bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a Workplace Sit–Stand Desk Intervention on Health and Productivity
Authors: Ma Jiameng , Ma Dongmei , Li Zhi , Kim Hyunshik
Published: November 2021

In Japan, standing while working has not yet become commonplace, and there is little evidence to support the benefits of standing during the workday. Therefore, this study assessed the relationship between the introduction of a sit–stand desk and its ability to reduce the negative effects of sitting too long and increase employees’ general health and productivity. Seventy-four Japanese desk workers participated in this three-month intervention study. Using a randomized controlled trial, the participants were divided into intervention (n = 36) and control (n = 38) groups. The participant characteristics were ascertained using a questionnaire. The intervention effectiveness was assessed by measuring health-, physical activity-, and work-related outcomes. The results indicate that the intervention group significantly decreased their sitting time at work (p = 0.002) and had reduced neck and shoulder pain (p = 0.001). There was a significant increase in subjective health (p = 0.002), vitality in work-related engagement (p < 0.001), and self-rated work performance over a four-week period (p = 0.017). These findings indicate a significant difference between the two groups, demonstrating the effectiveness of a sit–stand desk in reducing sedentary behavior and improving workers’ health and productivity. Future research can accumulate further evidence of best practice use of sit–stand desks.
Sprouty3, but Not Sprouty1, Expression Is Beneficial for the Malignant Potential of Osteosarcoma Cells
Authors: Kamptner Anna Zita Mehira , Mayer Christoph-Erik , Sutterlüty Hedwig
Published: November 2021

Sprouty proteins are widely accepted modulators of receptor tyrosine kinase-associated pathways and fulfill diversified roles in cancerogenesis dependent on the originating cells. In this study we detected a high expression of Sprouty3 in osteosarcoma-derived cells and addressed the question of whether Sprouty3 and Sprouty1 influence the malignant phenotype of this bone tumor entity. By using adenoviruses, the Sprouty proteins were expressed in two different cell lines and their influence on cellular behavior was assessed. Growth curve analyses and Scratch assays revealed that Sprouty3 accelerates cell proliferation and migration. Additionally, more colonies were grown in Soft agar if the cells express Sprouty3. In parallel, Sprouty1 had no significant effect on the measured endpoints of the study in osteosarcoma-derived cells. The promotion of the tumorigenic capacities in the presence of Sprouty3 coincided with an increased activation of signaling as measured by evaluating the phosphorylation of extracellular signal-regulated kinases (ERKs). Ectopic expression of a mutated Sprouty3 protein, in which the tyrosine necessary for its activation was substituted, resulted in inhibited migration of the treated cells. Our findings identify Sprouty3 as a candidate for a tumor promoter in osteosarcoma.
Assessment of the Contribution of a Thermodynamic and Mechanical Destabilization of Myosin-Binding Protein C Domain C2 to the Pathomechanism of Hypertrophic Cardiomyopathy-Causing Double Mutation MYBPC3Δ25bp/D389V
Authors: Schwäbe Frederic V. , Peter Emanuel K. , Taft Manuel H. , Manstein Dietmar J.
Published: November 2021

Mutations in the gene encoding cardiac myosin-binding protein-C (MyBPC), a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function, are a common cause for the development of hypertrophic cardiomyopathy. About 10% of carriers of the Δ25bp variant of MYBPC3, which is common in individuals from South Asia, are also carriers of the D389V variant on the same allele. Compared with noncarriers and those with MYBPC3Δ25bp alone, indicators for the development of hypertrophic cardiomyopathy occur with increased frequency in MYBPC3Δ25bp/D389V carriers. Residue D389 lies in the IgI-like C2 domain that is part of the N-terminal region of MyBPC. To probe the effects of mutation D389V on structure, thermostability, and protein–protein interactions, we produced and characterized wild-type and mutant constructs corresponding to the isolated 10 kDa C2 domain and a 52 kDa N-terminal fragment that includes subdomains C0 to C2. Our results show marked reductions in the melting temperatures of D389V mutant constructs. Interactions of construct C0–C2 D389V with the cardiac isoforms of myosin-2 and actin remain unchanged. Molecular dynamics simulations reveal changes in the stiffness and conformer dynamics of domain C2 caused by mutation D389V. Our results suggest a pathomechanism for the development of HCM based on the toxic buildup of misfolded protein in young MYBPC3Δ25bp/D389V carriers that is supplanted and enhanced by C-zone haploinsufficiency at older ages.
BRAF and MEK Inhibitors Affect Dendritic-Cell Maturation and T-Cell Stimulation
Authors: Hoyer Stefanie , Eberlein Valentina , Schuler Gerold , Berking Carola , Heinzerling Lucie , Schaft Niels , Dörrie Jan
Published: November 2021

