bluuebunny/crossref_metadata_2025 huggingface dataset:
Study Protocol for a Multicenter, Randomized Controlled Trial to Improve Upper Extremity Hemiparesis in Chronic Stroke Patients by One-to-One Training (NEURO®) with Repetitive Transcranial Magnetic Stimulation
Authors: Sakamoto Daigo , Hamaguchi Toyohiro , Murata Kai , Ishikawa Atsushi , Nakayama Yasuhide , Abo Masahiro
Published: November 2022

During recovery from upper limb motor paralysis after stroke, it is important to (1) set the exercise difficulty level according to the motor paralysis severity, (2) provide adequate exercises, and (3) motivate the patient to achieve the goal. However, these factors have not been well-formulated. This multicenter, randomized controlled trial study aims to examine the therapeutic effects of these three factors on patients undergoing a novel intervention using repetitive transcranial magnetic stimulation and intensive one-to-one training (NEURO®) and to formulate a corresponding research protocol. The control group will receive conventional NEURO® occupational therapy. In the intervention group, four practice plans will be selected according to the Fugl-Meyer assessment (FMA-UE) scores of the upper extremity. The goal is to predict the post-treatment outcomes based on the pre-treatment FMA-UE scores. Based on the degree of difficulty and amount of practice required, we can formulate a practice plan to promote upper limb motor recovery. This occupational therapy plan will be less influenced by the therapist’s skill, facilitating effective rehabilitation. The study findings may be utilized to promote upper limb motor paralysis recovery and provide a basis for proposing activities of daily living adapted to upper limb function.
Nuclear Medicine and Radiological Imaging of Pancreatic Neuroendocrine Neoplasms: A Multidisciplinary Update
Authors: Prosperi Daniela , Gentiloni Silveri Guido , Panzuto Francesco , Faggiano Antongiulio , Russo Vincenzo , Caruso Damiano , Polici Michela , Lauri Chiara , Filice Angelina , Laghi Andrea , Signore Alberto
Published: November 2022

Pancreatic neuroendocrine neoplasms (panNENs) are part of a large family of tumors arising from the neuroendocrine system. PanNENs show low–intermediate tumor grade and generally high somatostatin receptor (SSTR) expression. Therefore, panNENs benefit from functional imaging with 68Ga-somatostatin analogues (SSA) for diagnosis, staging, and treatment choice in parallel with morphological imaging. This narrative review aims to present conventional imaging techniques and new perspectives in the management of panNENs, providing the clinicians with useful insight for clinical practice. The 68Ga-SSA PET/CT is the most widely used in panNENs, not only fr diagnosis and staging purpose but also to characterize the biology of the tumor and its responsiveness to SSAs. On the contrary, the 18F-Fluordeoxiglucose (FDG) PET/CT is not employed systematically in all panNEN patients, being generally preferred in G2–G3, to predict aggressiveness and progression rate. The combination of 68Ga-SSA PET/CT and 18F-FDG PET/CT can finally suggest the best therapeutic strategy. Other radiopharmaceuticals are 68Ga-exendin-4 in case of insulinomas and 18F-dopamine (DOPA), which can be helpful in SSTR-negative tumors. New promising but still-under-investigation radiopharmaceuticals include radiolabeled SSTR antagonists and 18F-SSAs. Conventional imaging includes contrast enhanced CT and multiparametric MRI. There are now enriched by radiomics, a new non-invasive imaging approach, very promising to early predict tumor response or progression.
Trends in Well-Child Visits and Routine Vaccination among Children of U.S. Military Members: An Evaluation of the COVID-19 Pandemic Effects
Authors: Sexton Kyle , Susi Apryl , Lee Elizabeth , Hisle-Gorman Elizabeth , Rajnik Michael , Krishnamurthy Jayasree , Nylund Cade M.
Published: November 2022

The COVID-19 pandemic has drastically impacted administration of healthcare including well-child visits and routine vaccinations. The purpose of this study was to determine the impact of COVID-19 pandemic disruption on childhood health maintenance: well-child visits and scheduled vaccinations. We queried the TRICARE Management Activity’s Military Health System (MHS) database for outpatient well-child visits and vaccinations for all children 0 to 23 months of age eligible for TRICARE healthcare. The median rate of well-child visits, during the COVID-19 period (March 2020–July 2021), was significantly declined for all demographic groups: all ages, parental military ranks, sex, and regions as compared to the pre-COVID-19 period (February 2019–February 2020). Similar to rates of well-child visits, the rate of vaccinations declined during the COVID-19 period as compared to the pre-COVID-19 period for all demographic groups, except children 12–23 months. Rates of well-child visits for military dependent children under 2 years of age were decreased during the 16 month COVID-19 period, with large increases seen in the first 2 months of the pandemic; the consequences of missed well-child visits and vaccination are unknown.
Cardiovascular/Stroke Risk Stratification in Diabetic Foot Infection Patients Using Deep Learning-Based Artificial Intelligence: An Investigative Study
Authors: Khanna Narendra N. , Maindarkar Mahesh A. , Viswanathan Vijay , Puvvula Anudeep , Paul Sudip , Bhagawati Mrinalini , Ahluwalia Puneet , Ruzsa Zoltan , Sharma Aditya , Kolluri Raghu , Krishnan Padukone R. , Singh Inder M. , Laird John R. , Fatemi Mostafa , Alizad Azra , Dhanjil Surinder K. , Saba Luca , Balestrieri Antonella , Faa Gavino , Paraskevas Kosmas I. , Misra Durga Prasanna , Agarwal Vikas , Sharma Aman , Teji Jagjit S. , Al-Maini Mustafa , Nicolaides Andrew , Rathore Vijay , Naidu Subbaram , Liblik Kiera , Johri Amer M. , Turk Monika , Sobel David W. , Miner Martin , Viskovic Klaudija , Tsoulfas George , Protogerou Athanasios D. , Mavrogeni Sophie , Kitas George D. , Fouda Mostafa M. , Kalra Mannudeep K. , Suri Jasjit S.
Published: November 2022

