bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of macrophages in pulmonary arterial hypertension
Authors: Zhang Meng-Qi , Wang Chen-Chen , Pang Xiao-Bin , Shi Jun-Zhuo , Li Hao-Ran , Xie Xin-Mei , Wang Zhe , Zhang Hong-Da , Zhou Yun-Feng , Chen Ji-Wang , Han Zhi-Yan , Zhao Lu-Ling , He Yang-Yang
Published: April 2023

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.
CCL13 and human diseases
Authors: Li Laifu , Dai Fei , Wang Lianli , Sun Yating , Mei Lin , Ran Yan , Ye Fangchen
Published: April 2023

CCL13/MCP-4 belongs to the CC chemokine family, which induces chemotaxis in many immune cells. Despite extensive research into its function in numerous disorders, a thorough analysis of CCL13 is not yet accessible. The role of CCL13 in human disorders and existing CCL13-focused therapies are outlined in this study. The function of CCL13 in rheumatic diseases, skin conditions, and cancer is comparatively well-established, and some studies also suggest that it may be involved in ocular disorders, orthopedic conditions, nasal polyps, and obesity. We also give an overview of research that found very little evidence of CCL13 in HIV, nephritis, and multiple sclerosis. Even though CCL13-mediated inflammation is frequently linked to disease pathogenesis, it’s fascinating to note that in some conditions, like primary biliary cholangitis (PBC) and suicide, it might even act as a preventative measure.
Understanding species responses in a changing world by examining the predatory behaviour of southern calamari to changes in temperature
Authors: Peinado Patricia , Fitzgibbon Quinn P. , Semmens Jayson M. , Tracey Sean , Pecl Gretta T.
Published: April 2023

Predator–prey interactions are key drivers in structuring communities, with the potential to substantially impact the whole ecosystem when important predators and prey are involved. Squid are voracious predators and also important prey for other top predators. To date, the available data suggests that under current and projected ocean warming, the behaviour of ectotherms could be modified (for example, through individual movement, predator avoidance and escape speed), yet little is known of the influence of temperature on the predatory behaviour of cephalopods. Here, the predatory behaviour of adult southern calamari (Sepioteuthis australis) under different thermal scenarios was examined demonstrating that squid exhibited different behaviour and performance capabilities across temperature treatments. Overall, attempts of squid to capture prey were faster and more persistent at higher temperature treatments (25°C), suggesting that individuals need to increase their food consumption rate, presumably associated with the higher energetic costs of living at elevated temperatures. However, we also observed a possible decrease in capture efficiency and increased prey handling time at higher temperatures suggesting that implications for energetic balance are not straightforward and that trade-offs need to be carefully explored. As cephalopods are ecologically important species acting as key links in food webs around the world, the results here could have important implications for the dynamics of many marine ecosystems in future.
Wind-induced evaporative cooling passive system for tropical hot and humid climate
Authors: Moh T. S. Y. , Jin J. J. Y. , Wong L. A. , Tiong M. C. , Chan C. K.
Published: April 2023

Over the years, the desire to have better thermal comfort in terms of living has been extensively discussed and is in high demand, especially in metropolitan cities. Alongside the desired outcomes, air conditioning facilities have been implemented, but they also bring negative consequences, such as a high energy bill and multi-dimensional environmental impacts. To counter these problems, a hybrid technique combining the evaporative cooling technique with a venturi-shaped natural ventilation tower is proposed. Evaporative cooling takes advantage of cooling in response to the wind blowing through a layer of wetted surface that is built with permeable materials. Combining with the specially designed venturi-shaped natural ventilation tower to improve the volume intake of wind externally, this system is aimed to reduce temperature and achieve thermal comfort by cooling down the air with circulation in a continuous accumulative mode. To gauge the efficiency and effectiveness of this hybrid technique, an evaporative system known as the wind-induced evaporative cooling (WIEC) system is directly fed into a testing chamber (installed with sensors) fabricated with a scale of 1:6. The system was tested in a hot and humid climate with a temperature range of 27°C–34°C. The finding shows that our system is able to reduce temperatures up to 3.873°C with an output cooling capacity of 9 W–476.3 W, which shows the feasibility of this study.
Global research trends on epigenetics and neuropathic pain: A bibliometric analysis
Authors: Zhu Chenchen , Zhong Weiquan , Gong Chan , Chen Binglin , Guo Jiabao
Published: April 2023

Objective

Neuropathic pain (NP) is a common disease that manifests with pathological changes in the somatosensory system. In recent years, the interactions of NP with the epigenetic mechanism have been increasingly elucidated. However, only a few studies have used bibliometric tools to systematically analyze knowledge in this field. The objective of this study is to visually analyze the trends, hotspots, and frontiers in epigenetics and NP research by using a bibliometric method.

Methods

Studies related to epigenetics and NP were searched from the Science Citation Index-Expanded of the Web of Science Core Collection database. Search time is from inception to November 30, 2022. No restrictions were placed on language. Only articles and reviews were included as document types. Data on institutions, countries, authors, journal distribution, and keywords were imported into CiteSpace software for visual analysis.

