bluuebunny/crossref_metadata_2025 huggingface dataset:
The Real Cause of Differential Aging in the Twin “paradox”
Authors: Liu Gordon
Published: February 2022

Physicists have employed various approaches to solve the “paradox” and offered a consistent conclusion that the traveller twin is younger than the homebody twin. However, some authors attribute the cause of differential aging to acceleration, while others believe that acceleration should not be regarded as the source of differential aging, but frame switch is. So far there is no agreement on this issue. Actually, acceleration and frame switch should not be regarded as the source of differential aging. The author will introduce a thought experiment in which two very long spacecraft are moving in opposite directions at a speed close to the speed of light to discuss the real cause of differential aging. The author found that the real cause of differential aging in the twin “paradox” is because of the asymmetry of destination choice. People always choose their destinations in the universe rather than in spacecraft. The destinations are always stationary relative to the homebody twin and moving relative to the traveller twin. Once we choose a destination in a reference frame, the distance is the proper length in this reference frame, but the distance will contract in another moving reference frame, thus the recording time will be shorter.
The Influence of Self-Efficacy in Ethical Consideration and Decision-Making Processes
Authors: Eyo Nsini Anselem , Hasan Nurul Ain Mohd
Published: February 2022

The study explores factors influencing PR practitioners’ ethical consideration in decision-making process. In line with the theoretical approach of self-efficacy, practitioner’s performances emanate from individual self-efficacy aligned with organization culture and objectives. Thus, self-efficacy inspires individual behavior based upon their belief and capacity to execute or perform actions essential to produce expected results. Based on 20 semi-structured interviews with Malaysian PR practitioners, questions were based on a set of collected and collated reviews of the literature as well as guided by responsible advocacy theory and self-efficacy theory to facilitate the interview process. Data from the interviews were transcribed, coded, and thematically analyzed. Findings of the study indicate that organizational interest, goals, and business focus, corporate politics, boss-influenced clients or stakeholder pressure and practitioners’ personal values were influential factors affecting practitioner’s ethical and decision-making dispositions. Further findings showed that the level of discretions practitioners processed in decision-making process is based on a combination of internal factors like organization business focus and external factors like client needs and pressure. Given that practitioners are bounded by organization laws as employees; it is recommended that independent bodies be put in place other than national public relations associations to serve as a regulator over unethical practices and protection of practitioners against corporate powers.
Student Worksheets Based on Virtual Labs: Efforts to Optimize Science Practicum in Pandemic Times
Authors: Astriani Dyah , Nurita Tutut , Rosdiana Laily , F An Nuril Maulida , Hidayati Siti Nurul , M Roihanna Waliyyul
Published: February 2022

The use of virtual lab-based students worksheet in science learning aims to optimize practicum activities during the pandemic. Virtual-based students worksheet take advantage of the features that are already available and adapted to the material to be practiced, so knowledge is needed to develop virtual lab-based students worksheet s. The activity of compiling virtual lab-based students worksheet was attended by science teacher participants from private schools in Gresik Regency, with the One Group Pretest Posttest design. Activity participants were given a pretest and then compiled a virtual lab-based students worksheet and posttest. The resulting students worksheet is assessed for feasibility using the students worksheet assessment instrument. The pretest and posttest data were analyzed by N-gain showing an increase of 0.64 in the medium category. The assessment of the participant students worksheet shows that the virtual lab-based students worksheet that have been created are in accordance with the instructions, the category is very feasible, so that it can be implemented as an effort to optimize science practicum during the pandemic.
Impact of Temperature and Material Variation on Mechanical Properties of Parts Fabricated with Fused Deposition Modelling (FDM) Additive Manufacturing
Authors: Sehhat M. Hossein , Mahdianikhotbesara Ali , Yadegari Farzad
Published: February 2022

Additive Manufacturing (AM) can be deployed for space exploration purposes, such as fabricating different components of robots’ bodies. The produced AM parts should have desirable thermal and mechanical properties to withstand the extreme environmental conditions, including the severe temperature variations on moon or other planets which cause changes in parts’ strengths and may fail their operation. Therefore, the correlation between operational temperature and mechanical properties of AM fabricated parts should be evaluated. In this study, three different types of polymers, including polylactic acid (PLA), polyethylene terephthalate glycol (PETG), and acrylonitrile butadiene styrene (ABS), were used in Fused Deposition Modeling (FDM) process to fabricate several parts. The mechanical properties of produced parts were then investigated at various temperatures to generate knowledge on the correlation between temperature and type of material. When varying the operational temperature during tensile tests, the material’s glass transition temperature was found influential in determining the type of material failure. Among the materials used, ABS showed the best mechanical properties at all temperatures due to its highest glass transition temperatures. The results of statistical analysis indicated the temperature as the significant factor on tensile strength while the type of material was not a significant factor.
Selenium-integrated multi-resonance induced TADF emitters boost EQE of electroluminescence to 40.5% with ultra-low efficiency roll-off
Authors: Hu Yu Xuan , Miao Jingsheng , Hua Tao , Huang Zhongyan , Qi Yanyu , Zou Yang , Qiu Yuntao , Xia Han , Liu He , Cao Xiaosong , Yang Chuluo
Published: February 2022

