bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the development of the digital economy improve carbon emission efficiency?
Authors: Han Jun , Jiang Tianhe
Published: December 2022

The improvement of carbon emission efficiency is guided by high-quality economic development, and the organic integration of ecology and economy is an important goal of putting sustainable economic development into action. Based on China's provincial panel data from 2008 to 2019, this article constructs a digital economy development index from the perspective of the digital economy and analyzes its impacts on carbon emission efficiency. The conclusion is that the development of the digital economy has significantly improved carbon emission efficiency. Through the analysis of the spatial spillover effect, it is found that regional carbon emission efficiency has a spatial correlation, but the development of the digital economy has no significant impact on the carbon emission efficiency of neighboring regions. Industrial structure adjustment, the energy structure, and technological progress are further analyzed as three mechanisms affecting carbon emission efficiency. It is found that the quality of industrial structure adjustment significantly promotes the improvement of carbon emission efficiency, while the energy structure significantly inhibits its improvement, and the range of industrial structure adjustment and technological progress have no significant impact on carbon emission efficiency. Based on the threshold effect, carbon emission efficiency be promoted only when the energy structure is in the interval unit (0.1288, 0.2441) and technological progress is >1.0591. Based on the above conclusion, we put forward corresponding policy suggestions.
Initial characterization of immune microenvironment in pheochromocytoma and paraganglioma
Authors: Jin Bo , Han Wencong , Guo Jingjing , Tian Jie , He Shiming , Gong Yanqing , Zhou Jingcheng , He Qun , Shen Qi , Zhang Zheng
Published: December 2022

Due to fewer adverse events, faster onset of action, and longer durable responses compared to chemotherapy, immunotherapy has been widely used to treat advanced solid tumors. Moreover, immunotherapy can improve the autoimmune status, thus allowing patients to benefit from the treatment in the long term. The immune microenvironment status is closely associated with the response to chemotherapies. Here, we analyzed the characteristics of the immune microenvironment in pheochromocytoma and paraganglioma (PPGL). Immunohistochemistry showed that PD-L1 is sparely expressed in PPGL with low positive rates and low expression levels, an expression pattern, that is, not correlated with tumor malignancy. Moreover, the level of intratumoral CD4+ and CD8+ lymphocyte infiltration in PPGL is low, suggesting that the immune microenvironment in PPGL may be in “immune desertification” or “immune rejection” states in which CD4+ and CD8+ lymphocyte infiltration is prevented, rendering immunotherapy less effective. In sum, our results indicate that PPGL is a microsatellite-stable tumor with low tumor mutational burden (TMB) levels, weak neoantigen production, and poor tumor antigenicity, hinting at a poor response of PPGL to chemotherapies.
Comprehensive analysis of a novel cuproptosis-related lncRNA signature associated with prognosis and tumor matrix features to predict immunotherapy in soft tissue carcinoma
Authors: Liu Binfeng , Pang Ke , Feng Chengyao , Liu Zhongyue , Li Chenbei , Zhang Haixia , Liu Ping , Li Zhihong , He Shasha , Tu Chao
Published: December 2022

Background: A crucial part of the malignant processes of soft tissue sarcoma (STS) is played by cuproptosis and lncRNAs. However, the connection between cuproptosis-related lncRNAs (CRLs) and STS is nevertheless unclear. As a result, our objective was to look into the immunological activity, clinical significance, and predictive accuracy of CRLs in STS.

Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, respectively, provided information on the expression patterns of STS patients and the general population. Cuproptosis-related lncRNA signature (CRLncSig) construction involved the univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analysis. The predictive performance of the CRLncSig was evaluated using a serial analysis. Further research was done on the connections between the CRLncSig and the tumor immune milieu, somatic mutation, immunotherapy response, and chemotherapeutic drug susceptibility. Notably, an in vitro investigation served to finally validate the expression of the hallmark CRLs.

Results: A novel efficient CRLncSig composed of seven CRLs was successfully constructed. Additionally, the low-CRLncSig group’s prognosis was better than that of the high-CRLncSig group’s based on the new CRLncSig. The innovative CRLncSig then demonstrated outstanding, consistent, and independent prognostic and predictive usefulness for patients with STS, according to the evaluation and validation data. The low-CRLncSig group’s patients also displayed improved immunoreactivity phenotype, increased immune infiltration abundance and checkpoint expression, and superior immunotherapy response, whereas those in the high-CRLncSig group with worse immune status, increased tumor stemness, and higher collagen levels in the extracellular matrix. Additionally, there is a noticeable disparity in the sensitivity of widely used anti-cancer drugs amongst various populations. What’s more, the nomogram constructed based on CRLncSig and clinical characteristics of patients also showed good predictive ability. Importantly, Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) demonstrated that the signature CRLs exhibited a significantly differential expression level in STS cell lines.

