bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding Heavy Hearts
Authors:   , de Leeuw Anne Elisabeth
Published: March 2024

Hypertrophic cardiomyopathy (HCM) is a prevalent heart disease often caused by a mutation and is characterized by thickening of the heart muscle . This remodeling nearly always takes place in the myocardial wall. While many mutation carriers remain asymptomatic, others suffer severe symptoms, potentially requiring myectomy or heart transplant. Despite its prevalence, there is no clear understanding of what triggers the remodeling and how to detect this.
In this research, it was attempted to better understand the genes that might regulate this pathology. This was done by dispersing mycectomy tissue from patients into single cells. Subsequentially cardiomyocytes were selected for single cell sequencing to distinguish between healthy and diseased cells. It was discovered that MYL2 is a marker for more hypertrophic cells and this allowed to make predictions about the genes which may orchestrate the genetic pathways activated in these cells. Afterwards it was studied why the septum is more prone to thickening. With Tomo-sequencing, gene expression patterns in septum and free wall were studied, pinpointing NR2F2 as a potential regulator of remodeling in the septum. Lastly, mouse models carrying two of the most prevalent HCM-causing mutations in the Netherlands were generated. The homozygous mice in this model developed clear cardiac dysfunction and hypertrophic remodeling, while heterozygous mice failed to do so, indicating an extra trigger is required in this model.

Ultimately, we were able to distinguish between more stressed cardiomyocytes and myocardial areas and make prediction on which genes could be driving this pathological state. We generated a model to study the onset and the progression of HCM. Together, these models can help us to get more insight on the molecular mechanisms of this complex disease.
Exploring biosurfactant from Halobacterium jilantaiense as drug against HIV and zika virus: fabrication, characterization, cytosafety property, molecular docking, and molecular dynamics simulation
Authors: Almuhayawi Mohammed S. , Elshafey Naglaa , Hagagy Nashwa , Selim Samy , Al Jaouni Soad K. , Sofy Ahmed R. , Samy Mennatalla , Gattan Hattan S. , Alruhaili Mohammed H. , Alharbi Mohanned Talal , Nagshabandi Mohammed K. , Tarabulsi Muyassar K. , Elnosary Mohamed E.
Published: March 2024

Biosurfactants are surface-active molecules with unique qualities and various uses. Many microorganisms produce secondary metabolites with surface-active characteristics that serve various antiviral functions. The HIV and Zika viruses were chosen for this study because they can spread from mother to child and result in potentially fatal infections in infants. Halophilic bacteria from the Red Sea solar saltern in Egypt were screened using drop collapse, emulsification activity, and oil displacement assays to produce biosurfactants and emulsifiers. Halobacterium jilantaiense strain JBS1 was the most effective strain of the Halobacteriaceae family. It had the best oil displacement test and emulsification activity against kerosene and crude oil, respectively. Among the ten isolates, it produced the most promising biosurfactant, also recognized by the GC-MASS library. This study evaluated biosurfactants from halophilic bacteria as potential antiviral drugs. Some of the computer methods we use are molecular docking, ADMET, and molecular dynamics. We use model organisms like the HIV reverse transcriptase (PDB: 5VZ6) and the Zika virus RNA-dependent RNA polymerase (ZV-RdRP). Molecular docking and molecular dynamics make the best complexes with 5VZ6 HIV-RT and flavone (C25) and 5wz3 ZV-RdRP and ethyl cholate (C8). Testing for ADMET toxicity on the complex revealed that it is the safest medicine conceivable. The 5VZ6-C25 and 5wz3-C8 complexes also followed the Lipinski rule. They made five hydrogen bond donors and ten hydrogen bond acceptors with 500 Da MW and a 5:1 octanol/water partition coefficient. Finally, extreme settings require particular adaptations for stability, and extremophile biosurfactants may be more stable.
Bioprinting of gelatin-based materials for orthopedic application
Authors: Waidi Yusuf Olatunji , Kariim Ishaq , Datta Sudipto
Published: March 2024

Bio-printed hydrogels have evolved as one of the best regenerative medicine and tissue engineering platforms due to their outstanding cell-friendly microenvironment. A correct hydrogel ink formulation is critical for creating desired scaffolds that have better fidelity after printing. Gelatin and its derivatives have sparked intense interest in various biomedical sectors because of their biocompatibility, biodegradability, ease of functionalization, and rapid gelling tendency. As a result, this report emphasizes the relevance of gelatin-based hydrogel in fabricating bio-printed scaffolds for orthopedic applications. Starting with what hydrogels and bio-printing are all about. We further summarized the different gelatin-based bio-printing techniques explored for orthopedic applications, including a few recent studies. We also discussed the suitability of gelatin as a biopolymer for both 3D and 4D printing materials. As extrusion is one of the most widely used techniques for bio-printing gelatin-based, we summarize the rheological features of gelatin-based bio-ink. Lastly, we also elaborate on the recent bio-printed gelatin-based studies for orthopedics applications, the potential clinical translation issues, and research possibilities.
Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis
Authors: Lee Sun-Ah , Cho Gi-Ju , Kim Doyoung , Kim Dong-Hwee
Published: March 2024