A diabetic foot infection (DFI) is among the most serious, incurable, and costly to treat conditions. The presence of a DFI renders machine learning (ML) systems extremely nonlinear, posing difficulties in CVD/stroke risk stratification. In addition, there is a limited number of well-explained ML paradigms due to comorbidity, sample size limits, and weak scientific and clinical validation methodologies. Deep neural networks (DNN) are potent machines for learning that generalize nonlinear situations. The objective of this article is to propose a novel investigation of deep learning (DL) solutions for predicting CVD/stroke risk in DFI patients. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) search strategy was used for the selection of 207 studies. We hypothesize that a DFI is responsible for increased morbidity and mortality due to the worsening of atherosclerotic disease and affecting coronary artery disease (CAD). Since surrogate biomarkers for CAD, such as carotid artery disease, can be used for monitoring CVD, we can thus use a DL-based model, namely, Long Short-Term Memory (LSTM) and Recurrent Neural Networks (RNN) for CVD/stroke risk prediction in DFI patients, which combines covariates such as office and laboratory-based biomarkers, carotid ultrasound image phenotype (CUSIP) lesions, along with the DFI severity. We confirmed the viability of CVD/stroke risk stratification in the DFI patients. Strong designs were found in the research of the DL architectures for CVD/stroke risk stratification. Finally, we analyzed the AI bias and proposed strategies for the early diagnosis of CVD/stroke in DFI patients. Since DFI patients have an aggressive atherosclerotic disease, leading to prominent CVD/stroke risk, we, therefore, conclude that the DL paradigm is very effective for predicting the risk of CVD/stroke in DFI patients.
Childhood Pemphigus Vulgaris during COVID-19 Outbreak Successfully Treated with Prednisone and Azathioprine: A Case Report and Literature Review
Authors: Vezzoli Pamela , Parietti Michele , Carugno Andrea , Di Mercurio Marco , Benaglia Chiara , Zussino Martina , Cavalli Riccardo , Sena Paolo , Berti Emilio
Published: November 2022

Introduction: pemphigus vulgaris is a rare autoimmune blistering disease that involves the skin and mucous membranes and rarely occurs in pediatric age. Methods: we present a case of childhood pemphigus in a 9-year-old patient from Burkina Faso, which initially manifested with erosive lesions symmetrically distributed in the oral cavity. After a few months, we also observed hyperchromic lesions of the back. Histopathological examination of skin samples showed intraepidermal acantholysis, while direct immunofluorescence showed deposits of complement (C3) and immunoglobulins G (IgG) in the epidermidis; an ELISA test highlighted the presence of circulating autoantibodies against desmoglein 3. Results: the follow-up of this patient was made difficult by the advent of the COVID-19 outbreak. However, after about one year of combined therapy with systemic steroids and azathioprine the patient reached clinical remission.
Comparison of In Vitro Approaches to Assess the Antibacterial Effects of Nanomaterials
Authors: Masri Abdulkader , Brown David M. , Smith David G. E. , Stone Vicki , Johnston Helinor J.
Published: November 2022

The antibacterial properties of nanomaterials (NMs) can be exploited in a range of consumer products (e.g., wound dressings, food packaging, textiles, medicines). There is also interest in the exploitation of NMs as treatments for infectious diseases to help combat antibiotic resistance. Whilst the antibacterial activity of NMs has been assessed in vitro and in vivo in numerous studies, the methodology used is very varied. Indeed, while numerous approaches are available to assess the antibacterial effect of NMs in vitro, they have not yet been systematically assessed for their suitability and sensitivity for testing NMs. It is therefore timely to consider what assays should be prioritised to screen the antibacterial properties of NMs. The majority of existing in vitro studies have focused on investigating the antibacterial effects exhibited by silver (Ag) NMs and have employed a limited range of assays. We therefore compared the antibacterial effects of copper oxide (CuO) NMs to Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis at various concentrations (12.5–200 µg/mL) using a battery of tests (well and disc diffusion, plate counts—time-kill method, optical density measurement—OD, Alamar Blue and live/dead viability assays, and quantitative polymerase chain reaction). CuO NMs were most toxic to B. subtilis and E. coli, while P. aeruginosa was the least sensitive strain. All assays employed detected the antibacterial activity of CuO NMs; however, they varied in their sensitivity, time, cost, technical difficulty and requirement for specialized equipment. In the future, we suggest that a combination of approaches is used to provide a robust assessment of the antibacterial activity of NMs. In particular, we recommend that the time-kill and OD assays are prioritised due to their greater sensitivity. We also suggest that standard operating protocols are developed so that the antibacterial activity of NMs can be assessed using a harmonised approach.
Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review
Authors: Satkunananthan Shobha Elizabeth , Suppiah Vijayaprakash , Toh Gaik-Theng , Yow Hui-Yin
Published: November 2022

