bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial ASD-related genes are involved in oligodendrocyte differentiation
Authors: Takanezawa Yuta , Tanabe Shogo , Kato Daiki , Ozeki Rie , Komoda Masayo , Suzuki Tatsunori , Baba Hiroko , Muramatsu Rieko 
Published: September 2021

AbstractAutism spectrum disorders (ASD) are associated with mutations of chromodomain-helicase DNA-binding protein 8 (Chd8) and tuberous sclerosis complex 2 (Tsc2). Although these ASD-related genes are detected in glial cells such as microglia, the effect of Chd8 or Tsc2 deficiency on microglial functions and microglia-mediated brain development remains unclear. In this study, we investigated the role of microglial Chd8 and Tsc2 in cytokine expression, phagocytosis activity, and neuro/gliogenesis from neural stem cells (NSCs) in vitro. Chd8 or Tsc2 knockdown in microglia reduced insulin-like growth factor-1(Igf1) expression under lipopolysaccharide (LPS) stimulation. In addition, phagocytosis activity was inhibited by Tsc2 deficiency, microglia-mediated oligodendrocyte development was inhibited, in particular, the differentiation of oligodendrocyte precursor cells to oligodendrocytes was prevented by Chd8 or Tsc2 deficiency. These results suggest that ASD-related gene expression in microglia is involved in oligodendrocyte differentiation, which may contribute to the white matter pathology relating to ASD.
Carbamylation of elastic fibers is a molecular substratum of aortic stiffness
Authors: Doué Manon , Okwieka Anaïs , Berquand Alexandre , Gorisse Laëtitia , Maurice Pascal , Velard Frédéric , Terryn Christine , Molinari Michaël , Duca Laurent , Piétrement Christine , Gillery Philippe , Jaisson Stéphane 
Published: September 2021

AbstractBecause of their long lifespan, matrix proteins of the vascular wall, such as elastin, are subjected to molecular aging characterized by non-enzymatic post-translational modifications, like carbamylation which results from the binding of cyanate (mainly derived from the dissociation of urea) to protein amino groups. While several studies have demonstrated a relationship between increased plasma concentrations of carbamylated proteins and the development of cardiovascular diseases, molecular mechanisms explaining the involvement of protein carbamylation in these pathological contexts remain to be fully elucidated. The aim of this work was to determine whether vascular elastic fibers could be carbamylated, and if so, what impact this phenomenon would have on the mechanical properties of the vascular wall. Our experiments showed that vascular elastin was carbamylated in vivo. Fiber morphology was unchanged after in vitro carbamylation, as well as its sensitivity to elastase degradation. In mice fed with cyanate-supplemented water in order to increase protein carbamylation within the aortic wall, an increased stiffness in elastic fibers was evidenced by atomic force microscopy, whereas no fragmentation of elastic fiber was observed. In addition, this increased stiffness was also associated with an increase in aortic pulse wave velocity in ApoE−/− mice. These results provide evidence for the carbamylation of elastic fibers which results in an increase in their stiffness at the molecular level. These alterations of vessel wall mechanical properties may contribute to aortic stiffness, suggesting a new role for carbamylation in cardiovascular diseases.
Metabolic flexibility during sleep
Authors: Zhang Simeng , Tanaka Yoshiaki , Ishihara Asuka , Uchizawa Akiko , Park Insung , Iwayama Kaito , Ogata Hitomi , Yajima Katsuhiko , Omi Naomi , Satoh Makoto , Yanagisawa Masashi , Sagayama Hiroyuki , Tokuyama Kumpei 
Published: September 2021

AbstractKnown as metabolic flexibility, oxidized substrate is selected in response to changes in the nutritional state. Sleep imposes an extended duration of fasting, and oxidized substrates during sleep were assumed to progressively shift from carbohydrate to fat, thereby gradually decreasing the respiratory quotient (RQ). Contrary to this assumption, whole-room indirect calorimetry with improved time resolution revealed that RQ re-ascended prior to awakening, and nadir of RQ in non-obese young adults occurred earlier in women than men after bedtime. The transient decrease in RQ during sleep was blunted in metabolically inflexible men with smaller amplitude of diurnal rhythm in RQ. Similarly, the effect of 10 years difference in age on RQ became significant during sleep; the decrease in RQ during sleep was blunted in older subjects. Inter-individual difference in RQ become apparent during sleep, and it might serve as a window to gain insight into the early-stage pathogenesis of metabolic inflexibility.
Rational design of a nanoparticle platform for oral prophylactic immunotherapy to prevent immunogenicity of therapeutic proteins
Authors: Nguyen Nhan H. , Glassman Fiona Y. , Dingman Robert K. , Shenoy Gautam N. , Wohlfert Elizabeth A. , Kay Jason G. , Bankert Richard B. , Balu-Iyer Sathy V. 
Published: September 2021

