bluuebunny/crossref_metadata_2025 huggingface dataset:
STING Operation at the ER/Golgi Interface
Authors: Taguchi Tomohiko , Mukai Kojiro , Takaya Eiko , Shindo Ruri
Published: May 2021

DNA is present in the nucleus and mitochondria of eukaryotic cells. There are, however, certain instances in which DNA emerges in the cytosol. The two major sources of cytosolic DNA are self DNA that is leaked out from the nucleus or mitochondria, and non-self DNA from DNA viruses. The cytosolic DNA triggers the host immune response. Recent studies have identified two key molecules, cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) in this immune response. STING is an endoplasmic reticulum (ER) protein. After STING binding to cGAMP, STING exits the ER and translocates to the Golgi, where STING triggers the type I interferon- and proinflammatory responses through the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB). STING also activates other cellular responses including cell senescence, autophagy, and cell death. In this review, we focus on emerging issues regarding the regulation of STING by membrane traffic, with a particular focus on the retrograde membrane traffic from the Golgi to the ER. The retrograde membrane traffic is recently shown by us and others to be critical for silencing the STING signaling pathway and the defect in this traffic underlies the pathogenesis of the COPA syndrome, a monogenic autoinflammatory disease caused by missense mutations of coatomer protein complex subunit α (COP-α).
Lower IgA Levels in Chronic Spontaneous Urticaria Are Associated With Lower IgE Levels and Autoimmunity
Authors: Sauer Merle , Scheffel Jörg , Frischbutter Stefan , Kolkhir Pavel , Xiang Yi-Kui , Siebenhaar Frank , Altrichter Sabine , Maurer Marcus , Metz Martin , Krause Karoline
Published: May 2021

Background

The pathogenesis of chronic spontaneous urticaria (CSU) is still insufficiently understood. Recent findings suggest that immunoglobulins, in particular IgE but also IgA, play a role in the development of CSU.

Objective

Our aim was to assess differences in clinical and laboratory markers between CSU patients with and without lower levels of serum IgA and IgE.

Methods

We analyzed the data of 606 patients with CSU by dividing them into four groups based on their IgA and IgE levels. The groups were compared for their spectrum of symptoms, disease activity, concomitant autoimmunity and routine laboratory markers. Autoreactivity was assessed by basophil activation test (BAT). Moreover, IgE-anti-thyroid peroxidase (TPO) was measured.

Results

Of the patients with lower IgE levels, 66.5% also had lower IgA levels (r=0.316, p<0.001). Patients with lower IgA and lower IgE levels showed a higher prevalence of recurrent angioedema (p=0.03, p=0.04) and concomitant autoimmunity (p=0.006, p<0.001). Autoreactivity was also found more frequently in patients with lower IgA and lower IgE levels (p=0.003, p<0.001). Reduced basophil counts were linked to both, lower IgA and lower IgE levels (p<0.001), whereas low eosinophil counts were primarily present in patients with lower IgE levels (p=0.04, p<0.001). Patients with elevated IgE-anti-TPO levels had lower IgA (p=0.007) and IgE levels (p=0.001).

Conclusion

Lower IgA levels in CSU are linked to lower IgE levels and features of autoimmune urticaria. Our findings encourage to screen CSU patients for serum IgA and IgE levels and to further assess their role as disease biomarkers.
Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients
Authors: Martín-Sánchez Esperanza , Garcés Juan José , Maia Catarina , Inogés Susana , López-Díaz de Cerio Ascensión , Carmona-Torre Francisco , Marin-Oto Marta , Alegre Félix , Molano Elvira , Fernandez-Alonso Mirian , Perez Cristina , Botta Cirino , Zabaleta Aintzane , Alcaide Ana Belen , Landecho Manuel F. , Rua Marta , Pérez-Warnisher Teresa , Blanco Laura , Sarvide Sarai , Vilas-Zornoza Amaia , Alignani Diego , Moreno Cristina , Pineda Iñigo , Sogbe Miguel , Argemi Josepmaria , Paiva Bruno , Yuste José Ramón
Published: May 2021

Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients.
Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?
Authors: Loke Justin , Buka Richard , Craddock Charles
Published: May 2021

Although the majority of patients with acute myeloid leukemia (AML) treated with intensive chemotherapy achieve a complete remission (CR), many are destined to relapse if treated with intensive chemotherapy alone. Allogeneic stem cell transplant (allo-SCT) represents a pivotally important treatment strategy in fit adults with AML because of its augmented anti-leukemic activity consequent upon dose intensification and the genesis of a potent graft-versus-leukemia effect. Increased donor availability coupled with the advent of reduced intensity conditioning (RIC) regimens has dramatically increased transplant access and consequently allo-SCT is now a key component of the treatment algorithm in both patients with AML in first CR (CR1) and advanced disease. Although transplant related mortality has fallen steadily over recent decades there has been no real progress in reducing the risk of disease relapse which remains the major cause of transplant failure and represents a major area of unmet need. A number of therapeutic approaches with the potential to reduce disease relapse, including advances in induction chemotherapy, the development of novel conditioning regimens and the emergence of the concept of post-transplant maintenance, are currently under development. Furthermore, the use of genetics and measurable residual disease technology in disease assessment has improved the identification of patients who are likely to benefit from an allo-SCT which now represents an increasingly personalized therapy. Future progress in optimizing transplant outcome will be dependent on the successful delivery by the international transplant community of randomized prospective clinical trials which permit examination of current and future transplant therapies with the same degree of rigor as is routinely adopted for non-transplant therapies.
Navigating the Complexity of Regional Ocean Governance Through the Large Marine Ecosystems Approach
Authors: Degger Natalie , Hudson Andrew , Mamaev Vladimir , Hamid Mish , Trumbic Ivica
Published: May 2021

