bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychiatric symptoms in multiple sclerosis: a biological perspective on synaptic and network dysfunction
Authors: Menculini Giulia , Mancini Andrea , Gaetani Lorenzo , Bellingacci Laura , Tortorella Alfonso , Parnetti Lucilla , Di Filippo Massimiliano
Published: January 2023

Psychiatric symptoms frequently occur in multiple sclerosis (MS), presenting with a complex phenomenology that encompasses a large clinical spectrum from clear-cut psychiatric disorders up to isolated psychopathological manifestations. Despite their relevant impact on the overall disease burden, such clinical features are often misdiagnosed, receive suboptimal treatment and are not systematically evaluated in the quantification of disease activity. The development of psychiatric symptoms in MS underpins a complex pathogenesis involving both emotional reactions to a disabling disease and structural multifocal central nervous system damage. Here, we review MS psychopathological manifestations under a biological perspective, highlighting the pathogenic relevance of synaptic and neural network dysfunction. Evidence obtained from human and experimental disease models suggests that MS-related psychiatric phenomenology is part of a disconnection syndrome due to diffuse inflammatory and neurodegenerative brain damage.
Comparative effectiveness of anesthetic technique on outcomes after lumbar spine surgery: a retrospective propensity score-matched analysis of the National Surgical Quality Improvement Program, 2009–2019
Authors: Amoroso Krizia , Okano Ichiro , Sarin Michele , Hughes Alexander P , Zelenty William D , Shue Jennifer , Sama Andrew A , Cammisa Frank P , Girardi Federico P , Soffin Ellen M
Published: January 2023

Background

The impact of anesthetic technique on spine surgery outcomes is controversial. Using a large national sample of patients, we compared outcomes after lumbar decompression under regional anesthesia (RA: spinal or epidural) or general anesthesia (GA).

Methods

A retrospective population-based study of American College of Surgeons National Surgical Quality Improvement Program data (2009–2019). Patients were propensity score (PS) matched 3:1 (GA:RA) on demographic and surgical variables. The primary outcome was the association between anesthetic type and any complication (cardiac, pulmonary, renal, transfusion, stroke, infectious, deep vein thrombosis/pulmonary embolus). Secondary outcomes included the association between anesthetic type and individual complications, readmission and length of stay (LOS). Unadjusted comparisons (OR, 95% CI), logistic regression and adjusted generalized linear modeling (parameter estimate, PE, 95% CI) were performed before and after PS matching.

Results

Of 1 51 010 cases, 149 996 (99.3%) were performed under GA, and 1014 (0.67%) under RA. After matching, 3042 patients with GA were compared with 1014 patients with RA. On unadjusted analyses, RA was associated with lower odds of complications (OR 0.43, 0.3 to 0.6, p<0.001), shorter LOS (RA: 1.1±3.8 days vs GA: 1.3±3.0 days; p<0.001) and fewer blood transfusions (RA: 3/1014, 0.3% vs GA: 40/3042, 1.3%; p=0.004). In adjusted analyses, RA was associated with fewer complications (PE −0.43, –0.81 to −0.06, p=0.02) and shorter LOS (PE −0.76, –0.90 to −0.63, p<0.001). There was no significant association between anesthetic type and readmission (PE −0.34, –0.74 to 0.05, p=0.09).

Conclusions

Compared with GA, RA was associated with fewer complications, less blood transfusion and shorter LOS after spine surgery. Although statistically significant, the magnitude of effects was small and requires further prospective study.
Citing retracted literature: a word of caution
Authors: De Cassai Alessandro , Volpe Francesco , Geraldini Federico , Dost Burhan , Boscolo Annalisa , Navalesi Paolo
Published: January 2023

Introduction

Inappropriate citation of retracted literature is a common problem in the general medical literature. In 2020, more than 2300 articles were retracted, a dramatic increase from 38 in 2000. By exploring a contemporary series of retractions by one research group, we aimed to evaluate if citations of retracted articles is occurring in the area of regional anesthesiology.

Methods

Using the Scopus database, we examined the full text of all the articles citing research articles coauthored by an anesthesiologist who had multiple articles retracted in 2022. After excluding the research articles citing non-retracted articles authored by the above mentioned anesthesiologist, we included in our analysis all the articles containing a retracted citation and published after the retraction notice.

Results

The search was performed on October 30, 2022, retrieving a total of 121 articles citing the researcher’s work. Among the retrieved articles, 53 correctly cited non-retracted research and 37 were published before the retraction notice. Among the 31 remaining articles, 42 retracted research papers were cited. Twenty-five of the retracted articles were cited in the Discussion section of the manuscripts, 15 in the Introduction section, 1 in the Methods section (description of a technique), and one was cited in a review. No manuscript used the flawed data to calculate the sample size.

Discussion

In this contemporary example from the regional anesthesia literature, we identified that citation of retracted work remains a common phenomenon.
Effectiveness and cost-effectiveness of palliative care in natural experiments: a systematic review
Authors: Jiang Jingjing , Kim Narae , Garrido Melissa M , Jacobson Mireille , Mockler David , May Peter
Published: January 2023

Context

Investigators in palliative care rely heavily on routinely collected data, which carry risk of unobserved confounding and selection bias. ‘Natural experiments’ offer opportunities to generate credible causal treatment effect estimates from observational data.

