bluuebunny/crossref_metadata_2025 huggingface dataset:
PAI-1 as a critical factor in the resolution of sepsis and acute kidney injury in old age
Authors: Bruno Maria E. C. , Mukherjee Sujata , Sturgill Jamie L. , Cornea Virgilius , Yeh Peng , Hawk Gregory S. , Saito Hiroshi , Starr Marlene E.
Published: January 2024

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and levels positively correlate with disease severity and mortality. Our prior work demonstrated that PAI-1 in plasma is positively associated with acute kidney injury (AKI) in septic patients and mice. The objective of this study was to determine if PAI-1 is causally related to AKI and worse sepsis outcomes using a clinically-relevant and age-appropriate murine model of sepsis. Sepsis was induced by cecal slurry (CS)-injection to wild-type (WT, C57BL/6) and PAI-1 knockout (KO) mice at young (5–9 months) and old (18–22 months) age. Survival was monitored for at least 10 days or mice were euthanized for tissue collection at 24 or 48 h post-insult. Contrary to our expectation, PAI-1 KO mice at old age were significantly more sensitive to CS-induced sepsis compared to WT mice (24% vs. 65% survival, p = 0.0037). In comparison, loss of PAI-1 at young age had negligible effects on sepsis survival (86% vs. 88% survival, p = 0.8106) highlighting the importance of age as a biological variable. Injury to the kidney was the most apparent pathological consequence and occurred earlier in aged PAI-1 KO mice. Coagulation markers were unaffected by loss of PAI-1, suggesting thrombosis-independent mechanisms for PAI-1-mediated protection. In summary, although high PAI-1 levels are clinically associated with worse sepsis outcomes, loss of PAI-1 rendered mice more susceptible to kidney injury and death in a CS-induced model of sepsis using aged mice. These results implicate PAI-1 as a critical factor in the resolution of sepsis in old age.
Stimuli-responsive hydrogel based on natural polymers for breast cancer
Authors: Asadi Khatereh , Samiraninezhad Nazafarin , Akbarizadeh Amin Reza , Amini Abbas , Gholami Ahmad
Published: January 2024

Aims: Breast cancer is the most common malignancy among women in both high- and low-resource settings. Conventional breast cancer therapies were inefficient and had low patient compliance. Stimuli-responsive hydrogels possessing similar physicochemical features as soft tissue facilitate diagnostic and therapeutic approaches for breast cancer subtypes.

Scope: Polysaccharides and polypeptides are major natural polymers with unique biocompatibility, biodegradability, and feasible modification approaches utilized frequently for hydrogel fabrication. Alternating the natural polymer-based hydrogel properties in response to external stimuli such as pH, temperature, light, ultrasonic, enzyme, glucose, magnetic, redox, and electric have provided great potential for the evolution of novel drug delivery systems (DDSs) and various advanced technologies in medical applications. Stimuli-responsive hydrogels are triggered by specific cancer tissue features, promote target delivery techniques, and modify release therapeutic agents at localized sites. This narrative review presented innovation in preparing and characterizing the most common stimuli-responsive natural polymer-based hydrogels for diagnostic and therapeutic applications in the breast cancer area.

Conclusion: Stimuli-responsive hydrogels display bioinspiration products as DDSs for breast cancer subtypes, protect the shape of breast tissue, provide modified drug release, enhance therapeutic efficacy, and minimize chemotherapy agents’ side effects. The potential benefits of smart natural polymer-based hydrogels make them an exciting area of practice for breast cancer diagnosis and treatment.
Gut microbiota and its metabolites in non-small cell lung cancer and brain metastasis: from alteration to potential microbial markers and drug targets
Authors: Jiang Haixiao , Zeng Wei , Zhang Xiaoli , Li Yuping , Wang Yilun , Peng Aijun , Cao Demao
Published: January 2024

Background

The elevated mortality rate associated with non–small-cell lung cancer (NSCLC) is a well-established global concern. Considerable attention has been directed toward exploring the association between gut microbiota and various malignant tumors. We herein investigated the associations between the intestinal microbiome and its metabolites, particularly short-chain fatty acids (SCFAs), in patients with NSCLC at different stages, including early and brain metastasis (BM) stages. The findings aim to offer a fresh perspective on the diagnosis and management of NSCLC.

Methods

Fecal samples were collected from 115 participants, comprising healthy controls (n = 35) and patients with treatment-naive NSCLC at the early stage (ELC, n = 40) and the BM stage (n = 40). Characterization of the intestinal microbiome and fecal SCFA levels was performed using 16S rRNA gene sequencing and gas chromatography.

Results

The microbial diversity in patients with NSCLC was found to be less abundant and uniform, particularly in the BM stage. Significant alterations in the community structure of the gut microbiota were observed in patients with NSCLC, with an increase in pathogens in Fusobacteria and Proteobacteria and a decrease in SCFA-producing bacteria in Firmicutes and Actinobacteria, particularly in the BM stage. Meanwhile, microbial communities displayed intricate associations in patients with NSCLC. A biomarker panel (Faecalibacterium, Bifidobacterium, Butyricicoccus, Klebsiella, Streptococcus, and Blautia) successfully distinguished patients in the ELC and BM stages from healthy controls (area under the curve: 0.884). The overall concentration of fecal SCFAs was significantly lower in patients with BM compared to patients with ELC and healthy controls. Subgroup analysis of acetate and butyrate yielded similar results. Moreover, multiple disrupted pathways in the NSCLC group were identified using the Kyoto Encyclopedia of Genes and Genomes annotation, including lipid metabolism and genetic information processing, specifically in the BM stage.

