bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: NFIL3 Facilitates Neutrophil Autophagy, Neutrophil Extracellular Trap Formation and Inflammation During Gout via REDD1-Dependent mTOR Inactivation
Authors: Tang Honghu , Tan Chunyu , Cao Xue , Liu Yi , Zhao Hua , Liu Yi , Zhao Yi
Published: September 2021

Autophagy pathways play an important role in immunity and inflammation via pathogen clearance mechanisms mediated by immune cells, such as macrophages and neutrophils. In particular, autophagic activity is essential for the release of neutrophil extracellular traps (NETs), a distinct form of active neutrophil death. The current study set out to elucidate the mechanism of the NFIL3/REDD1/mTOR axis in neutrophil autophagy and NET formation during gout inflammation. Firstly, NFIL3 expression patterns were determined in the peripheral blood neutrophils of gout patients and monosodium urate (MSU)-treated neutrophils. Interactions between NFIL3 and REDD1 were identified. In addition, gain- or loss-of-function approaches were used to manipulate NFIL3 and REDD1 in both MSU-induced neutrophils and mice. The mechanism of NFIL3 in inflammation during gout was evaluated both in vivo and in vitro via measurement of cell autophagy, NET formation, MPO activity as well as levels of inflammatory factors. NFIL3 was highly-expressed in both peripheral blood neutrophils from gout patients and MSU-treated neutrophils. NFIL3 promoted the transcription of REDD1 by binding to its promoter. REDD1 augmented neutrophil autophagy and NET formation by inhibiting the mTOR pathway. In vivo experimental results further confirmed that silencing of NFIL3 reduced the inflammatory injury of acute gouty arthritis mice by inhibiting the neutrophil autophagy and NET formation, which was associated with down-regulation of REDD1 and activation of the mTOR pathway. Taken together, NFIL3 can aggravate the inflammatory reaction of gout by stimulating neutrophil autophagy and NET formation via REDD1/mTOR, highlighting NFIL3 as a potential therapeutic target for gout.
Helicobacter pylori Infection in Geriatric Patients: Current Situation and Treatment Regimens
Authors: Huang Qiuyue , Jia Xiaofen , Chu Yingming , Zhang Xuezhi , Ye Hui
Published: September 2021

Helicobacter pylori (H. pylori) has so far infected more than half the global population. It is the most important and controllable risk factor for gastric cancer. The elderly, who are at a higher incidence of the infection, are also commonly found to develop antibiotic resistance. The symptoms, diagnosis, clinical features (of gastric or extra-digestive diseases), and treatment of H. pylori infection in the elderly, are different from that in the non-elderly. Health conditions, including comorbidities and combined medication have limited the use of regular therapies in elderly patients. However, they can still benefit from eradication therapy, thus preventing gastric mucosal lesions and gastric cancer. In addition, new approaches, such as dual therapy and complementary therapy, have the potential to treat older patients with H. pylori infection.
The COVID-19 Assessment for Survival at Admission (CASA) Index: A 12 Months Observational Study
Authors: Bagnato Gianluca , La Rosa Daniela , Ioppolo Carmelo , De Gaetano Alberta , Chiappalone Marianna , Zirilli Natalia , Viapiana Valeria , Tringali Maria Concetta , Tomeo Simona , Aragona Caterina Oriana , Napoli Francesca , Lillo Sara , Irrera Natasha , Roberts William Neal , Imbalzano Egidio , Micari Antonio , Ventura Spagnolo Elvira , Squadrito Giovanni , Gangemi Sebastiano , Versace Antonio Giovanni
Published: September 2021

Objective: Coronavirus disease 2019 (COVID-19) is a disease with a high rate of progression to critical illness. However, the stratification of patients at risk of mortality is not well defined. In this study, we aimed to define a mortality risk index to allocate patients to the appropriate intensity of care.

Methods: This is a 12 months observational longitudinal study designed to develop and validate a pragmatic mortality risk score to stratify COVID-19 patients aged ≥18 years and admitted to hospital between March 2020 and March 2021. Main outcome was in-hospital mortality.

Results: 244 patients were included in the study (mortality rate 29.9%). The Covid-19 Assessment for Survival at Admission (CASA) index included seven variables readily available at admission: respiratory rate, troponin, albumin, CKD-EPI, white blood cell count, D-dimer, Pa02/Fi02. The CASA index showed high discrimination for mortality with an AUC of 0.91 (sensitivity 98.6%; specificity 69%) and a better performance compared to SOFA (AUC = 0.76), age (AUC = 0.76) and 4C mortality (AUC = 0.82). The cut-off identified (11.994) for CASA index showed a negative predictive value of 99.16% and a positive predictive value of 57.58%.

