bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of cerebral collateral circulation in acute ischemic stroke due to large vessel occlusion
Authors: Sperti Martina , Arba Francesco , Acerbi Amedeo , Busto Giorgio , Fainardi Enrico , Sarti Cristina
Published: May 2023

Introduction

Cerebral collateral circulation has a central role in ischemic stroke pathophysiology, and it is considered to correlate with infarct size, the success of reperfusion therapies, and clinical outcomes. Our aim was to study the factors influencing the development of collaterals in patients with acute ischemic stroke eligible for endovascular treatment.

Materials and methods

We enrolled patients with acute ischemic stroke and large vessel occlusion of anterior circulation potentially eligible for endovascular treatment. Included patients performed multiphase CT angiography to assess collaterals that were graded by the Menon Grading Score. We investigated the associations between clinical factors and collaterals and tested independent associations with logistic (good vs. poor collaterals) and ordinal (collateral grade grouped, Menon 0–2, 3, 4–5) regression analysis adjusting for age, sex, stroke severity, and onset to CT time (OCTT).

Results

We included 520 patients, the mean age was 75 (±13.6) years, 215 (41%) were men, and the median (IQR) NIHSS was 17 (11–22). Good collaterals were present in 323 (62%) patients and were associated with lower NIHSS (median 16 vs. 18; p < 0.001) and left hemisphere involvement (60% vs. 45%; p < 0.001), whereas previous stroke/TIA was more frequent in patients with poor collaterals (17 vs. 26%; p = 0.014). These results were confirmed in both logistic and ordinal regression analyses where good collaterals were associated with lower NIHSS (OR = 0.94; 95% CI = 0.91–0.96; cOR = 0.95; 95% CI = 0.92–0.97, respectively) and left hemisphere stroke (OR = 2.24; 95% CI = 1.52–3.28; cOR = 2.11; 95% CI = 1.46–3.05, respectively), while previous stroke/TIA was associated with poor collaterals (OR = 0.57; 95% CI = 0.36–0.90; cOR = 0.61; 95% CI = 0.40–0.94, respectively). Vascular risk factors, demographics, and pre-stroke treatments did not influence the collateral score.

Discussion

The results of our study suggest that risk factors and demographics do not influence the development of collateral circles, except for a negative relation with previous ischemic events. We confirm an already reported observation of a possible protective effect of collaterals on tissue damage assuming NIHSS as its surrogate. The association between left hemispheric stroke and better collaterals deserves to be further explored. Further efforts are needed to identify the factors that favor the development of collaterals.
Structural and functional improvement of amygdala sub-regions in postpartum depression after acupuncture
Authors: Huang Xingxian , Zhuo Yuanyuan , Wang Xinru , Xu Jinping , Yang Zhuoxin , Zhou Yumei , Lv Hanqing , Ma Xiaoming , Yan Bin , Zhao Hong , Yu Haibo
Published: May 2023

Objective

This study aimed to analyze the changes in structure and function in amygdala sub-regions in patients with postpartum depression (PPD) before and after acupuncture.

Methods

A total of 52 patients with PPD (All-PPD group) were included in this trial, 22 of which completed 8 weeks of acupuncture treatment (Acu-PPD group). An age-matched control group of 24 healthy postpartum women (HPW) from the hospital and community were also included. Results from the 17-Hamilton Depression Scale (17-HAMD) and the Edinburgh Postnatal Depression Scale (EPDS) were evaluated, and resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed at baseline and after the acupuncture treatment. Sub-regions of the amygdala were used as seed regions to measure gray matter volume (GMV) and analyzed for resting-state functional connectivity (RSFC) values separately. Finally, correlation analyses were performed on all patients with PPD to evaluate association values between the clinical scale scores, GMV, and RSFC values, while controlling for age and education. Pearson's correlation analyses were conducted to investigate the relevance between GMV and RSFC values of brain regions that differed before and after acupuncture treatment and clinical scale scores in Acu-PPD patients.

Results

The HAMD scores for Acu-PPD were reduced after acupuncture treatment (P < 0.05), suggesting the positive effects of acupuncture on depression symptoms. Structurally, the All-PPD group showed significantly decreased GMV in the left lateral part of the amygdala (lAMG.L) and the right lateral part of the amygdala (lAMG.R) compared to the HPW group (P < 0.05). In addition, the GMV of lAMG.R was marginally increased in the Acu-PPD group after acupuncture (P < 0.05). Functionally, the Acu-PPD group showed a significantly enhanced RSFC between the left medial part of the amygdala (mAMG.L) and the left vermis_6, an increased RSFC between the right medial part of the amygdala (mAMG.R) and left vermis_6, and an increased RSFC between the lAMG.R and left cerebelum_crus1 (P < 0.05). Moreover, correlation studies revealed that the GMV in the lAMG.R was significantly related to the EPDS scores in the All-PPD group (P < 0.05).

Conclusion

Our findings demonstrated that the structure of amygdala sub-regions is impaired in patients with PPD. Acupuncture may improve depressive symptoms in patients with PPD, and the mechanism may be attributed to changes in the amygdala sub-region structure and the functional connections of brain areas linked to the processing of negative emotions. The fMRI-based technique can provide comprehensive neuroimaging evidence to visualize the central mechanism of action of acupuncture in PPD.
Decreased FGF19 and FGF21: possible underlying common pathogenic mechanism of metabolic and cognitive dysregulation in depression
Authors: Tang Mimi , Cheng Shuqiao , Wang Lu , Tang Hui , Liu Ting , Zhao Tingyu , Dang Ruili
Published: May 2023

Background

Accumulating studies suggested that major depressive disorder (MDD) was closely related to metabolic syndrome (MetS). Important endogenous regulators fibroblast growth factors (FGFs) 19 and 21 were also reported to participate in psychiatric disorders. This study aimed to investigate the role of FGF19 and FGF21 in MDD and to explore the possible pathogenic mechanism of metabolic and cognitive dysregulation in depression.