Conclusion

Compared with healthy controls, distinct host-microbe interactions were evident in different phases of patients with NSCLC. Furthermore, specific forms of the gut microbiome and SCFAs may serve as valuable biomarkers and therapeutic targets in the diagnosis and treatment of NSCLC.
Characterization of viral infections in children with influenza-like-illness during December 2018–January 2019
Authors: Chao Shuang , Wang Yuejiao , Wu Baolei , Li Runqing , Dong Jingxiao , Ji Lina , Li Xuejun , Li Ran , Yin Xiaomei , Zhao Xiuying , Liang Wannian
Published: January 2024

Introduction

Respiratory viral infection (RVI) is of very concern after the outbreak of COVID-19, especially in pediatric departments. Learning pathogen spectrum of RVI in children previous the epidemic of COVID-19 could provide another perspective for understanding RVI under current situation and help to prepare for the post COVID-19 infection control.

Methods

A nucleic acid sequence-based amplification (NASBA) assay, with 19 pairs of primers targeting various respiratory viruses, was used for multi-pathogen screening of viral infections in children presenting influenza-like illness (ILI) symptoms. Children with ILI at the outpatient department of Beijing Tsinghua Changgung Hospital during the influenza epidemic from 12/2018 to 01/2019 were included. Throat swabs were obtained for both the influenza rapid diagnostic test (IRDT) based on the colloidal gold immunochromatographic assay and the NASBA assay, targeting various respiratory viruses with an integrated chip technology.

Results and discussion

Of 519 patients, 430 (82.9%) were positive in the NASBA assay. The predominant viral pathogens were influenza A H1N1 pdm1/2009 (pH1N1) (48.4%) and influenza A (H3N2) (18.1%), followed by human metapneumovirus (hMPV) (8.8%) and respiratory syncytial virus (RSV) (6.1%). Of the 320 cases identified with influenza A by NASBA, only 128 (40.0%) were positive in the IRDT. The IRDT missed pH1N1 significantly more frequently than A (H3N2) (P<0.01). Influenza A pH1N1 and A (H3N2) were the major pathogens in <6 years and 6-15 years old individuals respectively (P<0.05). In summary, influenza viruses were the major pathogens in children with ILI during the 2018-2019 winter influenza epidemic, while hMPV and RSV were non-negligible. The coexistence of multiple pathogen leading to respiratory infections is the normalcy in winter ILI cases.
Methods for molecular characterization of dissolved organic matter in the alpine water environment: an overview
Authors: Zhang Yongbao , Du Jianqing , Xiao Kang
Published: January 2024

The alpine area has become a sensitive indicator and amplifier of global climate change and human activities because of its unique geographical and climatic conditions. Being an essential part of biochemical cycling, dissolved organic matter (DOM) could effectively help understand the process, structure, and function of alpine aquatic ecosystems. Due to the low content and sampling difficulties, the analysis of DOM in alpine water demands high sensitivity with low sample volume, which has not been comprehensively reviewed. This review summarizes the DOM sampling, pretreatment, and analysis methods involving the characterization of concentration, spectroscopy, and molecular structure. Overall, conventional parameters are the basis of advanced characterization methods. Spectroscopic tests can reveal the optical properties of DOM in response to lights from ultraviolet to infrared wavelengths, to distinguish the chemical composition. Molecular structure characterizations can provide microscopic information such as functional groups, element ratios, and molecular weights. The combination of multiple methods can depict DOM composition from multiple perspectives. In sum, optimized sampling and pretreatment, high-sensitivity molecular characterization, and method integration are crucial for effectively analyzing DOM components in alpine waters. These perspectives help to standardize the DOM characterization process and to understand the correlation between DOM composition and its properties, as well as the migration and transformation of DOM.
Assessing the existing guidelines of environmental impact assessment and mitigation measures for future hydropower projects in Pakistan
Authors: Butt Asim Qayyum , Shangguan Donghui , Ding Yongjian , Banerjee Abhishek , Sajjad Wasim , Mukhtar Muhammad Ahsan
Published: January 2024

Introduction: More than 16% of the total electricity used worldwide is met by hydropower, having local to regional environmental consequences. With positive indicators that energy is becoming more broadly available and sustainable, the world is moving closer to achieving Sustainable Development Goal 7 (SDG 7). Pakistan became the first nation to include the Sustainable Development Goals (SDGs) in its national development strategy.

Methodology: The current study sought to investigate the structural limits of Environmental Impact Assessment (EIA) guidelines for hydropower development in Pakistan. The study included the document review of the EIA reports about hydropower projects in Pakistan, scientific questionnaires from decision-makers, and public consultation.