Conclusions: A quick and readily available index has been identified to help clinicians stratify COVID-19 patients according to the appropriate intensity of care and minimize hospital admission to patients at high risk of mortality.
Optimization of BCG Therapy Targeting Neutrophil Extracellular Traps, Autophagy, and miRNAs in Bladder Cancer: Implications for Personalized Medicine
Authors: Mao Chenyu , Xu Xin , Ding Yongfeng , Xu Nong
Published: September 2021

Bladder cancer (BC) is the ninth most common cancer and the thirteenth most common cause of mortality worldwide. Bacillus Calmette Guerin (BCG) instillation is a common treatment option for BC. BCG therapy is associated with the less adversary effects, compared to chemotherapy, radiotherapy, and other conventional treatments. BCG could inhibit the progression and recurrence of BC by triggering apoptosis pathways, arrest cell cycle, autophagy, and neutrophil extracellular traps (NETs) formation. However, BCG therapy is not efficient for metastatic cancer. NETs and autophagy were induced by BCG and help to suppress the growth of tumor cells especially in the primary stages of BC. Activated neutrophils can stimulate autophagy pathway and release NETs in the presence of microbial pathogenesis, inflammatory agents, and tumor cells. Autophagy can also regulate NETs formation and induce production of reactive oxygen species (ROS) and NETs. Moreover, miRNAs are important regulator of gene expression. These small non-coding RNAs are also considered as an essential factor to control the levels of tumor development. However, the interaction between BCG and miRNAs has not been well-understood yet. Therefore, the present study discusses the roles of miRNAs in regulations of autophagy and NETs formation in BCG therapy in the treatment of BC. The roles of autophagy and NETs formation in BC treatment and efficiency of BCG are also discussed.
Advances in Multi-Omics Applications in HBV-Associated Hepatocellular Carcinoma
Authors: Cui Dawei , Li Wei , Jiang Daixi , Wu Jianguo , Xie Jue , Wu Yingping
Published: September 2021

Hepatitis B virus (HBV) specifically infects liver cells, leading to progressive liver cirrhosis and significantly increasing the risk of hepatocellular carcinoma (HCC). The maturity of sequencing technology, improvement in bioinformatics data analysis and progress of omics technologies had improved research efficiency. The occurrence and progression of HCC are affected by multisystem and multilevel pathological changes. With the application of single-omics technologies, including genomics, transcriptomics, metabolomics and proteomics in tissue and body fluid samples, and even the novel development of multi-omics analysis on a single-cell platform, HBV-associated HCC changes can be better analyzed. The review summarizes the application of single omics and combined analysis of multi-omics data in HBV-associated HCC and proposes the importance of multi-omics analysis in the type of HCC, which provide the possibility for the precise diagnosis and therapy of HBV-associated HCC.
Metagenomic Analysis Reveals Microbial Interactions at the Biocathode of a Bioelectrochemical System Capable of Simultaneous Trichloroethylene and Cr(VI) Reduction
Authors: Matturro Bruna , Zeppilli Marco , Lai Agnese , Majone Mauro , Rossetti Simona
Published: September 2021

Bioelectrochemical systems (BES) are attractive and versatile options for the bioremediation of organic or inorganic pollutants, including trichloroethylene (TCE) and Cr(VI), often found as co-contaminants in the environment. The elucidation of the microbial players’ role in the bioelectroremediation processes for treating multicontaminated groundwater is still a research need that attracts scientific interest. In this study, 16S rRNA gene amplicon sequencing and whole shotgun metagenomics revealed the leading microbial players and the primary metabolic interactions occurring in the biofilm growing at the biocathode where TCE reductive dechlorination (RD), hydrogenotrophic methanogenesis, and Cr(VI) reduction occurred. The presence of Cr(VI) did not negatively affect the TCE degradation, as evidenced by the RD rates estimated during the reactor operation with TCE (111±2 μeq/Ld) and TCE/Cr(VI) (146±2 μeq/Ld). Accordingly, Dehalococcoides mccartyi, the primary biomarker of the RD process, was found on the biocathode treating both TCE (7.82E+04±2.9E+04 16S rRNA gene copies g−1 graphite) and TCE/Cr(VI) (3.2E+07±2.37E+0716S rRNA gene copies g−1 graphite) contamination. The metagenomic analysis revealed a selected microbial consortium on the TCE/Cr(VI) biocathode. D. mccartyi was the sole dechlorinating microbe with H2 uptake as the only electron supply mechanism, suggesting that electroactivity is not a property of this microorganism. Methanobrevibacter arboriphilus and Methanobacterium formicicum also colonized the biocathode as H2 consumers for the CH4 production and cofactor suppliers for D. mccartyi cobalamin biosynthesis. Interestingly, M. formicicum also harbors gene complexes involved in the Cr(VI) reduction through extracellular and intracellular mechanisms.
Quantitative Description of Surface Complementarity of Antibody-Antigen Interfaces
Authors: Di Rienzo Lorenzo , Milanetti Edoardo , Ruocco Giancarlo , Lepore Rosalba
Published: September 2021

Antibodies have the remarkable ability to recognise their cognate antigens with extraordinary affinity and specificity. Discerning the rules that define antibody-antigen recognition is a fundamental step in the rational design and engineering of functional antibodies with desired properties. In this study we apply the 3D Zernike formalism to the analysis of the surface properties of the antibody complementary determining regions (CDRs). Our results show that shape and electrostatic 3DZD descriptors of the surface of the CDRs are predictive of antigen specificity, with classification accuracy of 81% and area under the receiver operating characteristic curve (AUC) of 0.85. Additionally, while in terms of surface size, solvent accessibility and amino acid composition, antibody epitopes are typically not distinguishable from non-epitope, solvent-exposed regions of the antigen, the 3DZD descriptors detect significantly higher surface complementarity to the paratope, and are able to predict correct paratope-epitope interaction with an AUC = 0.75.
Partial Clipping Occlusion Including Rupture Point Is an Effective Strategy for Ruptured Giant Fusiform Basilar Artery Aneurysm: A Technical Case Report
Authors: Izumo Tsuyoshi , Fujimoto Takashi , Morofuji Yoichi , Tateishi Yohei , Matsuo Takayuki
Published: September 2021