Methods

A total of 59 MDD patients and 55 healthy control participants were recruited. The serum levels of FGF19 and FGF21 and lipid profiles were measured by means of enzymatic methods. Cognitive function was measured by repeatable battery for the assessment of neuropsychological status (RBANS) scores. The gene expression of PGC-1α and FNDC5 was determined by quantitative polymerase chain reaction (PCR).

Results

We found that plasma FGF19 and FGF21 levels were significantly decreased in patients with MDD. Meanwhile, triglyceride (TG) was significantly elevated and PGC-1α was significantly downregulated in MDD patients. Correlation analyses showed negative associations between TG and FGF19 levels. As for cognitive performance, both FGF19 and FGF21 levels were positively correlated with immediate memory. However, FGF19 levels were negatively correlated with language, and FGF21 levels were also negatively correlated with attention and delayed memory. Additionally, negative associations were found between FGF19 levels and PGC-1α. FGF21 levels were positively associated with PGC-1α and negatively associated with FNDC5.

Conclusion

This study elucidated the role of FGF19 and FGF21 in MDD. MDD patients were confirmed to have metabolic and cognitive dysregulation, and this abnormality was linked to the decreased concentrations of FGF19 and FGF21 through the PGC-1α/FNDC5 pathway. Our results showed that the alterations of FGF19 and FGF21 levels may be a common pathogenic mechanism of metabolic and cognitive disturbances in patients with MDD.
Vestibular prosthesis: from basic research to clinics
Authors: Soto Enrique , Pliego Adriana , Vega Rosario
Published: May 2023

Balance disorders are highly prevalent worldwide, causing substantial disability with high personal and socioeconomic impact. The prognosis in many of these patients is poor, and rehabilitation programs provide little help in many cases. This medical problem can be addressed using microelectronics by combining the highly successful cochlear implant experience to produce a vestibular prosthesis, using the technical advances in micro gyroscopes and micro accelerometers, which are the electronic equivalents of the semicircular canals (SCC) and the otolithic organs. Reaching this technological milestone fostered the possibility of using these electronic devices to substitute the vestibular function, mainly for visual stability and posture, in case of damage to the vestibular endorgans. The development of implantable and non-implantable devices showed diverse outcomes when considering the integrity of the vestibular pathways, the device parameters (current intensity, impedance, and waveform), and the targeted physiological function (balance and gaze). In this review, we will examine the development and testing of various prototypes of the vestibular implant (VI). The insight raised by examining the state-of-the-art vestibular prosthesis will facilitate the development of new device-development strategies and discuss the feasibility of complex combinations of implantable devices for disorders that directly affect balance and motor performance.
Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization study
Authors: Gou Zhaoyang , Li Fan , Qiao Fengzhen , Maimaititusvn Gulinuer , Liu Fang
Published: May 2023

Background

Insulin-like growth factor 1 (IGF-1) plays a vital role in the attainment and maintenance of bone mass throughout life and is closely related to the stature of children. 25-Hydroxyvitamin D (25-OHD) is an intermediate of vitamin D (Vit D) metabolism and a key indicator of Vit D nutritional status. Multiple studies have revealed that IGF-1 levels undergo a non-significant increase after Vit D supplementation. Here, we analyzed the causal and reverse causal relationships between 25-OHD and IGF-1 levels using Mendelian randomization (MR).

Methods

Two-sample MR was used to estimate an unconfounded bidirectional causal relationship between the level of IGF-1 and those of Vit D and 25-OHD. Single nucleotide polymorphisms (SNPs) were filtered from genome-wide association studies (GWAS) after a comprehensive search of the Integrative Epidemiology Unit GWAS database. Several MR methods were employed, including inverse-variance weighted (IVW) method, and a sensitivity analysis was undertaken to detect whether pleiotropy or heterogeneity biased the MR results.

Results

Genetically predicted IGF-1 was found to have a causal association with Vit D and serum 25-OHD levels, where Vit D and serum 25-OHD levels increased with increasing IGF-1 concentrations (Vit D: IVW β:0.021, 95% CI: 0.005–0.036, p = 7.74 × 10–3; 25-OHD: IVW β: 0.041, 95% CI: 0.026–0.057, p = 2.50 × 10–7). A reverse causal effect was also found, indicating Vit D and serum 25-OHD have a positive causal relationship with IGF-1 (Vit D: IVW β:0.182, 95% CI: 0.061–0.305, p = 3.25 × 10–3; 25-OHD: IVW β: 0.057, 95% CI = 0.017–0.096, p = 4.73 × 10–3). The sensitivity analysis showed that horizontal pleiotropy was unlikely to bias the causality in this study (MR-Egger: Vit D intercept p = 5.1 × 10–5, 25-OHD intercept p = 6.4 × 10–4 in forward analysis; Vit D intercept p = 6.6 × 10–4, 25-OHD intercept p = 1.9 × 10–3 in reverse analysis), and a leave-one-out analysis did not identify evidence of bias in the results.

