bluuebunny/crossref_metadata_2025 huggingface dataset:
Communication About End of Life for Patients Living With Amyotrophic Lateral Sclerosis: A Scoping Review of the Empirical Evidence
Authors: Genuis Shelagh K. , Luth Westerly , Campbell Sandra , Bubela Tania , Johnston Wendy S.
Published: August 2021

Background: Communication about end of life, including advance care planning, life-sustaining therapies, palliative care, and end-of-life options, is critical for the clinical management of amyotrophic lateral sclerosis patients. The empirical evidence base for this communication has not been systematically examined.

Objective: To support evidence-based communication guidance by (1) analyzing the scope and nature of research on health communication about end of life for amyotrophic lateral sclerosis; and (2) summarizing resultant recommendations.

Methods: A scoping review of empirical literature was conducted following recommended practices. Fifteen health-related and three legal databases were searched; 296 articles were screened for inclusion/exclusion criteria; and quantitative data extraction and analysis was conducted on 211 articles with qualitative analysis on a subset of 110 articles that focused primarily on health communication. Analyses summarized article characteristics, themes, and recommendations.

Results: Analysis indicated a multidisciplinary but limited evidence base. Most reviewed articles addressed end-of-life communication as a peripheral focus of investigation. Generic communication skills are important; however, substantive and sufficient disease-related information, including symptom management and assistive devices, is critical to discussions about end of life. Few articles discussed communication about specific end-of-life options. Communication recommendations in analyzed articles draw attention to communication processes, style and content but lack the systematized guidance needed for clinical practice.

Conclusions: This review of primary research articles highlights the limited evidence-base and consequent need for systematic, empirical investigation to inform effective communication about end of life for those with amyotrophic lateral sclerosis. This will provide a foundation for actionable, evidence-based communication guidelines about end of life. Implications for research, policy, and practice are discussed.
Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID) After Stroke: Rationale, Design and Protocol for a Prospective Randomized Controlled Trial
Authors: Cai Lipeng , Rajah Gary , Duan Honglian , Gao Jie , Cheng Zhe , Xin Ruiqiang , Jiang Shangqian , Palmer Peter , Geng Xiaokun , Ding Yuchuan
Published: August 2021

Background: Despite intravenous thrombolysis and endovascular therapy for acute ischemic stroke (AIS), many survivors still have varying degrees of disability. Glyceryl trinitrate (GTN), a nitric oxide (NO) donor, has been previously reported to induce neuroprotection after AIS. The use of GTN to reduce brain damage after stroke remains yet to be elucidated. This study was designed to explore the safety, feasibility, and preliminary efficacy of intravenous administration of GTN after AIS.

Methods: A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to GTN group and control group with a 1:1 ratio (n = 40). Both groups will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the GTN group will receive intravenous administration of GTN (5 mg GTN in 50 ml saline at a rate of 0.4 mg/h that is continued for 12.5 h/day for 2 days) within 24 h of symptom onset. Participants allocated to the control group will receive intravenous administration at equal capacity of 0.9% normal saline (NS) (total 50 ml/day at 4 ml/h that is continued for 12.5 h/day for 2 days). The primary outcome is safety [systolic blood pressure (SBP) <110 mmHg, headache], while the secondary outcomes include changes in functional outcome and infarction volume.

Discussion: Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID) is a prospective randomized controlled trial that aims to ascertain the safety, feasibility, and preliminary efficacy of intravenous GTN as a neuroprotection strategy after AIS. These results will provide parameters for future studies as well as provide insights into treatment effects. Any possible neuroprotective qualities of GTN in AIS will also be elucidated.

Trial Registration:www.chictr.org.cn, identifier: ChiCTR2100046271.
Quantification of Cervical Cord Cross-Sectional Area: Which Acquisition, Vertebra Level, and Analysis Software? A Multicenter Repeatability Study on a Traveling Healthy Volunteer
Authors: Lukas Carsten , Bellenberg Barbara , Prados Ferran , Valsasina Paola , Parmar Katrin , Brouwer Iman , Pareto Deborah , Rovira Àlex , Sastre-Garriga Jaume , Gandini Wheeler-Kingshott Claudia A. M. , Kappos Ludwig , Rocca Maria A. , Filippi Massimo , Yiannakas Marios , Barkhof Frederik , Vrenken Hugo
Published: August 2021

Background: Considerable spinal cord (SC) atrophy occurs in multiple sclerosis (MS). While MRI-based techniques for SC cross-sectional area (CSA) quantification have improved over time, there is no common agreement on whether to measure at single vertebral levels or across larger regions and whether upper SC CSA can be reliably measured from brain images.

Aim: To compare in a multicenter setting three CSA measurement methods in terms of repeatability at different anatomical levels. To analyze the agreement between measurements performed on the cervical cord and on brain MRI.

Method: One healthy volunteer was scanned three times on the same day in six sites (three scanner vendors) using a 3T MRI protocol including sagittal 3D T1-weighted imaging of the brain (covering the upper cervical cord) and of the SC. Images were analyzed using two semiautomated methods [NeuroQLab (NQL) and the Active Surface Model (ASM)] and the fully automated Spinal Cord Toolbox (SCT) on different vertebral levels (C1–C2; C2/3) on SC and brain images and the entire cervical cord (C1–C7) on SC images only.

