bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmasking vaccine hesitancy and refusal: a deep dive into Anti-vaxxer perspectives on COVID-19 in Spain
Authors: Prieto-Campo Ángela , Vázquez-Cancela Olalla , Roque Fátima , Herdeiro Maria Teresa , Figueiras Adolfo , Zapata-Cachafeiro Maruxa
Published: July 2024

Background

At the time of the emergence of COVID-19, denialist and anti-vaccine groups have also emerged and are shaking public confidence in vaccination.

Methods

A qualitative study was conducted using online focus groups. Participants had not received any doses of vaccination against the disease. A total of five focus group sessions were conducted with 28 participants. They were recruited by snowball sampling and by convenience sampling.

Results

The two major topics mentioned by the participants were adverse effects and information. The adverse effects described were severe and included sudden death. In the case of information, participants reported: (1) consultation of websites on which scientists posted anti-vaccination content; and (2) distrust.

Conclusions

At a time when anti-vaccine groups pose a major challenge to public health in general, and to COVID-19 vaccination campaigns in particular, this study is a first step towards gaining deeper insight into the factors that lead to COVID-19 vaccine refusal.
Prevalence of hysterectomy and associated factors in Brazilian women aged 50 and older: findings from the Brazilian Longitudinal Study of Ageing (ELSI-Brazil)
Authors: Afonso Letícia Oliveira , Beirith Victória Wollf , de Andrade Claudia Rosa , Traebert Eliane , de Oliveira Cesar , Traebert Jefferson
Published: July 2024

Background

Hysterectomy is a gynaecological surgical procedure in which the uterus is removed as a treatment for both malignant and benign gynaecological diseases. A hysterectomy is also performed to minimise risks in women with problems related to the uterus. This study aimed to estimate the prevalence of reported hysterectomy and associated risk factors in Brazilian women aged 50 and older.

Methods

A cross-sectional study using data from the Brazilian Longitudinal Study of Ageing (ELSI-Brazil) was conducted. A total of 5,293 women aged 50 and over who participated in the ELSI-Brazil study in 2015 and 2016 were included. The prevalence rate of hysterectomy was estimated and the main reasons for performing the surgery were identified. The bivariate analyses utilised the chi-square test, while multivariate analyses employed Poisson regression with a robust estimator.

Results

The reported prevalence of hysterectomy was 17.8%. The most prevalent reason for the surgery was the presence of uterine myoma. Significant and independent associations were observed in women aged 63 and older, married, having undergone preventive exams, hormonal treatment, had up to three deliveries and having a private health plan.

Conclusion

The main objective of the study was achieved. The prevalence of hysterectomy in Brazilian women aged 50 and older was 17.8%. Significant associations were observed with participants’ sociodemographic and clinical characteristics reinforcing the importance of considering the reproductive characteristics of women as indicators of health status.
Experienced and internalized weight stigma among Spanish adolescents
Authors: Anastasiadou Dimitra , Tárrega Salomé , Fornieles-Deu Albert , Moncada-Ribera Albert , Bach-Faig Anna , Sánchez-Carracedo David
Published: July 2024

Background and objective

Weight stigma has negative consequences for both physiological and psychological health. Studies on weight stigma in adolescence, particularly from general populations, are scarce in the Mediterranean area. The main aim of this study is to describe the prevalence of experienced and internalized weight stigma among a representative sample of adolescents from the Spanish city of Terrassa, and to determine its association with sociodemographic variables and weight status.

Methods

Drawing on data from the initial assessment of a longitudinally funded project on weight stigma in adolescents, a cross-sectional survey-based study was conducted using random multistage cluster sampling. Weight stigma experiences, their frequency and sources, and weight bias internalization with the Modified Weight Bias Internalization Scale (WBISM) were assessed in a sample of 1016 adolescents. Adjusted odds ratios (AOR) between sociodemographic variables, weight status and having experienced weight stigma, and having reported high scores of WBISM (WBISM ≥ 4) were estimated by multiple logistic regression models.

Results

The prevalence of weight-related stigma experiences was 43.2% in the sample (81.8 in adolescents with obesity) and the prevalence of high levels of weight bias internalization was 19.4% (50.7 in adolescents with obesity). Other kids and school were the most prevalent sources of weight stigma, with society and family being other significant sources of stigma reported by girls. A significantly higher risk of having experienced weight stigma was observed in girls (AOR = 2.6) and in older adolescents (AOR = 1.9). Compared to normal weight adolescents, all weight statuses showed higher risk, being 3.4 times higher in adolescents with underweight and reaching 11.4 times higher risk in those with obesity. Regarding high levels of weight bias internalization, girls had a risk 6.6 times higher than boys. Once again, a “J-shaped” pattern was observed, with a higher risk at the lowest and highest weight statuses. The risk was 6.3 times higher in adolescents with underweight, and 13.1 times higher in adolescents with obesity compared to those with normal weight.