Conclusion

The results of the MR analysis provide evidence that IGF-1 has positive causal and reverse causal relationships with Vit D and serum 25-OHD, respectively, in European populations. Our findings also provide guidance for the prevention and treatment of short stature and other related diseases.
A process mining approach for clinical guidelines compliance: real-world application in rectal cancer
Authors: Savino Mariachiara , Chiloiro Giuditta , Masciocchi Carlotta , Capocchiano Nikola Dino , Lenkowicz Jacopo , Gottardelli Benedetta , Gambacorta Maria Antonietta , Valentini Vincenzo , Damiani Andrea
Published: May 2023

In the era of evidence-based medicine, several clinical guidelines were developed, supporting cancer management from diagnosis to treatment and aiming to optimize patient care and hospital resources. Nevertheless, individual patient characteristics and organizational factors may lead to deviations from these standard recommendations during clinical practice. In this context, process mining in healthcare constitutes a valid tool to evaluate conformance of real treatment pathways, extracted from hospital data warehouses as event log, to standard clinical guidelines, translated into computer-interpretable formats. In this study we translate the European Society of Medical Oncology guidelines for rectal cancer treatment into a computer-interpretable format using Pseudo-Workflow formalism (PWF), a language already employed in pMineR software library for Process Mining in Healthcare. We investigate the adherence of a real-world cohort of rectal cancer patients treated at Fondazione Policlinico Universitario A. Gemelli IRCCS, data associated with cancer diagnosis and treatment are extracted from hospital databases in 453 patients diagnosed with rectal cancer. PWF enables the easy implementation of guidelines in a computer-interpretable format and visualizations that can improve understandability and interpretability of physicians. Results of the conformance checking analysis on our cohort identify a subgroup of patients receiving a long course treatment that deviates from guidelines due to a moderate increase in radiotherapy dose and an addition of oxaliplatin during chemotherapy treatment. This study demonstrates the importance of PWF to evaluate clinical guidelines adherence and to identify reasons of deviations during a treatment process in a real-world and multidisciplinary setting.
Prognostic impact of the loss of E-cadherin and de novo expression of N-cadherin at the invasive front of primary and recurrent oral squamous cell carcinoma
Authors: Hakim Samer George , Taubitz Clara , Hoppe Steffen , Steller Daniel , Rades Dirk , Ribbat-Idel Julika , Alsharif Ubai , Falougy Mohamed
Published: May 2023

The epithelial-mesenchymal transition (EMT) is a biological mechanism in multiple pathophysiological diseases. Related alterations in cadherin expression play a crucial role in carcinogenesis, progression, angiogenesis, and immune response. EMT cells exhibit a transition from an epithelial to a mesenchymal phenotype (cadherin-switch). This process is characterized by the de novo development of N-cadherin (N-CAD), which replaces E-cadherin (E-CAD) and signifies an increased migratory capacity and malignant transformation. The cadherin switch is a hallmark of EMT and has been studied in various cancer entities. We predicted that the cadherin switch in the primary and recurrent oral squamous cell carcinoma (re-OSCC) tissues is an inherent characteristic of the tumor, affects the biologic behavior, and further reflects the post-recurrence survival outcome of these patients. Survival outcome was analyzed by calculating the post-recurrence survival of the high-risk group and correlating the standardized h-score-based IHC expression of both cadherin types with the clinical follow-up. 94 patients with re-OSCC were observed within the cohort. Tissue samples from both primary and recurring tumors were collected. There was a significant association between loss of E-CAD expression and both oral cancer-specific and overall survival, (HR=2.72, CI:1.50-4.95, p=0.001) and (HR=3.84, CI:1.93-7.63, p=0.001), respectively, for expression loss higher than 60%. There was no statistically significant correlation between N-CAD de novo expression and Overall, oral cancer-specific and disease-free post-recurrence survival. The current study clearly shows that cadherin-switch, identified as E-CAD loss and N-CAD de novo expression in the invasion front of a re-OSCC, appears to be an inherent histological hallmark that does not change from primary manifestation to recurrence within the same tumor, regardless of the form of adjuvant therapy used for the primary tumor. The loss of E-CAD expression in re-OSCC is an independent risk factor for poor survival, and may be used to stratify therapy and de/escalate the multimodal treatment.
The role of tumor microenvironment in drug resistance: emerging technologies to unravel breast cancer heterogeneity
Authors: Salemme Vincenzo , Centonze Giorgia , Avalle Lidia , Natalini Dora , Piccolantonio Alessio , Arina Pietro , Morellato Alessandro , Ala Ugo , Taverna Daniela , Turco Emilia , Defilippi Paola
Published: May 2023

Breast cancer is a highly heterogeneous disease, at both inter- and intra-tumor levels, and this heterogeneity is a crucial determinant of malignant progression and response to treatments. In addition to genetic diversity and plasticity of cancer cells, the tumor microenvironment contributes to tumor heterogeneity shaping the physical and biological surroundings of the tumor. The activity of certain types of immune, endothelial or mesenchymal cells in the microenvironment can change the effectiveness of cancer therapies via a plethora of different mechanisms. Therefore, deciphering the interactions between the distinct cell types, their spatial organization and their specific contribution to tumor growth and drug sensitivity is still a major challenge. Dissecting intra-tumor heterogeneity is currently an urgent need to better define breast cancer biology and to develop therapeutic strategies targeting the microenvironment as helpful tools for combined and personalized treatment. In this review, we analyze the mechanisms by which the tumor microenvironment affects the characteristics of tumor heterogeneity that ultimately result in drug resistance, and we outline state of the art preclinical models and emerging technologies that will be instrumental in unraveling the impact of the tumor microenvironment on resistance to therapies.
Optimal treatment strategy for hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer patients with 1–2 suspicious axillary lymph node metastases on breast magnetic resonance imaging: upfront surgery vs. neoadjuvant chemotherapy
Authors: Lee Seung Eun , Ahn Sung Gwe , Ji Jung Hwan , Kook Yoonwon , Jang Ji Soo , Baek Seung Ho , Jeong Joon , Bae Soong June
Published: May 2023

Background

It is unclear whether upfront surgery or neoadjuvant chemotherapy is appropriate for first treatment in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with 1–2 suspicious axillary lymph node (ALN) metastases on preoperative breast magnetic resonance imaging (MRI).