Results

A total of 867 publications met the inclusion criteria, which spanned the period from 2000 to 2022. Over the years, the number of publications and the frequency of citations exhibited a clear upward trend in general, reaching a peak in 2021. The major contributing countries in terms of the number of publications were China, the United States, and Japan. The top three institutions were Rutgers State University, Xuzhou Medical University, and Nanjing Medical University. Molecular Pain, Pain, and Journal of Neuroinflammation contributed significantly to the volume of issues. Among the top 10 authors in terms of the number of publications, Tao Yuan-Xiang contributed 30 entries, followed by Zhang Yi with 24 and Wu Shao-Gen with 20. On the basis of the burst and clusters of keywords, “DNA methylation,” “Circular RNA,” “acetylation,” “long non-coding RNA,” and “microglia” are global hotspots in the field.

Conclusion

The bibliometric analysis indicates that the number of publications related to epigenetics and NP is exhibiting a rapid increase. Keyword analysis shows that “DNA methylation,” “Circular RNA,” “acetylation,” “long non-coding RNA” and “microglia” are the most interesting terms for researchers in the field. More rigorous clinical trials and additional studies that explore relevant mechanisms are required in the future.
Long-term and real-life incidence of cancer therapy-related cardiovascular toxicity in patients with breast cancer: a Swedish cohort study
Authors: Hubbert Laila , Mallios Panagiotis , Karlström Patric , Papakonstantinou Andri , Bergh Jonas , Hedayati Elham
Published: April 2023

Background

The administration of anticancer drugs in females with comorbidity increases the risk for cancer therapy-related cardiovascular toxicity (CTR-CVT), which in turn contributes to cardiovascular disease (CVD). Furthermore, a pathophysiological connection between cancer and cardiovascular disease may exist.

Objective

To assess the long-term risks and predictors of CTR-CVT, including clinical hypertension (HT), coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), as well as all-cause mortality in women diagnosed with early breast cancer (BC) and eligible for adjuvant chemotherapy in Sweden.

Methods

Data were extracted from Swedish registers and medical records on 433 women, 18-60 years of age, diagnosed 1998-2002 with lymph node-positive BC, and considered for adjuvant chemotherapy. CTR-CVT was defined as HT, CAD, HF, or AF after the diagnosis of BC. Follow-up was from the date of BC diagnosis until November 30, 2021, or death. Prevalence of CTR-CVT and all-cause mortality were calculated. Hazard ratios (HR) were determined for factors associated with CTR-CVT.

Results

The median age was 50 (interquartile range (IQR) 32) years. 910 CTR-CVT events were diagnosed in 311 women with a median of 19.3 (IQR 15,3) years follow-up. The proportions of CTR-CVT events were: HT 281 (64%); CAD 198 (46%); HF 206 (47%); and AF 225 (51%). The cumulative incidence of CTR-CVT was 71.8%, and 50% of all 433 patients developed CTR-CVT within 11.7 years of BC diagnosis (standard deviation (SD) 0.57, 95% confidence interval (CI) 10.6-12.9). Age was a risk factor for CTR-CVT. Anthracycline increased the risk for HF (p=0,001; HR 2,0; 95%CI 1,4-2,8), CAD (p= 0,002; HR 1,7; 95% CI 1,2-2,4), and AF (p=0,013; HR 1,5; 95% CI 1,0-2,0). At the end of the 24-year study period, 227 of the 433 women were alive, and the total cumulative mortality was 47,6%.

Conclusion

The prevalence of CTR-CVT and all-cause mortality is high after BC diagnosis and treatment, particularly in older patients and those receiving anthracyclines. These findings and the onset of CTR-CVT support cardio-oncology guidelines recommending initial risk stratification and cardiovascular monitoring during treatment, followed by long-term annual screening for cardiovascular risk factors and CTR-CVT among BC survivors.
Intra-fraction motion of pelvic oligometastases and feasibility of PTV margin reduction using MRI guided adaptive radiotherapy
Authors: Snyder Jeffrey , Smith Blake , St-Aubin Joel , Dunkerley David , Shepard Andrew , Caster Joseph , Hyer Daniel
Published: April 2023

Purpose

This study assesses the impact of intra-fraction motion and PTV margin size on target coverage for patients undergoing radiation treatment of pelvic oligometastases. Dosimetric sparing of the bowel as a function of the PTV margin is also evaluated.

Materials and methods

Seven patients with pelvic oligometastases previously treated on our MR-linac (35 Gy in 5 fractions) were included in this study. Retrospective adaptive plans were created for each fraction on the daily MRI datasets using PTV margins of 5 mm, 3 mm, and 2 mm. Dosimetric constraint violations and GTV coverage were measured as a function of PTV margin size. The impact of intra-fraction motion on GTV coverage was assessed by tracking the GTV position on the cine MR images acquired during treatment delivery and creating an intra-fraction dose distribution for each IMRT beam. The intra-fraction dose was accumulated for each fraction to determine the total dose delivered to the target for each PTV size.

Results

All OAR constraints were achieved in 85.7%, 94.3%, and 100.0% of fractions when using 5 mm, 3 mm, and 2 mm PTV margins while scaling to 95% PTV coverage. Compared to plans with a 5 mm PTV margin, there was a 27.4 ± 12.3% (4.0 ± 2.2 Gy) and an 18.5 ± 7.3% (2.7 ± 1.4 Gy) reduction in the bowel D0.5cc dose for 2 mm and 3 mm PTV margins, respectively. The target dose (GTV V35 Gy) was on average 100.0 ± 0.1% (99.6 – 100%), 99.6 ± 1.0% (97.2 – 100%), and 99.0 ± 1.4% (95.0 – 100%), among all fractions for the 5 mm, 3 mm, and 2 mm PTV margins on the adaptive plans when accounting for intra-fraction motion, respectively.

