bluuebunny/crossref_metadata_2025 huggingface dataset:
Prueba de Papanicolau: Mejoras en la atención diagnóstica en tiempos de pandemia
Authors: Espinoza Calero Julio César , Quispe-Bravo Bernardo , Vásquez-Velásquez Cinthya
Published: October 2022

Actualmente, el cáncer de cuello uterino es un problema de salud pública mundial. Por ende, las políticas de detección, diagnóstico y tratamiento preventivo deben ser efectivos para evitar la metástasis de esta enfermedad. Solo en el 2020, la incidencia de contraer cáncer de cuello uterino en mujeres fue del 0.0133% con una mortalidad de 0.0073% ocupando el cuarto lugar a nivel mundial.
Atención Primaria de la Salud: 40 años después de Alma Ata, y desafíos para su implementación actual
Authors: Bustíos-Romaní Carlos
Published: October 2022

En el Derecho Internacional se reconoce jurídicamente que "el disfrute del más alto nivel posible de salud" es un derecho humano fundamental e indispensable por el valor que tiene la salud en sí misma, así como por ser una condición para el ejercicio efectivo de los demás derechos humanos. El objetivo de un enfoque de la Salud Pública basado en este reconocimiento jurídico es, entonces, garantizar que todas las políticas, estrategias y programas vinculados con la salud colectiva se rijan, de manera auténtica, por los principios de: no discriminación, disponibilidad, accesibilidad, aceptabilidad, calidad, rendición de cuentas y universalidad. Principios normativos que sustentaron y sustentan los compromisos asumidos en 1978 por los gobiernos del mundo en la Reunión de Alma Ata, para lograr la "salud para todos" a través de una estrategia de participación comunitaria denominada "Atención Primaria de la Salud" (APS), que garantizara la eficacia, la equidad y la solidaridad social de los sistemas nacionales de salud.
Hemorragia digestiva alta no variceal
Authors: Huerta-Mercado Tenorio Jorge , Guzmán-Calderón Edson , Vesco-Monteagudo Eduardo
Published: October 2022

La hemorragia digestiva alta es el diagnóstico gastroenterológico más frecuente que requiere hospitalización. Un estudio poblacional en países occidentales reporta una incidencia de 103 casos por 100 000 adultos por año y una mortalidad de 14%. Se esperaría que la incidencia esté disminuyendo debido a las mejoras en el campo del tratamiento, sin embargo la mortalidad se mantiene estable, y esto debido al aumento de la hemorragia digestiva en adultosmayores.
An Optimization of Machine Learning Approaches in the Forecasting of Global Financial Stability
Authors: Ranjan Adyant
Published: October 2022

In the current data-driven world, the significance of machine learning as a mechanism for making predictions is vital. This research dives into how supervised learning techniques can be used to predict whether a banking crisis will occur in areas of Africa, which can be generalized to determining the status of financial stability in all areas around the world. By applying different machine learning mechanisms, along with tuning the hyperparameters, the optimal machine learning technique was found to be a neural network with two hidden layers, both hidden layers having the ReLU activation function. These results demonstrate that through widespread implementation of this neural network, governmental and financial organizations can develop significant trends and predict when a state is in economic peril, allowing for sufficient financial, social, or other aid to be administered before situations deteriorate.
PENDIDIKAN KEWIRAUSAHAAN DAN PELATIHAN STRATEGI PEMASARAN PRODUK PADA SANTRI PONDOK PESANTREN QODIRIYAH SULAIMANIAH SINGOSARI KABUPATEN MALANG
Authors: Dani Andi Asdani , Yunia Afiatin  , Atika Syuliswati  , Jaswadi  , Mika Marsely
Published: October 2022

The Qodiriyah Sulaimaniah Singosari Islamic Boarding School, Malang Regency is one of the large Islamic boarding schools located in Kreweh Singosari Village, Malang Regency. The existence of this Islamic boarding school makes a high contribution to producing young people who have a deep understanding of the Islamic religion. However, the Qodiriyah Sulaimaniah Singosari Islamic boarding school has a desire to provide more provisions to its students, namely the ability to entrepreneurship so that it can produce prospective entrepreneurs who have a good Islamic education. In addition, the Qodiriyah Sulaimaniah Singosari Islamic boarding school also has a desire to develop small businesses that have been owned in the Islamic boarding school. Therefore, PKM activities are carried out by providing training in the field of entrepreneurship, namely marketing strategy training for students at the Qodiriyah Sulaimaniah Singosari Islamic boarding school. In addition, this PkM activity also provides training on skills to make contemporary food, namely rice bowls which are expected to be useful for use as a product of the Qodiriyah Sulaimaniah Singosari Islamic boarding school. The results of this PKM activity are expected to produce students who have the ability to carry out marketing techniques so as to launch entrepreneurial activities that are carried out.
BIMBINGAN TEKNIS PERENCANAAN MENARA MASJID RADEN RAHMAD MERJOSARI LOWOKWARU KOTA MALANG
Authors: Khamim Moch. , Winda Harsanti  , Mohamad Zenurianto
Published: October 2022

