bluuebunny/crossref_metadata_2025 huggingface dataset:
Medial artery calcification in peripheral artery disease
Authors: Kim Tanner I. , Guzman Raul J.
Published: January 2023

Medial artery calcification (MAC) is a distinct, highly regulated process that is often identified in small and mid-sized arteries of the lower extremities. It is associated with advanced age, diabetes, and chronic kidney disease. MAC often occurs in conjunction with atherosclerotic occlusive disease in lower extremity arteries, and when seen together or in isolation, long-term limb outcomes are negatively affected. In patients with peripheral artery disease (PAD), the extent of MAC independently correlates with major amputation and mortality rates, and it predicts poor outcomes after endovascular interventions. It is associated with increased arterial stiffness and decreased pedal perfusion. New endovascular methods aimed at treating calcified lower-extremity lesions may improve our ability to treat patients with limb-threatening ischemia. Although recent developments have increased our understanding of the mechanisms contributing to MAC, further investigations are needed to understand the role of medial calcification in PAD, and to develop strategies aimed at improving patient outcomes.
Mechanism of Tao Hong Decoction in the treatment of atherosclerosis based on network pharmacology and experimental validation
Authors: Li SiJin , Liu Ping , Feng Xiaoteng , Du Min , Zhang Yifan , Wang YiRu , Wang JiaRou
Published: January 2023

Background

Atherosclerosis (AS) has long been recognized as a cardiovascular disease and stroke risk factor. A well-known traditional Chinese medicine prescription, Tao Hong decoction (THD), has been proven effective in treating AS, but its mechanism of action is still unclear.

Objective

To assess the effects, explore THD’s primary mechanism for treating AS, and provide a basis for rational interpretation of its prescription compatibility.

Methods

Based on network pharmacology, we evaluated the mechanism of THD on AS by data analysis, target prediction, the construction of PPI networks, and GO and KEGG analysis. AutoDockTools software to conduct Molecular docking. Then UPLC-Q-TOF-MS was used to identify significant constituents of THD. Furthermore, an AS mice model was constructed and intervened with THD. Immunofluorescence, RT-qPCR, and Western blot were used to verify the critical targets in animal experiments.

Results

The network pharmacology results indicate that eight core targets and seven core active ingredients play an essential role in this process. The GO and KEGG analysis results suggested that the mechanism is mainly involved in Fluid shear stress and atherosclerosis and Lipid and atherosclerosis. The molecular docking results indicate a generally strong affinity. The animal experiment showed that THD reduced plaque area, increased plaque stability, and decreased the levels of inflammatory cytokines (NF-κB, IL-1α, TNF-α, IL-6, IL-18, IL-1β) in high-fat diet -induced ApoE-/-mice. Decreased levels of PTGS2, HIF-1α, VEGFA, VEGFC, FLT-4, and the phosphorylation of PI3K, AKT, and p38 were detected in the THD-treated group.

Conclusion

THD plays a vital role in treating AS with multiple targets and pathways. Angiogenesis regulation, oxidative stress regulation, and immunity regulation consist of the crucial regulation cores in the mechanism. This study identified essential genes and pathways associated with the prognosis and pathogenesis of AS from new insights, demonstrating a feasible method for researching THD’s chemical basis and pharmacology.
Coronary microvascular dysfunction: A review of recent progress and clinical implications
Authors: Rehan Rajan , Yong Andy , Ng Martin , Weaver James , Puranik Rajesh
Published: January 2023

The coronary microcirculation plays a cardinal role in regulating coronary blood flow to meet the changing metabolic demands of the myocardium. Coronary microvascular dysfunction (CMD) refers to structural and functional remodeling of the coronary microcirculation. CMD plays a role in the pathogenesis of obstructive and non-obstructive coronary syndromes as well as myocardial diseases, including heart failure with preserved ejection fraction (HFpEF). Despite recent diagnostic advancements, CMD is often under-appreciated in clinical practice, and may allow for the development of novel therapeutic targets. This review explores the diagnosis and pathogenic role of CMD across a range of cardiovascular diseases, its prognostic significance, and the current therapeutic landscape.
Evaluation and attribution of historical surface air temperature changes over China simulated by coupled and uncoupled models
Authors: Zuo Ling , Li Lijuan , Wang Bin , Feng Tao , Chang Youli
Published: January 2023

The increase in the average surface air temperature anomaly (SATA) over China is higher than the global average. However, the accurate simulation and attribution of regional SATA evolution remain challenging for current global climate models. This study simulates historical SATA variations over China using the coupled (FGOALS-g3) and uncoupled (atmospheric component, GAMIL3) models and examines their possible causes. Results show that both models reproduce the historical SATA variation with higher correlation coefficients (0.735 and 0.782) than many global climate models (0.25–0.56), although they overestimate or underestimate the changes of SATA to some extent in different periods. The results show that the cooling trend during 1941–1970 is well simulated with the coupled model while poorly presented with the uncoupled model; the coupled simulations particularly produce stronger long-term trends than the uncoupled ones during 1870–2014 considering full interaction among the atmosphere, ocean, and sea ice. In contrast, the uncoupled simulations reproduce better decadal and multi-decadal SATA variations owing to the constraints of the observed sea surface temperature (SST), such as the Atlantic multidecadal oscillation, and sea ice cover. Using Detection and Attribution Model Intercomparison Project (DAMIP) experiments, we found that the warming in the early 20th century and the recent 50 years is mainly driven by natural forcings and greenhouse gases (GHGs), whereas the cooling during 1941–1970 is caused by natural factors and anthropogenic aerosols. The cooling effects of anthropogenic aerosols are mainly attributed from the indirect SST-mediated responses through the atmosphere-ocean interactions in the coupled model.
Sealing of oil-gas reservoir caprock: Destruction of shale caprock by micro-fractures
Authors: Tao Ye , He Youbin , Zhao Zhongxiang , Wu Dongsheng , Deng Qiao
Published: January 2023

