bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of PON1, PON2, PON3 and MPO Genes in Patients with Depressive Disorders
Authors: Bliźniewska-Kowalska Katarzyna , Gałecki Piotr , Su Kuan-Pin , Halaris Angelos , Szemraj Janusz , Gałecka Małgorzata
Published: June 2022

Background: Taking into account the role of oxidative stress in neurodegeneration, we sought to evaluate the expression of genes for select enzymes with antioxidant properties (paraoxonases PON1, PON2 and PON3 and myeloperoxidase MPO) at the mRNA and protein levels in patients with depressive disorders. We further sought to determine the impact of oxidative stress in the etiopathogenesis of this group of mood disorders. Methods: A total of 290 subjects (190 depressed patients, 100 healthy controls) took part in the study. Sociodemographic and clinical data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Venous blood was collected. RT-PCR was used to assess gene expression at the mRNA level, while enzyme-linked immunosorbent assay (ELISA) was used to assess gene expression at the protein level. Results: The expression of the PON2 and PON3 genes at the protein level was significantly higher in depressive patients than in healthy controls. mRNA expression of the PON1, PON2 and PON3 genes was slightly higher in patients with depressive disorders than in the control group, however, this relationship was not statistically significant. On the other hand, the expression of the MPO gene at both mRNA and protein levels was significantly lower in patients with depressive disorder than in the control group. Conclusions: Our results are not in agreement with many studies on enzymes involved in maintaining oxidative balance. Our findings may not support the utility of paraoxonases (PON) or myeloperoxidase (MPO) as promising biomarker candidates of depression pending larger and well controlled studies.
Procedural Feasibility and Long-Term Efficacy of Catheter Ablation of Atypical Atrial Flutters in a Wide Spectrum of Heart Diseases: An Updated Clinical Overview
Authors: De Ponti Roberto , Marazzi Raffaella , Vilotta Manola , Angeli Fabio , Marazzato Jacopo
Published: June 2022

Atypical atrial flutters (AAFL) are difficult-to-manage atrial arrhythmias, yet potentially amenable to effective radiofrequency catheter ablation (CA). However, data on CA feasibility are only sparingly reported in the literature in different clinical settings, such as AAFL related to surgical correction of congenital heart disease. The aim of this review was to provide an overview of the clinical settings in which AAFL may occur to help the cardiac electrophysiologist in the prediction of the tachycardia circuit location before CA. Moreover, the role and proper implementation of cutting-edge technologies in this setting were investigated as well as which procedural and clinical factors are associated with long-term failure to maintain sinus rhythm (SR) to find out which patients may, or may not, benefit from this procedure. Not only different surgical and non-surgical scenarios are associated with peculiar anatomical location of AAFL, but we also found that CA of AAFL is generally feasible. The success rate may be as low as 50% in surgically corrected congenital heart disease (CHD) patients but up to about 90% on average after pulmonary vein isolation (PVI) or in patients without structural heart disease. Over the years, the progressive implementation of three-dimensional mapping systems and high-density mapping tools has also proved helpful for ablation of these macro-reentrant circuits. However, the long-term maintenance of SR may still be suboptimal due to the progressive electroanatomic atrial remodeling occurring after cardiac surgery or other interventional procedures, thus limiting the likelihood of successful ablation in specific clinical settings.
Comment on Topyła-Putowska et al. Echocardiography in Pulmonary Arterial Hypertension: Comprehensive Evaluation and Technical Considerations. J. Clin. Med. 2021, 10, 3229
Authors: Manzi Giovanna , Vizza Carmine Dario , Badagliacca Roberto
Published: June 2022

A comprehensive PAH echocardiographic examination of patients with pulmonary arterial hypertension (PAH) should include a set of parameters resembling the pathophysiological changes occurring in the course of the disease. This approach could help clinicians build a complete picture of the patient, test the effects of targeted therapies and identify patients who need a more aggressive therapeutic approach to achieve a low risk-status.
Early Reoperation Rates and Its Risk Factors after Instrumented Spinal Fusion Surgery for Degenerative Spinal Disease: A Nationwide Cohort Study of 65,355 Patients
Authors: Kim Jihye , Ryu Hwan , Kim Tae-Hwan
Published: June 2022

Reoperation is a major concern in spinal fusion surgery for degenerative spinal disease. Earlier reported reoperation rates were confined to a specific spinal region without comprehensive analysis, and their prediction models for reoperation were not statistically validated. Our study aimed to present reasonable base rates for reoperation according to all possible risk factors and build a validated prediction model for early reoperation. In our nationwide population-based cohort study, data between 2014 and 2016 were obtained from the Korean National Health Insurance claims database. Patients older than 19 years who underwent instrumented spinal fusion surgery for degenerative spinal diseases were included. The patients were divided into cases (patients who underwent reoperation) and controls (patients who did not undergo reoperation), and risk factors for reoperation were determined by multivariable analysis. The estimates of all statistical models were internally validated using bootstrap samples, and sensitivity analyses were additionally performed to validate the estimates by comparing the two prediction models (models for 1st-year and 3rd-year reoperation). The study included 65,355 patients: 2939 (4.5%) who underwent reoperation within 3 years after the index surgery and 62,146 controls. Reoperation rates were significantly different according to the type of surgical approach and the spinal region. The third-year reoperation rates were 5.3% in the combined lumbar approach, 5.2% in the posterior lumbar approach, 5.0% in the anterior lumbar approach, 3.0% in the posterior thoracic approach, 2.8% in the posterior cervical approach, 2.6% in the anterior cervical approach, and 1.6% in the combined cervical approach. Multivariable analysis identified older age, male sex, hospital type, comorbidities, allogeneic transfusion, longer use of steroids, cages, and types of surgical approaches as risk factors for reoperation. Clinicians can conduct comprehensive risk assessment of early reoperation in patients who will undergo instrumented spinal fusion surgery for degenerative spinal disease using this model.
Diffusion-Weighted Magnetic Resonance Imaging: Clinical Potential and Applications
Authors: Caroli Anna
Published: June 2022

