bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Concepts in Systemic Sclerosis Pathogenesis: Role for miRNAs
Authors: Szabo Iulia , Muntean Laura , Crisan Tania , Rednic Voicu , Sirbe Claudia , Rednic Simona
Published: October 2021

Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without interfering with the DNA sequence. Epigenetic marks may be reversible and their differential response to external stimuli could explain the protean clinical manifestations of SSc while offering the opportunity of targeted drug development. Small, non-coding RNA sequences (miRNAs) have demonstrated complex interactions between vasculature, immune activation, and extracellular matrices. Distinct miRNA profiles were identified in SSc skin specimens and blood samples containing a wide variety of dysregulated miRNAs. Their target genes are mainly involved in profibrotic pathways, but new lines of evidence also confirm their participation in impaired angiogenesis and aberrant immune responses. Research approaches focusing on earlier stages of the disease and on differential miRNA expression in various tissues could bring novel insights into SSc pathogenesis and validate the clinical utility of miRNAs as biomarkers and therapeutic targets.
Biomechanical and Physiological Evaluation of a Multi-Joint Exoskeleton with Active-Passive Assistance for Walking
Authors: Cao Wujing , Zhang Zhewen , Chen Chunjie , He Yong , Wang Dashuai , Wu Xinyu
Published: October 2021

How to improve the walking efficiency while ensuring the wearability is an important issue of lower limb exoskeletons. Active devices can provide greater forces, while the passive devices have advantage in weight. We presented a multi-joint exoskeleton with active hip extension assistance and passive ankle plantarflexion assistance in this work. An admittance controller based on a feedforward model was proposed to track the desired active force of the hip extension. An underfoot clutch mechanism was adapted to realize the passive ankle plantarflexion assistance. To assess the efficacy of the multi-joint exoskeleton in assisting walking, we conducted comprehensive experiments to evaluate the force tracking performance, lower limb muscle activities and metabolic cost. The results demonstrated that: (i) The average tracking error of the peak hip extension assistance force from three subjects was less than 3%. (ii) The reductions of normalized root-mean-square EMG in the lateral soleus, medial soleus and gluteus maximus of eight subjects achieved 15.33%, 11.11%, and 3.74%, respectively. (iii) The average metabolic cost of six subjects was reduced by 10.41% under exoskeleton on (EO) condition comparing to the condition of walking with no exoskeleton (NE). This work proved that the concept of the multi-joint exoskeleton with active-passive assistance can improve the walking efficiency.
Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC)
Authors: Sardarabadi Parvaneh , Kojabad Amir Asri , Jafari Davod , Liu Cheng-Hsien
Published: October 2021

Globally, non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths. Despite advancements in chemotherapy and targeted therapies, the 5-year survival rate has remained at 16% for the past forty years. Minimal residual disease (MRD) is described as the existence of either isolated tumour cells or circulating tumour cells in biological liquid of patients after removal of the primary tumour without any clinical signs of cancer. Recently, liquid biopsy has been promising as a non-invasive method of disease monitoring and treatment guidelines as an MRD marker. Liquid biopsy could be used to detect and assess earlier stages of NSCLC, post-treatment MRD, resistance to targeted therapies, immune checkpoint inhibitors (ICIs) and tumour mutational burden. MRD surveillance has been proposed as a potential marker for lung cancer relapse. Principally, biosensors provide the quantitative analysis of various materials by converting biological functions into quantifiable signals. Biosensors are usually operated to detect antibodies, enzymes, DNA, RNA, extracellular vesicles (EVs) and whole cells. Here, we present a category of biosensors based on the signal transduction method for identifying biosensor-based biomarkers in liquid biopsy specimens to monitor lung cancer treatment.
Management of Cancer-Related Cognitive Impairment: A Systematic Review of Computerized Cognitive Stimulation and Computerized Physical Activity
Authors: Binarelli Giulia , Joly Florence , Tron Laure , Lefevre Arbogast Sophie , Lange Marie
Published: October 2021

Cancer-related cognitive impairment (CRCI) occurs frequently in patients living with cancer, with consequences on quality of life. Recently, research on the management of these difficulties has focused on computerized cognitive stimulation and computerized physical activity programs. This systematic review presents the state of knowledge about interventions based on computerized-cognitive stimulation and/or physical activity to reduce CRCI. The review followed the PRISMA guidelines. A search was conducted in PUBMED and Web of Science databases. Risk of bias analysis was conducted using the Rob2 tool and the quality of evidence was conducted following the GRADE approach. A total of 3776 articles were initially identified and 20 of them met the inclusion criteria. Among them, sixteen investigated computerized-cognitive stimulation and four computerized-physical activity. Most of the studies were randomized controlled trials and assessed the efficacy of a home-based intervention on objective cognition in adults with cancer. Overall, cognitive improvement was found in 11/16 computerized-cognitive stimulation studies and 2/4 computerized-physical activity studies. Cognitive stimulation or physical activity improved especially cognitive complaints, memory, and attention. These results suggest the efficacy of both computerized-cognitive stimulation and physical activity. However, we report a high risk of bias for the majority of studies and a low level of quality of evidence. Therefore, further investigations are needed to confirm the efficacy of these interventions and to investigate the possible added benefit on cognition of a combined computerized-cognitive/physical intervention.
Recent Progress in the Neoadjuvant Treatment Strategy for Locally Advanced Esophageal Cancer
Authors: Hou Sicong , Pan Ziyin , Hao Xin , Hang Qinglei , Ding Yanbing
Published: October 2021