Treatment of fusiform basilar artery aneurysms is still challenging today. The authors present a case of a patient with a ruptured giant fusiform basilar artery aneurysm successfully treated by clipping occlusion of the rupture point. A 62-year-old man suddenly fell into a coma due to subarachnoid hemorrhage (SAH) with a ruptured giant fusiform basilar artery aneurysm with a bleb on the right shoulder. We considered treating the lesion with stent-assisted coil embolization because of the aneurysm's shape, but we had to give up because stents were off-label in the acute phase SAH in our country. Instead, we successfully performed clipping surgery to partially occlude the aneurysm, including the rupture point via the anterior transpetrosal approach. His postoperative course was uneventful, without rerupture of the aneurysm, and his conscious level tended to improve. The postoperative imaging studies showed no complications and disappearance of the rupture point of the aneurysm. Although direct surgery for the giant fusiform basilar artery aneurysms is one of the challenging operations, it is an essential and highly effective treatment as a last resort for complex aneurysms if other treatments are not available.
Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 Mice
Authors: Zeng Qing , Fang Qin , Zhou Xincai , Yang Hongfa , Dou Yang , Zhang Wenhao , Gong Pu , Rong Xianfang
Published: September 2021

Increasing evidence has shown a correlation between chronic periodontitis (CP) and Alzheimer’s disease (AD). Nevertheless, there is still a lack of direct evidence, and especially key molecules to connect the two diseases. This study aims to investigate potential protein links between CP and AD within the inflammatory aspect. The hippocampus of CP model mice and controls were collected, and changes in protein expression were evaluated using two-dimensional differential in-gel electrophoresis (2D-DIGE) analysis combined with liquid chromatography tandem mass spectrometry. A total of 15 differentially expressed proteins were identified in CP model mice, as compared with the controls. Among them, S100-A9, transthyretin, Cofilin 2, peroxiredoxin 2, and lipocalin-2 were validated by Western blot according to their dual function both in inflammation and AD. Based on 2D-DIGE analysis, CP animal model had higher levels of S100-A9, Cofilin 2, peroxiredoxin 2, and lipocalin-2 compared to controls. The level of Cofilin 2, one of the well-established proteins in the pathology of AD, was strongly correlated with the time course of CP pathology, indicating a specific molecular correlation between CP and AD. Moreover, the in vivo results showed the level of Cofilin 2 increased significantly along with a prominent increase of the phosphorylation of protein phosphatase 2 (PP2A) and tau protein in the cell lysates of Porphyromonas gingivalis (P.g-LPS)-treated SK-N-SH APPwt cells. Cofilin 2 inhibition resulted in a sharp decrease in PP2A dependent of tau phosphorylation. Furthermore, tumor growth factor (TGF)-β1 was one of the most important inflammatory cytokines for the Pg-LPS-induced Cofilin 2 upregulation in SK-N-SH APPwt cells. These results showed inflammation served as the bond between CP and AD, whereas inflammatory related proteins could be the key linkers between the two diseases. Determining the association between CP and AD at the molecular mechanism will not only hold the direct evidence of the association between the two diseases but also provide a new way of preventing and treating AD: the effective prevention and treatment of CP could serve as a useful method to alleviate the development of AD.
Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses
Authors: Yang Zijiang , Gong Weiyi , Zhang Ting , Gao Heng
Published: September 2021

Gliomas are among the most common intracranial tumors which originated from neuroepithelial cells. Increasing evidence has revealed that long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA module regulation and tumor-infiltrating immune cells play important regulatory roles in the occurrence and progression of gliomas. However, the precise underlying molecular mechanisms remain largely unknown. Data on gliomas in The Cancer Genome Atlas lack normal control samples; to overcome this limitation, we combined 665 The Cancer Genome Atlas glioma RNA sequence datasets with 188 Genotype-Tissue Expression normal brain RNA sequences to construct an expression matrix profile after normalization. We systematically analyzed the expression of mRNAs, lncRNAs, and miRNAs between gliomas and normal brain tissues. Kaplan–Meier survival analyses were conducted to screen differentially expressed mRNAs, lncRNAs, and miRNAs. A prognostic miRNA-related competitive endogenous RNA network was constructed, and the core subnetworks were filtered using 6 miRNAs, 3 lncRNAs, and 11 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to investigate the biological functions of significantly dysregulated mRNAs. Co-expression network analysis was performed to analyze and screen the core genes. Furthermore, single-sample Gene Set Enrichment Analysis and immune checkpoint gene expression analysis were performed, as co-expression analysis indicated immune gene dysregulation in glioma. Finally, the expression of representative dysregulated genes was validated in U87 cells at the transcriptional level, establishing a foundation for further research. We identified 7017 mRNAs, 437 lncRNAs, and 9 miRNAs that were differentially expressed in gliomas. Kaplan–Meier survival analysis revealed 5684 mRNAs, 61 lncRNAs, and 7 miRNAs with potential as prognostic signatures in patients with glioma. The hub subnetwork of the competing endogenous RNA network between PART1-hsa-mir-25-SLC12A5/TACC2/BSN/TLN2/ZDHHC8 was screened out. Gene co-expression network, single-sample Gene Set Enrichment Analysis, and immune checkpoint expression analysis demonstrated that tumor-infiltrating immune cells are closely related to gliomas. We identified novel potential biomarkers to predict survival and therapeutic targets for patients with gliomas based on a large-scale sample. Importantly, we filtered pivotal genes that provide valuable information for further exploration of the molecular mechanisms underlying glioma tumorigenesis and progression.
LongTerm Outcomes of Three-Port Laparoscopic Right Hemicolectomy Versus Five-Port Laparoscopic Right Hemicolectomy: A Retrospective Study
Authors: Zhang Tao , Zhang Yaqi , Shen Xiaonan , Shi Yi , Ji Xiaopin , Wang Shaodong , Song Zijia , Jing Xiaoqian , Ye Feng , Zhao Ren
Published: September 2021

Purpose

The aim of this study is to compare the long-term outcomes of three-port laparoscopic right hemicolectomy (TPLRC) and five-port laparoscopic right hemicolectomy (FPLRC) with retrospective analysis.

