bluuebunny/crossref_metadata_2025 huggingface dataset:
Interrelation of urban farming and urbanization: an alternative solution to urban food and environmental problems due to urbanization in Indonesia
Authors: Giyarsih Sri Rum , Armansyah  , Zaelany Andy Ahmad , Latifa Ade , Setiawan Bayu , Saputra Dani , Haqi Muamar , Lamijo  , Fathurohman Apit
Published: January 2024

Urbanization is the process of increasing the population migrating to urban areas, and urban farming is a farming practice carried out within the city. Both concepts have significant impacts on urban life and the environment. This research aims to analyze the interrelation of the positive impacts of urban farming and the negative impacts of urbanization. The analysis focuses on food and environmental aspects as alternative problem-solving methods in the cities of Bandung, Denpasar, and Palembang. This research uses qualitative method. Data collection uses field interview techniques with 30 informants, as well as a review of several scientific articles, previous research results, and reports from data-providing agencies such as the Indonesian Central Bureau of Statistics. Data analysis used the Miles and Huberman Model, with the stages of reduction, display, and conclusion drawing. The results of the analysis show that there is an interrelation between the positive impacts of urban farming and the negative impacts of urbanization in the cities of Bandung, Denpasar, and Palembang. In terms of food aspect, urban farming can provide various types of easily accessible food for urban dwellers, such as vegetables, fruits, fisheries, and small-scale livestock. The food produced is relatively close to residential areas, so the quality is still fresh and healthy and the price is affordable as well. In the environmental aspect, urban farming can optimize the use of limited or vacant land in residential areas into productive land, such as for green spaces, farming activities, gardening, fisheries, and livestock. Other functions include enhancing the beauty of the environment, reducing household waste, and preserving organism biodiversity.
Quantitative and qualitative initial validation of the accountable talk questionnaire
Authors: Kofman Talmy Ayelet , Mashal Nira
Published: January 2024

Introduction

Accountable Talk (AT) has been extensively studied as a tool for improving argumentation and respectful discourse. While several research tools exist for evaluating AT, as of yet there no self-report assessment tool to measure AT directly, on a large-scale basis, and without significant costs. The aim of the current study was to develop and provide initial validation for a self-report AT questionnaire (ATQ).

Methods

One hundred students aged 11–12 years participated in the study. Exploratory Factor Analysis, content validity, and test- retest reliability were assessed. 50 students were also randomly assigned to the qualitative part of the study. These students were recorded while discussing in small groups a topic provided by the experimenter (animal research). The qualitative data was coded and then correlated with the quantitative data obtained from the self-report questionnaire.

Results

The results indicated that a 12-items questionnaire can reliably assess three separate and independent qualities of AT: accountability to a learning community, accountability to rigorous thinking, and accountability to accurate knowledge. The reliability of the ATQ was high with α = 0.80. The Test-retest reliability was assessed at two time points separated by a 3-week interval with Pearson correlation. Excellent correlations (r > 0.98) between the ATQ scores were found. The correlation coefficients between the three components of the self-reported ATQ and the observed data obtained from the group discussions were significant positive medium-high.

Discussion

We have shown that a concise 12-item questionnaire can assess the three main components of Accountable Talk within the framework of respectful discourse. The questionnaire showed good reliability and structural validity, with weak correlations between sub-topics supporting the distinction between different aspects of Accountable Talk. We suggest that the ATQ can be used to evaluate the effectiveness of intervention programs aiming to improve students' acquisition of Accountable Talk skills.
Associations of antidiabetic drugs with diabetic retinopathy in people with type 2 diabetes: an umbrella review and meta-analysis
Authors: Tan Luyuan , Wang Zhaonan , Okoth Kelvin , Toulis Konstantinos A. , Denniston Alastair K. , Singh Baldev M. , Crowe Francesca L. , Sainsbury Christopher , Wang Jingya , Nirantharakumar Krishnarajah
Published: January 2024

Background

Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes.

Methods

A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052).

Results

With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99).

Conclusion

Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.
A study of the relationship between cytokine levels and the response to anti-VEGF therapy in polypoid choroidal vasculopathy with different choroidal thicknesses
Authors: Dong Su , Fan Pan , Yu Haotian , Jiang Bo , Sun Dawei
Published: January 2024

Purpose

Polypoidal choroidal vasculopathy (PCV) is an irreversible retinal choroidal disease. Individuals with PCV exhibit diverse baseline characteristics, including systemic characteristics, ocular traits, metabolic factor levels, and different responses to intravitreal anti-VEGF therapy. This study aims to investigate the pathogenesis of PCV by analyzing the systemic characteristics, ocular traits, and cytokine levels at baseline within a cohort of patients who exhibit different responses to anti-VEGF treatment.

