bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgically treated gastric melanoma of unknown primary: A case report from a 10‐year survivor
Authors: Takahashi Toshiyuki , Sugita Shintaro , Kagaya Hidetoshi , Morita Takayuki
Published: August 2020

We describe an extremely rare case of simultaneous double melanoma of the stomach with no other obvious primary source. The patient has survived for more than 12 years post‐complete gastrectomy. The patient was a woman in her seventies who was referred for anemia by another clinic. Esophagogastroscopy revealed an ulcerated gastric tumor that was diagnosed as a gastrointestinal stromal tumor (GIST) by endoscopic biopsy. She was admitted to our hospital for further examination and treatment. Gastroscopy at our institution revealed two submucosal tumors in the gastric wall. Since no metastatic lesions were detected after systemic exploration, multiple GIST of the stomach was diagnosed, and a total gastrectomy was performed. Malignant melanoma was diagnosed in both lesions by a histopathological study of the resected stomach. The patient's postoperative progress was good, and thorough examination of the skin did not result in the discovery of any systemic neoplastic lesions which could be regarded as the source for the primary tumor. No anticancer treatments were used. The patient has survived, with no recurrence for over ten years postsurgery. Strong evidence is presented in this case for the diagnosis and treatment of gastric malignant melanoma.
A case of Langerhans cell sarcoma on the scalp: Whole‐exome sequencing reveals a role of ultraviolet in the pathogenesis
Authors: Katsuragawa Hiroyuki , Yamada Yosuke , Ishida Yoshihiro , Kaku Yo , Fujimoto Masakazu , Kataoka Tatsuki R. , Haga Hironori
Published: August 2020

Langerhans cell sarcoma (LCS) is a high‐grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway‐related genes, CDKN2A and TP53 have been reported. Here we present a 70‐year‐old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD‐L1, and the Ki‐67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole‐exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion of CDKN2A and TP53 mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD‐L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS.
Artificial Neural Network to Predict the Thermal Drawdown of Enhanced Geothermal System
Authors: Pandey S. N. , Singh M.
Published: August 2020

This work presents the prediction of thermal drawdown of an enhanced geothermal system (EGS) using artificial neural network (ANN). A three-dimensional numerical model of EGS was developed to generate the training and testing data sets for ANN. We have performed a quantitative study of geothermal energy production for various injection operating conditions and reservoir fracture aperture. Input parameters for ANN include temperature, mass flux, pressure, and fracture transmissivity, while the production well temperature is the output parameter. The Levenberg–Marquardt back-propagation learning algorithm, the tan-sigmoid, and the linear transfer function were used for the ANN optimization. The best results were obtained with an ANN architecture composed of eight hidden layers and 20 neurons in the hidden layer, which made it possible to predict the production temperature with a satisfactory range (R2 > 0.99). An appropriate accuracy of the ANN model was obtained with a percentage error less than (± 4.5). The results from the numerical simulations suggest that fracture transmissivity has less effect on thermal drawdown than the injection mass flux and temperature. From our results, we confirm that ANN modeling may predict the thermal drawdown of an EGS system with high accuracy.
Use of Machine Learning and Data Analytics to Detect Downhole Abnormalities While Drilling Horizontal Wells, With Real Case Study
Authors: Alsaihati Ahmed , Elkatatny Salaheldin , Mahmoud Ahmed Abdulhamid , Abdulraheem Abdulazeez
Published: August 2020

The standard torque and drag (T&D) modeling programs have been extensively used in the oil and gas industry to predict and monitor the T&D forces. In the majority of cases, there has been variability in the accuracy between the pre-calculated (based on a T&D model) and actual T&D values, because of the dependence of the model’s predictability on guessed inputs (matching parameters) which may not be correctly predicted. Therefore, to have a reliable model, program users must alter the model inputs and mainly the friction coefficient to match the actual T&D. This, however, can conceal downhole conditions such as cutting beds, tight holes, and sticking tendencies. The objective of this study is to develop an intelligent machine to predict the continuous profile of the surface drilling torque to enable the detection of operational problems ahead of time. This paper details the development and evaluation of an intelligent system that could promote safer operation and extend the response time limit to prevent undesired events. Actual field data of Well-1, starting from the time of drilling a 5-7/8-in. horizontal section until 1 day prior to the stuck pipe incident, were used to train and test three models: random forest, artificial neural network, and functional network, with an 80/20 training-to-testing data ratio, to predict the surface drilling torque. The independent variables for the model are the drilling surface parameters, namely: flow rate (Q), hook load (HL), rate of penetration (ROP), rotary speed (RS), standpipe pressure (SPP), and weight-on-bit (WOB). The prediction capability of the models was evaluated in terms of correlation of coefficient (R) and average absolute error percentage (AAPE). The model with the highest R and lowest AAPE was selected to continue with the analysis to detect downhole abnormalities. The best-developed model was used to predict the surface drilling torque on the last day leading up to the incident in Well-1, which represents the normal and healthy trend. Then, the model was coupled with a multivariate metric distance called “Mahalanobis” to be used as a classification tool to measure how close an actual observation is to the predictive normal and healthy trend. Based on a pre-determined threshold, each actual observation was labeled “NORMAL” or “ANOMAL.” Well-2 with a stuck pipe incident was used to assess the capability of the developed system in detecting downhole abnormalities. The results showed that in Well-1, where a stuck pipe incident was reported, a continuous alarm was detected by the developed system 9 h before the drilling crew observed any abnormality, while the alarm was detected 7 h prior to any observation by the crew in Well-2. The developed intelligent system could help the drilling crew to detect downhole abnormalities in real-time, react, and take corrective action to mitigate the problem promptly.
Experiment and Field Application of Inhibitior Liquid in Spontaneous Combustion Process of Coal Based on Thermogravimetric Analysis
Authors: Du Wenzhou , Niu Kuo , Wang Houwang , Zhang Yansong , Song Haizhou
Published: August 2020