BRAF and MEK inhibitor (BRAFi/MEKi) combinations are currently the standard treatment for patients with BRAFV600 mutant metastatic melanoma. Since the RAS/RAF/MEK/ERK-pathway is crucial for the function of different immune cells, we postulated an effect on their function and thus interference with anti-tumor immunity. Therefore, we examined the influence of BRAFi/MEKi, either as single agent or in combination, on the maturation of monocyte-derived dendritic cells (moDCs) and their interaction with T cells. DCs matured in the presence of vemurafenib or vemurafenib/cobimetinib altered their cytokine secretion and surface marker expression profile. Upon the antigen-specific stimulation of CD8+ and CD4+ T cells with these DCs or with T2.A1 cells in the presence of BRAFi/MEKi, we detected a lower expression of activation markers on and a lower cytokine secretion by these T cells. However, treatment with any of the inhibitors alone or in combination did not change the avidity of CD8+ T cells in peptide titration assays with T2.A1 cells. T-helper cell/DC interaction is a bi-directional process that normally results in DC activation. Vemurafenib and vemurafenib/cobimetinib completely abolished the helper T-cell-mediated upregulation of CD70, CD80, and CD86 but not CD25 on the DCs. The combination of dabrafenib/trametinib affected DC maturation and activation as well as T-cell activation less than combined vemurafenib/cobimetinib did. Hence, for a potential combination with immunotherapy, our data indicate the superiority of dabrafenib/trametinib treatment.
Probing the Structural Dynamics of the Activation Gate of KcsA Using Homo-FRET Measurements
Authors: Díaz-García Clara , Renart Maria Lourdes , Poveda José Antonio , Giudici Ana Marcela , González-Ros José M. , Prieto Manuel , Coutinho Ana
Published: November 2021

The allosteric coupling between activation and inactivation processes is a common feature observed in K+ channels. Particularly, in the prokaryotic KcsA channel the K+ conduction process is controlled by the inner gate, which is activated by acidic pH, and by the selectivity filter (SF) or outer gate, which can adopt non-conductive or conductive states. In a previous study, a single tryptophan mutant channel (W67 KcsA) enabled us to investigate the SF dynamics using time-resolved homo-Förster Resonance Energy Transfer (homo-FRET) measurements. Here, the conformational changes of both gates were simultaneously monitored after labelling the G116C position with tetramethylrhodamine (TMR) within a W67 KcsA background. At a high degree of protein labeling, fluorescence anisotropy measurements showed that the pH-induced KcsA gating elicited a variation in the homo-FRET efficiency among the conjugated TMR dyes (TMR homo-FRET), while the conformation of the SF was simultaneously tracked (W67 homo-FRET). The dependence of the activation pKa of the inner gate with the ion occupancy of the SF unequivocally confirmed the allosteric communication between the two gates of KcsA. This simple TMR homo-FRET based ratiometric assay can be easily extended to study the conformational dynamics associated with the gating of other ion channels and their modulation.
ENPP2 Methylation in Health and Cancer
Authors: Panagopoulou Maria , Fanidis Dionysios , Aidinis Vassilis , Chatzaki Ekaterini
Published: November 2021

Autotaxin (ATX) encoded by Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) is a key enzyme in Lysophosphatidic Acid (LPA) synthesis implicated in cancer. Although its aberrant expression has been reported, ENPP2 methylation profiles in health and malignancy are not described. We examined in silico the methylation of ENPP2 analyzing publicly available methylome datasets, to identify Differentially Methylated CpGs (DMCs) which were then correlated with expression at gene and isoform levels. Significance indication was set to be FDR corrected p-value < 0.05. Healthy tissues presented methylation in all gene body CGs and lower levels in Promoter Associated (PA) regions, whereas in the majority of the tumors examined (HCC, melanoma, CRC, LC and PC) the methylation pattern was reversed. DMCs identified in the promoter were located in sites recognized by multiple transcription factors, suggesting involvement in gene expression. Alterations in methylation were correlated to an aggressive phenotype in cancer cell lines. In prostate and lung adenocarcinomas, increased methylation of PA CGs was correlated to decreased ENPP2 mRNA expression and to poor prognosis parameters. Collectively, our results corroborate that methylation is an active level of ATX expression regulation in cancer. Our study provides an extended description of the methylation status of ENPP2 in health and cancer and points out specific DMCs of value as prognostic biomarkers.
Density Functional Theory Study on the Adsorption Mechanism of Sulphide Gas Molecules on α-Fe2O3(001) Surface
Authors: Zhou Li , Zhu Huadong , Zeng Wen
Published: November 2021

Sulphide gas is an impurity that affects the quality of natural gas, which needs reasonable storage and transportation. In this work, we investigated the adsorption structure and electronic behavior of hydrogen sulfide (H2S), carbonyl sulfur (COS), and methyl mercaptan (CH3SH) on sulphide gas molecules on pure and vacant α-Fe2O3(001) surfaces by density functional theory with geometrical relaxations. The results show that H2S and CH3SH are mainly adsorbed in the form of molecules on the pure Fe2O3(001) surface. On the vacant α-Fe2O3(001) surface, they can be adsorbed on Fe atoms in molecular form and by dissociation. The absolute value of the adsorption energy of H2S and CH3SH on the vacancy defect α-Fe2O3 surface is larger, and the density of states show that the electron orbital hybridization is more significant, and the adsorption is stronger. The charge differential density and Mulliken charge population analysis show that the charge is rearranged and chemical bonds are formed. The affinity of H2S to the vacancy α-Fe2O3(001) surface is slightly higher than that of CH3SH, while COS molecules basically do not adsorb on the α-Fe2O3(001) surface, which may be related to the stable chemical properties of the molecules themselves.
Ultramorphological Comparison of Proboscis and Associated Sensilla of Scotogramma trifolii and Protoschinia scutosa (Lepidoptera: Noctuidae)
Authors: Zhang Chuan-Min , Niu Yue , Hu Gui-Lin , Lu Ji-Qi
Published: November 2021