Methods

We conducted a retrospective analysis involving 80 eyes diagnosed with PCV. Patients were categorized into two groups based on responses to suboptimal intravitreal ranibizumab injection therapy: those with suboptimal responses and optimal responses. Aqueous humor samples were collected from the experimental eyes, and cytokine expression levels were assessed using cytometric bead array analysis. All subjects were further stratified into two groups according to the median choroidal thickness. Subsequently, logistic regression analysis and the ROC curve were employed to examine the relationship between cytokine expression levels, choroidal thickness, and anti-VEGF response.

Results

The results revealed that compared to the group of optimal anti-VEGF response, the choroid in the suboptimal response group exhibited a significantly greater thickness. Additionally, compared to the suboptimal anti-VEGF response group, the expression levels of VEGF and VCAM-1 were markedly lower observed in the optimal anti-VEGF response group, while TNF-α showed the opposite trend. Logistic regression analysis indicated that VEGF, VCAM-1, and TNF-α in the aqueous humor were independent risk factors for a suboptimal anti-VEGF response. After adjusting other risk factors, the risk of suboptimal anti-VEGF response decreased to 0.998-fold, 0.997-fold, and 1.294-fold. The AUC values for VEGF, VCAM-1, and TNF-α were determined to be 0.805, 0.846, and 0.897, respectively. Furthermore, the risk of VEGF, VCAM-1, and TNF-α were significantly associated with an increased risk of suboptimal anti-VEGF response after correction for risk factors in the thick choroid group.

Conclusions

Our study demonstrated that PCV exhibits systemic and ocular characteristics variations based on different anti-VEGF responses. The levels of cytokines in aqueous humor were found to have a significant correlation with the anti-VEGF response in PCV. VEGF, VCAM-1, and TNF-α are potential targets for assessing treatment response in thick choroidal PCV.
Low-carbon operation optimization of integrated energy system considering CCS-P2G and multi-market interaction
Authors: Qin Lidong , Ma Hengrui , Huang Cunqiang , Li Hongxia , Wu Shidong , Wang Gangfei
Published: January 2024

Integrated energy system is crucial in realizing China’s “dual carbon” targets. Considering the carbon capture based electricity to gas and the interaction of multiple markets, this paper proposes a low-carbon operation optimization method of integrated energy system. In terms of market policy, a coupling trading mechanism for carbon trade and green certificates is established. This approach is intended to delve into the profound significance of utilizing green certificates in carbon emission reduction. In terms of equipment models, the coupling model of carbon capture equipment with coal-fired cogeneration unit, as well as power-to-gas equipment with renewable energy, is con-structed. In addition, this equipment model is introduced into the operation optimization scheduling of the comprehensive energy systems. A low-carbon economic operational strategy is further proposed to minimize the daily operational costs, by which the integrated energy system is eco-nomically, environmental protection optimized. To verify the effectiveness and feasibility of the proposed model, this paper sets up several comparison scenarios and conducts the simulations using GUROBI solver. The results show that the proposed strategy can effectively improve the uptake rate of renewable energy, reduce the carbon emission, improve the operation economy, and realize the complementary incentive effect between markets.
Genetics in the X-Men film franchise: mutants as allegories of difference
Authors: Grimsted Sonora R. , Krizner Katerina G. , Porter Cynthia D. , Clayton Jay
Published: January 2024

This article analyzes the complete corpus of live-action X-Men movies for their depictions of genetics and otherness. The researchers watched and qualitatively coded all thirteen movies produced by 20th Century Fox that take place in the same shared cinematic universe, beginning with X-Men (2000) and ending with The New Mutants (2020). The X-Men movies are unusual summer blockbusters since they explore genetic topics through their central characters, mutants, who are genetically different from their non-mutant peers. Mutants in the films evoke a plurality of analogies, such as mutant-as-Black and mutant-as-queer. These intersecting metaphors build upon a core of genetic difference to create a versatile but limited picture of prejudice, solidarity, and otherness.
Platelet derived exosomes disrupt endothelial cell monolayer integrity and enhance vascular inflammation in dengue patients
Authors: Vedpathak Sayali , Sharma Archana , Palkar Sonali , Bhatt Varsha R. , Patil Vishwanath Chandrashekhar , Kakrani Arjun L. , Mishra AkhileshChandra , Bhosle Deepak , Arankalle Vidya A. , Shrivastava Shubham
Published: January 2024

Background

Thrombocytopenia is the most notable phenomenon in dengue. Activation status of platelets and interaction of platelets with endothelium contribute towards dengue disease pathogenesis. Platelets are the major cell types known to release extracellular vesicles, especially exosomes in circulation. However, the role of platelet derived exosomes (PLT-EXOs) in endothelial dysfunction during dengue infection remains unknown.

