bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS
Authors: Vasilopoulou Christina , McDaid-McCloskey Sarah L. , McCluskey Gavin , Duguez Stephanie , Morris Andrew P. , Duddy William
Published: February 2023

Amyotrophic lateral sclerosis (ALS) is a fatal late-onset motor neuron disease characterized by the loss of the upper and lower motor neurons. Our understanding of the molecular basis of ALS pathology remains elusive, complicating the development of efficient treatment. Gene-set analyses of genome-wide data have offered insight into the biological processes and pathways of complex diseases and can suggest new hypotheses regarding causal mechanisms. Our aim in this study was to identify and explore biological pathways and other gene sets having genomic association to ALS. Two cohorts of genomic data from the dbGaP repository were combined: (a) the largest available ALS individual-level genotype dataset (N = 12,319), and (b) a similarly sized control cohort (N = 13,210). Following comprehensive quality control pipelines, imputation and meta-analysis, we assembled a large European descent ALS-control cohort of 9244 ALS cases and 12,795 healthy controls represented by genetic variants of 19,242 genes. Multi-marker analysis of genomic annotation (MAGMA) gene-set analysis was applied to an extensive collection of 31,454 gene sets from the molecular signatures database (MSigDB). Statistically significant associations were observed for gene sets related to immune response, apoptosis, lipid metabolism, neuron differentiation, muscle cell function, synaptic plasticity and development. We also report novel interactions between gene sets, suggestive of mechanistic overlaps. A manual meta-categorization and enrichment mapping approach is used to explore the overlap of gene membership between significant gene sets, revealing a number of shared mechanisms.
Germline NUP98 Variants in Two Siblings with a Rothmund–Thomson-Like Spectrum: Protein Functional Changes Predicted by Molecular Modeling
Authors: Colombo Elisa Adele , Valiante Michele , Uggeri Matteo , Orro Alessandro , Majore Silvia , Grammatico Paola , Gentilini Davide , Finelli Palma , Gervasini Cristina , D’Ursi Pasqualina , Larizza Lidia
Published: February 2023

Two adult siblings born to first-cousin parents presented a clinical phenotype reminiscent of Rothmund–Thomson syndrome (RTS), implying fragile hair, absent eyelashes/eyebrows, bilateral cataracts, mottled pigmentation, dental decay, hypogonadism, and osteoporosis. As the clinical suspicion was not supported by the sequencing of RECQL4, the RTS2-causative gene, whole exome sequencing was applied and disclosed the homozygous variants c.83G>A (p.Gly28Asp) and c.2624A>C (p.Glu875Ala) in the nucleoporin 98 (NUP98) gene. Though both variants affect highly conserved amino acids, the c.83G>A looked more intriguing due to its higher pathogenicity score and location of the replaced amino acid between phenylalanine-glycine (FG) repeats within the first NUP98 intrinsically disordered region. Molecular modeling studies of the mutated NUP98 FG domain evidenced a dispersion of the intramolecular cohesion elements and a more elongated conformational state compared to the wild type. This different dynamic behavior may affect the NUP98 functions as the minor plasticity of the mutated FG domain undermines its role as a multi-docking station for RNA and proteins, and the impaired folding can lead to the weakening or the loss of specific interactions. The clinical overlap of NUP98-mutated and RTS2/RTS1 patients, accounted by converging dysregulated gene networks, supports this first-described constitutional NUP98 disorder, expanding the well-known role of NUP98 in cancer.
The Comparison of Retinal Microvascular Findings in Acute COVID-19 and 1-Year after Hospital Discharge Assessed with Multimodal Imaging—A Prospective Longitudinal Cohort Study
Authors: Jevnikar Kristina , Meglič Andrej , Lapajne Luka , Logar Mateja , Vidovič Valentinčič Nataša , Globočnik Petrovič Mojca , Jaki Mekjavić Polona
Published: February 2023

This study aimed to quantify possible long-term impairment of the retinal microcirculation and microvasculature by reassessing a cohort of patients with acute COVID-19 without other known comorbidities one year after their discharge from the hospital. Thirty patients in the acute phase of COVID-19 without known systemic comorbidities were enrolled in this prospective longitudinal cohort study. Fundus photography, SS-OCT, and SS-OCTA using swept-source OCT (SS-OCT, Topcon DRI OCT Triton; Topcon Corp., Tokyo, Japan) were performed in the COVID-19 unit and 1-year after hospital discharge. The cohort’s median age was 60 years (range 28–65) and 18 (60%) were male. Mean vein diameter (MVD) significantly decreased over time, from 134.8 μm in the acute phase to 112.4 μm at a 1-year follow-up (p < 0.001). A significantly reduced retinal nerve fiber layer (RNFL) thickness was observed at follow-up in the inferior quadrant of the inner ring (mean diff. 0.80 95% CI 0.01–1.60, p = 0.047) and inferior (mean diff. 1.56 95% CI 0.50–2.61, p < 0.001), nasal (mean diff. 2.21 95% CI 1.16–3.27, p < 0.001), and superior (mean diff. 1.69 95% CI 0.63–2.74, p < 0.001) quadrants of the outer ring. There were no statistically significant differences between the groups regarding vessel density of the superior and deep capillary plexuses. The transient dilatation of the retinal vessels in the acute phase of COVID-19, as well as RNFL thickness changes, could become a biomarker of angiopathy in patients with severe COVID-19.
The Conserved Cysteine-Rich Secretory Protein MaCFEM85 Interacts with MsWAK16 to Activate Plant Defenses
Authors: Cai Ni , Nong Xiangqun , Liu Rong , McNeill Mark Richard , Wang Guangjun , Zhang Zehua , Tu Xiongbing
Published: February 2023