Method

We identified 282 patients with HR+HER2- breast cancer and 1–2 suspicious ALN metastases on baseline breast MRI (147 received upfront surgery; 135 received neoadjuvant chemotherapy). We evaluated the predictive clinicopathological factors for pN2-3 in the adjuvant setting and axillary pathologic complete response (pCR) in the neoadjuvant setting.

Results

Lymphovascular invasion (LVI)-positive and clinical tumors >3 cm were significantly associated with pN2-3 in patients who received upfront surgery. The pN2-3 rate was 9.3% in patients with a clinical tumor ≤ 3 cm and LVI-negative versus 34.7% in the others (p < 0.001). The pN2-3 rate in patients with a clinical tumor ≤ 3 cm and LVI-negative and in the others were 9.3% versus 34.7% in all patients (p < 0.001), 10.7% versus 40.0% (p = 0.033) in patients aged < 50 years, and 8.5% versus 31.0% in patients aged ≥ 50 years (p < 0.001), respectively. In the neoadjuvant setting, patients with tumor-infiltrating lymphocytes (TILs) ≥ 20% had a higher axillary pCR than those with TILs < 20% (46.7% vs. 15.3%, p < 0.001). A similar significant finding was also observed in patients < 50 years.

Conclusions

Upfront surgery may be preferable for patients aged ≥ 50 years with a clinical tumor < 3 cm and LVI-negative, while neoadjuvant chemotherapy may be preferable for those aged < 50 years with TILs ≥ 20%.
On determining the mechanical nociceptive threshold in pigs: a reliability study
Authors: Rettore Andreis Felipe , Mørch Carsten Dahl , Jensen Winnie , Meijs Suzan
Published: May 2023

Background

A pressure algometer is a valuable tool for assessing the mechanical nociceptive threshold (MNT) in clinical pain studies. Recent research has turned to large animal models of pain because of the closer anatomy and physiology to humans. Although the reliability and usefulness of the MNT have been extensively validated in humans, similar data from large animals is still sparse.

Objective

Therefore, the aim of the current study was to evaluate the reliability (within- and between-session) of MNT in the forelimb of pigs using a pressure algometer.

Methods

Nine animals were used (23–40 kg), and MNTs were measured at both the right and left limbs at three different sessions, with three repetitions per session. The intraclass correlation coefficient (ICC) was used as a metric for relative reliability. The standard error of measurement (SEM) and coefficient of variation (CV) was used to assess absolute reliability. Systematic bias was also evaluated.

Results

The average ICC was found to be 0.71 and 0.45 for the between-session and within-session, respectively. CV ranged from 17.9% to 20.5%, with a grand average of 19.1%. The grand average SEM was 249.5 kPa (16.6%). No systematic differences were found for the MNT between sessions, which suggests that there was no habituation to the stimulus.

Conclusion

The reliability indices obtained in this study are comparable to results obtained in other species or anatomical regions and substantiate the use of the pressure algometer as a valuable tool to investigate the nociceptive system in pigs and translation to the human nociceptive withdrawal reflex.
Angiopoietin-like protein 3: a novel potential biomarker for nephrotic syndrome in children
Authors: Wen Fujie , Liu Junchao , Dai Rufeng , Hong Sha , Ji Baowei , Liu Jiaojiao , Zhang Jun , Han Xinli , Lv Qianying , Liu Jialu , Shen Qian , Xu Hong
Published: May 2023

Background

Angiopoietin-like 3 (ANGPTL3) is a secretory glycoprotein. It has been demonstrated that ANGPTL3 level was upregulated in minimal change nephrotic syndrome (MCNS) kidney tissues. Subsequently, our group found that ANGPTL3 level was closely correlated with nephropathy in vivo and in vitro. Hence, whether ANGPTL3 level could be correlated with the proteinuria level, and assessment of disease severity of nephrotic syndrome (NS) remained to be investigated. This study aimed to analyzed the correlation between the levels of ANGPTL3 in serum and urine of patients with nephrotic syndrome and proteinuria, and assessed the severity of the patients' disease. In future clinical translation, the level of ANGPTL3 in serum, urine will be used as a biomarker to better predict the development of nephrotic syndrome.

Methods

A total of 200 NS patients and 80 healthy controls (age, 1–18 years) were admitted to our institution between 2021 and 2022. The etiology of NS included primary nephrotic syndrome (PNS, n = 144) and NS with other causes (n = 56). A total of 280 serum samples and 244 urinary samples were collected to determine ANGPTL3 level using enzyme-linked immunosorbent assay (ELISA).

Results

Serum ANGPTL3 and urinary ANGPTL3/Cre were remarkably elevated in NS patients compared with those in healthy controls. Furthermore, serum ANGPTL3 and urinary ANGPTL3/Cre were significantly correlated with proteinuria level. Additionally, multivariate linear regression analysis demonstrated that serum ALB was independently correlated with serum ANGPTL3 and PRO/CR was independently correlated with urinary ANGPTL3/Cre in NS patients.