Since its discovery in the 1980s [...]
Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review
Authors: Bellini Alice , Mazzarra Sara , Sterrantino Sara , Argnani Desideria , Stella Franco
Published: June 2022

Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.
Applicability of the Thrombin Generation Test to Evaluate the Hemostatic Status of Hemophilia A Patients in Daily Clinical Practice
Authors: Bernardo Ángel , Caro Alberto , Martínez-Carballeira Daniel , Corte José Ramón , Vázquez Sonia , Palomo-Antequera Carmen , Andreu Alfredo , Fernández-Pardo Álvaro , Oto Julia , Gutiérrez Laura , Soto Inmaculada , Medina Pilar
Published: June 2022

Hemophilia A (HA) is a rare bleeding disorder caused by factor VIII (FVIII) deficiency due to various genetic mutations in the F8 gene. The disease severity inversely correlates with the plasma levels of functional FVIII. The treatment of HA patients is based on FVIII replacement therapy, either following a prophylactic or on-demand regime, depending on the severity of the disease at diagnosis and the patient’s clinical manifestations. The hemorrhagic manifestations are widely variable amongst HA patients, who may require monitoring and treatment re-adjustment to minimize bleeding symptoms. Notably, laboratory monitoring of the FVIII activity is difficult due to a lack of sensitivity to various FVIII-related molecules, including non-factor replacement therapies. Hence, patient management is determined mainly based on clinical manifestations and patient–clinician history. Our goal was to validate the ST Genesia® automated thrombin generation analyzer to quantify the relative hemostatic status in HA patients. We recruited a cohort of HA patients from the Principality of Asturias (Spain), following treatment and at a stable non-bleeding phase. The entire cohort (57 patients) had been comprehensively studied at diagnosis, including FVIII and VWF activity assays and F8 genetic screening, and then clinically monitored until the Thrombin Generation Test (TGT) was performed. All patients were recruited prior to treatment administration, at the maximum time-window following the previous dose. Interestingly, the severe/moderate patients had a similar TGT compared to the mild patients, reflecting the non-bleeding phase of our patient cohort, regardless of the initial diagnosis (i.e., the severity of the disease), treatment regime, and FVIII activity measured at the time of the TGT. Thus, TGT parameters, especially the peak height (Peak), may reflect the actual hemostatic status of a patient more accurately compared to FVIII activity assays, which may be compromised by non-factor replacement therapies. Furthermore, our data supports the utilization of combined TGT variables, together with the severity of patient symptoms, along with the F8 mutation type to augment the prognostic capacity of TGT. The results from this observational study suggest that TGT parameters measured with ST Genesia® may represent a suitable tool to monitor the hemostatic status of patients requiring a closer follow-up and a tailored therapeutic adjustment, including other hemophilia subtypes or bleeding disorders.
Bile or Acid Reflux Post One-Anastomosis Gastric Bypass: What Must We Do? Still an Unsolved Enigma
Authors: Poghosyan Tigran , Krivan Sylvia , Baratte Clement
Published: June 2022

Obesity is a global scourge, affecting over 15% of the world’s population [...]
Thyroid-Stimulating Hormone Predicts Total Cholesterol and Low-Density Lipoprotein Cholesterol Reduction during the Acute Phase of COVID-19
Authors: Mannarino Massimo Raffaele , Bianconi Vanessa , Cosentini Elena , Figorilli Filippo , Colangelo Cecilia , Giglioni Francesco , Lombardini Rita , Paltriccia Rita , Pirro Matteo
Published: June 2022

A complex dysregulation of lipid metabolism occurs in COVID-19, leading to reduced total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) levels, along with a derangement of thyroid function, leading to reduced thyroid-stimulating hormone (TSH) levels. This study aimed to explore the association between TSH levels during COVID-19 and the variation (Δ) of lipid profile parameters in the period preceding (from 1 month up to 1 year) hospital admission due to COVID-19. Clinical data of 324 patients (mean age 76 ± 15 years, 54% males) hospitalized due to COVID-19 between March 2020 and March 2022 were retrospectively analyzed. The association between TSH levels at hospital admission and either Δ-TC, Δ-LDL-C, or Δ-HDL-C over the selected time frame was assessed through univariable and multivariable analyses. TSH levels were below the lower reference limit of 0.340 μUI/mL in 14% of COVID-19 patients. A significant reduction of plasma TC, LDL-C, and HDL-C was recorded between the two time points (p < 0.001 for all the comparisons). TSH was directly associated with Δ-TC (rho = 0.193, p = 0.001), Δ-LDL-C (rho = 0.201, p = 0.001), and Δ-HDL-C (rho = 0.160, p = 0.008), and inversely associated with C-reactive protein (CRP) (rho = −0.175, p = 0.004). Moreover, TSH decreased with increasing COVID-19 severity (p < 0.001). CRP and COVID-19 severity were inversely associated with Δ-TC, Δ-LDL-C, and Δ-HDL-C (p < 0.05 for all associations). A significant independent association was found between TSH and either Δ-TC (β = 0.125, p = 0.044) or Δ-LDL-C (β = 0.131, p = 0.036) after adjusting for multiple confounders including CRP and COVID-19 severity. In conclusion, lower levels of TSH may contribute to explain TC and LDL-C reduction in the acute phase of COVID-19.
Marking the Profile of the Microflora of the Endometrium and Uterine Cervix in Women as a Potential Factor Determining the Effectiveness of In Vitro Fertilization
Authors: Bednarska-Czerwińska Anna , Czerwiński Michał , Morawiec Emilia , Łach Aleksandra , Ziaja Anna , Kusaj Adrian , Strączyńska Patrycja , Sagan Dorota , Boroń Dariusz , Grabarek Beniamin Oskar
Published: June 2022