AbstractThe safety and efficacy of several life-saving therapeutic proteins are compromised due to their immunogenicity. Once a sustained immune response against a protein-based therapy is established, clinical options that are safe and cost-effective become limited. Prevention of immunogenicity of therapeutic proteins prior to their initial use is critical as it is often difficult to reverse an established immune response. Here, we discuss a rational design and testing of a phosphatidylserine-containing nanoparticle platform for novel oral prophylactic reverse vaccination approach, i.e., pre-treatment of a therapeutic protein in the presence of nanoparticles to prevent immunogenicity of protein therapies.
Computational simulation and modelling of uranium extraction using tributylphosphate through membrane extractor
Authors: Syah Rahmad , Ramadan Dadan , Elveny Marischa , Cao Yan , Khan Afrasyab , Abdi Hamid , Ghadiri Mahdi 
Published: September 2021

AbstractNon-disperse solvent extraction is an effective technique for the extraction of metal ions from aqueous solution. In this study, uranium extraction using n-dodecane solvent containing tributylphosphate extractant in a membrane contactor was investigated. A 2D mathematical model was developed for the fluid flow and mass transfer in the hollow fibre membrane extractor. The equations of the created model were solved using the finite element method. The uranium concentration distribution in the extractor at different extractant concentrations as well as feed acidity was studied. The results showed that there is reasonable good agreement between experimental uranium extraction and modelling outputs at different extractant concentrations. Increasing extractant concentration from 5 to 30% led to the enhancement of uranium extraction from 2.60 to 34.13%. Also, there was an increase in the uranium extraction with increasing feed acidity in the range of 1–3 M. Furthermore, based on the radial uranium concentration distribution, it was found that the main mass transfer resistance in the system was microporous membrane section. Finally, it was obtained that the uranium extraction efficiency could be improved significantly by increasing porosity-to-tortuosity ratio. It was concluded that the membrane specification plays the most important role as the dominant mass transfer resistant was in the membrane subdomain.
Effect of sildenafil added to antifibrotic treatment in idiopathic pulmonary fibrosis
Authors: Kang Jieun , Song Jin Woo 
Published: September 2021

AbstractSildenafil is a phosphodiesterase-5 inhibitor used to treat idiopathic pulmonary arterial hypertension; however, its benefits are unclear in patients with advanced idiopathic pulmonary fibrosis (IPF). We aimed to evaluate its effect as an add-on to antifibrotic agents on clinical outcomes of real-world IPF patients. Among a total of 607 IPF patients treated with antifibrotic agent, 66 concurrently received sildenafil. Propensity score matching was performed to adjust for differences in age, sex, body mass index, forced vital capacity (FVC), and diffusing capacity (DLCO) between the sildenafil and no-sildenafil groups. The outcomes of these groups in terms of FVC decline rate, all-cause mortality, hospitalization, and acute exacerbation were compared. Propensity score matching identified 51 matched pairs. The mean age of the patients was 69.5 years and 80.4% were male. Mean FVC and DLCO were 51.7% and 29.5% of the predicted values, respectively. The FVC decline rates did not differ significantly (p = 0.714) between the sildenafil (− 101 mL/year) and no-sildenafil (− 117 mL/year) groups. In multivariable analyses adjusted for comorbidities and presence of pulmonary hypertension, sildenafil had no significant impact on all-cause mortality, hospitalization, or acute exacerbation. Sildenafil add-on to antifibrotic treatment had no significant effects on the clinical outcomes of IPF patients.
Exploring the dark: detecting long-lived Nile Red 3ILCT states in Ru(ii) polypyridyl photosensitisers
Authors: Condon Claire , Conway-Kenny Robert , Cui Xiaoneng , Hallen Lukas J. , Twamley Brendan , Zhao Jianzhang , Watson Graeme W. , Draper Sylvia M. 
Published: September 2021