Metarhizium anisopliae is an entomopathogenic fungus which may enhance plant growth and resistance when acting as an endophyte in host plants. However, little is known about the protein interactions nor their activating mechanisms. Common in fungal extracellular membrane (CFEM) proteins have been identified as plant immune regulators that suppress or activate plant resistance responses. Here, we identified a CFEM domain-containing protein, MaCFEM85, which was mainly localized in the plasma membrane. Yeast two-hybrid (Y2H), glutathione-S-transferase (GST) pull-down, and bimolecular fluorescence complementation assays demonstrated that MaCFEM85 interacted with the extracellular domain of a Medicago sativa (alfalfa) membrane protein, MsWAK16. Gene expression analyses showed that MaCFEM85 and MsWAK16 were significantly upregulated in M. anisopliae and M. sativa, respectively, from 12 to 60 h after co-inoculation. Additional yeast two-hybrid assays and amino acid site-specific mutation indicated that the CFEM domain and 52th cysteine specifically were required for the interaction of MaCFEM85 with MsWAK16. Defense function assays showed that JA was up-regulated, but Botrytis cinerea lesion size and Myzus persicae reproduction were suppressed by transient expression of MaCFEM85 and MsWAK16 in the model host plant Nicotiana benthamiana. Collectively, these results provide novel insights into the molecular mechanisms underlying interactions of M. anisopliae with host plants.
Inhibition of Succinate Dehydrogenase by Pesticides (SDHIs) and Energy Metabolism
Authors: Bouillaud Frederic
Published: February 2023

Succinate dehydrogenase (SDH) is one of the enzymes of the tricarboxylic acid cycle (Krebs cycle) and complex II of the mitochondrial respiratory chain. A class of fungicides (SDHIs) targets the complex II reaction in the SDH. A large number of those in use have been shown to inhibit SDH in other phyla, including humans. This raises questions about possible effects on human health and non-target organisms in the environment. The present document will address metabolic consequences in mammals; it is neither a review on SDH nor is it about the toxicology of SDHIs. Most clinically relevant observations are linked to a severe decrease in SDH activity. Here we shall examine the mechanisms for compensating a loss of SDH activity and their possible weaknesses or adverse consequences. It can be expected that a mild inhibition of SDH will be compensated by the kinetic properties of this enzyme, but this implies a proportionate increase in succinate concentration. This would be relevant for succinate signaling and epigenetics (not reviewed here). With regard to metabolism, exposure of the liver to SDHIs would increase the risk for non-alcoholic fatty liver disease (NAFLD). Higher levels of inhibition may be compensated by modification of metabolic fluxes with net production of succinate. SDHIs are much more soluble in lipids than in water; consequently, a different diet composition between laboratory animals and humans is expected to influence their absorption.
Specific Forms of Graphene Quantum Dots Induce Apoptosis and Cell Cycle Arrest in Breast Cancer Cells
Authors: Ku Tien-Hsiung , Shen Wen-Ting , Hsieh Chien-Te , Chen Grace Shiahuy , Shia Wei-Chung
Published: February 2023

Graphene quantum dots (GQDs), nanomaterials derived from graphene and carbon dots, are highly stable, soluble, and have exceptional optical properties. Further, they have low toxicity and are excellent vehicles for carrying drugs or fluorescein dyes. Specific forms of GQDs can induce apoptosis and could be used to treat cancers. In this study, three forms of GQDs (GQD (nitrogen:carbon = 1:3), ortho-GQD, and meta-GQD) were screened and tested for their potential to inhibit breast cancer cell (MCF-7, BT-474, MDA-MB-231, and T-47D) growth. All three GQDs decreased cell viability after 72 h of treatment and specifically affected breast cancer cell proliferation. An assay for the expression of apoptotic proteins revealed that p21 and p27 were up-regulated (1.41-fold and 4.75-fold) after treatment. In particular, ortho-GQD-treated cells showed G2/M phase arrest. The GQDs specifically induced apoptosis in estrogen receptor-positive breast cancer cell lines. These results indicate that these GQDs induce apoptosis and G2/M cell cycle arrest in specific breast cancer subtypes and could potentially be used for treating breast cancers.
Gut Microbiota and Alzheimer’s Disease: How to Study and Apply Their Relationship
Authors: Nguyen Ngoc Minh , Cho Jungsook , Lee Choongho
Published: February 2023

Gut microbiota (GM), the microorganisms in the gastrointestinal tract, contribute to the regulation of brain homeostasis through bidirectional communication between the gut and the brain. GM disturbance has been discovered to be related to various neurological disorders, including Alzheimer’s disease (AD). Recently, the microbiota-gut-brain axis (MGBA) has emerged as an enticing subject not only to understand AD pathology but also to provide novel therapeutic strategies for AD. In this review, the general concept of the MGBA and its impacts on the development and progression of AD are described. Then, diverse experimental approaches for studying the roles of GM in AD pathogenesis are presented. Finally, the MGBA-based therapeutic strategies for AD are discussed. This review provides concise guidance for those who wish to obtain a conceptual and methodological understanding of the GM and AD relationship with an emphasis on its practical application.
Nanostructure Mediated Piezoelectric Effect of Tetragonal BaTiO3 Coatings on Bone Mesenchymal Stem Cell Shape and Osteogenic Differentiation
Authors: Zheng Yafei , Zhao Lingzhou , Li Ying , Zhang Xinyuan , Zhang Wei , Wang Jing , Liu Lipeng , An Weikang , Jiao Hua , Ma Chufan
Published: February 2023