The sealing ability of caprock is affected by many factors, such as cap thickness, displacement pressure, fracture development, and lithology of caprock. Shale is one of the ideal materials for oil and gas sealing cap formation due to its low porosity and permeability. Microfractures can destroy the sealing property of shale caprock. When buried deep enough, shale will change from toughness to brittleness. In general, the greater the brittleness of shale, the more developed the fractures will be. In areas with high tectonic stress, such as the anticline axis, syncline axis and stratum dip end, the strata stress is high and concentrated, and it is easier to generate fractures. When the stress state of the caprock changes, new micro-cracks are formed or previously closed cracks are re-opened, reducing the displacement pressure of the caprock. These micro-fractures are interconnected to form microleakage spaces, which reduces the sealing capacity of the caprock.
Brief analysis of the development characteristics and deformation mechanism of ground fissures on the MH Highway in the Ethiopian Rift Valley
Authors: Liu Weimin , Xu Cheng , Huang Xiaonian
Published: January 2023

Ground fissures are widely developed in the Ethiopian Rift Valley, posing a major threat to the construction of the proposed Modjo−Hawassa (MH) Highway. The development characteristics, distribution, and communication law of ground fissures along the highway are studied using the comprehensive investigation method and technology. On this basis, the deformation mechanism and evolution of ground fissures are analyzed, which can provide geological support for the prevention and control of highway cracks in the area where ground fissures are developed.
The influence of the precipitation recycling process on the shift to heavy precipitation over the Tibetan Plateau in the summer
Authors: Zhang Boyuan , He Yongli , Ren Yu , Huang Bo , Peng Yangrui , Wang Shanshan , Guan Xiaodan
Published: January 2023

On the Tibetan Plateau (TP), precipitation intensity has shifted to heavy precipitation due to global warming. However, the influence of the precipitation recycling process on this phenomenon remains unknown. Using the Water Accounting Model-2layers (WAM2layers) model and ERA5 reanalysis, this study investigates the contributions of the precipitation recycling process to precipitation shifts over the TP during 1979–2019. The precipitation shift rate was proposed to quantify this process, and the results reveal that the positive precipitation shift (1.384 mm/41 years) over the TP consists of a positive shift over the western TP (5.666 mm/41 years) and a negative shift (−3.485 mm/41 years) over the eastern TP. Considering the source of moisture, either a local source or a remote source, precipitation was decomposed into internal and external cycles of the precipitation recycling process based on the WAM2layers model. Further analysis indicates that the internal cycle (87.2%) contributes more to the shift than the external cycle (12.8%) over the TP. The contributions of the precipitation recycling ratio (PRR) and precipitation amount to the precipitation shift rate induced by the internal cycle were further investigated. The results indicate that PRR changes contribute more to heavy precipitation over the TP, while precipitation amount changes contribute more to light precipitation. The precipitation recycling process contributes to the shift by increasing atmospheric moisture and increasing (decreasing) the dependency on local evaporation in heavy (light) precipitation. Increased dependence of heavy precipitation on evaporation increases the risk of extreme precipitation, and the government should take preventative actions to mitigate these adverse effects.
Building playful resilience in higher education: Learning by doing and doing by playing
Authors: Heljakka Katriina
Published: January 2023

Playful approaches include many benefits for higher education. Here, they denote elements of playful learning that invite students to engage with various challenges related to imagination, innovation, and co-creation. As stated in earlier research, playful learning follows the constructivism approach seeking students be active participants in their learning process, and tries to offer them surmountable challenges to learn while being intrinsically motivated—throughlearning by doing. Again, playful approaches include experimentation with uncertainty—throughdoing by playing. As particular instances of creative endeavors, they offer students joyful moments of discovery and possibilities to learn in a novel, but safe and failure-free situation and environment. This exploratory study presents new ideas on how playful learning methods, such as playful approaches may be used in higher education to contribute to the formation of playful resilience through playful activation. To substantiate this argument, we propose that playful learning approaches are similar to those used in the context of entrepreneurial education that aim to support the growth of a flexible, entrepreneurial mindset among students. Our suggestions for using playful approaches in higher education focus particularly on how a combination of playful tactics, tools, and tasks allow students to ideate, innovate, and create solutions to novel challenges. The contribution of the study is in linking the previously unconnected areas of higher education, playful approaches, playful resilience, and entrepreneurialism achieved through learning by doing, and doing by playing.
The early impact of COVID-19 on the intellectual and developmental disabilities community in California
Authors: Salinas Giselle , Bolourian Yasamin , Burt Beth , Eichelberger Marcia , Blacher Jan
Published: January 2023

Introduction

During the early beginnings of COVID-19, service providers were forced to close their doors and move their services online, causing significant disruptions for many families and communities, such as those with intellectual and developmental disabilities (IDD). In this study, we examined the extent to which COVID-19 disrupted services for the IDD community in California.

