bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Vitamin D Level Is Associated with Acute Deep Venous Thrombosis in Patients with Traumatic Brain Injury
Authors: Moore Matthew , Goldin Yelena , Patel Harsh , Greenwald Brian D.
Published: June 2021

Vitamin D and its association with venous thromboembolism (VTE) have been studied in common rehabilitation populations, such as spinal cord injury and ischemic stroke groups. This study explores the relationship between vitamin D levels and acute deep venous thrombosis (DVT) in the traumatic brain injury (TBI) population. This is a retrospective cohort study that analyzes the relationship between vitamin D levels and the prevalence of DVT during acute inpatient rehabilitation. In this population, 62% (117/190) of patients had low vitamin D levels upon admission to acute rehabilitation. Furthermore, 21% (24/117) of patients in the low vitamin D group had acute DVT during admission to acute rehabilitation. In contrast, only 8% (6/73) of patients in the normal vitamin D group had acute DVT during admission to acute rehabilitation. Fisher’s exact tests revealed significant differences between individuals with low and normal vitamin D levels (p = 0.025). In conclusion, a vitamin D level below 30 ng/mL was associated with increased probability of the occurrence of acute DVT in individuals with moderate–severe TBI.
Metabolic Surgery and Cancer Risk: An Opportunity for Mechanistic Research
Authors: Sauter Edward R. , Heckman-Stoddard Brandy
Published: June 2021

Metabolic (bariatric) surgery (MBS) is recommended for individuals with a BMI > 40 kg/m2 or those with a BMI 35–40 kg/m2 who have one or more obesity related comorbidities. MBS leads to greater initial and sustained weight loss than nonsurgical weight loss approaches. MBS provides dramatic improvement in metabolic function, associated with a reduction in type 2 diabetes mellitus and cardiovascular risk. While the number of MBS procedures performed in the U.S. and worldwide continues to increase, they are still only performed on one percent of the affected population. MBS also appears to reduce the risk of certain obesity related cancers, although which cancers are favorably impacted vary by study, who benefits most is uncertain, and the mechanism(s) driving this risk reduction are mostly speculative. The goal of this manuscript is to highlight (1) emerging evidence that MBS influences cancer risk, and that the potential benefit appears to vary based on cancer, gender, surgical procedure, and likely other variables; (2) the role of the NIH in MBS research in T2DM and CV risk for many years, and more recently in cancer; and (3) the opportunity for research to understand the mechanism(s) by which MBS influences cancer. There is evidence that women benefit more from MBS than men, that MBS may actually increase the risk of colorectal cancer in both women and men, and there is speculation that the benefit in cancer risk reduction may vary according to which MBS procedure an individual undergoes. Herein, we review what is currently known, the historical role of government, especially the National Institutes of Health (NIH), in driving this research, and provide suggestions that we believe could lead to a better understanding of whether and how MBS impacts cancer risk, which cancers are impacted either favorably or unfavorably, the role of the NIH and other research agencies, and key questions to address that will help us to move the science forward.
Discovery of Spatial Peptide Signatures for Neuroblastoma Risk Assessment by MALDI Mass Spectrometry Imaging
Authors: Wu Zhiyang , Hundsdoerfer Patrick , Schulte Johannes H. , Astrahantseff Kathy , Boral Senguel , Schmelz Karin , Eggert Angelika , Klein Oliver
Published: June 2021

Risk classification plays a crucial role in clinical management and therapy decisions in children with neuroblastoma. Risk assessment is currently based on patient criteria and molecular factors in single tumor biopsies at diagnosis. Growing evidence of extensive neuroblastoma intratumor heterogeneity drives the need for novel diagnostics to assess molecular profiles more comprehensively in spatial resolution to better predict risk for tumor progression and therapy resistance. We present a pilot study investigating the feasibility and potential of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to identify spatial peptide heterogeneity in neuroblastoma tissues of divergent current risk classification: high versus low/intermediate risk. Univariate (receiver operating characteristic analysis) and multivariate (segmentation, principal component analysis) statistical strategies identified spatially discriminative risk-associated MALDI-based peptide signatures. The AHNAK nucleoprotein and collapsin response mediator protein 1 (CRMP1) were identified as proteins associated with these peptide signatures, and their differential expression in the neuroblastomas of divergent risk was immunohistochemically validated. This proof-of-concept study demonstrates that MALDI-MSI combined with univariate and multivariate analysis strategies can identify spatially discriminative risk-associated peptide signatures in neuroblastoma tissues. These results suggest a promising new analytical strategy improving risk classification and providing new biological insights into neuroblastoma intratumor heterogeneity.
Using MoS2/Fe3O4 as Ion-Electron Transduction Layer to Manufacture All-Solid-State Ion-Selective Electrode for Determination of Serum Potassium
Authors: Su Yan , Liu Ting , Song Caiqiao , Fan Aiqiao , Zhu Nan , Sun Bingbing , Yang Cheng
Published: June 2021