Conclusion

Serum ANGPTL3 and urinary ANGPTL3/Cre showed a promising performance in the diagnosis of NS, and served as novel potential noninvasive biomarkers to assess disease severity of NS. Further exploration of the role of ANGPTL3 level may shed a new light on the treatment of NS.
The olfactory Olfr-78/51E2 receptor interacts with the adenosine A2A receptor. Effect of menthol and 1,8-cineole on A2A receptor-mediated signaling
Authors: Lillo Jaume , García-Pérez Irene , Lillo Alejandro , Serrano-Marín Joan , Martínez-Pinilla Eva , Navarro Gemma , Franco Rafael
Published: May 2023

Heteromer formation is unknown for the olfactory family of G protein-coupled receptors (GPCRs). We here identified, in a heterologous system, heteromers formed by the adenosine A2A receptor (A2AR), which is a target for neuroprotection, and an olfactory receptor. A2AR interacts with the receptor family 51, subfamily E, member 2 (OR51E2), the human ortholog of the mouse Olfr-78, whose mRNA is differentially expressed in activated microglia treated with adenosine receptor ligands. Bioluminescence resonance energy transfer (BRET) assays were performed in HEK-293T cells expressing the human version of the receptors, OR51E2 and A2AR, fused, respectively, to Renilla luciferase (RLuc) and the yellow fluorescent protein (YFP). BRET data was consistent with a receptor-receptor interaction whose consequences at the functional level were measured by cAMP level determination in CHO cells. Results showed an olfactory receptor-mediated partial blockade of Gs coupling to the A2AR, i.e., the effect of the A2AR selective agonist on intracellular levels of cAMP was significantly reduced. Two odorants, menthol and 1,8-cineole, which failed to show Golf-mediated OR51E2 activation because they did not increase cytosolic cAMP levels, reduced the BRET readings in cells expressing A2AR-YFP and OR51E2-Rluc, most likely suggesting a conformational change of at least one receptor. These odorants led to an almost complete block of A2AR coupling to Gs.
Acacetin exerts antitumor effects on gastric cancer by targeting EGFR
Authors: Zhang Guangtao , Dong Jiahuan , Lu Lu , Liu Yujing , Hu Dan , Wu Yuanmin , Zhao Aiguang , Xu Hanchen
Published: May 2023

Background: Gastric cancer (GC) is a common malignant tumor with a poor prognosis. Combination treatments may prolong the survival of patients with GC. Acacetin, which is a flavonoid, exerts potent inhibitory effects on several types of cancer cells; however, the mechanisms of action remain poorly understood.

Methods: Network pharmacology and RNA sequencing were used to predict the targets of acacetin, which were then verified by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking. The biological functions of acacetin in MKN45 and MGC803 cells were investigated using TUNEL assays, crystal staining and colony formation assays. The pathways affected by acacetin were verified through reverse experiments. The in vivo antitumor efficacy of acacetin was assessed in a subcutaneous xenotransplanted tumor model.

Results: In this study, we identified EGFR from more than a dozen predicted targets as a protein that directly binds to acacetin. Moreover, acacetin affected the level of phosphorylated EGFR. In vitro, acacetin promoted the apoptosis of GC cells. Importantly, EGFR agonists reversed the inhibitory effects of acacetin on the STAT3 and ERK pathways. In vivo, acacetin decreased the protein levels of pEGFR in tumors, resulting in increased GC xenograft tumor regression without obvious toxicity.

Conclusion: Our findings highlight EGFR as one of the direct targets of acacetin in GC cells. Acacetin inhibited the phosphatase activity of EGFR in vitro and in vivo, which played a role in the antitumor effects of acacetin. These studies provide new evidence for the use of acacetin as a potential reagent for the treatment of GC.
Cost-effectiveness analysis of toripalimab plus chemotherapy as the first-line treatment in patients with advanced non-small cell lung cancer (NSCLC) without EGFR or ALK driver mutations from the Chinese perspective
Authors: Zhou Kexun , Shu Pei , Zheng Hanrui , Li Qiu
Published: May 2023

Objectives: The results of a CHOICE-1 study demonstrated the superior efficacy of toripalimab (anti-PD-1 antibody) plus chemotherapy for patients with advanced non–small cell lung cancer (NSCLC), with a manageable safety profile. This study was performed to evaluate the economic value of this treatment for this patient population from the Chinese payer’s perspective.

Materials and methods: Basic data were derived from the CHOICE-1 study. Markov models were developed to simulate the process of advanced NSCLC, including the progression-free survival (PFS), progressive disease (PD), and death in intention-to-treat (ITT) populations, as well as patients with squamous or non-squamous NSCLC. The cost was obtained from the local institution, and the value of utilities referred to previous studies. Monte Carlo simulations were performed to depict the probabilistic scatter plots of the incremental cost-effectiveness ratio (ICER) and acceptability curves, aiming to address the uncertainty of model inputs.

Results: Compared with standard chemotherapy, toripalimab plus chemotherapy yields an ICER of $21,563 per quality-adjusted life year (QALY) in the ITT population. For patients with squamous NSCLC, comparing the combined therapy with chemotherapy led to an ICER of $18,369 per QALY, while the ICER was $24,754 per QALY in patients with non-squamous NSCLC. With the threshold of willingness to pay we set ($37,653 per QALY), toripalimab plus chemotherapy was cost-effective in these patient populations.

