bluuebunny/crossref_metadata_2025 huggingface dataset:
Singer’s Nodules: Investigating the Etiopathogenetic Markers Progressing Their Pathogenesis and Clinical Manifestations
Authors: Pilmane Mara , Sumerags Dins , Jain Nityanand , Jain Shivani , Sumeraga Gunta
Published: December 2021

Vocal nodules (or Singer’s nodules) are benign vocal cord structures which are commonly encountered by clinicians. Though phonetic trauma/abuse is thought to be the main cause of the development of vocal nodules, the exact etiopathogenesis remains unknown. Hence, we compared the immunohistochemical markers for proliferation (Ki-67), apoptosis (TUNEL), growth (EGFR), ischemia (VEGF), inflammation (IL-1α and 10), and immunoreactive innervation (PGP 9.5), in vocal nodule tissue samples obtained from 10 females (17–56 years) and vocal cord tissue from seven controls. A statistically significant increase in Ki-67, TUNEL, EGFR, VEGF and IL-1α expression was noted (p < 0.05) between nodule tissue and control tissue in both epithelial and subepithelial layers. However, the difference was non-significant for both IL-10 and PGP 9.5 (p > 0.05). All markers demonstrated moderate to strong positive correlations, except for IL-10. These findings suggest increased cellular growth and proliferation in vocal nodules coupled with a persistent presence of inflammatory and ischemic environment. Furthermore, global prevalence of apoptotic cells and decreased anti-inflammatory cytokines highlight the presence of underlying complex mechanisms in the etiopathogenesis of vocal nodules, with age having a negligible impact on the marker levels. Our results could potentially further our knowledge in understanding the effects of different treatment modalities available at the cellular level.
Evaluation of Global DNA Methylation and Gene Expression of Izumo1 and Izumo1r in Gonads after High- and Low-Dose Radiation in Neonatal Mice
Authors: Nakata Akifumi , Sato Keisuke , Fujishima Yohei , Ting Valerie Goh Swee , Nakayama Kanade , Ariyoshi Kentaro , Tsuruoka Chizuru , Shang Yi , Iizuka Daisuke , Kakinuma Shizuko , Yamashiro Hideaki , Miura Tomisato
Published: December 2021

The intergenerational effects from chronic low-dose exposure are matters of concern. It is thus important to elucidate the radiation-induced effects of germ cell maturation, fertilization and embryonic development. It is well known that DNA methylation levels in CpG sites in gametes are reprogrammed in stages during their maturity. Furthermore, the binding of Izumo on the surface of sperm and Juno on the surface of oocytes is essential for fertilization. Thus, there is a possibility that these genes are useful indicators to evaluate fertility in mice after irradiation exposure. Therefore, in this study, we analyzed global DNA methylation patterns in the testes and gene expression of Izumo1 and Izumo1r (Juno) in the gonads of mice after neonatal acute high-dose ionizing radiation (HDR) and chronic low-dose ionizing radiation (LDR). One-week-old male and female mice were irradiated with a total dose of 4 Gy, with acute HDR at 7 days at a dose rate of 30 Gy/h and LDR continuously at a dose rate of 6 mGy/h from 7 to 35 days. Their gonads were subsequently analyzed. The results of global DNA methylation patterns in the testes showed that methylation level increased with age in the control group, the LDR group maintained its DNA methylation level, and the HDR group showed decreased DNA methylation levels with age. In the control group, the gene expression level of Izumo1 in the testis did not show age-related changes, although there was high expression at 100 days of age. However, in the LDR group, the expression level recovered after the end of irradiation, while it remained low regardless of age in the HDR group. Conversely, gene expression of Izumo1r (Izumo1 receptor) in the ovary decreased with age in the control group. Although the gene expression of Izumo1r decreased with age in the LDR group, it remained low in the HDR group. Our results indicate that LDR can induce different DNA methylation patterns, and both high- and low-dose radiation before sexual maturity might affect gametogenesis and fertility.
At the Origins of Tobacco-Smoking and Tea Consumption in a Virgin Population (Yakutia, 1650–1900 A.D.): Comparison of Pharmacological, Histological, Economic and Cultural Data
Authors: Macé Matthias , Richeval Camille , Alcouffe Ameline , Romanova Liubomira , Gérard Patrice , Duchesne Sylvie , Cannet Catherine , Boyarskikh Irina , Géraut Annie , Zvénigorosky Vincent , Nikolaeva Darya , Stepanoff Charles , Allorge Delphine , Debrenne Michele , Telmon Norbert , Ludes Bertrand , Alexeev Anatoly , Gaulier Jean-Michel , Crubézy Eric
Published: December 2021

