bluuebunny/crossref_metadata_2025_split huggingface dataset:
First detection of V410L kdr mutation in Aedes aegypti populations of Argentina supported by toxicological evidence
Authors: Gonzalez Paula V. , Loureiro Aline C. , Gómez-Bravo Andrea , Castillo Paola , Espinosa Manuel , Gil José F. , Martins Ademir J. , Harburguer Laura V. 
Published: August 2024

Abstract
Background
Aedes aegypti (L.) is the main vector of dengue, yellow fever, Zika, and chikungunya viruses in many parts of the world, impacting millions of people worldwide each year. Insecticide-based interventions have been effective in controlling Aedes mosquito populations for several years, but in recent times, resistance to these compounds has developed, posing a global threat to the control of this mosquito.

Methods
Ovitraps were used to collect A. aegypti eggs in the cities of Tartagal and San Ramón de la Nueva Orán (Salta), Puerto Iguazú (Misiones), and Clorinda (Formosa). World Health Organization (WHO)-impregnated papers with the discriminating concentration (DC) of permethrin, 5X, 10X and pirimiphos methyl were used for the toxicological bioassays. We also genotyped each sample for the three kdr single nucleotide polymorphisms (SNP): V410L, V1016I, and F1534C in individual TaqMan quantitative PCR (qPCR) reactions.

Results
All investigated A. aegypti populations were highly resistant to permethrin, as the mortality percentage with the permethrin 10×DC remained below 98%. However, all populations were 100% susceptible to pirimiphos-methyl. Kdr genotyping demonstrated the presence of the V410L mutation for the first time in Argentina in all the populations studied. A prevalence of the triple mutant genotype (LL + II + CC) was observed in the northeastern cities of Clorinda (83.3%) and Puerto Iguazú (55.6%).

Conclusions
This study demonstrates for the first time the presence and intensity of resistance to permethrin in different populations from Argentina, and correlates the observed phenotype with the presence of kdr mutations (genotype).

Graphical Abstract
Gene regulatory networks reveal sex difference in lung adenocarcinoma
Authors: Saha Enakshi , Ben Guebila Marouen , Fanfani Viola , Fischer Jonas , Shutta Katherine H. , Mandros Panagiotis , DeMeo Dawn L. , Quackenbush John , Lopes-Ramos Camila M. 
Published: August 2024

Abstract
Background
Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively.

Methods
Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data.

Results
We found that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also discovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database.

Conclusions
These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.

Graphical Abstract
Public involvement in an aggregate and individual participant data meta-analysis of mindfulness-based programmes for mental health promotion
Authors: Friedrich Claire , Fairbairn Toni , Denton Graham , Geddes Mary , Thomas-Carr Darren , Jones Peter B. , Galante Julieta 
Published: August 2024

Abstract
Background
Involving the public in evidence synthesis research is challenging due to the highly analytic nature of the projects, so it is important that involvement processes are documented, reflected upon, and shared to devise best practices. There is a literature gap on the involvement of the public in individual participant data meta-analyses, particularly in public health projects. We aimed to document and reflect on our collective experiences of involving and being involved as public stakeholders at all stages of a systematic review and individual participant data meta-analysis project.

Methods
We formed a stakeholder group made of four members of the public at the beginning of our evidence synthesis project comprising a systematic review, an aggregate data meta-analysis, and an individual participant data meta-analysis of mindfulness-based programmes for mental health promotion in non-clinical adults. Following each group meeting, members and participating researchers completed written reflections; one group member collected and collated these. At the end of the project, a reflective writing workshop was held before all members completed their final reflections. Everyone completed an adapted, open-ended questionnaire which asked about what did and did not work well, the overall experience, what could be improved, and the felt impact the stakeholder group had on the research.

Results
Overall, the stakeholders and researchers reported a positive experience of working together. Positives from the stakeholders’ point of view included learning new skills, experiencing research, and making new friends. For the researchers, stakeholders helped them focus on what matters to the public and were reinvigorating research partners. The challenges stakeholders experienced included having long gaps between meetings and feeling overwhelmed. The researchers found it challenging to strike the balance between asking stakeholders to be involved and for them to learn research-related skills without overburdening them and making sure that the learning was engaging. When looking back at their experience, stakeholders described seeing their impact on the project in hindsight but that this was not felt while the project was being carried out.