Objectives

We aimed first to review studies that employed ‘natural experiments’ to evaluate palliative care, and second to consider implications for expanding use of these methods.

Methods

We searched systematically seven databases to identify studies using ‘natural experiments’ to evaluate palliative care’s effect on outcomes and costs. We searched three grey literature repositories, and hand-searched journals and prior systematic reviews. We assessed reporting using the Strengthening the Reporting of Observational Studies in Epidemiology checklist and a bespoke methodological quality tool, using two reviewers at each stage. We combined results in a narrative synthesis.

Results

We included 17 studies, which evaluated a wide range of interventions and populations. Seven studies employed a difference-in-differences design; five each used instrumental variables and interrupted time series analysis. Outcomes of interest related mostly to healthcare use. Reporting quality was variable. Most studies reported lower costs and improved outcomes associated with palliative care, but a third of utilisation and place of death evaluations found no effect.

Conclusion

Among the large number of observational studies in palliative care, a small minority have employed causal mechanisms. High-volume routine data collection, the expansion of palliative care services worldwide and recent methodological advances offer potential for increased use of ‘natural experiments’. Such studies would improve the quality of the evidence base.
Age structure augments the predictive power of time series for fisheries and conservation
Authors: Dolan Tara E. , Palkovacs Eric P. , Rogers Tanya L. , Munch Stephan B.
Published: January 2023

Ecological forecasts are potentially of great value for managing fisheries and for stakeholders dependent on their long-term sustainability. Yet, most forecasting approaches are data-intensive, requiring information not just on the focal species but also on ecological interactions and the physical environment. Empirical dynamic modeling (EDM) is an equation-free approach to forecasting species’ abundance using only data on past abundance, but the time series required for this approach must be long enough to reconstruct the dynamics of the system. This requirement is rarely met, especially for long-lived species. Here we used simulations and empirical data to demonstrate that incorporating time series from multiple age classes can improve our ability to forecast abundance compared to a single age class or index of total abundance. Including data from multiple age classes produced the greatest gains in forecast accuracy when time series were the shortest. Overall, our results show that the incorporation of age structure could allow EDM to be applied to many species for which relatively short time series would have previously been a limiting factor.
Searches for QCD instantons with forward proton tagging
Authors: Tasevsky Marek , Khoze Valery , Milne Daniel , Ryskin Michail
Published: January 2023

We study the possibility to observe heavy ($$M_{\textrm{inst}}> 60$$

M
inst

>
60

 GeV) QCD instantons at the LHC in events with one or two tagged leading protons including fast simulation of detector and pile-up effects. We show that the expected instanton signal in a single-tagged configuration is strongly affected by central detector and pile-up effects. For double-tagged approach, where larger integrated luminosities and hence larger pile-up contaminations need to be considered, the combinatorial background overwhelms the expected signal. We suggest that additional time information about tracks at central and forward rapidities would be crucial for potential improvements.
Massive particle pair production and oscillation in Friedman Universe: its effect on inflation
Authors: Xue She-Sheng
Published: January 2023

We study the classical Friedman equations for the time-varying cosmological term $$\tilde{\Lambda }$$

Λ
~

and Hubble function H, together with quantised field equations for the production of massive $$M\gg H$$

M
≫
H

particles, namely, the $$\tilde{\Lambda }$$

Λ
~

CDM scenario of dark energy and matter interactions. Classical slow components $${\mathcal O}(H^{-1})$$

O
(

H

-
1

)

are separated from quantum fast components $${\mathcal O}(M^{-1})$$

O
(

M

-
1

)

. The former obeys the Friedman equations, and the latter obeys a set of nonlinear differential equations. Numerically solving equations for quantum fast components, we find the production and oscillation of massive particle-antiparticle pairs in microscopic time scale $${\mathcal O}(M^{-1})$$

O
(

M

-
1

)

. Their density and pressure averages over microscopic time do not vanish. It implies the formation of a massive pair plasma state in macroscopic time scale $${\mathcal O}(H^{-1})$$

O
(

H

-
1

)

, whose effective density and pressure contribute to the Friedman equations. Considering the inflation driven by the time-varying cosmological term and slowed down by the massive pair plasma state, we obtain the relation of spectral index and tensor-to-scalar ratio in agreement with recent observations. We discuss the singularity-free pre-inflation, the CMB large-scale anomaly, and dark-matter density perturbations imprinting on power spectra.
Alternative to Buy-and-Hold: Predicting Indices Direction and Improving Returns Using a Novel Hybrid LSTM Model
Authors: Beniwal Mohit , Singh Archana , Kumar Nand
Published: January 2023

Predicting stock direction is challenging as stock price time series are extremely noisy. Moreover, the widely accepted efficient market hypothesis states that it is impossible to consistently generate excess returns than the market over a long-term horizon. Hence, the best approach for investors is thought to be the passive buy-and-hold strategy in indices. However, some researchers suggest that the market does have a predictable component.

This paper’s objective is to provide investors with an alternative predictive system that generates an excess return over the classical buy-and-hold strategy and reduces risk. The authors propose an alternative investing model, Average True Range (ATR) and Momentum-based Long Short-Term Memory online (a-m-LSTM-o), that innovatively uses the technical indicators with Long Short-Term Memory (LSTM). Further, this study experiments with multiple other LSTM investing models using daily indices data of the world’s top five economies.

