bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging trends and hot spots of sleep and genetic research: a bibliometric analysis of publications from 2002 to 2022 in the field
Authors: Tao Ying , Qin Yi , Chen Sifan , Xu Tian , Lin Junhui , Su Diansan , Yu Weifeng , Chen Xuemei
Published: November 2023

Background

Sleep is an important biological process and has been linked to many diseases; however, very little is known about which and how genes control and regulate sleep. Although technology has seen significant development, this issue has still not been adequately resolved. Therefore, we conducted a bibliometric analysis to assess the progress in research on sleep quality and associated genes over the past 2 decades. Through our statistical data and discussions, we aimed to provide researchers with better research directions and ideas, thus promoting the advancement of this field.

Methods

On December 29, 2022, we utilized bibliometric techniques, such as co-cited and cluster analysis and keyword co-occurrence, using tools such as CiteSpace, VOSviewer, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com/), to conduct a thorough examination of the relevant publications extracted from the Web of Science Core Collection (WoSCC). Our analysis aimed to identify the emerging trends and hot spots in this field while also predicting their potential development in future.

Results

Cluster analysis of the co-cited literature revealed the most popular terms relating to sleep quality and associated genes in the manner of cluster labels; these included genome-wide association studies (GWAS), circadian rhythms, obstructive sleep apnea (OSA), DNA methylation, and depression. Keyword burst detection suggested that obstructive sleep apnea, circadian clock, circadian genes, and polygenic risk score were newly emergent research hot spots.

Conclusion

Based on this bibliometric analysis of the publications in the last 20 years, a comprehensive analysis of the literature clarified the contributions, changes in research hot spots, and evolution of research techniques regarding sleep quality and associated genes. This research can provide medical staff and researchers with revelations into future directions of the study on the pathological mechanisms of sleep-related diseases.
Unlocking the role of lactate: metabolic pathways, signaling, and gene regulation in postmitotic retinal cells
Authors: Rajala Raju V. S. , Rajala Ammaji
Published: November 2023

The Warburg effect, which was first described a century ago, asserts that mitotic tumor cells generate higher quantities of lactate. Intriguingly, even in typical physiological circumstances, postmitotic retinal photoreceptor cells also produce elevated levels of lactate. Initially classified as metabolic waste, lactate has since gained recognition as a significant intracellular signaling mediator and extracellular ligand. This current review endeavors to provide a concise overview and discourse on the following topics: the localization of lactate-producing enzymes, the functional significance of these enzymes, the signaling functions of lactate, and its impact on the gene expression of photoreceptors in retinal cells.
Predictors of length of hospital stay for preterm infants in Ethiopia: a competing risk analysis
Authors: Bonger Zelalem Tazu , Mamo Biniyam Tedla , Birra Sosna Bayu , Yalew Alemayehu Worku
Published: November 2023

Background

Length of hospital stay (LOS) is one of the essential indicators for evaluating the efficiency and the quality-of-care service delivered. predicting LOS is critical for resource allocation, decision-making, lowering neonatal morbidity and death, enhancing clinical outcomes and parent counseling. In addition, extended hospital stays (long LOS_NICU) place a burden on the healthcare systems decreasing bed turnover rates as well as their financial stand and the mental stress on families. In Ethiopia, there is limited evidence on the determinant factors that influence on LOS.

Objectives

To determine factors affecting neonatal intensive care unit length of stay for all preterm newborns who were discharged alive.

Method

The study used a secondary data source, was collected for the Study of Illness in Preterm (SIP) infants project. The research study was a multicenter, cross-sectional, observational clinical study that took place in five Ethiopia hospitals from July 1, 2016, to May 31, 2018. The predictors of LOS were determined using Fine-Gray's competing risk analysis.

Results

For this study 3,511 preterm infants admitted to the NICU were analyzed. About 28.8% of the preterm infants died during their time in neonatal care while 66.6% were discharged alive. At the end of the study 4.6% babies were still in the NICU. The overall median LOS (death or discharge) was 7 days, with an interquartile range of 8 days. The cumulative incidence of discharge rose with increasing in gestational age and birth weight, on the contrary, the rate of discharge was decreased by 45.7% with the development of RDS (SDH ratio: 0.543), by 75.9% with the development of apnea (SDH ratio: 0.241), by 36.2% with sepsis, and by 43.6% with pneumonia (SDH ratio: 0.564).

Conclusions

Preterm newborns with a low gestational age and birth weight have a greater probability of having a prolonged LOS. Complications of the medical conditions RDS, apnea, sepsis, pneumonia, anemia, asphyxia, and NEC substantially raise LOS considerably.
Efficacy of RUTI® immunotherapy against active tuberculosis in a mouse model challenges the Koch phenomenon
Authors: Soldevilla Pablo , Buisan Anna , Diaz Jorge , Saladrigas Sergi , Rosales Yaiza , Arias Lilibeth , Jimenez-Melsio Alexandra , Vilaplana Cristina , Amat Fabregat Merce , Cardona Pere-Joan
Published: November 2023

Objectives

The objective of this study was to evaluate the safety and efficacy of the therapeutic vaccine RUTI® with or without the standard of care (SOC) chemotherapy for TB in an experimental murine model.