In recent years, porous titanium (Ti) scaffolds with BaTiO3 coatings have been designed to promote bone regeneration. However, the phase transitions of BaTiO3 have been understudied, and their coatings have yielded low effective piezoelectric coefficients (EPCs < 1 pm/V). In addition, piezoelectric nanomaterials bring many advantages in eliciting cell-specific responses. However, no study has attempted to design a nanostructured BaTiO3 coating with high EPCs. Herein, nanoparticulate tetragonal phase BaTiO3 coatings with cube-like nanoparticles but different effective piezoelectric coefficients were fabricated via anodization combining two hydrothermal processes. The effects of nanostructure-mediated piezoelectricity on the spreading, proliferation, and osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMSCs) were explored. We found that the nanostructured tetragonal BaTiO3 coatings exhibited good biocompatibility and an EPC-dependent inhibitory effect on hJBMSC proliferation. The nanostructured tetragonal BaTiO3 coatings of relatively smaller EPCs (<10 pm/V) exhibited hJBMSC elongation and reorientation, broad lamellipodia extension, strong intercellular connection and osteogenic differentiation enhancement. Overall, the improved hJBMSC characteristics make the nanostructured tetragonal BaTiO3 coatings promising for application on implant surfaces to promote osseointegration.
The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans
Authors: Iden Jennifer Ana , Raphael-Mizrahi Bitya , Awida Zamzam , Naim Aaron , Zyc Dan , Liron Tamar , Kasher Melody , Livshits Gregory , Vered Marilena , Gabet Yankel
Published: February 2023

The endocannabinoid system, particularly cannabinoid receptor 2 (CB2 in mice and CNR2 in humans), has controversial pathophysiological implications in colon cancer. Here, we investigate the role of CB2 in potentiating the immune response in colon cancer in mice and determine the influence of CNR2 variants in humans. Comparing wild-type (WT) mice to CB2 knockout (CB2−/−) mice, we performed a spontaneous cancer study in aging mice and subsequently used the AOM/DSS model of colitis-associated colorectal cancer and a model for hereditary colon cancer (ApcMin/+). Additionally, we analyzed genomic data in a large human population to determine the relationship between CNR2 variants and colon cancer incidence. Aging CB2−/− mice exhibited a higher incidence of spontaneous precancerous lesions in the colon compared to WT controls. The AOM/DSS-treated CB2−/− and ApcMin/+CB2−/− mice experienced aggravated tumorigenesis and enhanced splenic populations of immunosuppressive myeloid-derived suppressor cells along with abated anti-tumor CD8+ T cells. Importantly, corroborative genomic data reveal a significant association between non-synonymous variants of CNR2 and the incidence of colon cancer in humans. Taken together, the results suggest that endogenous CB2 activation suppresses colon tumorigenesis by shifting the balance towards anti-tumor immune cells in mice and thus portray the prognostic value of CNR2 variants for colon cancer patients.
Influence of Preoperative Serum Albumin on Acute Kidney Injury after Aortic Surgery for Acute Type A Aortic Dissection: A Retrospective Cohort Study
Authors: Xu Shijun , Wu Zining , Liu Yongmin , Zhu Junming , Gong Ming , Sun Lizhong , Ran Dong , Zhang Hongjia
Published: February 2023

There are relatively few articles on the relationship between serum albumin and acute kidney injury (AKI). Therefore, the objective of this research was to study the relationship between serum albumin and AKI in patients who were undergoing surgery for acute type A aortic dissection. Methods: We retrospectively collected data from 624 patients attending a Chinese hospital between January 2015 and June 2017. The target independent variable was serum albumin measured before surgery after hospital admission, and the dependent variable was AKI, defined in accordance with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results: The mean age of these 624 selected patients was 48.5 ± 11.1 years, and almost 73.7% were male. A nonlinear association was detected between serum albumin and AKI; the turning point was 32 g/L. The risk of AKI decreased gradually as the serum albumin level increased up to 32 g/L (adjusted OR = 0.87; 95% CI 0.82–0.92; p < 0.001). When the serum albumin level exceeded 32 g/L, the level of serum albumin was not associated with the risk of AKI (OR = 1.01, 95% CI 0.94–1.08; p = 0.769). Conclusions: The findings suggest that preoperative serum albumin below 32 g/L was an independent risk factor for AKI in patients undergoing surgery for acute type A aortic dissection. Trial registration: A retrospective cohort study.
The Effect of Bimanual Intensive Functional Training on Somatosensory Hand Function in Children with Unilateral Spastic Cerebral Palsy: An Observational Study
Authors: Steinbusch Catherine V. M. , Defesche Anke , van der Leij Bertie , Rameckers Eugene A. A. , Knijnenburg Annemarie C. S. , Vermeulen Jeroen R. J. , Janssen-Potten Yvonne J. M.
Published: February 2023

