bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in the Delivery Carriers and Chemical Conjugation Strategies for Nucleic Acid Drugs
Authors: Oyama Shota , Yamamoto Tsuyoshi , Yamayoshi Asako
Published: August 2021

With the development of new anticancer medicines, novel modalities are being explored for cancer treatment. For many years, conventional modalities, such as small chemical drugs and antibody drugs, have worked by “inhibiting the function” of target proteins. In recent years, however, nucleic acid drugs, such as ASOs and siRNAs, have attracted attention as a new modality for cancer treatment because nucleic acid drugs can directly promote the “loss of function” of target genes. Recently, nucleic acid drugs for use in cancer therapy have been extensively developed and some of them have currently been under investigation in clinical trials. To develop novel nucleic acid drugs for cancer treatment, it is imperative that cancer researchers, including ourselves, cover and understand those latest findings. In this review, we introduce and provide an overview of various DDSs and ligand modification technologies that are being employed to improve the success and development of nucleic acid drugs, then we also discuss the future of nucleic acid drug developments for cancer therapy. It is our belief this review will increase the awareness of nucleic acid drugs worldwide and build momentum for the future development of new cancer-targeted versions of these drugs.
Interactions Networks for Primary Heart Sarcomas
Authors: Geronikolou Styliani A. , Pavlopoulou Athanasia , Chrousos George P. , Cokkinos Dennis V.
Published: August 2021

Personalized medicine incorporates genetic information into medical practice so as to optimize the management of chronic diseases. In rare diseases, such as heart cancer (incidence 0.0017–0.33%), this may be elusive. Ninety-five percent of the cases are due to secondary involvementwith the neoplasm originating in the lungs, breasts, kidney, blood, or skin. The clinical manifestations of heart tumors (benign or malignant) include heart failure, hypertension, and cardiac arrhythmias of varying severity, frequently resulting in blood vessel emboli, including strokes. This study aims to explain the pathophysiology and contribute to a P4 medicine model for use by cardiologists, pathologists, and oncologists. We created six gene/protein heart-related and tumor-related targets high-confidence interactomes, which unfold the main pathways that may lead to cardiac diseases (heart failure, hypertension, coronary artery disease, arrhythmias), i.e., the sympathetic nervous system, the renin-angiotensin-aldosterone axis and the endothelin pathway, and excludes others, such as the K oxidase or cytochrome P450 pathways. We concluded that heart cancer patients could be affected by beta-adrenergic blockers, ACE inhibitors, QT-prolonging antiarrhythmic drugs, antibiotics, and antipsychotics. Interactomes may elucidate unknown pathways, adding to patient/survivor wellness during/after chemo- and/or radio-therapy.
Tumor and Peripheral Immune Status in Soft Tissue Sarcoma: Implications for Immunotherapy
Authors: Sousa Luana Madalena , Almeida Jani Sofia , Fortes-Andrade Tânia , Santos-Rosa Manuel , Freitas-Tavares Paulo , Casanova José Manuel , Rodrigues-Santos Paulo
Published: August 2021

Soft Tissue Sarcomas (STS) are a heterogeneous and rare group of tumors. Immune cells, soluble factors, and immune checkpoints are key elements of the complex tumor microenvironment. Monitoring these elements could be used to predict the outcome of the disease, the response to therapy, and lead to the development of new immunotherapeutic approaches. Tumor-infiltrating B cells, Natural Killer (NK) cells, tumor-associated neutrophils (TANs), and dendritic cells (DCs) were associated with a better outcome. On the contrary, tumor-associated macrophages (TAMs) were correlated with a poor outcome. The evaluation of peripheral blood immunological status in STS could also be important and is still underexplored. The increased lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR), higher levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and Tim-3 positive CD8 T cells appear to be negative prognostic markers. Meanwhile, NKG2D-positive CD8 T cells were correlated with a better outcome. Some soluble factors, such as cytokines, chemokines, growth factors, and immune checkpoints were associated with the prognosis. Similarly, the expression of immune-related genes in STS was also reviewed. Despite these efforts, only very little is known, and much research is still needed to clarify the role of the immune system in STS.
Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era
Authors: Refeno Valéry , Lamuraglia Michele , Terrisse Safae , Bonnet Clément , Dumont Clément , Doucet Ludovic , Pouessel Damien , Culine Stephane
Published: August 2021

Background: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment. Methods: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line. Results: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53–37.6) and the median follow-up duration was 40.83 months (range 11.33–88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line. Conclusions: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.
Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea
Authors: Díaz-García Elena , García-Tovar Sara , Casitas Raquel , Jaureguizar Ana , Zamarrón Ester , Sánchez-Sánchez Begoña , Sastre-Perona Ana , López-Collazo Eduardo , Garcia-Rio Francisco , Cubillos-Zapata Carolina
Published: August 2021