Governance is a multifaceted and complex process, involving a wide range of stakeholders from numerous institutions and individuals with different interests, agendas and sets of skills. A number of barriers exist for states to work together on securing their shared coastal and marine ecosystems, with discussions often becoming clouded when disputes arise over Exclusive Economic Zones, borders, oil and gas resources, continental shelves, maritime transport, and fisheries. Over the last twenty-six years, the Global Environment Facility’s (GEF) International Waters focal area has utilized the Large Marine Ecosystem (LME) approach to navigate the complex problems related to transboundary issues affecting the world’s marine ecosystems, of which forty-one out of sixty-six are shared (62%) by one or more countries. To overcome the disputes and assumptions about the intentions of neighboring states, the GEF developed the Transboundary Diagnostic Analysis-Strategic Action Programme (TDA-SAP) assessment and strategic planning processes to help countries learn how to work together and build trust. This formal and inclusive process analyses all pertinent factual and scientific information to set priorities for action. This practical method for integrating science into management has provided an effective approach to inform and advance sustainable LME management and governance regimes; however, there is not a one size fits all approach. This review presents six examples from the GEF International Waters portfolio that demonstrate how the LME Approach and TDA-SAP process have helped countries find the best way to mainstream ecosystem-based management approaches into existing contexts and politics. While these examples span a wide range of different settings (geographic, political, socio-economic, temporal), they have all applied the LME Approach and TDA-SAP process to tackle complex regional ocean governance issues. Each example provides a historical perspective, the key results achieved, and their unique lessons learned/best practices. Furthermore, the review identifies some of the overall shortcomings of the process and the common lessons learned, underscoring the complex and daunting challenge of achieving effective governance for multi-country LMEs. The experience provided by these examples shows that practical ecosystem-based management of the ocean and its coasts not only requires flexibility and adaptability, but also time, associated long-term vision and commitment.
Geopolymer Concrete Compressive Strength via Artificial Neural Network, Adaptive Neuro Fuzzy Interface System, and Gene Expression Programming With K-Fold Cross Validation
Authors: Khan Mohsin Ali , Zafar Adeel , Farooq Furqan , Javed Muhammad Faisal , Alyousef Rayed , Alabduljabbar Hisham , Khan M. Ijaz
Published: May 2021

The ultrafine fly ash (FA) is a hazardous material collected from coal productions, which has been proficiently employed for the manufacturing of geopolymer concrete (GPC). In this study, the three artificial intelligence (AI) techniques, namely, artificial neural network (ANN), adaptive neuro-fuzzy interface (ANFIS), and gene expression programming (GEP) are used to establish a reliable and accurate model to estimate the compressive strength (f′c) of fly ash–based geopolymer concrete (FGPC). A database of 298 instances is developed from the peer-reviewed published work. The database consists of the ten most prominent explanatory variables and f′c of FGPC as a response parameter. The statistical error checks and criteria suggested in the literature are considered for the verification of the predictive strength of the models. The statistical measures considered in this study are MAE, RSE, RMSE, RRMSE, R, and performance index (ρ). These checks verify that the ANFIS predictive model gives an outstanding performance followed by GEP and ANN predictive models. In the validation stage, the coefficient of correlation (R) for ANFIS, GEP, and ANN model is 0.9783, 0.9643, and 0.9314, respectively. All three models also fulfill the external verification criterion suggested in the literature. Generally, the GEP predictive model is ideal as it delivers a simplistic and easy mathematical equation for future use. The k-fold cross-validation (CV) of the GEP model is also conducted, which verifies the robustness of the GEP predictive model. Furthermore, the parametric study is carried via proposed GEP expression. This confirms that the GEP model accurately covers the influence of all the explanatory variables used for the prediction of f′c of FGPC. Thus, the proposed GEP equation can be used in the preliminary design of FGPC.
Theoretical and Experimental Study of the Vibration Dynamics of a 3D-Printed Sandwich Beam With an Hourglass Lattice Truss Core
Authors: Guo Zhenkun , Hu Guobiao , Jiang Jingchao , Yu Liuding , Li Xin , Liang Junrui
Published: May 2021