(1) Background: Next to motor impairments, children with unilateral spastic cerebral palsy (CP) often experience sensory impairments. Intensive bimanual training is well known for improving motor abilities, though its effect on sensory impairments is less known. (2) Objective: To investigate whether bimanual intensive functional therapy without using enriched sensory materials improves somatosensory hand function. (3) Methods: A total of twenty-four participants with CP (12–17 years of age) received 80–90 h of intensive functional training aimed at improving bimanual performance in daily life. Somatosensory hand function was measured before training, directly after training, and at six months follow-up. Outcome measures were: proprioception, measured by thumb and wrist position tasks and thumb localization tasks; vibration sensation; tactile perception; and stereognosis. (4) Results: Next to improving on their individual treatment goals, after training, participants also showed significant improvements in the perception of thumb and wrist position, vibration sensation, tactile perception, and stereognosis of the more affected hand. Improvements were retained at six months follow-up. Conversely, proprioception measured by the thumb localization tasks did not improve after training. (5) Conclusions: Intensive functional bimanual training without environmental tactile enrichment may improve the somatosensory function of the more affected hand in children with unilateral spastic CP.
Single-Stage Externalized Locked Plating for Treatment of Unstable Meta-Diaphyseal Tibial Fractures
Authors: Makelov Biser , Mischler Dominic , Varga Peter , Apivatthakakul Theerachai , Fletcher James , Veselinov Deyan , Berk Till , Raykov Dimitur , Gueorguiev Boyko
Published: February 2023

(1) Background: Unstable meta-diaphyseal tibial fractures represent a heterogeneous group of injuries. Recently, good clinical results have been reported when applying a technique of externalized locked plating in appropriate cases, highlighting its advantage in terms of less additional tissue injury compared with conventional methods of fracture fixation. The aims of this prospective clinical cohort study were, firstly, to investigate the biomechanical and clinical feasibility and, secondly, to evaluate the clinical and functional outcomes of single-stage externalized locked plating for treatment of unstable, proximal (intra- and extra-articular) and distal (extra-articular), meta-diaphyseal tibial fractures. (2) Methods: Patients, who matched the inclusion criteria of sustaining a high-energy unstable meta-diaphyseal tibial fracture, were identified prospectively for single-stage externalized locked plating at a single trauma hospital in the period from April 2013 to December 2022. (3) Results: Eighteen patients were included in the study. Average follow-up was 21.4 ± 12.3 months, with 94% of the fractures healing without complications. The healing time was 21.1 ± 4.6 weeks, being significantly shorter for patients with proximal extra- versus intra-articular meta-diaphyseal tibial fractures, p = 0.04. Good and excellent functional outcomes in terms of HSS and AOFAS scores, and knee and ankle joints range of motion were observed among all patients, with no registered implant breakage, deep infection, and non-union. (4) Conclusions: Single-stage externalized locked plating of unstable meta-diaphyseal tibial fractures provides adequate stability of fixation with promising clinical results and represents an attractive alternative to the conventional methods of external fixation when inclusion criteria and rehabilitation protocol are strictly followed. Further experimental studies and randomized multicentric clinical trials with larger series of patients are necessary to pave the way of its use in clinical practice.
Risk Factors for Surgical Site Infections in Elective Orthopedic Foot and Ankle Surgery: The Role of Diabetes Mellitus
Authors: Soldevila-Boixader Laura , Viehöfer Arnd , Wirth Stephan , Waibel Felix , Yildiz Inci , Stock Mike , Jans Peter , Uçkay Ilker
Published: February 2023

Surgical site infection (SSI) after elective orthopedic foot and ankle surgery is uncommon and may be higher in selected patient groups. Our main aim was to investigate the risk factors for SSI in elective orthopedic foot surgery and the microbiological results of SSI in diabetic and non-diabetic patients, in a tertiary foot center between 2014 and 2022. Overall, 6138 elective surgeries were performed with an SSI risk of 1.88%. The main independent associations with SSI in a multivariate logistic regression analysis were an ASA score of 3–4 points, odds ratio (OR) 1.87 (95% confidence interval (CI) 1.20–2.90), internal, OR 2.33 (95% CI 1.56–3.49), and external material, OR 3.08 (95% CI 1.56–6.07), and more than two previous surgeries, OR 2.86 (95% CI 1.93–4.22). Diabetes mellitus showed an increased risk in the univariate analysis, OR 3.94 (95% CI 2.59–5.99), and in the group comparisons (three-fold risk). In the subgroup of diabetic foot patients, a pre-existing diabetic foot ulcer increased the risk for SSI, OR 2.99 (95% CI 1.21–7.41), compared to non-ulcered diabetic patients. In general, gram-positive cocci were the predominant pathogens in SSI. In contrast, polymicrobial infections with gram-negative bacilli were more common in contaminated foot surgeries. In the latter group, the perioperative antibiotic prophylaxis by second-generation cephalosporins did not cover 31% of future SSI pathogens. Additionally, selected groups of patients revealed differences in the microbiology of the SSI. Prospective studies are required to determine the importance of these findings for optimal perioperative antibiotic prophylactic measures.
Preparation and Properties of Flame-Retardant Polyurethane Pressure Sensitive Adhesive and Its Application
Authors: Zeng Lijuan , Yang Liu , Liu Junbang , Lu Shangkai , Ai Lianghui , Dong Yang , Ye Zhibin , Liu Ping
Published: February 2023