The proboscis is an important feeding organ for the glossatan moths, mainly adapted to the flower and non-flower visiting habits. The clover cutworm, Scotogramma trifolii Rottemberg, and the spotted clover moth, Protoschinia scutosa (Denis & Schiffermuller), are serious polyphagous pests, attacking numerous vegetables and crops, resulting in huge economic losses. However, the feeding behavior and mechanisms of the adult stage remain unsatisfactorily explored. In this study, the proboscis morphology of S. trifolii and P. scutosa are described in detail using scanning electron microscopy, with the aim of investigating the morphological differences and feeding behavior of these two species. The proboscises of S. trifolii and P. scutosa are similar in morphology and structure and are divided into three zones (Zone 1–3) based on the morphological changes of the dorsal legulae. Three sensillum types are located on the proboscises of both species, sensilla chaetica, sensilla basiconica, and sensilla styloconica. Significant differences were observed in the length of the proboscis and each zone between these two species, as well as in sensilla size and number. Based on the morphology of the proboscis and associated sensilla, S. trifolii and P. scutosa are potential flower visitors, which was also reinforced by the pollen observed at the proboscis tip. These results will strengthen our understanding of the structure of the proboscis related to the feeding behavior of Noctuidae.
Incidence of Mortality, Acute Kidney Injury and Graft Loss in Adult Kidney Transplant Recipients with Coronavirus Disease 2019: Systematic Review and Meta-Analysis
Authors: Chen Jia-Jin , Kuo George , Lee Tao Han , Yang Huang-Yu , Wu Hsin Hsu , Tu Kun-Hua , Tian Ya-Chung
Published: November 2021

The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19−23%), an intensive care unit admission rate of 26% (95% CI: 22–31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62–81%), an acute kidney injury rate of 44% (95% CI: 39–49%), a kidney replacement therapy rate of 12% (95% CI: 9–15%), and a graft loss rate of 8% (95% CI: 5–15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.
Open Hip Abductor Repair Hitting the Sack-Abductor Tendon Repair Significantly Improves Sleep Quality
Authors: Zimmerer Alexander , Navas Luis , Pfeil Dominic , Hauschild Matthias
Published: November 2021

Purpose: To (1) describe the prevalence of abnormal sleep quality in patients with hip abductor tears (HAT), to (2) determine whether sleep quality improves after open HAT repair, and to (3) to report clinical short-term outcomes in patients undergoing open HAT repair. Methods: The data of 28 patients (29 hips) who underwant open HAT repair were prospectively analyzed at midterm follow-up. The Pittsburgh Sleep Quality Index (PSQI), modified Harris Hip Score (mHHS), the University of California, Los Angeles activity scale (UCLA), and Visual Analog Scale (VAS) for pain were determined via questionnaire. Paired t-tests were applied to compare preoperative and post-operative Patient-reported Outcome Measures (PROMs). Logistic regression was performed to determine the association between PSQI improvement achievement and demographic variables (laterality, sex, age, body-mass-index (BMI), and preoperative mHHS). The minimal clinically important difference (MCID) was calculated for the mHHS. Results: A total of 28 patients were included. Four patients (14.3%) suffered post-operative complications after open HAT repair. The predominance of patients was female (77.4%), with a mean age of 60 ± 13 years. The average follow-up was 30.35 ± 16.62 months. Preoperatively, 27 (96.4%) patients experienced poor sleep quality (PSQI > 5); at follow-up, 7 (25%) patients experienced poor sleep quality. Univariate logistical regression analysis demonstrated no significant association between preoperative demographic data and achieving postoperative PSQI < 5. The MCID of mHHS was calculated to be 12.5. Overall, 90% of patients achieved MCID for mHHS. Conclusion: Preoperative sleep quality was impaired in 96.4% of HAT patients (PSQI > 5). However, these patients showed an improvement in sleep disturbances after open HAT repair in the early postoperative period. Ninety percent of patients showed significant improvements in mHHS and achieved the corresponding MCID. Level of Evidence: Case series; Level IV.
Implant Survival in Immediately Loaded Full-Arch Rehabilitations Following an Anatomical Classification System—A Retrospective Study in 1200 Edentulous Jaws
Authors: Caramês João Manuel Mendez , Marques Duarte Nuno da Silva , Caramês Gonçalo Bartolo , Francisco Helena Cristina Oliveira , Vieira Filipe Araújo
Published: November 2021

