bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvements in Diurnal Cycle and Its Impact on Seasonal Mean by Incorporating COARE Flux Algorithm in CFS
Authors: Pradhan Maheswar , Rao Suryachandra A. , Bhattacharya Amitabh , Balasubramanian Sridhar
Published: February 2022

The variability of predicted variables at daily to seasonal scales in coupled models is primarily governed by surface boundary conditions between the ocean and atmosphere, namely, sea surface temperature (SST), turbulent heat, and momentum fluxes. Although efforts have been made to achieve good accuracy in surface fluxes and SST in observation and reanalysis products, less attention has been paid toward achieving improved accuracy in coupled model simulations. Improper diurnal phase and amplitude in intra-daily SST and precipitation are well-known problems in most global coupled general circulation models, including the Climate Forecast System v2 (CFSv2) model. The present study attempts to improve the representation of ocean-atmosphere surface boundary conditions in CFSv2, primarily used for India's operational forecasts at different temporal/spatial scales. In this direction, the diurnal warm layer and cool skin temperature correction scheme are implemented along with the surface flux parameterization scheme following Coupled Ocean-Atmosphere Response Experiment (COARE) v 3.0. The coupled model re-forecasts with a revised flux scheme showed better characteristics in various ocean-atmosphere parameters and processes at diurnal and seasonal time scales. At the diurnal scale, the phase and amplitude of intra-daily SST and mixed layer depth variabilities are improved over most tropical oceans. Improved diurnal SSTs helped in enhancing the diurnal range of precipitation by triggering stronger intra-daily convection. The corrected diurnal ocean-atmospheric boundary state translated into a reduction in seasonal mean dry bias over Indian landmass and the wet bias over tropical oceans. Better simulation of non-linearity associated with El Niño–Southern Oscillation (ENSO), Indian Ocean Dipole (IOD), ENSO-Indian Summer Monsoon Rainfall (ISMR), and IOD-ISMR relation is among the most critical improvements achieved by revising the turbulent flux parameterization. The revised flux scheme showed enhanced prediction skills for tropical SST indices and ISMR.
Cognitive and Affective Aspects of Verbal Humor: A Visual-World Eye-Tracking Study
Authors: Israel Laura , Konieczny Lars , Ferstl Evelyn C.
Published: February 2022

Many theories of verbal humour postulate that the funniness of jokes is caused by an incongruency in the punchline whose resolution yields a feeling of mirth. While there are studies testing the prediction that this situation model updating leads to increases in processing costs, there are few studies directly assessing the time course of when the alternative situation models are entertained. In a visual world paradigm, stories were presented auditorily and displays were presented illustrating either the situation implied by the context or the final interpretation after the punchline. Eye movement data confirmed the switch from the initial to the final interpretation for jokes as well as for non-funny control stories that also required a situation model revision. In addition to these effects of the cognitive revision requirements, the pupil dilations were sensitive to the affective component of joke comprehension. These results are discussed in light of incongruency theories of verbal humour.
T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies
Authors: Neves Eula G. A. , Koh Carolina C. , Souza-Silva Thaiany G. , Passos Lívia Silva Araújo , Silva Ana Carolina C. , Velikkakam Teresiama , Villani Fernanda , Coelho Janete Soares , Brodskyn Claudia Ida , Teixeira Andrea , Gollob Kenneth J. , Nunes Maria do Carmo P. , Dutra Walderez O.
Published: February 2022

Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4+, CD8+, and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8+ T-cells were highly activated in CCC as compared to IDC, CD4+ T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.
Targeting ApoC3 Paradoxically Aggravates Atherosclerosis in Hamsters With Severe Refractory Hypercholesterolemia
Authors: Xu Yitong , Guo Jiabao , Zhang Ling , Miao Guolin , Lai Pingping , Zhang Wenxi , Liu Lili , Hou Xinlin , Wang Yuhui , Huang Wei , Liu George , Gao Mingming , Xian Xunde
Published: February 2022

Rationale

ApoC3 plays a central role in the hydrolysis process of triglyceride (TG)-rich lipoproteins mediated by lipoprotein lipase (LPL), which levels are positively associated with the incidence of cardiovascular disease (CVD). Although targeting ApoC3 by antisense oligonucleotide (ASO), Volanesorsen markedly reduces plasma TG level and increase high-density lipoprotein cholesterol (HDL-C) in patients with hypertriglyceridemia (HTG), the cholesterol-lowering effect of ApoC3 inhibition and then the consequential outcome of atherosclerotic cardiovascular disease (ASCVD) have not been reported in patients of familial hypercholesterolemia (FH) with severe refractory hypercholesterolemia yet.

Objective

To investigate the precise effects of depleting ApoC3 on refractory hypercholesterolemia and atherosclerosis, we crossed ApoC3-deficient hamsters with a background of LDLR deficiency to generate a double knockout (DKO) hamster model (LDLR−/−, XApoC3−/−, DKO).