Mechanical properties of the tumor microenvironment play a critical role in cancer progression by activation of cancer mechano-responses. The biophysical interactions between cancer cells and their dynamic microenvironment are attributed to force-dependent alterations in molecular pathways that trigger the structural reorganization of intracellular organelles and their associated genetic modifications. Recent studies underscore the role of oxygen concentration in cancer metastasis. Suppressed oxygen levels promote the development of invasive phenotypes and aggressive proliferation of cancer cells, accompanied by remodeling of tumor microenvironment encompassing the modulation of physical settings of extracellular matrix. This review summarizes the role of biophysical interactions between cancer cells and their surroundings in determining cancer progression. Biophysical interpretation of the tumor microenvironment and cancer progression could provide further insights into the development of novel biomedical technologies for therapeutic cancer treatment.
MicroRNAs in maxillofacial bone modeling and remodeling: implications for malocclusion development and orthodontic treatment
Authors: Chen Baike , Zhang Yuxin , Liu Ousheng
Published: March 2024

Modeling and remodeling are essential processes in the development and refinement of maxillofacial bones. Dysregulated bone modeling during the developmental stage may lead to maxillofacial bone malformations and malocclusion. Bone remodeling under mechanical loading serves as the biological basis for orthodontic treatment. Although previous reviews have indicated the significance of microRNAs (miRNAs) in bone metabolism, their roles in orchestrating maxillofacial bone modeling and remodeling remain unclear. This review aims to discuss the mechanisms by which miRNAs regulate the morphogenesis and development of maxillofacial bones, as well as their implications for maxillofacial malformations and malocclusion. Moreover, miRNAs participating in maxillofacial bone remodeling and their impacts on cell mechanosensing are also summarized. Given the intricate interplay of cells and signaling pathways, exosomal miRNAs emerge as the orchestrators of the modeling and remodeling processes. The diagnostic and therapeutic potentials of miRNAs are also highlighted in this review for future clinical applications.
Exploring the neuroprotective activity of a lignanamides-rich extract in human neuroblastoma SH-SY5Y cells under dimethyl sulfoxide-induced stress
Authors: Mallardo Marta , Pacifico Severina , Piccolella Simona , Di Meo Irene , Rizzo Maria Rosaria , Daniele Aurora , Nigro Ersilia
Published: March 2024

Introduction: Dimethyl sulfoxide (DMSO) is widely used as a diluent and/or solvent for pharmacological compounds. Furthermore, DMSO crosses the blood-brain barrier acting on the nervous system. The natural compounds phenylamides and lignanamides (LnHS) have protective effects on neuronal health, being promising neuroprotective candidates. In this scenario, we evaluated the impact of DMSO and/or LnHS on SH-SY5Y and U-87 cells, taken as in vitro model of neurons and glia.

Methods: Cells were treated with DMSO and/or LnHS at different doses and proliferation (MTT and trypan blue counting, colony forming ability, autophagy, oxidative stress (NO, ROS determination) and inflammatory (IL8, IL6, TNFα mRNA expression) response was evaluated.

Results: We found that DMSO reduces both neuronal and glial cell viability, while LnHS does not affect viability of SH-SY5Y cells but reduces that of U-87 cells. Therefore, we focused on SHSY5Y cells and investigated whether LnHS could counteract DMSO toxicity. LnHS partially attenuates the inhibitory effects of DMSO on cell viability and restores the colony-forming ability of SH-SY5Y cells exposed to DMSO. Furthermore, we found that co-administration of LnHS modulates the expression of SIRT3 and SOD2 enzymes, reduces nitrite release and ROS generation increasing IL-8 levels. Interestingly, co-administration of LnHS counteracts the DMSO-induced production of IL-6, while no modification in TNF-α was found.

Discussion: Our study indicates LnHS as a potential feasible compound to support neuronal health as it counteracts DMSO induced cytotoxic effects by improving SH-SY5Y cells survival. Further studies are needed to clarify the molecular mechanisms underlying the LnHS biological activities.
From flexibility to adaptive learning: a pre-COVID-19 perspective on distance education in Latin America
Authors: Miralrio Alan , Muñoz-Villota Jessica , Camacho-Zuñiga Claudia
Published: March 2024