One promising research trend involves evaluating the influence of microbiota in the reproductive system of women on becoming pregnant and maintaining pregnancy. The goal of this study was to define the microflora profile of the endometrium and uterine cervix in women qualified for an in vitro fertilization (IVF) procedure, which is expected to contribute to increasing the percentage of successful IVF implantations. Based on the conducted molecular analysis in the collected swabs, 22 bacterial strains were identified. Eleven strains (57%) that were isolated belong to the physiological microflora, the most common strain of which was Lactobacillus. Eight of the isolated strains (33%) were pathological microflora, among which the most common bacteria were from the Enterobacteriaceae family (which includes E. coli, Shigella, and Salmonella). Finally, three of the bacterial strains (10%) may be a component of both physiological or pathological microflora of the vagina: Bifidobacterium breve, Bifidobacterium longum group, and Alloscardovia omnicolens. The presence of Escherichia coli was detected in six women, Staphylococcus aureus also in six patients, Atopobium parvulum in three, Streptococcus salivarius group in three, Enterococcus faecalis in four, and Aerococcus christensenii in two patients. We found statistically significant relationships (p < 0.05) between Lactobacillus fermentum and Enterococcus faecalis, Lactobacillus delbrueckii and Escherichia coli groups, Lactobacillus FN667084_s and Staphylococcus aureus groups, as well as Lactobacillus fermentum and Streptococcus agalactiae. Based on the conducted study, it may be confirmed that the endometrium is, to a large extent, colonized by lactic acid bacilli. Apart from that, endometrial dysbiosis was not noted in patients qualified for the IVF procedure.
Validity and Utility of Non-Invasive Prenatal Testing for Copy Number Variations and Microdeletions: A Systematic Review
Authors: Zaninović Luca , Bašković Marko , Ježek Davor , Katušić Bojanac Ana
Published: June 2022

Valid data on prenatal cell-free DNA-based screening tests for copy number variations and microdeletions are still insufficient. We aimed to compare different methodological approaches concerning the achieved diagnostic accuracy measurements and positive predictive values. For this systematic review, we searched the Scopus and PubMed databases and backward citations for studies published between 2013 and 4 February 2022 and included articles reporting the analytical and clinical performance of cfDNA screening tests for CNVs and microdeletions. Of the 1810 articles identified, 32 met the criteria. The reported sensitivity of the applied tests ranged from 20% to 100%, the specificity from 81.62% to 100%, and the PPV from 3% to 100% for cases with diagnostic or clinical follow-up information. No confirmatory analysis was available in the majority of cases with negative screening results, and, therefore, the NPVs could not be determined. NIPT for CNVs and microdeletions should be used with caution and any developments regarding new technologies should undergo strict evaluation before their implementation into clinical practice. Indications for testing should be in correlation with the application guidelines issued by international organizations in the field of prenatal diagnostics.
Differential Expression of Tissular miRNA-155 in Pediatric Gastritis
Authors: Oana Săsăran Maria , Claudia Bănescu , Lelia Riza Anca , Simona Mocan , Claudia Cârstea , Daniela Dobru Ecaterina
Published: June 2022

Background: MicroRNA molecules, among them the intensely studied miRNA-155 (miR-155), are regarded as potential biomarkers of chronic gastric inflammation and premalignant lesion progression. However, literature data are scarce in terms of pediatric studies and in the evaluation of the predictive role of miRNA in early gastric inflammation. This study aims to assess the differential expression of miR-155 in relation to pediatric gastritis. Methods: The present research was conducted on 192 patients with chronic dyspeptic symptoms who underwent upper digestive endoscopy. Bioptic samples were harvested for histopathological analysis and tissue miR-155 depiction. MiR-155 expression analysis was carried out through quantitative real-time polymerase chain reaction (qRT-PCR). The study population was divided into two groups: controls (93 patients) and study group (99 patients) with inflammatory modifications. Results: MiR-155 expression was augmented in patients with gastritis but did not differ significantly from controls (p = 0.16). An increase in miR-155 expression was noted in relation to chronic gastritis, H. pylori infection, or increase in gastritis severity, but these variations were not important (p = 0.30, p = 0.44, and p = 0.45, respectively). Conclusions: According to our study, pediatric gastritis increases, but does not greatly influence, miR-155 expression. Dynamic evaluation of miR-155 might enlighten its prognostic role in pediatric gastritis.
Risk of SARS-CoV-2 Reinfections in a Prospective Inception Cohort Study: Impact of COVID-19 Vaccination
Authors: Casado José L. , Haemmerle Johannes , Vizcarra Pilar , Ramirez-Alonso Gema , Salazar-Tosco Andrea , Romero-Hernandez Beatriz , Blasco Magdalena , Rodriguez-Dominguez Mario , Mirabella Itria G. , Vallejo Alejandro , Fernandez-Escribano Marina
Published: June 2022