In advanced cancer, pain is a poor prognostic factor, significantly impacting patients’ quality of life. It has been shown that up to 30% of cancer patients in Southeast Asian countries may receive inadequate analgesia from opioid therapy. This significant under-management of cancer pain is largely due to the inter-individual variability in opioid dosage and relative efficacy of available opioids, leading to unpredictable clinical responses to opioid treatment. Single nucleotide polymorphisms (SNPs) cause the variability in opioid treatment outcomes, yet their association in Asian populations remains unclear. Therefore, this review aimed to evaluate the association of SNPs with variability in opioid treatment responses in Asian populations. A literature search was conducted in Medline and Embase databases and included primary studies investigating the association of SNPs in opioid treatment outcomes, namely pharmacokinetics, opioid dose requirements, and pain control among Asian cancer patients. The results show that CYP2D6*10 has the most clinical relevance in tramadol treatment. Other SNPs such as rs7439366 (UGT2B7), rs1641025 (ABAT) and rs1718125 (P2RX7) though significant have limited pharmacogenetic implications due to insufficient evidence. OPRM1 rs1799971, COMT rs4680 and ABCB1 (rs1045642, rs1128503, and rs2032582) need to be further explored in future for relevance in Asian populations.
Early-Stage Oral Tongue Squamous Cell Carcinoma and a Positive Sentinel Lymph Node Biopsy: Description of a Prognostic Correlation between Pre-Treatment Inflammatory Biomarkers, the Depth of Invasion and the Worst Pattern of Invasion
Authors: Salzano Giovanni , Togo Giulia , Maffia Francesco , Vaira Luigi Angelo , Maglitto Fabio , Committeri Umberto , Fusco Roberta , Maglione Maria Grazia , Nocini Riccardo , De Luca Pietro , Guida Agostino , Di Stadio Arianna , Ferrara Gerardo , Califano Luigi , Ionna Franco
Published: November 2022

The aim of this study was to investigate the correlation between pre-treatment inflammatory biomarkers and the post-operative depth of invasion (DOI) and worst pattern of invasion (WPOI) in early-stage oral tongue squamous cell carcinoma (OTSCC) by means of positive sentinel lymph node biopsy (SLNB). A retrospective analysis of patients affected by cN0 T1-T2 OTSCC who had undergone an SLNB at the National Cancer Institute of Naples was performed. The patients were studied using an evaluation of the pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and a histopathological analysis of the DOI and WPOI. The statistical analysis showed that among the prognostic biomarkers, the NLR was a significant predictor of high WPOI values (p = 0.002). The cut-off NLR value was 2.52 with a probability of developing a positive sentinel lymph node biopsy (SLNB) of 30.3%. In contrast, the DOI value was 5.20 with a probability of developing a positive SLNB of 31.82%. Regarding the WPOI, increasing the WPOI class increased the likelihood of a positive SLNB occurrence, and a positive significant correlation was found between the WPOI and SLNB (Csp = 0.342; p < 0.001). Pre-treatment NLR, together with post-surgical DOI and WPOI, can be a reliable predictor of occult neck metastasis in patients affected by early-stage OTSCC with a clinically negative neck. Further prospective studies with a larger series will be needed to confirm the results obtained and to better define the NLR, WPOI and DOI cut-off values in order for elective neck dissection to be recommended in relation to a clinically negative neck.
Complications and Adverse Events of Gonadal Vein Embolization with Coils
Authors: Gavrilov Sergey G. , Mishakina Nadezhda Y. , Efremova Oksana I. , Kirsanov Konstantin V.
Published: November 2022

Background: The efficacy and safety of gonadal vein embolization (GVE) with coils in the treatment of pelvic venous disease (PeVD) has not been fully investigated, and the outcomes after GVE do not always meet expectations of both doctors and patients. The study was aimed at assessing the incidence and causes of the complications after GVE with coils in patients with PeVD. Methods: This retrospective cohort study included 150 female patients with PeVD who underwent GVE with coils in 2000–2020. A total of 4975 patients with chronic pelvic pain (CPP) were examined, of which 1107 patients had the PeVD-related CPP and 305 underwent surgical or endovascular interventions on the gonadal veins. Complication rates were evaluated 30 days after GVE and classified according to the Society for Interventional Radiology (SIR) adverse event classification system. The pain severity before and after GVE was assessed using a visual analogue scale (VAS). All patients underwent duplex ultrasound after GVE, while patients with persisting pain syndrome and suspected perforation of the gonadal vein were also evaluated using computed tomographic venography. Results: At 30 days after GVE, the CPP was decreased in 109 (72.6%) patients (from 8.2 ± 1.5 at baseline to 1.7 ± 0.8 scores, p = 0.0001) and persisted in 41 (27.4%) patients (mean change from 8.1 ± 0.7 at baseline to 7.8 ± 0.4 scores; p = 0.71). Post-embolic syndrome (PES) occurred in 22% of patients and was completely resolved in 1 month after GVE. The efficacy of GVE in the CPP relief after resolving PES was 94.6%. The GVE complications were identified in 52 (34.6%) patients. Minor complications included access-site hematoma (4%) and allergic reactions (1.3%), and major complications included protrusion of coils (5.3%), thrombosis of the parametrial/uterine veins (21.3%) and deep veins of the calf (2.7%). Conclusions: Gonadal vein embolization with coils in the treatment of PeVD is associated with the development of specific complications and adverse events. The most common complication was pelvic vein thrombosis. Post-embolization syndrome should be considered as an adverse event of this procedure.
The Influence of Body Mass Index on Glucocorticoid Insensitivity in Chronic Rhinosinusitis with Nasal Polyps
Authors: Zhang Yuling , Shen Shen , Liu Yating , Wang Zaichuan , Wang Qiqi , Li Yan , Wang Chengshuo , Lan Feng , Zhang Luo
Published: November 2022