Neoadjuvant therapies, primarily chemotherapy and chemoradiotherapy, are able to improve the overall survival (OS) in patients with locally advanced resectable esophageal cancer (EC) based on the results of several randomized clinical trials. The advantage of neoadjuvant therapy is chiefly attributed to the decreased risk of local–regional recurrence and distant metastasis. Thus, it has been recommended as standard treatment for patients with resectable EC. However, several fundamental problems remain. First, the combination of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), and surgery for EC patients with different histological types remain controversial. Furthermore, to reduce the toxicity of preoperative chemotherapy and the risk of complications caused by preoperative radiation therapy, the treatment protocols of nCT and nCRT still need to be investigated and optimized by prospective trials. Moreover, for patients with complete clinical response following neoadjuvant therapy, it is worth ascertaining whether a “watch and wait” surveillance plus surgery-as-needed policy is more favorable, as well as, in addition to preoperative chemoradiotherapy, whether immunotherapy, especially when combined with the traditional neoadjuvant therapy regimens, brings new prospects for EC treatment. In this review, we summarize the recent insights into the research progress and existing problems of neoadjuvant therapy for locally advanced resectable EC.
Development of a MicroRNA Signature Predictive of Recurrence and Survival in Pancreatic Ductal Adenocarcinoma
Authors: Sebastian Nikhil T. , Webb Amy , Merrell Kenneth W. , Koay Eugene J. , Wolfe Adam R. , Zhang Lizhi , Wilhite Tyler J. , Elganainy Dalia , Robb Ryan , Chen Wei , Cloyd Jordan , Dillhoff Mary , Tsung Allan , Abushahin Laith , Noonan Anne , Williams Terence M.
Published: October 2021

Background: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. Methods: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three institutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoString, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training cohort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). Results: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34; 95%CI 1.27–11.38; p = 0.017) and OS (HR = 2.89; 95%CI 1.10–4.76; p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39; 95%CI 1.03–5.54; p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71; 95%CI 1.14–6.48; p = 0.025), DR (HR = 1.93; 95%CI 1.10–3.38; p = 0.022), and OS (HR = 1.97; 95%CI 1.17–3.34; p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p < 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. Conclusions: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.
Fractal and Multifractal Analysis of PET-CT Images for Therapy Assessment of Metastatic Melanoma Patients under PD-1 Inhibitors: A Feasibility Study
Authors: Kosmou Anastasia , Sachpekidis Christos , Pan Leyun , Matsopoulos George K. , Hassel Jessica C. , Dimitrakopoulou-Strauss Antonia , Provata Astero
Published: October 2021

Longitudinal whole-body PET-CT scans with F-18-fluorodeoxyglucose (18F-FDG) in patients suffering from metastatic melanoma were analyzed and the tracer distribution in patients was compared with that of healthy controls. Nineteen patients with metastatic melanoma were scanned before, after two and after four cycles of treatment with PD-1 inhibitors (pembrolizumab, nivolumab) applied as monotherapy or as combination treatment with ipilimumab. For comparison eight healthy controls were analyzed. As quantitative measures for the comparison between controls and patients, the nonlinear fractal dimension (FD) and multifractal spectrum (MFS) were calculated from the digitized PET-CT scans. The FD and MFS measures, which capture the dispersion of the tracer in the body, decreased with disease progression, since the tracer particles tended to accumulate around metastatic sites in patients, while the measures increased when the patients’ clinical condition ameliorate. The MFS measure gave better predictions and were consistent with the PET Response Evaluation Criteria for Immunotherapy (PERCIMT) in 81% of the cases, while FD agreed in 77% of all cases. These results agree, qualitatively, with a previous study of our group when treatment with ipilimumab monotherapy was considered.
The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead
Authors: Nelson Adam , Lukacs Jordan D. , Johnston Brent
Published: October 2021

NKT cells are a specialized subset of lipid-reactive T lymphocytes that play direct and indirect roles in immunosurveillance and anti-tumor immunity. Preclinical studies have shown that NKT cell activation via delivery of exogenous glycolipids elicits a significant anti-tumor immune response. Furthermore, infiltration of NKT cells is associated with a good prognosis in several cancers. In this review, we aim to summarize the role of NKT cells in cancer as well as the current strategies and status of NKT cell immunotherapy. This review also examines challenges and future directions for improving the therapy.
Photocatalytic Degradation of Tetracycline in Aqueous Solution Using Copper Sulfide Nanoparticles
Authors: Ravele Murendeni P. , Oyewo Opeyemi A. , Ramaila Sam , Mavuru Lydia , Onwudiwe Damian C.
Published: October 2021

