bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Management of Jugular Foramen Schwannomas
Authors: Aftahy Amir Kaywan , Groll Maximilian , Barz Melanie , Bernhardt Denise , Combs Stephanie E. , Meyer Bernhard , Negwer Chiara , Gempt Jens
Published: August 2021

Background: Resection of jugular foramen schwannomas (JFSs) with minimal cranial nerve (CN) injury remains difficult. Reoperations in this vital region are associated with severe CN deficits. Methods: We performed a retrospective analysis at a tertiary neurosurgical center of patients who underwent surgery for JFSs between June 2007 and May 2020. We included nine patients (median age 60 years, 77.8% female, 22.2% male). Preoperative symptoms included hearing loss (66.6%), headache (44.4%), hoarseness (33.3%), dysphagia (44.4%), hypoglossal nerve palsy (22.2%), facial nerve palsy (33.3%), extinguished gag reflex (22.2%), and cerebellar dysfunction (44.4%). We observed Type A, B, C, and D tumors in 3, 1, 1, and 4 patients, respectively. A total of 77.8% (7/9) underwent a retrosigmoid approach, and 33.3% (3/9) underwent an extreme lateral infrajugular transcondylar (ELITE) approach. Gross total resection (GTR) was achieved in all cases. The rate of shunt-dependent hydrocephalus was 22.2% (2/9). No further complications requiring surgical intervention occurred during follow-up. The median follow-up time was 16.5 months (range 3–84 months). Conclusions: Considering the satisfying outcome, the GTR of JFSs is feasible in performing well-known skull base approaches. Additional invasive and complicated approaches were not needed. Radiosurgery may be an effective alternative for selected patients.
Duration of Reduced CA19-9 Levels Is a Better Prognostic Factor Than Its Rate of Reduction for Unresectable Locally Advanced Pancreatic Cancer
Authors: Tomishima Ko , Ishii Shigeto , Fujisawa Toshio , Ikemura Muneo , Ota Hiroto , Kabemura Daishi , Ushio Mako , Fukuma Taito , Takahashi Sho , Yamagata Wataru , Takasaki Yusuke , Suzuki Akinori , Ito Koichi , Saito Hiroaki , Nagahara Akihito , Isayama Hiroyuki
Published: August 2021

A decrease in carbohydrate antigen (CA) 19-9 levels has been proposed as a prognostic marker for survival and recurrence in patients with pancreatic cancer. We evaluated the association between duration of reduced CA 19-9 levels during 6 months after treatment and long-term survival for 79 patients with unresectable locally advanced pancreatic cancer (LAPC). We calculated the differences between pretreatment and monthly CA19-9 levels. We categorized 71 patients with decreases in CA19-9 levels into three groups based on the duration of these reduced levels (>2, >3, and >4 months). The cut-off level for long-term (more than 2 years) survival was identified as a 44% reduction from the baseline, using a ROC curve. A reduction duration >2 months was not associated with overall survival (p = 0.1), while >3 months was significantly associated with survival (p =.04). In multivariate analysis, a reduction duration >3 months predicted a good long-term prognosis (odds ratio = 5.75; 95% confidence interval = 1.47–22.36; p < 0.01). In patients with unresectable LAPC, the duration of reduced CA19-9 levels for more than 3 months, rather than the rate of reduction in CA19-9 levels, during 6 months after treatment was significantly associated with good prognosis.
Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma
Authors: Tsai Joseph C. , Saad Omar A. , Magesh Shruti , Xu Jingyue , Lee Abby C. , Li Wei Tse , Chakladar Jaideep , Fuster Mark M. , Chang Eric Y. , Wang-Rodriguez Jessica , Ongkeko Weg M.
Published: August 2021

Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA expression in relation to LUSC outcomes. We extracted eRNA counts from RNA-sequencing data of tumor/adjacent normal tissue and before/after e-cigarette tissue from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. Tobacco-mediated LUSC eRNAs were correlated to patient survival, clinical variables, and immune-associated elements. eRNA expression was also correlated to mutation rates through the Repeated Evaluation of Variables Conditional Entropy and Redundance (REVEALER) algorithm and methylated sites through methylationArrayAnalysis. Differential expression analysis was then completed for the e-cigarette data to compare with key tobacco-mediated eRNAs. We identified 684 downregulated eRNAs and 819 upregulated eRNAs associated with tobacco-mediated LUSC, specifically, with the cancer pathological stage. We also observed a decrease in immune cell abundance in tobacco-mediated LUSC. Yet, we found an increased association of eRNA expression with immune cell abundance in tobacco-mediated LUSC. We identified 16 key eRNAs with significant correlations to 8 clinical variables, implicating these eRNAs in LUSC malignancy. Furthermore, we observed that these 16 eRNAs were highly associated with chromosomal alterations and reduced CpG site methylation. Finally, we observed large eRNA expression upregulation with e-cigarette use, which corresponded to the upregulation of the 16 key eRNAs. Our findings provide a novel mechanism by which tobacco and e-cigarette smoke influences eRNA interactions to promote LUSC pathogenesis and provide insight regarding disease progression at a molecular level.
Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications
Authors: Basheer Abdul Samad , Abas Faridah , Othman Iekhsan , Naidu Rakesh
Published: August 2021

