bluuebunny/crossref_metadata_2025 huggingface dataset:
How Severe Plastic Deformation Changes the Mechanical Properties of Thermoelectric Skutterudites and Half Heusler Alloys
Authors: Rogl Gerda , Rogl Peter F.
Published: November 2020

Thermoelectric leg materials with a high figure of merit, ZT, are the essential basis to build thermoelectric generators, directly converting waste heat into electricity. Skutterudites and half-Heusler alloys are promising candidates because they can be used in a wide temperature range, the starting material is available and cheap and in addition they are environmentally friendly. Severe plastic deformation via high-pressure torsion (HPT) is a technique to achieve very fine grains in micro- or even nano size with small and high angle grain boundaries and in parallel introduces a high level of defects like vacancies and dislocations. Therefore, this method was applied not only to enhance ZT of ball-milled and hot-pressed skutterudites and half-Heusler alloys but so far was also successful to directly produce dense nanostructured bulks from skutterudite powders. Although HPT compacted samples are chemically homogeneous, they are not homogeneous with respect to the shear strain increasing from the center to the rim. HPT changes the microstructure and density and thereby not only influences the thermoelectric but also the mechanical properties. In this work an overview is given of the influence of HPT on hardness, elastic moduli, indentation fracture toughness, thermal expansion and thermal shock resistance. The corresponding properties of hot-pressed skutterudites and half-Heusler alloys are compared with those after severe plastic deformation, dependent on the processing properties and position of the specimen in respect to shear strain. Data are collected from earlier investigations of the authors and from the literature, but also newly achieved and evaluated data are included.
Gastrointestinal Endoscopy in the Era of COVID-19
Authors: Perisetti Abhilash , Goyal Hemant , Sharma Neil
Published: November 2020

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which led to a worldwide pandemic that started in early 2020. Healthcare systems across the world encountered an unprecedented surge of COVID-19 patients resulting in more than half a million deaths globally. COVID-19 has affected multiple sub-specialties and procedure-related fields, including gastroenterology. Gastrointestinal (GI) endoscopy centers are specialized units where thousands of endoscopies are performed annually. A significant proportion of these procedures are affected due to the national and regional lockdowns across the globe. To adapt to this rapidly evolving situation, endoscopy centers have undergone significant changes and have taken unprecedented precautions to avoid the transmission of the virus. However, endoscopy centers are going through financial strain due to a reduction in the number of procedures from lockdowns and fear of virus transmission. Theoretically, endoscopies could add to the disease transmission as SARS-CoV-2 has shown to be present in the GI secretions. Multiple precautions such as mandatory use of face masks, safe distancing, use of barriers between the endoscopists and patients, negative pressure rooms, extended use of personal protective equipment, and volume reduction have been taken to decrease the risk of disease transmission by these centers. Moreover, pre-endoscopy COVID-19 testing has now become the norm. In this review, we highlight the significant changes assumed by the endoscopy center. Furthermore, we discuss cost-related concerns of pre-endoscopy COVID-19 testing, the downtime and delays related to the procedures, and effects of rescheduling. As the pandemic progresses through multiple phases, endoscopy centers should use a dynamic approach to adapt and strive to provide the best patient care.
Biofilm Producing Rhizobacteria With Multiple Plant Growth-Promoting Traits Promote Growth of Tomato Under Water-Deficit Stress
Authors: Haque Md. Manjurul , Mosharaf Md Khaled , Khatun Moriom , Haque Md. Amdadul , Biswas Md. Sanaullah , Islam Md. Shahidul , Islam Md. Mynul , Shozib Habibul Bari , Miah Md. Main Uddin , Molla Abul Hossain , Siddiquee Muhammad Ali
Published: November 2020

Plant growth-promoting rhizobacteria (PGPR) not only enhance plant growth but also control phytopathogens and mitigate abiotic stresses, including water-deficit stress. In this study, 21 (26.9%) rhizobacterial strains isolated from drought-prone ecosystems of Bangladesh were able to form air–liquid (AL) biofilms in the glass test tubes containing salt-optimized broth plus glycerol (SOBG) medium. Based on 16S rRNA gene sequencing,Pseudomonas chlororaphis(ESR3 and ESR15),P. azotoformansESR4,P. poaeESR6,P. fluorescens(ESR7 and ESR25),P. gessardiiESR9,P. cedrina(ESR12, ESR16, and ESR23),P. veronii(ESR13 and ESR21),P. parafulvaESB18,Stenotrophomonas maltophiliaESR20,Bacillus cereus(ESD3, ESD21, and ESB22),B. horikoshiiESD16,B. aryabhattaiESB6,B. megateriumESB9, andStaphylococcus saprophyticusESD8 were identified. Fourier transform infrared spectroscopy studies showed that the biofilm matrices contain proteins, polysaccharides, nucleic acids, and lipids. Congo red binding results indicated that these bacteria produced curli fimbriae and nanocellulose-rich polysaccharides. Expression of nanocellulose was also confirmed by Calcofluor binding assays and scanning electron microscopy.In vitrostudies revealed that all these rhizobacterial strains expressed multiple plant growth-promoting traits including N2fixation, production of indole-3-acetic acid, solubilization of nutrients (P, K, and Zn), and production of ammonia, siderophores, ACC deaminase, catalases, lipases, cellulases, and proteases. Several bacteria were also tolerant to multifarious stresses such as drought, high temperature, extreme pH, and salinity. Among these rhizobacteria,P. cedrinaESR12,P. chlororaphisESR15, andB. cereusESD3 impeded the growth ofXanthomonas campestrispv.campestrisATCC 33913, whileP. chlororaphisESR15 andB. cereusESD21 prevented the progression ofRalstonia solanacearumATCC®11696TM. In a pot experiment, tomato plants inoculated withP. azotoformansESR4,P. poaeESR6,P. gessardiiESR9,P. cedrinaESR12,P. chlororaphisESR15,S. maltophiliaESR20,P. veroniiESR21, andB. aryabhattaiESB6 exhibited an increased plant growth compared to the non-inoculated plants under water deficit-stressed conditions. Accordingly, the bacterial-treated plants showed a higher antioxidant defense system and a fewer tissue damages than non-inoculated plants under water-limiting conditions. Therefore, biofilm-producing PGPR can be utilized as plant growth promoters, suppressors of plant pathogens, and alleviators of water-deficit stress.
The Response of Estuarine Ammonia-Oxidizing Communities to Constant and Fluctuating Salinity Regimes
Authors: Santos João Pereira , Sousa António G. G. , Ribeiro Hugo , Magalhães Catarina
Published: November 2020