The minarets are a distinctive traditional feature of many mosques, although they vary in height, style, and number. Towers can be square, round, hexagonal, octagonal, or even spiral and towers are usually covered with a gabled roof. Mosque minarets Generally a tall minaret with a cone or onion-shaped crown, usually standing alone or higher than the surrounding structures. The basic form of the tower includes a base, shaft, and gallery. The style varies according to region and time period. The minaret provides a visual focal point and is traditionally used for the Muslim call to prayer (Azan). A good tower must be designed according to the shape of the mosque and the structural needs are calculated.
Function-based classification of hazardous biological sequences: Demonstration of a new paradigm for biohazard assessments
Authors: Gemler Bryan T. , Mukherjee Chiranjit , Howland Carrie A. , Huk Danielle , Shank Zachary , Harbo Lela Johnson , Tabbaa Omar P. , Bartling Craig M.
Published: October 2022

Bioengineering applies analytical and engineering principles to identify functional biological building blocks for biotechnology applications. While these building blocks are leveraged to improve the human condition, the lack of simplistic, machine-readable definition of biohazards at the function level is creating a gap for biosafety practices. More specifically, traditional safety practices focus on the biohazards of known pathogens at the organism-level and may not accurately consider novel biodesigns with engineered functionalities at the genetic component-level. This gap is motivating the need for a paradigm shift from organism-centric procedures to function-centric biohazard identification and classification practices. To address this challenge, we present a novel methodology for classifying biohazards at the individual sequence level, which we then compiled to distinguish the biohazardous property of pathogenicity at the whole genome level. Our methodology is rooted in compilation of hazardous functions, defined as a set of sequences and associated metadata that describe coarse-level functions associated with pathogens (e.g., adherence, immune subversion). We demonstrate that the resulting database can be used to develop hazardous “fingerprints” based on the functional metadata categories. We verified that these hazardous functions are found at higher levels in pathogens compared to non-pathogens, and hierarchical clustering of the fingerprints can distinguish between these two groups. The methodology presented here defines the hazardous functions associated with bioengineering functional building blocks at the sequence level, which provide a foundational framework for classifying biological hazards at the organism level, thus leading to the improvement and standardization of current biosecurity and biosafety practices.
Thermal degradation behavior and flame retardant properties of PET/DiDOPO conjugated flame retardant composites*
Authors: Xiang Yushu , Gao Yun , Xu Guomin , He Min , Qin Shuhao , Yu Jie
Published: October 2022

PET/DIDOPO conjugated flame retardant composites were prepared by melt blending of styrene bridged DOPO (DIDOPO) into polyethylene terephthalate (PET). The flame retardancy, rheological behavior, and thermal degradation behavior of the composite were characterized by vertical combustion test (UL-94), limit oxygen index test (LOI), rotational rheometer, and thermogravimetry (TG). The results showed that the flame retardant composite with V-0 grade was obtained when the amount of DIDOPO is 12.5wt%, and the corresponding LOI value was 56.87% higher than that of PET. The thermogravimetry-fourier infrared spectroscopy (TG-FTIR) test results showed that DIDOPO could promote the degradation of PET/DIDOPO materials, and release phosphorus-containing free radicals to quench the flame, therefore slowing down the combustion process, and mainly playing the key flame retardant role in gas-phase.
Thermal mechanism in magneto radiated [(Al2O3-Fe3O4)/blood]hnf over a 3D surface: Applications in Biomedical Engineering
Authors: Guedri Kamel , Adnan  , Raizah Zehba , Eldin Elsayed Tag , EL-Shorbagy M. A. , Abbas Waseem , Khan Umar
Published: October 2022

Nanofluids are a new generation of fluids which help in improving the efficiency of thermal systems by improving heat transport rate and extensive applications of this class extensively fall in biomedical engineering, the electronics industry, applied thermal and mechanical engineering, etc. The core concern of this study is to examine the interaction of Al2O3-Fe3O4 hybrid nanoparticles of lamina shaped with blood over a 3D surface by impinging novel impacts of non-linear thermal radiations, stretching, velocity slippage, and magnetic field. This leads to a mathematical flow model in terms of highly non-linear differential equations via nanofluid-effective characteristics and similarity rules. To know the actual behavior of (Al2O3-Fe3O4)/blood inside the concerned region, mathematical investigation is performed via numerical technique and the results are obtained for different parameter ranges. The imposed magnetic field of high strength is a better tool to control the motion of (Al2O3-Fe3O4)/blood inside the boundary layer, whereas, stretching of the surface is in direct proportion of the fluid movement. Furthermore, thermal radiations (Rd) and γ1 are observed to be beneficial for thermal enhancement for both (Al2O3-Fe3O4)/blood and (Al2O3)/blood.
Dynamic risk framework for cascading compounding climate-geological hazards: A perspective on coastal communities in subduction zones
Authors: De Risi Raffaele , Muhammad Ario , De Luca Flavia , Goda Katsuichiro , Mori Nobuhito
Published: October 2022

