bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Soft Cervical Collar among Whiplash Patients in Two Italian Emergency Departments Is Associated with Persistence of Symptoms: A Propensity Score Matching Analysis
Authors: Mourad Firas , Rossettini Giacomo , Galeno Erasmo , Patuzzo Alberto , Zolla Giuseppe , Maselli Filippo , Ciolan Federica , Guerra Michele , Tosato Giacomo , Palese Alvisa , Testa Marco , Ricci Giorgio , Zaboli Arian , Bonora Antonio , Turcato Gianni
Published: October 2021

Purpose: Although the use of soft cervical collars in the emergency department (ED), for whiplash-associated disorders (WAD), is controversial, it is still widely adopted. The purpose of our study was to investigate the impact of the early use of soft cervical collars on the return to the ED, within three months of a road traffic collision. Methods: We conducted a retrospective observational study on WAD patients from two EDs in Verona (Italy). Patients in the earlier acute phase of WAD (within 48 h from the trauma) were included; those with serious conditions (WAD IV) were excluded. As an end point, we considered patients who returned to the ED complaining of WAD symptoms within three months as positive outcome for WAD persistence. Results: 2162 patients were included; of those, 85.4% (n = 1847/2162) received a soft cervical collar prescription. Further, 8.4% (n = 156/1847) of those with a soft cervical collar prescription, and 2.5% (n = 8/315) of those without a soft cervical collar (p < 0.001) returned to the ED within three months. The use of the soft cervical collar was an independent risk factor for ED return within three months, with an OR, adjusted for possible clinical confounders, equal to 3.418 (95% CI 1.653–7.069; p < 0.001). After the propensity score matching, 25.5% of the patients (n = 25/98) using the soft cervical collar returned to the ED at three months, compared to the 6.1% (n = 6/98) that did not adopt the soft cervical collar. The use of a soft cervical collar was associated with ED return with an OR = 4.314 (95% CI 2.066–11.668; p = 0.001). Conclusions: Our study shows that the positioning of the soft collar in a cohort of patients with acute WAD, following a rear-end car collision, is an independent potential risk factor to the return to the ED. Clinically, the use of the collar is a non-recommended practice and seems to be related to an increased risk of delayed recovery. There is a need to inform healthcare providers involved in the ED of the aim to limit the use of the soft cervical collar. A closer collaboration between clinicians (e.g., physicians, physical therapists, nurses) is suggested in the ED. Future primary studies should determine differences between having used or not having used the collar, and compare early physical therapy in the ED compared with the utilization of the collar.
Impact of Nursing Professionalism on Perception of Patient Privacy Protection in Nursing Students: Mediating Effect of Nursing Informatics Competency
Authors: Park Hyun-Kyeong , Jeong Yeo-Won
Published: October 2021

In recent times, as the healthcare system becomes more informational, the importance of patient privacy protection increases, making it necessary to identify factors that affect the perception of patient privacy protection. This study aimed to evaluate the relationship between nursing professionalism and the perception of patient privacy protection and the mediating role of nursing informatics competency. The study recruited 242 nursing students who had experienced dealing with patient information during clinical practice. The mediating model using the Hayes’ PROCESS macro (Model 4) was employed to test the study hypothesis. Nursing professionalism was found to be positively and significantly associated with the perception of patient privacy protection (β = 0.09, p = 0.021) with the mediation of nursing informatics (β = 0.18, p < 0.001). Our findings showed that nursing professionalism and nursing informatics competency determined the perception of patient privacy protection. The mediating role of nursing informatics competency implies that curricula designed to enhance nursing informatics competency of nursing students may increase their perception of patient privacy protection.
A Reporting Quality Assessment of Systematic Reviews and Meta-Analyses in Sports Physical Therapy: A Review of Reviews
Authors: Cho Sung-Hyoun , Shin In-Soo
Published: October 2021

This review of reviews aimed to evaluate the reporting quality of published systematic reviews and meta-analyses in the field of sports physical therapy using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review of reviews included a literature search; in total, 2047 studies published between January 2015 and December 2020 in the top three journals related to sports physical therapy were screened. Among the 125 identified articles, 47 studies on sports physical therapy were included in the analysis (2 systematic reviews and 45 meta-analyses). There were several problems areas, including a lack of reporting for key components of the structured summary (10/47, 21.3%), protocol and registration (18/47, 38.3%), risk of bias in individual studies (28/47, 59.6%), risk of bias across studies (24/47, 51.1%), effect size and variance calculations (5/47, 10.6%), additional analyses (25/47, 53.2%), and funding (10/47, 21.3%). The quality of the reporting of systematic reviews and meta-analyses of studies on sports physical therapy was low to moderate. For better evidence-based practice in sports physical therapy, both authors and readers should examine assumptions in more detail, and report valid and adequate results. The PRISMA guideline should be used more extensively to improve reporting practices in sports physical therapy.
Microbiome Forensic Biobanking: A Step toward Microbial Profiling for Forensic Human Identification
Authors: Caenazzo Luciana , Tozzo Pamela
Published: October 2021