At the time of this writing, emerging Generative Artificial Intelligence (GenAI) technologies, such as ChatGPT, Bard, and DALL-E, are shaping education. Despite their great potential for enhancing education, the discussion on the risks for the Society is an ongoing debate. Remote or distance education (DE) in developed countries has evolved in parallel to the permeation of Information and Communication Technologies (ICT). In Latin America (LATAM), a deep understanding of this interrelated evolution will encourage an efficient implementation of innovative policies, pedagogies, and technologies, including GenAI. This paper presents the historical development of DE in LATAM, drawing connections with milestones along the evolution of ICT in the region. This evolution is described across five generations: Correspondence, Audiovisual, ICTs-based, Web-based, and Interactive. Each generation offered incremental benefits to students, from flexibility and well-designed instructional materials to adaptive, interactive, and cost-effective education. This research encompassed a comprehensive search on Scopus, Web of Science, Google Scholar, ScienceDirect, Latindex, Dialnet, Redalyc, and SciELO with an historical approach. It yielded 97 peer-reviewed articles, books, and reports from recognized international organizations, published in Spanish or English and covering a period spanning from the end of the 19th century to the onset of COVID-19 lockdown. The analysis confirms the critical role of Higher Education Institutions (HEIs) in LATAM in supporting ICT integration, demonstrating a synergistic interplay with DE. Notwithstanding, the region’s social inequality and digital divide have delayed the full deployment of DE’s advantages, in comparison to USA and Europe. The paper exposes different scenarios and tech-educational requirements of DE, showcasing Mexico, Brazil, and Colombia, as well as other countries with smaller populations. Notably, by 2019, Tecnologico de Monterrey in Mexico, and Universidade de São Paulo and Universidade Federal da Paraíba in Brazil have pioneered the implementation of the Fifth Generation of DE in the region. The findings of this research highlight the value of DE as a cost-effective solution to traditional education, addressing social barriers and broadening educational access in LATAM, especially during emergencies. This research poses significant implications that can equip digital technology providers, HEIs, governments, and policymakers as they navigate the ongoing educational challenges.
Effect of statin add-on therapy on cardiovascular mortality
Authors: Nelson John R. , Le Viet , Anderson Jeffrey L. , Ciffone Nicole
Published: March 2024

Introduction

Cardiovascular (CV) disease remains a leading cause of mortality despite statin therapy. Statin add-on lipid-lowering therapies have been investigated for CV risk reduction, but their effect on CV mortality has not been reviewed.

Methods

This review describes CV outcomes trials of add-on therapies to statins, highlighting findings related to the primary composite CV endpoints and the more patient-centric endpoint of CV-related mortality.

Results

Add-on ezetimibe met its primary composite CV endpoint vs. statin alone (P = 0.016); however, the individual endpoint of death from CV causes did not differ between groups. Add-on therapy with proprotein convertase subtilisin/kexin type 9 inhibitors achieved the primary composite CV endpoints in the respective CV outcomes trials for alirocumab (P < 0.001) and evolocumab (P < 0.001); however, neither CV outcomes trial found a difference vs. placebo in CV-related mortality. In its CV outcomes trial, icosapent ethyl added to statin therapy significantly reduced the occurrence of the primary composite CV endpoint (P < 0.001) and the individual endpoint of risk of CV-related death (P = 0.03) vs. placebo. A CV outcomes trial of bempedoic acid monotherapy achieved its primary composite CV endpoint vs. placebo (P = 0.004) but not the endpoint of death from CV causes.

Discussion

Statin add-on therapies achieved their CV outcomes trial composite CV endpoints. Proprotein convertase subtilisin/kexin type 9 inhibitors and icosapent ethyl have approved indications for CV risk reduction. Only add-on therapy with icosapent ethyl demonstrated a significant reduction in CV mortality in the overall intent-to-treat population, possibly due to the unique pleiotropic mechanisms of eicosapentaenoic acid independent of lipid-lowering effects.
Learning from (re)experience: What mobile eye-tracking video can help us learn about the cognitive processes of teaching
Authors: Miller Kevin F. , Correa Chris , Cortina Kai , Phelps Lauren , Chamberlain Lynn
Published: March 2024

Introduction

Classroom teachers need to monitor a group of students varying in interest, knowledge, and behavior at the same time that they present a lesson and adapt it on the fly to student questions and understanding. Many areas of expertise are associated with special kinds of perceptual skills, and teaching presents its own perceptual challenges. We discuss the special nature of the expert looking that teachers must develop and how it relates to more general models of expertise. Standard methods of classroom video are limited in their support of teacher professional looking, and we explore an alternative using mobile eyetracking that overcomes many of these limits. The combination of mobile eyetracking records and standard video enables the participant to “re-experience” a situation in a vivid way, while also seeing things they missed the first time through.

Methods

We report a study in which pairs of novice and experienced teachers teaching the same students watched their own mobile eyetracking recordings while performing a retrospective think-aloud task.

Results

Experienced teachers were better able to describe high-level features and their significance in the lessons, while novices were more likely to talk about in-the-moment events such as things they failed to see while teaching. This is consistent with work on expertise that suggests there are both costs and benefits to expert looking.

Discussion

Our results suggest that the ability to quickly grasp the meaning of a classroom situation may be associated with less awareness of some of the lower-level features on which those inferences are based. Novice and experienced teachers notice different things and have different perspectives on classroom processes; understanding the cognitive process of teachers will require combining insights from each. The methods used in this study are quickly becoming less costly and more accessible, and they have a unique role to play in research and in teacher professional development.
Predictive value of ultrasonic artificial intelligence in placental characteristics of early pregnancy for gestational diabetes mellitus
Authors: Zhou Huien , Chen Wanming , Chen Chen , Zeng Yanying , Chen Jialin , Lin Jianru , He Kun , Guo Xinmin
Published: March 2024

Background

To explore the predictive value of placental features in early pregnancy for gestational diabetes mellitus (GDM) using deep and radiomics-based machine learning (ML) applied to ultrasound imaging (USI), and to develop a nomogram in conjunction with clinical features.