In this paper, spherical-shaped pure phase djurleite (Cu31S16) and roxbyite (Cu7S4) nanoparticles were prepared by a solvothermal decomposition of copper(II) dithiocarbamate complex in dodecanthiol (DDT). The reaction temperature was used to control the phases of the samples, which were represented as Cu31S16 (120 °C), Cu31S16 (150 °C), Cu7S4 (220 °C), and Cu7S4 (250 °C) and were characterized by using X-ray diffraction (XRD), scanning and transmission electron microscopy (SEM and TEM), and absorption spectroscopy. The samples were used as photocatalysts for the degradation of tetracycline (TC) under visible light irradiation. The results of the study showed that Cu7S4 (250 °C) exhibited the best activity in the reaction system with the TC degradation rate of up to 99% within 120 min of light exposure, while the Cu31S16 (120 °C) system was only 46.5% at the same reaction condition. In general, roxbyite Cu7S4 (250 °C) could be considered as a potential catalyst for the degradation of TC in solution.
Screening of Acetyl Donors and the Robust Enzymatic Synthesis of Acetyl-CoA by 10-Deacetylbaccatin III-10-β-O-acetyltransferase
Authors: Zhang Bo-Yong , Wang Hao , Gong Ting , Chen Tian-Jiao , Chen Jing-Jing , Yang Jin-Ling , Zhu Ping
Published: October 2021

Acetyl-CoA is the precursor of many bio-manufacturing products and is also the hub of the cellular metabolism of energy and substances. However, acetyl-CoA is not a bulk commodity and its application is hindered due to its high cost and low yield. In this study, we screened acetyl donor candidates and utilized 10-deacetylbaccatin III-10-β-O-acetyltransferase (DBAT) in the synthesis of acetyl-CoA with CoASH as the acetyl acceptor. Among the tested candidates, acetylsalicylic acid methyl ester was identified to be the best acetyl donor, followed by acetyl-trans-resveratrol, acetylsalicylic acid ethyl ester, acetylsalicylsalicylic acid, and 4-acetoxyacetanilide. The enzymatic reaction conditions were optimized and the maximum yield of acetyl-CoA reached 14.82 mg/mL, which is the highest yield among all reported approaches to date. Meanwhile, 4.22 mg/mL of the by-product salicylic acid methyl ester, which is another industrial material, was produced. Additionally, a preliminary purification process for acetyl-CoA was established, in which 40 mg acetyl-CoA (HPLC purity > 98%) was acquired from the finished 20 mL reaction system (feeding 46 mg CoASH and 34 mg ASME) with a recovery rate of 86%. Our study lays the foundation for the large-scale production of acetyl-CoA by an enzymatic approach and will promote its application in different fields.
Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides
Authors: Ryu Hyang-Joo , Kim Sun-Il , Jang Hyung-Ook , Kim Se-Hoon , Oh Sang-Ho , Park Sujin , Kim Sang-Kyum
Published: October 2021

The International Society for Cutaneous Lymphoma (ISCL) proposes a diagnostic algorithm for early mycosis fungoides (MF) that includes clinical, histological, immunophenotypical, and molecular criteria. Here, we analyzed the immunologic markers and features of T-cell clonality in 38 early MF cases and 22 non-MF cases to validate the ISCL algorithm. We found that CD5 and CD7 expression differed significantly between early MF and non-MF cases, with epidermal discordance of CD7 expression more frequently identified in early MF. Notably, increasing the cut-off value for CD7 expression from 10% to 22.5% improved its sensitivity. Furthermore, TCR-γ and β chain rearrangements were more frequently detected in early MF than in non-MF cases. Based on these findings, we propose CD5 and CD7 deficiency as mandatory immunopathologic criteria and PCR-based testing for TCR-γ and β chains as required molecular/biologic criteria to improve the efficiency of early MF diagnosis using the ISCL algorithm.
The Role of Epithelial Damage in the Pulmonary Immune Response
Authors: Burgoyne Rachel Ann , Fisher Andrew John , Borthwick Lee Anthony
Published: October 2021

Pulmonary epithelial cells are widely considered to be the first line of defence in the lung and are responsible for coordinating the innate immune response to injury and subsequent repair. Consequently, epithelial cells communicate with multiple cell types including immune cells and fibroblasts to promote acute inflammation and normal wound healing in response to damage. However, aberrant epithelial cell death and damage are hallmarks of pulmonary disease, with necrotic cell death and cellular senescence contributing to disease pathogenesis in numerous respiratory diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and coronavirus disease (COVID)-19. In this review, we summarise the literature that demonstrates that epithelial damage plays a pivotal role in the dysregulation of the immune response leading to tissue destruction and abnormal remodelling in several chronic diseases. Specifically, we highlight the role of epithelial-derived damage-associated molecular patterns (DAMPs) and senescence in shaping the immune response and assess their contribution to inflammatory and fibrotic signalling pathways in the lung.
Sildenafil-Mediated Neuroprotection from Adult to Neonatal Brain Injury: Evidence, Mechanisms, and Future Translation
Authors: Zinni Manuela , Pansiot Julien , Léger Pierre-Louis , El Kamouh Marina , Baud Olivier
Published: October 2021

Cerebral stroke, traumatic brain injury, and hypoxic ischemic encephalopathy are among the most frequently occurring brain injuries. A complex pathogenesis, characterized by a synergistic interaction between alterations of the cerebrovascular system, cell death, and inflammation, is at the basis of the brain damage that leads to behavioral and neurodevelopmental disabilities in affected subjects. Sildenafil is a selective inhibitor of the enzyme phosphodiesterase 5 (PDE5) that is able to cross the blood–brain barrier. Preclinical data suggest that sildenafil may be a good candidate for the prevention or repair of brain injury in both adults and neonates. The aim of this review is to summarize the evidence supporting the neuroprotective action of sildenafil and discuss the possible benefits of the association of sildenafil with current therapeutic strategies.
Timing and Composition of Last Meal before Bedtime Affect Sleep Parameters of Night Workers
Authors: Nogueira Luciana F. R. , Pellegrino Pollyanna , Cipolla-Neto José , Moreno Claudia R. C. , Marqueze Elaine C.
Published: October 2021