Multi-resonance induced thermally activated delayed fluorescent (MR-TADF) materials have shown great potential in high-efficiency and narrowband organic light-emitting diodes (OLEDs). However, obvious efficiency roll-off attributed to slow reverse intersystem crossing (RISC) process hinders MR-TADF materials from practical applications. Here, we report a heavy-atom incorporating emitter, namely BNSeSe, based on selenium-integrated boron-nitrogen skeleton, showing 100% photoluminescence quantum yield and the highest rate of RISC (kRISC) of 2.0 × 106 s-1 among MR-TADF molecules. The corresponding OLEDs exhibit excellent external quantum efficiency (EQE) up to 36.8% and ultra-low roll-off character at high brightness (with very small roll-off values of 2.8% and 14.9% at 1000 cd m-2 and 10000 cd m-2, respectively). Furthermore, the outstanding capability to harvest triplet excitons also enables BNSeSe to be a superior sensitizer for hyperfluorescence (HF) device, which shows state-of-the-art performance with record high EQE of 40.5%, power efficiency (PE) beyond 200 lm W-1 and luminance close to 200000 cd m-2.
A Proficient Technique for Recognizing the Online Digital Signature in Project Registration System (PRS)
Authors: Chakravarthi R. Ravi , Palagan C. Anna , Dharamshi Ravindra Ratilal , Vadivelan N , Taware Shrikant
Published: February 2022

In recent education system, project submission is crucial for college students to complete their respective studies. The understudies needed to propose their undertaking before finishing the pre-last year. One of the critical assessment forms like course Project Registration System (PRS) helps the students and their education board to enhance the knowledge and skill level required for competitive world. During project submission, authentication is important to prevent the unauthorized submission of proposal and contrast the signature utilizing classification techniques such as Kernel Based Artificial Neural Network (K-ANN), Kernel Based K-Nearest Neighbor (K-KNN), Kernel Based Self Organizing Map (K-SOM) and Kernel based Support Vector Machine (K-SVM). The data collection based on online digital signature with various students and the proposed classification techniques gives better performance and accuracy compared with other techniques.
Chlorpheniramine maleate exerts an anti-keloid activity in vivo and in vitro
Authors: Zheng Min , Qian Huan , Wang Chen , Zhang Mengwen , Wang Zhefang , Fangjie Shao
Published: February 2022

Background: Keloid can cause numerous adverse consequences, severely affecting patients' physical and mental health. The mechanisms of keloid scarring remain unclear, as revealed by the inability of patients to satisfactorily manage this benign neoplastic disease. Studies suggest that H1 blockers, such as Tranilasts, inhibit keloid overgrowth and hyperplasia. Chlorpheniramine maleate (CPM) has been extensively employed as an H1 receptor blocker, whereas its treatment effects on keloid formation are unknown. The present study aimed to evaluate the inhibiting effect of CPM on keloid, which might provide a novel strategy for keloid treatment. Methods: In vitro, Cell Counting Kit-8 (CCK-8), apoptosis, cell cycle and migration assays of keloid fibroblasts (KFs) were performed to evaluate the effects of CPM on inhibiting the proliferation and apoptosis of dermal fibroblasts (DFs) and keloid fibroblasts (KFs), and the potential mechanism of action was analyzed by qPCR. In vivo, nude mice keloid scar model was built to assess the therapeutic effect of CPM and explore its possible mechanism.Results: CCK-8 and apoptosis experiments revealed that the concentration of 0.15 mM CPM could inhibit keloid fibroblasts proliferation and promote apoptosis with minimal impact on DFs. Cell cycle and migration experiments confirmed that a 0.15 mM CPM could inhibit the proliferation and migration of keloid fibroblasts. Moreover, qPCR revealed that CPM down-regulated the expressions of TGF-β, STAT3, JAK1, and Ki-67 genes in KFs. Together with in vitro experiments, CPM could inhibit keloid scar formation and down-regulate the expressions of TGF-β, STAT3, JAK1, and Ki-67 genes in the tissue.Conclusion: Chlorpheniramine maleate could be an ideal localized therapeutic strategy in keloid treatment.
Changes In And Asymmetry of The Proteome In The Human Foetal Frontal Lobe During Early Development
Authors: Liu Shuwei , Zhao Xiaotian , Liang Wenjia , Wang Wenjun , Liu Hailan , Zhang Xiaolei , Liu Chengxin , Zhu Caiting , Cui Baoxia , Tang Yuchun
Published: February 2022

Hemispheric asymmetry is an important feature of the human brain that develops before birth. The inherent asymmetry of the brain is of great significance for cognition, language and other functions in humans. An understanding of normal brain and asymmetry development in the earliest period will further our understanding of how the different hemispheres prioritize specific functions. However, the core genetic mechanism is still unknown. Here, we analysed the developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy. We found that during this period, the difference in expression between gestational weeks (GWs) increased, and the difference in asymmetric expression decreased. The patterns of protein expression changes in the bilateral frontal lobes were different. Our results show that brain asymmetry can be observed in the early stage of foetal development. Human brain asymmetry is the result of differential gene expression before birth in the early foetal stage and develops before functional asymmetry. Researchers can use these findings to further investigate the mechanisms of brain asymmetry. We propose that both sides of the brain should be analysed separately in future multiomics research and human brain mapping studies.
4-Ethylbenzaldehyde from the volatilome of Annona muricata against Meloidogyne incognita
Authors: Campos Vicente , de Paula Letícia , Terra Willian , Barros Aline , Pacheco Paulo , Silva Maysa Da , Pedroso Marcio
Published: February 2022