Aerobic nitrification is a fundamental nitrogen biogeochemical process that links the oxidation of ammonia to the removal of fixed nitrogen in eutrophicated water bodies. However, in estuarine environments there is an enormous variability of water physicochemical parameters that can affect the ammonia oxidation biological process. For instance, it is known that salinity can affect nitrification performance, yet there is still a lack of information on the ammonia-oxidizing communities behavior facing daily salinity fluctuations. In this work, laboratory experiments using upstream and downstream estuarine sediments were performed to address this missing gap by comparing the effect of daily salinity fluctuations with constant salinity on the activity and diversity of ammonia-oxidizing microorganisms (AOM). Activity and composition of AOM were assessed, respectively by using nitrogen stable isotope technique and 16S rRNA gene metabarcoding analysis. Nitrification activity was negatively affected by daily salinity fluctuations in upstream sediments while no effect was observed in downstream sediments. Constant salinity regime showed clearly higher rates of nitrification in upstream sediments while a similar nitrification performance between the two salinity regimes was registered in the downstream sediments. Results also indicated that daily salinity fluctuation regime had a negative effect on both ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) community’s diversity. Phylogenetically, the estuarine downstream AOM were dominated by AOA (0.92–2.09%) followed by NOB (0.99–2%), and then AOB (0.2–0.32%); whereas NOB dominated estuarine upstream sediment samples (1.4–9.5%), followed by AOA (0.27–0.51%) and AOB (0.01–0.23%). Analysis of variance identified the spatial difference between samples (downstream and upstream) as the main drivers of AOA and AOB diversity. Our study indicates that benthic AOM inhabiting different estuarine sites presented distinct plasticity toward the salinity regimes tested. These findings help to improve our understanding in the dynamics of the nitrogen cycle of estuarine systems by showing the resilience and consequently the impact of different salinity regimes on the diversity and activity of ammonia oxidizer communities.
Evaluation of Humoral Immunity to SARS-CoV-2: Diagnostic Value of a New Multiplex Addressable Laser Bead Immunoassay
Authors: Drouot Laurent , Hantz Sébastien , Jouen Fabienne , Velay Aurélie , Lamia Bouchra , Veber Benoit , Sibilia Jean , Lotellier Marlène , Candon Sophie , Alain Sophie , Fafi-Kremer Samira , Boyer Olivier
Published: November 2020

Despite efforts to develop anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody (Ab) immunoassays, reliable serological methods are still needed. We developed a multiplex addressable laser bead immunoassay (ALBIA) to detect and quantify anti-Spike S1 and nucleocapsid N Abs. Recombinant S1 and N proteins were bound to fluorescent beads (ALBIA-IgG-S1/N). Abs were revealed using class-specific anti-human Ig Abs. The performances of the test were analyzed on 575 serum samples including 192 from SARS-CoV-2 polymerase chain reaction–confirmed patients, 13 from seasonal coronaviruses, 70 from different inflammatory/autoimmune diseases, and 300 from healthy donors. Anti-S1 IgM were detected by monoplex ALBIA-IgM-S1. Comparison with chemiluminescent assays or enzyme-linked immunosorbent assays was performed using commercial tests. Multiplex ALBIA-IgG-S1/N was effective in detecting and quantifying anti–SARS-CoV-2 IgG Abs. Two weeks after first symptoms, sensitivity and specificity were 97.7 and 98.0% (anti-S1), and 100 and 98.7% (anti-N), respectively. Agreement with commercial tests was good to excellent, with a higher sensitivity of ALBIA. ALBIA-IgG-S1/N was positive in 53% of patients up to day 7, and in 75% between days 7 and 13. For ALBIA-IgM-S1, sensitivity and specificity were 74.4 and 98.7%, respectively. Patients in intensive care units had higher IgG Ab levels (Mann–Whitney test, p < 0.05). ALBIA provides a robust method for exploring humoral immunity to SARS-CoV-2. Serology should be performed after 2 weeks following first symptoms, when all COVID-19 (coronavirus disease 2019) patients had at least one anti-S1 or anti-N IgG Ab, illustrating the interest of a multiplex test.
Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer’s Disease Pathogenesis
Authors: Hu Rui-ting , Yu Qian , Zhou Shao-dan , Yin Yi-xin , Hu Rui-guang , Lu Hai-peng , Hu Bang-li
Published: November 2020

Background: The pathogenesis of Alzheimer’s disease (AD) remains to be elucidated. This study aimed to identify the hub genes in AD pathogenesis and determine their functions and pathways.