Methods

This retrospective multicenter study included 415 pregnant women at 11-13 weeks of gestation from two institutions: the discovery group from center 1 (n=305, control group n=166, GDM group n=139), and the independent validation cohort (n=110, control group n=57, GDM group n=53) from center 2. The 2D USI underwent pre-processed involving normalization and resampling. Subsequently, the study performed screening of radiomics features with Person correlation and mutual information methods. An RBF-SVM model based on radiomics features was constructed using the five-fold cross-validation method. Resnet-50 as the backbone network was employed to learn the region of interest and constructed a deep convolutional neural network (DLCNN) from scratch learning. Clinical variables were screened using one-way logistic regression, with P<0.05 being the threshold for statistical significance, and included in the construction of the clinical model. Nomogram was built based on ML model, DLCNN and clinical models. The performance of nomogram was assessed by calibration curves, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA).

Results

The AUCs for the ML model in the discovery cohort and independent validation cohort were 0.91 (0.88-0.94) and 0.86 (0.79-0.93), respectively. And 0.65 (0.59-0.71), 0.69 (0.59-0.79) for the DLCNN, 0.66 (0.59-0.72), 0.66 (0.55-0.76) for the clinical model, respectively. The nomogram exhibited the highest performance with AUCs of 0.93 (0.90-0.95) and 0.88 (0.81-0.94) The receiver operating characteristic curve (ROC) proved the superiority of the nomogram of clinical utility, and calibration curve showed the goodness of fit of the model. The DCA curve indicated that the nomogram outperformed other models in terms of net patient benefit.

Conclusions

The study emphasized the intrinsic relationship between early pregnancy placental USI and the development of GDM. The use of nomogram holds potential for clinical applications in predicting the development of GDM.
Causal relationship between Alzheimer’s disease and prostate cancer: a bidirectional Mendelian randomization analysis
Authors: Li Rongkang , Peng Lei , Deng Dashi , Li Guangzhi , Wu Song
Published: March 2024

Background

Previous observational researchers have found an inverse bidirectional link between Alzheimer’s disease (AD) and prostate cancer (PCa); yet, the causative nature of this link remains unclear. To investigate the causal interactions between AD and PCa, a bidirectional Mendelian randomization (MR) analysis was conducted.

Methods

This study comprised two Genome-Wide Association Study (GWAS) summary statistics for AD (17,008 cases and 37,154 controls) and PCa (79,148 cases and 61,106 controls) in individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as the primary approach, while MR-Egger, weighted median, weighted mode, and simple mode served as supplementary methods for estimating the causal effect. To assess pleiotropy, the MR-PRESSO global test and MR-Egger regression were used. Cochran’s Q test was adopted to check heterogeneity, MR Steiger test and the leave-one-out analysis was performed to confirm the robustness and reliability of the results.

Results

The causal association genetically inferred of AD on PCa was found using IVW (OR = 0.974, 95% CI = 0.958-0.991, p = 0.003) in forward MR analysis and the causal association genetically inferred of PCa on AD was not found using IVW (OR = 1.000, 95% CI: 0.954-1.049, P = 0.988) in reverse MR analysis. The sensitivity analysis showed that no pleiotropy and heterogeneity was observed. The leave-one-out analysis showed that the findings were not inordinately affected by any instrumental variables.

Conclusion

The results of this study demonstrated an absence of bidirectional causality between AD and PCa among the European population, suggested that a genetically predicted possibility of decreased PCa risk in AD patients, and no significant genetically predicted causal effect of PCa on AD.
Photocatalytic degradation of naproxen using TiO2 single nanotubes
Authors: Sepúlveda Marcela , Musiał Joanna , Saldan Ivan , Chennam Pavan Kumar , Rodriguez-Pereira Jhonatan , Sopha Hanna , Stanisz Beata J. , Macak Jan M.
Published: March 2024

Herein, TiO2 single-tube (TiO2 ST-NT) powders with and without magnetite Fe3O4 nanoparticles (TiO2 ST-NT@Fe3O4NPs) are presented for the first time as excellent photocatalysts for the degradation of one of the most popular non-steroidal anti-inflammatory drugs (NSAIDs), naproxen (NPX). The TiO2 ST-NT powders were synthesized by anodization followed by etching of the double wall, bending, sonication, ultra-centrifugation, and finally annealing at 600°C. A part of the obtained TiO2 ST-NT powders was decorated with Fe3O4 nanoparticles using a simple one-step decoration process. The best photocatalytic performance of TiO2 ST-NT and TiO2 ST-NT@Fe3O4NPs powders was obtained under the white light (6.2 × 10−4 s-1) and the blue light (2.7 × 10−4 s-1), respectively. During NPX photodegradation using TiO2 ST-NT powders, three main NPX transformation products (P1, P2, and P3) were detected. Upon excitation with the blue light illumination, TiO2 ST-NT@ Fe3O4NPs powders exhibited higher performance (∼80%) than TiO2 ST-NT powders (∼23%) within 1 h, resulting in an approximately three times increased photocatalytic rate constant. Moreover, under simulated sunlight conditions, TiO2 ST-NT powders demonstrated remarkable activity, achieving a 94% NPX degradation within 1 h. TiO2 ST-NT and TiO2 ST-NT@Fe3O4NPs powders represent excellent photocatalysts for NPX degradation.
TCRpred: incorporating T-cell receptor repertoire for clinical outcome prediction
Authors: Liu Meiling , Liu Yang , Hsu Li , He Qianchuan
Published: March 2024

