bluuebunny/crossref_metadata_2025 huggingface dataset:
Home Dust Mites Promote MUC5AC Hyper-Expression by Modulating the sNASP/TRAF6 Axis in the Airway Epithelium
Authors: Chen Ming-Zhen , Wang Shao-An , Hsu Shih-Chang , Silva Kleiton Augusto Santos , Yang Feng-Ming
Published: August 2022

House dust mites (HDMs) are a common source of respiratory allergens responsible for allergic asthma and innate immune responses in human diseases. Since HDMs are critical factors in the triggering of allergen-induced airway mucosa from allergic asthma, we aimed to investigate the mechanisms of Toll-like receptors (TLR) in the signaling of the HDM extract that is involved in mucus hypersecretion and airway inflammation through the engagement of innate immunity. Previously, we reported that the somatic nuclear autoantigenic sperm protein (sNASP)/tumor necrosis factor receptor-associated factor 6 (TRAF6) axis controls the initiation of TLRs to maintain the homeostasis of the innate immune response. The present study showed that the HDM extract stimulated the biogenesis of Mucin 5AC (MUC5AC) in bronchial epithelial cells via the TLR2/4 signaling pathway involving MyD88 and TRAF6. Specifically, sNASP binds to TRAF6 in unstimulated bronchial epithelial cells to prevent the activation of TRAF6-depenedent kinases. Upon on HDMs’ stimulation, sNASP is phosphorylated, leading to the activation of TRAF6 downstream of the p38 MAPK and NF-κB signaling pathways. Further, NASP-knockdown enhanced TRAF6 signaling and MUC5AC biogenesis. In the HDM-induced mouse asthma model, we found that the HDM extract promoted airway hyperresponsiveness (AHR), MUC5AC, and allergen-specific IgE production as well as IL-5 and IL-13 for recruiting inflammatory cells. Treatment with the PEP-NASP peptide, a selective TRAF6-blocking peptide, ameliorated HDM-induced asthma in mice. In conclusion, this study indicated that the sNASP/TRAF6 axis plays a regulatory role in asthma by modulating mucus overproduction, and the PEP-NASP peptide might be a potential target for asthma treatment.
The Histone Demethylase Inhibitor GSK-J4 Is a Therapeutic Target for the Kidney Fibrosis of Diabetic Kidney Disease via DKK1 Modulation
Authors: Hung Peir-Haur , Hsu Yung-Chien , Chen Tsung-Hsien , Ho Cheng , Lin Chun-Liang
Published: August 2022

Diabetic kidney disease (DKD) can cause inflammation and fibrosis, in addition to being the main complication of diabetes. Among many factors, epigenetic alterations in aberrant histone modifications play a key role in causing DKD. In this study, the mechanism of GSK-J4, a histone demethylase KDM6A inhibitor, was evaluated in streptozotocin-induced diabetic mice. It was confirmed that GSK-J4, via dickkopf-1 (DKK1) modulation, could significantly reduce proteinuria and glomerulosclerosis in diabetic mice. The mRNA accumulation levels of DKK1, TGF-β1, fibronectin, and collagen IV were significantly elevated in diabetic mice. In contrast, the mRNA accumulations of those genes were significantly reduced in diabetic mice treated with GSK-J4 compared to those in diabetic mice, relatively speaking. The protein accumulation levels of fibronectin and collagen IV were significantly elevated in diabetic mice. Furthermore, GSK-J4 attenuated the high glucose-induced expression of profibrotic factors in mesangial cells via DKK1. In conclusion, our study provides a novel strategy to eliminate fibrosis in the kidneys of DKD mice. Using GSK-J4 reduces DKK1 expression, thereby ameliorating renal insufficiency, glomerulosclerosis morphological abnormalities, inflammation, and fibrosis in diabetic mice.
Heparan Sulfate Facilitates Binding of hIFNγ to Its Cell-Surface Receptor hIFNGR1
Authors: Miladinova Elisaveta , Lilkova Elena , Krachmarova Elena , Malinova Kristina , Petkov Peicho , Ilieva Nevena , Nacheva Genoveva , Litov Leandar
Published: August 2022

Human interferon-gamma (hIFNγ) is a crucial signaling molecule with an important role in the initialization and development of the immune response of the host. However, its aberrant activity is also associated with the progression of a multitude of autoimmune and other diseases, which determines the need for effective inhibitors of its activity. The development of such treatments requires proper understanding of the interaction of hIFNγ to its cell-surface receptor hIFNGR1. Currently, there is no comprehensive model of the mechanism of this binding process. Here, we employ molecular dynamics simulations to study on a microscopic level the process of hIFNγ–hIFNGR1 complex formation in different scenarios. We find that the two molecules alone fail to form a stable complex, but the presence of heparan-sulfate-like oligosaccharides largely facilitates the process by both demobilizing the highly flexible C-termini of the cytokine and assisting in the proper positioning of its globule between the receptor subunits. An antiproliferative-activity assay on cells depleted from cell-surface heparan sulfate (HS) sulfation together with the phosphorylation levels of the signal transducer and activator of transcription STAT1 confirms qualitatively the simulation-based multistage complex-formation model. Our results reveal the key role of HS and its proteoglycans in all processes involving hIFNγ signalling.
Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion
Authors: Guo Beibei , Cao Jiaxin , Liu Yi , Wang Yuhang , Qian Yi , Chen Guangtong , Zhu Weizhong
Published: August 2022