Integrated disaster resilience approaches are paramount for enhancing risk management of coastal communities in subduction zones under climate-geological risks. Cascading compounding climate-geological risks are dynamic, interact, and evolve with time. Also, classical convolution of hazard, vulnerability, and exposure does not allow easy implementation of causalities and dependencies that are critical in modelling impact chains due to cascading compounding multi-hazards. A new dynamic multi-hazard catastrophe modelling framework is proposed to fill important research gaps in the temporal evolution of climate-geological risks. Systemic modelling is a key tool where time-dependent and interacting risks are explicitly modelled, and multiple risk metrics can be computed. Furthermore, a possible new entropy-based approach for harmonising risk metrics is presented. Such a harmonisation can facilitate the decision-making process for disaster risk reduction. Finally, a way forward for future implementation of the proposed methodologies is discussed with a focus on the need for the development of new numerical and analytical tools.
Extracting the geochemical characteristics of magmas in different global tectono-magmatic settings using sparse modeling
Authors: Ueki Kenta , Hino Hideitsu , Kuwatani Tatsu
Published: October 2022

In this study, key geochemical features of magmas formed in eight different tectono-magmatic settings (mid-ocean ridges, oceanic islands, oceanic plateaus, continental flood basalt provinces, intra-oceanic arcs, continental arcs, island arcs, and back-arc basins) are presented that were obtained using a machine-learning-based statistical model. We analyzed geochemical data for volcanic rocks compiled from the global geochemical databases based on statistical model fitting. We used the sparse modeling approach, with which we can objectively identify a small number of fundamental features from a large number of observations. This approach allowed us to identify a small number of representative geochemical features from a total of 857 variables, including major and trace element concentrations, isotope ratios, and all possible ratios and multiplications of elements. Based on the statistical analysis, we present a small number (2–4) of key geochemical features for each tectono-magmatic setting. The extracted geochemical features and associated diagrams can be used to examine geochemical similarities and differences between tectono-magmatic settings and to identify the geochemical characteristics of unknown samples. Based on the extracted geochemical characteristics, we discuss the processes that may lead to the formation of magmas in different tectono-magmatic settings. Our statistical analysis shows that the geochemical signatures of magmas vary with the tectono-magmatic setting, as do the geochemical processes involved in magma generation.
Alpha cell dysfunction in type 1 diabetes is independent of a senescence program
Authors: Brawerman Gabriel , Ntranos Vasilis , Thompson Peter J.
Published: October 2022

Type 1 Diabetes (T1D) is caused by insulin deficiency, due to progressive autoimmune destruction of pancreatic β cells. Glucagon-secreting α cells become dysfunctional in T1D and contribute to pathophysiology, however, the mechanisms involved are unclear. While the majority of β cells are destroyed in T1D, some β cells escape this fate and become senescent but whether α cell dysfunction involves a senescence program has not been explored. Here we addressed the question of whether α cells become senescent during the natural history of T1D in the non-obese diabetic (NOD) mouse model and humans. NOD mice had several distinct subpopulations of α cells, but none were defined by markers of senescence at the transcriptional or protein level. Similarly, α cells of human T1D donors did not express senescence markers. Despite the lack of senescence in α cells in vivo, using a human islet culture model, we observed that DNA damage-induced senescence led to alterations in islet glucagon secretion, which could be rescued by inhibiting the senescence-associated secretory phenotype (SASP). Together our results suggest that α cell dysfunction in T1D is not due to activation of a senescence program, however, senescent β cell accumulation in the islet microenvironment may have a negative effect on α cell function.
Real-world national trends and socio-economic factors preference of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in China
Authors: Li Cao , Guo Shanshan , Huo Jiping , Gao Yiming , Yan Yilong , Zhao Zhigang
Published: October 2022

Backgrounds

Robust evidence have demonstrated the beneficial effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in T2D patients with cardiovascular diseases and chronic kidney disease. Multiple studies analyzed patterns and predictors of SGLT2i and GLP-1RA in the US, Europe and worldwide. However, there is no study about the utilization of these two classes of drugs in real-world in China.

Method

A total of 181743 prescriptions of SGLT2i and 59720 GLP-1RA were retrospectively pooled from Hospital Prescription Analysis Cooperation Project from 2018 to 2021. The social-economic characteristics of patients and prescribers, including age, gender, residency, hospital level, insurance type, department visited, and payment amount, were collected and analyzed to study trends and risk factors associated with preference among two antidiabetics.

Results

Annual number of prescriptions of SGLT2i significantly increased to approximately 140 folds, while GLP-1RA increased to about 6.5 folds. After adjustment for socio-economic information, several patients or physician characteristics were positively associated with the preference of GLP-1RA, including female gender (OR 1.581, 95% CI 1.528-1.635), residents in second-tier cities (OR 1.194, 95% CI 1.148-1.142), visiting primary or secondary hospital level (OR 2.387, 95% CI 2.268-2.512); while other factors were associated with the preference of SGLT2i, including older adults (OR 0.713, 95% CI 0.688-0.739), uncovered by insurance (OR 0.310, 95% CI 0.293-0.329), visiting other departments compared with endocrinology. In addition, the share of SGLT2i and GLP-1RA was low but in an increasing tendency.

