bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidisciplinary meeting review in nonsmall cell lung cancer: a systematic review and meta-analysis
Authors: Stirling Rob G. , Harrison Amelia , Huang Joanna , Lee Vera , Taverner John , Barnes Hayley
Published: May 2024

Background:

Lung cancer diagnosis, staging and treatment may be enhanced by multidisciplinary participation and presentation in multidisciplinary meetings (MDM). We performed a systematic review and meta-analysis to explore literature evidence of clinical impacts of MDM exposure.

Methods:

A study protocol was registered (PROSPERO identifier CRD42021258069). Randomised controlled trials and observational cohort studies including adults with nonsmall cell lung cancer and who underwent MDM review, compared to no MDM, were included. MEDLINE, CENTRAL, Embase andClinicalTrials.govwere searched on 31 May 2021. Studies were screened and extracted by two reviewers. Outcomes included time to diagnosis and treatment, histological confirmation, receipt of treatments, clinical trial participation, survival and quality of life. Risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomised Studies – of Interventions) tool.

Results:

2947 citations were identified, and 20 studies were included. MDM presentation significantly increased histological confirmation of diagnosis (OR 3.01, 95% CI 2.30–3.95; p<0.00001) and availability of clinical staging (OR 2.55, 95% CI 1.43–4.56; p=0.002). MDM presentation significantly increased likelihood of receipt of surgery (OR 2.01, 95% CI 1.29–3.12; p=0.002) and reduced the likelihood of receiving no active treatment (OR 0.32, 95% CI 0.21–0.50; p=0.01). MDM presentation was protective of both 1-year survival (OR 3.23, 95% CI 2.85–3.68; p<0.00001) and overall survival (hazard ratio 0.63, 95% CI 0.55–0.72; p<0.00001).

Discussion:

MDM presentation was associated with increased likelihood of histological confirmation of diagnosis, documentation of clinical staging and receipt of surgery. Overall and 1-year survival was better in those presented to an MDM, although there was some clinical heterogeneity in participants and interventions delivered. Further research is required to determine the optimal method of MDM presentation, and address barriers to presentation.
African ancestry-derived APOL1 risk genotypes show proximal epigenetic associations
Authors: Breeze Charles E. , Lin Bridget M. , Winkler Cheryl A. , Franceschini Nora
Published: May 2024

Apolipoprotein L1 (APOL1) coding variants, termed G1 and G2, are established genetic risk factors for a growing spectrum of diseases, including kidney disease, in individuals of African ancestry. Evidence suggests that the risk variants, which show a recessive mode of inheritance, lead to toxic gain-of-function changes of the APOL1 protein. Disease occurrence and presentation vary, likely due to modifiers or second hits. To understand the role of the epigenetic landscape in relation to APOL1 risk variants, we performed methylation quantitative trait locus (meQTL) analysis to identify differentially methylated CpGs influenced by APOL1 risk variants in 611 African American individuals. We identified five CpGs that were significantly associated with APOL1 risk alleles in discovery and replication studies, and one CpG-APOL1 association was independent of other genomic variants. Our study highlights proximal DNA methylation alterations that may help explain the variable disease risk and clinical manifestation of APOL1 variants.
Healthcare utilization patterns of individuals with depression after national policy to increase the mental health workforce in primary care: a data linkage study
Authors: Dros Jesper T. , van Dijk Christel E. , Böcker Koen B.E. , Bruins Slot Lotte C.J.A.F , Verheij Robert A. , Meijboom Bert R. , Dik Jan-Willem , Bos Isabelle
Published: May 2024

Background

The deployment of the mental health nurse, an additional healthcare provider for individuals in need of mental healthcare in Dutch general practices, was expected to substitute treatments from general practitioners and providers in basic and specialized mental healthcare (psychologists, psychotherapists, psychiatrists, etc.). The goal of this study was to investigate the extent to which the degree of mental health nurse deployment in general practices is associated with healthcare utilization patterns of individuals with depression.

Methods

We combined national health insurers’ claims data with electronic health records from general practices. Healthcare utilization patterns of individuals with depression between 2014 and 2019 (N = 31,873) were analysed. The changes in the proportion of individuals treated after depression onset were assessed in association with the degree of mental health nurse deployment in general practices.