Methods

We assessed the efficacy of RUTI®, a vaccine based on pasteurized and freeze-dried cell-wall fragments from Mycobacterium tuberculosis (Mtb), the SOC for sensitive TB (isoniazid, rifampicin, ethambutol, and pyrazinamide) in the murine active TB model in C3HeB/FeJ strain (Kramnik model). We evaluated the bacillary load in the lungs and spleen, the immune response against specific Mtb antigens (PPD, HSP16.3, ESAT-6, and PsTS1), and lung damage in paraffined tissues for qualitative and quantitative analysis.

Results

RUTI® significantly reduces the pulmonary damage (x3) and the bacterial burden in the lungs (1.5 log10) and spleen (1 log10), and maintains the cellular immune response against ESAT-6, compared to SOC. There was also an additive effect when administered in combination with SOC, increasing the reduction of the lung damage (x2), the bacillary load in lungs (1 log10) and increasing the immune response against PPD, HSP16.3 and PsTS1.

Discussion

Therapeutic vaccination against TB has been avoided for decades due to fear of toxicity through the Koch phenomenon. These data show for the first time the safety of immunotherapy with Mtb antigens in an active TB model, adding efficacy to SOC. This encourages the beginning of clinical studies to evaluate the safety and efficacy of RUTI® in TB patients to improve their health, reduce its potential infectiousness, and reduce the length of treatment.
Identifying the Spatial Risk Patterns of Agricultural Non-Point Source Pollution in a Basin of the Upper Yangtze River
Authors: Wang Junli , Fu Zishi , Qiao Hongxia , Bi Yucui , Liu Fuxing
Published: November 2023

Agricultural non-point source pollution (ANPSP) is a primary cause of watershed water quality deterioration, and over 50% of NPS pollutants are estimated to come from ANPSP. Based on the “source-sink” theory and minimum cumulative resistance (MCR) model, ANPSP source and key resistance factors were integrated to identify areas at risk of ANPSP production and transportation into the waters of the upper Yangtze River basin. The results showed a spatial difference in the agricultural pollution sources of the basin, which were determined using both ANPSP loads and land-use types. Soil type, rainfall erosivity, and elevation were the three most important resistance factors in pollution transportation, weighting 0.373, 0.241, and 0.147, respectively. There was a spatial effect on the comprehensive resistance of ANPSP transportation, which was lower in mountainous terrain at the central basin. On the coupling of source and resistance processes, regions at serious risk of ANPSP were found to be concentrated in the southwest area. Areas at very high risk of NH3-N and TP pollution accounted for 37.6% and 38.1%, respectively, in the total town/street area. The spatial risk patterns identified in this study could be used for decision making and policy regulation of ANPSP and for aquatic environmental protection.
Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors
Authors: Zhang Yiyang , Zhou Manlin , Liang Yuxin , Li Rui , Zhang Lan , Chen Shuwu , Yang Kun , Ding Haie , Tan Xiao , Zhang Qian , Qiao Zilin
Published: November 2023

The aim of this study was to investigate the molecular mechanisms by which hypoxia affects the biological behavior of yak PASMCs, the changes in the histological structure of yak and cattle lungs, and the relationships and regulatory roles that exist regarding the differences in the distribution and expression of PDK1 and its hypoxia-associated factors screened for their role in the adaptation of yak lungs to the plateau hypoxic environment. The results showed that, at the level of transcriptome sequencing, the molecular regulatory mechanisms of the HIF-1 signaling pathway, glucose metabolism pathway, and related factors (HK2/PGK1/ENO1/ENO3/ALDOC/ALDOA) may be closely related to the adaptation of yaks to the hypoxic environment of the plateau; at the tissue level, the presence of filled alveoli and semi-filled alveoli, thicker alveolar septa and basement membranes, a large number of erythrocytes, capillary distribution, and collagen fibers accounted for all levels of fine bronchioles in the lungs of yaks as compared to cattle. A higher percentage of goblet cells was found in the fine bronchioles of yaks, and PDK1, HIF-1α, and VEGF were predominantly distributed and expressed in the monolayers of ciliated columnar epithelium in the branches of the terminal fine bronchioles of yak and cattle lungs, with a small amount of it distributed in the alveolar septa; at the molecular level, the differences in PDK1 mRNA relative expression in the lungs of adult yaks and cattle were not significant (p > 0.05), the differences in HIF-1α and VEGF mRNA relative expression were significant (p < 0.05), and the expression of PDK1 and HIF-1α proteins in adult yaks was stronger than that in adult cattle. PDK1 and HIF-1α proteins were more strongly expressed in adult yaks than in adult cattle, and the difference was highly significant (p < 0.01); the relative expression of VEGF proteins was not significantly different between adult yaks and cattle (p > 0.05). The possible regulatory relationship between the above results and the adaptation of yak lungs to the plateau hypoxic environment paves the way for the regulatory mechanisms of PDK1, HIF-1α, and VEGF, and provides basic information for studying the mechanism of hypoxic adaptation of yaks in the plateau. At the same time, it provides a reference for human hypoxia adaptation and a target for the prevention and treatment of plateau diseases in humans and plateau animals.
Technological Benefits Associated with the Use of Spray-Dried Animal Plasma in Fish-Based Chunks for Canned Pet Food
Authors: Rodríguez María-Carmen , Cámara Ciro , Morera Salvador , Saborido Neus , Polo Javier
Published: November 2023