Conclusions

SGLT2i and GLP-1RA prescription significantly increased from 2018 to 2021. The socio-economic risk factors in choosing SGLT2i or GLP-1RA highlight an effort required to reduce disparities and improve health outcomes.
Entropy generation investigation of MHD Ag– and Au–H2O nanofluid above an exponential porous stretchable surface with thermal radiation and stagnation point flow
Authors: Rashid I. , Zubair T. , Asjad M. I. , Awrejcewicz J.
Published: October 2022

The current study presents an entropy generation investigation of magnetohydrodynamic Ag- and Au-H2O nanofluid flows induced by an exponential stretchable sheet implanted in porous media accompanying suction/injection and heat radiation impact. Moreover, the stagnation point flow and silver and gold nanoparticles are considered. The consequences of ohmic heating and thermal radiation are also included as part of the heat transport examination. A physical process is transformed into a set of mathematical expressions using mathematical concepts, which can then be further simplified by using the necessary variables. Considering numerous physiological factors of interest, exact solutions for velocity and temperature profiles are calculated. Graphs and numerical tables are utilized to examine how different physical entities affect the distribution of velocity, temperature, and entropy. It is noted that enhancing the values of Ω reduces entropy inception. It is observed that the entropy inception field gains due to an increment in Ecrt.
Design optimization of district heating systems: A review
Authors: Sporleder Maximilian , Rath Michael , Ragwitz Mario
Published: October 2022

District heating systems offer the possibility of lowering emissions and support the goal of reaching a carbon-neutral energy system by integrating renewable heat sources. Therefore, this work provided a systematic literature review to identify potential research gaps and show the literature distribution over the relevant topics. The focus is on the design optimization with (non-)linear programming of district heating systems in the context of decarbonization. Furthermore, crucial energy balance equations were extracted from the literature for a potential optimization problem. The systematic literature review limited its search to two databases, 10 years timespan, a quality measure, and uses keywords regarding topic and method. Categories were derived based on the subject and literature to cluster the found publications and identify potential research gaps. The results showed potential research gaps in the depiction of different stakeholder decisions, reduction of computational efforts, and their resulting uncertainties. Additionally, they identified gaps in the integration of low-grade heat sources, thermal storage facilities, and energy converters, especially geothermal energy, large-scale heat pumps, and seasonal storages.
The mediating role of entrepreneurship in the link between high-speed rail and carbon emissions reduction
Authors: Chen Yu , Chen Wenqing , Chen Shan
Published: October 2022

Prior studies document that the development of transportation infrastructure, particularly the rapid development of high-speed rail, plays a key role in transforming an economy towards a low-carbon development mode, for example by reducing carbon emissions in China and other countries. However, to date, the mechanisms and paths that link high-speed rail to carbon emission reduction remain ambiguous. The present study seeks to clarify this path by proposing the mediating role of entrepreneurship, arguing that the rapid cycle of people, capital, knowledge, and technology induced by high-speed rail would be integrated by entrepreneurs as new start-ups, leading to industry agglomeration, upgrading, and innovations. These consequences of entrepreneurship would further result in carbon emission reductions. Employing a unique dataset in China, we provide strong evidence for our arguments by setting China’s prefecture-level cities as the unit of analysis. The research conclusions are as follows: First, the launch of high-speed rail services has a positive effect on a city’s carbon emission reduction. Second, entrepreneurship plays a mediating role in the relationship between high-speed rail and carbon emission reduction. Third, the administrative approval system reform would strengthen the effect of high-speed rail on entrepreneurship. This study therefore clarifies the path through which high-speed rail leads to carbon emission reduction, and reconfirms the role of transportation development in achieving the goal of sustainable development towards carbon neutrality.
Monitoring dryland trees with remote sensing. Part B: Combining tree cover and plant architecture data to assess degradation and recovery of Argania spinosa woodlands of South Morocco
Authors: Kirchhoff Mario , Marzolff Irene , Stephan Robin , Seeger Manuel , Aït Hssaine Ali , Ries Johannes B.
Published: October 2022

The argan woodlands of South Morocco represent an open-canopy dryland forest with traditional silvopastoral usage that includes browsing by goats, sheep and camels, oil production as well as agricultural use. In the past, these forests have undergone extensive clearing, but are now protected by the state. However, the remaining argan woodlands are still under pressure from intensive grazing and illegal firewood collection. Although the argan-forest area seems to be overall decreasing due to large forest clearings for intensive agriculture, little quantitative data is available on the dynamics and overall state of the remaining argan forest. To determine how the argan woodlands in the High Atlas and the Anti-Atlas had changed in tree-crown cover from 1972 to 2018 we used historical black and white HEXAGON satellite images as well as recent WorldView satellite images (see Part A of our study). Because tree shadows can oftentimes not be separated from the tree crown on panchromatic satellite images, individual trees were mapped in three size categories to determine if trees were unchanged, had decreased/increased in crown size or had disappeared or newly grown. The current state of the argan trees was evaluated by mapping tree architectures in the field. Tree-cover changes varied highly between the test sites. Trees that remained unchanged between 1972 and 2018 were in the majority, while tree mortality and tree establishment were nearly even. Small unchanged trees made up 48.4% of all remaining trees, of these 51% showed degraded tree architectures. 40% of small (re-) grown trees were so overbrowsed that they only appeared as bushes, while medium (3–7 m crown diameter) and large trees (>7 m) showed less degraded trees regardless if they had changed or not. Approaches like grazing exclusion or cereal cultivation lead to a positive influence on tree architecture and less tree-cover decrease. Although the woodland was found to be mostly unchanged 1972–2018, the analysis of tree architecture reveals that a lot of (mostly small) trees remained stable but in a degraded state. This stability might be the result of the small trees’ high degradation status and shows the heavy pressure on the argan forest.
RETRACTED: Green finance, green energy, and green revolution: An impulse response function of food security in developing economies
Authors: Huan Yu , Sun Zhaojun , Ali Muhammad , Yan Ran , Ur Rahman Zia
Published: October 2022