Methods: A co-expression network for an AD gene dataset with 401 samples was constructed, and the AD status-related genes were screened. The hub genes of the network were identified and validated by an independent cohort. The functional pathways of hub genes were analyzed.

Results: The co-expression network revealed a module that related to the AD status, and 101 status-related genes were screened from the trait-related module. Gene enrichment analysis indicated that these status-related genes are involved in synaptic processes and pathways. Four hub genes (ENO2, ELAVL4, SNAP91, and NEFM) were identified from the module, and these hub genes all participated in AD-related pathways, but the associations of each gene with clinical features were variable. An independent dataset confirmed the different expression of hub genes between AD and controls.

Conclusions: Four novel genes associated with AD pathogenesis were identified and validated, which provided novel therapeutic targets for AD.
Declining Trends of Heart Rate Variability According to Aging in Healthy Asian Adults
Authors: Choi Jungmi , Cha Wonseok , Park Min-Goo
Published: November 2020

Heart rate variability (HRV) indices correlate with aging and are related to the autonomic nervous system. However, the trend of HRV with age has not been explored for the Asian population. Therefore, we proposed a linear regression model of HRV indices that decreased with aging in healthy Asian adults. HRV parameters [High frequency (HF), Low frequency (LF), Very low frequency (VLF), Total power (TP), HRV triangular index (HRV-index), Standard deviation of the normal-to-normal interval (SDNN), and Proportion of normal-to-normal intervals greater than 50 ms (pNN50)] were measured in a total of 300 healthy participants (150 men and 150 women) aged 19–69 years stratified into five age groups: 19–29, 30–39, 40–49, 50–59, and 60–69 years comprising 60 people each in Seoul, South Korea. A simple regression analysis was performed to reveal the linear declining trend of HRV indices with age. Independent t-tests were conducted to investigate the gender differences in HRV values depending on each age group. The values of all HRV indices showed a decreasing trend with age in healthy Korean adults, as observed in the Western population (P < 0.001 for all indices); HF (Y = −0.039x + 6.833, R2 = 0.287), LF (Y = −0.047x + 7.197, R2 = 0.414), VLF (Y = −0.025x + 6.861, R2 = 0.177), TP (Y = −0.034x + 8.082, R2 = 0.352), HRV-index (Y = −0.125x + 15.628, R2 = 0.298), SDNN (Y = −0.502x + 53.907, R2 = 0.343), and pNN50 (Y = −0.650x + 53.852, R2 = 0.345) all decreased with age. There was no significant gender difference in any HRV parameter. A linear regression model of various HRV indices has been presented considering the age of healthy Asians, which may be useful to prevent diseases related to the autonomic nervous system by estimating or tracking autonomic functional degeneration in the Asian population.
Proof of Concept Study: Mesoporous Silica Nanoparticles, From Synthesis to Active Specific Immunotherapy
Authors: Seré Stephanie , Vounckx Ulrique , Seo Jin Won , Lenaerts Ilse , Van Gool Stefaan , Locquet Jean-Pierre
Published: November 2020

Nanomaterials are increasingly valued tools in drug delivery research as they offer enhanced stability, controlled release and more effective drug encapsulation. Though yet to be introduced in clinical trial, mesoporous silica nanoparticles are promising delivery systems, due to their high chemical and mechanical stability while remaining biodegradable. This work provides proof of concept for particle based vaccines as cost-effective alternatives for dendritic cell immunotherapy. Synthesis and surface chemistry of the nanoparticles are optimized for protein conjugation and nanoparticles are characterized for their physicochemical properties and biodegradation. Ovalbumin is used as a model protein to load nanoparticles to produce a nanovaccine. The vaccine is tested in vitro on dendritic cultures to verify particle and vaccine uptake, toxicity, maturation effects and explicitly ovalbumin cross-presentation on MHC class I molecules. The optimized synthesis protocol renders reproducible mesoporous silica nanoparticles, resistant against agglomeration, within the required size range and have carboxylic surface functionalization necessary for protein conjugation. They are biodegradable over a time span of 1 week. This period is adjustable by changing synthesis parameters. UV sterilization of the particles does not induce quality loss, nor does it have toxic effects on cells. Treatment with mesoporous silica nanoparticles increases expression of MHC and costimulatory molecules of dendritic cells, indicating an adjuvant effect of nanoparticles on the adaptive immune system. Nanovaccine uptake and cross-presentation of ovalbumin are observed and the latter is increased when delivered by nanoparticles as compared to control conditions. This confirms the large potential of mesoporous silica nanoparticle based vaccines to replace dendritic-based active specific immunotherapy, offering a more standardized production process and higher efficacy.
Investigating the Nanocomposite Thin Films of Hematite α-Fe2O3 and Nafion for Cholesterol Biosensing Applications
Authors: Sulania Indra , Pricilla R. Blessy , Lakshmi G. B. V. S.
Published: November 2020