Conclusions

Considering the high prevalence of experienced and internalized weight stigma among adolescents in Spain, especially in adolescents with obesity and girls, it seems important to implement preventive strategies in different settings and address all sources of stigma.
Real-time non-invasive hemoglobin prediction using deep learning-enabled smartphone imaging
Authors: Chen Yuwen , Hu Xiaoyan , Zhu Yiziting , Liu Xiang , Yi Bin
Published: July 2024

Background

Accurate measurement of hemoglobin concentration is essential for various medical scenarios, including preoperative evaluations and determining blood loss. Traditional invasive methods are inconvenient and not suitable for rapid, point-of-care testing. Moreover, current models, due to their complex parameters, are not well-suited for mobile medical settings, which limits the ability to conduct frequent and rapid testing. This study aims to introduce a novel, compact, and efficient system that leverages deep learning and smartphone technology to accurately estimate hemoglobin levels, thereby facilitating rapid and accessible medical assessments.

Methods

The study employed a smartphone application to capture images of the eye, which were subsequently analyzed by a deep neural network trained on data from invasive blood test data. Specifically, the EGE-Unet model was utilized for eyelid segmentation, while the DHA(C3AE) model was employed for hemoglobin level prediction. The performance of the EGE-Unet was evaluated using statistical metrics including mean intersection over union (MIOU), F1 Score, accuracy, specificity, and sensitivity. The DHA(C3AE) model’s performance was assessed using mean absolute error (MAE), mean-square error (MSE), root mean square error (RMSE), and R^2.

Results

The EGE-Unet model demonstrated robust performance in eyelid segmentation, achieving an MIOU of 0.78, an F1 Score of 0.87, an accuracy of 0.97, a specificity of 0.98, and a sensitivity of 0.86. The DHA(C3AE) model for hemoglobin level prediction yielded promising outcomes with an MAE of 1.34, an MSE of 2.85, an RMSE of 1.69, and an R^2 of 0.34. The overall size of the model is modest at 1.08 M, with a computational complexity of 0.12 FLOPs (G).

Conclusions

This system presents a groundbreaking approach that eliminates the need for supplementary devices, providing a cost-effective, swift, and accurate method for healthcare professionals to enhance treatment planning and improve patient care in perioperative environments. The proposed system has the potential to enable frequent and rapid testing of hemoglobin levels, which can be particularly beneficial in mobile medical settings.

Trial Registration

The clinical trial was registered on the Chinese Clinical Trial Registry (No. ChiCTR2100044138) on 20/02/2021.
Analysis of molecular epidemiological characteristics and antimicrobial susceptibility of vancomycin-resistant and linezolid-resistant Enterococcus in China
Authors: Pan Ping , Sun Long , Shi Xinyan , Huang Xian , Yin Yiping , Pan Beilei , Hu Lihua , Shen Qiang
Published: July 2024

Background

This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms.

Methods

A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS).

Results

Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage.

Conclusion

Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.
Roles of non-coding RNA in diabetic cardiomyopathy
Authors: Yao Xi , Huang Xinyue , Chen Jianghua , Lin Weiqiang , Tian Jingyan
Published: July 2024

In recent years, the incidence of diabetes has been increasing rapidly, posing a serious threat to human health. Diabetic cardiomyopathy (DCM) is characterized by cardiomyocyte hypertrophy, myocardial fibrosis, apoptosis, ventricular remodeling, and cardiac dysfunction in individuals with diabetes, ultimately leading to heart failure and mortality. However, the underlying mechanisms contributing to DCM remain incompletely understood. With advancements in molecular biology technology, accumulating evidence has shown that numerous non-coding RNAs (ncRNAs) crucial roles in the development and progression of DCM. This review aims to summarize recent studies on the involvement of three types of ncRNAs (micro RNA, long ncRNA and circular RNA) in the pathophysiology of DCM, with the goal of providing innovative strategies for the prevention and treatment of DCM.
Interplay between photosynthetic electron flux and organic carbon sinks in sucrose-excreting Synechocystis sp. PCC 6803 revealed by omics approaches
Authors: Muth-Pawlak Dorota , Kakko Lauri , Kallio Pauli , Aro Eva-Mari
Published: July 2024