In recent years many studies have highlighted the great potential of microbial analysis in human identification for forensic purposes, with important differences in microbial community composition and function across different people and locations, showing a certain degree of uncertainty. Therefore, further studies are necessary to enable forensic scientists to evaluate the risk of microbial transfer and recovery from various items and to further critically evaluate the suitability of current human DNA recovery protocols for human microbial profiling for identification purposes. While the establishment and development of microbiome research biobanks for clinical applications is already very structured, the development of studies on the applicability of microbiome biobanks for forensic purposes is still in its infancy. The creation of large population microbiome biobanks, specifically dedicated to forensic human identification, could be worthwhile. This could also be useful to increase the practical applications of forensic microbiology for identification purposes, given that this type of evidence is currently absent from most real casework investigations and judicial proceedings in courts.
Applications of Machine Learning in Ambulatory ECG
Authors: Xue Joel , Yu Long
Published: October 2021

The ambulatory ECG (AECG) is an important diagnostic tool for many heart electrophysiology-related cases. AECG covers a wide spectrum of devices and applications. At the core of these devices and applications are the algorithms responsible for signal conditioning, ECG beat detection and classification, and event detections. Over the years, there has been huge progress for algorithm development and implementation thanks to great efforts by researchers, engineers, and physicians, alongside the rapid development of electronics and signal processing, especially machine learning (ML). The current efforts and progress in machine learning fields are unprecedented, and many of these ML algorithms have also been successfully applied to AECG applications. This review covers some key AECG applications of ML algorithms. However, instead of doing a general review of ML algorithms, we are focusing on the central tasks of AECG and discussing what ML can bring to solve the key challenges AECG is facing. The center tasks of AECG signal processing listed in the review include signal preprocessing, beat detection and classification, event detection, and event prediction. Each AECG device/system might have different portions and forms of those signal components depending on its application and the target, but these are the topics most relevant and of greatest concern to the people working in this area.
The Utilisation of Pholiota nameko, Hypsizygus marmoreus, and Hericium erinaceus Spent Mushroom Substrates in Pleurotus ostreatus Cultivation
Authors: Lisiecka Jolanta , Prasad Raghavendra , Jasinska Agnieszka
Published: October 2021

The feasibility of utilising spent mushroom substrates (SMSs) as a growing medium component for Pleurotus ostreatus cultivation was investigated. P. ostreatus was cultivated on traditional wheat straw (control) and wheat straw substrate supplemented with SMSs from Pholiota nameko (N-SMS), Hypsizygus marmoreus (M-SMS), and Hericium erinaceus (E-SMS) in varying supplementation rates (10%, 20%, and 30%). The yield, biological efficiency (BE), dry matter, and protein content of P. ostreatus fruiting bodies grown on ten substrates were evaluated. Significant differences in yield, BE, protein content, and dry matter of P. ostreatus were found among the studied substrates. The highest yield was recorded in 20% E-SMS (254.33 g), 20% N-SMS (253.43 g), and 10% E-SMS (251.67 g). The biological efficiency ranged from 66.48% (30% M-SMS) to 72.67% (20% E-SMS) and followed a similar trend to yield. The highest protein content was recorded in 30% M-SMS (29.93 g∙100 g dry weight−1). The highest dry matter of P. ostreatus was noticed in 30% of M-SMS (23.74 g) and 10% of M-SMS (23.06 g). Therefore, the spent mushroom substrates of Ph. nameko, H. marmoreus, and H. erinaceus could be used as a potential, low-cost sustainable alternative (10–30%) and as a renewable component of traditional growing media for P. ostreatus cultivation.
Understanding Plum Rain’s Effects on Urban Public Bicycle Unavailability Considering Both Place Semantics and Riding Distance
Authors: Chen Lijun , Zhang Haiping , Wang Haoran , Wu Peng
Published: October 2021

The effect of the plum rain weather event on cycling trips reflects the climate resilience of the public bicycle system. However, quantitative studies regarding the impact of plum rain on public bicycle users and corresponding spatial heterogeneity have not been paid much attention. This paper explores the spatial pattern of affected levels from the perspective of cyclist number, place semantics and riding distance. Corresponding public bicycle trips in normal weather are predicted by spatial-temporal random forest prediction. GIS neighborhood statistics and clustering algorithms are adapted to analyze and visualize the affected levels using origin-destination data of public bicycle trips and point of interest data of city public facilities. It is proved that there is an obvious spatial difference in affected levels by plum rain from three dimensions. In the dimension of the number of cyclists, the docking stations with different affected levels are distributed across the whole urban area. In the place semantic dimension, the docking stations with high affected levels show a clustered zonal distribution in the city center. In the dimension of cycling distance, the docking stations with high affected levels are mainly distributed in the periphery of the central urban area. The study theoretically expands the impact mechanism of environment and active transport. It is beneficial for the early monitoring, warning and assessment of climate change risks for public bicycle planning and management.
Structure and Formation Mechanism of Antimicrobial Peptides Temporin B- and L-Induced Tubular Membrane Protrusion
Authors: Zhang Shan , Ma Ming , Shao Zhuang , Zhang Jincheng , Fu Lei , Li Xiangyuan , Fang Weihai , Gao Lianghui
Published: October 2021