Methods

A total of 182 patients who accepted laparoscopic right hemicolectomy with either three ports (86 patients) or five ports (96 patients) from January 2012 to June 2017 were non-randomly selected and analyzed retrospectively.

Results

More lymph nodes were harvested in the TPLRC group than in the FPLRC group [17.5 (7), 14 (8) ml, p < 0.001]. There was less blood loss in the TPLRC group [50 (80) vs. 100 (125) ml, p = 0.015]. There were no significant differences in the other short-term or oncological outcomes between the two groups. The overall survival and disease-free survival were equivalent.

Conclusions

TPLRC is recommendable as it guarantees short- and long-term equivalent outcomes compared with FPLRC.
Initial Adjustment to the COVID-19 Pandemic and the Associated Shutdown in Children and Adolescents With Chronic Pain and Their Families
Authors: Kaczynski Karen J. , Chang Cindy Yu Hsing , Chimoff Justin , Koike Camila , Berde Charles B. , Logan Deirdre E. , Nelson Sarah , Kossowsky Joe
Published: September 2021

Objectives: Youth with chronic pain often struggle to function in multiple domains due to pain and associated psychosocial distress. In 2020, schools and businesses shut down and people were encouraged to remain at home due to the COVID-19 pandemic, eliminating or reducing stress due to functional difficulties. This study assessed whether pain and associated psychosocial outcomes improved in youth with chronic pain during the shutdown, compared with before the pandemic.

Methods: Patients who completed clinical outcome measures during a multidisciplinary evaluation before the pandemic were readministered the same measures (PROMIS Anxiety, Depression, Sleep Disturbance, PCS, PedsQL) during the shutdown. At follow-up, patients also completed measures of adjustment to COVID-19 and their parents completed a measure of pandemic effects.

Results: Participants included 47 patients ages 8–18 and a parent/guardian. The pandemic impacted families in both positive (e.g., more quality time with family) and negative ways (e.g., social isolation, disruption in care). Pain intensity and pain catastrophizing significantly decreased during the shutdown (ps <0.01). Change in pain catastrophizing was correlated positively with change in psychological stress (p = 0.004) and anxiety (p = 0.005) and negatively with change in quality of life (p = 0.024).

Discussion: Pain and pain catastrophizing decreased initially during the shutdown related to the COVID-19 pandemic. Change in catastrophizing was associated with change in stress and anxiety. It may be that the reduction in functional demands contributed to this change. Functional difficulties should be addressed in treatment, including pain coping and also environmental modification to support optimal functioning in youth with chronic pain.
Current Paradigm of Hepatitis E Virus Among Pediatric and Adult Patients
Authors: Belei Oana , Ancusa Oana , Mara Adelina , Olariu Laura , Amaricai Elena , Folescu Roxana , Zamfir Carmen Lacramioara , Gurgus Daniela , Motoc Andrei G. , Stânga Livia Claudia , Strat Liliana , Marginean Otilia
Published: September 2021

Hepatitis E virus (HEV) infection is a polymorphic condition, present throughout the world and involving children and adults. Multiple studies over the last decade have contributed to a better understanding of the natural evolution of this infection in various population groups, several reservoirs and transmission routes being identified. To date, acute or chronic HEV-induced hepatitis has in some cases remained underdiagnosed due to the lower accuracy of serological tests and due to the evolutionary possibility with extrahepatic manifestations. Implementation of diagnostic tests based on nucleic acid analysis has increased the detection rate of this disease. The epidemiological and clinical features of HEV hepatitis differ depending on the geographical areas studied. HEV infection is usually a self-limiting condition in immunocompetent patients, but in certain categories of vulnerable patients it can induce a sudden evolution toward acute liver failure (pregnant women) or chronicity (immunosuppressed patients, post-transplant, hematological, or malignant diseases). In acute HEV infections in most cases supportive treatment is sufficient. In patients who develop chronic hepatitis with HEV, dose reduction of immunosuppressive medication should be the first therapeutic step, especially in patients with transplant. In case of unfavorable response, the initiation of antiviral therapy is recommended. In this review, the authors summarized the essential published data related to the epidemiological, clinical, paraclinical, and therapeutic aspects of HEV infection in adult and pediatric patients.
A Head-To-Head Comparison of Benzbromarone and Allopurinol on the Risk of Type 2 Diabetes Mellitus in People With Asymptomatic Hyperuricemia
Authors: Lai Shih-Wei , Liao Kuan-Fu , Kuo Yu-Hung , Lin Cheng-Li , Liu Chiu-Shong , Hwang Bing-Fang
Published: September 2021

Objective: The study aimed to thoroughly address the influence of benzbromarone and allopurinol on the risk of the development of type 2 diabetes mellitus (T2DM) in people with asymptomatic hyperuricemia.