Nanocomposite materials are multi-phase materials, usually solids, which have two or more component materials having different chemical and physical properties. When blended together, a newer material is formed with distinctive properties which make them an eligible candidate for many important applications. In the present study, thin films of nafion (polymer) and hematite or α-Fe2O3 (nanoparticles) nanocomposite is fabricated on indium tin oxide (ITO) coated glass substrates, due to its enhanced ionic conductivity, for cholesterol biosensor applications. Scanning electron microscopy and Atomic force microscopy revealed the formation of nanorod structured α-Fe2O3 in the films. The cyclic voltammetry (CV) studies of nafion-α-Fe2O3/ITO revealed the redox properties of the nanocomposites. The sensing studies were performed on nafion-α-Fe2O3/CHOx/ITO bioelectrode using differential pulse voltammetry (DPV) at various concentrations of cholesterol. The enzyme immobilization leaded to the selective detection of cholesterol with a sensitivity of 64.93 × 10−2 μA (mg/dl)−1 cm−2. The enzyme substrate interaction (Michaelis–Menten) constant Km, was obtained to be 19 mg/dl.
G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice
Authors: Zhang Chun , Liu Qiang , Yu Chun-Yang , Wang Feng , Shao Yu , Sun Kui-Sheng , Sun Tao , Liu Juan
Published: November 2020

The role of estrogen receptors in neuroprotection and cognition has been extensively studied in humans over the past 20 years. Recently, studies have shifted their focus to the use of selective estrogen receptor modulators in the treatment of mental illnesses in the central nervous system. We conducted this study to test the behavioral changes shown by G protein-coupled estrogen receptor 1 knockout (GPER1 KO) and wild-type (WT) mice with MK-801-induced schizophrenia (SZ). GPER1 KO and WT mice received intraperitoneal injections of MK-801 for 14 continuous days. Behavioral, learning and memory, and social interaction changes were evaluated by using the IntelliCage system, open-field, three-chamber social interaction, and novel object recognition tests (NORT). The protein expression levels of the NR2B/CaMKII/CREB signaling pathway were tested via Western blot analysis. The KO SZ group was more likely to show impaired long-term learning and memory function than the WT SZ group. Learning and memory functions were also impaired in the KO Con group. MK-801 administration to the GPER1-KO and WT groups resulted in memory deficiencies and declining learning capabilities. GPER1 deficiency downregulated the expression levels of proteins related to the NR2B/CaMKII/CREB signaling pathway. Our study suggested that GPER1 played an important role in cognitive, learning, and memory functions in the MK-801-induced mouse model of SZ. The mechanism of this role might partially involve the downregulation of the proteins related to the NR2B/CaMKII/CREB signaling pathway. Further studies should focus on the effect of GPER1 on the pathogenesis of SZ in vivo and in vitro.
Store-Operated Calcium Channels in Physiological and Pathological States of the Nervous System
Authors: Zhang Isis , Hu Huijuan
Published: November 2020

Store-operated calcium channels (SOCs) are widely expressed in excitatory and non-excitatory cells where they mediate significant store-operated calcium entry (SOCE), an important pathway for calcium signaling throughout the body. While the activity of SOCs has been well studied in non-excitable cells, attention has turned to their role in neurons and glia in recent years. In particular, the role of SOCs in the nervous system has been extensively investigated, with links to their dysregulation found in a wide variety of neurological diseases from Alzheimer’s disease (AD) to pain. In this review, we provide an overview of their molecular components, expression, and physiological role in the nervous system and describe how the dysregulation of those roles could potentially lead to various neurological disorders. Although further studies are still needed to understand how SOCs are activated under physiological conditions and how they are linked to pathological states, growing evidence indicates that SOCs are important players in neurological disorders and could be potential new targets for therapies. While the role of SOCE in the nervous system continues to be multifaceted and controversial, the study of SOCs provides a potentially fruitful avenue into better understanding the nervous system and its pathologies.
Optimized OPA1 Isoforms 1 and 7 Provide Therapeutic Benefit in Models of Mitochondrial Dysfunction
Authors: Maloney Daniel M. , Chadderton Naomi , Millington-Ward Sophia , Palfi Arpad , Shortall Ciara , O’Byrne James J. , Cassidy Lorraine , Keegan David , Humphries Peter , Kenna Paul , Farrar Gwyneth Jane
Published: November 2020

Optic Atrophy 1 (OPA1) is a mitochondrially targeted GTPase that plays a pivotal role in mitochondrial health, with mutations causing severe mitochondrial dysfunction and typically associated with Dominant Optic Atrophy (DOA), a progressive blinding disease involving retinal ganglion cell loss and optic nerve damage. In the current study, we investigate the use of codon-optimized versions of OPA1 isoform 1 and 7 as potential therapeutic interventions in a range of in vitro and in vivo models of mitochondrial dysfunction. We demonstrate that both isoforms perform equally well in ameliorating mitochondrial dysfunction in OPA1 knockout mouse embryonic fibroblast cells but that OPA1 expression levels require tight regulation for optimal benefit. Of note, we demonstrate for the first time that both OPA1 isoform 1 and 7 can be used independently to protect spatial visual function in a murine model of retinal ganglion cell degeneration caused by mitochondrial dysfunction, as well as providing benefit to mitochondrial bioenergetics in DOA patient derived fibroblast cells. These results highlight the potential value of OPA1-based gene therapy interventions.
Is So Called “Split Alpha” in EEG Spectral Analysis a Result of Methodological and Interpretation Errors?
Authors: Zalewska Ewa
Published: November 2020

