bluuebunny/crossref_metadata_2025 huggingface dataset:
Food and cover resources for small mammals on an industrially logged landscape in the Sierra Nevada of California
Authors: Fraik Alexandra K. , Facka Aaron N. , Powell Roger A.
Published: February 2023

The presence and abundance of organisms within an ecosystem often correlate with habitat variables that may have few, or unknown, functional values. Understanding the functional role of these variables is especially important for organisms occupying landscapes managed for timber production and containing diverse habitat patches of different quantities and structures of vegetation. We investigated the strength of associations reported in the literature between small mammal generalists and vegetation. On an industrially logged landscape in northern CA, we used occupancy and mark-recapture analyses across three years to estimate the presence and total numbers for woodrats ( Neotoma fuscipes Baird, 1858) and deer mice ( Peromyscus maniculatus (Wagner, 1845)) related to vegetative attributes on coniferous and non-coniferous sites. Abundances of the small mammals correlated positively with shrub cover and hardwoods for woodrats and with shrubs and masting species for deer mice. Indices describing the value of vegetation features for both food and cover, but not these resources independently, described both species’ presence and abundances best. We demonstrated that shrubs and non-coniferous trees are particularly important for small mammals and should be of particular focus to forest managers in the Sierras and mountains with similar forest structures.
Intelligent Techniques for Predicting Stock Market Prices: A Critical Survey
Authors: Alshabeeb Esra’a , Aljabri Malak , Mohammad Rami Mustafa A. , Alqarqoosh Fatemah S. , Alqahtani Aseel A. , Alibrahim Zainab T. , Alawad Najd Y. , Alzeer Mashael A.
Published: February 2023

The stock market is an exciting field of interest to many people regardless of their occupational background. It is a market where individuals with adequate knowledge can join and earn an additional income. Nowadays, life expenses have increased. Hence, the number of people investing in stocks is increasing dramatically. Anyone may indeed start participating in the stock market at any time, yet it is not ensured that they will profit from this investment. The stock market is a risky field of investment, given that it is unknown whether the stock will rise or fall. Stock market prediction using Artificial Intelligence techniques is a possible way to help people anticipate stock market directions. Current research showed that many factors aid in changing the stock market value in general and specifically in the Saudi stock market. To our knowledge, most research studies only consider historical data in predicting stock market trends. However, this research aims to enhance the accuracy of the daily closing price for three Saudi stock market sectors by considering historical and sentimental data. Several intelligent algorithms are considered, and their performance indicators are discussed and contrasted against each other. This research concluded that more accurate stock market prediction models could be produced by employing historical and sentimental data.
A Review of the Empirical Literature on Audit Market Concentration
Authors: Elbardan Hany , Kotb Amr , Ishaque Maria
Published: February 2023

Synopsis

The research problem

The extant audit market concentration (AMC) literature is quite scattered, which makes it challenging to comprehend the current state of knowledge and to highlight the areas that require further exploration. An improved understanding of AMC and its possible effects require a comprehensive review of the AMC literature, since no such review has yet been published. Therefore, our paper intends to: (a) synthesize the empirical work in the AMC literature; (b) determine the limitations in the ways AMC has been investigated; (c) identify avenues of inquiry that could guide future thinking on AMC; and (d) develop insights into how future AMC investigations can be further developed.

Motivation

The most noticeable developments in AMC occurred after the audit firm megamergers of the 1980s and 1990s and Andersen’s demise in 2002. This trend toward fewer and larger suppliers of auditing services has sparked intense debate about the costs and benefits of AMC. However, the literature provides mixed evidence on the determinants and consequences of AMC.

Adopted methodology

A structured literature review [Massaro, M., Dumay, J., & Guthrie, J. (2016). On the shoulders of giants: Undertaking a structured literature review. Accounting, Auditing and Accountability Journal, 29(5), 767–801. https://doi.org/10.1108/AAAJ-01-2015-1939 ] was employed to review the extant AMC literature.

Analyses

We analyzed 108 empirical papers published in 39 peer-reviewed quality accounting and auditing journals in the English language over a 55-year period (1967 to mid-2021).

Findings

The analysis suggests a consistent rise in AMC levels, leading to a tight oligopoly and, in rare cases, to a duopoly, across countries and over time. Studies of audit pricing and audit quality comprise the predominant part of the literature, and these report mixed findings as to whether AMC facilitates monopolistic pricing and allows audit-quality-threatening behaviors. This could be attributed to several factors, including the focus on short-term effects of AMC; substantial variations in how concentration was measured; and misguided use of proxies for audit competition and audit quality. The review identifies four key limitations that circumscribe our understanding of AMC: (a) the lack of investigation into the actual dynamic rivalry among audit firms; (b) great reliance on the positivistic approach and quantitative methods, and the lack of use of explicit theories aside from economic theories; (c) a focus on the audit of publicly listed companies in the United States, the U.K., and Australia; and thus; (d) the absence of key organizational settings and central regions in the AMC debate. To counter these limitations, this review puts forward possible future research avenues that can help to advance our understanding of AMC to address emerging challenges in the field.
Blended Learning Technologies in Dental Education: A case study in orofacial pain
Authors: Hawkins James Mark , Fallis Drew , Durning Steven
Published: February 2023

