bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of noradrenergic inhibition on neuroinflammation and pathophysiology in mouse models of Alzheimer’s disease
Authors: Evans Andrew K. , Park Heui Hye , Woods Claire E. , Lam Rachel K. , Rijsketic Daniel Ryskamp , Xu Christine , Chu Emily K. , Ciari Peter , Blumenfeld Sarah , Vidano Laura M. , Saw Nay Lui , Heifets Boris D. , Shamloo Mehrdad 
Published: December 2024

AbstractNorepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty and stress, and it also regulates neuroinflammation. We previously demonstrated behavioral and immunomodulatory effects of beta-adrenergic pharmacology in mouse models of Alzheimer’s disease (AD). The current studies were designed to block noradrenergic signaling in 5XFAD mice through (1) chemogenetic inhibition of the locus coeruleus (LC), (2) pharmacologic blocking of β-adrenergic receptors, and (3) conditional deletion of β1- or β2-adrenergic receptors (adrb1 or adrb2) in microglia.First, brain-wide AD pathology was mapped in 3D by imaging immunolabeled, cleared 5XFAD brains to assess the overlap between amyloid beta (Aβ) pathology, reactive microglia, and the loss of tyrosine hydroxylase (TH) expression in the catecholaminergic system. To examine the effects of inhibiting the LC NE system in the 5XFAD model, inhibitory (Gi) DREADD receptors were expressed specifically in LC NE neurons. LC NE neurons were chronically inhibited through the subcutaneous pump administration of the DREADD agonist clozapine-N-oxide (CNO). Plasma and brains were collected for assessment of neuroinflammation and pathology. A separate cohort of 5XFAD mice was chronically dosed with the beta-adrenergic antagonist propranolol or vehicle and evaluated for behavior, as well as post-mortem neuroinflammation and pathology. Finally, we used 5XFAD mice with conditional deletion of either adrb1 or adrb2 in microglia to assess neuroinflammation and pathology mediated by β-adrenergic signaling.Using iDISCO+, light sheet fluorescence microscopy, and novel analyses, we detected widespread microgliosis and Aβ pathology, along with modest TH downregulation in fibers across multiple brain regions, in contrast to the spatially limited TH downregulation observed in neurons. Both chemogenetic inhibition of LC adrenergic signaling and pharmacological inhibition of beta-adrenergic receptors potentiated neuroinflammation without altering Aβ pathology. Conditional deletion of adrb1 in microglia did not affect neuroinflammation. Conditional deletion of adrb2 in microglia attenuated inflammation and pathology in females but had no effect in males. Overall, these data support previous observations demonstrating the immunomodulatory effects of beta-adrenergic signaling in the pathophysiology of brain disorders and suggest that adrenergic receptors on cell types other than microglia, such as astrocytes, may mediate some of the disease-modifying effects of β-adrenergic agonists in the brain.
Barriers to advancing the sexual and reproductive health agenda in Latin America: a qualitative study of key informants’ perspectives
Authors: Alonso Juan Pedro , Cejas Cintia , Berrueta Mabel , Vazquez Paula , Perrotta Gabriela , Formia Sandra , Pirsch Sofía , Ballivian Jamile , Zavala Denise , López Analía , Belizán María 
Published: December 2024

Abstract
Background
The effective attainment of sexual, reproductive, and maternal health and rights (SRMHR) requires a holistic life-course approach. This approach should address disparities in healthcare access and rights, guarantee the delivery of high-quality care devoid of discrimination, and underscore rigorous accountability mechanisms throughout the implementation process. Latin American and Caribbean (LAC) countries face significant disparities in SRMHR within and between nations. Vulnerable populations, such as indigenous communities, Afro-descendants, LGBTQI + population, persons with disabilities, older adults, and migrants, often endure discrimination and stigmatization, severely impacting their access to healthcare and health rights. This paper presents the findings from the qualitative component of a broader mixed-methods scoping study aimed at establishing a priority research agenda to address healthcare gaps affecting the SRMHR of vulnerable populations. The qualitative component focused on identifying key challenges hindering progress in SRMHR and access to health services for these populations in the LAC region, drawing on the perspectives of key informants at both regional and national levels.

Methods
Qualitative research approach employing semi-structured interviews with key informants. A purposive sample comprised of stakeholders from relevant regional organizations and local stakeholders in selected countries (Argentina, Colombia, Peru, Mexico, Guatemala, Jamaica, and Guyana), encompassing government representatives, civil organizations, and academia. A rapid content thematic analysis was conducted to analyze the data obtained from the interviews.