This paper attempts to explain some methodological issues regarding EEG signal analysis which might lead to misinterpretation and therefore to unsubstantiated conclusions. The so called “split-alpha,” a “new phenomenon” in EEG spectral analysis described lately in few papers is such a case. We have shown that spectrum feature presented as a “split alpha” can be the result of applying improper means of analysis of the spectrum of the EEG signal that did not take into account the significant properties of the applied Fast Fourier Transform (FFT) method. Analysis of the shortcomings of the FFT method applied to EEG signal such as limited duration of analyzed signal, dependence of frequency resolution on time window duration, influence of window duration and shape, overlapping and spectral leakage was performed. Our analyses of EEG data as well as simulations indicate that double alpha spectra called as “split alpha” can appear, as spurious peaks, for short signal window when the EEG signal being studied shows multiple frequencies and frequency bands. These peaks have no relation to any frequencies of the signal and are an effect of spectrum leakage. Our paper is intended to explain the reasons underlying a spectrum pattern called as a “split alpha” and give some practical indications for using spectral analysis of EEG signal that might be useful for readers and allow to avoid EEG spectrum misinterpretation in further studies and publications as well as in clinical practice.
Nrf2 Mediates Metabolic Reprogramming in Non-Small Cell Lung Cancer
Authors: Zhao Jiangang , Lin Xu , Meng Di , Zeng Liping , Zhuang Runzhou , Huang Sha , Lv Wang , Hu Jian
Published: November 2020

Nuclear factor erythroid-2–related factor-2 (NFE2L2/Nrf2) is a transcription factor that regulates the expression of antioxidant genes. Both Kelch-like ECH-associated protein 1 (Keap1) mutations and Nrf2 mutations contribute to the activation of Nrf2 in non-small cell lung cancer (NSCLC). Nrf2 activity is associated with poor prognosis in NSCLC. Metabolic reprogramming represents a cancer hallmark. Increasing studies reveal that Nrf2 activation promotes metabolic reprogramming in cancer. In this review, we discuss the underlying mechanisms of Nrf2-mediated metabolic reprogramming and elucidate its role in NSCLC. Inhibition of Nrf2 can alter metabolic processes, thus suppress tumor growth, prevent metastasis, and increase sensitivity to chemotherapy in NSCLC. In conclusion, Nrf2 may serve as a therapeutic target for the treatment of NSCLC.
Hexokinase 2 Promotes Cell Growth and Tumor Formation Through the Raf/MEK/ERK Signaling Pathway in Cervical Cancer
Authors: Cui Nan , Li Lu , Feng Qian , Ma Hong-mei , Lei Dan , Zheng Peng-Sheng
Published: November 2020

Hexokinase 2 (HK2) is a member of the hexokinases (HK) that has been reported to be a key regulator during glucose metabolism linked to malignant growth in many types of cancers. In this study, stimulation of HK2 expression was observed in squamous cervical cancer (SCC) tissues, and HK2 expression promoted the proliferation of cervical cancer cells in vitro and tumor formation in vivo by accelerating cell cycle progression, upregulating cyclin A1, and downregulating p27 expression. Moreover, transcriptome sequencing analysis revealed that MAPK3 (ERK1) was upregulated in HK2-overexpressing HeLa cells. Further experiments found that the protein levels of p-Raf, p-MEK1/2, ERK1/2, and p-ERK1/2 were increased in HK2 over-expressing SiHa and HeLa cells. When ERK1/2 and p-ERK1/2 expression was blocked by an inhibitor (FR180204), reduced cyclin A1 expression was observed in HK2 over-expressing cells, with induced p27 expression and inhibited cell growth. Therefore, our data demonstrated that HK2 promoted the proliferation of cervical cancer cells by upregulating cyclin A1 and down-regulating p27 expression through the Raf/MEK/ERK signaling pathway.
Identification of Metabolism-Associated Prostate Cancer Subtypes and Construction of a Prognostic Risk Model
Authors: Zhang Yanlong , Zhang Ruiqiao , Liang Fangzhi , Zhang Liyun , Liang Xuezhi
Published: November 2020

Background

Despite being the second most common tumor in men worldwide, the tumor metabolism-associated mechanisms of prostate cancer (PCa) remain unclear. Herein, this study aimed to investigate the metabolism-associated characteristics of PCa and to develop a metabolism-associated prognostic risk model for patients with PCa.

Methods

The activity levels of PCa metabolic pathways were determined using mRNA expression profiling of The Cancer Genome Atlas Prostate Adenocarcinoma cohort via single-sample gene set enrichment analysis (ssGSEA). The analyzed samples were divided into three subtypes based on the partitioning around medication algorithm. Tumor characteristics of the subsets were then investigated using t-distributed stochastic neighbor embedding (t-SNE) analysis, differential analysis, Kaplan–Meier survival analysis, and GSEA. Finally, we developed and validated a metabolism-associated prognostic risk model using weighted gene co-expression network analysis, univariate Cox analysis, least absolute shrinkage and selection operator, and multivariate Cox analysis. Other cohorts (GSE54460, GSE70768, genotype-tissue expression, and International Cancer Genome Consortium) were utilized for external validation. Drug sensibility analysis was performed on Genomics of Drug Sensitivity in Cancer and GSE78220 datasets. In total, 1,039 samples and six cell lines were concluded in our work.

Results

Three metabolism-associated clusters with significantly different characteristics in disease-free survival (DFS), clinical stage, stemness index, tumor microenvironment including stromal and immune cells, DNA mutation (TP53 and SPOP), copy number variation, and microsatellite instability were identified in PCa. Eighty-four of the metabolism-associated module genes were narrowed to a six-gene signature associated with DFS, CACNG4, SLC2A4, EPHX2, CA14, NUDT7, and ADH5 (p <0.05). A risk model was developed, and external validation revealed the strong robustness our risk model possessed in diagnosis and prognosis as well as the association with the cancer feature of drug sensitivity.