Based on the prediction, the proposed model’s return is 172%, which is significantly higher than the buy-and-hold return of 139%, and it also has a lower drawdown of −49% compared to −51% for the buy-and-hold strategy. Hence, the authors suggest that the proposed model may be a good alternative to the passive approach of the investors.
Open bottom mesons in magnetized matter: Effects of (inverse) magnetic catalysis
Authors: De Sourodeep , Parui Pallabi , Mishra Amruta
Published: January 2023

In-medium masses of the pseudoscalar and vector open bottom mesons ([Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text], [Formula: see text]) are studied in the magnetized nuclear matter by considering the effects of Dirac sea, within the chiral effective model. The mass modifications arise due to the interactions of the open bottom mesons with the nucleons and the scalar mesons, calculated in terms of the scalar and number densities of the nucleons and the scalar fields fluctuations, within the chiral model. The effects of the magnetized Dirac sea lead to the considerable changes in the scalar fields with increasing magnetic field, which are related to the condensates of light quark–antiquark pairs. There is observed to be a (reduction) enhancement in the QCD light quark condensates with rising magnetic field, a phenomenon called (inverse) magnetic catalysis. The contribution of the magnetic field on the Fermi sea of nucleons is also taken into account through protons Landau energy levels and anomalous magnetic moments (AMMs) of the nucleons. The additional contribution of the lowest Landau level for the charged mesons is taken into account. In the presence of an external magnetic field, the spin–magnetic field interaction between the longitudinal component of the vector mesons and the pseudoscalar mesons ([Formula: see text], [Formula: see text] and [Formula: see text]) are studied, which lead to level repulsion between their masses with increasing magnetic field. The magnetic fields are observed to have significant contribution on the masses of the open bottom mesons through the Dirac sea effects taking into account the AMMs of nucleons. In vacuum, appreciable medium modifications are obtained due to the magnetized Dirac sea contribution with nonzero nucleonic AMMs.
Characteristics and current activation phenomenon of reduced graphite oxide membranes by low temperature thermal treatment for sodium ion battery electrodes
Authors: Sun Shuai , Wang Lei , Xu Han
Published: January 2023

After self-assembly and thermal treatment at low temperature (350∘C), reduced graphite oxide membranes (RGOM) with a specific surface area of 10.6 m2g[Formula: see text] and average interlayer distance of 0.372 nm were obtained. When used as free-standing electrodes for sodium ion battery (SIB), the RGOM could not show good electrochemical performances at high current density ([Formula: see text]52 mAh g[Formula: see text] at 200 mA g[Formula: see text] and [Formula: see text]22 mAh g[Formula: see text] at 500 mA g[Formula: see text]), which may be attributed to dense structure and low specific surface area. Cyclic voltammetry (CV) results showed that the energy storage of RGOM in SIB was ions’ diffusion-dependent. Thus, when the RGOM electrodes went through repeated charge/discharge cycles at 200 mA g[Formula: see text], an obvious improvement of specific capacity was found due to increase of Na[Formula: see text] diffusion speed. After [Formula: see text]300 times charge/discharge cycles, the specific capacity of RGOM was [Formula: see text]120 mAh g[Formula: see text]. Additionally, after the current activation at 200 mA g[Formula: see text], the electrodes also showed better performances at higher current density (from [Formula: see text]85 mAh g[Formula: see text] to [Formula: see text]68 mAh g[Formula: see text] at a current density of 500 mA g[Formula: see text] during 500 times charge/discharge cycles). The current activation phenomenon maybe a promising method for using RGOM as SIB electrodes on a large scale.
High-Frequency Permeability of Adjacent Narrow Strips Having an Inclined Magnetic Anisotropy
Authors: Nakai Tomoo
Published: January 2023

This study deals with a phenomenon of magnetic domain transition of adjacent narrow thin film strips with inclined uniaxial magnetic anisotropy. Our previous research shows that individual element with 70° inclined easy magnetization axis has a typical characteristic of the domain transition, and the transition can be controlled by the normal magnetic field. We also applied this phenomenon and controlling method to the two-dimensional configuration of line arrangement adjacent to many-body elements, in which mutual magnetic interaction exists. The result shows that the hidden inclined Landau–Lifshitz domain appears by applying a distributed normal field the same as an individual single element. This paper reports a comprehensive magnetic property, such as magnetic domains, magnetic hysteresis-loop (MH-loop), and high-frequency permeability of the adjacent many-body elements, in some fabrication conditions surrounding the exact condition where the hidden inclined Landau–Lifshitz domain appears. The result shows an estimation of a switched device of high-frequency permeability caused by the switched magnetic domain using the hidden domain and the control of distributed normal field. This phenomenon would be expected to apply functional devices, such as a switched inductor or a switched electromagnetic shielding, or a magnetic sensor.
jpf-logic
Authors: Walker Matt , Khazra Parssa , Nanah Ji Anto , Wang Hongru , van Breugel Franck
Published: January 2023