Gliomas are the most common, highly malignant, and deadliest forms of brain tumors. These intra-cranial solid tumors are comprised of both cancerous and non-cancerous cells, which contribute to tumor development, progression, and resistance to the therapeutic regimen. A variety of soluble inflammatory mediators (e.g., cytokines, chemokines, and chemotactic factors) are secreted by these cells, which help in creating an inflammatory microenvironment and contribute to the various stages of cancer development, maintenance, and progression. The major tumor infiltrating immune cells of the tumor microenvironment include TAMs and TANs, which are either recruited peripherally or present as brain-resident macrophages (microglia) and support stroma for cancer cell expansion and invasion. These cells are highly plastic in nature and can be polarized into different phenotypes depending upon different types of stimuli. During neuroinflammation, glioma cells interact with TAMs and TANs, facilitating tumor cell proliferation, survival, and migration. Targeting inflammatory mediators along with the reprogramming of TAMs and TANs could be of great importance in glioma treatment and may delay disease progression. In addition, an inhibition of the key signaling pathways such as NF-κB, JAK/STAT, MAPK, PI3K/Akt/mTOR, and TLRs, which are activated during neuroinflammation and have an oncogenic role in glioblastoma (GBM), can exert more pronounced anti-glioma effects.
MET Mutation Is a Potential Therapeutic Target for Advanced Endometrial Cancer
Authors: Yeh Yu-Min , Wu Pei-Ying , Lin Peng-Chan , Su Pei-Fang , Hsu Ya-Ting , Hsu Keng-Fu , Shen Meng-Ru
Published: August 2021

An optimal therapeutic regimen for endometrial cancer with extra-uterine metastasis is unavailable. This study aims to improve our understanding of the genomic landscape of advanced endometrial cancer and identify potential therapeutic targets. The clinical and genomic profiles of 81 patients with stage III or IV endometrial cancer were integrated. To identify genomic aberrations associated with clinical outcomes, Cox proportional hazard regression was used. The impacts of the genomic aberrations were validated in vitro and in vivo. The mutation status of MET, U2AF1, BCL9, PPP2R1A, IDH2, CBL, BTK, and CHEK2 were positively correlated with poor clinical outcomes. MET mutations occurred in 30% of the patients who presented with poor overall survival (hazard ratio, 2.606; 95% confidence interval, 1.167~5.819; adjusted p-value, 0.067). Concurrent MET and KRAS mutations presented with the worst outcomes. MET mutations in hepatocyte growth factor (HGF)-binding (58.1%) or kinase (16.2%) domains resulted in differential HGF-induced c-MET phosphorylation. Different types of MET mutations differentially affected tumor growth and displayed different sensitivities to cisplatin and tyrosine kinase inhibitors. MET N375S mutation is a germline variant that causes chemoresistance to cisplatin, with a high incidence in Eastern Asia. This study highlights the ethnic differences in the biology of the disease, which can influence treatment recommendations and the genome-guided clinical trials of advanced endometrial cancer.
Tumor Microenvironment in Breast Cancer—Updates on Therapeutic Implications and Pathologic Assessment
Authors: Li Joshua J. , Tsang Julia Y. , Tse Gary M.
Published: August 2021

The tumor microenvironment (TME) in breast cancer comprises local factors, cancer cells, immune cells and stromal cells of the local and distant tissues. The interaction between cancer cells and their microenvironment plays important roles in tumor proliferation, propagation and response to therapies. There is increasing research in exploring and manipulating the non-cancerous components of the TME for breast cancer treatment. As the TME is now increasingly recognized as a treatment target, its pathologic assessment has become a critical component of breast cancer management. The latest WHO classification of tumors of the breast listed stromal response pattern/fibrotic focus as a prognostic factor and includes recommendations on the assessment of tumor infiltrating lymphocytes and PD-1/PD-L1 expression, with therapeutic implications. This review dissects the TME of breast cancer, describes pathologic assessment relevant for prognostication and treatment decision, and details therapeutic options that interacts with and/or exploits the TME in breast cancer.
Volatile Fatty Acids from Lipid-Extracted Yeast Provide Additional Feedstock for Microbial Lipid Production
Authors: Park Gwon Woo , Son Seongsoo , Moon Myounghoon , Sin Subin , Min Kyoungseon , Lee Jin-Suk , Chang Ho Nam
Published: August 2021