Methods

In this study, we recruited 28 healthy subjects and 69 dengue patients categorized as WS- (n=31), WS+ (n=29) and SD (n=9). Platelets were isolated from platelet rich plasma of dengue patients and their activation was assessed by flow cytometry. PLT-EXOs were isolated by ultracentrifugation method. Western blot analyses were performed to characterize the exosomes. Exosome uptake experiment was carried out to see the internalization of exosomes inside endothelial cells (HUVECs). To observe the effect of exosomes on endothelial cells, exosomes were added on HUVECs and expression of adherens and tight junctional proteins were examined by immunofluorescence assay and western blot. Expression levels of vascular injury markers were measured in the culture supernatants of Exosome-HUVEC coculture and sera of dengue patients by MSD-multiplex assay.

Results

As compared to healthy subjects, CD41/CD61 expression was significantly reduced (p<0.0001) and CD62p expression was significantly increased (p<0.0001) on platelets in dengue patients. PLT-EXOs isolated from the dengue patients showed higher expression of CD63 and CD9 proteins than the healthy subjects. With in-vitro immunofluorescence assays, we illustrated the internalization of PLT-EXOs by the HUVECs and observed disruption of endothelial cell monolayer integrity in the presence of PLT-EXOs from WS+ and SD patients. Furthermore, the significant reduction in the expressions of ZO-2, VE-Cadherin and CD31 in endothelial cells following exposure to PLT-EXOs from the dengue patients provide direct evidence of PLT-EXOs mediated vascular permeability. PLT-EXOs stimulated the release of inflammatory markers CRP, SAA, sVCAM-1 and sICAM-1 in the supernatants of HUVEC cells. Importantly, significantly higher levels of CRP, sVCAM-1 and sICAM-1 in the sera of severe than mild dengue patients (p<0.0001) suggest their role in disease severity.

Conclusions

In summary, our data suggest that PLT-EXOs promote vascular leakage via release of proinflammatory mediators and compromise vascular barrier integrity in dengue patients.
Integrating single-cell and bulk transcriptomic analyses to develop a cancer-associated fibroblast-derived biomarker for predicting prognosis and therapeutic response in breast cancer
Authors: Li Chunzhen , Yang Lanjie , Zhang Yunyan , Hou Qianshan , Wang Siyi , Lu Shaoteng , Tao Yijie , Hu Wei , Zhao Liyuan
Published: January 2024

Background

Cancer-associated fibroblasts (CAFs) contribute to the progression and treatment of breast cancer (BRCA); however, risk signatures and molecular targets based on CAFs are limited. This study aims to identify novel CAF-related biomarkers to develop a risk signature for predicting the prognosis and therapeutic response of patients with BRCA.

Methods

CAF-related genes (CAFRGs) and a risk signature based on these genes were comprehensively analyzed using publicly available bulk and single-cell transcriptomic datasets. Modular genes identified from bulk sequencing data were intersected with CAF marker genes identified from single-cell analysis to obtain reliable CAFRGs. Signature CAFRGs were screened via Cox regression and least absolute shrinkage and selection operator (LASSO) analyses. Multiple patient cohorts were used to validate the prognosis and therapeutic responsiveness of high-risk patients stratified based on the CAFRG-based signature. In addition, the relationship between the CAFRG-based signature and clinicopathological factors, tumor immune landscape, functional pathways, chemotherapy sensitivity and immunotherapy sensitivity was examined. External datasets were used and sample experiments were performed to examine the expression pattern of MFAP4, a key CAFRG, in BRCA.

Results

Integrated analyses of single-cell and bulk transcriptomic data as well as prognostic screening revealed a total of 43 prognostic CAFRGs; of which, 14 genes (TLN2, SGCE, SDC1, SAV1, RUNX1, PDLIM4, OSMR, NT5E, MFAP4, IGFBP6, CTSO, COL12A1, CCDC8 and C1S) were identified as signature CAFRGs. The CAFRG-based risk signature exhibited favorable efficiency and accuracy in predicting survival outcomes and clinicopathological progression in multiple BRCA cohorts. Functional enrichment analysis suggested the involvement of the immune system, and the immune infiltration landscape significantly differed between the risk groups. Patients with high CAF-related risk scores (CAFRSs) exhibited tumor immunosuppression, enhanced cancer hallmarks and hyposensitivity to chemotherapy and immunotherapy. Five compounds were identified as promising therapeutic agents for high-CAFRS BRCA. External datasets and sample experiments validated the downregulation of MFAP4 and its strong correlation with CAFs in BRCA.