Results
We interviewed 27 key informants in SRMHR, six at a regional level and 21 at a country level. The region faces barriers around establishing and sustaining agency agendas, such as a lack of political will, political instability, and opposition from civil society groups regarding SRMHR agendas. Policy implementation presents difficulties due to insufficient and unstable funding, weaknesses in sexual and reproductive health programs, unequal policy implementation in federal countries, and the absence of evidence-based policies. The lack of high-quality data and quality indicators poses obstacles, leading to limitations in evidence generation. Access to SRMHR services faces barriers such as the low-quality provision of services, discrepancies between legislation and effective access, insufficient healthcare resources, and resistance from certain healthcare providers.

Conclusion
Addressing these multifaceted challenges will be crucial in advancing the agenda of sexual, reproductive, and maternal health rights and ensuring effective access to health services for the most vulnerable populations in the LAC region.
Outcomes of definitive radiotherapy vs. laryngectomy followed by adjuvant radiotherapy in patients with locally advanced laryngeal squamous cell carcinoma: real-world experience in a referral cancer center
Authors: Kazemian Ali , Esmati Ebrahim , Ghalehtaki Reza , Farazmand Borna , Mousavi-Darzikolaee Nima , Bayani Reyhaneh , Razmkhah Mahdieh , Taherioun Maryam , Saeedi Niloufar , Heidari Farrokh , Zakeri Kaveh 
Published: December 2024

Abstract
Background
Laryngeal cancer is a common head and neck cancer. Surgical treatment can impair patients’ voice and swallowing function, making definitive radiotherapy a viable alternative for locally advanced cases.

Methods
To compare the outcomes of definitive versus adjuvant radiotherapy in patients with primary locally advanced laryngeal cancer, we retrospectively evaluated consecutive patients treated from 2007 to 2020. We assessed and compared the median and 3-year overall survival (OS), disease-free survival (DFS), distant metastasis control (DMC), and local recurrence-free survival (LRC) in all patients and in T4 patients exclusively.

Results
One hundred patients were studied, including definitive (N = 64) and adjuvant (N = 36) radiotherapy. The median follow-up was 29 months. Overall, the median OS in the definitive vs. adjuvant group was 100 months (95%CI = 46.5-153.5) vs. not reached, respectively (log-rank P = 0.506). The median DFS in the definitive vs. adjuvant group was 20 months (95%CI = 7.7–32.3) vs. not reached, respectively (log-rank P = 0.148). Three-year OS and DFS rates in all patients were 64% (95%CI: 48–78) vs. 75% (95%CI: 55–95) and 43% (95%CI:29–57) vs. 61% (95%CI: 41–81) in the definitive vs. adjuvant groups, respectively. Among T4 patients, the median OS in the definitive RT group vs. adjuvant group was not reached vs. 48 (95%CI = 0-105.3), respectively (log-rank P = 0.788). The median DFS in the definitive RT group vs. adjuvant group was 12 months (95%CI = 9.34–14.65) vs. 36 months (95%CI = 4.4–67.5), respectively (log-rank P = 0.868). Three-year OS and DFS rates were 71% (95%CI: 42–100) vs. 75% (95%CI: 50–100) and 40% (95%CI:21–79) vs. 56% (95%CI: 25–87) in the definitive vs. adjuvant groups, respectively.

Conclusions
Our analysis suggests that definitive radiotherapy in laryngeal cancer does not lead to a poorer outcome than total laryngectomy followed by adjuvant radiotherapy. In T4 patients, our findings should reassure clinicians and patients about the viability of definitive radiotherapy as a treatment approach.
Automated age grading of female Culex pipiens by an optical sensor system coupled to a mosquito trap
Authors: González Pérez María I. , Faulhaber Bastian , Williams Mark , Encarnaçao Joao , Villalonga Pancraç , Aranda Carles , Busquets Núria 
Published: December 2024

Abstract
Background
The age distribution of a mosquito population is a major determinant of its vectorial capacity. To contribute to disease transmission, a competent mosquito vector, carrying a pathogen, must live longer than the extrinsic incubation period of that pathogen to enable transmission to a new host. As such, determining the age of female mosquitoes is of significant interest for vector-borne diseases surveillance and control programs.