Background: Reasons for glucocorticoid (GC) insensitivity in chronic rhinosinusitis with nasal polyps (CRSwNP) are not completely clear. Here, we investigate the influence of body mass index (BMI) on GC insensitivity in eosinophilic CRSwNP (eosCRSwNP) and noneosinophilic CRSwNP (noneosCRSwNP) patients. Methods: We recruited 699 CRSwNP patients and gave them a course of oral methylprednisolone for 2 weeks (24 mg/day). Patient demographics and clinical features were analyzed in both GC-sensitive and GC-insensitive CRSwNP patients with different BMI levels and phenotypes. Results: 35.3% of recruited CRSwNP patients were GC-insensitive, and the majority of GC-insensitive patients were males or prone to overweight & obese. Logistic regression analysis further confirmed that being overweight & obese was an independent risk factor for GC-insensitive of CRSwNP patients (odds ratio = 1.584, p = 0.049). Compared to underweight & normal-weight patients, overweight & obese patients were more likely to be GC insensitivity, particularly in the eosCRSwNP group, but not in the noneosCRSwNP group. However, there was no significant difference between the underweight & normal weight and the overweight & obese GC-insensitive eosCRSwNP patients regarding the number of infiltrated eosinophils, neutrophils, and polyp recurrence rate. Conclusions: Collectively, our findings demonstrate for the first time that BMI contributes to GC insensitivity in eosCRSwNP patients.
Predictors of Mortality in Bicycle-Related Trauma: An Eight-Year Experience in a Level One Trauma Center
Authors: Reitano Elisa , Cioffi Stefano Piero Bernardo , Virdis Francesco , Altomare Michele , Spota Andrea , Chiara Osvaldo , Cimbanassi Stefania
Published: November 2022

Background: Bicycle-related trauma has increased during the last decades, mainly due to the antipollution environmental policies. This study investigates the outcome of bicycle-related trauma in our level-one trauma center over a period of eight years. Methods: Data from 446 consecutive bicycle-related trauma patients admitted to our trauma center from 2011 to 2019 were selected and retrospectively analyzed. The sample was divided into three age groups: <18 years, 18–54 years, and ≥55 years. Mortality rates were obtained for the overall population and patients with an Injury Severity Score (ISS) ≥ 25. Month and seasonal patients’ distribution was described to provide an epidemiological overview of bike-related trauma over the years. Results: Patients ≥ 55 years showed a lower pre-hospital and in-hospital GCS (p ≤ 0.001), higher levels of lactates (p < 0.019) and higher ISS (p ≤ 0.001), probability of death (p ≤ 0.001), and overall mortality (p ≤ 0.001). The head and chest Abbreviated Injury Scale (AIS) ≥ 3 injuries were predictors of mortality, especially in patients over 55 years (p < 0.010). Bicycle-related trauma was more frequent during the summer (34%), particularly in July and August. Conclusions: Age over 55 years old, head and chest injuries, and an ISS > 25 were independent predictors of mortality.
A Stress Hub in Scedosporium apiospermum: The High Osmolarity Glycerol (HOG) Pathway
Authors: Yaakoub Hajar , Mina Sara , Marot Agnès , Papon Nicolas , Calenda Alphonse , Bouchara Jean-Philippe
Published: November 2022

Scedosporium species are opportunistic filamentous fungi found in human-impacted areas. Clinically relevant species, such as S. apiospermum, rank as the second most frequent colonizers of the airways of patients with cystic fibrosis (CF), which are characterized by persistent oxidative stress. This raises the question of how Scedosporium species abate conditions imposed in hostile environments. Since the High Osmolarity Glycerol (HOG) pathway plays a central role in fungal adaptation to stress, we aimed to pheno-profile the involvement of the pathway in response to stress in S. apiospermum using Western blot. We show for the first time that a wide range of stress distinctively activates the HOG pathway in S. apiospermum, including oxidants (H2O2, menadione, cumene hydroperoxide, diamide, paraquat, and honokiol), osmotic agents (sorbitol and KCl), cell-wall stress agents (caffeine, calcofluor white, and Congo Red), heavy metals (cadmium and arsenite), fungicides (fludioxonil and iprodione), antifungals (voriconazole and amphotericin B), and acid stress (pH 4). We suggest that the function of the HOG pathway as a general stress regulator is also conserved in S. apiospermum.
Comprehensive Evaluation of the Implementation Effect of Commercial Street Quality Improvement Based on AHP-Entropy Weight Method—Taking Hefei Shuanggang Old Street as an Example
Authors: Zhang Le , Xu Xiaoxiao , Guo Yanlong
Published: November 2022