Temporins are a family of antimicrobial peptides (AMPs) isolated from frog skin, which are very short, weakly charged, and highly hydrophobic. They execute bactericidal activities in different ways from many other AMPs. This work investigated morphological changes of planar bilayer membranes composed of mixed zwitterionic and anionic phospholipids induced by temporin B and L (TB and TL) using all-atom and coarse-grained molecular dynamics simulations. We found that TB and TL fold to α-helices at the membrane surface and penetrate shallowly into the bilayer. These short AMPs have low propensity to induce membrane pore formation but possess high ability to extract lipids out. At relatively high peptide concentrations, the strong hydrophobicity of TB and TL promotes them to aggregate into clusters on the membrane surface. These aggregates attract a large amount of lipids out of the membrane to release compression induced by other dispersed peptides binding to the membrane. The extruded lipids mix evenly with the peptides in the cluster and form tubule-like protrusions. Certain water molecules follow the movement of lipids, which not only fill the cavities of the protrusion but also assist in maintaining the tubular structures. In contrast, the peptide-free leaflet remains intact. The present results unravel distinctive antimicrobial mechanisms of temporins disturbing membranes.
Adjunctive Thymosin Beta-4 Treatment Influences MΦ Effector Cell Function to Improve Disease Outcome in Pseudomonas aeruginosa-Induced Keratitis
Authors: Wang Yuxin , Carion Thomas W. , Ebrahim Abdul Shukkur , Sosne Gabriel , Berger Elizabeth A.
Published: October 2021

Our previous work has shown that topical thymosin beta 4 (Tβ4) as an adjunct to ciprofloxacin treatment reduces inflammatory mediators and inflammatory cell infiltrates (neutrophils/PMN and macrophages/MΦ) while enhancing bacterial killing and wound healing pathway activation in an experimental model of P. aeruginosa-induced keratitis. This study aimed to mechanistically examine how Tβ4 influences MΦ function in particular, leading to reduced inflammation and enhanced host defense following P. aeruginosa-induced infection of the cornea. Flow cytometry was conducted to profile the phenotype of infiltrating MΦ after infection, while generation of reactive nitrogen species and markers of efferocytosis were detected to assess functional activity. In vitro studies were performed utilizing RAW 264.7 cells to verify and extend the in vivo findings. Tβ4 treatment decreases MΦ infiltration and regulates the activation state in response to infected corneas. MΦ functional data demonstrated that the adjunctive Tβ4 treatment group significantly downregulated reactive nitrogen species (RNS) production and efferocytotic activity. In addition, the in vitro studies showed that both Tβ4 alone and adjunctive Tβ4 treatment influenced MΦ cellular function following LPS stimulation. Collectively, these data provide further evidence that adjunctive Tβ4 + ciprofloxacin treatment offers a more efficacious option for treating bacterial keratitis. Not only does the adjunctive therapy address both the infectious pathogen and corneal wound healing response, but it also influences MΦ infiltration, activation, and function, as revealed by the current study.
Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D
Authors: Amodeo Giuseppe Federico , Krilyuk Natalya , Pavlov Evgeny V.
Published: October 2021

The c subunit of the ATP synthase is an inner mitochondrial membrane (IMM) protein. Besides its role as the main component of the rotor of the ATP synthase, c subunit from mammalian mitochondria exhibits ion channel activity. In particular, c subunit may be involved in one of the pathways leading to the formation of the permeability transition pore (PTP) during mitochondrial permeability transition (PT), a phenomenon consisting of the permeabilization of the IMM due to high levels of calcium. Our previous study on the synthetic c subunit showed that high concentrations of calcium induce misfolding into cross-β oligomers that form low-conductance channels in model lipid bilayers of about 400 pS. Here, we studied the effect of cyclophilin D (CypD), a mitochondrial chaperone and major regulator of PTP, on the electrophysiological activity of the c subunit to evaluate its role in the functional properties of c subunit. Our study shows that in presence of CypD, c subunit exhibits a larger conductance, up to 4 nS, that could be related to its potential role in mitochondrial toxicity. Further, our results suggest that CypD is necessary for the formation of c subunit induced PTP but may not be an integral part of the pore.
The Effects of Photobiomodulation on Bone Defect Repairing in a Diabetic Rat Model
Authors: Lee Ji-Hua , Kong Su-Chii , Chen Chia-Hsin , Lin Ying-Chun , Lee Kun-Tsung , Wang Yan-Hsiung
Published: October 2021

The purpose of this study is to examine the prospective therapeutic effects of photobiomodulation on the healing of bone defects in diabetic mellitus (DM) using rat models to provide basic knowledge of photobiomodulation therapy (PBMT) during bone defect repair. For in vitro study, an Alizzarin red stain assay was used to evaluate the effect of PBMT on osteogenic differentiation. For in vivo study, micro-computed tomography (microCT) scan, H&E and IHC stain analysis were used to investigate the effect of PBMT on the healing of the experimental calvarial defect (3 mm in diameter) of a diabetic rat model. For in vitro study, the high glucose groups showed lower osteogenic differentiation in both irradiated and non-irradiated with PBMT when compared to the control groups. With the PBMT, all groups (control, osmotic control and high glucose) showed higher osteogenic differentiation when compared to the non-irradiated groups. For in vivo study, the hyperglycemic group showed significantly lower bone regeneration when compared to the control group. With the PBMT, the volume of bone regeneration was increasing and back to the similar level of the control group. The treatment of PBMT in 660 nm could improve the bone defect healing on a diabetic rat calvarial defect model.
Synthesis and Investigations of Building Blocks with Dibenzo[b,f] Oxepine for Use in Photopharmacology
Authors: Tobiasz Piotr , Borys Filip , Borecka Marta , Krawczyk Hanna
Published: October 2021