An effective way to slow down the process of coal spontaneous combustion (CSC) is by injecting inhibitor liquid into the coal body. Research on inhibitors has achieved good effects, but many have occurred only under laboratory conditions; for applications in actual underground coal mines, there may be many limitations. In this paper, MgCl2, CaCl2, and NH4H2PO4 are selected, and they are prepared as inhibitor liquids and injected into coal samples from three coal mines to obtain inhibitor coal samples. Industrial analysis (IA) and thermogravimetric analysis (TGA) of raw and inhibitor coal samples were carried out under laboratory conditions. Finally, MgCl2 was selected as the inhibitor to carry out a field test in a coal mine working face. The results show that the volatile content, fixed carbon content, and calorific value decrease and the ash content increases after injection of the inhibitor. NH4H2PO4 has the greatest influence on coal, which is more obvious in the Nantun coal samples. MgCl2 and CaCl2 have stronger inhibitory effects in the temperature range of 0–200 °C, and the inhibitory effects decrease in the high-temperature stage. This is due to the evaporation of water and the loss of active components under high temperature. The inhibitory effect of NH4H2PO4 at high temperature is stronger than those of MgCl2 and CaCl2. The CO concentration was significantly reduced after injection of the inhibitor liquid in an underground field, which delays the oxidation process of coal for approximately 10 days and greatly reduces the risk of CSC.
Investigation of the Structural, Optical, Electrical, and Dielectrical Properties of Aloe Vera Leaf Exudate
Authors: Hnawi Salma Kaotar , Nayad Abdallah , Aitdads Hoda , Agdad Abdelali , Afqir Mohamed , Nkhaili Lahcen , El Firdoussi Larbi , Oueriagli Amane , Ait Ali Mustapha
Published: August 2020

Organic solar cells are considered to be the promising solar technology for the coming year because of their ease of manufacture. In the present study, the Aloe Latex as a yellow orange Solid (ALS) collected from the leaves of Aloe Vera plant (aloe barbadensis miller) was used as a natural and cheap sensitizer thin film. The ALS powder was analyzed using X-ray diffraction,UHPLC-MS, and Fourier transform infrared (FT-IR) spectroscopy to determine the chemical composition and the structural properties. While the impedance spectroscopy was performed for the dielectrical properties. The optical properties were detemined using UV–Vis absorption of the ALS thin film deposited in a glass. For the first trial, a planar heterojunction solar cell using zinc oxide (ZnO) thin film as an electron selective layer was build. The band gap was found to be 1.88 eV. The electrical properties of the investigated cell by the current–voltage (I–V) measurements showed an open-circuit voltage (Voc) of 0.74 V, an important efficiency of 0.50%, and a great fill factor (FF) of 0.70.
Safety of Radioactive Materials Transportation and Storing Assisted by Internet of Things
Authors: Zorkany M. , Morsi Hassan F.
Published: August 2020

Nuclear newcomers need to verify the support infrastructure development keeps steady with the power plant construction and radioactive materials transportation. European power reactor's (EPR) spent fuel (SF) had been chosen in this paper for newcomers to determine the SF levels. Radioactive materials are causing harm to the environment, people, and property. These materials may be subject to terrorism, particularly during transportations. Therefore, solutions for the safety of storing and transporting radioactive materials will be proposed in this paper. Recently, the world is suffering from a new type of terrorist—known as “Lone Wolves”—which can attack these materials. Lone wolves harmful attack detection is extremely difficult at any attack stage. Existing surveillance systems are weak to counter the lone wolves, where they respond after the happening of the incident. Therefore, this paper proposed a design for Lone Wolves counter-system (LWCS) based on deep learning and assisted by internet of things to prevent these attacks. Also, an embedded system solution will be proposed based on existing infrastructure networks. The proposed embedded system can monitor and track the radioactive materials during storing and transportation in real-time. Simulation results for the proposed system will show improved performance in the transport of radioactive materials.
Radioactivity and Elements Measurements From Lagoon of Cocody Area District of Abidjan (Côte d'Ivoire)
Authors: Agbo Alfred Djoman Djama , N'Gouan Joseph Aka , Goulizan Bi Sévérin , Brigui Jean Claude Olkalé , Kakou Pierre Claver Konin
Published: August 2020