Results

The proportion of individuals with depression treated by the GP, in basic and specialized mental healthcare was lower in individuals in practices with high mental health nurse deployment. While the association between mental health nurse deployment and consultation in basic mental healthcare was smaller for individuals who depleted their deductibles, the association was still significant. Treatment volume of general practitioners was also lower in practices with higher levels of mental health nurse deployment.

Conclusion

Individuals receiving care at a general practice with a higher degree of mental health nurse deployment have lower odds of being treated by mental healthcare providers in other healthcare settings. More research is needed to evaluate to what extent substitution of care from specialized mental healthcare towards general practices might be associated with waiting times for specialized mental healthcare.
Greatly isolated heterogeneous circulating tumor cells using hybrid engineered cell membrane-camouflaged magnetic nanoparticles
Authors: Jiang Xinbang , Zhang Xiangyun , Guo Chen , Liu Zhuang , Guo Xiaofang , Tian Ziying , Wang Zimeng , Yang Jingxuan , Huang Xinglu , Ou Lailiang
Published: May 2024

Background

Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation.

Methods

To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis.

Conclusions

This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.

Graphical abstract
FGF21 attenuates neuroinflammation following subarachnoid hemorrhage through promoting mitophagy and inhibiting the cGAS-STING pathway
Authors: Ma Yue , Liu Zhiqin , Deng Lele , Du Jingjing , Fan Zenghui , Ma Tian , Xiong Jing , Xiuyun Xue , Gu Naibing , Di Zhengli , Zhang Yu
Published: May 2024

Background

Subarachnoid hemorrhage (SAH) represents a form of cerebrovascular event characterized by a notable mortality and morbidity rate. Fibroblast growth factor 21 (FGF21), a versatile hormone predominantly synthesized by the hepatic tissue, has emerged as a promising neuroprotective agent. Nevertheless, the precise impacts and underlying mechanisms of FGF21 in the context of SAH remain enigmatic.

Methods

To elucidate the role of FGF21 in inhibiting the microglial cGAS-STING pathway and providing protection against SAH-induced cerebral injury, a series of cellular and molecular techniques, including western blot analysis, real-time polymerase chain reaction, immunohistochemistry, RNA sequencing, and behavioral assays, were employed.

Results

Administration of recombinant fibroblast growth factor 21 (rFGF21) effectively mitigated neural apoptosis, improved cerebral edema, and attenuated neurological impairments post-SAH. Transcriptomic analysis revealed that SAH triggered the upregulation of numerous genes linked to innate immunity, particularly those involved in the type I interferon (IFN-I) pathway and microglial function, which were notably suppressed upon adjunctive rFGF21 treatment. Mechanistically, rFGF21 intervention facilitated mitophagy in an AMP-activated protein kinase (AMPK)-dependent manner, thereby preventing mitochondrial DNA (mtDNA) release into the cytoplasm and dampening the activation of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Conditional knockout of STING in microglia markedly ameliorated the inflammatory response and mitigated secondary brain injuries post-SAH.

Conclusion

Our results present the initial evidence that FGF21 confers a protective effect against neuroinflammation-associated brain damage subsequent to SAH. Mechanistically, we have elucidated a novel pathway by which FGF21 exerts this neuroprotection through inhibition of the cGAS-STING signaling cascade.
Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale
Authors: Tran Nhi T. , Penny Tayla R. , Chan Kyra YY. , Tang Tanya , Papagianis Paris C. , Sepehrizadeh Tara , Nekkanti Lakshmi , Zahra Valerie A. , Pham Yen , Yawno Tamara , Nitsos Ilias , Kelly Sharmony B. , Thiel Alison M. , de Veer Michael , Alahmari Dhafer M. , Fahey Michael C. , Jenkin Graham , Miller Suzanne L. , Galinsky Robert , Polglase Graeme R. , McDonald Courtney A.
Published: May 2024

Background

Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury.

Methods

Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively.

Results

In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls.

Conclusions

UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.
The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis
Authors: Zhuang Weisheng , Li Tianshu , Li Yuefang , Zhang Ying , Gao Jiahuan , Wang Xu , Ding Qixin , Li Wanyue
Published: May 2024

Objective

To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple injections.

Methods

One hundred twenty patients with grade I-III knee osteoarthritis were randomly assigned to three groups: PRP1 group, who received a single injection of platelet-rich plasma; PRP3 group, who received three PRP injections one week apart; PRP5 group, who received five PRP injections one week apart. The patients’ conditions were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index-VA3.1 version (WOMAC-VA3.1) at baseline and 6, 12, 24, and 52 weeks 52 weeks follow up.