(1) Background: The way tobacco and tea spread among virgin populations is of major interest our understanding of how ancient economic and cultural practices could have influenced current habits. (2) Methods: hair concentrations of theobromine, theophylline, caffeine, nicotine, and cotinine were measured in hair samples from 47 frozen bodies of people from eastern Siberia, dated from the contact with Europeans to the assimilation of people into Russian society. (3) Results: hair concentration of theobromine, theophylline, and caffeine vary with the type of beverage consumed: green, black, or local herbal teas. Shortly after the first contacts, a few heavy consumers of tobacco were found among light or passive consumers. Tobacco-related co-morbidities began to be recorded one century after and heavy tea users were only found from the 19th century (4) Conclusions: Economic factors and social and family contacts seem to have played a decisive role in tobacco consumption very early on. Behavioral evolution governed the process of substance integration into Siberian culture and was a determinant for the continuity of its use across long periods of time. Analyzing the respective contributions of social and economic processes in the use of these substances opens avenues of investigation for today’s public health.
Effects of High Intensity Exercise on Oxidative Stress and Antioxidant Status in Untrained Humans: A Systematic Review
Authors: Lu Yining , Wiltshire Huw D. , Baker Julien S. , Wang Qiaojun
Published: December 2021

Participation in exercise promotes health. High intensity exercise (HIE) has become increasingly popular among the general population, however, its effects on exercise-induced oxidative stress and antioxidant status in untrained humans is not clear. The aim of this systematic review was to investigate the influence of HIE on oxidative stress and antioxidant status in untrained humans. Web of Science, PubMed, MEDLINE, and Scopus were searched until March 2021. A methodological quality assessment valuation/estimation was additionally carried out in the final sample of studies. Following the PRISMA selection process, 21 studies were finally included. There was strong evidence that acute oxidative stress following the cessation of HIE exists when compared to resting states. The HIE-induced oxidative stress is transient and is most likely restored to normal levels within 24 h due to the stimulated endogenous antioxidant system whose response was lagging and lasting. Physically active humans had better antioxidant systems and suffered less oxidative stress after HIE. A physically active lifestyle was considered to enhance antioxidant capacity. For untrained humans, HIE with intensities above 70% VO2max are proposed for initial exercise levels based on the findings reported here.
Full-Length Transcriptome Sequencing of the Scleractinian Coral Montipora foliosa Reveals the Gene Expression Profile of Coral–Zooxanthellae Holobiont
Authors: Liu Yunqing , Liao Xin , Han Tingyu , Su Ao , Guo Zhuojun , Lu Na , He Chunpeng , Lu Zuhong
Published: December 2021

Coral–zooxanthellae holobionts are one of the most productive ecosystems in the ocean. With global warming and ocean acidification, coral ecosystems are facing unprecedented challenges. To save the coral ecosystems, we need to understand the symbiosis of coral–zooxanthellae. Although some Scleractinia (stony corals) transcriptomes have been sequenced, the reliable full-length transcriptome is still lacking due to the short-read length of second-generation sequencing and the uncertainty of the assembly results. Herein, PacBio Sequel II sequencing technology polished with the Illumina RNA-seq platform was used to obtain relatively complete scleractinian coral M. foliosa transcriptome data and to quantify M. foliosa gene expression. A total of 38,365 consensus sequences and 20,751 unique genes were identified. Seven databases were used for the gene function annotation, and 19,972 genes were annotated in at least one database. We found 131 zooxanthellae transcripts and 18,829 M. foliosa transcripts. A total of 6328 lncRNAs, 847 M. foliosa transcription factors (TFs), and 2 zooxanthellae TF were identified. In zooxanthellae we found pathways related to symbiosis, such as photosynthesis and nitrogen metabolism. Pathways related to symbiosis in M. foliosa include oxidative phosphorylation and nitrogen metabolism, etc. We summarized the isoforms and expression level of the symbiont recognition genes. Among the membrane proteins, we found three pathways of glycan biosynthesis, which may be involved in the organic matter storage and monosaccharide stabilization in M. foliosa. Our results provide better material for studying coral symbiosis.
A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19
Authors: Lobiuc Andrei , Șterbuleac Daniel , Sturdza Olga , Dimian Mihai , Covasa Mihai
Published: December 2021

The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69–70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinical manifestation. Molecular dynamics and computational structural analyses revealed that this mutation differentially alters ORF7a dynamics, suggesting a gain-of-function role that may explain its role in the severe form of COVID-19 disease.
RNR-R2 Upregulation by a Short Non-Coding Viral Transcript
Authors: Broennimann Karin , Ricardo-Lax Inna , Adler Julia , Michailidis Eleftherios , de Jong Ype , Reuven Nina , Shaul Yosef
Published: December 2021

DNA viruses require dNTPs for replication and have developed different strategies to increase intracellular dNTP pools. Hepatitis B virus (HBV) infects non-dividing cells in which dNTPs are scarce and the question is how viral replication takes place. Previously we reported that the virus induces the DNA damage response (DDR) pathway culminating in RNR-R2 expression and the generation of an active RNR holoenzyme, the key regulator of dNTP levels, leading to an increase in dNTPs. How the virus induces DDR and RNR-R2 upregulation is not completely known. The viral HBx open reading frame (ORF) was believed to trigger this pathway. Unexpectedly, however, we report here that the production of HBx protein is dispensable. We found that a small conserved region of 125 bases within the HBx ORF is sufficient to upregulate RNR-R2 expression in growth-arrested HepG2 cells and primary human hepatocytes. The observed HBV mRNA embedded regulatory element is named ERE. ERE in isolation is sufficient to activate the ATR-Chk1-E2F1-RNR-R2 DDR pathway. These findings demonstrate a non-coding function of HBV transcripts to support its propagation in non-cycling cells.
Mechanism of Zn2+ and Ca2+ Binding to Human S100A1
Authors: Baksheeva Viktoriia E. , Roman Andrei Yu. , Villard Claude , Devred François , Byrne Deborah , Yatoui Dahbia , Zalevsky Arthur O. , Vologzhannikova Alisa A. , Sokolov Andrey S. , Permyakov Sergei E. , Golovin Andrey V. , Shaw Gary S. , Tsvetkov Philipp O. , Zernii Evgeni Yu.
Published: December 2021