Myocardial ischemia–reperfusion injury (MIRI) leads to cardiac remodeling and heart failure associated with acute myocardial infarction, which is one of the leading causes of death worldwide. Betulinic acid (BA), a widely distributed lupane-type triterpenoid, has been reported to possess antioxidative activity and inhibit apoptosis in MIRI. Due to the low bioavailability and water insolubility of BA, a previous study found a series of BA-derivative compounds by microbial transformation. In this study, we observe whether there are anti-MIRI effects of BTA07, a BA derivative, on cardiac injuries induced by hypoxia/reoxygenation (H/R) in adult rat cardiomyocytes in vitro and in Langendorff-perfused hearts ex vivo, and further explore its mechanism of cardioprotection to find more efficient BA derivatives. The hemodynamic parameters of isolated hearts were monitored and recorded by a Lab Chart system. The markers of oxidative stress and apoptosis in isolated hearts and adult rat cardiomyocytes (ARCMs) were evaluated. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), protein kinase B (Akt) and phospho-Akt (pAkt, Ser473) induced by H/R were detected via Western blot. The Langendorff experiments showed that BTA07 improves hemodynamic parameters, reduces myocardium damage and infarct size, inhibits levels of myocardial tissue enzymes lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary outflow and reduces oxidative stress and the activation of caspase-3 in the myocardium. In vitro, BTA07 reduced cell death and caspase-3 activation and inhibited reactive oxygen species (ROS) generation. Furthermore, the protective effects of BTA07 were attenuated by inhibition of the PI3K/Akt signaling pathway with LY294002 in ARCMs. BTA07 protects ARCMs and isolated hearts from hypoxia–reperfusion partly by inhibiting oxidative stress and cardiomyocyte apoptosis.
Activation of ADRB2/PKA Signaling Pathway Facilitates Lipid Synthesis in Meibocytes, and Beta-Blocker Glaucoma Drug Impedes PKA-Induced Lipid Synthesis by Inhibiting ADRB2
Authors: Jun Ikhyun , Choi Young Joon , Kim Bo-Rahm , Seo Kyoung Yul , Kim Tae-im
Published: August 2022

Meibomian gland dysfunction is one of the main causes of dry eye disease and has limited therapeutic options. In this study, we investigated the biological function of the beta 2-adrenergic receptor (ADRB2)/protein kinase A (PKA) pathway in lipid synthesis and its underlying mechanisms in human meibomian gland epithelial cells (HMGECs). HMGECs were cultured in differentiation media with or without forskolin (an activator of adenylate cyclase), salbutamol (an ADRB2 agonist), or timolol (an ADRB2 antagonist) for up to 4 days. The phosphorylation of the cAMP-response element-binding protein (CREB) and the expression of peroxisome proliferator activator receptor (PPAR)γ and sterol regulatory element-binding protein (SREBP)-1 were measured by immunoblotting and quantitative PCR. Lipid synthesis was examined by LipidTOX immunostaining, AdipoRed assay, and Oil Red O staining. PKA pathway activation enhanced PPARγ expression and lipid synthesis in differentiated HMGECs. When treated with agonists of ADBR2 (upstream of the PKA signaling system), PPARγ expression and lipid synthesis were enhanced in HMGECs. The ADRB2 antagonist timolol showed the opposite effect. The activation of the ADRB2/PKA signaling pathway enhances lipid synthesis in HMGECs. These results provide a potential mechanism and therapeutic target for meibomian gland dysfunction, particularly in cases induced by beta-blocker glaucoma drugs.
Evolution of Graves’ Disease during Immune Reconstitution following Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation in a Boy Carrying Germline SAMD9L and FLT3 Variants
Authors: Ip Peng Peng , Fang Li-Hua , Shen Yi-Ling , Tung Kuan-Chiun , Lai Ming-Tsong , Juan Li-Ying , Chen Liuh-Yow , Chen Rong-Long
Published: August 2022

Graves’ disease, characterized by hyperthyroidism resulting from loss of immune tolerance to thyroid autoantigens, may be attributable to both genetic and environmental factors. Allogeneic hematopoietic stem cell transplantation (HSCT) represents a means to induce immunotolerance via an artificial immune environment. We present a male patient with severe aplastic anemia arising from a germline SAMD9L missense mutation who successfully underwent HSCT from his HLA-haploidentical SAMD9L non-mutated father together with nonmyeloablative conditioning and post-transplant cyclophosphamide at 8 years of age. He did not suffer graft-versus-host disease, but Graves’ disease evolved 10 months post-transplant when cyclosporine was discontinued for one month. Reconstitution of peripheral lymphocyte subsets was found to be transiently downregulated shortly after Graves’ disease onset but recovered upon antithyroid treatment. Our investigation revealed the presence of genetic factors associated with Graves’ disease, including HLA-B*46:01 and HLA-DRB1*09:01 haplotypes carried by the asymptomatic donor and germline FLT3 c.2500C>T mutation carried by both the patient and the donor. Given his current euthyroid state with normal hematopoiesis, the patient has returned to normal school life. This rare event of Graves’ disease in a young boy arising from special HSCT circumstances indicates that both the genetic background and the HSCT environment can prompt the evolution of Graves’ disease.
Saliency-Enabled Coding Unit Partitioning and Quantization Control for Versatile Video Coding
Authors: Li Wei , Jiang Xiantao , Jin Jiayuan , Song Tian , Yu Fei Richard
Published: August 2022