As an essential electrolyte for the human body, the potassium ion (K+) plays many physiological roles in living cells, so the rapid and accurate determination of serum K+ is of great significance. In this work, we developed a solid-contact ion-selective electrode (SC-ISE) using MoS2/Fe3O4 composites as the ion-to-electron transducer to determine serum K+. The potential response measurement of MoS2/Fe3O4/K+-ISE shows a Nernst response by a slope of 55.2 ± 0.1 mV/decade and a low detection limit of 6.3 × 10−6 M. The proposed electrode exhibits outstanding resistance to the interference of O2, CO2, light, and water layer formation. Remarkably, it also presents a high performance in potential reproducibility and long-term stability.
The Association between Parental Support and Adolescents’ Psychological Complaints: The Mediating Role of a Good School Climate
Authors: Ramberg Joacim
Published: June 2021

Parental support is an important factor affecting young people’s mental well-being, but the school climate also plays an important role. However, few studies have previously examined whether the school climate serves as a mediator for adolescents’ mental health problems. This study aimed to investigate the association between parental support and students’ psychological complaints, while also examining the possible mediating role that a good school climate may have. Data derives from 5783 senior-level students (age 15–16) distributed over 152 school units in Stockholm municipality. Regression linear analysis was used for the analysis and Baron and Kenny’s four-step mediation model has been applied. Sobel’s test was conducted in order to test the significance of the mediation effect. The results show that there is a significant negative association between parental support and students’ psychological complaints, and that school climate has a mediating role in this association. It can be concluded that school climate has a partly mediating role in the association between parental support and students’ psychological complaints. Therefore, it seems important to develop the school climate in order to strengthen this source of support to reduce mental health problems among adolescents.
Note on F-Graph Construction
Authors: Liska Vladimir , Vrabel Robert
Published: June 2021

The center of an F-graph contains at least two vertices, and the distance between any two central vertices is equal to the radius. In this short note, we describe one way of constructing these graphs.
In Vitro Cell Culture Models of Hyperoxaluric States: Calcium Oxalate and Renal Epithelial Cell Interactions
Authors: Petrović Ana , Kizivat Tomislav , Bilić Ćurčić Ines , Smolić Robert , Smolić Martina
Published: June 2021

Urolithiasis is a multifactorial disease with a high incidence and high recurrence rate, characterized by formation of solid deposits in the urinary tract. The most common type of these stones are calcium oxalate stones. Calcium oxalate crystals can, in hyperoxaluric states, interact with renal epithelial cells, causing injury to the renal epithelia. Pathogenesis of urolithiasis is widely investigated, but underlying mechanisms are still not completely clarified. In vitro models offer insight into molecular processes which lead to renal stone formation and are significant for evaluation of prophylactic and therapeutic management of patients with urolithiasis. In this review, we summarize recently published data from in vitro studies investigating interactions of calcium oxalate crystals with renal epithelial cell lines, anti-urolithiatic mechanisms, and the results from studies exploring possible therapeutic and prophylactic options for calcium oxalate urolithiasis in cell cultures.
Dental Anomalies’ Characteristics
Authors: Sella Tunis Tatiana , Sarne Ofer , Hershkovitz Israel , Finkelstein Tamar , Pavlidi Aikaterini Maria , Shapira Yehoshua , Davidovitch Moshe , Shpack Nir
Published: June 2021

The aim of this study was to characterize dental anomalies. The pretreatment records (photographs and radiographs) of 2897 patients (41.4% males and 58.6% females) were utilized to detect dental anomalies. The dental anomalies studied were related to number, size and shape, position, and eruption. A Chi-square test was carried out to detect associations between dental anomalies, jaw, and sex. A total of 1041 (36%) of the subjects manifested at least one dental anomaly. The prevalence of all dental anomalies was jaw-dependent and greater in the maxilla, except for submerged and transmigrated teeth. The most frequently missing teeth were the maxillary lateral incisor (62.3%) and the mandibular second premolars (60.6%). The most frequent supernumerary teeth were the incisors in the maxilla (97%) and the first premolars in the mandible (43%). Dental anomalies are more frequent in the maxilla and mainly involve the anterior teeth; in the mandible, however, it is the posterior teeth. These differences can be attributed to the evolutionary history of the jaws and their diverse development patterns.
Contrast Administration Impacts CT-Based Radiomics of Colorectal Liver Metastases and Non-Tumoral Liver Parenchyma Revealing the “Radiological” Tumour Microenvironment
Authors: Fiz Francesco , Costa Guido , Gennaro Nicolò , la Bella Ludovico , Boichuk Alexandra , Sollini Martina , Politi Letterio S. , Balzarini Luca , Torzilli Guido , Chiti Arturo , Viganò Luca
Published: June 2021