S100A1 is a member of the S100 family of small ubiquitous Ca2+-binding proteins, which participates in the regulation of cell differentiation, motility, and survival. It exists as homo- or heterodimers. S100A1 has also been shown to bind Zn2+, but the molecular mechanisms of this binding are not yet known. In this work, using ESI-MS and ITC, we demonstrate that S100A1 can coordinate 4 zinc ions per monomer, with two high affinity (KD~4 and 770 nm) and two low affinity sites. Using competitive binding experiments between Ca2+ and Zn2+ and QM/MM molecular modeling we conclude that Zn2+ high affinity sites are located in the EF-hand motifs of S100A1. In addition, two lower affinity sites can bind Zn2+ even when the EF-hands are saturated by Ca2+, resulting in a 2Ca2+:S100A1:2Zn2+ conformer. Finally, we show that, in contrast to calcium, an excess of Zn2+ produces a destabilizing effect on S100A1 structure and leads to its aggregation. We also determined a higher affinity to Ca2+ (KD~0.16 and 24 μm) than was previously reported for S100A1, which would allow this protein to function as a Ca2+/Zn2+-sensor both inside and outside cells, participating in diverse signaling pathways under normal and pathological conditions.
Epigenome-Wide Association Study of Prostate Cancer in African Americans Identifies DNA Methylation Biomarkers for Aggressive Disease
Authors: Xu Yifan , Tsai Chia-Wen , Chang Wen-Shin , Han Yuyan , Huang Maosheng , Pettaway Curtis A. , Bau Da-Tian , Gu Jian
Published: December 2021

DNA methylation plays important roles in prostate cancer (PCa) development and progression. African American men have higher incidence and mortality rates of PCa than other racial groups in U.S. The goal of this study was to identify differentially methylated CpG sites and genes between clinically defined aggressive and nonaggressive PCa in African Americans. We performed genome-wide DNA methylation profiling in leukocyte DNA from 280 African American PCa patients using Illumina MethylationEPIC array that contains about 860K CpG sties. There was a slight increase of overall methylation level (mean β value) with the increasing Gleason scores (GS = 6, GS = 7, GS ≥ 8, P for trend = 0.002). There were 78 differentially methylated CpG sites with P < 10−4 and 9 sites with P < 10−5 in the trend test. We also found 77 differentially methylated regions/genes (DMRs), including 10 homeobox genes and six zinc finger protein genes. A gene ontology (GO) molecular pathway enrichment analysis of these 77 DMRs found that the main enriched pathway was DNA-binding transcriptional factor activity. A few representative DMRs include HOXD8, SOX11, ZNF-471, and ZNF-577. Our study suggests that leukocyte DNA methylation may be valuable biomarkers for aggressive PCa and the identified differentially methylated genes provide biological insights into the modulation of immune response by aggressive PCa.
Integration and Spatial Organization of Signaling by G Protein-Coupled Receptor Homo- and Heterodimers
Authors: Maggio Roberto , Fasciani Irene , Carli Marco , Petragnano Francesco , Marampon Francesco , Rossi Mario , Scarselli Marco
Published: December 2021

Information flow from a source to a receiver becomes informative when the recipient can process the signal into a meaningful form. Information exchange and interpretation is essential in biology and understanding how cells integrate signals from a variety of information-coding molecules into complex orchestrated responses is a major challenge for modern cell biology. In complex organisms, cell to cell communication occurs mostly through neurotransmitters and hormones, and receptors are responsible for signal recognition at the membrane level and information transduction inside the cell. The G protein-coupled receptors (GPCRs) are the largest family of membrane receptors, with nearly 800 genes coding for these proteins. The recognition that GPCRs may physically interact with each other has led to the hypothesis that their dimeric state can provide the framework for temporal coincidence in signaling pathways. Furthermore, the formation of GPCRs higher order oligomers provides the structural basis for organizing distinct cell compartments along the plasma membrane where confined increases in second messengers may be perceived and discriminated. Here, we summarize evidence that supports these conjectures, fostering new ideas about the physiological role played by receptor homo- and hetero-oligomerization in cell biology.
Morphometric Analysis of Rat Prostate Development: Roles of MEK/ERK and Rho Signaling Pathways in Prostatic Morphogenesis
Authors: Hu Wen-Yang , Afradiasbagharani Parivash , Lu Ranli , Liu Lifeng , Birch Lynn A. , Prins Gail S.
Published: December 2021