Background

Advancing the engineering of photosynthesis-based prokaryotic cell factories is important for sustainable chemical production and requires a deep understanding of the interplay between bioenergetic and metabolic pathways. Rearrangements in photosynthetic electron flow to increase the efficient use of the light energy for carbon fixation must be balanced with a strong carbon sink to avoid photoinhibition. In the cyanobacterium Synechocystis sp. PCC 6803, the flavodiiron protein Flv3 functions as an alternative electron acceptor of photosystem I and represents an interesting engineering target for reorganizing electron flow in attempts to enhance photosynthetic CO2 fixation and increase production yield.

Results

We have shown that inactivation of Flv3 in engineered sucrose-excreting Synechocystis (S02:Δflv3) induces a transition from photoautotrophic sucrose production to mixotrophic growth sustained by sucrose re-uptake and the formation of intracellular carbon sinks such as glycogen and polyhydroxybutyrate. The growth of S02:Δflv3 exceeds that of the sucrose-producing strain (S02) and demonstrates unforeseen proteomic and metabolomic changes over the course of the nine-day cultivation. In the absence of Flv3, a down-regulation of proteins related to photosynthetic light reactions and CO2 assimilation occurred concomitantly with up-regulation of those related to glycolytic pathways, before any differences in sucrose production between S02 and S02:Δflv3 strains were observed. Over time, increased sucrose degradation in S02:Δflv3 led to the upregulation of respiratory pathway components, such as the plastoquinone reductase complexes NDH-11 and NDH-2 and the terminal respiratory oxidases Cyd and Cox, which transfer electrons to O2. While glycolytic metabolism is significantly up-regulated in S02:Δflv3 to provide energy for the cell, the accumulation of intracellular storage compounds and the increase in respiration serve as indirect sinks for photosynthetic electrons.

Conclusions

Our results show that the presence of strong carbon sink in the engineered sucrose-producing Synechocystis S02 strain, operating under high light, high CO2 and salt stress, cannot compensate for the lack of Flv3 by directly balancing the light transducing source and carbon fixing sink reactions. Instead, the cells immediately sense the imbalance, leading to extensive reprogramming of cellular bioenergetic, metabolic and ion transport pathways that favor mixotrophic growth rather than enhancing photoautotrophic sucrose production.
Reflexivity and positionality applied to medical practice: a study on implicit gender bias with medical students in a Swiss university
Authors: Arena Francesca , Geiser Elisa , Auer Silva , Clair Carole , Schwarz Joëlle
Published: July 2024

Background

An array of evidence shows how the presence of implicit bias in clinical encounters can negatively impact provider-patient communication, quality of care and ultimately contribute to health inequities. Reflexive practice has been explored as an approach to identify and address implicit bias in healthcare providers, including medical students. At the Lausanne School of Medicine, a clinically integrated module was introduced in 2019 to raise students’ awareness of gender bias in medical practice using a reflexivity and positionality approach. The purpose of this study is to describe the gender bias that were identified by medical students, analysing their types, places and modes of emergence during a clinical encounter. It further explores how positionality supported students’ reflection on the way in which social position modulates their relationship to patients.

Methods

As part of the teaching activity, medical students individually reflected on gender bias in a specific clinical encounter by answering questions in their electronic portfolio. The questionnaire included a section on positionality. We qualitatively analysed the students’ assignments (n=76), applying a thematic analysis framework.

Results

Medical students identified and described gender biases occurring at different moments of the clinical encounter (anamnesis (i.e. patient history), physical exam, differential diagnosis, final management). They causally associated these biases with wider social phenomena such as the gendered division of labour or stereotypes around sexuality and gender. Analysing students' reflections on how their position influenced their relationship with patients, we found that the suggested exercise revealed a major contradiction in the process of medical enculturation: the injunction to be neutral and objective erases the social and cultural context of patients and impedes an understanding of gender bias.

Conclusion

Gender biases are present in the different steps of a clinical consultation and are rooted in broader gendered social representations. We further conclude that the tension between a quest for objectivity and the reality of social encounters should be made explicit to students, because it is constitutive of medical practice.
Functional hydrogels for hepatocellular carcinoma: therapy, imaging, and in vitro model
Authors: Xu Xiaoying , Liu Yu , Liu Yanyan , Yu Yahan , Yang Mingqi , Lu Ligong , Chan Leung , Liu Bing
Published: July 2024

Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC.