Results and Discussion: The document evaluates that an adequate mechanism is available, and donors like the Asian Development Bank and World Bank observe the implementation process of EIA in Pakistan. However, a comprehensive analysis of the EIA system found several things that could be improved, not only in the institutional framework but also in actual implementation and practices. More than 20% of respondent decision-makers disagreed with the compliance of the current Institutional Framework with EIA guidelines, and 25% think that the existing guidelines followed in Pakistan are not aligned with international standards and practices for Hydropower in actual practice. EIA has a limited impact on decision-making due to insufficient technical and financial resources.

Recommendations: There should be a think tank with experts who can meet the needs of present and future epochs. The public should be communicated with and educated about EIA. For better efficiency, the officers and decision-makers should be trained internationally, i.e., the Water and Power Development Authority (WAPDA).
Pathological complete response to neoadjuvant therapy with serplulimab and chemotherapy in stage IIIB small cell lung cancer: a case report and literature review
Authors: Mei Ting , Wang Ting , Lei Chuanfen , Jiang Dan , Zhou Qinghua
Published: January 2024

Chemotherapy combined with immunotherapy has significantly improved survival in patients with extensive-stage small cell lung cancer (ES-SCLC), and neoadjuvant immunotherapy combined with chemotherapy has emerged as the standard treatment for those with resectable non-small cell lung cancer (NSCLC). However, the potential benefits of surgery following neoadjuvant immunotherapy combined with chemotherapy in locally advanced SCLC remain unclear. Herein, we report a patient diagnosed with stage IIIB SCLC, who was administered five cycles of neoadjuvant serplulimab combined with chemotherapy followed by surgery, and subsequently achieved a pathologic complete response (pCR). Within a follow-up duration of six months, the patient displayed neither recurrence nor metastasis and experienced no treatment-related adverse reactions of any grade. Based on this case, for locally advanced SCLC, neoadjuvant serplulimab combined with chemotherapy followed by surgery may present an effective, safe, and potentially curative treatment strategy. Nonetheless, further prospective studies are needed to verify our findings.
Inhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING
Authors: Pinjusic Katarina , Ambrosini Giovanna , Lourenco Joao , Fournier Nadine , Iseli Christian , Guex Nicolas , Egorova Olga , Nassiri Sina , Constam Daniel B.
Published: January 2024

The transforming growth factor-β (TGF-β) family member activin A (hereafter Activin-A) is overexpressed in many cancer types, often correlating with cancer-associated cachexia and poor prognosis. Activin-A secretion by melanoma cells indirectly impedes CD8+ T cell-mediated anti-tumor immunity and promotes resistance to immunotherapies, even though Activin-A can be proinflammatory in other contexts. To identify underlying mechanisms, we here analyzed the effect of Activin-A on syngeneic grafts of Braf mutant YUMM3.3 mouse melanoma cells and on their microenvironment using single-cell RNA sequencing. We found that the Activin-A-induced immune evasion was accompanied by a proinflammatory interferon signature across multiple cell types, and that the associated increase in tumor growth depended at least in part on pernicious STING activity within the melanoma cells. Besides corroborating a role for proinflammatory signals in facilitating immune evasion, our results suggest that STING holds considerable potential as a therapeutic target to mitigate tumor-promoting Activin-A signaling at least in melanoma.
Nucleated red blood cells are a late biomarker in predicting intensive care unit mortality in patients with COVID-19 acute respiratory distress syndrome: an observational cohort study
Authors: Schmidt Götz , Martens Arnd , Koch Christian , Markmann Melanie , Schneck Emmanuel , Matt Ulrich , Hecker Matthias , Tello Khodr , Wolff Matthias , Sander Michael , Vadász István
Published: January 2024

Background

Nucleated red blood cells (nRBC) are precursor cells of the erythropoiesis that are absent from the peripheral blood under physiological conditions. Their presence is associated with adverse outcomes in critically ill patients. This study aimed to evaluate the predictive value of nRBC on mortality in intensive care unit (ICU) patients with COVID-19 acute respiratory distress syndrome (ARDS).

Material and methods

This retrospective, observational cohort study analyzed data on 206 ICU patients diagnosed with COVID-19 ARDS between March 2020 and March 2022. The primary endpoint was ICU mortality, and secondary endpoints included ICU and hospital stay lengths, ventilation hours, and the time courses of disease severity scores and clinical and laboratory parameters.

Results

Among the included patients, 68.9% tested positive for nRBC at least once during their ICU stay. A maximum nRBC of 105 µl-1 had the highest accuracy in predicting ICU mortality (area under the curve of the receiver operating characteristic [AUCROC] 0.780, p < 0.001, sensitivity 69.0%, specificity 75.5%). Mortality was significantly higher among patients with nRBC >105 µl-1 than ≤105 µl-1 (86.5% vs. 51.3%, p = 0.008). Compared to patients negative for nRBC in their peripheral blood, those positive for nRBC required longer mechanical ventilation (127 [44 - 289] h vs. 517 [255 - 950] h, p < 0.001), ICU stays (12 [8 – 19] vs. 27 [13 – 51] d, p < 0.001), and hospital stays (19 [12 - 29] d vs. 31 [16 - 58] d, p < 0.001). Peak Sepsis-related Organ Failure Assessment (SOFA), Simplified Acute Physiology Score, PaO2/FiO2, interleukin-6, and procalcitonin values were reached before the peak nRBC level. However, the predictive performance of the SOFA (AUCROC 0.842, p < 0.001) was considerably improved when a maximum SOFA score >8 and nRBC >105 µl-1 were combined.