Microbial lipid production from oleaginous yeasts is a promising process for the sustainable development of the microbial biodiesel industry. However, the feedstock cost poses an economic problem for the production of microbial biodiesel. After lipid extraction, yeast biomass can be used as an organic source for microbial biodiesel production. In this study, volatile fatty acids (VFAs), produced via anaerobic digestion of a lipid-extracted yeast (LEY) residue, were utilized as a carbon source for the yeast Cryptococcus curvatus. The response surface methodology was used to determine the initial pH and inoculum volume for the optimal VFA production. The experimental result for VFA concentration was 4.51 g/L at an initial pH of 9 and an inoculation 25%. The optimization results from the response surface methodology showed that the maximal VFA concentration was 4.58 g/L at an initial pH of 8.40 and an inoculation of 39.49%. This study indicates that VFAs from LEY can be used as a carbon source for microbial biodiesel production, with the potential to significantly reduce feedstock costs.
Regiodivergent Organocatalytic Reactions
Authors: Viji Mayavan , Lanka Srinu , Sim Jaeuk , Jung Chanhyun , Lee Heesoon , Vishwanath Manjunatha , Jung Jae-Kyung
Published: August 2021

Organocatalysts are abundantly used for various transformations, particularly to obtain highly enantio- and diastereomeric pure products by controlling the stereochemistry. These applications of organocatalysts have been the topic of several reviews. Organocatalysts have emerged as one of the very essential areas of research due to their mild reaction conditions, cost-effective nature, non-toxicity, and environmentally benign approach that obviates the need for transition metal catalysts and other toxic reagents. Various types of organocatalysts including amine catalysts, Brønsted acids, and Lewis bases such as N-heterocyclic carbene (NHC) catalysts, cinchona alkaloids, 4-dimethylaminopyridine (DMAP), and hydrogen bond-donating catalysts, have gained renewed interest because of their regioselectivity. In this review, we present recent advances in regiodivergent reactions that are governed by organocatalysts. Additionally, we briefly discuss the reaction pathways of achieving regiodivergent products by changes in conditions such as solvents, additives, or the temperature.
Monapinone Coupling Enzyme Produces Non-Natural Heterodimers
Authors: Ohte Satoshi , Toyoda Masayuki , Kobayashi Keisuke , Fujii Isao , Ohshiro Taichi , Tomoda Hiroshi
Published: August 2021

The monapinone coupling enzyme (MCE), a fungal multicopper oxidase, catalyzes the regioselective C–C coupling between tricyclic monapinone A (the primary substrate) and other monapinones (secondary substrates) to produce atropisomeric biaryl homo- or heterodimers. In this study, mono-, bi- and tricyclic compounds were tested to determine whether they worked as secondary substrates for MCE. Among 14 cyclic compounds, MCE utilized semivioxanthin, YWA1, 1,3-naphthalenediol and flaviolin as secondary substrates to produce non-natural heterodimers. The atropisomeric biaryl heterodimers produced by MCE from monapinone A and semivioxanthin were isolated, and their structures were elucidated by NMR and MS. These findings indicate that MCE recognizes bi- and tricyclic compounds with a 1,3-dihydroxy or 1-hydroxy-3-methoxy benzene ring as a secondary substrate.
Identifying Energy Extraction Optimisation Strategies of Actinobacillus succinogenes
Authors: Lexow Waldo Gideon , Mokwatlo Sekgetho Charles , Brink Hendrik Gideon , Nicol Willie
Published: August 2021

A. succinogenes is well known for utilising various catabolic pathways. A multitude of batch fermentation studies confirm flux shifts in the catabolism as time proceeds. It has also been shown that continuous cultures exhibit flux variation as a function of dilution rate. This indicates a direct influence of the external environment on the proteome of the organism. In this work, ATP production efficiency was explored to evaluate the extent of bio-available energy on the production behaviour of A. succinogenes. It was found that the microbe successively utilised its most-to-least efficient energy extraction pathways, providing evidence of an energy optimisation survival strategy. Moreover, data from this study suggest a pyruvate overflow mechanism as a means to throttle acetic and formic acid production, indicating a scenario in which the external concentration of these acids play a role in the energy extraction capabilities of the organism. Data also indicates a fleeting regime where A. succinogenes utilises an oxidised environment to its advantage for ATP production. Here it is postulated that the energy gain and excretion cost of catabolites coupled to the changing environment is a likely mechanism responsible for the proteome alteration and its ensuing carbon flux variation. This offers valuable insights into the microbe’s metabolic logic gates, providing a foundation to understand how to exploit the system.
FDA-Approved Drug Screening for Compounds That Facilitate Hematopoietic Stem and Progenitor Cells (HSPCs) Expansion in Zebrafish
Authors: Feng Zhi , Lin Chenyu , Tu Limei , Su Ming , Song Chunyu , Liu Shengnan , Suryanto Michael Edbert , Hsiao Chung-Der , Li Li
Published: August 2021