Night workers tend to eat irregularly, both in terms of meal times and composition. The disruption in energy metabolism caused by inappropriate eating habits can negatively affect the sleep quality of these individuals. The objectives of this study were to determine the interval between the last meal and bedtime and its relationship with both diurnal and nocturnal sleep parameters, as well as to evaluate the association of the adequacy of this meal with sleep parameters. The analyses were carried out for a usual sleep routine on a workday and a day off. This cross-sectional study was part of a controlled, randomized, double-blind, crossover clinical trial. The sample comprised 30 female nursing professionals who worked permanent night shifts of 12 × 36 h. Timing and composition of the last meal were obtained from food diaries, and sleep parameters were collected via actigraphy. On multiple linear regression analysis, every hour decrease in the interval between the last meal and sleep onset there was an increase of 0.39 h on diurnal sleep duration. Regarding food intake, every 1 g of fat and 1 g of carbohydrate consumed was associated with an increase in diurnal sleep onset latency of 0.13 h and 0.02 h, respectively. These findings suggest that both timing and composition of the last meal before bedtime may be potential key factors for good diurnal and nocturnal sleep among night-shift workers.
Formation of Aligned α-Si3N4 Microfibers by Plasma Nitridation of Si (110) Substrate Coated with SiO2
Authors: Yu Chang-Hua , Chiu Kun-An , Do Thi-Hien , Chang Li , Chen Wei-Chun
Published: October 2021

Plasma nitridation of an amorphous SiO2 layer on Si (110) substrate can form well-aligned α-Si3N4 crystallites in fibrous morphology. Nitriding is performed at a temperature in the range of 800–1000 °C by using microwave plasma with a gas mixture of N2 and H2. Raman spectroscopy shows the characteristics of an α-Si3N4 phase without other crystalline nitrides. As shown by scanning electron microscopy, the formed α-Si3N4 microfibers on the Si substrate can be in a dense and straight array nearly along with Si <11¯0>, and can have a length over 2 mm with a diameter in the range of 5–10 μm. Structural characterization of scanning transmission electron microscopy in cross section view reveals that the elongated α-Si3N4 crystallites are formed on the surface of the nitrided SiO2/Si (110) substrate without any interlayers between Si3N4 and Si, and the longitudinal direction of α-Si3N4 appears mainly along <112¯0>, which is approximately parallel to Si <11¯0>.
Dataset on a Small-Scale Film-Coating Process Developed for Self-Expanding 4D Printed Drug Delivery Devices
Authors: Uboldi Marco , Melocchi Alice , Moutaharrik Saliha , Cerea Matteo , Gazzaniga Andrea , Zema Lucia
Published: October 2021

Film-coating is widely applied in pharmaceutics to enhance aspect/taste and mechanical properties of dosage forms, to protect them from the environment and to modify their release performance. In this respect, a film-coating process was recently involved in the development of 4D printed prolonged-release systems intended for organ retention. During coating processes, liquid formulations are sprayed onto moving cores, whose shape, weight and surface characteristics are essential to attain a homogeneous film. Devices of complex shapes, composed of smart materials and fabricated by hot-processing techniques, such as extrusion and fused deposition modeling 3D printing, might be poorly compatible with the requirements of traditional coating methods, e.g., need for spherical substrates with smooth surface and stable under process temperatures. This work was aimed at evaluating, at a small scale level, the feasibility of a versatile equipment for film-coating of rod-shaped extruded and printed prototypes with different section. Equipment design and set up of process parameters were performed starting from polymeric solutions and suspensions and selecting as cores 50 mm-long rod-shaped samples based on shape memory poly(vinyl alcohol). Integrity and thickness of the applied layer and its impact on shape memory and release performance of prototypes were investigated.
IoT Serverless Computing at the Edge: A Systematic Mapping Review
Authors: Kjorveziroski Vojdan , Filiposka Sonja , Trajkovik Vladimir
Published: October 2021

Serverless computing is a new concept allowing developers to focus on the core functionality of their code, while abstracting away the underlying infrastructure. Even though there are existing commercial serverless cloud providers and open-source solutions, dealing with the explosive growth of new Internet of Things (IoT) devices requires more efficient bandwidth utilization, reduced latency, and data preprocessing closer to the source, thus reducing the overall data volume and meeting privacy regulations. Moving serverless computing to the edge of the network is a topic that is actively being researched with the aim of solving these issues. This study presents a systematic mapping review of current progress made to this effect, analyzing work published between 1 January 2015 and 1 September 2021. Using a document selection methodology which emphasizes the quality of the papers obtained through querying several popular databases with relevant search terms, we have included 64 entries, which we then further categorized into eight main categories. Results show that there is an increasing interest in this area with rapid progress being made to solve the remaining open issues, which have also been summarized in this paper. Special attention is paid to open-source efforts, as well as open-access contributions.
A Methodology for Generating Systems Architectural Glimpse Statements Using the 5W1H Maxim
Authors: Voutyras Orfefs , Bokhari Aamir H. , Tsuge Akira , Palaiokrassas Georgios , Kawasaki Takafumi , Cases-Camats Xavier , Nakazawa Jin , Litke Antonios , Okoshi Tadashi , Varvarigou Theodora
Published: October 2021