Methods
In this contribution, an automated age-grading system was developed to classify the age of female Culex pipiens, which is the primary vector of West Nile virus and other pathogens of medical and veterinary importance in northern latitudes. The system comprises an optical wingbeat sensor coupled to the entrance of a mosquito trap and a machine learning model. Three age classes were used in the study: young (2–4 days), middle (7–9 days) and old (14–16 days). From a balanced dataset of flight data, four features were extracted: wingbeat fundamental frequency, spectrogram, power spectral density and Mel frequency cepstral coefficients. The features were used for training with the XGBoost algorithm to generate a model for age classification.

Results
The best performing model was trained with the power spectral density feature on two age classes, ≤ 4 days old and ≥ 7 days old, and had an accuracy of 71.8%.

Conclusions
An automated mosquito age-grading system was applied for the first time to our knowledge for automated age classification in mosquitoes; and complements the mosquito genus and sex classification capability of the system reported in our previous work. The system may find use in mosquito-borne disease surveillance and control to help to discriminate young mosquitoes (≤ 4 days old) from older mosquitoes, which may act as vectors of arboviruses.

Graphical Abstract
Chiglitazar diminishes the warburg effect through PPARγ/mTOR/PKM2 and increases the sensitivity of imatinib in chronic myeloid leukemia
Authors: Duan Hongpeng , Lai Qian , Jiang Yuelong , Yang Liuzhen , Deng Manman , Lin Zhijuan , Shan Weihang , Zhong Mengya , Yao Jingwei , Zhang Li , Xu Bing , Zha Jie 
Published: December 2024

Abstract
Background
A tyrosine kinase inhibitor (TKI) such as Imatinib (IM) is the preferred treatment for Chronic Myeloid Leukemia (CML). However, the emergence of IM resistance presents a significant challenge to disease management. A characteristic of cancer cells, including IM-resistant CMLs, are characterized by heightened uptake of glucose and aberrant glycolysis in the cytosol, which is known as the Warburg effect. In addition to its potential to modulate the Warburg effect, Chiglitazar (Chi), a compound that regulates glucose metabolism, has also been investigated for its implication in cancer treatment. This suggests that combining Chi with IM may be a therapeutic strategy for overcoming IM resistance in CML.

Methods
Sensitive and IM-resistance CML cells were treated with Chi in vitro, followed by detecting of extracellular acidification rate (ECAR) using a Seahorse XF Analyzer. CML cell proliferation, cell cycle distribution, and apoptosis were tested by CCK-8 assay and flow cytometry. RNA sequencing was utilized to investigate potential transcriptional changes induced by Chi usage. In vivo studies were conducted on immunodeficient mice implanted with CML cells and given Chi and/or IM later. Tumor growth was monitored, as well as tumor burden and survival rates between groups.

Results
Our metabonomic, transcriptomic, and molecular biology studies demonstrated that Chi, in part, diminished the Warburg effect by reducing glucose and lactate production in imatinib-resistant CML cells through the PPARγ/mTOR/PKM2 pathway. This modulation of glucose metabolism resulted in reduced cell proliferation and enhanced sensitivity to IM in imatinib-resistant CML cells in vitro. Rescue assay by introducing shPPARγ or mTOR activator verified the underlying regulatory pathway. Also, the combination of Chi and IM synergistically increased the sensitivity of IM in vivo and prolonged the survival of imatinib-resistance CML transplanted mice.

Conclusions
Our results demonstrated the potential of Chi to overcome IM resistance in vitro and in vivo. By inhibiting the Warburg effect through the PPARγ/mTOR/PKM2 pathway, Chi resensitizes CML cells towards imatinib treatment. Combining IM with Chi is an alternative therapeutic option for CML management, especially for IM-resistant CML patients.
Multiple sclerosis and self-alienation: a study based on self and others representations
Authors: Ziaie Leila , Mazaheri Mohammad Ali , Zabihzadeh Abbas , Etemadifar Masoud , Shokri Omid , Contrada Richard J. 
Published: December 2024

Abstract
Background
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. MS causes many changes in the lives of its patients, forcing them to renegotiate their lives. Part of these changes are related to patients’ self- and others- mental representations. Despite the importance of mental representations in changes caused by or adaptation to MS, limited research has been conducted to examine the mental representations of people with MS.