Conclusion: In summary, this study revealed the novel CRLncSig could be used as a promising predictor for prognosis prediction, immune activity, tumor immune microenvironment, immune response, and chemotherapeutic drug susceptibility in patients with STS. This may provide an important direction for the clinical decision-making and personalized therapy of STS.
Challenges to the implementation of telemedicine in abortion care for victims of sexual violence in Brazil
Authors: Galli Beatriz , Dillon Jina
Published: December 2022

The article focuses the recent dynamics resulting from state institutions adding more legal and regulatory barriers to abortion care access, particularly against the use of telemedicine for sexual violence victims in Brazil. It presents a case study from a lawsuit targeting a pioneer public health service on the city of Uberlandia to ban telemedicine in abortion care. The case study highlights human rights violations of women's right to health as well as the recent threats to the right to safe legal abortion care. It also provides legal arguments—based on scientific evidence and international human rights standards—that support the use of telemedicine for abortion care.
Upregulation of leucine-rich alpha-2 glycoprotein: A key regulator of inflammation and joint fibrosis in patients with severe knee osteoarthritis
Authors: Sarkar Ashish , Chakraborty Debolina , Kumar Vijay , Malhotra Rajesh , Biswas Sagarika
Published: December 2022

Introduction

Osteoarthritis (OA) is a degenerative disease of the joints mainly affecting older individuals. Since the etiology behind the progression of OA is not well understood, several associated consequences, such as synovial joint stiffness and its progression due to joint fibrosis, are still poorly understood. Although a lot of developments have been achieved in the diagnosis and management of OA, synovial fibrosis remains one of the major challenging consequences. The present study was therefore focused on understanding the mechanism of synovial fibrosis, which may further contribute to improving symptomatic treatments, leading to overall improvements in the treatment outcomes of patients with OA.

Methods

We used advanced proteomic techniques including isobaric tag for relative and absolute quantitation and sequential window acquisition of all theoretical mass spectra for the identification of differentially expressed proteins in the plasma samples of patients with OA. An in silico study was carried out to evaluate the association of the identified proteins with their biological processes related to fibrosis and remodeling of the extracellular matrix (ECM). The most significantly upregulated protein was then validated by Western blot and enzyme-linked immunosorbent assay. The target protein was then further investigated for its role in inflammation and joint fibrosis using an in vitro study model.

Results

Leucine-rich alpha-2 glycoprotein (LRG1) was found to be the most highly differentially expressed upregulated (9.4-fold) protein in the plasma samples of patients with OA compared to healthy controls. The knockdown of LRG1 followed by in vitro studies revealed that this protein promotes the secretion of the ECM in synovial cells and actively plays a role in wound healing and cell migration. The knockdown of LRG1 further confirmed the reduction of the inflammatory- and fibrosis-related markers in primary cells.

Conclusion

LRG1 was identified as a highly significant upregulated protein in the plasma samples of patients with OA. It was found to be associated with increased fibrosis and cell migration, leading to enhanced inflammation and joint stiffness in OA pathogenesis.
The CMV-encoded G protein-coupled receptors M33 and US28 play pleiotropic roles in immune evasion and alter host T cell responses
Authors: White Timothy M. , Bonavita Cassandra M. , Stanfield Brent A. , Farrell Helen E. , Davis-Poynter Nicholas J. , Cardin Rhonda D.
Published: December 2022

Introduction

Human cytomegalovirus (HCMV) is a global health threat due to its ubiquity and lifelong persistence in infected people. During latency, host CD8+ T cell responses to HCMV continue to increase in a phenomenon known as memory inflation. We used murine CMV (MCMV) as a model for HCMV to characterize the memory inflation response to wild-type MCMV (KP) and a latency-defective mutant (ΔM33stop), which lacks M33, an MCMV chemokine receptor homolog. M33 is essential for normal reactivation from latency and this was leveraged to determine whether reactivation in vivo contributes to T cell memory inflation.

Methods

Mice were infected with wild-type or mutant MCMV and T cell responses were analyzed by flow cytometry at acute and latent time points. Ex vivo reactivation and cytotoxicity assays were carried out to further investigate immunity and virus replication. Quantitative reverse-transcriptase polymerase chain reaction (q-RTPCR) was used to examine gene expression during reactivation. MHC expression on infected cells was analyzed by flow cytometry. Finally, T cells were depleted from latently-infected B cell-deficient mice to examine the in vivo difference in reactivation between wild-type and ΔM33stop.

Results

We found that ΔM33stop triggers memory inflation specific for peptides derived from the immediate-early protein IE1 but not the early protein m164, in contrast to wild-type MCMV. During ex vivo reactivation, gene expression in DM33stop-infected lung tissues was delayed compared to wild-type virus. Normal gene expression was partially rescued by substitution of the HCMV US28 open reading frame in place of the M33 gene. In vivo depletion of T cells in immunoglobulin heavy chain-knockout mice resulted in reactivation of wild-type MCMV, but not ΔM33stop, confirming the role of M33 during reactivation from latency. Further, we found that M33 induces isotype-specific downregulation of MHC class I on the cell surface suggesting previously unappreciated roles in immune evasion.

