bluuebunny/crossref_metadata_2025 huggingface dataset:
EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis
Authors: Wang Ye , Zhong Liangying , Xu Yan , Ding Lei , Ji Yuanjun , Schutz Sacha , Férec Claude , Cooper David N. , Xu Caixia , Chen Jian-Min , Luo Yanmin
Published: December 2020

Multiple osteochondromas (MO), the most common type of benign bone tumor, is an autosomal dominant skeletal disorder characterized by multiple cartilage-capped bony protuberances. In most cases,EXT1andEXT2, which encode glycosyltransferases involved in the biosynthesis of heparan sulfate, are the genes responsible. Here we describe the clinical, phenotypic and genetic characterization of MO in 22 unrelated Chinese families involving a total of 60 patients. Variant detection was performed by means of a battery of different techniques including Sanger sequencing and whole-exome sequencing (WES). The pathogenicity of the missense and splicing variants was explored by means ofin silicoprediction algorithms. Sixteen unique pathogenic variants, including 10 in theEXT1gene and 6 in theEXT2gene, were identified in 18 (82%) of the 22 families. Fourteen (88%) of the 16 variants were predicted to give rise to truncated proteins whereas the remaining two were missense. Seven variants were newly described here, further expanding the spectrum of MO-causing variants in theEXT1andEXT2genes. More importantly, the identification of causative variants allowed us to provide genetic counseling to 8 MO patients in terms either of preimplantation genetic testing (PGT) or prenatal diagnosis, thereby preventing the reoccurrence of MO in the corresponding families. This study is the first to report the successful implementation of PGT in MO families and describes the largest number of subjects undergoing prenatal diagnosis to date.
Nitrate-Enrichment Structures Phytoplankton Communities in the Shallow Eastern Mediterranean Coastal Waters
Authors: Rahav Eyal , Raveh Ofrat , Yanuka-Golub Keren , Belkin Natalia , Astrahan Peleg , Maayani Meor , Tsumi Noam , Kiro Yael , Herut Barak , Silverman Jacob , Angel Dror L.
Published: December 2020

Submarine groundwater discharge (SGD) has been shown to be an important source of nutrients in coastal environments, especially nitrogen and silica, and thereby relive nutrient limitation to phytoplankton. Here, we followed autotrophic microbial biomass, activity, and community composition at a site strongly influenced by SGD and a nearby nutrients-poor reference site at the oligotrophic Israeli shallow rocky coast [southeastern Mediterranean Sea (SEMS)] between 2011 and 2019. The surface water at the SGD-affected area had significantly higher NO3 + NO2 (∼10-fold) and Si(OH)4 (∼2-fold) levels compared to the reference site, while no significant differences were observed for PO4 or NH4. This resulted in a significant increase in algae biomass (∼3.5-fold), which was attributed to elevated Synechococcus (∼3.5-fold) and picoeukaryotes (∼2-fold) at the SGD-affected site, and in elevated primary production rates (∼2.5-fold). Contrary to most SGD-affected coastal areas, diatoms biomass remained unchanged between sites, despite the elevated N and Si, suggesting the dominance of picophytoplankton over microphytoplankton at the SEMS. DNA sequencing of the 16S and 18S rDNA supported these findings. These results highlight the influence of SGD on shallow-water microbial populations. Our observations are consistent with recent studies showing that phytoplankton along the Israeli coast are likely nitrogen + silica limited, and may have important ecological and regulatory implications for environmental policy and management of coastal aquifers.
RETRACTED: Long Non-coding RNA LINC00320 Inhibits Tumorigenicity of Glioma Cells and Angiogenesis Through Downregulation of NFKB1-Mediated AQP9
Authors: Chang Lisha , Bian Zhe , Xiong Xin , Liu Jian , Wang Dali , Zhou Fuling , Zhang Jiang , Zhang Yunhe
Published: December 2020

The inhibitory effect of long intergenic non-coding RNA 00320 (LINC00320) in glioma cell proliferation has been proposed in a recent study. However, the mechanisms by which LINC00320 regulate aquaporin 9 (AQP9) in glioma require further exploration. Hence, this study aims to investigate effects of LINC00320 on tumorigenicity of glioma cells and angiogenesis of microvascular endothelial cells (MVECs). Expression of LINC00320 and AQP9 in glioma tissues and cells was measured by reverse transcription–quantitative polymerase chain reaction and Western blot analysis. The relationship among LINC00320, nuclear factor κB subunit 1 (NFKB1) and AQP9 was examined by RNA immunoprecipitation, dual-luciferase reporter gene, and chromatin immunoprecipitation assays. The participation of LINC00320 and AQP9 in glioma cell proliferation and MVEC angiogenesis was analyzed using gain- and loss-of-function approaches. Finally, a nude mouse orthotopic xenograft model of glioma was established to investigate the effects of LINC00320 and AQP9 on glioma growth in vivo. LINC00320 was under-expressed and AQP9 was over-expressed in glioma tissues. Further mechanistic investigation showed that LINC00320 downregulated AQP9 by inhibiting the recruitment of NFKB1 to the promoter region of AQP9. LINC00320 overexpression or AQP9 silencing inhibited the proliferation of glioma cells and angiogenesis of MVECs. Also, upregulation of LINC00320 restrained tumor growth and angiogenesis in xenograft mice by downregulating AQP9. Taken together, LINC00320 acts as a tumor suppressor in glioma, thus presenting a novel therapeutic target.
Case Report: Daratumumab in a Patient With Severe Refractory Anti-NMDA Receptor Encephalitis
Authors: Ratuszny Dominica , Skripuletz Thomas , Wegner Florian , Groß Matthias , Falk Christine , Jacobs Roland , Ruschulte Heiner , Stangel Martin , Sühs Kurt-Wolfram
Published: December 2020

