bluuebunny/crossref_metadata_2025 huggingface dataset:
Will previous antimicrobial therapy reduce the positivity rate of metagenomic next-generation sequencing in periprosthetic joint infections? A clinical study
Authors: Hao Linjie , Bian Weiguo , Qing Zhong , Ma Tao , Li Hui , Xu Peng , Wen Pengfei
Published: January 2024

Background

Metagenomic next-generation sequencing (mNGS) is a culture-independent massively parallel DNA sequencing technology and it has been widely used for rapid etiological diagnosis with significantly high positivity rate. Currently, clinical studies on evaluating the influence of previous antimicrobial therapy on positivity rate of mNGS in PJIs are rarely reported. The present study aimed to investigate whether the positivity rate of mNGS is susceptible to previous antimicrobial therapy.

Methods

We performed a prospective trial among patients who undergone hip or knee surgery due to periprosthetic joint infection (PJI) to compare the positivity rate of culture and mNGS between cases with and without previous antimicrobial therapy, and the positivity rates between cases with different antimicrobial-free intervals were also analysed.

Results

Among 131 included PJIs, 91 (69.5%) had positive cultures and 115 (87.8%) had positive mNGS results. There was no significant difference in the positivity rate of deep-tissue culture and synovial fluid mNGS between cases with and without previous antimicrobial therapy. The positivity rate of synovial fluid culture was higher in cases with previous antimicrobial therapy. The positivity rates of mNGS in synovial fluid decreased as the antimicrobial-free interval ranged from 4 to 14 days to 0 to 3 days.

Conclusion

mNGS is more advantageous than culture with a higher pathogen detection rate. However, our data suggested that antimicrobial agents may need to be discontinued more than 3 days before sampling to further increase the positivity rate of mNGS for PJIs.
Development of embodied listening studies with multimodal and wearable haptic interfaces for hearing accessibility in music
Authors: Cavdir Doga
Published: January 2024

Introduction

The intersection of hearing accessibility and music research offers limited representations of the Deaf and Hard of Hearing (DHH) individuals, specifically as artists. This article presents inclusive design practices for hearing accessibility through wearable and multimodal haptic interfaces with participants with diverse hearing backgrounds.

Methods

We develop a movement-based sound design practice and audio-tactile compositional vocabulary, co-created with a Deaf co-designer, to offer a more inclusive and embodied listening experience. This listening experience is evaluated with a focus group whose participants have background in music, dance, design, or accessibility in arts. By involving multiple stakeholders, we survey the participants' qualitative experiences in relation to Deaf co-designer's experience.

Results

Results show that multimodal haptic feedback enhanced the participants' listening experience while on-skin vibrations provided more nuanced understanding of the music for Deaf participants. Hearing participants reported interest in understanding the Deaf individuals' musical experience, preferences, and compositions.

Discussion

We conclude by presenting design practices when working with movement-based musical interaction and multimodal haptics. We lastly discuss the challenges and limitations of access barrier in hearing accessibility and music.
Parallel computation to bidimensional heat equation using MPI/CUDA and FFTW package
Authors: Chakkour Tarik
Published: January 2024

In this study, we present a fast algorithm for the numerical solution of the heat equation. The heat equation models the heat diffusion over time and through a given region. We engage a finite difference method to solve this equation numerically. The performance of its parallel implementation is considered using Message Passing Interface (MPI), Compute Unified Device Architecture (CUDA), and time schemes, such as Forward Euler (FE) and Runge-Kutta (RK) methods. The originality of this study is research on parallel implementations of the fourth-order Runge-Kutta method (RK4) for sparse matrices on Graphics Processing Unit (GPU) architecture. The supreme proprietary framework for GPU computing is CUDA, provided by NVIDIA. We will show three metrics through this parallelization to compare the computing performance: time-to-solution, speed-up, and performance. The spectral method is investigated by utilizing the FFTW software library, based on the computation of the fast Fourier transforms (FFT) in parallel and distributed memory architectures. Our CUDA-based FFT, named CUFFT, is performed in platforms, which is a highly optimized FFTW implementation. We will give numerical tests to reveal that this method is up-and-coming for solving the heat equation. The final result demonstrates that CUDA has a significant advantage and performance since the computational cost is tiny compared with the MPI implementation. This vital performance gain is also achieved through careful attention of managing memory communication and access.
Escitalopram-induced sinus bradycardia in coronary heart disease combined with depression: a case report and review of literature
Authors: Li Liu-Cheng , Sun Wen , Lv Xiao-Qin , Xu Yao-Yao , Hu Ying , Shi Jia-Na
Published: January 2024