Methods

Secondary data were analyzed from a survey (N = 1,082) disseminated by the Autism Society of California in May 2020. Respondents were placed into two categories: autism spectrum disorder (ASD) only (n = 794) and IDD other than ASD (n = 288).

Results

There were significant differences in services between diagnostic groups (<.05). There was a threefold difference in loss of respite services in the ASD (4.3%) versus the IDD group (12.9%). In the ASD group, 48.5% reported no change at all in respite services received, whereas in the IDD group, 71.5% reported no change. Before the pandemic, a higher mean number of medical and therapeutic services was reported as received in the ASD group (M = 1.38) than in the IDD group (M = 1.04). However, at the time of the survey, the IDD group reported a higher mean number of such services (M = 1.32) than the ASD group (M = 1.02). Differences were also seen by race/ethnicity. Before lockdown, there were no significant differences in the mean number of services reported by race/ethnicity among the full sample. However, at the time of the survey, a significantly higher mean number of services was reported by respondents who identified as White (M = 1.26) compared to people of color (M = .91), p < .05.

Discussion

To our knowledge, this study is the first to compare services received by IDD diagnostic groups during COVID-19. Findings help elucidate the negative impact of COVID-19 on the IDD community in California, as well as inform strategies for the ongoing and post-pandemic periods.
Effect of thyroid dysfunction on N-terminal pro-B-type natriuretic peptide levels: A systematic review and meta-analysis
Authors: Zhang Hongling , Li Xiaotao , Zhang Nawen , Tian Limin
Published: January 2023

Purpose

Thyroid hormones (THs) significantly affect the cardiovascular system. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful biomarker for diagnosing, evaluating, and predicting outcomes in heart failure (HF). This comprehensive review and meta-analysis aimed to investigate the effects of thyroid dysfunction (hypothyroidism and hyperthyroidism) on NT-proBNP levels.

Methods

Two investigators independently searched PubMed, Embase, Cochrane Library, and Web of Science databases for studies published from inception to July 31, 2022, without any restrictions on language.

Results

21 studies were included. In participants without HF, NT-proBNP levels may be elevated in those with overt hyperthyroidism (standardized mean difference [SMD] 2.38, 95% confidence interval [CI]:1.0-3.76). Notably, among patients with preexisting HF, significantly higher NT-proBNP levels were found in patients with overt hyperthyroidism, overt hypothyroidism, or subclinical hypothyroidism than in euthyroid subjects (SMD [95%CI] = 0.31[0.01, 0.62], 0.32[0.08, 0.56], and 0.33[0.21, 0.46], respectively). Seven trials compared NT-proBNP levels in patients with thyroid dysfunction before and after therapy, and significant drops in NT-proBNP levels were observed in patients with hyperthyroidism (SMD [95%CI] = -1.53[-2.50, -0.55]) upon achieving a euthyroid state. In contrast, increased NT-proBNP levels were observed in hypothyroid patients after treatment (SMD [95%CI] = 1.07[0.28, 1.85]).

Conclusion

Thyroid dysfunction can significantly affect NT-proBNP levels, which may change upon achieving a euthyroid state. Notably, the effect of thyroid dysfunction on cardiac function may depend on the underlying cardiac status. Thus, timely recognition and effective treatment of cardiac symptoms in patients with thyroid dysfunction are mandatory because the prognosis of HF may be improved with appropriate treatment of thyroid dysfunction.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42022353700.
One-year follow-up comparison of two hybrid closed-loop systems in Italian children and adults with type 1 diabetes
Authors: Bassi Marta , Patti Luca , Silvestrini Irene , Strati Marina Francesca , Ponzano Marta , Minuto Nicola , Maggi Davide
Published: January 2023

Background and aims

Tandem Control-IQ and MiniMed 780G are the main Advanced Hybrid Closed Loop (AHCL) systems currently available in pediatric and adult patients with Type 1 Diabetes (T1D). The aim of our study was to evaluate glycemic control after 1-year of follow-up extending our previous study of 1-month comparison between the two systems.

Methods

We retrospectively compared clinical and continuous glucose monitoring (CGM) data from the patients included in the previous study which have completed 1-year observation period. The study population consisted of 74 patients, 42 Minimed 780G users and 32 Tandem Control-IQ users. Linear mixed models with random intercept were performed to study the variations over time and the interaction between time and system; Mann-Whitney or T-test were used to compare systems at 1-year.

Results

Both systems have been shown to be effective in maintaining the glycemic improvement achieved one month after starting AHCL. Significant changes over time were observed for TIR, TAR, TAR>250mg/dl, average glucose levels and SD (p<0.001). At 1-year follow-up Minimed 780G obtained better improvement in TIR (p<0.001), TAR (p=0.002), TAR>250mg/dl (p=0.001), average glucose levels (p<0.001). The comparison of the glycemic parameters at 1-year showed a significant superiority of Minimed 780G in terms of TIR (71% vs 68%; p=0.001), TAR (p=0.001), TAR>250 (p=0.009), average glucose levels(p=0.001) and SD (p=0.031).