Approach and Results

On the standard laboratory diet, DKO hamsters had reduced levels of plasma TG and total cholesterol (TC) relative to LDLR−/− hamsters. However, upon high-cholesterol/high-fat (HCHF) diet feeding for 12 weeks, ApoC3 deficiency reduced TG level only in female animals without affecting refractory cholesterol in the circulation, whereas apolipoprotein A1 (ApoA1) levels were significantly increased in DKO hamsters with both genders. Unexpectedly, loss of ApoC3 paradoxically accelerated diet-induced atherosclerotic development in female and male LDLR−/− hamsters but ameliorated fatty liver in female animals. Further analysis of blood biological parameters revealed that lacking ApoC3 resulted in abnormal platelet (PLT) indices, which could potentially contribute to atherosclerosis in LDLR−/− hamsters.

Conclusions

In this study, our novel findings provide new insight into the application of ApoC3 inhibition for severe refractory hypercholesterolemia and ASCVD.
Seafloor Structures and Static Stress Changes Associated With Two Recent Earthquakes in Offshore Southern Batangas, Philippines
Authors: Sarmiento Keanu Jershon S. , Aurelio Mario A. , Flores Paul Caesar M. , Carrillo Anne Drew V. , Marfito Bryan J. , Abigania Maria Isabel T. , Daag Arturo S. , Siringan Fernando P.
Published: February 2022

The 1994 Mw 7.1 Mindoro Earthquake and the 2017 Mw 5.9 Batangas Earthquake Sequence both occurred in offshore southern Batangas and devastated southern Luzon and Mindoro. These earthquakes exhibited NW-striking right-lateral slip in an area presumably defined by a WNW-striking left-lateral fault, therefore implying the existence of previously unmapped offshore faults. High resolution multibeam bathymetry grid and subbottom profiles revealed a conjugate strike-slip fault system under an approximately EW-directed extension. NW-striking right-lateral faults (F1 Faults: Central Mindoro Fault, Aglubang River Fault, and Batangas Bay Fault System) bound the western part of the study area. On the other hand, a series of almost parallel NE-trending left-lateral and normal faults (F2 Faults: Macolod Corridor, North Verde Fault System, Central Verde Fault System, South Verde Fault, and Northeast Mindoro Fault System) approach the F1 faults from the northeast. The distribution of the 1994 and 2017 earthquakes suggests that the possible rupture areas for these events are the Aglubang River Fault and the southwest Batangas Bay Fault System, respectively. These two traces appear to be connected and a restraining bend is suggested to have acted as a rupture barrier between the two events. Coulomb stress transfer modeling showed that the 1994 earthquake promoted the failure of the 2017 earthquake. Furthermore, results from the stress transfer models showed stress increase on the F1 faults (Batangas Bay Fault System and Central Mindoro Fault) and the northern F2 faults (North Verde Fault System and Central Verde Fault System). The newly recognized faults redefine the knowledge of the neotectonic structure of the area but are still consistent with the ongoing east-west extension in southern Luzon and the overall extension in northern Central Philippines. These faults pose seismic hazards, and more studies are needed to determine their seismogenic potential.
Composition Effect on the Pore Structure of Transitional Shale: A Case Study of the Permian Shanxi Formation in the Daning–Jixian Block at the Eastern Margin of the Ordos Basin
Authors: Zhang Qin , Qiu Zhen , Zhao Qun , Zhang Leifu , Dong Dazhong , Wang Yuman , Hou Wei , Li Shuxin , Li Xingtao
Published: February 2022

Marine–continental transitional (hereinafter referred to as transitional) Permian shales are important targets for shale gas in China because of the considerable volumes of shale gas resources present in them. In this study, transitional shale samples from the Permian Shanxi Formation in the Daning–Jixian block along the eastern margin of the Ordos Basin were collected to investigate the effects of organic and inorganic compositions on the development of their pore structures through organic petrographic analysis, X–ray diffraction, scanning electron microscope (SEM) observation, gas (N2 and CO2) adsorption, high-pressure mercury injection (HPMI), and methane adsorption experiments. The organic petrographic analysis reveals that the Permian Shanxi shale comprises Type-II2-III kerogens, and the average vitrinite reflectance (Ro) is 2.3% at the overmature stage or in the dry gas window. The shale interval at the bottom of the lagoon facies is considered the most favorable interval throughout the entire section because of its high total organic carbon (TOC) content (4.19–43.9%; an average of 16.9%) and high brittle mineral content (38.3–73.2%; an average of 55.8%). N2 and CO2 gas adsorption and HPMI tests reveal the pore size distribution characteristics of the shale. The full pore size distribution by the gas adsorption and HPMI test reveals that micropores (<2 nm) and mesopores (2–50 nm) were dominant in the pore system, and the contributions of the two pore sizes were nearly equivalent, accounting for 21.95–55.05% (an average of 42.3%) and 37.94–64.6% (an average of 49.64%) of the total pore volume, respectively. Additionally, the pore characteristics related to different phases (mainly as silicate, clays, and organic matter) are further clarified by SEM observation and correlation analysis of phase content and pore structure parameters. OM contains numerous SEM-invisible micropores, whereas clay minerals mainly develop mesopores and small macropores (50–100 nm). Furthermore, we calculated the contribution of different shale components to shale porosity. The OM pores account for 0.26–44.1% (an average of 18.7%), and clay mineral pores account for 53.8–93.3% (an average of 76.9%) of the shale porosity. In particular, the OM contributes 73.2% to the surface area and 33.5% to the pore volume. This implies that both OM and clay minerals are important for the storage capacity of adsorbed and free gas.
Study on the Structural Plane Characteristics and Disaster-Induced Mechanism of the Yellow River Jingtai Stone Forest, Northwestern Loess Plateau, China
Authors: Lyu Yan , Gu Gang , Wang Zuopeng , Leng Yanqiu , Ma Penghui , Peng Jianbing
Published: February 2022