The synthesis of photoswitchable azo-dibenzo[b,f]oxepine derivatives and microtubule inhibitors were described. Subsequently, we examined the reaction of methoxy derivative 3-nitrodibenzo[b,f]oxepine with different aldehydes and in the presence of BF3·OEt2 as a catalyst. Our study provided a very concise method for the construction of the azo-dibenzo[b,f]oxepine skeleton. The analysis of products was run using experimental and theoretical methods. Next, we evaluated the E/Z isomerization of azo-dibenzo[b,f]oxepine derivatives, which could be photochemically controlled using visible-wavelength light.
Synthesis of Si/Fe2O3-Anchored rGO Frameworks as High-Performance Anodes for Li-Ion Batteries
Authors: Yan Yajing , Chen Yanxu , Li Yongyan , Wu Xiaoyu , Jin Chao , Wang Zhifeng
Published: October 2021

By virtue of the high theoretical capacity of Si, Si-related materials have been developed as promising anode candidates for high-energy-density batteries. During repeated charge/discharge cycling, however, severe volumetric variation induces the pulverization and peeling of active components, causing rapid capacity decay and even development stagnation in high-capacity batteries. In this study, the Si/Fe2O3-anchored rGO framework was prepared by introducing ball milling into a melt spinning and dealloying process. As the Li-ion battery (LIB) anode, it presents a high reversible capacity of 1744.5 mAh g−1 at 200 mA g−1 after 200 cycles and 889.4 mAh g−1 at 5 A g−1 after 500 cycles. The outstanding electrochemical performance is due to the three-dimensional cross-linked porous framework with a high specific surface area, which is helpful to the transmission of ions and electrons. Moreover, with the cooperation of rGO, the volume expansion of Si is effectively alleviated, thus improving cycling stability. The work provides insights for the design and preparation of Si-based materials for high-performance LIB applications.
Evidence on the Bioaccessibility of Glucosinolates and Breakdown Products of Cruciferous Sprouts by Simulated In Vitro Gastrointestinal Digestion
Authors: Abellán Ángel , Domínguez-Perles Raúl , García-Viguera Cristina , Moreno Diego A.
Published: October 2021

Cruciferous vegetables are gaining importance as nutritious and sustainable foods, rich in phytochemical compounds such as glucosinolates (GSLs). However, the breakdown products of these sulfur-based compounds, mainly represented by isothiocyanates (ITC) and indoles, can contribute to human health. In the human digestive system, the formation of these compounds continues to varying extents in the different stages of digestion, due to the contact of GSLs with different gastric fluids and enzymes under the physicochemical conditions of the gastrointestinal tract. Therefore, the aim of the present work was to uncover the effect of gastrointestinal digestion on the release of glucosinolates and their transformation into their bioactive counterparts by applying a simulated in vitro static model on a range of brassica (red radish, red cabbage, broccoli, and mustard) sprouts. In this sense, significantly higher bioaccessibility of ITC and indoles from GSLs of red cabbage sprouts was observed in comparison with broccoli, red radish, and mustard sprouts, due to the aliphatic GSLs proportion present in the different sprouts. This indicates that the bioaccessibility of GSLs from Brasicaceae sprouts is not exclusively associated with the initial content of these compounds in the plant material (almost negligible), but also with the release of GSLs and the ongoing breakdown reactions during the gastric and intestinal phases of digestion, respectively. Additionally, aliphatic GSLs provided higher bioaccessibility of their corresponding ITC in comparison to indolic and aromatic GSLs.
Telomeric-Like Repeats Flanked by Sequences Retrotranscribed from the Telomerase RNA Inserted at DNA Double-Strand Break Sites during Vertebrate Genome Evolution
Authors: Sola Lorenzo , Nergadze Solomon G. , Cappelletti Eleonora , Piras Francesca M. , Giulotto Elena , Santagostino Marco
Published: October 2021

Interstitial telomeric sequences (ITSs) are stretches of telomeric-like repeats located at internal chromosomal sites. We previously demonstrated that ITSs have been inserted during the repair of DNA double-strand breaks in the course of evolution and that some rodent ITSs, called TERC-ITSs, are flanked by fragments retrotranscribed from the telomerase RNA component (TERC). In this work, we carried out an extensive search of TERC-ITSs in 30 vertebrate genomes and identified 41 such loci in 22 species, including in humans and other primates. The fragment retrotranscribed from the TERC RNA varies in different lineages and its sequence seems to be related to the organization of TERC. Through comparative analysis of TERC-ITSs with orthologous empty loci, we demonstrated that, at each locus, the TERC-like sequence and the ITS have been inserted in one step in the course of evolution. Our findings suggest that telomerase participated in a peculiar pathway of DNA double-strand break repair involving retrotranscription of its RNA component and that this mechanism may be active in all vertebrate species. These results add new evidence to the hypothesis that RNA-templated DNA repair mechanisms are active in vertebrate cells.
Blood-Based Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma, Including the Viral Genome and Glycosylated Proteins
Authors: Hayashi Sanae , Nagaoka Katsuya , Tanaka Yasuhito
Published: October 2021

Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) development and is a global public health issue. High performance biomarkers can aid the early detection of HCC development in HBV-infected individuals. In addition, advances in the understanding of the pathogenesis of HBV infection and in clinical laboratory techniques have enabled the establishment of disease-specific tests, prediction of the progression of liver diseases, including HCC, and auxiliary diagnosis of HCC, using blood-based methods instead of biopsies of liver or HCC tissues. Viral factors such as the HBV genotype, HBV genetic mutations, HBV DNA, and HBV-related antigens, as well as host factors, such as tumor-associated proteins and post-translational modifications, especially glycosylated proteins, can be blood-based, disease-specific biomarkers for HCC development in HBV-infected patients. In this review, we describe the clinical applications of viral biomarkers, including the HBV genome and glycosylated proteins, for patients at a risk of HBV-related HCC, based on their molecular mechanisms. In addition, we introduce promising biomarker candidates for practical use, including colony stimulating factor 1 receptor (CSF1R), extracellular vesicles, and cell-free, circulating tumor DNA. The clinical use of such surrogate markers may lead to a better understanding of the risk of disease progression and early detection of HCC in HBV-infected patients, thereby improving their prognosis.
High Resolution Structure of the Mature Capsid of Ralstonia solanacearum Bacteriophage ϕRSA1 by Cryo-Electron Microscopy
Authors: Effantin Grégory , Fujiwara Akiko , Kawasaki Takeru , Yamada Takashi , Schoehn Guy
Published: October 2021

The ϕRSA1 bacteriophage has been isolated from Ralstonia solanacearum, a gram negative bacteria having a significant economic impact on many important crops. We solved the three-dimensional structure of the ϕRSA1 mature capsid to 3.9 Å resolution by cryo-electron microscopy. The capsid shell, that contains the 39 kbp of dsDNA genome, has an icosahedral symmetry characterized by an unusual triangulation number of T = 7, dextro. The ϕRSA1 capsid is composed solely of the polymerization of the major capsid protein, gp8, which exhibits the typical “Johnson” fold first characterized in E. coli bacteriophage HK97. As opposed to the latter, the ϕRSA1 mature capsid is not stabilized by covalent crosslinking between its subunits, nor by the addition of a decoration protein. We further describe the molecular interactions occurring between the subunits of the ϕRSA1 capsid and their relationships with the other known bacteriophages.
NK Cell-Dependent Antibody-Mediated Immunotherapy Is Improved In Vitro and In Vivo When Combined with Agonists for Toll-like Receptor 2 in Head and Neck Cancer Models
Authors: Gruijs Mandy , Ganzevles Sonja H. , Stigter-van Walsum Marijke , van der Mast Richard , van Ostaijen-ten Dam Monique M. , Tuk Cornelis W. , Schilham Marco W. , Leemans C. René , Brakenhoff Ruud H. , van Egmond Marjolein , van de Ven Rieneke , Bakema Jantine E.
Published: October 2021

The immunosuppressive character of head and neck cancers may explain the relatively low response rates to antibody therapy targeting a tumor antigen, such as cetuximab, and anti-PD-1 checkpoint inhibition. Immunostimulatory agents that overcome tumor-derived inhibitory signals could augment therapeutic efficacy, thereby enhancing tumor elimination and improving patient survival. Here, we demonstrate that cetuximab treatment combined with immunostimulatory agonists for Toll-like receptor (TLR) 2 induces profound immune responses. Natural killer (NK) cells, isolated from healthy individuals or patients with head and neck cancer, harbored enhanced cytotoxic capacity and increased tumor-killing potential in vitro. Additionally, combination treatment increased the release of several pro-inflammatory cytokines and chemokines by NK cells. Tumor-bearing mice that received cetuximab and the TLR2 ligand Pam3CSK4 showed increased infiltration of immune cells into the tumors compared to mice that received cetuximab monotherapy, resulting in a significant delay in tumor growth or even complete tumor regression. Moreover, combination treatment resulted in improved overall survival in vivo. In conclusion, combining tumor-targeting antibody-based immunotherapy with TLR stimulation represents a promising treatment strategy to improve the clinical outcomes of cancer patients. This treatment could well be applied together with other therapeutic strategies such as anti-PD-(L)1 checkpoint inhibition to further overcome immunosuppression.
The Abscopal Effect: A Review of Pre-Clinical and Clinical Advances
Authors: Janopaul-Naylor James R. , Shen Yang , Qian David C. , Buchwald Zachary S.
Published: October 2021

Radiotherapy has been used for more than a hundred years to cure or locally control tumors. Regression of tumors outside of the irradiated field was occasionally observed and is known as the abscopal effect. However, the occurrence of systemic anti-tumor effects was deemed too rare and unpredictable to be a therapeutic goal. Recent studies suggest that immunotherapy and radiation in combination may enhance the abscopal response. Increasing numbers of cases are being reported since the routine implementation of immune checkpoint inhibitors, showing that combined radiotherapy with immunotherapy has a synergistic effect on both local and distant (i.e., unirradiated) tumors. In this review, we summarize pre-clinical and clinical reports, with a specific focus on the mechanisms behind the immunostimulatory effects of radiation and how this is enhanced by immunotherapy.
Insects as a New Complex Model in Hormonal Basis of Obesity
Authors: Walkowiak-Nowicka Karolina , Chowański Szymon , Urbański Arkadiusz , Marciniak Paweł
Published: October 2021