Blended learning in pain education is an effective teaching method to help learners grasp complex didactic and clinical topics. In this report, four educational strategies are examined that were successfully utilized to teach a postgraduate dental orofacial pain course. These strategies included using virtual presentations, hands-on training, virtual interactive case-based learning, and student created multimedia and peer-to-peer feedback.
Why Are Invasive Plants Successful?
Authors: Gioria Margherita , Hulme Philip E. , Richardson David M. , Pyšek Petr
Published: February 2023

Plant invasions, a byproduct of globalization, are increasing worldwide. Because of their ecological and economic impacts, considerable efforts have been made to understand and predict the success of non-native plants. Numerous frameworks, hypotheses, and theories have been advanced to conceptualize the interactions of multiple drivers and context dependence of invasion success with the aim of achieving robust explanations with predictive power. We review these efforts from a community-level perspective rather than a biogeographical one, focusing on terrestrial systems, and explore the roles of intrinsic plant properties in determining species invasiveness, as well as the effects of biotic and abiotic conditions in mediating ecosystem invasibility (or resistance) and ecological and evolutionary processes. We also consider the fundamental influences of human-induced changes at scales ranging from local to global in triggering, promoting, and sustaining plant invasions and discuss how these changes could alter future invasion trajectories.
What Four Decades of Meta-Analysis Have Taught Us About Youth Psychotherapy and the Science of Research Synthesis
Authors: Weisz John R. , Venturo-Conerly Katherine E. , Fitzpatrick Olivia M. , Frederick Jennifer A. , Ng Mei Yi
Published: February 2023

Intervention scientists have published more than 600 randomized controlled trials (RCTs) of youth psychotherapies. Four decades of meta-analyses have been used to synthesize the RCT findings and identify scientifically and clinically significant patterns. These meta-analyses have limitations, noted herein, but they have advanced our understanding of youth psychotherapy, revealing (a) mental health problems for which our interventions are more and less successful (e.g., anxiety and depression, respectively); (b) the beneficial effects of single-session interventions, interventions delivered remotely, and interventions tested in low- and middle-income countries; (c) the association of societal sexism and racism with reduced treatment benefit in majority-girl and majority-Black groups; and, importantly, (d) the finding that average youth treatment benefit has not increased across five decades of research, suggesting that new strategies may be needed. Opportunities for the future include boosting relevance to policy and practice and using meta-analysis to identify mechanisms of change and guide personalizing of treatment.
Immune Mechanisms in Inflammatory Anemia
Authors: Canny Susan P. , Orozco Susana L. , Thulin Natalie K. , Hamerman Jessica A.
Published: February 2023

Maintaining the correct number of healthy red blood cells (RBCs) is critical for proper oxygenation of tissues throughout the body. Therefore, RBC homeostasis is a tightly controlled balance between RBC production and RBC clearance, through the processes of erythropoiesis and macrophage hemophagocytosis, respectively. However, during the inflammation associated with infectious, autoimmune, or inflammatory diseases this homeostatic process is often dysregulated, leading to acute or chronic anemia. In each disease setting, multiple mechanisms typically contribute to the development of inflammatory anemia, impinging on both sides of the RBC production and RBC clearance equation. These mechanisms include both direct and indirect effects of inflammatory cytokines and innate sensing. Here, we focus on common innate and adaptive immune mechanisms that contribute to inflammatory anemias using examples from several diseases, including hemophagocytic lymphohistiocytosis/macrophage activation syndrome, severe malarial anemia during Plasmodium infection, and systemic lupus erythematosus, among others.
TGF-β Regulation of T Cells
Authors: Chen WanJun
Published: February 2023

Transforming growth factor β (TGF-β) is a key cytokine regulating the development, activation, proliferation, differentiation, and death of T cells. In CD4+ T cells, TGF-β maintains the quiescence and controls the activation of naive T cells. While inhibiting the differentiation and function of Th1 and Th2 cells, TGF-β promotes the differentiation of Th17 and Th9 cells. TGF-β is required for the induction of Foxp3 in naive T cells and the development of regulatory T cells. TGF-β is crucial in the differentiation of tissue-resident memory CD8+ T cells and their retention in the tissue, whereas it suppresses effector T cell function. In addition, TGF-β also regulates the generation or function of natural killer T cells, γδ T cells, innate lymphoid cells, and gut intraepithelial lymphocytes. Here I highlight the major findings and recent advances in our understanding of TGF-β regulation of T cells and provide a personal perspective of the field.
Therapeutic Potential of PTBP1 Inhibition, If Any, Is Not Attributed to Glia-to-Neuron Conversion
Authors: Wang Lei-Lei , Zhang Chun-Li
Published: February 2023

A holy grail of regenerative medicine is to replenish the cells that are lost due to disease. The adult mammalian central nervous system (CNS) has, however, largely lost such a regenerative ability. An emerging strategy for the generation of new neurons is through glia-to-neuron (GtN) conversion in vivo, mainly accomplished by the regulation of fate-determining factors. When inhibited, PTBP1, a factor involved in RNA biology, was reported to induce rapid and efficient GtN conversion in multiple regions of the adult CNS. Remarkably, PTBP1 inhibition was also claimed to greatly improve behaviors of mice with neurological diseases or aging. These phenomenal claims, if confirmed, would constitute a significant advancement in regenerative medicine. Unfortunately, neither GtN conversion nor therapeutic potential via PTBP1 inhibition was validated by the results of multiple subsequent replication studies with stringent methods. Here we review these controversial studies and conclude with recommendations for examining GtN conversion in vivo and future investigations of PTBP1.
Food and Inequality
Authors: Shostak Sara
Published: February 2023