Anti-NMDA receptor encephalitis is the most common type of antibody mediated autoimmune encephalitis (AIE). Patients often develop neuropsychiatric symptoms and seizures, women are affected about four times more than men, and in about 50% the disease is associated with a neoplasia, especially teratomas of the ovary. We describe the case of a 20-year-old woman suffering from a severe therapy refractory course of anti-NMDA receptor encephalitis. Treatment included glucocorticoids, plasma exchange, intravenous immunoglobulins, rituximab, and bortezomib without clinical improvement. Due to a therapy refractive course 28 weeks after disease onset, the patient received 10 cycles of daratumumab. Therapy escalation was performed with the anti-CD38 monoclonal antibody daratumumab as off label treatment, based on the therapy of refractory myeloma and led to an improvement of her clinical status. She spent about 200 days on the intensive care unit, followed by several weeks on the intermediate care unit with close follow ups every 4–6 weeks afterward. During follow-up, the patient was able to resume everyday and self-care activities, reflected by the modified Rankin scale (mRS) and Barthel index. Because this disease is potentially life threatening and can lead to irreversible brain atrophy, development of further therapy strategies are of great importance. Our case describes a successful treatment for therapy refractory anti-NMDA receptor encephalitis using the anti-CD38 antibody daratumumab.
Low Contrast Visual Acuity Might Help to Detect Previous Optic Neuritis
Authors: Park Soo-Hyun , Park Choul Yong , Shin Young Joo , Jeong Kyoung Sook , Kim Nam-Hee
Published: December 2020

Optic neuritis (ON) has been considered to be an important factor in the diagnosis of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), making ON detection increasingly critical for early diagnosis. Furthermore, subclinical ONs presenting no distinct decrease in visual acuity can be missed. Low contrast visual acuity (LC-VA) is known to be able to capture visual loss not seen in conventional high-contrast visual acuity (HC-VA) in MS. Therefore, to increase the sensitivity of ON detection, we investigated the advantage of LC-VA over conventional HC-VA. One hundred and eight patients with demyelinating disease (35 MS, 73 NMOSD) with ON at least 3 months prior and 35 controls underwent neuro-ophthalmic evaluation, including best-corrected conventional high contrast visual acuity (HC-VA) and 2.5% and 1.25% low contrast visual acuity (LC-VA). Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) of various visual functions were used to determine the most relevant visual function test for the detection of optic nerve involvement. Additionally, the optimal cutoff point was obtained from the Youden index (J-index) as the points with the best sensitivity-specificity balance. When distinguishing ON from non-ON, the area under the ROC curve (AUC) was highest for the 2.5% LC-VA (0.835, P < 0.001; sensitivity 71.5%, specificity 88.6%), while it was 0.710 (P < 0.001) for the HC-VA and 0.770 (P < 0.001) for the 1.25% LC-VA. In discriminating between controls and ON, the AUC was also highest for the 2.5% LC-VA 0.754 (P < 0.001; sensitivity 71.5%, specificity 78.5%), while it was 0.719 (P < 0.001) for HC-VA and 0.688 (P < 0.001) for 1.25% LC-VA. In eyes with a history of ON (n = 137), the HC-VA and 2.5% LC-VA were abnormal in 64.2 and 71.5%, respectively (P < 0.001), with their combination detecting abnormalities in approximately 85.4% (P < 0.001). The 2.5% LC-VA was superior to HC-VA in detecting ON when distinguishing ON from non-ON or control. The 2.5% LC-VA might be a useful, feasible, and rapid method to detect ON. Furthermore, combining 2.5% LC-VA with conventional HC-VA would be better for detecting optic nerve involvements.
Comparison of Overall Survival Between Invasive Lobular Breast Carcinoma and Invasive Ductal Breast Carcinoma: A Propensity Score Matching Study Based on SEER Database
Authors: Yang Ciqiu , Lei Chuqian , Zhang Yi , Zhang Junsheng , Ji Fei , Pan Weijun , Zhang Liulu , Gao Hongfei , Yang Mei , Li Jieqing , Wang Kun
Published: December 2020

Objective

Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most breast cancers. However, the overall survival (OS) differences between ILC and IDC remain controversial. This study aimed to compare nonmetastatic ILC to IDC in terms of survival and prognostic factors for ILC.