Discussion

Our results indicate that M33 is more polyfunctional than previously appreciated. In addition to its role in reactivation, which had been previously described, we found that M33 alters viral gene expression, host T cell memory inflation, and MHC class I expression. US28 was able to partially complement most functions of M33, suggesting that its role in HCMV infection may be similarly pleotropic.
PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort study
Authors: Chen Shubin , Wei Haowen , Zhao Wenhua , Jiang Wei , Ning Ruiling , Zhou Shaozhang , Tan Liping , Wang Huilin , Su Cuiyun , He Jianbo , Zeng Aiping , Zhao Yun , Yu Qitao
Published: December 2022

Background

The aim of this study was to assessment the efficacy and safety of Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer.

Methods

In this study, pre-treatment clinical and laboratory indicators from 73 patients with advanced non-small cell lung cancer were retrieved for retrospective analysis. According to the therapy regimes they received, the patients were separated into groups, PD-1/PD-L1 inhibitors plus chemotherapy group (PC group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents’ group (PA group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents plus chemotherapy group (PAC group). Cox’s proportional hazards regression model and Kaplan-Meier (KM) curves were used to assess the connection between treatment regimens and progression free survival (PFS) and overall survival (OS). In addition, the association of treatment regimens with the risk of disease progression and death was evaluated by subgroup analysis.

Results

The average age of the enrolled patients was 58.2 ± 10.2 years and 75.3% were male. Multivariate analyses showed that patients in PA group (Disease progression: HR 0.4, P=0.005. Death: HR 0.4, P=0.024) and PAC group (Disease progression: HR 0.3, P=0.012. Death: HR 0.3, P=0.045) had a statistically significant lower hazard ratio (HR) for disease progression and death compared to patients in PC group. Kaplan-Meier analysis showed that patients in PA group (mPFS:7.5 vs.3.5, P=0.00052. mOS:33.1 vs.21.8, P=0.093) and PAC group (mPFS:5.1 vs.3.5, P=0.075. mOS:37.3 vs.21.8, P=0.14) had a longer PFS and OS compared to patients in PC group. In all the pre-defined subgroups, patients in PA and PAC groups showed a decreasing trend in the risk of disease progression and death in most subgroups. The patients in PA group (DCR:96.3% vs.58.3%, P=0.001) and PAC group (DCR:100% vs.58.3%, P=0.019) had a better disease control rate (DCR) than patients in PC group.

Conclusion

PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy were superior to PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment in patients with advanced non-small cell lung cancer.
Optimal design of topological waveguides by machine learning
Authors: Du Zongliang , Ding Xianggui , Chen Hui , Liu Chang , Zhang Weisheng , Luo Jiachen , Guo Xu
Published: December 2022

Topological insulators supply robust edge states and can be used to compose novel waveguides to protect energy propagation against various defects. For practical applications, topological waveguides with a large working bandwidth and highly localized interface mode are desired. In the present work, mechanical valley Hall insulators are described by explicit geometry parameters using the moving morphable component method first. From the geometry parameters, artificial neural networks (ANN) are then well-trained to predict the topological property and the bounds of nontrivial bandgaps. Incorporating those ANN models, mathematical formulation for designing optimal mechanical topological waveguides can be solved efficiently, with an acceleration of more than 10,000 times than the traditional topology optimization approach.
A mucosal recovery software tool for endoscopic submucosal dissection in early gastric cancer
Authors: Zhao Yinuo , Wang Huogen , Fan Yanyan , Jin Chaohui , Xu Qinwei , Jing Jiyong , Zhang Tianqiao , Zhang Xuedong , Chen Wanyuan
Published: December 2022

Background

Due to the limited diagnostic ability, the low detection rate of early gastric cancer (EGC) is a serious health threat. The establishment of the mapping between endoscopic images and pathological images can rapidly improve the diagnostic ability to detect EGC. To expedite the learning process of EGC diagnosis, a mucosal recovery map for the mapping between ESD mucosa specimen and pathological images should be performed in collaboration with endoscopists and pathologists, which is a time-consuming and laborious work.

Methods

20 patients at the Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College from March 2020 to July 2020 were enrolled in this study. We proposed the improved U-Net to obtain WSI-level segmentation results, and the WSI-level results can be mapped to the macroscopic image of the specimen. For the convenient use, a software pipeline named as “Pathology Helper” for integration the workflow of the construction of mucosal recovery maps was developed.

Results

The MIoU and Dice of our model can achieve 0.955 ± 0.0936 and 0.961 ± 0.0874 for WSI-level segmentation, respectively. With the help of “Pathology Helper”, we can construct the high-quality mucosal recovery maps to reduce the workload of endoscopists and pathologists.