Conclusion: For patients with advanced NSCLC, toripalimab plus chemotherapy was an optimal choice as first-line treatment, regardless of histology.
Therapeutic mechanism of baicalein in peritoneal dialysis-associated peritoneal fibrosis based on network pharmacology and experimental validation
Authors: Lu Xiaohui , Wu Kefei , Jiang Simin , Li Yi , Wang Yating , Li Hongyu , Li Guanglan , Liu Qinghua , Zhou Yi , Chen Wei , Mao Haiping
Published: May 2023

Baicalein (5,6,7-trihydroxyflavone) is a traditional Chinese medicine with multiple pharmacological and biological activities including anti-inflammatory and anti-fibrotic effects. However, whether baicalein has a therapeutic impact on peritoneal fibrosis has not been reported yet. In the present study, network pharmacology and molecular docking approaches were performed to evaluate the role and the potential mechanisms of baicalein in attenuating peritoneal dialysis-associated peritoneal fibrosis. The results were validated in both animal models and the cultured human mesothelial cell line. Nine intersection genes among baicalein targets and the human peritoneum RNA-seq dataset including four encapsulating peritoneal sclerosis samples and four controls were predicted by network analysis. Among them, MMP2, BAX, ADORA3, HIF1A, PIM1, CA12, and ALOX5 exhibited higher expression in the peritoneum with encapsulating peritoneal sclerosis compared with those in the control, which might be crucial targets of baicalein against peritoneal fibrosis. Furthermore, KEGG and GO enrichment analyses suggested that baicalein played an anti-peritoneal fibrosis role through the regulating cell proliferation, inflammatory response, and AGE-RAGE signaling pathway. Moreover, molecular docking analysis revealed a strong potential binding between baicalein and MMP2, which was consistent with the predictive results. Importantly, using a mouse model of peritoneal fibrosis by intraperitoneally injecting 4.25% glucose dialysate, we found that baicalein treatment significantly attenuated peritoneal fibrosis, as evident by decreased collagen deposition, protein expression of α-SMA and fibronectin, and peritoneal thickness, at least, by reducing the expression of MMP2, suggesting that baicalein may have therapeutic potential in suppressing peritoneal dialysis-related fibrosis.
A novel glycyrrhizin acid-coated stent reduces neointimal formation in a rabbit iliac artery model
Authors: Teng Shuai , Zhu Zhaowei , Li Yang , Hu Xinqun , Fang Zhenfei , Liu Zhenjiang , Zhou Shenghua
Published: May 2023

Introduction: Most drug-eluting stents (DESs) inhibit intimal hyperplasia but impair re-endothelialization. This study aimed to evaluate in vivo strut coverage and neointimal growth in a new glycyrrhizin acid (GA)-eluting stent.

Methods: New Zealand White rabbits (n = 20) with atherosclerotic plaques were randomly divided into three groups based on implanted iliac artery stents: bare-metal stents (BMSs), rapamycin-eluting stents, and GA-eluting stents. After the in vivo intravascular ultrasound (IVUS) assessment at 28 days, the vessels were harvested for scanning electron microscopy (SEM) and histology. After 4 weeks of follow-up, the stent and external elastic lamina (EEL) areas were compared among the groups.

Results: The rapamycin- or GA-eluting stents significantly reduced the neointimal area compared with BMSs, though GA-eluting stents had the lowest reduction. There were more uncovered struts for rapamycin-eluting stents than those for GA-eluting stents and bare-metal stents. The endothelial nitric oxide synthase (eNOS) expression in GA-eluting stents was much higher than that in BMSs and rapamycin-eluting stents, even though the endothelial coverage between struts was equivalent between BMSs and GA-eluting stents. Moreover, GA-eluting stents markedly promoted re-endothelialization and improved arterial healing compared to rapamycin-eluting stents in a rabbit atherosclerotic model.

Conclusion: In conclusion, the novel GA-coated stent used in this study inhibited intimal hyperplasia and promoted re-endothelialization.
Thermodynamics modeling of deep learning systems for a temperature based filter pruning technique
Authors: Lapenna M. , Faglioni F. , Fioresi R.
Published: May 2023

We analyse the dynamics of convolutional filters’ parameters of a convolutional neural networks during and after training, via a thermodynamic analogy which allows for a sound definition of temperature. We show that removing high temperature filters has a minor effect on the performance of the model, while removing low temperature filters influences majorly both accuracy and loss decay. This result could be exploited to implement a temperature-based pruning technique for the filters and to determine efficiently the crucial filters for an effective learning.
Chromosome-level genome and high nitrogen stress response of the widespread and ecologically important wetland plant Typha angustifolia
Authors: Liao Yang , Zhao Shuying , Zhang Wenda , Zhao Puguang , Lu Bei , Moody Michael L. , Tan Ninghua , Chen Lingyun
Published: May 2023