Results

Out of the total participants, 106 patients (30 males and 76 females) completed the study. The primary outcome measure, WOMAC pain score, registered significant improvements across all groups when compared to pre-treatment levels. However, the application of 3 and 5 injections of platelet-rich plasma was substantially more effective than that of a single injection in reducing knee pain and stiffness, as well as enhancing physical function in patients with knee osteoarthritis. No statistically discernable difference was observed between PRP3 and PRP5 at all follow-up intervals, and there was no discernable difference between 3 and 5 PRP injections either. Mild side effects occurred in all three groups.

Conclusions

The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. Furthermore, no significant difference was observed in the efficacy of three or five injections. Therefore, we recommend using three injections of PRP in the treatment of patients with knee osteoarthritis of grade I-III.
Treatment characteristics of patients with hereditary transthyretin amyloidosis: a cohort study
Authors: Qarni Taha N. , Jones Felipe J. S. , Drachman Brian , Khella Sami , Pieretti Janice , Bustamante Nicolas Sarmiento , Karam Chafic
Published: May 2024

Background

There are novel medications approved for the treatment of hereditary transthyretin amyloidosis (ATTRv), classified as transthyretin (TTR) stabilizers or gene silencers. While many patients may be on both classes of medications, there is no data available on the safety and efficacy of combination therapy.

Objectives

To describe ATTRv patient and TTR-targeted therapy characteristics in a US cohort, and compare outcomes with combination therapy versus monotherapy.

Methods

We performed a retrospective cohort study with electronic health record data of patients with ATTRv seen at a single institution between January 2018 and December 2022. We collected data on symptomatology, gene mutation, disease severity, ATTRv treatment, hospitalizations, and mortality.

Results

One hundred sixty-two patients with ATTRv were identified. The average age at diagnosis was 65 years. 86 patients (53%) had the V122I variant. 119 patients were symptomatic, of whom 103 were started on ATTRv-specific treatment. 41 patients (40%) had cardiomyopathy only, and 53 (51%) had a mixed phenotype of cardiomyopathy and neuropathy. 38 patients (37%) received therapy with both a gene silencer and protein stabilizer. 9 patients (15%) in the monotherapy group had two or more cardiac hospitalizations after starting treatment, compared to 3 patients (9%) on combination therapy (p=0.26). The adjusted hazard ratio of all-cause mortality for the patients on combination therapy compared to monotherapy was 0.37 (0.08-1.8, p=0.21).

Conclusions

While the efficacy is unproven, over one-third of patients with ATTRv are on both a stabilizer and a silencer. There were no safety issues for combination therapy. There was a trend towards improved hospitalizations and survival in patients in the combination group but this was not statistically significant. Larger studies with longer follow-up are necessary to determine benefit of combination therapy.
Veno-venous extracorporeal membrane oxygenation (VV ECMO) cannula malposition identified with point-of-care ultrasound
Authors: Becker Taylor , Struble Roger D. , Rappaport Charles
Published: May 2024

Background

Point-of-care ultrasound (POCUS) has become a mainstay in the evaluation of critically ill patients in the intensive care unit (ICU). ECMO patients are susceptible to complications during prolonged ICU stay, including cannula malposition, which has deleterious consequences. Although the literature surrounding utility of ultrasound on ECMO patients is expansive, direct comparison between radiographic imaging versus ultrasound for identification of cannula malposition is lacking.

Case presentation

The authors identified four patients with cannula malposition discovered through POCUS that was missed on routine radiographic imaging. Identification and correction of malposition changed their ECMO course.

Conclusion

This case series is the first in literature demonstrating that ultrasound may be superior to radiographic images for ECMO cannula malposition. Further investigation into this subject is warranted.
The quality of COVID-19 systematic reviews during the coronavirus 2019 pandemic: an exploratory comparison
Authors: McDermott Kevin T. , Perry Mark , Linden Willemijn , Croft Rachel , Wolff Robert , Kleijnen Jos
Published: May 2024

Background

The unprecedented volume and speed at which COVID-19-related systematic reviews (SRs) may have been produced has raised questions regarding the quality of this evidence. It is feasible that pandemic-related factors may have led to an impairment in quality (reduced internal validity, increased risk of bias [RoB]). This may have serious implications for decision-making related to public health and individual healthcare.