Conclusion

“Pathology Helper” will accelerate the learning of endoscopists and pathologists, and rapidly improve their abilities to detect EGC. Our work can also improve the detection rate of early gastric cancer, so that more patients with gastric cancer will be treated in a timely manner.
Development and validation of a new set of indicators to assess the quality of maternal and child nutritional care at the primary care
Authors: Ancira-Moreno Monica , Omaña-Guzmán Isabel , Bautista-Morales Arturo Cuauhtémoc , Acosta-Ruiz Omar , Hernández Cordero Sonia , Burrola-Méndez Soraya , Vilar-Compte Mireya , Monterrubio Flores Eric , Kaufer-Horwitz Martha , Pérez Navarro Cecilia , Muñoz-Manrique Cinthya , Mazariegos Mónica , Trejo-Domínguez Alejandra , Sánchez Muzquiz Belen , Cajero Ariana , Brero Mauro , Sachse Matthias , Cobo Armijo Fernanda
Published: December 2022

Introduction

Maternal and child malnutrition is a worldwide public health problem with short, medium, and long-term adverse consequences for both mother and child. In Mexico, maternal and child malnutrition represents a serious public health problem that must be urgently addressed. In this context, Primary Health Care (PHC) plays an important role in the prevention, detection, monitoring, and treatment of the different forms of maternal and child malnutrition. Assessing the quality of nutritional care offered at this level of care is necessary in order to improve it; however, there are no indicators for the evaluation of this quality. Therefore, this study aimed at developing a set of indicators to assess the quality of maternal and child nutritional care at PHC.

Methods

We developed indicators for different stages of life: preconception, pregnancy, infancy, and preschool age. A systematic review of the literature on clinical guidelines for the prevention, diagnosis, and treatment of the different forms of malnutrition was carried out; the recommendations of the guidelines evaluated with good quality were extracted.

Results

Based on these recommendations, 22 indicators were constructed. A pilot study was carried out to validate the indicators and 16 indicators were selected to assess the maternal and child nutritional care at PHC.
Relative bradycardia presented as a clinical feature of Brucella melitensis infection: A case report
Authors: Huang Kai , Yu Xuxia , Yu Yushan , Cen Yin , Shu Jie , Yang Naibin , Chu Jinguo
Published: December 2022

Brucellosis, caused by Brucella species, is an infectious disease transmitted through contact with infected animals or their secretions. The clinical disease is characterized by fever and headache. Relative bradycardia is an inappropriate response of heart rate to body temperature, in which the heart rate does not increase proportionally despite a high fever. In this report, we document one case of Brucella melitensis infection demonstrating relative bradycardia. To our knowledge, this is the first report of relative bradycardia in a patient with brucellosis.
A practical guide to managing hypertension, hyperlipidemia, and hyperglycemia in patients with chronic myeloid leukemia
Authors: Ahmed Khalid , Kaddoura Rasha , Yassin Mohamed A.
Published: December 2022

Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML) since their approval. Although safe in general, TKIs carry concerns about cardiovascular adverse events. Hypertension, diabetes, and dyslipidemia are among the most common baseline comorbidities among CML patients. Guidelines for the management of the existing comorbidities or those related to TKI therapy are lacking. This paper will review hypertension, hyperglycemia and hyperlipidemia reported in CML patients or associated with TKI therapy and then propose a simple guide on their management.
A comparative study of gastric histopathology sub-size image classification: From linear regression to visual transformer
Authors: Hu Weiming , Chen Haoyuan , Liu Wanli , Li Xiaoyan , Sun Hongzan , Huang Xinyu , Grzegorzek Marcin , Li Chen
Published: December 2022

Introduction

Gastric cancer is the fifth most common cancer in the world. At the same time, it is also the fourth most deadly cancer. Early detection of cancer exists as a guide for the treatment of gastric cancer. Nowadays, computer technology has advanced rapidly to assist physicians in the diagnosis of pathological pictures of gastric cancer. Ensemble learning is a way to improve the accuracy of algorithms, and finding multiple learning models with complementarity types is the basis of ensemble learning. Therefore, this paper compares the performance of multiple algorithms in anticipation of applying ensemble learning to a practical gastric cancer classification problem.

Methods

The complementarity of sub-size pathology image classifiers when machine performance is insufficient is explored in this experimental platform. We choose seven classical machine learning classifiers and four deep learning classifiers for classification experiments on the GasHisSDB database. Among them, classical machine learning algorithms extract five different image virtual features to match multiple classifier algorithms. For deep learning, we choose three convolutional neural network classifiers. In addition, we also choose a novel Transformer-based classifier.

Results

The experimental platform, in which a large number of classical machine learning and deep learning methods are performed, demonstrates that there are differences in the performance of different classifiers on GasHisSDB. Classical machine learning models exist for classifiers that classify Abnormal categories very well, while classifiers that excel in classifying Normal categories also exist. Deep learning models also exist with multiple models that can be complementarity.

Discussion

Suitable classifiers are selected for ensemble learning, when machine performance is insufficient. This experimental platform demonstrates that multiple classifiers are indeed complementarity and can improve the efficiency of ensemble learning. This can better assist doctors in diagnosis, improve the detection of gastric cancer, and increase the cure rate.
Efficacy of positive airway pressure therapy and high flow nasal cannula oxygen in acute cardiogenic pulmonary oedema: A protocol for systematic review and network meta-analysis
Authors: Niu Jianyi , He Zhenfeng , Zha Shanshan , Huang Qiaoyun , Fu Wei , Feng Shengchuan , Guan Lili , Zhou Luqian , Chen Rongchang
Published: December 2022

Introduction

Positive airway pressure (PAP) therapy is currently the first-line respiratory support technique for acute respiratory failure (ARF) due to acute cardiogenic pulmonary edema (ACPE), but the accompanied adverse events and patient's intolerance with treatment in some cases limited its use in clinical practice. Some recent trials indicated that high-flow nasal cannula oxygen (HFNO) is a promising alternative to PAP therapy. In order to choose the optimum treatment for patients with ACPE, this network meta-analysis will firstly compares the efficacy of HFNO, PAP, and conventional oxygen therapy (COT).