Recently, it has been observed that fossil fuel utilization increased to manage the issue of food insecurity; however, it has increased the risk of environmental degradation and land availability. Therefore, the role of a farmer is to ensure food security (FS). With the assistance of the green revolution (GR), green finance (GF) and green energy have increased manifold. For this purpose, the current study utilized a time-series dataset between 2071 and 2019 to evaluate the relationship between green finance, green energy, and the green revolution with food security. This objective has been considered with modern econometric methods, including the Johansen cointegration model and impulse response. As a result, the Johansen model affirmed cointegration between the green revolution, green finance, and green energy with food security. According to the results, food security will rise by 0.17%, 2.05%, 0.006%, and 0.023%, with a 1% increase in fossil fuel utilization, green finance, improved seeds, and water availability, respectively. Furthermore, based on the diagnostic statistics, the Johansen model’s credibility, stability, and reliability were corrected. In light of these findings and the impulse response function, all relevant factors will favor future food security. Finally, this study suggested that the public and commercial sectors should invest significantly in R&D to produce organic chemicals and agricultural methods that preserve soil fertility and reduce environmental degradation.
Fungal species associated with grapevine trunk diseases in Washington wine grapes and California table grapes, with novelties in the genera Cadophora, Cytospora, and Sporocadus
Authors: Travadon Renaud , Lawrence Daniel P. , Moyer Michelle M. , Fujiyoshi Phillip T. , Baumgartner Kendra
Published: October 2022

Grapevine trunk diseases cause serious economic losses to grape growers worldwide. The identification of the causal fungi is critical to implementing appropriate management strategies. Through a culture-based approach, we identified the fungal species composition associated with symptomatic grapevines from wine grapes in southeastern Washington and table grapes in the southern San Joaquin Valley of California, two regions with contrasting winter climates. Species were confirmed through molecular identification, sequencing two to six gene regions per isolate. Multilocus phylogenetic analyses were used to identify novel species. We identified 36 species from 112 isolates, with a combination of species that are new to science, are known causal fungi of grapevine trunk diseases, or are known causal fungi of diseases of other woody plants. The novel speciesCadophora columbiana,Cytospora macropycnidia,Cytospora yakimana, andSporocadus incarnatusare formally described and introduced, six species are newly reported from North America, and grape is reported as a new host for three species. Six species were shared between the two regions:Cytospora viticola,Diatrype stigma,Diplodia seriata,Kalmusia variispora,Phaeoacremonium minimum, andPhaeomoniella chlamydospora. Dominating the fungal community in Washington wine grape vineyards were species in the fungal families Diatrypaceae, Cytosporaceae and Sporocadaceae, whereas in California table grape vineyards, the dominant species were in the families Diatrypaceae, Togniniaceae, Phaeomoniellaceae and Hymenochaetaceae. Pathogenicity tests demonstrated that 10 isolates caused wood discoloration similar to symptomatic wood from which they were originally isolated. Growth rates at temperatures from 5 to 35°C of 10 isolates per region, suggest that adaptation to local climate might explain their distribution.
Identification of resistance gene analogs of the NBS-LRR family through transcriptome probing and in silico prediction of the expressome of Dalbergia sissoo under dieback disease stress
Authors: Ijaz Siddra , Haq Imran Ul , Khan Iqrar Ahmad , Ali Hayssam M. , Kaur Sukhwinder , Razzaq Hafiza Arooj
Published: October 2022

Dalbergia sissoo is an important timber tree, and dieback disease poses a dire threat to it toward extinction. The genomic record of D. sissoo is not available yet on any database; that is why it is challenging to probe the genetic elements involved in stress resistance. Hence, we attempted to unlock the genetics involved in dieback resistance through probing the NBS-LRR family, linked with mostly disease resistance in plants. We analyzed the transcriptome of D. sissoo under dieback challenge through DOP-rtPCR analysis using degenerate primers from conserved regions of NBS domain-encoded gene sequences. The differentially expressed gene sequences were sequenced and in silico characterized for predicting the expressome that contributes resistance to D. sissoo against dieback. The molecular and bioinformatic analyses predicted the presence of motifs including ATP/GTP-binding site motif A (P-loop NTPase domain), GLPL domain, casein kinase II phosphorylation site, and N-myristoylation site that are the attributes of proteins encoded by disease resistance genes. The physicochemical characteristics of identified resistance gene analogs, subcellular localization, predicted protein fingerprints, in silico functional annotation, and predicted protein structure proved their role in disease and stress resistance.
A multiphase contrast-enhanced CT radiomics model for prediction of human epidermal growth factor receptor 2 status in advanced gastric cancer
Authors: Ma Tingting , Cui Jingli , Wang Lingwei , Li Hui , Ye Zhaoxiang , Gao Xujie
Published: October 2022

Background: Accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is of great importance for appropriate management of advanced gastric cancer (AGC) patients. This study aims to develop and validate a CT-based radiomics model for prediction of HER2 overexpression in AGC.