We present jpf-logic, an extension of the model checker Java PathFinder (JPF). Our extension jpf-logic provides a framework to check properties expressed in temporal logics such as linear temporal logic (LTL) and computation tree logic (CTL). To support a logic in our framework, we (1) implement a parser for the logic, (2) develop a hierarchy of classes that represent the abstract syntax of the logic and implement a transformation from parse trees of formulas to the corresponding abstract syntax trees, and (3) implement a model checking algorithm that takes as input an abstract syntax tree of a formula and a partial transition system. The latter represents a model of the Java application. All three components have been implemented for CTL. The first two have been implemented for LTL.
Social Sustainability Approaches for a Sustainable Software Product
Authors: Moises de Souza Ana Carolina
Published: January 2023

Sustainability is the use of existing resources without compromising them for future generations. Resources must be guaranteed in the environmental, economic, and social dimensions. Sustainable Software Engineering is an emerging research field aiming to minimize software development's negative impacts on society. Furthermore, software sustainability can be defined as a way of keeping something running at a certain level of quality in relation to these dimensions. From the social dimension perspective, it is necessary to confirm software's trade-offs, benefits, and impacts on society since it lacks empirical evidence of its achievements in software. In this research thesis, we will explore how the literature addresses the aspect of social sustainability during software development and understand how social sustainability approaches can be integrated into the context of agile software development. In the end, we expect to have a set of guidelines, activities, and practices that can be adopted by agile teams.
Transforming Monolithic Systems to a Microservices Architecture
Authors: Hamza Muhammad
Published: January 2023

Context: microservices architecture enables organizations to develop an application as a suite of loosely coupled small and independent services that can be developed, tested, and deployed independently. Various organizations are re-architecting their existing monolithic systems with microservices architecture. However, re-architecting the entire system can bring some indefinite challenges. Objective: the goal of this research project is to investigate (i) the need for migration from monolithic to microservices architecture, (ii) architectural description for adopting microservices, (iii) refactoring tools and methods (iv) potential challenges while transforming to microservices, and (v) effective patterns and strategies to adopt microservice successfully. Methodology: the industrial empirical (interviews, case study, and questionnaire survey) approach will be used to meet the research objective. Possible outcomes: the expected outcomes would be (i) an evidence-based decision-making framework for transforming monolithic architecture (ii) strategies to refactor the monolithic architecture (iii) prioritization-based taxonomy of challenges while transforming to microservices. Finally, (iv) the development of a decision model for selecting patterns and strategies for successful implementation of the microservices system.
Surviving While Black: Systemic Racism and Psychological Resilience
Authors: Jones James M.
Published: January 2023

This autobiographical essay traces my personal journey from grandson of a slave to a cultural psychologist examining racism. My journey includes growing up in a small Ohio town, training in social psychology, and an academic career that was launched with the publication of Prejudice and Racism in 1972. I weave my personal experiences with my analytical approach to racism that incorporates individual, institutional, and cultural factors that combine to explain systemic racism. The racism analysis is balanced by a narrative of mechanisms that confer resilience and psychological well-being on Black people as they navigate the obstacles of systemic racism. I also explore diversity as a form of psychological and behavioral competence required to live effectively in a diverse world. I conclude that these aspects of human relations can be better understood and addressed with advancement of diversity science.
Deletion of GABAB receptors from Kiss1 cells affects glucose homeostasis without altering reproduction in male mice
Authors: Di Giorgio Noelia P. , Bizzozzero-Hiriart Marianne , Surkin Pablo N. , Repetto Esteban , Bonaventura María M. , Tabares Florencia N. , Bourguignon Nadia S. , Converti Ayelén , Gomez Juan M. Riaño , Bettler Bernhard , Lux-Lantos Victoria
Published: January 2023

We developed a unique mouse lacking GABAB receptors specifically in Kiss1 cells to evaluate the impact on reproduction and metabolism. Knockout males showed a severe impact on glucose homeostasis, which worsened with aging. These results reinforce the proposed kisspeptin involvement in metabolic regulation and highlight the impact of GABA through GABABR in the regulation of the peripheral pancreas kisspeptin system.
Physically interacting humans regulate muscle coactivation to improve visuo-haptic perception
Authors: Börner Hendrik , Carboni Gerolamo , Cheng Xiaoxiao , Takagi Atsushi , Hirche Sandra , Endo Satoshi , Burdet Etienne
Published: January 2023

Our results reveal that interacting humans inconspicuously modulate muscle activation to extract accurate information about the common target while considering their own and the partner’s sensorimotor noise. A novel computational model was developed to decipher the underlying mechanism: muscle coactivation is adapted to combine haptic information from the interaction with the partner and own visual information in a stochastically optimal manner. This improves the prediction of the target position with minimal metabolic cost in each partner, resulting in the lead of the partner with the most accurate visual information.
Hierarchical differences in the encoding of sound and choice in the subcortical auditory system
Authors: Mackey Chase A. , Dylla Margit , Bohlen Peter , Grigsby Jason , Hrnicek Andrew , Mayfield Jackson , Ramachandran Ramnarayan
Published: January 2023

The cerebral cortex is widely recognized to play a role in sensory processing and decision-making. Accounts of the neural basis of auditory perception and its dysfunction are based on this idea. However, significantly less attention has been paid to midbrain and brainstem structures in this regard. Here, we find that subcortical auditory neurons represent stimulus information sufficient for detection and predict behavioral choice on a trial-by-trial basis.
Serotonergic current responses of neurons in rat oculomotor neural integrators
Authors: Saito Yasuhiko , Sugimura Taketoshi
Published: January 2023