Hematopoietic stem cells (HSCs) are a specialized subset of cells with self-renewal and multilineage differentiation potency, which are essential for their function in bone marrow or umbilical cord blood transplantation to treat blood disorders. Expanding the hematopoietic stem and progenitor cells (HSPCs) ex vivo is essential to understand the HSPCs-based therapies potency. Here, we established a screening system in zebrafish by adopting an FDA-approved drug library to identify candidates that could facilitate HSPC expansion. To date, we have screened 171 drugs of 7 categories, including antibacterial, antineoplastic, glucocorticoid, NSAIDS, vitamins, antidepressant, and antipsychotic drugs. We found 21 drugs that contributed to HSPCs expansion, 32 drugs’ administration caused HSPCs diminishment and 118 drugs’ treatment elicited no effect on HSPCs amplification. Among these drugs, we further investigated the vitamin drugs ergocalciferol and panthenol, taking advantage of their acceptability, limited side-effects, and easy delivery. These two drugs, in particular, efficiently expanded the HSPCs pool in a dose-dependent manner. Their application even mitigated the compromised hematopoiesis in an ikzf1−/− mutant. Taken together, our study implied that the larval zebrafish is a suitable model for drug repurposing of effective molecules (especially those already approved for clinical use) that can facilitate HSPCs expansion.
New Insights into Xenotransplantation for Cartilage Repair: Porcine Multi-Genetically Modified Chondrocytes as a Promising Cell Source
Authors: Tritschler Hanna , Fischer Konrad , Seissler Jochen , Fiedler Jörg , Halbgebauer Rebecca , Huber-Lang Markus , Schnieke Angelika , Brenner Rolf E.
Published: August 2021

Transplantation of xenogenic porcine chondrocytes could represent a future strategy for the treatment of human articular cartilage defects. Major obstacles are humoral and cellular rejection processes triggered by xenogenic epitopes like α-1,3-Gal and Neu5Gc. Besides knockout (KO) of genes responsible for the biosynthesis of respective epitopes (GGTA1 and CMAH), transgenic expression of human complement inhibitors and anti-apoptotic as well as anti-inflammatory factors (CD46, CD55, CD59, TNFAIP3 and HMOX1) could synergistically prevent hyperacute xenograft rejection. Therefore, chondrocytes from different strains of single- or multi-genetically modified pigs were characterized concerning their protection from xenogeneic complement activation. Articular chondrocytes were isolated from the knee joints of WT, GalTKO, GalT/CMAH-KO, human CD59/CD55//CD46/TNFAIP3/HMOX1-transgenic (TG), GalTKO/TG and GalT/CMAHKO/TG pigs. The tissue-specific effectiveness of the genetic modifications was tested on gene, protein and epitope expression level or by functional assays. After exposure to 20% and 40% normal human serum (NHS), deposition of C3b/iC3b/C3c and formation of the terminal complement complex (TCC, C5b-9) was quantified by specific cell ELISAs, and generation of the anaphylatoxin C5a by ELISA. Chondrocyte lysis was analyzed by Trypan Blue Exclusion Assay. In all respective KO variants, the absence of α -1,3-Gal and Neu5Gc epitope was verified by FACS analysis. In chondrocytes derived from TG animals, expression of CD55 and CD59 could be confirmed on gene and protein level, TNFAIP3 on gene expression level as well as by functional assays and CD46 only on gene expression level whereas transgenic HMOX1 expression was not evident. Complement activation in the presence of NHS indicated mainly effective although incomplete protection against C3b/iC3b/C3c deposition, C5a-generation and C5b-9 formation being lowest in single GalTKO. Chondrocyte viability under exposure to NHS was significantly improved even by single GalTKO and completely preserved by all other variants including TG chondrocytes without KO of xenoepitopes.
HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits
Authors: McLaurin Kristen A. , Harris Michael , Madormo Victor , Harrod Steven B. , Mactutus Charles F. , Booze Rosemarie M.
Published: August 2021

Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit observed following chronic HIV-1 viral protein exposure. An inclusive and critical evaluation of the literature, therefore, supports the fundamental conclusion that long-term HIV-1 viral protein exposure leads to a decreased dopaminergic state, which continues to persist despite the advent of cART. Thus, effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments must focus on strategies for rectifying decreases in dopamine function.
Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors
Authors: Cho Kyung-Ah , Choi Da-Won , Kim Yu-Hee , Kim Jungwoo , Ryu Kyung-Ha , Woo So-Youn
Published: August 2021

Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions.
A Novel Dialkylamino GFP Chromophore as an Environment-Polarity Sensor Reveals the Role of Twisted Intramolecular Charge Transfer
Authors: Chen Cheng , Boulanger Sean A. , Sokolov Anatolii I. , Baranov Mikhail S. , Fang Chong
Published: August 2021

We discovered a novel fluorophore by incorporating a dimethylamino group (–NMe2) into the conformationally locked green fluorescent protein (GFP) scaffold. It exhibited a marked solvent-polarity-dependent fluorogenic behavior and can potentially find broad applications as an environment-polarity sensor in vitro and in vivo. The ultrafast femtosecond transient absorption (fs-TA) spectroscopy in combination with quantum calculations revealed the presence of a twisted intramolecular charge transfer (TICT) state, which is formed by rotation of the –NMe2 group in the electronic excited state. In contrast to the bright fluorescent state (FS), the TICT state is dark and effectively quenches fluorescence upon formation. We employed a newly developed multivariable analysis approach to the FS lifetime in various solvents and showed that the FS → TICT reaction barrier is mainly modulated by H-bonding capability instead of viscosity of the solvent, accounting for the observed polarity dependence. These deep mechanistic insights are further corroborated by the dramatic loss of fluorogenicity for two similar GFP-derived chromophores in which the rotation of the –NMe2 group is inhibited by structural locking.
Nutritional Risks among Adolescent Athletes with Disordered Eating
Authors: Kontele Ioanna , Vassilakou Tonia
Published: August 2021