The production, consumption, materiality, and meanings of food are critical topics for sociological research on inequality, although they have not always been recognized as such. This article describes how food is implicated in the production of inequalities across scales and sites. It begins by considering how the global food system is inextricably imbricated with structures of power that create and sustain patterns of inequality, especially in regard to land and labor. It then reviews the literature on food access and food insecurity, not only as determinants of health but as lived experiences shaped by local food environments, intersectional identities, and the social meanings of food. Lastly, it considers how the food justice and food sovereignty movements challenge the inequalities and injustices engendered by the global industrial food system. The conclusions highlight how sociological research on food and inequality is essential to understanding the contexts and consequences of contemporary policy initiatives.
Effects of miR-107 on Breast Cancer Cell Growth and Death via Regulation of the PTEN/AKT Signaling Pathway
Authors: Pan Hua , Peng Hongwei , Dai Yun , Han Bin , Yang Guangming , Jiang Nian , Zhou Ping
Published: February 2023

Objective. Investigate the influence of miR-107 on breast cancer cell growth and death through the PTEN/AKT signaling pathway. Method. As study subjects, the human breast cancer cell line MCF-7 and the normal breast cell line Hs 578Bst were chosen, and MCF-7 cells were, respectively, transfected with control miRNA and miR-107 inhibitor. CCK-8, flow cytometry, scratch assay, and Transwell assay were used to analyze the proliferation, apoptosis, and invasion, and in order to identify the proteins associated with apoptosis in each of the three categories, we used western blot analysis. Bcl-2, cleaved caspase-3, and cleaved caspase-9 expression, as well as PTEN/AKT signaling pathway-associated protein expression, are correlated. Result. The expression of miR-107 in MCF-7 cells was significantly greater than that in Hs 578Bst cells, with a

P

 < 0.05 difference; compared to the blank and miRNA control groups, the miR-107 inhibitor group had a

P

 < 0.05 difference.

P

 < 0.05 showed a decrease in proliferation (42.52) but no difference in proliferation between the blank and miRNA control groups (

P

 > 0.05); the miR-107 inhibitor group had higher apoptosis (38.96) with

P

 < 0.05 than the blank group (4.85) and the miRNA control group (5.89); there was no difference in apoptosis between the blank and miRNA groups (

P

 > 0.05). There was no significant difference between the blank group and the miRNA control group with

P

 > 0.05; compared with the blank group, the miR-107 inhibitor group had a lower expression of Bcl-2 protein (0.18), in addition to the degraded paradigms (0.73) and caspase-9 protein concentrations (0.79), respectively. Conclusion. The PTEN/AKT signaling pathway may be regulated by miR-107 to limit breast cancer cell growth and increase apoptosis, which suggests that miR-107 may be exploited as a tumor marker for therapeutic therapy.
High Co-Expression of PDCD1/TIGIT/CD47/KIR3DL2 in Bone Marrow Is Associated with Poor Prognosis for Patients with Myelodysplastic Syndrome
Authors: Zhong Mengjun , Chen Cunte , Zhao Wenshu , Tan Jiaxiong , Chen Jie , Huang Xin , Li Yangqiu , Dai Min
Published: February 2023

Cellular immune disorder is a common characteristic of myelodysplastic syndrome (MDS). Abnormal natural killer (NK) cell function has been reported in MDS patients, and this is closely related to disease progression and poor prognosis. However, little is known about the association between the abnormal immune checkpoint (IC) that results in abnormal immune NK cell function and the prognosis of MDS. In this study, RNA-sequencing data from 80 patients in the GSE114922 dataset and bone marrow (BM) samples from 46 patients with MDS in our clinical center were used for overall survival (OS) analysis and validation. We found that the NK cell-related IC genes PDCD1, TIGIT, CD47, and KIR3DL2 had higher expression and correlated with poor OS for MDS patients. High expression of PDCD1 or TIGIT was significantly associated with poor OS for MDS patients younger than 60 years of age. Moreover, co-expression of PDCD1 and TIGIT had the greatest contribution to OS prediction. Interestingly, PDCD1, TIGIT, CD47, and KIR3DL2 and risk stratification based on the Revised International Prognostic Scoring System were used to construct a nomogram model, which could visually predict the 1-, 2-, and 3-year survival rates of MDS patients. In summary, high expression of IC receptors in the BM of MDS patients was associated with poor OS. The co-expression patterns of PDCD1, TIGIT, CD47, and KIR3DL2 might provide novel insights into designing combined targeted therapies for MDS.
Effects of Replacement Cold Press Poppy Seed (Papaver somniferum) Oil to Fish Oil at Different Proportions on the Growth Performance, Blood Parameters, and Digestive Tracks Histopathology in Juvenile Common Carp (Cyprinus carpio)
Authors: Kesbiç Osman Sabri , Acar Ümit , Demirci Beste , Terzi Funda , Tezel Rifat , Türker Ali , Güllü Kenan , Erol Hüseyin Serkan
Published: February 2023