Conclusions

A novel CAF-derived gene signature with favorable predictive performance was developed in this study. This signature may be used to assess prognosis and guide individualized treatment for patients with BRCA.
Extracellular vesicles and microvilli in the immune synapse
Authors: Ruiz-Navarro Javier , Calvo Víctor , Izquierdo Manuel
Published: January 2024

T cell receptor (TCR) binding to cognate antigen on the plasma membrane of an antigen-presenting cell (APC) triggers the immune synapse (IS) formation. The IS constitutes a dedicated contact region between different cells that comprises a signaling platform where several cues evoked by TCR and accessory molecules are integrated, ultimately leading to an effective TCR signal transmission that guarantees intercellular message communication. This eventually leads to T lymphocyte activation and the efficient execution of different T lymphocyte effector tasks, including cytotoxicity and subsequent target cell death. Recent evidence demonstrates that the transmission of information between immune cells forming synapses is produced, to a significant extent, by the generation and secretion of distinct extracellular vesicles (EV) from both the effector T lymphocyte and the APC. These EV carry biologically active molecules that transfer cues among immune cells leading to a broad range of biological responses in the recipient cells. Included among these bioactive molecules are regulatory miRNAs, pro-apoptotic molecules implicated in target cell apoptosis, or molecules triggering cell activation. In this study we deal with the different EV classes detected at the IS, placing emphasis on the most recent findings on microvilli/lamellipodium-produced EV. The signals leading to polarized secretion of EV at the synaptic cleft will be discussed, showing that the IS architecture fulfills a fundamental task during this route.
The regulatory role of eosinophils in adipose tissue depends on autophagy
Authors: Hosseini Aref , Germic Nina , Markov Nikita , Stojkov Darko , Oberson Kevin , Yousefi Shida , Simon Hans-Uwe
Published: January 2024

Introduction

Obesity is a metabolic condition that elevates the risk of all-cause mortality. Brown and beige adipose tissues, known for their thermogenic properties, offer potential therapeutic targets for combating obesity. Recent reports highlight the role of immune cells, including eosinophils, in adipose tissue homeostasis, while the underlying mechanisms are poorly understood.

Methods

To study the role of autophagy in eosinophils in this process, we used a genetic mouse model lacking autophagy-associated protein 5 (Atg5), specifically within the eosinophil lineage (Atg5eoΔ).

Results

The absence of Atg5 in eosinophils led to increased body weight, impaired glucose metabolism, and alterations in the cellular architecture of adipose tissue. Our findings indicate that Atg5 modulates the functional activity of eosinophils within adipose tissue rather than their abundance. Moreover, RNA-seq analysis revealed upregulation of arginase 2 (Arg2) in Atg5-knockout eosinophils. Increased Arg2 activity was shown to suppress adipocyte beiging. Furthermore, we observed enrichment of the purine pathway in the absence of Atg5 in eosinophils, leading to a pro-inflammatory shift in macrophages and a further reduction in beiging.

Discussion

The data shed light on the importance of autophagy in eosinophils and its impact on adipose tissue homeostasis by suppressing Arg2 expression and limiting inflammation in adipose tissue.
Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy
Authors: Dou Baitao , Ren Shihui , Qiu Ling , Zhang Xupai , Zhang Nan , Cai Jiao , Chen Dan , Zhang Qian , Yao Hao , Fan Fangyi
Published: January 2024

Background

Chimeric antigen receptor T (CAR-T) cell immunotherapy is becoming one of the most promising treatments for hematological malignancies, however, complications such as cytokine release syndrome (CRS) seriously threaten the lives of patients. Interleukin 6(IL-6) monoclonal antibody is the common and useful treatment of CRS, however, it is not clear whether prophylactic use IL-6 monoclonal antibody before CAR-T therapy can reduce the incidence of CRS.

Purpose

This study aims to systematically evaluate whether the prophylactic use of IL-6 monoclonal antibody can reduce the incidence of CRS.

Data sources and methods

We searched the PubMed, Embase, web of Science, and Cochrane Library databases for studies that reported the prophylactic use of IL-6 monoclonal antibody in the treatment of CRS-related complications of CAR-T cell immunotherapy before December 2022. The literature is screened according to the established inclusion and exclusion criteria, relevant data are extracted, and the quality of the literature is evaluated using the scale Cochrane bias risk assessment tool, and the Review Manager 5.3 is used to draw for related charts. Since the two experimental data only provide the median, the maximum and minimum values of the data, the mean and standard (Standard Deviation, SD) are calculated by this document Delai, and finally use Review Manager for data processing, and STATA software for supplementation.

Results

A total of 2 trials with a total of 37 participants were included in this study. Meta-analysis showed that compared with no use of IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced the incidence of CRS [RR: 0.41 95% confidence interval (0.20, 0.86) I[2] = 0.0% P = 0.338 z = −2.369 (p = 0.018)]. In subgroup analysis, compared with those who did not use IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced lactate dehydrogenase (LDH)[MD: −617.21, 95% confidence interval (−1104.41, −130.01) I[2] = 0% P = 0.88 Z = 2.48 (P = 0.01)], prophylactic use of IL-6 monoclonal antibody has a significant effect on reducing peak C-reactive protein (CRP) after CAR-T therapy [MD: −11.58, 95% confidence interval (−15.28, −7.88) I[2] = 0.0% P = 0.73 z = 6.14 (p < 0.00001)].