Using 10-(2,5-dihydroxyphenyl)-10-hydrogen-9-oxo-10-phosphine-10-oxide (DOPO-H Q), N,N-diethyl-bis(hydroxyethyl) aminomethylene phosphate diethyl (FRC-6), and (6-oxo- 6H-dibenzo[c,e][1,2]oxphosphine-6-yl) hydroxylmethyl-thiophene (DOPO-SF) as reactive flame retardants, the flame-retardant polyurethane pressure sensitive adhesive (FRPU-PSA) were prepared. The fourier transform infrared (FTIR), thermogravimetric analysis (TG), limiting oxygen index (LOI), vertical combustion (UL 94), 180° peeling, and inclined ball rolling were used to characterize and investigate the properties of FRPU-PSA. It was found that the LOI of PU/50mol%DOPO-HQ, PU/50mol%FRC-6, and PU/20wt%DOPO-SF were 30.7%, 29.3%, and 25.0%, respectively, the peel strength of PU/50mol%DOPO-HQ and PU/50mol%FRC-6 were 3.88N/25 mm and 3.42N/25 mm, respectively. FRPU-PSA not only had good bond strength, but also had good flame retardant performance.
Neural Network-Enabled Identification of Weak Inspiratory Efforts during Pressure Support Ventilation Using Ventilator Waveforms
Authors: Soundoulounaki Stella , Sylligardos Emmanouil , Akoumianaki Evangelia , Sigalas Markos , Kondili Eumorfia , Georgopoulos Dimitrios , Trahanias Panos , Vaporidi Katerina
Published: February 2023

During pressure support ventilation (PSV), excessive assist results in weak inspiratory efforts and promotes diaphragm atrophy and delayed weaning. The aim of this study was to develop a classifier using a neural network to identify weak inspiratory efforts during PSV, based on the ventilator waveforms. Recordings of flow, airway, esophageal and gastric pressures from critically ill patients were used to create an annotated dataset, using data from 37 patients at 2–5 different levels of support, computing the inspiratory time and effort for every breath. The complete dataset was randomly split, and data from 22 patients (45,650 breaths) were used to develop the model. Using a One-Dimensional Convolutional Neural Network, a predictive model was developed to characterize the inspiratory effort of each breath as weak or not, using a threshold of 50 cmH2O*s/min. The following results were produced by implementing the model on data from 15 different patients (31,343 breaths). The model predicted weak inspiratory efforts with a sensitivity of 88%, specificity of 72%, positive predictive value of 40%, and negative predictive value of 96%. These results provide a ‘proof-of-concept’ for the ability of such a neural-network based predictive model to facilitate the implementation of personalized assisted ventilation.
Liver Damage Associated with SARS-CoV-2 Infection—Myth or Reality?
Authors: Luca Mihaela Cătălina , Loghin Isabela Ioana , Mihai Ioana Florina , Popa Radu , Vâţă Andrei , Manciuc Carmen
Published: February 2023

(1) Introduction: While the primary impairment in COVID-19 is pulmonary, the ubiquitous distribution of angiotensin-converting enzyme 2 (ACE2) demonstrates the possible presence of systemic disease with involvement of the heart, kidneys, liver and other organs. (2) Methods: We retrospectively studied the observation sheets of patients diagnosed with SARS-CoV-2 infection hospitalized in the “Sf. Parascheva” Clinical Hospital of Infectious Diseases from Iasi for a period of 3 months. The aim of the study was to identify the frequency of liver injury due to SARS-CoV-2 infection among patients and its impact on the course of the disease. (3) Results: Out of the total number of hospitalized cases (1552), 207 (13.34%) were the subjects of our analysis. The severe form of SARS-CoV-2 infection predominated (108 cases; 52.17%) and in terms of liver damage, in all cases increased transaminase levels predominated and were determined to be secondary to the viral infection. We divided the lot into two groups, A (23 cases; 23.19%) and B (159 cases; 76.81%), depending on the time of onset of liver dysfunction, either at the time of hospitalization or during hospitalization. The evolution of liver dysfunction was predominant in most cases, with an average time of onset at 12.4 days of hospitalization. Death occurred in 50 cases. (4) Conclusions: This study revealed that high AST and ALT at hospital admission was associated with a high mortality risk in COVID-19 patients. Therefore, abnormal liver test results can be a significant prognostic indicator of outcomes in COVID-19 patients.
Guard Ring Design to Prevent Edge Breakdown in Double-Diffused Planar InGaAs/InP Avalanche Photodiodes
Authors: Chen Yu-Chun , Yan Ruei-Hong , Huang Hsu-Chia , Nieh Liang-Hsuan , Lin Hao-Hsiung
Published: February 2023

We report on the design of an attached guard ring (AGR) and a floating guard ring (FGR) in a planar separate absorption, grading, charge, and multiplication In0.53Ga0.47As/InP avalanche photodiode to prevent premature edge breakdowns. The depths of the two Zn diffusions were utilized to manipulate the guard ring structures. Results from TCAD simulation indicate that the optimal AGR diffusion depth is right at the turning point where the breakdown current shifts from the edge of active region to the AGR region. The devices with optimal AGR depth contain significantly higher breakdown voltages than those of devices either with shallower—or without any— AGR. For the FGR design, a series of devices with different spacings between AGR and FGR and different FGR opening widths for diffusion were fabricated and characterized. We show that when the spacing is longer than the critical value, the breakdown voltage can increase ~1.5 V higher than those of the APD devices without FGR. In addition, the wider the FGR opening width, the higher the breakdown voltage. TCAD simulations were also performed to study the effect of FGR, but showed less pronounced improvements, which could be due the discrepancy between the calculated and experimental diffusion profile.
Degradation of Carbon Fiber-Reinforced Polymer Composites in Salt Water and Rapid Evaluation by Electrochemical Impedance Spectroscopy
Authors: Zhang Hanlu , Kong Fabao , Dun Yuchao , Chen Xueping , Chen Quankai , Zhao Xuhui , Tang Yuming , Zuo Yu
Published: February 2023