The risk of reinfection could be related to the initial SARS-CoV-2 clinical presentation, but there are no data about the risk change after SARS-CoV-2 vaccination. We evaluated the rate of reinfection in an inception cohort study of 4943 health care workers (HCWs) according to symptoms and serologic results during March–May 2020. Incidence rates (IR) and IR ratios (IRR) before and after SARS-CoV-2 vaccination were determined by adjusting Poisson models. Overall, 1005 HCWs (20.3%) referred COVID-19 suggestive symptoms during the first surge of disease, and 33.5% and 55% presented a positive PCR or serology result, respectively. Meanwhile, 13% of asymptomatic HCWs had specific antibodies. During a follow up of 3422.2 person-years before vaccination, the rate of reinfection among seropositive individuals was 81% lower for those who were symptomatic compared with those who were asymptomatic (IRR of 0.19; 95% CI, 0.05–0.67; p = 0.003). During the 3100 person-years period after vaccination, an overall 74% decrease in the rate of infection was observed (IRR of 0.26; 95% CI, 0.21–0.32; p < 0.001), with a significant 83% and 70% decrease in seropositive and seronegative HCWs, respectively. In conclusion, the risk of SARS-CoV-2 reinfections is closely related to the clinical and serological presentation of COVID-19. COVID-19 vaccination further decreases the risk of reinfection more markedly among seropositive.
Genetic and Functional Evidence of Complement Dysregulation in Multiple Myeloma Patients with Carfilzomib-Induced Thrombotic Microangiopathy Compared to Controls
Authors: Gavriilaki Eleni , Dalampira Dimitra , Theodorakakou Foteini , Liacos Christine-Ivy , Kanellias Nikolaos , Eleutherakis-Papaiakovou Evangelos , Terpos Evangelos , Gavriatopoulou Maria , Verrou Evgenia , Triantafyllou Theodora , Sevastoudi Aggeliki , Koravou Evaggelia-Evdoxia , Touloumenidou Tasoula , Varelas Christos , Papalexandri Apostolia , Sakellari Ioanna , Dimopoulos Meletios A. , Kastritis Efstathios , Katodritou Eirini
Published: June 2022

Background: Carfilzomib, an irreversible proteasome inhibitor approved for the treatment of relapsed/refractory Multiple Myeloma (MM) has been associated with Thrombotic Microangiopathy (TMA). Several pathogenetic mechanisms of carfilzomib-induced TMA have been proposed; however, recently, there has been a shift of focus on the potential contribution of complement dysregulation. Our aim was to explore whether patients with carfilzomib-induced TMA harbor germline variants of complement-related genes, which have been characterized as risk factors for TMA. Methods: We retrospectively recruited consecutive MM patients with carfilzomib-induced TMA and compared them to MM patients who received ≥4 cycles of carfilzomib and did not develop signs/symptoms of TMA, in a 1:2 ratio. Genomic DNA from peripheral blood was analyzed using next generation sequencing (NGS) with a complement-related gene panel; ADAMTS13 activity and soluble C5b-9 were measured using ELISA. Results: Complement-related variants were more common in patients with carfilzomib-induced TMA compared to non-TMA controls, regardless of patient and treatment characteristics; ADAMTS13 activity and C5b-9 were compatible with the phenotype of complement-related TMA. Conclusions: We confirmed the previous findings that implicated complement-related genes in the pathogenesis of carfilzomib-induced TMA. Most importantly, by incorporating a control group of non-TMA MM patients treated with carfilzomib-based regimens and functional complement assays, we enhanced the credibility of our findings.
Collagenase Administration into Periodontal Ligament Reduces the Forces Required for Tooth Extraction in an Ex situ Porcine Jaw Model
Authors: Tohar Ran , Alali Hen , Ansbacher Tamar , Brosh Tamar , Sher Inbal , Gafni Yossi , Weinberg Evgeny , Gal Maayan
Published: June 2022

Minimally invasive exodontia is among the long-sought-for development aims of safe dental medicine. In this paper, we aim, for the first time, to examine whether the enzymatic disruption of the periodontal ligament fibers reduces the force required for tooth extraction. To this end, recombinantly expressed clostridial collagenase G variant purified from Escherichia coli was injected into the periodontal ligament of mesial and distal roots of the first and second split porcine mandibular premolars. The vehicle solution was injected into the corresponding roots on the contralateral side. Following sixteen hours, the treated mandibles were mounted on a loading machine to measure the extraction force. In addition, the effect of the enzyme on the viability of different cell types was evaluated. An average reduction of 20% in the applied force (albeit with a large variability of 50 to 370 newton) was observed for the enzymatically treated roots, reaching up to 50% reduction in some cases. Importantly, the enzyme showed only a minor and transient effect on cellular viability, without any signs of toxicity. Using an innovative model enabling the analytical measurement of extraction forces, we show, for the first time, that the enzymatic disruption of periodontal ligament fibers substantially reduces the force required for tooth extraction. This novel technique brings us closer to atraumatic exodontia, potentially reducing intra- and post-operative complications and facilitating subsequent implant placement. The development of novel enzymes with enhanced activity may further simplify the tooth extraction process and present additional clinical relevance for the broad range of implications in the oral cavity.
Graphene Oxide (GO) Materials—Applications and Toxicity on Living Organisms and Environment
Authors: Ghulam Aminah N. , dos Santos Otávio A. L. , Hazeem Layla , Pizzorno Backx Bianca , Bououdina Mohamed , Bellucci Stefano
Published: June 2022