Conclusion

A 2 mm PTV margin achieved a minimum of 95% GTV coverage while reducing the dose to the bowel for all patients.
Epidemiology and survival of cervical cancer in Iran based on national cancer registry data (2008-2014)
Authors: Akbari Atieh , Khayamzadeh Maryam , Salmanian Reza , Moradi Afshin , Akbari Mohammad Esmaeil
Published: April 2023

Background

Cervical cancer (CC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in females worldwide, associated with the incidence of human papillomavirus (HPV) infection. The CC incidence is low in Iran, ranking 11th among cancers. This study aimed to estimate the survival rate of CC and the reasons for its low survival rate based on the data retrieved from the Iranian National Cancer Registry System.

Methods

In this retrospective cohort study, data for patients diagnosed with CC from 2008 to 2014 were collected and analyzed. The Kaplan-Meier method was used for survival analysis based on epidemiological and clinical factors.

Results

A total of 5,304 women were diagnosed from March 10, 2008 to March 9, 2014 and 2,423 patients were followed. The mean age of the cases was 51.91 years, and 65.91% were alive. The 5- and 10-year survival rates were 58% and 50%, respectively, with no difference between younger cases with SCC or AC but better survival rates for older patients with SCC.

Conclusions

As a preventable disease, CC is related to biological factors and geographical and sociodemographic indices. Geographical, cultural, and religious behaviors affect the CC incidence and survival. In Iran, the 5-year survival rate ranges from 34% to 70% among different geographic regions. Hence, effective screening based on cultural and sociodemographic issues is recommended.
Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy in patients with extensive-stage small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials
Authors: Chen Chunlan , Tian Peng , Zhong Jiangshan , Fan Xianming
Published: April 2023

Objective

Many clinical trials of immune checkpoint inhibitors (ICIs) in combination with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) have been initiated, but the conclusions of these trials are not identical. This meta-analysis aimed to comprehensively collect these randomized clinical controlled trials (RCTs) to evaluate the efficacy and safety of ICIs combined with chemotherapy in the first-line treatment of ES-SCLC.

Methods

We systematically searched PubMed, Embase, and ClinicalTrials databases, to find relevant studies published until October 2022.RevMan 5.4 software was used for statistical analysis. The Cochrane Risk of Bias Tool was adopted to evaluate the risk of bias in the included studies. The primary outcome of this study was overall survival (OS), while the secondary outcomes were progression-free survival (PFS), objective response rate (ORR), all grand AEs (AEs), and ≥ 3 grand adverse events (≥ 3 AEs).

Results

A total of 780 articles were obtained in the initial examination, which was screened by layer and finally included 8 studies including 3367 patients. Six studies evaluated the efficacy of PD-1/PD-L1 inhibitors (Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, Adebrelimab, Serpulimab) combined with chemotherapy, and two studies evaluated the efficacy of CTLA-4 inhibitors (Ipilimumab) in combination with chemotherapy. The results showed that compared to chemotherapy alone, ICIs combined with chemotherapy significantly improved patients’ OS (HR=0.8, 95% CI (0.72-0.85), P<0.05), PFS (HR = 0.72, 95% CI (0.63-0.83), P < 0.05), and ORR(RR=1.08, 95% CI: 1.03-1.13, P<0.05), but patients would experience more any grand AEs and ≥3 grand AEs. Subgroup analysis showed that the PD-1/PD-L1 group performed better than the CTLA-4 group in both efficacy and safety. And ICIs plus chemotherapy significantly improved OS and PFS in patients regardless of age, gender, and performance status.

Conclusion

The addition of ICIs to chemotherapy resulted in significant improvements in both PFS and OS for patients with ES-SCLC, but patients would experience more AEs.
Bibliometric analysis of worldwide research trends on breast cancer about inflammation
Authors: Meng Guangran , Xu Huilin , Yang Shengtao , Chen Feixiang , Wang Wenyuan , Hu Furong , Zheng Gang , Guo Yixin
Published: April 2023

Background

The most prevalent cancer and the second-leading cause of cancer-related mortality in women is breast cancer. Growing interest has been shown in recent years in learning more about the processes behind the development of breast cancer. It has been shown that persistent inflammation may play a significant role in the advancement of breast cancer. However, a comprehensive and objective analysis on the state of inflammation in breast cancer research is still lacking. This study was aim to undertake a bibliometric analysis of breast cancer research associated with inflammation between 2013 and 2022 in order to identify the trends, dynamics, and scientific outputs in the field.

Methods

From 2013 to 2022, original and review publications on breast cancer and inflammation-associated research were retrieved from the Web of Science Core Collection (WOSCC) database. To examine the position of yearly publications, journals, nations, institutions, and authors, we employed two bibliometric tools (CiteSpace and VOSviewer). After that, by examining keyword visualization and keyword bursts, we determined the hot research fields related to inflammation in breast cancer.