Typha angustifolia L., known as narrowleaf cattail, is widely distributed in Eurasia but has been introduced to North America. Typha angustifolia is a semi-aquatic, wetland obligate plant that is widely distributed in Eurasia and North America. It is ecologically important for nutrient cycling in wetlands where it occurs and is used in phytoremediation and traditional medicine. In order to construct a high-quality genome for Typha angustifolia and investigate genes in response to high nitrogen stress, we carried out complete genome sequencing and high-nitrogen-stress experiments. We generated a chromosomal-level genome of T. angustifolia, which had 15 pseudochromosomes, a size of 207 Mb, and a contig N50 length of 13.57 Mb. Genome duplication analyses detected no recent whole-genome duplication (WGD) event for T. angustifolia. An analysis of gene family expansion and contraction showed that T. angustifolia gained 1,310 genes and lost 1,426 genes. High-nitrogen-stress experiments showed that a high nitrogen level had a significant inhibitory effect on root growth and differential gene expression analyses using 24 samples found 128 differentially expressed genes (DEGs) between the nitrogen-treated and control groups. DEGs in the roots and leaves were enriched in alanines, aspartate, and glutamate metabolism, nitrogen metabolism, photosynthesis, phenylpropanoid biosynthesis, plant-pathogen interaction, and mitogen−activated protein kinase pathways, among others. This study provides genomic data for a medicinal and ecologically important herb and lays a theoretical foundation for plant-assisted water pollution remediation.
Size regulation of the lateral organ initiation zone and its role in determining cotyledon number in conifers
Authors: Holloway David M. , Saunders Rebecca , Wenzel Carol L.
Published: May 2023

Introduction

Unlike monocots and dicots, many conifers, particularly Pinaceae, form three or more cotyledons. These are arranged in a whorl, or ring, at a particular distance from the embryo tip, with cotyledons evenly spaced within the ring. The number of cotyledons, nc, varies substantially within species, both in clonal cultures and in seed embryos. nc variability reflects embryo size variability, with larger diameter embryos having higher nc. Correcting for growth during embryo development, we extract values for the whorl radius at each nc. This radius, corresponding to the spatial pattern of cotyledon differentiation factors, varies over three-fold for the naturally observed range of nc. The current work focuses on factors in the patterning mechanism that could produce such a broad variability in whorl radius. Molecularly, work in Arabidopsis has shown that the initiation zone for leaf primordia occurs at a minimum between inhibitor zones of HD-ZIP III at the shoot apical meristem (SAM) tip and KANADI (KAN) encircling this farther from the tip. PIN1-auxin dynamics within this uninhibited ring form auxin maxima, specifying primordia initiation sites. A similar mechanism is indicated in conifer embryos by effects on cotyledon formation with overexpression of HD-ZIP III inhibitors and by interference with PIN1-auxin patterning.

Methods

We develop a mathematical model for HD-ZIP III/KAN spatial localization and use this to characterize the molecular regulation that could generate (a) the three-fold whorl radius variation (and associated nc variability) observed in conifer cotyledon development, and (b) the HD-ZIP III and KAN shifts induced experimentally in conifer embryos and in Arabidopsis.

Results

This quantitative framework indicates the sensitivity of mechanism components for positioning lateral organs closer to or farther from the tip. Positional shifting is most readily driven by changes to the extent of upstream (meristematic) patterning and changes in HD-ZIP III/KAN mutual inhibition, and less efficiently driven by changes in upstream dosage or the activation of HD-ZIP III. Sharper expression boundaries can also be more resistant to shifting than shallower expression boundaries.

Discussion

The strong variability seen in conifer nc (commonly from 2 to 10) may reflect a freer variation in regulatory interactions, whereas monocot (nc = 1) and dicot (nc = 2) development may require tighter control of such variation. These results provide direction for future quantitative experiments on the positional control of lateral organ initiation, and consequently on plant phyllotaxy and architecture.
Genomic insights into genetic diversity and local adaptation of a dominant desert steppe feather grass, Stipa breviflora Griseb.
Authors: Yan Dongqing , Liu Jiamei , Fan Yanyan , Lian Zhi , Dang Zhenhua , Niu Jianming
Published: May 2023

Investigating the genetic mechanisms of local adaptation is critical to understanding how species adapt to heterogeneous environments. In the present study, we analyzed restriction site-associated DNA sequencing (RADseq) data in order to explore genetic diversity, genetic structure, genetic differentiation, and local adaptation of Stipa breviflora. In total, 135 individual plants were sequenced and 25,786 polymorphic loci were obtained. We found low genetic diversity (He = 0.1284) within populations of S. breviflora. Four genetic clusters were identified along its distribution range. The Mantel test, partial Mantel test, and multiple matrix regression with randomization (MMRR) indicate that population differentiation was caused by both geographic distance and environmental factors. Through the FST outlier test and environmental association analysis (EAA), 113 candidate loci were identified as putatively adaptive loci. RPK2 and CPRF1, which are associated with meristem maintenance and light responsiveness, respectively, were annotated. To explore the effects of climatic factors on genetic differentiation and local adaptation of S. breviflora, gradient forest (GF) analysis was applied to 25,786 single nucleotide polymorphisms (SNPs) and 113 candidate loci, respectively. The results showed that both temperature and precipitation affected the genetic differentiation of S. breviflora, and precipitation was strongly related to local adaptation. Our study provides a theoretical basis for understanding the local adaptation of S. breviflora.
Relationship among positive self-esteem, physical literacy, and physical activity in college students: a study of a mediation model
Authors: She Xi , Gao Tian-Yu , Ma Rui-Si , Tang Di , Zhong Hua , Dong He-Ling
Published: May 2023

Background

In light of the substantial decline in physical activity during college years, this study aims to examine the relationship between positive self-esteem, physical literacy, and physical activity in order to investigate the mechanisms for improving physical activity in college students and to provide a foundation for future interventions.

Methods

A cross-sectional study design was employed in this study. A total of 5,184 Participants, aged between 17 and 21 years (M = 18.97, SD = 1.10), completed the Positive Version of Rosenberg Self-esteem Scales, Perceived Physical Literacy Instruments, and the International Physical Activity Questionnaires. A mediation model was utilized to explore the associations among the three concepts.