The aim of this study was to assess radio activity and elements levels of Ebrié lagoon water in Abidjan, Côte d'Ivoire. Eight bottles of water from Ebrié lagoon were taken for the study. This study was achieved by measuring of the activity concentration of 238U, 40K, and 232Th in Ebrié lagoon water samples using gamma spectrometry. Elements contents were determined too by Absorption Atomic Spectrometry technique. The activity concentrations of these radionuclides show that populations in these townships-villages are permanently exposed to diseases caused by the ionizing rays. The elemental analysis showed that the potential source of the pollutants is anthropogenic, intrusion from industrial and agricultural activities, materials and lubricants used near the lagoon are important factors of the pollution in this lagoon.
Investigations on Effect of Lift and Wall Lubrication Forces on the Subcooled Flow Boiling
Authors: Vadlamudi Sai Raja Gopal , Nayak Arun K.
Published: August 2020

Subcooled flow boiling is widely used as a mode of heat transfer in many industries, especially in nuclear reactors. Despite its advantages, the heat transfer is hampered beyond a certain flux due to a phenomenon known as departure from nucleate boiling (DNB). It is important to determine the void fraction profiles, especially the near-wall void fractions, to evaluate the limiting heat flux conditions. The two-fluid Eulerian model, coupled with the heat flux partitioning model, is widely used to predict subcooled flow boiling characteristics. Over the years, many researchers have not considered lift and wall lubrication forces in their modeling of subcooled flow boiling. Few researchers have considered the Tomiyama model for lift force; however, their results were not encouraging. Moreover, there is no systematic study in evaluating the impact of lift and wall lubrication forces on subcooled flow boiling. In this paper, various lift and wall lubrication models are compared to understand the implications of these forces on void distribution. The advantages and limitations of the models are discussed in detail.
Effects of Four-Day School Weeks on Physical Education Exposure and Childhood Obesity
Authors: Tomayko Emily J. , Gunter Katherine B. , Schuna John M. , Thompson Paul N.
Published: August 2020

Background: Use of 4-day school weeks (FDSWs) as a cost-saving strategy has increased substantially as many US school districts face funding declines. However, the impacts of FDSWs on physical activity exposure and related outcomes are unknown. This study examined physical education (PE) exposure and childhood obesity prevalence in 4- versus 5-day Oregon schools; the authors hypothesized lower PE exposure and higher obesity in FDSW schools, given reduced school environment exposure. Methods: The authors utilized existing data from Oregon to compare 4- versus 5-day models: t tests compared mean school-level factors (PE exposure, time in school, enrollment, and demographics) and complex samples weighted t tests compared mean child-level obesity data for a state representative sample of first to third graders (N = 4625). Results: Enrollment, time in school, and student–teacher ratio were significantly lower in FDSW schools. FDSW schools provided significantly more PE, both in minutes (120 vs 101 min/wk in 4- vs 5-d schools, P < .01) and relative to total time in school (6.9% vs 5.0%, P < .0001). Obesity prevalence did not differ significantly between school models. Conclusion: Greater PE exposure in FDSW schools was observed, and it remains unknown whether differences in PE exposure contributed to obesity prevalence in this sample of students. Efforts to better understand how FDSWs impact physical activity, obesity risk, and related factors are needed.
Saving species, one roll at a time
Endangered
Joe Hopkins
Grand Gamers Guild, 2020.
Authors: Chuang Angela
Published: August 2020

Players collaborate to rescue endangered animals in a new conservation-themed game
The unlikely role of dinosaurs in the diversity discourse
Catastrophic Thinking
David Sepkoski
University of Chicago Press, 2020. 360 pp.
Authors: Determann Jörg Matthias
Published: August 2020

Western civilization's appreciation of variety may be related to the discovery of sudden extinction events
John D. Gearhart (1943–2020)
Authors: Donovan Peter J. , Zaret Kenneth S.
Published: August 2020

Pioneer of human pluripotent stem cell research
Multilamellar and Multivesicular Outer Membrane Vesicles Produced by a Buttiauxella agrestis
tolB
Mutant
Authors: Takaki Kotaro , Tahara Yuhei O. , Nakamichi Nao , Hasegawa Yusuke , Shintani Masaki , Ohkuma Moriya , Miyata Makoto , Futamata Hiroyuki , Tashiro Yosuke
Published: August 2020

Membrane vesicle (MV) formation has been recognized as a common mechanism in prokaryotes, and MVs play critical roles in intercellular interaction. However, a broad range of MV types and their multiple production processes make it difficult to gain a comprehensive understanding of MVs. In this work, using vesicle separation and electron microscopic analyses, we demonstrated that diverse types of outer membrane vesicles (OMVs) were released from an engineered strain,
Buttiauxella agrestis
JCM 1090
T
Δ
tolB
mutant. We also discovered a previously undiscovered type of vesicle, multilamellar/multivesicular outer membrane vesicles (M-OMVs), which were released by this mutant using unconventional processes. These findings have facilitated considerable progress in understanding MV diversity and expanding the utility of MVs in biotechnological applications.
Induction of Daptomycin Tolerance in Enterococcus faecalis by Fatty Acid Combinations
Authors: Brewer William , Harrison Johnathan , Saito Holly E. , Fozo Elizabeth M.
Published: August 2020