The latest video coding standard, versatile video coding (VVC), has greatly improved coding efficiency over its predecessor standard high efficiency video coding (HEVC), but at the expense of sharply increased complexity. In the context of perceptual video coding (PVC), the visual saliency model that utilizes the characteristics of the human visual system to improve coding efficiency has become a reliable method due to advances in computer performance and visual algorithms. In this paper, a novel VVC optimization scheme compliant PVC framework is proposed, which consists of fast coding unit (CU) partition algorithm and quantization control algorithm. Firstly, based on the visual saliency model, we proposed a fast CU division scheme, including the redetermination of the CU division depth by calculating Scharr operator and variance, as well as the executive decision for intra sub-partitions (ISP), to reduce the coding complexity. Secondly, a quantization control algorithm is proposed by adjusting the quantization parameter based on multi-level classification of saliency values at the CU level to reduce the bitrate. In comparison with the reference model, experimental results indicate that the proposed method can reduce about 47.19% computational complexity and achieve a bitrate saving of 3.68% on average. Meanwhile, the proposed algorithm has reasonable peak signal-to-noise ratio losses and nearly the same subjective perceptual quality.
Optimized Screening for At-Risk Students in Mathematics: A Machine Learning Approach
Authors: Bulut Okan , Cormier Damien C. , Yildirim-Erbasli Seyma Nur
Published: August 2022

Traditional screening approaches identify students who might be at risk for academic problems based on how they perform on a single screening measure. However, using multiple screening measures may improve accuracy when identifying at-risk students. The advent of machine learning algorithms has allowed researchers to consider using advanced predictive models to identify at-risk students. The purpose of this study is to investigate if machine learning algorithms can strengthen the accuracy of predictions made from progress monitoring data to classify students as at risk for low mathematics performance. This study used a sample of first-grade students who completed a series of computerized formative assessments (Star Math, Star Reading, and Star Early Literacy) during the 2016–2017 (n = 45,478) and 2017–2018 (n = 45,501) school years. Predictive models using two machine learning algorithms (i.e., Random Forest and LogitBoost) were constructed to identify students at risk for low mathematics performance. The classification results were evaluated using evaluation metrics of accuracy, sensitivity, specificity, F1, and Matthews correlation coefficient. Across the five metrics, a multi-measure screening procedure involving mathematics, reading, and early literacy scores generally outperformed single-measure approaches relying solely on mathematics scores. These findings suggest that educators may be able to use a cluster of measures administered once at the beginning of the school year to screen their first grade for at-risk math performance.
Interactive Effects of Temperature and Plant Host on the Development Parameters of Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae)
Authors: Maharjan Rameswor , Ahn Jeongjoon , Yi Hwijong
Published: August 2022

This study investigated the effects of different temperatures (15, 20, 25, 27, 30, 35, and 40 °C) on the development rate of Spodoptera exigua (Hübner) eggs, larvae, pupae, and total immatures on plant hosts (soybean, maize, potato, and green pea). The eggs of S. exigua developed successfully at all the tested temperatures, except at 40 °C. The total developmental time (egg-adult) decreased with an increasing temperature from 15 to 35 °C on plant hosts. Stage-specific parameters such as the lower threshold temperature (TH) were determined using linear and nonlinear models (Sharpe-Schoolfield-Ikemoto [SSI]). The lower developmental threshold (LDT) and thermal constant (K) were determined using a linear model. The LDT and K for the total immature stage had respective values of 11.9 °C and 397.27° -day (DD) on soybean, 11.6 °C and 458.34° -day (DD) on maize, 11.2 °C and 446.23° -day (DD) on potato, 10.7 °C and 439.75° -day (DD) on green pea, and 12.2 °C and 355.82° -day (DD) on the artificial diet. The emergence frequency of adult S. exigua over the full range of constant temperatures was simulated using nonlinear developmental rate functions and the Weibull function. This study predicted the spring emergence date in the first to second weeks of June, with approximately five generations for plant hosts. The interaction of temperature and plant host also influenced the development and longevity of the adults. Overall, the findings of this study may be useful for predicting the number of generations, occurrence, population dynamics in crop fields, and management of S. exigua.
A Bombyx mori Infection Model for Screening Antibiotics against Staphylococcus epidermidis
Authors: Montali Aurora , Berini Francesca , Saviane Alessio , Cappellozza Silvia , Marinelli Flavia , Tettamanti Gianluca
Published: August 2022

The increasing number of microorganisms that are resistant to antibiotics is prompting the development of new antimicrobial compounds and strategies to fight bacterial infections. The use of insects to screen and test new drugs is increasingly considered a promising tool to accelerate the discovery phase and limit the use of mammalians. In this study, we used for the first time the silkworm, Bombyx mori, as an in vivo infection model to test the efficacy of three glycopeptide antibiotics (GPAs), against the nosocomial pathogen Staphylococcus epidermidis. To reproduce the human physiological temperature, the bacterial infection was performed at 37 °C and it was monitored over time by evaluating the survival rate of the larvae, as well the response of immunological markers (i.e., activity of hemocytes, activation of the prophenoloxidase system, and lysozyme activity). All the three GPAs tested (vancomycin, teicoplanin, and dalbavancin) were effective in curing infected larvae, significantly reducing their mortality and blocking the activation of the immune system. These results corroborate the use of this silkworm infection model for the in vivo studies of antimicrobial molecules active against staphylococci.
Fruit Fly in a Challenging Environment: Impact of Short-Term Temperature Stress on the Survival, Development, Reproduction, and Trehalose Metabolism of Bactrocera dorsalis (Diptera: Tephritidae)
Authors: Yu Chun , Zhao Runa , Zhou Wei , Pan Yingna , Tian Hui , Yin Zhengyan , Chen Wenlong
Published: August 2022