Results: CSA estimates were significantly smaller using SCT compared to NQL and ASM (p < 0.001), regardless of the cord level. Inter-scanner repeatability was best in C1–C7: coefficients of variation for NQL, ASM, and SCT: 0.4, 0.6, and 1.0%, respectively. CSAs estimated in brain MRI were slightly lower than in SC MRI (all p ≤ 0.006 at the C1–C2 level). Despite protocol harmonization between the centers with regard to image resolution and use of high-contrast 3D T1-weighted sequences, the variability of CSA was partly scanner dependent probably due to differences in scanner geometry, coil design, and details of the MRI parameter settings.

Conclusion: For CSA quantification, dedicated isotropic SC MRI should be acquired, which yielded best repeatability in the entire cervical cord. In the upper part of the cervical cord, use of brain MRI scans entailed only a minor loss of CSA repeatability compared to SC MRI. Due to systematic differences between scanners and the CSA quantification software, both should be kept constant within a study. The MRI dataset of this study is available publicly to test new analysis approaches.
Extrahippocampal Radiomics Analysis Can Potentially Identify Laterality in Patients With MRI-Negative Temporal Lobe Epilepsy
Authors: Cheong E-Nae , Park Ji Eun , Jung Da Eun , Shim Woo Hyun
Published: August 2021

Objective: The objective of the study was to investigate whether radiomics features of extrahippocampal regions differ between patients with epilepsy and healthy controls, and whether any differences can identify patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE).

Methods: Data from 36 patients with hippocampal sclerosis (HS) and 50 healthy controls were used to construct a radiomics model. A total of 1,618 radiomics features from the affected hippocampal and extrahippocampal regions were compared with features from healthy controls and the unaffected side of patients. Using a stepwise selection method with a univariate t-test and elastic net penalization, significant predictors for identifying TLE were separately selected for the hippocampus (H+) and extrahippocampal region (H–). Each model was independently validated with an internal set of MRI-negative adult TLE patients (n = 22) and pediatric validation cohort with MRI-negative TLE (n = 20) from another tertiary center; diagnostic performance was calculated using area under the curve (AUC) of the receiver-operating-characteristic curve analysis.

Results: Forty-eight significant H+ radiomic features and 99 significant H– radiomic features were selected from the affected side of patients and used to create a hippocampus model and an extrahippocampal model, respectively. Texture features were the most frequently selected feature. Training set showed slightly higher accuracy between hippocampal (AUC = 0.99) and extrahippocampal model (AUC = 0.97). In the internal validation and external validation sets, the extrahippocampal model (AUC = 0.80 and 0.92, respectively) showed higher diagnostic performance for identifying the affected side of patients than the hippocampus model (AUC = 0.67 and 0.69).

Significance: Radiomics revealed extrahippocampal abnormality in the affected side of patients with TLE and could potentially help to identify MRI-negative TLE.

Classification of Evidence: Class IV Criteria for Rating Diagnostic Accuracy Studies.
Multimodal Image Integration for Epilepsy Presurgical Evaluation: A Clinical Workflow
Authors: Jin Liri , Choi Joon Yul , Bulacio Juan , Alexopoulos Andreas V. , Burgess Richard C. , Murakami Hiroatsu , Bingaman William , Najm Imad , Wang Zhong Irene
Published: August 2021

Multimodal image integration (MMII) is a promising tool to help delineate the epileptogenic zone (EZ) in patients with medically intractable focal epilepsies undergoing presurgical evaluation. We report here the detailed methodology of MMII and an overview of the utility of MMII at the Cleveland Clinic Epilepsy Center from 2014 to 2018, exemplified by illustrative cases. The image integration was performed using the Curry platform (Compumedics Neuroscan™, Charlotte, NC, USA), including all available diagnostic modalities such as Magnetic resonance imaging (MRI), Positron Emission Tomography (PET), single-photon emission computed tomography (SPECT) and Magnetoencephalography (MEG), with additional capability of trajectory planning for intracranial EEG (ICEEG), particularly stereo-EEG (SEEG), as well as surgical resection planning. In the 5-year time span, 467 patients underwent MMII; of them, 98 patients (21%) had a history of prior neurosurgery and recurring seizures. Of the 467 patients, 425 patients underwent ICEEG implantation with further CT co-registration to identify the electrode locations. A total of 351 patients eventually underwent surgery after MMII, including 197 patients (56%) with non-lesional MRI and 223 patients (64%) with extra-temporal lobe epilepsy. Among 269 patients with 1-year post-operative follow up, 134 patients (50%) had remained completely seizure-free. The most common histopathological finding is focal cortical dysplasia. Our study illustrates the usefulness of MMII to enhance SEEG electrode trajectory planning, assist non-invasive/invasive data interpretation, plan resection strategy, and re-evaluate surgical failures. Information presented by MMII is essential to the understanding of the anatomo-functional-electro-clinical correlations in individual cases, which leads to the ultimate success of presurgical evaluation of patients with medically intractable focal epilepsies.
Gut Microbiota and Their Role in Health and Metabolic Disease of Dairy Cow
Authors: Xu Qingbiao , Qiao Qinqin , Gao Ya , Hou Jinxiu , Hu Mingyang , Du Yufeng , Zhao Ke , Li Xiang
Published: August 2021