In the present study, we demonstrated the potent nematicidal activity of volatile organic compounds (VOCs) released by the Annona muricata leaf macerate. In addition, the toxicity of the compound 4-ethylbenzaldehyde was reported in the various phases of the Meloidogyne incognita life cycle. By biofumigation, even the lowest concentration of soursop leaf macerate tested (1.0%) caused a reduction in nematode hatching, infectivity and reproduction. Analysis of the soursop volatilome performed by gas chromatography coupled with mass spectrometry revealed 41 compounds, of which three, were selected for studies against the nematode. Only 4-ethylbenzaldehyde showed nematicidal activity in vitro, against M. incognita J2 and hatching. As a soil fumigant, 4-ethylbenzaldehyde at dose of 1 mL per litre of substrate had an effect similar (P < 0.05) to that of the commercial fumigant Dazomet (250 µg mL−1). In addition, this molecule, when applied directly to M. incognita-infested soil, significantly reduced nematode infectivity and reproduction compared to the negative control. Therefore, 4-ethylbenzaldehyde shows potential for the development of a new commercial nematicide with reduced toxicity to the environment and high efficacy against plant parasitic nematodes. However, field assays are necessary to confirm these results, which were obtained under controlled conditions.
Multi-task Joint Strategies of Self-supervised Representation Learning on Biomedical Networks for Drug Discovery
Authors: Wang Xiaoqi , Cheng Yingjie , Yang Yaning , Li Fei , Peng Shaoliang
Published: February 2022

Self-supervised representation learning (SSL) on biomedical networks provides new opportunities for drug discovery that lacks available biology or clinic phenotype. However, how to effectively combine multiple SSL models is still challenging and has been rarely explored. Therefore, we propose multi-task joint strategies of self-supervised representation learning on biomedical networks for drug discovery, named MSSL2drug. We design six basic SSL tasks inspired by various modality features including structures, semantics, and attributes in heterogeneous biomedical networks.
In addition, fifteen combinations of multiple tasks are evaluated by a graph attention-based adversarial multi-task learning framework in two drug discovery scenarios. The results suggest two important findings. (1) Combinations of multimodal tasks achieve the best performance compared to other multi-task joint strategies. (2) The joint training of local and global SSL tasks yields higher performance than random task combinations. Therefore, we conjecture that the multimodal and local-global combination strategies can be treated as a guideline of multi-task SSL for drug discovery.
Soft-Tissue Tumor Reporting and Data System (St-Rads): Mri Reporting Guideline with Multi-Institutional Validation Study of Extremity Soft Tissue Tumors
Authors: Chhabra Avneesh , Ashikyan Oganes , Ratakonda Raghu , Bajaj Gitanjali , Thakur Uma , Pezeshk Parham , Xi Yin , Zaid Marwa , Callan Alexandra , Murphy William , Kumar Rajendra , Amini Behrang
Published: February 2022

BackgroundTo our knowledge, no current guideline exists in outlining follow-up or interventional strategies in musculoskeletal soft tissue tumor management. To develop and validate soft-tissue tumor reporting and data system (ST-RADS) with the hypothesis that the proposed guideline reliably and accurately assists in separating benign from malignant musculoskeletal soft tissue tumors.Methods This is a multi-institutional cross-sectional study of soft-tissue masses. An expert consensus agreement was reached for ST-RADS categories using the terminology from WHO classification. Adipocytic tumors, T2-hyperintense and T2-hypointense masses of extremities with a wide spectrum of histologies were assessed. MRI categories were: STRADS 0 - incomplete imaging, I – no lesion identified, II - definitely benign, III - probably benign, IV - indeterminate or suspicious for malignancy, V- highly suggestive of malignancy, and VI - known biopsy-proven malignancy or recurrence. Eight readers evaluated cases and ICC and AUC were calculated. Results 200 soft tissue masses were tested. There was good inter-reader agreement with ICC= 0.72 [95% CI=0.64-0.79] and 0.69 [95% CI=0.59-0.70] for adipocytic and T2-hyperintense, and fair, 0.48 [95% CI=0.35-0.62] for T2- hypointense masses. The sensitivity and specificity for detection of malignancy were 96% and 63%, 93% and 71%, 64% and 84% for adipocytic, T2-hyperintense, and T2-hypointense masses, respectively. The AUC was 0.79-0.89.Conclusion ST-RADS guideline using standardized terminology stratifies musculoskeletal tumors into benign and malignant categories and provides management strategy. This MRI-based guideline is meant to be a "dynamic" document that can be further refined and updated in response to future user feedback and as new scientific data becomes available.
Nononcological Advanced Chronic Disease and Palliative Needs: Survival Analysis
Authors: Morán-Tiesta Cristina , Sanz-Ventureira Lara , Jiménez-Domene Paula , Aira-Ferrer Pilar , Cano-Gonzalez Jose Manuel , Martínez-Cruz María Belén , Sanz-Peces Eva María , Diaz-Sierra Genoveva , Sedano-SanLlorente Begoña , Sánchez-Isac María , Gil-Moreno Juan Carlos , Cura-González Isabel Del , De Miguel-Sánchez Cristina , Group ECANO
Published: February 2022