An understanding of physiological damage and population development caused by uncomfortable temperature plays an important role in pest control. In order to clarify the adaptability of different temperatures and physiological response mechanism of B. dorsalis, we focused on the adaptation ability of this pest to environmental stress from physiological and ecological viewpoints. In this study, we explored the relationship between population parameters and glucose, glycogen, trehalose, and trehalose-6-phosphate synthase responses to high and low temperatures. Compared with the control group, temperature stress delayed the development duration of all stages, and the survival rates and longevity decreased gradually as temperature decreased to 0 °C and increased to 36 °C. Furthermore, with low temperature decrease from 10 °C to 0 °C, the average fecundity per female increased at 10 °C but decreased later. Reproduction of the species was negatively affected during high-temperature stresses, reaching the lowest value at 36 °C. In addition to significantly affecting biological characteristics, temperature stress influenced physiological changes of B. dorsalis in cold and heat tolerance. When temperature deviated significantly from the norm, the levels of substances associated with temperature resistance were altered: glucose, trehalose, and TPS levels increased, but glycogen levels decreased. These results suggest that temperature stresses exert a detrimental effect on the populations’ survival, but the metabolism of trehalose and glycogen may enhance the pest’s temperature resistance.
The Differential Effects of Tuta absoluta Infestations on the Physiological Processes and Growth of Tomato, Potato, and Eggplant
Authors: Mahlangu Lindiwe , Sibisi Phumzile , Nofemela Robert S. , Ngmenzuma Titus , Ntushelo Khayalethu
Published: August 2022

Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae) is a destructive insect pest toward crops and belongs to the Solanaceae family. Since it was first recorded in South Africa in 2016, the pest has spread extensively and caused tremendous damage to field and tunnel-grown tomato crops. This study aimed to investigate how T. absoluta affects the growth and physiology of three Solanaceae plant species: tomato, potato, and eggplant. These three crops were infested with L1 instar larvae, and their growth and physiology were assessed during insect feeding. The damage to the infested tomato host plant was severe, with T. absoluta destroying 100% of the plants. The tomato plants were distorted 15 days after infestation, that is, before the fruit set. For potato, the defoliation was moderate, but the infested plants produced fewer tubers compared to the uninfested host plants. Eggplant had fewer visible signs of feeding, resulting in no significant difference between the infested and uninfested host plants in terms of growth and physiological functions. Infested tomato and potato plants had stagnant growth, fewer and damaged leaves, a reduced chlorophyll content, a reduced photosynthesis rate, a poor transpiration rate, poor water conductance, and poor intercellular carbon dioxide concentrations. This study closes the knowledge gap on the morphological (growth) and physiological responses of different Solanaceae species to T. absoluta infestation, and it also demonstrates the differential risk of T. absoluta infestations in the production of tomato, potato, and eggplant.
Functional Role of AsAP in the Reproduction of Adelphocoris suturalis (Hemiptera: Miridae)
Authors: Qin Shidong , Zhu Bangqin , Huang Xingxing , Hull J. Joe , Chen Lizhen , Luo Jing
Published: August 2022

Adelphocoris suturalis Jakovlev (Hemiptera: Miridae) is an omnivorous agricultural pest that has severe economic impacts on a diverse range of agricultural crops. Although the targeted disruption of reproductive development among insects has been proposed as a novel control strategy for pest species, the current understanding of the physiology and molecular mechanisms of A. suturalis reproduction is very limited. In this study, we isolated a putative A. suturalisaspartic protease (AsAP) gene that is highly expressed in the fat body and ovaries of sexually mature females. The double-stranded RNA (dsRNA)-mediated knockdown of AsAP suppressed ovarian development and negatively impacted female fertility, which suggested that it plays an essential role in A. suturalis reproduction. The results of this study could help to expand our understanding of A. suturalis reproductive development and have the potential to facilitate the development of effective strategies for the better control of this pest species.
Urban Individuals of Three Rove Beetle Species Are Not More Exploratory or Risk-Taking Than Rural Conspecifics
Authors: Magura Tibor , Horváth Roland , Mizser Szabolcs , Tóth Mária , Nagy Dávid D. , Csicsek Réka , Balla Emőke , Lövei Gábor L.
Published: August 2022

Urbanization is creating changes in environmental and habitat conditions, as well as creating disturbance and threats to urban-associated species. Some traits, such as high exploratory and risk-taking behavior, are beneficial to allow colonization of urban habitats and coping with urbanization-derived pressures. In this study the exploratory and risk-taking behavior of rural and urban individuals of three forest-associated rove beetle species were tested during their main reproductive period by five frequently used behavioral measures. Individuals of all studied species were similarly ranked by all behavioral measures, indicating that the studied rove beetles responded consistently in the different contexts. However, the behavior of beetles was consistent over time for all/most studied species only by using two measures of exploratory behavior. These provide evidence for the existence of the exploratory dimension of personality in rove beetles. We found a higher exploratory behavior in males than females in Ocypus nitens which can be explained by the active searching of males for mating partners. There were no urbanization-related differences in the exploratory behavior of individuals, suggesting that behavioral changes (being more exploratory) may not yield additional fitness benefits in these rove beetle species with good dispersal capacity.
Recent Developments in 3D Printing of Rare-Earth-Free Permanent Magnets
Authors: Sirisathitkul Chitnarong , Sirisathitkul Yaowarat
Published: August 2022