Conclusion

The prophylactic use of IL-6 monoclonal antibody can significantly reduce the incidence of CRS complications after CAR-T therapy, can also reduce LDH vaule and peak CRP vaule after CAR-T therapy.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023487662, identifier CRD42023487662.
Fasting glucose variability and risk of dementia in Parkinson’s disease: a 9-year longitudinal follow-up study of a nationwide cohort
Authors: Kang Sung Hoon , Choi Yunjin , Chung Su Jin , Moon Seok-Joo , Kim Chi Kyung , Kim Ji Hyun , Oh Kyungmi , Yoon Joon Shik , Seo Sang Won , Cho Geum Joon , Koh Seong-Beom
Published: January 2024

Background

Diabetes is associated with an increased risk of Parkinson’s disease dementia (PDD); however, it is unknown whether this association is dependent on continuous hyperglycemia, hypoglycemic events, or glycemic variability. We aimed to investigate the relationship between visit-to-visit fasting glucose variability and PDD development in patients with Parkinson’s disease (PD).

Methods

Using data from the Korean National Health Insurance Service, we examined 9,264 patients aged ≥40 years with de novo Parkinson’s disease (PD) who underwent ≥3 health examinations and were followed up until December 2019. Glucose variability was measured using the coefficient of variation, variability independent of the mean, and average real variability. Fine and Gray competing regression analysis was performed to determine the effect of glucose variability on incident PDD.

Results

During the 9.5-year follow-up period, 1,757 of 9,264 (19.0%) patients developed PDD. Patients with a higher visit-to-visit glucose variability had a higher risk of future PDD. In the multivariable adjusted model, patients with PD in the highest quartile (subdistribution hazard ratio [SHR] = 1.50, 95% CI 1.19 to 1.88), quartile 3 (SHR = 1.29, 95% CI 1.02 to 1.62), and quartile 2 (SHR = 1.30, 95% CI 1.04 to 1.63) were independently associated with a higher risk of PDD than those in the lowest quartile.

Conclusion

We highlighted the effect of long-term glucose variability on the development of PDD in patients with PD. Furthermore, our findings suggest that preventive measures for constant glucose control may be necessary to prevent PDD.
Sensory temporal sampling in time: an integrated model of the TSF and neural noise hypothesis as an etiological pathway for dyslexia
Authors: Lasnick Oliver H. M. , Hoeft Fumiko
Published: January 2024

Much progress has been made in research on the causal mechanisms of developmental dyslexia. In recent years, the “temporal sampling” account of dyslexia has evolved considerably, with contributions from neurogenetics and novel imaging methods resulting in a much more complex etiological view of the disorder. The original temporal sampling framework implicates disrupted neural entrainment to speech as a causal factor for atypical phonological representations. Yet, empirical findings have not provided clear evidence of a low-level etiology for this endophenotype. In contrast, the neural noise hypothesis presents a theoretical view of the manifestation of dyslexia from the level of genes to behavior. However, its relative novelty (published in 2017) means that empirical research focused on specific predictions is sparse. The current paper reviews dyslexia research using a dual framework from the temporal sampling and neural noise hypotheses and discusses the complementary nature of these two views of dyslexia. We present an argument for an integrated model of sensory temporal sampling as an etiological pathway for dyslexia. Finally, we conclude with a brief discussion of outstanding questions.
Vibration-induced postural reactions: a scoping review on parameters and populations studied
Authors: Bertrand-Charette Michaël , Perron Marie-Pier , da Silva Rubens A. , Beaulieu Louis-David
Published: January 2024

Objective

Mechanical vibration is an effective way for externally activating Ia primary endings of the muscle spindles and skin mechanoreceptors. Despite its popularity in proprioception and postural control studies, there is still no review covering the wide variety of vibration parameters or locations used in studies. The main purpose of this scoping review was thus to give an overview of general vibration parameters and to identify, if available, the rationale for justifying methodological choices concerning vibration parameters.

Methods

Three databases (Pubmed, CINHAL, and SPORTDiscus) were searched from inception to July 2022. Included articles were to focus on the study of muscle spindles and skin mechanoreceptors vibration in humans and assess postural control. Following inclusion, data regarding demographic information, populations, vibration parameters and rationale were extracted and summarized.

Results

One hundred forty-seven articles were included, mostly targeting lower extremities (n= 137) and adults (n= 126). The parameters used varied widely but were most often around 80 Hz, at an amplitude of 1 mm for 10–20 s. Regarding rationales, nearly 50% of the studies did not include any, whereas those including one mainly cited the same two studies, without elaborating specifically on the parameter's choice.