T-cell receptor (TCR) plays critical roles in recognizing antigen peptides and mediating adaptive immune response against disease. High-throughput technologies have enabled the sequencing of TCR repertoire at the single nucleotide level, allowing researchers to characterize TCR sequences with high resolutions. The TCR sequences provide important information about patients’ adaptive immune system, and have the potential to improve clinical outcome prediction. However, it is challenging to incorporate the TCR repertoire data for prediction, because the data is unstructured, highly complex, and TCR sequences vary widely in their compositions and abundances across different individuals. We introduce TCRpred, an analytic tool for incorporating TCR repertoire for clinical outcome prediction. The TCRpred is able to utilize features that can be extracted from the TCR amino acid sequences, as well as features that are hidden in the TCR amino acid sequences and are hard to extract. Simulation studies show that the proposed approach has a good performance in predicting clinical outcome and tends to be more powerful than potential alternative approaches. We apply the TCRpred to real cancer datasets and demonstrate its practical utility in clinical outcome prediction.
Non-coding RNA and reprogrammed mitochondrial metabolism in genitourinary cancer
Authors: Thirunavukkarasu Sandiya , Banerjee Shouryarudra , Tantray Ishaq , Ojha Rani
Published: March 2024

Non-coding ribonucleic acids (ncRNAs) have been recently shown to contribute to tumorigenesis by mediating changes in metabolism. ncRNAs act as key molecules in metabolic pathways regulation. The dysregulation of ncRNAs during cancer progression contributes to altered metabolic phenotypes leading to reprogrammed metabolism. Since ncRNAs affect different tumor processes by regulating mitochondrial dynamics and metabolism, in the future ncRNAs can be exploited in disease detection, diagnosis, treatment, and resistance. The purpose of this review is to highlight the role of ncRNAs in mitochondrial metabolic reprogramming and to relate their therapeutic potential in the management of genitourinary cancer.
TIGIT regulates CD4+ T cell immunity against polymicrobial sepsis
Authors: Zhong Xuexin , Xie Haiping , Wang Shuang , Ren Tingting , Chen Junlin , Huang Yuefang , Yang Niansheng
Published: March 2024

Background

Sepsis is one of the major causes of death and increased health care burden in modern intensive care units. Immune checkpoints have been prompted to be key modulators of T cell activation, T cell tolerance and T cell exhaustion. This study was designed to investigate the role of the negative immune checkpoint, T cell immunoglobulin and ITIM domain (TIGIT), in the early stage of sepsis.

Method

An experimental murine model of sepsis was developed by cecal ligation and puncture (CLP). TIGIT and CD155 expression in splenocytes at different time points were assessed using flow cytometry. And the phenotypes of TIGIT-deficient (TIGIT-/-) and wild-type (WT) mice were evaluated to explore the engagement of TIGIT in the acute phase of sepsis. In addition, the characteristics were also evaluated in the WT septic mice pretreated with anti-TIGIT antibody. TIGIT and CD155 expression in tissues was measured using real-time quantitative PCR and immunofluorescence staining. Proliferation and effector function of splenic immune cells were evaluated by flow cytometry. Clinical severity and tissue injury were scored to evaluate the function of TIGIT on sepsis. Additionally, tissue injury biomarkers in peripheral blood, as well as bacterial load in peritoneal lavage fluid and liver were also measured.

Results

The expression of TIGIT in splenic T cells and NK cells was significantly elevated at 24 hours post CLP.TIGIT and CD155 mRNA levels were upregulated in sepsis-involved organs when mice were challenged with CLP. In CLP-induced sepsis, CD4+ T cells from TIGIT-/- mice shown increased proliferation potency and cytokine production when compared with that from WT mice. Meanwhile, innate immune system was mobilized in TIGIT-/- mice as indicated by increased proportion of neutrophils and macrophages with potent effector function. In addition, tissue injury and bacteria burden in the peritoneal cavity and liver was reduced in TIGIT-/- mice with CLP induced sepsis. Similar results were observed in mice treated with anti-TIGIT antibody.

Conclusion

TIGIT modulates CD4+ T cell response against polymicrobial sepsis, suggesting that TIGIT could serve as a potential therapeutic target for sepsis.
Cellular interactions in tumor microenvironment during breast cancer progression: new frontiers and implications for novel therapeutics
Authors: Akinsipe Tosin , Mohamedelhassan Rania , Akinpelu Ayuba , Pondugula Satyanarayana R. , Mistriotis Panagiotis , Avila L. Adriana , Suryawanshi Amol
Published: March 2024

