U-shaped relationship between HGI and outcome events. According to the stratified analysis, the interaction test revealed that the correlation between HGI and outcome events remained stable.

Conclusion
There was a significant correlation between HGI and all-cause mortality in patients with critical coronary artery disease, particularly in those with low HGI. HGI can be used as a potential indicator for assessing the short- and long-term risk of mortality in such patients.
Classification of vasovagal syncope from physiological signals on tilt table testing
Authors: Ferdowsi Mahbuba , Kwan Ban-Hoe , Tan Maw Pin , Saedon Nor’ Izzati , Subramaniam Sukanya , Abu Hashim Noor Fatin Izzati , Mohd Nasir Siti Sakinah , Zainal Abidin Imran , Chee Kok Han , Goh Choon-Hian 
Published: March 2024

Abstract
Background
The diagnostic test for vasovagal syncope (VVS), the most common cause of syncope is head-up tilt test (HUTT) assessment. During the test, subjects experienced clinical symptoms such as nausea, sweating, pallor, the feeling of palpitations, being on the verge of passing out, and fainting. The study's goal is to develop an algorithm to classify VVS patients based on physiological signals blood pressure (BP) and electrocardiography (ECG) obtained from the HUTT.

Methods
After 10 min of supine rest, the subject was tilted at a 70-degree angle on a tilt table for approximately a total of 35 min. 400 µg of glyceryl trinitrate (GTN) was administered sublingually after the first 20 min and monitoring continued for another 15 min. Mean imputation and K-nearest neighbors (KNN) imputation approaches to handle missing values. Next, feature selection techniques were implemented, including genetic algorithm, recursive feature elimination, and feature importance, to determine the crucial features. The Mann–Whitney U test was then performed to determine the statistical difference between two groups. Patients with VVS are categorized via machine learning models including Support Vector Machine (SVM), Gaussian Naïve Bayes (GNB), Multinomial Naïve Bayes (MNB), KNN, Logistic Regression (LR), and Random Forest (RF). The developed model is interpreted using an explainable artificial intelligence (XAI) model known as partial dependence plot.

Results
A total of 137 subjects aged between 9 and 93 years were recruited for this study, 54 experienced clinical symptoms were considered positive tests, while the remaining 83 tested negative. Optimal results were obtained by combining the KNN imputation technique and three tilting features with SVM with 90.5% accuracy, 87.0% sensitivity, 92.7% specificity, 88.6% precision, 87.8% F1 score, and 95.4% ROC (receiver operating characteristics) AUC (area under curve).

Conclusions
The proposed algorithm effectively classifies VVS patients with over 90% accuracy. However, the study was confined to a small sample size. More clinical datasets are required to ensure that our approach is generalizable.
An isothermal CRISPR- based lateral flow assay for detection of Neisseria meningitidis
Authors: Huyen Dao Thi , Reboud Julien , Quyen Dao Thanh , Cooper Jonathan M. , Velavan Thirumalaisamy P. , Trung Ngo Tat , Song Le Huu 
Published: March 2024

Abstract
Background
Neisseria meningitidis can cause life-threatening meningococcal meningitis and meningococcemia. Old standard microbiological results from CSF/blood cultures are time consuming. This study aimed to combine the sensitivity of loop-mediated isothermal nucleic acid amplification (LAMP) with the specificity of CRISPR/Cas12a cleavage to demonstrate a reliable diagnostic assay for rapid detection of N. meningitidis.

Methods
A total of n = 139 samples were collected from patients with suspected meningococcal disease and were used for evaluation. The extracted DNA was subjected to qualitative real-time PCR, targeting capsular transporter gene (ctrA) of N. meningitidis. LAMP-specific primer pairs, also targeting the ctrA, were designed and the LAMP products were subjected to CRISPR/Cas12 cleavage reaction. the readout was on a lateral flow strip. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of LAMP-CRISPR/Cas was compared with real-time PCR assays. The limit of detection (LOD) was established with serial dilutions of the target N. meningitidis DNA and calculated by Probit regression analysis.

Results
Six LAMP assay-specific primers were developed targeting the ctrA gene of N. meningitidis, which is conserved in all meningococcal serogroups. The LAMP primers did not amplify DNA from other bacterial DNA tested, showing 100% specificity. The use of 0.4 M betaine increased the sensitivity and stability of the reaction. LAMP-CRISPR/Cas detected meningococcal serogroups (B, C, W). The assay showed no cross-reactivity and was specific for N. meningitidis. The LOD was 74 (95% CI: 47–311) N. meningitidis copies. The LAMP-CRISPR/Cas performed well compared to the gold standard. In the 139 samples from suspected patients, the sensitivity and specificity of the test were 91% and 99% respectively.

Conclusion
This developed and optimized method can complement for the available gold standard for the timely diagnosis of meningococcal meningitis and meningococcemia.
Enhancing the efficacy of nano-curcumin on cancer cells through mixture design optimization of three emulsifiers
Authors: Sayyar Zahra , Jafarizadeh-Malmiri Hoda 
Published: March 2024