Serotonergic modulation of vertical gaze control (interstitial nucleus of Cajal, INC) is less understood than that of horizontal gaze control (prepositus hypoglossal nucleus, PHN). Here, we report 5-HT-induced fast inward currents in addition to the previously reported slow inward and outward currents. The distributions of these currents in INC neurons based on neurotransmitter phenotypes differ from those in PHN neurons. These results suggest distinct serotonergic modulation modes in horizontal and vertical gaze control centers.
Determination of Land Suitability Criteria for Maize Hybrid in Boalemo Regency Based on Optimum Yield and Selected Land Quality
Authors: Nurdin  , Rauf Asda , Rahim Yunnita , Adam Echan , Musa Nikmah , Jamin Fitriah Suryani , Dude Suyono , Rahman Rival , Katili Hidayat Arismunandar
Published: January 2023

The significant effect of land quality on maize production has not been fully considered in the existing land suitability criteria. Therefore, this study aims to determine land suitability criteria for hybrid maize in Boalemo Regency based on the optimum yield and land quality. It was carried out in Boalemo Regency, Indonesia, where the land unit of 67 units was surveyed to obtain land characteristics data. A partial least square of structural equation model (PLS-SEM) with SmartPLS 8.0 was used to select a robust land quality controlling hybrid maize yield, while the boundary line method was used to determine optimum yield and differentiating of land suitability criteria. The result showed that land qualities that define the optimum yield of hybrid maize were root conditions, nutrient availability, nutrient retentions, land preparation, and erosion hazard. The soil characteristics were effective depth, coarse material, organic C, total N, K exchangeable, slopes, soil erosion, rock outcrops, and surface rocks. Furthermore, the highest optimum yield of 8.54 ton/ha was achieved by the total N and slopes for a very suitable class (S1), while the lowest of 5.58 ton/ha was obtained by exchangeable K for class S1. This showed that the combination of PLS-SEM and boundary line analysis was a better approach to developing new land suitability criteria for hybrid maize.
Pollen Micromorphology among Amaranthaceous Species from Desert Rangeland: Exine Stratification and their Taxonomic Significance
Authors: Majeed Salman , Ahmad Mushtaq , Ali Alamdar , Althobaiti Ashwaq T. , Ramadan Mohamed Fawzy , Kilic Omer , Demirpolat Azize , Çobanoğlu Duygu Nur , Zafar Sadia , Afza Rabia , Makhkamov Trobjon , Yuldashev Akramjon , Gafforov Yusufjon , Khaydarov Khislat , Zafar Muhammad , Sultana Shazia
Published: January 2023

The aim of the study was to visualize the micromorphology of Amaranthaceous pollen using scanning electron microscopy collected from the Thal Desert. Field collection was conducted from July to September 2021. A total of 14 taxa of the family Amaranthaceae were collected which belong to nine genera. Achyranthes aspera, Aerva javanica, Aerva lanata, Amaranthus graecizans, Amaranthus retroflexus, Amaranthus viridis, Bassia indica, Chenopodium album, Chenopodium ficifolium, Chenopodium murale, Digera muricata, Haloxylon stocksii, Salsola tragus, and Suaeda fruticosa were studied in terms of pollen morphotypes. Pollen were acetolyzed and observed under optical and scanning microscopy. Qualitative and quantitative characters were measured to analyze the pollen to uncover its taxonomic significance. Qualitative characters observed were the shape of pollen in polar and equatorial views; the most frequent shape observed was spheroidal in the polar view, whereas in the equatorial view, prolate spheroidal was the dominant shape. Exine ornamentation is the key characteristic of pollen which is very helpful, and eight different types of ornamentations were observed in collected taxa: smooth sparsely granulate, scabrate‐spinulose, microspinulose perforate, microechinate scabrate to metareticulate, granulate, nanospinulate, granulate‐spinulose perforate, granulate‐perforate echinate, and microechinate perforate. Periporate‐type aperture was observed among all taxa. Mesoporia, ektexinous bodies, and tectum features also show variations among Amaranthaceous grains. In quantitative character, A. retroflexus recorded highest in polar view 26.3 μm and the lowest was of C. album 12.2 μm. Highest P/E index ratio was recorded in S. fruticosa (1.12) whereas the lowest for D. muricta (0.94). Exine thickness was highest in S. tragus 2.15 μm and lowest in A. graecizans 0.78 μm. The maximum number of pores was recorded as 32‐36 in D. muricata. Artificial taxonomic keys were constructed based on findings that reinforce the importance of the micromorphological ultrastructural diversity of pollen among Amaranthaceous taxa. It was concluded that the descriptions of pollen morphotypes presented greatly contribute to our understanding of desert species identification.
The Role of Purine Metabolism-Related Genes PPAT and IMPDH1 in the Carcinogenesis of Intrahepatic Cholangiocarcinoma Based on Metabonomic and Bioinformatic Analyses
Authors: Liu Chang-Jun , Ma Zhong-Zhi , Gong Wei-Zhi , Mao Xian-Hai , Wen Hao-Quan , Wang Xiao-Hui
Published: January 2023

