bluuebunny/crossref_metadata_2025 huggingface dataset:
How do citizens with low health insurance literacy choose a health insurance policy in the Netherlands? An interview study
Authors: Holst Laurens , Brabers Anne , Rademakers Jany , de Jong Judith
Published: December 2024

Various countries have implemented a choice-based health insurance system. For such systems to function as intended, it is crucial that all citizens have the opportunity to make well-informed decisions with regard to their health insurance policy. There is, however, ample research evidence to suggest that many citizens may lack the required skills to do so, thus increasing the likelihood of suboptimal insurance choices and incurring unexpected costs. The current study explored what barriers citizens in the Netherlands, with low health insurance literacy (HIL), face when selecting a health insurance policy, and what their specific needs and preferences are regarding information and support. Semi-structured interviews (online or telephone) were performed between January 2023 and April 2023 among sixteen with a low level of HIL. The data were analyzed using thematic analysis methods. Our results show that not all citizens with low HIL are sufficiently motivated to actively look for alternative health insurance options every year. This is partly due to the feeling that it is a task imposed upon them by the government, and because choosing a health insurance policy is perceived as too complicated and not sufficiently worthwhile. There is a need among citizens with low HIL for clear and practical information about health insurance policies, especially from the government and health insurers. In addition to this need, we recommend enhancing awareness regarding the consequences of neglecting to explore such health insurance options. Moreover, more personal attention for the process of selecting a health insurance policy should be offered to vulnerable groups such as those who possess insufficient digital skills.
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

Norepinephrine (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

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

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

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

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

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

This 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

Exploring 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

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

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.
Deep sedation in lateral position for preterm infants during cerebral magnetic resonance imaging: a pilot study
Authors: Sbaraglia Fabio , Gaudino Simona , Tiberi Eloisa , Maiellare Federica , Spinazzola Giorgia , Garra Rossella , Della Sala Filomena , Micci Daniela Maria , Russo Rosellina , Riitano Francesca , Ferrara Giuseppe , Vento Giovanni , Rossi Marco
Published: December 2024

Introduction

Respiratory adverse events are common during the sedation of preterm babies, often needing active airway support. During magnetic resonance imaging, this occurrence could extend the acquisition time, with a negative impact on the thermic and metabolic homeostasis. The aim of the study is to verify if lying in a lateral position instead of supine could improve the safe quality of sedation, without worsening the quality of imaging.

Methods

This study was performed as a single-center, prospective study at a university-affiliated tertiary care center. A consultant provided deep sedation with sevoflurane 3–4% delivered by an external mask, in the lateral decubitus position. All patients were evaluated for the incidence of apnea and desaturation, quality of imaging obtained, the timing of imaging acquisition, and thermic and metabolic homeostasis.

Results

We enrolled 23 consecutive preterm babies born < 37 weeks gestational age, candidates for sedation for elective brain magnetic resonance imaging. All patients completed the radiological procedure in 30 min (SD ± 6.39 min) without complications requiring exam interruption. Only one patient (4%) experienced a transient desaturation, while 2 neonates (9%) showed apnea lasting > 20 s. On average, there was a 1 °C decrease in body temperature and full enteral feeding was resumed within 1.5 h. Neuroradiologists rated the quality of the images obtained as high.

Conclusions

Lateral lying seems to be a viable option for sedated preterm babies during magnetic resonance imaging with a low risk of intervention for apnea and a reduced impact on thermic and metabolic homeostasis. Quality of imaging would be preserved maintaining correct scheduling of standard care.

Trial registration

The study was registered at www.ClinicalTrials.gov before enrollment (NCT05776238 on December, 21th 2023).
Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Recurrent Small Hepatocellular Carcinoma: A Randomized, Open-Label, Controlled Trial
Authors: Xi Mian , Yang Zhoutian , Hu Li , Fu Yizhen , Hu Dandan , Zhou Zhongguo , Liu Mengzhong , Zhao Jing , Shen Jingxian , Li Qiaoqiao , Chen Baoqing , Xu Li , Fang Aiping , Chen Minshan , Liu Shiliang , Zhang Yaojun
Published: December 2024

PURPOSE

To assess the efficacy and safety of radiofrequency ablation (RFA) versus stereotactic body radiotherapy (SBRT) in treating recurrent small hepatocellular carcinoma (HCC).

METHODS

In this trial, patients with recurrent small HCC (single lesion ≤5 cm) were randomly assigned to receive either SBRT or RFA. The primary end point was local progression-free survival (LPFS), and secondary end points were progression-free survival (PFS), overall survival (OS), local control rate, and safety.