Methods: We conducted a retrospective cohort study to examine the 2000–2015 national dataset containing all claims data of 23 million beneficiaries in Taiwan. Subjects who already had diabetes mellitus, gout-related diseases, and any cancer prior to the index date were excluded. Asymptomatic hyperuricemia was defined as subjects taking urate-lowering drugs who never had a gout flare. Subjects aged 20–84 with asymptomatic hyperuricemia who had benzbromarone prescriptions were selected as the benzbromarone group. Sex-matched and age-matched subjects with asymptomatic hyperuricemia who had allopurinol prescriptions were identified as the allopurinol group. The maximum follow-up duration was set as 5 years in our study. The outcome was set as subjects who had a new diagnosis of T2DM. The incidence density of T2DM was calculated in the benzbromarone and allopurinol groups. The hazard ratio (HR) and 95% confidence interval (CI) for T2DM was utilized to estimate the association between medications and the risk of T2DM.

Results: The incidence of T2DM among benzbromarone users was significantly lower than that of allopurinol users (7.91 versus 8.48 per 100 person-years, incidence rate ratio = 0.93, and 95% CI = 0.87–0.99). After adjustment for co-variables, the adjusted HR of T2DM would be 0.91 (95% CI = 0.85–0.98 and p = 0.008) in benzbromarone users as compared to allopurinol users.

Conclusion: There is a small but statistically significant risk reduction of developing T2DM in people with asymptomatic hyperuricemia taking benzbromarone as compared to those taking allopurinol during 5 years of follow-up. It indicates a future research direction for the use of individual urate-lowering drugs on the prevention of T2DM in the general population.
Convergence of Multiple Stimuli to a Single Gate in TREK1 and TRAAK Potassium Channels
Authors: Choveau Frank S , Ben Soussia Ismail , Bichet Delphine , Franck Chatelain C. , Feliciangeli Sylvain , Lesage Florian
Published: September 2021

Inhibitory potassium channels of the TREK1/TRAAK family are integrators of multiple stimuli, including temperature, membrane stretch, polyunsaturated fatty acids and pH. How these signals affect the gating of these channels is the subject of intense research. We have previously identified a cytoplasmic domain, pCt, which plays a major role in controlling channel activity. Here, we use pharmacology to show that the effects of pCt, arachidonic acid, and extracellular pH converge to the same gate within the channel. Using a state-dependent inhibitor, fluoxetine, as well as natural and synthetic openers, we provide further evidence that the “up” and “down” conformations identified by crystallography do not correspond to open and closed states of these channels.
Coherent Anti-Stokes Raman Scattering Microscopy: A Label-Free Method to Compare Spinal Cord Myelin in Different Species
Authors: Poulen Gaëtan , Gerber Yannick N , Perez Jean-Christophe , Oubarrahou Khadidja , Lonjon Nicolas , Vachiery-Lahaye Florence , Boukhaddaoui Hassan , Perrin Florence E.
Published: September 2021

Many histological techniques are used to identify and characterize myelin in the mammalian nervous system. Due to the high content of lipids in myelin sheaths, coherent anti-stokes Raman scattering (CARS) microscopy is a label-free method that allows identifying myelin within tissues. CARS excites the CH2 vibrational mode at 2845 cm−1 and CH2 bonds are found in lipids. In this study, we have used CARS for a new biological application in the field of spinal cord analysis. We have indeed compared several parameters of spinal cord myelin sheath in three different species, i.e., mouse, lemur, and human using a label-free method. In all species, we analyzed the dorsal and the lateral funiculi of the adult thoracic spinal cord. We identified g-ratio differences between species. Indeed, in both funiculi, g-ratio was higher in mice than in the two primate species, and the myelin g-ratio in lemurs was higher than in humans. We also detected a difference in g-ratio between the dorsal and the lateral funiculi only in humans. Furthermore, species differences between axon and fiber diameters as well as myelin thickness were observed. These data may reflect species specificities of conduction velocity of myelin fibers. A comparison of data obtained by CARS imaging and fluoromyelin staining, a method that, similar to CARS, does not require resin embedding and dehydration, displays similar results. CARS is, therefore, a label-free alternative to other microscopy techniques to characterize myelin in healthy and neurological disorders affecting the spinal cord.
Development and Validation of the Holistic Cognition Scale
Authors: Lux Andrei Alexander , Grover Steven Lee , Teo Stephen Tai Theng
Published: September 2021

This paper introduces a new scale to measure cognitive cultural differences, drawing on the theory of analytic versus holistic thought. Examining culture from a cognitive perspective is a challenge to traditional values-based approaches. Existing measures based on this framework are methodologically problematic and warrant renewal. This paper presents development and validation studies for a new instrument that measures analytic versus holistic cognitive tendencies at the individual level. The scale assesses four previously established dimensions: attention, causality, contradiction, and change. The present work follows well-established scale development protocols and the results show that the 16-item Holistic Cognition Scale (HCS) is a valid and reliable measure of analytic versus holistic thought. Three new studies with four unique samples (N = 41; 272; 454; and 454) provide evidence to support the content validity, reliability, and factor structure of the new instrument, as well as its convergent, discriminant, and concurrent validity against comparable constructs. Convergent validity is established against measures of compromise, intuition, complexity, and collectivism; predictive validity is established against Hofstede’s (1980) five cultural value dimensions; and discriminant validity is established using the average variance extracted from a confirmatory factor analysis. The new HCS is an improvement over previous attempts with a balanced number of forward- and reverse-scored items, superior reliability, less redundancy, and stronger factor loadings.
Psychological Adaptive Mechanism Maturity Predicts Good Outcomes in Treatment for Refractory PTSD
Authors: Beresford Thomas , Wahlberg Lawrence , Hipp Daniel , Ronan Patrick J.
Published: September 2021

Background: Post-traumatic Stress Disorder (PTSD) severity follows a bell-shaped curve ranging from mild to severe. Those in the severe range often receive the most intensive treatments, including targeted residential rehabilitation stays. These are expensive and welcome ways to improve their effectiveness. We hypothesized that positive change among subjects treated in a 45-day residential rehabilitation format would be associated with the maturity levels of measurable Psychological Adaptive Mechanisms (PAMs), alternately ego defense mechanisms.