Methods

This retrospective cohort study used data from the Surveillance, Epidemiology and End Results (SEER) Cancer Database (www.seer.cancer.gov). Women diagnosed with nonmetastatic ILC and IDC between 2006 and 2016 were included. A propensity score matching (PSM) method was used in our analysis to reduce baseline differences in clinicopathological characteristics and survival outcomes. Kaplan-Meier curves and log-rank test were used for survival analysis.

Results

Compared to IDC patients, ILC patients were diagnosed later in life with poorly differentiated and larger lesions, as well as increased expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). A lower rate of radiation therapy and chemotherapy was observed in ILC. After PSM, ILC, and IDC patients exhibited similar OS (HR=1.017, p=0.409, 95% CI: 0.967–1.069). In subgroup analysis of HR-negative, AJCC stage III, N2/N3 stage patients, or those who received radiotherapy, ILC patients exhibited worse OS compared to IDC patients. Furthermore, multivariate analysis revealed a 47% survival benefit for IDC compared to ILC in HR-negative patients who received chemotherapy (HR=1.47, p=0.01, 95% CI: 1.09–1.97).

Conclusions

Our results demonstrated that ILC and IDC patients had similar OS after PSM. However, ILC patients with high risk indicators had worse OS compared to IDC patients by subgroup analysis.
Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction
Authors: Nian Keqing , Harding Ian C. , Herman Ira M. , Ebong Eno E.
Published: December 2020

Ischemic stroke, a major cause of mortality in the United States, often contributes to disruption of the blood-brain barrier (BBB). The BBB along with its supportive cells, collectively referred to as the “neurovascular unit,” is the brain’s multicellular microvasculature that bi-directionally regulates the transport of blood, ions, oxygen, and cells from the circulation into the brain. It is thus vital for the maintenance of central nervous system homeostasis. BBB disruption, which is associated with the altered expression of tight junction proteins and BBB transporters, is believed to exacerbate brain injury caused by ischemic stroke and limits the therapeutic potential of current clinical therapies, such as recombinant tissue plasminogen activator. Accumulating evidence suggests that endothelial mechanobiology, the conversion of mechanical forces into biochemical signals, helps regulate function of the peripheral vasculature and may similarly maintain BBB integrity. For example, the endothelial glycocalyx (GCX), a glycoprotein-proteoglycan layer extending into the lumen of bloods vessel, is abundantly expressed on endothelial cells of the BBB and has been shown to regulate BBB permeability. In this review, we will focus on our understanding of the mechanisms underlying BBB damage after ischemic stroke, highlighting current and potential future novel pharmacological strategies for BBB protection and recovery. Finally, we will address the current knowledge of endothelial mechanotransduction in BBB maintenance, specifically focusing on a potential role of the endothelial GCX.
Endoplasmic Reticulum-Localized PURINE PERMEASE1 Regulates Plant Height and Grain Weight by Modulating Cytokinin Distribution in Rice
Authors: Xiao Yunhua , Zhang Junwen , Yu Guiyuan , Lu Xuedan , Mei Wentao , Deng Huabing , Zhang Guilian , Chen Guihua , Chu Chengcai , Tong Hongning , Tang Wenbang
Published: December 2020

Cytokinins (CKs) are a class of phytohormones playing essential roles in various biological processes. However, the mechanisms underlying CK transport as well as its function in plant growth and development are far from being fully elucidated. Here, we characterize the function of PURINE PERMEASE1 (OsPUP1) in rice (Oryza sativa L.). OsPUP1 was predominantly expressed in the root, particularly in vascular cells, and CK treatment can induce its expression. Subcellular localization analysis showed that OsPUP1 was predominantly localized to the endoplasmic reticulum (ER). Overexpression of OsPUP1 resulted in growth defect of various aerial tissues, including decreased leaf length, plant height, grain weight, panicle length, and grain number. Hormone profiling revealed that the CK content was decreased in the shoot of OsPUP1-overexpressing seedling, but increased in the root, compared with the wild type. The CK content in the panicle was also decreased. Quantitative reverse transcription-PCR (qRT-PCR) analysis using several CK type-A response regulators (OsRRs) as the marker genes suggested that the CK response in the shoot of OsPUP1-overexpressing seedling is decreased compared to the wild type when CKs are applied to the root. Genetic analysis revealed that BG3/OsPUP4, a putative plasma membrane-localized CK transporter, overcomes the function of OsPUP1. We hypothesize that OsPUP1 might be involved in importing CKs into ER to unload CKs from the vascular tissues by cell-to-cell transport.
A Cooperative Learning Intervention to Promote Social Inclusion in Heterogeneous Classrooms
Authors: Klang Nina , Olsson Ingrid , Wilder Jenny , Lindqvist Gunilla , Fohlin Niclas , Nilholm Claes
Published: December 2020