Nowadays, one of the biggest problems in healthcare is an obesity epidemic. Consumption of cheap and low-quality energy-rich diets, low physical activity, and sedentary work favor an increase in the number of obesity cases within many populations/nations. This is a burden on society, public health, and the economy with many deleterious consequences. Thus, studies concerning this disorder are extremely needed, including searching for new, effective, and fitting models. Obesity may be related, among other factors, to disrupting adipocytes activity, disturbance of metabolic homeostasis, dysregulation of hormonal balance, cardiovascular problems, or disorders in nutrition which may lead to death. Because of the high complexity of obesity, it is not easy to find an ideal model for its studies which will be suitable for genetic and physiological analysis including specification of different compounds’ (hormones, neuropeptides) functions, as well as for signaling pathways analysis. In recent times, in search of new models for human diseases there has been more and more attention paid to insects, especially in neuro-endocrine regulation. It seems that this group of animals might also be a new model for human obesity. There are many arguments that insects are a good, multidirectional, and complex model for this disease. For example, insect models can have similar conservative signaling pathways (e.g., JAK-STAT signaling pathway), the presence of similar hormonal axis (e.g., brain–gut axis), or occurrence of structural and functional homologues between neuropeptides (e.g., neuropeptide F and human neuropeptide Y, insulin-like peptides, and human insulin) compared to humans. Here we give a hint to use insects as a model for obesity that can be used in multiple ways: as a source of genetic and peptidomic data about etiology and development correlated with obesity occurrence as well as a model for novel hormonal-based drug activity and their impact on mechanism of disease occurrence.
Comparison of the Effects of Chemokine Receptors CXCR2 and CXCR3 Pharmacological Modulation in Neuropathic Pain Model—In Vivo and In Vitro Study
Authors: Piotrowska Anna , Ciapała Katarzyna , Pawlik Katarzyna , Kwiatkowski Klaudia , Rojewska Ewelina , Mika Joanna
Published: October 2021

Recent findings have highlighted the roles of CXC chemokine family in the mechanisms of neuropathic pain. Our studies provide evidence that single/repeated intrathecal administration of CXCR2 (NVP-CXCR2-20) and CXCR3 ((±)-NBI-74330) antagonists explicitly attenuated mechanical/thermal hypersensitivity in rats after chronic constriction injury of the sciatic nerve. After repeated administration, both antagonists showed strong analgesic activity toward thermal hypersensitivity; however, (±)-NBI-74330 was more effective at reducing mechanical hypersensitivity. Interestingly, repeated intrathecal administration of both antagonists decreased the mRNA and/or protein levels of pronociceptive interleukins (i.e., IL-1beta, IL-6, IL-18) in the spinal cord, but only (±)-NBI-74330 decreased their levels in the dorsal root ganglia after nerve injury. Furthermore, only the CXCR3 antagonist influenced the spinal mRNA levels of antinociceptive factors (i.e., IL-1RA, IL-10). Additionally, antagonists effectively reduced the mRNA levels of pronociceptive chemokines; NVP-CXCR2-20 decreased the levels of CCL2, CCL6, CCL7, and CXCL4, while (±)-NBI-74330 reduced the levels of CCL3, CCL6, CXCL4, and CXCL9. Importantly, the results obtained from the primary microglial and astroglial cell cultures clearly suggest that both antagonists can directly affect the release of these ligands, mainly in microglia. Interestingly, NVP-CXCR2-20 induced analgesic effects after intraperitoneal administration. Our research revealed important roles for CXCR2 and CXCR3 in nociceptive transmission, especially in neuropathic pain.
An Insight into Anti-Inflammatory Activities and Inflammation Related Diseases of Anthocyanins: A Review of Both In Vivo and In Vitro Investigations
Authors: Ma Zilong , Du Bin , Li Jun , Yang Yuedong , Zhu Fengmei
Published: October 2021

Anthocyanin is a type of flavonoid pigment widely present in fruits and vegetables. It can not only be used as natural pigment, but also has a variety of health functions, for instance, anti-oxidant, anti-inflammatory, anti-tumor, and neuroprotective activities. Persistent proinflammatory status is a major factor in the development, progression, and complications of chronic diseases. Not surprisingly, there are thus many food ingredients that can potentially affect inflammation related diseases and many studies have shown that anthocyanins play an important role in inflammatory pathways. In this paper, the inflammation related diseases (such as, obesity, diabetes, cardiovascular disease, and cancer) of anthocyanins are introduced, and the anti-inflammatory effect of anthocyanins is emphatically introduced. Moreover, the anti-inflammatory mechanism of anthocyanins is elaborated from the aspects of NF-κB, toll like receptor, MAPKs, NO, and ROS and the main efficacy of anthocyanins in inflammation and related diseases is determined. In conclusion, this review aims to get a clear insight into the role of anthocyanins in inflammation related diseases.
Finite Mixture Models Based on Pain Intensity, Functional Disability and Psychological Distress Composite Assessment Allow Identification of Two Distinct Classes of Persistent Spinal Pain Syndrome after Surgery Patients Related to Their Quality of Life
Authors: Ounajim Amine , Billot Maxime , Louis Pierre-Yves , Slaoui Yousri , Frasca Denis , Goudman Lisa , Roulaud Manuel , Naiditch Nicolas , Lorgeoux Bertille , Baron Sandrine , Nivole Kevin , Many Mathilde , Adjali Nihel , Page Philippe , Bouche Bénédicte , Charrier Elodie , Poupin Laure , Rannou Delphine , de Montgazon Géraldine Brumauld , Roy-Moreau Brigitte , Wood Chantal , Rigoard Raphaël , David Romain , Moens Maarten , Rigoard Philippe
Published: October 2021