In the global context of sustainable urban development, urban regeneration is an activity to improve the form and function of urban space in built-up areas. Commercial streets are one of the most active factors in urban space and an important factor in promoting urban prosperity and reflecting urban vitality, yet these streets have not kept pace with the public’s quest for quality through theoretical change, and this can even affect public comfort and well-being. In order to effectively undertake urban regeneration and improve the quality of urban streets and residents’ satisfaction, design factors for the quality enhancement of commercial streets are explored in order to rationalise residents’ demand preferences and their priorities, enhance residents’ sense of belonging, and provide suggestions for the optimisation of the design of subsequent urban street regeneration in China. By summarising the literature and the content requirements of the quality enhancement scheme for Shuanggang Old Street in Hefei, this study applied a questionnaire survey and scientifically developed an index system containing five evaluation indicators, including spatial carrying capacity, street attractiveness, travel safety, environmental comfort, and social interaction. A combination of hierarchical analysis and entropy weighting was used to identify the most influential factors on the implementation of the quality improvement of the commercial street and design optimisation suggestions. The evaluation results show that travel safety and social interaction significantly affect the evaluation of the quality improvement of commercial streets, as well as highlighting the needs of residents for street environments and services and the role of local governments.
Application of Machine Learning to Ranking Predictors of Anti-VEGF Response
Authors: Arslan Janan , Benke Kurt K.
Published: November 2022

Age-related macular degeneration (AMD) is a heterogeneous disease affecting the macula of individuals and is a cause of irreversible vision loss. Patients with neovascular AMD (nAMD) are candidates for the anti-vascular endothelial growth factor (anti-VEGF) treatment, designed to regress the growth of abnormal blood vessels in the eye. Some patients fail to maintain vision despite treatment. This study aimed to develop a prediction model based on features weighted in order of importance with respect to their impact on visual acuity (VA). Evaluations included an assessment of clinical, lifestyle, and demographic factors from patients that were treated over a period of two years. The methods included mixed-effects and relative importance modelling, and models were tested against model selection criteria, diagnostic and assumption checks, and forecasting errors. The most important predictors of an anti-VEGF response were the baseline VA of the treated eye, the time (in weeks), treatment quantity, and the treated eye. The model also ranked the impact of other variables, such as intra-retinal fluid, haemorrhage, pigment epithelium detachment, treatment drug, baseline VA of the untreated eye, and various lifestyle and demographic factors. The results identified variables that could be targeted for further investigation in support of personalised treatments based on patient data.
New PAM Improves the Single-Base Specificity of crRNA-Guided LbCas12a Nuclease
Authors: Misiurina Mariia A. , Chirinskaite Angelina V. , Fotina Aleksandra S. , Zelinsky Andrey A. , Sopova Julia V. , Leonova Elena I.
Published: November 2022

The RNA-guided Cas12a nuclease forms a complex with a CRISPR RNA (crRNA) to cleave the double-stranded DNA target. Among others, Cas12a protein from Lachnospiraceae bacterium (LbCas12a) is widely used for biomedical research. For target recognition, LbCas12a requires a specific nucleotide sequence, named a protospacer adjacent motif (PAM). Besides the canonical TTTV PAM, LbCas12a can recognize other suboptimal PAMs. We examined a novel TTAA PAM for the LbCas12a nuclease and found that the specificity of cleavage was increased. We found that single nucleotide substitutions at all positions of the guide RNA except the 20th position blocked the cleavage of the target DNA. The type of nucleotide substitutions (U-A, U-C or U-G) did not affect the efficiency of cleavage in the 20th position. When we used the canonical PAM under the same conditions, we observed the cleavage of target DNA by LbCas12a in many positions, showing less specificity in given conditions. The efficiency and specificity of the LbCas12a nuclease were evaluated both by gel-electrophoresis and using FAM-labeled single-stranded probes. We were able to assess the change in fluorescence intensity only for several variants of guide RNAs. High specificity allows us to type single nucleotide substitutions and small deletions/insertions (1–2 nucleotides) and look for target mutations when knocking out.
Improving Survival in Cardiogenic Shock—A Propensity Score-Matched Analysis of the Impact of an Institutional Allocation Protocol to Short-Term Mechanical Circulatory Support
Authors: Ott Sascha , Lewin Daniel , Nersesian Gaik , Stein Julia , Just Isabell A. , Hommel Matthias , Schoenrath Felix , Starck Christoph T. , O’Brien Benjamin , Falk Volkmar , Potapov Evgenij , Lanmueller Pia
Published: November 2022

Temporary mechanical circulatory support (tMCS) is a life-saving treatment option for patients in cardiogenic shock (CS), but many aspects such as patient selection, initiation threshold and optimal modality selection remain unclear. This study describes a standard operating procedure (SOP) for tMCS allocation for CS patients and presents outcome data before and after implementation. Data from 421 patients treated for CS with tMCS between 2018 and 2021 were analyzed. In 2019, we implemented a new SOP for allocating CS patients to tMCS modalities. The association between the time of SOP implementation and the 30-day and 1-year survival as well as hospital discharge was evaluated. Of the 421 patients included, 189 were treated before (pre-SOP group) and 232 after implementation of the new SOP (SOP group). Causes of CS included acute myocardial infarction (n = 80, 19.0%), acute-on-chronic heart failure in patients with dilated or chronic ischemic heart failure (n = 139, 33.0%), valvular cardiomyopathy (n = 14, 3.3%) and myocarditis (n = 5, 1.2%); 102 patients suffered from postcardiotomy CS (24.2%). The SOP group was further divided into an SOP-adherent (SOP-A) and a non-SOP-adherent group (SOP-NA). The hospital discharge rate was higher in the SOP group (41.7% vs. 29.7%), and treating patients according to the SOP was associated with an improved 30-day survival (56.9% vs. 38.9%, OR 2.21, 95% CI 1.01–4.80, p = 0.044). Patient allocation according to the presented SOP significantly improved 30-day survival.
Analysis of Human Clinical Mutations of Mitochondrial ND1 in a Bacterial Model System for Complex I
Authors: Alkhaldi Hind A. , Phan Duong H. , Vik Steven B.
Published: November 2022