In their attempt to achieve the optimum weight or body shape for their activity, athletes frequently use harmful weight-control practices that may lead to the development of disordered eating or eating disorders. These practices are linked to several medical and mental consequences that may be more serious in adolescent athletes, as their bodies must meet both intensive growth demands and training requirements at the same time. Among other consequences, adolescent athletes may be at nutritional risk, due to their high nutrient needs and unhealthy eating behaviors. A literature review was conducted to examine the main nutritional risks and malnutrition issues faced by adolescent athletes that present disordered eating attitudes or eating disorders. Most studies refer to adult elite athletes, however research on adolescent athletes also indicates that the most common nutritional risks that may arise due to disordered eating include energy, macronutrient and micronutrient deficiencies, dehydration and electrolyte imbalances and changes in body composition that may lead to menstrual abnormalities, and decreased bone mass density. Educational programs and early detection of disordered eating and eating disorders are crucial to avoid the emergence and ensure timely management of nutrition-related problems in the vulnerable group of adolescent athletes.
Cardiac Manifestations in Children with SARS-COV-2 Infection: 1-Year Pediatric Multicenter Experience
Authors: Cantarutti Nicoletta , Battista Virginia , Adorisio Rachele , Cicenia Marianna , Campanello Claudia , Listo Elisa , Campana Andrea , Trocchio Gianluca , Drago Fabrizio
Published: August 2021

Since the spread of COVID-19, pediatric patients were initially considered less affected by SARS-COV-2, but current literature reported subsets of children with multisystem inflammatory syndrome (MIS-C). This study aims to describe the cardiac manifestation of SARS-COV-2 infection in a large cohort of children admitted to two Italian pediatric referral centers. Between March 2020 and March 2021, we performed a cardiac evaluation in 294 children (mean age 9 ± 5.9 years, male 60%) with active or previous SARS-COV-2 infection. Twenty-six showed ECG abnormalities: 63 repolarization anomalies, 13 Long QTc, five premature ventricular beats, two non-sustained ventricular tachycardia, and one atrial fibrillation. In total, 146 patients underwent cardiac biomarkers: NT-proBNP was elevated in 57, troponin in 34. An echocardiogram was performed in 98, showing 54 cardiac anomalies: 27 left-ventricular dysfunction, 42 pericarditis, 16 coronaritis. MIS-C was documented in 46 patients (mean age 9 ± 4.8 years, male 61%) with cardiac manifestations in 97.8%: 27 ventricular dysfunctions, 32 pericarditis, 15 coronaritis, 3 arrhythmias. All patients recovered, and during follow-up, no cardiac anomalies were recorded. Our experience showed that cardiac involvement is not rare in children with SARS-COV-2, and occurred in almost all patients with MIS-C. However, patients’ recovery is satisfactory and no additional events were reported during FU.
Capillary Blood Gas Predicts Risk of Intensive Care in Children with Bronchiolitis
Authors: Wrotek August , Kobiałka Małgorzata , Jackowska Teresa
Published: August 2021

Background: Bronchiolitis may result in respiratory failure diagnosed with arterial blood gas (ABG). ABG is not routinely performed in general paediatric wards but is closely reflected by capillary blood gas (CBG). We sought to assess the usefulness of CBG results in prediction of intensive care unit (ICU) transfer, antibiotic treatment, and length of stay in children hospitalized due to bronchiolitis. Methods: The optimal cutoff values were estimated with an ROC analysis, while a multiple regression model calculated the odds of an ICU transfer, prolonged hospitalization, and antibiotic treatment related with hypercapnia (pCO2 ≥ 45 mmHg) and acidosis (pH ≤ 7.35). The correlation between the CBG (pH, pCO2, and SatO2) and the clinical/laboratory parameters (breath rate, heart rate, pulse oximetry, white blood cells, CRP, and procalcitonin) was calculated. Results: The CBG was performed in 485 children aged 8 days–22 months (median 2 months). The pCO2 was significantly higher in ICU transferred patients (median 44.8 mmHg vs. 36.2 mmHg, p < 0.01), and showed AUC = 0.773, (95% CI: 0.638–0.907, p < 0.01) for ICU transfer (67% sensitivity, 82% specificity, 10.8% positive and 98.7% negative predictive value at cutoff 41.8 mmHg). Hypercapnia (OR = 6.63, 95% CI: 2.15–20.46, p < 0.01) and acidosis (OR = 5.01, 95% CI: 1.26–19.9, p = 0.022) predicted the ICU transfer independently. The CBG parameters were not related to prolonged hospitalization or antibiotic treatment, and showed only a weak and clinically irrelevant correlation with other laboratory and clinical parameters. Conclusions: Acidosis and hypercapnia indicate patients at risk of an ICU transfer, and the pCO2 levels (including values lower than hypercapnia) seem to be a promising marker in ICU risk assessment.
Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster
Authors: Solovev Ilya A. , Shaposhnikov Mikhail V. , Moskalev Alexey A.
Published: August 2021