The major goal of the study is to determine the potential use of poppy seed oil as a main lipid source in common carp diets. To investigate this, five different experimental diets (PO0, PO25, PO50, PO75, and PO100) with various proportions of fish oil and poppy seed oil blended as oil sources were provided and supplied to common carp for 90 days. In triplicate groups of 60 fish, 300 common carp weighing 1.15 ± 0.06 g were randomly placed in 100 L aquariums. At the end of the feeding trial, blood and tissue samples were collected from the fish after gravimetric measurements of the fish. The growth and feed utilization performance of the fish were calculated by gravimetric measurements, and tissue samples were examined by hematological, micromorphometric, and histopathological methods. According to the results, poppy seed oil enhanced the quantity of linoleic acid (18 : 2 ω−6) in the diet, and fish fed with the diet consisting completely of poppy seed oil (PO100) had the significantly greatest growth and feed utilization performance (

P
<
0.05

). Furthermore, no significant differences in hematological or liver pathology were detected between all groups that were fed with experimental diets (

P
>
0.05

). However, as compared to the control group, the digestive system micromorphometry and histomorphometric measurements of the fish fed with PO100 group diets showed a significant increase (

P
<
0.05

). In conclusion, it was determined that the carp fed with feeds produced by using only poppy oil as the main fat source improved their digestive system, growth, and feed utilization performance without any negative effects.
Developing an Intelligent Model Based on Fuzzy Multilayer Neural Network for Improving Credit Risk Management under Uncertain Conditions
Authors: Ghasemi Zohreh , Afshar Kermani Mozhdeh , Allahviranloo Tofigh
Published: February 2023

This study utilizes the advantages of soft calculations, represented as intelligent combined methods and computational intelligence methods, to enhance credit risk management. For this purpose, the proposed method contains the fuzzy regression and artificial neural network (ANN). In this way, the parameters of neural network are fuzzy, encompassing weights and errors to model under uncertain conditions. Then, fuzzy neural networks form the system where the optimal decision is obtained using the highest degree of superiority by fuzzy inferences. Finally, using the credit information of some countries, the efficiency of the proposed combined model in credit scoring analysis has been shown.
AI in the Foreign Language Classroom: A Pedagogical Overview of Automated Writing Assistance Tools
Authors: Alharbi Wael
Published: February 2023

Recent technological advances in artificial intelligence (AI) have paved the way for improved and in many cases the creation of entirely new and innovative, electronic writing tools. These writing support systems assist during and after the writing process making them indispensable to many writers in general and to students in particular who can get human-like sentence completion suggestions and text generation. Although the wide adoption of these tools by students has been faced with a steady growth of scientific publications in the field, the results of these studies are often contradictory and their validity may be questioned. To gain a deeper understanding of the validity of AI-powered writing assistance tools, we conducted a systematic review of the recent empirical AI-powered writing assistance studies. The purpose of this review is twofold. First, we wanted to explore the recent scholarly publications that evaluated the use of AI-powered writing assistance tools in the classroom in terms of their types, uses, limits, and potential for improving students’ writing skills. Second, the review also sought to explore the perceptions of educators and researchers about learners’ use of AI-powered writing tools and review their recommendations on how to best ingrate these tools into the contemporary and future classroom. Using the Scopus research database, a total of 104 peer-reviewed papers were identified and analyzed. The findings indicate that students are increasingly using a variety of AI-powered writing assistance tools for improving their writing. The tools they are using can be categorized into four main groups: (1) automated writing evaluation tools, (2) tools that provide automated writing corrective feedback, (3) AI-powered machine translators, and (4) GPT-3 automatic text generators. The analysis also highlighted the scholars’ recommendations regarding dealing with learners’ use of AI-powered writing assistance tools and grouped the recommendations into two groups for researchers and educators.
A Baseline-Free Lamb Wave Damage Localization Method Based on Compressed Sensing
Authors: Cui Xiushi , Song Bo , Li Dongsheng , Liu Jiahe
Published: February 2023

In conventional Lamb wave-based damage detection, estimation is generally performed using the difference between the measured and baseline signals. However, it is difficult to maintain consistent measurement conditions between the measured and baseline signals, likely leading to large measurement errors. This paper proposed a baseline-free Lamb wave-based detection method for locating damage to structures. The damage scattering waves are extracted according to their features in the frequency-wavenumber spectrum and the damage locations are visualized using probability imaging. To reduce the complications of full wavefield acquisition, wavefield data are acquired using piezoelectric transducer (PZT) arrays at sampling rates much lower than the Nyquist frequency, and the original wavefield is reconstructed by applying compressed sensing. Experimental results on an aluminum plate indicate that the proposed method can provide the damage probability at each plate position without requiring a reference signal, suggesting its applicability to damage diagnosis of structures. Moreover, the proposed method achieves a compression ratio of 86.7% compared with the use of Nyquist sampling.
IoT Based System for Heart Monitoring and Arrhythmia Detection Using Machine Learning
Authors: Cañón-Clavijo Ruben Enrique , Montenegro-Marin Carlos Enrique , Gaona-Garcia Paulo Alonso , Ortiz-Guzmán Johan
Published: February 2023