Conclusions

The identified metabolism-associated subtypes reflected the pathogenesis, essential features, and heterogeneity of PCa tumors. Our metabolism-associated risk model may provide clinicians with predictive values for diagnosis, prognosis, and treatment guidance in patients with PCa.
Control of Complement Activation by the Long Pentraxin PTX3: Implications in Age-Related Macular Degeneration
Authors: Stravalaci Matteo , Davi Francesca , Parente Raffaella , Gobbi Marco , Bottazzi Barbara , Mantovani Alberto , Day Anthony J. , Clark Simon J. , Romano Mario R. , Inforzato Antonio
Published: November 2020

Dysregulation of the complement system is central to age-related macular degeneration (AMD), the leading cause of blindness in the developed world. Most of the genetic variation associated with AMD resides in complement genes, with the greatest risk associated with polymorphisms in the complement factor H (CFH) gene; factor H (FH) is the major inhibitor of the alternative pathway (AP) of complement that specifically targets C3b and the AP C3 convertase. Long pentraxin 3 (PTX3) is a soluble pattern recognition molecule that has been proposed to inhibit AP activation via recruitment of FH. Although present in the human retina, if and how PTX3 plays a role in AMD is still unclear. In this work we demonstrated the presence of PTX3 in the human vitreous and studied the PTX3-FH-C3b crosstalk and its effects on complement activation in a model of retinal pigment epithelium (RPE). RPE cells cultured in inflammatory AMD-like conditions overexpressed the PTX3 protein, and up-regulated AP activating genes. PTX3 bound RPE cells in a physiological setting, however this interaction was reduced in inflammatory conditions, whereby PTX3 had no complement-inhibiting activity on inflamed RPE. However, on non-cellular surfaces, PTX3 formed a stable ternary complex with FH and C3b that acted as a “hot spot” for complement inhibition. Our findings suggest a protective role for PTX3 in response to complement dysregulation in AMD and point to a novel mechanism of complement regulation by this pentraxin with potential implications in pathology and pharmacology of AMD.
Animal Models of Cancer-Related Pain: Current Perspectives in Translation
Authors: Pineda-Farias Jorge B. , Saloman Jami L. , Scheff Nicole N.
Published: November 2020

The incidence of pain in cancer patients during diagnosis and treatment is exceedingly high. Although advances in cancer detection and therapy have improved patient prognosis, cancer and its treatment-associated pain have gained clinical prominence. The biological mechanisms involved in cancer-related pain are multifactorial; different processes for pain may be responsible depending on the type and anatomic location of cancer. Animal models of cancer-related pain have provided mechanistic insights into the development and process of pain under a dynamic molecular environment. However, while cancer-evoked nociceptive responses in animals reflect some of the patients’ symptoms, the current models have failed to address the complexity of interactions within the natural disease state. Although there has been a recent convergence of the investigation of carcinogenesis and pain neurobiology, identification of new targets for novel therapies to treat cancer-related pain requires standardization of methodologies within the cancer pain field as well as across disciplines. Limited success of translation from preclinical studies to the clinic may be due to our poor understanding of the crosstalk between cancer cells and their microenvironment (e.g., sensory neurons, infiltrating immune cells, stromal cells etc.). This relatively new line of inquiry also highlights the broader limitations in translatability and interpretation of basic cancer pain research. The goal of this review is to summarize recent findings in cancer pain based on preclinical animal models, discuss the translational benefit of these discoveries, and propose considerations for future translational models of cancer pain.
Postharvest Properties of Ultra-Late Maturing Peach Cultivars and Their Attributions to Melting Flesh (M) Locus: Re-evaluation of M Locus in Association With Flesh Texture
Authors: Nakano Ryohei , Kawai Takashi , Fukamatsu Yosuke , Akita Kagari , Watanabe Sakine , Asano Takahiro , Takata Daisuke , Sato Mamoru , Fukuda Fumio , Ushijima Koichiro
Published: November 2020