Ruminants are mostly herbivorous animals that employ rumen fermentation for the digestion of feed materials, including dairy cows. Ruminants consume plant fibre as their regular diet, but lack the machinery for their digestion. For this reason, ruminants maintain a symbiotic relation with microorganisms that are capable of producing enzymes to degrade plant polymers. Various species of microflora including bacteria, protozoa, fungi, archaea, and bacteriophages are hosted at distinct concentrations for accomplishing complete digestion. The ingested feed is digested at a defined stratum. The polysaccharic plant fibrils are degraded by cellulolytic bacteria, and the substrate formed is acted upon by other bacteria. This sequential degradative mechanism forms the base of complete digestion as well as harvesting energy from the ingested feed. The composition of microbiota readily gets tuned to the changes in the feed habits of the dairy cow. The overall energy production as well as digestion is decided by the intactness of the resident communal flora. Disturbances in the homogeneity gastrointestinal microflora has severe effects on the digestive system and various other organs. This disharmony in communal relationship also causes various metabolic disorders. The dominance of methanogens sometimes lead to bloating, and high sugar feed culminates in ruminal acidosis. Likewise, disruptive microfloral constitution also ignites reticuloperitonitis, ulcers, diarrhoea, etc. The role of symbiotic microflora in the occurrence and progress of a few important metabolic diseases are discussed in this review. Future studies in multiomics provides platform to determine the physiological and phenotypical upgradation of dairy cow for milk production.
The Feasibility of a Fast Liver MRI Protocol for Lesion Detection of Adults at 3.0-T
Authors: Li Jing , Ma Chao , Chen Yukun , Fu Caixia , Wang Xinrui , Kuehn Bernd , Yang Qingsong , Lu Jianping
Published: August 2021

Purpose

To investigate the feasibility of a fast liver magnetic resonance imaging (MRI) protocol for lesion detection in adults using 3.0-T MRI.

Methods

A fast liver MRI exam protocol was proposed. The protocol included motion-resistant coronal T2-w sequence, axial T2-w fast spin echo sequence with fat suppression, axial in-op phase gradient recalled echo (GRE) T1, axial diffusion weighted imaging (DWI), and axial contrast-enhanced T1 sequences. To evaluate the diagnostic capacity of the proposed protocol, 31 consecutive patients (20 males and 11 females; mean age, 53.2 years) underwent a liver MRI exam with conventional sequences, including the proposed protocol as a subset. Images from the conventional protocol and extracted abbreviated protocol were independently read, and the diagnostic concordance rate was assessed for each patient. The concordance analysis is presented as the proportion of concordant cases between the two protocols.

Results

The net measurement time of the fast liver MRI protocol without adjustment and waiting time were 4 min and 28 s. In the 31 patients included in this study, 139 suspicious findings were found from both the conventional liver MR protocol and the fast liver MRI protocol. The diagnostic concordance rate was 96.4%.

Conclusions

The fast liver MRI protocol is feasible at 3.0-T, with a shorter exam time and high diagnostic concordance compared to the conventional liver MRI workflow.
Efficacy and Safety of Astragalus-Containing Traditional Chinese Medicine Combined With Platinum-Based Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis
Authors: Cheng Mengqi , Hu Jiaqi , Zhao Yuwei , Jiang Juling , Qi Runzhi , Chen Shuntai , Li Yaoyuan , Zheng Honggang , Liu Rui , Guo Qiujun , Zhang Xing , Qin Yinggang , Hua Baojin
Published: August 2021

Background

Astragalus-containing traditional Chinese medicine (TCM) is widely used as adjunctive treatment to platinum-based chemotherapy (PBC) in patients with advanced gastric cancer (AGC) in China. However, evidence regarding its efficacy remains limited. This study aimed to evaluate the efficacy and safety of Astragalus-containing TCM combined with PBC in AGC treatment.

Methods

We searched for literature (up to July 19, 2020) in eight electronic databases. The included studies were reviewed by two researchers. The main outcomes were the objective response rate (ORR), disease control rate (DCR), survival rate, quality of life (QOL), adverse drug reactions (ADRs), and peripheral blood lymphocyte levels. The effect estimate of interest was the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Trial sequential analysis (TSA) was used to detect the robustness of the primary outcome and to calculate the required information size (RIS). Certainty of the evidence was assessed using the GRADE profiler.