This retrospective study analyzed implant survival of immediate implant-supported fixed complete denture (IFCD) treatment options (TOs) based on the level of alveolar atrophy (CC). Records of 882 patients receiving a total of 6042 implants at one private referral clinic between 2004 and 2020 were considered. The mean follow-up period was 3.8 ± 2.7 years. Cumulative implant survival rates (CSRs) were analyzed as a function of CCs and TOs according to Mantel-Haenszel and Mantel-Cox. Hazard risk ratios for implant loss were compared using Cox regression. Confounding factors were identified using mixed Cox regression models. The 2- and 5-year CSRs were 98.2% and 97.9%, respectively. Maxillary 2- and 5-year CSRs were lower (97.7% and 97.3%) compared to mandibular CSRs (99.8% and 98.6%) (p = 0.030 and 0.0020, respectively). The CC did not influence CSRs of IFCDs in the mandible (p = 0.1483 and 0.3014, respectively) but only in the maxilla (p = 0.0147 and 0.0111), where CSRs decreased with increasing atrophy. TOs did not statistically differ in terms of survival rate for a given level of alveolar atrophy. The adaption of IFCD treatments to the level of atrophy and patient-specific risk factors can result in high CSRs, even at different levels of bone atrophy.
CyBERT: Cybersecurity Claim Classification by Fine-Tuning the BERT Language Model
Authors: Ameri Kimia , Hempel Michael , Sharif Hamid , Lopez Jr. Juan , Perumalla Kalyan
Published: November 2021

We introduce CyBERT, a cybersecurity feature claims classifier based on bidirectional encoder representations from transformers and a key component in our semi-automated cybersecurity vetting for industrial control systems (ICS). To train CyBERT, we created a corpus of labeled sequences from ICS device documentation collected across a wide range of vendors and devices. This corpus provides the foundation for fine-tuning BERT’s language model, including a prediction-guided relabeling process. We propose an approach to obtain optimal hyperparameters, including the learning rate, the number of dense layers, and their configuration, to increase the accuracy of our classifier. Fine-tuning all hyperparameters of the resulting model led to an increase in classification accuracy from 76% obtained with BertForSequenceClassification’s original architecture to 94.4% obtained with CyBERT. Furthermore, we evaluated CyBERT for the impact of randomness in the initialization, training, and data-sampling phases. CyBERT demonstrated a standard deviation of ±0.6% during validation across 100 random seed values. Finally, we also compared the performance of CyBERT to other well-established language models including GPT2, ULMFiT, and ELMo, as well as neural network models such as CNN, LSTM, and BiLSTM. The results showed that CyBERT outperforms these models on the validation accuracy and the F1 score, validating CyBERT’s robustness and accuracy as a cybersecurity feature claims classifier.
Parasitic Capillary Waves on Small-Amplitude Gravity Waves with a Linear Shear Current
Authors: Murashige Sunao , Choi Wooyoung
Published: November 2021

This paper describes a numerical investigation of ripples generated on the front face of deep-water gravity waves progressing on a vertically sheared current with the linearly changing horizontal velocity distribution, namely parasitic capillary waves with a linear shear current. A method of fully nonlinear computation using conformal mapping of the flow domain onto the lower half of a complex plane enables us to obtain highly accurate solutions for this phenomenon with the wide range of parameters. Numerical examples demonstrated that, in the presence of a linear shear current, the curvature of surface of underlying gravity waves depends on the shear strength, the wave energy can be transferred from gravity waves to capillary waves and parasitic capillary waves can be generated even if the wave amplitude is very small. In addition, it is shown that an approximate model valid for small-amplitude gravity waves in a linear shear current can reasonably well reproduce the generation of parasitic capillary waves.
Detection of Cytokines and Collectins in Bronchoalveolar Fluid Samples of Patients Infected with Histoplasma capsulatum and Pneumocystis jirovecii
Authors: Carreto-Binaghi Laura E. , Tenorio Eda P. , Morales-Villarreal Fernando R. , Aliouat El Moukhtar , Zenteno Edgar , Martínez-Orozco José-Arturo , Taylor Maria-Lucia
Published: November 2021

Histoplasmosis and pneumocystosis co-infections have been reported mainly in immunocompromised humans and in wild animals. The immunological response to each fungal infection has been described primarily using animal models; however, the host response to concomitant infection is unknown. The present work aimed to evaluate the pulmonary immunological response of patients with pneumonia caused either by Histoplasma capsulatum, Pneumocystis jirovecii, or their co-infection. We analyzed the pulmonary collectin and cytokine patterns of 131 bronchoalveolar lavage samples, which included HIV and non-HIV patients infected with H. capsulatum, P. jirovecii, or both fungi, as well as healthy volunteers and HIV patients without the studied fungal infections. Our results showed an increased production of the surfactant protein-A (SP-A) in non-HIV patients with H. capsulatum infection, contrasting with HIV patients (p < 0.05). Significant differences in median values of SP-A, IL-1β, TNF-α, IFN-γ, IL-18, IL-17A, IL-33, IL-13, and CXCL8 were found among all the groups studied, suggesting that these cytokines play a role in the local inflammatory processes of histoplasmosis and pneumocystosis. Interestingly, non-HIV patients with co-infection and pneumocystosis alone showed lower levels of SP-A, IL-1β, TNF-α, IFN-γ, IL-18, IL-17A, and IL-23 than histoplasmosis patients, suggesting an immunomodulatory ability of P. jirovecii over H. capsulatum response.
Machine Learning Algorithms to Predict In-Hospital Mortality in Patients with Traumatic Brain Injury
Authors: Hsu Sheng-Der , Chao En , Chen Sy-Jou , Hueng Dueng-Yuan , Lan Hsiang-Yun , Chiang Hui-Hsun
Published: November 2021