Graphene-based materials have attracted much attention due to their fascinating properties such as hydrophilicity, high dispersion in aqueous media, robust size, high biocompatibility, and surface functionalization ability due to the presence of functional groups and interactions with biomolecules such as proteins and nucleic acid. Modified methods were developed for safe, direct, inexpensive, and eco-friendly synthesis. However, toxicity to the environment and animal health has been reported, raising concerns about their utilization. This review focuses primarily on the synthesis methods of graphene-based materials already developed and the unique properties that make them so interesting for different applications. Different applications are presented and discussed with particular emphasis on biological fields. Furthermore, antimicrobial potential and the factors that affect this activity are reviewed. Finally, questions related to toxicity to the environment and living organisms are revised by highlighting factors that may interfere with it.
Cu2+ Release from Polylactic Acid Coating on Titanium Reduces Bone Implant-Related Infection
Authors: Zhang Chengdong , Li Xingping , Xiao Dongqin , Zhao Qiao , Chen Shuo , Yang Fei , Liu Jinhui , Duan Ke
Published: June 2022

Implant-related infection (IRI) is a major problem in orthopedics. Copper (Cu) is an essential trace element with strong bactericidal activity and, thus, presents potential for reducing IRI. The present study explored a straightforward strategy for releasing Cu2+ from titanium (Ti) implants, and we conducted a preliminary study to assess the feasibility of this approach in clinical translation. Polylactic acid (PLA) coatings containing different concentrations of copper ions were prepared on Ti discs. The antibacterial activity and biocompatibility of the copper ion-incorporated Ti implants were evaluated using Staphylococcus aureus (S. aureus), bone marrow mesenchymal stem cells (BMSCs) and animal models. In vitro, the coatings produced burst release of Cu2+ in 12 h, and inhibited S. aureus growth in a dose-dependent manner. The coatings prepared from PLA solutions containing 0.5 or 1.0 mg/mL reduced the viability and osteogenic differentiation of BMSCs, but these effects were negated after the coatings were immersed in culture medium for 6 h. Four weeks after implantation, the Cu-free K-wires challenged with S. aureus had persistent infection and inferior fracture healing to the other three groups, while Cu-coated wires had no evidence of infection. Furthermore, the Cu-coated wires placed in rabbits without S. aureus challenge showed superior fracture healing to the other three groups. These results suggest that PLA coatings containing Cu2+ may be an effective design for reducing IRI without adversely affecting adjacent bone healing.
An Efficient Opportunistic Routing Based on Prediction for Nautical Wireless Ad Hoc Networks
Authors: Ge Lige , Jiang Shengming
Published: June 2022

Nautical wireless ad hoc networks are becoming increasingly popular in oceans due to their easy deployment and self-curing capability. They may alternate frequently between connected mobile ad hoc networks and partitioned opportunistic networks due to mobility in large spaces. Traditional mobile ad hoc network routing is used to find the shortest route for connected networks. However, for opportunistic networks, routing schemes with a broadcast nature mainly exploit the reduction in message duplication and the local relaying technologies described in the literature, which may lead to unnecessary resource waste and low packet delivery ratios. To solve the problem, we propose an efficient opportunistic routing scheme based on prediction for nautical wireless ad hoc networks. The scheme first develops an effective candidate intermediate region to recognize the unavailability of some apparently qualified intermediate nodes, and then takes into account the packet reception ratio between nodes and relay advancement prediction, to improve packet delivery. The proposed scheme achieves performance improvements regarding packet loss ratio and throughput with a tolerable latency increase, compared to other schemes.
Research on Improving the Accuracy of Welding Residual Stress of Deep-Sea Pipeline Steel by Blind Hole Method
Authors: Ma Wenbo , Bai Tianwen , Li Yuyang , Zhang Heng , Zhu Wei
Published: June 2022

For a typical pipeline-lifting deep-sea mining system, marine mining pipelines have higher requirements for steel welding. After the pipeline steel is welded, a large amount of residual stress will be generated inside the component because the heat treatment is not carried out, causing the pipeline to form stress corrosion cracks in the seawater environment. For high residual stress, the blind hole method has inaccurate measurement accuracy. Based on the theory of solid mechanics, this paper comprehensively considers the distance between the strain grid and the center of the hole. It introduces the ratio γ of the applied stress to the yield strength of the specimen. The strain relief coefficients under the values were investigated. The variation trend of the strain release coefficient distribution with the γ value of the three kinds of strain gauge flowers commonly used in China was discussed. Finally, the variation law of strain release coefficient with γ value was obtained by fitting. The strain release coefficient was corrected to improve the accuracy of the blind hole method for measuring high residual stress, which provides a reference value for the engineering application of the blind hole method. This has important theoretical significance and engineering value for guiding the welding construction of high-strength pipeline steel in a deep-sea environment.
Comparison of Lightweight Structures in Bearing Impact Loads during Ice–Hull Interaction
Authors: Cheemakurthy Harsha , Barsoum Zuheir , Burman Magnus , Garme Karl
Published: June 2022