Conclusions

The use of AHCL systems led to a significant improvement of glycemic control at 1-month, which is maintained at 1-year follow-up. MiniMed is more effective than Tandem in reaching the International recommended glycemic targets. Continuous training and education in the use of technology is essential to get the best out of the most advanced technological tools.
Numerical simulation of Rayleigh–Bénard convection with supercritical carbon dioxide in a shallow cavity
Authors: Zhou Litao , Xu Hong , Zhang Yaoli , Hong Gang
Published: January 2023

A numerical simulation of Rayleigh–Bénard convection with supercritical carbon dioxide is presented in this paper. A shallow cavity with an aspect ratio of 4 is selected as a container that is fully filled with supercritical carbon dioxide. The influences of the bottom heat flux on the flow stability, flow pattern evolution, and heat transfer ability of Rayleigh–Bénard convection are analyzed. Meanwhile, the transient and steady-state fluid behaviors are obtained. The results show that the bottom heat flux plays a dominating role in the stability of the convection. A transition from stable evolution to significant oscillation is found with the increase of the heat flux. The flow pattern evolution also strongly relies on the heat flux. A four-cell structure to a six-cell structure transformation accompanied by the orderly multicellular flow is observed with increasing heat flux. In addition, the local Nusselt number on the bottom wall is strongly related to the cell structure in the cavity.
Impact of large-scale photovoltaic-energy storage power generation system access on differential protection of main transformer under symmetrical faults
Authors: Yang Guosheng , Zhang Jiaqi , Zhang Hao , Wang Congbo , Zhu Yujia , Chen Xiaolong
Published: January 2023

The low voltage ride-through (LVRT) requirements demand large-scale photovoltaic (PV) power generation system remain connected to the grid during faults. It results in considerable impact on the characteristics of fault current. This paper combines charge-discharge characteristics of the energy storage (ES) with PV generation system to enhance the LVRT capability. Based on the inverter control strategy and specific LVRT requirements, fault current characteristics of the PV-ES power generation system is discussed in this paper. In order to analyze the fault characteristic, the fault current expression as three-phase short-circuit faults occurs on both sides of the main transformer is calculated. Furthermore, taking the winding connection of the transformer into account, the ratio of differential current to braking current is further derived to find out the factors influencing the performance of the transformer differential protection. It is found that factors influencing the transformer differential protection include the rated capacity of the PV-ES generation system, fault severity, the length of transmission line and so on. And as the rated capacity of the PV-ES power generation system increase, the transformer differential protection would experience reduced sensitivity or even do not trip. The findings of this paper can lay a foundation for further improvement of the transformer differential protection. The elaborate performance evaluation of transformer differential protection, including the operation condition of the second harmonic braking element, is presented and verified by simulation using MATLAB/Simulink.
Optimization of activated carbon production from corn cob using response surface methodology
Authors: He Xiaoxue , Chen Xuexue , Wang Xinran , Jiang Li
Published: January 2023

Waste management and valorization of waste is a major global issue. Low-cost and renewable adsorbent activated carbon (AC) from agriculture residues is a focus of worldwide concern. Microwave heating is an efficient technology for production of AC. CCAC was synthesized from corn cob via microwave vacuum pyrolysis under ambient vacuum, and the optimization process for maximized CCAC yield and its iodine number was developed using response surface methodology (RSM). These regression models have high Fisher test value and lower p-value, which ensure its reliability and applicability. The optimized parameters obtained are 550.62 W, 9.26 min, -0.05 Mpa, and 1.7 IR with responses of 37.57% yield and 933.38 mg/g iodine number. The predicted results were validated, and it was found that the experimental data varied only by 4.21% in yield and 4.02% in iodine number from the predicted values. The prepared adsorbent was characterized using instrumental techniques like FT-IR, BET, and SEM. The pyrolysis approach produced CCAC containing regular and homogeneous porous structure with a specific surface area of up to 995.05 m2/g and total volume of 0.708 cm3/g.
Origin and evolution of intercrystalline brine in the northern Qaidam Basin based on hydrochemistry and stable isotopes
Authors: Ren Qianhui , Li Binkai , Zhang Yan , Wu Haitao
Published: January 2023

The Kunteyi Basin, located in northern Qaidam, is known as a significant potash ore deposit in China. It is of great significance to study the origin of the potassium-rich intercrystalline brine to support the exploitation of potassium salts. In this study, the major ion concentrations and isotopic ratios (δ2H, δ18O, and δ11B) of intercrystalline brine were used to analyze the evolution of the brine. The results show that the intercrystalline brine has a much higher concentration of total dissolved solids compared with the oil-field brine. Most of the ions are enriched except Ca2+ and Br−. The value of δ2H and δ18O are much negative while the δ11B values are positive. The analysis of CNa/CCl, CBr/CCl, Cl/(Na + K + Mg) and isotopes ratios, indicate that (1) Atmospheric precipitation is the primary source of water in brine; (2) The salinity of the brine is mainly influenced by halite dissolution; (3) The study area was influenced by the deep hydrothermal fluids. The thermal water recharged the Pleistocene layer, reacted with polyhalite, and formed Mg- and K-rich brine. The solution rose along the channel formed by the Shuangqiquan Fault and was supplied to the shallow intercrystalline brine.
New indicators of ecological resilience and invasion resistance to support prioritization and management in the sagebrush biome, United States
Authors: Chambers Jeanne C. , Brown Jessi L. , Bradford John B. , Board David I. , Campbell Steven B. , Clause Karen J. , Hanberry Brice , Schlaepfer Daniel R. , Urza Alexandra K.
Published: January 2023