RESULTS

Between August 2019 and April 2022, 166 patients were assigned to SBRT (n = 83) and RFA (n = 83) groups. After a median follow-up time of 42.8 and 42.9 months in the SBRT and RFA groups, respectively, SBRT demonstrated a significantly better LPFS than that of RFA (hazard ratio [HR], 0.45 [95% CI, 0.24 to 0.87];
P
= .014). The 2-year LPFS rates were 92.7% (95% CI, 87.3 to 98.5) with SBRT and 75.8% (95% CI, 67.2 to 85.7) with RFA. The median PFS time of the SBRT and RFA groups was 37.6 (95% CI, 26.0 to 49.2) and 27.6 (95% CI, 20.3 to 34.8) months, respectively (HR, 0.76 [95% CI, 0.50 to 1.15];
P
= .190). Nine patients in the SBRT group and 10 in the RFA group died during the follow-up. The 2-year OS rates were 97.6% (95% CI, 94.3 to 100.0) in the SBRT group and 93.9% (95% CI, 88.9 to 99.2) in the RFA group (HR, 0.91 [95% CI, 0.37 to 2.22];
P
= .830). The incidences of both acute and late adverse events were comparable between the groups (
P
= .436 and
P
= .715, respectively).

CONCLUSION

SBRT achieved better LPFS than that of RFA in patients with single recurrent HCC ≤5 cm, especially in HCC ≤2 cm, whereas PFS, OS, and safety were comparable between the two treatments.
Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment
Authors: Finan Jennifer M. , Guo Yifei , Goodyear Shaun M. , Brody Jonathan R.
Published: December 2024

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a 5-year survival rate of 13%. Surgical resection remains the only curative option as systemic therapies offer limited benefit. Poor response to chemotherapy and immunotherapy is due, in part, to the dense stroma and heterogeneous tumor microenvironment (TME). Opportunities to target the PDAC stroma may increase the effectiveness of existing or novel therapies. Current strategies targeting the stromal compartment within the PDAC TME primarily focus on degrading extracellular matrix or inhibiting stromal cell activity, angiogenesis, or hypoxic responses. In addition, extensive work has attempted to use immune targeting strategies to improve clinical outcomes. Preclinically, these strategies show promise, especially with the ability to alter the tumor ecosystem; however, when translated to the clinic, most of these trials have failed to improve overall patient outcomes. In this review, we catalog the heterogenous elements of the TME and discuss the potential of combination therapies that target the heterogeneity observed in the TME between patients and how molecular stratification could improve responses to targeted and combination therapies.
Phase II Study of Defactinib (VS6063) in Patients With Tumors With
NF2
Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U
Authors: Zauderer Marjorie G. , Jegede Opeyemi , Jackman David M. , Zwiebel James A. , Gray Robert J. , Wang Victoria , McShane Lisa M. , Rubinstein Larry V. , Patton David R. , Williams P. Mickey , Hamilton Stanley R. , Takebe Naoko , Huang Raymond , Carrillo Jose A. , Brenner Andrew J. , Tricoli James V. , Conley Barbara A. , Arteaga Carlos L. , Harris Lyndsay N. , O'Dwyer Peter J. , Chen Alice P. , Flaherty Keith T.
Published: December 2024

PURPOSE

The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models,
neurofibromatosis 2
(
NF2
)–inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with
NF2
-altered tumors.

METHODS

Patients whose tumors harbored an inactivating
NF2
mutation on next-generation sequencing were assigned to subprotocol U. Defactinib 400 mg was given orally twice a day until progression or intolerable toxicity. The primary end point was objective response rate (ORR), secondary end points included toxicity, progression-free survival (PFS), and 6-month PFS.

RESULTS

Of 5,548 patients with sufficient tissue for genomic analysis, 57 patients were found to have
NF2
alterations. Thirty-five patients ultimately enrolled and 33 were treated, with one not having central confirmation and two ineligible for outcome analysis. All patients had received previous treatment, with 52% having received three or more previous lines of therapy. The most common treatment-related toxicities were fatigue (36%), nausea (33%), and hyperbilirubinemia (27%), with 27% of patients having grade 3 toxicities. Median follow-up was 35.9 months with an ORR of 3% from one partial response in a patient with choroid meningioma. Among the 12 patients (40%) with a best response of stable disease, eight demonstrated some tumor shrinkage. Median PFS was 1.9 months, and six patients achieved a PFS >5.5 months. No correlation was identified between clinical outcomes and tumor histology or specific
NF2
genotype.