The postharvest properties of two ultra-late maturing peach cultivars, “Tobihaku” (TH) and “Daijumitsuto” (DJ), were investigated. Fruit were harvested at commercial maturity and held at 25°C. TH exhibited the characteristics of normal melting flesh (MF) peach, including rapid fruit softening associated with appropriate level of endogenous ethylene production In contrast, DJ did not soften at all during 3 weeks experimental period even though considerable ethylene production was observed. Fruit of TH and DJ were treated with 5,000 ppm of propylene, an ethylene analog, continuously for 7 days. TH softened rapidly whereas DJ maintained high flesh firmness in spite of an increase in endogenous ethylene production, suggesting that DJ but not TH lacked the ability to be softened in response to endogenous and exogenous ethylene/propylene. DNA-seq analysis showed that tandem endo-polygalacturonase (endoPG) genes located atmelting flesh (M)locus,Pp-endoPGM(PGM), andPp-endoPGF(PGF), were deleted in DJ. TheendoPGgenes atMlocus are known to control flesh texture of peach fruit, and it was suggested that the non-softening property of DJ is due to the lack ofendoPGgenes. On the other hand, TH possessed an unidentifiedMhaplotype that is involved in determination of MF phenotype. Structural identification of the unknownMhaplotype, designated asM0, through comparison with previously reportedMhaplotypes revealed distinct differences betweenPGMonM0haplotype (PGM-M0) andPGMon other haplotypes (PGM-M1). PeachMhaplotypes were classified into four main haplotypes:M0withPGM-M0;M1with bothPGM-M1andPGF;M2withPGM-M1; andM3lacking bothPGMandPGF. Re-evaluation ofMlocus in association with MF/non-melting flesh (NMF) phenotypes in more than 400 accessions by using whole genome shotgun sequencing data on database and/or by PCR genotyping demonstrated thatM0haplotype was the common haplotype in MF accessions, andM0andM1haplotypes were dominant overM2andM3haplotypes and co-dominantly determined the MF trait. It was also assumed on the basis of structural comparison ofMhaplotypes amongPrunusspecies that the ancestral haplotype ofM0diverged from those of the other haplotypes before the speciation ofPrunus persica.
Comprehensive Model for Physical and Cognitive Frailty: Current Organization and Unmet Needs
Authors: Lauretani Fulvio , Longobucco Yari , Ferrari Pellegrini Francesca , De Iorio Aurelio Maria , Fazio Chiara , Federici Raffaele , Gallini Elena , La Porta Umberto , Ravazzoni Giulia , Roberti Maria Federica , Salvi Marco , Zucchini Irene , Pelà Giovanna , Maggio Marcello
Published: November 2020

Aging is characterized by the decline and deterioration of functional cells and results in a wide variety of molecular damages and reduced physical and mental capacity. The knowledge on aging process is important because life expectancy is expected to rise until 2050. Aging cannot be considered a homogeneous process and includes different trajectories characterized by states of fitness, frailty, and disability. Frailty is a dynamic condition put between a normal functional state and disability, with reduced capacity to cope with stressors. This geriatric syndrome affects physical, neuropsychological, and social domains and is driven by emotional and spiritual components. Sarcopenia is considered one of the determinants and the biological substrates of physical frailty. Physical and cognitive frailty are separately approached during daily clinical practice. The concept of motoric cognitive syndrome has partially changed this scenario, opening interesting windows toward future approaches. Thus, the purpose of this manuscript is to provide an excursus on current clinical practice, enforced by aneddoctical cases. The analysis of the current state of the art seems to support the urgent need of comprehensive organizational model incorporating physical and cognitive spheres in the same umbrella.
Interactive Psychometrics for Autism With the Human Dynamic Clamp: Interpersonal Synchrony From Sensorimotor to Sociocognitive Domains
Authors: Baillin Florence , Lefebvre Aline , Pedoux Amandine , Beauxis Yann , Engemann Denis A. , Maruani Anna , Amsellem Frédérique , Kelso J. A. Scott , Bourgeron Thomas , Delorme Richard , Dumas Guillaume
Published: November 2020

The human dynamic clamp (HDC) is a human–machine interface designed on the basis of coordination dynamics for studying realistic social interaction under controlled and reproducible conditions. Here, we propose to probe the validity of the HDC as a psychometric instrument for quantifying social abilities in children with autism spectrum disorder (ASD) and neurotypical development. To study interpersonal synchrony with the HDC, we derived five standardized scores following a gradient from sensorimotor and motor to higher sociocognitive skills in a sample of 155 individuals (113 participants with ASD, 42 typically developing participants; aged 5 to 25 years; IQ > 70). Regression analyses were performed using normative modeling on global scores according to four subconditions (HDC behavior “cooperative/competitive,” human task “in-phase/anti-phase,” diagnosis, and age at inclusion). Children with ASD had lower scores than controls for motor skills. HDC motor coordination scores were the best candidates for stratification and diagnostic biomarkers according to exploratory analyses of hierarchical clustering and multivariate classification. Independently of phenotype, sociocognitive skills increased with developmental age while being affected by the ongoing task and HDC behavior. Weaker performance in ASD for motor skills suggests the convergent validity of the HDC for evaluating social interaction. Results provided additional evidence of a relationship between sensorimotor and sociocognitive skills. HDC may also be used as a marker of maturation of sociocognitive skills during real-time social interaction. Through its standardized and objective evaluation, the HDC not only represents a valid paradigm for the study of interpersonal synchrony but also offers a promising, clinically relevant psychometric instrument for the evaluation and stratification of sociomotor dysfunctions.
Do Suicide Attempts of Mood Disorder Patients Directly Increase the Risk for a Reattempt?
Authors: Aaltonen Kari I. , Rosenström Tom , Jylhä Pekka , Holma Irina , Holma Mikael , Pallaskorpi Sanna , Riihimäki Kirsi , Suominen Kirsi , Vuorilehto Maria , Isometsä Erkki T.
Published: November 2020

Background: Preceding suicide attempts strongly predict future suicidal acts. However, whether attempting suicide per se increases the risk remains undetermined. We longitudinally investigated among patients with mood disorders whether after a suicide attempt future attempts occur during milder depressive states, indicating a possible lowered threshold for acting.

Methods: We used 5-year follow-up data from 581 patients of the Jorvi Bipolar Study, Vantaa Depression Study, and Vantaa Primary Care Depression Study cohorts. Lifetime suicide attempts were investigated at baseline and during the follow-up. At follow-up interviews, life-chart data on the course of the mood disorder were generated and suicide attempts timed. By using individual-level data and multilevel modeling, we investigated at each incident attempt the association between the lifetime ordinal number of the attempt and the major depressive episode (MDE) status (full MDE, partial remission, or remission).