Ecosystem transformations to altered or novel ecological states are accelerating across the globe. Indicators of ecological resilience to disturbance and resistance to invasion can aid in assessing risks and prioritizing areas for conservation and restoration. The sagebrush biome encompasses parts of 11 western states and is experiencing rapid transformations due to human population growth, invasive species, altered disturbance regimes, and climate change. We built on prior use of static soil moisture and temperature regimes to develop new, ecologically relevant and climate responsive indicators of both resilience and resistance. Our new indicators were based on climate and soil water availability variables derived from process-based ecohydrological models that allow predictions of future conditions. We asked: (1) Which variables best indicate resilience and resistance? (2) What are the relationships among the indicator variables and resilience and resistance categories? (3) How do patterns of resilience and resistance vary across the area? We assembled a large database (n = 24,045) of vegetation sample plots from regional monitoring programs and derived multiple climate and soil water availability variables for each plot from ecohydrological simulations. We used USDA Natural Resources Conservation Service National Soils Survey Information, Ecological Site Descriptions, and expert knowledge to develop and assign ecological types and resilience and resistance categories to each plot. We used random forest models to derive a set of 19 climate and water availability variables that best predicted resilience and resistance categories. Our models had relatively high multiclass accuracy (80% for resilience; 75% for resistance). Top indicator variables for both resilience and resistance included mean temperature, coldest month temperature, climatic water deficit, and summer and driest month precipitation. Variable relationships and patterns differed among ecoregions but reflected environmental gradients; low resilience and resistance were indicated by warm and dry conditions with high climatic water deficits, and moderately high to high resilience and resistance were characterized by cooler and moister conditions with low climatic water deficits. The new, ecologically-relevant indicators provide information on the vulnerability of resources and likely success of management actions, and can be used to develop new approaches and tools for prioritizing areas for conservation and restoration actions.
MaxEnt modeling to show patterns of coastal habitats of reef-associated fish in the South and East China Seas
Authors: Wang Jia , Tabeta Shigeru
Published: January 2023

Reef-associated fish are a crucial source of protein for coastal residents and play an important role in the economy and ecology of marine ecosystems. However, human activities and climate change have led to the degradation of their habitats in the South China Sea (SCS) and East China Sea (ECS). This study models the potential habitats of reef-associated fish in the SCS and ECS between 1993 and 2019 using high-spatial-resolution environmental factors and fish presence data, estimates the importance of environmental factors on habitat distribution and identifies seasonal variation and distribution shifts over recent decades, the results show moderate and highly suitable areas for reef-associated fish in the region total 360,000 km2. Sea body temperature, chlorophyll-α concentration, and seawater salinity are crucial for determining the distribution of reef-associated fish. Moreover, reef-associated fish are also sensitive to seawater temperature in winter. Suitable areas for reef-associated fish near coastlines have decreased due to environmental changes within the region. The findings of this study offer valuable resource for developing fishery management and conservation strategies for this important functional group.
Sawfly egg deposition extends the insect life cycle and alters hormone and volatile emission profiles
Authors: Dávila Camila , Fiorenza Juan E. , Gershenzon Jonathan , Reichelt Michael , Zavala Jorge A. , Fernández Patricia C.
Published: January 2023

Introduction

Insect oviposition can enhance plant defenses and decrease plant quality in response to future feeding damage by hatched larvae. Induced resistance triggered by egg deposition and its negative effect on insect herbivore performance is known for several annual plants but has been much less studied in woody perennials, such as species of the Salicaceae. Here we studied the response of the willow Salix babylonica to oviposition by the specialist willow sawfly Nematus oligospilus and its impact on insect performance.

Methods

We measured the effect of oviposition on larval feeding and pupa formation and evaluated its influence on plant phytohormones and volatile emission profile.

Results

We showed that oviposition reduced neonate larval growth and increased the proportion of prepupae that delayed their transition to pupae, thus extending the length of the sawfly cocoon phase. Oviposited willows increased jasmonic acid levels and changed their volatile profile through enhanced concentrations of the terpenoids, (E/E)-α-farnesene, (Z)- and (E)-β-ocimene. Volatile profiles were characteristic for each type of insect damage (oviposition vs. feeding), but no priming effect was found.