This article reviews the advances in additive manufacturing of magnetic ceramics and alloys without rare-earth elements. Near-net-shaped permanent magnets with varying shapes and dimensions overcome traditional limitations of the cast, sintered, and bonded magnets. The published articles are categorized based on material types and 3D printing techniques. Selective laser melting and electron beam melting were predominantly used to produce alnico magnets. In addition to the electron beam melting, manganese aluminium-based alloys were successfully printed by fuse filament fabrication. By incorporating magnetic powders in polymers and then printing via extrusion, the fuse filament fabrication was also used to produce strontium ferrite magnets. Moreover, hard ferrites were printed by stereolithography and extrusion free-forming, without drawing composites into filaments. Magnetic properties in some cases are comparable to those of conventional magnets with the same compositions. Currently, available software packages can simulate magnetic fields for designing magnets and optimize the integration in electrical machines. These developments open up opportunities for next-generation permanent magnet applications.
Equivalent Scheme of the Fuel Cell Taking into Account the Influence of Eddy Currents and A Practical Way to Determine Its Parameters
Authors: Pavlenko Alexander , Burtsev Yuri , Vasyukov Ivan , Puzin Vladimir , Gummel Andrew
Published: August 2022

The aim of this work is to develop a dynamic equivalent scheme of the fuel cell, taking into account eddy currents in the conductive parts of the structure, to offer a practical way to determine the parameters of this circuit and also to show the adequacy of the scheme and parameters by numerical simulation and comparison with experiment. Fuel cells, as a rule, are connected to the voltage converters, which create a high-frequency component of the main fuel cell current and eddy currents in the conductive parts. The problem is that the effect of these currents on the characteristics of the fuel cell-based power plants has not been studied. To determine the parameters of the proposed equivalent scheme, we use experiments and calculations of transient modes of the fuel cell. The main result of the work is the possibility and feasibility of calculating circuits with fuel cells, taking into account the influence of eddy currents. This effect depends both on the design of the fuel cell and on the parameters of the circuit to which it is connected. From this it follows that, in general, it is necessary to take into account the influence of eddy currents of the fuel cell. The refusal of this accounting is possible, but in each specific case it must be justified.
Vascular and Vasogenic Manifestations of Systemic ANCA-Associated Vasculitis with Renal Involvement in Non-Contrast Brain MRI in Patients with Acute Disease Onset
Authors: Lubas Arkadiusz , Staszewski Jacek , Maliborski Artur , Mosakowska Magdalena , Spłocharski Grzegorz , Bilbin-Bukowska Anna , Wołoszyńska Izabela , Piusińska-Macoch Renata , Pałka Daniel , Zegadło Arkadiusz , Niemczyk Stanisław
Published: August 2022

Background. Data concerning central nervous system (CNS) alterations in ANCA-associated vasculitis with renal involvement (AAVR) are sparse. The study aimed to assess vascular and vasogenic brain alterations in patients with acute onset of AAVR and the applicability of non-contrast magnetic resonance imaging (MRI) techniques in this diagnosis. Methods. Thirty-eight patients with acute onset of AAVR were included in the study. BVAS/WG, c-ANCA, p-ANCA, renal function and perfusion, neurological assessment, and brain MRI were performed. Results. Cerebral vascular alternating narrowing and dilatation (VAND) was detected in 42.1% of patients, and the black-blood was significantly more diagnostic than the TOF technique (p < 0.001). VAND occurrence was independently associated with the concentration of p-ANCA. The vasogenic white matter lesions (VWML) were found in 94.4% of patients, and in their detection, SWAN was significantly better than the FLAIR technique (p = 0.002). The number of VWML correlated with age and cranial nerve damage. Hemosiderin deposits were found in 21.6% of patients and were associated with a gait impairment and paresthesia. Conclusions. Vascular and vasogenic alterations in the CNS are frequent in patients with acute onset of systemic ANCA-associated vasculitis with renal involvement. Non-contrast MRI is useful in the diagnosis of brain vasculitis.
Hand Ownership Is Altered in Teenagers with Unilateral Cerebral Palsy
Authors: Gerber Corinna N. , Gasser Didier L. , Newman Christopher John
Published: August 2022

We explored hand ownership in teenagers with unilateral cerebral palsy (UCP) compared with typically developing teenagers. Eighteen participants with UCP and 16 control teenagers participated. We used the rubber hand illusion to test hand ownership (HO). Both affected/non-affected hands (UCP) and dominant/non-dominant hands (controls) were tested during synchronous and asynchronous strokes. HO was assessed by measuring the proprioceptive drift toward the fake hand (as a percentage of arm length) and conducting a questionnaire on subjective HO. Both groups had significantly higher proprioceptive drift in the synchronous stroking condition for both hands. Teenagers with UCP showed a significantly higher proprioceptive drift when comparing their paretic hand (median 3.4% arm length) with the non-dominant hand of the controls (median 1.7% arm length). The questionnaires showed that synchronous versus asynchronous stroking generated a robust change in subjective HO in the control teenagers, but not in the teenagers with UCP. Teenagers with UCP have an altered sense of HO and a distorted subjective experience of HO that may arise from the early dysfunction of complex sensory–motor integration related to their brain lesions. HO may influence motor impairment and prove to be a target for early intervention.
Exercise Hypertension in Athletes
Authors: Keller Karsten , Hartung Katharina , del Castillo Carillo Luis , Treiber Julia , Stock Florian , Schröder Chantal , Hugenschmidt Florian , Friedmann-Bette Birgit
Published: August 2022