Graphical Abstract
Comprehensive investigation of malignant epithelial cell-related genes in clear cell renal cell carcinoma: development of a prognostic signature and exploration of tumor microenvironment interactions
Authors: Liu Songyang , Li Ge , Yin Xiaomao , Zhou Yihan , Luo Dongmei , Yang Zhenggang , Zhang Jin , Wang Jianfeng
Published: July 2024

Clear cell renal cell carcinoma (ccRCC) is a prevalent malignancy with complex heterogeneity within epithelial cells, which plays a crucial role in tumor progression and immune regulation. Yet, the clinical importance of the malignant epithelial cell-related genes (MECRGs) in ccRCC remains insufficiently understood. This research aims to undertake a comprehensive investigation into the functions and clinical relevance of malignant epithelial cell-related genes in ccRCC, providing valuable understanding of the molecular mechanisms and offering potential targets for treatment strategies. Using data from single-cell sequencing, we successfully identified 219 MECRGs and established a prognostic model MECRGS (MECRGs’ signature) by synergistically analyzing 101 machine-learning models using 10 different algorithms. Remarkably, the MECRGS demonstrated superior predictive performance compared to traditional clinical features and 92 previously published signatures across six cohorts, showcasing its independence and accuracy. Upon stratifying patients into high- and low-MECRGS subgroups using the specified cut-off threshold, we noted that patients with elevated MECRGS scores displayed characteristics of an immune suppressive tumor microenvironment (TME) and showed worse outcomes after immunotherapy. Additionally, we discovered a distinct ccRCC tumor cell subtype characterized by the high expressions of PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) and SAA1 (Serum Amyloid A1), which we further validated in the Renji tissue microarray (TMA) cohort. Lastly, ‘Cellchat’ revealed potential crosstalk patterns between these cells and other cell types, indicating their potential role in recruiting CD163 + macrophages and regulatory T cells (Tregs), thereby establishing an immunosuppressive TME. PLOD2 + SAA1 + cancer cells with intricate crosstalk patterns indeed show promise for potential therapeutic interventions.
Comparative analysis of the analgesic effects of intercostal nerve block, ultrasound-guided paravertebral nerve block, and epidural block following single-port thoracoscopic lung surgery
Authors: Shen Liang , Ye Zi , Wang Fei , Sun Gao-Feng , Ji Cheng
Published: July 2024

Objective

In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery.

Method

A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects.

Results

In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P < 0.05). However, there was a higher incidence of side effects observed in the EB group (P < 0.05).

Conclusion

The analgesic effect of PVB and EB following single-port thoracoscopic lung surgery is better than that of ICNB. PVB causes fewer side effects and complications and is safer and more effective.
Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments
Authors: Rasmussen Torben Sølbeck , Mao Xiaotian , Forster Sarah , Larsen Sabina Birgitte , Von Münchow Alexandra , Tranæs Kaare Dyekær , Brunse Anders , Larsen Frej , Mejia Josue Leonardo Castro , Adamberg Signe , Hansen Axel Kornerup , Adamberg Kaarel , Hansen Camilla Hartmann Friis , Nielsen Dennis Sandris
Published: July 2024

Background

Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases.

Methods

To overcome these challenges, we developed methods to broaden FVT’s clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline.

Results

FVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy.

Conclusions

This proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches.
Microbial signatures and continuum in endometrial cancer and benign patients
Authors: Semertzidou Anita , Whelan Eilbhe , Smith Ann , Ng Sherrianne , Roberts Lauren , Brosens Jan J. , Marchesi Julian R. , Bennett Phillip R. , MacIntyre David A. , Kyrgiou Maria
Published: July 2024

Background

Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. The endometrial cancer microbiome has been poorly characterised so far and studies have often overestimated bacterial biomass due to lack of integration of appropriate contamination controls. There is also a scarcity of evidence on the functionality of microbial microenvironments in endometrial cancer. This work addresses that knowledge gap by interrogating the genuine, contamination-free microbial signatures in the female genital tract and rectum of women with endometrial cancer and the mechanistic role of microbiome on carcinogenic processes.

Results

Here we sampled different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) and rectum of 61 patients (37 endometrial cancer; 24 benign controls). We performed 16S rRNA gene sequencing of the V1–V2 hypervariable regions and qPCR of the 16S rRNA gene to qualitatively and quantitatively assess microbial communities and used 3D benign and endometrial cancer organoids to evaluate the effect of microbial products of L. crispatus, which was found depleted in endometrial cancer patients following primary analysis, on endometrial cell proliferation and inflammation. We found that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of Lactobacillus species relative abundance, including L. crispatus, increased bacterial diversity and enrichment of Porphyromonas, Prevotella, Peptoniphilus and Anaerococcus in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with L. crispatus conditioned media exerted an anti-proliferative effect at high concentrations but had minimal impact on cytokine and chemokine profiles.