The commercial dye Nile Red has been used to produce two Ru(ii) polypyridyl complexes with long-lived “dark” (non-emissive) triplet excited states. The latter localised on the Nile Red moiety are used for efficient singlet oxygen generation.
Hemodynamic phenotyping of transgenic rats with ubiquitous expression of an angiotensin-(1-7)-producing fusion protein
Authors: Alves Daniele T. , Mendes Luiz Felipe , Sampaio Walkyria O. , Coimbra-Campos Leda M.C. , Vieira Maria Aparecida R. , Ferreira Anderson J. , Martins Almir S. , Popova Elena , Todiras Mihail , Qadri Fatimunnisa , Alenina Natalia , Bader Michael , Santos Robson A.S. , Campagnole-Santos Maria Jose 
Published: September 2021

Abstract
Activation of the angiotensin (Ang)-converting enzyme (ACE) 2/Ang-(1-7)/MAS receptor pathway of the renin–angiotensin system (RAS) induces protective mechanisms in different diseases. Herein, we describe the cardiovascular phenotype of a new transgenic rat line (TG7371) that expresses an Ang-(1-7)-producing fusion protein. The transgene-specific mRNA and the corresponding protein were shown to be present in all evaluated tissues of TG7371 with the highest expression in aorta and brain. Plasma Ang-(1-7) levels, measured by radioimmunoassay (RIA) were similar to control Sprague–Dawley (SD) rats, however high Ang-(1-7) levels were found in the hypothalamus. TG7371 showed lower baseline mean arterial pressure (MAP), assessed in conscious or anesthetized rats by telemetry or short-term recordings, associated with increased plasma atrial natriuretic peptide (ANP) and higher urinary sodium concentration. Moreover, evaluation of regional blood flow and hemodynamic parameters with fluorescent microspheres showed a significant increase in blood flow in different tissues (kidneys, mesentery, muscle, spleen, brown fat, heart and skin), with a resulting decrease in total peripheral resistance (TPR). TG7371 rats, on the other hand, also presented increased cardiac and global sympathetic tone, increased plasma vasopressin (AVP) levels and decreased free water clearance. Altogether, our data show that expression of an Ang-(1-7)-producing fusion protein induced a hypotensive phenotype due to widespread vasodilation and consequent fall in peripheral resistance. This phenotype was associated with an increase in ANP together with an increase in AVP and sympathetic drive, which did not fully compensate the lower blood pressure (BP). Here we present the hemodynamic impact of long-term increase in tissue expression of an Ang-(1-7)-fusion protein and provide a new tool to investigate this peptide in different pathophysiological conditions.
Before, During, and After the First Wave of COVID-19: Mortality Analyses Reveal Relevant Trends in Germany and its States until June 2020
Authors: Morfeld Peter , Timmermann Barbara , Groß J. Valérie , Lewis Philip , Erren Thomas C 
Published: September 2021

ABSTRACTObjective Well-established mortality ratio methodology can contribute to a fuller picture of the SARS-CoV-2/COVID-19 burden of disease by revealing trends and informing mitigation strategies. This work examines respective data from Germany by way of example.Methods Using monthly and weekly all-cause mortality data from January 2016 to June 2020 (published by the German Federal Statistical Institute) for all ages,<65 years and≥65 years, and specified for Germany’s federal states, we explored mortality as sequela of COVID-19. We analysed standardized mortality ratios (SMRs) comparing 2020 with 2016–2019 as reference years with a focus on trend detection.Results In Germany as a whole, elevated mortality in April (most pronounced for Bavaria) declined in May. The states of Hamburg and Bremen had increased SMRs in all months under study. In Mecklenburg-Western Pomerania, decreased SMRs in January turned monotonically to increased SMRs by June. Irrespective of age group, this trend was pronounced and significant.Conclusions Increased SMRs in Hamburg and Bremen must be interpreted with caution because of potential upward distortions due to a “catchment bias”. A pronounced excess mortality in April across Germany was confirmed and a hitherto undetected trend of increasing SMRs for Mecklenburg-Western Pomerania was revealed. To meet the pandemic challenge and to benefit from research based on data collected in standardized ways, national authorities should regularly conduct SMR analyses. For independent analyses, national authorities should also expedite publishing raw mortality and population data, including detailed information on age, sex, and cause of death, in the public domain.
Intraoperative Fractures of the Tibia and Femur in Knee Revision Surgery
Authors: Müller Michael , Kahl Uwe , von Roth Philipp , Hube Robert 
Published: September 2021