Background: An exaggerated blood pressure response (EBPR) during exercise testing is not well defined, and several blood pressure thresholds are used in different studies and recommended in different guidelines. Methods: Competitive athletes of any age without known arterial hypertension who presented for preparticipation screening were included in the present study and categorized for EBPR according to American Heart Association (AHA), European Society of Cardiology (ESC), and American College of Sports Medicine (ACSM) guidelines as well as the systolic blood pressure/MET slope method. Results: Overall, 1137 athletes (mean age 21 years; 34.7% females) without known arterial hypertension were included April 2020–October 2021. Among them, 19.6%, 15.0%, and 6.8% were diagnosed EBPR according to ESC, AHA, and ACSM guidelines, respectively. Left ventricular hypertrophy (LVH) was detected in 20.5% of the athletes and was approximately two-fold more frequent in athletes with EBPR than in those without. While EBPR according to AHA (OR 2.35 [95%CI 1.66–3.33], p < 0.001) and ACSM guidelines (OR 1.81 [95%CI 1.05–3.09], p = 0.031) was independently (of age and sex) associated with LVH, EBPR defined according to ESC guidelines (OR 1.49 [95%CI 1.00–2.23], p = 0.051) was not. In adult athletes, only AHA guidelines (OR 1.96 [95%CI 1.32–2.90], p = 0.001) and systolic blood pressure/MET slope method (OR 1.73 [95%CI 1.08–2.78], p = 0.023) were independently predictive for LVH. Conclusions: Diverging guidelines exist for the screening regarding EBPR. In competitive athletes, the prevalence of EBPR was highest when applying the ESC (19.6%) and lowest using the ACSM guidelines (6.8%). An association of EBPR with LVH in adult athletes, independently of age and sex, was only found when the AHA guideline or the systolic blood pressure/MET slope method was applied.
Cerebral Tissue Oxygen Saturation Correlates with Emergence from Propofol-Remifentanil Anesthesia: An Observational Cohort Study
Authors: Zhang Jianxi , Cheng Zhigang , Tian Ying , Weng Lili , Zhang Yiying , Yang Xin , Schäfer Michael K. E. , Guo Qulian , Huang Changsheng
Published: August 2022

Anesthesia emergence is accompanied by changes in cerebral circulation. It is unknown whether cerebral tissue oxygen saturation (SctO2) could be an indicator of emergence. Changes in SctO2, bispectral index (BIS), mean arterial pressure (MAP), and heart rate (HR) were evaluated during the emergence from propofol-remifentanil anesthesia. At the time of cessation of anesthetic delivery, SctO2, BIS, MAP, and HR values were recorded as baseline. The changes of these parameters from the baseline were recorded as Δ SctO2, Δ BIS, Δ MAP, and Δ HR. The behavioral signs (body movement, coughing, or eye opening) and response to commands (indicating regaining of consciousness) were used to define emergence states. Prediction probability (Pk) was used to examine the accuracy of SctO2, BIS, MAP, and HR as indicators of emergence. SctO2 showed an abrupt and distinctive increase when appearing behavioral signs. BIS, MAP, and HR, also increased but with a large inter-individual variability. Pk value of Δ SctO2 was 0.97 to predict the appearance behavioral signs from 2 min before that, which was much higher than the Pk values of Δ BIS (0.81), Δ MAP (0.71) and Δ HR (0.87). The regaining of consciousness was associated with a further increase in the SctO2 value.
Conventional, Speed Sintering and High-Speed Sintering of Zirconia: A Systematic Review of the Current Status of Applications in Dentistry with a Focus on Precision, Mechanical and Optical Parameters
Authors: Al-Haj Husain Nadin , Özcan Mutlu , Dydyk Nataliya , Joda Tim
Published: August 2022

The aim of this systematic review was to provide an overview of the technical and clinical outcomes of conventional, speed sintering and high-speed sintering protocols of zirconia in the dental field. Data on precision, mechanical and optical parameters were evaluated and related to the clinical performance of zirconia ceramic. The PICOS search strategy was applied using MEDLINE to search for in vitro and in vivo studies using MeSH Terms by two reviewers. Of 66 potentially relevant studies, 5 full text articles were selected and 10 were further retrieved through a manual search. All 15 studies included in the systematic review were in vitro studies. Mechanical, precision and optical properties (marginal and internal fit, fracture strength and modulus, wear, translucency and opalescence, aging resistance/hydrothermal aging) were evaluated regarding 3-, 4- and 5-YTZP zirconia material and conventional, high- and high-speed sintering protocols. Mechanical and precision results were similar or better when speed or high-speed sintering methods were used for 3-, 4- and 5-YTZP zirconia. Translucency is usually reduced when 3 Y-TZP is used with speed sintering methods. All types of zirconia using the sintering procedures performed mechanically better compared to lithium disilicate glass ceramics but glass ceramics showed better results regarding translucency.
Outcomes of Octogenarians with Primary Malignant Cardiac Tumors: National Cancer Database Analysis
Authors: Rahouma Mohamed , Baudo Massimo , Dabsha Anas , Dimagli Arnaldo , Mohamed Abdelrahman , Mick Stephanie , Girardi Leonard , Gaudino Mario , Lorusso Roberto
Published: August 2022