3D printing (also known as additive manufacturing) has been developed for more than 30 years. The applications of 3D printing have been increasingly extended to a variety of engineering fields in recent years. The sandwich material with a high strength and overall low density is a kind of artificial material that has been extensively used in various industrial and daily life applications. This paper presents a comprehensive vibration analysis and passive control technique for a cantilevered sandwich beam with an hourglass lattice truss core fabricated with 3D printing technology. The governing equation of the beam is established by using a homogenized model and the Hamilton's principle, from which the natural frequencies are determined. The theoretical model is verified by the results from the existing literature and the finite element analysis. The frequency response of the sandwich beam measured experimentally further validates the proposed model. Subsequently, a non-linear energy sink (NES) is proposed for being employed to passively suppress the vibration of the sandwich beam. A parametric study based on the theoretical model confirms the viability of using NES to effectively control the vibration of the sandwich beam. This work presents a good demonstration of using 3D printing technology for fabricating sandwich beams with a complicated lattice core. More importantly, some guidelines regarding the dynamic analysis of sandwich beams are provided. In addition, the analytical method presented in this work provides a potential means to theoretically explore the advantages of using sandwich beams for energy harvesting in the future.
Time-Dependent Recruitment of Prelimbic Prefrontal Circuits for Retrieval of Fear Memory
Authors: Quiñones-Laracuente Kelvin , Vega-Medina Alexis , Quirk Gregory J.
Published: May 2021

The long-lasting nature of fear memories is essential for survival, but the neural circuitry for retrieval of these associations changes with the passage of time. We previously reported a time-dependent shift from prefrontal-amygdalar circuits to prefrontal-thalamic circuits for the retrieval of auditory fear conditioning. However, little is known about the time-dependent changes in the originating site, the prefrontal cortex. Here we monitored the responses of prelimbic (PL) prefrontal neurons to conditioned tones at early (2 h) vs. late (4 days) timepoints following training. Using c-Fos, we find that PL neurons projecting to the amygdala are activated early after learning, but not later, whereas PL neurons projecting to the paraventricular thalamus (PVT) show the opposite pattern. Using unit recording, we find that PL neurons in layer V (the origin of projections to amygdala) showed cue-induced excitation at earlier but not later timepoints, whereas PL neurons in Layer VI (the origin of projections to PVT) showed cue-induced inhibition at later, but not earlier, timepoints, along with an increase in spontaneous firing rate. Thus, soon after conditioning, there are conditioned excitatory responses in PL layer V which influence the amygdala. With the passage of time, however, retrieval of fear memories shifts to inhibitory responses in PL layer VI which influence the midline thalamus.
Expert-Level Intracranial Electroencephalogram Ictal Pattern Detection by a Deep Learning Neural Network
Authors: Constantino Alexander C. , Sisterson Nathaniel D. , Zaher Naoir , Urban Alexandra , Richardson R. Mark , Kokkinos Vasileios
Published: May 2021

Background: Decision-making in epilepsy surgery is strongly connected to the interpretation of the intracranial EEG (iEEG). Although deep learning approaches have demonstrated efficiency in processing extracranial EEG, few studies have addressed iEEG seizure detection, in part due to the small number of seizures per patient typically available from intracranial investigations. This study aims to evaluate the efficiency of deep learning methodology in detecting iEEG seizures using a large dataset of ictal patterns collected from epilepsy patients implanted with a responsive neurostimulation system (RNS).

Methods: Five thousand two hundred and twenty-six ictal events were collected from 22 patients implanted with RNS. A convolutional neural network (CNN) architecture was created to provide personalized seizure annotations for each patient. Accuracy of seizure identification was tested in two scenarios: patients with seizures occurring following a period of chronic recording (scenario 1) and patients with seizures occurring immediately following implantation (scenario 2). The accuracy of the CNN in identifying RNS-recorded iEEG ictal patterns was evaluated against human neurophysiology expertise. Statistical performance was assessed via the area-under-precision-recall curve (AUPRC).

Results: In scenario 1, the CNN achieved a maximum mean binary classification AUPRC of 0.84 ± 0.19 (95%CI, 0.72–0.93) and mean regression accuracy of 6.3 ± 1.0 s (95%CI, 4.3–8.5 s) at 30 seed samples. In scenario 2, maximum mean AUPRC was 0.80 ± 0.19 (95%CI, 0.68–0.91) and mean regression accuracy was 6.3 ± 0.9 s (95%CI, 4.8–8.3 s) at 20 seed samples. We obtained near-maximum accuracies at seed size of 10 in both scenarios. CNN classification failures can be explained by ictal electro-decrements, brief seizures, single-channel ictal patterns, highly concentrated interictal activity, changes in the sleep-wake cycle, and progressive modulation of electrographic ictal features.