Conclusions

Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology and what is the functional significance of this finding remain to be elucidated to guide future screening tools and microbiome-based therapeutics﻿.
Long-acting Erwinia chrysanthemi, Pegcrisantaspase, induces alternate amino acid biosynthetic pathways in a preclinical model of pancreatic ductal adenocarcinoma
Authors: Bollino Dominique , Hameed Kanwal , Bhat Anusha , Zarrabi Arveen , Casildo Andrea , Ma Xinrong , Tighe Kayla M , Carter-Cooper Brandon , Strovel Erin T. , Lapidus Rena G. , Emadi Ashkan
Published: July 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease without meaningful therapeutic options beyond the first salvage therapy. Targeting PDAC metabolism through amino acid restriction has emerged as a promising new strategy, with asparaginases, enzymes that deplete plasma glutamine and asparagine, reaching clinical trials. In this study, we investigated the anti-PDAC activity of the asparaginase formulation Pegcrisantaspase (PegC) alone and in combination with standard-of-care chemotherapeutics.

Methods

Using mouse and human PDAC cell lines, we assessed the impact of PegC on cell proliferation, cell death, and cell cycle progression. We further characterized the in vitro effect of PegC on protein synthesis as well as the generation of reactive oxygen species and levels of glutathione, a major cellular antioxidant. Additional cell line studies examined the effect of the combination of PegC with standard-of-care chemotherapeutics. In vivo, the tolerability and efficacy of PegC, as well as the impact on plasma amino acid levels, was assessed using the C57BL/6-derived KPC syngeneic mouse model.

Results

Here we report that PegC demonstrated potent anti-proliferative activity in a panel of human and murine PDAC cell lines. This decrease in proliferation was accompanied by inhibited protein synthesis and decreased levels of glutathione. In vivo, PegC was tolerable and effectively reduced plasma levels of glutamine and asparagine, leading to a statistically significant inhibition of tumor growth in a syngeneic mouse model of PDAC. There was no observable in vitro or in vivo benefit to combining PegC with standard-of-care chemotherapeutics, including oxaliplatin, irinotecan, 5-fluorouracil, paclitaxel, and gemcitabine. Notably, PegC treatment increased tumor expression of asparagine and serine biosynthetic enzymes.

Conclusions

Taken together, our results demonstrate the potential therapeutic use of PegC in PDAC and highlight the importance of identifying candidates for combination regimens that could improve cytotoxicity and/or reduce the induction of resistance pathways.
Preliminary protocol for measuring the reproducibility and accuracy of flow values on digital PET/CT systems in [15O]H2O myocardial perfusion imaging using a flow phantom
Authors: Siekkinen Reetta , Partanen Heidi , Kukola Linda , Tolvanen Tuula , Fenwick Andrew , Smith Nadia A. S. , Teräs Mika , Saraste Antti , Teuho Jarmo
Published: July 2024

Background

Several factors may decrease the accuracy of quantitative PET myocardial perfusion imaging (MPI). It is therefore essential to ensure that myocardial blood flow (MBF) values are reproducible and accurate, and to design systematic protocols to achieve this. Until now, no systematic phantom protocols have been available to assess the technical factors affecting measurement accuracy and reproducibility in MPI.

Materials and methods

We implemented a standard measurement protocol, which applies a flow phantom in order to compare image-derived flow values with respect to a ground truth flow value with [15O]H2O MPI performed on both a Discovery MI (DMI-20, GE Healthcare) and a Biograph Vision 600 (Vision-600, Siemens Healthineers) system. Both systems have automatic [15O]H2O radio water generators (Hidex Oy) individually installed, allowing us to also study the differences occurring due to two different bolus delivery systems. To investigate the technical factors contributing to the modelled flow values, we extracted the [15O]H2O bolus profiles, the flow values from the kinetic modeling (Qin and Qout), and finally calculated their differences between test-retest measurements on both systems.

Results

The measurements performed on the DMI-20 system produced Qin and Qout values corresponging to each other as well as to the reference flow value across all test-retest measurements. The repeatability differences on DMI-20 were 2.1% ± 2.6% and 3.3% ± 4.1% for Qin and Qout, respectively. On Vision-600 they were 10% ± 8.4% and 11% ± 10% for Qin and Qout, respectively. The measurements performed on the Vision-600 system showed more variation between Qin and Qout values across test-retest measurements and exceeded 15% difference in 7/24 of the measurements.