The most common causes of mitochondrial dysfunction and disease include mutations in subunits and assembly factors of Complex I. Numerous mutations in the mitochondrial gene ND1 have been identified in humans. Currently, a bacterial model system provides the only method for rapid construction and analysis of mutations in homologs of human ND1. In this report, we have identified nine mutations in human ND1 that are reported to be pathogenic and are located at subunit interfaces. Our hypothesis was that these mutations would disrupt Complex I assembly. Seventeen mutations were constructed in the homologous nuoH gene in an E. coli model system. In addition to the clinical mutations, alanine substitutions were constructed in order to distinguish between a deleterious effect from the introduction of the mutant residue and the loss of the original residue. The mutations were moved to an expression vector containing all thirteen genes of the E. coli nuo operon coding for Complex I. Membrane vesicles were prepared and rates of deamino-NADH oxidase activity and proton translocation were measured. Samples were also tested for assembly by native gel electrophoresis and for expression of NuoH by immunoblotting. A range of outcomes was observed: Mutations at four of the sites allow normal assembly with moderate activity (50–76% of wild type). Mutations at the other sites disrupt assembly and/or activity, and in some cases the outcomes depend upon the amino acid introduced. In general, the outcomes are consistent with the proposed pathogenicity in humans.
A Polymorphism in the Gene Encoding Heat Shock Factor 1 (HSF1) Increases the Risk of Type 2 Diabetes: A Pilot Study Supports a Role for Impaired Protein Folding in Disease Pathogenesis
Authors: Klyosova Elena , Azarova Iuliia , Polonikov Alexey
Published: November 2022

The aim of this pilot study was to investigate whether polymorphisms in the gene encoding heat shock factor 1 (HSF1), a transcriptional activator of molecular chaperones, play a role in the development of type 2 diabetes (T2D). A total of 3229 unrelated individuals of Slavic origin, including 1569 T2D patients and 1660 age- and sex-matched healthy controls, were enrolled for the study. Five common single nucleotide polymorphisms (SNPs) of the HSF1 gene were genotyped using the MassArray-4 system. SNPs rs7838717 (p = 0.002) and rs3757971 (p = 0.005) showed an association with an increased risk of T2D in females with a body mass index ≥ 25 kg/m2. The rs7838717T-rs4279640T-rs3757971C and rs7838717T-rs4279640T-rs3757971T haplotypes were associated with increased and decreased disease risk in overweight or obese females, respectively. The associations were replicated as disease susceptibility genes in large cohorts from the UK Biobank (p = 0.008), DIAMANTE (p = 2.7 × 10−13), and DIAGRAM (p = 0.0004) consortiums. The functional annotation of the SNPs revealed that the rs7838717-T and rs3757971C alleles correlated with increased expression of the genes involved in unfolded protein response. The present study showed, for the first time, that genetic variation of HSF1 is associated with the risk of type 2 diabetes, supporting a role for impaired protein folding in disease pathogenesis.
SnS2 Nanosheets as a Template for 2D SnO2 Sensitive Material: Nanostructure and Surface Composition Effects
Authors: Vasiliev Roman , Kurtina Darya , Udalova Nataliya , Platonov Vadim , Nasriddinov Abulkosim , Shatalova Tatyana , Novotortsev Roman , Li Xiaogan , Rumyantseva Marina
Published: November 2022

Two-dimensional nanosheets of semiconductor metal oxides are considered as promising for use in gas sensors, because of the combination of a large surface-area, high thermal stability and high sensitivity, due to the chemisorption mechanism of gas detection. In this work, 2D SnO2 nanosheets were synthesized via the oxidation of template SnS2 nanosheets obtained by surfactant-assisted one-pot solution synthesis. The 2D SnO2 was characterized using transmission and scanning electron microscopy (TEM, SEM), X-ray diffraction (XRD), low-temperature nitrogen adsorption, X-ray photoelectron spectroscopy (XPS) and IR spectroscopy. The sensor characteristics were studied when detecting model gases CO and NH3 in dry (RH25 = 0%) and humid (RH25 = 30%) air. The combination of high specific-surface-area and increased surface acidity caused by the presence of residual sulfate anions provides a high 2D SnO2 sensor’s signal towards NH3 at a low temperature of 200 °C in dry air, but at the same time causes an inversion of the sensor response when detecting NH3 in a humid atmosphere. To reveal the processes responsible for sensor-response inversion, the interaction of 2D SnO2 with ammonia was investigated using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) in dry and humid air at temperatures corresponding to the maximum “positive” and maximum “negative” sensor response.
Comminution of Polymetallic Nodules with a High-Pressure Water Jet
Authors: Borkowski Przemysław J. , Abramowski Tomasz , Szada-Borzyszkowska Monika , Szada-Borzyszkowski Wiesław
Published: November 2022

This paper presents an original method for the comminution of polymetallic nodules in a hydro-jet mill of our own design, having the water jet pressure in the range of 70–200 MPa. The best comminution results are ensured by equipping the mill with a water jet having a diameter dw = 0.7 mm and a comminution-homogenization tube having a diameter dh = 2.4 mm, and by setting a distance s = 10 mm from the outlet of the homogenization tube to the comminuting disc. Particles of concretions comminuted under such conditions are characterized by a fairly regular isometric shape and favorable morphology represented by intense development of the specific surface.
Charge Trap States of SiC Power TrenchMOS Transistor under Repetitive Unclamped Inductive Switching Stress
Authors: Marek Juraj , Kozarik Jozef , Minarik Michal , Chvála Aleš , Matus Matej , Donoval Martin , Stuchlikova Lubica , Weis Martin
Published: November 2022