Conclusions: We developed a deep learning neural network that performs personalized detection of RNS-derived ictal patterns with expert-level accuracy. These results suggest the potential for automated techniques to significantly improve the management of closed-loop brain stimulation, including during the initial period of recording when the device is otherwise naïve to a given patient's seizures.
Remote Ischemic Conditioning With Exercise (RICE)—Rehabilitative Strategy in Patients With Acute Ischemic Stroke: Rationale, Design, and Protocol for a Randomized Controlled Study
Authors: Han Zhenzhen , Zhao Wenbo , Lee Hangil , Wills Melissa , Tong Yanna , Cheng Zhe , Dai Qingqing , Li Xiaohua , Wang Qingzhu , Geng Xiaokun , Ji Xunming , Ding Yuchuan
Published: May 2021

Objective: Exercise rehabilitation is an effective therapy in reducing the disability rate after stroke and should be carried out as early as possible. However, very early rehabilitation exercise exacerbates brain injury and is difficult to conduct in stroke patients due to their weakened and potentially disabled state. It is valuable to explore additional early rehabilitation strategies. Remote Ischemic Conditioning (RIC) is a novel therapy designed to protect vital organs from severe lethal ischemic injury by transient sublethal blood flow to non-vital organs, including the distal limbs, in order to induce endogenous protection. RIC has previously been conducted post-stroke for neuroprotection. However, whether combined early RIC and exercise (RICE) therapy enhances stroke rehabilitation remains to be determined.

Methods: This is a single-center, double-blinded, randomized controlled trial that will enroll acute ischemic stroke patients within 24 h of symptom onset or symptom exacerbation. All enrolled patients will be randomly assigned to either the RICE group (exercise with RIC) or the control group (exercise with sham RIC) at a ratio of 1:1, with 20 patients in each group. Both groups will receive RIC or sham RIC within 24 h after stroke onset or symptom exacerbation, once a day, for 14 days. All patients will begin exercise training on the fourth day, twice a day, for 11 days. Their neurological function [Modified Rankin Scale (mRS) score, National Institutes of Health Stroke Scale (NIHSS) score, Barthel Index, and walking ability], infarct volume (nuclear magnetic resonance, MRI), and adverse events will be evaluated at different time points in their post-stroke care.

Results: The primary outcome is safety, measured by the incidence of any serious RICE-related adverse events and decreased adverse events during hospitalization. The secondary outcome is a favorable prognosis within 90 days (mRS score < 2), determined by improvements in the mRS score, NIHSS score, Barthel Index, walking ability after 90 days, and infarct volume after 12 ± 2 days.

Conclusion: This study is a prospective randomized controlled trial to determine the rehabilitative effect of early RIC followed by exercise on patients with acute ischemic stroke.

Trial Registration:www.chictr.org.cn, identifier: ChiCTR2000041042
LncRNA PCIR Is an Oncogenic Driver via Strengthen the Binding of TAB3 and PABPC4 in Triple Negative Breast Cancer
Authors: Guo Wenhui , Li Jingyi , Huang Haobo , Fu Fangmeng , Lin Yuxiang , Wang Chuan
Published: May 2021

Long non-coding RNAs (LncRNA) as the key regulators in all stages of tumorigenesis and metastasis. However, the underlying mechanisms are largely unknown. Here, we report a lncRNA RP11-214F16.8, which renamed Lnc-PCIR, is upregulated and higher RNA level of Lnc-PCIR was positively correlated to the poor survival of patients with triple negative breast cancer (TNBC) tissues. Lnc-PCIR overexpression significantly promoted cell proliferation, migration, and invasion in vitro and in vivo. RNA pulldown, RNA immunoprecipitation (RIP) and RNA transcriptome sequencing technology (RNA-seq) was performed to identify the associated proteins and related signaling pathways. Mechanistically, higher Lnc-PCIR level of blocks PABPC4 proteasome-dependent ubiquitination degradation; stable and highly expressed PABPC4 can further increase the stability of TAB3 mRNA, meanwhile, overexpression of Lnc-PCIR can disrupt the binding status of TAB3 and TAB2 which lead to activate the TNF-α/NF-κB pathway in TNBC cells. Our findings suggest that Lnc-PCIR promotes tumor growth and metastasis via up-regulating the mRNA/protein level of TAB3 and PABPC4, activating TNF-α/NF-κB signaling pathway in TNBC.
Canine Parvovirus and Its Non-Structural Gene 1 as Oncolytic Agents: Mechanism of Action and Induction of Anti-Tumor Immune Response
Authors: Arora Richa , Malla Waseem Akram , Tyagi Arpit , Mahajan Sonalika , Sajjanar Basavaraj , Tiwari Ashok Kumar
Published: May 2021

The exploration into the strategies for the prevention and treatment of cancer is far from complete. Apart from humans, cancer has gained considerable importance in animals because of increased awareness towards animal health and welfare. Current cancer treatment regimens are less specific towards tumor cells and end up harming normal healthy cells. Thus, a highly specific therapeutic strategy with minimal side effects is the need of the hour. Oncolytic viral gene therapy is one such specific approach to target cancer cells without affecting the normal cells of the body. Canine parvovirus (CPV) is an oncolytic virus that specifically targets and kills cancer cells by causing DNA damage, caspase activation, and mitochondrial damage. Non-structural gene 1 (NS1) of CPV, involved in viral DNA replication is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis. In this review, we discuss the oncolytic properties of Canine Parvovirus (CPV or CPV2), the structure of the NS1 protein, the mechanism of oncolytic action as well as role in inducing an antitumor immune response in different tumor models.
Cost-Effectiveness of Anti-Epidermal Growth Factor Receptor Therapy Versus Bevacizumab in KRAS Wild-Type (WT), Pan-RAS WT, and Pan-RAS WT Left-Sided Metastatic Colorectal Cancer
Authors: Lee Shing Fung , Choi Horace C. W. , Chan Sik Kwan , Lam Ka On , Lee Victor H. F. , Wong Irene O. L. , Chiang Chi Leung
Published: May 2021

Objectives

We aimed to compare the economic value of chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) against chemotherapy with bevacizumab (Bev, an anti-vascular endothelial growth factor mAb) as first-line treatment in KRAS wild-type (WT), pan-RAS WT and pan-RAS WT left-sided metastatic colorectal cancer (mCRC) patients from the Hong Kong societal perspective.