The molecular mechanisms underlying prostate development can provide clues for prostate cancer research. It has been demonstrated that MEK/ERK signaling downstream of androgen-targeted FGF10 signaling directly induces prostatic branching during development, while Rho/Rho-kinase can regulate prostate cell proliferation. MEK/ERK and Rho/Rho kinase regulate myosin light chain kinase (MLCK), and MLCK regulates myosin light chain phosphorylation (MLC-P), which is critical for cell fate, including cell proliferation, differentiation, and apoptosis. However, the roles and crosstalk of the MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis have not been examined. In the present study, we used numerical and image analysis to characterize lobe-specific rat prostatic branching during postnatal organ culture and investigated the roles of FGF10-MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis. Prostates exhibited distinctive lobe-specific growth and branching patterns in the ventral (VP) and lateral (LP) lobes, while exogenous FGF10 treatment shifted LP branching towards a VP branching pattern. Treatment with inhibitors of MEK1/2, Rho, Rho kinase, or MLCK significantly inhibited VP growth and blocked branching morphogenesis, further supporting critical roles for MEK/ERK and Rho/Rho kinase signaling pathways in prostatic growth and branching during development. We propose that MLCK-regulated MLC-P may be a central downstream target of both signaling pathways in regulating prostate morphogenesis.
In Silico Drug Repurposing for Anti-Inflammatory Therapy: Virtual Search for Dual Inhibitors of Caspase-1 and TNF-Alpha
Authors: Speck-Planche Alejandro , Kleandrova Valeria V. , Scotti Marcus T.
Published: December 2021

Inflammation involves a complex biological response of the body tissues to damaging stimuli. When dysregulated, inflammation led by biomolecular mediators such as caspase-1 and tumor necrosis factor-alpha (TNF-alpha) can play a detrimental role in the progression of different medical conditions such as cancer, neurological disorders, autoimmune diseases, and cytokine storms caused by viral infections such as COVID-19. Computational approaches can accelerate the search for dual-target drugs able to simultaneously inhibit the aforementioned proteins, enabling the discovery of wide-spectrum anti-inflammatory agents. This work reports the first multicondition model based on quantitative structure–activity relationships and a multilayer perceptron neural network (mtc-QSAR-MLP) for the virtual screening of agency-regulated chemicals as versatile anti-inflammatory therapeutics. The mtc-QSAR-MLP model displayed accuracy higher than 88%, and was interpreted from a physicochemical and structural point of view. When using the mtc-QSAR-MLP model as a virtual screening tool, we could identify several agency-regulated chemicals as dual inhibitors of caspase-1 and TNF-alpha, and the experimental information later retrieved from the scientific literature converged with our computational results. This study supports the capabilities of our mtc-QSAR-MLP model in anti-inflammatory therapy with direct applications to current health issues such as the COVID-19 pandemic.
Atrial Natriuretic Peptides, Right Atrial Infarction and Prognosis of Patients with Myocardial Infarction—A Single-Center Study
Authors: Kacprzak Michal , Brzeczek Magdalena , Zielinska Marzenna
Published: December 2021

Atrial natriuretic peptide (ANP) is secreted in response to the stretching of the atrial wall. Atrial ischemia most likely impairs the ability of atrial myocytes to produce ANP. Atrial infarction (AI) is rarely diagnosed but not infrequently associated with myocardial infarction (MI). The aim of the study was to assess the association between AI and the prognostic value of N-terminal proANP (NT-proANP) in patients with MI treated with primary percutaneous coronary intervention (PCI). We evaluated data of 100 consecutive patients. Plasma levels of NT-proANP were measured by the ELISA method. ECG recordings were interpreted to diagnose AI according to Liu’s criteria. All patients were followed-up prospectively for 12 months for the manifestation of major adverse cardiovascular events (MACE), defined as unplanned coronary revascularization, stroke, reinfarction or all-cause death. AI was diagnosed in 36 patients. 14% of patients developed MACE. AI did not affect the incidence of MACE or any of its components, nor the patients’ prognosis. NT-proANP revealed to be a strong predictor of death but was not associated with other adverse events. Conclusions: AI in patients with MI treated with primary PCI is not connected with their prognosis nor affects the usefulness of NT-proANP in predicting death during the 12-month follow-up.
Supercritical Carbon Dioxide Decellularized Bone Matrix Seeded with Adipose-Derived Mesenchymal Stem Cells Accelerated Bone Regeneration
Authors: Liu Keng-Fan , Chen Rong-Fu , Li Yun-Ting , Lin Yun-Nan , Hsieh Dar-Jen , Periasamy Srinivasan , Lin Sin-Daw , Kuo Yur-Ren
Published: December 2021