Traumatic brain injury (TBI) can lead to severe adverse clinical outcomes, including death and disability. Early detection of in-hospital mortality in high-risk populations may enable early treatment and potentially reduce mortality using machine learning. However, there is limited information on in-hospital mortality prediction models for TBI patients admitted to emergency departments. The aim of this study was to create a model that successfully predicts, from clinical measures and demographics, in-hospital mortality in a sample of TBI patients admitted to the emergency department. Of the 4881 TBI patients who were screened at the emergency department at a high-level first aid duty hospital in northern Taiwan, 3331 were assigned in triage to Level I or Level II using the Taiwan Triage and Acuity Scale from January 2008 to June 2018. The most significant predictors of in-hospital mortality in TBI patients were the scores on the Glasgow coma scale, the injury severity scale, and systolic blood pressure in the emergency department admission. This study demonstrated the effective cutoff values for clinical measures when using machine learning to predict in-hospital mortality of patients with TBI. The prediction model has the potential to further accelerate the development of innovative care-delivery protocols for high-risk patients.
Poor-Prognosis Patients Affected by Glioblastoma: Retrospective Study of Hypofractionated Radiotherapy with Simultaneous Integrated Boost and Concurrent/Adjuvant Temozolomide
Authors: Gregucci Fabiana , Surgo Alessia , Bonaparte Ilaria , Laera Letizia , Ciliberti Maria Paola , Carbonara Roberta , Gentile Maria Annunziata , Giraldi David , Calbi Roberto , Caliandro Morena , Sasso Nicola , D’Oria Salvatore , Somma Carlo , Martinelli Gaetano , Surico Giammarco , Lombardi Giuseppe , Fiorentino Alba
Published: November 2021

Background: Glioblastoma (GBM) is a very poor-prognosis brain tumor. To date, maximal excision followed by radiochemotherapy, in 30 fractions, is the standard approach. Limited data are present in the literature about hypofractionated radiotherapy (hypo-RT) in GBM poor prognosis patients. Thus, this retrospective study was conducted to evaluate efficacy and toxicity of hypo-RT with simultaneous integrated boost (SIB) in association with temozolomide (TMZ) in this patient setting. Methods: Poor-prognosis GBM patients underwent surgery (complete, subtotal or biopsy) followed by SIB-hypo-RT and concomitant/adjuvant TMZ. The prescription dose was 40.05 Gy (15 fractions) with a SIB of 52.5 Gy (3.5 Gy/fraction) on surgical cavity/residual/macroscopic disease. Volumetric modulated arc therapy was performed. Results: From July 2019 to July 2021, 30 poor-prognosis patients affected by GBM were treated by SIB-hypo-RT; 25 were evaluated in the present analysis due to a minimum follow up of 6 months. The median age and KPS were 65 years and 60%, respectively. At the median follow-up time of 15 months (range 7–24), median and 1-year overall survival and progression-free survival were 13 months and 54%, and 8.4 months and 23%, respectively. No acute or late neurological side effects of grade ≥ 2 were reported. Grade 3–4 hematologic toxicity occurred in three cases. Conclusion: SIB-hypo-RT associated with TMZ in poor-prognosis patients affected by GBM is an effective and safe treatment. Prospective studies could be warranted.
Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations
Authors: Laukhtina Ekaterina , Lemberger Ursula , Bruchbacher Andreas , Ilijazi Dafina , Korn Stephan , Berndl Florian , D’Andrea David , Susani Martin , Enikeev Dmitry , Compérat Eva , Shariat Shahrokh F. , Hassler Melanie R.
Published: November 2021

The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate KMT2D expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in KMT2D exons. Cox regression was used to assess the relationship of KMT2D protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, p = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic KMT2D variants and tumor location (p = 0.02). Pathogenic KMT2D variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic KMT2D alterations. Both IHC and NGS analyses of KMT2D failed to detect a statistically significant association between KMT2D protein or KMT2D gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all p > 0.05). KMT2D alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and KMT2D mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy.
Pharmaco-Metabolomics of Inhaled Corticosteroid Response in Individuals with Asthma
Authors: Kachroo Priyadarshini , Sordillo Joanne E. , Lutz Sharon M. , Weiss Scott T. , Kelly Rachel S. , McGeachie Michael J. , Wu Ann Chen , Lasky-Su Jessica A.
Published: November 2021