Materials and Methods

We developed Markov models and 10-year horizon to estimate costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of chemotherapy plus anti-EGFR therapy against chemotherapy plus Bev in KRAS WT, pan-RAS WT, and pan-RAS WT left-sided mCRC. We considered two times of the local gross domestic product per capita (GDPpc) as the willingness-to-pay (WTP) threshold (2× GDPpc; US$97,832).

Results

Adding anti-EGFR mAb to chemotherapy provides additional 0.24 (95% confidence interval [CI] 0.19–0.29), 0.32 (95% CI 0.27–0.37), and 0.57 (95% CI 0.49–0.63) QALY compared to adding Bev in KRAS WT, pan-RAS WT, and left-sided pan-RAS WT mCRC populations respectively. The corresponding ICER is US$106,847 (95% CI 87,806–134,523), US$88,565 (95% CI 75,678–105,871), US$76,537 (95% CI 67,794–87,917) per QALY gained, respectively.

Conclusions

Anti-EGFR therapy is more cost-effective than Bev as a first-line targeted therapy in left-sided pan-RAS WT and pan-RAS WT, with ICER <US$100,000/QALY, compared to KRAS WT mCRC population.
Calcitonin Gene–Related Peptide Monoclonal Antibody Versus Botulinum Toxin for the Preventive Treatment of Chronic Migraine: Evidence From Indirect Treatment Comparison
Authors: Lu Jiajie , Zhang Quanquan , Guo Xiaoning , Liu Wei , Xu Chunyang , Hu Xiaowei , Ni Jianqiang , Lu Haifeng , Zhao Hongru
Published: May 2021

Background: The previously approved botulinum toxin and nowadays promising calcitonin gene-related peptide (CGRP) monoclonal antibody have shown efficacy for preventing chronic migraine (CM). However, there is no direct evidence for their relative effectiveness and safety. In this study, we conducted an indirect treatment comparison to compare the efficacy and safety of CGRP monoclonal antibody with botulinum toxin for the preventive treatment of chronic migraine.

Methods: Up to August 31, 2020, we systematically searched PubMed, Embase, and Cochrane Library Central Register of Controlled Trials (Central). Weighted mean difference (WMD) and relative risk (RR) were used to evaluate clinical outcomes. Indirect treatment comparison (ITC) software was used to conduct indirect treatment comparison.

Results: Ten studies were pooled with 6,325 patients in our meta-analysis. Both botulinum toxin and CGRP monoclonal antibody demonstrated favorable efficacy in the change of migraine days, headache days, HIT-6 score, and 50% migraine responder rate compared with placebo. In indirect treatment comparison, CGRP monoclonal antibody was superior to botulinum toxin in the frequency of acute analgesics intake (WMD = −1.31, 95% CI: −3.394 to 0.774, p = 0.02113), the rate of treatment-related adverse events (AEs) (RR = 0.664, 95% CI: 0.469 to 0.939, p = 0.04047), and the rate of treatment-related serious adverse events (RR = 0.505, 95% CI: 0.005 to 46.98, p < 0.001).

Conclusion: For chronic migraine patients, CGRP monoclonal antibody was slightly better than botulinum toxin in terms of efficacy and safety. In the future, head-to-head trials would be better to evaluate the efficacy and safety between different medications in the prevention of chronic migraine.
Pulmonary Arterial Remodeling Is Related to the Risk Stratification and Right Ventricular-Pulmonary Arterial Coupling in Patients With Pulmonary Arterial Hypertension
Authors: Grignola Juan C. , Domingo Enric , López-Meseguer Manuel , Trujillo Pedro , Bravo Carlos , Pérez-Hoyos Santiago , Roman Antonio
Published: May 2021

Background

Pulmonary arterial (PA) stiffness has an essential contribution to the right ventricular (RV) failure pathogenesis. A comprehensive and multiparameter risk assessment allows predicting mortality and guiding treatment decisions in PA hypertension (PAH). We characterize PA remodeling with intravascular ultrasound (IVUS) in prevalent and stable patients with PAH according to the ESC/ERS risk table and analyze the RV-PA coupling consequences.