Spray-dried animal plasma (SDAP) and wheat gluten (WG) are common binders in wet pet food that provide amino acids and energy, as well as texture and cohesiveness due to their gelling strength, water retention and fat emulsion properties. Binder use is a valuable tool especially in recipes based on ingredients with low technological properties such as fish by-products containing spines and scales and soft texture after cooking. Two basal recipes for chunks in gravy were produced to evaluate experimental treatments. One basal recipe used a mixture of salmon and tuna by-products as the only animal protein sources without binders or with a 20 g/kg inclusion of SDAP or WG. The other basal recipe mimicked a more typical commercial recipe containing meat animal ingredients and a 40 g/kg salmon by-product to develop experimental treatments with and 0, 10, 20, 30 or 40 g/kg inclusions of SDAP. Dry matter, protein, and viscosity were evaluated in raw emulsions. After a 1 h retorting at 121 °C, hardness was measured in emulsions and in cooked chunks, juiciness, and Texture Profile Analysis (TPA) were assessed. Results demonstrated the viability of producing quality chunks in gravy containing only fish by-products including 20 g/kg of SDAP, which significantly increased hardness, elasticity, cohesiveness, and juiciness. There was a positive linear correlation of increased SDAP inclusion rate in the commercial recipe for most of the quality parameters evaluated. Based on these results, the inclusion of SDAP in fish recipes can help manufacturers achieve technological quality control targets for commercial wet pet food and may help producers to successfully formulate new recipes for wet pet food products using fish by-products as the sole animal protein source.
Multi-Omics Analysis of the Mechanism of Mentha Haplocalyx Briq on the Growth and Metabolic Regulation of Fattening Sheep
Authors: Yi Mingliang , Cao Zhikun , Zhou Jialu , Ling Yinghui , Zhang Zijun , Cao Hongguo
Published: November 2023

Mentha haplocalyx Briq (MHB) and its components have been proven to improve the growth performance of livestock and poultry. The aim of this experiment was to investigate the effects of MHB addition on growth performance, rumen and fecal microbiota, rumen fluid, serum and urine metabolism, and transcriptomics of rumen epithelial cells in meat sheep. Twelve Hu sheep were selected for the experiment and fed with basic diet (CON) and a basal diet supplemented with 80 g/kg DM of Mentha haplocalyx Briq (MHB). The experimental period was 10 weeks with the first 2 weeks as the pre-trial period. The results showed that compared with the CON group, the average daily weight gain of meat sheep in the MHB group increased by 20.1%; the total volatile fatty acid (VFA) concentration significantly increased (p < 0.05); The thickness of the cecal mucosal layer was significantly reduced (p < 0.01), while the thickness of the colonic mucosal layer was significantly increased (p < 0.05), the length of ileal villi significantly increased (p < 0.01), the thickness of colonic mucosal layer and rectal mucosal muscle layer significantly increased (p < 0.05), and the thickness of cecal mucosal layer significantly decreased (p < 0.05); The serum antioxidant capacity has increased. At the genus level, the addition of MHB changed the composition of rumen and fecal microbiota, increased the relative abundance of Paraprevotella, Alloprevotella, Marinilabilia, Saccharibacteria_genera_incertae_sedis, Subdivision5_genera_incertae_sedis and Ornatilinea in rumen microbiota, and decreased the relative abundance of Blautia (p < 0.05). The relative abundance of Prevotella, Clostridium XlVb and Parasutterella increased in fecal microbiota, while the relative abundance of Blautia and Coprococcus decreased (p < 0.05). There were significant differences in the concentrations of 105, 163, and 54 metabolites in the rumen, serum, and urine between the MHB group and the CON group (p < 0.05). The main metabolic pathways of the differences were pyrimidine metabolism, taurine and taurine metabolism, glyceride metabolism, and pentose phosphate pathway (p < 0.05), which had a significant impact on protein synthesis and energy metabolism. The transcriptome sequencing results showed that differentially expressed genes were mainly enriched in immune regulation, energy metabolism, and protein modification. Therefore, adding MHB improved the growth performance of lambs by altering rumen and intestinal microbiota, rumen, serum and urine metabolomics, and transcriptome.
Plasma Analyzer for the Chinese FY-3E Satellite: In-Orbit Performance and Ground Calibration
Authors: Wang Xinyue , Zhang Xiaoxin , Wang Jinhua , Huang Cong , Li Jiawei , Zhang Aibing , Kong Linggao , Du Dan , Yang Yong , Zhang Pengfei , Su Bin , Liu Bin , Tian Zheng
Published: November 2023

The plasma analyzer (PMA) on the Fengyun-3E (FY-3E) meteorological satellite series is a critical sensor of the space environment monitoring package that is capable of the comprehensive in situ detection of the thermal plasma environment and surface discharge effects. In this paper, we conducted a thorough evaluation of the PMA’s performance and reliability through a combination of ground-based laboratory calibration and in-orbit testing. During the ground-based calibration, the PMA underwent assessments for the energy range, field of view (FOV), and measurement accuracy, and obtained the detection accuracy and the geometric factors. During the in-orbit testing, the PMA successfully obtained the typical distribution characteristics of low-energy ions and electrons in orbital space regions, as well as the precipitating particles in the middle and high latitudes of both hemispheres. Notably, the PMA observed an expansion of the particle distribution in the high-latitude regions during a moderate geomagnetic storm. The results from both the ground-based calibration and in-orbit testing demonstrated that the PMA met the requirements for thermal plasma detection, with reliable and scientifically valid in-orbit detection data. These results provide a crucial foundation for studying spatial weather variations, improving the accuracy of space environment forecasts and enhancing disaster detection and monitoring capabilities.
Flood Simulation Study of China’s Data-Deficient Mountainous Watersheds Based on CMPA-Hourly
Authors: Yuan Yibin , Chen Ting , Ao Tianqi , Yang Kebi
Published: November 2023