Chronobiotics are a group of drugs, which are utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes in connection with aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p < 0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p < 0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagoes (p < 0.05), elevated morning activity peak in aged imagoes and modified robustness of their circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p < 0.01), while median resistance was elevated by 50% (p < 0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001.
Review on Surface Treatment for Implant Infection via Gentamicin and Antibiotic Releasing Coatings
Authors: Tiwari Abhishek , Sharma Prince , Vishwamitra Bhagyashree , Singh Gaurav
Published: August 2021

Surface treatment of metallic implants plays a crucial role in orthopedics and orthodontics. Metallic implants produce side-effects such as physical, chemical/electro-chemical irritations, oligodynamic/catalytic and carcinogenic effects. These effects cause bacterial infections and account for huge medical expenses. Treatment for these infections comprises repeated radical debridement, replacement of the implant device and intravenous or oral injection antibiotics. Infection is due to the presence of bacteria in the patient or the surrounding environment. The antibiotic-based medication prevents prophylaxis against bacterial colonization, which is an emphatic method that may otherwise be catastrophic to a patient. Therefore, preventive measures are essential. A coating process was developed with its drug infusion and effect opposing biofilms. Modification in the medical implant surface reduces the adhesion of bacterial and biofilms, the reason behind bacterial attachment. Other polymer-based and nanoparticle-based carriers are used to resolve implant infections. Therefore, using an implant coating is a better approach to prevent infection due to biofilm.
Hierarchical Two-Dimensional Layered Double Hydroxide Coated Polydopamine Nanocarriers for Combined Chemodynamic and Photothermal Tumor Therapy
Authors: Busa Prabhakar , Koutavarapu Ravindranadh , Lee Dong-Yeon , Shim Jaesool , Kuthati Yaswanth
Published: August 2021

The combination of chemodynamic therapy (CDT) and photothermal therapy (PTT) has proven to be successful in combating the challenges associated with cancer therapy. A combination of these therapies can maximize the benefits of each therapeutic modality through endogenous reduction-oxidation (redox) reaction and external laser power induction. In the current work, we have designed a copper-aluminum layered double hydroxide (CuAl-LDH) loaded doxorubicin (DOX) by a co-precipitation method; the surface was coated with polydopamine (PDA). The synthesized CuAl-LDH@DOX@PDA nanocarrier (NC) served as a Fenton-like catalyst with photothermal properties. It is well known that metal ion incorporated NCs can induce intracellular depletion of reduced glutathione (GSH) levels along with the reduction of Cu2+ to Cu+. The Cu+ ions in turn react with DOX leading to the generation of intracellular hydrogen peroxide (H2O2) molecules to produce the highly toxic hydroxyl radicals (•OH) through a Fenton-like reaction. The enhanced absorption of CuAl@DOX@PDA at 810 nm, greatly improved the photothermal efficiency in comparison with bare CuAl-LDH and CuAl-LDH@DOX. In vitro studies revealed the tremendous CDT/PTT efficacy of CuAl@DOX@PDA in suppressing A549 cancer cells. Furthermore, reactive oxygen species (ROS) assays and intracellular levels of various ROS cascade biomolecules support our findings in the efficient destruction of cancer cells through synergistic CDT/PTT therapy.
Can ‘On-Farm’ Seed Priming and Chitosan Seed Treatments Induce Host Defences in Winter Barley (Hordeum vulgare L.) under Field Conditions?
Authors: Carrillo-Reche Javier , Newton Adrian C. , Ferrando-Molina Francesc , Quilliam Richard S.
Published: August 2021

Enhancing host defences through induced resistance, disease tolerance, and/or escape, in combination with current disease management regimes may be a valuable strategy to reduce pesticide use. Since both ‘on-farm’ seed priming (OSP) and chitosan priming (CHP) have been reported to confer varying levels of host defence, this study sought to investigate their potential to deliver disease control as a strategy for sustainable management of foliar pathogens in winter barley. Field experiments were conducted to determine the effects of OSP and CHP at two different field sites using three different cultivars under fungicide/non-fungicide regimes. Overall, no evidence was found to suggest that CHP or OSP can induce effective resistance in temperate field conditions. However, these field trials enabled the identification of candidate traits to deliver disease tolerance (and escape) for the primary and secondary spread of powdery mildew, i.e., large canopies and rapid stem elongation respectively. Thus, these seed treatments may deliver disease tolerance and escape traits, but these benefits are dependent upon successful establishment and vigour first. The integration of seed treatments into sustainable crop protection may be better undertaken with spring crops or in semi-arid agriculture where the added vigour at emergence can help compensate for negative environmental interactions.
Implementing Privacy-Preserving Genotype Analysis with Consideration for Population Stratification
Authors: Ostrak Andre , Randmets Jaak , Sokk Ville , Laur Sven , Kamm Liina
Published: August 2021