CONCLUSION

This protocol did not meet its prespecified primary end point. Defactinib monotherapy had limited clinical activity in this cohort of previously treated patients with solid tumors exhibiting
NF2
loss.
To FM2030
Authors: Mameni Salar
Published: December 2024

A letter to the futurologist FM 2030 written by a young martyr.
Culture, Nature, and Environmental Humanities
Authors: Wang Ban
Published: December 2024

Touting the technological fix for environmental crises overlooks the role of society, history, culture, production, and geography. Anthropocene, presuming all civilizations as ecologically destructive, ignores the historical, social, and cultural differences in human-nature relations. The contributors of this issue mount a humanistic critique of structural inequalities, alienating social relations, and environmental injustice in environmental crises while articulating cultural and religious legacies in human-nature relations.
Neuromuscular Fatigue in Hamstring and Quadriceps Muscles Following Simulated Soccer Match-Play and Typical Training Sessions
Authors: Massamba Anasthase , Kouzkouz Nabil , Geny Bernard , Favret Fabrice , Hureau Thomas J.
Published: December 2024

Purpose

This study investigated the mechanisms of neuromuscular fatigue and recovery in quadriceps and hamstring muscles following soccer match-play and typical training sessions dedicated to the physical development of players.

Methods

Fifteen male professional academy soccer players completed at different visits a 90-minute simulated soccer match-play (MATCH) and four training sessions modulating the metabolic nature (HIIT vs. SPRINT) and the mechanical load (number of changes of direction [COD]). Neuromuscular fatigue was evaluated via changes in pre to postexercise maximal voluntary contraction (MVC), potentiated twitch force (PTw, peripheral fatigue) and voluntary activation (VA, central fatigue) evoked by electrical stimulation in quadriceps and hamstring muscles. External load was assessed via GPS units.

Results

Following MATCH, ΔMVC was similar between quadriceps (-18.3 ± 11.6%) and hamstring (-23.2 ± 10.6%) muscles. However, hamstring muscles displayed greater ΔPTw (-27.2 ± 25.0% vs. -17.2 ± 10.9%), but lower ΔVA (-8.2 ± 14.0% vs. -18.1 ± 12.7%) than quadriceps muscles. Quadriceps and hamstring muscles fatigue recovered 24 h post-match. Increasing the mechanical load (number of COD) increased the magnitude of neuromuscular fatigue in quadriceps but not in hamstring muscles. Modulating the metabolic nature of the session (SPRINT vs. HIIT) did not influence neuromuscular fatigue in either muscle group. No correlation was found between ΔMVC and a fatigue index derived from GPS metrics for any muscle groups (r
2 < 0.06, P > 0.38).

Conclusions

The magnitude and etiology of neuromuscular fatigue were modulated by the muscle group investigated and the mechanical load of the exercise task. Moreover, the ‘fatigue index’ derived from GPS metrics is not a valid surrogate of neuromuscular fatigue on the field.
Spike(s) protein gene microevolution of SARS CoV-2 virus in Bolivian Population
Authors: Terán Aneliz Ninahuanca , Tola Emma Torres , Voigt Daniela Andrea Arteaga , Barrón Ruddy Luna
Published: December 2024

Objective: analyze the population gene structure and phylogeny of the S gene of the SARS CoV-2 virus of COVID-19 (+) patients from the Plurinational State of Bolivia and then correlate its phylogeny with the different waves of contagion. Methods: three SARS-CoV-2 samples obtained by nasopharyngeal swabs from positive COVID-19 patients were sequenced by Sanger sequencing. 488 sequences of Bolivian SARS-CoV-2 were downloaded from GISAID until September 25, 2023. The genetic structure and phylogeny were analyzed to correlate the presence of the different variants with the waves of contagion. Results: three (3) sequences of 623pb, 1557pb, and 3060pb of the S gene were obtained, and the last one was analyzed with the sequences downloaded from GISAID, obtaining a phylogenetic tree and a network of haplogroups that revealed the formation of clades and nodes that gave rise to variants of the six waves that Bolivian inhabitants faced. The Y508S mutation was identified as new since it was not identified in the CoVariants® and CoV-Glue® databases. Conclusions: the phylogeny, haplogroup network, and Person's correlation coefficient revealed the existence of a positive correlation between the microevolution of the analyzed fragment and the appearance of the different waves of contagion.
Methods: Three SARS-CoV-2 samples obtained by nasopharyngeal swab from positive COVID-19 patients were sequenced by Sanger sequencing. 488 sequences of Bolivian SARS-CoV-2 were downloaded from GISAID until September 25, 2023. The genetic structure and phylogeny were analyzed to then correlate the presence of the different variants with the waves of contagion.
Results: 3 sequences of 623pb, 1557pb and 3060pb of the S gene were obtained, the last one was analyzed with the sequences downloaded from GISAID, obtaining a phylogenetic tree and a network of haplogroups that revealed the formation of clades and nodes that gave rise to variants of the six waves that Bolivian inhabitants faced. The Y508S mutation was identified as new, since it was not identified in the CoVariants® and CoV-Glue® databases.
Conclusions: The phylogeny, haplogroup network and Person's correlation coefficient revealed the existence of a positive correlation between the microevolution of the analyzed fragment and the appearance of the different waves of contagion.
Semi-empirical method of studying the D-layer aeronomy. II. Evidence-based calibration of the method
Authors: Kozlov Stanislav , Nikolaishvily Sergey
Published: December 2024