With an increasing prevalence of antibiotic resistance in the clinic, we strive to understand more about microbial defensive mechanisms. A nongenetic tolerance to the antibiotic daptomycin was discovered in
Enterococcus faecalis
that results in the increased survival of bacterial populations after treatment with the drug. This tolerance mechanism likely synergizes with antibiotic resistance in the clinic. Given that this tolerance phenotype is induced by incorporation of fatty acids present in the host, it can be assumed that infections by this organism require a higher dose of antibiotic for successful eradication. The mixture of fatty acids in human fluids is quite diverse, with little understanding between the interplay of fatty acid combinations and the tolerance phenotype we observe. It is crucial to understand the effects of fatty acid combinations on
E. faecalis
physiology if we are to suppress the tolerance physiology in the clinic.
Antigenicity and Immunogenicity of HIV-1 Envelope Trimers Complexed to a Small-Molecule Viral Entry Inhibitor
Authors: Alam S. Munir , Cronin Kenneth , Parks Robert , Anasti Kara , Ding Haitao , Go Eden P. , Desaire Heather , Eaton Amanda , Montefiori David , Sodroski Joseph , Kappes John , Haynes Barton F. , Saunders Kevin O.
Published: August 2020

Soluble forms of HIV-1 envelope trimers exhibit conformational heterogeneity and undergo CD4-induced (CD4i) exposure of epitopes of non-neutralizing antibodies that can potentially hinder induction of broad neutralizing antibody responses. These limitations have been mitigated through recent structure-guided approaches and include trimer-stabilizing mutations that resist trimer conformational transition and exposure of CD4i epitopes. The use of small-molecule viral inhibitors that allosterically block CD4 binding represents an alternative strategy for stabilizing Env trimer in the pre-CD4-triggered state of both soluble and membrane-bound trimers. In this study, we report that the viral entry inhibitor BMS-626529 restricts trimer conformational transition and improves the immunogenicity of select Env trimer immunogens.
Pathogenesis of Human Papillomaviruses Requires the ATR/p62 Autophagy-Related Pathway
Authors: Hong Shiyuan , Li Yan , Kaminski Paul J. , Andrade Jorge , Laimins Laimonis A.
Published: August 2020

High-risk human papillomaviruses (HPVs) infect epithelial cells and induce viral genome amplification upon differentiation. HPV proteins activate the ATR DNA damage repair pathway, and this is required for HPV genome amplification. In the present study, we show that HPV-induced ATR activation also leads to suppression of expression of inflammatory response genes. This suppression results from HPV-induced phosphorylation of the autophagosome cargo protein p62 which regulates the levels of the transcription factor GATA4. Activation of p62 in normal fibroblasts results in senescence, but this is not seen in HPV-positive keratinocytes. Importantly, knockdown of p62 or overexpression of GATA4 in HPV-positive cells abrogates viral replication. This study demonstrates that activation of ATR in HPV-positive cells triggers a p62-directed pathway inducing suppression of inflammatory gene expression independent of DNA repair and facilitating HPV replication.
Cyclophosphamide Increases
Lactobacillus
in the Intestinal Microbiota in Chickens
Authors: Mesa Dany , Beirão Breno C. B. , Balsanelli Eduardo , Sesti Luiz , Caron Luiz F. , Cruz Leonardo M. , Souza Emanuel M.
Published: August 2020

Poultry production is a very intensive industry. Due to the substantial number of animals being raised by any one producer, even small variations in productivity lead to important economical outcomes. The intestinal microbiota of birds is under intense scrutiny by the immune system. Therefore, it is a factor that can influence the states of health and disease of the host. The body of knowledge on the interactions between these systems is gradually bringing practical guidance for poultry production.
Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study
Authors: DeBarmore Bailey , Longchamps Ryan J , Zhang Yiyi , Kalyani Rita R , Guallar Eliseo , Arking Dan E , Selvin Elizabeth , Young J Hunter
Published: August 2020

Introduction

Mitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes.

Research design and methods

We assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black participants in the Atherosclerosis Risk in Communities (ARIC) study, an observational cohort study. Follow-up for incident analyses was complete through visit 6, 2016.

Results

Mean age at mtDNA-CN measurement was 57 years and 59% were female. Prevalence of diabetes at time of mtDNA-CN measurement was higher in blacks (563/2444, 23%) than whites (855/8954, 10%). The fully adjusted odds of prevalent diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.05 (95% CI 0.74 to 1.49) among black and 1.49 (95% CI 1.20 to 1.85) among white participants. Over a median follow-up time of 19 years (Q1, Q3: 11, 24 years), we observed 617 incident diabetes cases among 1744 black and 2121 cases among 7713 white participants free of diabetes at baseline. The fully adjusted hazard of incident diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.07 (95% CI 0.84 to 1.38) among black and 0.97 (95% CI 0.86 to 1.10) among white participants.