Results

we discovered 6902 publications regarding inflammation in breast cancer by using our retrieval approach. In terms of the number of publications, The United States ranked first in the global study, followed by China and Italy. In terms of institutions, the University of Texas System, UT MD Anderson Cancer Center, and University of California System are in the top 3 for the quantity of publications published. The most popular journal for this field research is “CANCERS.” Ueno NT, Woodward WA, Cristofanilli M, and others have made significant contributions to the understanding of inflammation in breast cancer. In the end, we conducted a biclustering analysis on keywords and discovered three clusters that represent research hotspots.

Conclusion

According to the global trend, the research output of inflammation in breast cancer is increasing. The information provided in this article, including the cooperation network information of authors, nations, journals, and institutions, may help researchers to better understand hotspots and developing patterns in this discipline. At present, the focus of study gradually shifts from “phenotype study” to “therapeutic research”. It is recommended to pay attention to the latest hot spots, such as targeted therapy, antimicrobial activity and nanoparticle.
Receptor–ligand pair typing and prognostic risk model of response or resistance to immune checkpoint inhibitors in lung adenocarcinoma
Authors: Mao Shengqiang , Zeng Lingyan , Yang Ying , Liu Zhiqiang , Zhang Li
Published: April 2023

Introduction

Currently, programmed cell death-1 (PD-1)-targeted treatment is ineffective for a sizable minority of patients, and drug resistance still cannot be overcome.

Methods

To explore the mechanisms of immunotherapy and identify new therapeutic opportunities in lung adenocarcinoma (LUAD), data from patients who did and did not respond to the anti-PD-1 treatment were evaluated using single-cell RNA sequencing, and bulk RNA sequencing were collected.

Results

We investigated the gene expression that respond or not respond to immunotherapy in diverse cell types and revealed transcriptional characteristics at the single-cell level. To ultimately explore the molecular response or resistance to anti-PD-1 therapy, cell-cell interactions were carried out to identify the different LRIs (ligand-receptor interactions) between untreated patients vs. no-responders, untreated patients vs. responders, and responders vs. non-responders. Next, two molecular subgroups were proposed based on 73 LRI genes, and subtype 1 had a poor survival status and was likely to be the immunosuppressive tumor subtype. Furthermore, based on the LASSO Cox regression analysis results, we found that TNFSF13, AXL, KLRK1, FAS, PROS1, and CDH1 can be distinct prognostic biomarkers, immune infiltration levels, and responses to immunotherapy in LUAD.

Discussion

Altogether, the effects of immunotherapy were connected to LRIs scores, indicating that potential medications targeting these LRIs could contribute to the clinical benefit of immunotherapy. Our integrative omics analysis revealed the mechanisms underlying the anti-PD-1 therapy response and offered abundant clues for potential strategies to improve precise diagnosis and immunotherapy.
Case report: Blue rubber bleb nevus syndrome with Kasabach-Merritt phenomenon in a neonate
Authors: Pi Mengqi , Zhao Lei , Xu Weiyang , Xu Miao , Ding Yu
Published: April 2023

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterized by multifocal venous malformations that can affect any organ or tissue. Kasabach-Merritt phenomenon (KMP) is a serious and extremely rare complication of BRBNS. This report describes a neonate with BRBNS with KMP who was successfully diagnosed and treated with low-dose sirolimus and glucocorticoids. A 13-day-old female infant was born with multiple tumors on her head, neck, shoulder, back, abdomen, limbs, perineum, etc. some of which were blue. Laboratory examinations showed thrombocytopenia, anemia and coagulopathy. BRBNS with KMP was diagnosed. Oral low-dose sirolimus combined with glucocorticoids was administered. After 6 months of regular follow-up, the lesions in the child were significantly decreased, and there were no signs of KMP recurrence. The presence of KMP should be considered in patients diagnosed with BRBNS who present with thrombocytopenia, anemia and coagulopathy. Sirolimus combined with glucocorticoid therapy can be administered to save the patient's life.
Reducing the time delay of oxygen transport to the neonate on continuous positive airway pressure support: A bench study
Authors: Tejkl Leos , Kudrna Petr , Rafl Jakub , Bachman Thomas E.
Published: April 2023

Background

Premature newborns often require oxygen support as part of their therapy. Systems for oxygen administration are developed to assure adequate oxygenation of newborns. Several factors were identified in the systems that contribute to the time delay between the change in the set inspiratory oxygen fraction and its actual delivery to tissues. In this study, we aimed to reduce the physical delay in oxygen delivery to newborns.

Methods

We developed an O2 Flush System (O2-FS) that brings the source of oxygen as close to a patient as possible to make oxygen available for rapid delivery that compensates for the physical delay in the ventilator circuit. The O2-FS system is built around an electromechanical on/off valve. We validated the O2-FS concept in experiments with non-invasive Continuous Positive Airways Pressure (CPAP) ventilators.

Results

The O2-FS accelerated oxygen delivery with all the tested systems and arrangements, typically by 5–15 s. We also observed that the application of supplemental oxygen increased the pressure in the ventilator circuit by 3–4 cmH2O which may mitigate the apneic pauses that are common in premature newborns.