Concerning challenges with the social inclusion of children with special educational needs (SEN), it is imperative to evaluate teacher interventions that promote social inclusion. This study aimed to investigate the effects of cooperative learning (CL) intervention on social inclusion. In addition, it was investigated to what degree CL implementation affected the outcomes. Fifty-six teachers of 958 fifth-grade children were randomly selected to intervention and control groups upon recruitment to the study. The intervention teachers received training and coaching in CL and implemented this approach three to four times a week for 15 weeks. The results showed a significant but small effect of CL on children’s social acceptance, but no significant effect on children’s friendships and perceptions of classroom relationships. The degree of CL implementation had effect on children’s social acceptance, but the effect was not consistent across social acceptance measures as a friend or a groupmate. Thus, it can be concluded that CL, conducted with the length and intensity of this study, may not lead to substantial changes in the social inclusion of children with SEN. In future studies, more focus needs to be devoted to teacher implementation of the CL approach.
Dopamine Multilocus Genetic Profile, Spontaneous Activity of Left Superior Temporal Gyrus, and Early Therapeutic Effect in Major Depressive Disorder
Authors: Liu Xiaoyun , Hou Zhenghua , Yin Yingying , Xie Chunming , Zhang Haisan , Zhang Hongxing , Zhang Zhijun , Yuan Yonggui
Published: December 2020

Objectives: This study aimed to examine the interactive effects of dopamine (DA) pathway gene and disease on spontaneous brain activity and further to explore the relationship between spontaneous brain activity and the early antidepressant therapeutic effect in patients with major depressive disorder (MDD).

Methods: A total of 104 patients with MDD and 64 healthy controls (HCs) were recruited. The Hamilton Depression Scale-24 (HAMD-24) was used to measure the depression severity. Both groups were given resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuation (ALFF) was calculated to reflect the spontaneous brain activity based on the rs-fMRI data. After treatment for 2 weeks, depression severity was evaluated again, and HAMD-24 reductive rate was used to measure the therapeutic effect of antidepressants. Multilocus genetic profile scores (MGPS) were used to assess the multi-site cumulative effect of DA pathway gene. The interactive effects of MDD and DA pathway gene on the ALFF of regional brain areas were measured by the multivariate linear regression analysis. Finally, partial correlation analysis (age, sex, education, and illness durations as covariates) was performed to identify the relationship between regional ALFF and therapeutic effect.

Results: MDD and DA-MGPS had interactive effects on the left fusiform gyrus (FG_L), right calcarine sulcus (CS_R), left superior temporal gyrus (STG_L), bilateral cerebellum posterior lobe (CPL), bilateral inferior frontal gyrus (IFG), and bilateral superior frontal gyrus (SFG). Partial correlation analysis revealed that the ALFF of STG_L had a significant negative correlation with 2-week HAMD-24 reductive rate (r = −0.211, P = 0.035).

Conclusions: The spontaneous activity of STG_L may be a potential biomarker of antidepressant-related early therapeutic effect underlying the influence of DA pathway genes in MDD.
Indicative Value of the Dominant Plant Species for a Rapid Evaluation of the Nutritional Value of Soils
Authors: Cano-Ortiz Ana , Musarella Carmelo M. , Piñar Fuentes José C. , Pinto Gomes Carlos J. , Quinto-Canas Ricardo , del Río Sara , Cano Eusebio
Published: December 2020

A study was conducted on 14 grassland communities located in the south of the Iberian Peninsula and their edaphology, which is identified as specific plant associations. The edaphic study of each association allows a rapid evaluation of the nutrient content in the soil without the need for laboratory edaphic analysis. For each phytosociological relevé and soil, samplings were carried out. The field data were subjected to various statistical analysis—canonical correspondence analysis (CCA), Bayesian networks, and decision trees—to establish nutrient content. When the abundance value of the species is 9 in the Van der Maarel scale, there is an increase in the values of several soil parameters. In the case of Hordeum leporinum, when the Van der Maarel index is 9, the Kc (exchangeable potassium in cmol/kg) undergoes the greatest variation, to a value of up to 0.729 cmol/kg. The application of the decision tree to this species reveals that the soil attributes with the greatest influence in the classification are conductivity, %_si (silt texture), pH, and pF 15 atm (pressure at 15 atmospheres (water retention capacity) in %). Indeed, this interlaced edaphic and phytosociological study provides us with a high-value tool to obtain quick information on the content of nutrients in the soil.
Analytical Evaluation of MCE Collapse Performance of Seismically Base Isolated Buildings Located at Low-to-Moderate Seismicity Regions
Authors: Kim Hyung-Joon , Shin Dong-Hyeon
Published: December 2020