Materials and Methods: Seven hundred and forty-five consecutive AGC patients (median age, 59 years; interquartile range, 52–66 years; 515 male and 230 female) were enrolled and separated into training set (n = 521) and testing set (n = 224) in this retrospective study. Radiomics features were extracted from three phases images of contrast-enhanced CT scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator method. Univariable and multivariable logistical regression analysis were used to establish predictive model with independent risk factors of HER2 overexpression. The predictive performance of radiomics model was assessed in the training and testing sets.

Results: The positive rate of HER2 was 15.9% and 13.8% in the training set and testing set, respectively. The positive rate of HER2 in intestinal-type GC was significantly higher than that in diffuse-type GC. The radiomics signature comprised eight robust features demonstrated good discrimination ability for HER2 overexpression in the training set (AUC = 0.84) and the testing set (AUC = 0.78). A radiomics-based model that incorporated radiomics signature and pathological type showed good discrimination and calibration in the training (AUC = 0.85) and testing (AUC = 0.84) sets.

Conclusion: The proposed radiomics model showed favorable accuracy for prediction of HER2 overexpression in AGC.
Speciation of pelagic zooplankton: Invisible boundaries can drive isolation of oceanic ctenophores
Authors: Johnson Shannon B. , Winnikoff Jacob R. , Schultz Darrin T. , Christianson Lynne M. , Patry Wyatt L. , Mills Claudia E. , Haddock Steven H. D.
Published: October 2022

The study of evolution and speciation in non-model systems provides us with an opportunity to expand our understanding of biodiversity in nature. Connectivity studies generally focus on species with obvious boundaries to gene flow, but in open-ocean environments, such boundaries are difficult to identify. Due to the lack of obvious boundaries, speciation and population subdivision in the pelagic environment remain largely unexplained. Comb jellies (Phylum Ctenophora) are mostly planktonic gelatinous invertebrates, many of which are considered to have freely interbreeding distributions worldwide. It is thought that the lobate ctenophoreBolinopsis infundibulumis distributed throughout cooler northern latitudes andB. vitreawarmer. Here, we examined the global population structure for species ofBolinopsiswith genetic and morphological data. We found distinct evolutionary patterns within the genus, whereB. infundibulumhad a broad distribution from northern Pacific to Atlantic waters despite many physical barriers, while other species were geographically segregated despite few barriers. Divergent patterns of speciation within the genus suggest that oceanic currents, sea-level, and geological changes over time can act as either barriers or aids to dispersal in the pelagic environment. Further, we used population genomic data to examine evolution in the open ocean of a distinct lineage ofBolinopsisctenophores from the North Eastern Pacific. Genetic information and morphological observations validated this as a separate species,Bolinopsis microptera, which was previously described but has recently been calledB. infundibulum. We found that populations ofB. micropterafrom California were in cytonuclear discordance, which indicates a secondary contact zone for previously isolated populations. Discordance at this scale is rare, especially in a continuous setting.
Case Report: Novel splicing mutations in RFX5 causing MHC class II deficiency
Authors: Chen Shan , Xu Yuqing , Qian Yeqing , Li Zhaohui , Dong Minyue
Published: October 2022

Mutations of the Regulatory Factor X5 (RFX5) have been associated with the autosomal recessive major histocompatibility class II (MHC-II) deficiency, which is a severe immunodeficiency characterized by constitutive and interferon-gamma induced MHC II expression disorder and leads to the absence of cellular and humoral T-cell response to antigen challenge. The compound heterozygous splicing mutations of RFX5: c.353 + 6T>G (maternally inherited) and c.757 + 1G>A (paternally inherited) were identified in an infant diagnosed severe immunodeficiency. The mutation c.757 + 1G>A was classified as likely pathogenic while c.353 + 6T>G was classified as the variant of uncertain significance according to American College of Medical Genetics and Genomics (ACMG). To investigate the pathogenicity of RFX5: c.353 + 6T>G, reverse transcription PCR (RT-PCR) was conducted with the mother’s peripheral blood. An insertion of 191-bp intronic sequence (intron 6) was found in the transcripts, and this resulted in a frameshift and premature truncation of the protein, especially reduced the DNA-binding domain (DBD) of the RFX5 protein. Our data expanded the spectrum of pathogenic mutations in MHC-II deficiency and put new insights into the genetic counseling, prenatal diagnosis and preimplantation genetic testing (PGT) for the disease.
An enhanced adaptive Bi-clustering algorithm through building a shielding complex sub-matrix
Authors: Xu Kaijie , Tang Xiaoan , Yin Xukun , Zhang Rui
Published: October 2022