Conclusions

The O2-FS system may work as a universal accessory of the CPAP lung ventilator and shorten the distribution of oxygen to the patient during oxygen desaturation events, possibly eliminating or interrupting apneic pauses in neonates, for whom oxygen therapy is an essential treatment. In clinical practice, the O2-FS could help maintain normoxemic saturation values through adequate oxygen dosing in preterm neonates, thus reducing morbidity and mortality.
NeuroProtect, a Candidate Formula From Traditional Chinese Medicine, Attenuates Amyloid-β and Restores Synaptic Structures in APP/PS1 Transgenic Mice
Authors: Tan Yan , Wang Xu , Zhang Jiani , Zhang Huawei , Li Haiyan , Peng Tiantian , Chen Weihang , Wei Peng , Liu Zhaoheng , He Fang , Li Jiao , Ding Haimin , Li Na , Wang Zhaoyang , Zhang Zhenqiang , Hua Qian
Published: April 2023

Background: Alzheimer’s disease (AD) is the most common cause of dementia. The emerging data suggest that cognitive decline occurred in the setting of Aβ accumulation with synaptic dysfunction, which started to happen at preclinical stages. Then, presymptomatic intervention is more critical to postponing AD processing. Traditional Chinese medicine has a long history of treating and preventing dementia. Findings have shown that the decoction of Panax notoginseng and Gardenia jasminoides Ellis enhances memory functions in patients with stroke, and their main components, Panax notoginseng saponins (PNS) and geniposide (GP), improved memory abilities in experimental AD models. Since herbal medicine has advantages in protection with few side effects, we wish to extend observations of the NeuroProtect (NP) formulation for reducing amyloid-β and restoring synaptic structures in APP/PS1 transgenic mice.

Methods: APP/PS1 transgenic mice and their wild-type littermates were fed with control, NP, and their components from 4 to 7 months of age. We assessed the synaptic structure by Golgi staining, analyzed the amyloid deposits by Thioflavin-S staining, and measured related protein levels by Western blot or ELISA. We used the Morris water maze and shuttle box test to evaluate cognitive functions.

Results: Compared to WT mice, APP/PS1 mice are characterized by the accumulation of amyloid plaques, reducing synaptic structure richness and memory deficits. NP prevents these changes and ameliorates cognitive deficits. These effects may have been due to the contribution of its components by inhibition of insoluble amyloid-β deposition and restoration of synaptic structures.

Conclusion: These findings reveal a beneficial effect of NP on AD progression under an early intervention strategy and provide a food supplement for AD prevention.
Extended Application of Genomic Selection to Screen Multi-Omics Data for the Development of Novel Pyroptosis-Immune Signatures and Predicting Immunotherapy of Glioma
Authors: Ma Shuai , Wang Fang , Wang Nan , Jin Jiaqi , Yan Xiuwei , Wang Lili , Zheng Xiangrong , Hu Shaoshan , Du Jianyang
Published: April 2023

Glioma is one of the most human malignant diseases and the leading cause of cancer-related deaths worldwide. Nevertheless, the present stratification systems do not accurately predict the prognosis and treatment benefit of glioma patients. Currently, no comprehensive analyses of multi-omics data have been performed to better understand the complex link between pyroptosis and immune. In this study, we constructed four pyroptosis immune subgroups by pyroptosis regulators and obtained nine pyroptosis immune signatures by analyzing the differentially expressed genes between the four pyroptosis immune subgroups. Nine novel pyroptosis immune signatures were provided for assessing the complex heterogeneity of glioma by the analyses of multi-omics data. The pyroptosis immune prognostic model (PIPM) was constructed by pyroptosis immune signatures, and the PIPM risk score was established for glioma cohorts with a total of 1716 samples. Then, analyses of the tumor microenvironment revealed an unanticipated correlation of the PIPM risk score with stemness, immune checkpoint expression, infiltrating the immune system, and therapy response in glioma. The low PIPM risk score patients had a better response to immunotherapy and showed sensitivity to radio-chemotherapy. The results of the pan-cancer analyses revealed the significant correlation between the PIPM risk score and clinical outcome, immune infiltration, and stemness. Taken together, we conclude that pyroptosis immune signatures may be a helpful tool for overall survival prediction and treatment guidance for glioma and other tumors patients.
VPA improves ferroptosis in tubular epithelial cells after cisplatin-induced acute kidney injury
Authors: Li Yan , Li Ke , Zhao Weihao , Wang Haodong , Xue Xiaodong , Chen Xianghui , Li Wantao , Xu Peihao , Wang Kexin , Liu Pengfei , Tian Xuefei , Fu Rongguo
Published: April 2023

Background: As a novel non-apoptotic cell death, ferroptosis has been reported to play a crucial role in acute kidney injury (AKI), especially cisplatin-induced AKI. Valproic acid (VPA), an inhibitor of histone deacetylase (HDAC) 1 and 2, is used as an antiepileptic drug. Consistent with our data, a few studies have demonstrated that VPA protects against kidney injury in several models, but the detailed mechanism remains unclear.

Results: In this study, we found that VPA prevents against cisplatin-induced renal injury via regulating glutathione peroxidase 4 (GPX4) and inhibiting ferroptosis. Our results mainly indicated that ferroptosis presented in tubular epithelial cells of AKI humans and cisplatin-induced AKI mice. VPA or ferrostatin-1 (ferroptosis inhibitor, Fer-1) reduced cisplatin-induced AKI functionally and pathologically, which was characterized by reduced serum creatinine, blood urea nitrogen, and tissue damage in mice. Meanwhile, VPA or Fer-1 treatment in both in vivo and in vitro models, decreased cell death, lipid peroxidation, and expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), reversing downregulation of GPX4. In addition, our study in vitro indicated that GPX4 inhibition by siRNA significantly weakened the protective effect of VPA after cisplatin treatment.