Methods and analysis

The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement and its extension for network meta-analysis will be followed in the conduct of this investigation. We will examine these databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. The ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform Search Portal will be used to search ongoing trials. Only randomized controlled trials meeting the eligibility criteria will be included. Through the Cochrane Collaboration's tool, the included studies' risk of bias will be assessed. The pairwise meta-analysis will be performed with RevMan 5.4.1 software. A Bayesian network meta-analysis will use random-effects models to derive odds ratios for the treatment effects of all interventions compared to each other using R software (version 3.6.1), and the rjags and gemtc packages. The Q statistic and I2 index will be used for investigating the heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence.
Metaproteomics reveals methyltransferases implicated in dichloromethane and glycine betaine fermentation by ‘Candidatus Formimonas warabiya’ strain DCMF
Authors: Holland Sophie I. , Vázquez-Campos Xabier , Ertan Haluk , Edwards Richard J. , Manefield Michael J. , Lee Matthew
Published: December 2022

Dichloromethane (DCM; CH2Cl2) is a widespread pollutant with anthropogenic and natural sources. Anaerobic DCM-dechlorinating bacteria use the Wood–Ljungdahl pathway, yet dechlorination reaction mechanisms remain unclear and the enzyme(s) responsible for carbon-chlorine bond cleavage have not been definitively identified. Of the three bacterial taxa known to carry out anaerobic dechlorination of DCM, ‘Candidatus Formimonas warabiya’ strain DCMF is the only organism that can also ferment non-chlorinated substrates, including quaternary amines (i.e., choline and glycine betaine) and methanol. Strain DCMF is present within enrichment culture DFE, which was derived from an organochlorine-contaminated aquifer. We utilized the metabolic versatility of strain DCMF to carry out comparative metaproteomics of cultures grown with DCM or glycine betaine. This revealed differential abundance of numerous proteins, including a methyltransferase gene cluster (the mec cassette) that was significantly more abundant during DCM degradation, as well as highly conserved amongst anaerobic DCM-degrading bacteria. This lends strong support to its involvement in DCM dechlorination. A putative glycine betaine methyltransferase was also discovered, adding to the limited knowledge about the fate of this widespread osmolyte in anoxic subsurface environments. Furthermore, the metagenome of enrichment culture DFE was assembled, resulting in five high quality and two low quality draft metagenome-assembled genomes. Metaproteogenomic analysis did not reveal any genes or proteins for utilization of DCM or glycine betaine in the cohabiting bacteria, supporting the previously held idea that they persist via necromass utilization.
Indocyanine green as a near-infrared theranostic agent for ferroptosis and apoptosis-based, photothermal, and photodynamic cancer therapy
Authors: Tseng Hsiang-Ching , Kuo Chan-Yen , Liao Wei-Ting , Chou Te-Sen , Hsiao Jong-Kai
Published: December 2022

Ferroptosis is a recently discovered programmed cell death pathway initiated by reactive oxygen species (ROS). Cancer cells can escape ferroptosis, and strategies to promote cancer treatment are crucial. Indocyanine green (ICG) is a near-infrared (NIR) fluorescent molecule used in the imaging of residual tumor removal during surgery. Growing attention has been paid to the anticancer potential of ICG-NIR irradiation by inducing ROS production and theranostic effects. Organic anion transmembrane polypeptide (OATP) 1B3 is responsible for ICG metabolism. Additionally, the overexpression of OATP1B3 has been reported in several cancers. However, whether ICG combined with NIR exposure can cause ferroptosis remains unknown and the concept of treating OATP1B3-expressing cells with ICG-NIR irradiation has not been validated. We then used ICG as a theranostic molecule and an OATP1B3-transfected fibrosarcoma cell line, HT-1080 (HT-1080-OATP1B3), as a cell model. The HT-1080-OATP1B3 cell could promote the uptake of ICG into the cytoplasm. We observed that the HT-1080-OATP1B3 cells treated with ICG and exposed to 808-nm laser irradiation underwent apoptosis, as indicated by a reduction in mitochondrial membrane potential, and upregulation of cleaved Caspase-3 and Bax but downregulation of Bcl-2 expression. Moreover, lipid ROS production and consequent ferroptosis and hyperthermic effect were noted after ICG and laser administration. Finally, in vivo study findings also revealed that ICG with 808-nm laser irradiation has a significant effect on cancer suppression. ICG is a theranostic molecule that exerts synchronous apoptosis, ferroptosis, and hyperthermia effects and thus can be used in cancer treatment. Our findings may facilitate the development of treatment modalities for chemo-resistant cancers.
CT after interhospital transfer in acute ischemic stroke: Imaging findings and impact of prior intravenous contrast administration
Authors: Mueller Franziska , Fabritius Matthias P. , Stueckelschweiger Lena , Kiesl Sophia , Moench Sebastian , Tiedt Steffen , Rémi Jan , Kellert Lars , Herzberg Moriz , Küpper Clemens , Dimitriadis Konstantinos , Ricke Jens , Puhr-Westerheide Daniel , Liebig Thomas , Kunz Wolfgang G. , Reidler Paul
Published: December 2022

Objectives

Large vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients.