In this study, we investigated the role of tumor microenvironment and serum differential metabolites in intrahepatic cholangiocarcinoma (ICC) carcinogenesis, providing new evidence for ICC treatment. Serum samples from healthy individuals and ICC patients were collected for metabolomic analysis. The purine metabolites such as inosine, guanosine, hypoxanthine, and xanthine were increased in patient serum. TCGA database samples were collected, and the correlation between purine metabolism-related genes and ICC clinical features was analyzed using R language to obtain the differential genes including PPAT, PFAS, ATIC, and IMPDH2. High PPAT expression was associated with poor ICC prognosis. A PPAT silencing model in HCCC-9810 cells was constructed. The cell phenotype was examined by qRT-PCR, CCK-8, transwell, and flow cytometry, showing a decrease in IMPDH1 expression, colony and invasive cells numbers, and an increase in apoptosis. Guanosine reversed IMPDH1 expression in HCCC-9810 cells, promoting the secretion of inflammatory factors IL-6, IL-8, OPN, VEGF, and VCAM-1 and intensifying epithelial-mesenchymal transition (EMT) progression in the cells. In nude mice, the IMPDH1 inhibitory drug MMF inhibited tumor growth and reduced the expression of tumor stem cell characteristic markers CD133 and SOX2. Guanosine accelerated the malignant progression of ICC inhibition of purine metabolism-related genes, PPAT and IMPDH2, suppressed the malignant phenotype in HCCC-9810 cells, and inhibited tumor growth.
The Association between Threatened Abortion and the Risk of Autism Spectrum Disorders among Children: A Meta‐Analysis
Authors: Ahmadvand Mahshad , Eghbalian Fatemeh , Nasrolahi Shahla , Jenabi Ensiyeh
Published: January 2023

Background. The current study is aimed at updating the observational studies on the relationship between threatened abortion and the risk of ASD. Methods. The search keywords were covered in three electronic databases PubMed, Web of Science, and Scopus up to April 2022. The modified Newcastle–Ottawa scale (NOS) was applied to detect the quality of epidemiological studies. We used the chi‐square test and the I2 statistic to show the heterogeneity among articles. I2 more than 50% was considered high heterogeneity. Egger’s and Begg’s line regression tests were used for evaluating the publication bias. The random‐effects model was applied for the analysis of the findings. The Stata 13.0 software package was applied for analysis and indicated p value less than 0.05 as a significant level. Results. The pooled analysis reported significant differences between threatened abortion and the risk of ASD in adjusted studies (OR = 1.93; 95% CI: 1.12, 2.73; I2 = 59.5.0%) and in crude studies (OR = 2.17; 95% CI: 1.46, 2.88; I2 = 39.5%). The evidence of publication bias was not found. Conclusions. The findings suggest that threatened abortion is a risk factor for ASD. As a result, screening tools to detect are necessary in mothers facing a threatened abortion.
Functional Nanorealgar Quantum Dots with Aggregation-Induced Emission Enhancement for Tumor Neovascular-Targeted Theranostics
Authors: Pu Shengyan , Wu Wenwen , Shi Dongsheng , Dai Yanqi , Zhang Jun , Zhao Mingyan , Liu Shuangyu , Zheng Guihong , Wang Xingqi , Yan Yu , Xie Jun
Published: January 2023

Realgar, a traditional Chinese medicine, has notable antitumor activity and can be used in various hematologic tumor and solid tumor therapies in a wide range of clinical applications. Nanosized realgar possesses higher surface activity and enhanced therapeutic effects on cancer cells compared with those of bulk realgar. In this study, we reported the design of high-performance nanorealgar quantum dots (NR QDs) with aggregation-induced emission enhancement of crystal units (CUs) with the addition of hydrochloric acid. The enhanced fluorescence characteristics of NR QDs are associated with an optimized crystal structure obtained by accelerating the growth process of NR CUs in which the smaller NR CUs facilitate a self-assembling arrangement and a complete structural optimization process, ultimately forming regular crystallization with a size quantization effect. To improve the theranostic efficiency of NR QDs, we synthesized NR QDs coupled with a tripeptide of arginine–glycine–aspartic acid (RGD) with tumor neovascular targeting. We intravenously injected NR@RGD QDs into BALB/c mice bearing a subcutaneously transplanted breast tumor (4T1). Our results indicate that functional NR@RGD QDs are effective chemotherapeutic drugs that can anchor into the tumor endothelial cells through an active targeting effect, inhibit the angiogenesis in the tumor, and eventually “cut-off” the nutrient-rich blood supply to the tumor. This promising antiangiogenesis therapeutic strategy induces NR@RGD QDs to penetrate tumor-fenestrated vascular networks and has potential clinical value.
The Correlation between Helicobacter pylori Immunoglobulin G Seropositivity and Plasma Homocysteine Levels in Adults
Authors: Huang Jinke , Yang Xuefei , Zhang Jiaqi , Wang Fengyun , Tang Xudong
Published: January 2023

Objectives. Helicobacter pylori (H. pylori) immunoglobulin G (IgG) seropositivity is prevalent, but its correlation with homocysteine (Hcy), a biomarker of vascular risk events, is unclear. This study is aimed at exploring the correlation of H. pylori IgG seropositivity and plasma Hcy levels in adults. Methods. Data was obtained from the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Hcy was measured by the Abbott homocysteine assay, and H. pylori IgG was measured by enzyme-linked immunosorbent assays. The weighted multiple logistic regression analyses with adjustments for potential confounders were conducted. Subgroup analyses stratified by gender, age, and race were performed. Results. A total of 4029 subjects aged 20-85 years were included. Population prevalence of H. pylori IgG seropositivity was 44.7% in the overall population with higher prevalence found in those with older age, Mexican Americans, lower education, and lower household income. Levels of plasma Hcy were not elevated in those with H. pylori IgG seropositivity versus seronegativity (β -0.120 (-0.438, 0.199)