Bi-clustering refers to the task of finding sub-matrices (indexed by a group of columns and a group of rows) within a matrix of data such that the elements of each sub-matrix (data and features) are related in a particular way, for instance, that they are similar with respect to some metric. In this paper, after analyzing the well-known Cheng and Church bi-clustering algorithm which has been proved to be an effective tool for mining co-expressed genes. However, Cheng and Church bi-clustering algorithm and summarizing its limitations (such as interference of random numbers in the greedy strategy; ignoring overlapping bi-clusters), we propose a novel enhancement of the adaptive bi-clustering algorithm, where a shielding complex sub-matrix is constructed to shield the bi-clusters that have been obtained and to discover the overlapping bi-clusters. In the shielding complex sub-matrix, the imaginary and the real parts are used to shield and extend the new bi-clusters, respectively, and to form a series of optimal bi-clusters. To assure that the obtained bi-clusters have no effect on the bi-clusters already produced, a unit impulse signal is introduced to adaptively detect and shield the constructed bi-clusters. Meanwhile, to effectively shield the null data (zero-size data), another unit impulse signal is set for adaptive detecting and shielding. In addition, we add a shielding factor to adjust the mean squared residue score of the rows (or columns), which contains the shielded data of the sub-matrix, to decide whether to retain them or not. We offer a thorough analysis of the developed scheme. The experimental results are in agreement with the theoretical analysis. The results obtained on a publicly available real microarray dataset show the enhancement of the bi-clusters performance thanks to the proposed method.
Lipids for CD8+ TILs: Beneficial or harmful?
Authors: Wu Duojiao , Chen Yuwen
Published: October 2022

Lipids and lipid metabolism play crucial roles in regulating T cell function and are tightly related to the establishment of immune memory. It is reported that tumor-infiltrating CD8+T lymphocytes (CD8+TILs) burn fats to restore their impaired effector function due to the lack of glucose. Conversely, fatty acids (FAs) and cholesterol in the tumor microenvironment (TME) drive the CD8+ TILs dysfunction. The origin of dysfunctional CD8+ TILs shares important features with memory T cell’s precursor, but whether lipids and/or lipid metabolism reprogramming directly influence the memory plasticity of dysfunctional CD8+ TILs remains elusive. It is necessary to understand the interplay between cellular lipid metabolism and dysfunction of CD8+ TILs in the case of targeting T cell’s metabolism to synergize cancer immunotherapy. Therefore, in this review, we summarize the latest research on CD8+ TILs lipid metabolism, evaluate the impacts of lipids in the TME to CD8+ TILs, and highlight the significance of promoting memory phenotype cell formation by targeting CD8+ T cells lipid metabolism to provide longer duration of cancer immunotherapy efficacy.
A randomized, double-blind, placebo-controlled, dose-escalating phase I trial to evaluate safety and immunogenicity of a plant-produced, bivalent, recombinant norovirus-like particle vaccine
Authors: Leroux-Roels Isabel , Maes Cathy , Joye Jasper , Jacobs Bart , Jarczowski Franziska , Diessner André , Janssens Yorick , Waerlop Gwenn , Tamminen Kirsi , Heinimäki Suvi , Blazevic Vesna , Leroux-Roels Geert , Klimyuk Victor , Adachi Hiroshi , Hiruta Kazuyuki , Thieme Frank
Published: October 2022

Noroviruses (NoV) are the leading cause of epidemic acute gastroenteritis in humans worldwide and a safe and effective vaccine is needed. Here, a phase I, double-blind, placebo-controlled clinical trial was performed in 60 healthy adults, 18 to 40 years old. Safety (primary objective) and immunogenicity (secondary and exploratory objectives) of a bivalent (GI.4 and GII.4), plant-produced, virus-like particle (VLP), NoV vaccine candidate formulation were investigated at two dose levels (50 µg + 50 µg and 150 µg + 150 µg) without adjuvant. Overall, 13 subjects (65.0%) in the 50 µg group, 16 subjects (80.0%) in the 150 µg group, and 14 subjects (70.0%) in the placebo group reported at least 1 solicited local or general symptom during the 7-day post-vaccination periods following each dose. Severe solicited adverse events (AEs) were rare (2 events in the 50 µg group). A total of 8 subjects (40.0%) in each group reported at least one unsolicited AE during the 28-day post-vaccination periods. Immunogenicity was assessed on days 1, 8, 29, 57, 183 and 365. All subjects were pre-exposed to norovirus as indicated by baseline levels of the different immunological parameters examined. Vaccine-specific humoral and cellular immune responses increased after the first dose but did not rise further after the second vaccination. Increased GI.4- and GII.4-specific IgG titers persisted until day 365. The vaccine elicited cross-reactive IgG antibodies against non-vaccine NoV VLPs, which was more pronounced for NoV strains of the same genotype as the GII.4 vaccine strain than for non-vaccine genotypes. Significant blocking anti-GI.4 and anti-GII.4 VLP titers were triggered in both dose groups. Lymphoproliferation assays revealed strong cell-mediated immune responses that persisted until day 365. In conclusion, both dose levels were safe and well-tolerated, and no higher incidence of AEs was observed in the higher dose group. The data show that a single dose of the vaccine formulated at 50 µg of each VLP is sufficient to reach a peak immune response after 8 to 28 days. The results of this Phase I study warrant further evaluation of the non-adjuvanted vaccine candidate.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/record/NCT05508178, identifier (NCT05508178).
A necroptosis related prognostic model of pancreatic cancer based on single cell sequencing analysis and transcriptome analysis
Authors: Chen Liang , Zhang Xueming , Zhang Qixiang , Zhang Tao , Xie Jiaheng , Wei Wei , Wang Ying , Yu Hongzhu , Zhou Hongkun
Published: October 2022