Metabolomic indicators of asthma treatment responses have yet to be identified. In this study, we aimed to uncover plasma metabolomic profiles associated with asthma exacerbations while on inhaled corticosteroid (ICS) treatment. We determined whether these profiles change with age from adolescence to adulthood. We utilized data from 170 individuals with asthma on ICS from the Mass General Brigham Biobank to identify plasma metabolites associated with asthma exacerbations while on ICS and examined potential effect modification of metabolite-exacerbation associations by age. We used liquid chromatography–high-resolution mass spectrometry-based metabolomic profiling. Sex-stratified analyses were also performed for the significant associations. The age range of the participating individuals was 13–43 years with a mean age of 33.5 years. Of the 783 endogenous metabolites tested, eight demonstrated significant associations with exacerbation after correction for multiple comparisons and adjusting for potential confounders (Bonferroni p value < 6.2 × 10−4). Potential effect modification by sex was detected for fatty acid metabolites, with males showing a greater reduction in their metabolite levels with ICS exacerbation. Thirty-eight metabolites showed suggestive interactions with age on exacerbation (nominal p-value < 0.05). Our findings demonstrate that plasma metabolomic profiles differ for individuals who experience asthma exacerbations while on ICS. The differentiating metabolites may serve as biomarkers of ICS response and may highlight metabolic pathways underlying ICS response variability.
A Study on Cultural Urban Regeneration Using Modern Industrial Resources: Focusing on the Site-Specific Cultural Places of Gunsan, South Korea
Authors: Chung Hokyung , Lee Jongoh
Published: November 2021

Gunsan is a port city located on the west coast of South Korea. After the port was opened in 1899, foreign concessions were formed there, and the modern city began to be formed in accordance with Japanese colonial policy. This region grew into a modern port city by exporting rice harvested from the plains in the hinterland to Japan and managed and controlled commercial and industrial products of the surrounding area. Modern industrial facilities such as warehouses, financial, and administration facilities necessary for seizing the food resources for the colony were built there, and Gunsan developed as a hub city in the southwestern region of South Korea during the 1930s. However, after liberation in 1945, the number of modern industrial facilities in this area, which contained traces of Japanese imperialism, gradually declined. In the 2000s, as urbanisation accelerated, the problem of abandoned modern industrial facilities was raised, and the necessity of urban regeneration by utilizing the modern industrial facilities scattered in the original downtown of Gunsan emerged. The purpose of this paper is to examine the regional activation and cultural regeneration of the city by using modern industrial facilities as cultural places and targeting the case of Gunsan, which was developed as a colonial-planned city. In particular, through field studies, this paper examines those cultural spaces, utilising modern industrial facilities that contribute to the formation of regional uniqueness, mediate local communities, and create future values of sustainable cultural regeneration.
One in a Million: Genetic Diversity and Conservation of the Reference Crassostrea angulata Population in Europe from the Sado Estuary (Portugal)
Authors: Chiesa Stefania , Lucentini Livia , Chainho Paula , Plazzi Federico , Angélico Maria Manuel , Ruano Francisco , Freitas Rosa , Costa José Lino
Published: November 2021

The production of cupped oysters is an important component of European aquaculture. Most of the production relies on the cultivation of the Pacific oyster Crassostrea gigas, although the Portuguese oyster Crassostrea angulata represents a valuable product with both cultural and economic relevance, especially in Portugal. The authors of the present study investigated the genetic diversity of Portuguese oyster populations of the Sado estuary, both from natural oyster beds and aquaculture facilities, through cox1 gene fragment sequencing. Then, a comparison with a wide dataset of cupped oyster sequences obtained from GenBank (up to now the widest available dataset in literature for the Portuguese oyster) was performed. Genetic data obtained from this work confirmed that the Pacific oyster does not occur in the natural oyster beds of the Sado estuary but showed that the species occasionally occurs in the oyster hatcheries. Moreover, the results showed that despite the founder effect and the bottleneck events that the Sado populations have experienced, they still exhibit high haplotype diversity. Risks are arising for the conservation of the Portuguese oyster reference populations of the Sado estuary due to the occurrence of the Pacific oyster in the local hatcheries. Therefore, researchers, local authorities, and oyster producers should work together to avoid the loss of this valuable resource.
Expression of Kisspeptin 1 in the Brain of the Adult Sea Lamprey Petromyzon marinus
Authors: Sobrido-Cameán Daniel , Yáñez-Guerra Luis , Deber Alexandre , Rodicio María , Barreiro-Iglesias Antón
Published: November 2021

Kisspeptin peptides play major roles in the regulation of reproduction and puberty onset in mammals. While most mammals only have one kisspeptin gene, other jawed vertebrates present two or three genes. Recent data also revealed the presence of two genes in lampreys (jawless vertebrates). However, apart from gene sequence data, there is almost no information on the kisspeptinergic system of lampreys. Here, we report phylogenetic and cluster-based analyses showing that the duplication of the ancestral kisspeptin gene occurred before the separation of jawless and jawed vertebrates. We also studied the expression of the kisspeptin transcripts in the brain of post-metamorphic juveniles and upstream migrating adult sea lampreys. Our in situ hybridization results revealed expression of kisspeptin 1 in hypothalamic neurons, which indicates that the hypothalamic expression of kisspeptins is an ancestral character in vertebrates. We also observed the presence of kisspeptin 1 expressing neurons in the paratubercular (posterior tubercle) nucleus of the diencephalon. This is the first description of the presence of kisspeptin 1 expressing neurons in this brain region in any vertebrate. We did not detect expression of kisspeptin 2 in the juvenile or adult sea lamprey brain with in situ hybridization. Our data provides an anatomical basis to study the role of kisspeptin 1 in the hypothalamic-pituitary system of lampreys and the contribution of diencephalic kisspeptinergic neurons to different circuits of the lamprey brain.
Systematic Investigation of Plant-Parasitic Nematodes Associated with Main Subtropical Crops in Guangxi Province, China
Authors: Mo Yi-Xue , Mo Ai-Su , Qiu Zhuo-Qiu , Li Bing-Xue , Wu Hai-Yan
Published: November 2021

Plant parasitic nematodes (PPNs) are a pathogenic group that causes momentous crop yield loss by retarding plant growth and development through plant parasitization. In this study, the distribution of PPNs based on the main crops in Guangxi Province of China was investigated. A total of 425 samples of soil or roots from sugarcane, rice, maize, and soybean were collected in 68 counties, and a total of 48 order/family/genera of PPNs were identified, of which some genera were found in more than one crop. A total of 31 order/family/genera of PPNs were found in rice, among which Hirschmanniella was the most abundant, accounting for 79.23%, followed by Tylenchorhynchus (34.43%). Forty order/family/genera were observed in maize, of which the dominant genera were Pratylenchus and Tylenchorhynchus at 45.14% and 32.64%, respectively. In addition, 30 order/family/genera of PPNs were detected from sugarcane, and the percentages of Tylenchorhynchus and Helicotylenchus were 70.42% and 39.44%, respectively. The main crop of Eastern ecological regions was rice, with a high frequency of Hirschmanniella. The greatest frequency of Pratylenchus was found in the Western eco-region, which had a large area of maize. In the Northern eco-region, rice and maize were popular, with abundant Hirschmanniella and Helicotylenchus. In the Central eco-region, Pratylenchus was detected on the main crop of sugarcane. Hirschmanniella (72.94%) was dominant in clay, and Tylenchorhynchus (54.17%) showed the highest frequency in loam. The distribution of PPNs varied with different altitudes. The diversity of this phenomenon was closely related to host plants. These results could improve understanding of the distribution of PPNs and provide important information for controlling PPNs.
Potential Biomarkers of Metastasizing Paragangliomas and Pheochromocytomas
Authors: Snezhkina Anastasiya , Pavlov Vladislav , Dmitriev Alexey , Melnikova Nataliya , Kudryavtseva Anna
Published: November 2021

Paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors originating from paraganglionic tissue in many sites of the body. Most PPGLs are characterized by nonaggressive behavior but all of them have the potential to metastasize. PPGLs represent a great diagnostic dilemma as it is difficult to recognize tumors that are likely to be metastasizing; criteria of malignancy can be found both in benign and metastatic forms. This review aims to analyze the current knowledge of the nature of metastasizing PPGLs paying particular attention to head and neck paragangliomas (HNPGLs). Potential predictors of the malignancy risk for PPGLs were summarized and discussed. These data may also help in the development of diagnostic and prognostic strategies, as well as in the identification of novel potential therapeutic targets for patients with PPGLs.
Na+-Taurocholate Co-Transporting Polypeptide (NTCP) in Livers, Function, Expression Regulation, and Potential in Hepatitis B Treatment
Authors: Zhao Xiaoyu , Iqbal Waqas , Sun Pingnan , Zhou Xiaoling
Published: November 2021

Chronic hepatitis B virus (HBV) infection has become one of the leading causes of liver cirrhosis and hepatocellular carcinoma globally. The discovery of sodium taurocholate co-transporting polypeptide (NTCP), a solute carrier, as a key receptor for HBV and hepatitis D virus (HDV) has opened new avenues for HBV treatment. Additionally, it has led researchers to generate hepatoma cell lines (including HepG2-NTCP and Huh-7-NTCP) susceptible to HBV infection in vitro, hence, paving the way to develop and efficiently screen new and novel anti-HBV drugs. This review summarizes the history, function and critical findings regarding NTCP as a viral receptor for HBV/HDV, and it also discusses recently developed drugs targeting NTCP.
Study of Concrete under Combined Action of Aggressive Environment and Long-Term Loading
Authors: Blikharskyy Yaroslav , Selejdak Jacek , Kopiika Nadiia , Vashkevych Rostyslav
Published: November 2021