Heavy rainfall and flood disasters are frequent in mountainous watersheds in southwest China, and forecasting runoff floods in some mountainous watersheds is difficult. In this study, a typical watershed in the southwest mountainous region, the Qingyi River (13,000 km2), was selected for the lack of precipitation observation data in the watershed, and the BTOPMC (block-wise use of the topographic-based hydrologic model (TOPMODEL)) was used, using CMPA-Hourly (China Hourly Merged Precipitation Analysis combining observations from automatic weather stations, meteorological satellite, and weather radar at 0.05° × 0.05° grid) to improve the accuracy of flood forecasting. The results show that the Nash–Sutcliffe efficiency (NSE) of the flood forecast for the verification period in the Jiajiang section of the Qingyi River using CMPA-Hourly improved from 0.66 to 0.78, the flood error reduced from 18% to 9%, and the overall accuracy reached grade B or above. The results indicate that CMPA-Hourly, which integrates ground observation–radar–satellite precipitation, effectively combined the advantages of different sources of data to improve the resolution and accuracy of precipitation data, and then CMPA-Hourly can be used to improve the accuracy of runoff and flood forecasting.
Machine Learning Approaches to Differentiate Sellar-Suprasellar Cystic Lesions on Magnetic Resonance Imaging
Authors: Jiang Chendan , Zhang Wentai , Wang He , Jiao Yixi , Fang Yi , Feng Feng , Feng Ming , Wang Renzhi
Published: November 2023

Cystic lesions are common lesions of the sellar region with various pathological types, including pituitary apoplexy, Rathke’s cleft cyst, cystic craniopharyngioma, etc. Suggested surgical approaches are not unique when dealing with different cystic lesions. However, cystic lesions with different pathological types were hard to differentiate on MRI with the naked eye by doctors. This study aimed to distinguish different pathological types of cystic lesions in the sellar region using preoperative magnetic resonance imaging (MRI). Radiomics and deep learning approaches were used to extract features from gadolinium-enhanced MRIs of 399 patients enrolled at Peking Union Medical College Hospital over the past 15 years. Paired imaging differentiations were performed on four subtypes, including pituitary apoplexy, cystic pituitary adenoma (cysticA), Rathke’s cleft cyst, and cystic craniopharyngioma. Results showed that the model achieved an average AUC value of 0.7685. The model based on a support vector machine could distinguish cystic craniopharyngioma from Rathke’s cleft cyst with the highest AUC value of 0.8584. However, distinguishing cystic apoplexy from pituitary apoplexy was difficult and almost unclassifiable with any algorithms on any feature set, with the AUC value being only 0.6641. Finally, the proposed methods achieved an average Accuracy of 0.7532, which outperformed the traditional clinical knowledge-based method by about 8%. Therefore, in this study, we first fill the gap in the existing literature and provide a non-invasive method for accurately differentiating between these lesions, which could improve preoperative diagnosis accuracy and help to make surgery plans in clinical work.
Preoperative Grading of Rectal Cancer with Multiple DWI Models, DWI-Derived Biological Markers, and Machine Learning Classifiers
Authors: Song Mengyu , Wang Qi , Feng Hui , Wang Lijia , Zhang Yunfei , Liu Hui
Published: November 2023

Background: this study aimed to utilize various diffusion-weighted imaging (DWI) techniques, including mono-exponential DWI, intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI), for the preoperative grading of rectal cancer. Methods: 85 patients with rectal cancer were enrolled in this study. Mann–Whitney U tests or independent Student’s t-tests were conducted to identify DWI-derived parameters that exhibited significant differences. Spearman or Pearson correlation tests were performed to assess the relationships among different DWI-derived biological markers. Subsequently, four machine learning classifier-based models were trained using various DWI-derived parameters as input features. Finally, diagnostic performance was evaluated using ROC analysis with 5-fold cross-validation. Results: With the exception of the pseudo-diffusion coefficient (Dp), IVIM-derived and DKI-derived parameters all demonstrated significant differences between low-grade and high-grade rectal cancer. The logistic regression-based machine learning classifier yielded the most favorable diagnostic efficacy (AUC: 0.902, 95% Confidence Interval: 0.754–1.000; Specificity: 0.856; Sensitivity: 0.925; Youden Index: 0.781). Conclusions: utilizing multiple DWI-derived biological markers in conjunction with a strategy employing multiple machine learning classifiers proves valuable for the noninvasive grading of rectal cancer.
The Controversial Nature of Some Non-Starter Lactic Acid Bacteria Actively Participating in Cheese Ripening
Authors: Dimov Svetoslav G.
Published: November 2023