Results

We included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p < 0.001) and lower ASPECTS (median: 8 vs. 9, p < 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (β = −0.25, p = 0.004) but not with TFSO (β = −0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (β = −0.39 vs. β = −0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p < 0.001).

Conclusion

Imaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core.
Development and validation of a dynamic risk prediction system for constipation in patients with amyotrophic lateral sclerosis
Authors: Niu Tongyang , Zhou Xiaomeng , Li Xin , Liu Tingting , Liu Qi , Li Rui , Liu Yaling , Dong Hui
Published: December 2022

Introduction

Although constipation is a common non-motor symptom in patients with amyotrophic lateral sclerosis (ALS), it is poorly valued. Moreover, there is a bidirectional effect between constipation and neuropsychiatric and sleep disturbances. Thus, these symptoms are better treated simultaneously. Therefore, this study aimed to develop and validate a model for predicting the risk of constipation in ALS patients, to help clinicians identify and treat constipation early.

Methods

Data of 118 ALS admissions from an observational prospective cohort, registered between March 2017 and December 2021, were analyzed. Demographic data were obtained. Constipation was assessed using the Knowles–Eccersley–Scott Symptom Questionnaire. The severity of ALS was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). The Pittsburgh Sleep Quality Index (PSQI) was used to assess patients' sleep status. The least absolute shrinkage and selection operator (LASSO) regression model was used to select factors and construct a nomogram. Nomogram model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC). The model was internally validated using bootstrap validation in the current cohort.

Results

Age, family history of constipation, total ALSFRS-R score, site of onset, total PSQI score, and depressed, were identified as significant predictors of the risk of constipation in ALS patients. The prediction model was validated to have good accuracy (Hosmer–Lemeshow test: χ2 = 11.11, P > 0.05) and discrimination (AUC = 0.856, 95% confidence interval: 0.784–0.928). DCA and CIC showed that the nomogram model had excellent clinical performance.

Conclusions

A web-based ALS constipation risk calculator with good predictive performance was constructed to identify patients at high risk of constipation and to allow early intervention in a clinical context.
Type I interferon signaling in SARS-CoV-2 associated neurocognitive disorder (SAND): Mapping host-virus interactions to an etiopathogenesis
Authors: Vavougios George D. , Erausquin Gabriel A. de , Snyder Heather M.
Published: December 2022

Epidemiological, clinical, and radiological studies have provided insights into the phenomenology and biological basis of cognitive impairment in COVID-19 survivors. Furthermore, its association with biomarkers associated with neuroinflammation and neurodegeneration supports the notion that it is a distinct aspect of LongCOVID syndrome with specific underlying biology. Accounting for the latter, translational studies on SARS-CoV-2's interactions with its hosts have provided evidence on type I interferon dysregulation, which is seen in neuroinflammatory and neurodegenerative diseases. To date, studies attempting to describe this overlap have only described common mechanisms. In this manuscript, we attempt to propose a mechanistic model based on the host-virus interaction hypothesis. We discuss the molecular basis for a SARS-CoV-2-associated neurocognitive disorder (SAND) focusing on specific genes and pathways with potential mechanistic implications, several of which have been predicted by Vavougios and their research group. Furthermore, our hypothesis links translational evidence on interferon-responsive gene perturbations introduced by SARS-CoV-2 and known dysregulated pathways in dementia. Discussion emphasizes the crosstalk between central and peripheral immunity via danger-associated molecular patterns in inducing SAND's emergence in the absence of neuroinfection. Finally, we outline approaches to identifying targets that are both testable and druggable, and could serve in the design of future clinical and translational studies.
Moxibustion alleviates depression-like behavior in rats with Crohn’s disease by inhibiting the kynurenine pathway metabolism in the gut-brain axis
Authors: Bao Chunhui , Huang Jin , Wu Huangan , Ma Yueying , Zhou Hongyu , Chen Liming , Yang Dandan , Liu Huirong , Shi Yin , Lu Yuan
Published: December 2022

Background

Moxibustion is a potential therapy for inflammatory bowel disease-related depression, but its specific mechanism of action is unclear. This study aimed to investigate the molecular mechanism by which moxibustion alleviates depressive behavior in rats with Crohn’s disease (CD).