Discussion

nRBC predict ICU mortality and indicate disease severity among patients with COVID-19 ARDS, and they should be considered a clinical alarm signal for a worse outcome. nRBC are a late predictor of ICU mortality compared to other established clinical scoring systems and laboratory parameters but improve the prediction accuracy when combined with the SOFA score.
Gasdermins: a dual role in pyroptosis and tumor immunity
Authors: Yang Jiayi , Jiang Jingting
Published: January 2024

The gasdermin (GSDM) protein family plays a pivotal role in pyroptosis, a process critical to the body’s immune response, particularly in combatting bacterial infections, impeding tumor invasion, and contributing to the pathogenesis of various inflammatory diseases. These proteins are adept at activating inflammasome signaling pathways, recruiting immune effector cells, creating an inflammatory immune microenvironment, and initiating pyroptosis. This article serves as an introduction to the GSDM protein-mediated pyroptosis signaling pathways, providing an overview of GSDMs’ involvement in tumor immunity. Additionally, we explore the potential applications of GSDMs in both innovative and established antitumor strategies.
Genomic and phenotypic characterization of multidrug-resistant Salmonella enterica serovar Reading isolates involved in a turkey-associated foodborne outbreak
Authors: Sivasankaran Sathesh K. , Bearson Bradley L. , Trachsel Julian M. , Nielsen Daniel W. , Looft Torey , Bearson Shawn M. D.
Published: January 2024

Salmonella is a global bacterial foodborne pathogen associated with a variety of contaminated food products. Poultry products are a common source of Salmonella-associated foodborne illness, and an estimated 7% of human illnesses in the United States are attributed to turkey products. From November 2017 to March 2019, the Centers for Disease Control and Prevention reported a turkey-associated outbreak of multidrug-resistant (MDR; resistant to ≥3 antimicrobial classes) Salmonella enterica serovar Reading (S. Reading) linked to 358 human infections in 42 US states and Canada. Since S. Reading was seldom linked to human illness prior to this outbreak, the current study compared genomic sequences of S. Reading isolates prior to the outbreak (pre-outbreak) to isolates identified during the outbreak period, focusing on genes that were different between the two groups but common within a group. Following whole-genome sequence analysis of five pre-outbreak and five outbreak-associated turkey/turkey product isolates of S. Reading, 37 genes located within two distinct chromosomal regions were identified only in the pre-outbreak isolates: (1) an ~5 kb region containing four protein-coding genes including uidA which encodes beta-glucuronidase, pgdA encoding peptidoglycan deacetylase, and two hypothetical proteins and (2) an ~28 kb region comprised of 32 phage-like genes and the xerC gene, which encodes tyrosine recombinase (frequently associated with phage genes). The five outbreak isolates also had a deletional event within the cirA gene, introducing a translational frame shift and premature stop codon. The cirA gene encodes a protein with dual receptor functions: a siderophore receptor for transport of dihydroxybenzoylserine as well as a colicin Ia/b receptor. Significant differences for the identified genetic variations were also detected in 75 S. Reading human isolates. Of the 41 S. Reading isolates collected before or in 2017, 81 and 90% of the isolates contained the uidA and pgdA genes, respectively, but only 24% of the isolates collected after 2017 harbored the uidA and pgdA genes. The truncation event within the cirA gene was also significantly higher in isolates collected after 2017 (74%) compared to before or in 2017 (5%). Phenotypic analysis of the S. Reading isolates for colicin and cefiderocol sensitivities (CirA) and β-methyl-D-glucuronic acid utilization (UidA and accessory proteins) supported the genomic data. Overall, a similar genome reduction pattern was generally observed in both the turkey and human isolates of S. Reading during the outbreak period, and the genetic differences were present in genes that could potentially promote pathogen dissemination due to variation in Salmonella colonization, fitness, and/or virulence.
Navigating the brain: the role of exosomal shuttles in precision therapeutics
Authors: Fatima Shaheera , Qaiser Ariba , Andleeb Saadia , Hashmi Asraf Hussain , Manzoor Sobia
Published: January 2024