This mini review deals with some controversial non-starter lactic acid bacteria (NSLAB) species known to be both human and animal pathogens but also health-promoting and probiotic. The focus is on Lactococcus garvieae, two Streptococcus species (S. uberis and S. parauberis), four Weissella species (W. hellenica, W. confusa, W. paramesenteroides, and W. cibaria), and Mammalicoccus sciuri, which worldwide, are often found within the microbiotas of different kinds of cheese, mainly traditional artisanal cheeses made from raw milk and/or relying on environmental bacteria for their ripening. Based on literature data, the virulence and health-promoting effects of these bacteria are examined, and some of the mechanisms of these actions are reviewed. Additionally, their possible roles in cheese ripening are also discussed. The analysis of the literature data available so far showed that, in general, the pathogenic and the beneficial strains, despite belonging to the same species, show somewhat different genetic constitutions. Yet, when the safety of a given strain is assessed, genomic analysis on its own is not enough, and a polyphasic approach including additional physiological and functional tests is needed.
Predictive Biomarkers of Treatment Response in Major Depressive Disorder
Authors: Stolz Louise A. , Kohn Jordan N. , Smith Sydney E. , Benster Lindsay L. , Appelbaum Lawrence G.
Published: November 2023

Major depressive disorder (MDD) is a highly prevalent, debilitating disorder with a high rate of treatment resistance. One strategy to improve treatment outcomes is to identify patient-specific, pre-intervention factors that can predict treatment success. Neurophysiological measures such as electroencephalography (EEG), which measures the brain’s electrical activity from sensors on the scalp, offer one promising approach for predicting treatment response for psychiatric illnesses, including MDD. In this study, a secondary data analysis was conducted on the publicly available Two Decades Brainclinics Research Archive for Insights in Neurophysiology (TDBRAIN) database. Logistic regression modeling was used to predict treatment response, defined as at least a 50% improvement on the Beck’s Depression Inventory, in 119 MDD patients receiving repetitive transcranial magnetic stimulation (rTMS). The results show that both age and baseline symptom severity were significant predictors of rTMS treatment response, with older individuals and more severe depression scores associated with decreased odds of a positive treatment response. EEG measures contributed predictive power to these models; however, these improvements in outcome predictability only trended towards statistical significance. These findings provide confirmation of previous demographic and clinical predictors, while pointing to EEG metrics that may provide predictive information in future studies.
Investigating Sex-Based Neural Differences in Autism and Their Extended Reality Intervention Implications
Authors: Razzak Rehma , Li Joy , He Selena , Sokhadze Estate
Published: November 2023

Autism Spectrum Disorder (ASD) affects millions of individuals worldwide, and there is growing interest in the use of extended reality (XR) technologies for intervention. Despite the promising potential of XR interventions, there remain gaps in our understanding of the neurobiological mechanisms underlying ASD, particularly in relation to sex-based differences. This scoping review synthesizes the current research on brain activity patterns in ASD, emphasizing the implications for XR interventions and neurofeedback therapy. We examine the brain regions commonly affected by ASD, the potential benefits and drawbacks of XR technologies, and the implications of sex-specific differences for designing effective interventions. Our findings underscore the need for ongoing research into the neurobiological underpinnings of ASD and sex-based differences, as well as the importance of developing tailored interventions that consider the unique needs and experiences of autistic individuals.
Evolution of Pharmacological Treatments and Associated Costs for Multiple Myeloma in the Public Healthcare System of Catalonia: A Retrospective Observational Study
Authors: Garrido-Alejos Gemma , Saborit-Canals Guillem , Guarga Laura , de Pando Thais , Umbria Miriam , Oriol Albert , Feliu Anna , Pontes Caridad , Vallano Antonio
Published: November 2023

(1) Background: Our understanding of and treatment for multiple myeloma (MM) has advanced significantly, and new pharmacological treatments have promising benefits but high price tags. This study analyzes prescription patterns and pharmaceutical expenditure for MM treatments in Catalonia’s public healthcare system over eight years. (2) Methods: A retrospective observational study examined MM treatment data from 2015 to 2022 in Catalonia, using healthcare registries from the Catalan Health Service to collect information on patients, medicines used, and treatment costs. (3) Results: A total of 4556 MM patients received treatment, with a rising trend in the number of treated patients each year from 902 in 2015 to 1899 in 2022. The mean age was 68.9 years, and patients were almost evenly distributed by gender (51.5% male). Most patients were treated with bortezomib (3338 patients), lenalidomide (2952), and/or daratumumab (1093). Most drugs showed increased utilization annually, most significantly for lenalidomide and daratumumab. The total pharmacological treatment cost throughout the entire study period was EUR 321,811,249, with lenalidomide leading with the highest total cost (EUR 157,236,784), and daratumumab exhibiting the highest increase in annual expenditure. (5) Conclusions: The study reveals a progressive increase in the number of MM patients treated and rising pharmaceutical costs. Lenalidomide and daratumumab incurred the highest costs. The findings highlight MM treatment’s economic impact and the need to monitor prescription patterns and expenditures to optimize healthcare resources and decision making. Understanding these trends can guide resource allocation effectively.
Antiproliferative Modulation and Pro-Apoptotic Effect of BR2 Tumor-Penetrating Peptide Formulation 2-Aminoethyl Dihydrogen Phosphate in Triple-Negative Breast Cancer
Authors: Cabral Laertty Garcia de Sousa , Oliveira Cyntia Silva , Freire Katielle Albuquerque , Alves Monique Gonçalves , Oliveira Vani Xavier , Poyet Jean-Luc , Maria Durvanei Augusto
Published: November 2023