As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)β-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFβ, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFβ induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFβ activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSA.
Deep Learning Fast Screening Approach on Cytological Whole Slides for Thyroid Cancer Diagnosis
Authors: Lin Yi-Jia , Chao Tai-Kuang , Khalil Muhammad-Adil , Lee Yu-Ching , Hong Ding-Zhi , Wu Jia-Jhen , Wang Ching-Wei
Published: August 2021

Thyroid cancer is the most common cancer in the endocrine system, and papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer, accounting for 70 to 80% of all thyroid cancer cases. In clinical practice, visual inspection of cytopathological slides is an essential initial method used by the pathologist to diagnose PTC. Manual visual assessment of the whole slide images is difficult, time consuming, and subjective, with a high inter-observer variability, which can sometimes lead to suboptimal patient management due to false-positive and false-negative. In this study, we present a fully automatic, efficient, and fast deep learning framework for fast screening of papanicolaou-stained thyroid fine needle aspiration (FNA) and ThinPrep (TP) cytological slides. To the authors’ best of knowledge, this work is the first study to build an automated deep learning framework for identification of PTC from both FNA and TP slides. The proposed deep learning framework is evaluated on a dataset of 131 WSIs, and the results show that the proposed method achieves an accuracy of 99%, precision of 85%, recall of 94% and F1-score of 87% in segmentation of PTC in FNA slides and an accuracy of 99%, precision of 97%, recall of 98%, F1-score of 98%, and Jaccard-Index of 96% in TP slides. In addition, the proposed method significantly outperforms the two state-of-the-art deep learning methods, i.e., U-Net and SegNet, in terms of accuracy, recall, F1-score, and Jaccard-Index (p<0.001). Furthermore, for run-time analysis, the proposed fast screening method takes 0.4 min to process a WSI and is 7.8 times faster than U-Net and 9.1 times faster than SegNet, respectively.
Platinum Recovery Techniques for a Circular Economy
Authors: Granados-Fernández Rafael , Montiel Miguel A. , Díaz-Abad Sergio , Rodrigo Manuel A. , Lobato Justo
Published: August 2021

Platinum and other metals are very scarce materials widely used in the energy and transportation sector among other sectors. Obtaining Platinum is becoming more difficult due to its scarcity on earth and because of the high amount of energy and water used for its extraction. In this regard, the recycling of platinum is necessary for sustainable technologies and for reaching a circular economy towards this expensive and rare metal. Conventional methods for platinum recycling make use of enormous amounts of energy for its recovery, which makes them not very attractive for industry implementation. Furthermore, these processes generate very toxic liquid streams and gas wastes that must be further treated, which do not meet the green environmental point of view of platinum recycling. Consequently, new advanced technologies are arising aiming to reach very high platinum recovery rates while being environmentally friendly and making a huge reduction of energy use compared with the conventional methods. In this review, conventional platinum recovery methods are summarized showing their limitations. Furthermore, new and promising approaches for platinum recovery are reviewed to shed light on about new and greener ways for a platinum circular economy.
Human Vascular Smooth Muscle Function and Oxidative Stress Induced by NADPH Oxidase with the Clinical Implications
Authors: Takaishi Kazumi , Kinoshita Hiroyuki , Kawashima Shingo , Kawahito Shinji
Published: August 2021

Among reactive oxygen species, superoxide mediates the critical vascular redox signaling, resulting in the regulation of the human cardiovascular system. The reduced form of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) is the source of superoxide and relates to the crucial intracellular pathology and physiology of vascular smooth muscle cells, including contraction, proliferation, apoptosis, and inflammatory response. Human vascular smooth muscle cells express NOX1, 2, 4, and 5 in physiological and pathological conditions, and those enzymes play roles in most cardiovascular disorders caused by hypertension, diabetes, inflammation, and arteriosclerosis. Various physiologically active substances, including angiotensin II, stimulate NOX via the cytosolic subunits’ translocation toward the vascular smooth muscle cell membrane. As we have shown, some pathological stimuli such as high glucose augment the enzymatic activity mediated by the phosphatidylinositol 3-kinase-Akt pathway, resulting in the membrane translocation of cytosolic subunits of NOXs. This review highlights and details the roles of human vascular smooth muscle NOXs in the pathophysiology and clinical aspects. The regulation of the enzyme expressed in the vascular smooth muscle cells may lead to the prevention and treatment of human cardiovascular diseases.
A Leptin Receptor Antagonist Attenuates Adipose Tissue Browning and Muscle Wasting in Infantile Nephropathic Cystinosis-Associated Cachexia
Authors: Gonzalez Alex , Cheung Wai W. , Perens Elliot A. , Oliveira Eduardo A. , Gertler Arieh , Mak Robert H.
Published: August 2021