Large bone fractures with segmental defects are a vital phase to accelerate bone integration. The present study examined the role of supercritical carbon dioxide (scCO2) decellularized bone matrix (scDBM) seeded with allogeneic adipose-derived mesenchymal stem cells (ADSC) as bio-scaffold for bone regeneration. Bio-scaffold produced by seeding ADSC to scDBM was evaluated by scanning electron microscopy (SEM). Rat segmental femoral defect model was used as a non-union model to investigate the callus formation in vivo. Histological analysis and osteotomy gap closure in the defect area were analyzed at 12 and 24 weeks post-surgery. Immunohistochemical expression of Ki-67, BMP-2 and osteocalcin was evaluated to assess the ability of new bone formation scDBM. ADSC was found to attach firmly to scDBM bioscaffold as evidenced from SEM images in a dose-dependent manner. Callus formation was observed using X-ray bone imaging in the group with scDBM seeded with 2 × 106 and 5 × 106 ASCs group at the same time-periods. H&E staining revealed ASCs accelerated bone formation. IHC staining depicted the expression of Ki-67, BMP-2, and osteocalcin was elevated in scDBM seeded with 5 × 106 ASCs group at 12 weeks after surgery, relative to other experimental groups. To conclude, scDBM is an excellent scaffold that enhanced the attachment and recruitment of mesenchymal stem cells. scDBM seeded with ASCs accelerated new bone formation.
Plasminogen Deficiency Significantly Reduces Vascular Wall Disease in a Murine Model of Type IIa Hypercholesterolemia
Authors: Iwaki Takayuki , Arakawa Tomohiro , Sandoval-Cooper Mayra J. , Smith Denise L. , Donahue Deborah , Ploplis Victoria A. , Umemura Kazuo , Castellino Francis J.
Published: December 2021

The fibrinolytic system has been implicated in the genesis and progression of atherosclerosis. It has been reported that a plasminogen (Pg) deficiency (Plg−/−) exacerbates the progression of atherosclerosis in Apoe−/− mice. However, the manner in which Plg functions in a low-density lipoprotein-cholesterol (LDL-C)-driven model has not been evaluated. To characterize the effect of Pg in an LDL-C-driven model, mice with a triple deficiency of the LDL-receptor (LDLr), along with the active component (apobec1) of the apolipoprotein B editosome complex, and Pg (L−/−/A−/−/Plg−/−), were generated. Atherosclerotic plaque formation was severely retarded in the absence of Pg. In vitro studies demonstrated that LDL uptake by macrophages was enhanced by plasmin (Pm), whereas circulating levels of LDL were enhanced, relative to L−/−/A−/− mice, and VLDL synthesis was suppressed. These results indicated that clearance of lipoproteins in the absence of LDLr may be regulated by Pg/Pm. Conclusions: The results from this study indicate that Pg exacerbates atherosclerosis in an LDL-C model of atherosclerosis and also plays a role in lipoprotein modification and clearance. Therefore, controlling the Pg system on macrophages to prevent foam cell formation would be a novel therapeutic approach.
Determinants of Pulmonary Emphysema Severity in Taiwanese Patients with Chronic Obstructive Pulmonary Disease: An Integrated Epigenomic and Air Pollutant Analysis
Authors: Wu Sheng-Ming , Sun Wei-Lun , Lee Kang-Yun , Lin Cheng-Wei , Feng Po-Hao , Chuang Hsiao-Chi , Ho Shu-Chuan , Chen Kuan-Yuan , Chen Tzu-Tao , Liu Wen-Te , Tseng Chien-Hua , Bamodu Oluwaseun Adebayo
Published: December 2021

Background: Chronic obstructive pulmonary disease (COPD) continues to pose a therapeutic challenge. This may be connected with its nosological heterogeneity, broad symptomatology spectrum, varying disease course, and therapy response. The last three decades has been characterized by increased understanding of the pathobiology of COPD, with associated advances in diagnostic and therapeutic modalities; however, the identification of pathognomonic biomarkers that determine disease severity, affect disease course, predict clinical outcome, and inform therapeutic strategy remains a work in progress. Objectives: Hypothesizing that a multi-variable model rather than single variable model may be more pathognomonic of COPD emphysema (COPD-E), the present study explored for disease-associated determinants of disease severity, and treatment success in Taiwanese patients with COPD-E. Methods: The present single-center, prospective, non-randomized study enrolled 125 patients with COPD and 43 healthy subjects between March 2015 and February 2021. Adopting a multimodal approach, including bioinformatics-aided analyses and geospatial modeling, we performed an integrated analysis of selected epigenetic, clinicopathological, geospatial, and air pollutant variables, coupled with correlative analyses of time-phased changes in pulmonary function indices and COPD-E severity. Results: Our COPD cohort consisted of 10 non-, 57 current-, and 58 ex-smokers (median age = 69 ± 7.76 years). Based on the percentages of low attenuation area below − 950 Hounsfield units (%LAA-950insp), 36 had mild or no emphysema (%LAA-950insp < 6), 22 were moderate emphysema cases (6 ≤ %LAA-950insp < 14), and 9 presented with severe emphysema (%LAA-950insp ≥ 14). We found that BMI, lnc-IL7R, PM2.5, PM10, and SO2 were differentially associated with disease severity, and are highly-specific predictors of COPD progression. Per geospatial levels, areas with high BMI and lnc-IL7R but low PM2.5, PM10, and SO2 were associated with fewer and ameliorated COPD cases, while high PM2.5, PM10, and SO2 but low BMI and lnc-IL7R characterized places with more COPD cases and indicated exacerbation. The prediction pentad effectively differentiates patients with mild/no COPD from moderate/severe COPD cases, (mean AUC = 0.714) and exhibited very high stratification precision (mean AUC = 0.939). Conclusion: Combined BMI, lnc-IL7R, PM2.5, PM10, and SO2 levels are optimal classifiers for accurate patient stratification and management triage for COPD in Taiwan. Low BMI, and lnc-IL7R, with concomitant high PM2.5, PM10, and SO2 levels is pathognomonic of exacerbated/aggravated COPD in Taiwan.
iPSC Therapy for Myocardial Infarction in Large Animal Models: Land of Hope and Dreams
Authors: Martínez-Falguera Daina , Iborra-Egea Oriol , Gálvez-Montón Carolina
Published: December 2021