The impact of the contrast medium on the radiomic textural features (TF) extracted from the CT scan is unclear. We investigated the modification of TFs of colorectal liver metastases (CLM), peritumoral tissue, and liver parenchyma. One hundred and sixty-two patients with 409 CLMs undergoing resection (2017–2020) into a single institution were considered. We analyzed the following volumes of interest (VOIs): The CLM (Tumor-VOI); a 5-mm parenchyma rim around the CLM (Margin-VOI); and a 2-mL sample of parenchyma distant from CLM (Liver-VOI). Forty-five TFs were extracted from each VOI (LIFEx®®). Contrast enhancement affected most TFs of the Tumor-VOI (71%) and Margin-VOI (62%), and part of those of the Liver-VOI (44%, p = 0.010). After contrast administration, entropy increased and energy decreased in the Tumor-VOI (0.93 ± 0.10 vs. 0.85 ± 0.14 in pre-contrast; 0.14 ± 0.03 vs. 0.18 ± 0.04, p < 0.001) and Margin-VOI (0.89 ± 0.11 vs. 0.85 ± 0.12; 0.16 ± 0.04 vs. 0.18 ± 0.04, p < 0.001), while remaining stable in the Liver-VOI. Comparing the VOIs, pre-contrast Tumor and Margin-VOI had similar entropy and energy (0.85/0.18 for both), while Liver-VOI had lower values (0.76/0.21, p < 0.001). In the portal phase, a gradient was observed (entropy: Tumor > Margin > Liver; energy: Tumor < Margin < Liver, p < 0.001). Contrast enhancement affected TFs of CLM, while it did not modify entropy and energy of parenchyma. TFs of the peritumoral tissue had modifications similar to the Tumor-VOI despite its radiological aspect being equal to non-tumoral parenchyma.
Josephson Currents and Gap Enhancement in Graph Arrays of Superconductive Islands
Authors: Lucci Massimiliano , Cassi Davide , Merlo Vittorio , Russo Roberto , Salina Gaetano , Cirillo Matteo
Published: June 2021

Evidence is reported that topological effects in graph-shaped arrays of superconducting islands can condition superconducting energy gap and transition temperature. The carriers giving rise to the new phase are couples of electrons (Cooper pairs) which, in the superconducting state, behave as predicted for bosons in our structures. The presented results have been obtained both on star and double comb-shaped arrays and the coupling between the islands is provided by Josephson junctions whose potential can be tuned by external magnetic field or temperature. Our peculiar technique for probing distribution on the islands is such that the hopping of bosons between the different islands occurs because their thermal energy is of the same order of the Josephson coupling energy between the islands. Both for star and double comb graph topologies the results are in qualitative and quantitative agreement with theoretical predictions.
Restorative Justice Education from Intrajudicial Criminal Mediation Associated Factors
Authors: Matás Castillo Mercedes , Méndez Inmaculada , Esteban Cecilia Ruiz , Soto Gloria
Published: June 2021

The restorative justice (RJ) paradigm requires coherence among legal, justice, and educational systems to promote a culture of restorative dialogue with victims of violence and to reintegrate aggressors into the community. The objective of this study, from an evolutionary social perspective, was to examine criminal mediation files in the archives of the Murcia Intrajudicial Criminal Mediation Service (UMIM), Spain, to see which variables are associated with which types of violence and understand the contents and adoption of agreements. In this study the sociodemographic, procedural, and interpersonal variables of 216 people who used criminal mediation were analysed. The results showed statistically significant differences concerning age, the procedural moment of referral, and the participants’ relationship. The main conclusions are that the youngest group had a more significant number of encounters with physical violence; most agreements occurred in the initial phase of a judicial procedure; and the majority of agreements had moral content regardless of the age of the parties involved. These factors are of interest to the establishment of judicial and educational restorative models.
TSPEM Parameter Extraction Method and Its Applications in the Modeling of Planar Schottky Diode in THz Band
Authors: Liu Xiaoyu , Zhang Yong , Wang Haoran , Qi Luwei , Wang Bo , Zhou Jingtao , Ding Wuchang , Jin Zhi , Xiao Fei
Published: June 2021

In this paper, a new method for the parameter extraction of Schottky barrier diode (SBD) is presented to eliminate the influence of parasitic parameters on the intrinsic capacitance-voltage (C-V) characteristics of the Schottky diodes at high frequencies. The method is divided into the de-embedding and parameter extraction, including six auxiliary configurations and, is referred tos as Two-step Six-configuration Parameter Extraction Method (TSPEM). Compared to the traditional junction capacitance extraction method, this method can extract the value of junction capacitance at higher frequencies with higher accuracy. At the same time, compared to the other de-embedding methods, this method shows better performance in de-embedding the contributions of parasitic structures from the transmission line measurements. The intrinsic junction capacitances obtained by this method and the three-dimensional (3-D) electromagnetic model are combined to form a diode simulation model, which accurately characterizes the capacitance characteristics of the SBD. It was verified with a 200 GHz double frequency multiplier, and the simulation results and measurement results showed good consistency.
Object Identification and Localization Using Grad-CAM++ with Mask Regional Convolution Neural Network
Authors: Inbaraj Xavier Alphonse , Villavicencio Charlyn , Macrohon Julio Jerison , Jeng Jyh-Horng , Hsieh Jer-Guang
Published: June 2021