Conclusion
Successfully involving the public in complex evidence synthesis projects is possible and valuable from the points of view of the researchers and the stakeholders. However, it requires a significant time, skill, and resource investment that needs to be factored in from project inception. Further guidance and stakeholder training materials would be helpful. Specific suggestions are provided.
Measurable therapeutic antibody in serum as potential predictive factor of response to anti-CD38 therapy in non-IgG-k myeloma patients
Authors: Gigliotta Emilia , Plano Federica , Corsale Giusy , Corsale Anna Maria , Aquilina Cristina , Speciale Maria , Rizzuto Andrea , Martino Enrica Antonia , Leotta Dario , Solimando Antonio Giovanni , Ria Roberto , Gentile Massimo , Siragusa Sergio , Botta Cirino 
Published: August 2024

AbstractMultiple myeloma (MM) is a hematologic malignancy characterized by abnormal plasma cell proliferation in the bone marrow. Recent advancements in anti-CD38 monoclonal antibody therapies, such as daratumumab and isatuximab, have significantly improved MM patient survival. However, the lack of predictive factors of response to these therapies remains a challenge. Notably, anti-CD38 antibodies can interfere with laboratory tests, complicating response assessment. We conducted a retrospective study to evaluate the association between the appearance of positive IgGk (therapeutic antibody) on immunofixation/immunosubtraction (IF) and clinical parameters in 87 non-IgGk MM patients treated with anti-CD38 therapy. Positive IgGk IF was observed in 42 patients after a median of three treatment courses. Patients with positive IgGk IF had higher rates of complete/very good partial responses (p = 0.03) and improved progression-free survival (median not reached vs. 21.83 months, p < 0.01). High BMI (p = 0.03), higher hemoglobin (p = 0.02), lower CRP (p = 0.04), and lower monoclonal protein levels (p = 0.03) were associated with positive IgGk IF. Our findings suggest that monitoring therapeutic antibody appearance on IF may predict and optimize anti-CD38 therapy in MM. Potential explanations include the impact of patient factors (e.g. BMI) on drug pharmacokinetics, the relationship between antibody levels and immune response, and the influence of tumor biology. Further research is needed to elucidate the underlying mechanisms and clinical utility of this biomarker. Nonetheless, our results highlight the importance of considering therapeutic antibody detection when interpreting laboratory tests and managing MM patients receiving anti-CD38 therapies.
Engineering a dysbiotic biofilm model for testing root caries interventions through microbial modulation
Authors: Dame‐Teixeira Naile , El-Gendy Reem , de Oliveira Andressa Souza , Holanda Cleonice Andrade , Romeiro Luiz Antonio Soares , Do Thuy 
Published: August 2024

Abstract
Background
This study aimed to engineer and optimise a dysbiotic biofilm model to develop in vitro root caries for investigating microbial modulation strategies. The model involved growing complex biofilms from a saliva inoculum collected from four volunteers using two strategies. In the first strategy (“pre-treatment strategy”), bovine root slabs were used, and two natural compounds were incorporated at time 0 of the 10-day biofilm experiment, which included sucrose cycles mimicking the cariogenic environment. In the second strategy (“post-treatment strategy”), mature biofilms were grown in a modified Calgary biofilm device coated with collagen and hydroxyapatite for 7 days and then were exposed to the same natural compounds. The metatranscriptome of each biofilm was then determined and analysed. Collagenase activity was examined, and the biofilms and dentine were imaged using confocal and scanning electron microscopy (SEM). Mineral loss and lesion formation were confirmed through micro-computed tomography (μ-CT).