Discussion

We demonstrated that willows could perceive sawfly oviposition per se as a primary factor activating defense signaling via the jasmonic acid pathway. This induced response ultimately determined changes in pupation dynamics that may affect the whole insect population cycle.
The built environment’s nonlinear effects on the elderly’s propensity to walk
Authors: Zang Peng , Qiu Hualong , Zhang Haifan , Chen Kaihan , Xian Fei , Mi Jianghui , Guo Hongxu , Qiu Yanan , Liao Kaihuai
Published: January 2023

The increased ageing of the population is a vital and upcoming challenge for China. Walking is one of the easiest and most common forms of exercise for older people, and promoting walking among older people is important for reducing medical stress. Streetscape green visibility and the normalised difference vegetation index (NDVI) are perceptible architectural elements, both of which promote walking behaviour. Methodologically we used Baidu Street View images and extracted NDVI from streetscape green visibility and remote sensing to scrutinize the nonlinear effects of streetscape green visibility and NDVI on older people’s walking behaviour. The study adopted a random forest machine learning model. The findings indicate that the impact of streetscape green visibility on elderly walking is superior to NDVI, while both have a favourable influence on senior walking propensity within a particular range but a negative effect on elderly walking inside that range. Overall the built environment had a non-linear effect on the propensity to walk of older people. Therefore, this study allows the calculation of optimal thresholds for the physical environment, which can be used by governments and planners to formulate policies and select appropriate environmental thresholds as indicators to update or build a community walking environment that meets the needs of local older people, depending on their own economic situation.
Detailed genetic and clinical analysis of a novel de novo variant in HPRT1: Case report of a female patient from Saudi Arabia with Lesch–Nyhan syndrome
Authors: AlBakheet Albandary , AlQudairy Hanan , Alkhalifah Joud , Almoaily Sheikhah , Kaya Namik , Rahbeeni Zuhair
Published: January 2023

Background: Hypoxanthine-guanine phosphoribosyltransferase (HPRT1) deficiency is an inborn error of purine metabolism responsible for Lesch–Nyhan syndrome (LNS). The disease is inherited in an X-linked recessive manner and predominantly affects male individuals. Female individuals can carry a mutation as heterozygotes, but typically, they are asymptomatic because of the random inactivation of the affected allele. Nevertheless, although rare, heterozygote female individuals may manifest LNS with full characteristics. Herein, we describe a female patient from Saudi Arabia with LNS.

Results: The patient (a 4-year-old girl) presented with typical characteristics of the disease, which include global developmental delay, self-mutilation, hyperuricemia, hypotonia, speech delay, spasticity, and seizures. Her general biochemical laboratory results were normal except for high levels of uric acid. The abdominal MRI\MRS, mostly unremarkable, showed bilateral echogenic foci within the renal collecting system. Genetic testing (whole-exome sequencing, iterative variant filtering, segregation analysis, and Sanger sequencing) pointed a novel de novo frameshift variant in HPRT1. X-inactivation assay using HpaII showed the presence of a 100% skewed X chromosome carrying the affected allele. RT-PCR of the cDNA indicated complete loss of the expression of the normal allele.

Conclusion: Our study presents a female patient who has a severe case of LNSand found to be the 15th female patient with the disease in the world. The study emphasizethe need for a streamlined protocol that will help an early and accurate diagnosis of female LNS patients to avoid unnecessary interventions that lead to costly patient care.
Ethical layering in AI-driven polygenic risk scores—New complexities, new challenges
Authors: Fritzsche Marie-Christine , Akyüz Kaya , Cano Abadía Mónica , McLennan Stuart , Marttinen Pekka , Mayrhofer Michaela Th. , Buyx Alena M.
Published: January 2023

Researchers aim to develop polygenic risk scores as a tool to prevent and more effectively treat serious diseases, disorders and conditions such as breast cancer, type 2 diabetes mellitus and coronary heart disease. Recently, machine learning techniques, in particular deep neural networks, have been increasingly developed to create polygenic risk scores using electronic health records as well as genomic and other health data. While the use of artificial intelligence for polygenic risk scores may enable greater accuracy, performance and prediction, it also presents a range of increasingly complex ethical challenges. The ethical and social issues of many polygenic risk score applications in medicine have been widely discussed. However, in the literature and in practice, the ethical implications of their confluence with the use of artificial intelligence have not yet been sufficiently considered. Based on a comprehensive review of the existing literature, we argue that this stands in need of urgent consideration for research and subsequent translation into the clinical setting. Considering the many ethical layers involved, we will first give a brief overview of the development of artificial intelligence-driven polygenic risk scores, associated ethical and social implications, challenges in artificial intelligence ethics, and finally, explore potential complexities of polygenic risk scores driven by artificial intelligence. We point out emerging complexity regarding fairness, challenges in building trust, explaining and understanding artificial intelligence and polygenic risk scores as well as regulatory uncertainties and further challenges. We strongly advocate taking a proactive approach to embedding ethics in research and implementation processes for polygenic risk scores driven by artificial intelligence.
Aging augments obesity-induced thymic involution and peripheral T cell exhaustion altering the “obesity paradox”
Authors: Vick Logan V. , Collins Craig P. , Khuat Lam T. , Wang Ziming , Dunai Cordelia , Aguilar Ethan G. , Stoffel Kevin , Yendamuri Sai , Smith Randall , Mukherjee Sarbajit , Barbi Joseph , Canter Robert J. , Monjazeb Arta M. , Murphy William J.
Published: January 2023

Introduction

The incidence of obesity, a condition characterized by systemic chronic inflammation, has reached pandemic proportions and is a poor prognostic factor in many pathologic states. However, its role on immune parameters has been diverse and at times contradictory. We have previously demonstrated that obesity can result in what has been called the “obesity paradox” which results in increased T cell exhaustion, but also greater efficacy of immune checkpoint blockade in cancer treatment.

Methods

The role of obesity, particularly in the context of aging, has not been robustly explored using preclinical models. We therefore evaluated how age impacts the immune environment on T cell development and function using diet-induced obese (DIO) mice.