The electrochemical impedance spectroscopy and weight gain tests were performed on carbon fiber/vinyl ester and carbon fiber/bismaleimide composites in 3.5% NaCl solution to study the electrochemical and water absorption behaviors. The microstructure morphology and the flexural property of the composites in the long-term exposure process were analyzed with the scanning electron microscope and four-point bending tests. The results revealed that after long-time immersion (>200 d), the water absorption of the two composites is less than 0.5%. This has little effect on the microstructural integrity, only with slight damage on the fiber/resin interfaces, but results in a significant decrease (about 84%) in the composite flexural property. The variation of the water absorption percentage shows good consistency with that of the resin capacitance (Qc) and is negatively related to the variation of the resin resistance (Rpo) and the low-frequency impedance (|Z|0.01Hz) of the composites. A good linear relationship exists between the variations of phase angles in the middle-frequency range (0.1−10 Hz) and the |Z|0.01Hz. The phase angle at 10 Hz (θ10Hz) may be suggested as a suitable parameter to rapidly evaluate the performance of carbon fiber-reinforced polymer composites, just like for evaluating the protective performance of polymer-coated metals in the literature.
Piezoelectric Response and Cycling Fatigue Resistance of Low-Temperature Sintered PZT-Based Ceramics
Authors: Lin Zirui , Zhu Zhe , Yao Zhonghua , Zhang Hao , Hao Hua , Cao Minghe , Liu Hanxing
Published: February 2023

The preparation of low-cost multilayer piezoelectric devices requires using cheap internal electrodes between the dielectric layers. A general strategy is to reduce the sintering temperature Ts of the ceramic layer by sintering aids which can form a liquid phase. Here, 0.2 wt% Li2CO3 was added as a sintering aid to tailor the sinterability and piezoelectricity of the commercial PZT ceramics. As verified from experiments, the piezoelectric ceramics could be densified at a sintering temperature above 940 °C, suitable for co-firing with the cheap internal electrode. The optimized sintering temperature of 980 °C can be confirmed for the 0.2 wt% Li2CO3-modified PZT ceramics due to its high piezoelectric coefficient d33 ~ 701 pC/N, planar coupling factor kp ~ 66.7%, and a low mechanical quality factor Qm ~ 71 with a transition temperature of Tc ~ 226 °C, presenting the characteristics of typical soft piezoelectric ceramics. Moreover, both the potential piezoelectric strain ~0.13% under 20 kV/cm and the good cycling fatigue characteristic (>104 cycles) of the studied piezo compositions indicates strong competitiveness in the field of multilayer piezoelectric devices.
Usage Durability and Comfort Properties of Socks Made from Differently Spun Modal and Micro Modal Yarns
Authors: Tomljenović Antoneta , Živičnjak Juro , Mihaljević Ivan
Published: February 2023

Socks, being a necessary item of clothing, must be comfortable and maintain their quality throughout their life. Since the applicability of modal fibers and microfibers, as well as yarns produced using unconventional processes, in sock knitting has been insufficiently researched, this paper evaluated three groups of medium sized socks knitted in a plain single jersey pattern produced with the highest percentage of ring, rotor and air-jet spun modal or micro modal yarns of the same linear density in full plating with different textured polyamide 6.6 yarns compared to conventional cotton socks. The sock quality was evaluated through an investigation of the physical properties, wear resistance and dimensional stability, as well as the water vapor absorption, air permeability and thermal resistance using the thermal foot model before and after five repeated washing and drying cycles, according to the proposed methodology. The results showed that the fiber fineness, the structure of the differently spun yarns and the sock plain knits, the polyamide content and the implementation of the pretreatment of the socks had an influence on the obtained results. The socks made from modal and micro modal yarns differed in their properties. Compared to cotton socks, they have better comfort properties, a generally better pilling resistance and, after pretreatment, a comparable abrasion resistance.
Analog Resistive Switching and Artificial Synaptic Behavior of ITO/WOX/TaN Memristors
Authors: Cho Youngboo , Kim Jihyung , Kang Myounggon , Kim Sungjun
Published: February 2023

In this work, we fabricated an ITO/WOX/TaN memristor device by reactive sputtering to investigate resistive switching and conduct analog resistive switching to implement artificial synaptic devices. The device showed good pulse endurance (104 cycles), a high on/off ratio (>10), and long retention (>104 s) at room temperature. The conduction mechanism could be explained by Schottky emission conduction. Further, the resistive switching characteristics were performed by additional pulse-signal-based experiments for more practical operation. Lastly, the potentiation/depression characteristics were examined for 10 cycles. The results thus indicate that the WOX-based devices are appropriate candidates for synaptic devices as well as next-generation nonvolatile memory.
Expanded Polytetrafluoroethylene Membranes for Vascular Stent Coating: Manufacturing, Biomedical and Surgical Applications, Innovations and Case Reports
Authors: Cassano Roberta , Perri Paolo , Esposito Antonio , Intrieri Francesco , Sole Roberta , Curcio Federica , Trombino Sonia
Published: February 2023