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with one-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n = 136), and by pain perception for second class patients (n = 62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.
More than 50% of Persistent Myocardial Scarring at One Year in “Infarct-like” Acute Myocarditis Evaluated by CMR
Authors: Pommier Thibaut , Leclercq Thibault , Guenancia Charles , Tisserand Simon , Lairet Céline , Carré Max , Lalande Alain , Bichat Florence , Maza Maud , Zeller Marianne , Cochet Alexandre , Cottin Yves
Published: October 2021

Background: Cardiac magnetic resonance (CMR) has emerged as a reference tool for the non-invasive diagnosis of myocarditis. However, its role in follow-up (FU) after the acute event is unclear. The objectives were to assess the evolution of CMR parameters between the acute phase of infarct-like myocarditis and 12 months thereafter and to identify the predictive factors of persistent myocardial scarring at one year. Methods: All patients with infarct-like acute myocarditis confirmed by CMR were included. CMR was performed within 8 days following symptom onset, at 3 months and at one year. One-year FU included ECG, a cardiac stress test, Holter recording, biological assessments, medical history and a quality-of-life questionnaire. Patients were classified according to the presence or absence of complete recovery at one year based on the CMR evaluation. Results: A total of 174 patients were included, and 147 patients had three CMR. At one year, 79 patients (54%) exhibited persistent myocardial scarring on CMR. A multivariate analysis showed that high peak troponin at the acute phase (OR: 3.0—95%CI: 1.16–7.96—p = 0.024) and the initial extent of late gadolinium enhancement (LGE) (OR: 1.1—95%CI: 1.03–1.19—p = 0.006) were independent predictors of persistent myocardial scarring. Moreover, patients with myocardial scarring on the FU CMR were more likely to have premature ventricular contractions during the cardiac stress test (25% versus 9%, p = 0.008). Conclusion: Less than 50% of patients with infarct-like acute myocarditis showed complete recovery at one year. Although major adverse cardiac events were rare, ventricular dysrhythmias at one year were more frequent in patients with persistent myocardial scarring.
Early Administration of Bamlanivimab in Combination with Etesevimab Increases the Benefits of COVID-19 Treatment: Real-World Experience from the Liguria Region
Authors: Vena Antonio , Cenderello Giovanni , Balletto Elisa , Mezzogori Laura , Santagostino Barbone Alessandro , Berruti Marco , Ball Lorenzo , Battaglini Denise , Bonsignore Alessandro , Dentone Chiara , Giacobbe Daniele Roberto , Eldin Tarek Kamal , Mikulska Malgorzata , Rebesco Barbara , Robba Chiara , Scintu Ambra , Stimamiglio Andrea , Taramasso Lucia , Pelosi Paolo , Artioli Stefania , Bassetti Matteo
Published: October 2021

Monoclonal antibodies, such as bamlanivimab and etesevimab combination (BEC), have been proposed for patients with mild or moderate coronavirus disease 2019 (COVID-19). However, few studies have assessed the factors associated with the early administration of BEC or the impact of early BEC treatment on the clinical evolution of the patients. We conducted a retrospective cohort study of all adults with COVID-19 who received BEC at three institutions in the Liguria region. The primary endpoint was to investigate the clinical variables associated with early BEC infusion. Secondary endpoints were 30-day overall mortality and the composite endpoint of requirement of hospital admission or need for supplemental oxygen during the 30-day follow-up period. A total of 127 patients (median age 70 years; 56.7% males) received BEC. Of those, 93 (73.2%) received BEC within 5 days from symptoms onset (early BEC). Patients with a higher Charlson comorbidity index were more likely to receive early treatment (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.04–2.45; p = 0.03) in contrast to those reporting fever at presentation (OR 0.26, 0.08–0.82; p = 0.02). Early BEC was associated with lower likelihood of hospital admission or need for supplemental oxygen (OR 0.19, 0.06–0.65; p = 0.008). Five patients who received early BEC died during the follow-up period, but only one of them due to COVID-19-related causes. Early bamlanivimab and etesevimab combination was more frequently administered to patients with a high Charlson comorbidity index. Despite this, early BEC was associated with a lower rate of hospital admission or need for any supplementary oxygen compared to late administration. These results suggest that efforts should focus on encouraging early BEC use in patients with mild–moderate COVID-19 at risk for complications.
Association between Severity of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of Other Spinal Ligaments in Patients with Ossification of the Posterior Longitudinal Ligament
Authors: Nishimura Soraya , Hirai Takashi , Nagoshi Narihito , Yoshii Toshitaka , Hashimoto Jun , Mori Kanji , Maki Satoshi , Katsumi Keiichi , Takeuchi Kazuhiro , Ushio Shuta , Furuya Takeo , Watanabe Kei , Nishida Norihiro , Kaito Takashi , Kato Satoshi , Nagashima Katsuya , Koda Masao , Nakashima Hiroaki , Imagama Shiro , Murata Kazuma , Matsuoka Yuji , Wada Kanichiro , Kimura Atsushi , Ohba Tetsuro , Katoh Hiroyuki , Watanabe Masahiko , Matsuyama Yukihiro , Ozawa Hiroshi , Haro Hirotaka , Takeshita Katsushi , Matsukura Yu , Inose Hiroyuki , Yamazaki Masashi , Watanabe Kota , Matsumoto Morio , Nakamura Masaya , Okawa Atsushi , Kawaguchi Yoshiharu
Published: October 2021