Breast cancer is the most common cancer in women, the so-called “Triple-Negative Breast Cancer” (TNBC) subtype remaining the most challenging to treat, with low tumor-free survival and poor clinical evolution. Therefore, there is a clear medical need for innovative and more efficient treatment options for TNBC. The aim of the present study was to evaluate the potential therapeutic interest of the association of the tumor-penetrating BR2 peptide with monophosphoester 2-aminoethyl dihydrogen phosphate (2-AEH2P), a monophosphoester involved in cell membrane turnover, in TNBC. For that purpose, viability, migration, proliferative capacity, and gene expression analysis of proteins involved in the control of proliferation and apoptosis were evaluated upon treatment of an array of TNBC cells with the BR2 peptide and 2-AEH2P, either separately or combined. Our data showed that, while possessing limited single-agent activity, the 2-AEH2P+BR2 association promoted significant cytotoxicity in TNBC cells but not in normal cells, with reduced proliferative potential and inhibition of cell migration. Mechanically, the 2-AEH2P+BR2 combination promoted an increase in cells expressing p53 caspase 3 and caspase 8, a reduction in cells expressing tumor progression and metastasis markers such as VEGF and PCNA, as well as a reduction in mitochondrial electrical potential. Our results indicate that the combination of the BR2 peptide with 2-AEH2P+BR2 may represent a promising therapeutic strategy in TNBC with potential use in clinical settings.
The Complex Interaction between Proton Pump Inhibitors and Cancer Treatment
Authors: Chen Hao , Kondo Masaaki , Horita Nobuyuki , Takahashi Kenichi , Kaneko Takeshi
Published: November 2023

We have read the article authored by Rizzo et al [...]
Towards Realistic 3D Models of Tumor Vascular Networks
Authors: Lindemann Max C. , Glänzer Lukas , Roeth Anjali A. , Schmitz-Rode Thomas , Slabu Ioana
Published: November 2023

For reliable in silico or in vitro investigations in, for example, biosensing and drug delivery applications, accurate models of tumor vascular networks down to the capillary size are essential. Compared to images acquired with conventional medical imaging techniques, digitalized histological tumor slices have a higher resolution, enabling the delineation of capillaries. Volume rendering procedures can then be used to generate a 3D model. However, the preparation of such slices leads to misalignments in relative slice orientation between consecutive slices. Thus, image registration algorithms are necessary to re-align the slices. Here, we present an algorithm for the registration and reconstruction of a vascular network from histologic slices applied to 169 tumor slices. The registration includes two steps. First, consecutive images are incrementally pre-aligned using feature- and area-based transformations. Second, using the previous transformations, parallel registration for all images is enabled. Combining intensity- and color-based thresholds along with heuristic analysis, vascular structures are segmented. A 3D interpolation technique is used for volume rendering. This results in a 3D vascular network with approximately 400–450 vessels with diameters down to 25–30 µm. A delineation of vessel structures with close distance was limited in areas of high structural density. Improvement can be achieved by using images with higher resolution and or machine learning techniques.
Conservative Axillary Surgery May Prevent Arm Lymphedema without Increasing Axillary Recurrence in the Surgical Management of Breast Cancer
Authors: Noguchi Masakuni , Inokuchi Masafumi , Yokoi-Noguchi Miki , Morioka Emi , Haba Yusuke
Published: November 2023

Axillary lymph node dissection (ALND) has been associated with postoperative morbidities, including arm lymphedema, shoulder dysfunction, and paresthesia. Sentinel lymph node (SLN) biopsy emerged as a method to assess axillary nodal status and possibly obviate the need for ALND in patients with clinically node-negative (cN0) breast cancer. The majority of breast cancer patients are eligible for SLN biopsy only, so ALND can be avoided. However, there are subsets of patients in whom ALND cannot be eliminated. ALND is still needed in patients with three or more positive SLNs or those with gross extranodal or matted nodal disease. Moreover, ALND has conventionally been performed to establish local control in clinically node-positive (cN+) patients with a heavy axillary tumor burden. The sole method to avoid ALND is through neoadjuvant chemotherapy (NAC). Recently, various forms of conservative axillary surgery have been developed in order to minimize arm lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, conventional ALND may not be necessary in either cN0 or cN+ patients. Further studies with a longer follow-up period are needed to determine the safety of conservative axillary surgery.
Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis
Authors: Sharma Aditya Kumar , Ismail Nahed
Published: November 2023