One of the fundamental advancements in the deployment of object detectors in real-time applications is to improve object recognition against obstruction, obscurity, and noises in images. In addition, object detection is a challenging task since it needs the correct detection of objects from images. Semantic segmentation and localization are an important module to recognizing an object in an image. The object localization method (Grad-CAM++) is mostly used by researchers for object localization, which uses the gradient with a convolution layer to build a localization map for important regions on the image. This paper proposes a method called Combined Grad-CAM++ with the Mask Regional Convolution Neural Network (GC-MRCNN) in order to detect objects in the image and also localization. The major advantage of proposed method is that they outperform all the counterpart methods in the domain and can also be used in unsupervised environments. The proposed detector based on GC-MRCNN provides a robust and feasible ability in detecting and classifying objects exist and their shapes in real time. It is found that the proposed method is able to perform highly effectively and efficiently in a wide range of images and provides higher resolution visual representation than existing methods (Grad-CAM, Grad-CAM++), which was proven by comparing various algorithms.
An Approach to Analyze Diagnosis Errors in Advanced Main Control Room Operations Using the Cause-Based Decision Tree Method
Authors: Arigi Awwal Mohammed , Park Gayoung , Kim Jonghyun
Published: June 2021

Advancements in the nuclear industry have led to the development of fully digitized main control rooms (MCRs)—often termed advanced MCRs—for newly built nuclear power plants (NPPs). Diagnosis is a major part of the cognitive activity in NPP MCRs. Advanced MCRs are expected to improve the working environment and reduce human error, especially during the diagnosis of unexpected scenarios. However, with the introduction of new types of tasks and errors by digital MCRs, a new method to analyze the diagnosis errors in these new types of MCRs is required. Task analysis for operator diagnosis in an advanced MCR based on emergency operation was performed to determine the error modes. The cause-based decision tree (CBDT) method—originally developed for analog control rooms—was then revised to a modified CBDT (MCBDT) based on the error mode categorizations. This work examines the possible adoption of the MCBDT method for the evaluation of diagnosis errors in advanced MCRs. We have also provided examples of the application of the proposed method to some common human failure events in emergency operations. The results show that with some modifications of the CBDT method, the human reliability in advanced MCRs can be reasonably estimated.
A Comparative Study on Thermochemical Valorization Routes for Spent Coffee Grounds
Authors: Yang Jie , Chen Hao , Niu Haibo , McNutt Josiah , He Quan
Published: June 2021

Extracting oil from spent coffee grounds (SCG) for biodiesel production has recently attracted much research interest. Large amounts of organic solvents are involved for oil extraction and biodiesel synthesis. Hydrothermal liquefaction (HTL) is an emerging thermochemical technology with great potential for biocrude production from a broad range of feedstocks. This study attempted to compare two SCG valorization options: route 1, oil extraction for biodiesel production followed by HTL of defatted SCG; and route 2, direct HTL of raw SCG. The microwave-assisted extraction conditions were optimized to effectively remove oil from SCG using response surface methodology. Under optimal conditions, an SCG oil yield of 8.4 wt.% could be achieved. HTL of defatted SCG generated less biocrude (18.9 wt.%) than that of raw SCG (28.1 wt.%). The biochemical compositions of resultant biocrudes were largely different from each other. The life cycle assessment was conducted on each of the SCG valorization routes and showed that the greenhouse gas emissions from direct HTL of raw SCG were only 35% of the other valorization route, suggesting that direct HTL is a favorable valorization route for SCG within this study’s scope.
Photovoltaic Maximum Penetration Limits on Medium Voltage Overhead and Underground Cable Distribution Feeders: A Comparative Study
Authors: Alanzi Sultan Sh. , Kamel Rashad M.
Published: June 2021

This paper investigates the maximum photovoltaic (PV) penetration limits on both overhead lines and underground cables medium voltage radial distribution system. The maximum PV penetration limit is estimated considering both bus voltage limit (1.05 p.u.) and feeder current ampacity (1 p.u.). All factors affect the max PV penetration limit are investigated in detail. Substation voltage, load percentage, load power factor, and power system frequency (50 Hz or 60 Hz) are analyzed. The maximum PV penetration limit associated with overhead lines is usually higher than the value associated with the underground cables for high substation voltage (substation voltage = 1.05 and 1.04 p.u.). The maximum PV penetration limit decreases dramatically with low load percentage for both feeder types but still the overhead lines accept PV plant higher than the underground cables. Conversely, the maximum PV penetration increases with load power factor decreasing and the overhead lines capability for hosting PV plant remains higher than the capability of the underground cables. This paper proved that the capability of the 60-Hz power system for hosting the PV plant is higher than the capability of 50 Hz power system. MATLAB software has been employed to obtain all results in this paper. The Newton-Raphson iterative method was the used method to solve the power flow of the investigated systems.
Developing a Descriptive Sensory Characterization of Flour Tortilla Applying Flash Profile
Authors: Rodríguez-Noriega Sanjuana , Buenrostro-Figueroa José J. , Rebolloso-Padilla Oscar Noé , Corona-Flores José , Camposeco-Montejo Neymar , Flores-Naveda Antonio , Ruelas-Chacón Xochitl
Published: June 2021