Results: A total of 197 suicide attempts occurred among 90 patients, most during MDEs. When the dependencies between observations and individual liabilities were modeled, no association was found between the number of past suicide attempts at the time of each attempt and partial remissions. No association between adjusted inter-suicide attempt times and the number of past attempts emerged during follow-up. No indication for direct risk-increasing effects was found.

Conclusion: Among mood disorder patients, repeated suicide attempts do not tend to occur during milder depressive states than in the preceding attempts. Previous suicide attempts may indicate underlying diathesis, future risk being principally set by the course of the disorder itself.
Catastrophic Health Impacts of Spiraling Climate Change: How Certain Can We Be About Their Magnitudes?
Authors: Chalabi Zaid , Foss Anna M.
Published: November 2020

Recently, there has been a strong interest in the climate emergency and the human health impacts of climate change. Although estimates have been quoted, the modeling methods used have either been simplistic or opaque, making it difficult for policy makers to have confidence in these estimates. Providing central estimates of health impacts, without any quantification of their uncertainty, is deficient because such an approach does not acknowledge the inherent uncertainty in extreme environmental exposures associated with spiraling climate change and related health impacts. Furthermore, presenting only the uncertainty bounds around central estimates, without information on how the uncertainty in each of the model parameters and assumptions contribute to the total uncertainty, is insufficient because this approach hides those parameters and assumptions which contribute most to the total uncertainty. We propose a framework for calculating the catastrophic human health impacts of spiraling climate change and the associated uncertainties. Our framework comprises three building blocks: (A) a climate model to simulate the environmental exposure extremes of spiraling climate change; (B) a health impact model which estimates the health burdens of the extremes of environmental exposures; and (C) an analytical mathematical method which characterizes the uncertainty in (A) and (B), propagates the uncertainty in-between and through these models, and attributes the proportion of uncertainty in the health outcomes to model assumptions and parameter values. Once applied, our framework can be of significant value to policy makers because it handles uncertainty transparently while taking into account the complex interactions between climate and human health.
Assessing the Value of a Novel Augmented Reality Application for Presurgical Planning in Adolescent Elbow Fractures
Authors: Laguna Benjamin , Livingston Kristin , Brar Ravinder , Jagodzinski Jason , Pandya Nirav , Sabatini Coleen , Courtier Jesse
Published: November 2020

Objectives: We retrospectively assess the potential impact of a novel, investigational Augmented Reality (AR) software application, Radiology with Holographic Augmentation (RadHA), on pediatric orthopedic surgeon's confidence in surgical planning, hardware selection, hardware fit, and estimated potential intraoperative time savings in the setting of complex adolescent elbow fractures.

Methods: After study selection, 12 individual cases of complex elbow fractures in adolescent pediatric patients were identified for review. AR models were generated for each case derived from the patient's CT. Five fellowship-trained pediatric orthopedic surgeons reviewed each case for a total of 60 separate observations. Surgeons reviewed clinical data, radiologic imaging, and AR models and then answered Likert Scale questions on measures of confidence in presurgical planning and projected potential time savings. These data were reviewed and analyzed using various statistical tools.

Results: Surgeons reported high confidence in the quality of the AR models created. Additionally, surgeons reported increased confidence in their surgical plan, increased confidence in hardware selection, and increased confidence in hardware fit. Within the sub-analysis of complex (comminuted) fractures, surgeons reported greater expected increases in confidence of their surgical plan and hardware fit. Overall, surgeons estimated potential intraoperative time savings, averaging 17.3 min for all fracture types and 17.6 min for complex fractures.

Conclusions: Preoperative planning using AR-based models can increase surgeon confidence in preoperative planning, hardware selection, and confidence in hardware fit.
Downscaling Satellite and Reanalysis Precipitation Products Using Attention-Based Deep Convolutional Neural Nets
Authors: Sun Alexander Y. , Tang Guoqiang
Published: November 2020

High-quality and high-resolution precipitation products are critically important to many hydrological applications. Advances in satellite remote sensing instruments and data retrieval algorithms continue to improve the quality of the operational precipitation products. However, most satellite products existing today are still too coarse to be ingested for local water management and planning purposes. Recent advances in deep learning algorithms enable the fusion of multi-source, high-dimensional data for statistical learning. In this study, we investigated the efficacy of an attention-based, deep convolutional neural network (AU-Net) for learning spatial and temporal mappings from coarse-resolution to fine-resolution precipitation products. The skills of AU-Net models, developed using combinations of static and dynamic predictors, were evaluated over a 3 × 3° study area in Central Texas, U.S., a region known for its complex precipitation patterns and low predictability. Three coarse-resolution satellite/reanalysis precipitation products, ERA5-Land (0.1°), TRMM (0.25°), and IMERG (0.1°), are used as part of the inputs, while the predictand is the 1-km PRISM data. Auxiliary predictors include elevation, vegetation index, and air temperature. The study period includes 18 years of data (2001–2018) at the monthly scale for training, validation, and testing. Results show that the trained AU-Net models achieve different degrees of success in downscaling the baseline coarse-resolution products, depending on the total precipitation, the accuracy of large-scale patterns captured by the baseline products, and the amount of information transferable from predictors. Higher precipitation rate tends to affect AU-Net model performance negatively. Use of the attention mechanism in the AU-Net models allows for infilling of multiscale features and generation of sharper images. Correction using gauge data, if there is any, can further improve the results significantly.