Results

The three regression models were as follows: Physical literacy = 18.03 + 0.98 *Self-esteem, Physical activity = 43.23 + 0.16 *Self-esteem, and Physical activity = 28.18 + 0.11 *Physical literacy. Positive self-esteem, physical literacy, and physical activity were significantly linked with each other. Physical literacy mediated 26.93% of the effect, indicating a partial mediator in the relationship between positive self-esteem and physical activity.

Conclusion

The mediating effect of physical literacy on the relationship between positive self-esteem and physical activity was identified. Our findings support the development of positive self-esteem and physical literacy in college physical education curricula as part of an overall program to address students’ physical inactivity at school and in the future. This study provides a new intervention perspective for improving physical inactivity in college students.
Comparison of two brief mindfulness interventions for anxiety, stress and burnout in mental health professionals: a randomised crossover trial
Authors: Ruiz-Íñiguez Raquel , Carralero Montero Ana , Burgos-Julián Francisco A. , Fabelo Roche Justo R. , Santed Miguel Á.
Published: May 2023

Background

Anxiety, stress and burnout are a growing reality among mental health professionals, impacting negatively on them and their clients. Mindfulness-based interventions (MBIs) have demonstrated effectiveness in mitigating these sufferings. Nevertheless, there is a lack of knowledge on the impact of MBIs in Cuba.

Objectives

To compare the effectiveness of two brief mindfulness-based interventions for reducing anxiety, work stress and burnout.

Methods

A total of 104 mental health professionals from Havana (Cuba) participated in a randomised crossover trial. Group A received first an intervention involving body-centred practices (body scan and Hatha yoga) and a second intervention involving mind-centred practices (focused attention and open monitoring meditation). Group B received the same interventions but in reverse order. Four measures (anxiety, stress, burnout syndrome, and antecedents of burnout) were measured at baseline, posttest1, posttest2, and 6-months follow-up.

Results

After the first intervention, there was a between-group difference for burnout syndrome, but the ES was similar for both groups. After the second intervention (implementing both practises), groups showed the largest effect sizes, and there was a between-group difference for antecedents of burnout. Results were partially maintained at 6-month follow-up.

Conclusion

These results suggest that mind-centred practises can be as effective as body-centred practises for stress, anxiety and burnout reduction. The combination of both types of practises could be the most effective way of teaching mindfulness. About the sequence of implementation, teaching mind-centred practises first and then body-centred practises could be most effective for reducing antecedents of burnout.

Clinical Trial Registration: www.clinicaltrials.gov NCT03296254.
Development and validation of the social media perception scale for preservice physical education teachers
Authors: Xu Yue , Li Fangfei , Yin Zhihua , Sun Mingzhu , Guo Zhen , Liu Bo
Published: May 2023

Background

Social media has become a mainstay of preservice physical education teachers’ professional development. However, previous studies have been dominated by qualitative research, and there is still a lack of quantitative research based on samples from eastern countries. The objective of this study is to develop and validate of the Social Media Perception Scale for Preservice Physical Education teachers (SMPS-PPE).

Method

Items of questionnaire created from 70 concepts of the perception model described in our previous study. Questionnaire survey was used to collect quantitative data from a sample of 977 preservice physical education teachers through surveys. We analyzed the data using SPSS 26.0 and AMOS 24.0, conducting item analysis, exploratory factor analysis and confirmatory factor analysis to examine the data.

Results

SMPS-PPE consists of 26 items grouped into three factors: value perception, risk perception, and overall perception. Our findings indicate that SMPS-PPE has acceptable content validity, internal structure validity, and internal consistency.

Conclusion

SMPS-PPE is a reliable and valid measurement to evaluate social media perception among preservice physical education teachers. Future studies should include larger and more diverse teacher samples to enhance generalizability. The SMPS-PPE should also be modified to better cater to the specific requirements of school teachers and university-based teacher educators in the field of physical education.
The relationship between anxiety and internet gaming disorder in children during COVID-19 lockdown: a network analysis
Authors: Yang Tianqi , He Yang , He Chunyan , Yang Yueqi , Wu Lin , Wei Bin , Dong Ruina , Yang Mengyuan , Pu Zhaojun , Wang Saiming , Li Jing , Xu Tao , Liu Xufeng , Wu Shengjun
Published: May 2023

Background

Internet gaming disorder (IGD) has become a social problem in children. Evidence from previous studies has proven that anxiety is associated with IGD. However, IGD was always assessed as a whole based on total scores, and the fine-grained relationship between anxiety and IGD was hidden.

Objective

The present study aims to investigate the fine-grained relationship between anxiety and IGD in elementary school students during the COVID-19 lockdown, and to identify potential targets for psychological interventions.

Methods

During the lockdown caused by the COVID-19 pandemic, 667 children from a primary school in China were investigated by the Spence Children’s Anxiety Scale-Short Version and Internet Gaming Disorder Scale. R4.1.1 software was used to construct a network model, assess bridge centrality, and test the robustness of the network and conduct a network.

Results

There were 23 cross-community edges (weight ranged from −0.03 to 0.12), and each node of anxiety was connected to different nodes of IGD. The nodes with the top 80th percentile bridge expected influence were A2 “social phobia” (0.20), A3 “panic disorder” (0.21) and IGD5 “escape” (0.22). The robustness of the network was acceptable.

Conclusion

From the perspective of network analysis, the present study explored the correlation pathways between anxiety and IGD in children and identified social phobia and panic disorder as the best targets for intervention to reduce IGD.