The Yellow River Jingtai Stone Forest (YJSF) is situated in the northwestern margin of the Chinese Loess Plateau, and it is not only one of the most precious and rare types of natural landforms in the Loess Plateau but also a protected area of valuable geological relics and landscapes in northwest China. Massive rock structural planes are present in the stone forest. However, few studies have been conducted on the rock mass structural planes for the slope’s stability. Based on the detailed field investigation, structural planes and their combination types are classified based on the rock mass. On this basis, combined with physical, mechanical, and hydraulic tests, the disaster-induced mechanism of the rock mass structural planes is classified and discussed. Results show that the structural planes of the YJSF can be divided into three types, namely, the primary structural plane, tectonic structural plane, and secondary plane. They not only combine with each other to cut the rock mass into different shape blocks but also jointly control the stability of the rock mass slope. The physical and mechanical tests and water sensitivity characteristics show that the conglomerates and muddy sandstones which are the main components of the YJSF have strong tensile and shear strengths under natural situations, while their strengths are reduced under immersion infiltration; in particular, the muddy sandstones are more sensitive to water and have a lower strength than that of the conglomerates. Finally, the disaster-induced mechanism of the YJSF is mainly related to the combination of various structural planes, which can be divided into four failure patterns, namely, creeping slide-tension failure, gradual failure, slipping failure, and dumping failure; coupling action of endogenic and exogenic geodynamic processes was responsible for their formation. The studied results will provide critical, theoretical, and technical support for the slope stability analysis, scenic geological heritage protection, and disaster warning in this area.
Research on Failure Precursor Based on Characteristics of Energy Dissipation Rate for Rock
Authors: Liu Xiaohui , Xue Yang , Zheng Yu , Li Hongying
Published: February 2022

Research on early warning of rock disaster based on the energy theory is closer to the essence of rock failure. In this paper, static compression tests and acoustic emission (AE) tests of coal rock under 0, 8, 16, and 25 MPa confining pressures were carried out on the MTS815 test system. Energy evolution law in the rock failure process was analyzed according to the relationship between mechanical parameters, AE parameters, and energy dissipation rate (EDR) in the rock failure process. Eventually, a new index for evaluating rock failure precursors was proposed based on EDR. The results show that the EDR has a good correlation with mechanical strength and AE events under different confining pressures. The deformation and failure characteristics of coal rock can be truly characterized by EDR. The variation of EDR can be divided into a quiet stage, a stable increasing stage, an active stage, and a stable stage. The EDR level in the quiet stage is obviously enhanced by confining pressure. When EDR reaches the peak, AE events increase rapidly. In the active stage, the EDR peak value is concentrated and large, the AE event is highly active, and stress drops abruptly, indicating that the EDR is reliable for evaluating the rock failure process. Compared with AE test results, it is found that the warning stress and warning time of the EDR failure precursor occur later than that of the AE failure precursor, and the former is closer to the peak stress of rock, which is more universal in engineering and could provide a better reference value for preventing rock disaster.
Diachronic Change in the Utilization of Ostrich Eggshell at the Late Paleolithic Shizitan Site, North China
Authors: Song Yanhua , Cohen David J. , Shi Jinming
Published: February 2022

Forty-one ostrich eggshell (OES) artifacts excavated at five localities of the late Paleolithic Shizitan site, on the North China Loess Plateau, allow the observation of diachronic changes in the utilization of ostrich eggs in the production and use of ornaments considered to be technologies of social signaling, beginning during the Last Glacial Maximum (LGM) and continuing through the Younger Dryas. Based on changes in dimensions, production techniques such as drilling, coloration through heat treatment or the application of ochre, and stringing techniques, the OES pendant and bead use at Shizitan is divided into four phases. Phases 1–3 feature only completed ornaments, usually with heavy usewear. Only in Phase 4, during the Younger Dryas, blanks and drilled preforms are found that indicate local production. While Phase 1 features the use of larger pendants colored grey/black by burning, subsequent phases see beads replacing pendants, no heat coloration, and the use of the ochre pigment. The switch to beads corresponds with the change to microblade technology at Shizitan 29. Phase 3 shows a trend toward a larger relative surface display area and maturation of techniques to produce visual effects of roundedness and weightiness. Phase 4 local production shows technological developments that allowed drilling smaller apertures while also decreasing the bead diameter and increased standardization, implying changing display objectives (stringing beads together with a uniform appearance). The changes observed in the Shizitan diachronic dataset may relate to changing requirements in social signaling—part of the adaptations the hunter–gatherer groups made to survive the challenges of climatic change from the LGM through the Terminal Pleistocene in North China.
Deep External Fluid Source Along the Gubbio Normal Fault (Italy): Implications for Slip Along the Altotiberina Active Low-Angle Normal Fault System
Authors: Riegel Hannah , Casale Gabriele , Mirabella Francesco , Hyland Ethan , Talegalli Lorenzo
Published: February 2022