Methods

Ten control subjects and 20 prevalent PAH adult patients underwent right heart catheterization (RHC) with simultaneous IVUS study. We estimated cardiac index (CI), pulmonary vascular resistance, and compliance (PVR, PAC) by standard formulas. From IVUS and RHC data, PA diameter, wall thickness/luminal diameter ratio, and indexes of stiffness (pulsatility, compliance, distensibility, incremental elastic modulus - Einc-, and the stiffness index β) were measured. We evaluated RV-PA coupling by the ratio of tricuspid annular plane systolic excursion to systolic pulmonary arterial pressure (TAPSE/sPAP). The individual average risk was calculated by assigning a score of 1 (low-risk -LR-), 2 (intermediate-risk -IR-), and 3 (high-risk -HR-) for each of seven variables (functional class, six-minute walking test, brain natriuretic peptide, right atrial area and pressure, CI, and PA oxygen saturation) and rounding the average value to the nearest integer.

Results

All PA segments interrogated showed increased vessel diameter, wall cross-sectional area (WCSA), and stiffness in patients with PAH compared to control subjects. 45% corresponded to LR, and 55% corresponded to IR PAH patients. The different measurements of PA stiffness showed significant correlations with TAPSE/sPAP (r = 0.6 to 0.76) in PAH patients. The IR group had higher PA stiffness and lower relative WCSA than LR patients (P < 0.05), and it is associated with a lower PAC and TAPSE/sPAP (P < 0.05).

Conclusion

In prevalent PAH patients, the severity of proximal PA remodeling is related to the risk stratification and associated with PAC and RV-PA coupling impairment beyond the indirect effect of the mean PA pressure. The concomitant assessment of IVUS and hemodynamic parameters at diagnosis and follow-up of PAH patients could be a feasible and safe tool for risk stratification and treatment response of the PA vasculopathy during serial hemodynamic measurements.
Metformin Increases Sarcolemma Integrity and Ameliorates Neuromuscular Deficits in a Murine Model of Duchenne Muscular Dystrophy
Authors: Dong Xia , Hui Tiankun , Chen Jie , Yu Zheng , Ren Dongyan , Zou Suqi , Wang Shunqi , Fei Erkang , Jiao Huifeng , Lai Xinsheng
Published: May 2021

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disease characterized by progressive muscle weakness and wasting. Stimulation of AMP-activated protein kinase (AMPK) has been demonstrated to increase muscle function and protect muscle against damage in dystrophic mice. Metformin is a widely used anti-hyperglycemic drug and has been shown to be an indirect activator of AMPK. Based on these findings, we sought to determine the effects of metformin on neuromuscular deficits in mdx murine model of DMD. In this study, we found metformin treatment increased muscle strength accompanied by elevated twitch and tetanic force of tibialis anterior (TA) muscle in mdx mice. Immunofluorescence and electron microscopy analysis of metformin-treated mdx muscles revealed an improvement in muscle fiber membrane integrity. Electrophysiological studies showed the amplitude of miniature endplate potentials (mEPP) was increased in treated mice, indicating metformin also improved neuromuscular transmission of the mdx mice. Analysis of mRNA and protein levels from muscles of treated mice showed an upregulation of AMPK phosphorylation and dystrophin-glycoprotein complex protein expression. In conclusion, metformin can indeed improve muscle function and diminish neuromuscular deficits in mdx mice, suggesting its potential use as a therapeutic drug in DMD patients.
Rasch Analysis of Work-Family Conflict Scale Among Chinese Prison Police
Authors: Chen Wei , Zhang Guyin , Tian Xue , Wang Li , Luo Jie
Published: May 2021

As a special group of police officer, prison police have to endure more work stress and have significant work-family conflict, which may lead to more physical and mental health problems and need to be noticed by the society. The Work-Family Conflict Scale (WFCS) is a brief self-report scale that measures the conflict that an individual experiences between their work and family roles and the extent they interfere with one another. However, there is limited data on the scale’s psychometric properties. The aim of this study was to examine the dimensionality and reliability of the Chinese version of the WFCS. The study sample was made up of a total of 717 Chinese prison police (64.7% male, M = 41.73 years, SD = 8.30 years). The Rasch Rating Scale Model (RSM) was used to determine the latent structure and estimate the quality of items and reliability of scale. The principle component analysis (PCA) showed that the assumption of unidimensionality was fulfilled. The infit and outfit mean square (MNSQ) statistics (0.84–1.47) were of a reasonable range, and point-measure correlations (0.64–0.79) indicted good model fit of each item. The item-person separation and reliability indices both met psychometric standards, illustrating good reliability. The person-item map indicated acceptable fit of items and persons, suggesting an alignment between persons and items. In addition, no evidence emerged of differential item functioning across different gender groups. Overall, the WFCS has good reliability and validity, and can be used to accurately evaluate the level of work-family conflict in Chinese prison police.
A Systematic Review of Fear of Cancer Recurrence Among Indigenous and Minority Peoples
Authors: Anderson Kate , Smith Allan ‘Ben' , Diaz Abbey , Shaw Joanne , Butow Phyllis , Sharpe Louise , Girgis Afaf , Lebel Sophie , Dhillon Haryana , Burhansstipanov Linda , Tighe Boden , Garvey Gail
Published: May 2021