The current study focuses on the impact loading phase characteristic of thin first year ice in inland waterways. We investigate metal grillages, fibre reinforced plastic (FRP) composites and nature-inspired composites using LS Dyna. The impact mode is modelled as (a) simplified impact model with a rigid-body impactor and (b) an experimentally validated ice model represented by cohesive zone elements. The structural concepts are investigated parametrically for strength and stiffness using the simplified model, and an aluminium alloy grillage is analysed with the ice model. The metal–FRP composite was found to be the most favourable concept that offered impact protection as well as being light weight. By weight, FRP composites with a Bouligand ply arrangement were the most favourable but prone to impact damage. Further, aluminium grillage was found to be a significant contender for a range of ice impact velocities. While the ice model is experimentally validated, a drawback of the simplified model is the lack of experimental data. We overcame this by limiting the scope to low velocity impact and investigating only relative structural performance. By doing so, the study identifies significant parameters and parametric trends along with material differences for all structural concepts. The outcomes result in the creation of a viable pool of lightweight variants that fulfil the impact loading phase. Together with outcomes from quasi-static loading phase, it is possible to develop a lightweight ice-going hull concept.
A Novel Wellbore-Wall Heating Method without External Energy Injection for Natural Gas Hydrate Production—A Heat Transfer Device
Authors: Ye Hongyu , Wu Xuezhen , Guo Gaoqiang , Li Dayong , Jiang Yujing
Published: June 2022

Natural gas hydrate (NGH) dissociation is a heat-absorbing process, and the cooling around the wellhead is more pronounced during depressurization production. Low temperature will cause NGH regeneration or ice formation, blocking gas flow paths and reducing extraction efficiency. In this study, a novel heat transfer device (HTD) was innovatively proposed to alleviate this problem. Theoretical analysis and numerical simulations were used to research the methodological principles, applicable conditions, and expected benefits of the HTD. Results show that the HTD utilizes the characteristics of the geothermal gradient to rapidly transfer energy from the lower reservoir to the wellbore wall, which in turn raises the temperature and prevents the ice and NGH regeneration causing the blockage from adhering to the wellbore wall. The heat transfer radius, the length of the endothermic section, and the operating temperature difference make a tremendous difference in the heat transfer efficiency of the HTD. The HTD may be more suitable for Class 1 reservoir conditions and help to improve gas production under the depressurization method in the Shenhu sea of the South China Sea. The device can achieve continuous self-heat transfer without external energy injection to significantly reduce costs, which provides a new idea for marine NGH production.
Geochemical Analysis of Cretaceous Shales from the Hazara Basin, Pakistan: Provenance Signatures and Paleo-Weathering Conditions
Authors: Fazal Abdul , Umar Muhammad , Shah Faisal , Miraj Muhammad , Janjuhah Hammad , Kontakiotis George , Jan Abdul
Published: June 2022

The geochemical investigation of shales from the Early to Middle Cretaceous Chichali Formation in the Hazara Basin was conducted to determine the origin, tectonic setting and evolution, paleo-weathering conditions, and paleo-oceanographic reconstruction. The research included a comprehensive field survey, sample collection, and analysis of a variety of main, trace, and rare-earth elements using an X-ray fluorescence spectrometer (XRF). Bivariate plots and ternary diagrams were used to determine the provenance, tectonic setting, and paleo-weathering conditions that existed during the development of the Chichali Formation in the Hazara Basin. The values of Ba/Sc, Ba/Co, Th/Sc, Cr/Th, Cr/Zr, Th/Co, Th/Cr, Sc/Th, bivariate plots of Al2O3 vs. TiO2, TiO2 vs. Zr, TiO2 vs. Ni, Df1–Df2, Zr vs. Nb, and La/Sc vs. Th/Co, and ternary diagram of K2O–Fe2O3–Al2O3 were used to illustrate the passive continental margin setting of Chichali Formation shales. The detailed chemical analysis also provides an understanding of the marine geochemical cycle, which reflects the origin of these sediments. The average K2O/Al2O3 value is less than 0.4, indicating that the shale contains clay minerals. The Chichali Formation’s Chemical Index of Alteration (mean = 71) and Index of Compositional Variation (mean = 1.12) values show a modest degree of chemical weathering in the source locations. From an environmental standpoint, the Chichali Formation is richer in toxic elements such as Ba, Zn, Ni, Cr, and Cu, which may be damaging to agricultural soils and drinking water when present in excess. These metals are incorporated into the formation during the weathering process.
Marine Natural Product Antimycin A Suppresses Wheat Blast Disease Caused by Magnaporthe oryzae Triticum
Authors: Paul Sanjoy Kumar , Chakraborty Moutoshi , Rahman Mahfuzur , Gupta Dipali Rani , Mahmud Nur Uddin , Rahat Abdullah Al Mahbub , Sarker Aniruddha , Hannan Md. Abdul , Rahman Md. Mahbubur , Akanda Abdul Mannan , Ahmed Jalal Uddin , Islam Tofazzal
Published: June 2022