Brain diseases have become one of the leading roots of mortality and disability worldwide, contributing a significant part of the disease burden on healthcare systems. The blood-brain barrier (BBB) is a primary physical and biological obstacle that allows only small molecules to pass through it. Its selective permeability is a significant challenge in delivering therapeutics into the brain for treating brain dysfunction. It is estimated that only 2% of the new central nervous system (CNS) therapeutic compounds can cross the BBB and achieve their therapeutic targets. Scientists are exploring various approaches to develop effective cargo delivery vehicles to promote better therapeutics targeting the brain with minimal off-target side effects. Despite different synthetic carriers, one of the natural brain cargo delivery systems, “exosomes,” are now employed to transport drugs through the BBB. Exosomes are naturally occurring small extracellular vesicles (EVs) with unique advantages as a therapeutic delivery system for treating brain disorders. They have beneficial innate aspects of biocompatibility, higher stability, ability to cross BBB, low cytotoxicity, low immunogenicity, homing potential, targeted delivery, and reducing off-site target effects. In this review, we will discuss the limitations of synthetic carriers and the utilization of naturally occurring exosomes as brain-targeted cargo delivery vehicles and highlight the methods for modifying exosome surfaces and drug loading into exosomes. We will also enlist neurodegenerative disorders targeted with genetically modified exosomes for their treatment.
Unraveling the gut health puzzle: exploring the mechanisms of butyrate and the potential of High-Amylose Maize Starch Butyrate (HAMSB) in alleviating colorectal disturbances
Authors: Cheng Junrui , Zhou Jing
Published: January 2024

Colorectal disturbances encompass a variety of disorders that impact the colon and rectum, such as colitis and colon cancer. Butyrate, a short-chain fatty acid, plays a pivotal role in supporting gut health by nourishing colonocytes, promoting barrier function, modulating inflammation, and fostering a balanced microbiome. Increasing colorectal butyrate concentration may serve as a critical strategy to improve colon function and reduce the risk of colorectal disturbances. Butyrylated high-amylose maize starch (HAMSB) is an edible ingredient that efficiently delivers butyrate to the colon. HAMSB is developed by esterifying a high-amylose starch backbone with butyric anhydride. With a degree of substitution of 0.25, each hydroxy group of HAMSB is substituted by a butyryl group in every four D-glucopyranosyl units. In humans, the digestibility of HAMSB is 68% (w/w), and 60% butyrate molecules attached to the starch backbone is absorbed by the colon. One clinical trial yielded two publications, which showed that HAMSB significantly reduced rectal O6-methyl-guanine adducts and epithelial proliferation induced by the high protein diet. Fecal microbial profiles were assessed in three clinical trials, showing that HAMSB supplementation was consistently linked to increased abundance of Parabacteroides distasonis. In animal studies, HAMSB was effective in reducing the risk of diet- or AOM-induced colon cancer by reducing genetic damage, but the mechanisms differed. HAMSB functioned through affecting cecal ammonia levels by modulating colon pH in diet-induced cancer, while it ameliorated chemical-induced colon cancer through downregulating miR19b and miR92a expressions and subsequently activating the caspase-dependent apoptosis. Furthermore, animal studies showed that HAMSB improved colitis via regulating the gut immune modulation by inhibiting histone deacetylase and activating G protein-coupled receptors, but its role in bacteria-induced colon colitis requires further investigation. In conclusion, HAMSB is a food ingredient that may deliver butyrate to the colon to support colon health. Further clinical trials are warranted to validate earlier findings and determine the minimum effective dose of HAMSB.
A prognostic model based on DNA methylation-related gene expression for predicting overall survival in hepatocellular carcinoma
Authors: Luo Jin , Zhu Wan-Cui , Chen Qiu-Xia , Yang Chang-Fu , Huang Bi-Jun , Zhang Shi-Jun
Published: January 2024

Background

Hepatocellular carcinoma (HCC) continues to increase in morbidity and mortality among all types of cancer. DNA methylation, an important epigenetic modification, is associated with cancer occurrence and progression. The objective of this study was to establish a model based on DNA methylation risk scores for identifying new potential therapeutic targets in HCC and preventing cancer progression.

Methods

Transcriptomic, clinical, and DNA methylation data on 374 tumor tissues and 50 adjacent normal tissues were downloaded from The Cancer Genome Atlas–Liver Hepatocellular Carcinoma database. The gene expression profiles of the GSE54236 liver cancer dataset, which contains data on 161 liver tissue samples, were obtained from the Gene Expression Omnibus database. We analyzed the relationship between DNA methylation and gene expression levels after identifying the differentially methylated and expressed genes. Then, we developed and validated a risk score model based on the DNA methylation-driven genes. A tissue array consisting of 30 human hepatocellular carcinoma samples and adjacent normal tissues was used to assess the protein and mRNA expression levels of the marker genes by immunohistochemistry and qRT-PCR, respectively.

Results

Three methylation-related differential genes were identified in our study: GLS, MEX3B, and GNA14. The results revealed that their DNA methylation levels were negatively correlated with local gene expression regulation. The gene methylation levels correlated strongly with the prognosis of patients with liver cancer. This was confirmed by qRT-PCR and immunohistochemical verification of the expression of these genes or proteins in tumors and adjacent tissues. These results revealed the relationship between the level of relevant gene methylation and the prognosis of patients with liver cancer as well as the underlying cellular and biological mechanisms. This allows our gene signature to provide more accurate and appropriate predictions for clinical applications.