This paper presents the results of evidence-based calibration of a new semi-empirical method for studying the D-layer aeronomy. We use simultaneous measurements of altitude profiles of electron density Ne(h) and ionization rate q(h) under disturbed conditions (case 1) and mean  under various heliogeophysical conditions at low (LSA) and high (HSA) solar activity (case 2). The experimental data and methods are described in detail. It is shown that it is necessary to include temperature dependences of rate constants T(h) for all heliogeophysical conditions. Care should be taken when choosing the T(h) distribution with due regard to most of known factors having an effect on it, wherever possible. We draw a conclusion on the practicability of the use of new photodetachment rates that depend on the solar zenith angle and h. The unknown dissociative recombination rate for cluster positive ions and the photodetachment rate can be reasonably considered as free parameters, of course within due limits. Under disturbed ionospheric conditions, the evidence shows a fall in Ne at all altitudes h when q≈(1.3÷2)⋅10² cm⁻³ s⁻¹ with further increase in the parameters with q, which is confirmed by calculations using the semi-empirical model, yet for a wider range of q variations. The theoretical model that explains the aforementioned effect is the subject of future study. The results for dayside  coincide qualitatively with our knowledge on the behavior of aeronomy parameters in the D layer. The studies suggest that the presented method allows qualitative estimations under all heliogeophysical conditions and even wholly satisfactory quantitative estimations under disturbed ionospheric conditions.
Analysis of meteorological effects of cosmic ray neutron component based on data from mid-latitude stations
Authors: Kobelev Pavel , Hamraev Yuldash , Yanke Viktor
Published: December 2024

Precision neutron monitors providing continuous monitoring with a statistical accuracy of ~0.15 %/hr are effective for studying cosmic ray variations; therefore, contributions from other error sources should not exceed the contribution of this statistical error. Such possible sources primarily include changes in atmospheric pressure and humidity. The aim of the work is to estimate the barometric effect of the neutron component of cosmic rays for the low-latitude stations Tashkent and Alma-Ata (mountain), including periods of maximum solar activity. The technique developed on the basis of multifactor correlation analysis is applicable to processing data from any detectors of the worldwide network of neutron monitors. As a result, we have obtained annual average barometric coefficients of the neutron component at the stations Tashkent and Alma-Ata. The humidity effect was also estimated for the mid-latitude station Moscow. The study draws the conclusion that the approach considered can effectively solve the problem.
Experiencias innovadoras en la enseñanza de narrativa y reescrituras en el Grado de Primaria
Authors: Calzada Borrallo Carmen
Published: December 2024

En este capítulo se describe el diseño, aplicación y evaluación de un CIMA de
8 horas para impartir el bloque de narrativa en la asignatura de Literatura Española del Grado en Educación Primaria. Durante el CIMA se trabajó el concepto de
narrativa y se exploró el fenómeno de la reescritura literaria como centro en el
que ejemplificar y reflexionar las características del género y sus posibilidades
como herramienta de cuestionamiento social.
Ciclo de mejora en dificultades del desarrollo y del aprendizaje: el caso del autismo
Authors: Rodríguez Martínez Elena Isabel
Published: December 2024

Este Ciclo de Mejora en el Aula (CIMA) se desarrolla e implementa en la asignatura de Dificultades del Desarrollo y del Aprendizaje del Grado de Educación
Primaria. Supone un cambio en el modelo docente para mejorar el proceso de
enseñanza/aprendizaje de los estudiantes, para pasar de un modelo transmisivo a uno constructivo. En concreto, se tratará el tema del Trastorno del Espectro
Autista (TEA). Se han empleado cuestionarios iniciales y finales para saber cuáles
son los conocimientos previos de los estudiantes y sus modelos mentales a la vez
que para poder evaluar su progreso. Se ha utilizado una metodología en la que
los estudiantes son agentes activos de su propio aprendizaje. Como resultado se
ha obtenido una mejora en el aprendizaje de los futuros maestros y maestras de
Educación Primaria, así como, se han podido conocer los obstáculos, que en muchas ocasiones no permiten dicha mejora, de manera que, como docentes, podamos actuar sobre ellos, mejorando así el aprendizaje de nuestros estudiantes.
Experiencia de innovación docente en la asignatura de Acondicionamiento Físico en la Escuela del grado en Educación Primaria
Authors: Bianchi Paula
Published: December 2024