P
=
0.462

). This difference was not significant after stratifying by gender and age. However, in the subgroup analyses stratified by race, a negative correlation between H. pylori seropositivity and plasma Hcy levels was observed in Mexican Americans (β -0.802 (-1.253, -0.352)

P
<
0.001

). Conclusions. H. pylori IgG seropositivity was not associated with plasma Hcy levels in the general population, but there may be a negative correlation in Mexican Americans. These findings provide new insights to advance the research of the link between plasma Hcy levels and stomach health.
Multiview Deep Forest for Overall Survival Prediction in Cancer
Authors: Li Qiucen , Du Zedong , Chen Zhikui , Huang Xiaodi , Li Qiu
Published: January 2023

Overall survival (OS) in cancer is crucial for cancer treatment. Many machine learning methods have been applied to predict OS, but there are still the challenges of dealing with multiview data and overfitting. To overcome these problems, we propose a multiview deep forest (MVDF) in this paper. MVDF can learn the features of each view and fuse them with integrated learning and multiple kernel learning. Then, a gradient boost forest based on the information bottleneck theory is proposed to reduce redundant information and avoid overfitting. In addition, a pruning strategy for a cascaded forest is used to limit the impact of outlier data. Comprehensive experiments have been carried out on a data set from West China Hospital of Sichuan University and two public data sets. Results have demonstrated that our method outperforms the compared methods in predicting overall survival.
LINC01278 Induces Autophagy to Inhibit Tumour Progression by Suppressing the mTOR Signalling Pathway
Authors: Liu Bo , Yao Xueting , Zhang Chaoyang , Li Wenzhe , Wang Yanan , Liao Qianling , Li Ziwei , Huang Qinying , Zhang Yanchen , Wu Wencan
Published: January 2023

Uveal melanoma (UM) is an aggressive intraocular malignant tumour that is closely related to autophagic dysfunction. We aimed to identify autophagy-related long noncoding RNAs (lncRNAs) to elucidate the molecular mechanism of UM. Here, we show that LINC01278 is a new potential biomarker with clinical prognostic value in UM through bioinformatics analysis. Application of an autophagy inhibitor (3-MA) and an autophagy agonist (MG-132) indicated that LINC01278 can inhibit UM cell proliferation, migration, and invasion by inducing autophagy. A xenograft nude mouse model was used to examine the tumorigenesis of UM cells in vivo. Mechanistically, LINC01278 can inhibit the mTOR signalling pathway to activate autophagy, as shown by experiments with an mTOR agonist (MHY1485) and mTOR inhibitor (rapamycin) treatment. Our findings indicate that LINC01278 functions as a tumour suppressor by inhibiting the mTOR signalling pathway to induce autophagy. Targeting the LINC01278-mTOR axis might be a novel and promising therapeutic approach for UM.
Active Remodeling of Capillary Endothelium via Cancer Cell–Derived MMP9 Promotes Metastatic Brain Colonization
Authors: Karreman Matthia A. , Bauer Alexander T. , Solecki Gergely , Berghoff Anna S. , Mayer Chanté D. , Frey Katharina , Hebach Nils , Feinauer Manuel J. , Schieber Nicole L. , Tehranian Cedric , Mercier Luc , Singhal Mahak , Venkataramani Varun , Schubert Marc C. , Hinze Daniel , Hölzel Michael , Helfrich Iris , Schadendorf Dirk , Schneider Stefan W. , Westphal Dana , Augustin Hellmut G. , Goetz Jacky G. , Schwab Yannick , Wick Wolfgang , Winkler Frank
Published: January 2023

Crossing the blood–brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding of the mechanisms of cancer cell extravasation from brain microcapillaries is limited as the underlying cellular and molecular processes cannot be adequately investigated using in vitro models and endpoint in vivo experiments. Using ultrastructural and functional imaging, we demonstrate that dynamic changes of activated brain microcapillaries promote the mandatory first steps of brain colonization. Successful extravasation of arrested cancer cells occurred when adjacent capillary endothelial cells (EC) entered into a distinct remodeling process. After extravasation, capillary loops were formed, which was characteristic of aggressive metastatic growth. Upon cancer cell arrest in brain microcapillaries, matrix-metalloprotease 9 (MMP9) was expressed. Inhibition of MMP2/9 and genetic perturbation of MMP9 in cancer cells, but not the host, reduced EC projections, extravasation, and brain metastasis outgrowth. These findings establish an active role of ECs in the process of cancer cell extravasation, facilitated by cross-talk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.

Significance:

Tracking single extravasating cancer cells using multimodal correlative microscopy uncovers a brain seeding mechanism involving endothelial remodeling driven by cancer cell–derived MMP9, which might enable the development of approaches to prevent brain metastasis.