Conclusion

This scoping review provided a comprehensive description of the population recruited and parameters used for vibration protocols in current studies with humans. Despite many studies, there remain important gaps of knowledge that needs to be filled, especially for vibration amplitude and duration parameters in various populations.
Ambient melting behavior of stoichiometric uranium oxides
Authors: Burakovsky Leonid , Ramsey Scott D. , Baty Roy S.
Published: January 2024

As UO2 is easily oxidized during the nuclear fuel cycle it is important to have a detailed understanding of the structures and properties of the oxidation products. Experimental work over the years has revealed many stable uranium oxides including UO2, U4O9 (UO2.25), U3O7 (UO2.33), U2O5 (UO2.5), U3O8 (UO2.67), and UO3, all with a number of different polymorphs. These oxides are broadly split into two categories, fluorite-based structures with stoichiometries in the range of UO2 to UO2.5 and less dense layered-type structures with stoichiometries in the range of UO2.5 to UO3. While UO2 is well characterized, both experimentally and computationally, there is a paucity of data concerning higher stoichiometry oxides in the literature. In this work we determine the ambient melting points of all the six stoichiometric uranium oxides listed above and compare them to the available experimental and/or theoretical data. We demonstrate that a family of the six ambient melting points map out a solid-liquid transition boundary consistent with the high-temperature portion of the phase diagram of uranium-oxygen system suggested by Babelot et al.
Comparing quality of life in lower extremity tumor patients undergoing limb salvage surgery and amputation: a meta-analysis
Authors: Banskota Nishant , Lei Senlin , Yuan Dechao , Fang Xiang , Banskota Sonali , Zhang Wenli , Duan Hong
Published: January 2024

Purpose

Limb salvage surgery and amputation are two commonly performed procedures for lower extremity tumors. When comparing these procedures in tumor patients, it is important to consider their impact on quality of life (QOL) and functional mobility. These patients often experience physical, emotional, and psychological challenges, making these factors crucial in determining the most suitable treatment approach.

Method

The outcomes of lower extremity tumors patients for QOL were collected from PubMed, MEDLINE, EMBASE, Cochrane, and Google Scholar until 28 February 2023. The physical function, mental health, role function, social function, emotional function, Toronto Extremity Salvage Score, and Musculoskeletal Tumor Society Score outcomes were analyzed to determine the differences between the two procedures.

Results

Five articles were included according to the selection criteria with a total of 245 patients. The standard mean difference (SMD) values of each parameter were slightly higher in limb salvage surgery patients but not higher enough to produce statistically significant results; the SMD values for physical function and mental health were 0.72 and 0.04, respectively. This study did not report any heterogeneity or publication bias.

Conclusions

QOL is a large and enhanced term, which carries its importance and is challenging to compare between any procedures. The minimal rise in SMD of different QOL parameters highlighted only a slight advantage of limb salvage surgery over amputation. Therefore, further research is required to explore the impact of this crucial topic.
Fraisinib: a calixpyrrole derivative reducing A549 cell-derived NSCLC tumor in vivo acts as a ligand of the glycine-tRNA synthase, a new molecular target in oncology
Authors: Ben Toumia Iméne , Bachetti Tiziana , Chekir-Ghedira Leila , Profumo Aldo , Ponassi Marco , Di Domizio Alessandro , Izzotti Alberto , Sciacca Salvatore , Puglisi Caterina , Forte Stefano , Giuffrida Raffaella , Colarossi Cristina , Milardi Danilo , Grasso Giuseppe , Lanza Valeria , Fiordoro Stefano , Drago Giacomo , Tkachenko Kateryna , Cardinali Barbara , Romano Paolo , Iervasi Erika , Vargas Gabriela Coronel , Barboro Paola , Kohnke Franz Heinrich , Rosano Camillo
Published: January 2024

Background and purpose: Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-small-cell lung cancer accounts for 85%–90% of all lung cancers. We propose a compound that successfully fights tumor growth in vivo by targeting the enzyme GARS1.

Experimental approach: We present an in-depth investigation of the mechanism through which Fraisinib [meso-(p-acetamidophenyl)-calix(4)pyrrole] affects the human lung adenocarcinoma A549 cell line. In a xenografted model of non-small-cell lung cancer, Fraisinib was found to reduce tumor mass volume without affecting the vital parameters or body weight of mice. Through a computational approach, we uncovered that glycyl-tRNA synthetase is its molecular target. Differential proteomics analysis further confirmed that pathways regulated by Fraisinib are consistent with glycyl-tRNA synthetase inhibition.

Key results: Fraisinib displays a strong anti-tumoral potential coupled with limited toxicity in mice. Glycyl-tRNA synthetase has been identified and validated as a protein target of this compound. By inhibiting GARS1, Fraisinib modulates different key biological processes involved in tumoral growth, aggressiveness, and invasiveness.