Results
The pH confirmed the cariogenic condition. In the metatranscriptome, we achieved a biofilm compositional complexity, showing a great diversity of the metabolically active microbiome in both pre- and post-treatment strategies, including reads mapped to microorganisms other than bacteria, such as archaea and viruses. Carbohydrate esterases had increased expression in the post-treated biofilms and in samples without sugar cycles, while glucosyltransferases were highly expressed in the presence of sucrose cycles. Enrichment for functions related to nitrogen compound metabolism and organic cyclic component metabolism in groups without sucrose compared to the sucrose-treated group. Pre-treatment of the roots with cranberry reduced microbial viability and gelatinase (but not collagenase) activity (p < 0.05). SEM images showed the complexity of biofilms was maintained, with a thick extracellular polysaccharides layer.

Conclusions
This root caries model was optimized to produce complex cariogenic biofilms and root caries-like lesions, and could be used to test microbial modulation in vitro. Pre-treatments before biofilm development and cariogenic challenges were more effective than post-treatments. The clinical significance lies in the potential to apply the findings to develop varnish products for post-professional tooth prophylaxis, aiming at implementing a strategy for dysbiosis reversal in translational research.
Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation
Authors: Steininger J. , Buszello C. , Oertel R. , Meinhardt M. , Schmid S. , Engellandt K. , Herold S. , Stasik S. , Ebrahimi A. , Renner B. , Thiede C. , Eyüpoglu I.Y. , Schackert G. , Beissert S. , Meier F. , Radke J. , Westphal D. , Juratli T. A. 
Published: August 2024

AbstractEpithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography–tandem mass spectrometry analysis confirmed the drugs’ presence in the patient’s cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.
Choroidal vascular changes in early-stage myopic maculopathy from deep learning choroidal analysis: a hospital-based SS-OCT study
Authors: Li Yan , Li Haoer , Rui Xue , Wang Yuan , Zhu Shenju , Huang Mengge , Liang Jianqiang , Zhu Yangfeifei , Shi Jiajia , Yu Le , Huang Shenghai , Yang Chun , Dong Mengmeng , Gao Hebei , Shen Meixiao , Wu Hao , Zhou Xiangtian 
Published: August 2024

Abstract
Background
The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them.

Methods
This study included 1418 highly myopic eyes from 720 participants aged 18 − 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm.

Results
DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P < 0.001). An increase in choroidal vascular index (CVI) was observed in all regions, except for the nasal perifoveal (N2) and inferior perifoveal (I2) regions (all P < 0.01). Multivariable logistic regression analysis revealed a negative association between the presence of DCA and increases in choroidal LA and SA (odds ratio ≤ 0.099, P < 0.001). Multivariable linear regression analysis showed that the mean deviation of the visual field test was positively associated with LA and SA at the vertical meridian (B = 1.512, P < 0.001 for LA; B = 1.956, P < 0.001 for SA). Furthermore, the receiver operating characteristic curve analyses showed the optimal ChT to diagnose pathological myopia was 82.4 µm in the N2 region, the LA was 0.076 mm2 and the SA was 0.049 mm2, with area under the curves of 0.916, 0.908, and 0.895, respectively.

Conclusions
The results of this study indicated that both the presence of DCA and visual function impairment were associated with reductions in choroidal perfusion and stromal components. Moreover, we established threshold values for choroidal parameters in diagnosing pathological myopia, offering valuable references for clinical diagnosis and management.
Guidance of development, validation, and evaluation of algorithms for populating health status in observational studies of routinely collected data (DEVELOP-RCD)
Authors: Wang Wen , Jin Ying-Hui , Liu Mei , He Qiao , Xu Jia-Yue , Wang Ming-Qi , Li Guo-Wei , Fu Bo , Yan Si-Yu , Zou Kang , Sun Xin 
Published: August 2024

Abstract
Background
In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked.

Methods
We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it.

Results
A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm’s suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance.

Conclusions
The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.
The reliability and validity of Child-to-parent Violence Questionnaire (CPV-Q) among Chinese adolescents
Authors: Xie Weishi , Wang Mengxuan , Wang Linya , Yang Li , Luo Min 
Published: August 2024

Abstract
Objective
To test the reliability and validity of the Chinese version of the Child-to-parent Violence Questionnaire (CPV-Q) in a group of Chinese adolescents.