Activating inflammatory caspases and releasing pro-inflammatory mediators are two essential functions of inflammasomes which are triggered in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The canonical inflammasome pathway involves the activation of inflammasome and its downstream pathway via the adaptor ASC protein, which causes caspase 1 activation and, eventually, the cleavage of pro-IL-1b and pro-IL-18. The non-canonical inflammasome pathway is induced upon detecting cytosolic lipopolysaccharide (LPS) by NLRP3 inflammasome in Gram-negative bacteria. The activation of NLRP3 triggers the cleavage of murine caspase 11 (human caspase 4 or caspase 5), which results in the formation of pores (via gasdermin) to cause pyroptosis. Ehrlichia is an obligately intracellular bacterium which is responsible for causing human monocytic ehrlichiosis (HME), a potentially lethal disease similar to toxic shock syndrome and septic shock syndrome. Several studies have indicated that canonical and non-canonical inflammasome activation is a crucial pathogenic mechanism that induces dysregulated inflammation and host cellular death in the pathophysiology of HME. Mechanistically, the activation of canonical and non-canonical inflammasome pathways affected by virulent Ehrlichia infection is due to a block in autophagy. This review aims to explore the significance of non-canonical inflammasomes in ehrlichiosis, and how the pathways involving caspases (with the exception of caspase 1) contribute to the pathophysiology of severe and fatal ehrlichiosis. Improving our understanding of the non-canonical inflammatory pathway that cause cell death and inflammation in ehrlichiosis will help the advancement of innovative therapeutic, preventative, and diagnostic approaches to the treatment of ehrlichiosis.
MAP3K19 Affects TWEAK-Induced Response in Cultured Bronchial Epithelial Cells and Regulates Allergic Airway Inflammation in an Asthma Murine Model
Authors: Sandhu Yuuki , Harada Norihiro , Harada Sonoko , Nishimaki Takayasu , Sasano Hitoshi , Tanabe Yuki , Takeshige Tomohito , Matsuno Kei , Ishimori Ayako , Katsura Yoko , Ito Jun , Akiba Hisaya , Takahashi Kazuhisa
Published: November 2023

The mitogen-activated protein kinase (MAPK) signaling pathway is involved in the epithelial–mesenchymal transition (EMT) and asthma; however, the role of mitogen-activated protein kinase kinase kinase 19 (MAP3K19) remains uncertain. Therefore, we investigated the involvement of MAP3K19 in in vitro EMT and ovalbumin (OVA)-induced asthma murine models. The involvement of MAP3K19 in the EMT and the production of cytokines and chemokines were analyzed using a cultured bronchial epithelial cell line, BEAS-2B, in which MAP3K19 was knocked down using small interfering RNA. We also evaluated the involvement of MAP3K19 in the OVA-induced asthma murine model using Map3k19-deficient (MAP3K19−/−) mice. Transforming growth factor beta 1 (TGF-β1) and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) induced the MAP3K19 messenger RNA (mRNA) expression in the BEAS-2B cells. The knockdown of MAP3K19 enhanced the reduction in E-cadherin mRNA and the production of regulated upon activation normal T cell express sequence (RANTES) via stimulation with TWEAK alone or with the combination of TGF-β1 and TWEAK. Furthermore, the expression of MAP3K19 mRNA was upregulated in both the lungs and tracheas of the mice in the OVA-induced asthma murine model. The MAP3K19−/− mice exhibited worsened eosinophilic inflammation and an increased production of RANTES in the airway epithelium compared with the wild-type mice. These findings indicate that MAP3K19 suppressed the TWEAK-stimulated airway epithelial response, including adhesion factor attenuation and RANTES production, and suppressed allergic airway inflammation in an asthma mouse model, suggesting that MAP3K19 regulates allergic airway inflammation in patients with asthma.
T-Cell Receptor Repertoire as a Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma
Authors: Kobayashi Takuro , Nagata Masayoshi , Ikehata Yoshihiro , Nagashima Yuki , Nagaya Naoya , Lu Yan , Horie Shigeo
Published: November 2023

Immune checkpoint inhibitors (ICIs) are effective in treating renal cell carcinoma (RCC) but can also cause immune-related adverse events (irAEs). The relationship between irAEs and the T-cell receptor (TCR) repertoire in RCC patients treated with ICIs remains unclear. We analyzed the relationship between the severity and diversity of irAEs and the TCR repertoire in RCC patients who received dual checkpoint inhibitors (ipilimumab + nivolumab). The TCRβ (TRB) repertoires were characterized in peripheral blood samples from six patients with RCC before the initiation of ICI therapy. The diversity and clonality of the TCR repertoire were compared between patients with grade 2 and grade 3 irAEs. The median proportion of top 10 unique reads in the TCR repertoire was significantly higher in grade 3 compared with grade 2 irAEs in RCC patients receiving immune checkpoint inhibitors (grade 2: 0.196%; grade 3: 0.346%; p = 0.0038). We provide insight into the relationship between TCR repertoire and irAEs in RCC patients treated with ICIs. TCR repertoire clonality may be associated with the development of irAEs in RCC patients.
Modelling Risk for Commodities in Brazil: An Application for Live Cattle Spot and Futures Prices
Authors: Alcoforado Renata G. , Egídio dos Reis Alfredo D. , Bernardino Wilton , Santos José António C.
Published: November 2023