Fluids play a critical role in fault slip, fault and damage zone development, and the distribution of seismicity in regional fault systems; however, determining the source of fluids within fault damage zones is complicated by superposition of fluid-related fabrics. Clumped isotopes applied to tectonic studies offer an opportunity to distinguish between fluid sources based on temperature and stable isotopic composition. Here we use the clumped isotope geothermometer and field observations and compare them with microstructural analysis to investigate the Gubbio normal-fault (GuF) core, a major SW-dipping epidetachment fault conjugate to the active Altotiberina low-angle normal fault in central Italy. Several distinct calcite vein sets reveal the incorporation of multiple generations of fluids during development of the damage zone. Clumped isotope results from these various precipitation phases record crystallization temperatures ranging from 87–154°C. These temperatures are broadly consistent with the presence of calcite deformation twin types II and III and are higher than estimates of regional peak burial temperatures. Additionally, stable isotope compositions within vein calcite are distinct from published isotopic values of the Apennine sedimentary succession, which constitutes the local bedrock. We propose that these observations suggest hydrothermal fluids migrated from depths greater than 6 km, which requires hydraulic connectivity along structural pathways between the shallow and deep crust, and fluid overpressures. These fluids reach the GuF via migration along the Altotiberina low-angle normal fault plane ​​and they may be either of diagenetic or of deeper subduction origin. We suggest they possibly originated from the proximal retreating Apennine subduction system, implying that subduction processes exert spatial control on the distribution of fluid-assisted normal faulting and related seismicity which is consistent with the co-migration of closely coupled subduction and hinterland extension in the Apennines from Miocene to Present.
Lived Experiences of Learners With Cerebral Palsy Educated in Inclusive Classrooms in the Czech Republic
Authors: Sedláčková Dagmar , Kantor Jiří
Published: February 2022

Changes in legislation in the Czech Republic in 2016 moved the system of education towards inclusion and created more favorable conditions for joint education, but we still do not have enough information about experiences of learners with cerebral palsy educated in an inclusive environment. A qualitative design was chosen to explore the lived experiences of Czech learners with cerebral palsy educated in inclusive schools. Semi-structured interviews combined with biographical narration of learners with cerebral palsy, aged 12–20, and a brief questionnaire for demographic data were used for data collection. Data analyses were carried out according to van Manen’s approach, including defining the main themes and description of the lived experiences of learners. The following four themes were identified: 1) barriers, 2) strategies for overcoming obstacles, 3) values in relation to peers, 4) and the future. The results of this qualitative study point to a number of obstacles and pressures that these learners face in their education, as well as to the ways of solving some problems. The results indicate that it is important to realize that the consequences of interpersonal relationships significantly influence the formation of self-concept and personality development of these learners, and therefore it is necessary for teaching staff to deal with the support of positive relationships at schools. When creating a supportive inclusive environment, it is also necessary to pay attention to the learners’ future, because the present Czech society does not offer sufficiently inclusive conditions in further education and occupation.
Large-Volume Lateral Lymph Node Metastasis Predicts Worse Prognosis in Papillary Thyroid Carcinoma Patients With N1b
Authors: Gao Luying , Li Xiaoyi , Xia Yu , Liu Ruifeng , Liu Chunhao , Shi Xinlong , Wu Yanjiao , Ma Liyuan , Jiang Yuxin
Published: February 2022

We aimed to evaluate the relevance of large-volume lateral lymph node metastases (LLNMs) at risk of recurrence/persistence in papillary thyroid carcinoma (PTC) with LLNMs (N1b). This retrospective study included 448 PTC patients, who had positive LLNMs confirmed by histology and suspected of LLNMs by preoperative ultrasound. According to the number of pathological LLNMs, patients were divided into large-volume LLNM (number of LLNMs >5) and low-volume LLNM (number of LLNMs ≤5). Risk factors of recurrence/persistence in PTC patients with N1b were analyzed. Preoperative ultrasound features of PTC with large-volume LLNM were analyzed. For the patients with a mean follow-up of 44.0 months, the risk of recurrence/persistence was 25.1% in PTC patients with N1b. The recurrence/persistence rate was significantly higher in patients with large-volume LLNM than in patients with low-volume LLNM by multivariate analysis (37.3% vs. 17.1%; HR = 2.451, 95% CI 1.41–4.261, p = 0.001). The 3-year and 5-year recurrence/persistence-free survival for those with large-volume LLNM were 93.2% and 47.2%, respectively. Moreover, we found that multilevel suspected LLNMs and loss of fatty hilum were independent preoperative indicative factors of large-volume LLNM (OR = 6.239, 95% CI 3.547–10.977, p < 0.001; OR = 5.149, 95% CI 1.859–14.261, p = 0.002). In conclusion, multilevel suspected LLNM and loss of fatty hilum on ultrasound tended to be more common in patients with large-volume LLNM. PTC patients with large-volume LLNM are at a higher recurrent/persistent risk than those with low-volume LLNM. Large-volume LLNM may be used to stratify the risk of recurrence/persistence in PTC.
Study on Hydraulic Characteristics of Reactor Coolant Pump Shutdown Transition Process Based on Primary Circuit Closed System
Authors: Li Dong-hao , Li Yi-bin , Zhang Fan , Guo Yan-lei , Yang Cong-xin , Wang Xiu-yong
Published: February 2022