For patients with cardiovascular disease, using the antidepressant escitalopram may lead to unexpected adverse events. Here, a rare repeated sinus bradycardia event due to escitalopram is first reported. In an 82-year-old female patient with cardiac dysfunction using digoxin, tachycardia (average heart rate of 93 beats/min) was demonstrated by electrocardiogram (ECG). She began to take escitalopram and lorazepam due to depression, but sinus bradycardia (93.7% heart rate was <60 beats/min) and sinus arrest were first detected after 3 months. Its proportion decreased to 0.1% after discontinuation of digoxin and escitalopram for 1 day, and the rhythm returned to normal 2 weeks later. After 2 months, escitalopram was prescribed again in combination with quetiapine; then, 17.1% heart rate was <60 beats/min. After escitalopram and quetiapine withdrawal, the ECG showed the heart rhythm had normalized again. No other drug changes were made during these periods. Escitalopram was deemed to be a highly possible cause of sinus bradycardia according to its Naranjo's Algorithm score. Furthermore, literature on escitalopram-mediated cardiovascular adverse events was reviewed and analyzed. Empirically, escitalopram should be discontinued immediately if iatrogenic causes cannot be ruled out. Furthermore, ECG monitoring in escitalopram-related cardiovascular adverse events is highlighted, especially in patients receiving certain drug classes simultaneously (i.e., sinoatrial node inhibitors, antipsychotics).
Constructing a competitive endogenous RNA network of EndMT-related atherosclerosis through weighted gene co-expression network analysis
Authors: Li Yawei , Wu Yubiao , Qin Xiude , Gu Jinchao , Liu Aijun , Cao Jiahui
Published: January 2024

Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction and plaque formation. Under pro-inflammatory conditions, endothelial cells can undergo endothelial-to-mesenchymal transition (EndMT), contributing to atherosclerosis development. However, the specific regulatory mechanisms by which EndMT contributes to atherosclerosis remain unclear and require further investigation. Dan-Shen-Yin (DSY), a traditional Chinese herbal formula, is commonly used for cardiovascular diseases, but its molecular mechanisms remain elusive. Emerging evidence indicates that competing endogenous RNA (ceRNA) networks play critical roles in atherosclerosis pathogenesis. In this study, we constructed an EndMT-associated ceRNA network during atherosclerosis progression by integrating gene expression profiles from the Gene Expression Omnibus (GEO) database and weighted gene co-expression network analysis. Functional enrichment analysis revealed this EndMT-related ceRNA network is predominantly involved in inflammatory responses. ROC curve analysis showed the identified hub genes can effectively distinguish between normal vasculature and atherosclerotic lesions. Furthermore, Kaplan-Meier analysis demonstrated that high expression of IL1B significantly predicts ischemic events in atherosclerosis. Molecular docking revealed most DSY bioactive components can bind key EndMT-related lncRNAs, including AC003092.1, MIR181A1HG, MIR155HG, WEE2-AS1, and MIR137HG, suggesting DSY may mitigate EndMT in atherosclerosis by modulating the ceRNA network.
Wnt/β-catenin signaling pathway in the tumor progression of adrenocortical carcinoma
Authors: Tai Yanghao , Shang Jiwen
Published: January 2024

Adrenocortical carcinoma (ACC) is an uncommon, aggressive endocrine malignancy with a high rate of recurrence, a poor prognosis, and a propensity for metastasis. Currently, only mitotane has received certification from both the US Food and Drug Administration (FDA) and the European Medicines Agency for the therapy of advanced ACC. However, treatment in the advanced periods of the disorders is ineffective and has serious adverse consequences. Completely surgical excision is the only cure but has failed to effectively improve the survival of advanced patients. The aberrantly activated Wnt/β-catenin pathway is one of the catalysts for adrenocortical carcinogenesis. Research has concentrated on identifying methods that can prevent the stimulation of the Wnt/β-catenin pathway and are safe and advantageous for patients in view of the absence of effective treatments and the frequent alteration of the Wnt/β-catenin pathway in ACC. Comprehending the complex connection between the development of ACC and Wnt/β-catenin signaling is essential for accurate pharmacological targets. In this review, we summarize the potential targets between adrenocortical carcinoma and the Wnt/β-catenin signaling pathway. We analyze the relevant targets of drugs or inhibitors that act on the Wnt pathway. Finally, we provide new insights into how drugs or inhibitors may improve the treatment of ACC.
A multiscale geographically weighted regression kriging method for spatial downscaling of satellite-based ozone datasets
Authors: Cheng Shuang , Zhang Guoqiao , Yang Xuexi , Lei Bingfeng
Published: January 2024

Accurate monitoring of ozone (O3) concentrations by remote sensing is essential for achieving pollution control and ecological protection. However, the existing O3 remote sensing data with a low spatial resolution do not facilitate fine-grained studies of small-scale urban clusters. In this study, the multiscale geographically weighted regression kriging (MGWRK) method was used to spatially downscale O3 remote sensing products (10 km × 10 km). Downscaling factors were selected from meteorological factors and vegetation, aerosol optical thickness (AOD), and air pollutant emission inventory data. Spatial heterogeneity and scale differences among the factors were considered and compared via multiple regression kriging (MLRK) and geographically weighted regression kriging (GWRK) to generate 1-km annual and seasonal O3 remote sensing products. The results showed that I) the downscaling accuracy of each model can be expressed as MGWRK > GWRK > MLRK; the local downscaling model yields data that are more consistent with the actual spatial distribution of O3 after considering the spatial heterogeneity of the influencing factors; and the downscaled annual and seasonal data exhibit satisfactory spatial texture characteristics and consistency with the original spatial distribution of O3, while the distribution boundary problem of image elements is eliminated. II) Nitrogen oxide (NOx) and volatile organic compound emissions and temperature exhibit strong positive correlations with O3, while wind speed, humidity, the normalized difference vegetation index, and AOD indicate weak positive correlations with O3. Moreover, precipitation exhibits a weak negative correlation with O3. III) The coefficient of determination (R2) of the 1-km resolution annual O3 concentration data after downscaling based on the MGWRK model reaches 0.93, while the RRMSE and MAE values are only 3% and 1.86, respectively, with a coefficient of variation of 9.55%; the downscaling accuracy of the seasonal O3 concentration data is higher in summer and winter than during the other seasons, with R2 greater than 0.85, further confirming the spatial and temporal downscaling advantages of the MGWRK model for O3 in the Chang-Zhu-Tan city cluster. This further corroborates the feasibility of the MGWRK model for spatial and temporal O3 downscaling in the Chang-Zhu-Tan urban area.
Impact of landscape patterns on ecosystem services in China: a case study of the central plains urban agglomeration
Authors: Zhong Mingxing
Published: January 2024