Methods

The CD rat model was established with 2,4,6-trinitrobenzenesulfonic acid. Treatment with moxibustion was applied to Tianshu (ST25, bilateral), Qihai (CV6), and Baihui (GV20) acupoints, and the effect of moxibustion was compared with that of the combination of moxibustion plus indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, 1-methyltryptophan (1-MT). The effects of moxibustion and moxibustion plus 1-MT combination on colonic inflammation and depressive behavior (assessed by forced swimming test, sucrose preference test, and open field test) were investigated. The changes in IDO1, TNF-α, and IL-1β in rat colon and hippocampus were assessed by Western blot (WB). Gas chromatography-mass spectrometry, immunofluorescence staining, and WB were applied to detect kynurenine pathway (KP) metabolites, hippocampal neuronal activity, and microglia activation, respectively.

Results

Both moxibustion and moxibustion plus 1-MT combination significantly alleviated intestinal inflammation and depressive behavior, downregulated the levels of IDO1 in the colon and hippocampus, and inhibited inflammation-inducing factors IL-1β and TNF-α, as well as the kynurenine/tryptophan (KYN/TRP) ratio of KP metabolites, and upregulated the kynurenic acid (KYNA)/KYN ratio and the KYNA/quinolinic acid (QUIN) ratio in the hippocampus in rats with CD; Hippocampal ionized calcium-binding adaptor molecule-1 (Iba-1), c-fos protein expression, activated microglia, and neuronal activation was also significantly reduced by moxibustion and moxibustion plus 1-MT. The addition of 1-MT did not significantly increase the therapeutic effect of moxibustion.

Conclusion

Moxibustion can improve depressive behavior in rats with CD, which may be related to its regulation of KP metabolism in the gut-brain axis and inhibition of hippocampal microglia activation and neuronal activation.
Modular organization of locomotor networks in people with severe spinal cord injury
Authors: Sun Soo Yeon , Giszter Simon F. , Harkema Susan J. , Angeli Claudia A.
Published: December 2022

Introduction

Previous studies support modular organization of locomotor circuitry contributing to the activation of muscles in a spatially and temporally organized manner during locomotion. Human spinal circuitry may reorganize after spinal cord injury; however, it is unclear if reorganization of spinal circuitry post-injury affects the modular organization. Here we characterize the modular synergy organization of locomotor muscle activity expressed during assisted stepping in subjects with complete and incomplete spinal cord injury (SCI) of varying chronicity, before any explicit training regimen. We also investigated whether the synergy characteristics changed in two subjects who achieved independent walking after training with spinal cord epidural stimulation.

Methods

To capture synergy structures during stepping, individuals with SCI were stepped on a body-weight supported treadmill with manual facilitation, while electromyography (EMGs) were recorded from bilateral leg muscles. EMGs were analyzed using non-negative matrix factorization (NMF) and independent component analysis (ICA) to identify synergy patterns. Synergy patterns from the SCI subjects were compared across different clinical characteristics and to non-disabled subjects (NDs).

Results

Results for both NMF and ICA indicated that the subjects with SCI were similar among themselves, but expressed a greater variability in the number of synergies for criterion variance capture compared to NDs, and weaker correlation to NDs. ICA yielded a greater number of muscle synergies than NMF. Further, the clinical characteristics of SCI subjects and chronicity did not predict any significant differences in the spatial synergy structures despite any neuroplastic changes. Further, post-training synergies did not become closer to ND synergies in two individuals.

Discussion

These findings suggest fundamental differences between motor modules expressed in SCIs and NDs, as well as a striking level of spatial and temporal synergy stability in motor modules in the SCI population, absent the application of specific interventions.
VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety
Authors: Abdul Mannan , Yan Hao-Qi , Zhao Wei-Nan , Lyu Xiao-Bin , Xu Zheng , Yu Xiao-Lu , Gao Yi-Hong , Cao Jun-Li
Published: December 2022

Background

Besides the established role of dopamine neurons and projections in nociceptive stimuli, the involvement of ventral tegmental area (VTA) glutamatergic projections to nucleus accumbens (NAc) in pain remains unknown. In the present study, we aimed to examine the role of VTA glutamatergic projections to NAc in painful stimuli and its related behavioral changes.

Methods

Unilateral chronic constrictive injury (CCI) of sciatic nerve or intraplantar hind paw injections (i.pl.) of complete Freund’s adjuvant (CFA) were used to develop pathological pain models in wild-type and VGluT2-Cre mice. The involvement of VTA glutamatergic neurons with projections to NAc in CCI-induced pain model was noted by c-Fos labeling and firing rate recordings. Pain response and pain-related behavior changes to the artificial manipulation of the VTA glutamatergic projections to NAc were observed by Hargreaves tests, von Frey tests, open field tests, elevated maze tests, and sucrose preference tests.

Results

Glutamatergic neurons in VTA had efferent inputs to shell area of the NAc. The CCI pain model significantly increased neuronal activity and firing rate in VTA glutamate neurons with projections to NAc. The photoinhibition of these glutamatergic projections relieved CCI-induced neuropathic pain and CFA-induced acute and chronic inflammatory pain. Moreover, pathological neuropathic pain-induced anxiety and less sucrose preference were also relieved by inhibiting the VTA glutamatergic projections to NAc.