According to the structural characteristics of a steam generator and a reactor pressure vessel, the reactor primary circuit system of HPR1000 is simplified to make the reactor coolant pump (RCP) characteristics match the resistance characteristics of the system pipeline, so a simplified model of reactor primary circuit closed system is formed. On this basis, the RCP shutdown accident in a single circuit of the reactor is numerically simulated. Results show that the pressure in the pipeline system has changed greatly compared. The flow rate drops rapidly and decreases to 1.7% of stable operation at 10s. The torque drops sharply to −51.89% of stable operation, and then rises slowly to zero. The pressure at the inlet and outlet of the impeller changes dramatically which leads to the change of blade load and the velocity in the impeller passage decreases gradually. The pressure and velocity in the guide vane continue to decrease.
Day-Ahead Optimal Dispatch for Active Distribution Network Considering Probability Model of Controllable Distributed Generation
Authors: Wang Jianxi , Zhang Shida , Sun Yonghui , Du Xinye , Wu Pengpeng , Mahfoud Rabea Jamil
Published: February 2022

In this paper, the probabilistic model of the controllable distributed generation in active distribution network is developed and applied to the daily stochastic optimal dispatch. The probabilistic characteristics of photovoltaic power generation system with active control capability are explored, and the relationship between the reference value of active power and its cumulative distribution function and mean value is obtained. The active power probability model of wind power generation system is improved according to the actual wind speed power curve. By fully utilizing the inverter capacity and coordinating active power, the reactive power of distributed generation is actively controlled under the constraint of power factor. Then considering the chance constraints, a daily optimal scheduling model for active distribution network with the goal of minimizing the operating cost of distribution network is developed, and the constraints that can calculate the charge and discharge times of the energy storage system are designed. The chance constrained programming is solved by the heuristic method, and the deterministic optimization steps are solved by the second-order cone programming method, respectively. The probabilistic power flow method based on stochastic response surface method is utilized to test chance constraints. Finally, the modified IEEE33 node distribution system example shows that the obtained models and algorithms are correct and can meet the requirements of safe and economic operation.
Load Capacity Factor and Financial Globalization in Brazil: The Role of Renewable Energy and Urbanization
Authors: Xu Dace , Salem Sultan , Awosusi Abraham Ayobamiji , Abdurakhmanova Gulnora , Altuntaş Mehmet , Oluwajana Dokun , Kirikkaleli Dervis , Ojekemi Opeoluwaseun
Published: February 2022

To mitigate environmental challenges and fulfill the Sustainable Development Goals, a broader and holistic ecological assessment is required. As a result, this research utilizes the load capacity factor, which is a distinct proxy of environmental deterioration that offers a detailed environmental evaluation measurement by comparing biocapacity and ecological footprint simultaneously. Moreover, the load capacity factor provides the combined attributes of the demand and supply-side of environmental quality. Therefore, this research scrutinized the effect of financial globalization, urbanization, economic growth, and renewable and nonrenewable energy usage on load capacity factor for the period stretching between 1970 and 2017 in Brazil. The bounds testing procedure for cointegration in combination with the critical approximation p-values of Kripfganz and Schneider (2018) disclosed a cointegrating association between load capacity and its regressors. The outcome of the ARDL method uncovered that economic growth, non-renewable and renewable energy reduce the load capacity factor, whereas urbanization has no impact on load capacity factor in Brazil. However, financial globalization has a positive effect on load capacity factor in Brazil. Finally, the study uses the spectral causality test to assess the causality interaction between the observed parameters. The policymakers should take advantage of the opportunity by developing policies that encourage the openness of the economy to foreign investors.
Hemp Genome Editing—Challenges and Opportunities
Authors: Shiels Donal , Prestwich Barbara Doyle , Koo Okjae , Kanchiswamy Chidananda Nagamangala , O'Halloran Roisin , Badmi Raghuram
Published: February 2022