See related commentary by McCarty, p. 1167
Event-Free Survival as a Surrogate for Overall Survival in Gastric and Gastroesophageal Junction Adenocarcinoma: A Meta-analysis in the Neoadjuvant ± Adjuvant Setting
Authors: Wainberg Zev A. , Xie Jipan , Valderrama Adriana , Yin Lei , Zhang Shujing , Shih Chie-Schin , Bhagia Pooja , Gu Qianqian , Shitara Kohei , Janjigian Yelena Y. , Tabernero Josep
Published: January 2023

Purpose:

This study assessed the trial-level association between event-free survival (EFS) and overall survival (OS) in gastric or gastroesophageal junction (GEJ) adenocarcinoma in the neoadjuvant ± adjuvant settings.

Experimental Design:

A systematic literature review was conducted to identify randomized controlled trials (RCT) that evaluated neoadjuvant therapies with or without adjuvant therapies for gastric or GEJ adenocarcinoma. A meta-analysis was performed using weighted linear regressions of the treatment effect of OS on the treatment effect of EFS. The coefficient of determination (R²) and associated 95% confidence interval (CI) were used to evaluate the association between treatment effects of EFS and OS. The threshold used for defining good trial-level surrogacy was a correlation coefficient (R) of 0.8 or R² of 0.65, based on prior literature. Sensitivity analyses were performed to assess the robustness of the association with divergent study designs, including study population, inclusion of adjuvant therapy, and definitions of EFS and OS.

Results:

The main analysis included 16 comparisons from 15 RCTs. The log(HR) of EFS was a significant predictor of log(HR) of OS, with an estimated coefficient of 0.72 (P < 0.001) and R² = 0.75 (95% CI, 0.49–0.95), indicating that EFS was a good surrogate outcome for OS. The results of the sensitivity analyses were consistent with the primary results, with R² ranging from 0.76 to 0.89.

Conclusions:

This study suggests that EFS is a good surrogate for OS in gastric or GEJ adenocarcinoma in the neoadjuvant ± adjuvant setting.
Abstract IA015: The tick-tock of epigenetic clocks in patients with cancer
Authors: Burd Christin E.
Published: January 2023

There is a growing need to understand how aging influences cancer outcomes in older adults. Prior work shows that older adults with cancer would elect to forgo life-prolonging therapies that would lead to cognitive or physical disability. Here, we hypothesized that aging biomarkers would define individuals at risk for impairment and identify therapeutic regimens associated with accelerated aging. We first tested whether published epigenetic clocks would maintain validity in isolated CD3+ T cells. Potential advantages of using this approach in cancer patients include reduced sample complexity, the ability to survey aging in the context of clonal B cell expansions, and the critical importance of this cell population in cancer control. The Hannum, Horvath, GrimAge, PhenoAge, and PACE clocks increased with chronologic age in CD3+ T cells from 185 healthy donors. However, accelerated epigenetic age varied in PBMCs and CD3+ T cells isolated from the same blood sample. Next, we conducted a longitudinal analysis of adults ≥60 years of age newly diagnosed with non-small cell lung cancer (n=41) or hematologic malignancy (n=94). Standard clinical tools were used to assess fitness (ECOG performance, IADLs, SPPB), comorbidities, cognition (BOMC), and potential for therapeutic toxicity (CARG chemo-toxicity calculator). Relationships between these metrics and baseline CD3+ T cell epigenetic age were investigated. These analyses revealed a direct correlation between epigenetic age and increasing ECOG performance score. Cancer therapies, including high-dose chemotherapy, immunotherapies, and hypomethylating agents, significantly impacted patient epigenetic age. No relationship between outcome and baseline epigenetic age was observed in either population. These data support the use of the Hannum, Horvath, GrimAge, PhenoAge, and PACE clocks to measure aging in CD3+ T cells, though differences in PBMC and CD3+ T cell measurements suggest that the rate of epigenetic aging may differ in each sample type. The inability of epigenetic clocks to consistently measure physical function and cognition or predict patient outcomes implies that new clocks may be required to circumvent the heterogeneity of disease, therapies, and comorbidities in older adults with cancer.

Citation Format: Christin E. Burd. The tick-tock of epigenetic clocks in patients with cancer [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr IA015.
Endoplasmic Reticulum Stress in the Brain Tumor Immune Microenvironment
Authors: Petrosyan Edgar , Fares Jawad , Fernandez Luis G. , Yeeravalli Ragini , Dmello Crismita , Duffy Joseph T. , Zhang Peng , Lee-Chang Catalina , Miska Jason , Ahmed Atique U. , Sonabend Adam M. , Balyasnikova Irina V. , Heimberger Amy B. , Lesniak Maciej S.
Published: January 2023

Immunotherapy has emerged as a powerful strategy for halting cancer progression. However, primary malignancies affecting the brain have been exempt to this success. Indeed, brain tumors continue to portend severe morbidity and remain a globally lethal disease. Extensive efforts have been directed at understanding how tumor cells survive and propagate within the unique microenvironment of the central nervous system (CNS). Cancer genetic aberrations and metabolic abnormalities provoke a state of persistent endoplasmic reticulum (ER) stress that in turn promotes tumor growth, invasion, therapeutic resistance, and the dynamic reprogramming of the infiltrating immune cells. Consequently, targeting ER stress is a potential therapeutic approach. In this work, we provide an overview of how ER stress response is advantageous to brain tumor development, discuss the significance of ER stress in governing antitumor immunity, and put forth therapeutic strategies of regulating ER stress to augment the effect of immunotherapy for primary CNS tumors.