In bioinformatics, genome-wide association studies (GWAS) are used to detect associations between single-nucleotide polymorphisms (SNPs) and phenotypic traits such as diseases. Significant differences in SNP counts between case and control groups can signal association between variants and phenotypic traits. Most traits are affected by multiple genetic locations. To detect these subtle associations, bioinformaticians need access to more heterogeneous data. Regulatory restrictions in cross-border health data exchange have created a surge in research on privacy-preserving solutions, including secure computing techniques. However, in studies of such scale, one must account for population stratification, as under- and over-representation of sub-populations can lead to spurious associations. We improve on the state of the art of privacy-preserving GWAS methods by showing how to adapt principal component analysis (PCA) with stratification control (EIGENSTRAT), FastPCA, EMMAX and the genomic control algorithm for secure computing. We implement these methods using secure computing techniques—secure multi-party computation (MPC) and trusted execution environments (TEE). Our algorithms are the most complex ones at this scale implemented with MPC. We present performance benchmarks and a security and feasibility trade-off discussion for both techniques.
Crystal Plasticity with Micromorphic Regularization in Assessing Scale Dependent Deformation of Polycrystalline Doped Copper Alloys
Authors: Lindroos Matti , Andersson Tom , Metsäjoki Jarkko , Laukkanen Anssi
Published: August 2021

It is planned that doped copper overpacks will be utilized in the spent nuclear fuel repositories in Finland and in Sweden. The assessment of long-term integrity of the material is a matter of importance. Grain structure variations, segregation and any possible manufacturing defects in microstructure are relevant in terms of susceptibility to creep and damage from the loading evolution imposed by its operating environment. This work focuses on studying the microstructure level length-scale dependent deformation behavior of the material, of particular significance with respect to accumulation of plasticity over the extensive operational period of the overpacks. The reduced micromorphic crystal plasticity model, which is similar to strain gradient models, is used in this investigation. Firstly, the model’s size dependent plasticity effects are evaluated. Secondly, different microstructural aggregates presenting overpack sections are analyzed. Grain size dependent hardening responses, i.e., Hall-Petch like behavior, can be achieved with the enhanced hardening associated with the micromorphic model at polycrystalline level. It was found that the nominally large grain size in the base material of the overpack shows lower strain hardening potential than the fine grained region of the welded microstructure with stronger strain gradient related hardening effects. Size dependent regularization of strain localization networks is indicated as a desired characteristic of the model. The findings can be utilized to provide an improved basis for modeling the viscoplastic deformation behavior of the studied copper alloy and to assess the microstructural origins of any integrity concerns explicitly by way of full field modeling.
High-Performance Flexible Transparent Electrodes Fabricated via Laser Nano-Welding of Silver Nanowires
Authors: Wang Tao , Yan Yinzhou , Zhu Liye , Li Qian , He Jing , Zhang Xiaoxia , Li Xi , Zhang Xiaohua , Pan Yongman , Wang Yue
Published: August 2021

Silver nanowires (Ag-NWs), which possess a high aspect ratio with superior electrical conductivity and transmittance, show great promise as flexible transparent electrodes (FTEs) for future electronics. Unfortunately, the fabrication of Ag-NW conductive networks with low conductivity and high transmittance is a major challenge due to the ohmic contact resistance between Ag-NWs. Here we report a facile method of fabricating high-performance Ag-NW electrodes on flexible substrates. A 532 nm nanosecond pulsed laser is employed to nano-weld the Ag-NW junctions through the energy confinement caused by localized surface plasmon resonance, reducing the sheet resistance and connecting the junctions with the substrate. Additionally, the thermal effect of the pulsed laser on organic substrates can be ignored due to the low energy input and high transparency of the substrate. The fabricated FTEs demonstrate a high transmittance (up to 85.9%) in the visible band, a low sheet resistance of 11.3 Ω/sq, high flexibility and strong durability. The applications of FTEs to 2D materials and LEDs are also explored. The present work points toward a promising new method for fabricating high-performance FTEs for future wearable electronic and optoelectronic devices.
Binding Strength and Hydrogen Bond Numbers between COVID-19 RBD and HVR of Antibody
Authors: Wang Ryan Taoran , Xu Alex Fan , Zhou Qi , Song Tinglu , Xu Kelvin J. , Xu Gu
Published: August 2021

The global battle against the COVID-19 pandemic relies strongly on the human defense of antibody, which is assumed to bind the antigen’s receptor binding domain (RBD) with its hypervariable region (HVR). Due to the similarity to other viruses such as SARS, however, our understanding of the antibody-virus interaction has been largely limited to the genomic sequencing, which poses serious challenges to containment and rapid serum testing. Based on the physical/chemical nature of the interaction, infrared spectroscopy was employed to reveal the binding disparity, the real cause of the antibody-virus specificity at the molecular level, which is inconceivable to be investigated otherwise. Temperature dependence was discovered in the absorption value from the 1550 cm−1 absorption band, attributed to the hydrogen bonds by carboxyl/amino groups, binding the SARS-CoV-2 spike protein and closely resembled SARS-CoV-2 or SARS-CoV-1 antibodies. The infrared absorption intensity, associated with the number of hydrogen bonds, was found to increase sharply between 27 °C and 31 °C, with the relative absorbance matching the hydrogen bonding numbers of the two antibody types (19 vs. 12) at 37 °C. Meanwhile, the ratio of bonds at 27 °C, calculated by thermodynamic exponentials, produces at least 5% inaccuracy. Beyond genomic sequencing, the temperature dependence, as well as the bond number match at 37 °C between relative absorbance and the hydrogen bonding numbers of the two antibody types, is not only of clinical significance in particular but also as a sample for the physical/chemical understanding of vaccine–antibody interactions in general.
Research on Shock Acceleration Limit of an Ultra-Stable Optical Cavity for Space Applications Based on the Finite Element Methodology
Authors: Xu Guanjun , Jiao Dongdong , Chen Long , Zhang Linbo , Liu Jun , Dong Ruifang , Liu Tao , Wang Junbiao
Published: August 2021