Conclusion

Through bioinformatics analysis and experimental validation, we obtained three DNA methylation marker: GLS, MEX3B, and GNA14. This helps to predict the prognosis and may be a potential therapeutic target for HCC patients.
HMGA2 promotes nasopharyngeal carcinoma progression and is associated with tumor resistance and poor prognosis
Authors: Ouyang Xinting , Li Kangxin , Wang Jiaqi , Zhu Weijian , Yi Qiang , Zhong Jinghua
Published: January 2024

Nasopharyngeal carcinoma (NPC), as one of the most prevalent malignancies in the head and neck region, still lacks a complete understanding of its pathogenesis. Presently, radiotherapy, concurrent chemoradiotherapy, and targeted therapy stand as the primary modalities for treating NPC. With advancements in medicine, the cure rates for nasopharyngeal carcinoma have been steadily increasing. Nevertheless, recurrence and metastasis persist as the primary reasons for treatment failure. Consequently, a profound exploration of the molecular mechanisms underlying the occurrence and progression of nasopharyngeal carcinoma, along with the exploration of corresponding therapeutic approaches, becomes particularly imperative in the quest for comprehensive solutions to combat this disease. High mobility group AT-hook 2 (HMGA2) is a pivotal protein capable of altering chromatin structure, regulating gene expression, and influencing transcriptional activity. In the realm of cancer research, HMGA2 exhibits widespread dysregulation, playing a crucial role in nearly all malignant tumors. It is implicated in various tumorigenic processes, including cell cycle regulation, cell proliferation, epithelial-mesenchymal transition, angiogenesis, tumor invasion, metastasis, and drug resistance. Additionally, HMGA2 serves as a molecular marker and an independent prognostic factor in certain malignancies. Recent studies have increasingly unveiled the critical role of HMGA2 in nasopharyngeal carcinoma (NPC), particularly in promoting malignant progression, correlating with tumor resistance, and serving as an independent adverse prognostic factor. This review focuses on elucidating the oncogenic role of HMGA2 in NPC, suggesting its potential association with chemotherapy resistance in NPC, and proposing its candidacy as an independent factor in nasopharyngeal carcinoma prognosis assessment.
In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations
Authors: Al Awadh Ahmed Abdullah , Sakagami Hiroshi , Amano Shigeru , Sayed Ahmed M. , Abouelela Mohamed E. , Alhasaniah Abdulaziz Hassan , Aldabaan Nayef , Refaey Mohamed S. , Abdelhamid Reda A. , Khalil Heba M. A. , Hamdan Dalia I. , Abdel-Sattar El-Shaymaa , Orabi Mohamed A. A.
Published: January 2024

Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC50 = 51.8 and 40.1 μg/mL, respectively), which is relatively the same effect as 5-FU at CC50 = 69.4 μM and melphalan at CC50 = 36.3 μM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 μg/mL) exerted morphological changes and induced subG1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D (18) and O (12), and the flavonoid kaempferol (11). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera’s potential as an affordable source of therapeutic agents for a range of oral malignancies.
Insights into the differences related to the resistance mechanisms to the highly toxic fruit Hippomane mancinella (Malpighiales: Euphorbiaceae) between the larvae of the sister species Anastrepha acris and Anastrepha ludens (Diptera: Tephritidae) through comparative transcriptomics
Authors: García-Saldaña Essicka A. , Cerqueda-García Daniel , Ibarra-Laclette Enrique , Aluja Martín
Published: January 2024

The Manchineel, Hippomane mancinella (“Death Apple Tree”) is one of the most toxic fruits worldwide and nevertheless is the host plant of the monophagous fruit fly species Anastrepha acris (Diptera: Tephritidae). Here we aimed at elucidating the detoxification mechanisms in larvae of A. acris reared on a diet enriched with the toxic fruit (6% lyophilizate) through comparative transcriptomics. We compared the performance of A. acris larvae with that of the sister species A. ludens, a highly polyphagous pest species that is unable to infest H. mancinella in nature. The transcriptional alterations in A. ludens were significantly greater than in A. acris. We mainly found two resistance mechanisms in both species: structural, activating cuticle protein biosynthesis (chitin-binding proteins likely reducing permeability to toxic compounds in the intestine), and metabolic, triggering biosynthesis of serine proteases and xenobiotic metabolism activation by glutathione-S-transferases and cytochrome P450 oxidoreductase. Some cuticle proteins and serine proteases were not orthologous between both species, suggesting that in A. acris, a structural resistance mechanism has been selected allowing specialization to the highly toxic host plant. Our results represent a nice example of how two phylogenetically close species diverged over recent evolutionary time related to resistance mechanisms to plant secondary metabolites.
A 16-week school-based intervention improves physical fitness in Slovenian children: a randomized controlled trial
Authors: Petrušič Tanja , Novak Dario
Published: January 2024

Introduction: The aim of this study was to evaluate the effects of a 16-week school-based physical activity (PA) intervention on physical fitness (PF) (speed, hand-eye coordination, flexibility) of 8– to 9-year-olds.