Objective

The primary objective was to compare the quality of SRs published during the pandemic that were related to COVID-19 with SRs published during the pandemic that were unrelated to COVID-19 (all of which were fully appraised in the KSR Evidence database of SRs in healthcare). Our secondary objective was to compare the quality of SRs published during the pandemic (regardless of research topic), with SRs published pre-pandemic.

Methods

We compared all SRs related to COVID-19 to all SRs unrelated to COVID-19 that (i) were published during the pandemic (between 1st March 2020 and September 14, 2022), (ii) were included in KSR Evidence, and (iii) had been appraised using the ROBIS tool. We then compared all SRs published during the pandemic (regardless of research topic) with a pre-pandemic sample of SRs.

Results

For SRs published during the pandemic, we found there was no statistically significant difference in quality between those SRs tagged as being related to COVID-19 and those that were not [relative risk (RR) of low RoB for COVID-19 versus COVID-19-unrelated reviews: 0.94; 95% confidence interval (CI): 0.66 to 1.34]. Generally, COVID-19 SRs and COVID-19-unrelated SRs were both of low quality with only 10% of COVID-19 reviews and 11% of COVID-19-unrelated reviews rated as low RoB. However, SRs (regardless of topic) published during the pandemic were of lower quality than those published pre-pandemic (RR for low RoB for ‘during pandemic’ versus ‘pre-pandemic’: 0.30; 95% CI: 0.26 to 0.34) with 11% of pandemic and 36% of pre-pandemic SRs rated as low RoB.

Conclusion

These results suggest COVID-19 and COVID-19-unrelated SRs published during the pandemic are equally of low quality. SRs published during the pandemic were generally lower quality compared with SRs published pre-pandemic irrespective of COVID-19 focus. Moreover, SR quality in general is seriously lacking, and considerable efforts need to be made to substantially improve the quality and rigour of the SR process.
Sequential inertial linear ADMM algorithm for nonconvex and nonsmooth multiblock problems with nonseparable structure
Authors: Xue Zhonghui , Yang Kaiyuan , Ma Qianfeng , Dang Yazheng
Published: May 2024

The alternating direction method of multipliers (ADMM) has been widely used to solve linear constrained problems in signal processing, matrix decomposition, machine learning, and many other fields. This paper introduces two linearized ADMM algorithms, namely sequential partial linear inertial ADMM (SPLI-ADMM) and sequential complete linear inertial ADMM (SCLI-ADMM), which integrate linearized ADMM approach with inertial technique in the full nonconvex framework with nonseparable structure. Iterative schemes are formulated using either partial or full linearization while also incorporating the sequential gradient of the composite term in each subproblem’s update. This adaptation ensures that each iteration utilizes the latest information to improve the efficiency of the algorithms. Under some mild conditions, we prove that the sequences generated by two proposed algorithms converge to the critical points of the problem with the help of KŁ property. Finally, some numerical results are reported to show the effectiveness of the proposed algorithms.
Single-port-plus-one robot-assisted laparoscopic Lich–Gregoir direct nipple ureteral extravesical reimplantation in pediatric primary obstructive megaureter, comparing to laparoscopic cohen
Authors: Lin Shan , Xu Huihuang , He Yufeng , Xu Xinru , You Guangxu , Chen Jianglong , Xu Di
Published: May 2024

Purpose

To compare the effects of a single-port-plus-one robotic laparoscopic-modified Lich–Gregoir direct nipple approach and traditional laparoscopic Cohen in treating pediatric primary obstructive megaureter.

Materials and methods

The clinical data of 24 children with primary obstructive megaureter from January 2021 to November 2021 were analyzed retrospectively. Among them, 12 children (8 boys and 4 girls, the average age were 17.17 ± 6.31 months) treated with the laparoscopic Cohen method were defined as group C. The remaining 12 children (7 boys and 5 girls, the average age was 17.33 ± 6.99 months) underwent single-port-plus-one robotic laparoscopic-modified Lich–Gregoir direct nipple ureteral extravesical reimplantation were defined as group L. The parameters of pre-operation, intraoperative and postoperative were compared.