The promising seismic response emerged by the concept of base isolation leads to increasing practical applications into buildings located at low-to-moderate seismicity regions. However, it is questionable that their collapse capacities can be ensured with reasonable reliability, although they would be designed according to a current seismic design code. This paper aims to investigate the collapse capacities of isolated buildings governed by the prescribed design criteria on the displacement and strength capacities of the employed isolation systems. In order to evaluate their collapse capacity under maximum considered earthquakes (MCEs), simplified numerical models are constructed for a larger number of nonlinear incremental dynamic analyses. The influential factors on the collapse probabilities of the prototype buildings are found out to specifically suggest the potential modifications of the design requirements. Although the MCE collapse probabilities of all isolated buildings are smaller than those expected for typical non-isolated buildings, these values are significantly different according to the degree of seismicity. The MCE collapse probabilities are dependent upon the governing collapse mechanism and the total system uncertainty. For the prototype buildings located at low-to-moderate seismicity regions, this study proposed the acceptable uncertainty to achieve a similar collapse performance to the corresponding buildings built at high seismicity regions.
Electrical Resistivity and Electrical Impedance Measurement in Mortar and Concrete Elements: A Systematic Review
Authors: Cosoli Gloria , Mobili Alessandra , Tittarelli Francesca , Revel Gian Marco , Chiariotti Paolo
Published: December 2020

This paper aims at analyzing the state-of-the-art techniques to measure electrical impedance (and, consequently, electrical resistivity) of mortar/concrete elements. Despite the validity of the concept being widely proven in the literature, a clear standard for this measurement is still missing. Different methods are described and discussed, highlighting pros and cons with respect to their performance, reliability, and degree of maturity. Both monitoring and inspection approaches are possible by using electrical resistivity measurements; since electrical resistivity is an important indicator of the health status of mortar/concrete, as it changes whenever phenomena modifying the conductivity of mortar/concrete (e.g., degradation or attacks by external agents) occur, this review aims to serve as a guide for those interested in this type of measurements.
Retro-Reflective-Marker-Aided Target Pose Estimation in a Safety-Critical Environment
Authors: Ribeiro Laura Gonçalves , Suominen Olli J. , Durmush Ahmed , Peltonen Sari , Ruiz Morales Emilio , Gotchev Atanas
Published: December 2020

Visual technologies have an indispensable role in safety-critical applications, where tasks must often be performed through teleoperation. Due to the lack of stereoscopic and motion parallax depth cues in conventional images, alignment tasks pose a significant challenge to remote operation. In this context, machine vision can provide mission-critical information to augment the operator’s perception. In this paper, we propose a retro-reflector marker-based teleoperation aid to be used in hostile remote handling environments. The system computes the remote manipulator’s position with respect to the target using a set of one or two low-resolution cameras attached to its wrist. We develop an end-to-end pipeline of calibration, marker detection, and pose estimation, and extensively study the performance of the overall system. The results demonstrate that we have successfully engineered a retro-reflective marker from materials that can withstand the extreme temperature and radiation levels of the environment. Furthermore, we demonstrate that the proposed maker-based approach provides robust and reliable estimates and significantly outperforms a previous stereo-matching-based approach, even with a single camera.
The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases
Authors: Cuollo Lorenzo , Antonangeli Fabrizio , Santoni Angela , Soriani Alessandra
Published: December 2020

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.
Mitochondrial microRNAs: A Putative Role in Tissue Regeneration
Authors: Rodrigues Sílvia C. , Cardoso Renato M. S. , Duarte Filipe V.
Published: December 2020

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.
The Regulation of Fat Metabolism during Aerobic Exercise
Authors: Muscella Antonella , Stefàno Erika , Lunetti Paola , Capobianco Loredana , Marsigliante Santo
Published: December 2020

Since the lipid profile is altered by physical activity, the study of lipid metabolism is a remarkable element in understanding if and how physical activity affects the health of both professional athletes and sedentary subjects. Although not fully defined, it has become clear that resistance exercise uses fat as an energy source. The fatty acid oxidation rate is the result of the following processes: (a) triglycerides lipolysis, most abundant in fat adipocytes and intramuscular triacylglycerol (IMTG) stores, (b) fatty acid transport from blood plasma to muscle sarcoplasm, (c) availability and hydrolysis rate of intramuscular triglycerides, and (d) transport of fatty acids through the mitochondrial membrane. In this review, we report some studies concerning the relationship between exercise and the aforementioned processes also in light of hormonal controls and molecular regulations within fat and skeletal muscle cells.
Development and Mechanical Testing of Porous-Lightweight Geopolymer Mortar
Authors: Qadir Ghulam , Rashid Yasir , Hassan Ahmed , Vall Esma , Saleh Shamsa , Salim Khadega
Published: December 2020