Results

Results based on available literature showed that, compared with patients treated with PBC alone, those treated with Astragalus-containing TCM had a better ORR (RR: 1.24, 95% CI: 1.15–1.34, P < 0.00001), DCR (RR: 1.10, 95% CI: 1.06–1.14, P < 0.00001), 1-year survival rate (RR: 1.41, 95% CI: 1.09–1.82, P = 0.009), 2-year survival rate (RR: 3.13, 95% CI: 1.80–5.46, P < 0.0001), and QOL (RR: 2.03, 95% CI: 1.70–2.43, P < 0.00001 and MD: 12.39, 95% CI: 5.48–19.30, P = 0.0004); higher proportions of CD3+ T cells and CD3+ CD4+ T cells; higher ratio of CD4+/CD8+ T cells; nature killer cells; and lower incidence of ADRs. Subgroup analysis showed that both oral and injection administration of Astragalus-containing TCM increased tumor response. Whether treatment duration was ≥8 weeks or <8 weeks, Astragalus-containing TCM could increase tumor response in AGC patients. Furthermore, Astragalus-containing TCM combined with oxaliplatin-based chemotherapy could increase the ORR and DCR; when with cisplatin, it could only increase the ORR.

Conclusion

Current low to moderate evidence revealed that Astragalus-containing TCM combined with PBC had better efficacy and less side effects in the treatment of AGC; however, more high-quality randomized studies are warranted.

Systematic Review Registration

PROSPERO, identifier CRD42020203486.
Targeting Adipokines in Obesity-Related Tumors
Authors: Pu Xi , Chen Deyu
Published: August 2021

Obesity, a global epidemic, is an independent risk factor for the occurrence and development of a variety of tumors, such as breast cancer, pancreatic cancer, ovarian cancer and colorectal cancer. Adipocytes are important endocrine cells in the tumor microenvironment of obesity-related tumors, which can secrete a variety of adipokines (such as leptin, adiponectin, estrogen, resistin, MIF and MCP-1, etc.), among which leptin, adiponectin and estrogen are the most in-depth and valuable ones. These adipokines are closely related to tumorigenesis and the progression of tumors. In recent years, more and more studies have shown that under chronic inflammatory conditions such as obesity, adipocytes secrete more adipokines to promote the tumorigenesis and development of tumors. However, it is worth noting that although adiponectin is also secreted by adipocytes, it has an anti-tumor effect, and can cross-talk with other adipokines (such as leptin and estrogen) and insulin to play an anti-tumor effect together. In addition, obesity is the main cause of insulin resistance, which can lead to the increase of the expression levels of insulin and insulin-like growth factor (IGF). As important regulators of blood glucose and lipid metabolism, insulin and IGF also play an important role in the progress of obesity related tumors. In view of the important role of adipokines secreted by adipocytes and insulin/IGF in tumors, this article not only elaborates leptin, adiponectin and estrogen secreted by adipocytes and their mechanism of action in the development of obesity- related tumors, but also introduces the relationship between insulin/IGF, a regulator of lipid metabolism, and obesity related tumors. At the same time, it briefly describes the cancer-promoting mechanism of resistin, MIF and MCP-1 in obesity-related tumors, and finally summarizes the specific treatment opinions and measures for various adipokines and insulin/insulin-like growth factors in recent years.
Non-Melanoma Skin Cancer in People Living With HIV: From Epidemiology to Clinical Management
Authors: Venanzi Rullo Emmanuele , Maimone Maria Grazia , Fiorica Francesco , Ceccarelli Manuela , Guarneri Claudio , Berretta Massimiliano , Nunnari Giuseppe
Published: August 2021

Skin cancers represent the most common human tumors with a worldwide increasing incidence. They can be divided into melanoma and non-melanoma skin cancers (NMSCs). NMSCs include mainly squamous cell (SCC) and basal cell carcinoma (BCC) with the latest representing the 80% of the diagnosed NMSCs. The pathogenesis of NMSCs is clearly multifactorial. A growing body of literature underlies a crucial correlation between skin cancer, chronic inflammation and immunodeficiency. Intensity and duration of immunodeficiency plays an important role. In immunocompromised patients the incidence of more malignant forms or the development of multiple tumors seems to be higher than among immunocompetent patients. With regards to people living with HIV (PLWH), since the advent of combined antiretroviral therapy (cART), the incidence of non-AIDS-defining cancers (NADCs), such as NMSCs, have been increasing and now these neoplasms represent a leading cause of illness in this particular population. PLWH with NMSCs tend to be younger, to have a higher risk of local recurrence and to have an overall poorer outcome. NMSCs show an indolent clinical course if diagnosed and treated in an early stage. BCC rarely metastasizes, while SCC presents a 4% annual incidence of metastasis. Nevertheless, metastatic forms lead to poor patient outcome. NMSCs are often treated with full thickness treatments (surgical excision, Mohs micro-graphic surgery and radiotherapy) or superficial ablative techniques (such as cryotherapy, electrodesiccation and curettage). Advances in genetic landscape understanding of NMSCs have favored the establishment of novel therapeutic strategies. Concerning the therapeutic evaluation of PLWH, it’s mandatory to evaluate the risk of interactions between cART and other treatments, particularly antiblastic chemotherapy, targeted therapy and immunotherapy. Development of further treatment options for NMSCs in PLWH seems needed. We reviewed the literature after searching for clinical trials, case series, clinical cases and available databases in Embase and Pubmed. We review the incidence of NMSCs among PLWH, focusing our attention on any differences in clinicopathological features of BCC and SCC between PLWH and HIV negative persons, as well as on any differences in efficacy and safety of treatments and response to immunomodulators and finally on any differences in rates of metastatic disease and outcomes.
Tumor Burden Measured by 18F-FDG PET/CT in Predicting Efficacy and Adverse Effects of Chimeric Antigen Receptor T-Cell Therapy in Non-Hodgkin Lymphoma
Authors: Hong Ruimin , Tan Su Yin Elaine , Wang Linqin , Zhao Xin , Zhou Linghui , Wang Guangfa , Zhang Mingming , Zhao Houli , Wei Guoqing , Wang Yiyun , Wu Wenjun , Zhang Yafei , Ni Fang , Hu Yongxian , Huang He , Zhao Kui
Published: August 2021