Methods
This study examines the mental representations that Healthy Controls (HC) and people with MS (PWMS) have of themselves and others, including childhood and current self-images, as well as those of their mothers, love partners, and close friends. In both groups (HC (n = 82) and PWMS (n = 82)), participants completed demographic variables as well as a modified version of the comfortable interpersonal distance (CID) task in both passive (when protagonists approached them) and active modes (when participants approach protagonists). Participants estimated the point at which they felt discomforted.

Results
The PWMS group preferred a significantly larger interpersonal distance than the HC group for both current self-image and love partner. There is no difference between the two groups in preferring interpersonal distance from their childhood self-image, mother, and friends.

Conclusions
Based on the research results, it seems that PWMS experience a kind of alienation at the level of self-mental representations. This research can be helpful in modifying MS interventions and increasing the engagement of support systems.
Eco-friendly green synthesis of silver nanoparticles from guajava leaves extract for controlling organophosphorus pesticides hazards, characterization, and in-vivo toxicity assessment
Authors: Albadawi Emad Ali , Musa Eid Nassar Ali , Ghaban Hadel Mahroos , Ebrahim Neven A. , Albadrani Muayad Saud , El-Tokhy Ahmed I. 
Published: December 2024

AbstractThis study explores an eco-friendly approach to mitigate risks associated with organophosphorus insecticides, particularly Chlorpyrifos, by synthesizing silver nanoparticles (AgNPs) using Psidium guajava leaf extract and preparing a nanocomposite (AgNPs/S18) with Chlorpyrifos pesticide. The green-synthesized AgNPs and AgNPs/S18 nanocomposite were characterized using various analytical techniques, confirming the successful synthesis of AgNPs with an average size of 37 nm and forming a stable nanocomposite. Antibacterial assays demonstrated significant activity against Staphylococcus aureus, with AgNPs showing an 87.8% reduction and the nanocomposite achieving a 72% reduction in bacterial population. Cytotoxicity evaluations on normal liver and liver cancer cell lines revealed enhanced cytotoxicity of the nanocomposite compared to AgNPs alone, suggesting potential applications in targeted therapies. In vivo studies on rats revealed the protective effects of AgNPs and the nanocomposite against Chlorpyrifos-induced toxicity in liver and kidney tissues. Histopathological and ultrastructural analyses showed both treatments, particularly the nanocomposite, significantly mitigated cellular damage caused by Chlorpyrifos exposure. These findings suggest that green-synthesized AgNPs and their nanocomposite with Chlorpyrifos offer a promising approach to reducing pesticide hazards while maintaining efficacy. This research contributes to developing safer alternatives in pest management, addressing the need for more environmentally friendly agricultural practices while protecting human health and ecosystems.
Exploring IAA biosynthesis and plant growth promotion mechanism for tomato root endophytes with incomplete IAA synthesis pathways
Authors: Feng Yanhui , Tian Baoyu , Xiong Juan , Lin Guoqin , Cheng Linjie , Zhang Ting , Lin Bilian , Ke Zhenhua , Li Xin 
Published: December 2024

AbstractExploring indoleacetic acid (IAA) biosynthesis pathways of plant growth promoting bacteria and their ability to synthesize IAA is crucial for understanding the promotion mechanism and for developing more efficient microbial fertilizer. In this study, 118 bacterial endophytic strains were isolated from tomato root and 68 isolates were identified as members of Bacillus and Pseudomonas genus. After screening abilities to synthesize IAA in vitro and promote plant growth for these identified Bacillus and Pseudomonas strains, 7 endophytic strains Bacillus sp. Y_21, B. paramycoides Y_29, B. albus Y_96, B. cereus Y_121, P. plecoglossicida Y_157, Bacillus sp. Y_165 and B. aryabhattai Y_170 strains showed a significant promotion role on wheat root or leaf, including 4 endophytic strains with the potential ability to utilize intermediate metabolites, such as tryptamine and indole acetamide, to produce IAA. Genomic sequencing analysis for selected representative plant growth promoting endophytes showed that IAA-producing bacteria B. cereus mr31 and P. putida Y_166 separately harbored a complete indoleacetamide (IAM) and complete tryptamine (TAM) pathway; whereas, Bacillus sp. Y_165 and B. aryabhattai Y_170, two strains producing IAA not using tryptophan but with indole-3-acetamide, had an incomplete IAM pathway. Fermentation experiments of three genome-sequenced strains using wheat or tomato root extracts as substrate, and combining with UHPLC–MS/MS analysis for wheat root extracts, demonstrated that Bacillus sp. Y_165 strain might produce IAA by using the plant-derived indole-3-acetamide. Our study first demonstrated a novel potential mechanism for the plant growth promoting endophytes to biosynthesize IAA using plant-derived intermediates. This additional mechanism has deepened our understanding of how bacterial endophytes promote plant health and resilience, offering valuable insights about how plants regulate IAA homeostasis within their internal tissues in association with bacterial endophytes.
Graphical Abstract
Fibromyalgia comorbidity in Systemic Lupus Erythematosus patients: assessing impact on quality of life
Authors: Monteiro Jade A. M. , Gama Alexia L. H. , Oliveira Joao C. S. , Falcao Matheus V. , Melo Ana Karla G. , Egypto Danielle C. S. , Braz Alessandra S. 
Published: December 2024