Conclusions

A preliminary protocol for measuring the accuracy and reproducibility of flow values in [15O]H2O MPI between digital PET/CT systems was assessed. The test-retest reproducibility falls below 15% in majority of the measurements conducted between two individual injector systems and two digital PET/CT systems. This study highlights the importance of implementing a standardized bolus injection and delivery protocol and importance of assessing technical factors affecting flow value reproducibility, which should be carefully investigated in a multi-center setting.
Kinetic model-informed deep learning for multiplexed PET image separation
Authors: Pan Bolin , Marsden Paul K. , Reader Andrew J.
Published: July 2024

Background

Multiplexed positron emission tomography (mPET) imaging can measure physiological and pathological information from different tracers simultaneously in a single scan. Separation of the multiplexed PET signals within a single PET scan is challenging due to the fact that each tracer gives rise to indistinguishable 511 keV photon pairs, and thus no unique energy information for differentiating the source of each photon pair.

Methods

Recently, many applications of deep learning for mPET image separation have been concentrated on pure data-driven methods, e.g., training a neural network to separate mPET images into single-tracer dynamic/static images. These methods use over-parameterized networks with only a very weak inductive prior. In this work, we improve the inductive prior of the deep network by incorporating a general kinetic model based on spectral analysis. The model is incorporated, along with deep networks, into an unrolled image-space version of an iterative fully 4D PET reconstruction algorithm.

Results

The performance of the proposed method was evaluated on a simulated brain image dataset for dual-tracer [$$^{18}$$

18

F]FDG+[$$^{11}$$

11

C]MET PET image separation. The results demonstrate that the proposed method can achieve separation performance comparable to that obtained with single-tracer imaging. In addition, the proposed method outperformed the model-based separation methods (the conventional voxel-wise multi-tracer compartment modeling method (v-MTCM) and the image-space dual-tracer version of the fully 4D PET image reconstruction algorithm (IS-F4D)), as well as a pure data-driven separation [using a convolutional encoder-decoder (CED)], with fewer training examples.

Conclusions

This work proposes a kinetic model-informed unrolled deep learning method for mPET image separation. In simulation studies, the method proved able to outperform both the conventional v-MTCM method and a pure data-driven CED with less training data.
Enhanced content-based fashion recommendation system through deep ensemble classifier with transfer learning
Authors: Suvarna Buradagunta , Balakrishna Sivadi
Published: July 2024

With the rise of online shopping due to the COVID-19 pandemic, Recommender Systems have become increasingly important in providing personalized product recommendations. Recommender Systems face the challenge of efficiently extracting relevant items from vast data. Numerous methods using deep learning approaches have been developed to classify fashion images. However, those models are based on a single model that may or may not be reliable. We proposed a deep ensemble classifier that takes the probabilities obtained from five pre-trained models such as MobileNet, DenseNet, Xception, and the two varieties of VGG. The probabilities obtained from the five pre-trained models are then passed as inputs to a deep ensemble classifier for the prediction of the given item. Several similarity measures have been studied in this work and the cosine similarity metric is used to recommend the products for a classified product given by a deep ensemble classifier. The proposed method is trained and validated using benchmark datasets such as Fashion product images dataset and Shoe dataset, demonstrating superior accuracy compared to existing models. The results highlight the potential of leveraging transfer learning and deep ensemble techniques to enhance fashion recommendation systems. The proposed model achieves 96% accuracy compared to the existing models.
Comparing blood pressure measurements between sitting in chairs and sitting on the floor
Authors: Kim Byung Sik , Lim Young-Hyo , Kim Woohyeun , Kook Hyungdon , Shin Jeong-Hun , Lee Yonggu , Heo Ran , Kim Hyun-Jin , Shin Jinho
Published: July 2024

Background

The current standard approach to measuring home blood pressure (BP) involves taking measurements while sitting in a chair. In cultures where floor sitting is common, including Korea, assessing BP while sitting on the floor would be more feasible. However, there is still a lack of research investigating whether BP measurements obtained while seated in a chair and while sitting on the floor can be regarded as interchangeable. The aim of the study was to evaluate whether there is a difference between BP measurements taken while sitting in a chair and while sitting on the floor in a Korean adult.