Methods: In this association study, adult male patients (N = 115) with a history of combat related PTSD treated in a residential rehabilitation setting completed the Defense Style Questionnaire (DSQ) on admission, as well as the Post-Traumatic Stress Disorder Checklist-Military Version (PCL-M) and the Mississippi Scale for Combat-Related Post-traumatic Stress Disorder (M-PTSD) on admission and again at discharge. This allowed prospectively calculated change scores on each of the PTSD measures for each patient. The change scores allowed association testing with averaged admission DSQ scores using Pearson's correlation probability with significance held at p < 0.05.

Results: As hypothesized, averaged individual Mature scores on the DSQ were associated with improved change scores on both the PCL-M (p = 0.03) and the M-PTSD (p = 0.04). By contrast neither averaged DSQ Neurotic or Immature scores associated significantly with either PTSD scale change scores.

Conclusion: These results, the first of their kind to our knowledge, suggest that patients presenting with predominantly Mature level PAMs are likely to benefit from residential rehabilitation treatment of PTSD. By contrast, those presenting with Neurotic or Immature PAMs predominantly are less likely to encounter positive change in this type of treatment. Although residential treatment is often reserved for the most refractory PTSD cases, it appears that those endorsing Mature level PAMs will make use of residential treatment whereas other forms of treatment may be better suited to those with Neurotic and Immature adjustment mechanisms.
Exploring Coping Strategies of Different Generations of Students Starting University
Authors: Takács Rita , Takács Szabolcs , T Kárász Judit , Horváth Zoltán , Oláh Attila
Published: September 2021

Introduction: Coping strategies and adaptation skills are key features in successfully adjusting to university challenges. Coping skills are an essential part of the Psychological immune system, which leads to successful adaptation. Due to COVID-19 most universities have changed their face-to-face teaching for online education. Nevertheless, there is little concrete empirical evidence on how this generation of students with the ongoing impacts of disruptive changes can cope with it. Colleges and universities need to make changes in order to retain this new generation of students. Our aim was to explore the characteristics and changes in coping skills of university students from three different age groups.

Method: Psychological coping skills were measured by the Psychological Immune Competence Inventory (PICI). Differences were detected between generations. Group comparisons (pre-2004, pre-Covid, and post-Covid) groups were compared) using PICI subscales using independent sample analysis of variance. The sample consisted of 4,731 university students, 2,768 (58.5%) were men and 1,730 (36.56%) were women.

Results: Students from 2004 showed significantly higher scores in the Self-regulation subsystem scale compared to students in the pre-Covid and post-Covid groups. Self-regulation subsystem: F(2, 2,569.607) = 444.375, p < 0.001, η2 = 0.27: small effect, ω2 = 0.27; Resilience: F(2, 2,372.117) = 1171.855, p < 0.001, η2 = 0.14: small effect, ω2 = 0.14. Based on the results, the explained variance ratio was at least 10% based on self-regulation and resilience.

Conclusions: Psychological immune capacity of students seems to decrease through the years. Nonetheless, interventions may have a further facilitating role in the maintenance and development of psychological immunity during college years.
Stigma, Social Support, Illicit Drug Use, and Other Predictors of Anxiety and Depression Among HIV/AIDS Patients in Pakistan: A Cross-Sectional Study
Authors: Ahmed Ali , Saqlain Muhammad , Umair Malik Muhammad , Hashmi Furqan Khurshid , Saeed Hamid , Amer Muhammad , Blebil Ali Qais , Dujaili Juman Abdulelah
Published: September 2021

Introduction: Anxiety and depression in people living with HIV/AIDS (PLWHA) can lead to non-adherence to antiretroviral therapy (ART), morbidity, and mortality. Therefore, assessing the stigma, social support, and other determinants of anxiety and depression in PLWHA are important for developing further interventions.

Methods: An institution-based cross-sectional study was conducted in 505 PLWHA, approached through systematic sampling, who paid routine visits to the ART center, Pakistan Institute of Medical Sciences (PIMS), Islamabad. Data was collected by pretested validated hospital anxiety and depression scale (HADS). Version 26 of the SPSS was used to apply Logistic regression analysis to identify determinants, and the 95% confidence interval (CI) adjusted odds ratio (AOR) was calculated to assess the magnitude of the relationships.