The breast cancer tumor microenvironment (TME) is dynamic, with various immune and non-immune cells interacting to regulate tumor progression and anti-tumor immunity. It is now evident that the cells within the TME significantly contribute to breast cancer progression and resistance to various conventional and newly developed anti-tumor therapies. Both immune and non-immune cells in the TME play critical roles in tumor onset, uncontrolled proliferation, metastasis, immune evasion, and resistance to anti-tumor therapies. Consequently, molecular and cellular components of breast TME have emerged as promising therapeutic targets for developing novel treatments. The breast TME primarily comprises cancer cells, stromal cells, vasculature, and infiltrating immune cells. Currently, numerous clinical trials targeting specific TME components of breast cancer are underway. However, the complexity of the TME and its impact on the evasion of anti-tumor immunity necessitate further research to develop novel and improved breast cancer therapies. The multifaceted nature of breast TME cells arises from their phenotypic and functional plasticity, which endows them with both pro and anti-tumor roles during tumor progression. In this review, we discuss current understanding and recent advances in the pro and anti-tumoral functions of TME cells and their implications for developing safe and effective therapies to control breast cancer progress.
Case report: Long-term follow-up of patients who received a FimCH vaccine for prevention of recurrent urinary tract infections caused by antibiotic resistant Enterobacteriaceae: a case report series
Authors: Perer Elise , Stacey Helen , Eichorn Terri , Hughey Heidi , Lawrence Julie , Cunningham Eric , Johnson Mark O’Neil , Bacon Kevin , Kau Andrew , Hultgren Scott J. , Hooton Thomas M. , Harris Jennifer L.
Published: March 2024

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status and UTI occurrence. The study was later amended to allow additional follow-up of up to five years post vaccine administration to assess long-term health status, UTI occurrences and to obtain blood samples for anti-FimH antibody testing. In our population of 4 study participants, the number of symptomatic UTI occurrences caused by gram-negative bacteria in the 12-month period following peak anti-FimH antibody response were approximately 75% lower than the 12-month period preceding study enrollment. These results are consistent with the 30-patient cohort of a Phase 1 study with the same FimCH Vaccine. UTI occurrences increased during the long-term follow-up period for all 4 participants but did not reach the rate observed pre-vaccination. No new safety concerns related to the FimCH Vaccine were identified during long-term follow-up. This case series has clinical importance and public health relevance since it examines and reports on UTI frequency and recurrence following vaccination with the FimCH Vaccine in a high-risk population of patients with recurrent UTI. Additionally, participants described improved well-being following vaccination which was maintained in the long-term follow-up period.
Recent advances in different interactions between toll-like receptors and hepatitis B infection: a review
Authors: Soleiman-Meigooni Saeed , Yarahmadi Aref , Kheirkhah Amir-Hossein , Afkhami Hamed
Published: March 2024

Hepatitis B virus (HBV) B infections remain a primary global health concern. The immunopathology of the infection, specifically the interactions between HBV and the host immune system, remains somewhat unknown. It has been discovered that innate immune reactions are vital in eliminating HBV. Toll-like receptors (TLRs) are an essential category of proteins that detect pathogen-associated molecular patterns (PAMPs). They begin pathways of intracellular signals to stimulate pro-inflammatory and anti-inflammatory cytokines, thus forming adaptive immune reactions. HBV TLRs include TLR2, TLR3, TLR4, TLR7 and TLR9. Each TLR has its particular molecule to recognize; various TLRs impact HBV and play distinct roles in the pathogenesis of the disease. TLR gene polymorphisms may have an advantageous or disadvantageous efficacy on HBV infection, and some single nucleotide polymorphisms (SNPs) can influence the progression or prognosis of infection. Additionally, it has been discovered that similar SNPs in TLR genes might have varied effects on distinct populations due to stress, diet, and external physical variables. In addition, activation of TLR-interceded signaling pathways could suppress HBV replication and increase HBV-particular T-cell and B-cell reactions. By identifying these associated polymorphisms, we can efficiently advance the immune efficacy of vaccines. Additionally, this will enhance our capability to forecast the danger of HBV infection or the threat of dependent liver disease development via several TLR SNPs, thus playing a role in the inhibition, monitoring, and even treatment guidance for HBV infection. This review will show TLR polymorphisms, their influence on TLR signaling, and their associations with HBV diseases.
Applications of emerging extracellular vesicles technologies in the treatment of inflammatory diseases
Authors: Lou Kecheng , Luo Hui , Jiang Xinghua , Feng Shangzhi
Published: March 2024

The emerging extracellular vesicles technologies is an advanced therapeutic approach showing promising potential for addressing inflammatory diseases. These techniques have been proven to have positive effects on immune modulation and anti-inflammatory responses. With these advancements, a comprehensive review and update on the role of extracellular vesicles in inflammatory diseases have become timely. This review aims to summarize the research progress of extracellular vesicle technologies such as plant-derived extracellular vesicles, milk-derived extracellular vesicles, mesenchymal stem cell-derived extracellular vesicles, macrophage-derived extracellular vesicles, etc., in the treatment of inflammatory diseases. It elucidates their potential significance in regulating inflammation, promoting tissue repair, and treating diseases. The goal is to provide insights for future research in this field, fostering the application and development of extracellular vesicle technology in the treatment of inflammatory diseases.
The role of foam cells in spinal cord injury: challenges and opportunities for intervention
Authors: Wang Xiao-Xin , Li Ze-Hui , Du Hua-Yong , Liu Wu-Bo , Zhang Chun-Jia , Xu Xin , Ke Han , Peng Run , Yang De-Gang , Li Jian-Jun , Gao Feng
Published: March 2024