Chimeric antigen receptor (CAR) T-cell therapy has exhibited promising clinical outcomes in treating relapsed/refractory (R/R) B-cell hematologic malignancies. Current studies have shown a close correlation between baseline tumor burden and therapeutic response in CAR-T cell therapy. However, the roles of PET/CT metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), remain unclear in this setting. In this study, we retrospectively reviewed 41 R/R NHL patients. 18F-FDG PET/CT was used to measure the average standardized uptake value (SUVavg), MTV, and TLG of the lymphomatous lesions. These patients were divided into two groups according to the optimal cutoff values of respective PET/CT metabolic parameters. The multivariate analysis depicted that early post-therapy SUVavg (HR: 1.418, 95% CI: 1.029, 1.955; p = 0.033) and MTV (HR: 1.001, 95% CI: 1.000, 1.002; p = 0.041) were independent risk factors associated with OS and PFS, respectively. Patients with baseline SUVavg < 4.36 achieved a superior 1-year OS rate than the SUVavg ≥ 4.36 group (100.0% vs. 44.9%, p = 0.019). For the patients with lower values in early post-therapy SUVavg (<2.60) (51.1% vs. 0%, p < 0.001), MTV (<0.55 cm3) (53.6% vs. 0.0%, p = 0.001), and TLG (<1.54) (53.6% vs. 0.0%, p = 0.001), their 1-year PFS rates were higher than the compared groups. Moreover, patients with higher baseline tumor burdens were found to have significantly increased CRS incidence and cytokine levels. In conclusion, the PET/CT metabolic parameters are closely related to OS, PFS, and CRS in R/R NHL patients treated with CAR-T cells. This study may pave the way for building a comprehensive assessment system of tumor burden using 18F-FDG PET/CT, which can optimize therapeutic and supportive approaches in CAR-T cell therapy.
Novel Antimicrobial Treatment Strategy Based on Drug Delivery Systems for Acute Otitis Media
Authors: Kono Masamitsu , Umar Nafisa K. , Takeda Saori , Ohtani Makiko , Murakami Daichi , Sakatani Hideki , Kaneko Fumie , Nanushaj Denisa , Hotomi Muneki
Published: August 2021

Despite tremendous success of pneumococcal conjugated vaccine and antimicrobial treatment by amoxicillin, acute otitis media (AOM) still remains as a great medical concern. Failure of antimicrobial treatment includes several factors. The middle ear cavity is surrounded by bone tissue, which makes it difficult to maintain sufficient concentration of antibiotics. Tympanic membrane of AOM patients thickens and actually becomes a barrier for topical therapy. This review discusses novel antimicrobial treatment strategies based on drug delivery systems (DDS) for AOM. To deliver drugs enough to kill the pathogenic bacteria without systemic side effects, the development of new antimicrobial treatment strategy applying innovative drug DDS has been expected. The sustained-release DDS can achieve sufficient time for antimicrobial concentrations to exceed minimum inhibitory concentration (MIC) for time-dependent antibiotics as well as enough maximum concentration for dose-dependent antibiotics to eradicate causative pathogens in the middle ear. The development of trans-tympanic membranes of DDS, such as hydrogels with chemical permeation enhancers (CPEs), is another attractive strategy. Phage is a promising strategy for developing DDS-based therapies. The DDS formulations enable antimicrobial treatment of AOM by a single dose and thus, an attractive future antimicrobial treatment for AOM.
Targeting Fatty Acid Synthase Modulates Metabolic Pathways and Inhibits Cholangiocarcinoma Cell Progression
Authors: Tomacha Jittima , Dokduang Hasaya , Padthaisong Sureerat , Namwat Nisana , Klanrit Poramate , Phetcharaburanin Jutarop , Wangwiwatsin Arporn , Khampitak Tueanjit , Koonmee Supinda , Titapun Attapol , Jarearnrat Apiwat , Khuntikeo Narong , Loilome Watcharin
Published: August 2021