Hemp (Cannabis sativa L.) is a multipurpose crop with many important uses including medicine, fibre, food and biocomposites. This plant is currently gaining prominence and acceptance for its valuable applications. Hemp is grown as a cash crop for its novel cannabinoids which are estimated to be a multibillion-dollar downstream market. Hemp cultivation can play a major role in carbon sequestration with good CO2 to biomass conversion in low input systems and can also improve soil health and promote phytoremediation. The recent advent of genome editing tools to produce non-transgenic genome-edited crops with no trace of foreign genetic material has the potential to overcome regulatory hurdles faced by genetically modified crops. The use of Artificial Intelligence - mediated trait discovery platforms are revolutionizing the agricultural industry to produce desirable crops with unprecedented accuracy and speed. However, genome editing tools to improve the beneficial properties of hemp have not yet been deployed. Recent availability of high-quality Cannabis genome sequences from several strains (cannabidiol and tetrahydrocannabinol balanced and CBD/THC rich strains) have paved the way for improving the production of valuable bioactive molecules for the welfare of humankind and the environment. In this context, the article focuses on exploiting advanced genome editing tools to produce non-transgenic hemp to improve the most industrially desirable traits. The challenges, opportunities and interdisciplinary approaches that can be adopted from existing technologies in other plant species are highlighted.
Role of Circular RNAs in the Regulation of Immune Cells in Response to Cancer Therapies
Authors: Carlos-Reyes Ángeles , Romero-Garcia Susana , Contreras-Sanzón Estefania , Ruiz Víctor , Prado-Garcia Heriberto
Published: February 2022

Circular RNAs (CircRNAs) are a class of small endogenous noncoding RNA that are formed by means of either the spliceosome or lariat-type splicing. CircRNAs have multiple regulatory functions and have been detected in different cell types, like normal, tumor and immune cells. CircRNAs have been suggested to regulate T cell functions in response to cancer. CircRNAs can enter into T cells and promote the expression of molecules that either trigger antitumoral responses or promote suppression and the consequent evasion to the immune response. Additionally, circRNAs may promote tumor progression and resistance to anticancer treatment in different types of neoplasias. In this minireview we discuss the impact of circRNAs and its function in the regulation of the T-cells in immune response caused by cancer therapies.
Comprehensive Analysis of Sinonasal Inverted Papilloma Expression Profiles Identifies Long Non-Coding RNA AKTIP as a Potential Biomarker
Authors: He Hanyi , Wang Xinlu , Lu Yueyue , Lin Xiaojiang , Li Yuandong , Li Yong , Lin Zhihong , Ma Zhiqi , Cao Xiaolin , Teng Yaoshu
Published: February 2022

Long noncoding RNAs (lncRNAs) are a novel class of potential biomarkers and therapeutic targets for the treatment of neoplasms. The purpose of this study was to explore the expression profile, potential functions, and diagnostic and clinical significance of lncRNAs in sinonasal inverted papilloma (SNIP). The expression profiles of lncRNAs and mRNAs were analyzed using a microarray. The potential functions and clinical implications of specific lncRNAs were further analyzed by bioinformatics and statistical methods. Microarray analysis identified 1,668 significantly upregulated and 1,767 downregulated lncRNAs in SNIP. Several mRNAs coexpressed with lncRNAs were enriched in some biological processes and cellular signaling pathways related to tumorigenesis. Lnc-AKTIP might interact with a variety of tumor-associated proteins and transcription factors, such as PCBP2, IRF-1, and p53. Receiver operating characteristic curve analysis for lnc-AKTIP showed an area under the curve of 0.939. Notably, its expression level was significantly decreased in SNIP tissues versus normal tissues and was associated with SNIP staging. Lnc-AKTIP may serve as a valuable diagnostic biomarker and a therapeutic target for SNIP.
Predicting Treatment Response in Schizophrenia With Magnetic Resonance Imaging and Polygenic Risk Score
Authors: Wang Meng , Hu Ke , Fan Lingzhong , Yan Hao , Li Peng , Jiang Tianzi , Liu Bing
Published: February 2022

Background: Prior studies have separately demonstrated that magnetic resonance imaging (MRI) and schizophrenia polygenic risk score (PRS) are predictive of antipsychotic medication treatment outcomes in schizophrenia. However, it remains unclear whether MRI combined with PRS can provide superior prognostic performance. Besides, the relative importance of these measures in predictions is not investigated.

Methods: We collected 57 patients with schizophrenia, all of which had baseline MRI and genotype data. All these patients received approximately 6 weeks of antipsychotic medication treatment. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up. We divided these patients into responders (N = 20) or non-responders (N = 37) based on whether their percentages of PANSS total reduction were above or below 50%. Nine categories of MRI measures and PRSs with 145 different p-value thresholding ranges were calculated. We trained machine learning classifiers with these baseline predictors to identify whether a patient was a responder or non-responder.

Results: The extreme gradient boosting (XGBoost) technique was applied to build binary classifiers. Using a leave-one-out cross-validation scheme, we achieved an accuracy of 86% with all MRI and PRS features. Other metrics were also estimated, including sensitivity (85%), specificity (86%), F1-score (81%), and area under the receiver operating characteristic curve (0.86). We found excluding a single feature category of gray matter volume (GMV), amplitude of low-frequency fluctuation (ALFF), and surface curvature could lead to a maximum accuracy drop of 10.5%. These three categories contributed more than half of the top 10 important features. Besides, removing PRS features caused a modest accuracy drop (8.8%), which was not the least decrease (1.8%) among all feature categories.