Methods

Among the participants who visited for evaluation of pulse wave velocity, a total of 116 participants who agreed to participate in the study were randomly selected. All subjects rested for 5 min, and BP measurements were taken at 1-min intervals according to a randomly assigned order of standard method (chair-sitting) and BP in a seated on the floor (floor-sitting).

Results

Of the 116 participants, the median age was 68 (with an interquartile range of 59 to 75), and 82% were men. There were no significant differences in systolic BP (SBP, 129.1 ± 17.8 mmHg in chair-sitting and 130.1 ± 18.9 mmHg in floor-sitting, P = 0.228) and diastolic BP (DBP, 73.9 ± 11.4 mmHg in chair-sitting and 73.7 ± 11.4 mmHg in floor-sitting, P = 0.839) between the two positions. In addition, there was a high level of agreement between BP measurements taken in the two positions (intraclass correlation coefficients: 0.882 for SBP and 0.890 for DBP).

Conclusion

These findings provide important insights into securing the reliability of home BP measurements through the commonly practiced floor-sitting posture in cultures where floor sitting is common. Furthermore, this could serve as substantial evidence for providing specific home BP measurement guidelines to patients who adhere to a floor-sitting lifestyle.
Developing inclusive public involvement and engagement activities with secondary school students and educational professionals: a protocol
Authors: Cross Lauren , Banham Dale , Melendez-Torres G. J. , Ford Tamsin , van Sluijs Esther , Liabo Kristin
Published: July 2024

Background

Public involvement and engagement (PI&E) is increasingly recognised as an important component of research. It can offer valuable insights from those with experiential knowledge to improve research quality, relevance, and reach. Similarly, schools are ever more common sites for health research and, more recently, PI&E. However, ‘gold-standard’ practice is yet to be established, and activities/approaches remain underreported. As a result, knowledge can remain localised or lost. Diversity and inclusion also remains a challenge.

Methods

This protocol has been informed by UK national guidance, evidence-based frameworks and available implementation literature. It describes both rationale and approach to conducting PI&E activities within a secondary school context. Activities are designed to be engaging, safe and accessible to young people with diverse experiences, with scope to be iteratively developed in line with public collaborator preference.

Discussion

Young people should be architects of their involvement and engagement. Ongoing appraisal and transparency of approaches to PI&E in school settings is crucial. Expected challenges of implementing this protocol include facilitating a safe space for the discussion of sensitive topics, absence and attrition, recruiting students with a diverse range of experiences, and potential knowledge and capacity barriers of both facilitator and contributors. Activities to mitigate these risks are suggested and explored.
7 T and beyond: toward a synergy between fMRI-based presurgical mapping at ultrahigh magnetic fields, AI, and robotic neurosurgery
Authors: Seghier Mohamed L.
Published: July 2024

Presurgical evaluation with functional magnetic resonance imaging (fMRI) can reduce postsurgical morbidity. Here, we discuss presurgical fMRI mapping at ultra-high magnetic fields (UHF), i.e., ≥ 7 T, in the light of the current growing interest in artificial intelligence (AI) and robot-assisted neurosurgery. The potential of submillimetre fMRI mapping can help better appreciate uncertainty on resection margins, though geometric distortions at UHF might lessen the accuracy of fMRI maps. A useful trade-off for UHF fMRI is to collect data with 1-mm isotropic resolution to ensure high sensitivity and subsequently a low risk of false negatives. Scanning at UHF might yield a revival interest in slow event-related fMRI, thereby offering a richer depiction of the dynamics of fMRI responses. The potential applications of AI concern denoising and artefact removal, generation of super-resolution fMRI maps, and accurate fusion or coregistration between anatomical and fMRI maps. The latter can benefit from the use of T1-weighted echo-planar imaging for better visualization of brain activations. Such AI-augmented fMRI maps would provide high-quality input data to robotic surgery systems, thereby improving the accuracy and reliability of robot-assisted neurosurgery. Ultimately, the advancement in fMRI at UHF would promote clinically useful synergies between fMRI, AI, and robotic neurosurgery.

Relevance statement This review highlights the potential synergies between fMRI at UHF, AI, and robotic neurosurgery in improving the accuracy and reliability of fMRI-based presurgical mapping.

Key points

• Presurgical fMRI mapping at UHF improves spatial resolution and sensitivity.

• Slow event-related designs offer a richer depiction of fMRI responses dynamics.

• AI can support denoising, artefact removal, and generation of super-resolution fMRI maps.

• AI-augmented fMRI maps can provide high-quality input data to robotic surgery systems.