Background

As a tumor type with high mortality and poor therapeutic effect, the pathogenesis of pancreatic cancer is still unclear. It is necessary to explore the significance of necroptosis in pancreatic cancer.

Methods

Pancreatic cancer transcriptome data were obtained from the TCGA database, ICGC database, and GSE85916 in the GEO database. The TCGA cohort was set as a training cohort, while the ICGC and GSE85916 cohort were set as the validation cohorts. Single-cell sequencing data of pancreatic cancer were obtained from GSE154778 in the GEO database. The genes most associated with necroptosis were identified by weighted co-expression network analysis and single-cell sequencing analysis. COX regression and Lasso regression were performed for these genes, and the prognostic model was established. By calculating risk scores, pancreatic cancer patients could be divided into NCPTS_high and NCPTS_low groups, and survival analysis, immune infiltration analysis, and mutation analysis between groups were performed. Cell experiments including gene knockdown, CCK-8 assay, clone formation assay, transwell assay and wound healing assay were conducted to explore the role of the key gene EPS8 in pancreatic cancer. PCR assays on clinical samples were further used to verify EPS8 expression.

Results

We constructed the necroptosis-related signature in pancreatic cancer using single-cell sequencing analysis and transcriptome analysis. The calculation formula of risk score was as follows: NCPTS = POLR3GL * (-0.404) + COL17A1 * (0.092) + DDIT4 * (0.007) + PDE4C * (0.057) + CLDN1 * 0.075 + HMGA2 * 0.056 + CENPF * 0.198 +EPS8 * 0.219. Through this signature, pancreatic cancer patients with different cohorts can be divided into NCPTS_high and NCPTS_low group, and the NCPTS_high group has a significantly poorer prognosis. Moreover, there were significant differences in immune infiltration level and mutation level between the two groups. Cell assays showed that in CAPAN-1 and PANC-1 cell lines, EPS8 knockdown significantly reduced the viability, clonogenesis, migration and invasion of pancreatic cancer cells. Clinical PCR assay of EPS8 expression showed that EPS8 expression was significantly up-regulated in pancreatic cancer (*P<0.05).

Conclusion

Our study can provide a reference for the diagnosis, treatment and prognosis assessment of pancreatic cancer.
Case report: Systemic muscle involvement as the primary clinical manifestation of chronic active Epstein–Barr virus infection: A case-based review
Authors: Shi Shanfen , Li Liangda , Pan Cuiping , Yang Yandi , Chen Gun , He Yongping
Published: October 2022

Chronic active Epstein–Barr virus infection (CAEBV) is common in Asian countries and characterized by recurrent or persistent infectious mononucleosis-like symptoms. Here, we describe a rare case of CAEBV-associated generalized myositis with extranodal NK/T-cell lymphoma, who initially presented with swelling and muscle soreness in the extremities and was diagnosed as polymyositis at the initial stage. CAEBV-associated generalized myositis is different from polymyositis and other types of myositis. Furthermore, it is prone to lymphoma with poor prognosis.
GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC
Authors: Xie Huaying , Yan Tingting , Lu Xinxin , Du Yueyao , Xu Shuguang , Kong Yu , Yu Liangjie , Sun Jian , Zhou Liheng , Ma Jun
Published: October 2022

Background

TNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors involved in regulating the progression of TNBC.

Methods

We analyzed the expression profiles of TNBC in TCGA and the prognoses values of GLDC. Correlations of GLDC and tumor immune infiltration were also identified. CCK8 and BrdU incorporation assays were utilized to determine cell proliferation. The mRNA and protein levels were examined by using Real-time PCR and Western blot analysis.

Results

In the present study, we analyzed the mRNA expression profiles of TNBC in TCGA and found that GLDC, a key enzyme in glycine cleavage system, was significantly up-regulated in TNBC tissues and higher expression of GLDC was correlated with a worse prognosis in TNBC. Moreover, the expression of GLDC was negatively correlated with macrophage and monocyte and positively correlated with activated CD4 T cell and type 2 T helper cell in TNBC. Overexpression of GLDC facilitated the proliferation of TNBC cells, whereas GLDC knockdown had the opposite effects. Additionally, miR-30e acts as a functional upstream regulator of GLDC and the inhibitory effects of miR-30e on cell proliferation were mitigated by the reintroduction of GLDC.

Conclusions

These results imply that miR-30e-depressed GLDC acts as a tumor suppressive pathway in TNBC and provides potential targets for the treatment of TNBC.