In this study, a novel porous geopolymer mortar (GP) was produced and tested experimentally. Industrial waste materials/by-products were used as constituents of the GP, along with dune sand. One sample was produced as a control sample for benchmarking. For the rest of the samples, 15%, 30%, and 45% by volume, the solid constituents were replaced with expanded polystyrene foam (EPS) beads. These mortar samples were heat cured to depolymerize the EPS to cause porosity inside the samples. Indoor experiments were conducted to evaluate the response of produced porous GP to high heat flux. The porous samples were able to reduce heat transmission across the opposite surfaces. Induced porosity resulted in a decrement in compressive strength from 77.2 MPa for the control sample to 15.8 MPa for 45% porous sample. However, the limit lies within the standards for partitioning walls in buildings and pavements in urban areas to absorb rainwater.
Adjuvant Pancreatic Cancer Management: Towards New Perspectives in 2021
Authors: Turpin Anthony , el Amrani Mehdi , Bachet Jean-Baptiste , Pietrasz Daniel , Schwarz Lilian , Hammel Pascal
Published: December 2020

Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or gemcitabine-nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/– chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.
Performance of Comprehensive Complication Index and Clavien-Dindo Complication Scoring System in Liver Surgery for Hepatocellular Carcinoma
Authors: Giani Alessandro , Cipriani Federica , Famularo Simone , Donadon Matteo , Bernasconi Davide Paolo , Ardito Francesco , Fazio Federico , Nicolini Daniele , Perri Pasquale , Giuffrida Mario , Pontarolo Nicholas , Zanello Matteo , Lai Quirino , Conci Simone , Molfino Sarah , Germani Paola , Pinotti Enrico , Romano Maurizio , La Barba Giuliano , Ferrari Cecilia , Patauner Stefan , Manzoni Alberto , Sciannamea Ivano , Fumagalli Luca , Troci Albert , Ferraro Valentina , Floridi Antonio , Romano Fabrizio , Ciulli Cristina , Braga Marco , Ratti Francesca , Costa Guido , Razionale Francesco , Russolillo Nadia , Marinelli Laura , De Peppo Valerio , Cremaschi Elena , Calabrese Francesco , Larghi Laureiro Zoe , Lazzari Giovanni , Cosola Davide , Montuori Mauro , Salvador Luca , Cucchetti Alessandro , Franceschi Angelo , Ciola Michele , Sega Valentina , Calcagno Pietro , Pennacchi Luca , Tedeschi Michele , Memeo Riccardo , Crespi Michele , Chiarelli Marco , Antonucci Adelmo , Zimmitti Giuseppe , Frena Antonio , Percivale Andrea , Ercolani Giorgio , Zanus Giacomo , Zago Mauro , Tarchi Paola , Baiocchi Gian Luca , Ruzzenente Andrea , Rossi Massimo , Jovine Elio , Maestri Marcello , Dalla Valle Raffaele , Grazi Gian Luca , Vivarelli Marco , Ferrero Alessandro , Giuliante Felice , Torzilli Guido , Aldrighetti Luca , Gianotti Luca
Published: December 2020

Background: We aimed to assess the ability of comprehensive complication index (CCI) and Clavien-Dindo complication (CDC) scale to predict excessive length of hospital stay (e-LOS) in patients undergoing liver resection for hepatocellular carcinoma. Methods: Patients were identified from an Italian multi-institutional database and randomly selected to be included in either a derivation or validation set. Multivariate logistic regression models and ROC curve analysis including either CCI or CDC as predictors of e-LOS were fitted to compare predictive performance. E-LOS was defined as a LOS longer than the 75th percentile among patients with at least one complication. Results: A total of 2669 patients were analyzed (1345 for derivation and 1324 for validation). The odds ratio (OR) was 5.590 (95%CI 4.201; 7.438) for CCI and 5.507 (4.152; 7.304) for CDC. The AUC was 0.964 for CCI and 0.893 for CDC in the derivation set and 0.962 vs. 0.890 in the validation set, respectively. In patients with at least two complications, the OR was 2.793 (1.896; 4.115) for CCI and 2.439 (1.666; 3.570) for CDC with an AUC of 0.850 and 0.673, respectively in the derivation cohort. The AUC was 0.806 for CCI and 0.658 for CDC in the validation set. Conclusions: When reporting postoperative morbidity in liver surgery, CCI is a preferable scale.
Efficacy of the CDK4/6 Dual Inhibitor Abemaciclib in EGFR-Mutated NSCLC Cell Lines with Different Resistance Mechanisms to Osimertinib
Authors: La Monica Silvia , Fumarola Claudia , Cretella Daniele , Bonelli Mara , Minari Roberta , Cavazzoni Andrea , Digiacomo Graziana , Galetti Maricla , Volta Francesco , Mancini Maicol , Petronini Pier Giorgio , Tiseo Marcello , Alfieri Roberta
Published: December 2020

Abemaciclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6 that inhibits the transition from the G1 to the S phase of the cell cycle by blocking downstream CDK4/6-mediated phosphorylation of Rb. The effects of abemaciclib alone or combined with the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib were examined in a panel of PC9 and HCC827 osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines carrying EGFR-dependent or -independent mechanisms of intrinsic or acquired resistance. Differently from sensitive cells, all the resistant cell lines analyzed maintained p-Rb, which may be considered as a biomarker of osimertinib resistance and a potential target for therapeutic intervention. In these models, abemaciclib inhibited cell growth, spheroid formation, colony formation, and induced senescence, and its efficacy was not enhanced in the presence of osimertinib. Interestingly, in osimertinib sensitive PC9, PC9T790M, and H1975 cells the combination of abemaciclib with osimertinib significantly inhibited the onset of resistance in long-term experiments. Our findings provide a preclinical support for using abemaciclib to treat resistance in EGFR mutated NSCLC patients progressed to osimertinib either as single treatment or combined with osimertinib, and suggest the combination of osimertinib with abemaciclib as a potential approach to prevent or delay osimertinib resistance in first-line treatment.
Roles of the HOX Proteins in Cancer Invasion and Metastasis
Authors: Paço Ana , Aparecida de Bessa Garcia Simone , Leitão Castro Joana , Costa-Pinto Ana Rita , Freitas Renata
Published: December 2020

Invasion and metastasis correspond to the foremost cause of cancer-related death, and the molecular networks behind these two processes are extremely complex and dependent on the intra- and extracellular conditions along with the prime of the premetastatic niche. Currently, several studies suggest an association between the levels of HOX genes expression and cancer cell invasion and metastasis, which favour the formation of novel tumour masses. The deregulation of HOX genes by HMGA2/TET1 signalling and the regulatory effect of noncoding RNAs generated by the HOX loci can also promote invasion and metastasis, interfering with the expression of HOX genes or other genes relevant to these processes. In this review, we present five molecular mechanisms of HOX deregulation by which the HOX clusters products may affect invasion and metastatic processes in solid tumours.
Crude Glycerol/Guishe Based Catalysts for Biodiesel Production: Conforming a Guishe Biorefinery
Authors: Figueroa-Díaz Andrea Belén , Carlos-Hernández Salvador , Díaz-Jiménez Lourdes
Published: December 2020

Biodiesel production imposes some challenges, such as the crude glycerol management and cleaning requirements of biodiesel produced by homogeneous transesterification. Heterogeneous catalysts based on residual biomass have been proposed to tackle these challenges; in addition, biomass revalorization is fundamental for biorefineries development. In this research, two organic wastes (crude glycerol and guise) are used to synthesize carbonaceous catalysts. Four catalysts, with different crude glycerol/guishe proportions, were prepared by pyrolysis at 800 and 900 °C, followed by a chemical functionalization with H2SO4. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) were used to characterize the catalysts. The performance of the catalysts was evaluated in a soybean oil transesterification reaction. The crude glycerol/guishe based catalysts lead to similar biodiesel yields than the obtained with a conventional homogeneous catalyst (CH3NaO). The catalyst identified as BS-25-8 (a mixture of 25% guishe and 75% crude glycerol, pyrolyzed at 800 °C and sulfonated), in a proportion of 1 wt%, achieved the highest fatty acid methyl esters (FAME) yield (99%) in the transesterification reaction, even surpassing the performance of the CH3NaO (yield of 93%).
Modeling CNS Involvement in Pompe Disease Using Neural Stem Cells Generated from Patient-Derived Induced Pluripotent Stem Cells
Authors: Cheng Yu-Shan , Yang Shu , Hong Junjie , Li Rong , Beers Jeanette , Zou Jizhong , Huang Wenwei , Zheng Wei
Published: December 2020

Pompe disease is a lysosomal storage disorder caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene. Acid alpha-glucosidase deficiency leads to abnormal glycogen accumulation in patient cells. Given the increasing evidence of central nervous system (CNS) involvement in classic infantile Pompe disease, we used neural stem cells, differentiated from patient induced pluripotent stem cells, to model the neuronal phenotype of Pompe disease. These Pompe neural stem cells exhibited disease-related phenotypes including glycogen accumulation, increased lysosomal staining, and secondary lipid buildup. These morphological phenotypes in patient neural stem cells provided a tool for drug efficacy evaluation. Two potential therapeutic agents, hydroxypropyl-β-cyclodextrin and δ-tocopherol, were tested along with recombinant human acid alpha-glucosidase (rhGAA) in this cell-based Pompe model. Treatment with rhGAA reduced LysoTracker staining in Pompe neural stem cells, indicating reduced lysosome size. Additionally, treatment of diseased neural stem cells with the combination of hydroxypropyl-β-cyclodextrin and δ-tocopherol significantly reduced the disease phenotypes. These results demonstrated patient-derived Pompe neural stem cells could be used as a model to study disease pathogenesis, to evaluate drug efficacy, and to screen compounds for drug discovery in the context of correcting CNS defects.
Surface Modification of Aluminum 6061-O Alloy by Plasma Electrolytic Oxidation to Improve Corrosion Resistance Properties
Authors: Dzhurinskiy Dmitry V. , Dautov Stanislav S. , Shornikov Petr G. , Akhatov Iskander Sh.
Published: December 2020