For any food, it is important to know consumption, preference, and the characteristics as quality parameters that are important to consumers of a product. The descriptive methodologies are an important tool to know the quality attributes of the products. Within these methodologies is the flash profile (FP), which is based on the generation of the distinctive attributes of the products without any expensive and time-consuming training sessions. The aim of this research was to study the consumption and preference of flour tortillas by consumers and to develop the descriptive characterization of the tortillas by using the flash profile method. The wheat flour tortillas used were two commercial and two handcrafted samples. Ten experienced panelists participated as the FP panel. The panelists generated 22 descriptors, six for texture, seven for appearance, five for odor, and four for flavor. These descriptors differentiate the samples of the flour tortillas. The panelists’ performance was assessed using the consensus index (Rc = 0.508). The first two dimensions of the Generalized Procrustes Analysis represent 83.78% of the data variability. Flash profile proved to be an easy and rapid technique that allowed the distinctive attributes of flour tortillas to be obtained.
Significance of Sodium Bisulfate (SBS) Tempering in Reducing the Escherichia coli O121 and O26 Load of Wheat and Its Effects on Wheat Flour Quality
Authors: Rivera Jared , Deliephan Aiswariya , Dhakal Janak , Aldrich Charles Gregory , Siliveru Kaliramesh
Published: June 2021

The occurrence of recalls involving pathogenic Escherichia coli-contaminated wheat flours show the need for incorporating antimicrobial interventions in wheat milling. The objectives of this study were to assess the efficacy of sodium bisulfate (SBS) tempering in reducing E. coli O121 (ATCC 2219) and O26 (ATCC 2196) wheat load and to evaluate the impact of effective (≥3.0 log reductions) SBS treatments on wheat flour quality. Wheat grains were inoculated with E. coli (~6 log CFU/g) and tempered (17% moisture, 24 h) using the following SBS concentrations (%wheat basis): 0, 0.5, 0.75, 1.0, 1.25, and 1.5% SBS. Reductions in E. coli O121 and O26 wheat load at different time intervals (0.5, 2, 6, 12, 18, and 24 h) during tempering were evaluated. The addition of SBS during tempering resulted in E. coli (O121 and O26) log reductions of 2.0 (0.5% SBS) to >4.0 logs (1.5% SBS) (p ≤ 0.05). SBS tempering (1.25 and 1.5% SBS) produced acidic wheat flours (pH = 4.51–4.60) but had comparable wheat flour properties in terms of composition, dough, and bread-making properties relative to the control (0% SBS). SBS tempering reduced the E. coli O121 and O26 load of wheat after tempering with minimal effects on wheat flour quality.
Consumer Profile and Product Knowledge Affect the Usefulness of a Quality Label as a Tool to Differentiate a Product: A Chilean Survey
Authors: Panea Begoña , Subiabre Ignacio , Haudorf Andrea , Morales Rodrigo
Published: June 2021

Quality labels are useful tools to differentiate food products, but only if consumers recognise them and associate them with specific characteristics. An online survey was conducted to investigate whether Chilean consumers knew about Novillo de Osorno, for which a quality label is being developed. The survey was divided into five blocks: lifestyles, meat consumption and purchase habits, meat choice behaviour, knowledge about Novillo de Osorno, and consumers’ socio-demographic information. The place of residence and consumer gender, age, or income were important cues in defining consumers’ lifestyles, meat consumption and purchase habits. Respondents could be grouped into three main groups: 1. Younger people: urban with medium-high incomes, which search only for pleasure; 2. Foodies uninvolved and Females uninvolved: females with the highest income level that chose food for nutritional reasons; and 3. Traditional people: men older than 55 with low incomes, living in the Northern areas and interested in taste and in the meat’s origin. Nearly 60% of respondents had never heard about Novillo de Osorno. Hence, the supply chain has an opportunity to extend the market. Since price and confidence in the origin are important cues, they must be considered in the design of promotion strategies.
Protective Effect of Water-Soluble C60 Fullerene Nanoparticles on the Ischemia-Reperfusion Injury of the Muscle Soleus in Rats
Authors: Nozdrenko Dmytro , Matvienko Tetiana , Vygovska Oksana , Bogutska Kateryna , Motuziuk Olexandr , Nurishchenko Natalia , Prylutskyy Yuriy , Scharff Peter , Ritter Uwe
Published: June 2021

The biomechanical parameters of muscle soleus contraction in rats and their blood biochemical indicators after the intramuscular administration of water-soluble C60 fullerene at doses of 0.5, 1, and 2 mg/kg 1 h before the onset of muscle ischemia were investigated. In particular, changes in the contraction force of the ischemic muscle soleus, the integrated power of the muscle, the time to achieve the maximum force response, the dynamics of fatigue processes, and the parameters of the transition from dentate to smooth tetanus, levels of creatinine, creatine kinase, lactate and lactate dehydrogenase, and parameters of prooxidant–antioxidant balance (thiobarbituric acid reactive substances, hydrogen peroxide, and reduced glutathione and catalase) were analyzed. The positive therapeutic changes in the studied biomechanical and biochemical markers were revealed, which indicate the possibility of using water-soluble C60 fullerenes as effective prophylactic nanoagents to reduce the severity of pathological conditions of the muscular system caused by ischemic damage to skeletal muscles.
Beyond RAS and BRAF: HER2, a New Actionable Oncotarget in Advanced Colorectal Cancer
Authors: Guarini Chiara , Grassi Teresa , Pezzicoli Gaetano , Porta Camillo
Published: June 2021