The application of chemical pesticides to protect agricultural crops from pests and diseases is discouraged due to their harmful effects on humans and the environment. Therefore, alternative approaches for crop protection through microbial or microbe-originated pesticides have been gaining momentum. Wheat blast is a destructive fungal disease caused by the Magnaporthe oryzae Triticum (MoT) pathotype, which poses a serious threat to global food security. Screening of secondary metabolites against MoT revealed that antimycin A isolated from a marine Streptomyces sp. had a significant inhibitory effect on mycelial growth in vitro. This study aimed to investigate the inhibitory effects of antimycin A on some critical life stages of MoT and evaluate the efficacy of wheat blast disease control using this natural product. A bioassay indicated that antimycin A suppressed mycelial growth (62.90%), conidiogenesis (100%), germination of conidia (42%), and the formation of appressoria in the germinated conidia (100%) of MoT at a 10 µg/mL concentration. Antimycin A suppressed MoT in a dose-dependent manner with a minimum inhibitory concentration of 0.005 μg/disk. If germinated, antimycin A induced abnormal germ tubes (4.8%) and suppressed the formation of appressoria. Interestingly, the application of antimycin A significantly suppressed wheat blast disease in both the seedling (100%) and heading stages (76.33%) of wheat at a 10 µg/mL concentration, supporting the results from in vitro study. This is the first report on the inhibition of mycelial growth, conidiogenesis, conidia germination, and detrimental morphological alterations in germinated conidia, and the suppression of wheat blast disease caused by a Triticum pathotype of M. Oryzae by antimycin A. Further study is required to unravel the precise mode of action of this promising natural compound for considering it as a biopesticide to combat wheat blast.
Diagnosis and Treatment of Fungus and Virus Interaction
Authors: Lai Chih-Cheng , Yu Wen-Liang
Published: June 2022

Many viruses can have a serious impact on human respiratory disease, e [...]
Peroxins in Peroxisomal Receptor Export System Contribute to Development, Stress Response, and Virulence of Insect Pathogenic Fungus Beauveria bassiana
Authors: Hou Jia , Lin Haiyan , Ding Jinli , Feng Mingguang , Ying Shenghua
Published: June 2022

In filamentous fungi, recycling of receptors responsible for protein targeting to peroxisomes depends on the receptor export system (RES), which consists of peroxins Pex1, Pex6, and Pex26. This study seeks to functionally characterize these peroxins in the entomopathogenic fungus Beauveria bassiana. BbPex1, BbPex6, and BbPex26 are associated with peroxisomes and interact with each other. The loss of these peroxins did not completely abolish the peroxisome biogenesis. Three peroxins were all absolutely required for PTS1 pathway; however, only BbPex6 and BbPex26 were required for protein translocation via PTS2 pathway. Three gene disruption mutants displayed the similar phenotypic defects in assimilation of nutrients (e.g., fatty acid, protein, and chitin), stress response (e.g., oxidative and osmotic stress), and virulence. Notably, all disruptant displayed significantly enhanced sensitivity to linoleic acid, a polyunsaturated fatty acid. This study reinforces the essential roles of the peroxisome in the lifecycle of entomopathogenic fungi and highlights peroxisomal roles in combating the host defense system.
Whole-Genome Sequencing Reveals Age-Specific Changes in the Human Blood Microbiota
Authors: Lee Eun-Ju , Sung Joohon , Kim Hyung-Lae , Kim Han-Na
Published: June 2022

Based on several reports that indicate the presence of blood microbiota in patients with diseases, we became interested in identifying the presence of bacteria in the blood of healthy individuals. Using 37 samples from 5 families, we extracted sequences that were not mapped to the human reference genome and mapped them to the bacterial reference genome for characterization. Proteobacteria account for more than 95% of the blood microbiota. The results of clustering by means of principal component analysis showed similar patterns for each age group. We observed that the class Gammaproteobacteria was significantly higher in the elderly group (over 60 years old), whereas the arcsine square root-transformed relative abundance of the classes Alphaproteobacteria, Deltaproteobacteria, and Clostridia was significantly lower (p < 0.05). In addition, the diversity among the groups showed a significant difference (p < 0.05) in the elderly group. This result provides meaningful evidence of a consistent phenomenon that chronic diseases associated with aging are accompanied by metabolic endotoxemia and chronic inflammation.
The Association of HLA-B*35 and GSTT1 Genotypes and Hepatotoxicity in Thai People Living with HIV
Authors: Chanhom Noppadol , Jittikoon Jiraphun , Wattanapokayakit Sukanya , Mahasirimongkol Surakameth , Charoenyingwattana Angkana , Udomsinprasert Wanvisa , Chaikledkaew Usa , Suvichapanich Supharat , Mushiroda Taisei , Kiertiburanakul Sasisopin , Rojanawiwat Archawin , Wangsomboonsiri Wittaya , Manosuthi Weerawat , Kantipong Pacharee , Apisarnthanarak Anucha , Sangsirinakakul Wilawan , Wongprasit Pawinee , Chaiwarith Romanee , Tantisiriwat Woraphot , Sungkanuparph Somnuek , Chantratita Wasun
Published: June 2022