Methods
A total of 1138 adolescents (15.24 ± 1.17 years old) were tested with the Chinese version of CPV-Q, Parent-Adolescent Conflict Scale, and Adolescent Aggressive Behavior Scale of which 201 adolescents were retested 1 month later. The Chinese version of CPV-Q contains psychological, physical, financial, and control/domain factors with 14 items.

Results
The four-factor model has good main fit indicators (father: χ2/df = 3.28, CFI = 0.96, RMSEA = 0.06; mother: χ2/df = 3.30, CFI = 0.96, RMSEA = 0.06); the scale has good criterion-related validity. The Cronbach’s α coefficients of the Chinese version of CPV-Q were 0.89 (father) and 0.88 (mother), and the Cronbach’s α coefficients of the four subscales were 0.81 ~ 0.84 (father) and 0.76 ~ 0.85 (mother). The test–retest reliability of the Chinese version of CPV-Q was 0.85 (father) and 0.83 (mother), and the test–retest reliability of the four subscales was 0.80 ~ 0.83 (father) and 0.75 ~ 0.84 (mother).

Conclusion
Therefore, the CPV-Q has good reliability and validity for Chinese adolescents and can be used as an effective tool to evaluate Chinese adolescents’ violence toward their parents.
Quality and safety of cheese shipped to the United Arab Emirates
Authors: Osaili Tareq M. , Bani Odeh Wael A. , Mohd Khalid Abdulla , Shahdad Mohamed K. , Bin Meskin Fatma S. B. , Garimella Vaidehi , Bahir Wedad S. , Obaid Reyad S. , Holley Richard , Darra Nada El 
Published: August 2024

AbstractDuring an examination of 3299 cheeses imported into the United Arab Emirates (UAE) from 2017 to 2021 for compliance with regulations regarding moisture and fat content, microbial quality, acidity, the presence of quinoline (a non-permitted colorant), sorbic acid, and the presence of rust discoloration, it was found that 91% of cheeses were compliant with UAE legislation. However, 9% were in violation of one or more of the mandated quality parameters, suggesting that adulteration had occurred. Within product categories the greatest level of non-conformity at 13% was noted for processed cheese, primarily due to violations caused by high moisture and low-fat content. This is important because moisture levels in processed cheese can influence its texture and shelf life. The microbial assessment of cheese showed that 85.7% of semi-hard and 77.5% of soft cheeses had non-compliant levels of E. coli. It was notable that 21.8% of non-compliant products originated from Turkey. Cheeses from Germany had the lowest level of non-conformity at 0.6%. This study illustrates the need for border scrutiny to include physicochemical examinations of cheese samples. The current initiative aims to promote the need for equity in global trade and to prevent the marketing of adulterated food items.
Graphical Abstract
Survival benefit of IABP in pre- versus post-primary percutaneous coronary intervention in patients with cardiogenic shock
Authors: Azazy Ahmed , Farid Walaa Abdaziz , Ibrahim Walid Abdu , El Shafey Wassam ELDin Hadad 
Published: August 2024

Abstract
Background
Cardiogenic shock (CS) remains a major cause of in-hospital mortality in the setting of acute myocardial infarction (AMI). However, little evidence is available regarding the optimal order of intra-aortic balloon counter-pulsation (IABP) insertion and primary percutaneous coronary intervention (PPCI). The aim of this study was to assess the hospital and short-term survival benefits of two different IABP insertion approaches, before versus after PPCI in patients with acute myocardial infarction and cardiogenic shock.

Results
Total mortality was 80 patients representing 48.4% of the total 165 studied patients; 60 patients died during the hospital admission period, while the remaining 20 patients died post-discharge. In-hospital mortality was significantly higher in Post-PPCI–IABP group 40 (49.4%) versus Pre-PPCI–IABP group 20 (23.8%) (P = 0.001). Moreover, the mortality difference between the two groups was sustained over six-month follow-up period, where 15 patients (18.5%) died in the Post-PPCI–IABP group, while only 5 patients 6.0% died in the Pre-PPCI–IABP (P = 0.001).

Conclusions
Early IABP insertion before PPCI is associated with improved in-hospital and long-term survival when used for patients presenting with AMI complicated by hemodynamic instability.