Coated stents are defined as innovative stents surrounded by a thin polymer membrane based on polytetrafluoroethylene (PTFE)useful in the treatment of numerous vascular pathologies. Endovascular methodology involves the use of such devices to restore blood flow in small-, medium- and large-calibre arteries, both centrally and peripherally. These membranes cross the stent struts and act as a physical barrier to block the growth of intimal tissue in the lumen, preventing so-called intimal hyperplasia and late stent thrombosis. PTFE for vascular applications is known as expanded polytetrafluoroethylene (e-PTFE) and it can be rolled up to form a thin multilayer membrane expandable by 4 to 5 times its original diameter. This membrane plays an important role in initiating the restenotic process because wrapped graft stent could be used as the treatment option for trauma devices during emergency situations and to treat a number of pathological vascular disease. In this review, we will investigate the multidisciplinary techniques used for the production of e-PTFE membranes, the advantages and disadvantages of their use, the innovations and the results in biomedical and surgery field when used to cover graft stents.
The Nitrate-Dependent Impact of Carbon Source Starvation on EH40 Steel Corrosion Induced by the Coexistence of Desulfovibrio vulgaris and Pseudomonas aeruginosa
Authors: Wang Wenkai , Sun Zhihua , Wu Jiajia , Zhang Dun , Wang Peng , Li Ce , Zhu Liyang , Gao Yaohua , Sun Yan
Published: February 2023

Carbon source starvation can promote steel corrosion in the presence of a pure culture through extracellular electron transfer (EET). However, the impact of carbon source starvation on corrosion induced by mixed strains is still unknown. This work investigated the impact of carbon source starvation on EH40 steel corrosion in the presence of Desulfovibrio vulgaris and Pseudomonas aeruginosa, typical species of sulfate- and nitrate-reducing bacteria. It was found that the impact of carbon source starvation on corrosion depended on nitrate addition. When nitrate (5 g∙L−1 NaNO3) was not added, the corrosion was promoted by carbon source starvation. However, the corrosion was initially promoted by carbon source starvation, but later inhibited with nitrate addition. The corrosion behaviors in different systems were closely related to different numbers of the strains in biofilms and their metabolic activities, and the mechanisms were revealed.
The (Poly)phenol-Carbohydrate Combination for Diabetes: Where Do We Stand?
Authors: de Matos Ana Marta , Menezes Regina
Published: February 2023

The type 2 diabetes epidemic is real and hardly coming to an end in the upcoming years. The efforts of the scientific community to develop safer and more effective compounds for type 2 diabetes based on the structure of natural (poly)phenols are remarkable and have indeed proven worthwhile after the introduction of gliflozins in clinical practice. However, low-quality reports on the antidiabetic potential of plant-derived lipophilic (poly)phenols continue to pile up in the literature. Many of these compounds continue to be published as promising functional nutrients and antidiabetic pharmaceutical leads without consideration of their Pan-Assay Interference Compounds (PAINS) profile. This evidence-based opinion article conveys the authors’ perspectives on the natural (poly)phenol artillery as a valuable and reliable source of bioactive compounds for diabetes. Ultimately, in light of the already established membrane-perturbing behavior of lipophilic (poly)phenols, together with the multiple benefits that may come with the introduction of a C-glucosyl moiety in bioactive compounds, we aim to raise awareness of the importance of contemplating the shift to (poly)phenol–carbohydrate combinations in the development of functional nutrients, as well as in the early stages of antidiabetic drug discovery.
Plant-Dominant Low Protein Diet: A Potential Alternative Dietary Practice for Patients with Chronic Kidney Disease
Authors: Sakaguchi Yusuke , Kaimori Jun-Ya , Isaka Yoshitaka
Published: February 2023

Dietary protein restriction has long been a cornerstone of nutritional therapy for patients with chronic kidney diseases (CKD). However, the recommended amount of dietary protein intake is different across guidelines. This is partly because previous randomized controlled trials have reported conflicting results regarding the efficacy of protein restriction in terms of kidney outcomes. Interestingly, a vegetarian, very low protein diet has been shown to reduce the risk of kidney failure among patients with advanced CKD, without increasing the incidence of hyperkalemia. This finding suggests that the source of protein may also influence the kidney outcomes. Furthermore, a plant-dominant low-protein diet (PLADO) has recently been proposed as an alternative dietary therapy for patients with CKD. There are several potential mechanisms by which plant-based diets would benefit patients with CKD. For example, plant-based diets may reduce the production of gut-derived uremic toxins by increasing the intake of fiber, and are useful for correcting metabolic acidosis and hyperphosphatemia. Plant proteins are less likely to induce glomerular hyperfiltration than animal proteins. Furthermore, plant-based diets increase magnesium intake, which may prevent vascular calcification. More evidence is needed to establish the efficacy, safety, and feasibility of PLADO as a new adjunct therapy in real-world patients with CKD.
Iodine Deficiency and Iodine Prophylaxis: An Overview and Update
Authors: Lisco Giuseppe , De Tullio Anna , Triggiani Domenico , Zupo Roberta , Giagulli Vito Angelo , De Pergola Giovanni , Piazzolla Giuseppina , Guastamacchia Edoardo , Sabbà Carlo , Triggiani Vincenzo
Published: February 2023