An aberrant regulation of lipid metabolism is involved in the pathogenesis and progression of cancer. Up-regulation of lipid biosynthesis enzymes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN) and HMG-CoA reductase (HMGCR), has been reported in many cancers. Therefore, elucidating lipid metabolism changes in cancer is essential for the development of novel therapeutic targets for various human cancers. The current study aimed to identify the abnormal expression of lipid-metabolizing enzymes in cholangiocarcinoma (CCA) and to evaluate whether they can be used as the targets for CCA treatment. Our study demonstrated that a high expression of FASN was significantly correlated with the advanced stage in CCA patients. In addition, survival analysis showed that high expression of FASN and HMGCR was correlated with shorter survival of CCA patients. Furthermore, FASN knockdown inhibited the growth, migration and invasion in CCA cell lines, KKU055 and KKU213, as well as induced cell cycle arrest and apoptosis in the CCA cell lines. In addition, metabolomics study further revealed that purine metabolism was the most relevant pathway involved in FASN knockdown. Adenosine diphosphate (ADP), glutamine and guanine levels significantly increased in KKU213 cells while guanine and xanthine levels remarkably increased in KKU055 cells showing a marked difference between the control and FASN knockdown groups. These findings provide new insights into the mechanisms associated with FASN knockdown in CCA cell lines and suggest that targeting FASN may serve as a novel CCA therapeutic strategy.
Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression
Authors: Qian He-Ya , Zhou Fang , Wu Rui , Cao Xiao-Jun , Zhu Tao , Yuan Hao-Dong , Chen Ya-Nan , Zhang Ping-An
Published: August 2021

Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (**p < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (**p < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (**p < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (**p < 0.01 vs. BCP + NS). What’s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.
Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis
Authors: Zhao Zhengde , Fu Qining , Hu Liangzhu , Liu Yangdong
Published: August 2021

Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis.

Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein–protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions.

Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1.

Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.
Circumventricular Organ Apelin Receptor Knockdown Decreases Blood Pressure and Sympathetic Drive Responses in the Spontaneously Hypertensive Rat
Authors: Griffiths Philip R. , Lolait Stephen J. , Paton Julian F. R. , O’Carroll Anne-Marie
Published: August 2021

The central site(s) mediating the cardiovascular actions of the apelin-apelin receptor (APJ) system remains a major question. We hypothesized that the sensory circumventricular organs (CVOs), interfacing between the circulation and deeper brain structures, are sites where circulating apelin acts as a signal in the central nervous system to decrease blood pressure (BP). We show that APJ gene (aplnr) expression was elevated in the CVOs of spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto (WKY) controls, and that there was a greater mean arterial BP (MABP) decrease following microinjection of [Pyr1]apelin-13 to the CVOs of SHRs compared to WKY rats. Lentiviral APJ-specific-shRNA (LV-APJ-shRNA) was used to knockdown aplnr expression, both collectively in three CVOs and discretely in individual CVOs, of rats implanted with radiotelemeters to measure arterial pressure. LV-APJ-shRNA-injection decreased aplnr expression in the CVOs and abolished MABP responses to microinjection of [Pyr1]apelin-13. Chronic knockdown of aplnr in any of the CVOs, collectively or individually, did not affect basal MABP in SHR or WKY rats. Moreover, knockdown of aplnr in any of the CVOs individually did not affect the depressor response to systemic [Pyr1]apelin-13. By contrast, multiple knockdown of aplnr in the three CVOs reduced acute cardiovascular responses to peripheral [Pyr1]apelin-13 administration in SHR but not WKY rats. These results suggest that endogenous APJ activity in the CVOs has no effect on basal BP but that functional APJ in the CVOs is required for an intact cardiovascular response to peripherally administered apelin in the SHR.
Metabolomic Analysis Provides New Insight Into Tolerance of Huanglongbing in Citrus
Authors: Suh Joon Hyuk , Tang Xixuan , Zhang Yi , Gmitter Frederick G. , Wang Yu
Published: August 2021

There have been efforts to develop citrus cultivars that are tolerant of Huanglongbing (HLB), a catastrophic phloem-limited disease. Previous studies demonstrated that continuous plant growth with phloem regeneration is one of the major characteristics of HLB tolerance. In this study, the metabolic mechanisms of HLB tolerance in citrus were elucidated using a multiple pathway-targeted metabolomic approach. Comparative analysis of healthy and infected HLB-tolerant and HLB-sensitive mandarin cultivars (Citrus reticulata) revealed differentially expressed metabolic responses among different groups. Pathway enrichment analysis indicated aspartate and glutamate metabolism, purine metabolism, and biosynthesis of plant hormones were upregulated in the tolerant group, except salicylic acid signaling. Catabolic pathways linked to energy-yielding metabolism were also upregulated in the tolerant group. These metabolisms and pathways were interconnected with each other, unveiling a pivotal metabolic network associated with HLB tolerance. In the network, auxins and cytokinins, the plant hormones responsible for plant growth and phloem regeneration, were accumulated. In addition, purine metabolites serving as energy carriers and nitrogen sources of plants were increased. Only salicylic acid-related metabolites for plant defense responses were decreased in the tolerant group. Our findings may evidence the strategy of HLB-tolerant cultivars that sustain plant growth and phloem formation rather than displaying direct plant defense to overcome the disease.
Family Life in Lockdown
Authors: Biroli Pietro , Bosworth Steven , Della Giusta Marina , Di Girolamo Amalia , Jaworska Sylvia , Vollen Jeremy
Published: August 2021