Conclusion

Together, glutamatergic inputs from VTA to NAc contribute to chronic neuropathic and inflammatory pain and pain-related anxiety and depressive behaviors, providing a mechanism for developing novel therapeutic methods.
Complementary feeding methods and introduction of ultra-processed foods: A randomized clinical trial
Authors: Moreira Paula Ruffoni , Nunes Leandro Meirelles , Giugliani Elsa Regina Justo , Gomes Erissandra , Führ Jordana , Neves Renata Oliveira , Belin Christy Hannah Sanini , Bernardi Juliana Rombaldi
Published: December 2022

Introduction

Complementary feeding (CF) is defined as a period when foods, other than milk, are introduced to the infant’s diet. Unfortunately, frequent consumption of ultra-processed foods (UPF) has become highly prevalent early in an infant’s life. The aim was to verify the association of CF methods with the introduction of UPF in early childhood.

Methods

This randomized clinical trial involved pairs of mother-infants, allocated in groups receiving different CF interventions: strict Parent-Led Weaning (PLW); strict Baby-Led Introduction to SolidS (BLISS), or mixed-method. The intervention consisted of a counseling session on healthy eating at the child’s 5.5 months of age. A structured questionnaire was created based on the NOVA classification for the definition of UPF and applied at 9 and 12 months. The effect of the CF method intervention was measured by a survival curve for UPF offered for the first time in early childhood between groups. Cox regression was used to estimate its magnitude. The primary analysis was done in three groups (PLW, BLISS, and Mixed) and the secondary analysis was done in two groups (PLW, and BLISS + Mixed).

Results

A total of 139 mother-infant pairs were eligible and 129 followed the study. The prevalence of infants who were exposed to UPF in early childhood was 58.9% (n = 76), being 71.4% in the PLW group, 53.3% in the BLISS group, and 52.4% in the Mixed group, without differences between them (p = 0.133). The PLW group intervention had a greater chance of exposure to ice cream or popsicles (p = 0.032) and sweet crackers (p = 0.009), compared with the other two CF groups. The Cox regression did not find significant differences between the three groups. However, the regression with two groups estimated a 38% reduction in the offer of UPF in the BLISS + Mixed group intervention (p = 0.049).

Discussion

The CF intervention promoting greater infant autonomy (BLISS and Mixed) was associated with a reduction in the offer of UPF in early childhood. This knowledge may contribute to supporting strategies aimed at reducing UPF consumption by the young infant.

Brazilian registry of clinical trials (ReBEC)

[https://ensaiosclinicos.gov.br/rg/RBR-229scm], identifier [RBR-229scm U1111-1226-9516].
An instant beverage rich in nutrients and secondary metabolites manufactured from stems and leaves of Panax notoginseng
Authors: Liang Zhengwei , Liu Kunyi , Li Ruoyu , Ma Baiping , Zheng Wei , Yang Shengchao , Zhang Guanghui , Zhao Yinhe , Chen Junwen , Zhao Ming
Published: December 2022

Introduction

Radix Notoginseng, one of the most famous Chinese traditional medicines, is the dried root of Panax notoginseng (Araliaceae). Stems and leaves of P. notoginseng (SLPN) are rich in secondary metabolites and nutrients, and authorized as a food resource, however, its utilization needs further research.

Methods

A SLPN-instant beverage was manufactured from SLPN through optimization by response surface design with 21-fold of 48.50% ethanol for 39 h, and this extraction was repeated twice; the extraction solution was concentrated to 1/3 volume using a vacuum rotatory evaporator at 45°C, and then spray dried at 110°C. Nutritional components including 14 amino acids, ten mineral elements, 15 vitamins were detected in the SLPN-instant beverage; forty-three triterpenoid saponins, e.g., ginsenoside La, ginsenoside Rb3, notoginsenoside R1, and two flavonoid glycosides, as well as dencichine were identified by UPLC-MS.

Results

The extraction rate of SLPN-instant beverage was 37.89 ± 0.02%. The majority nutrients were Gly (2.10 ± 0.63 mg/g), His (1.23 ± 0.07 mg/g), α-VE (18.89 ± 1.87 μg/g), β-VE (17.53 ± 1.98 μg/g), potassium (49.26 ± 2.70 mg/g), calcium (6.73 ± 0.27 mg/g). The total saponin of the SLPN-instant beverage was 403.05 ± 34.98 mg/g, majority was notoginsenoside Fd and with contents of 227 ± 2.02 mg/g. In addition, catechin and γ-aminobutyric acid were detected with levels of 24.57 ± 0.21 mg/g and 7.50 ± 1.85 mg/g, respectively. The SLPN-instant beverage showed good antioxidant activities with half maximal inhibitory concentration (IC50) for scavenging hydroxyl (OH–) radicals, superoxide anion (O2–) radicals, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS+) radicals were 0.1954, 0.2314, 0.4083, and 0.3874 mg/mL, respectively.

Conclusion

We optimized an analytical method for in depth analysis of the newly authorized food resource SLPN. Together, an instant beverage with antioxidant activity, rich in nutrients and secondary metabolites, was manufactured from SLPN, which may improve the utilization of SLPN.