Conclusion: Ferroptosis plays an essential role in cisplatin-induced AKI and inhibiting ferroptosis through VPA to protect against renal injury is a viable treatment in cisplatin-induced AKI.
Strategy insight: Mechanical properties of biomaterials’ influence on hydrogel-mesenchymal stromal cell combination for osteoarthritis therapy
Authors: Ying Haoli , Shen Chengchun , Pan Ruolang , Li Xiongfeng , Chen Ye
Published: April 2023

Osteoarthritis (OA) is a kind of degenerative joint disease usually found in older adults and those who have received meniscal surgery, bringing great suffering to a number of patients worldwide. One of the major pathological features of OA is retrograde changes in the articular cartilage. Mesenchymal stromal cells (MSCs) can differentiate into chondrocytes and promote cartilage regeneration, thus having great potential for the treatment of osteoarthritis. However, improving the therapeutic effect of MSCs in the joint cavity is still an open problem. Hydrogel made of different biomaterials has been recognized as an ideal carrier for MSCs in recent years. This review focuses on the influence of the mechanical properties of hydrogels on the efficacy of MSCs in OA treatment and compares artificial materials with articular cartilage, hoping to provide a reference for further development of modified hydrogels to improve the therapeutic effect of MSCs.
Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids
Authors: Abugomaa Amira , Elbadawy Mohamed , Ishihara Yusuke , Yamamoto Haru , Kaneda Masahiro , Yamawaki Hideyuki , Shinohara Yuta , Usui Tatsuya , Sasaki Kazuaki
Published: April 2023

Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is necessary. Chaga mushrooms are popular to have several health-promoting and anti-cancer potentials. Organoid culture can recapitulate tumor heterogeneity, epithelial environment, and genetic and molecular imprints of the original tissues. In the previous study, we generated dog bladder cancer organoids (DBCO) as a novel experimental model of muscle-invasive BCO. Therefore, the present study aimed to examine the anti-tumor potentials of Chaga mushroom extract (Chaga) against DBCO. Four strains of DBCO were used in the present study. Treatment with Chaga inhibited the cell viability of DBCO in a concentration-dependent way. Treatment of DBCO with Chaga has significantly arrested its cell cycle and induced apoptosis. Expression of bladder CSC markers, CD44, C-MYC, SOX2, and YAP1, declined in the Chaga-treated DBCO. Also, Chaga inhibited the phosphorylation of ERK in DBCO. Expression of downstream signals of ERK, C-MYC, and Cyclins (Cyclin-A2, Cyclin-D1, Cyclin-E1, and CDK4) was also inhibited by Chaga in DBCO. Interestingly, the combinational treatment of DBCO with Chaga and anti-cancer drugs, vinblastine, mitoxantrone, or carboplatin, showed a potentiating activity. In vivo, Chaga administration decreased tumor growth and weight of DBCO-derived xenograft in mice with the induction of necrotic lesions. In conclusion, Chaga diminished the cell viability of DBCO by inhibiting proliferation-related signals and stemness conditions as well as by arresting the cell cycle. Collectively, these data suggest the value of Chaga as a promising natural supplement that could potentiate the effect of adjuvant chemotherapy, lower its adverse effects, and thus, limit the recurrence and metastasis of BC.
Ethnobotanical uses, phytochemistry and biological activity of the genus Euclea: A review
Authors: Taye Abebe Dagne , Bizuneh Gizachew Kassahun , Kasahun Asmamaw Emagn
Published: April 2023

Euclea (Ebenaceae) is a genus of flowering shrubs and trees widely distributed in Africa, the Comoro Islands, and Arabia. This review aimed to evaluate the ethnobotanical uses, phytochemistry, and biological activities of the genus Euclea on available research reports. This was achieved through PubMed, Medline, Google Scholar, Science Direct, Taylor and Francis Online, Wiley Online Library which provides access to scientific and medical research. The extensive literature survey revealed that plants that belong to this genus are used as folkloric medicine for the treatment of diabetes mellitus, toothache, diarrhea, cancer, malaria, leprosy, and genital and oral diseases in the case of HIV/AIDS-related diseases. To date, more than 40 secondary metabolites have been isolated and identified from these plants, especially from E natalensis and E. divinorum. Among these, naphthoquinones, terpenes, and flavonoids are potential secondary metabolites with profound biological activities. Euclea plant extracts and their bioactive compounds possess outstanding pharmacological properties, especially antimalarial, antidiabetic, anticancer, antimicrobial, and antioxidant properties.
Overview of CW electron guns and LCLS-II RF gun performance
Authors: Zhou F. , Adolphsen C. , Dowell D. , Xiang R.
Published: April 2023

Various continuous-wave (CW) electron gun technologies are reviewed, including DC, superconducting radio frequency RF (SRF), hybrid DC-SRF and normal-conducting RF. Also, the SLAC Linac Coherent Light Source II (LCLS-II) normal-conducting RF gun and injector are described, and the performance to date, including the bunch emittance achieved and the dark current observed, is presented.
Genomic analyses provide insights into the genome evolution and environmental adaptation of the tobacco moth Ephestia elutella
Authors: Xu Jiadan , Li Bo , Jiang Zhimin , Wang Weimin , Yang Yi , Yang Maofa , Ye Xinhai
Published: April 2023