The lockdown imposed following the COVID-19 pandemic of spring 2020 dramatically changed the daily lives and routines of millions of people worldwide. We analyze how such changes contributed to patterns of activity within the household using a novel survey of Italian, British, and American families in lockdown. A high percentage report disruptions in the patterns of family life, manifesting in new work patterns, chore allocations, and household tensions. Though men have taken an increased share of childcare and grocery shopping duties, reallocations are not nearly as stark as disruptions to work patterns might suggest, and families having to reallocate duties report greater tensions. Our results highlight tightened constraints budging up against stable and gendered patterns of intra-household cooperation norms. While the long-run consequences of the COVID-19 lockdown on family life cannot be assessed at this stage, we point toward the likely opportunities and challenges.
Predicting Collective Action in a Secessionist Context: Different Motives for Two Opposed Stances
Authors: Dono Marcos , Alzate Monica , Sabucedo José-Manuel
Published: August 2021

Engagement in collective action is essential in the scenario of a secessionist struggle. In this scenario, two groups contend for an incompatible goal and one of them is favoured by the current status quo. Therefore, this context represents an excellent opportunity to compare the motives for participation among two groups whose situation and objectives differ drastically. We examined the motivations to participate in collective action of Catalan participants in the days leading to the independence referendum held in Catalonia (Spain) on the first of October 2017 (n= 719). As hypothesized, participation predicted by different motivations for each group. Regarding participation in the referendum, Catalan identity was the only predictor among pro-independence ranks, while those against independence showed a solidarity-based motivation. This work contributes to the literature by adapting previously researched collective action motivations to the context of a secessionist contention and providing evidence of their effect. Crucially, the motivations are different between supporters and opponents of independence, highlighting the need for examining the status and the stance on the system of groups when studying collective action.
Exploring the Multidimensional Links Between Trait Mindfulness and Trait Empathy
Authors: Himichi Toshiyuki , Osanai Hidekazu , Goto Takayuki , Fujita Hiroyo , Kawamura Yuta , Smith Adam , Nomura Michio
Published: August 2021

Empathy and mindfulness are currently major topics of scientific interest. Although it is well-known that mindfulness—typically as an outcome related to meditation—generates empathy at the state level, only a small number of studies have documented the trait (i.e., personality) level association between mindfulness and empathy. Furthermore, the underlying mechanisms (subcomponents and mediator variables) that support this association remain unclear. Thus, here, with a focus on the trait level, we investigated relationships among multiple subcomponents of trait mindfulness and trait empathy (Study 1). Next, we reexamined the aforementioned relationships in an independent sample, with the further aim of investigating relevant mediation factors (Study 2). We found that two attention-related components of trait mindfulness—observing and acting with awareness—reliably and positively related to both affective and cognitive dimensions of trait empathy (i.e., empathic concern and perspective taking). Furthermore, we found that effortful control, reappraisal, and trait alexithymia mediated relationships between the aforementioned attention-related components of trait mindfulness and empathic concern. Taken together, our results suggest that the links between mindfulness and empathy are multidimensional and complex. These findings may ultimately contribute to an understanding of the mechanisms underlying the positive effects of meditation on empathy.
Psychosocial Factors Associated With Resilience Among Iranian Nurses During COVID-19 Outbreak
Authors: Afshari Davood , Nourollahi-darabad Maryam , Chinisaz Niloofar
Published: August 2021

Background: In the face of COVID-19, healthcare workers need to cope with the ongoing stressors at play and keep psychological distress at a minimum level. This study examined the psychosocial and demographic factors associated with nurse's resilience in the hospitals of Ahvaz that is one of the top cities infected with COVID-19 in Iran.

Methods: The present cross-sectional study was conducted on 387 Iranian nurses in Ahvaz city. For data collection purposes, three online questionnaires (including Copenhagen Psychosocial, Demographic, and Connor–Davidson Resilience Scale) were distributed among the participants.

Results: The mean resilience score was equal to 61.8 ± 14.8 for 387 nurses. Resilience had a statistically significant negative correlation with quantitative demand (r = −0.273, P < 0.008), work pace (r = −0.262, P < 0.011), emotional demand (r = −0.226, P < 0.030), stress (r = −0.458, P < 0.000), and burnout (r = −0.287, P < 0.005). Multiple linear regression analysis indicated that stress, job satisfaction, burnout and age were the main predictors of nurses' resilience during the (COVID-19) pandemic (R2 = 0.45).