Mice lacking the functional cystinosin gene (Ctns−/−), a model of infantile nephropathic cystinosis (INC), exhibit the cachexia phenotype with adipose tissue browning and muscle wasting. Elevated leptin signaling is an important cause of chronic kidney disease-associated cachexia. The pegylated leptin receptor antagonist (PLA) binds to but does not activate the leptin receptor. We tested the efficacy of this PLA in Ctns−/− mice. We treated 12-month-old Ctns−/− mice and control mice with PLA (7 mg/kg/day, IP) or saline as a vehicle for 28 days. PLA normalized food intake and weight gain, increased fat and lean mass, decreased metabolic rate and improved muscle function. It also attenuated perturbations of energy homeostasis in adipose tissue and muscle in Ctns−/− mice. PLA attenuated adipose tissue browning in Ctns−/− mice. PLA increased gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns−/− mice. This was accompanied by correcting the increased expression of muscle wasting signaling while promoting the decreased expression of myogenesis in gastrocnemius of Ctns−/− mice. PLA attenuated aberrant expressed muscle genes that have been associated with muscle atrophy, increased energy expenditure and lipolysis in Ctns−/− mice. Leptin antagonism may represent a viable therapeutic strategy for adipose tissue browning and muscle wasting in INC.
Implications of a ‘Third Signal’ in NK Cells
Authors: Khalil Mohamed , Wang Dandan , Hashemi Elaheh , Terhune Scott S. , Malarkannan Subramaniam
Published: August 2021

Innate and adaptive immune systems are evolutionarily divergent. Primary signaling in T and B cells depends on somatically rearranged clonotypic receptors. In contrast, NK cells use germline-encoded non-clonotypic receptors such as NCRs, NKG2D, and Ly49H. Proliferation and effector functions of T and B cells are dictated by unique peptide epitopes presented on MHC or soluble humoral antigens. However, in NK cells, the primary signals are mediated by self or viral proteins. Secondary signaling mediated by various cytokines is involved in metabolic reprogramming, proliferation, terminal maturation, or memory formation in both innate and adaptive lymphocytes. The family of common gamma (γc) cytokine receptors, including IL-2Rα/β/γ, IL-7Rα/γ, IL-15Rα/β/γ, and IL-21Rα/γ are the prime examples of these secondary signals. A distinct set of cytokine receptors mediate a ‘third’ set of signaling. These include IL-12Rβ1/β2, IL-18Rα/β, IL-23R, IL-27R (WSX-1/gp130), IL-35R (IL-12Rβ2/gp130), and IL-39R (IL-23Rα/gp130) that can prime, activate, and mediate effector functions in lymphocytes. The existence of the ‘third’ signal is known in both innate and adaptive lymphocytes. However, the necessity, context, and functional relevance of this ‘third signal’ in NK cells are elusive. Here, we define the current paradigm of the ‘third’ signal in NK cells and enumerate its clinical implications.
Insights on the Regeneration Potential of Müller Glia in the Mammalian Retina
Authors: Salman Ahmed , McClements Michelle , MacLaren Robert
Published: August 2021

Müller glia, the major glial cell types in the retina, maintain retinal homeostasis and provide structural support to retinal photoreceptors. They also possess regenerative potential that might be used for retinal repair in response to injury or disease. In teleost fish (such as zebrafish), the Müller glia response to injury involves reprogramming events that result in a population of proliferative neural progenitors that can regenerate the injured retina. Recent studies have revealed several important mechanisms for the regenerative capacity of Müller glia in fish, which may shed more light on the mechanisms of Müller glia reprogramming and regeneration in mammals. Mammalian Müller glia can adopt stem cell characteristics, and in response to special conditions, be persuaded to proliferate and regenerate, although their native regeneration potential is limited. In this review, we consider the work to date revealing the regenerative potential of the mammalian Müller glia and discuss whether they are a potential source for cell regeneration therapy in humans.
Selective Determination of Hydrogen Sulfide Using SnO2–Ag Sensor Working in Non-Stationary Temperature Regime
Authors: Shaposhnik Alexey V. , Moskalev Pavel V. , Zviagin Alexey A. , Duykova Margarita V. , Ryabtsev Stanislav V. , Ghareeb Dina A. A. , Vasiliev Alexey A.
Published: August 2021

The application of a non-stationary regime of temperature modulation in metal oxide semiconductor sensor based on SnO2–Ag leads not only to a strongly increased sensor response, but also to a considerably improved sensor selectivity toward hydrogen sulfide. Selectivity with respect to other reducing gases (CO, NH3, H2) is about five orders of magnitude, enabling a correct selective determination of H2S in the presence of interfering gas components.
Hydrophilic Surface Treatment of Carbon Powder Using CO2 Plasma Activated Gas
Authors: Yoo Seungryul , Seok Dongchan , Jung Yongho , Lee Kiyong
Published: August 2021

Carbon powders exhibit electrical conductivity that causes the powders to agglomerate due to the applied electrostatic forces and discharges capacitance when used for surface treatments with plasma sources. To avoid this obstacle, a non-direct method is used with active gas that is generated through plasma. This active gas is in contact with the carbon powder so that the hydrophilic characteristics are formed. It is the carboxyl COO− functional group that causes hydrophilic improvement and it is shown to increase in the carbon surface after soft oxidation. The wettability of carbon powder gradually improves with more plasma treatment time. This is shown through a simple water dispersion test. Eventually, the dispersed aqueous solution gradually separates the powder, which either floats or sinks. The sample treated for 60 min is shown to continuously sustain dispersibility in water over a long period of time.
Predicting Interfacial Thermal Resistance by Ensemble Learning
Authors: Chen Mingguang , Li Junzhu , Tian Bo , Al-Hadeethi Yas Mohammed , Arkook Bassim , Tian Xiaojuan , Zhang Xixiang
Published: August 2021