This study analyses a series of live cattle spot and futures prices from the Boi Gordo Index (BGI) in Brazil. The objective is to develop a model that best portrays this commodity’s behaviour to estimate futures prices more accurately. The database created contains 2010 daily entries in which trade in futures contracts occurs, as well as BGI spot sales in the market, from 1 December 2006 to 30 April 2015. One of the most important reasons why this type of risk needs to be measured is to set loss limits. To identify patterns in price behaviour in order to improve future transaction results, investors must analyse fluctuations in asset values for longer periods. Bibliographic research reveals that no other study has conducted a comprehensive analysis of this commodity using this approach. Cattle ranching is big business in Brazil given that in 2021, this sector moved BRL 913.14 billion (USD 169.29 billion). In that year, agribusiness contributed 26.6% of Brazil’s total gross domestic product. Using the proposed risk modelling technique, economic agents can make the best decision about which options within these investors’ reach produce more effective risk management. The methodology is based on Holt–Winters exponential smoothing algorithm, autoregressive integrated moving-average (ARIMA), ARIMA with exogenous inputs, generalised autoregressive conditionally heteroskedastic and generalised autoregressive moving-average (GARMA) models. More specifically, five different methods are applied that allow a comparison of 12 different models as ways to portray and predict the BGI commodity behaviours. The results show that GARMA with order c(2,1) and without intercept is the best model. Investors equipped with such precise modelling insights stand at an advantageous position in the market, promoting informed investment decisions and optimising returns.
Creation of a Métis-Specific Instrument for Cancer Screening: A Scoping Review of Cancer-Screening Programs and Instruments
Authors: Letendre Angeline , Khan Momtafin , Bartel Reagan , Chiang Bonnie , James Ashton , Shewchuk Brittany , Kima June , Macphail Meghan , Vaska Marcus , Schwann Monica , Yang Huiming , Kopciuk Karen A.
Published: November 2023

Understanding the barriers to and facilitators of cancer screening programs among Indigenous populations remains limited. In the spirit of mutual respect, this co-led, collaborative project was carried out between the Métis Nation of Alberta and Screening Programs from Alberta Health Services (AHS). This scoping review assessed the cancer screening literature for available questionnaires and then identified themes and suitable questions for a Métis-specific cancer screening questionnaire. Literature searches on cervical, breast, and colorectal cancer screening programs and related concepts were conducted in electronic databases, including the Native Health Database, MEDLINE (Ovid), PsycINFO, PubMed, PubMed Central, CINAHL, MEDLINE (Ebsco), Psychology & Behavioral Sciences Collection, and Web of Science. Grey literature was collected from AHS Insite, Open Archives Initiative repository, American Society of Clinical Oncology, European Society of Medical Oncology, Google, and Google Scholar. 135 articles were screened based on the eligibility criteria with 114 articles selected, including 14 Indigenous-specific ones. Knowledge, attitude, belief, behaviour, barrier, and facilitator themes emerged from the review, but no Métis-specific cancer screening instruments were found. Thus, one was developed using existing cancer screening instruments, with additional questions created by the project team. A survey of the Métis population in Alberta will use this questionnaire and provide data to address the burden of cancer among Métis people.
Historical Perspective and Current State Review: Advancing Lifelong Learning and Continuing Professional Education in Nutrition and Dietetics to Expand Opportunities, Equity, Access, and Future Transformations
Authors: Gonzalez Andie , Lynch Patricia , Dorner Becky , Arensberg Mary
Published: November 2023

Lifelong learning has been integral to advancement of the nutrition and dietetics profession and its practitioners. Both the United States (US) Commission on Dietetic Registration (CDR) and the Academy of Nutrition and Dietetics (Academy) advocate for continuous skill development and professional growth. Responding to evolving environmental trends and diverse practice perspectives, the CDR joined the Joint Accreditation for Interprofessional Continuing Education organization in 2020, and the CDR is transforming its own continuing professional education (CPE) requirements and prior-approval program. This paper presents a historical perspective and a current state narrative review, chronicling past and recent developments in nutrition and dietetics CPE in the US, including opportunities for reflective learning and interprofessional continuing education (IPCE). Also explored are the establishment and expansion of the Joint Accreditation organization and its standards, as well as applicable case examples. Additionally, this paper outlines the CDR and the Academy’s strategies for advancing inclusion, diversity, equity, and access (IDEA) within the profession and identifies how CPE advancements may facilitate accessible and equitable CPE for an increasingly diverse membership of practitioners. Nutrition and dietetics professionals stand to benefit from a more comprehensive understanding of changes in CPE and the opportunities they may bring to the future of the profession.
Work Fluctuations in Ergotropic Heat Engines
Authors: Chesi Giovanni , Macchiavello Chiara , Sacchi Massimiliano Federico
Published: November 2023

We study the work fluctuations in ergotropic heat engines, namely two-stroke quantum Otto engines where the work stroke is designed to extract the ergotropy (the maximum amount of work by a cyclic unitary evolution) from a couple of quantum systems at canonical equilibrium at two different temperatures, whereas the heat stroke thermalizes back the systems to their respective reservoirs. We provide an exhaustive study for the case of two qutrits whose energy levels are equally spaced at two different frequencies by deriving the complete work statistics. By varying the values of temperatures and frequencies, only three kinds of optimal unitary strokes are found: the swap operator U1, an idle swap U2 (where one of the qutrits is regarded as an effective qubit), and a non-trivial permutation of energy eigenstates U3, which indeed corresponds to the composition of the two previous unitaries, namely U3=U2U1. While U1 and U2 are Hermitian (and hence involutions), U3 is not. This point has an impact on the thermodynamic uncertainty relations (TURs), which bound the signal-to-noise ratio of the extracted work in terms of the entropy production. In fact, we show that all TURs derived from a strong detailed fluctuation theorem are violated by the transformation U3.