Internet of Things (IoT) technologies allow building a digital representation of people, objects, or physical phenomena to be available on the Internet. Thus, stakeholders can access this information from remote places or computational systems could analyze this data to find patterns, make decisions, or execute actions. For instance, a doctor could diagnose patients by analyzing the received data from an IoT system even when patients are located in a remote place. This article proposes an IoT system for monitoring electrocardiogram (ECG) signal and processing heart data in order to generate an alert when an arrhythmia is present. This system involves a Polar H10 heart sensor, machine-learning models to classify heart events, and communication technology to share and store patient’s information. In the first place, the architecture of the IoT monitoring system and the communication between the components are described by discussing the designing criteria. Second, the experimentation process performs the training and the assessment of three classification algorithms, random forest, convolutional neural network, and k-nearest neighbors. The results show that k-nearest neighbor has the best accuracy percentage classifying the arrhythmias under study (premature ventricular contraction 94%, fusion of ventricular beat 81%, and supraventricular premature beat 82%); also, it is able to discern normal and unclassifiable beats with 93% and 97%, respectively.
Calculation Model of Bottom Hole Flowing Pressure of Double-Layer Combined Production in Coalbed Methane Wells
Authors: Zhang Peng , Wang Xiangchun , Zhang Yan , Wang Chao , Zheng Lihui , Gan Maozong , Liao Yamin
Published: February 2023

Bottom hole flowing pressure (BHFP) is the key factor to determine a reasonable working system and achieve long-term stable production of coalbed methane (CBM) wells. However, there is no special BHFP model for double-layer combined production (DLCP). Generally, the constant mass model (CMM) for single-layer production is applied to treat the double reservoirs as a whole, ignoring the changes of fluid mass in each section and the acceleration pressure drop in the reservoir section. The calculation results have great errors, and the BHFP of the lower reservoir is used to adjust the production system of the two reservoirs, which does not meet the requirements of the upper reservoir. In this paper, the expression of acceleration pressure drop assumed to be zero in CMM is decomposed and derived, the relationship between acceleration pressure drop and unit length radial flow is established, and then the pressure drop formula of reservoir section with radial inflow is obtained. The reservoir is divided into several sublayers, and the pressure drop equation for each sublayer is established. According to the water flow and gas flow in the reservoir and nonreservoir sections, the corresponding velocity equations of water phase and gas phase are derived. The above equations are combined to establish the variable mass model (VMM) for DLCP with three stages. The field data are substituted into the VMM and the CMM, and the accuracy of the new model is verified. The results show that in the stages of double-layer water production and double-layer gas production, the errors of the two models are less than 5%, while in the stage of gas-water coproduction, the error of the VMM is 2.75%-6.58%, and the error of the CMM is 7.15%-15.18%. The VMM is more accurate. In addition, in the stages of water production and gas-water coproduction during DLCP, the BHFP of the two reservoirs differs greatly, with a maximum difference of 49.1%. Therefore, the two reservoirs need to adjust the production rule according to their respective BHFP. To sum up, the VMM can accurately give the BHFP of each reservoir, which is more realistic. It also solves the problem that one BHFP cannot accurately adjust the production rule of the two reservoirs, so as to provide technical support for the formulation of optimal production rule and the realization of high production.
P7C3-A20 Attenuates Microglial Inflammation and Brain Injury after ICH through Activating the NAD+/Sirt3 Pathway
Authors: Wu Yang , Hu Qing , Wu Xun , Cai Ya-ning , Zhang Yun-ze , Wu Ying-xi , Zhu Gang , Luo Jia-ning , Cheng Hong-bo , Yu Jie-gang , Wang Xiao-liang , Gao Li , Gao Guo-dong
Published: February 2023

Intracerebral hemorrhage (ICH) is lethal but lacks effective therapies. Nicotinamide adenine dinucleotide (NAD+) is a central metabolite indispensable for a broader range of fundamental intracellular biological functions. Reduction of NAD+ usually occurs after acute brain insults, and supplementation of NAD+ has been proven neuroprotective. P7C3-A20 is a novel compound featuring its ability to facilitate the flux of NAD+. In this study, we sought to determine the potential therapeutic value of P7C3-A20 in ICH. In collagenase-induced ICH mouse models, we found that P7C3-A20 treatment could diminish lesion volume, reduce blood-brain barrier (BBB) damage, mitigate brain edema, attenuate neural apoptosis, and improve neurological outcomes after ICH. Further, RNA sequencing and subsequent experiments revealed that ICH-induced neuroinflammation and microglial proinflammatory activities were significantly suppressed following P7C3-A20 treatment. Mitochondrial damage is an important trigger of inflammatory response. We examined mitochondrial morphology and function and found that P7C3-A20 could attenuate OxyHb-induced impairment of mitochondrial dynamics and functions in vitro. Mechanistically, Sirt3, an NAD+-dependent deacetylase located in mitochondria, was then found to play a vital role in the protection of P7C3-A20 against mitochondrial damage and inflammatory response. In rescue experiments, P7C3-A20 failed to exert those protective effects in microglia-specific Sirt3 conditional knockout (CKO) mice. Finally, preclinical research revealed a correlation between the plasma NAD+ level and the neurological outcome in ICH patients. These results demonstrate that P7C3-A20 is a promising therapeutic agent for neuroinflammatory injury after ICH and exerts protective actions, at least partly, in a Sirt3-dependent manner.
Inhibitor of Apoptosis Proteins Antagonist Induces T-cell Proliferation after Cross-Presentation by Dendritic Cells
Authors: Hoefsmit Esmée P. , van Royen Paula T. , Rao Disha , Stunnenberg Johanna A. , Dimitriadis P. , Lieftink Cor , Morris Ben , Rozeman Elisa A. , Reijers Irene L.M. , Lacroix Ruben , Shehwana Huma , Ligtenberg Maarten A. , Beijersbergen Roderick L. , Peeper Daniel S. , Blank Christian U.
Published: February 2023