Glutathione s-transferase (GST) is a family of drug-metabolizing enzymes responsible for metabolizing and detoxifying drugs and xenobiotic substances. Therefore, deletion polymorphisms of GSTs can be implicated in developing several pathological conditions, including antiretroviral drug-induced liver injury (ARVDILI). Notably, GST polymorphisms have been shown to be associated with ARVDILI risk. However, data on GST polymorphisms in the Thai population are limited. Therefore, this study investigated possible associations between GST genetic polymorphisms and ARVDILI development. A total of 362 people living with HIV (PLHIV) and 85 healthy controls from multiple centers were enrolled. GSTM1 and GSTT1 genetic polymorphisms were determined using polymerase chain reactions. In addition, HLA genotypes were determined using a sequence-based HLA typing method. After comparing GST genotypic frequencies, there was no significant difference between PLHIV and healthy volunteers. However, while observing the PLHIV group, GSTT1 wild type was significantly associated with a 2.04-fold increased risk of ARVDILI (95%CI: 1.01, 4.14; p = 0.045). Interestingly, a combination of GSTT1 wild type and HLA-B*35:05 was associated with a 2.28-fold higher risk of ARVDILI (95%CI: 1.15, 4.50; p = 0.02). Collectively, GSTT1 wild type and a combination of GSTT1 wild type plus HLA-B*35:05 were associated with susceptibility to ARVDILI in the Thai population.
Association of Serum 25-Hydroxyvitamin D Concentration with Breast Cancer Risk in Postmenopausal Women in the US
Authors: Ganji Vijay , Sukik Layan , Hoque Bushra , Boutefnouchet Linda , Shi Zumin
Published: June 2022

The association between serum 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer risk in postmenopausal women is not well understood. The aim of this study was to investigate the association between serum 25(OH)D concentration and breast cancer in postmenopausal women in the United States using nationally representative sample surveys. We used the data from seven cycles of National Health and Nutrition Examination Surveys from 2001 to 2014. Participants were non-institutionalized postmenopausal women (n = 8108). In restricted cubic spline analysis, a significant, nonlinear, invert ‘U’ relationship was observed between serum 25(OH)D concentrations and breast cancer in postmenopausal women (p = 0.029). Overall, breast cancer risk was highest (OR = 1.5) between 70 nmol/L and 80 nmol/L of serum 25(OH)D concentration. Then after serum 25(OH)D 80 nmol/L concentration, the breast cancer risk declined. In multivariate-adjusted logistic regression, the risk of having breast cancer was significantly higher in serum 25(OH)D 75–˂100 nmol/L category compared to the 25(OH)D < 30 nmol/L category [OR and 95% CI: 2.4 (1.4–4.0)]. In conclusion, serum vitamin D concentrations ≥ 100 nmol/L are associated with reduced risk of breast cancer in postmenopausal women. Controlled trials are required to verify if serum 25(OH)D ≥ 100 nmol/L offers protection against breast cancer in postmenopausal women.
Development of a Machine Learning Model to Predict Non-Durable Response to Anti-TNF Therapy in Crohn’s Disease Using Transcriptome Imputed from Genotypes
Authors: Park Soo Kyung , Kim Yea Bean , Kim Sangsoo , Lee Chil Woo , Choi Chang Hwan , Kang Sang-Bum , Kim Tae Oh , Bang Ki Bae , Chun Jaeyoung , Cha Jae Myung , Im Jong Pil , Kim Min Suk , Ahn Kwang Sung , Kim Seon-Young , Park Dong Il
Published: June 2022

Almost half of patients show no primary or secondary response to monoclonal anti-tumor necrosis factor α (anti-TNF) antibody treatment for inflammatory bowel disease (IBD). Thus, the exact mechanisms of a non-durable response (NDR) remain inadequately defined. We used our genome-wide genotype data to impute expression values as features in training machine learning models to predict a NDR. Blood samples from various IBD cohorts were used for genotyping with the Korea Biobank Array. A total of 234 patients with Crohn’s disease (CD) who received their first anti-TNF therapy were enrolled. The expression profiles of 6294 genes in whole-blood tissue imputed from the genotype data were combined with clinical parameters to train a logistic model to predict the NDR. The top two and three most significant features were genetic features (DPY19L3, GSTT1, and NUCB1), not clinical features. The logistic regression of the NDR vs. DR status in our cohort by the imputed expression levels showed that the β coefficients were positive for DPY19L3 and GSTT1, and negative for NUCB1, concordant with the known eQTL information. Machine learning models using imputed gene expression features effectively predicted NDR to anti-TNF agents in patients with CD.
Cost–Utility Analysis of Dupilumab for the Treatment of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in Italy
Authors: De Corso Eugenio , Furneri Gianluca , Salsi Daria , Fanelli Francesca , Ronci Gianluca , Sala Giovanna , Bitonti Rossella , Cuda Domenico
Published: June 2022

The objective of this analysis was to estimate the incremental cost–utility ratio (ICUR) of dupilumab as an add-on treatment to best supportive care (BSC), versus BSC alone, in Italy for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). A simulation of outcomes and costs was undertaken using a 1-year decision tree, followed by a lifetime horizon Markov model. Clinical data were derived from a pooled analysis of two studies (SINUS-24 NCT02912468 and SINUS-52 NCT02898454). The Italian National Healthcare Service (NHS) perspective was considered. Model robustness was tested through sensitivity analyses. In the base-case analysis, treatment with dupilumab + BSC resulted in an increase in quality of life-adjusted survival (+1.02 quality-adjusted life years (QALY-gained)), compared to the BSC alone. The resulted ICUR was €21,817 per QALY-gained and it is below the acceptability threshold commonly used in Italy. Both one-way deterministic and probabilistic sensitivity analyses confirmed the robustness of base-case results. The cost–utility analysis showed that dupilumab, as an add-on treatment to BSC, is a cost-effective therapeutic alternative to BSC in the treatment of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps, confirming that it is economically sustainable.