Urban agglomeration is the highest stage of urban development, which reasonable planning will be conducive to the rapid and healthy development of the regional economy. However, in recent years, unreasonable urban agglomeration planning has changed landscape patterns and brought huge challenges to ecosystem services. Moreover, there is currently a lack of understanding of the relationship between landscape patterns and ecosystem services, especially in the process of urban agglomeration construction. In this study, we attempt to reveal the impact of landscape patterns on ecosystem services value (ESV) based on many years of remote sensing data in the Central Plains Urban Agglomeration (CPUA). The results show that landscape patterns have significant spatiotemporal evolution characteristics, and there are significant differences between different landscape patterns in the CPUA. Moreover, most of landscape patterns show significant east-west differences. Total ESV has decreased from USD 838.53 million in 2000 to USD 792.32 million in 2018. From a spatial perspective, the areas with high ESV are mostly distributed in the western mountainous and southern hilly areas, but low ESV area are mainly concentrated in the central and northern plains. In addition, the results of model analysis reveal that there is a remarkable positive correlation between ESV and patch density, interspersion juxtaposition index, cohesion index, and splitting index, but a remarkable negative correlation between ESV and total edge. These results provide critical guidance and suggestions for the improvement of future urban agglomeration construction.
Development and deployment of an improved Anopheles gambiae s.l. field surveillance by adaptive spatial sampling design
Authors: Monteiro Gabriel M. , Djogbénou Luc S. , Donnelly Martin J. , Sedda Luigi
Published: January 2024

Introduction

Accurate assessments of vector occurrence and abundance, particularly in widespread vector-borne diseases such as malaria, are crucial for the efficient deployment of disease surveillance and control interventions. Although previous studies have explored the benefits of adaptive sampling for identifying disease hotspots (mostly through simulations), limited research has been conducted on field surveillance of malaria vectors.

Methods

We developed and implemented an adaptive spatial sampling design in southwestern Benin, specifically targeting potential and uncertain Anopheles gambiae hotspots, a major malaria vector in sub-Saharan Africa. The first phase of our proposed design involved delineating ecological zones and employing a proportional lattice with close pairs sampling design to maximize spatial coverage, representativeness of ecological zones, and account for spatial dependence in mosquito counts. In the second phase, we employed a spatial adaptive sampling design focusing on high-risk areas with the greatest uncertainty.

Results

The adaptive spatial sampling design resulted in a reduced sample size from the first phase, leading to improved predictions for both out-of-sample and training data. Collections of Anopheles gambiae in high-risk and low-uncertainty areas were nearly tripled compared to those in high-risk and high-uncertainty areas. However, the overall model uncertainty increased.

Discussion

While the adaptive sampling design allowed for increased collections of Anopheles gambiae mosquitoes with a reduced sample size, it also led to a general increase in uncertainty, highlighting the potential trade-offs in multi-criteria adaptive sampling designs. It is imperative that future research focuses on understanding these trade-offs to expedite effective malaria control and elimination efforts.
Fast soil recovery after a fire: case study in Maritime Alps (Piedmont, Italy) using microarthropods and QBS-ar index
Authors: Fusco Tommaso , Fortini Lorenzo , Casale Francesca , Jacomini Carlo , Di Giulio Andrea
Published: January 2024

Soil is a very fragile ecosystem, often subject to many threats. Wildfires can affect edaphic communities depending on the intensity and seasonality of the fire. Different groups of soil fauna tend to respond differently to this type of disturbance, but the lack of data prevents to fully analyze the impact of fire. Soil microarthropods show a particular sensitivity to disturbances of different nature, making them excellent biological indicators. That is why in recent years many biotic indices to assess soil quality, like QBS-ar (Soil Biological Quality based on arthropods), have been developed. The objective of this study was to evaluate whether there might be a significant difference between areas affected or not by fire in the locality of Andonno (Piedmont, Italy) in terms of QBS-ar values, 18 years after this disturbance, and whether the reforestation intervention is having a positive effect on soil quality. Two sampling sites were selected within the sampling area and in each, six soil samples were taken. Microarthropods were extracted with a Berlese-Tüllgren extractor and soil biological quality was calculated using the QBS-ar index. No significant difference in QBS-ar values were found between the fire burned and unburned areas (p=0.37). The number of biological and euedaphic forms in the two sites was similar. It appears that microarthropod communities manage to recover in a short time, indicating that in the study area soil fauna has shown a fast recovery after extreme events like wildfires.
Genetics and clinical phenotypes in common variable immunodeficiency
Authors: Cunningham-Rundles Charlotte , Casanova Jean-Laurent , Boisson Bertrand
Published: January 2024