Graphical Abstract
Referrals for rheumatologic evaluation following a positive antinuclear antibody test result. A cross-sectional single center Brazilian study
Authors: Vecchia Leonardo Borgato Della , Assis Caio Delano Campos Oliveira , Salatiel Fernando de Oliveira , Cirino Maria Thereza Santos , Scarpante Maria Eduarda Vogel , Oliveira Vanessa Monteiro , Meneghin Letícia Pedroso , Silva Maria Júlia Gonçalves , Santos Victória Ferini dos , Catardo Natália Pavoni , Nemesio Isabela Pulini , Paula Lívia Loamí Ruyz Jorge de , Sasdelli Carolina Borges Garcia , Bacchiega Ana Beatriz Santos
Published: July 2024

Background

In general, patients are referred for rheumatological evaluation due to isolated laboratory abnormalities, especially antinuclear antibody (ANA) positivity, with the risk of more severe patients remaining on the waiting list for longer than desired. The aim of this study was to analyze the demographic, clinical, and laboratory information of patients referred to a specialized rheumatological care unit because of positive antinuclear antibody.

Methods

This is a retrospective study of 99 out of 1670 patients seen by the same rheumatologist between 01/01/2011 and 01/01/2019. Patients whose referrals were exclusively due to the ANA test result and the specialist’s final diagnosis being “abnormal finding of serum immunological test” (ICD-10 R769) were included. Sociodemographic, clinical, and laboratory information were extracted from the consulting rheumatologist’s chart. Descriptive statistics were used for data analysis.

Results

A total of 99 patients were included, most of whom were female (84.8%) with a median age of 49 years. At the moment of specialist’s appointment, 97 patients (97.9%) repeated the ANA test, and 77 patients remained positive. Of these, only 35 (35.35%) were in a high titer range (greater than or equal to 1:320). Complete blood count for cytopenia’s investigation was not performed in a high percentage of patients (22.2%), as well as urinalysis (31.3%). In addition, more than 70% of patients score 0 to 1 classification criteria for Systemic Lupus Erythematosus, according to SLE - ACR 1987 (American College of Rheumatology) and SLICC 2012 (Systemic Lupus International Collaborating Clinics).

Conclusions

Most patients are still referred for specialized evaluation due to the misinterpretation of laboratory tests that were inappropriately requested in patients without clinical evidence of autoimmune rheumatic disease.
The ability of biostimulants and copper-containing fungicide to protect cotton against chilling stress
Authors: Ergin Nurgül , Kulan Engin Gökhan , Harmanci Pınar , Kaya Mehmet Demir
Published: July 2024

Background

Cotton (Gossypium hirsutum L.), adapted to tropical and subtropical regions of the world, is highly sensitive to low temperatures throughout its life cycle. The objective of this study was to evaluate the mitigating effects of different doses of animal-derived (0.25%, 0.50%, and 1.00% Isabion® ), seaweed-based (0.165%, 0.330%, and 0.660% Proton®) biostimulants, as well as a copper (Cu)-containing fungicide application, on cotton cultivar Lazer seedlings at the four true leaves (V4) stage. The plants were exposed to a low temperature of 5 °C for 48 h, and the changes in morphological (seedling fresh and dry weight, plant height, and stem diameter) and physiological parameters (leaf temperature, chlorophyll content, relative water content, electrolyte leakage, and relative injury) were examined.

Results

The results revealed that chilling stress reduced plant growth, while biostimulants helped protect the plants and overcome the adverse effects of chilling. Under chilling stress, there was a considerable reduction in seedling fresh weight (SFW), seedling dry weight (SDW), plant height (PH), stem diameter (SD), leaf temperature (LT), and relative water content (RWC). Cotton seedlings treated with the animal-derived biostimulants showed significantly enhanced SFW, SDW, PH, SD, LT, chlorophyll content (Chl), electrolyte leakage (EL), and relative injury (RI), although there were no positive changes in RWC. No significant differences in the morphological traits were observed among the doses of seaweed biostimulants. For SDW, PH, EL, and RI, the best results were obtained with the application of a fungicide containing copper.

Conclusion

These results show the efficiency of the biostimulant and fungicide treatments in mitigating low-temperature stress in cotton seedlings. Applying a copper-containing fungicide to cotton seedlings helped to counteract the negative effects of low-temperature stress and to protect the plants from damage by maintaining electrolyte balance. Among the biostimulant applications, all levels of animal-derived biostimulant applications, as well as the 0.660% level of the seaweed-derived biostimulant, led to increased tolerance of cotton plants to chilling stress.