Attempts to facilitate and streamline systems architecting have resulted in a great number of reusable principles, practices, mechanisms, frameworks, and tools. Such a practice is the use of architectural viewpoints and views. However, as systems change, these practices should also evolve. The increasing scale and complexity of systems resulting from an ever-growing pool of human needs and breakthroughs may lead, in some cases, to an increased gap between the abstraction activities attempting to capture the whole of a system, and the instantiation activities that produce concrete and detailed descriptions of a system’s architecture. To address this issue, this article introduces a new notion, that of architectural glimpse statements, fundamental questions acting as the building blocks for architectural views and products. This notion can help architects ask the right questions in the right manner to create fundamental statements, the elaboration on which can lead directly to concrete architectural products. Working on top of standardized and common approaches, the article introduces a language for the creation of architectural glimpse statements using the 5W1H maxim. Based on this language, a tool and guidelines are also provided to facilitate the usage of glimpses. Finally, the overall methodology is demonstrated in two case studies.
Performance Improvement of Amorphous Ga2O3/P-Si Deep Ultraviolet Photodetector by Oxygen Plasma Treatment
Authors: Cao Jin , Chen Liang , Chen Xin , Zhu Yu , Dong Jianqi , Wang Baoyu , He Miao , Wang Xingfu
Published: October 2021

Gallium oxide (Ga2O3) is an attractive semiconductor that is very suitable for deep ultraviolet (DUV) inspection. However, due to the existence of many types of oxygen vacancies in the amorphous Ga2O3 (a-Ga2O3) film, it greatly limits the performance of the a-Ga2O3-based photodetector. Here, we perform oxygen plasma treatment on the a-Ga2O3/p-Si photodetector to reduce the concentration of oxygen vacancies in the a-Ga2O3 film, so that the dark current is reduced by an order of magnitude (from 1.01 × 10−3 A to 1.04 × 10−4 A), and the responsivity is increased from 3.7 mA/W to 9.97 mA/W. In addition, oxygen plasma processing makes the photodetector operate well at 0 V bias. The response speed is that the rise time is 2.45 ms and the decay time is 1.83 ms, while it does not respond to the DUV illumination without oxygen plasma treating at a zero bias. These results are attributed to the fact that oxygen plasma treatment can reduce the Schottky barrier between a-Ga2O3 and the electrode indium tin oxide (ITO), which promotes the separation and collection efficiency of photo-generated carriers. Therefore, this work proposes a low-cost method to improve the performance of Ga2O3 film-based DUV photodetectors.
Recent Invaders in Small Mediterranean Islands: Wild Boars Impact Snakes in Port-Cros National Park
Authors: Ballouard Jean-Marie , Kauffman Cécile , Besnard Aurélien , Ausanneau Mathieu , Amiguet Manon , Billy Gopal , Caron Sébastien , Fosseries Guillaume , Ferrari Thomas , Mariani Vincent , Garnier Gilles , Maxime Laurent , Dorr Francis , Geoffroy David , Bonnet Xavier
Published: October 2021

Mediterranean islands host unique ecosystems that are particularly vulnerable to invasive species. However, knowledge regarding the precise impact of invasive species on local biodiversity remains limited for many of these systems. Here we report on the negative impacts of invasive wild boars (Sus scrofa) on native snakes on islands in the Mediterranean basin. Capture-mark-recapture was initiated in 2012 on two snake species (Montpellier snake, Malpolon monspessulanus and Ladder snake, Zamenis scalaris) across two islands of Port-Cros National Park. Several wild boars, an invasive species, reached the islands in 2007. They remained confined to small areas of the islands for several years. In Port-Cros, the numbers of wild boars suddenly increased in 2015, and rapidly colonized the whole island damaging vast land surfaces. In Porquerolles, wild boars did not proliferate. This offered an opportunity to examine the impact of wild boar outbreak with a Before-After Control-Impact design (BACI). Snake counts and mark-recapture modeling showed that demographic traits were stable before 2016 for both snake species on both islands. As well as abundance, recruitment, and population growth rate of Montpellier snakes significantly declined where wild boars proliferated but remained constant on the island where they did not. Wild boars probably impacted snake numbers through habitat destruction and direct killing. The rapid decline of snakes (apex predators) and intensive uprooting that strongly damage ground dwelling species (plants, animals) suggest that wild boars represent a serious threat to island biodiversity. As elsewhere around the world, these invasive ungulates proliferate in the Mediterranean basin, they are proficient swimmers and exhibit a remarkably high invasive potential. We recommend vigilance and fast eradication to prevent population outburst; even a few a localized non-proliferating individuals contain the latent potential for devastating outbreaks.
ALADA Dose Optimization in the Computed Tomography of the Temporal Bone: The Diagnostic Potential of Different Low-Dose CT Protocols
Authors: Kofler Barbara , Jenetten Laura , Runge Annette , Degenhart Gerald , Fischer Natalie , Hörmann Romed , Steurer Michael , Widmann Gerlig
Published: October 2021