Common variable immunodeficiency (CVID) is one of the most common symptomatic groups of inborn errors of immunity. In addition to infections resulting from insufficient levels of immune globulins and antibodies, many patients develop inflammatory or autoimmune conditions, which are associated with increased mortality. This aspect of CVID has been the focus of many studies, and dissecting the clinical phenotypes of CVID, has had the goal of providing biomarkers to identify these subjects, potentially at the time of diagnosis. With the application of whole exome (WES) and whole genome analyses, an increasing number of monogenic causes of CVID have been elucidated. From the standpoint of the practicing physician, an important question is whether the clinical phenotype, particularly the occurrence of autoinflammation of autoimmunity, might suggest the likelihood of identifying a causative mutation, and if possible the gene most likely to underlie CVID. We addressed this question in a patient group of 405 subjects diagnosed with CVID from one medical center.
Genotoxin-producing Salmonella enterica induces tissue-specific types of DNA damage and DNA damage response outcomes
Authors: Lopez Chiloeches Maria , Bergonzini Anna , Martin Océane C. B. , Bergstein Nicole , Erttmann Saskia F. , Aung Kyaw Min , Gekara Nelson O. , Avila Cariño Javier F. , Pateras Ioannis S. , Frisan Teresa
Published: January 2024

Introduction

Typhoid toxin-expressing Salmonella enterica causes DNA damage in the intestinal mucosa in vivo, activating the DNA damage response (DDR) in the absence of inflammation. To understand whether the tissue microenvironment constrains the infection outcome, we compared the immune response and DDR patterns in the colon and liver of mice infected with a genotoxigenic strain or its isogenic control strain.

Methods

In situ spatial transcriptomic and immunofluorescence have been used to assess DNA damage makers, activation of the DDR, innate immunity markers in a multiparametric analysis.

Result

The presence of the typhoid toxin protected from colonic bacteria-induced inflammation, despite nuclear localization of p53, enhanced co-expression of type-I interferons (IfnbI) and the inflammasome sensor Aim2, both classic features of DNA-break-induced DDR activation. These effects were not observed in the livers of either infected group. Instead, in this tissue, the inflammatory response and DDR were associated with high oxidative stress-induced DNA damage.

Conclusions

Our work highlights the relevance of the tissue microenvironment in enabling the typhoid toxin to suppress the host inflammatory response in vivo.
Biological response of nonhuman primates to controlled levels of acute blood loss
Authors: Roh Juhye , Park Eun Mi , Lee Haneulnari , Hwang Jeong Ho , Kim Hyung-Sun , Park Jinyoung , Kang Hee Jung
Published: January 2024

Introduction

The global shortage of human blood for medical use has prompted the development of alternative blood sources. Nonhuman primates (NHPs) are commonly used owing to their physiological similarities to humans. The objective of the current study was to establish a controlled-blood-loss model in NHPs to explore their clinical and biological responses.

Methods

Blood was sequentially withdrawn from 10 cynomolgus monkeys (10, 14, 18, 22, and 25% of the total blood volume); their vital signs were monitored, and blood parameters were serially analyzed. Humoral mediators in the blood were measured using flow cytometry and enzyme-linked immunosorbent assays.

Results

In NHPs subjects to 25% blood loss and presenting with related clinical symptoms, the systolic blood pressure ratio on day 0 after bleeding was significantly lower than that of the animals from the other groups (median: 0.65 vs. 0.88, P = 0.0444). Red blood cell counts from day 0–14 and hematocrit levels from day 0–7 were markedly decreased relative to the baseline (P < 0.01). These parameters showed a direct correlation with the extent of blood loss. The levels of creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase exhibited increases in response to blood loss and had a stronger correlation with the hemoglobin ratio than the volume of blood loss. The levels of C3a and C4a, as well as interleukin (IL)-1α and IL-15, displayed a strong correlation, with no apparent association with blood loss.

Conclusion

The findings of the present study showed that only NHPs with 25% blood loss exhibited clinical decompensation and significant systolic blood pressure reduction without fatalities, suggesting that this level of blood loss is suitable for evaluating blood transfusion efficacy or other treatments in NHP models. In addition, the ratio of hemoglobin may serve as a more dependable marker for predicting clinical status than the actual volume of blood loss. Thus, our study could serve as a basis for future xenotransfusion research and to predict biological responses to massive blood loss in humans where controlled experiments cannot be ethically performed.
Mechanisms of immune response and cell death in ischemic stroke and their regulation by natural compounds
Authors: Gong Zhaoyuan , Guo Jing , Liu Bin , Guo Yang , Cheng Cuicui , Jiang Yin , Liang Ning , Hu Mingzhi , Song Tian , Yang Lu , Li Huizhen , Zhang Haili , Zong Xingyu , Che Qianzi , Shi Nannan
Published: January 2024