Conclusions

Lower mtDNA-CN in buffy coat was associated with prevalent diabetes in white but not black ARIC participants. Lower mtDNA-CN was not associated with incident diabetes over 20 years of follow-up in whites or blacks.
Intersectoral policy on industries that produce unhealthy commodities: governing in a new era of the global economy?
Authors: Lencucha Raphael , Thow Anne Marie
Published: August 2020

Tobacco, alcohol and unhealthy foods are key contributors to non-communicable diseases globally. Public health advocates have been proactive in recent years, developing systems to monitor and mitigate both health harms and influence by these industries. However, establishing and implementating strong government regulation of these unhealthy product-producing industries remains challenging. The relevant regulatory instruments lie not only with ministries of health but with agriculture, finance, industry and trade, largely driven by economic concerns. These policy sectors are often unreceptive to public health imperatives for restrictions on industry, including policies regarding labelling, marketing and excise taxes. Heavily influenced by traditional economic paradigms, they have been more receptive to industry calls for (unfettered) market competition, the rights of consumers to choose and the need for government to allow industry free rein; at most to establish voluntary standards of consumer protection, and certainly not to directly regulate industry products and practices. In recent years, the status quo of a narrow economic rationality that places economic growth above health, environment or other social goals is being re-evaluated by some governments and key international economic agencies, leading to windows of opportunity with the potential to transform how governments approach food, tobacco and alcohol as major, industry-driven risk factors. To take advantage of this window of opportunity, the public health community must work with different sectors of government to(1) reimagine policy mandates, drawing on whole-of-government imperatives for sustainable development, and (2) closely examine the institutional structures and governance processes, in order to create points of leverage for economic policies that also support improved health outcomes.
Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly syndrome is caused by de novo mutations in protein kinase D1
Authors: Alter Svenja , Zimmer Andreas David , Park Misun , Gong Jianli , Caliebe Almuth , Fölster-Holst Regina , Torrelo Antonio , Colmenero Isabel , Steinberg Susan F , Fischer Judith
Published: August 2020

Background

We describe two unrelated patients who display similar clinical features including telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease.

Methods

We performed trio whole exome sequencing and functional analysis using in vitro kinase assays with recombinant proteins.

Results

We identified two different de novo mutations in protein kinase D1 (PRKD1, NM_002742.2): c.1774G>C, p.(Gly592Arg) and c.1808G>A, p.(Arg603His), one in each patient. PRKD1 (PKD1, HGNC:9407) encodes a kinase that is a member of the protein kinase D (PKD) family of serine/threonine protein kinases involved in diverse cellular processes such as cell differentiation and proliferation and cell migration as well as vesicle transport and angiogenesis. Functional analysis using in vitro kinase assays with recombinant proteins showed that the mutation c.1808G>A, p.(Arg603His) represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The mutation c.1774G>C, p.(Gly592Arg) in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

Conclusion

The present cases represent a syndrome, which associates symptoms from several different organ systems: skin, teeth, bones and heart, caused by heterozygous de novo mutations in PRKD1 and expands the clinical spectrum of PRKD1 mutations, which have hitherto been linked to syndromic congenital heart disease and limb abnormalities.
Pathogenic variants inIMPG1cause autosomal dominant and autosomal recessive retinitis pigmentosa
Authors: Olivier Guillaume , Corton Marta , Intartaglia Daniela , Verbakel Sanne K , Sergouniotis Panagiotis I , Le Meur Guylène , Dhaenens Claire-Marie , Naacke Hélène , Avila-Fernández Almudena , Hoyng Carel B , Klevering Jeroen , Bocquet Béatrice , Roubertie Agathe , Sénéchal Audrey , Banfi Sandro , Muller Agnès , Hamel Christian L , Black Graeme C , Conte Ivan , Roosing Susanne , Zanlonghi Xavier , Ayuso Carmen , Meunier Isabelle , Manes Gaël
Published: August 2020

Background

Inherited retinal disorders are a clinically and genetically heterogeneous group of conditions and a major cause of visual impairment. Common disease subtypes include vitelliform macular dystrophy (VMD) and retinitis pigmentosa (RP). Despite the identification of over 90 genes associated with RP, conventional genetic testing fails to detect a molecular diagnosis in about one third of patients with RP.

Methods

Exome sequencing was carried out for identifying the disease-causing gene in a family with autosomal dominant RP. Gene panel testing and exome sequencing were performed in 596 RP and VMD families to identified additionalIMPG1variants. In vivo analysis in the medaka fish system by knockdown assays was performed to screenIMPG1possible pathogenic role.

Results

Exome sequencing of a family with RP revealed a splice variant inIMPG1. Subsequently, the same variant was identified in individuals from two families with either RP or VMD. A retrospective study of patients with RP or VMD revealed eight additional families with different missense or nonsense variants inIMPG1. In addition, the clinical diagnosis of theIMPG1retinopathy-associated variant, originally described as benign concentric annular macular dystrophy, was also revised to RP with early macular involvement. Using morpholino-mediated ablation ofImpg1and its paralogImpg2in medaka fish, we confirmed a phenotype consistent with that observed in the families, including a decreased length of rod and cone photoreceptor outer segments.

Conclusion

This study discusses a previously unreported association between monoallelic or biallelicIMPG1variants and RP. Notably, similar observations have been reported forIMPG2.
Can population BRCA screening be applied in non-Ashkenazi Jewish populations? Experience in Macau population
Authors: Qin Zixin , Kuok Cheong Nang , Dong Hui , Jiang Luhan , Zhang Li , Guo Maoni , Leong Hio Kuan , Wang Lei , Meng Grace , Wang San Ming
Published: August 2020

Background

Pathogenic mutation in BRCA genes causes high cancer risk. Identifying the mutation carriers plays key roles in preventing BRCA mutation-related cancer. Population screening has demonstrated its power for comprehensive identification of the mutation carriers. However, it is only recommended for the Ashkenazi Jewish population with high prevalence of three founder mutations, but not for non-Ashkenazi Jewish populations as the cost-effectiveness could be too low due to their lower mutation prevalence and lack of founder mutation. Population screening would not benefit the majority of the human population for BRCA mutation-related cancer prevention.