Cross-presentation of tumor antigens by dendritic cells (DC) is crucial to prime, stimulate and restimulate CD8+ T cells. This process is important in initiating and maintaining an antitumor response. Here, we show that the presence of conventional type 1 DCs (cDC1), a DC subtype that excels in cross-presentation, in the tumor correlated with response to neoadjuvant immune checkpoint blockade (ICB) in melanoma. This led us to hypothesize that patients failing to respond to ICB could benefit from enhanced cross-presentation of tumor antigens. We therefore established a cross-presentation assay to screen over 5,500 compounds for enhancers of DC cross-presentation using induced T-cell proliferation as the readout. We identified 145 enhancers, including AZD5582, an antagonist of inhibitor of apoptosis proteins (IAP) cIAP1, cIAP2, and XIAP. AZD5582 treatment led to DC activation of the noncanonical NF-kB pathway, enhanced antigen import from endolysosomes into the cytosol, and increased expression of genes involved in cross-presentation. Furthermore, it upregulated expression of CD80, CD86, MHC class II, CD70 and secretion of TNF by DCs. This enhanced DC activation and maturation program was observed also in tumor-bearing mice upon AZD5582 treatment, culminating in an increased frequency of systemic tumor antigen–specific CD8+ T cells. Our results merit further exploration of AZD5582 to increase antigen cross-presentation for improving the clinical benefit of ICB in patients who are unlikely to respond to ICB.
Sex Differences in Long-Term Functional Decline after Ischemic Stroke: A Longitudinal Observational Study from the Fukuoka Stroke Registry
Authors: Irie Fumi , Matsuo Ryu , Nakamura Kuniyuki , Wakisaka Yoshinobu , Ago Tetsuro , Kitazono Takanari , Kamouchi Masahiro ,   on behalf of the Fukuoka Stroke Registry Investigators
Published: February 2023

Introduction: Data on sex differences in poststroke functional status for a period longer than 1 year based on large cohorts are sparse. This study aimed to determine whether there are sex differences in long-term functional decline after ischemic stroke. Methods: We tracked functional status for 5 years among 3-month survivors of acute ischemic stroke and compared outcomes between women and men using a large-scale hospital-based stroke registry in Fukuoka, Japan. Functional status was assessed using the modified Rankin Scale (mRS). Functional dependency was defined as an mRS score of 3, 4, or 5. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals of outcomes after adjusting for possible confounders. Results: A total of 8,446 patients (71.9 ± 12.5 years, 3,377 (40.0%) female patients) were enrolled in this study. Female sex was associated with a higher risk of functional dependency at 5 years poststroke even when adjusting for age, 3-month mRS score, and other confounding factors (multivariable-adjusted OR vs. men, 1.56 [95% confidence interval, 1.26–1.93]). This significant association of female sex with higher dependency at 5 years was also found among patients who were independent at 3 months poststroke. Subgroup analysis showed that increased risk of functional dependency in female patients was more marked in patients aged ≥75 years than in those aged <75 years (p for heterogeneity = 0.02). Conversely, female sex was associated with a lower risk of death. No sex difference was observed in stroke recurrence during 5 years poststroke. Discussion/Conclusion: This longitudinal observational study suggests that female sex was independently associated with an increased risk of functional decline in the chronic phase of stroke, especially in older patients. There was no sex difference in 5-year stroke recurrence, and thus, other factors might be involved in more significant deterioration of functional status in female survivors of ischemic stroke. Further studies are needed to elucidate underlying causes of sex differences in long-term functional decline after stroke.
Advances in Futile Reperfusion following Endovascular Treatment in Acute Ischemic Stroke due to Large Vessel Occlusion
Authors: Wang Liyuan , Xiong Yunyun
Published: February 2023

Background: Futile reperfusion (FR) is becoming an urgent issue for acute ischemic stroke patients who underwent endovascular treatment (EVT). Although the recanalization rate has improved after EVT, it is far from translating to increased tissue reperfusion and functional independence. Summary: Many underlying mechanisms including the “no-reflow” phenomenon, poor collateral flow, venous dysfunction, and inflammation were proposed, but the pathophysiology of FR is still unclear. Clinically, reliable predictors are still yet to be identified, and ongoing trials on shortening the time delay and cytoprotection may provide novel ideas for interventions of FR. Key Messages: This review will summarize the latest advances in FR and hopefully shed light on potential interventions.
Impact of Geriatric Assessment on the Tolerability of Combination Chemotherapy in Older Patients with Advanced Cancer: A Matched-Pair Analysis
Authors: Stahl Michael Konrad , Ertl Sebastian Willy , Engelmeyer Pouneh , Heuer Hans-Christoph , Christoph Daniel Christian
Published: February 2023