The human epidermal growth factor receptor 2 (HER2) is a well-established oncogenic driver and a successful therapeutic target in several malignancies, such as breast and gastric cancers. HER2 alterations, including amplification and somatic mutations, have also been detected in a small but not negligible subset of patients affected by advanced colorectal cancer (aCRC). However, to date, there are no available oncotargets in this malignancy beyond RAS and BRAF that are available. Here we present an overview on the present predictive and prognostic role of HER2 expression in aCRC, as well as on its consequent potential therapeutic implications from preclinical investigations towards ongoing trials testing anti-HER2 agents in aCRC. While HER2′s role as a molecular predictive biomarker for anti-EGFR therapies in CRC is recognized, HER2 prognostic value remains controversial. Moreover, thanks to the impressive and growing body of clinical evidence, HER2 is strongly emerging as a new potential actionable oncotarget in aCRC. In conclusion, in the foreseeable future, HER2-targeted therapeutic strategies may integrate the algorithm of aCRC treatment towards an increasingly tailored therapeutic approach to this disease.
An Ancestry Perspective of the Evolution of PBS1 Proteins in Plants
Authors: Villegas-Vázquez Edgar Yebrán , Xoconostle-Cázares Beatriz , Ruiz-Medrano Roberto
Published: June 2021

The AVRPPHB SUSCEPTIBLE1 (PBS1) and RESISTANCE TO PSEUDOMONAS SYRINGAE 5 (RPS5) proteins are involved in signal transduction to evoke innate plant immune response. In Arabidopsis, PBS1 is cleaved by the AvrPphB (Pseudomonas phaseolicola Avirulence protein B) protease, activating RPS5 and turning in a hypersensitive response (HR). We searched for PBS1 orthologs to trace their origin and evolution. PBS1 orthologs were found in embryophytes and in other plant taxa but with lower similarity. PBS1 phylogenetic analysis indicates high divergence, suggesting that the decoy function described for Arabidopsis PBS1 might be associated with a small fraction of orthologs. Ancestral reconstruction analysis suggests an elevated diversity in the amino acid sequence within the described motifs. All the orthologs contain the conserved PBS1 kinase subdomains, whereas the cleavage motif is present in several embryophyte orthologs but absent in most other taxa. The putative resistance recognition motifs in PBS1 orthologs are highly diverse. PBS1 cleavage site motif is exposed in some 3D structure predictions, whereas it is not in others, suggesting different modes of regulation and functions in PBS1 orthologs. Our findings suggest that PBS1 originated in the lineage that gave rise to embryophytes, with the angiosperm sequences forming a separate clade from pteridophyte proteins.
Annexin A2 in Fibrinolysis, Inflammation and Fibrosis
Authors: Lim Hana I. , Hajjar Katherine A.
Published: June 2021

As a cell surface tissue plasminogen activator (tPA)-plasminogen receptor, the annexin A2 (A2) complex facilitates plasmin generation on the endothelial cell surface, and is an established regulator of hemostasis. Whereas A2 is overexpressed in hemorrhagic disease such as acute promyelocytic leukemia, its underexpression or impairment may result in thrombosis, as in antiphospholipid syndrome, venous thromboembolism, or atherosclerosis. Within immune response cells, A2 orchestrates membrane repair, vesicle fusion, and cytoskeletal organization, thus playing a critical role in inflammatory response and tissue injury. Dysregulation of A2 is evident in multiple human disorders, and may contribute to the pathogenesis of various inflammatory disorders. The fibrinolytic system, moreover, is central to wound healing through its ability to remodel the provisional matrix and promote angiogenesis. A2 dysfunction may also promote tissue fibrogenesis and end-organ fibrosis.
A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu2+-Mediated Aβ Aggregation
Authors: Zhang Xiaoyu , Zhang Xiancheng , Zhong Manli , Zhao Pu , Guo Chuang , Li You , Xu He , Wang Tao , Gao Huiling
Published: June 2021

Copper (Cu) has been implicated in the progression of Alzheimer’s disease (AD), and aggregation of Cu and amyloid β peptide (Aβ) are considered key pathological features of AD. Metal chelators are considered to be potential therapeutic agents for AD because of their capacity to reduce metal ion-induced Aβ aggregation through the regulation of metal ion distribution. Here, we used phage display technology to screen, synthesize, and evaluate a novel Cu(II)-binding peptide that specifically blocked Cu-triggered Aβ aggregation. The Cu(II)-binding peptide (S-A-Q-I-A-P-H, PCu) identified from the phage display heptapeptide library was used to explore the mechanism of PCu inhibition of Cu2+-mediated Aβ aggregation and Aβ production. In vitro experiments revealed that PCu directly inhibited Cu2+-mediated Aβ aggregation and regulated copper levels to reduce biological toxicity. Furthermore, PCu reduced the production of Aβ by inhibiting Cu2+-induced BACE1 expression and improving Cu(II)-mediated cell oxidative damage. Cell culture experiments further demonstrated that PCu had relatively low toxicity. This Cu(II)-binding peptide that we have identified using phage display technology provides a potential therapeutic approach to prevent or treat AD.
Plant–Microbiome Crosstalk: Dawning from Composition and Assembly of Microbial Community to Improvement of Disease Resilience in Plants
Authors: Noman Muhammad , Ahmed Temoor , Ijaz Usman , Shahid Muhammad , Azizullah  , Li Dayong , Manzoor Irfan , Song Fengming
Published: June 2021