While cancer survivors commonly experience fear and anxiety, a substantial minority experience an enduring and debilitating fear that their cancer will return; a condition commonly referred to as fear of cancer recurrence (FCR). Despite recent advances in this area, little is known about FCR among people from Indigenous or other ethnic and racial minority populations. Given the high prevalence and poor outcomes of cancer among people from these populations, a robust understanding of FCR among people from these groups is critical. The current review identified and aggregated existing literature on FCR amongst adult cancer survivors from Indigenous and minority populations. The protocol of this review was registered with PROSPERO in July 2020 (Registration number: CRD42020161655). A systematic search of bibliographic databases was conducted for relevant articles published from 1997 to November 2019. Data from eligible articles were extracted and appraised for quality by two independent reviewers. Nineteen articles from four countries (United States of America, Canada, Australia and the United Kingdom) met the inclusion criteria, including 14 quantitative, 4 qualitative and 1 mixed-methods study. Only one article reported on an Indigenous population. Few studies reported on FCR prevalence (n = 3) or severity (n = 9). While the variation in tools used to measure FCR hindered a robust estimate of severity, results suggested some differences in FCR severity between minority and dominant populations, although these may have been due to study metholodological differences. Few factors were reported as being associated with FCR in minorities across multiple studies. The qualitative synthesis found five themes associated with the lived experience of FCR: (i) variations in the lived experience of FCR; (ii) spirituality and worldview impacting on FCR; (iii) the importance of staying positive; (iv) complexities around support; and (v) increasing cancer knowledge. The findings of this review highlight differences in FCR across cultures and contexts, which reinforces the need for culturally-specific approaches to this condition. The dearth of research in this area is of concern given the significant burden of cancer in these populations. A deeper understanding of this condition among Indigenous and minority populations is critical to developing and delivering appropriate and effective psychosocial care for cancer survivors from these groups. Systematic Review Registration: identifier [CRD42020161655].
End of Life Intervention Program During COVID-19 in Vall d'Hebron University Hospital
Authors: Beneria Anna , Castell-Panisello Eudald , Sorribes-Puertas Marta , Forner-Puntonet Mireia , Serrat Laia , García-González Sara , Garriga Maria , Simon Carmen , Raya Consuelo , Montes Maria José , Rios Giuliana , Bosch Rosa , Citoler Bárbara , Closa Helena , Corrales Montserrat , Daigre Constanza , Delgado Mercedes , Dip Maria Emilia , Estelrich Neus , Jacas Carlos , Lara Benjamin , Lugo-Marin Jorge , Nieto-Fernández Zaira , Regales Christina , Ibáñez Pol , Blanco Eunice , Ramos-Quiroga Josep Antoni
Published: May 2021

Introduction: The coronavirus disease 19 (COVID-19) and its consequences have placed our societies and healthcare systems under pressure. Also, a major impact on the individual and societal experience of death, dying, and bereavement has been observed. Factors such as social distancing, unexpected death or not being able to say goodbye, which might predict Prolonged Grief Disorder (PGD), are taking place. Moreover, hospitals have become a habitual place for End of Life (EOL) situations but not in the usual conditions because, for example, mitigation measures prevent families from being together with hospitalized relatives. Therefore, we implemented an EOL program with a multidisciplinary team involving health social workers (HSW) and clinical psychologists (CP) in coordination with the medical teams and nursing staff.

Objectives: We aim to describe an EOL intervention program implemented during COVID-19 in the Vall d'Hebron University Hospital (HUVH). We present its structure, circuit, and functions. Descriptive analyses of the sample and the interventions that required psychological and social attention are reported.

Material and methods: The total sample consists of 359 relatives of 219 EOL patients. Inclusion criteria were families cared for during the COVID-19 pandemic with family patients admitted to the HUVH in an EOL situation regardless of whether or not the patient was diagnosed with COVID-19.

Results: Our program is based on family EOL care perceptions and the COVID-19 context features that hinder EOL situations. The program attended 219 families, of which 55.3% were COVID-19 patients and 44.7% had other pathologies. The EOL intervention program was activated in most of the EOL situations, specifically, in 85% of cases, and 78% of relatives were able to come and say goodbye to their loved ones. An emotional impact on the EOL team was reported. It is necessary to dignify the EOL situation in the COVID-19 pandemic, and appropriate psychosocial attention is needed to try to minimize future complications in grief processes and mitigate PGD.
Assessment of the Minimum Clinically Important Difference in Symptoms and Functions of Patients With Acute Schizophrenia: A Post hoc Analysis of an Open-Label, Single-Arm Multicenter Study
Authors: Si Tianmei , Shi Chuan , Sun Ling , Zhang Yilong , Zhang Lili
Published: May 2021