Conclusions: We identified psychosocial and demographic predictive factors that may contribute to greater resilience among nurses during the COVID-19 outbreak. The findings of this study can be used to implement psychosocial interventions to amplify the resilience of medical staff during the COVID-19 outbreak.
The Hungry Snail, the Fragile Coral, and the Friendly Microbe
Authors: Bettarel Yvan , Boudin Elyse , Halary Sébastien , Auguet Jean-Christophe , Péronnin Jean , Bouvier Thierry , Rochelle-Newall Emma , Bui Van Ngoc , Desnues Christelle
Published: August 2021

Off the coast of Vietnam, two recent events seem to have contributed to the death of coral reefs: the rapid invasion of a small marine snail called Drupella, and the emergence of a disease that spreads over corals. We decided to investigate whether there is a link between the corals, the snails, and the disease. We analyzed the mucus covering the surface of corals, both in healthy corals and those infested by Drupella snails. Mucus produced by corals is usually full of helpful microbes, protecting the corals from harmful microbes that can make them ill or kill them. Our analyses showed that, when Drupella eats corals, the snail also removes one of the corals’ primary defenses by eliminating most of the tiny protectors in their mucus. This allows harmful microbes to cause additional damage to the corals.
Counterstreaming Cold H+, He+, O+, and N+ Outflows in the Plasmasphere
Authors: Krall J. , Huba J. D.
Published: August 2021

The Naval Research Laboratory (NRL) Sami3 is Also a Model of the Ionosphere (SAMI3) ionosphere/plasmasphere code is used to examine H+, He+, N+, and O+ thermal outflows during a storm. Here, H+ and He+ outflows are associated with refilling while O+ and N+ outflows are associated with ring current heating. An improved model of counterstreaming H+ outflows from the two hemispheres is presented, using an implementation of SAMI3 with two fluid species for H+. The two-fluid H+ model avoids nonphysical high-altitude “top-down refilling” density peaks seen in one-fluid H+ simulations. Counterstreaming cold ion populations are found in all cases. In these fully three-dimensional simulations with realistic magnetosphere boundary conditions, nonphysical top-down refilling density peaks were milder than those found in previous single-field-line or single-magnetic-longitude simulations. In the present two-fluid H+ case, “bottom-up refilling” density peaks were so mild as to be difficult to detect. For O+ and N+, the nonphysical high-altitude density peak is a brief (1–2 h) transient that occurs when heating-driven northward and southward flows first meet. In general, He+ outflows mimic H+ outflows while N+ outflows mimic O+ outflows.
Soil and Pest Management in French Polynesian Farming Systems and Drivers and Barriers for Implementation of Practices Based on Agroecological Principles
Authors: Surchat Mélanie , Wezel Alexander , Tolon Vincent , Breland Tor Arvid , Couraud Philippe , Vian Jean-François
Published: August 2021

In the context of climate change, French Polynesia is committed to increasing qualitatively and quantitatively local food production. In this regard, agroecology is perceived as a sustainable pathway to improve farming practices. This article proposes first a theoretical framework to analyze the proximity of farmers' management to agroecological principles. Second, it describes the current use of agroecological pest and soil management practices by French Polynesian farmers. And third, it explains which agronomic and socio-economic factors drive the implementation of agroecological practices. For this, qualitative interviews were conducted with 32 farmers on three islands, and statistical analyses were carried for correlation between the use of practices and socio-economic variables. Results show that French Polynesian farmers implement different soil and pest management practices that are in line with agroecological principles. Farmers scored better in terms of pest management with high plant diversity, implementation of crop rotations, and mechanical weed management. There is a significant influence of the “cropping system” and the “production system” (organic, integrated, and conventional) on the use of practices as well as proximity to agroecological principles. Identified pathways for an agroecological transition are implementing farmer to farmer knowledge exchange, farmer networks, and farm demonstrations as well as training of extension services staff.
Effects of Intraoperative Fluid Management on Postoperative Outcomes After Pericardiectomy
Authors: Fang Likui , Zheng Hong , Yu Wenfeng , Chen Gang , Zhong Fangming
Published: August 2021

Background: The effects of intraoperative fluid management on the patients with constrictive pericarditis undergoing pericardiectomy remain unclear. This study explored the relationship between intraoperative fluid management and postoperative outcomes in these patients.

Methods: We retrospectively studied 92 patients with constrictive pericarditis undergoing pericardiectomy and assigned them to the restrictive group and the liberal group according to the intraoperative total fluid infusion rate. Postoperative outcomes were compared between the two groups. Binary logistic regression analysis was performed to determine the relationship between the intraoperative total fluid infusion rate and postoperative outcomes.

Results: There were 46 (50.0%) cases in the restrictive group and 46 (50.0%) cases in the liberal group. Compared with the liberal group, the restrictive group had significantly lower incidences of postoperative complications and cardiac complications (P = 0.005 and P = 0.006, respectively). Binary logistics regression analysis also showed the increased risks of postoperative complications (OR, 3.551; 95% CI, 1.192–10.580; P = 0.023) and cardiac complications (OR, 6.037; 95% CI, 1.472–25.052; P = 0.013) at the liberal group. In addition, the restrictive group had shorter postoperative hospital stay (P = 0.026) in comparison to the liberal group.

Conclusion: In patients with constrictive pericarditis undergoing pericardiectomy the intraoperative total fluid infusion rate was significantly associated with postoperative outcomes. Restrictive fluid management strategy was related to the positive effects on enhanced recovery after surgery and could be advised as the preferred intraoperative fluid management policy.