Objective: Repeated computed tomography (CT) is essential for diagnosis, surgical planning and follow-up in patients with middle and inner ear pathology. Dose reduction to “as low as diagnostically acceptable” (ALADA) is preferable but challenging. We aimed to compare the diagnostic quality of images of subtle temporal bone structures produced with low doses (LD) and reference protocols (RP). Methods: Two formalin-fixed human cadaver heads were scanned using a 64-slice CT scanner and cone-beam CT (CBCT). The protocols were: RP (120 kV, 250 mA, CTDIvol 83.72 mGy), LD1 (100 kV, 80 mA, CTDIvol 26.79 mGy), LD2 (100 kV, 35 mA, CTDIvol 7.66 mGy), LD3 (80 kV, 40 mA, CTDIvol 4.82 mGy), and CBCT standard protocol. Temporal bone structures were assessed using a 5-point scale. Results: A median score of ≥2 was achieved with protocols such as the tendons of m. tensor tympani (RP/LD1/LD2/CBCT) and m. stapedius (CBCT), the incudostapedial joint (RP/LD1/CBCT), the incudomalleolar joint (RP/LD1/LD2/CBCT), the stapes feet (RP/LD1/CBCT), the stapes head (RP/LD1/LD2/CBCT), the tympanic membrane (RP/LD1/LD2/CBCT), the lamina spiralis ossea (none), the chorda tympani (RP/LD1/CBCT), and the modiolus (RP/LD1/LD2/CBCT). Adaptive statistical iterative reconstructions did not show advantages over the filtered back projection. Conclusions: LD protocols using a CTDIvol of 7.66 mGy may be sufficient for the identification of temporal bone structures.
Epidemiological, Physiological and Diagnostic Comparison of Plasmodium ovale curtisi and Plasmodium ovale wallikeri
Authors: Hawadak Joseph , Dongang Nana Rodrigue Roman , Singh Vineeta
Published: October 2021

Nowadays, Plasmodium ovale is divided into two non-recombinant sympatric species: Plasmodium ovale wallikeri and Plasmodium ovale curtisi. In this mini review, we summarize the available knowledge on the clinical/biological aspects of P. ovale spp. malaria and current techniques for the diagnosis/characterisation of P. ovale curtisi and P. ovale wallikeri. P. ovale wallikeri infections are characterized by a deeper thrombocytopenia and shorter latency compared to P. ovale curtisi infections, indicating that P. ovale wallikeri is more pathogenic than P. ovale curtisi. Rapid diagnosis for effective management is difficult for P. ovale spp., since specific rapid diagnostic tests are not available and microscopic diagnosis, which is recognized as the gold standard, requires expert microscopists to differentiate P. ovale spp. from other Plasmodium species. Neglect in addressing these issues in the prevalence of P. ovale spp. represents the existing gap in the fight against malaria.
Is It Possible to Establish a Reliable Correlation between Maximum Standardized Uptake Value of 18-Fluorine Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and Histological Types of Non-Small Cell Lung Cancer? Analysis of the Italian VATS Group Database
Authors: Divisi Duilio , Rinaldi Marta , Necozione Stefano , Curcio Carlo , Rea Federico , Zaraca Francesco , De Vico Andrea , Zaccagna Gino , Di Leonardo Gabriella , Crisci Roberto ,   on behalf of the Italian VATS Group
Published: October 2021

Background. Although positron emission tomography/computed tomography, often integrated with 2-deoxy-2-[fluorine-18] fluorine-D-glucose (18F-FDG-PET/CT), is fundamental in the assessment of lung cancer, the relationship between metabolic avidity of different histotypes and maximum standardized uptake value (SUVmax) has not yet been thoroughly investigated. The aim of the study is to establish a reliable correlation between Suvmax and histology in non-small cell lung cancer (NSCLC), in order to facilitate patient management. Methods. We retrospectively assessed the data about lung cancer patients entered in the Italian Registry of VATS Group from January 2014 to October 2019, after establishing the eligibility criteria of the study. In total, 8139 patients undergoing VATS lobectomy were enrolled: 3260 females and 4879 males. The relationship between SUVmax and tumor size was also analyzed. Results. The mean values of SUVmax in the most frequent types of lung cancer were as follows: (a) 4.88 ± 3.82 for preinvasive adenocarcinoma; (b) 5.49 ± 4.10 for minimally invasive adenocarcinoma; (c) 5.87 ± 4.18 for invasive adenocarcinoma; and (d) 8.85 ± 6.70 for squamous cell carcinoma. Processing these data, we displayed a statistically difference (p < 0.000001) of FDG avidity between adenocarcinoma and squamous cell carcinoma. Moreover, by classifying patients into five groups based on tumor diameter and after evaluating the SUVmax value for each group, we noted a statistical correlation (p < 0.000001) between size and FDG uptake, also confirmed by the post hoc analysis. Conclusions. There is a correlation between SUVmax, histopathology outcomes and tumor size in NSCLC. Further clinical trials should be performed in order to confirm our data.
A Multi-mRNA Prognostic Signature for Anti-TNFα Therapy Response in Patients with Inflammatory Bowel Disease
Authors: Sakaram Suraj , Hasin-Brumshtein Yehudit , Khatri Purvesh , He Yudong D. , Sweeney Timothy E.
Published: October 2021