Abstract
Introduction
The prevalence of Fibromyalgia in patients with Systemic Lupus Erythematosus (SLE) is significantly higher compared to the general population. Despite this frequent association, Fibromyalgia remains underdiagnosed and consequently inadequately treated, negatively affecting the quality of life of these patients.

Objective
This study aims to evaluate the occurrence of Fibromyalgia and its impact on the quality of life of Brazilian patients with SLE treated at a University Hospital in the state of Paraiba.

Materials and methods
This descriptive, observational, and cross-sectional study included patients with SLE diagnosed according to the 2012 criteria of the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC). The occurrence of Fibromyalgia was assessed using the American College of Rheumatology (ACR) criteria of 1990 and 2010/2011, revised in 2016. Quality of life was evaluated using the Short-Form 36 (SF-36) questionnaire for all patients, while the Fibromyalgia Impact Questionnaire (FIQ) was applied to those diagnosed with Fibromyalgia.

Results
The sample comprised 107 SLE patients, with an average age of 54.1 years (SD:12.1), of whom 95.4% (102) were women. The prevalence of Fibromyalgia among SLE patients was 19.1% (21), all of whom were women with a mean age of 45.6 years (SD 9.6). The SF-36 scores of SLE patients with Fibromyalgia were consistently lower across all eight domains compared to those without Fibromyalgia, indicating a significant negative impact of this comorbidity. Conclusion: These findings are consistent with existing literature, highlighting the significant negative impact of Fibromyalgia on the quality of life of patients with SLE.

Conclusion
These findings are consistent with existing literature, highlighting the significant negative impact of Fibromyalgia on the quality of life of patients with SLE.
The hepatocyte nuclear factor 1 homeobox A (HNF1A) gene polymorphism and AFP serum levels in Egyptian HCC patients
Authors: Bedair Hanan M. , Sayed Ibrahim El-Tantawy El , Hendy Olfat M. , Abdel-Samiee Mohmed , Sayad Islam Abd El Hamid El , Mandour Sally S. 
Published: December 2024

Abstract
Background
Hepatocyte nuclear factors were first identified as liver-enriched transcription factors that might participate in various activities related to the transcription of genes unique to the liver.

Objective
The study aimed to reveal the impact of HNF1A gene variations on disease progression in hepatocellular carcinoma (HCC) patients and its relation to serum alpha-fetoprotein level.

Methods
Participants in the study were classified as Group I, 32 HCC patients; Group II, 36 chronic hepatitis C patients; and Group III, 26 healthy volunteers as a control group.
Each patient underwent full history taking, thorough clinical examination, and radiological examination. Furthermore, tumor staging was done using BCLC staging system. HNF1A gene polymorphisms (rs 2,464,196 and rs 1,169,310) were genotyped by real-time PCR.

Results
The findings revealed the highest frequency of AA and GA genotypes of HNF1A (rs2464196) polymorphism in both HCC (P = 0.002) and chronic HCV (P = 0.004) patients in comparison with controls. Regarding rs1169310gene polymorphism, no significant variation was observed across various genotypes when comparing the experimental groups to the control group. Additionally, HCC patients harboring the AA genotype for rs2464196 had significantly increased AFP (≥ 200 ng/ml) levels, whereas HCC patients with rs1169310 SNPs for HNF1A had no significant association regarding the AFP level.

Conclusion
The rs2464196 polymorphism of HNF1 is associated with increased AFP levels and HCC disease progression, which may be a prognostic and diagnostic genetic indicator.