Silicon carbide (SiC) has been envisioned as an almost ideal material for power electronic devices; however, device reliability is still a great challenge. Here we investigate the reliability of commercial 1.2-kV 4H-SiC MOSFETs under repetitive unclamped inductive switching (UIS). The stress invoked degradation of the device characteristics, including the output and transfer characteristics, drain leakage current, and capacitance characteristics. Besides the shift of steady-state electrical characteristics, a significant change in switching times points out the charge trapping phenomenon. Transient capacitance spectroscopy was applied to investigate charge traps in the virgin device as well as after UIS stress. The intrinsic traps due to metal impurities or Z1,2 transitions were recognized in the virgin device. The UIS stress caused suppression of the second stage of the Z1,2  transition, and only the first stage, Z10, was observed. Hence, the UIS stress is causing the reduction of multiple charging of carbon vacancies in SiC-based devices.
External Confined Concrete Cylinders Behavior under Axial Compression Using CFRP Wrapping
Authors: Karouche Abdelhamid , Hebbache Kamel , Belebchouche Cherif , Lahbari Noureddine , Kessal Oussama , Czarnecki Slawomir
Published: November 2022

Carbon-fiber-reinforced polymer (CFRP) is a composite material used to mend and strengthen concrete structural elements in civil engineering. The prime aim of this experimental study is to investigate the comportment of confined concrete cylinders (CCC) under uniaxial loads by altering the concrete strength, the CFRP angle orientation, and the volumetric ratio, following the externally bonded reinforcement technique (EBR). We present the results of the confinement effect and failure mechanisms issue of more than 150 specimens of CFRP confined concrete cylinders that have been undertaken and in which several parameters were altered. Totally and partially confined concrete cylinders were tested for failure under axial compressive loads and indirect tensile tests. Four different ratios of water/cement (0.33, 0.36, 0.401, and 0.522) were investigated. In addition, three sand–resin ratios were prepared to improve the mechanical properties and the adhesion of the CFRP and the concrete. The obtained results revealed a clear improvement in the compressive strength of the specimens made with low strength concrete (from 38% to 66%) compared to those made of high strength concrete (from 11% to 31%), where the improvements are relatively low. Furthermore, the transversally confined concrete cylinders presented significant gains in strength over those confined longitudinally. Lastly, adding sand to the resin increases the compressive strength of confined concrete cylinders (1.19% to 54.62%) and reduces the cost of the resin used for fixing CFRP materials.
A Novel Technique for the Preparation of Iron Carbide and Carbon Concentrate from Blast Furnace Dust
Authors: Chen Dong , Guo Hongwei , Li Peng , Wu Feibao , Lv Yanan , Yan Bingji , Zhao Wei , Su Yifan
Published: November 2022

Blast furnace (BF) dust is a typical refractory iron resource. A novel technology-based utilization of BF dust as iron carbide and carbon concentrate by applying carburization roasting followed by magnetic separation and acid leaching is proposed. Under optimized conditions, an electric arc furnace (EAF) burden assaying 80.79% Fe and 7.63% C with a corresponding iron recovery rate of 87.26% and a carbon concentrate assaying 67.06% C with a corresponding carbon recovery rate of 81.23% were prepared. Furthermore, the carburization behavior and separation mechanism were revealed using X-ray powder diffraction, scanning electron microscopy, and optical microscopy. The results show that the separation efficiency of iron carbide, gangue, and carbon is very low. Na2SO4 is a highly effective additive to strengthen the separation efficiency as it can enhance the carburization index, enlarge the iron carbide particle size, improve the embed embedded relationship of iron carbide and gangue, and promote the gangue leaching efficiency. The study demonstrates that preparation of iron carbide and carbon concentrate from BF dust using the proposed technology is a feasible method.
Assessment of Aging Impact on Wax Crystallization in Selected Asphalt Binders
Authors: Wang Wenqi , Rahman Ali , Ding Haibo , Qiu Yanjun
Published: November 2022

For a better understanding of the changing trend in crystalline components of asphalt binders, asphalt binders originating from the SHRP Materials Reference Library with different oxidation degrees (unaged, 20 h PAV, and 60 h PAV) were prepared. The native asphalt binders and their oxidized residues were characterized by liquid-state nuclear magnetic resonance (NMR) spectroscopy and high-temperature gas chromatography (HTGC). The results showed that, compared with other carbon types, the content of internal methylene carbons of long paraffinic chains between different SHRP binders was quite different. The NMR average length of a long paraffinic internal methylene chain showed a good correlation with the wax content obtained at −20 °C using the methyl ethyl ketone (MEK) precipitation method and also the recently developed variable-temperature Fourier-transform infrared spectroscopy (VT-FTIR) method. In most cases, the average length of straight internal methylene carbons of a long paraffinic chain terminated by a methyl group increased with the oxidation of the asphalt binder. However, the difference caused by oxidation was significantly smaller than the difference caused by the source of the asphalt binder. In general, oxidation will make the n-alkanes distributed in asphalt binder fall within a narrower range. The carbon number of n-alkanes in the asphalt binder generally grew with oxidation.
A Cross-Scale Framework for Modelling Chloride Ions Diffusion in C-S-H: Combined Effects of Slip, Electric Double Layer and Ion Correlation
Authors: Qi Yunchao , Peng Weihong , Zhang Wei , Jing Yawen , Hu Liangyu
Published: November 2022