Conclusions: Our classifier using both MRI and PRS features was stable and not biased to predicting either responder or non-responder. Combining with MRI measures, PRS could provide certain extra predictive power of antipsychotic medication treatment outcomes in schizophrenia. PRS exhibited medium importance in predictions, lower than GMV, ALFF, and surface curvature, but higher than measures of cortical thickness, cortical volume, and surface sulcal depth. Our findings inform the contributions of PRS in predictions of treatment outcomes in schizophrenia.
Photobiomodulation Therapy Restores IL-10 Secretion in a Murine Model of Chronic Asthma: Relevance to the Population of CD4+CD25+Foxp3+ Cells in Lung
Authors: de Brito Aurileia Aparecida , Gonçalves Santos Tawany , Herculano Karine Zanella , Estefano-Alves Cintia , de Alvarenga Nascimento Cristiano Rodrigo , Rigonato-Oliveira Nicole Cristine , Chavantes Maria Cristina , Aimbire Flávio , da Palma Renata Kelly , Ligeiro de Oliveira Ana Paula
Published: February 2022

It is largely known that photobiomodulation (PBM) has beneficial effects on allergic pulmonary inflammation. Our previous study showed an anti-inflammatory effect of the PBM in an acute experimental model of asthma, and we see that this mechanism is partly dependent on IL-10. However, it remains unclear whether the activation of regulatory T cells is mediated by PBM in a chronic experimental model of asthma. In this sense, the objective of this study was to verify the anti-inflammatory role of the PBM in the pulmonary inflammatory response in a chronic experimental asthma model. The protocol used for asthma induction was the administration of OVA subcutaneously (days 0 and 14) and intranasally (3 times/week, for 5 weeks). On day 50, the animals were sacrificed for the evaluation of the different parameters. The PBM used was the diode, with a wavelength of 660 nm, a power of 100 mW, and 5 J for 50 s/point, in three different application points. Our results showed that PBM decreases macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid (BALF). Moreover, PBM decreased the release of cytokines by the lung, mucus, and collagen in the airways and pulmonary mechanics. When we analyzed the percentage of Treg cells in the group irradiated with laser, we verified an increase in these cells, as well as the release of IL-10 in the BALF. Therefore, we conclude that the use of PBM therapy in chronic airway inflammation attenuated the inflammatory process, as well as the pulmonary functional and structural parameters, probably due to an increase in Treg cells.
Evaluation of Oropharyngeal Dysphagia in Older Patients for Risk Stratification of Pneumonia
Authors: Lin Tai-Han , Yang Chih-Wei , Chang Wei-Kuo
Published: February 2022

Objective

Nasogastric tube (NGT) and percutaneous endoscopic gastrostomy (PEG) are widely used techniques to feed older patients with oropharyngeal dysphagia. Aspiration pneumonia is the most common cause of death in these patients. This study aimed to evaluate the role of oropharyngeal dysphagia in older patients on long-term enteral feeding for risk stratification of pneumonia requiring hospitalization.

Methods

We performed modified flexible endoscopic evaluation of swallowing to evaluate oropharyngeal dysphagia in older patients and conducted prospective follow-up for pneumonia requiring hospitalization. A total of 664 oral-feeding patients and 155 tube-feeding patients were enrolled. Multivariate Cox analysis was performed to identify risk factors of pneumonia requiring hospitalization.

Results

Multivariate analyses showed that the risk of pneumonia requiring hospitalization significantly increased in older patients and in patients with neurological disorders, tube feeding, and oropharyngeal dysphagia. Subgroup analysis revealed that the risk of pneumonia requiring hospitalization was significantly lower in patients with PEG than in those with NGT among the patients with oropharyngeal dysphagia (adjusted hazard ratio 0.26, 95% confidence interval: 0.11–0.63, P = 0.003).

Conclusions

For older patients with oropharyngeal dysphagia requiring long-term enteral tube feeding, PEG is a better choice than NGT. Further research is needed to elucidate the role of oropharyngeal dysphagia in enteral feeding in older patients.
Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria
Authors: Ramani Kritika , Cormack Taylor , Cartwright Adam N. R. , Alami Aula , Parameswaran Pooja , Abdou Marynawal , Wang Iris , Hilliard-Barth Kristie , Argueta Shannon , Raghunathan Divya , Caffry Will , Davitt Christopher J. H. , Romano Fabian B. , Ng Aylwin , Kravitz Valeria , Rommel Tyler , Sizova Maria , Kiran Esra Uckun , Pradeep Pallavi , Ponichtera Holly E. , Ganguly Tanmoy , Bodmer Mark , Itano Andrea
Published: February 2022