Background: Although diffuse idiopathic skeletal hyperostosis (DISH) is known to coexist with the ossification of spinal ligaments (OSLs), details of the radiographic relationship remain unclear. Methods: We prospectively collected data of 239 patients with symptomatic cervical ossification of the posterior longitudinal ligament (OPLL) and analyzed the DISH severity on whole-spine computed tomography images, using the following grades: grade 0, no DISH; grade 1, DISH at T3–T10; grade 2, DISH at both T3–T10 and C6–T2 and/or T11–L2; and grade 3, DISH beyond C5 and/or L3. Ossification indices were calculated as the sum of vertebral and intervertebral levels with OSL for each patient. Results: DISH was found in 107 patients (44.8%), 65 (60.7%) of whom had grade 2 DISH. We found significant associations of DISH grade with the indices for cervical OPLL (r = 0.45, p < 0.0001), thoracic ossification of the ligamentum flavum (OLF; r = 0.41, p < 0.0001) and thoracic ossification of the supra/interspinous ligaments (OSIL; r = 0.53, p < 0.0001). DISH grade was also correlated with the index for each OSL in the whole spine (OPLL: r = 0.29, p < 0.0001; OLF: r = 0.40, p < 0.0001; OSIL: r = 0.50, p < 0.0001). Conclusion: The DISH grade correlated with the indices of OSL at each high-prevalence level as well as the whole spine.
Prognostic Value of Interleukin-32 Expression and Its Correlation with the Infiltration of Natural Killer Cells in Cutaneous Melanoma
Authors: Kang Ji Young , Kim Kyung Eun
Published: October 2021

Interleukin-32 (IL-32) is well known as a proinflammatory cytokine that is expressed in various immune cells and cancers. However, the clinical relevance of IL-32 expression in cutaneous melanoma has not been comprehensively studied. Here, we identified the prognostic value of IL32 expression using various systematic multiomic analyses. The IL32 expressions were significantly higher in cutaneous melanoma than in normal tissue, and Kaplan–Meier survival analysis showed a correlation between IL32 expression and good prognosis in cutaneous melanoma patients. In addition, we analyzed the correlation between IL32 expression and the infiltration of natural killer (NK) cells to identify a relevant mechanism between IL32 expression and prognosis in cutaneous melanoma (p = 0.00031). In the relationship between IL32 expression and the infiltration of NK cells, a negative correlation was found in resting NK cells (rho = −0.38, p = 3.95 × 10−17) whereas a strong positive correlation was observed only in active NK cells (rho = 0.374, p = 1.23 × 10−16). Moreover, IL32 expression was markedly positively correlated with the cytolytic molecules, such as granzyme and perforin. These data suggest that IL32 expression may increase patient survival through the infiltration and activation of NK cells, representative anticancer effector cells, in cutaneous melanoma. Collectively, this study provides the prognostic value of IL32 expression and its potential role as an effective predictive biomarker for NK cell infiltration in cutaneous melanoma.
Impact of the Pre-Transplant Circulatory Supportive Strategy on Post-Transplant Outcome: Double Bridge May Work
Authors: Chou Nai-Kuan , Chou Heng-Wen , Tsao Chuan-I , Wang Chih-Hsien , Chen Kevin Po-Hsun , Chi Nai-Hsin , Huang Shu-Chien , Yu Hsi-Yu , Chen Yih-Sharng
Published: October 2021

Background: The number of waitlisted patients requiring mechanical circulatory support (MCS) as a bridge to heart transplantation is increasing. The data concerning the results of the double-bridge strategy are limited. We sought to investigate the post-transplant outcomes across the different bridge strategies. Methods: We retrospectively reviewed a heart transplantation database from Jan 2009 to Jan 2019. Intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), and ventricular assist devices (VAD) were the MCS that we investigated. The pre- and post-transplant characteristics and variables of patients bridged with the different types of MCS were collected. The post-transplant survival was compared using Kaplan–Meier survival analysis. Results: A total of 251 heart transplants were reviewed; 115 without MCS and 136 with MCS. The patients were divided to five groups: Group 1 (no MCS): n = 115; Group 2 (IABP): n = 15; Group 3 (ECMO): n = 33; Group 4 (ECMO-VAD): double-bridge (n = 59); Group 5 (VAD): n = 29. Survival analysis demonstrated that the 3-year post-transplant survival rates were significantly different among the groups (Log-rank p < 0.001). There was no difference in survival between group 4(ECMO-VAD) and group 1(no MCS)1 (p = 0.136), or between group 4(ECMO-VAD) and group 5(VAD) (p = 0.994). Group 3(ECMO) had significantly inferior 3-year survival than group 4(ECMO-VAD) and group 5(VAD). Conclusion: Double bridge may not lead to worse mid-term results in patients who could receive a transplantation. Initial stabilization with ECMO for critical patients before implantation of VAD might be considered as a strategy for obtaining an optimal post-transplant outcome.