Water and chloride ions within pores of cementitious materials plays a crucial role in the damage processes of cement pastes, particularly in the binding material comprising calcium-silicate-hydrates (C-S-H). The migration mechanism of water and chloride ions restricted in C-S-H nanopores is complicated due to the presence of interfacial effects. The special mechanical properties of the solid–liquid interface determine the importance of boundary slip and Electric Double Layer (EDL) and ion diversity in pore solutions determines the difference of the EDL and the stability of water film slip. A cross-scale model covering slip effects, time-varying of EDL and ion correlation needs to be developed so that the interfacial effects concentrated at the pore scale can be extended to affect the overall diffusivity of C-S-H. The statistics of pore size distribution and fractal dimension were used to quantitatively compare the similarities between model and C-S-H structure, thus proving the reliability of cross-scale reconstructed C-S-H transmission model. The results show that the slip effect is the dominant factor affecting the diffusion ability of C-S-H, the contribution of the slip effect is up to 60% and the contribution rate of EDL time-varying only up to about 15%. Moreover, the slip effect is sensitive to both ion correlation and C-S-H inhomogeneity and EDL time-varying is almost insensitive to ion correlation changes. This quantification provides a necessary benchmark for understanding the destructiveness of cement-based materials in the salt rich environment and provides new insights into improving the durability of concrete by changing the solid–liquid interface on the micro-nanoscale.
Clinical Features of Infectious Uveitis in Children Referred to a Hospital-Based Eye Clinic in Italy
Authors: Paroli Maria , Restivo Lucia , Ottaviani Eleonora , Nardella Chiara , Abicca Irene , Spadea Luca , Paroli Marino
Published: November 2022

Background and Objectives: To investigate the etiology, clinical features, ocular complications, and visual outcomes in children with infectious uveitis referred to a tertiary uveitis hospital-based service. Materials and Methods: Children with infectious uveitis were included in a retrospective cohort study. The data set was obtained after reviewing the medical records of pediatric patients with uveitis of different causes referred to our center during the period from 2009 to 2019. Clinical evaluations were performed at the time of diagnosis and the end of follow-up. Results: Uveitis of infectious origin was present in 57 (72 eyes) of 314 (18.1%) patients examined. The median age at presentation was 10.9 years (6.1–15.8), 52.6% of patients were female, and 47.4% were male. The main cause of infectious uveitis was viral (56.1% of cases), followed by Toxoplasma gondii infection (24.5%). The anatomical location of uveitis was posterior in 40.3%, anterior in 36.8%, panuveitis in 15.7%, and intermediate in 7% of cases. Ocular involvement was unilateral in 42 children (73.7%) and bilateral in 15 (26.3%) cases. The main causes of reduced visual acuity were cataract and maculopathy in 57.1% and 28.5% of cases, respectively. During the follow-up period, 75% of patients showed significant improvements in visual acuity. Conclusions: Specialist management in a tertiary referral eye care center facilitates early diagnosis and effective treatment of this serious cause of morbidity and vision loss in children.
Heritability of Subcortical Grey Matter Structures
Authors: Strelnikov David , Alijanpourotaghsara Amirreza , Piroska Marton , Szalontai Laszlo , Forgo Bianka , Jokkel Zsofia , Persely Alíz , Hernyes Anita , Kozak Lajos Rudolf , Szabo Adam , Maurovich-Horvat Pal , Tarnoki David Laszlo , Tarnoki Adam Domonkos
Published: November 2022

Background and Objectives: Subcortical grey matter structures play essential roles in cognitive, affective, social, and motoric functions in humans. Their volume changes with age, and decreased volumes have been linked with many neuropsychiatric disorders. The aim of our study was to examine the heritability of six subcortical brain volumes (the amygdala, caudate nucleus, pallidum, putamen, thalamus, and nucleus accumbens) and four general brain volumes (the total intra-cranial volume and the grey matter, white matter, and cerebrospinal fluid (CSF) volume) in twins. Materials and Methods: A total of 118 healthy adult twins from the Hungarian Twin Registry (86 monozygotic and 32 dizygotic; median age 50 ± 27 years) underwent brain magnetic resonance imaging. Two automated volumetry pipelines, Computational Anatomy Toolbox 12 (CAT12) and volBrain, were used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Age- and sex-adjusted monozygotic and dizygotic intra-pair correlations were calculated, and the univariate ACE model was applied. Pearson’s correlation test was used to compare the results obtained by the two pipelines. Results: The age- and sex-adjusted heritability estimates, using CAT12 for the amygdala, caudate nucleus, pallidum, putamen, and nucleus accumbens, were between 0.75 and 0.95. The thalamus volume was more strongly influenced by common environmental factors (C = 0.45−0.73). The heritability estimates, using volBrain, were between 0.69 and 0.92 for the nucleus accumbens, pallidum, putamen, right amygdala, and caudate nucleus. The left amygdala and thalamus were more strongly influenced by common environmental factors (C = 0.72−0.85). A strong correlation between CAT12 and volBrain (r = 0.74−0.94) was obtained for all volumes. Conclusions: The majority of examined subcortical volumes appeared to be strongly heritable. The thalamus was more strongly influenced by common environmental factors when investigated with both segmentation methods. Our results underline the importance of identifying the relevant genes responsible for variations in the subcortical structure volume and associated diseases.