The purpose of this study was to evaluate the application of the minimum clinically important difference (MCID) concept to clinical results in Chinese patients with acutely exacerbated schizophrenia. The original study was an 8-week, open-label, single-arm, multicenter study of flexible doses of paliperidone-extended release (pali-ER) in Chinese patients with acutely exacerbated schizophrenia. This is a post hoc analysis to determine the MCID value of PANSS, PSP and evaluate the responsiveness of each outcome measurements in the acute phase of schizophrenia. The responsiveness of the four measurements (PANSS, PANSS reduction rate, PSP, CGI-S) was analyzed. Four hundred ninety nine patients completed the 8-week follow-up and were finally used for this post hoc analysis. The MCID calculated by different approaches varied from 14.02 to 31.50 for PANSS, 15.14 to 42.79% for PANSS reduction rate, and 7.62 to 13.13% for PSP. In addition, the improvement of the CGI-S owned the highest responsiveness of the four outcome measurements. The threshold value of MCID for schizophrenia patients was determined by choice of the assessment method to an extent. In addition, the CGI-S score appeared to be the most valid and responsive measure of effectiveness for the acute phase of schizophrenia when take the treatment satisfaction of patients as anchor.
Unified Approach to the Motion Design for a Snake Robot Negotiating Complicated Pipe Structures
Authors: Inazawa Mariko , Takemori Tatsuya , Tanaka Motoyasu , Matsuno Fumitoshi
Published: May 2021

A unified method for designing the motion of a snake robot negotiating complicated pipe structures is presented. Such robots moving inside pipes must deal with various “obstacles,” such as junctions, bends, diameter changes, shears, and blockages. To surmount these obstacles, we propose a method that enables the robot to adapt to multiple pipe structures in a unified way. This method also applies to motion that is necessary to pass between the inside and the outside of a pipe. We designed the target form of the snake robot using two helices connected by an arbitrary shape. This method can be applied to various obstacles by designing a part of the target form specifically for given obstacles. The robot negotiates obstacles under shift control by employing a rolling motion. Considering the slip between the robot and the pipe, the model expands the method to cover cases where two helices have different properties. We demonstrated the effectiveness of the proposed method in various experiments.
Women’s Empowerment, Agency and Self-Determination in Afrobeats Music Videos: A Multimodal Critical Discourse Analysis
Authors: Rens Simphiwe Emmanuel
Published: May 2021

Stemming from a broader PhD project, this article argues that neoliberal post-feminist cultural sensibilities–entrenched in contemporary popular culture–about empowered, agentic and self-determining women, are regressive for the feminist advancement of gender-relational equality in the African context. To arrive at this conclusion, the central aim was to elucidate whether the gender-performative representations prioritised in the multimodal discourses of Afrobeats music videos are implicated in post-feminist sensibilities and if so, in what ways and to what effect? Given the continent’s richly diverse, yet largely heteropatriarchal, sociocultural formations, I argue that ideas about empowered, agentic and self-determining (black) African women are–based on the limited purview offered through the multimodal discourses of a small corpus of Afrobeats music videos–no more than sociocultural façades as opposed to gender-relational realities in our context. The article relied on a multimodal critical discourse analysis of a total of nine music videos drawn from the PhD project’s larger corpus of 25 Afrobeats music videos, their accompanying song lyrics, as well as a selection of YouTube viewer comments extracted from the analysed music videos. In critically exploring the gender-relational depictions prioritised in the analysed music videos, I argue for the consideration of what I am coining “misogyrom”; a gender-relational cultural sensibility which, in tandem with a post-feminist sensibility partly undergirding the multimodal discourses of these music videos, effectively veil this popular musical genre’s evidently sexist and misogynistic undertones that subvert potentialities of empowered, agentic and self-determining black African women.
EGFR Alterations Influence the Cetuximab Treatment Response and c-MET Tyrosine-Kinase Inhibitor Sensitivity in Experimental Head and Neck Squamous Cell Carcinomas
Authors: Nelhűbel Györgyi A. , Cserepes Mihály , Szabó Balázs , Türk Dóra , Kárpáti Adél , Kenessey István , Rásó Erzsébet , Barbai Tamás , Hegedűs Zita , László Viktória , Szokol Bálint , Dobos Judit , Őrfi László , Tóvári József
Published: May 2021

Background: Anti-EGFR antibody therapy is still one of the clinical choices in head and neck squamous cell carcinoma (HNSCC) patients, but the emergence of cetuximab resistance questioned its effectiveness and reduced its applicability. Although several possible reasons of resistance against the antibody treatment and alternative therapeutic proposals have been described (EGFR alterations, activation of other signaling pathways), there is no method to predict the effectiveness of anti-EGFR antibody treatments and to suggest novel therapeutics. Our study investigated the effect of EGFR R521K alteration on efficiency of cetuximab therapy of HNSCC cell lines and tried to find alternative therapeutic approaches against the resistant cells.

Methods: After genetic characterization of HNSCC cells, we chose one wild type and one R521K+ cell line for in vitro proliferation and apoptosis tests, and in vivo animal models using different therapeutic agents.

Results: Although the cetuximab treatment affected EGFR signalization in both cells, it did not alter in vitro cell proliferation or apoptosis. In vivo cetuximab therapy was also ineffective on R521K harboring tumor xenografts, while blocked the tumor growth of EGFR-wild type xenografts. Interestingly, the cetuximab-resistant R521K tumors were successfully treated with c-MET tyrosine kinase inhibitor SU11274.

Conclusion: Our results suggest that HNSCC cell line expressing the R521K mutant form of EGFR does not respond well to cetuximab treatment in vitro or in vivo, but hopefully might be targeted by c-MET tyrosine kinase inhibitor treatment.