Because of their individual vulnerabilities, treatment decisions for older patients can be difficult. Geriatric assessment (GA) may help to select patients for systemic treatment, but its value is still unproven. Older cancer patients (≥65 years of age) with and without complex GA followed by discussion in the geriatric-oncologic conference, who had been treated in palliative intention with standard combination chemotherapy at the Evang. Kliniken Essen-Mitte, were retrospectively evaluated. All patients had been orally informed about the treatment options and had chosen chemotherapy beside supportive care. To reduce selection bias, the method of propensity-score matching was performed. Patient groups treated in the years 2011–2013 (without GA, group 1) and in the years 2014–2015 (with GA, group 2) were compared regarding different toxicity endpoints. The primary endpoint of the study was defined as numbers of patients with unplanned admission to the hospital or death during first-line chemotherapy and GA should reduce these events by 15%. Overall, 114 patients were evaluated in both groups. The median age was 74 years. Patients suffered from gastrointestinal carcinomas (47%), lung cancer (28%), breast cancer (12%), and other cancer types (3%). Consequently, most patients were treated with platinum-based (41%), fluoropyrimidine-based (35%), or anthracycline-based (13%) combination chemotherapy. In group 2, the events were numerically lower for all toxicity endpoints. The need for a premature stop of treatment was 54.4% in group 1 compared to 29.8% in group 2 (p < 0.01) and also the treatment-related mortality was significantly lower in group 2 (17.5% vs. 5.3%; p = 0.04). The primary endpoint, the rate of unplanned hospital admission, and death was 49.1% versus 35.1% (difference 14.0%), which did not reach the predefined border of 15%. There was a nonsignificant overall survival benefit in the group with GA (22.6 vs. 18.4 months). GA appears useful to better select older patients with advanced cancer for combination chemotherapy. The significant reduction of mortality during chemotherapy justifies the efforts and costs which need to be expended. To evaluate the effect of GA on overall survival, prospective trials are required.
Predictive Value of Body Composition Parameters for Postoperative Complications in Patients Who Received Pancreaticoduodenectomy
Authors: Cai Zhenghua , Yang Yifei , Fu Xu , Mao Liang , Qiu Yudong
Published: February 2023

Introduction: Sarcopenia and visceral obesity have been identified as risk factors for postoperative complications following hepatobiliary and colon surgery. However, the correlation between body composition parameters and morbidity following pancreatectomy remains unclear. This study aimed to assess the predictive value of body composition parameters measured from preoperative CT images for postoperative complications following pancreaticoduodenectomy (PD). Methods: A retrospective study of patients who underwent PD between January 2018 and January 2021 was performed. Areas of subcutaneous adipose tissue, visceral adipose tissue, total abdominal muscle area, and mean muscle radio-attenuation were measured from preoperative CT images. Postoperative complications were categorized according to the Clavien-Dindo classification, and comprehensive complication index (CCI) scores were calculated. Logistic regression analysis was performed to identify factors associated with clinically relevant postoperative pancreatic fistula (CR-POPF) and high CCI score (≥26.2). Results: From the data collected on 129 study patients, sarcopenia, visceral obesity, and myosteatosis were detected in 47 (36.4%), 38 (29.4%), and 50 (38.7%) patients, respectively. CR-POPF developed in 51 (39.5%) patients, the overall median CCI score was 30.8 (22.6–36.2), and high CCI scores were identified in 70 (54.3%) patients. Multivariate analysis indicated sarcopenia and visceral obesity were independent risk variables for CR-POPF. Preoperative sarcopenia, visceral obesity, age, preoperative biliary drainage, and a positive culture of postoperative drainage were predictors of high CCI scores. Conclusion: Sarcopenia and visceral obesity were significant predictors of CR-POPF and high CCI score. Preoperative body composition assessment by CT images may help identify high-risk patients who undergo PD.
Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization in Infantile Hydrocephalus: An Experience from Mali
Authors: Diallo Oumar , Dama Mahamadou , Konan Landry , Coulibaly Oumar , Sissoko Daouda , Maiga Abdoulaye Hima
Published: February 2023