Background: Anti-TNF-alpha (anti-TNFα) therapies have transformed the care and management of inflammatory bowel disease (IBD). However, they are expensive and ineffective in greater than 50% of patients, and they increase the risk of infections, liver issues, arthritis, and lymphoma. With 1.6 million Americans suffering from IBD and global prevalence on the rise, there is a critical unmet need in the use of anti-TNFα therapies: a test for the likelihood of therapy response. Here, as a proof-of-concept, we present a multi-mRNA signature for predicting response to anti-TNFα treatment to improve the efficacy and cost-to-benefit ratio of these biologics. Methods: We surveyed public data repositories and curated four transcriptomic datasets (n = 136) from colonic and ileal mucosal biopsies of IBD patients (pretreatment) who were subjected to anti-TNFα therapy and subsequently adjudicated for response. We applied a multicohort analysis with a leave-one-study-out (LOSO) approach, MetaIntegrator, to identify significant differentially expressed (DE) genes between responders and non-responders and then used a greedy forward search to identify a parsimonious gene signature. We then calculated an anti-TNFα response (ATR) score based on this parsimonious gene signature to predict responder status and assessed discriminatory performance via an area-under-receiver operating-characteristic curve (AUROC). Results: We identified 324 significant DE genes between responders and non-responders. The greedy forward search yielded seven genes that robustly distinguish anti-TNFα responders from non-responders, with an AUROC of 0.88 (95% CI: 0.70–1). The Youden index yielded a mean sensitivity of 91%, mean specificity of 76%, and mean accuracy of 86%. Conclusions: Our findings suggest that there is a robust transcriptomic signature for predicting anti-TNFα response in mucosal biopsies from IBD patients prior to treatment initiation. This seven-gene signature should be further investigated for its potential to be translated into a predictive test for clinical use.
The Levels of Circulating MicroRNAs at 6-Hour Cardiac Arrest Can Predict 6-Month Poor Neurological Outcome
Authors: Oh Sang Hoon , Kim Ho-Shik , Park Kyu Nam , Ji Sanghee , Park Ji-Young , Choi Seung Pill , Lim Jee Yong , Kim Han Joon ,   on behalf of CROWN Investigators
Published: October 2021

Early prognostication in cardiac arrest survivors is challenging for physicians. Unlike other prognostic modalities, biomarkers are easily accessible and provide an objective assessment method. We hypothesized that in cardiac arrest patients with targeted temperature management (TTM), early circulating microRNA (miRNA) levels are associated with the 6-month neurological outcome. In the discovery phase, we identified candidate miRNAs associated with cardiac arrest patients who underwent TTM by comparing circulating expression levels in patients and healthy controls. Next, using a larger cohort, we validated the prognostic values of the identified early miRNAs by measuring the serum levels of miRNAs, neuron-specific enolase (NSE), and S100 calcium-binding protein B (S100B) 6 h after cardiac arrest. The validation cohort consisted of 54 patients with TTM. The areas under the curve (AUCs) for poor outcome were 0.85 (95% CI (confidence interval), 0.72–0.93), 0.82 (95% CI, 0.70–0.91), 0.78 (95% CI, 0.64–0.88), and 0.77 (95% CI, 0.63–0.87) for miR-6511b-5p, -125b-1-3p, -122-5p, and -124-3p, respectively. When the cut-off was based on miRNA levels predicting poor outcome with 100% specificity, sensitivities were 67.7% (95% CI, 49.5–82.6), 50.0% (95% CI, 32.4–67.7), 35.3% (95% CI, 19.7–53.5), and 26.5% (95% CI, 12.9–44.4) for the above miRNAs, respectively. The models combining early miRNAs with protein biomarkers demonstrated superior prognostic performance to those of protein biomarkers.
Intelligent Reflecting Surface Assisted Multi-User Robust Secret Key Generation for Low-Entropy Environments
Authors: Gao Yuwei , Guo Dengke , Xiong Jun , Ma Dongtang
Published: October 2021

Channel secret key generation (CSKG), assisted by the new material intelligent reflecting surface (IRS), has become a new research hotspot recently. In this paper, the key extraction method in the IRS-aided low-entropy communication scenario with adjacent multi-users is investigated. Aiming at the problem of low key generation efficiency due to the high similarity of channels between users, we propose a joint user allocation and IRS reflection parameter adjustment scheme, while the reliability of information exchange during the key generation process is also considered. Specifically, the relevant key capability expressions of the IRS-aided communication system is analyzed. Then, we study how to adjust the IRS reflection matrix and allocate the corresponding users to minimize the similarity of different channels and ensure the robustness of key generation. The simulation results show that the proposed scheme can bring higher gains to the performance of key generation.
Dynein-Inspired Multilane Exclusion Process with Open Boundary Conditions
Authors: Nandi Riya , Täuber Uwe C. , Priyanka
Published: October 2021