Ephestia elutella is a major pest responsible for significant damage to stored tobacco over many years. Here, we conduct a comparative genomic analysis on this pest, aiming to explore the genetic bases of environmental adaptation of this species. We find gene families associated with nutrient metabolism, detoxification, antioxidant defense and gustatory receptors are expanded in the E. elutella genome. Detailed phylogenetic analysis of P450 genes further reveals obvious duplications in the CYP3 clan in E. elutella compared to the closely related species, the Indianmeal moth Plodia interpunctella. We also identify 229 rapidly evolving genes and 207 positively selected genes in E. elutella, respectively, and highlight two positively selected heat shock protein 40 (Hsp40) genes. In addition, we find a number of species-specific genes related to diverse biological processes, such as mitochondria biology and development. These findings advance our understanding of the mechanisms underlying processes of environmental adaptation on E. elutella and will enable the development of novel pest management strategies.
Ectopic expression of DnaJ type-I protein homolog of Vigna aconitifolia (VaDJI) confers ABA insensitivity and multiple stress tolerance in transgenic tobacco plants
Authors: Gautam Ranjana , Meena Rajesh Kumar , Rampuria Sakshi , Shukla Pawan , Kirti P. B.
Published: April 2023

Reduced crop productivity results from altered plant physiological processes caused by dysfunctional proteins due to environmental stressors. In this study, a novel DnaJ Type-I encoding gene, VaDJI having a zinc finger motif in its C-terminal domain was found to be induced early upon treatment with heat stress (within 5 min) in a heat tolerant genotype of Vigna aconitifolia RMO-40. VaDJI is induced by multiple stresses. In tobacco, ectopic expression of VaDJI reduced ABA sensitivity during seed germination and the early stages of seedling growth of transgenic tobacco plants. Concomitantly, it also improved the ability of transgenic tobacco plants to withstand drought stress by modulating the photosynthetic efficiency, with the transgenic plants having higher Fv/Fm ratios and reduced growth inhibition. Additionally, transgenic plants showed a reduced build-up of H2O2 and lower MDA levels and higher chlorophyll content during drought stress, which attenuated cell damage and reduced oxidative damage. An analysis using the qRT-PCR study demonstrated that VaDJI overexpression is associated with the expression of some ROS-detoxification-related genes and stress-marker genes that are often induced during drought stress responses. These findings suggest a hypothesis whereby VaDJI positively influences drought stress tolerance and ABA signalling in transgenic tobacco, and suggests that it is a potential gene for genetic improvement of drought and heat stress tolerance in crop plants.
The Impact of Post-traumatic Stress of SARS-CoV-2 Affliction on Psychological and Mental Health of Student Survivors: Cross Sectional Study
Authors: Dixit Snehil , Musa Alamin , Sillva Audrey Borghi , Reddy Ravi Shankar , Abohashrh Mohammed , Kakaraparthi Venkata Nagaraj , Asiri Faisal , Caruso Flavia Rossi , Govindappa Shashi Kumar , Mohammed Arif Ahmad
Published: April 2023

Graphical Abstract

Psychological, mental health, and academic performance evaluation post COVID-19 infection among students.
Precision neuromodulation: Promises and challenges of spinal stimulation for multi-modal rehabilitation
Authors: Bandres Maria F. , Gomes Jefferson L. , Moreno Romero Gerson N. , Twyman Avery R. , McPherson Jacob Graves
Published: April 2023

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar presentations when developing spinal stimulation-based therapies. We also motivate advancement of multi-modal rehabilitation paradigms, which leverage the dense interconnectivity of sensorimotor spinal networks and the unique ability of electrical stimulation to modulate these networks to facilitate and guide simultaneous rehabilitation across domains.
Development and validation of a prognostic nomogram for rectal cancer patients who underwent surgical resection
Authors: Zhao Bochao , Wang Jingchao , Ma Zhicheng , Ye Haikun , Yang Tao , Meng Kewei
Published: April 2023

Objective: The purpose of this study was to develop and validate a nomogram model for the prediction of survival outcome in rectal cancer patients who underwent surgical resection.

Methods: A total of 9,919 consecutive patients were retrospectively identified using the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were determined by the univariate and multivariate Cox analysis. The nomogram model for the prediction of cancer-specific survival (CSS) in rectal cancer patients were developed based on these prognostic variables, and its predictive power was assessed by the concordance index (C-index). Calibration curves were plotted to evaluate the associations between predicted probabilities and actual observations. The internal and external cohort were used to further validate the predictive performance of the prognostic nomogram.

Results: All patients from the SEER database were randomly split into a training cohort (n = 6,944) and an internal validation cohort (n = 2,975). The baseline characteristics of two cohorts was comparable. Independent prognostic factors were identified as age, pT stage, lymph node metastasis, serum CEA level, tumor size, differentiation type, perineural invasion, circumferential resection margin involvement and inadequate lymph node yield. In the training cohort, the C-index of the nomogram was 0.719 (95% CI: 0.696–0.742), which was significantly higher than that of the TNM staging system (C-index: 0.606, 95% CI: 0.583–0.629). The nomogram had a C-index of 0.726 (95% CI: 0.691–0.761) for the internal validation cohort, indicating a good predictive power. In addition, an independent cohort composed of 202 rectal cancer patients from our institution were enrolled as the external validation. Compared with the TNM staging system (C-index: 0.573, 95% CI: 0.492–0.654), the prognostic nomogram still showed a better predictive performance, with the C-index of 0.704 (95% CI: 0.626–0.782). Calibration plots showed a good consistency between predicted probability and the actual observation in the training and two validation cohorts.