Plants host diverse but taxonomically structured communities of microorganisms, called microbiome, which colonize various parts of host plants. Plant-associated microbial communities have been shown to confer multiple beneficial advantages to their host plants, such as nutrient acquisition, growth promotion, pathogen resistance, and environmental stress tolerance. Systematic studies have provided new insights into the economically and ecologically important microbial communities as hubs of core microbiota and revealed their beneficial impacts on the host plants. Microbiome engineering, which can improve the functional capabilities of native microbial species under challenging agricultural ambiance, is an emerging biotechnological strategy to improve crop yield and resilience against variety of environmental constraints of both biotic and abiotic nature. This review highlights the importance of indigenous microbial communities in improving plant health under pathogen-induced stress. Moreover, the potential solutions leading towards commercialization of proficient bioformulations for sustainable and improved crop production are also described.
The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities
Authors: Bruno Samantha , Mancini Manuela , De Santis Sara , Monaldi Cecilia , Cavo Michele , Soverini Simona
Published: June 2021

Acute myeloid leukemia (AML) is a hematologic malignancy caused by a wide range of alterations responsible for a high grade of heterogeneity among patients. Several studies have demonstrated that the hypoxic bone marrow microenvironment (BMM) plays a crucial role in AML pathogenesis and therapy response. This review article summarizes the current literature regarding the effects of the dynamic crosstalk between leukemic stem cells (LSCs) and hypoxic BMM. The interaction between LSCs and hypoxic BMM regulates fundamental cell fate decisions, including survival, self-renewal, and proliferation capacity as a consequence of genetic, transcriptional, and metabolic adaptation of LSCs mediated by hypoxia-inducible factors (HIFs). HIF-1α and some of their targets have been associated with poor prognosis in AML. It has been demonstrated that the hypoxic BMM creates a protective niche that mediates resistance to therapy. Therefore, we also highlight how hypoxia hallmarks might be targeted in the future to hit the leukemic population to improve AML patient outcomes.
Sub-3 Å Cryo-EM Structures of Necrosis Virus Particles via the Use of Multipurpose TEM with Electron Counting Camera
Authors: Wang Chun-Hsiung , Chen Dong-Hua , Huang Shih-Hsin , Wu Yi-Min , Chen Yi-Yun , Hwu Yeukuang , Bushnell David , Kornberg Roger , Chang Wei-Hau
Published: June 2021

During this global pandemic, cryo-EM has made a great impact on the structure determination of COVID-19 proteins. However, nearly all high-resolution results are based on data acquired on state-of-the-art microscopes where their availability is restricted to a number of centers across the globe with the studies on infectious viruses being further regulated or forbidden. One potential remedy is to employ multipurpose microscopes. Here, we investigated the capability of 200 kV multipurpose microscopes equipped with a direct electron camera in determining the structures of infectious particles. We used 30 nm particles of the grouper nerve necrosis virus as a test sample and obtained the cryo-EM structure with a resolution as high as ∼2.7 Å from a setting that used electron counting. For comparison, we tested a high-end cryo-EM (Talos Arctica) using a similar virus (Macrobrachium rosenbergii nodavirus) to obtain virtually the same resolution. Those results revealed that the resolution is ultimately limited by the depth of field. Our work updates the density maps of these viruses at the sub-3Å level to allow for building accurate atomic models from de novo to provide structural insights into the assembly of the capsids. Importantly, this study demonstrated that multipurpose TEMs are capable of the high-resolution cryo-EM structure determination of infectious particles and is thus germane to the research on pandemics.
A Client/Server Malware Detection Model Based on Machine Learning for Android Devices
Authors: Fournier Arthur , El Khoury Franjieh , Pierre Samuel
Published: June 2021

The rapid adoption of Android devices comes with the growing prevalence of mobile malware, which leads to serious threats to mobile phone security and attacks private information on mobile devices. In this paper, we designed and implemented a model for malware detection on Android devices to protect private and financial information, for the mobile applications of the ATISCOM project. This model is based on client/server architecture, to reduce the heavy computations on a mobile device by sending data from the mobile device to the server for remote processing (i.e., offloading) of the predictions. We then gradually optimized our proposed model for better classification of the newly installed applications on Android devices. We at first adopted Naive Bayes to build the model with 92.4486% accuracy, then the classification method that gave the best accuracy of 93.85% for stochastic gradient descent (SGD) with binary class (i.e., malware and benign), and finally the regression method with numerical values ranging from −100 to 100 to manage the uncertainty predictions. Therefore, our proposed model with random forest regression gives a good accuracy in terms of performance, with a good correlation coefficient, minimum computation time and the smallest number of errors for malware detection.
Diagonal Earlobe Crease (Frank’s Sign) for Diagnosis of Coronary Artery Disease: A Systematic Review of Diagnostic Test Accuracy Studies
Authors: Więckowski Krzysztof , Gallina Tomasz , Surdacki Andrzej , Chyrchel Bernadeta
Published: June 2021