Conclusion and implications: The overall results indicate that Fraisinib is a powerful inhibitor of non-small-cell lung cancer growth by exerting its action on the enzyme GARS1 while displaying marginal toxicity in animal models. Together with the proven ability of this compound to cross the blood–brain barrier, we can assess that Fraisinib can kill two birds with one stone: targeting the primary tumor and its metastases “in one shot.” Taken together, we suggest that inhibiting GARS1 expression and/or GARS1 enzymatic activity may be innovative molecular targets for cancer treatment.
Iron scavenging and suppression of collagen cross-linking underlie antifibrotic effects of carnosine in the heart with obesity
Authors: Berdaweel Islam A. , Monroe T. Blake , Alowaisi Amany A. , Mahoney Jolonda C. , Liang I-Chau , Berns Kaitlyn A. , Gao Dylan , McLendon Jared M. , Anderson Ethan J.
Published: January 2024

Oral consumption of histidyl dipeptides such as l-carnosine has been suggested to promote cardiometabolic health, although therapeutic mechanisms remain incompletely understood. We recently reported that oral consumption of a carnosine analog suppressed markers of fibrosis in liver of obese mice, but whether antifibrotic effects of carnosine extend to the heart is not known, nor are the mechanisms by which carnosine is acting. Here, we investigated whether oral carnosine was able to mitigate the adverse cardiac remodeling associated with diet induced obesity in a mouse model of enhanced lipid peroxidation (i.e., glutathione peroxidase 4 deficient mice, GPx4+/−), a model which mimics many of the pathophysiological aspects of metabolic syndrome and T2 diabetes in humans. Wild-type (WT) and GPx4+/−male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks. Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study. Carnosine treatment led to a moderate improvement in glycemic control in WT and GPx4+/−mice on HFHS diet, although insulin sensitivity was not significantly affected. Interestingly, while our transcriptomic analysis revealed that carnosine therapy had only modest impact on global gene expression in the heart, carnosine substantially upregulated cardiac GPx4 expression in both WT and GPx4+/−mice on HFHS diet. Carnosine also significantly reduced protein carbonyls and iron levels in myocardial tissue from both genotypes on HFHS diet. Importantly, we observed a robust antifibrotic effect of carnosine therapy in hearts from mice on HFHS diet, which further in vitro experiments suggest is due to carnosine’s ability to suppress collagen-cross-linking. Collectively, this study reveals antifibrotic potential of carnosine in the heart with obesity and illustrates key mechanisms by which it may be acting.
Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model
Authors: Adamcova Michaela , Parova Helena , Lencova-Popelova Olga , Kollarova-Brazdova Petra , Baranova Ivana , Slavickova Marcela , Stverakova Tereza , Mikyskova Petra Sauer , Mazurova Yvona , Sterba Martin
Published: January 2024

Background: Anthracycline cardiotoxicity is a well-known complication of cancer treatment, and miRNAs have emerged as a key driver in the pathogenesis of cardiovascular diseases. This study aimed to investigate the expression of miRNAs in the myocardium in early and late stages of chronic anthracycline induced cardiotoxicity to determine whether this expression is associated with the severity of cardiac damage.

Method: Cardiotoxicity was induced in rabbits via daunorubicin administration (daunorubicin, 3 mg/kg/week; for five and 10 weeks), while the control group received saline solution. Myocardial miRNA expression was first screened using TaqMan Advanced miRNA microfluidic card assays, after which 32 miRNAs were selected for targeted analysis using qRT-PCR.

Results: The first subclinical signs of cardiotoxicity (significant increase in plasma cardiac troponin T) were observed after 5 weeks of daunorubicin treatment. At this time point, 10 miRNAs (including members of the miRNA-34 and 21 families) showed significant upregulation relative to the control group, with the most intense change observed for miRNA-1298-5p (29-fold change, p < 0.01). After 10 weeks of daunorubicin treatment, when a further rise in cTnT was accompanied by significant left ventricle systolic dysfunction, only miR-504-5p was significantly (p < 0.01) downregulated, whereas 10 miRNAs were significantly upregulated relative to the control group; at this time-point, the most intense change was observed for miR-34a-5p (76-fold change). Strong correlations were found between the expression of multiple miRNAs (including miR-34 and mir-21 family and miR-1298-5p) and quantitative indices of toxic damage in both the early and late phases of cardiotoxicity development. Furthermore, plasma levels of miR-34a-5p were strongly correlated with the myocardial expression of this miRNA.