Methods: A total of seventy-eight boys and girls (boys: n = 45, aged 8.4 ± 4.9 years; girls: n = 42, aged 8.6 ± 0.5 years) from a school in Slovenia were randomly assigned to either a group with an after-school PA program (EXP) or a control group (CON) that participated exclusively in mandatory physical education (PE). The EXP group engaged in the extracurricular PA program for 60 min twice a week for 16 weeks, concurrent with regular PE classes. The program primarily involved elementary PE games that included elements of athletics (e.g., skipping, push- off running, hopping, crossstepping, and jumping) and gymnastics (e.g., handstand, forward roll, backward roll, hand support jumps, squat jump on a vault box, climbing on horizontal bars, incline benches and ropes, crawling, and jumping rope). Standardized tests appropriate for this age group were used to assess PF, including the sit and reach test (SAR), the 30-meter sprint, and the alternate hand wall toss test at distances of 1.0 and 2.0 m (AHWT 1.0 and 2.0).

Results: There was a significant group-time interaction for SAR test (EXP group increase: +1.6 cm, +6.3%; CON group decrease: −0.1 cm, −0.4%; p < 0.001, ηp2 = 0.361), and the 30 m sprint (EXP group improvement: −0.4 s, −6.3%; CON group decrease: +0.1 s, +1.6%; p < 0.001, ηp2 = 0.193). Similarly, the EXP group improved by +2.1 points (+25.6%) in the 1.0 m wall throw with the alternating hand, while the CON group showed only minimal changes (−0.2 points, −2.4%; p < 0.001, ηp2 = 0.545). No significant interaction was found for the 2.0 m toss (EXP and CON group both −0.1 points, −2.6%; p = 0.888, ηp2 = 0.001). Post-hoc analyses with paired t-tests revealed that the EXP group showed significant improvements in SAR test (p < 0.001), 30 m sprint (p < 0.001) and AHWT 1.0 test (p < 0.001), while the CON group showed no significant changes in SAR test (p = 0.533), 30 m sprint (p = 0.150), AHWT 1.0 test (p = 0.186) and AHWT 2.0 test (p = 0.430).

Discussion: The results of the study showed that the extracurricular program with only two additional weekly sessions significantly improved the components of PF in 8- to 9-year olds. Significant improvements were observed in the areas of flexibility, speed and coordination, as shown in the SAR test, 30-meter sprint and 1.0-meter handwall toss tests. However, no similar improvements were observed in the 2.0-meter handwall toss, which illustrates the specific areas of impact of the program.
Recentering responsible and explainable artificial intelligence research on patients: implications in perinatal psychiatry
Authors: Turchioe Meghan Reading , Hermann Alison , Benda Natalie C.
Published: January 2024

In the setting of underdiagnosed and undertreated perinatal depression (PD), Artificial intelligence (AI) solutions are poised to help predict and treat PD. In the near future, perinatal patients may interact with AI during clinical decision-making, in their patient portals, or through AI-powered chatbots delivering psychotherapy. The increase in potential AI applications has led to discussions regarding responsible AI and explainable AI (XAI). Current discussions of RAI, however, are limited in their consideration of the patient as an active participant with AI. Therefore, we propose a patient-centered, rather than a patient-adjacent, approach to RAI and XAI, that identifies autonomy, beneficence, justice, trust, privacy, and transparency as core concepts to uphold for health professionals and patients. We present empirical evidence that these principles are strongly valued by patients. We further suggest possible design solutions that uphold these principles and acknowledge the pressing need for further research about practical applications to uphold these principles.
Sexual harassment exposure among junior high school students in Norway: prevalence and associated factors
Authors: Bonsaksen Tore , Steigen Anne Mari , Granrud Marie Dahlen , Dangmann Cecilie Ruud , Stea Tonje Holte
Published: January 2024

Background

Sexual harassment is common in most countries and cultures. Less is known about sexual harassment, its risk factors, and psychosocial outcomes among young adolescents. The aim of the study was to examine the 12-month prevalence of sexual harassment exposure, and sociodemographic and psychosocial factors associated with exposure among junior high school students in Norway.

Methods

A comprehensive cross-sectional study was completed by 83,297 Norwegian adolescents in junior high school in 2021. Data on exposure to sexual harassment were used in combination with sociodemographic measures and psychosocial outcomes: depressive symptoms, loneliness, self-esteem, and well-being. Group differences were analyzed with Chi Square tests, and sociodemographic risk factors were analyzed with logistic regression. Psychosocial outcomes were assessed with multivariate and univariate ANOVAs, and dose–response relationships were assessed with linear regression.

Results

Among the adolescents, 32.6% had experienced sexual harassment during the past year. Girls had higher odds of exposure (OR: 1.90, 95% CI: 1.84–1.96), whereas adolescents whose parents had higher education had lower odds (OR: 0.95, 95% CI: 0.90–0.99). Exposure was associated with higher levels of depressive symptoms (partial η2 [ES] = 0.11) and loneliness (ES = 0.07), and with lower self-esteem (ES = 0.06) and well-being (ES = 0.06). Among exposed adolescents, more frequent exposure was associated with poorer outcomes.