Motivated by the sidewise motions of dynein motors shown in experiments, we use a variant of the exclusion process to model the multistep dynamics of dyneins on a cylinder with open ends. Due to the varied step sizes of the particles in a quasi-two-dimensional topology, we observe the emergence of a novel phase diagram depending on the various load conditions. Under high-load conditions, our numerical findings yield results similar to the TASEP model with the presence of all three standard TASEP phases, namely the low-density (LD), high-density (HD), and maximal-current (MC) phases. However, for medium- to low-load conditions, for all chosen influx and outflux rates, we only observe the LD and HD phases, and the maximal-current phase disappears. Further, we also measure the dynamics for a single dynein particle which is logarithmically slower than a TASEP particle with a shorter waiting time. Our results also confirm experimental observations of the dwell time distribution: The dwell time distribution for dyneins is exponential in less crowded conditions, whereas a double exponential emerges under overcrowded conditions.
A Network Theory Approach to Curriculum Design
Authors: O’Meara John , Vaidya Ashwin
Published: October 2021

In this paper we hypothesize that education, especially at the scale of curriculum, should be treated as a complex system composed of different ideas and concepts which are inherently connected. Therefore, the task of a good teacher lies in elucidating these connections and helping students make their own connections. Such a pedagogy allows students to personalize learning and strive to be ‘creative’ and make meaning out of old ideas. The novel contribution of this work lies in the mathematical approach we undertake to verify our hypothesis. We take the example of a precalculus course curriculum to make our case. We treat textbooks as exemplars of a specific pedagogy and map several texts into networks of isolated (nodes) and interconnected concepts (edges) thereby permitting computations of metrics which have much relevance to the education theorists, teachers and all others involved in the field of education. We contend that network metrics such as average path length, clustering coefficient and degree distribution provide valuable insights to teachers and students about the kind of pedagogy which encourages good teaching and learning.
Modeling Hospital Resource Management during the COVID-19 Pandemic: An Experimental Validation
Authors: Calabuig J. M. , Jiménez-Fernández E. , Sánchez-Pérez E. A. , Manzanares S.
Published: October 2021

One of the main challenges posed by the healthcare crisis generated by COVID-19 is to avoid hospital collapse. The occupation of hospital beds by patients diagnosed by COVID-19 implies the diversion or suspension of their use for other specialities. Therefore, it is useful to have information that allows efficient management of future hospital occupancy. This article presents a robust and simple model to show certain characteristics of the evolution of the dynamic process of bed occupancy by patients with COVID-19 in a hospital by means of an adaptation of Kaplan-Meier survival curves. To check this model, the evolution of the COVID-19 hospitalization process of two hospitals between 11 March and 15 June 2020 is analyzed. The information provided by the Kaplan-Meier curves allows forecasts of hospital occupancy in subsequent periods. The results shows an average deviation of 2.45 patients between predictions and actual occupancy in the period analyzed.
The Effect of Financial Risk Taking on Profitability in the Pharmaceutical Industry
Authors: Tömöri Gergő , Lakatos Vilmos , Mártha Bernadett Béresné
Published: October 2021

The significance of the pharmaceutical and commercial sectors in the national economy has noticeably intensified, as a result of the COVID-19 pandemic. The main objective of this study was to gain a better insight into the main management characteristics of the actors in the sector. It was assumed that more efficient management of financial investments (acquisitions, loans) caused higher risk financial investment decisions in the pharmaceutical industry in order to place companies in a better position in view of equity investors, illustrated best as the profitability of equity (ROE). This paper examined one possible means of covering the extremely high indirect costs (R&D, marketing) of pharmaceutical companies, also justified by the restructuring of the industry and the effect of investments in long term financial instruments on the ROE of the same business entities. Built on the EMIS database, the analysis only used the indicators of those companies operating in the pharmaceutical industry in Visegrad countries for 2019. The authors sought to draw conclusions about possible management characteristics of the entire pharmaceutical sector of these countries using cluster analysis and linear regression. The initial assumption, or main hypothesis of the study, was that in one of the countries studied or for those businesses operating above a certain revenue category, the impact of a company’s risk-taking (which can also be expressed in terms of asset-based financial income) on profitability, may appear or intensify. The performed studies did not show a strong correlation between the explanatory and profit variables either at the national level or at the level of groups formed by regional market position. In other words, the extremely high level of indirect costs were mostly covered by sales of successful cash products, and companies not indebted to suppliers undertook significant risks in the field of financial investments, thereby offsetting the positive impact of the latter on earnings.
Optimal Reduction in the Number of Test Vectors for Soft Processor Cores Implemented in FPGA
Authors: Węgrzyn Mariusz , Jamro Ernest , Dąbrowska-Boruch Agnieszka , Wiatr Kazimierz
Published: October 2021

Testing FPGA-based soft processor cores requires a completely different methodology in comparison to standard processors. The stuck-at fault model is insufficient, as the logic is implemented by lookup tables (LUTs) in FPGA, and this SRAM-based LUT memory is vulnerable to single-event upset (SEU) mainly caused by cosmic radiations. Consequently, in this paper, we used combined SEU-induced and stuck-at fault models to simulate every possible fault. The test program written in an assembler was based on the bijective property. Furthermore, the fault detection matrix was determined, and this matrix describes the detectability of every fault by every test vector. The major novelty of this paper is the optimal reduction in the number of required test vectors in such a way that fault coverage is not reduced. Furthermore, this paper also studied the optimal selection of test vectors when only 95% maximal fault coverage is acceptable; in such a case, only three test vectors are required. Further, local and global test vector selection is also described.