Background: Professionals who care for patients with advanced chronic nononcological disease need accurate prognostic tools. There are validated prognostic indices for nononcological pathology in the fields of internal medicine (PALIAR and PROFUND indices) and palliative care (PPI indices, PaP score, ECOG, PPS, KI). The objective of this study is to describe survival and analyzsed factors associated with mortality in advanced chronic nononcological disease patients in palliative care services in the Community of Madrid.Methods: Multilongitudinal observational study of a prospective cohort with a 6-month follow-up. Sociodemographic, clinical, analytical, service use, functionality, and prognostic indices were measured. Survival was analysed at 3 and 6 weeks and at 1, 2, 3, 4, 5, and 6 months through Kaplan–Meier curves. After the bivariate analysis, a Cox proportional-hazards multivariate regression analysis was performed. Results: 217 patients were included. The mean age (SD) was 78.8 (12.6), and 47.5% were women. Some 129 patients died. Mean survival (SD) at 6 months was 146.12 (130.14) days, median (IQR) survival 111.5 (17.50-254.50). All prognostic indices (PALIAR p<0.001, PROFUND p<0.005, PPI p<0.016, PaP Score p<0.001, ECOG p<0.002, PPS p<0.018, and KI p<0.016) predicted mortality at 6 months. The variables that explained survival at less than 3 months were PPS (HR (CI) 0.96 (0.95-0.98), p<0.000), leukocytes (HR (CI) 1.06 (1.02-1.10), p<0.000), delirium at the last admission (HR (CI) 1.79 (1.02-3.09) p<0.030), and ≥4 hospitalization in the last year (HR (CI) 1.82 (1.16-2.88) p<0.010). The variables that explained 6-month survival were PPS (HR (CI) 0.96 (0.94-0.97), p<0.000), leukocytes (HR (CI) 1.06 (1.03-1.09), p<0.000), and haemoglobin (HR (CI) 0.88 (0.82-0.97) p<0.005).Conclusions: Clinical and resource use variables were predictors of mortality in survivals shorter than 3 months, but not in survivals longer than 3 months.
Does Environmental Pollution Affect Resident Well-Being?
Authors: Leng Pinyi , Zhu Yifan , Zhang Haoyuan , Zhou Qian
Published: February 2022

The Ordered Logit regression model was constructed based on the data from Chinese General Social Survey and China Statistical Yearbook 2017. The empirical analysis shows that air pollution positively affects resident well-being through economic growth, water pollution and solid waste pollution negatively affects resident well-being, and environmental pollution can reduce resident well-being by damaging their health. The impact of environmental pollution on resident well-being is heterogeneous.The low-income people have lower requirements for environmental quality, while the high-income people are more affected, and the eastern region is more affected in the three regions. In addition, residents' subjective environmental pollution perception will negatively affect their well-being. In order to improve the resident well-being, it is necessary to strengthen the management of the environment and improve the quality of the environment so as to realize the increase of resident well-being and economic development.
Algorithm for Automatic Analysis of Smooth Pursuit Eye Movements Using a Combination of Video-oculography and Deep Learning–Based Object Detection
Authors: Hirota Masakazu , Kato Kanako , Fukushima Megumi , Ikeda Yuka , Hayashi Takao , Mizota Atsushi
Published: February 2022

In the evaluation of smooth pursuit eye movements (SPEMs), recording the stimulus onset time is mandatory. In the laboratory, the stimulus onset time is recorded by electrical signal or programming, and video-oculography (VOG) and the visual stimulus are synchronized. Nevertheless, because the examiner must manually move the fixation target, recording the stimulus onset time is challenging in daily clinical practice. Thus, this study aimed to develop an algorithm for evaluating SPEMs while testing the nine-direction eye movements without recording the stimulus onset time using VOG and deep learning–based object detection (single-shot multibox detector), which can predict the location and types of objects in a single image. The algorithm of peak fitting–based detection correctly classified the directions of target orientation and calculated the latencies and gains within the normal range while testing the nine-direction eye movements in healthy individuals. These findings suggest that the algorithm of peak fitting–based detection has sufficient accuracy for the automatic evaluation of SPEM in clinical settings.
Biochemical determinants of thrombin generation in a general population with arterial and venous disease background
Authors: Paridon Pauline C.S. van , Panova-Noeva Marina , Oerle Rene van , Schulz Andreas , Prochaska Jürgen H. , Arnold Natalie , Schmidtmann Irene , Beutel Manfred , Pfeiffer Norbert , Münzel Thomas , Lackner Karl J. , Cate Hugo ten , Wild Philipp S. , Spronk Henri M.H.
Published: February 2022

Background: The current study aims to identify the biochemical determinants of plasma thrombin generation in a large population-based study by comparing individuals with a history of arterial or venous thrombosis to cardiovascular healthy individuals. Methods: This study comprised 502 individuals with a history of arterial disease, 195 with history of venous thrombosis and 1402 cardiovascular healthy individuals (reference sample) from the population-based Gutenberg Health Study (GHS). Calibrated Automated Thrombography was assessed and coagulation factors were measured by means of BCS XP Systems. To assess the biochemical determinants of TG variables, a multiple linear regression analysis, adjusted for age, sex and antithrombotic therapy, was conducted. Results: The lag time was mainly positively associated with the natural coagulant and anti-coagulant factors in the reference sample, i.e. higher factors result in a longer lag time. The same determinants were negative for individuals with a history of arterial or venous thrombosis, with a 10 times higher effect size. ETP was predominantly positively determined by factor II, VIII, X and IX in all subsamples. However, the effect sizes of the reported associations were 4 times higher for the arterial and venous subsamples in comparison to the reference sample.Conclusion: This large-scale analysis demonstrated a stronger effect of the coagulant and natural anti-coagulant factors on the thrombin potential in individuals with a history of arterial or venous thrombosis as compared to healthy individuals, which implicates sustained alterations in the plasma coagulome in subjects with a history of thrombotic vascular disease, despite intake of antithrombotic therapy.
Association of EPHA3 mutations with tumor mutational burden and efficacy of immune checkpoint inhibitors in cancer patients
Authors: Han Fujun , Zhang Siqi , Zheng Mengge , Nie Deheng , Tian Huimin , Liu Wenjia , Pei Fengli , Liu Wenhui
Published: February 2022