Results: In PLWHA, the prevalence of co-morbid depression and anxiety was 80%. Separately, 89.9% had depression, and 80.3% had anxiety. Use of illicit drugs [AOR = 1.87, 95% CI (1.01, 3.27)], low social support [AOR = 1.21, 95% CI (1.02, 2.25)], being male [AOR = 2.21, 95% CI (1.11, 5.49)], and HIV related stigma [AOR = 2.48, 95% CI (1.25, 6.02)] were significant predictors of depression. Having detectable viral load [AOR = 3.04, 95% CI (1.04, 8.86)], young age [AOR = 5.31, 95% CI (1.19, 29.39)], no formal education [AOR = 21.78, 95% CI (4.03, 117.62)], low [AOR = 1.70, 95% CI (1.12, 6.93)] or moderate [AOR = 2.20, 95% CI (1.79, 6.09)] social support, illicit drugs addiction [AOR = 1.17, 95% CI (1.03, 2.55)], and HIV stigma [AOR = 54.3, 95% CI (21.20, 139.32)] had a remarkable association with anxiety.

Conclusions: Given the high prevalence of anxiety and depression among PLWHA, the Pakistan Ministry of Health should focus more on monitoring mental health, expanding mental health services, and developing interventions based on identified factors to treat depression and anxiety among PLWHA.
Youth Mental Health Peer Support Work: A Qualitative Study Exploring the Impacts and Challenges of Operating in a Peer Support Role
Authors: Tisdale Calvert , Snowdon Nicole , Allan Julaine , Hides Leanne , Williams Philip , de Andrade Dominique
Published: September 2021

Youth aged 16–24 years have the highest prevalence of mental illness in Australia, accounting for 26% of all mental illness. Youth mental health peer support work is a promising avenue of support for this population. However, limited research has examined impacts on those who provide youth mental health peer support work. We aimed to identify the benefits and challenges of working in a youth mental health peer support role. Semi-structured qualitative interviews with seven purposefully sampled peer workers from a national youth mental health organisation in Australia were conducted. The interviews were thematically analysed. Six key themes were identified: (1) personal growth, (2) interpersonal factors, (3) organisational factors, (4) boundaries, (5) role acknowledgement, and (6) challenging situations. Key supportive factors included financial reimbursement, training, support, and role-related flexibility. Identified challenges included lack of role acknowledgement, role-related stress, and boundaries. Operating within a youth mental health peer support role is perceived to have positive impacts on personal growth and interpersonal factors, enhanced through financial reimbursement, supervision, and role-related flexibility. Perspectives on the most effective form of role boundaries were diverse however their importance in addressing challenges was emphasised.
Analytical and FEM Analyses of High-Speed Impact Behaviour of Al 2024 Alloy
Authors: Gara Navya , Ramachandran Velmurugan , Rengaswamy Jayaganthan
Published: September 2021

The present work investigates the impact behaviour of Al 2024-T3 alloy using FEM analysis performed through LS DYNA software. Johnson–Cookvisco-plastic model is used to study the ballistic impact resistance of target Al alloy impacted by a rigid steel cylindrical projectile. The tensile properties of Al 2024-T3 alloy reported in the literature are used to estimate the J.C. model parameters. Impact velocities within a range of 50 m/s–900 m/s of the projectile were triggered onto Al alloy target thicknesses in the range of 3.18 mm–6.35 mm. To understand the accuracy of the FEM model, an analytical model proposed by Chen et al. for blunt-nosed projectiles on the ductile targets was used to compare with the obtained residual velocities from FEM simulations. It was observed that the ballistic limit velocities have led to the highest energy absorption behaviour of the Al 2024-T3 alloy for an impact velocity of 183 m/s and a 6.35 mm target thickness. The ballistic limit velocities have increased from 97 m/s to 183 m/s for the considered thickness range of 3.18 mm–6.35 mm. The impact failure was observed to have a petalling formation with two petals for thinner targets, while a full-fledged plugging with no petal formation for the 4.00 mm and 6.35 mm target thicknesses was observed.
Towards Cellular Ultrastructural Characterization in Organ-on-a-Chip by Transmission Electron Microscopy
Authors: Glinkowska Mares Adrianna , Feiner-Gracia Natalia , Muela Yolanda , Martínez Gema , Delgado Lidia , Albertazzi Lorenzo , Pujals Silvia
Published: September 2021

Organ-on-a-chip technology is a 3D cell culture breakthrough of the last decade. This rapidly developing field of bioengineering intertwined with microfluidics provides new insights into disease development and preclinical drug screening. So far, optical and fluorescence microscopy are the most widely used methods to monitor and extract information from these models. Meanwhile transmission electron microscopy (TEM), despite its wide use for the characterization of nanomaterials and biological samples, remains unexplored in this area. In our work we propose a TEM sample preparation method, that allows to process a microfluidic chip without its prior deconstruction, into TEM-compatible specimens. We demonstrated preparation of tumor blood vessel-on-a-chip model and consecutive steps to preserve the endothelial cells lining microfluidic channel, for the chip’s further transformation into ultrathin sections. This approach allowed us to obtain cross-sections of the microchannel with cells cultured inside, and to observe cell adaptation to the channel geometry, as well as the characteristic for endothelial cells tight junctions. The proposed sample preparation method facilitates the electron microscopy ultrastructural characterization of biological samples cultured in organ-on-a-chip device.
Paracetamol and Ibuprofen in the Treatment of Fever and Acute Mild–Moderate Pain in Children: Italian Experts’ Consensus Statements
Authors: Doria Mattia , Careddu Domenico , Iorio Raffaele , Verrotti Alberto , Chiappini Elena , Barbero Giulio Michele , Ceschin Flavia , Dell’Era Laura , Fabiano Valentina , Mencacci Michele , Carlomagno Francesco , Libranti Maria , Mazzone Teresa , Vitale Antonio
Published: September 2021