Methods

We used population BRCA screening in 6000 residents, 1% of the Macau population, an ethnic Chinese population with unique genetic, linguistic and cultural features, and its BRCA mutation has not been analysed before.

Results

We called BRCA variants, identified 18 carriers with 14 pathogenic mutations and determined the prevalence of 0.29% in the population (95% CI 0.15% to 0.42%). We compared the testing cost between the Ashkenazi Jewish population, the Sephardi Jewish population and the Macau population, and observed only a few fold differences.

Conclusion

Our study shows that testing cost is not the most important factor in considering population BRCA screening, at least for the populations in the developed countries/regions, regardless of the status of mutation prevalence and founder mutation.
Presumed bilateral patella cubiti in a six‐month‐old German shepherd dog
Authors: Levy Alice , Irubetagoyena Iban , Harran Nathaniel
Published: August 2020

A six‐month‐old entire male German shepherd dog was presented for lameness of left thoracic limb and bilateral elbow deformity without trauma reported. Elbow radiographs and CT showed a large bony fragment comprising both the anconeal process and the olecranon separated from the proximal ulna bilaterally. The proximal physis of the ulna was still present but smaller than usual. A part of the triceps tendon had its insertion on the fragment. Based on radiological findings, a bilateral patella cubiti was suspected. Patella cubiti is a rare elbow anomaly described in people and in dogs. Surgical treatment may be warranted if pain or stiffness is present. No recent report is available in veterinary literature.
Creating a performance indicator for temporary housing
Authors: Afkhamiaghda Mahdi , Elwakil Emad , Kereshmeh Afsari
Published: August 2020

Eighty percent of the cities in the world are located in areas that are affected at least once a year by natural disasters. As a natural disaster occurs, dislodged people need a place to stay. Between the timeframe of people living in congregate emergency shelters and going back to living in permanent housing, there is a long period where people need to live in temporary houses. Most research works have focused predominantly on categorizing temporary houses and have neglected to create an assessment tool for selecting the most optimal temporary housing option based on their performances. This research aims to: (i) investigate the relevant vital indicators affecting the post-disaster temporary house construction process; (ii) create a performance indicator (PI) table to help in creating more sustainable and resilient temporary houses; (iii) examine each of the existing temporary houses based on the factors derived from the PI table; and (iv) create a numerical scale from the evaluation table to compare options and measure their performance. This research would act as a guide for stakeholders to find the most appropriate option for the region based on the unique characteristics of the event and the available equipment and facilities.
Dielectric Properties of Binary Solvent Mixtures
Authors: Nambu Noritoshi
Published: August 2020

The relative permittivity is a measure of the solvent’s ability to insulate opposite charges from each other and has a very significant effect on the strength of the interactions between ions especially in dilute solution. I describe the relative permittivities, εr(sln) of nonaqueous mixtures as a function of the composition at 25 ºC. Experimental data were fitted with the Redlich-Kister equation. I explained the deviation from the ideal solution in terms of the magnitude of the coefficient a0. a0 is a dominant factor governing the Redlich-Kister equation. The decrease in a0 made a plot of εr(sln) vs. x2 close to a straight line, which corresponded to the ideal solution. The cohesive forces between dissimilar components resulted in the increased effective dipole moment and, consequently, in the small negative value of a0.
On the roughness analysis of high-index silicon wafers using KOH-IPA solutions
Authors: Mateo Hiram Enrique Martínez , de la Hidalga Wade Francisco Javier , Islas Carlos Zúñiga , Moreno Mario Moreno , Reyes Joel Molina , Ramírez Netzahualcóyotl Carlos , CALLEJA-ARRIAGA WILFRIDO
Published: August 2020

Bulk Micromachining on some stable high-index silicon substrates are ever more interesting because they are opening new possibilities for the development of novel 3D microstructures and surface nanostructures useful for diverse quantum applications. Considering crystallography-oriented etching, several mechanisms are poorly understood and hence, some experimental work leading to 3D device fabrication, are being developed and reported without analyzing the morphology evolution. For bulk micromachining, when 3D etching is developed using some anisotropic solution, the structure evolution takes place under a competition of fast-etching planes and unstable facets against slow-etching planes; according to the etchant composition, the resulting surface roughness can be considered as one of the main issues to be addressed. Wet chemical etching on (1 1 4}, (1 1 3), and (5 5 12) silicon substrates at 60°C, using aqueous KOH and KOH+IPA solutions, is realized in this work. The absolute etching rate trends and surface roughness were compared to reported data obtained from (0 0 1) silicon substrates. The overall etching mechanism is analyzed following some crystallographic rules and compared with high-index surfaces obtained from (0 0 1) silicon substrates. According to the best etching conditions achieved on this study, some novel 3D microstructures are presented.
Simultaneous Determination of Six Uncaria Alkaloids in Mouse Blood by UPLC–MS/MS and Its Application in Pharmacokinetics and Bioavailability
Authors: Chen Lianguo , Ma Jianshe , Wang Xianqin , Zhang Meiling
Published: August 2020