Conclusion: To the best of our knowledge, this is the first study that describes alterations in miRNA expression in the myocardium during the transition from subclinical, ANT-induced cardiotoxicity to an overt cardiotoxic phenotype; we also revealed how these changes in miRNA expression are strongly correlated with quantitative markers of cardiotoxicity.
Renal and survival benefits of seventeen prescribed Chinese herbal medicines against oxidative-inflammatory stress in systemic lupus erythematosus patients with chronic kidney disease: a real-world longitudinal study
Authors: Chen Hsiao-Tien , Tung Chien-Hsueh , Yu Ben-Hui , Chang Ching-Mao , Chen Yi-Chun
Published: January 2024

Background: Systemic lupus erythematosus (SLE) significantly links to LN, a type of CKD with high mortality despite modern Western treatments. About 70% of SLE patients develop LN, and 30% advance to end-stage renal disease (ESRD). Concerns about glucocorticoid side effects and LN worsening due to oxidative stress prompt alternative treatment searches. In Taiwan, over 85% of SLE patients opt for complementary methods, especially Chinese herbal medicine (CHM). We pinpointed seventeen CHMs for SLE (PRCHMSLE) with antioxidative and anti-inflammatory properties from national health insurance data (2000–2017). Our primary aim was to assess their impact on renal and survival outcomes in SLE patients progressing to CKD (SLE-CKD), with a secondary focus on the risks of hospitalization and hyperkalemia.

Methods: We established a propensity-matched cohort of 1,188 patients with SLE-CKD, comprising 594 PRCHMSLE users and 594 nonusers. We employed Cox proportional hazards models and restricted mean survival time (RMST) analyses to assess the renal and survival outcomes of PRCHMSLE users. Moreover, we performed pooling and network analyses, specifically focusing on the renal effects linked to PRCHMSLE.

Results: PRCHMSLE use was associated with decreased adjusted hazard ratios for ESRD (0.45; 95% confidence interval, 0.25–0.79, p = 0.006), all-cause mortality (0.56; 0.43–0.75, p < 0.0001), non-cardiovascular mortality (0.56; 0.42–0.75, p < 0.0001), and hospitalization (0.72; 0.52–0.96, p = 0.009). Hyperkalemia risk did not increase. Significant differences in RMST were observed: 0.57 years (95% confidence interval, 0.19–0.95, p = 0.004) for ESRD, 1.22 years (0.63–1.82, p < 0.0001) for all-cause mortality, and 1.21 years (0.62–1.80, p < 0.0001) for non-cardiovascular mortality, favoring PRCHMSLE use. Notably renoprotective PRCHMSLE included Gan-Lu-Ying, Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), Jia-Wei-Xiao-Yao-San, and Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi). Network analysis highlighted primary treatment strategies with central components like Liu-Wei-Di-Huang-Wan, Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi), Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), and Zhi-Bai-Di-Huang-Wan.

Conclusion: This work underscores the pronounced renal and survival benefits associated with the seventeen PRCHMSLE in the treatment of SLE-CKD, concurrently mitigating the risks of hospitalization and hyperkalemia. This highlights their potential as alternative treatment options for individuals with this condition.
The frequency of atrial fibrillatory waves is modulated by the spatiotemporal pattern of acetylcholine release: a 3D computational study
Authors: Celotto Chiara , Sánchez Carlos , Abdollahpur Mostafa , Sandberg Frida , Rodriguez Mstas Jose F. , Laguna Pablo , Pueyo Esther
Published: January 2024

In atrial fibrillation (AF), the ECG P-wave, which represents atrial depolarization, is replaced with chaotic and irregular fibrillation waves (f waves). The f-wave frequency, Ff, shows significant variations over time. Cardiorespiratory interactions regulated by the autonomic nervous system have been suggested to play a role in such variations. We conducted a simulation study to test whether the spatiotemporal release pattern of the parasympathetic neurotransmitter acetylcholine (ACh) modulates the frequency of atrial reentrant circuits. Understanding parasympathetic involvement in AF may guide more effective treatment approaches and could help to design autonomic markers alternative to heart rate variability (HRV), which is not available in AF patients. 2D tissue and 3D whole-atria models of human atrial electrophysiology in persistent AF were built. Different ACh release percentages (8% and 30%) and spatial ACh release patterns, including spatially random release and release from ganglionated plexi (GPs) and associated nerves, were considered. The temporal pattern of ACh release, ACh(t), was simulated following a sinusoidal waveform of frequency 0.125 Hz to represent the respiratory frequency. Different mean concentrations (ACh̄) and peak-to-peak ranges of ACh (ΔACh) were tested. We found that temporal variations in Ff, Ff(t), followed the simulated temporal ACh(t) pattern in all cases. The temporal mean of Ff(t), F̄f, depended on the fibrillatory pattern (number and location of rotors), the percentage of ACh release nodes and ACh̄. The magnitude of Ff(t) modulation, ΔFf, depended on the percentage of ACh release nodes and ΔACh. The spatial pattern of ACh release did not have an impact on F̄f and only a mild impact on ΔFf. The f-wave frequency, being indicative of vagal activity, has the potential to drive autonomic-based therapeutic actions and could replace HRV markers not quantifiable from AF patients.