Ultra-stable optical cavities (USOCs) as fragile precision instruments have many important applications in space. In order to protect them from being damaged during a rocket launch, we analyzed a USOC by means of finite element methodology. The shock acceleration limits that the USOC can withstand in different directions and under various conditions are given. To increase the shock acceleration limit, the midplane thickness and the fixed hole diameter should be selected to be as high as possible. It is worth noting that the launch direction of the USOC should be selected as the horizontal direction, for which the shock acceleration limit that the USOC can withstand is approximately two times that of the vertical direction. In this paper, results provide guidance for the design of USOCs for space applications, especially the design to prevent the damage caused by a shock. The method could then be applied to other space optical cavities, providing a tool to improve the effect of shock at high accelerations.
Effects of the Rare Earth Y on the Structural and Tensile Properties of Mg-based Alloy: A First-Principles Study
Authors: Gao Yan , Wu Chuang , Feng Wenjiang , He Yan , He Haisheng , Yang Jingyu , Chen Xiuyan
Published: August 2021

In order to investigate the effect of the rare earth element Y on the strengthening potency of magnesium alloys and its strengthening mechanism under tension. In this paper, the solid solution structures with Y atom content of 1.8 at.% and 3.7 at.% were built, respectively, and their cohesive energies and stress-strain curve were calculated in the strain range of 0–20%. The calculation results of the cohesive energies showed that the structure of element Y is more stable with the increase of strains. The calculation results of stress and strain showed that Y element can improve the yield strength and tensile strength of the Mg-based alloy, and the strengthening effect is better when the Y content is 3.7 at.%.
The Towakkalak System, A Hotspot of Subterranean Biodiversity in Sulawesi, Indonesia
Authors: Deharveng Louis , Rahmadi Cahyo , Suhardjono Yayuk Rahayuningsih , Bedos Anne
Published: August 2021

The Towakkalak System located in the Maros karst of South Sulawesi is currently the richest of Southeast Asia in obligate subterranean species. It comprises several caves and shafts that give access to the subterranean Towakkalak river as well as many unconnected fossil caves, stream sinks, and springs located within its footprint. The total length of the caves linked to the active system is 24,319 m and comprises two of the longest caves of Indonesia, Gua Salukkan Kallang and Gua Tanette. Studies of its fauna began in 1985. There are 10 stygobionts and 26 troglobionts that are known from the system. The smaller adjacent system of Saripa has 6 stygobionts and 18 troglobionts, of which 1 and 3, respectively, are absent from Towakkalak. Like all tropical cave inventories, our dataset has limits due to identification uncertainties, gaps in habitat (waters, guano) and taxonomic coverage (micro-crustaceans, mites), sampling methods (pitfall trapping, Karaman–Chappuis), and problems of ecological assignment. A number of additional species are therefore expected to be found in the future. The Towakkalak and Saripa cave systems are included in the Bantimurung-Bulusaraung National Park and are under efficient protection, but parts of the Maros karst outside the park are under serious threat, mainly from quarrying.
Using Paleoecological Data to Inform the Conservation Strategy for Floristic Diversity and Isoetes taiwanensis in Northern Taiwan
Authors: Wang Liang-Chi
Published: August 2021

Paleoecological data can be used to inform nature conservation practice. Dream Lake (DL) is the best-preserved peat bog in the Tatun Volcanic Group of northern Taiwan. We analyzed continuous pollen and charcoal data from a well-dated sediment core from DL to reconstruct the changes in climate, lacustrine condition, and floristic diversity during the last 4500 cal BP. An absence of volcanic ash from all sediments indicates weak volcanic activity. Significant changes in lithology and pollen composition show that DL changed from a deep lake to a shallow peat bog from 3000 cal BP onwards. The palynological diversity index was negatively correlated with fire frequency. A substantial decline in Isoetes (quillwort) spores suggests increased vulnerability during the peat bog period. Natural terrestrialization will lower the mean water depth of DL below the minimum required for Isoetes taiwanensis survival within 300 years. Our findings indicate that winter precipitation driven by intense East Asian winter monsoons is the critical force determining the long-term variation in floristic diversity and abundance of I. taiwanensis. This long-term ecological history of DL, derived using paleoecological techniques, will be used to inform conservation practice in the Tatun Volcanic Group.