A specific ultraperformance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) method has been developed for the simultaneous determination of six Uncaria alkaloids in mouse blood with midazolam as the internal standard (IS). Only 20 μL blood was needed for sample preparation, and the protein was precipitated with acetonitrile. The UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) was used for chromatographic separation. The mobile phase consisted of 0.1% formic acid and acetonitrile with gradient elution within 5.5 min. Multiple reaction monitoring (MRM) and the positive electrospray ionization model were used for quantitative analysis. The accuracy of the UPLC‐MS/MS method ranged from 86.5% to 110.4%. The precision for intraday and interday was ≤15% each. The mean recovery and the matrix effects were found to be 64.4‐86.8% and 94.1‐109.4%, respectively. The calibration curves in blood were linear in the range of 1‐1000 ng/mL with a favorable correlation coefficient (r2) of 0.995. The pharmacokinetic results showed that six Uncaria alkaloids metabolized rapidly in mice with a half‐life between 0.6 h and 4.4 h. The bioavailability of corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsutine, and hirsuteine was 27.3%, 32.7%, 49.4%, 29.5%, 68.9%, and 51.0%, respectively, which showed satisfactory oral absorption of each alkaloid.
Multiple Criteria Decision-Making Based on Vector Similarity Measures under the Framework of Dual Hesitant Fuzzy Sets
Authors: Guirao Juan Luis García , Sarwar Sindhu M. , Rashid Tabasam , Kashif Agha
Published: August 2020

Similarity measures have a great importance in the decision-making process. In order to identify the similarity between the options, many experts have established several types of similarity measures on the basis of vectors and distances. The Cosine, Dice, and Jaccard are the vector similarity measures. The present work enclosed the modified Jaccard and Dice similarity measures. Founded on the Dice and Jaccard similarity measures, we offered a multiple criteria decision-making (MCDM) model under the dual hesitant fuzzy sets (DHFSs) situation, in which the appraised values of the alternatives with respect to criteria are articulated by dual hesitant fuzzy elements (DHFEs). Since the weights of the criteria have a much influence in making the decisions, therefore decision makers (DMs) allocate the weights to each criteria according to their knowledge. In the present work, we get rid of the doubt to allocate the weights to the criteria by taking an objective function under some constraints and then extended the linear programming (LP) technique to evaluate the weights of the criteria. The Dice and Jaccard weighted similarity measures are practiced amongst the ideal and each alternative to grade all the alternatives to get the best one. Eventually, two practical examples, about investment companies and selection of smart phone accessories are assumed to elaborate the efficiency of the proposed methodology.
Incidence, Outcomes, and Factors Associated with Intra-Abdominal Hypertension and Primary Abdominal Compartment Syndrome in Abdominopelvic Injury Patients
Authors: Kanlerd Amonpon , Nakornchai Krissada , Auksornchart Karikarn , Watkwaw Warapan
Published: August 2020

Background. The primary aim was to identify the incidence of intra-abdominal hypertension (IAH) and primary abdominal compartment syndrome (1oACS) of abdominopelvic injury patients at Thammasat University Hospital (TUH), Thailand, and the secondary objective was to evaluate those factors that contributed to developing these conditions. Methods. The retrospective cohort of 38 abdominopelvic injury cases was admitted to the intensive care unit at Thammasat University Hospital, from January 1st to December 31st, 2018. The bladder pressure was recorded every 4 hours until the urethral catheter was removed. Data of age, gender, weight, height, body mass index, injury mechanisms, initial vital signs, imaging, laboratory data, blood component requirements, abdominal organs involved, treatments including surgery and intervention radiology, abbreviated injury scale (AIS) and injury severity score (ISS), length of ICU stays, and results of treatment were all analyzed. Results. The patients were mostly young (mean age 31.5 years), male (68.4%), and suffering from blunt trauma (89.5%). The mean maximum bladder pressure was 8.3 ± 5.2 mmHg. Six patients (15.8%) developed IAH, and one patient (2.6%) was diagnosed with 1oACS. Two patients expired. The multivariate analysis showed the patient who had initial Cr ≥ 1.5 g/dL, lower extremity including pelvis AIS ≥3, and ISS >15 was significantly associated with the developing of IAH. Conclusions. The incidence of IAH and 1oACS was 15.8% and 2.6%. Predicted factors to find developing IAH were initial Cr ≥ 1.5 g/dL, lower extremity AIS ≥3, and ISS >15. We should consider awareness of IAH and 1oACS in abdominopelvic injury patients.
Endocan and Lumican in Relation to Cardiometabolic Risk in a Pediatric Overweight and Obese Cohort: A Cross‐Sectional Study
Authors: Bălănescu Anca , Codreanu Ioana Florentina , Comanici Valentina Daniela , Stan Iustina Violeta , Bălănescu Eugenia , Bălănescu Paul
Published: August 2020