Ischemic stroke (IS), which is the third foremost cause of disability and death worldwide, has inflammation and cell death as its main pathological features. IS can lead to neuronal cell death and release factors such as damage-related molecular patterns, stimulating the immune system to release inflammatory mediators, thereby resulting in inflammation and exacerbating brain damage. Currently, there are a limited number of treatment methods for IS, which is a fact necessitating the discovery of new treatment targets. For this review, current research on inflammation and cell death in ischemic stroke was summarized. The complex roles and pathways of the principal immune cells (microglia, astrocyte, neutrophils, T lymphocytes, and monocytes/macrophage) in the immune system after IS in inflammation are discussed. The mechanisms of immune cell interactions and the cytokines involved in these interactions are summarized. Moreover, the cell death mechanisms (pyroptosis, apoptosis, necroptosis, PANoptosis, and ferroptosis) and pathways after IS are explored. Finally, a summary is provided of the mechanism of action of natural pharmacological active ingredients in the treatment of IS. Despite significant recent progress in research on IS, there remain many challenges that need to be overcome.
Bispecific antibodies in indolent B-cell lymphomas
Authors: Radhakrishnan Vivek S. , Davies Andrew J.
Published: January 2024

The advent of immunotherapy in lymphomas, beginning with Rituximab, have led to paradigm shifting treatments that are increasingly bringing a greater number of affected patients within the ambit of durable disease control and cure. Bispecific antibodies harness the properties of the immunoglobulin antibody structure to design molecules which, apart from engaging with the target tumour associated antigen, engage the host’s T-cells to cause tumour cell death. Mosunetuzumab, an anti-CD20 directed bispecific antibody was the first to be approved in follicular lymphoma, this has now been followed by quick approvals of Glofitamab and Epcoritamab in diffuse large B-cell lymphomas. This article reviews contemporary data and ongoing studies evaluating the role of bispecific antibodies in indolent b-cell non Hodgkin lymphomas. This is an area of active research and presents many opportunities in advancing the treatment of indolent lymphomas and potentially forge a chemo-free treatment paradigm in this condition.
Tick innate immune responses to hematophagy and Ehrlichia infection at single-cell resolution
Authors: Adegoke Abdulsalam , Ribeiro Jose M. C. , Smith Ryan C. , Karim Shahid
Published: January 2024

Introduction

Ticks rely on robust cellular and humoral responses to control microbial infection. However, several aspects of the tick's innate immune system remain uncharacterized, most notably that of the immune cells (called hemocytes), which are known to play a significant role in cellular and humoral responses. Despite the importance of hemocytes in regulating microbial infection, our understanding of their basic biology and molecular mechanisms remains limited. Therefore, we believe that a more detailed understanding of the role of hemocytes in the interactions between ticks and tick-borne microbes is crucial to illuminating their function in vector competence and to help identify novel targets for developing new strategies to block tick-borne pathogen transmission.

Methods

This study examined hemocytes from the lone star tick (Amblyomma americanum) at the transcriptomic level using the 10X genomics single-cell RNA sequencing platform to analyze hemocyte populations from unfed, partially blood-fed, and Ehrlichia chaffeensis-infected ticks. The functional role of differentially expressed hemocyte markers in hemocyte proliferation and Ehrlichia dissemination was determined using an RNA interference approach.

Results and discussion

Our data exhibit the identification of fourteen distinct hemocyte populations. Our results uncover seven distinct lineages present in uninfected and Ehrlichia-infected hemocyte clusters. The functional characterization of hemocytin, cystatin, fibronectin, and lipocalin demonstrate their role in hemocyte population changes, proliferation, and Ehrlichia dissemination.

Conclusion

Our results uncover the tick immune responses to Ehrlichia infection and hematophagy at a single-cell resolution. This work opens a new field of tick innate immunobiology to understand the role of hemocytes, particularly in response to prolonged blood-feeding (hematophagy), and tick-microbial interactions.
Ceramide on the road to insulin resistance and immunometabolic disorders in transition dairy cows: driver or passenger?
Authors: Zhao Yuchao , Zhao Huiying , Li Liuxue , Yu Shiqing , Liu Ming , Jiang Linshu
Published: January 2024

Dairy cows must undergo profound metabolic and endocrine adaptations during their transition period to meet the nutrient requirements of the developing fetus, parturition, and the onset of lactation. Insulin resistance in extrahepatic tissues is a critical component of homeorhetic adaptations in periparturient dairy cows. However, due to increased energy demands at calving that are not followed by a concomitant increase in dry matter intake, body stores are mobilized, and the risk of metabolic disorders dramatically increases. Sphingolipid ceramides involved in multiple vital biological processes, such as proliferation, differentiation, apoptosis, and inflammation. Three typical pathways generate ceramide, and many factors contribute to its production as part of the cell’s stress response. Based on lipidomic profiling, there has generally been an association between increased ceramide content and various disease outcomes in rodents. Emerging evidence shows that ceramides might play crucial roles in the adaptive metabolic alterations accompanying the initiation of lactation in dairy cows. A series of studies also revealed a negative association between circulating ceramides and systemic insulin sensitivity in dairy cows experiencing severe negative energy balance. Whether ceramide acts as a driver or passenger in the metabolic stress of periparturient dairy cows is an unknown but exciting topic. In the present review, we discuss the potential roles of ceramides in various metabolic dysfunctions and the impacts of their perturbations. We also discuss how this novel class of bioactive sphingolipids has drawn interest in extrahepatic tissue insulin resistance and immunometabolic disorders in transition dairy cows. We also discuss the possible use of ceramide as a new biomarker for predicting metabolic diseases in cows and highlight the remaining problems.
Epigenetic modulation of antitumor immunity and immunotherapy response in breast cancer: biological mechanisms and clinical implications
Authors: Yin Jun , Gu Tiezheng , Chaudhry Norin , Davidson Nancy E. , Huang Yi
Published: January 2024