AbstractCurcumin, a vital bioactive compound found naturally, has diverse biological applications. However, a major limitation of curcumin is its low bioavailability caused by its limited solubility in water. Hence, it is possible to overcome this problem through preparing oil in water nanodispersion of curcumin that emulsifier can play key role to produce nanodispersion. In the present study, the effect of three emulsifiers of Tween 80, Arabic Gum and Polyethylene glycol on preparing nanodispersions with desirable properties was investigated using subcritical water method and a mixture design. Zeta-potential and particle size of the achieved nanodispersions were taken into account as outcome factors. The optimum values for emulsifiers of Tween 80, Arabic Gum and Polyethylene glycol were obtained as 0.588 g, 0.639 g and 0.273 g, respectively, using the suggested model, so that obtained nanodispersion had minimum particle size (101.89 nm) and maximum zeta-potential (−24.99 mV). In fact, 102.5 nm and − 24.7 mV were obtained from experimental data at these values of emulsifiers. In addition, maximum loading potential (0.199 g/L), efficiency (99.5%), and minimum total curcumin loss (0.5%) were acquired at these optimum values. The results also show that the nanodispersion had a powerful antioxidant activity (65.27%) with extra antibacterial activity in facing with both E. coli and S. aureus strains. Moreover, curcumin nanodispersion was significantly taken up by HT-29 cells and resulted in the production of oxidative stress in the cells, leading to a decrease in the growth of cancer cells.
QSAR analysis of VEGFR-2 inhibitors based on machine learning, Topomer CoMFA and molecule docking
Authors: Ding Hao , Xing Fei , Zou Lin , Zhao Liang 
Published: March 2024

AbstractVEGFR-2 kinase inhibitors are clinically approved drugs that can effectively target cancer angiogenesis. However, such inhibitors have adverse effects such as skin toxicity, gastrointestinal reactions and hepatic impairment. In this study, machine learning and Topomer CoMFA, which is an alignment-dependent, descriptor-based method, were employed to build structural activity relationship models of potentially new VEGFR-2 inhibitors. The prediction ac-curacy of the training and test sets of the 2D-SAR model were 82.4 and 80.1%, respectively, with KNN. Topomer CoMFA approach was then used for 3D-QSAR modeling of VEGFR-2 inhibitors. The coefficient of q2 for cross-validation of the model 1 was greater than 0.5, suggesting that a stable drug activity-prediction model was obtained. Molecular docking was further performed to simulate the interactions between the five most promising compounds and VEGFR-2 target protein and the Total Scores were all greater than 6, indicating that they had a strong hydrogen bond interactions were present. This study successfully used machine learning to obtain five potentially novel VEGFR-2 inhibitors to increase our arsenal of drugs to combat cancer.
Complex effects of testosterone level on ectoparasite load in a ground squirrel: an experimental test for the immunocompetence handicap hypothesis
Authors: Wang Li-Qing , Liu Zhi-Tao , Wang Jian-Jun , Fang Yu-Han , Zhu Hao , Shi Ke , Zhang Fu-Shun , Shuai Ling-Ying 
Published: March 2024

Abstract
Background
The immunocompetence handicap hypothesis suggests that males with a higher testosterone level should be better at developing male secondary traits, but at a cost of suppressed immune performance. As a result, we should expect that males with an increased testosterone level also possess a higher parasite load. However, previous empirical studies aimed to test this prediction have generated mixed results. Meanwhile, the effect of testosterone level on parasite load in female hosts remains poorly known.

Methods
In this study, we tested this prediction by manipulating testosterone level in Daurian ground squirrels (Spermophilus dauricus), a medium-sized rodent widely distributed in northeast Asia. S. dauricus is an important host of ticks and fleas and often viewed as a considerable reservoir of plague. Live-trapped S. dauricus were injected with either tea oil (control group) or testosterone (treatment group) and then released. A total of 10 days later, the rodents were recaptured and checked for ectoparasites. Fecal samples were also collected to measure testosterone level of each individual.

Results
We found that testosterone manipulation and sex of hosts interacted to affect tick load. At the end of the experiment, male squirrels subjected to testosterone implantation had an averagely higher tick load than males from the control group. However, this pattern was not found in females. Moreover, testosterone manipulation did not significantly affect flea load in S. dauricus.

Conclusions
Our results only lent limited support for the immunocompetence handicap hypothesis, suggesting that the role of testosterone on regulating parasite load is relatively complex, and may largely depend on parasite type and gender of hosts.

Graphical Abstract
Conventional herniorrhaphy followed by laparoscopic appendectomy for a variant of Amyand’s hernia: a case report
Authors: Chang Yau-Ren , Wu Yu-Tung , Hsieh Chi-Hsun 
Published: March 2024

Abstract
Background
Amyand’s hernia (AH) is an appendix (with or without acute inflammation) trapped within an inguinal hernia. Most AH with acute appendicitis had a preexisting appendix within the hernia sac. We herein report a variant of AH that has never been described before. An inflamed appendix that was managed conservatively was found to have migrated and trapped in the sac of a previously unrecognized right inguinal hernia 6 weeks after the index admission, resulting in a secondary Amyand’s hernia.

Case presentation
A 25-year-old healthy Taiwanese woman had persistent right lower abdominal pain for 1 week and was diagnosed with perforated appendicitis with a localized abscess by abdominal computed tomography (CT). No inguinal hernia was noted at that time. Although the inflamed appendix along with the abscess was deeply surrounded by bowel loops so that percutaneous drainage was not feasible, it was treated successfully with antibiotics. However, she was rehospitalized 6 weeks later for having a painful right inguinal bulging mass for a week. Abdominal CT revealed an inflamed appendix with abscess formation in an indirect inguinal hernia raising the question of a Amyand’s hernia with a perforated appendicitis. Via a typical inguinal herniorrhaphy incision, surgical exploration confirmed the diagnosis, and it was managed by opening the hernial sac to drain the abscess and reducing the appendix into the peritoneal cavity, followed by conventional tissue-based herniorrhaphy and a laparoscopic appendectomy. She was then discharged uneventfully and remained well for 11 months.

Conclusions
Unlike the traditional definition of Amyand’s hernia, where the appendix is initially in the hernia sac, the current case demonstrated that Amyand’s hernia could be a type of delayed presentation following initial medical treatment of acute appendicitis. However, it can still be managed successfully by a conventional tissue-based herniorrhaphy followed by laparoscopic appendectomy.