AbstractIntra-operative fractures in knee revision surgery are relatively rare and have not been well studied. They may occur during joint exposition, removal of the prosthesis or cement, or implantation of trial or original components. The fractures affect both the metaphyseal area and diaphysis of the tibia and femur. Tibial fractures are slightly more common than femur fractures. On the femur, the medial condyle is most frequently affected, followed by the femur diaphysis. The use of non-cemented stems is associated with a greater risk of intra-operative diaphyseal fractures than that of cemented stems. Overall, women and patients with an osteopenic bone structure have a higher risk of fractures. It is common that fractures are diagnosed post-operatively. In these cases, conservative therapy may be successful, depending on the stability of the prosthesis and bones. The most common surgical fixation options are cerclages and screws, followed by stem extensions for bridging the
fracture. Plate fixation or use of strut grafts are also sensible therapy options. Overall, intraoperative fractures have a high healing potential with stable and good joint function. The revision rate is still 15%, which is most often caused by peri-prosthetic infection.
The Role of Delayed Radiotherapy Initiation in Patients with Newly Diagnosed Glioblastoma with Residual Tumor Mass
Authors: Kasper Johannes , Frydrychowicz Clara , Jähne Katja , Wende Tim , Wilhelmy Florian , Arlt Felix , Seidel Clemens , Hoffmann Karl-Titus , Meixensberger Jürgen 
Published: September 2021

Abstract
Objective Treatment for newly diagnosed isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) includes maximum safe resection, followed by adjuvant radio(chemo)therapy (RCx) with temozolomide. There is evidence that it is safe for GBM patients to prolong time to irradiation over 4 weeks after surgery. This study aimed at evaluating whether this applies to GBM patients with different levels of residual tumor volume (RV).
Methods Medical records of all patients with newly diagnosed GBM at our department between 2014 and 2018 were reviewed. Patients who received adjuvant radio (chemo) therapy, aged older than 18 years, and with adequate perioperative imaging were included. Initial and residual tumor volumes were determined. Time to irradiation was dichotomized into two groups (≤28 and >28 days). Univariate analysis with Kaplan–Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression.
Results One hundred and twelve patients were included. Adjuvant treatment regimen, extent of resection, residual tumor volume, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation were statistically significant factors for overall survival (OS). Time to irradiation had no impact on progression-free survival (p = 0.946) or OS (p = 0.757). When stratified for different thresholds of residual tumor volume, survival predication via Cox regression favored time to irradiation below 28 days for patients with residual tumor volume above 2 mL, but statistical significance was not reached.
Conclusion Time to irradiation had no significant influence on OS of the entire cohort. Nevertheless, a statistically nonsignificant survival prolongation could be observed in patients with residual tumor volume > 2 mL when admitted to radiotherapy within 28 days after surgery.
Matrix Metalloproteinase-9 is Involved in the Fibrotic Process in Denervated Muscles after Sciatic Nerve Trauma and Recovery
Authors: Goncharuk Oleksii , Savosko Serhii , Tykhomyrov Artem , Guzyk Mykhailo , Medvediev Volodymyr , Tsymbaliuk Vitaliy , Chaikovsky Yuri 
Published: September 2021

AbstractFibrosis of the injured muscles is a problem of recovery from trauma and denervation. The aim of the work was to investigate the interconnection of matrix metalloproteinase-9 (ММР-9) activity in denervated muscles with fibrosis and to estimate its role in nerve restoration by the epineurial suture, fibrin-based glue, and polyethylene glycol hydrogel. The activity of matrix metalloproteinases was estimated by gelatin zymography. Collagen density in muscles was determined histochemically. An increased level of the active MMP-9 is associated with the fibrous changes in the denervated skeletal muscles and after an epineurial suture. The use of fibrin glue and polyethylene glycol hydrogel resulted in a lower level of collagen and ММР-9 activity, which may be a therapeutic target in the treatment of neuromuscular lesions, and has value in fibrosis analysis following microsurgical intervention for peripheral nerve reconstruction.
Telemedicine Adoption during the COVID-19 Pandemic: Gaps and Inequalities
Authors: Luo Jake , Tong Ling , Crotty Bradley H. , Somai Melek , Taylor Bradley , Osinski Kristen , George Ben 
Published: September 2021