Results

We observed that DIO mice initially displayed greater thymopoiesis but then developed greater thymic involution over time compared to their lean counterparts. Both aging and obesity resulted in increased T cell memory conversion combined with increased expression of T cell exhaustion markers and Treg expansion. This increased T cell immunosuppression with age then resulted in a loss of anti-tumor efficacy by immune checkpoint inhibitors (ICIs) in older DIO mice compared to the younger DIO counterparts.

Discussion

These results suggest that both aging and obesity contribute to T cell dysfunction resulting in increased thymic involution. This combined with increased T cell exhaustion and immunosuppressive parameters affects immunotherapy efficacy reducing the advantage of obesity in cancer immunotherapy responses.
Myeloid-derived suppressor cells are associated with impaired Th1 and Th17 responses and severe pulmonary paracoccidioidomycosis which is reversed by anti-Gr1 therapy
Authors: Preite Nycolas Willian , Kaminski Valéria de Lima , Borges Bruno Montanari , Calich Vera Lúcia Garcia , Loures Flávio Vieira
Published: January 2023

Previous studies on paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Latin America, revealed that host immunity is tightly regulated by several suppressive mechanisms mediated by tolerogenic plasmacytoid dendritic cells, the enzyme 2,3 indoleamine dioxygenase (IDO-1), and regulatory T-cells (Tregs). IDO-1 orchestrates local and systemic immunosuppressive effects through the recruitment and activation of myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid cells possessing a potent ability to suppress T-cell responses. However, the involvement of MDSCs in PCM remains uninvestigated. The presence, phenotype, and immunosuppressive activity of MDSCs were evaluated at 96 h, 2 weeks, and 8 weeks of pulmonary infection in C57BL/6 mice. Disease severity and immune responses were assessed in MDSC-depleted and nondepleted mice using an anti-Gr1 antibody. Both monocytic-like MDSCs (M-MDSCs) and polymorphonuclear-like MDSCs (PMN-MDSCs) massively infiltrated the lungs during Paracoccidioides brasiliensis infection. Partial reduction of MDSC frequency led to a robust Th1/Th17 lymphocyte response, resulting in regressive disease with a reduced fungal burden on target organs, diminishing lung pathology, and reducing mortality ratio compared with control IgG2b-treated mice. The suppressive activity of MDSCs on CD4 and CD8 T-lymphocytes and Th1/Th17 cells was also demonstrated in vitro using coculture experiments. Conversely, adoptive transfer of MDSCs to recipient P. brasiliensis-infected mice resulted in a more severe disease. Taken together, our data showed that the increased influx of MDSCs into the lungs was linked to more severe disease and impaired Th1 and Th17 protective responses. However, protective immunity was rescued by anti-Gr1 treatment, resulting in a less severe disease and controlled tissue pathology. In conclusion, MDSCs have emerged as potential target cells for the adjuvant therapy of PCM.
Efficacy of interferon alpha for the treatment of hospitalized patients with COVID-19: A meta-analysis
Authors: Buchynskyi Mykhailo , Kamyshna Iryna , Lyubomirskaya Katerina , Moshynets Olena , Kobyliak Nazarii , Oksenych Valentyn , Kamyshnyi Aleksandr
Published: January 2023

Introduction

IFN-α intervention may block SARS-CoV-2 replication and normalize the deregulated innate immunity of COVID-19.

Aim

This meta-analysis aimed to investigate the efficacy of interferon IFN-α–containing regimens when treating patients with moderate-to-severe COVID-19.

Material and methods

PubMed, SCOPUS, and ClinicalTrials.gov were searched from inception to 15 January 2022. A systematic literature search was conducted by applying relevant terms for ‘COVID-19’ and ‘interferon-α’. The primary outcome enclosed the all-cause hospital mortality. The secondary outcomes constituted the length of hospital stay; hospital discharge; nucleic acid negative conversion.

Results

Eleven studies are enclosed in the meta-analysis. No significant difference in the all-cause mortality rate was found between the study and control groups (OR 0.2; 95% CI 0.05-1.2; I2 = 96%). The implementation of interferon did not influence such outcomes as the length of hospital stay (OR 0.9; 95% CІ, 0.3-2.6; I2 = 91%), nucleic acid negative conversion (OR 0.8; 95% CI, 0.04-17.2; I2 = 94%). Nevertheless, IFN-α treatment resulted in a higher number of patients discharged from the hospital (OR 26.6; 95% CІ, 2.7-254.3; I2 = 95%).

Conclusions

Thus, IFN-α does not benefit the survival of hospitalized COVID-19 patients but may increase the number of patients discharged from the hospital.

Systematic review registration

www.crd.york.ac.uk/prospero, identifier (CRD42022374589).
Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis
Authors: Lopes Sébastien , Pabst Lucile , Dory Anne , Klotz Marion , Gourieux Bénédicte , Michel Bruno , Mascaux Céline
Published: January 2023

Introduction

Gut microbiota can significantly affect the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. Recently, antibiotics were shown to decrease survival rate of patients treated by ICIs. Proton pump inhibitors (PPIs) can indeed modulate microbiota’s diversity, therefore altering ICIs response. A meta-analysis was performed based on published data to verify this hypothesis.