Breast cancer (BC) is the most common non-skin cancer and the second leading cause of cancer death in American women. The initiation and progression of BC can proceed through the accumulation of genetic and epigenetic changes that allow transformed cells to escape the normal cell cycle checkpoint control. Unlike nucleotide mutations, epigenetic changes such as DNA methylation, histone posttranslational modifications (PTMs), nucleosome remodeling and non-coding RNAs are generally reversible and therefore potentially responsive to pharmacological intervention. Epigenetic dysregulations are critical mechanisms for impaired antitumor immunity, evasion of immune surveillance, and resistance to immunotherapy. Compared to highly immunogenic tumor types, such as melanoma or lung cancer, breast cancer has been viewed as an immunologically quiescent tumor which displays a relatively low population of tumor-infiltrating lymphocytes (TIL), low tumor mutational burden (TMB) and modest response rates to immune checkpoint inhibitors (ICI). Emerging evidence suggests that agents targeting aberrant epigenetic modifiers may augment host antitumor immunity in BC via several interrelated mechanisms such as enhancing tumor antigen presentation, activation of cytotoxic T cells, inhibition of immunosuppressive cells, boosting response to ICI, and induction of immunogenic cell death (ICD). These discoveries have established a highly promising basis for using combinatorial approaches of epigenetic drugs with immunotherapy as an innovative paradigm to improve outcomes of BC patients. In this review, we summarize the current understanding of how epigenetic processes regulate immune cell function and antitumor immunogenicity in the context of the breast tumor microenvironment. Moreover, we discuss the therapeutic potential and latest clinical trials of the combination of immune checkpoint blockers with epigenetic agents in breast cancer.
Acquisition of antibodies that block Plasmodium falciparum adhesion to placental receptor chondroitin sulfate A with increasing gravidity in Malian women
Authors: Mahamar Almahamoudou , Traore Moussa , Swihart Bruce , Attaher Oumar , Diarra Bacary Soumana , Santara Gaoussou , Issiaka Djibrilla , Barry Amadou , Sidibé Youssoufa , Dicko Yahia T. , Keita Sekouba , Ndiaye Oulematou , Dicko Alassane , Duffy Patrick E. , Fried Michal
Published: January 2024

In malaria-endemic areas, pregnant women are more susceptible to Plasmodium falciparum infection, especially primigravidae. During pregnancy, parasites sequester in the placenta and bind to the receptor chondroitin sulfate (CSA). This unique adhesion is mediated by the parasite protein VAR2CSA expressed on the surface of infected erythrocytes (IE). Placental malaria is associated with poor pregnancy outcomes including perinatal mortality, preterm delivery, small for gestational age (SGA) and low birthweight deliveries. Over successive pregnancies, women acquire functional antibodies that inhibit IE adhesion to CSA. Here, we examine the development of anti-adhesion activity and the breadth of anti-adhesion activity as a function of number of previous pregnancies, using samples collected from pregnant women living in an area with high seasonal malaria transmission. Women reached plateau levels of anti-adhesion activity and breadth of anti-adhesion activity after 5 pregnancies. We related the level of anti-adhesion activity and reactivity with surface IE to SGA 19/232 pregnancies resulted in SGA, and report that an increase of 10% in median anti-adhesion activity reduced the odds of SGA by 13% and this relationship approached significance. Further, at an anti-adhesion activity level of 43.7%, an increase of 10% in the breadth of activity significantly reduced the odds of SGA by 21.5%. Antibodies that recognize IE surface increased over successive pregnancies, but were not associated with a reduction in SGA. These results can serve as a guideline for assessing vaccine candidates aiming to reduce poor pregnancy outcomes associated with placental malaria.
Comparative cost-effectiveness of first-line pembrolizumab plus chemotherapy vs. chemotherapy alone in persistent, recurrent, or metastatic cervical cancer
Authors: Lin Ying-tao , Wang Chang , He Xiao-yan , Yao Qi-min , Chen Jian
Published: January 2024

Background

Treating persistent, recurrent, or metastatic cervical cancer remains challenging. Although pembrolizumab, combined with chemotherapy and bevacizumab, offers a promising first-line option, its cost-effectiveness within the Chinese healthcare system has not been established.

Methods

A partitioned survival model was constructed using patient data from the KEYNOTE-826 trial. Efficacy, safety, and economic data from both trial and real-world practices were utilized to determine the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of the treatment strategies. Comprehensive insights were gained through the sensitivity and subgroup analyses.

Results

Over five years, the combination of pembrolizumab, chemotherapy, and bevacizumab offered an additional 1.18 QALYs compared to that provided by standard treatments. This regimen increased the costs by US$ 134,502.57, resulting in an ICER of US$ 114,275.67 per QALY, relative to traditional treatment costs. The ICER for the pembrolizumab regimen was further calibrated to be US$ 52,765.69 per QALY. Both ICER values surpassed China’s established willingness-to-pay threshold. Importantly, subgroup analysis revealed enhanced cost-effectiveness in patients presenting with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥10.