Conclusion: The nomogram showed an excellent predictive ability for survival outcome of rectal cancer patients, and it might provide an accurate prognostic stratification and help clinicians determine individualized treatment strategies.
Studies of Satellite Position Measurements of LEO CubeSat to Identify the Motion Mode Relative to Its Center of Mass
Authors: Belokonov Igor , Timbai Ivan , Nikolaev Petr
Published: April 2023

This paper addresses the possibility of reconstructing motion relative to the center of mass of a low Earth orbit (LEO) nanosatellite of the CubeSat 3U standard using satellite position measurements (Two-Line Element Set (TLE)). This kind of task needs to be performed in the case where it is not possible to establish radio communication with the nanosatellite after it is launched into orbit. Therefore, it is important for the nanosatellite developers to develop some understanding of what is going on with the nanosatellite in order to be able to analyze the current situation after deployment. The study was carried out on the example of the aerodynamically stabilized SamSat-218D nanosatellite developed by the professors and students of Samara National Research University. SamSat-218D was launched into a near-circular orbit with an average altitude of 486 km on April 2016 during the first launch campaign from the Vostochny cosmodrome. Knowledge of CubeSat aerodynamics allows estimating the nature of its possible motion relative to the CubeSat center of mass by ballistic coefficient changes, evaluated with the use of satellite position measurements. The analysis showed that SamSat-218D performed spatial rotation with an angular velocity of more than two degree per second and had not stabilized aerodynamically by 2 March 2022, when it entered the atmosphere and was destroyed.
Attrition Risk and Aircraft Suitability Prediction in U.S. Navy Pilot Training Using Machine Learning
Authors: Prasad-Rao Jubilee , Pinon Fischer Olivia J. , Rowe Neil C. , Williams Jesse R. , Puranik Tejas G. , Mavris Dimitri N. , Natali Michael W. , Tindall Mitchell J. , Atkinson Beth W.
Published: April 2023

The cost to train a basic qualified U.S. Navy fighter aircraft pilot is nearly USD 10 M. The training includes primary, intermediate, and advanced stages, with the advanced stage involving extensive flight training, and, thus, is very expensive as a result. Despite the screening tests in place and early-stage attrition, 4.5% of aviators undergo attrition in this most expensive stage. Key reasons for aviator attrition include poor flight performance, voluntary withdrawals, and medical reasons. The reduction in late-stage attrition offers several financial and operational benefits to the U.S. Navy. To that end, this research leverages feature extraction and machine learning techniques on the very sparse flight test grades of student aviators to identify those with a high risk of attrition early in training. Using about 10 years of historical U.S. Navy pilot training data, trained models accurately predicted 50% of attrition with a 4% false positive rate. Such models could help the U.S. Navy save nearly USD 20 M a year in attrition costs. In addition, machine learning models were trained to recommend a suitable training aircraft type for each student aviator. These capabilities could help better answer the need for pilots and reduce the time and cost to train them.
Responses of Micropropagated Rhubarb (Rheum rhaponticum) Plantlets to Different Growing Media and Light Conditions in the Greenhouse
Authors: Wojtania Agnieszka , Matysiak Bożena , Mieszczakowska-Frąc Monika , Nowak Jacek S. , Szwejda-Grzybowska Justyna
Published: April 2023

Cultivating red-stalked rhubarb plants is an important source of raw materials for producing health-promoting foods. The quality and quantity of rhubarb crops are significantly dependent on planting material. To obtain high-quality planting material for the value selection of the rhubarb ‘Raspberry’, we evaluated the morphological and physiological responses of micropropagated plantlets to different growth substrates and light quality during early growth ex vitro in the greenhouse. The plantlets were grown in high-EC (GM1) and low-EC (GM2) peat substrates under four light-emitting diodes (LED) light treatments as supplementary lighting (SL) in the wintertime: 100% red (R), 100% blue (B), white light [44.4% green (G), 24.4% B, 28.9% R; 2.2% far red (FR)] and R+B+G+FR (49.4/16.3/10.3/23.8%) light. Compared to the control (natural sunlight), applied LED lighting significantly increased all growth parameters, but only in plantlets grown in GM1 substrate. Among LED treatments, R+B+G+FR light had the most stimulative effect on all growth parameters (length of leaf petioles, leaf area, biomass) and soluble sugar production. Still, it decreased the levels of phenolic compounds in the leaf petioles. Phenolic synthesis, mainly anthocyanins, was the highest under white light (622.8 mg·100 g−1 dry mass), followed by red (601.8 mg·100 g−1), blue (464.4 mg·100 g−1), and R+B+G+FR light (416.4 mg·100 g−1). High anthocyanin accumulation under R-LED light was associated with high antioxidant activity and growth cessation. Hence, for optimal effects related to plant growth and anthocyanin biosynthesis, the use of W-LED lighting is recommended for the early growth ex vitro of micropropagated rhubarb plantlets.