Myocardial infarction is the main driver of heart failure due to ischemia and subsequent cell death, and cell-based strategies have emerged as promising therapeutic methods to replace dead tissue in cardiovascular diseases. Research in this field has been dramatically advanced by the development of laboratory-induced pluripotent stem cells (iPSCs) that harbor the capability to become any cell type. Like other experimental strategies, stem cell therapy must meet multiple requirements before reaching the clinical trial phase, and in vivo models are indispensable for ensuring the safety of such novel therapies. Specifically, translational studies in large animal models are necessary to fully evaluate the therapeutic potential of this approach; to empirically determine the optimal combination of cell types, supplementary factors, and delivery methods to maximize efficacy; and to stringently assess safety. In the present review, we summarize the main strategies employed to generate iPSCs and differentiate them into cardiomyocytes in large animal species; the most critical differences between using small versus large animal models for cardiovascular studies; and the strategies that have been pursued regarding implanted cells’ stage of differentiation, origin, and technical application.
Kinetics of Bilirubin and Ammonia Elimination during Hemadsorption Therapy in Secondary Sclerosing Cholangitis Following ECMO Therapy and Severe COVID-19
Authors: Tampe Désirée , Korsten Peter , Bremer Sebastian C. B. , Winkler Martin S. , Tampe Björn
Published: December 2021

In critically ill patients, liver dysfunction often results in coagulopathy and encephalopathy and is associated with high mortality. Extracorporeal clearance of hepatotoxic metabolites, including bilirubin and ammonia, aims to attenuate further hepatocyte damage and liver injury, resulting in decreased mortality. The efficacy of hemadsorption combined with conventional hemodialysis to eliminate bilirubin and ammonia to support the liver’s excretory function in acute liver injury has been described previously. However, the optimal use of liver support systems in chronic liver dysfunction due to secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has not been defined yet. We herein describe the kinetics of successful bilirubin and ammonia elimination by hemadsorption in a patient with SSC-CIP after extracorporeal membrane oxygenation (ECMO) therapy for severe acute respiratory distress syndrome (ARDS) in a patient with coronavirus disease 2019 (COVID-19). During the course of the disease, the patient developed laboratory signs of liver injury during ECMO therapy before clinically detectable jaundice or elevated bilirubin levels. A diagnosis of SSC-CIP was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) based on intraductal filling defects in the intrahepatic bile ducts due to biliary casts. The patient showed stable elevations of bilirubin and ammonia levels thereafter, but presented with progressive nausea, vomiting, weakness, and exhaustion. Based on these laboratory findings, hemadsorption was combined with hemodialysis treatment and successfully eliminated bilirubin and ammonia. Moreover, direct comparison revealed that ammonia is more efficiently eliminated by hemadsorption than bilirubin levels. Clinical symptoms of nausea, vomiting, weakness, and exhaustion improved. In summary, bilirubin and ammonia were successfully eliminated by hemadsorption combined with hemodialysis treatment in SSC-CIP following ECMO therapy and severe COVID-19. This observation is particularly relevant since it has been reported that a considerable subset of critically ill patients with COVID-19 suffer from liver dysfunction associated with high mortality.
Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
Authors: Schümann Franziska Lea , Groß Elisabeth , Bauer Marcus , Rohde Christian , Sandmann Sarah , Terziev Denis , Müller Lutz P. , Posern Guido , Wienke Andreas , Fend Falko , Hansmann Martin-Leo , Klapper Wolfram , Rosenwald Andreas , Stein Harald , Dugas Martin , Müller-Tidow Carsten , Wickenhauser Claudia , Binder Mascha , Weber Thomas
Published: December 2021

T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044–0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898–35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients.
RF Remote Blood Glucose Sensor and a Microfluidic Vascular Phantom for Sensor Validation
Authors: Yunos Muhammad Farhan Affendi Mohamad , Manczak Rémi , Guines Cyril , Mansor Ahmad Fairuzabadi Mohd , Mak Wing Cheung , Khan Sheroz , Ramli Noor Amalina , Pothier Arnaud , Nordin Anis Nurashikin
Published: December 2021