Background: The erythropoietin-producing human hepatocellular receptor A3 (EPHA3), which was identified as a tumor antigen targeted by a lytic T-cell response in melanoma patients, is relatively tumor specific. Moreover, EPHA3 is frequently mutated in human cancers, and the association of EPHA3 mutations with immunotherapy efficacy in cancer patients has not been reported to date. Methods: We conducted a retrospective analysis of 1756 patients with 11 cancer types after immune checkpoint inhibitor (ICI) monotherapy identified from The Cancer Genome Atlas (TCGA) data portal in April 2021. The associations between EPHA3 mutations and tumor mutational burden (TMB), durable clinical benefit (DCB), and overall survival (OS) was assessed. Results: Among all 1756 patients, the mutational frequency of EPHA3 was 6.7%. The TMB of patients with EPHA3 mutations was substantially higher than that in patients without the mutations (odds ratio [OR], 5.35, 95% confidence interval [CI], 3.58–8.04; P < .001). EPHA3 mutations were significantly associated with better DCB (median: 52.3% vs 32.8%; OR, 2.24; 95%CI, 1.15–4.41; P = .011) and OS (median: 40.0 vs 16.0 months; hazard ratio, 0.57; 95% CI, 0.42–0.77; P < .001) compared with EPHA3 wild-type. Multivariable and subgroup analyses showed that these associations were independent of all known covariates, including TMB. Conclusions: These findings indicate that EPHA3 mutations may be associated with higher TMB, better immune response, and better survival than EPHA3 wild-type. Despite the need for validation, cancer patients with EPHA3 mutations might be appropriate candidates for ICI monotherapy.
CFTR heterozygosity in severe airways disease with recurrent airway infections: a retrospective review
Authors: Priel Eldar , Adatia Adil , Kjarsgaard Melanie , Nair Parameswaran
Published: February 2022

Rationale: Patients with asthma who have neutrophilic bronchitis may have an underlying cause leading to increased susceptibility to airway infections. Methods: Retrospective review of patients with asthma who had a previous history of recurrent exacerbations that had been associated with airway or sinus infections referred to a tertiary asthma center between 2005-2020. Demographics, clinical features, and airway inflammation type determined by sputum cytometry were compared between CFTR carriers and non-carriers. Multiple linear regression was used to identify clinical predictors of CFTR carrier status. Response to nebulized hypertonic saline was assessed by comparing the number of infective exacerbations before and after its initiation. Results: 75 patients underwent CFTR mutation testing. Of these, 13 (17%) were CFTR carriers. The most common mutation was ∆F508. CFTR carriers were older (adjusted odds ratio 1.06 (CI 95% 1.01, 1.13)) and had more frequent flares requiring hospitalization (4.19 (1.34, 24.74)). Neutrophilic airway inflammation was the most common inflammatory subtype in CFTR carriers, though 8/13 also had eosinophilic bronchitis. Nebulized hypertonic saline was well tolerated by most and reduced the frequency of infective exacerbations.Conclusions: The prevalence of CFTR heterozygosity in this cohort with recurrent neutrophilic bronchitis is higher than in the general population. Respiratory disease in CFTR carriers is associated with older age and may cause significant morbidity. Airway neutrophilia is the most common inflammatory subtype, but >50% had eosinophilic bronchitis requiring treatment. Hypertonic saline appears to be well tolerated and effective in reducing the number of infective exacerbations.
Relationship between Crustal Temperature and Depth of Seismogenic Layer Estimated from the Inland Earthquakes along the Sea of Japan Beneath Japanese Islands
Authors: Yano Tomoko Elizabeth , Matsubara Makoto , Matsumoto Takumi , Ishiyama Tatsuya
Published: February 2022

We found the depth of the seismogenic layer based on D95, the cut-off depth at which 95% of the earthquakes occurred, from the event catalog before the mainshock of five major earthquakes, such as the 2003 Northern Miyagi, the 2004 Chuetsu, the 2008 Iwate-Miyagi, the 2016 Kumamoto, and the 2016 central Tottori earthquakes. Our results show that the main event depth, aftershock distribution, and main slip area are confined above the base of the seismogenic zone. A simple modelling of the geothermal gradient based on surface heat flow shows that the temperature at the base of the seismogenic zone is constrained to a range of 250-450 ºC. We confirmed that mainshock depths for five cases nucleated at the deepest portion of the seismogenic layer, and large rupture areas occurred within the seismogenic layer. Some aftershock streaks of the 2016 Kumamoto earthquake occurred at 5 km deeper than the bottom of seismogenic depth.
Clinical and Humanistic Impact of Pharmacotherapeutic Follow-Up in Patients with Type 1 Diabetes Mellitus Treated Judicially
Authors: Mendonça Thays Santos , Oliveira William Neves , Belo Vinícius Silva , Silva Eduardo Sérgio , Pereira Mariana Linhares , Obreli-Neto Paulo Roque , Baldoni André Oliveira
Published: February 2022