Data concerning age-related populations affected with primary malignant cardiac tumors (PMCTs) are still scarce. The aim of the current study was to analyze mortality differences amongst different age groups of patients with PMCTs, as reported by the National Cancer Database (NCDB). The NCDB was retrospectively reviewed for PMCTs from 2004 to 2017. The primary outcome was late mortality differences amongst different age categories (octogenarian, septuagenarian, younger age), while secondary outcomes included differences in treatment patterns and perioperative (30-day) mortality. A total of 736 patients were included, including 72 (9.8%) septuagenarians and 44 (5.98%) octogenarians. Angiosarcoma was the most prevalent PMCT. Surgery was performed in 432 (58.7%) patients (60.3%, 55.6%, and 40.9% in younger age, septuagenarian, and octogenarian, respectively, p = 0.04), with a corresponding 30-day mortality of 9.0% (7.0, 15.0, and 38.9% respectively, p < 0.001) and a median overall survival of 15.7 months (18.1, 8.7, and 4.5 months respectively). Using multivariable Cox regression, independent predictors of late mortality included octogenarian, governmental insurance, CDCC grade II/III, earlier year of diagnosis, angiosarcoma, stage III/IV, and absence of surgery/chemotherapy. With increasing age, patients presented a more significant comorbidity burden compared to younger ones and were treated more conservatively. Early and late survival outcomes progressively declined with advanced age.
Is the Erector Spinae Plane Block Effective for More than Perioperative Pain? A Retrospective Analysis
Authors: Hochberg Uri , Brill Silviu , Ofir Dror , Salame Khalil , Lidar Zvi , Regev Gilad , Khashan Morsi
Published: August 2022

Introduction: The thoracic Erector Spinae Plane Block (ESPB) is an ultrasound-guided block that has gained popularity and is widely used in acute pain setups. However, data regarding its role in chronic and cancer-related pain are anecdotal. Material and Methods: The study is a retrospective analysis of patients who underwent ESPB. The cohort was divided into subgroups based on three determinants: etiology, pain type, and chronicity. Results: One hundred and ten patients were included, and genders were affected equally. The average age was 61.2 ± 16.1 years. The whole group had a statistically significant reduction in a numerical rating scale (NRS) (7.4 ± 1.4 vs. 5.0 ± 2.6, p-value > 0.001). NRS reduction for 45 patients (41%) exceeded 50% of the pre-procedural NRS. The mean follow-up was 7.9 ± 4.6 weeks. Baseline and post-procedure NRS were comparable between all subgroups. The post-procedural NRS was significantly lower than the pre-procedural score within each group. The proportion of patients with over 50% improvement in NRS was lower for those with symptom duration above 12 months (p-value = 0.02). Conclusions: Thoracic ESPB is a simple and safe technique. The results support the possible role of ESPB for chronic as well as cancer-related pain.
Dual Targeting of the EGFR/HER2 Pathway in Combination with Systemic Chemotherapy in Refractory Pancreatic Cancer—The CONKO-008 Phase I Investigation
Authors: Striefler Jana , Stieler Jens , Neumann Christopher , Geisel Dominik , Ghadjar Pirus , Sinn Marianne , Malinka Thomas , Pratschke Johann , Stintzing Sebastian , Oettle Helmut , Riess Hanno , Pelzer Uwe
Published: August 2022

Background: Primary objective of this present trial was to define the maximum tolerable dose of lapatinib in combination with oxaliplatin, 5-fluorouracil, and folinic acid (OFF) in refractory pancreatic cancer. The secondary objective was to assess the safety and efficacy of lapatinib plus OFF. Methods: We conducted a phase I trial using an accelerated dose escalation design in patients with refractory pancreatic cancer. Lapatinib was given on days 1 to 42 in combination with folinic acid 200 mg/m2 day + 5-fluorouracil 2000 mg/m2 (24 h) on days 1, 8, 15, and 22, and oxaliplatin 85 mg/m2 days 8 and 22 of a 43-day cycle (OFF). Toxicity and efficacy were evaluated. Results: In total, eighteen patients were enrolled: dose level 1 (1000 mg) was assigned to seven patients, dose level 2 (1250 mg), five patients; and dose level 3 (1500 mg), six patients. Dose-limiting toxicities were diarrhea and/or neutropenic enterocolitis observed in two of six patients: one diarrhea III°, one diarrhea IV°, as well as neutropenic enterocolitis. The maximum tolerable dose of lapatinib was 1250 mg OD. Conclusions: The combination of lapatinib 1250 mg OD with platinum-containing chemotherapy is safe and feasible in patients with refractory pancreatic cancer and warrants further investigation.
Use of the Thyromental Height Test for Prediction of Difficult Laryngoscopy: A Systematic Review and Meta-Analysis
Authors: Chen Wenxuan , Tian Tian , Li Xintao , Jiang Tianyu , Xue Fushan
Published: August 2022