Methods

In this study, over 41 publications, exploring the impact of concomitant PPI treatment on outcomes of ICI-treated patients, were analyzed. Evaluated endpoints were overall survival (OS) and progression-free survival (PFS). Pooled hazard ratios (HRs) with a 95% confidence interval (CI) were reported in ICIs in PPI users versus non-PPI users. Subgroup analyses were performed to minimize the impact of study heterogeneity and to investigate the influence of PPI on the different groups of interest. There was no evidence of publication bias for OS and PFS analysis in subgroup analysis.

Results

Forty-one studies were included in the meta-analysis, including a total of 20,042 patients. OS of patients receiving ICIs was negatively correlated in patients concomitantly treated with PPI (HR=1.37; 95%CI, 1.23–1.52). PFS of cancer patients receiving ICIs was also negatively correlated with PPI treatment (HR=1.28; 95%CI, 1.15–1.42). PPI and ICI use was associated with worst OS and PFS not only for non-small-cell lung cancer (NSCLC) or urothelial cancer patients but also for patients treated with anti PD-1 (OS) and anti PD-L1 (OS and PFS) immunotherapies when administered in non-first line and when PPI was received as baseline treatment or in 60 days before ICI initiation. PPI and ICI use also showed the worst OS and PFS for patients from Europe and Asia.

Conclusion

This meta-analysis suggests that PPI treatment leads to significantly worse outcomes in advanced cancer patients treated by ICIs in terms of PFS and OS.
Mapping of DNA methylation-sensitive cellular processes in gingival and periodontal ligament fibroblasts in the context of periodontal tissue homeostasis
Authors: Lagosz-Cwik Katarzyna B. , Melnykova Mariia , Nieboga Elwira , Schuster Aureliusz , Bysiek Agnieszka , Dudek Slawomir , Lipska Weronika , Kantorowicz Malgorzata , Tyrakowski Michal , Darczuk Dagmara , Kaczmarzyk Tomasz , Gilijamse Marjolijn , de Vries Teun J. , Potempa Jan , Grabiec Aleksander M.
Published: January 2023

Interactions between gingival fibroblasts (GFs) and oral pathogens contribute to the chronicity of inflammation in periodontitis. Epigenetic changes in DNA methylation are involved in periodontitis pathogenesis, and recent studies indicate that DNA methyltransferase (DNMT) inhibitors may protect against epithelial barrier disruption and bone resorption. To assess the impact of DNMT inhibition on GFs, cells were cultured with decitabine (5-aza-2’-deoxycytidine, DAC) for 12 days to induce DNA hypomethylation. We observed several potentially detrimental effects of DAC on GF biological functions. First, extended treatment with DAC reduced GF proliferation and induced necrotic cell death. Second, DAC amplified Porphyromonas gingivalis- and cytokine-induced expression and secretion of the chemokine CCL20 and several matrix metalloproteinases (MMPs), including MMP1, MMP9, and MMP13. Similar pro-inflammatory effects of DAC were observed in periodontal ligament fibroblasts. Third, DAC upregulated intercellular adhesion molecule-1 (ICAM-1), which was associated with increased P. gingivalis adherence to GFs and may contribute to bacterial dissemination. Finally, analysis of DAC-induced genes identified by RNA sequencing revealed increased expression of CCL20, CCL5, CCL8, CCL13, TNF, IL1A, IL18, IL33, and CSF3, and showed that the most affected processes were related to immune and inflammatory responses. In contrast, the genes downregulated by DAC were associated with extracellular matrix and collagen fibril organization. Our observations demonstrate that studies of DNMT inhibitors provide important insights into the role of DNA methylation in cells involved in periodontitis pathogenesis. However, the therapeutic potential of hypomethylating agents in periodontal disease may be limited due to their cytotoxic effects on fibroblast populations and stimulation of pro-inflammatory pathways.
Factors affecting IgG4-mediated complement activation
Authors: Oskam Nienke , Damelang Timon , Streutker Marij , Ooijevaar-de Heer Pleuni , Nouta Jan , Koeleman Carolien , Van Coillie Julie , Wuhrer Manfred , Vidarsson Gestur , Rispens Theo
Published: January 2023

Of the four human immunoglobulin G (IgG) subclasses, IgG4 is considered the least inflammatory, in part because it poorly activates the complement system. Regardless, in IgG4 related disease (IgG4-RD) and in autoimmune disorders with high levels of IgG4 autoantibodies, the presence of these antibodies has been linked to consumption and deposition of complement components. This apparent paradox suggests that conditions may exist, potentially reminiscent of in vivo deposits, that allow for complement activation by IgG4. Furthermore, it is currently unclear how variable glycosylation and Fab arm exchange may influence the ability of IgG4 to activate complement. Here, we used well-defined, glyco-engineered monoclonal preparations of IgG4 and determined their ability to activate complement in a controlled system. We show that IgG4 can activate complement only at high antigen and antibody concentrations, via the classical pathway. Moreover, elevated or reduced Fc galactosylation enhanced or diminished complement activation, respectively, with no apparent contribution from the lectin pathway. Fab glycans slightly reduced complement activation. Lastly, we show that bispecific, monovalent IgG4 resulting from Fab arm exchange is a less potent activator of complement than monospecific IgG4. Taken together, these results imply that involvement of IgG4-mediated complement activation in pathology is possible but unlikely.