Abstract
Background The telemedicine industry has been experiencing fast growth in recent years. The outbreak of coronavirus disease 2019 (COVID-19) further accelerated the deployment and utilization of telemedicine services. An analysis of the socioeconomic characteristics of telemedicine users to understand potential socioeconomic gaps and disparities is critical for improving the adoption of telemedicine services among patients.
Objectives This study aims to measure the correlation of socioeconomic determinants with the use of telemedicine services in Milwaukee metropolitan area.
Methods Electronic health record review of patients using telemedicine services compared with those not using telemedicine services within an academic-community health system: patient demographics (e.g., age, gender, race, and ethnicity), insurance status, and socioeconomic determinants obtained through block-level census data in Milwaukee area. The telemedicine users were compared with all other patients using regression analysis. The telemedicine adoption rates were calculated across regional ZIP codes to analyze the geographic patterns of telemedicine adoption.
Results A total of 104,139 patients used telemedicine services during the study period. Patients who used video visits were younger (median age 48.12), more likely to be White (odds ratio [OR] 1.34; 95% confidence interval [CI], 1.31–1.37), and have private insurance (OR 1.43; CI, 1.41–1.46); patients who used telephone visits were older (median age 57.58), more likely to be Black (OR 1.31; CI 1.28–1.35), and have public insurance (OR 1.30; CI 1.27–1.32). In general, Latino and Asian populations were less likely to use telemedicine; women used more telemedicine services in general than men. In the multiple regression analysis of social determinant factors across 126 ZIP codes, college education (coefficient 1.41, p = 0.01) had a strong correlation to video telemedicine adoption rate.
Conclusion Adoption of telemedicine services was significantly impacted by the social determinant factors of health, such as income, education level, race, and insurance type. The study reveals the potential inequities and disparities in telemedicine adoption.
Impact of Serum Amylase Level in the Outcome of Acute Organophosphorus Poisoning: 2-Year Cross-Sectional Study at Rural Teaching Hospital
Authors: Patil Aniket , Kumar Sunil , Inamdar Anil , Acharya Sourya , Wanjari Anil , Bawankule Shilpa , Agrawal Sachin , Sontakke Tushar 
Published: September 2021

Abstract
Introduction Prompt recognition and aggressive management of acute intoxication due to organophosphorus poisoning are essential to minimize the morbidity and mortality. The present study was undertaken to know the prognosis and outcome of organophosphorus poisoning patients with the estimation of low-cost enzymes like the serum amylase level in a population with financial constraints.
Methods In this cross-sectional study, we had enrolled 100 cases that had a history of exposure to organophosphorus compounds, and the serum amylase level was measured in all the patients. We assessed the outcome of all the patients in the form of discharge, need of ventilators, intensive care unit stay, and death.
Results The mean serum amylase level in discharge patients was 335.40 ± 192.45, and in the patients who died it was 843.37 ± 22.60. It was significant to predict the outcome (t-value 7.07, p-value 0.0001, statistically significant).
Conclusion Serum amylase level shows significant correlation with clinical outcomes in organophosphorus poisoning.
Nuances of Arteriovenous Fistula Creation for Vascular Access in Hemodialysis
Authors: Sahasrabudhe Parag , Bindu Ameya 
Published: September 2021

Abstract
Background With rising incidence and increased life expectancy of patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), the number of patients requiring hemodialysis has increased substantially. Vascular access is the lifeline for a patient on hemodialysis (HD), and an arteriovenous fistula (AVF) is the undisputed gold standard for HD access. An effective and long-lasting fistula serves to increase the life expectancy of ESRD patients and improves their quality of life.
Learning Objectives This paper aims to give a comprehensive overview of AVF creation, including the various techniques, patient selection, troubleshooting with decision-making, and common complications. Authors share their experience from previous publications and over 2000 AVF surgeries. They have not only described a new modification of the technique of proximal fistula but have also established a direct correlation between bruit and thrill on operation table and success of fistula surgery.
Conclusion A standardized, protocol-driven multidisciplinary approach with careful patient and site selection, guided by outcome predictors, is vital in AVF surgery. Knowledge about the potential complications of AVFs contributes to their timely detection and allows measures to be taken that might prevent deleterious consequences that range from loss of vascular access to serious morbidity and mortality.