Conclusion

Introducing pembrolizumab alongside chemotherapy and bevacizumab may not be a cost-effective primary strategy for advanced cervical cancer against current standards. However, for patients with a PD-L1 CPS ≥10, the therapeutic and economic outcomes could be improved by adjusting the pembrolizumab price.
Cell death proteins in sepsis: key players and modern therapeutic approaches
Authors: Yang Chloe S. , Coopersmith Craig M. , Lyons John D.
Published: January 2024

Cell death proteins play a central role in host immune signaling during sepsis. These interconnected mechanisms trigger cell demise via apoptosis, necroptosis, and pyroptosis while also driving inflammatory signaling. Targeting cell death mediators with novel therapies may correct the dysregulated inflammation seen during sepsis and improve outcomes for septic patients.
Stable isotopes reveal intertidal fish and crabs use bivalve farms as foraging habitat in Puget Sound, Washington
Authors: Veggerby Karl B. , Scheuerell Mark D. , Sanderson Beth L. , Kiffney Peter M.
Published: January 2024

Bivalves such as oysters and clams have been farmed in intertidal zones across the Puget Sound region of the Salish Sea for thousands of years. The variety of gear types used on bivalve farms creates complex vertical structure and attachment points for aquatic epiphytes and invertebrates which increases habitat structural complexity, but may alter eelgrass cover in areas where bivalve farms and eelgrass meadows overlap. Eelgrass meadows are highly productive and ecologically foundational nearshore habitats that provide valuable ecosystem services including the provision of nursery, refuge, and foraging habitat. Aquaculture has been a key feature of the environment in the Puget Sound for millennia, however, little is known about how well aquaculture practices are integrated into the system, and what services they provide to mobile species assemblages relative to unfarmed eelgrass meadows. We used stable isotope mixing models to estimate, for several species of nearshore fish and crab in two areas of North Puget Sound, Washington, the percent diet originating from either a natural bottom habitat (eelgrass meadows), farm habitat (oyster farms), or pelagic planktonic sources. Our results indicate that several species of nearshore fish such as surf perch and staghorn sculpin derive a significant proportion of their diets from farm areas, while crabs derive most of their diets from eelgrass habitat, and stickleback derive a significant proportion of their diets from planktonic sources. The results indicate that foraging habitat uses are species specific, and that several species that spatially overlap bivalve farms obtained a large percentage of their diets from adjacent bivalve farm habitat.
A simplified decision feedback Chebyshev function link neural network with intelligent initialization for underwater acoustic channel equalization
Authors: Zhou Manli , Zhang Hao , Lv Tingting , Huang Wei , Duan Yingying , Gao Yong
Published: January 2024

Introduction

In shallow-water environments, the reliability of underwater communication links is often compromised by significant multipath effects. Some equalization techniques such as decision feedback equalizer, and deep neural network equalizer suffer from slow convergence and high computational complexity.

Methods

To address this challenge, this paper proposes a simplified decision feedback Chebyshev function link neural network equalizer (SDF-CFLNNE). The structure of the SDF-CFLNNE employs Chebyshev polynomial function expansion modules to directly and non-linearly transform the input signals into the output layer, without the inclusion of hidden layers. Additionally, it feeds the decision signal back to the input layer rather than the function expansion module, which significantly reduces computational complexity. Considering that, in the training phase of neural networks, the random initialization of weights and biases can substantially impact the training process and the ultimate performance of the network, this paper proposes a chaotic sparrow search algorithm combining the osprey optimization algorithm and Cauchy mutation (OCCSSA) to optimize the initial weights and thresholds of the proposed equalizer. The OCCSSA utilizes the Piecewise chaotic population initialization and combines the exploration strategy of the ospreywith the Cauchy mutation strategy to enhance both global and local search capabilities.

Rseults

Simulations were conducted using underwater multipath signals generated by the Bellhop Acoustic Toolbox. The results demonstrate that the performance of the SDFCFLNNE initialized by OCCSSA surpasses that of CFLNN-based and traditional nonlinear equalizers, with a notable improvement of 2-6 dB in terms of signal-to-noise ratio at a bit error rate (BER) of 10−4 and a reduced mean square error (MSE). Furthermore, the effectiveness of the proposed equalizer was validated using the lake experimental data, demonstrating lower BER and MSE with improved stability.

Discussion

This underscores thepromise of employing the SDFCFLNNE initialized by OCCSSA as a promising solution to enhance the robustness of underwater communication in challenging environments.
Structural control of nanoporous frameworks consisting of minimally stacked graphene walls
Authors: Pirabul Kritin , Pan Zheng-Ze , Nishihara Hirotomo
Published: January 2024

This mini-review provides an in-depth analysis of the formation and post-processing of nanoporous graphene materials via methane chemical vapor deposition (CH4-CVD) using nanostructured metal oxide templates, including Al2O3, MgO, and SiO2. Initially, the formation of graphene sheets is discussed in terms of the role of CH4-CVD, the influence of templates, and the underlying mechanism for tailoring the structures of the graphene-based materials. Following this, the discussion extends to the post-graphene formation process. We focus on key steps, including template removal and graphene repair via zipping reactions at high temperatures. Additionally, we evaluate the conditions to prevent undesired structural transformations. The correlation between the structural features and transformations occurring during post-processing is also examined. The materials fabricated through these methods exhibit impressive properties of high porosity, minimal edge sites, superior oxidation resistance, and elasticity, positioning them as promising materials in various applications.
Characteristics of retracted research papers before and during the COVID-19 pandemic
Authors: Furuse Yuki
Published: January 2024

Objectives

During the COVID-19 pandemic, a large number of research papers were published, and some of them were retracted. The present study aims to reveal the characteristics of retracted papers before and during the pandemic.