The gastrointestinal tract represents one of the largest body surfaces that is exposed to the outside world. It is the only mucosal surface that is required to simultaneously recognize and defend against pathogens, while allowing nutrients containing foreign antigens to be tolerated and absorbed. It differentiates between these foreign substances through a complex system of pattern recognition receptors expressed on the surface of the intestinal epithelial cells as well as the underlying immune cells. These immune cells actively sample and evaluate microbes and other particles that pass through the lumen of the gut. This local sensing system is part of a broader distributed signaling system that is connected to the rest of the body through the enteric nervous system, the immune system, and the metabolic system. While local tissue homeostasis is maintained by commensal bacteria that colonize the gut, colonization itself may not be required for the activation of distributed signaling networks that can result in modulation of peripheral inflammation. Herein, we describe the ability of a gut-restricted strain of commensal bacteria to drive systemic anti-inflammatory effects in a manner that does not rely upon its ability to colonize the gastrointestinal tract or alter the mucosal microbiome. Orally administered EDP1867, a gamma-irradiated strain of Veillonella parvula, rapidly transits through the murine gut without colonization or alteration of the background microbiome flora. In murine models of inflammatory disease including delayed-type hypersensitivity (DTH), atopic dermatitis, psoriasis, and experimental autoimmune encephalomyelitis (EAE), treatment with EDP1867 resulted in significant reduction in inflammation and immunopathology. Ex vivo cytokine analyses revealed that EDP1867 treatment diminished production of pro-inflammatory cytokines involved in inflammatory cascades. Furthermore, blockade of lymphocyte migration to the gut-associated lymphoid tissues impaired the ability of EDP1867 to resolve peripheral inflammation, supporting the hypothesis that circulating immune cells are responsible for promulgating the signals from the gut to peripheral tissues. Finally, we show that adoptively transferred T cells from EDP1867-treated mice inhibit inflammation induced in recipient mice. These results demonstrate that an orally-delivered, non-viable strain of commensal bacteria can mediate potent anti-inflammatory effects in peripheral tissues through transient occupancy of the gastrointestinal tract, and support the development of non-living bacterial strains for therapeutic applications.
Ferroptosis in Rheumatoid Arthritis: A Potential Therapeutic Strategy
Authors: Zhao Ting , Yang Qi , Xi Yujiang , Xie Zhaohu , Shen Jiayan , Li Zhenmin , Li Zhaofu , Qin Dongdong
Published: February 2022

Ferroptosis is one of the newly discovered forms of cell-regulated death characterized by iron-dependent lipid peroxidation. Extensive research has focused on the roles of ferroptosis in tumors, blood diseases, and neurological diseases. Some recent findings have indicated that ferroptosis may also be related to the occurrence and development of inflammatory arthritis. Ferroptosis may be a potential therapeutic target, and few studies in vitro and animal models have shown implications in the pathogenesis of inflammatory arthritis. This mini review discussed the common features between ferroptosis and the pathogenesis of rheumatoid arthritis (RA), and evaluated therapeutic applications of ferroptosis regulators in preclinical and clinical research. Some critical issues worth paying attention to were also raised to guide future research efforts.
Calcium Signaling Is Impaired in PTEN-Deficient T Cell Acute Lymphoblastic Leukemia
Authors: Pankaew Saran , Potier Delphine , Grosjean Clémence , Nozais Mathis , Quessada Julie , Loosveld Marie , Remy Élisabeth , Payet-Bornet Dominique
Published: February 2022

PTEN (Phosphatase and TENsin homolog) is a well-known tumor suppressor involved in numerous types of cancer, including T-cell acute lymphoblastic leukemia (T-ALL). In human, loss-of-function mutations of PTEN are correlated to mature T-ALL expressing a T-cell receptor (TCR) at their cell surface. In accordance with human T-ALL, inactivation of Pten gene in mouse thymocytes induces TCRαβ+ T-ALL development. Herein, we explored the functional interaction between TCRαβ signaling and PTEN. First, we performed single-cell RNA sequencing (scRNAseq) of PTEN-deficient and PTEN-proficient thymocytes. Bioinformatic analysis of our scRNAseq data showed that pathological Ptendel thymocytes express, as expected, Myc transcript, whereas inference of pathway activity revealed that these Ptendel thymocytes display a lower calcium pathway activity score compared to their physiological counterparts. We confirmed this result using ex vivo calcium flux assay and showed that upon TCR activation tumor Ptendel blasts were unable to release calcium ions (Ca2+) from the endoplasmic reticulum to the cytosol. In order to understand such phenomena, we constructed a mathematical model centered on the mechanisms controlling the calcium flux, integrating TCR signal strength and PTEN interactions. This qualitative model displays a dynamical behavior coherent with the dynamics reported in the literature, it also predicts that PTEN affects positively IP3 (inositol 1,4,5-trisphosphate) receptors (ITPR). Hence, we analyzed Itpr expression and unraveled that ITPR proteins levels are reduced in PTEN-deficient tumor cells compared to physiological and leukemic PTEN-proficient cells. However, calcium flux and ITPR proteins expression are not defective in non-leukemic PTEN-deficient T cells indicating that beyond PTEN loss an additional alteration is required. Altogether, our study shows that ITPR/Calcium flux is a part of the oncogenic landscape shaped by PTEN loss and pinpoints a putative role of PTEN in the regulation of ITPR proteins in thymocytes, which remains to be characterized.