Interfacial thermal resistance (ITR) plays a critical role in the thermal properties of a variety of material systems. Accurate and reliable ITR prediction is vital in the structure design and thermal management of nanodevices, aircraft, buildings, etc. However, because ITR is affected by dozens of factors, traditional models have difficulty predicting it. To address this high-dimensional problem, we employ machine learning and deep learning algorithms in this work. First, exploratory data analysis and data visualization were performed on the raw data to obtain a comprehensive picture of the objects. Second, XGBoost was chosen to demonstrate the significance of various descriptors in ITR prediction. Following that, the top 20 descriptors with the highest importance scores were chosen except for fdensity, fmass, and smass, to build concise models based on XGBoost, Kernel Ridge Regression, and deep neural network algorithms. Finally, ensemble learning was used to combine all three models and predict high melting points, high ITR material systems for spacecraft, automotive, building insulation, etc. The predicted ITR of the Pb/diamond high melting point material system was consistent with the experimental value reported in the literature, while the other predicted material systems provide valuable guidelines for experimentalists and engineers searching for high melting point, high ITR material systems.
Urbanization and Vulnerability of Architectural Heritage: The Case of Dar es Salaam CBD
Authors: Ombeni Swai , Mbosha Dorothea , Mpyanga Simon
Published: August 2021

The architectural heritage present in Dar es Salaam Central Business District (CBD) spans across Arab, German, British, and post-colonial eras. The city is rich in buildings with combined architectural styles. Over the past few decades, Dar es Salaam has been experiencing considerable pressure from urbanization. This has resulted in a boom of contemporary construction approaches, yet little concern has been given to the existing old buildings and historical fabric in general. Although urbanization is an unstoppable reality due to the forces it carries with it, it is necessary to find ways to strike a balance between urbanization and its impact on the original urban setting which is less explored in Dar es Salaam. This study investigated the relationship between urbanization and architectural heritage with the intention to balance the two, and set to answer questions about how the two can co-exist. Through a case study approach, changes such as physical transformation, elimination, and replacement of architectural heritage buildings were investigated and analyzed through maps, graphs, and charts. The results have indicated that the driving forces of urbanization such as population, policies, and economy have been influencing each other in physical transformation and demolition of architectural heritage buildings throughout the period between 1967 and 2020. The study suggests that activities such as ecotourism which will enhance social economic benefits should be promoted to support both the urbanization process and architectural heritage conservation.
COVID-19 Related Knowledge, Risk Perceptions, and Practices amongst Irish Residents
Authors: Temple Emma , Jaiswal Amit , Jaiswal Swarna
Published: August 2021

The COVID-19 disease was declared a global pandemic by the 11th of February 2020, presenting a major threat to public health worldwide. Success in the battle against COVID-19 depends on public adherence to control measures. Their adherence is greatly affected by their knowledge, perceptions, and practices; therefore, the aim of this study was to assess and understand the knowledge, perceptions, practices, and trusted information sources of COVID-19 among Irish residents. A quantitative survey was performed by means of an online questionnaire, which comprised five sections to collect data regarding demographics, knowledge, perceptions, practices, and information sources. A total of 1007 participants completed the online survey between February and March 2021. The majority of respondents (69.4% female and 30.3% male) had a correct rate of knowledge (88%) and practices (68.1%), with health organisations being the most trusted information source (70.7%); 87.4% understand good mask etiquette. Only 53.7% agreed that closing schools or mass gathering events are an effective way to reduce the spread of the virus, while 81.3% are aware that COVID-19 is more severe than the flu; 64% of respondents said that the pandemic has negatively affected their mental health. It was observed that a higher level of knowledge is positively correlated with good practices. The study concludes that most of the respondents have shown a good level of knowledge and right practices towards the COVID-19 pandemic, and that the higher the level of knowledge of individuals, the better the COVID-19 safety practices are that they perform. It has been observed that the continuous improvement on an individual’s level of knowledge of COVID-19 is essential to maintain good safety practices and reduce the spread.
Laser Operation of Tm: LuAG Single-Crystal Fiber Grown by the Micro-Pulling down Method
Authors: Liu Jian , Dong Jifei , Wang Yinyin , Yuan Hangqi , Song Qingsong , Xue Yanyan , Xu Jie , Liu Peng , Li Dongzhen , Lebbou Kheirreddine , Wang Zhanxin , Zhao Yongguang , Xu Xiaodong , Xu Jun
Published: August 2021

Single crystals fiber (SCF) of LuAG doped with 2.0 at.% thulium has been grown by using micro-pulling down (µ-PD) technique. A continuous-wave output power of 2.44 W was achieved with a slope efficiency of 11.7% using a 783-nm diode laser as pump source. The beam quality factors M2 were 1.14 and 1.67 in the x and y directions, respectively. This is, to the best of our knowledge, the first report on the Tm:LuAG SCF laser. Using ray tracing analysis, the influence of laser performance by the pump intensity distribution in the SCF was also studied.
Synthetic BiOBr/Bi2S3/CdS Crystalline Material and Its Degradation of Dye under Visible Light
Authors: Jin Yunhan , Xing Zhe , Li Yinhui , Han Jian , Lorenz Heike , Chen Jianxin
Published: August 2021

Constructing heterojunction has attracted widespread concerns in photocatalysis research. BiOBr/Bi2S3/CdS composite material with a sea urchin shape was directly obtained by first synthesizing BiOBr microspheres. The morphology, structure and composition of the composite material were characterized by XRD, EDX, SEM and XPS. Dye degradation experiments showed that 83.3% of methylene blue removal was achieved after 2 h of visible light irradiation. The reaction rate under optimal conditions was 0.014 min−1 and the photocatalytic degradation process follows a pseudo-first-order kinetic model. Based on the EPR test results, the main active species involved in the reaction were •O2− and h+. The conduction band and valence band edge potential calculations confirmed the key role of CdS in the production of •O2−.
Mid-IR Optical Property of Dy:CaF2-SrF2 Crystal Fabricated by Multicrucible Temperature Gradient Technology
Authors: Zheng Lihe , Zhao Jianbin , Wang Yangxiao , Chen Weichao , Ruan Fangfang , Lin Hui , Xue Yanyan , Liu Jian , Liu Yang , Yang Ruiqin , Lu Haifeng , Xu Xiaodong , Su Liangbi
Published: August 2021

Dy3+-doped CaF2-SrF2 crystals with various Dy3+ dopant concentrations were synthesized by multicrucible temperature gradient technology (MC-TGT). Dy:CaF2-SrF2 crystals were fluorite structured and crystallized in cubic Fm3¯m space group, as characterized by X-ray diffraction. The crystallographic site concentration was calculated from the measured density by Archimedes’ hydrostatic weighing principle. The optical transmission reached over 90% with a sample thickness of 1.0 mm. The Sellmeier dispersion formula was obtained following the measured refractive index in a mid-IR range of 1.7–11 μm. Absorption coefficients of 6.06 cm−1 and 12.71 cm−1 were obtained at 804 nm and 1094 nm in 15% Dy:CaF2-SrF2 crystal. The fluorescence spectra of 15 at.% Dy:CaF2-SrF2 showed the strongest wavelength peak at 2919 nm with a full width at half maximum (FWHM) of 267 nm under an excitation wavelength of 808 nm. The fluorescence lifetimes were illustrated for different Dy3+ dopant levels of 5%, 10% and 15%. The results indicate that the Dy:CaF2-SrF2 crystal is a promising candidate for compact mid-IR lasers.
Hand-Held Ultrasound of the Lung: A Systematic Review
Authors: Haji-Hassan Mariam , Lenghel Lavinia Manuela , Bolboacă Sorana D.
Published: August 2021

Background: The ultrasound examination is a surface technique with an accurate diagnosis of pathological processes adjacent to the pleural line. The purpose of the study was to evaluate the role of hand-held ultrasound devices (visual stethoscopes) in the diagnosis of peripheral lung disease. Methods: We conducted a systematic search of literature comparing the diagnostic accuracy of truly hand-held ultrasound devices compared to conventional high-end ultrasound devices, chest X-rays, thoracic CT (computer tomography), or physical examinations to diagnose peripheral lung lesions. ScienceDirect, PubMed, and PubMed Central bibliographic databases were searched within a time limit of 15 years. Results: The applied search strategy retrieved 439 studies after removing duplicates; 34 were selected for full-text review, and 15 articles met all inclusion criteria and were included in the analysis. When comparing hand-held ultrasound devices to chest X-rays, negative predictive values were above 90%, while positive predictive values tended to be lower (from 35% to 75.8%). Hand-held ultrasound reached a correlation of 0.99 as associated with conventional ultrasound with a Bland–Altman bias close to zero. Conclusions: Being accessible, radiation-free, and comparatively easy to decontaminate, hand-held ultrasound devices could represent a reliable tool for evaluating peripheral lung diseases. This method can be successfully employed as an alternative to repeated X-ray examinations for peripheral lung disease monitoring.
Machine Learning Approaches to Identify Patient Comorbidities and Symptoms That Increased Risk of Mortality in COVID-19
Authors: Aktar Sakifa , Talukder Ashis , Ahamad Md. Martuza , Kamal A. H. M. , Khan Jahidur Rahman , Protikuzzaman Md. , Hossain Nasif , Azad A. K. M. , Quinn Julian M. W. , Summers Mathew A. , Liaw Teng , Eapen Valsamma , Moni Mohammad Ali
Published: August 2021

Providing appropriate care for people suffering from COVID-19, the disease caused by the pandemic SARS-CoV-2 virus, is a significant global challenge. Many individuals who become infected may have pre-existing conditions that may interact with COVID-19 to increase symptom severity and mortality risk. COVID-19 patient comorbidities are likely to be informative regarding the individual risk of severe illness and mortality. Determining the degree to which comorbidities are associated with severe symptoms and mortality would thus greatly assist in COVID-19 care planning and provision. To assess this we performed a meta-analysis of published global literature, and machine learning predictive analysis using an aggregated COVID-19 global dataset. Our meta-analysis suggested that chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CEVD), cardiovascular disease (CVD), type 2 diabetes, malignancy, and hypertension as most significantly associated with COVID-19 severity in the current published literature. Machine learning classification using novel aggregated cohort data similarly found COPD, CVD, CKD, type 2 diabetes, malignancy, and hypertension, as well as asthma, as the most significant features for classifying those deceased versus those who survived COVID-19. While age and gender were the most significant predictors of mortality, in terms of symptom–comorbidity combinations, it was observed that Pneumonia–Hypertension, Pneumonia–Diabetes, and Acute Respiratory Distress Syndrome (ARDS)–Hypertension showed the most significant associations with COVID-19 mortality. These results highlight the patient cohorts most likely to be at risk of COVID-19-related severe morbidity and mortality, which have implications for prioritization of hospital resources.
TransMed: Transformers Advance Multi-Modal Medical Image Classification
Authors: Dai Yin , Gao Yifan , Liu Fayu
Published: August 2021

Over the past decade, convolutional neural networks (CNN) have shown very competitive performance in medical image analysis tasks, such as disease classification, tumor segmentation, and lesion detection. CNN has great advantages in extracting local features of images. However, due to the locality of convolution operation, it cannot deal with long-range relationships well. Recently, transformers have been applied to computer vision and achieved remarkable success in large-scale datasets. Compared with natural images, multi-modal medical images have explicit and important long-range dependencies, and effective multi-modal fusion strategies can greatly improve the performance of deep models. This prompts us to study transformer-based structures and apply them to multi-modal medical images. Existing transformer-based network architectures require large-scale datasets to achieve better performance. However, medical imaging datasets are relatively small, which makes it difficult to apply pure transformers to medical image analysis. Therefore, we propose TransMed for multi-modal medical image classification. TransMed combines the advantages of CNN and transformer to efficiently extract low-level features of images and establish long-range dependencies between modalities. We evaluated our model on two datasets, parotid gland tumors classification and knee injury classification. Combining our contributions, we achieve an improvement of 10.1% and 1.9% in average accuracy, respectively, outperforming other state-of-the-art CNN-based models. The results of the proposed method are promising and have tremendous potential to be applied to a large number of medical image analysis tasks. To our best knowledge, this is the first work to apply transformers to multi-modal medical image classification.
Automated Adenoid Hypertrophy Assessment with Lateral Cephalometry in Children Based on Artificial Intelligence
Authors: Zhao Tingting , Zhou Jiawei , Yan Jiarong , Cao Lingyun , Cao Yi , Hua Fang , He Hong
Published: August 2021

Adenoid hypertrophy may lead to pediatric obstructive sleep apnea and mouth breathing. The routine screening of adenoid hypertrophy in dental practice is helpful for preventing relevant craniofacial and systemic consequences. The purpose of this study was to develop an automated assessment tool for adenoid hypertrophy based on artificial intelligence. A clinical dataset containing 581 lateral cephalograms was used to train the convolutional neural network (CNN). According to Fujioka’s method for adenoid hypertrophy assessment, the regions of interest were defined with four keypoint landmarks. The adenoid ratio based on the four landmarks was used for adenoid hypertrophy assessment. Another dataset consisting of 160 patients’ lateral cephalograms were used for evaluating the performance of the network. Diagnostic performance was evaluated with statistical analysis. The developed system exhibited high sensitivity (0.906, 95% confidence interval [CI]: 0.750–0.980), specificity (0.938, 95% CI: 0.881–0.973) and accuracy (0.919, 95% CI: 0.877–0.961) for adenoid hypertrophy assessment. The area under the receiver operating characteristic curve was 0.987 (95% CI: 0.974–1.000). These results indicated the proposed assessment system is able to assess AH accurately. The CNN-incorporated system showed high accuracy and stability in the detection of adenoid hypertrophy from children’ lateral cephalograms, implying the feasibility of automated adenoid hypertrophy screening utilizing a deep neural network model.
miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls
Authors: Serna Eva , Parra-Llorca Anna , Panadero Joaquín , Vento Máximo , Cernada María
Published: August 2021

Background and Objectives. Neonatal sepsis is a serious condition with a high rate of mortality and morbidity. Currently, the gold standard for sepsis diagnosis is a positive blood culture, which takes 48–72 h to yield results. We hypothesized that identifying differentially expressed miRNA pattern in neonates with late-onset Gram-positive sepsis would help with an earlier diagnosis and therapy. Methods. This is a prospective observational study in newborn infants with late-onset Gram positive bacterial sepsis and non-septic controls. Complementary to blood culture, an aliquot of 0.5 mL of blood was used to determine small non-coding RNA expression profiling using the GeneChip miRNA 4.0 Array. Results. A total of 11 very low birth-weight neonates with late-onset Gram-positive sepsis and 16 controls were analyzed. Further, 217 differentially expressed miRNAs were obtained between both groups. Subsequently, a combined analysis was performed with these miRNAs and 4297 differentially expressed genes. We identified 33 miRNAs that regulate our mRNAs, and the most relevant biological processes are associated with the immune system and the inflammatory response. Conclusions. The miRNA profiling in very low birth-weight neonates distinguishes late-onset Gram-positive sepsis versus control neonates.
Liquid Biopsy: A Family of Possible Diagnostic Tools
Authors: Michela Battistelli
Published: August 2021

Liquid biopsies could be considered an excellent diagnostic tool, in different physiological or pathological conditions. The possibility of using liquid biopsies for non-invasive clinical purposes is quite an old idea: indeed many years ago it was already being used in the field of non-invasive prenatal tests (NIPT) for autosomal fetal aneuploidy evaluation. In 1997 Lo et al. had identified fetal DNA in maternal plasma and serum, showing that about 10–15% of cfDNA in maternal plasma is derived from the placenta, and biologic fluid represents an important and non-invasive technique to evaluate state diseases and possible therapies. Nowadays, several body fluids, such as blood, urine, saliva and other patient samples, could be used as liquid biopsy for clinical non-invasive evaluation. These fluids contain numerous and various biomarkers and could be used for the evaluation of pathological and non-pathological conditions. In this review we will analyze the different types of liquid biopsy, their potential role in clinical diagnosis and the functional involvement of extracellular vesicles in these fluids as carriers.
Narrow Band Active Contour Attention Model for Medical Segmentation
Authors: Le Ngan , Bui Toan , Vo-Ho Viet-Khoa , Yamazaki Kashu , Luu Khoa
Published: August 2021

Medical image segmentation is one of the most challenging tasks in medical image analysis and widely developed for many clinical applications. While deep learning-based approaches have achieved impressive performance in semantic segmentation, they are limited to pixel-wise settings with imbalanced-class data problems and weak boundary object segmentation in medical images. In this paper, we tackle those limitations by developing a new two-branch deep network architecture which takes both higher level features and lower level features into account. The first branch extracts higher level feature as region information by a common encoder-decoder network structure such as Unet and FCN, whereas the second branch focuses on lower level features as support information around the boundary and processes in parallel to the first branch. Our key contribution is the second branch named Narrow Band Active Contour (NB-AC) attention model which treats the object contour as a hyperplane and all data inside a narrow band as support information that influences the position and orientation of the hyperplane. Our proposed NB-AC attention model incorporates the contour length with the region energy involving a fixed-width band around the curve or surface. The proposed network loss contains two fitting terms: (i) a high level feature (i.e., region) fitting term from the first branch; (ii) a lower level feature (i.e., contour) fitting term from the second branch including the (ii1) length of the object contour and (ii2) regional energy functional formed by the homogeneity criterion of both the inner band and outer band neighboring the evolving curve or surface. The proposed NB-AC loss can be incorporated into both 2D and 3D deep network architectures. The proposed network has been evaluated on different challenging medical image datasets, including DRIVE, iSeg17, MRBrainS18 and Brats18. The experimental results have shown that the proposed NB-AC loss outperforms other mainstream loss functions: Cross Entropy, Dice, Focal on two common segmentation frameworks Unet and FCN. Our 3D network which is built upon the proposed NB-AC loss and 3DUnet framework achieved state-of-the-art results on multiple volumetric datasets.
Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods
Authors: Liu Chih-Yi , Chen Chien-Chin , Bychkov Andrey , Agarwal Shipra , Zhu Yun , Hang Jen-Fan , Lai Chiung-Ru , Na Hee Young , Park So Yeon , Li Weiwei , Liu Zhiyan , Jain Deepali , Suzuki Ayana , Hirokawa Mitsuyoshi , Chia Noel , Nga Min En , Jitpasutham Tikamporn , Keelawat Somboon , Satoh Shinya , Gunawardena Dilini , Kumarasinghe Priyanthi , Jung Chan Kwon , Kakudo Kennichi
Published: August 2021

(1) Background: Accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to a spectrum of cytomorphologic features. However, there is a scarcity of studies describing the cytomorphologic features as seen on fine-needle aspiration (FNA) smears prepared using different staining methods. (2) Methods: We performed a retrospective study on MTC cases with available FNA slides from 13 hospitals distributed across 8 Asia-Pacific countries. The differences in the constitutive cytomorphologic features of MTC with each cytopreparatory method were recorded. A comparative analysis of cytologic characteristics was carried out with appropriate statistical tests. (3) Results: Of a total of 167 MTC samples retrospectively recruited, 148 (88.6%) were interpreted as MTC/suspicious for MTC (S-MTC). The staining methods used were Papanicolaou, hematoxylin-eosin, and Romanowsky stains. Seven out of the eleven cytologic criteria can be readily recognized by all three cytopreparatory methods: high cellularity, cellular pleomorphism, plasmacytoid cells, round cells, dyshesive cells, salt-and-pepper chromatin, and binucleation or multinucleation. An accurate diagnosis was achieved in 125 (84.5%) of the 148 samples whose FNAs exhibited five or more atypical features. Conclusions: The present work is the first study on MTC to compare the morphological differences among the cytologic staining techniques. We investigated the constitutive features and the reliability of diagnostic parameters. A feasible scoring system based upon cytomorphologic data alone is proposed to achieve a high degree of diagnostic accuracy.
The Associations of Periodontopathic Bacteria and Oral Candida with Periodontal Inflamed Surface Area in Older Adults Receiving Supportive Periodontal Therapy
Authors: Shigeishi Hideo , Nakamura Mariko , Oka Iori , Su Cheng-Yih , Yano Kanako , Ishikawa Momoko , Kaneyasu Yoshino , Sugiyama Masaru , Ohta Kouji
Published: August 2021

The periodontal inflamed surface area (PISA) has been proposed for assessment of the total periodontal inflammatory status in people with periodontitis. This study was performed to investigate the associations of periodontopathic bacteria and candida with PISA in older people. We enrolled 100 patients aged ≥ 60 years who visited Hiroshima University Hospital. PISA and periodontal epithelial surface area (PESA) were calculated in each patient. Oral rinse samples were collected for DNA extraction. Periodontopathic bacteria and candida were detected by polymerase chain reaction. The mean values of PISA and PESA were significantly greater in T.forsythia-positive patients than in T.forsythia-negative patients. T.forsythia/C. albicans double-positive patients exhibited significantly greater PISA values than did non-double-positive patients. Additionally, PISA values were significantly greater in T. forsythia//T. denticola/C. albicans triple-positive patients than in T. forsythia//T. denticola/C. albicans non-triple-positive patients (p = 0.02). Propensity score-matching was performed between periodontopathic bacteria-positive and -negative patients using propensity scores generated from clinical factors. Importantly, T.forsythia/T. denticola double-positive patients exhibited significantly greater PISA values than non-double-positive patients among 72 propensity score-matched patients. Our preliminary results highlight the importance of the presence of T.forsythia and T. denticola for periodontal inflammation severity in older Japanese people.
Promoting the Diversity, Equity, and Inclusion in Organic Chemistry Education through Undergraduate Research Experiences at WSSU
Authors: Guo Fenghai , Young Jayla , Deese Nichele , Pickens-Flynn Ti’Bran , Sellers Dustin , Perkins Dexter , Yakubu Mamudu
Published: August 2021

Undergraduate research is well recognized as an effective high-impact educational practice associated with student success in higher education. Actively engaging students in research experiences is considered as one of the several high-impact practices by many agencies including the American Chemical Society. Developing and maintaining an active undergraduate research program benefits both the faculty and students especially those from under-represented minority groups (URM). The infusion of research experiences into undergraduate curriculum enables students from all backgrounds to develop independent critical thinking skills, written and oral communications skills that are very important for successful careers in “STEM” area. Several strategies and activities such as a Peer Mentoring Program (PMP), funded research activities, the infusion of research into organic chemistry labs, undergraduate professional development, research group meetings, presentations at regional/national conferences, and publishing as co-authors on peer-review papers are vital in creating a welcoming research group that promotes the diversity, equity, and inclusion in organic chemistry education. The experiences working on funded research projects, presenting their research data at conferences and publishing papers as co-authors will greatly increase the under-represented minority (URM) students’ chance in landing a job or getting admitted into graduate/professional programs in STEM area.
“There Isn’t Really Anything around Here…”: Autism, Education and the Experience of Families Living in Rural Coastal England
Authors: Preece David , Lessner Lištiaková Ivana
Published: August 2021

Autism affects over 2% of the school population in England. Education has proven to be an effective intervention strategy that improves the quality of life of children with autism and their families. However, governmental austerity policies have increased disadvantage in coastal areas of England with a detrimental impact on people with disabilities. This qualitative study explored the lives of families living with autism in rural coastal England. Mothers, fathers, grandparents and young people from 21 families living with autism in West Norfolk and Cornwall shared their experience through semi-structured interviews that were conducted in early 2019. Families identified positive and negative aspects of living in these areas, including barriers preventing access to and inclusion in education. Barriers were related to poor infrastructure, sparse specialised services (resulting in diagnostic delay and difficulties), limited autism awareness, lack of trained professionals, and the impact of austerity across health, social care and education. Families’ struggles are amplified by the intersectionality of (a) autism-specific needs, (b) physical distance and small-community life related to rurality and (c) the seasonal and peripheral nature of coastal life. Access to education for children with autism in rural coastal areas of England could be improved by acknowledging and addressing the intersecting factors intensifying their marginalisation.