Este capítulo presenta los resultados de la aplicación de un Ciclo de Mejora en el Aula en la asignatura de Acondicionamiento Físico en la Escuela, del
cuarto curso del Grado en Educación Primaria llevado a cabo durante el primer
cuatrimestre del curso 2023/2024. Este CIMA fue diseñado para 8 horas distribuidas en 6 sesiones de 1 hora y 20 minutos aplicadas al grupo 1 de teoría. Metodológicamente para el diseño de esta propuesta se ha utilizado el modelo basado
en actividades de contraste. La evaluación del CIMA se realizó a partir de instrumentos como cuestionarios, escaleras de aprendizaje del alumnado y diario de
la profesora
Aplicación didáctica de la Taxonomía de Bloom para el análisis Ecofeminista de textos literarios
Authors: Muñoz Rodríguez María del Carmen
Published: December 2024

Dos de las problemáticas principales a las que se enfrentan los estudiantes
de las asignaturas del área de literatura del Grado en Estudios Ingleses son una
gran dificultad a la hora de analizar textos complejos y un desconocimiento general de las teorías críticas y filosóficas actuales que se utilizan para llevar a cabo
dichos análisis. Este proyecto pone solución a ambos problemas utilizando como
marco teórico los principios de la Taxonomía de Bloom para la adquisición de
conocimiento. Se ha perseguido que, mediante el desarrollo de las habilidades
cognitivas presentes en el proceso de aprendizaje, los estudiantes mejoren su capacidad para comprender y analizar dichos textos. Debido a su actual relevancia,
la teoría de crítica literaria en la que se les ha adentrado ha sido la ecofeminista,
que combina el estudio de la relación del ser humano y su producción cultural
con el medio ambiente, incorporando a la vez una perspectiva feminista. Los resultados que arroja este proyecto ponen en evidencia la utilidad de usar este
marco teórico, así como la importancia del empleo de actividades guiadas basadas en el trabajo cooperativo para el correcto desarrollo del aprendizaje.
Aprender a investigar con fuentes documentales y herramientas tecnológicas para la traducción de la lengua inglesa
Authors: Rosal Bustamante Inmaculada
Published: December 2024

Esta experiencia de innovación docente recoge el Ciclo de Mejora en el Aula
(CIMA) de doce horas en la asignatura Fundamentos y Práctica de la Traducción
Inglés-Español del Grado en Estudios Ingleses de la Universidad de Sevilla durante el segundo cuatrimestre del curso 2023/2024. Se aplicó en dos bloques de
contenido sobre fuentes documentales y herramientas tecnológicas usadas habitualmente en traducción para así promover algunas de las competencias traductoras de búsqueda e investigación necesarias para esta labor. Como resultado, se
ha conseguido mejorar la implicación y participación del alumnado en la asignatura. Además, el alumnado ha demostrado cierta evolución a nivel conceptual,
actitudinal y procedimental sobre el manejo de recursos y herramientas tecnológicas para la traducción, con especial énfasis en el uso crítico y ético de estas
últimas. Por lo tanto, esta experiencia se valora positivamente, pues han logrado
relacionar los conceptos de ambos bloques de contenido mediante el desarrollo
de habilidades de búsqueda e investigación para la traducción y su aplicación en
las prácticas de traducción.
Potenciando la enseñanza del Patrimonio Arqueológico a través de un Ciclo de Mejora en el Aula
Authors: Ramírez Cañas Carmen
Published: December 2024

La innovación docente ha cobrado un notable protagonismo en los últimos
años. Su método proporciona al docente las herramientas necesarias para la obtención de mejores resultados tanto para el alumnado como para el profesorado. En este capítulo aportamos la experiencia obtenida tras la aplicación del
Ciclo de Mejora en el Aula (CIMA) a una asignatura que suele resultar compleja
para el alumnado: la Protección y Gestión del Patrimonio Arqueológico, del Grado
en Arqueología. El objetivo es mejorar la docencia universitaria través de cambios en el modelo metodológico aplicado a un bloque temático concreto, la Legislación del Patrimonio Histórico en Andalucía. Se plantea así una docencia en
la que el alumnado se transforma en un sujeto activo, promoviendo su participación y razonamiento crítico en contra de la tradicional memorización mecanizada de conceptos.