Introduction: Pediatric hydrocephalus is a common disease in sub-Saharan Africa. In Mali, 350–400 new cases are diagnosed in our center yearly. With a total land mass of 1,241,000 km2, patients in remote areas must travel up to 1,500 km to access neurosurgical care. Hence, treatment and follow-ups of “shunted” patients are difficult. In this context, endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) provides an opportunity for an affordable and less constraining treatment for hydrocephalus children under 12 months of age. Methods: We performed a retrospective analysis of ETV/CPC performed on infants from July 2013 to January 2015. Patients were followed postoperatively on day 15, month 6, and month 12. Statistical analysis was conducted using Prism 9 GraphPad software. ETV successes were categorized according to the patient’s age into 3 groups: ≤3 months, 3–6 months, and 6–12 months. Statistical significance was defined at p < 0.05. Results: During the study period, 199 patients were included with 40% of patients aged between 0 and 6 months. The head circumference ranged from 35 cm to 79 cm. The etiology was congenital malformation in 55%. ETV/CPC was a success in 69% of 6- to 12-month-old patients, 54% in the 3- to 6-month-old patients, and 29% in ≤3-month-old patients. Overall, 94 (47%) patients were successfully treated without a shunt. The postoperative infection rate was 1% and mortality at 12 months was 8%. Conclusion: In a low-income environment such as Mali, ETV/CPC stands as a viable and alternative treatment option for pediatric hydrocephalus patients; our findings suggest that age is an important factor in predicting ETV success.
Altered Neuronal Discharge in the Organum Vasculosum of the Lamina Terminalis Contributes to Dahl Salt-Sensitive Hypertension
Authors: Stocker Sean D.
Published: February 2023

Background:

Salt-sensitive hypertension in humans and experimental models is associated with higher plasma and cerebrospinal fluid sodium chloride (NaCl) concentrations. Changes in extracellular NaCl concentrations are sensed by specialized neurons in the organum vasculosum of the lamina terminalis (OVLT). Stimulation of OVLT neurons increases sympathetic nerve activity (SNA) and arterial blood pressure (ABP), whereas chronic activation produces hypertension. Therefore, the present study tested whether OVLT neuronal activity was elevated and contributed to SNA and ABP in salt-sensitive hypertension.

Methods:

Male Dahl salt-sensitive (Dahl S) and Dahl salt-resistant (Dahl R) rats were fed 0.1% or 4.0% NaCl diets for 3 to 4 weeks and used for single-unit recordings of OVLT neurons or simultaneous recording of multiple sympathetic nerves during pharmacological inhibition of the OVLT.

Results:

Plasma and cerebrospinal fluid Na+ and Cl− concentrations were higher in Dahl S rats fed 4% versus 0.1% or Dahl R rats fed either diet. In vivo single-unit recordings revealed a significantly higher discharge of NaCl-responsive OVLT neurons in Dahl S rats fed 4% versus 0.1% or Dahl R rats. Interestingly, intracarotid infusion of hypertonic NaCl evoked greater increases in OVLT neuronal discharge of Dahl S versus Dahl R rats regardless of NaCl diet. The activity of non–NaCl-responsive OVLT neurons was not different across strain or diets. Finally, inhibition of OVLT neurons by local injection of the gamma-aminobutyric acid agonist muscimol produced a greater decrease in renal SNA, splanchnic SNA, and ABP of Dahl S rats fed 4% versus 0.1% or Dahl R rats.

Conclusions:

A high salt diet activates NaCl-responsive OVLT neurons to increase SNA and ABP in salt-sensitive hypertension.
Informing Use of Telehealth for Managing Chronic Conditions: Mixed‐Methods Evaluation of Telehealth Use to Manage Heart Failure During COVID‐19
Authors: Leonard Chelsea , Liu Wenhui , Holstein Ariel , Alliance Slande , Nunnery Mary , Rohs Carly , Sloan Marilyn , Winchester David E.
Published: February 2023

Background

The COVID‐19 pandemic forced Veterans Health Administration facilities to rapidly adopt and deploy telehealth alternatives to provide continuity of care to veterans while minimizing physical contact. The impact of moving to virtual visits on patients with congestive heart failure (HF) is unknown. The goal of this study was to understand how patients with HF and their providers experienced the shift to telehealth for managing a chronic condition, and to inform best practices for continued telehealth use.

Methods and Results

We identified Veterans Health Administration Medical Centers with high telehealth use before COVID‐19 and sites that were forced to adopt telehealth in response to COVID‐19, and interviewed cardiology providers and veterans with HF about their experiences using telehealth. Interviews were recorded, transcribed, and analyzed using team‐based rapid content analysis. We identified 3 trajectory patterns for cardiology telehealth use before and during COVID‐19. They were the low‐use class (low to low), high‐use class (relatively high to higher), and increased‐use class (low to high). The high‐use and increased‐use classes fit the criteria for sites that had high telehealth use before COVID‐19 and sites that rapidly adopted telehealth in response to COVID‐19. There were 12 sites in the high‐use class and 4 sites in the increased‐use class. To match with the number of sites in the increased‐use class, we selected the top 4 sites by looking at the months before COVID‐19. We identified 3 themes related to telehealth use among patients with HF and cardiology providers: (1) technology was the primary barrier for both patients and providers; (2) infrastructural support was the primary facilitator for providers; and (3) both patients and providers had largely neutral opinions on how telehealth compares to in‐person care but described situations in which telehealth is not appropriate.

Conclusions

Only 12 sites fit the criteria of high telehealth use in cardiology before COVID‐19, and 4 fit the criteria of low use that increased in response to COVID‐19. Patients and providers at both site types were largely satisfied using telehealth to manage HF. Understanding best practices for managing ambulatory care–sensitive conditions through virtual visits can help the Veterans Health Administration prepare for long‐term impacts of COVID‐19 on in‐person visits, as well as improve access to care for veterans who live remotely or who have difficulty traveling to in‐person appointments.