The aim of the study was to evaluate serum Endocan and Lumican levels as biomarkers for pediatric Nonalcoholic Fatty Liver Disease (NAFLD) and to explore their associations with pediatric cardiometabolic risk factors. We conducted a cross‐sectional study on 68 pediatric obese and overweight (O&O) patients. Ten healthy controls were recruited. Serum Lumican and Endocan levels were analyzed using ELISA kits. O&O patients had lower levels of Endocan compared to healthy controls (p < 0.001). There were no differences between serum Endocan levels in O&O patients with NAFLD and those without (p = 0.53). Patients considered having Nonalcoholic Steatohepatitis (NASH) had lower Endocan levels compared to O&O patients without NASH (p = 0.026). Patients with metabolic syndrome had lower levels of Endocan (p = 0.003). There were no significant differences between serum Lumican levels in O&O children compared to healthy controls. Lumican levels were higher in patients with hypertension (p = 0.04). In O&O patients, Lumican levels were negatively correlated with Endocan levels (r = −0.37, p = 0.002). Endocan seems a promising biomarker for the evaluation of pediatric NASH. Lumican was not confirmed as a biomarker for NAFLD in our cohort but was associated with higher arterial pressure. Low Endocan levels are accompanied by high serum Lumican levels, and this could be an early signature of cardiometabolic risk.
Mining Database for the Expression and Clinical Significance of NF-κB Family in Hepatocellular Carcinoma
Authors: Chen Xu , Zhou Yufan , Li Zhecheng , Wang Zhiming
Published: August 2020

Background. Hepatocellular carcinoma (HCC) is one of the deadliest diseases affecting humans. Its incidence has been increasing over the last decade. It is characterized by poor prognosis as well as lack of therapeutic regimens for patients in the advanced stages. It is therefore important to develop effective biomarkers for diagnosis, prognosis, and immunotherapy of HCC. Research suggests that the NF-κB family plays vital roles in immune response, inflammation, tumorigenesis, and the progress of malignancy in various cancers. However, its role in HCC remains unidentified. Methodology. The expression and clinical significance of the NF-κB family in HCC were analyzed using several bioinformatics tools including UALCAN, The Human Protein Atlas, GEPIA, GSCALite, David, GeneMANIA, and TIMER. Results. The mRNA expression levels of RelA, RelB, NF-κB1, and NF-κB2 were significantly elevated in HCC. The mRNA levels of RelB and NF-κB2 were significantly upregulated in HCC tissues compared to normal liver tissues in subgroup analyses based on patient’s race, gender, age, weight, tumor grade, cancer stage, and nodal metastasis status. Moreover, HCC patients with elevated levels of RelB and NF-κB2 had a worse overall survival and disease-free survival. Methylation downregulated the expressions of RelA, RelB, and NF-κB1 in HCC. NF-κB family was also significantly involved in various hallmark cancer-related pathways such as the apoptosis, EMT, RTK, and cell cycle pathways. Similarly, the expression of RelB and NF-κB2 was positively correlated with the abundance of immune cells and the expression of immune biomarkers. Several kinase and miRNA targets of RelB and NF-κB2 were also identified. Conclusion. RelB and NF-κB2 are potential biomarkers for the diagnosis, prognosis, and immunotherapy of HCC.
Longitudinal Associations between Obesity, Inflammation, and the Incidence of Type 2 Diabetes Mellitus among US Black and White Adults in the CARDIA Study
Authors: Jackson Sharon H. , Bellatorre Anna , McNeel Timothy , Nápoles Anna María , Choi Kelvin
Published: August 2020

Aim. Assess prospective relationships between obesity and inflammation on the incidence of type 2 diabetes mellitus (T2DM). Methods. A cohort of nondiabetic respondents from the Coronary Artery Risk Development in Young Adults (CARDIA) study was followed from 2005-2006 (wave 7) to 2010-2011 (wave 8). Diabetes status was determined in wave 8 based on self-report, blood glucose level, and anti-hyperglycemic medication use in conjunction with a homeostatic model assessment-based classification for distinguishing diabetes subtype. We performed a series of multivariable logistic regression analyses to assess the relative influence of obesity (waist circumference) and individual inflammatory biomarkers (i.e., C-reactive protein, fibrinogen, and sex-specific serum uric acid and gamma-glutamyltransferase) on the odds of developing incident T2DM between waves 7 and 8. Results. Among 2784 nondiabetic CARDIA respondents, 146 (5.2%) new cases of T2DM were identified between waves. Having a high waist circumference (AOR=6.15; 95%CI=4.14,9.14) and being Black (vs. White) (AOR=1.60; 95%CI=1.05,2.44) were associated with T2DM. Adjusting for inflammation biomarkers attenuated the effects of waist circumference and race with T2DM. Clinically elevated CRP (AOR=1.83; 95%CI=1.18,2.82) and uric acid (AOR=2.57; 95%CI=1.70,3.89) predicted T2DM among all respondents. However, stratification by race showed greater attenuation of the effects of waist circumference on T2DM in Whites than in Blacks when inflammation biomarkers were accounted for in the model. Conclusion. Targeted control of systemic inflammation may reduce the risk of developing T2DM, especially among Blacks, and could help address Black-White disparities in diabetes care and outcomes.