Diabetes has become a major health problem in society. Invasive glucometers, although precise, only provide discrete measurements at specific times and are unsuitable for long-term monitoring due to the injuries caused on skin and the prohibitive cost of disposables. Remote, continuous, self-monitoring of blood sugar levels allows for active and better management of diabetics. In this work, we present a radio frequency (RF) sensor based on a stepped impedance resonator for remote blood glucose monitoring. When placed on top of a human hand, this RF interdigital sensor allows detection of variation in blood sugar levels by monitoring the changes in the dielectric constant of the material underneath. The designed stepped impedance resonator operates at 3.528 GHz with a Q factor of 1455. A microfluidic device structure that imitates the blood veins in the human hand was fabricated in PDMS to validate that the sensor can measure changes in glucose concentrations. To test the RF sensor, glucose solutions with concentrations ranging from 0 to 240 mg/dL were injected into the fluidic channels and placed underneath the RF sensor. The shifts in the resonance frequencies of the RF sensor were measured using a network analyzer via its S11 parameters. Based on the change in resonance frequencies, the sensitivity of the biosensor was found to be 264.2 kHz/mg·dL−1 and its LOD was calculated to be 29.89 mg/dL.
An Instrumented Glove-Controlled Portable Hand-Exoskeleton for Bilateral Hand Rehabilitation
Authors: Yang Shih-Hung , Koh Chia-Lin , Hsu Chun-Hang , Chen Po-Chuan , Chen Jia-Wei , Lan Yu-Hao , Yang Yi , Lin Yi-De , Wu Chun-Hung , Liu Hsien-Kuang , Lo Yu-Chun , Liu Guan-Tze , Kuo Chao-Hung , Chen You-Yin
Published: December 2021

Effective bilateral hand training is desired in rehabilitation programs to restore hand function for people with unilateral hemiplegia, so that they can perform daily activities independently. However, owing to limited human resources, the hand function training available in current clinical settings is significantly less than the adequate amount needed to drive optimal neural reorganization. In this study, we designed a lightweight and portable hand exoskeleton with a hand-sensing glove for bilateral hand training and home-based rehabilitation. The hand-sensing glove measures the hand movement of the less-affected hand using a flex sensor. Thereafter, the affected hand is driven by the hand exoskeleton using the measured hand movements. Compared with the existing hand exoskeletons, our hand exoskeleton improves the flexible mechanism for the back of the hand for better wearing experience and the thumb mechanism to make the pinch gesture possible. We designed a virtual reality game to increase the willingness of repeated movement practice for rehabilitation. Our system not only facilitates bilateral hand training but also assists in activities of daily living. This system could be beneficial for patients with hemiplegia for starting correct and sufficient hand function training in the early stages to optimize their recovery.
Surgical Aspects of Corpus Callosotomy
Authors: Uda Takehiro , Kunihiro Noritsugu , Umaba Ryoko , Koh Saya , Kawashima Toshiyuki , Ikeda Shohei , Ishimoto Kotaro , Goto Takeo
Published: December 2021

Corpus callosotomy (CC) is one of the options in epilepsy surgeries to palliate patient seizures, and is typically applied for drop attacks. The mechanisms of seizure palliation involve disrupting the propagation of epileptic activity to the contralateral side of the brain. This review article focuses on the surgical aspects of CC. As a variations of CC, anterior two-thirds, posterior one-third, and total callosotomy are described with intraoperative photographs. As less-invasive surgical variations, recent progress in endoscopic CC, and CC without craniotomy, is described. CC remains acceptable under the low prevalence of complications, and surgeons should make the maximum effort to minimize the complication rate.
Blockchain and Information Integration: Applications in New Zealand’s Prefabrication Supply Chain
Authors: Bakhtiarizadeh Ehsan , Shahzad Wajiha Mohsin , Poshdar Mani , Khalfan Malik , Rotimi James Olabode Bamidele
Published: December 2021

New Zealand’s rising demand for new and affordable homes is driving innovative and effective methods for project delivery. Prefabrication or off-site construction is considered an innovative approach to project delivery that eliminates the limitations of traditional construction methods. However, the prefabrication industry struggles with several challenges, including poor coordination and low supply chain integration amongst its partner organisations. There has been previous literature on improving the prefabrication supply chain integration, but few studies about the role of technology in this sector. Therefore, this article provides intuitions into the applicability and benefits of advanced technologies, namely blockchain, for improving supply chain integration in the context of prefabrication in New Zealand. A questionnaire survey was used to identify the channels used for information exchange between clients and contractors. Moreover, the questionnaire ascertained the positive effects of blockchain on enhancing supply chain integration between the two partners. Blockchain has proven to be a secure information integration instrument that can improve the integration of the prefabrication supply chain by fostering collaboration between organisations.
Effects of Different Surface Heat Transfer Coefficients on Predicted Heating and Cooling Loads towards Sustainable Building Design
Authors: Wu Yanwen , Jian Wenna , Yang Liu , Zhang Tengyue , Liu Yan
Published: December 2021

The transfer of surface heat between a building and the outdoor environment is the energy transfer channel and it is important for the energy efficiency of buildings. Early stage building design is a critical stage and it can directly determine the energy consumption by a building. Therefore, selecting appropriate surface heat transfer coefficients (SHTCs) is a key issue in building energy consumption prediction. In this study, EnergyPlus was employed to investigate the building load in Chinese cities with different SHTCs: (1) constant SHTCs based on national standards; and (2) dynamically changing SHTCs based on the Thermal Analysis Research Program (TARP). Based on investigations of the hourly load, daily cumulative load in a typical day, and annual cumulative load with different SHTCs, corrections for the annual cumulative load were obtained according to the relative deviations between the results produced with the TARP model and traditional SHTCs. The greatest relative deviations were 67.5% and 25.3% for the building shape factor φ = 0.49 and 0.29 in Lhasa. The relative deviations were 13.3% and 12.0% for φ = 0.49 in Xi’an and Beijing, respectively. Corrections were not essential for other conditions because the relative deviations were lower than 5.0%. Considering the current characteristics of engineering calculations and the need to obtain more accurate design results, dynamically changing SHTCs should be applied. These correction factors can obtain more accurate results for the current building energy efficiency system with traditional SHTCs.
Evaluation of Non-Autoclaved Aerated Concrete for Energy Behaviors of a Residential House in Nur-Sultan, Kazakhstan
Authors: Shon Chang-Seon , Mukangali Inzhu , Zhang Dichuan , Ulykbanov Anuar , Kim Jong
Published: December 2021