The thyromental height test (TMHT) has been proposed as a novel single clinical test for predicting difficult laryngoscopy (DL), though consequent studies have put forward various estimates when verifying its reliability. This systematic review and meta-analysis aimed to provide a comprehensive evaluation of the predictive value of TMHT for DL. A computerized search of CNKI, CQVIP, EBSCO, PubMed, SinoMed, and Wanfang Data was conducted on 1 June 2022. Prospective cohort studies reporting diagnostic properties of TMHT in relation to Cormack and Lehane grading in patients aged more than 16 years, either sex, scheduled for surgery under general anesthesia, requiring tracheal intubation with direct laryngoscopy were included in this analysis. Data was extracted or calculated, and meta-analysis was done by the Stata MIDAS module. A total of 23 studies with 5896 patients were included in this analysis. Summary estimates of all included studies are as follows: sensitivity 74% (95% CI, 68–79%); specificity 88% (95% CI, 81–92%); diagnostic odd ratio, 20 (95% CI, 10–40); positive likelihood ratio, 5.9 (95% CI, 3.6–9.6); and negative likelihood ratio, 0.30 (95% CI, 0.23–0.39). Summary sensitivity and specificity for studies with a prespecified threshold were 82% (95% CI, 71–89%) and 94% (95% CI, 87–98%), respectively. The estimated area under curve (AUC) was 85% (95% CI, 81–88%). There was no significant threshold effect but significant heterogeneity in both sensitivity and specificity. Heterogeneity in sensitivity became insignificant after removing two outliers of sensitivity analysis. It is concluded that THMT has an overall optimal predictive value for DL in adult patients with diverse ethnicity and various risk factors, displaying better predictive values in a large patient population comparing to other recent reported bedside assessments and a previous meta-analysis. As significant heterogeneity brought by un-standardized application of external laryngeal manipulations in the included studies may have biased the results of this meta-analysis, the actual predictive value of TMHT for DL still awaits further studies with good designs and large sample sizes for better determination.
New Insights on the Minimal-Invasive Therapy of Cervical Cancer
Authors: Gasimli Khayal , Wilhelm Lisa , Becker Sven , De Wilde Rudy Leon , Tahmasbi Rad Morva
Published: August 2022

Objective: The ideal management of early-stage cervical cancer has become the subject of a global controversy following the publication of a prospective study in 2018 that reported a worse oncologic outcome when comparing the minimally invasive approach to the laparotomy approach. The discussion involves both prospective and retrospective data and general and theoretical considerations. We wanted to look at the data available today and review the different opinions, offering an impartial assessment of the ongoing controversy. Methods: The available literature was reviewed, focusing on articles arguing for and against minimally invasive surgery in cervical cancer. We tried to avoid any fundamental bias, as is often evident in the available reviews on the subject. Literature both before and after the 2018 publication was taken into consideration. Results: As is usual in discussions of concepts, the literature that is now available provides arguments for both sides of this challenging issue, depending on one’s standpoint. Science-related writing is not immune to trends. There is a curious shift in opinion seen before and after 2018. One must question whether there was a prejudice in favor of minimally invasive surgery prior to the publication of the NEJM articles and a bias against it afterward. Conclusion: Whether further minimally invasive surgery for cervical cancer is invariable is tied to the more pressing question of how this surgery will have to be centralized in the future. Unless these questions are linked, no satisfactory solution can be found.
Reply to Fabbris et al. A Viable Alternative. Comment on “Kohmer et al. Self-Collected Samples to Detect SARS-CoV-2: Direct Comparison of Saliva, Tongue Swab, Nasal Swab, Chewed Cotton Pads and Gargle Lavage. J. Clin. Med. 2021, 10, 5751”
Authors: Hoehl Sebastian , Kohmer Niko , Eckermann Lisa , Gottschalk Rene , Ciesek Sandra
Published: August 2022

We thank Fabbris et al. for their remarks [...]
Occult Neck Metastases in Head and Neck Adenoid Cystic Carcinoma: A Systematic Review and Meta-Analysis
Authors: Zocchi Jacopo , Campa Matteo , Bianchi Giulia , Iocca Oreste , Di Maio Pasquale , Petruzzi Gerardo , Moretto Silvia , Campo Flaminia , De Virgilio Armando , Vander Poorten Vincent , Pellini Raul
Published: August 2022

Introduction: Adenoid cystic carcinoma (AdCC) is a rare tumor whose clinical course is burdened by local recurrence and distant dissemination. Lymph node metastasis is not believed to be common and its clinical impact is controversial. The aim of this study was to determine: (1) the prevalence of occult metastasis at diagnosis in cN0 head and neck AdCC, (2) its prognostic role, and (3) the consequent need to perform elective neck dissection (END). Material and Methods: A systematic review and meta-analyses following PRISMA guidelines was performed. PubMed, Embase, and Central databases were questioned up to July 2021 to identify studies reporting on the prevalence of occult neck metastases in head and neck AdCC. A single-arm meta-analysis was then performed to determine the pooled prevalence of occult lymph node metastases among the retained studies. Results: Of the initial 6317 studies identified, 16 fulfilled the inclusion criteria, and they were included in the meta-analysis. Of a population of 7534 patients, 2530 cN0 patients were treated with END, which revealed 290/2530 cases of occult metastases (pN+/cN0). Meta-analysis of the results of END in the 16 studies estimated an overall prevalence of occult metastases at diagnosis of 17%. No further subgroup analysis was possible to identify factors influencing lymph node involvement and the prognostic role of END. Conclusions: Taking 20% as an historically proposed cut off, a 17% prevalence of occult metastases represents a borderline percentage to get a definitive conclusion about the indication to END for head and neck AdCC. A more advanced UICC stage, an oropharyngeal minor salivary glands origin, and a high-grade transformation are factors to be considered in a comprehensive patient’s tailored therapeutic strategy. Multicenter prospective studies are the key to finding stronger recommendations on this topic.