Background: There is a lack of studies that assess the effectiveness of pharmacotherapeutic follow-up in the context of the judicialization of insulin analogues. Aims: To evaluate the clinical and humanistic impact of pharmacotherapeutic follow-up in patients with type 1 diabetes mellitus who receive insulin analogues by judicial decision in a Brazilian municipality. Methods: A quasi-experimental study of the before-and-after type was carried out through pharmacotherapeutic follow-up. Patients who accepted to participate in the study underwent laboratory tests of glycemic and lipid profile before and after the intervention, and underwent five pharmaceutical consultations. In addition, quality of life and health, knowledge, and skills related to insulin application techniques were analyzed. Results: 28 patients participated in all stages. Of these, most were female (53.6 %), with a mean age of 32.8 ± 11.6 years. After the intervention, there was a reduction in blood glucose levels, blood pressure and increased body mass index. In addition, there was greater knowledge and skills regarding insulin application techniques, improved quality of life, health, greater number of medications used, reduction of pharmacotherapeutic problems and improvement in eating habits. Conclusion: The pharmacotherapeutic follow-up promoted clinical and humanistic benefits, with improvement in quality of life and health.
Novel Association of Lyme Disease, Age, and Atopic Dermatitis
Authors: Lee Brandon T , Galloway Sarah , Strausz Satu , Hansen Paige , Torrez-Dulgeroff Laughing Bear , Blacker Grace , Yiu Ying Ying , Mansfield Paul , Affiliation FinnGen , Saleem Atif , Gars Eric , Sanders Erin , Weissman Irving L , Ollila Hanna , Tal Michal Caspi
Published: February 2022

Background
Borrelia burgdorferi is a bacterial spirochete that can cause Lyme disease after infecting a susceptible host. Immune responses to the bacteria are highly variable and host specific. The murine substrain, C3H/HeJ, is one of the most frequently utilized mouse models for Lyme disease. In this study, we sought to investigate the correlation of age with onset and severity of dermatitis, both in C3H/HeJ mice infected with B. burgdorferi as well as humans who have had a diagnosis of Lyme disease.
Methods
Female C3H/HeJ mice aged 6-8 weeks, 1 year, or 2 years were infected intraperitoneally with 105 B. burgdorferi. Dermatitis of the tail was evaluated by gross examination and histology. Human data via electronic health records of 342,499 Finnish individuals was tested and analyzed for associations between Lyme disease and atopic dermatitis.
Results
Dermatitis worsened over the course of untreated infection, with ulceration, hemorrhaging, flaking, hair loss, and dark lesions as well as spongiosis and acanthosis. These features of dermatitis were present in infected mice after 1 year of age. This relationship among Lyme disease, atopic dermatitis, and host age seen in the C3H/HeJ mouse model is consistent with a large pool (342,499) of human epidemiological data from Finland. We identified 5,248 individuals with Lyme disease and 17,233 with atopic dermatitis in FinnGen. Retrospective analysis shows Lyme disease is associated with atopic dermatitis (OR = 1.91 [1.68 -2.37], P < 2e−16). More visits due to Lyme disease complications (3 or more visits versus 1 visit) were associated with atopic dermatitis (OR = 2.19 [1.35-3.55], P = 0.0014) and risk of developing atopic dermatitis over time (HR=2.26 [1.54-3.95], P = 0.0017).
Conclusion
Data from mice and humans reveal a novel relationship among Lyme disease, age, and atopic dermatitis. Through defined pathological scoring, we demonstrate the onset of murine atopic dermatitis with B. burgdorferi infection, which is further exacerbated by host age at time of infection. In humans, a diagnosis of Lyme disease in FinnGen was associated with atopic dermatitis and further research is warranted to establish causation.
β-Elemene prevented cisplatin resistance of small cell lung cancer cell H446 by regulating MiR-199a-5p-mediated autophagy
Authors: Li Honglin
Published: February 2022

Background Multidrug resistance (MDR) in small cell lung cancer (SCLC) is a clinical dilemma in chemotherapy. A natural compound, β-elemene has been found to inhibit MDR cancers. We hypothesized that β-elemene regulated cisplatin-resistant SCLC by targeting autophagy-related miR-199a-5p. Methods We assessed the IC50 of multiple chemotherapeutic agents toward SCLC cells H446 and MDR SCLC cells H446/EP with or without β-elemene using CCK-8. We overexpressed (OE) and knocked down (KD) miR-199a-5p in H446 and H446/EP and determined the expression of miR-199a-5p, autophagy-related proteins, and the formation of autophagolysosomes using QPCR, western blotting, and MDC staining respectively. We validate the binding of miR-199a-5p to p62 using the Dual-Luciferase assay. Results β-Elemene decreased drug resistance of H446 to cisplatin, etoposide, paclitexal, epirubicin, irinotecan, and vinorelbine. Cisplatin increased LC3II/LC3I, ATG5, p62, and the formation of autophagolysosomes in H446 cells, but not in H446/EP cells, and these effects were blocked by β-elemene. The OE of miR-199a-5p reduced cisplatin-induced increase of LC3II/LC3I, ATG5, p62, and the formation of autophagolysosomes while the KD of miR-199a-5p did the opposite. the OE of miR-199a-5p reduced the luciferase signal of wild-type p62, but not that of p62 with mutations at the predicted binding site. The effect of β-elemene on cisplatin-induced autophagy was validated in OE-H446 and KD-H446/EP. Conclusions β-Elemene prevented MDR in H446 and it prevents cisplatin resistance of H446 by targeting the autophagy regulation of miR-199a-5p.
The Swarm Langmuir Probe Ion Drift, Density and Effective Mass (SLIDEM) Product
Authors: Pakhotin Ivan , Burchill J. K. , Förster M. , Lomidze L.
Published: February 2022