Results

There were no differences in the patient characteristics and average follow-up time between the two groups (P > 0.05).The obstruction resolution rate was 100% in both groups. The total operation time in group L is slightly longer than that in group C(P < 0.001),but the intraperitoneal operation time of the two groups was comparable(P > 0.05). The postoperative parameters included blood loss, gross haematuria time, indwelling catheterization time and hospitalization time in group L is shorter than group C(P < 0.05). One year post-operation, decreasing in ureteral diameter and APRPD, and increasing in DRF were remarkably observed in both two groups(P < 0.05). Ureteral diameter, APRPD, and DRF were not significantly different both in pre-operation and post-operation between Group L and Group C(P > 0.05).

Conclusion

Single-port-plus-one robot-assisted laparoscopic-modified Lich–Gregoir direct nipple approach and traditional laparoscopic Cohen are both dependable techniques for ureteral reimplantation in the treatment of pediatric primary obstructive megaureter. Since Lich–Gregoir can preserve the physiological direction of the ureter and direct nipple reimplantation enhances the effect of anti-refluxing, this technique is favorable for being promoted and applied in robot surgery.
Development of Sustainable Slag-based Geopolymer Concrete Using Different Types of Chemical Admixtures
Authors: Amer Ismail , Abdelkhalik Amr , Mayhoub Ola A. , Kohail Mohamed
Published: May 2024

Geopolymer concrete (GPC) has achieved a wide popularity since innovating it as an alternative to conventional concrete because of its superior mechanical characteristics and durability, in addition to being a green concrete due to its low negative impact on the environment. However, GPC still suffers from the problem of its poor workability which suppresses its spread in construction applications. This study investigated the most effective parameters on the workability of GPC including GGBFS content, water to binder ratio, and dosage of different types of chemical admixtures, Naphthalene-Based Admixture (NPA) and Polycarboxylate-Based Admixture (PCA), using Taguchi approach and Analysis of Variance (ANOVA) analysis considering the compressive strength at the different concrete ages. It was observed that NPA, in the geopolymer concrete, improved the compressive strength compared to PCA. The NPA-based mixes achieved the highest 28-day compressive strength, 69 MPa, with about 27.8% more than the highest 28-day compressive strength achieved by the PCA-based mixes, 54 MPa. The obtained results revealed that the NPA has achieved the best improvement for both the workability, in terms of initial slump value and slump loss rate, and the compressive strength of GPC mixes compared to PCA.
Determination of the temporal–spatial distribution patterns of ancient heritage sites in China and their influencing factors via GIS
Authors: Li Xiaojia
Published: May 2024

In this paper, we analysed the temporal and spatial distributions of ancient archaeological sites in China as well as their influencing factors. Our aim was to reveal the developmental trajectory of Chinese civilisation and to explore the natural and cultural factors affecting human distribution, with the goal of providing insights for the conservation and development of ancient relics. We employed spatial analysis methods using ArcGIS 10.8 software, such as kernel density analysis and trend surface analysis, to analyse 1194 historical ancient sites listed in the National Cultural Relics Protection Units of China. The research findings are as follows: (1) the distribution of ancient sites demonstrates an agglomerative spatial pattern. The nearest neighbour index (R < 1) for sites from various historical periods indicates an agglomerative spatial distribution of ancient sites across historical periods, with the clustering degree being relatively poor for sites from the Wei-Jin, Northern and Southern Dynasties and in the Ming and Qing periods. The regions with a concentration of ancient sites are the middle and lower reaches of the Yangtze River and Yellow River Basins. Furthermore, there is a higher abundance of ancient sites in the southeastern region than in the northwestern region. (2) The distribution of ancient sites in different historical periods also exhibits an imbalance, with an overall decreasing trend in the number of ancient sites in China. Notably, more ancient sites were found for the prehistoric and pre-Qin periods. The temporal trend of ancient sites during historical periods follows a trajectory from northeast to northwest, northeast to southwest, etc. (3) The temporal and spatial distributions of ancient sites are influenced by multiple factors, including social development, the natural environment, geographical elements, and socioeconomic and political factors. Finally, based on an understanding of the spatiotemporal distribution pattern of ancient sites and the factors that influence this pattern, recommendations for conservation and development can be proposed and supported by modern technological methods, with the aim of offering insights for the protection and sustainable development of heritage sites.
Establishment of an automatic diagnosis system for corneal endothelium diseases using artificial intelligence
Authors: Qu Jing-hao , Qin Xiao-ran , Xie Zi-jun , Qian Jia-he , Zhang Yang , Sun Xiao-nan , Sun Yu-zhao , