bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic Management of Early Childhood Caries in Thailand: A Critical Overview
Authors: Sitthisettapong Thanya , Tasanarong Parinda , Phantumvanit Prathip
Published: June 2021

The aim of this report was to advocate early childhood caries (ECC) and share strategic management in Thailand, despite over two decades of free Universal Health Coverage including oral healthcare. The recent Thai national oral health survey in 2017 indicates the very high prevalence of ECC, with an average of three carious teeth affected in 53% of 3-year-old children. This is despite the efforts of the Ministry of Public Health that has launched several interventional programs ranging from an upstream policy that prohibits sugar additions in baby formula milk to downstream remediations such as advocating and encouraging toothbrushing with fluoride toothpastes. Nevertheless, ECC is strongly predicated by other key factors including the family and community commitment and participation, as embodied in the current World Health Organization guidelines. These encompass three different tiers of community-level prevention: primary, secondary, and tertiary. Accordingly, the following strategies for ECC management in Thailand should be based at primary care clusters (PCC) in sub-district health centers, with the assistance of inter-professional health teams. These include community education on the importance of deciduous teeth and effective toothbrushing with fluoride toothpaste (primary prevention), regular examination and detection of ECC lesions and early intervention (secondary prevention), insertion of non-invasive preventive restorations using cost-effective atraumatic restorative treatment (ART) or simplified and modified ART (SMART) (tertiary prevention), and, finally, effective follow-up and monitoring systems. It is anticipated that this triple tier approach to ECC management will improve not only the oral health but also the overall children's health.
Towards a Blockchain-Based Multi-UAV Surveillance System
Authors: Santos De Campos Mário Gabriel , Chanel Caroline P. C. , Chauffaut Corentin , Lacan Jérôme
Published: June 2021

This study describes a blockchain-based multi-unmanned aerial vehicle (multi-UAV) surveillance framework that enables UAV coordination and financial exchange between system users. The objective of the system is to allow a set of Points-Of-Interest (POI) to be surveyed by a set of autonomous UAVs that cooperate to minimize the time between successive visits while exhibiting unpredictable behavior to prevent external agents from learning their movements. The system can be seen as a marketplace where the UAVs are the service providers and the POIs are the service seekers. This concept is based on a blockchain embedded on the UAVs and on some nodes on the ground, which has two main functionalities. The first one is to plan the route of each UAV through an efficient and computationally cheap game-theoretic decision algorithm implemented into a smart contract. The second one is to allow financial transactions between the system and its users, where the POIs subscribe to surveillance services by buying tokens. Conversely, the system pays the UAVs in tokens for the provided services. The first benchmarking experiments show that the IOTA blockchain is a potential blockchain candidate to be integrated in the UAV embedded system and that the chosen decentralized decision-making coordination strategy is efficient enough to fill the mission requirements while being computationally light.
Automated Quantitative Analysis of Blood Flow in Extracranial–Intracranial Arterial Bypass Based on Indocyanine Green Angiography
Authors: Jiang Zhuoyun , Lei Yu , Zhang Liqiong , Ni Wei , Gao Chao , Gao Xinjie , Yang Heng , Su Jiabin , Xiao Weiping , Yu Jinhua , Gu Yuxiang
Published: June 2021

Microvascular imaging based on indocyanine green is an important tool for surgeons who carry out extracranial–intracranial arterial bypass surgery. In terms of blood perfusion, indocyanine green images contain abundant information, which cannot be effectively interpreted by humans or currently available commercial software. In this paper, an automatic processing framework for perfusion assessments based on indocyanine green videos is proposed and consists of three stages, namely, vessel segmentation based on the UNet deep neural network, preoperative and postoperative image registrations based on scale-invariant transform features, and blood flow evaluation based on the Horn–Schunck optical flow method. This automatic processing flow can reveal the blood flow direction and intensity curve of any vessel, as well as the blood perfusion changes before and after an operation. Commercial software embedded in a microscope is used as a reference to evaluate the effectiveness of the algorithm in this study. A total of 120 patients from multiple centers were sampled for the study. For blood vessel segmentation, a Dice coefficient of 0.80 and a Jaccard coefficient of 0.73 were obtained. For image registration, the success rate was 81%. In preoperative and postoperative video processing, the coincidence rates between the automatic processing method and commercial software were 89 and 87%, respectively. The proposed framework not only achieves blood perfusion analysis similar to that of commercial software but also automatically detects and matches blood vessels before and after an operation, thus quantifying the flow direction and enabling surgeons to intuitively evaluate the perfusion changes caused by bypass surgery.
The Association Between French Veterinary Practice Characteristics and Their Revenues and Veterinarian's Time Use
Authors: Abdouttalib Ikram , Ndiaye Youba , Ferchiou Ahmed , Raboisson Didier , Lhermie Guillaume
Published: June 2021

The provision of healthcare by veterinarians consists of a blend of activities ensuring welfare for animals. It also contributes in the control of infectious diseases and food safety. In general practices, most of the activities generate incomes for veterinarians, notably acts (consultations, surgery, etc.) and sales (drugs, pet food, etc.). Increased size of veterinary practices and the arrival of corporate companies modify the veterinary landscape in many countries. In a context of rapid growth of the companion animal health market, the question of the profitability of veterinary activities is relevant. Indeed, beyond a certain threshold, veterinarians may be tempted to leave behind food-producing animals' acts and focus on companion animals' acts, which are generally recognized to be more profitable and more attractive for new generations of veterinarians. A survey was conducted in French veterinary mixed practices, and a regression analysis was used to quantify the relationships between the turnover and the characteristics of veterinary practices, the time to perform veterinary acts, and the characteristics of veterinarians. We found that the characteristics of veterinary practices are positively associated with the turnover and the price of acts, and that there was an association between the status of veterinarians (associate, collaborator, or employee) and the time required to perform companion animals' and food-producing animals' acts. The present study is the first study showing the association between the characteristics of veterinary practices and the turnover, by investigating the price of veterinary acts and the time required.
Comparing Blanket vs. Selective Dry Cow Treatment Approaches for Elimination and Prevention of Intramammary Infections During the Dry Period: A Systematic Review and Meta-Analysis
Authors: Kabera Fidèle , Roy Jean-Philippe , Afifi Mohamed , Godden Sandra , Stryhn Henrik , Sanchez Javier , Dufour Simon
Published: June 2021

A systematic review and a series of meta-analyses were conducted to investigate the efficacy of selective dry cow antimicrobial treatment (SDCT) (in which only infected quarters/cows were treated with an antimicrobial) compared with blanket dry cow treatment (BDCT) (all quarters/all cows received an antimicrobial, regardless of their infection status). A full detailed protocol was published before initiating this review. Studies reporting on the (1) proportion of untreated quarters or cows when using SDCT, (2) intramammary infection (IMI) incidence risk over the dry period, (3) IMI elimination risk, (4) post-calving IMI prevalence, (5) early lactation clinical mastitis incidence, or (6) subsequent lactation milk yield and somatic cell counts were considered eligible. Thirteen articles representing 12 controlled trials, whether randomized or not, were available for analyses. SDCT reduced the use of antimicrobials at dry off by 66% (95% CI: 49–80). There was no difference in the elimination of existing IMI at dry off, between SDCT and BDCT. Meta-regression showed that the risk of IMI incidence during the dry period, IMI risk at calving, early lactation clinical mastitis risk, and early lactation milk yield and somatic cell counts did not differ between SDCT and BDCT as long as an internal teat sealant (65% bismuth subnitrate) was administered to untreated healthy quarters/cows at dry off. For trials not using internal teat sealants, SDCT resulted in higher risk than BDCT of acquiring a new IMI during the dry period and of harboring an IMI at calving. Lines of evidence strongly support that SDCT would reduce the use of antimicrobials at dry off, without any detrimental effect on udder health or milk production during the 1st months of the subsequent lactation, if, and only if, internal teat sealants are used for healthy, untreated quarters/cows.
Biological Control May Fail on Pests Applied with High Doses of Insecticides: Effects of Sub-Lethal Concentrations of a Pyrethroid on the Host-Searching Behavior of the Aphid Parasitoid Aphidius colemani (Hymenoptera, Braconidae) on Aphid Pests
Authors: Alfaro-Tapia Armando , Alvarez-Baca Jeniffer K. , Fuentes-Contreras Eduardo , Figueroa Christian C.
Published: June 2021

The use of synthetic insecticides may cause failures in the biological control of insect pests due to undesired side effects on natural enemies and the rapid evolution of insecticide resistance in agroecosystems. Residues of neurotoxic insecticides can interfere with the recognition of chemical cues used by natural enemies to find pests. We investigated the effects of sub-lethal concentrations of the pyrethroid lambda-cyhalothrin on the interaction between the aphid parasitoid wasp Aphidius colemani and the peach potato aphid Myzus persicae. We studied changes in host-searching and oviposition behavior through laboratory bioassays when susceptible and kdr-resistant aphids are offered to parasitoid females, evaluating the effect of applying insecticides on the interacting species. The patch residence time, exploration, oviposition, and grooming were significantly disturbed when the parasitoids were offered resistant aphids sprayed with sub-lethal doses, but not when the parasitoids were offered susceptible M. persicae exposed to sub-lethal doses. We discuss how the effects of insecticides on parasitism behavior may result in failures of biological control if natural enemy populations are not adequately managed, particularly for the management of insecticide-resistant pest populations. Efforts to introduce biological control in integrated pest management (IPM) programs are also discussed.
Various Perspectives on Microbial Lipase Production Using Agri-Food Waste and Renewable Products
Authors: Szymczak Tomasz , Cybulska Justyna , Podleśny Marcin , Frąc Magdalena
Published: June 2021

Lipases are enzymes that catalyze various types of reactions and have versatile applications. Additionally, lipases are the most widely used class of enzymes in biotechnology and organic chemistry. Lipases can be produced by a wide range of organisms including animals, plants and microorganisms. Microbial lipases are more stable, they have substrate specificity and a lower production cost as compared to other sources of these enzymes. Although commercially available lipases are widely used as biocatalysts, there are still many challenges concerning the production of microbial lipases with the use of renewable sources as the main component of microbial growth medium such as straw, bran, oil cakes and industrial effluents. Submerged fermentation (SmF) and solid-state fermentation (SSF) are the two important technologies for the production of lipases by microorganisms. Therefore, this review focuses on microbial lipases, especially their function, specificity, types and technology production, including the use of renewable agro-industrial residues and waste materials.
Chromosomal Instability at Fragile Sites in Blue Foxes, Silver Foxes, and Their Interspecific Hybrids
Authors: Kuchta-Gładysz Marta , Wójcik Ewa , Grzesiakowska Anna , Rymuza Katarzyna , Szeleszczuk Olga
Published: June 2021

A cytogenetic assay based on fragile sites (FS) enables the identification of breaks, chromatid gaps, and deletions. In healthy individuals, the number of these instabilities remains low. Genome stability in these species is affected by Robertsonian translocations in the karyotype of the blue fox and by B chromosomes in the silver fox. The aims of the study were to characterise the karyotype of blue foxes, silver foxes, and their hybrids and to identify chromosomal fragile sites used to evaluate genome stability. The diploid number of A chromosomes in blue foxes ranged from 48 to 50, while the number of B chromosomes in silver foxes varied from one to four, with a constant number of A chromosomes (2n = 34). In interspecific hybrids, both types of karyotypic variation were identified, with the diploid number of A chromosomes ranging from 40 to 44 and the number of B chromosomes varying from 0 to 3. The mean frequency of FS in foxes was 4.06 ± 0.19: 4.61 ± 0.37 in blue foxes, 3.46 ± 0.28 in silver foxes, and 4.12 ± 0.22 in hybrids. A relationship was identified between an increased number of A chromosomes in the karyotype of the hybrids and the frequency of chromosomal breaks. The FS assay was used as a biomarker for the evaluation of genomic stability in the animals in the study.
Seroprevalence and Associated Risk Factors of Bovine Brucellosis in District Gujranwala, Punjab, Pakistan
Authors: Khan Muhammad Rashid , Rehman Abdul , Khalid Salman , Ahmad Mansur Ud Din , Avais Muhammad , Sarwar Mobeen , Awan Farhat Nazir , Melzer Falk , Neubauer Heinrich , Jamil Tariq
Published: June 2021

Bovine brucellosis is a contagious zoonotic disease that causes economic losses through abortion and infertility. A cross-sectional study was designed to determine the seroprevalence and associated risk factors of bovine brucellosis in district Gujranwala of Punjab, Pakistan. A total of 220 bovine sera (112 from buffaloes, 108 from cattle) from 46 unvaccinated herds were collected. Parallel testing by the Rose Bengal Plate Test (RBPT) and Indirect Enzyme-linked Immunosorbent Assay (I-ELISA) showed a 58.7% (27/46) herd-level and 22.7% (50/220) animal-level seroprevalence. Seroprevalence was higher (p < 0.001, OR = 7.62) in adult animals (37.2%) compared to younger animals (4.9%). A herd size of >10 animals (p = 0.021, OR = 7.83), less housing space (p = 0.037, OR = 6.39) and history of abortion at the farm (p = 0.023, OR = 5.6) were found as risk factors associated with the seropositivity of brucellosis. There was a substantial agreement between the RBPT and I-ELISA results (Cohen’s kappa coefficient (κ) = 64.16, percent agreement = 89.5%). In conclusion, a relatively higher seroprevalence was found compared to the previous reports from the country. Standardization and validation of the advanced diagnostic tests would be needed. Biosecurity, personal protection, quarantine measures and routine screening of animals at the farm level and disease awareness programs and consumption of pasteurized milk in the human population will be helpful in preventing the transmission/zoonosis of the disease.
Measurement of Selected Renal Biochemical Parameters in Healthy Adult Donkeys Considering the Influence of Gender, Age and Blood Freezing
Authors: Frączkowska Kaja , Trzebuniak Zuzanna , Żak Agnieszka , Siwińska Natalia
Published: June 2021

The reference values of the serum and urine biochemical parameters have not been well-studied in donkeys. This study aimed to assess the normal values of the selected renal biomarkers, such as: serum creatinine, blood urea nitrogen (BUN), albumin, total protein (TP), electrolytes and symmetric dimethylarginine (SDMA), urine protein concentration (UPC), urine protein/creatinine ratio (UPCR), the urine gamma-glutamyl transferase (GGTP)-to-creatinine ratio, serum creatinine-to-urine creatinine ratio (sCr/uCr), serum BUN-to-serum creatinine ratio (sBUN/sCr) and UPC-to-TP ratio, as well as the fractional electrolyte excretion of sodium (FENa) and potassium (FEK) in donkeys. The effects of age, gender and deep freezing of the serum material were investigated. Sixty-five healthy adult donkeys were involved in this study. The results showed higher BUN and TP values and lower albumin, UPCR, FENa and FEK levels in donkeys when compared to the reference values in horses. A significant gender relationship for creatinine and BUN was found. Age influenced the values of albumin, TP, potassium and chlorine. Potassium, sodium and SDMA did not show significant concentration changes after freezing. The study results demonstrated that horse reference range values for some parameters cannot be applied to donkey samples. Only a few of the serum parameters were not affected by freezing, and this should be taken into account when storing biological materials.
Evaluation of a Product Derived from Porcine Plasma Protein and a Yeast Product with Similar Biological Activity in Diets of Growing Broilers
Authors: Waldroup Park , Vaughn Mathew , McNaughton James
Published: June 2021

The post-hatch period of a broiler is an integral point in their development and for the programming of musculoskeletal and immune cells. Therefore, the efficacy of two bioactive protein products, betaGRO® (BG) and celluTEIN® (CT) to impact post-hatch and lifelong development was evaluated. Birds were grown under a low stress environment using clean wood shavings litter and a high stress environment with used litter from a commercial farm that had suffered high mortality. Each additive was fed at 300 g/ton from day 1–14 and 50 g/ton from day 15–42. Growing birds in the high stress environment had a negative impact on performance (p < 0.05); however, addition of either BG or CT successfully mitigated the detriments of the high stress environment (p < 0.05), and in many cases, the performance was equal to or better than the performance of birds on the control diet in the low stress environment. Birds fed BG and CT experienced improvements in 42-day feed conversion, and were more uniform than birds grown consuming the control diet (p < 0.05). Mortality of birds in the high stress environment was reduced by addition of BG or CT (p < 0.05). Addition of BG and CT resulted in improvements in carcass and breast meat yield (p < 0.05). Together, these data suggest that BG and CT can be used interchangeably to improve broiler health and performance.
An Analysis of the Infections and Determination of Empiric Antibiotic Therapy in Cats and Dogs with Cancer-Associated Infections
Authors: Curran Katie , Leeper Haley , O’Reilly Kathy , Jacob Joelle , Bermudez Luiz E.
Published: June 2021

Cancer patients commonly develop infectious complications over the course of the disease. One thousand patients receiving treatment for an oncologic disease at a single veterinary teaching hospital were retrospectively reviewed for concurrent infections. A total of 153 confirmed bacterial infections were identified, 82 of which were abscesses or wounds, 13 of which were respiratory infections, 3 of which were ear infections, and 55 of which were urinary tract infections. It was observed that the majority of the infections were caused by bacteria that are normally associated with that specific site location. Escherichia coli was the most common pathogen linked to infections in general, but Staphylococcus pseudintermedius was a frequently identified pathogen associated with wound infections. The susceptibility to diverse antimicrobials varied with the site of infection. Eleven cases (7.1%) were caused by opportunistic infections of the site, and E. coli and Pseudomonas aeruginosa were the pathogens isolated. Those bacteria were resistant to many antibiotics but showed susceptibility to aminoglycosides, imipenem, quinolones, and polymyxin B. In conclusion, veterinary patients with cancer or those under treatment for tumors develop infections by commonly encountered bacteria in the different sites of the body, with a susceptibility to antibiotics that is not out of line from what is expected. A small subset of cases developed opportunistic infections, with microbes that were more resistant to many classes of antibiotics.
A Leaf Extract of Harrisonia abyssinica Ameliorates Neurobehavioral, Histological and Biochemical Changes in the Hippocampus of Rats with Aluminum Chloride-Induced Alzheimer’s Disease
Authors: Anwar Hend Mohamed , Georgy Gehan S. , Hamad Sherin Ramadan , Badr Wafaa K. , El Raey Mohamed A. , Abdelfattah Mohamed A. O. , Wink Michael , Sobeh Mansour
Published: June 2021

Aluminum (Al) is an omnipresent mineral element in the environment. The brain is a central target of Al toxicity, being highly susceptible to oxidative damage. Therefore, recognition of drugs or natural products that guard against Al-mediated neuronal cell death is a powerful strategy for prevention and treatment of neurodegenerative disorders. This work aimed to explore the potential of a leaf extract from Harrisonia abyssinica to modulate the neurobehavioral, biochemical and histopathological activities induced experimentally by Al in vivo. Rats subjected to Al treatment displayed a reduction in learning and memory performance in a passive avoidance test accompanied by a decrease in the hippocampal monoamine and glutamate levels in addition to suppression of Bcl2 expression. Moreover, malondialdehyde (MDA), inflammatory markers (TNF-α, IL-1β), apoptotic markers (caspase-3 and expression of Bax) and extracellular regulated kinase (ERK1/2) levels were elevated along with acetylcholinesterase (AChE) activity, histological changes and marked deposition of amyloid β plaques in the hippocampus region of the brain tissues being observed in Al-treated animals. Concomitant administration of the high dose of H. abyssinica (200 mg/kg b.w.) restored nearly normal levels of all parameters measured, rather than the low dose (100 mg/kg b.w.), an effect that was comparable to the reference drug (rivastigmine). Molecular docking revealed the appropriate potential of the extract components to block the active site of AChE and ERK2. In conclusion, H. abyssinica leaf extract conferred neuroprotection against Al-induced neurotoxic effects, most likely due to its high phenolic and flavonoid content.
Effect of Photofunctionalization with 6 W or 85 W UVC on the Degree of Wettability of RBM Titanium in Relation to the Irradiation Time
Authors: Sanchez-Perez Arturo , Cano-Millá Nuria , Moya Villaescusa María José , Montoya Carralero José María , Navarro Cuellar Carlos
Published: June 2021

Photoactivation with ultraviolet C light can reverse the effects derived from biological ageing by restoring a hydrophilic surface. Ten titanium discs were randomly divided into three groups: a control group, a 6 W group, and an 85 W group. A drop of double-distilled, deionized, and sterile 10 µL water was applied to each of the discs. Each disc was immediately photographed in a standardized and perpendicular manner. Measurements were taken based on the irradiation time (15, 30, 60, and 120 min). UVC irradiation improved the control values in both groups. There was no difference in its effect between the 6 W group and the other groups during the first 30 min. However, after 60 min and up to 120 min, 85 W had a significantly stronger effect. The contact angles with the 85 W ultraviolet light source at 60 and 120 min were 19.43° and 31.41°, respectively, whereas the contact angles for the 6 W UVC source were 73.8° and 61.45°. Power proved to be the most important factor, and the best hydrophilicity result was obtained with a power of 85 W for 60 min at a wavelength of 254 nm.
Real Driving Emission Calibration—Review of Current Validation Methods against the Background of Future Emission Legislation
Authors: Claßen Johannes , Krysmon Sascha , Dorscheidt Frank , Sterlepper Stefan , Pischinger Stefan
Published: June 2021

Reducing air pollution caused by emissions from road traffic, especially in urban areas, is an important goal of legislators and the automotive industry. The introduction of so-called “Real Driving Emission” (RDE) tests for the homologation of vehicles with internal combustion engines according to the EU6d legislation was a fundamental milestone for vehicle and powertrain development. Due to the introduction of non-reproducible on-road emission tests with “Portable Emission Measurement Systems” (PEMS) in addition to the standardized emission tests on chassis dynamometers, emission aftertreatment development and validation has become significantly more complex. For explicit proof of compliance with the emission and fuel consumption regulations, the legislators continue to require the “Worldwide Harmonized Light Duty Vehicle Test Cycle” (WLTC) on a chassis dynamometer. For calibration purposes, also various RDE profiles are conducted on the chassis dynamometer. However, the combination of precisely defined driving profiles on the chassis dynamometer and the dynamics-limiting boundary conditions in PEMS tests on the road still lead to discrepancies between the certified test results and the real vehicle behavior. The expected future emissions standards to replace EU6d will therefore force even more realistic RDE tests. This is to be achieved by significantly extending the permissible RDE test boundary conditions, such as giving more weight to the urban section of an RDE test. In addition, the introduction of limit values for previously unregulated pollutants such as nitrogen dioxide (NO2), nitrous oxide (N2O), ammonia (NH3) and formaldehyde (CH2O) is being considered. Furthermore, the particle number (for diameters of solid particles > 10 nm: PN10), the methane (CH4) emissions and emissions of non-methane organic gases (NMOG) shall be limited and must be tested. To simplify the test procedure in the long term, the abandonment of predefined chassis dyno emission tests to determine the pollutant emission behavior is under discussion. Against this background, current testing, validation, and development methods are reviewed in this paper. New challenges and necessary adaptations of current approaches are discussed and presented to illustrate the need to consider future regulatory requirements in today’s approaches. Conclusions are drawn and suggestions for a robust RDE validation procedure are formulated.
Stereo-DIC Measurements of a Vibrating Bladed Disk: In-Depth Analysis of Full-Field Deformed Shapes
Authors: Neri Paolo , Paoli Alessandro , Santus Ciro
Published: June 2021

Vibration measurements of turbomachinery components are of utmost importance to characterize the dynamic behavior of rotating machines, thus preventing undesired operating conditions. Local techniques such as strain gauges or laser Doppler vibrometers are usually adopted to collect vibration data. However, these approaches provide single-point and generally 1D measurements. The present work proposes an optical technique, which uses two low-speed cameras, a multimedia projector, and three-dimensional digital image correlation (3D-DIC) to provide full-field measurements of a bladed disk undergoing harmonic response analysis (i.e., pure sinusoidal excitation) in the kHz range. The proposed approach exploits a downsampling strategy to overcome the limitations introduced by low-speed cameras. The developed experimental setup was used to measure the response of a bladed disk subjected to an excitation frequency above 6 kHz, providing a deep insight in the deformed shapes, in terms of amplitude and phase distributions, which could not be feasible with single-point sensors. Results demonstrated the system’s effectiveness in measuring amplitudes of few microns, also evidencing blade mistuning effects. A deeper insight into the deformed shape analysis was provided by considering the phase maps on the entire blisk geometry, and phase variation lines were observed on the blades for high excitation frequency.
A Review on Medical Textual Question Answering Systems Based on Deep Learning Approaches
Authors: Mutabazi Emmanuel , Ni Jianjun , Tang Guangyi , Cao Weidong
Published: June 2021

The advent of Question Answering Systems (QASs) has been envisaged as a promising solution and an efficient approach for retrieving significant information over the Internet. A considerable amount of research work has focused on open domain QASs based on deep learning techniques due to the availability of data sources. However, the medical domain receives less attention due to the shortage of medical datasets. Although Electronic Health Records (EHRs) are empowering the field of Medical Question-Answering (MQA) by providing medical information to answer user questions, the gap is still large in the medical domain, especially for textual-based sources. Therefore, in this study, the medical textual question-answering systems based on deep learning approaches were reviewed, and recent architectures of MQA systems were thoroughly explored. Furthermore, an in-depth analysis of deep learning approaches used in different MQA system tasks was provided. Finally, the different critical challenges posed by MQA systems were highlighted, and recommendations to effectively address them in forthcoming MQA systems were given out.
A Simple New Method for Calculating Precipitation Scavenging Effect on Particulate Matter: Based on Five-Year Data in Eastern China
Authors: Zhou Bin , Liu Duanyang , Yan Wenlian
Published: June 2021

A “rain-only” method is proposed to find out the precipitation effect on particle aerosol removal from the atmosphere, and this method is not only unique and novel but also very simple and can be easily adapted to predict aerosol particle scavenging over any region across the world irrespective of the topographical, orographical, and climatic features. By using this simple method, the influences of the rain intensity and particle mass concentration on the aerosol scavenging efficiency are discussed. The results show that a higher concentration, a higher rain intensity, and a larger particle size lead to a higher scavenging efficiency and a higher scavenging rate. The greater the rain intensity, the higher the scavenging efficiency. The scavenging efficiency of PM10 by precipitation is better than that of PM2.5. When the rain intensity is 10 mm h−1, the scavenging efficiency of PM2.5 reaches 5.1 μg m−3 h−1, and the scavenging efficiency of PM10 reaches 15.8 μg m−3 h−1. The scavenging rate increases faster when accumulative precipitation is below 15 mm. The scavenging rate has obvious monthly variation, and the scavenging rate of coastal areas is less than that of inland Jiangsu. The growth of the particle mass concentration after precipitation is divided into two stages: the rapid growth stage after precipitation ends, and the slow growth stage about 24 h after precipitation ends.
Metformin Targets Foxo1 to Control Glucose Homeostasis
Authors: Guo Xiaoqin , Li Xiaopeng , Yang Wanbao , Liao Wang , Shen James Zheng , Ai Weiqi , Pan Quan , Sun Yuxiang , Zhang Kebin , Zhang Rui , Qiu Yuyang , Dai Qian , Zheng Hongting , Guo Shaodong
Published: June 2021

Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus (T2D). Metformin exerts its glucose-lowering effect primarily through decreasing hepatic glucose production (HGP). However, the precise molecular mechanisms of metformin remain unclear due to supra-pharmacological concentration of metformin used in the study. Here, we investigated the role of Foxo1 in metformin action in control of glucose homeostasis and its mechanism via the transcription factor Foxo1 in mice, as well as the clinical relevance with co-treatment of aspirin. We showed that metformin inhibits HGP and blood glucose in a Foxo1-dependent manner. Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA→Foxo1 signaling pathway. In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP. We further showed that metformin attenuates PKA activity, decreases Foxo1-S273 phosphorylation, and improves glucose homeostasis in diet-induced obese mice. We also provided evidence that salicylate suppresses HGP and blood glucose through the PKA→Foxo1 signaling pathway, but it has no further additive improvement with metformin in control of glucose homeostasis. Our study demonstrates that metformin inhibits HGP through PKA-regulated transcription factor Foxo1 and its S273 phosphorylation.
The Use of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Evaluation of Blood-Brain Barrier Disruption in Traumatic Brain Injury: What Is the Evidence?
Authors: Oh Sung Suk , Lee Eun-Hee , Kim Jong-Hoon , Seo Young Beom , Choo Yoo Jin , Park Juyoung , Chang Min Cheol
Published: June 2021

(1) Background: Blood brain barrier (BBB) disruption following traumatic brain injury (TBI) results in a secondary injury by facilitating the entry of neurotoxins to the brain parenchyma without filtration. In the current paper, we aimed to review previous dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies to evaluate the occurrence of BBB disruption after TBI. (2) Methods: In electronic databases (PubMed, Scopus, Embase, and the Cochrane Library), we searched for the following keywords: dynamic contrast-enhanced OR DCE AND brain injury. We included studies in which BBB disruption was evaluated in patients with TBI using DCE-MRI. (3) Results: Four articles were included in this review. To assess BBB disruption, linear fit, Tofts, extended Tofts, or Patlak models were used. KTrans and ve were increased, and the values of vp were decreased in the cerebral cortex and predilection sites for diffusion axonal injury. These findings are indicative of BBB disruption following TBI. (4) Conclusions: Our analysis supports the possibility of utilizing DCE-MRI for the detection of BBB disruption following TBI.
DNA Methylation Markers from Negative Surgical Margins Can Predict Recurrence of Oral Squamous Cell Carcinoma
Authors: Sorroche Bruna Pereira , Talukdar Fazlur Rahman , Lima Sheila Coelho Soares , Melendez Matias Eliseo , de Carvalho Ana Carolina , de Almeida Gisele Caravina , De Marchi Pedro , Lopes Monique , Ribeiro Pinto Luis Felipe , Carvalho André Lopes , Herceg Zdenko , Arantes Lidia Maria Rebolho Batista
Published: June 2021

The identification of molecular markers in negative surgical margins of oral squamous cell carcinoma (OSCC) might help in identifying residual molecular aberrations, and potentially improve the prediction of prognosis. We performed an Infinium MethylationEPIC BeadChip array on 32 negative surgical margins stratified based on the status of tumor recurrence in order to identify recurrence-specific aberrant DNA methylation (DNAme) markers. We identified 2512 recurrence-associated Differentially Methylated Positions (DMPs) and 392 Differentially Methylated Regions (DMRs) which were enriched in cell signaling and cancer-related pathways. A set of 14-CpG markers was able to discriminate recurrent and non-recurrent cases with high specificity and sensitivity rates (AUC 0.98, p = 3 × 10−6; CI: 0.95–1). A risk score based on the 14-CpG marker panel was applied, with cases classified within higher risk scores exhibiting poorer survival. The results were replicated using tumor-adjacent normal HNSCC samples from The Cancer Genome Atlas (TCGA). We identified residual DNAme aberrations in the negative surgical margins of OSCC patients, which could be informative for patient management by improving therapeutic intervention. This study proposes a novel DNAme-based 14-CpG marker panel as a promising predictor for tumor recurrence, which might contribute to improved decision-making for the personalized treatment of OSCC cases.
Multiparametric Integrated 18F-FDG PET/MRI-Based Radiomics for Breast Cancer Phenotyping and Tumor Decoding
Authors: Umutlu Lale , Kirchner Julian , Bruckmann Nils Martin , Morawitz Janna , Antoch Gerald , Ingenwerth Marc , Bittner Ann-Kathrin , Hoffmann Oliver , Haubold Johannes , Grueneisen Johannes , Quick Harald H. , Rischpler Christoph , Herrmann Ken , Gibbs Peter , Pinker-Domenig Katja
Published: June 2021

Background: This study investigated the performance of simultaneous 18F-FDG PET/MRI of the breast as a platform for comprehensive radiomics analysis for breast cancer subtype analysis, hormone receptor status, proliferation rate and lymphonodular and distant metastatic spread. Methods: One hundred and twenty-four patients underwent simultaneous 18F-FDG PET/MRI. Breast tumors were segmented and radiomic features were extracted utilizing CERR software following the IBSI guidelines. LASSO regression was employed to select the most important radiomics features prior to model development. Five-fold cross validation was then utilized alongside support vector machines, resulting in predictive models for various combinations of imaging data series. Results: The highest AUC and accuracy for differentiation between luminal A and B was achieved by all MR sequences (AUC 0.98; accuracy 97.3). The best results in AUC for prediction of hormone receptor status and proliferation rate were found based on all MR and PET data (ER AUC 0.87, PR AUC 0.88, Ki-67 AUC 0.997). PET provided the best determination of grading (AUC 0.71), while all MR and PET analyses yielded the best results for lymphonodular and distant metastatic spread (0.81 and 0.99, respectively). Conclusion: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for breast cancer phenotyping and tumor decoding, utilizing the perks of simultaneously acquired morphologic, functional and metabolic data.
Frequency, Treatment and Outcome of Immune-Related Toxicities in Patients with Immune-Checkpoint Inhibitors for Advanced Melanoma: Results from an Institutional Database Analysis
Authors: Dimitriou Florentia , Staeger Ramon , Ak Melike , Maissen Matias , Kudura Ken , Barysch Marjam J. , Levesque Mitchell P. , Cheng Phil F. , Dummer Reinhard , Mangana Joanna
Published: June 2021

Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs), which may result in treatment discontinuation. We sought to describe the onset, frequency, and kinetics of irAEs in melanoma patients in a real-life setting and to further investigate the prognostic role of irAEs in treatment outcomes. In this retrospective single-center cohort study, we included 249 melanoma patients. Onset, grade, and resolution of irAEs and their treatment were analyzed. A total of 191 (74.6%) patients in the non-adjuvant and 65 (25.3%) in the adjuvant treatment setting were identified. In the non-adjuvant setting, 29 patients (59.2%) with anti-CTLA4, 43 (58.1%) with anti-PD1, and 54 (79.4%) with anti-PD1/anti-CTLA4 experienced some grade of irAE and these had an improved outcome. In the adjuvant setting, the frequency of irAEs was 84.6% in anti-CTLA4 and 63.5% in anti-PD1, but no correlation with disease relapse was observed. Patients with underlying autoimmune conditions have a risk of disease exacerbation. Immunomodulatory agents had no impact on treatment efficacy. IrAEs are correlated with increased treatment efficacy in the non-adjuvant setting. Application of steroids and immunomodulatory agents, such as anti-TNF-alpha or anti-IL6, did not affect ICI efficacy. These data support irAEs as possible prognostic markers for ICI treatment.
Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome
Authors: Mautone Lorenza , Ferravante Carlo , Tortora Anna , Tarallo Roberta , Giurato Giorgio , Weisz Alessandro , Vitale Mario
Published: June 2021

Integrins are cell-extracellular matrix adhesion molecules whose expression level undergoes quantitative changes upon neoplastic transformation and are considered functionally related to the development of cancer metastasis. We analyzed the largest mRNA-seq dataset available to determine the expression pattern of integrin family subunits in papillary thyroid carcinomas (PTC). ITGA2, 3, 6, V, and ITGB1 integrin subunits were overexpressed in PTC compared to normal thyroid tissue. The PTC histology variants “classical” and “tall cell” displayed a similar integrin expression profile with a higher level of ITGA3, ITGAV, and ITGB1, which differed from that of the “follicular” variant. Interestingly, compared to RAS mutations, BRAFV600E mutation was associated with a significantly higher expression of integrins. Some integrin subunits were associated with advanced disease stage, lymph node metastasis, extrathyroidal extension, and high-risk groups. Among them, ITGA3 expression displayed the highest correlation with advanced disease and was associated with a negative prognosis. In vitro scratch assay and Matrigel invasion assay in two different PTC cell lines confirmed α3β1 role in cell motility and invasion, supporting its involvement during tumor progression. These results demonstrate the existence of a PTC-specific integrin expression signature correlated to histopathology, specific driver gene mutations, and aggressiveness of the disease.
PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy
Authors: Widjaja Liam , Werner Rudolf A. , Ross Tobias L. , Bengel Frank M. , Derlin Thorsten
Published: June 2021

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.
Proposal of a New Prognostic Model for Differentiated Thyroid Cancer with TERT Promoter Mutations
Authors: Park Jun , Lee Sungjoo , Park Jiyun , Park Hyunju , Ki Chang-Seok , Oh Young-Lyun , Shin Jung-Hee , Kim Jee-Soo , Kim Sun-Wook , Chung Jae-Hoon , Kim Kyunga , Kim Tae-Hyuk
Published: June 2021

The role of telomerase reverse transcriptase (TERT) promoter mutations as an independent poor prognostic factor in differentiated thyroid cancer (DTC) patients is well known, but there is no prognostic system that combines the TERT promoter mutation status with tumor-node-metastasis (TNM) stage to predict cancer-specific survival (CSS). A total of 393 patients with pathologically confirmed DTC after thyroidectomy were enrolled. After incorporating wild-type TERT and mutant TERT with stages I, II, and III/IV of the AJCC TNM system 8th edition (TNM-8), we generated six combinations and calculated 10-year and 15-year CSS and adjusted hazard ratios (HRs) for cancer-related death using Cox regression. Then, a new mortality prediction model termed TNM-8T was derived based on the CSS and HR of each combination in the four groups. Of the 393 patients, there were 27 (6.9%) thyroid cancer-related deaths during a median follow-up of 14 years. Patients with a more advanced stage had a lower survival rate (10-year CSS for TNM-8T stage 1, 2, 3, and 4: 98.7%, 93.5%, 77.3%, and 63.0%, respectively; p < 0.001). TNM-8T showed a better spread of CSS (p < 0.001) than TNM-8 (p = 0.002) in the adjusted survival curves. The C-index for mortality risk predictability was 0.880 (95% CI, 0.665–0.957) in TNM-8T and 0.827 (95% CI, 0.622–0.930) in TNM-8 (p < 0.001). TNM-8T, a new prognostic system that incorporates the TERT mutational status into TNM-8, showed superior predictability to TNM-8 in the long-term survival of DTC patients.
Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Esagian Stepan M. , Kakos Christos D. , Giorgakis Emmanouil , Burdine Lyle , Barreto J. Camilo , Mavros Michail N.
Published: June 2021

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.