Current methods for estimating ion density on Swarm rely on the assumption of 100% O+ and no along-track ion velocity flows. These assumptions are routinely violated, particularly on the nightside and during high-latitude and polar cap traversals, compromising the accuracy of the measurements. The use of faceplate current data along with the Langmuir probe ion admittance measurements, and orbital-motion limited (OML) theory, make it possible to relax some of the assumptions inherent in current ESA Swarm density estimates. This further yields along-track ion drift and effective ion mass estimates. This paper describes the theoretical basis for estimating revised ion density, providing a new estimate for effective ion mass, as well as an alternative way of estimating along-track ion drift. The complete Swarm historical dataset has been generated and validated using empirical models (International Reference Ionosphere (IRI-2016), and Weimer (2005)), as well as ground-spacecraft conjunctions. Case studies and statistical results reveal clear geophysical signatures in the new product of light ions at low- and mid-latitudes and along-track ion drift at high latitudes, and their response to space weather.
Key Modulators of the Stress Granule Response TIA1, TDP-43, and G3BP1 are Altered by Polyglutamine Expanded ATXN7
Authors: Niss Frida , Piñero-Paez Laura , Zaidi Wajiha , Hallberg Einar , Ström Anna-Lena
Published: February 2022

Spinocerebellar ataxia type ATXN7 (SCA7) and other polyglutamine (polyQ) diseases are caused by expansions of polyQ repeats in disease specific proteins. Aggregation of the polyQ proteins resulting in various forms of cellular stress, that could induce the stress granule (SG) response, is believed to be a common pathological mechanism in these disorders. SGs can contribute to cell survival, but have also been suggested to exacerbate disease pathology by seeding protein aggregation. In this study, we show that two SG related proteins, TDP-43 and TIA1, are sequestered into the aggregates formed by polyQ expanded ATXN7 in SCA7 cells. Interestingly, mutant ATXN7 also localises to induced SGs and this association altered the shape of the SGs. In spite of this, neither the ability to induce nor disassemble SGs, in response to arsenite stress induction or relief, was affected in SCA7 cells. Moreover, we could only detect a small, non-significant, increase in ATXN7 aggregation following SG induction. However, mutant ATXN7 expression in itself increased the speckling of the SG nucleating protein G3BP1 and the SG response. Taken together, our results indicate that the SG response is induced, and although some key modulators of SGs show altered behaviour, the dynamics appear normal in the presence of mutant ATXN7.
Photo-electrochemical reduction of CO2 to Methanol on Quaternary chalcogenide loaded Graphene-TiO2 ternary nanocomposite fabricated via Pechini method
Authors: Otgonbayar Zambaga , Oh Won-Chun
Published: February 2022

Nano-sized catalysts have been widely studied for CO2 reduction to hydrocarbon fuels. Herein, we study the new-modeled ternary nanocomposite that can use in photocatalytic and electrochemical CO2 reduction. In order to adjust the energy of the catalyst band and the characteristics of the effective charge carrier, we firstly synthesized the AgFeNi2S4 quaternary nanocomposite and then used it to model the ternary nanocomposites, and all the nanocomposites were synthesized using the Pechini method. The activity of the nanocomposites is directly related to the output of methanol productions. In a photocatalytic CO2 reduction experiment, the methanol yield under UV radiation was 8.679, 6.349, 4.136%, and under Vis-light it was 6.291, 4.738, and 2.339%, respectively. The stability and reusability of the catalysts are the main factors that can define the sturdiness of a photocatalyst in practical applications. The sturdiness of the catalyst has been tested four times by recycling tests, and as a result, the yield of the final product (methanol) has not decreased, confirming the stability of the catalyst. In electrochemical CO2 reduction, the Faraday efficiency is the main parameter that defines the performance of the working electrode and the evolution of methanol. The Faraday efficiency of the AFNSGT ternary nanocomposite was 44.25%; this is an increase in the value of the Faraday efficiency, which proves that the design of the new nanocomposite successfully increases the activity of the working electrode and has a positive effect on the electrochemical reduction of CO2. The photocatalytic and electrochemical CO2 reduction data show that the preparation method, morphological state, and charge carrier properties of the photocatalyst are important for the catalytic activity and efficiency of the methanol evolution pathway.
Effects of COX and 5-LOX Pathways on Different Seizure Models
Authors: Taskiran Mehmet
Published: February 2022