Coronary artery disease is a global challenge for healthcare systems. Early diagnosis is a key issue to improve quality of life and reduce morbidity and mortality. Diagonal earlobe crease, a wrinkle extending obliquely across the earlobe, was linked by many authors to various atherosclerotic diseases. This systematic review aimed at summarizing the diagnostic accuracy of diagonal earlobe crease for diagnosis of chronic and acute coronary syndromes in adults. Cochrane’s recommendations for systematic reviews of diagnostic test accuracy studies were followed. The protocol was registered on PROSPERO. Seven electronic databases were searched up to April 2021. The risk of bias and applicability were assessed using the QUADAS-2 tool. Meta-analysis was not performed. Finally, 13 cross-sectional studies evaluating 3951 patients were analyzed, all of which focused on chronic coronary syndromes defined as anatomically significant coronary stenosis. Invasive coronary angiography was used as a reference in most studies, except one which utilized computed tomography angiography. Sensitivity ranged from 26% to 90%, and specificity from 32% to 96%. Positive likelihood ratios varied from 1.11 to 7.03, but most results were below 2. Negative likelihood ratios were from 0.84 to 0.30, but most values exceeded 0.5. Diagnostic accuracy of diagonal earlobe crease for the detection of chronic coronary syndromes is insufficient. It only slightly changes pre-test probability, and its mere presence or absence should not affect the clinical management of the patients. However, for its feasibility and easy interpretation, Frank’s sign could be considered as a part of physical examination.
Global Mapping of Seaport Operability Risk Indicators Using Open-Source Metocean Data
Authors: Wiegel Matijs , de Boer Wiebe , van Koningsveld Mark , van der Hout Arne , Reniers Ad
Published: June 2021

Seaport operability is key to the economic viability of ports. Metocean conditions (e.g., wind, short waves, and infragravity waves) affect this operability when certain thresholds are exceeded. This paper describes a method for the global mapping of seaport operability risk indicators using open-source metocean data. This global-scale assessment provides a geographic overview of operability risks and first-order insights into the most relevant metocean risk indicators at each location. The results show that locations around the equator and inland seas have lower operability risk than locations farther away from the equator. “Hotspots” are mainly located along the southern capes (Cape of Good Hope, Leeuwin, Horn), around the ‘Roaring Forties’, and at exposed locations along the oceans. Of the metocean parameters considered, short waves are found to be the most critical risk indicator for port operability at most locations. Using (the insights of) this study, port authorities, operators, and designers can prepare for metocean risks at an early stage and effectively respond with mitigation measures and layout adjustments to improve port operability.
Elevation Calculation of Bottom Deck Based on Stochastic Process and Compound Distribution
Authors: Liu Guilin , Nie Chi , Kou Yi , Yang Yi , Zhao Daniel , Wu Fang , Yu Pubing
Published: June 2021

In the design of offshore platforms, the height of the bottom deck directly affects the safety and engineering cost of the entire platform. It is a very important scale parameter in platform planning. The American Petroleum Institute (API) specification shows that the key to determining the height of the bottom deck lies in the wave height and calculation of the return level of the water increase. Based on the perspective of stochastic processes, this paper constructs a new distribution function model for joint parameter estimation of the marine environment. The new model uses a family of random variables to show the statistical characteristics of design wave height and water increase in both time and space, with extreme value expanded EED-I type distribution used as marginal distribution. The new model performs statistical analysis on the measured hydrological data of the Naozhou Station during the flood period from 1990 to 2016. The Gumbel–Copula structure function is used as the connection function, and the compound distribution model of the wave height and the water increase is used to obtain the joint return level of the wave height and the water increase and through which the bottom deck height of the area is calculated. The results show that the stochastic compound distribution improves the issue of the high design value caused by simple superposition of univariate return levels. The EED-I type distribution still has good stability under the condition of less measured data. Thus, under the premise of ensuring the safety of the offshore platform, less measured data can still be used to calculate the height of the bottom deck more accurately.
Evaluation of a Meta-Analysis of Ambient Air Quality as a Risk Factor for Asthma Exacerbation
Authors: Kindzierski Warren , Young Stanley , Meyer Terry , Dunn John
Published: June 2021

Background: An irreproducibility crisis currently afflicts a wide range of scientific disciplines, including public health and biomedical science. A study was undertaken to assess the reliability of a meta-analysis examining whether air quality components (carbon monoxide, particulate matter 10 µm and 2.5 µm (PM10 and PM2.5), sulfur dioxide, nitrogen dioxide and ozone) are risk factors for asthma exacerbation. Methods: The number of statistical tests and models were counted in 17 randomly selected base papers from 87 used in the meta-analysis. Confidence intervals from all 87 base papers were converted to p-values. p-value plots for each air component were constructed to evaluate the effect heterogeneity of the p-values. Results: The number of statistical tests possible in the 17 selected base papers was large, median = 15,360 (interquartile range = 1536–40,960), in comparison to results presented. Each p-value plot showed a two-component mixture with small p-values < 0.001 while other p-values appeared random (p-values > 0.05). Given potentially large numbers of statistical tests conducted in the 17 selected base papers, p-hacking cannot be ruled out as explanations for small p-values. Conclusions: Our interpretation of the meta-analysis is that random p-values indicating null associations are more plausible and the meta-analysis is unlikely to replicate in the absence of bias.