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.
Phenotypic plasticity and carryover effects in an ecologically important bivalve in response to changing environments
Authors: Alma Lindsay , McElhany Paul , Crim Ryan N. , Newton Jan A. , Maher Michael , Mickett John B. , Padilla-Gamiño Jacqueline L.
Published: March 2024

Phenotypic plasticity can improve an organism’s fitness when exposed to novel environmental conditions or stress associated with climate change. Our study analyzed spatiotemporal differences in phenotypic plasticity and offspring performance in Olympia oysters Ostrea lurida. This species is an ecosystem engineer and is of great interest for commercial and restoration aquaculture. We used a multidisciplinary approach to examine acute and long-term physiological differences in O. lurida in response to in situ oceanographic conditions in a dynamic inland sea. We outplanted oysters to different areas in Puget Sound, Washington, affixing cages to anchor lines of oceanographic monitoring buoys. This allowed us to couple high-resolution oceanographic data with organism’s phenotypic response. To assess spatiotemporal differences in oyster physiological performance, we collected oysters after six-months and one year of acclimatization at four field sites. During each collection period we evaluated changes in shell properties, diet, metabolism, and reproduction. Adult growth, δ13C and δ15N isotopic signatures, and gametogenesis were affected by both seasonal and environmental conditions. In the winter, oysters from all sites had higher respiration rates when exposed to acute thermal stress, and lower respiration response to acute pH stress. Lipid content, sex ratio and shell strength were unchanged across locations. Offspring growth rates between sites at experimental temperature 20°C closely reflected parental growth rate patterns. Offspring survival was not correlated with growth rates suggesting different energetic trade-offs in oyster offspring. The metabolic response (respiration) of larvae reached its highest point at 20°C but sharply decreased at 25°C. This indicates that larvae are more sensitive to temperature stress, as adults did not exhibit a reduction in metabolic response at 25°C. By deploying genetically similar oysters into distinct environments and employing a wide range of physiological methodologies to examine performance and fitness, our results indicate that Olympia oysters exhibit a high degree of phenotypic plasticity and show evidence of parental carryover.
Mapping seabird vulnerability to offshore wind farms in Norwegian waters
Authors: Fauchald Per , Ollus Victoria Marja Sofia , Ballesteros Manuel , Breistøl Arild , Christensen-Dalsgaard Signe , Molværsmyr Sindre , Tarroux Arnaud , Systad Geir Helge , Moe Børge
Published: March 2024

Introduction

Offshore wind energy development (OWED) has been identified as a major contributor to the aspired growth in Norwegian renewable energy production. Spatially explicit vulnerability assessments are necessary to select sites that minimize the harm to biodiversity, including seabird populations. Distributional data of seabirds in remote areas are scarce, and to identify vulnerable areas, species, and seasons it is necessary to combine data sets and knowledge from different sources.

Methods

In this study, we combined seabird tracking data, data from dedicated coastal and seabird at-sea surveys, and presence-only data from citizen science databases to develop habitat suitability maps for 55 seabird species in four seasons throughout the Norwegian exclusive economic zone; in total 1 million km2 in the Northeast Atlantic. The habitat suitability maps were combined with species-specific vulnerability indicators to yield maps of seabird vulnerability to offshore wind farms (OWFs). The resulting map product can be used to identify the relative vulnerability of areas prospected for OWED with respect to seabird collision and habitat displacement. More detailed assessments can be done by splitting the spatial indicators into seasonal and species-specific components.

Results and discussion

Associated with higher diversity of seabirds near the coast, the cumulative vulnerability indicator showed a strong declining gradient from the coast to offshore waters while the differences in vulnerability between ocean areas and seasons were negligible. Although the present map product represents the best currently available knowledge, the indicators are associated with complex uncertainties related to known and unknown sampling biases. The indicators should therefore be used cautiously, they should be updated regularly as more data become available, and we recommend that more detailed environmental impact assessments based on dedicated seabird surveys, tracking of birds from potentially affected populations and population viability analyses are conducted in areas ultimately selected for OWED.
Enhancing climate change planning and adaptive management in marine protected areas through targets, thresholds, and social-ecological objectives
Authors: Bryce Kaia , Hunter Karen L.
Published: March 2024

Marine Protected Areas (MPAs) are being deployed globally to protect the Earth’s biodiversity in rapidly changing oceans. Nesting climate change considerations within adaptive MPA management and monitoring is becoming a more common approach, and while climate change is increasingly addressed in MPA planning, implementation gaps remain. This study applied the climate robustness index (CRI) to MPA monitoring plans to assess how climate change is outlined within site- and regional-level plans. Previously developed to assess MPA management plans, the CRI scores plans based on their degree of incorporation of climate change adaptation principles, including core elements of adaptive management. We supplemented our CRI findings for monitoring plans by associating index scores of MPAs in the United States with selected MPA traits, as well as by examining specific physical, ecological, and sociological climate change impacts that were being considered within the monitoring scope of a subset of monitoring plans. We found considerable gaps in actionable targets and thresholds in MPA monitoring plans, consistent with a previous study evaluating MPA management plans, demonstrating that the adaptive management cycle is incomplete in many cases. We consider the importance of completing the adaptive management cycle as a core climate adaptation strategy, and explore the roles of social-ecological objectives and local partnerships as avenues to continue to improve MPA outcomes in a changing world.
Aging effects on the encoding/retrieval flip in associative memory: fMRI evidence from incidental contingency learning
Authors: Schneider Else , Rajkovic Marko , Krug Rudolf , Caviezel Marco P. , Reichert Carolin F. , Bieri Oliver , Schmidt André , Borgwardt Stefan , Leyhe Thomas , Linnemann Christoph , Brühl Annette B. , Lang Undine E. , Melcher Tobias
Published: March 2024