PurposeThis study aimed to examine the relationship between epilepsy and COX/5-LOX inflammation pathways in the penicillin and pentylenetetrazole (PTZ) induced epilepsy models.MethodsFor this purpose, forty-two albino male Wistar rats were used in this study. In the penicillin and PTZ-induced epilepsy models, epileptiform activity was induced by injection of penicillin (500 IU, i.c) and PTZ (35 mg/kg, i.p, three times a week), respectively. Licofelone (20 mg/kg, i.p), a dual inhibitor of COX/5-LOX, and esculetin (20 mg/kg, i.p), a 5-LOX inhibitor, were given. In the penicillin-induced epilepsy model, ECoG activity was recorded for 180 min. In the PTZ-induced epilepsy model, both ECoG activity was recorded and behavioral parameters were performed. ResultsIn the penicillin groups, both licofelone and esculetin decreased the mean spike frequency and amplitude during the experiments. In the PTZ groups, licofelone (20 mg/kg, i.p) was more effective than esculetin (20 mg/kg, i.p). Licofelone showed its protective effects both in ECoG activity and in behavioral parameters. Esculetin was less effective when compared to licofelone.ConclusionThe electrophysiological and behavioral data from the present study indicated that inflammation pathways might have a crucial role in controlling epileptiform activity in rats. Licofelone might be a valuable candidate in advanced studies.
Clinical Outcomes of Ankle Distraction Arthroplasty Versus Supramalleolar Osteotomy for Treatment of Post-traumatic Ankle Arthritis in Young Adult Patients
Authors: Shao Xinzhong , Yang Zongyu , Cui Liang , Tao Shiwu , Wang Li , Zhang Fengqi , Zhao Jianyong
Published: February 2022

BackgroundIn the late stage of traumatic ankle arthritis, the pain symptoms are aggravated and the joint function is obviously limited. However, in the face of young patients with high activity requirements, there are still great challenges in how to preserve the joint and effectively treat traumatic ankle arthritis. Ankle distraction arthroplasty and supramalleolar osteotomy are both options for such medical condition, but the studies comparing their clinical outcomes have been scarce. The purpose of this study is to compare the clinical outcomes of ankle distraction arthroplasty and supramalleolar osteotomy in the treatment of severe traumatic ankle arthritis in young adult patients.MethodsThis was designed a retrospective study, enrolling 73 consecutive young adult patients who underwent ankle distraction arthroplasty (n=32) or supramalleolar osteotomy (n=41) for post-traumatic ankle arthritis from January 2017 to December 2020. All patients had at least 24-month follow-ups. The outcome measures were the comparisons of the pre- and postoperative visual analog scale (VAS) for pain relief, the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, angle range of motion (ROM), complications, patient-rated overall satisfaction and radiological evaluation of changes in ankle joint space width (JSW).ResultsSeventy-three patients (73 ankles) (100%) returned for final evaluation at an average of 32 months (range, 24 to 48 months) follow-up. At an average of 6 months follow-up, both groups achieved significantly improved VAS, AOFAS, ROM and JSW scores compared to those at baseline ( p<0.05), but not significantly differed between groups (all p>0.05). Either, both groups did not differ in in the tibial anterior surface angle(TAS), talar tilt angle(TT), tibial lateral surface angle(TLS), except for the correcting the load-bearing line of the ankle and hindfoot. However, at the last follow-up, patient satisfaction and ankle function scores in the ankle distraction arthroplasty group showed a downward trend, while the function scores in the supramalleolar osteotomy group showed an increasing trend, which was statistically significant.ConclusionsBoth ankle distraction arthroplasty and supramalleolar osteotomy are effective treatment options for the severe post-traumatic ankle arthritis in the young adult patients. From the long-term follow-up, however, supramalleolar osteotomy is better than ankle distraction arthroplasty in ankle score and patient satisfaction evaluation.Level of evidence: Level III, retrospective comparative series.
Longitudinal Changes In Pulmonary Function And Patient Reported Outcomes After Lung Cancer Surgery
Authors: Shin Sumin , Kong Sunga , Kang Danbee , Lee Genehee , Cho Jong Ho , Shim Young Mog , Cho Juhee , Kim Hong Kwan , Park Hye Yun
Published: February 2022

Background: Surgery is the mainstay of treatment for non-small cell lung cancer, but the decline in pulmonary function after surgery is noticeable and needs attention. The aim of this study was to evaluate longitudinal changes in pulmonary function and its integrated patient-reported outcomes (PROs) after lung cancer surgery. Methods: The data were obtained from a prospective cohort study, Coordinate Approach to Cancer Patients’ Health for Lung Cancer. Changes in forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1) 2 weeks, 6 months, and 1 year after surgery and the corresponding modified Medical Research Council (mMRC) dyspnea scale and chronic obstructive lung disease assessment test (CAT) score were evaluated. Mixed effect models were used to investigate the changes in pulmonary function and PROs.Results: Among 620 patients, 477 (76.9%) underwent lobectomy, while 120 (19.4%) and 23 (3.7%) were treated with limited resection and bilobectomy/pneumonectomy, respectively. Both FVC and FEV1 markedly decreased 2 weeks after surgery and improved thereafter but did not recover to baseline values. The corresponding mMRC dyspnea scale and CAT score also showed worsening immediately after surgery. The dyspnea scale was still higher, while the CAT score returned to baseline 1 year after surgery, although the breathlessness and lack of energy persisted. Patients treated with bilobectomy/pneumonectomy showed -2.3%, -6.8%, and -6.0% more decrease in FEV1 (% predicted) compared to the patients who underwent lobectomy at each time point. Moreover, worsening quality of life including dyspnea was also robust in patients treated with pneumonectomy/bilobectomy.Conclusions: After lung cancer surgery, pulmonary function and PROs was remarkable decreased at immediate post-operative period and improved thereafter except for dyspnea and lack of energy. The proper information on timeline of change in lung function and symptoms following lung cancer surgery could guide patient care approach following lung cancer surgery. Trial Registration: ClinicalTrials.gov; No.: NCT03705546; URL: www.clinicaltrials.gov