Methods

The study investigated 24,542,394 publications from 1999 to 2022 and analyzed the profiles of retracted papers from the perspectives of year, disease category, country, and journal.

Results

Retraction rates were generally increasing at least until 2019, and were the highest for “Neoplasms.” The number of publications for “Infections” and “Respiratory Tract Diseases” dramatically rose during the COVID-19 pandemic; however, the retraction rates in the two categories or of COVID-19-related papers were not especially high compared to other diseases. The association with retraction was strongest for China in most disease categories, whereas for COVID-19 papers, other countries showed higher retraction rates than China. In recent years, retracted papers have become less likely to be published in high-impact journals.

Conclusion

The COVID-19 pandemic does not seem to affect the retractions of research papers much. We should keep monitoring retractions and analyze the effects of pandemics for better science.
Allergic rhinitis and other comorbidities associated with asthma control in Thailand
Authors: Sriprasart Thitiwat , Saiphoklang Narongkorn , Kawamatawong Theerasuk , Boonsawat Watchara , Mitthamsiri Wat , Chirakalwasan Naricha , Chiewchalermsri Chirawat , Athipongarporn Athipat , Kamalaporn Harutai , Kornthatchapong Kumpol , Kulpraneet Manaphol , Sompornrattanaphan Mongkhon , Oer-Areemitr Nittha , Rerkpattanapipat Ticha , Silairatana Santi , Thawanaphong Sarita , Gaensan Thanate , Jirakran Ketsupar , Poachanukoon Orapan
Published: January 2024

Background

Asthma and allergic rhinitis (AR) can coexist and cause disabilities. This study aimed to assess the association between AR, asthma control, asthma-related quality of life, and other comorbidities.

Methods

A cross-sectional study was conducted in adults with asthma in six hospitals in Thailand. The outcomes were association of asthma control assessed by the asthma control test (ACT), AR, and asthma comorbidities. Not-well-controlled asthma was defined as ACT scores ≤22. The severity of AR was determined by visual analog scale (VAS). Severe AR was defined as VAS ≥5. Asthma-related quality of life (AQLQ), comorbidities, and total IgE were recorded.

Results

A total of 682 asthmatic patients were included. Median (IQR) age was 58.0 (47.0–64.0) years. 69.9% were female. Not-well-controlled asthma was present in 44.7%. The prevalence of AR was 86.1%. Moderate/severe persistent AR was diagnosed in 21.7% and severe AR was diagnosed in 30.2% of the patients. Inhaled corticosteroid-containing regimens were prescribed in 97.7% of patients. Intranasal corticosteroid and antihistamine were prescribed in 65.7 and 31.7%, respectively. Patients with not-well-controlled asthma had higher body mass index, VAS scores, proportions of pollution exposure, aeroallergen sensitization, severe AR, nasal polyp, urticaria, food allergy, gastroesophageal reflux disease, depression and anxiety, peptic ulcer, and asthma exacerbations, but younger age, lower AQLQ scores, and lower FEV1. Correlation was found between AR severity and ACT (r = −0.461, p < 0.001), AQLQ (r = −0.512, p < 0.001), and total IgE (r = 0.246, p < 0.023). Multiple regression analysis revealed that ACT, AQLQ, and percentage of FEV1/FVC were significantly associated with severe AR.

Conclusion

Allergic rhinitis is prevalent in Thai asthmatic patients. AR severity is associated with asthma control, quality of life, and pulmonary function. Comprehensive care is essential for patients with uncontrolled asthma, particularly when coexisting with conditions.
Application of propidium monoazide quantitative PCR to discriminate of infectious African swine fever viruses
Authors: Li Yang , Wang Zewei , Qing Jie , Hu Dajun , Vo Hong Trang , Thi Kim Thanh , Wang Xinglong , Li Xiaowen
Published: January 2024

Introduction

The detection of African swine fever virus (ASFV) is commonly performed using quantitative real-time PCR (qPCR), a widely used virological method known for its high sensitivity and specificity. However, qPCR has a limitation in distinguishing between infectious and inactivated virus, which can lead to an overestimation of viral targets.

Methods

To provide insights into ASFV infectivity, we evaluated the suitability of PMAxx, an improved version of propidium monoazide (PMA), as a means to differentiate between infectious and non-infectious ASFV. Pre-treatment with 50 μM PMAxx for 15 min significantly reduced the qPCR signal of ASFV in the live vaccine. Additionally, thermal treatment at 85°C for 5 min effectively inactivated the live ASFV in the vaccine. Based on a standard curve, the sensitivity of the PMAxx-qPCR assay was estimated to be approximately 10 copies/μL. Furthermore, we observed a strong agreement between the results obtained from PMAxx-qPCR and pig challenge experiments. Moreover, we utilized the PMAxx-qPCR assay to investigate the persistence of ASFV, revealing a close relationship between viral persistence and factors such as temperature and type of piggery materials.

Conclusion

The findings of this study suggest that pre-treating viruses with PMAxx prior to qPCR is a reliable method for distinguishing between infectious and non-infectious ASFV. Thus, integrating of PMAxx-qPCR into routine diagnostic protocols holds potential for improving the interpretation of positive ASFV results obtained through qPCR.