Introduction

Associative memory is arguably the most basic memory function and therein constitutes the foundation of all episodic and semantic memory processes. At the same time, the decline of associative memory represents a core feature of age-related cognitive decline in both, healthy and pathological (i.e., dementia-related) aging. The neural mechanisms underlying age-related impairments in associative memory are still not fully understood, especially regarding incidental (i.e., non-intentional) learning.

Methods

We investigated the impact of age on the incidental learning and memory retrieval of face-name combinations in a total sample of 46 young (N = 23; mean age = 23.39 years) and elderly (N = 22, mean age = 69.05 years) participants. More specifically, particular interest was placed in age-related changes in encoding/retrieval (E/R) flips, which denote a neural antagonism of opposed activation patterns in the same brain region during memory encoding and retrieval, which were assessed using fMRI.

Results

According to our hypothesis, the results showed a significant age-related decline in the retrieval performance in the old group. Additionally, at the neural level, we discovered an abolished E/R flip in the right anterior insula and a joint but reduced E/R flip activation magnitude in the posterior middle cingulate cortex in older subjects.

Discussion

In conclusion, the present findings suggest that the impaired neural modulation of the E/R flip in the right aIC might be a sensitive marker in the early detection of neural aging.
Overlapping and distinct phenotypic profiles in Alzheimer’s disease and late onset epilepsy: a biologically-based approach
Authors: Liu Anli A. , Barr William B.
Published: March 2024

Due to shared hippocampal dysfunction, patients with Alzheimer’s dementia and late-onset epilepsy (LOE) report memory decline. Multiple studies have described the epidemiological, pathological, neurophysiological, and behavioral overlap between Alzheimer’s Disease and LOE, implying a bi-directional relationship. We describe the neurobiological decline occurring at different spatial in AD and LOE patients, which may explain why their phenotypes overlap and differ. We provide suggestions for clinical recognition of dual presentation and novel approaches for behavioral testing that reflect an “inside-out,” or biologically-based approach to testing memory. New memory and language assessments could detect—and treat—memory impairment in AD and LOE at an earlier, actionable stage.
Association between oxidative balance score and metabolic syndrome and its components in US adults: a cross-sectional study from NHANES 2011–2018
Authors: Lu Yi , Wang Meixiang , Bao Jiaxin , Chen Dashuang , Jiang Hao
Published: March 2024

Background

Metabolic syndrome (MetS) is a global health concern that threatens human well-being. The oxidative balance score (OBS) is a tool to identify the level of oxidative stress that is correlated with MetS risk. However, association between OBS and MetS and its components has not been reported.

Methods

This cross-sectional study included adult individuals with complete OBS and MetS data from National Health and Nutrition Examination Survey (NHANES) 2011–2018. A weighted logistic regression analysis was conducted to identify the association of the total, dietary, and lifestyle OBS scores with MetS. Subgroup analyses and restricted cubic splines were used to further explore associations.

Results

In total, 10,025 eligible adult individuals (51.48% were males at a median age of 46 years) were included, with a MetS prevalence of 29.98%. In fully adjusted model, higher total OBS was associated with reduced risk of MetS (Q3 vs. Q1: odds ratio [OR] = 0.57, 95% confidence interval [CI], 0.46–0.71, p < 0.001; Q4 vs. Q1: OR = 0.42, 95% CI, 0.33–0.53, p < 0.001; P for trend <0.001). Significant differences were observed in the relationship between dietary OBS and lifestyle OBS and MetS risk (continuous dietary OBS: OR = 0.97, 95% CI, 0.96–0.98, p < 0.001; continuous lifestyle OBS: OR = 0.61, 95% CI, 0.58–0.64, p < 0.001), as well as negative relationship between total OBS and risk of five MetS components (all p < 0.05). Subgroup analysis showed marital status modified the negative association between OBS and MetS in subgroup analysis (P for interaction = 0.014). Moreover, a nonlinear correlation between OBS and MetS (including its components) was found, further elucidating associations (all p < 0.05). Restricted cubic splines demonstrated not obviously U-shape correlation between OBS and MetS components (elevated triglyceride and blood pressure).

Conclusion

This study suggests a strong association between the OBS and MetS and its components. Our data indicated that a higher OBS score was correlated with a decreased risk of MetS and its components in a nonlinear manner. Hence, the OBS may serve as an effective marker for identifying individuals with MetS, with a higher score indicating a predominance of more antioxidants.