Autoclaved aerated concrete (AAC) is commonly used as a modern, energy-efficient construction material in Nur-Sultan, Kazakhstan—the second-coldest national capital in the world after Ulaanbaatar, Mongolia. The autoclave curing method used to manufacture the AAC has potential risks and is environmentally costly because of its high-pressure and -temperature operation. Therefore, for phase I and II studies, non-autoclaved aerated concrete (NAAC) was cast, and its properties were evaluated in terms of compressive strength, density, porosity, and thermal conductivity. Moreover, the thermal conductivity prediction model of NAAC was successfully developed. In this Phase III study, the energy behavior of the NAAC was evaluated by energy simulation for a typical two-story residential house model in Kazakhstan. Different wall materials, such as fired brick and normal concrete, were adapted to compare the energy performance of NAAC. Finally, the annual heat loss and amount of heat transferred through the wall of the house were calculated to cross-check the energy-saving effect of NAAC. It was found that the NAAC conserved energy, because the heating and cooling loads, annual heat loss, and amount of heat transfer of NACC were lower than those of fired brick and normal concrete.
Use of AI Algorithms in Different Building Typologies for Energy Efficiency towards Smart Buildings
Authors: Bagheri Ali , Genikomsakis Konstantinos N. , Koutra Sesil , Sakellariou Vasileios , Ioakimidis Christos S.
Published: December 2021

Buildings’ heating and cooling systems account for an important part of total energy consumption. The EU’s directives and engagements motivate building owners and relevant stakeholders in the energy and construction sectors towards net zero energy buildings by maximizing the use of renewable energy sources, ICT, and automation systems. However, the high costs of investment for the renovation of buildings, in situ use of renewable energy production, and installation of expensive ICT infrastructure and automation systems in small–medium range buildings are the main obstacles for the wide adoption of EU building directives in small- and medium-range buildings. On the other hand, the concept of sharing computational and data storage resources among various buildings can be an alternative approach to achieving smart buildings and smart cities where the main control power resides on a server. Unlike other studies that focus on the implementation of AI techniques in a building or separated buildings with local processing resources and data storage, in this work a corporate server was employed to control the heating systems in three building typologies and to examine the potential benefits of controlling existing buildings in a unified energy-savings platform. The key finding of this work is that the AI algorithms incorporated into the proposed system achieved significant energy savings in the order of 20–40% regardless of building typology, building functionality, and type of heating system, despite the COVID-19 measures for frequent ventilation of the buildings, even in cases with older-type heating systems.
Prognostic Risk Assessment and Prediction of Radiotherapy Benefit for Women with Ductal Carcinoma In Situ (DCIS) of the Breast, in a Randomized Clinical Trial (SweDCIS)
Authors: Wärnberg Fredrik , Karlsson Per , Holmberg Erik , Sandelin Kerstin , Whitworth Pat W. , Savala Jess , Barry Todd , Leesman Glen , Linke Steven P. , Shivers Steven C. , Vicini Frank , Shah Chirag , Weinmann Sheila , Mann Gregory Bruce , Bremer Troy
Published: December 2021

Prediction of radiotherapy (RT) benefit after breast-conserving surgery (BCS) for DCIS is crucial. The aim was to validate a biosignature, DCISionRT®, in the SweDCIS randomized trial. Women were randomly assigned to RT or not after BCS, between 1987 and 2000. Tumor blocks were collected, and slides were sent to PreludeDxTM for testing. In 504 women with complete data and negative margins, DCISionRT divided 52% women into Elevated (DS > 3) and 48% in Low (DS ≤ 3) Risk groups. In the Elevated Risk group, RT significantly decreased relative 10-year ipsilateral total recurrence (TotBE) and 10-year ipsilateral invasive recurrence (InvBE) rates, HR 0.32 and HR 0.24, with absolute decreases of 15.5% and 9.3%. In the Low Risk group, there were no significant risk differences observed with radiotherapy. Using a cutoff of DS > 3.0, the test was not predictive for RT benefit (p = 0.093); however, above DS > 2.8 RT benefit was greater for InvBE (interaction p = 0.038). Recurrences at 10 years without radiotherapy increased significantly per 5 DS units (TotBE HR:1.5 and InvBE HR:1.5). Continuous DS was prognostic for TotBE risk although categorical DS did not reach significance. Absolute 10-year TotBE and InvBE risks appear sufficiently different to indicate that DCISionRT can aid physicians in selecting individualized adjuvant DCIS treatment strategies. Further analyses are planned in combined cohorts to increase statistical power.