Conclusion

Exposure to sexual harassment affects one third of junior high school students in Norway. Those who are exposed have poorer psychosocial outcomes, and there is a dose–response relationship between exposure and outcomes. Awareness of sexual harassment among young adolescents, and interventions to prevent and reduce it, are needed.
Gravitationally decoupled charged anisotropic solutions in Rastall gravity
Authors: Sadiq Sobia , Waseem Arfa , Javed Faisal , Errehymy Abdelghani , Abdel-Aty Abdel-Haleem
Published: January 2024

This paper develops the stellar interior geometry for charged anisotropic spherical matter distribution by developing an exact solution of the field equations of Rastall gravity using the notion of gravitational decoupling. The main purpose of this investigation is the extension of the well-known isotropic model within the context of charged isotropic Rastall gravity solutions. The second aim of this work is to apply gravitational decoupling via a minimal geometric deformation scheme in Rastall gravity. Finally, the third one is to derive an anisotropic version of the charged isotropic model previously obtained by applying gravitational decoupling technology. We construct the field equations which are divided into two sets by employing the geometric deformation in radial metric function. The first set corresponds to the seed (charged isotropic) source, while the other one relates the deformation function with an extra source. We choose a known isotropic solution for spherical matter configuration including electromagnetic effects and extend it to an anisotropic model by finding the solution of the field equations associated with a new source. We construct two anisotropic models by adopting some physical constraints on the additional source. To evaluate the unknown constants, we use the matching of interior and exterior spacetimes. We investigate the physical feasibility of the constructed charged anisotropic solutions by the graphical analysis of the metric functions, density, pressure, anisotropy parameter, energy conditions, stability criterion, mass function, compactness, and redshift parameters. For the considered choice of parameters, it is concluded that the developed solutions are physically acceptable as all the physical aspects are well-behaved.
Pedestrian Detection Based on Feature Enhancement in Complex Scenes
Authors: Su Jiao , An Yi , Wu Jialin , Zhang Kai
Published: January 2024

Pedestrian detection has always been a difficult and hot spot in computer vision research. At the same time, pedestrian detection technology plays an important role in many applications, such as intelligent transportation and security monitoring. In complex scenes, pedestrian detection often faces some challenges, such as low detection accuracy and misdetection due to small target sizes and scale variations. To solve these problems, this paper proposes a pedestrian detection network PT-YOLO based on the YOLOv5. The pedestrian detection network PT-YOLO consists of the YOLOv5 network, the squeeze-and-excitation module (SE), the weighted bi-directional feature pyramid module (BiFPN), the coordinate convolution (coordconv) module and the wise intersection over union loss function (WIoU). The SE module in the backbone allows it to focus on the important features of pedestrians and improves accuracy. The weighted BiFPN module enhances the fusion of multi-scale pedestrian features and information transfer, which can improve fusion efficiency. The prediction head design uses the WIoU loss function to reduce the regression error. The coordconv module allows the network to better perceive the location information in the feature map. The experimental results show that the pedestrian detection network PT-YOLO is more accurate compared with other target detection methods in pedestrian detection and can effectively accomplish the task of pedestrian detection in complex scenes.
Efficient Multi-Objective Simulation Metamodeling for Researchers
Authors: Ho Ken Jom , Özcan Ender , Siebers Peer-Olaf
Published: January 2024

Solving multiple objective optimization problems can be computationally intensive even when experiments can be performed with the help of a simulation model. There are many methodologies that can achieve good tradeoffs between solution quality and resource use. One possibility is using an intermediate “model of a model” (metamodel) built on experimental responses from the underlying simulation model and an optimization heuristic that leverages the metamodel to explore the input space more efficiently. However, determining the best metamodel and optimizer pairing for a specific problem is not directly obvious from the problem itself, and not all domains have experimental answers to this conundrum. This paper introduces a discrete multiple objective simulation metamodeling and optimization methodology that allows algorithmic testing and evaluation of four Metamodel-Optimizer (MO) pairs for different problems. For running our experiments, we have implemented a test environment in R and tested four different MO pairs on four different problem scenarios in the Operations Research domain. The results of our experiments suggest that patterns of relative performance between the four MO pairs tested differ in terms of computational time costs for the four problems studied. With additional integration of problems, metamodels and optimizers, the opportunity to identify ex ante the best MO pair to employ for a general problem can lead to a more profitable use of metamodel optimization.
Neurobiology of Pathogen Avoidance and Mate Choice: Current and Future Directions
Authors: Cantini Dante , Choleris Elena , Kavaliers Martin
Published: January 2024

Animals are under constant threat of parasitic infection. This has influenced the evolution of social behaviour and has strong implications for sexual selection and mate choice. Animals assess the infection status of conspecifics based on various sensory cues, with odours/chemical signals and the olfactory system playing a particularly important role. The detection of chemical cues and subsequent processing of the infection threat that they pose facilitates the expression of disgust, fear, anxiety, and adaptive avoidance behaviours. In this selective review, drawing primarily from rodent studies, the neurobiological mechanisms underlying the detection and assessment of infection status and their relations to mate choice are briefly considered. Firstly, we offer a brief overview of the aspects of mate choice that are relevant to pathogen avoidance. Then, we specifically focus on the olfactory detection of and responses to conspecific cues of parasitic infection, followed by a brief overview of the neurobiological systems underlying the elicitation of disgust and the expression of avoidance of the pathogen threat. Throughout, we focus on current findings and provide suggestions for future directions and research.