Fever and pain are challenging symptoms in children and adolescents and are common reasons for consultations in primary care and hospital. Paracetamol and ibuprofen are currently the only recommended drugs for treating fever in Italy, but the therapeutic approaches are discrepant in the different settings. In Italy, paracetamol and ibuprofen are the most prescribed analgesics for acute mild–moderate pain in children; however, their use is often inappropriate in that fever is over-treated and pain is under-treated. An Italian board of experts analyzed the motivations for the misalignment between daily practice and guidelines of fever and acute mild–moderate pain management of the territory and hospitals. The expert opinion consensus process underscored the appropriate use of paracetamol and ibuprofen according to clinical scenarios, patients’ profiles, and the safety features of the drugs. Although patients’ profiles can indicate different benefits from paracetamol or ibuprofen, critical issues of fever and acute mild–moderate pain management persist in primary care and hospitals. These expert opinion consensus statements can be an across-the-board tool to harmonize the routine practice between the territory and hospitals, especially under special conditions (at-risk for dehydration, coagulation disorder patients, etc.). It can also promote educational activity about fever and acute mild–moderate pain management to enhance the milestones already achieved by Italian pediatricians.
SDN-Based Resilient Smart Grid: The SDN-microSENSE Architecture
Authors: Grammatikis Panagiotis Radoglou , Sarigiannidis Panagiotis , Dalamagkas Christos , Spyridis Yannis , Lagkas Thomas , Efstathopoulos Georgios , Sesis Achilleas , Pavon Ignacio Labrador , Burgos Ruben Trapero , Diaz Rodrigo , Sarigiannidis Antonios , Papamartzivanos Dimitris , Menesidou Sofia Anna , Ledakis Giannis , Pasias Achilleas , Kotsiopoulos Thanasis , Drosou Anastasios , Mavropoulos Orestis , Subirachs Alba Colet , Sola Pol Paradell , Domínguez-García José Luis , Escalante Marisa , Alberto Molinuevo Martin , Caracuel Benito , Ramos Francisco , Gkioulos Vasileios , Katsikas Sokratis , Bolstad Hans Christian , Archer Dan-Eric , Paunovic Nikola , Gallart Ramon , Rokkas Theodoros , Arce Alicia
Published: September 2021

The technological leap of smart technologies and the Internet of Things has advanced the conventional model of the electrical power and energy systems into a new digital era, widely known as the Smart Grid. The advent of Smart Grids provides multiple benefits, such as self-monitoring, self-healing and pervasive control. However, it also raises crucial cybersecurity and privacy concerns that can lead to devastating consequences, including cascading effects with other critical infrastructures or even fatal accidents. This paper introduces a novel architecture, which will increase the Smart Grid resiliency, taking full advantage of the Software-Defined Networking (SDN) technology. The proposed architecture called SDN-microSENSE architecture consists of three main tiers: (a) Risk assessment, (b) intrusion detection and correlation and (c) self-healing. The first tier is responsible for evaluating dynamically the risk level of each Smart Grid asset. The second tier undertakes to detect and correlate security events and, finally, the last tier mitigates the potential threats, ensuring in parallel the normal operation of the Smart Grid. It is noteworthy that all tiers of the SDN-microSENSE architecture interact with the SDN controller either for detecting or mitigating intrusions.
Multi-Gene Phylogeny and Taxonomy of Hydnellum (Bankeraceae, Basidiomycota) from China
Authors: Mu Yan-Hong , Yu Jia-Rui , Cao Ting , Wang Xiang-Hua , Yuan Hai-Sheng
Published: September 2021

The genus Hydnellum is an important group of stipitate hydnaceous fungi which can form ectomycorrhiza with many species of woody plants. In recent decades, the frequency and number of basidiocarps observed in China have been declining significantly. So far, however, we know little about the species diversity of Hydnellum in China. In this study, we conducted molecular phylogenetic analyses based on sections of multiple loci, including the large subunit of nuclear ribosomal RNA gene (nLSU), the internal transcribed spacer regions (ITS), the small subunit of nuclear ribosomal RNA gene (SSU) and the second-largest subunit of RNA polymerase II gene (RPB2), as well as morphological studies, of collected samples of Hydnellum from China. We also inferred Maximum Likelihood and Bayesian phylogenies for the order Thelephorales from the dataset of the combined nLSU and ITS. This study has revealed the phylogenetic position of Hydnellum in the order Thelephorales, and phylogenetically confirmed ten major clades in Thelephorales; Twenty-nine taxa are proposed, described or reported, including 10 new subgenera (Hydnellum subgenus Hydnellum, subg. Caesispinosum, subg. Croceum, subg. Inflatum, subg. Rhizomorphum, subg. Scabrosum, subg. Spongiosum, subg. Subindufibulatum, subg. Violaceum and subg. Zonatum), 11 new species (Hydnellum atrorubrum, H. atrospinosum, H. bomiense, H. brunneorubrum, H. fibulatum, H. granulosum, H. inflatum, H. rubidofuscum, H. squamulosum, H. sulcatum and H. yunnanense), 3 newly recorded species (H. caeruleum, H. peckii and H. spongiosipes) and 5 notable specimens (Hydnellum sp 1, H. sp 2, H. sp 3, H. sp 4 and H. sp 5). A classification system based on the morphological characteristics (especially the hyphal structure types) and molecular analyses is proposed to accommodate most species in Hydnellum. The distinguishing characters of the subgenera and the new species with their closely related taxa are discussed. A key to the species of Hydnellum from China is provided.