A significant part of reinforced concrete structures is subjected to intensive environmental impact during operation. This can cause local destruction and failure of buildings if obligatory measures are not taken to protect them from corrosion. This is especially true for industrial buildings, where the environment could be contaminated with aggressive products or waste. An important issue is the development of methods for calculating the load-bearing capacity and serviceability of reinforced concrete structures with corrosion damage. The main reason for this is the necessity to determine the durability and reliability of buildings and structures and the estimation of their safe operation time. As corrosion damages of concrete are a critical issue, more detailed experimental studies are needed. This paper presents experimental studies of concrete prisms under the simultaneous action of an aggressive environment and a constant level of compressive force. In total, 32 prisms under different loading conditions and in different aggressive medium were tested. Samples were divided in series, for which different load levels were chosen (0.25fck, 0.35fck, 0.45fck). Additionally, control samples in the air and immersed in water were tested. During the experiment, different parameters were monitored and recorded: decrease of cross-sectional size, the temperature and environmental humidity. Results of the study showed that destruction occurred due to the presence of corrosion damages of concrete and a reduction of the cross-sectional area. The stresses in the concrete at the destruction stage were less than the value of the prism strength by 10–12%. It was established that along the contour of the section, there is a partially degraded layer of concrete of 1.5–3.7 mm thickness, with corrosion microcracks and corrosion products. Additionally, experimental and theoretical diagrams of concrete with corrosion damages were obtained and compared. The ultimate deformations of concrete with corrosion damage, which correspond to the prismatic strength of concrete, in comparison with undamaged concrete were lower by 11–18%. Therefore, the concrete strength is decreased during exploitation under loading in an aggressive environment, which needs to be taken into account during calculations.
Optimal Placement of Viscoelastic Vibration Dampers for Kirchhoff Plates Based on PSO Method
Authors: Lenartowicz Agnieszka , Przychodzki Maciej , Guminiak Michał , Garbowski Tomasz
Published: November 2021

The main subject of this study is to determine the optimal position of a fixed number of viscoelastic dampers on the surface of a thin (Kirchhoff-Love) plate. It is assumed that the dampers are described according to the generalized Maxwell model. In order to determine the optimal position of the dampers, a metaheuristic optimization method is used, called the particle swarm optimization method. The non-dimensional damping ratio of the first mode of the plate vibrations is assumed as an objective function in the task. The dynamic characteristics of the plate with dampers are determined by solving the non-linear eigenproblem using the continuation method. The finite element method is used to determine the stiffness matrix and the mass matrix occurring in the considered eigenproblem. The results of exemplary numerical calculations are also presented, where the final optimal arrangement of dampers on the surface of sample plates with different boundary conditions is shown graphically.
Comparative Analysis of the Phase Interaction in Plasma Surfaced NiBSi Overlays with IVB and VIB Transition Metal Carbides
Authors: Bober Mariusz , Senkara Jacek , Li Hong
Published: November 2021

Important applications of transition metal carbides (TMCs) are as wear resistant composite layers deposited by plasma transferred arc welding (PTAW) and laser methods. Growing interest in them has also been observed in additive manufacturing and in HEA technology (bulk composite materials and layers), and in the area of energy conversion and storage. This paper presents the results of comparative studies on interfacial interactions in the NiBSi−TMCs system for two border IVB and VIB TM groups of the periodic table. Model (wettability and spreadability) and application experiments (testing of the PTAW-obtained carbide particle−matrix boundaries) were performed. Fe from partially melted steel substrates is active in the liquid NiBSi−TMCs system. It was revealed that the interaction of TMCs with the liquid NiBSi matrix tends to increase with the group number, and from the top to bottom inside individual groups. Particles of IVB TMCs are decomposed by penetration of the liquid along the grain boundaries, whereas those of VIB are decomposed by solubility in the matrix and secondary crystallization. No transition zones formed at the interfacial boundaries of the matrix−IVB group TMCs, unlike in the case of the VIB group. The experimental results are discussed using the data on the TMC electronic structure and the physicochemical properties.
Heterogeneity in Lateral Distribution of Polycations at the Surface of Lipid Membrane: From the Experimental Data to the Theoretical Model
Authors: Molotkovsky Rodion J. , Galimzyanov Timur R. , Ermakov Yury A.
Published: November 2021

Natural and synthetic polycations of different kinds attract substantial attention due to an increasing number of their applications in the biomedical industry and in pharmacology. The key characteristic determining the effectiveness of the majority of these applications is the number of macromolecules adsorbed on the surface of biological cells or their lipid models. Their study is complicated by a possible heterogeneity of polymer layer adsorbed on the membrane. Experimental methods reflecting the structure of the layer include the electrokinetic measurements in liposome suspension and the boundary potential of planar bilayer lipid membranes (BLM) and lipid monolayers with a mixed composition of lipids and the ionic media. In the review, we systematically analyze the methods of experimental registration and theoretical description of the laterally heterogeneous structures in the polymer layer published in the literature and in our previous studies. In particular, we consider a model based on classical theory of the electrical double layer, used to analyze the available data of the electrokinetic measurements in liposome suspension with polylysines of varying molecular mass. This model suggests a few parameters related to the heterogeneity of the polymer layer and allows determining the conditions for its appearance at the membrane surface. A further development of this theoretical approach is discussed.