In the present investigation, the plasma electrolytic oxidation (PEO) process was employed to form aluminum oxide coating layers to enhance corrosion resistance properties of high-strength aluminum alloys. The formed protective coating layers were examined by means of scanning electron microscopy (SEM) and characterized by several electrochemical techniques, including open circuit potential (OCP), linear potentiodynamic polarization (LP) and electrochemical impedance spectroscopy (EIS). The results were reported in comparison with the bare 6061-O aluminum alloy to determine the corrosion performance of the coated 6061-O alloy. The PEO-treated aluminum alloy showed substantially higher corrosion resistance in comparison with the untreated substrate material. A relationship was found between the coating formation stage, process parameters and the thickness of the oxide-formed layers, which has a measurable influence on enhancing corrosion resistance properties. This study demonstrates promising results of utilizing PEO process to enhance corrosion resistance properties of high-strength aluminum alloys and could be recommended as a method used in industrial applications.
Hydrophilic Biocompatible Poly(Acrylic Acid-co-Maleic Acid) Polymer as a Surface-Coating Ligand of Ultrasmall Gd2O3 Nanoparticles to Obtain a High r1 Value and T1 MR Images
Authors: Jang Yeong-Ji , Liu Shuwen , Yue Huan , Park Ji Ae , Cha Hyunsil , Ho Son Long , Marasini Shanti , Ghazanfari Adibehalsadat , Ahmad Mohammad Yaseen , Miao Xu , Tegafaw Tirusew , Chae Kwon-Seok , Chang Yongmin , Lee Gang Ho
Published: December 2020

The water proton spin relaxivity, colloidal stability, and biocompatibility of nanoparticle-based magnetic resonance imaging (MRI) contrast agents depend on the surface-coating ligands. Here, poly(acrylic acid-co-maleic acid) (PAAMA) (Mw = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd2O3) nanoparticles. Owing to the numerous carboxylic groups in PAAMA, which allow its strong conjugation with the nanoparticle surfaces and the attraction of abundant water molecules to the nanoparticles, the synthesized PAAMA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.8 nm and aavg = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r1) of 40.6 s−1mM−1 (r2/r1 = 1.56, where r2 = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T1 MR images at the 3.0 T MR field.
The Role of Urine F2-isoprostane Concentration in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Haemorrhage—A Poor Prognostic Factor
Authors: Wiśniewski Karol , Popęda Marta , Tomasik Bartłomiej , Bieńkowski Michał , Bobeff Ernest J. , Stefańczyk Ludomir , Tybor Krzysztof , Hupało Marlena , Jaskólski Dariusz J.
Published: December 2020

Background: The pathophysiology of delayed cerebral ischemia (DCI) remains unclear. One of the hypotheses suggests that reactive oxygen species play a role in its onset. Thus, we studied F2-isoprostanes (F2-IsoPs)—oxidative stress biomarkers. Our goal was to improve the early diagnosis of DCI in a non-invasive way. Methods: We conducted a prospective single center analysis of 38 aneurysmal subarachnoid hemorrhage patients. We assessed urine F2-IsoP concentration using immunoenzymatic arrays between the first and fifth day after bleeding. A correlation between urine F2-IsoP concentration and DCI occurrence was examined regarding clinical conditions and outcomes. Results: The urine F2-IsoP concentrations were greater than those in the control groups (p < 0.001). The 3rd day urine F2-IsoPs concentrations were correlated with DCI occurrence (p < 0.001) and long term outcomes after 12 months (p < 0.001). Conclusions: High levels of urine F2-IsoPs on day 3 can herald DCI.
A Paper-Based Analytical Device for Analysis of Paraquat in Urine and Its Validation with Optical-Based Approaches
Authors: Wang Tse-Yao , Lee Yi-Tzu , Chen Hsien-Yi , Ko Cheng-Hao , Hong Chi-Tsung , Wen Jyun-Wei , Yen Tzung-Hai , Cheng Chao-Min
Published: December 2020

Paraquat is a highly toxic herbicide. Paraquat poisoning is often fatal and is an important public health threat in many places. The quick identification and timely initiation of treatment based on timely analysis of the paraquat concentration in urine/serum could improve the prognosis for patients. However, current paraquat concentration measurements are time-consuming and difficult to implement due to the expensive and bulky equipment required. To address these practical challenges, paper-based devices have emerged as alternative diagnostic tools for improving point-of-care testing. In this study, we demonstrate the successful use of a paper-based analytical device for the accurate detection of urine paraquat concentration. The developed paper-based analytical device employs colorimetric paraquat concentration measurements. The R2 value for the urine paraquat standard curve was 0.9989, with a dynamic range of 0–100 ppm. The limit of detection was 3.01 ppm. Two other optical-based approaches, Spectrochip and NanoDrop, were used for comparison. The results suggest that the developed paper-based analytical device is comparable to other colorimetric measurements, as determined by Bland–Altman analysis. The device was clinically validated using urine from six paraquat-poisoned patients. The results prove that the developed paper-based analytical device is accurate, easy-to-use, and efficient for urine paraquat concentration measurement, and may enable physicians to improve clinical management.