The thyroid gland requires iodine to synthesize thyroid hormones, and iodine deficiency results in the inadequate production of thyroxine and related thyroid, metabolic, developmental, and reproductive disorders. Iodine requirements are higher in infants, children, and during pregnancy and lactation than in adult men and non-pregnant women. Iodine is available in a wide range of foods and water and is susceptible to almost complete gastric and duodenal absorption as an iodide ion. A healthy diet usually provides a daily iodine consumption not exceeding 50% of the recommended intake. Iodine supplementation is usually necessary to prevent iodine deficiency disorders (IDDs), especially in endemic areas. The community-based strategy of iodine fortification in salt has eradicated IDDs, such as endemic goiter and cretinism, in countries providing adequate measures of iodine prophylaxis over several decades in the 20th century. Iodized salt is the cornerstone of iodine prophylaxis in endemic areas, and the continuous monitoring of community iodine intake and its related clinical outcomes is essential. Despite the relevant improvement in clinical outcomes, subclinical iodine deficiency persists even in Western Europe, especially among girls and women, being an issue in certain physiological conditions, such as pregnancy and lactation, and in people consuming unbalanced vegetable-based or salt-restricted diets. Detailed strategies to implement iodine intake (supplementation) could be considered for specific population groups when iodized salt alone is insufficient to provide adequate requirements.
Development and Validation of a Food Frequency Questionnaire for Evaluating the Nutritional Status of Patients with Cancer
Authors: Lee Se-A , Choi Hyo-Kyoung , Park Seon-Joo , Lee Hae-Jeung
Published: February 2023

Patients with cancer need to maintain proper nutritional status to overcome cancer, alleviate the side effects of chemotherapy, and prevent a recurrence. As such, it is necessary to manage nutritional status. This study aimed to develop a dish-based semi-quantitative food frequency questionnaire (FFQ) to evaluate the nutritional status of patients with cancer and assess the validity of the FFQ. A total of 109 dish items were selected through contribution and variability analyses using the 2016–2018 Korea National Health and Nutrition Examination Survey data. The FFQ was validated against the average 3-day dietary records of 100 patients with cancer. Pearson correlation coefficients and quartile agreements between FFQ and 3-day dietary records were calculated for intake of energy, macronutrients, and micronutrients. Age and energy-adjusted Pearson correlation coefficients ranged from 0.20 (iron) to 0.54 (potassium). The percentage of participants who were classified into the same or adjacent quartile between the FFQ and the 3-day dietary record ranged from 68% (protein) to 81% (energy, dietary fiber). The results suggest that the FFQ is an appropriate tool for assessing nutritional status in Korean cancer patients.
Automated Interlaboratory Comparison of Therapeutic Drug Monitoring Data and Its Use for Evaluation of Published Therapeutic Reference Ranges
Authors: Larsen Jens Borggaard , Hoffmann-Lücke Elke , Aaslo Per Hersom , Jørgensen Niklas Rye , Greibe Eva
Published: February 2023

Therapeutic drug monitoring is a tool for optimising the pharmacological treatment of diseases where the therapeutic effect is difficult to measure or monitor. Therapeutic reference ranges and dose-effect relation are the main requirements for this drug titration tool. Defining and updating therapeutic reference ranges are difficult, and there is no standardised method for the calculation and clinical qualification of these. The study presents a basic model for validating and selecting routine laboratory data. The programmed algorithm was applied on data sets of antidepressants and antipsychotics from three public hospitals in Denmark. Therapeutic analytical ranges were compared with the published therapeutic reference ranges by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) and in additional literature. For most of the drugs, the calculated therapeutic analytical ranges showed good concordance between the laboratories and to published therapeutic reference ranges. The exceptions were flupentixol, haloperidol, paroxetine, perphenazine, and venlafaxine + o-desmethyl-venlafaxine (total plasma concentration), where the range was considerably higher for the laboratory data, while the calculated range of desipramine, sertraline, ziprasidone, and zuclopenthixol was considerably lower. In most cases, we identified additional literature supporting our data, highlighting the need of a critical re-examination of current therapeutic reference ranges in Denmark. An automated approach can aid in the evaluation of current and future therapeutic reference ranges by providing additional information based on big data from multiple laboratories.
A Single Injection with Sustained-Release Microspheres and a Prime-Boost Injection of Bovine Serum Albumin Elicit the Same IgG Antibody Response in Mice
Authors: van der Kooij Renée S. , Beukema Martin , Huckriede Anke L. W. , Zuidema Johan , Steendam Rob , Frijlink Henderik W. , Hinrichs Wouter L. J.
Published: February 2023

Although vaccination is still considered to be the cornerstone of public health care, the increase in vaccination coverage has stagnated for many diseases. Most of these vaccines require two or three doses to be administered across several months or years. Single-injection vaccine formulations are an effective method to overcome the logistical barrier to immunization that is posed by these multiple-injection schedules. Here, we developed subcutaneously (s.c.) injectable microspheres with a sustained release of the model antigen bovine serum albumin (BSA). The microspheres were composed of blends of two novel biodegradable multi-block copolymers consisting of amorphous, hydrophilic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) blocks and semi-crystalline poly(dioxanone) (PDO) blocks of different block sizes. In vitro studies demonstrated that the release of BSA could be tailored over a period of approximately four to nine weeks by changing the blend ratio of both polymers. Moreover, it was found that BSA remained structurally intact during release. Microspheres exhibiting sustained release of BSA for six weeks were selected for the in vivo study in mice. The induced BSA-specific IgG antibody titers increased up to four weeks after administration and were of the same magnitude as found in mice that received a priming and a booster dose of BSA in phosphate-buffered saline (PBS). Determination of the BSA concentration in plasma showed that in vivo release probably took place up to at least four weeks, although plasma concentrations peaked already one week after administration. The sustained-release microspheres might be a viable alternative to the conventional prime-boost immunization schedule, but a clinically relevant antigen should be incorporated to assess the full potential of these microspheres in practice.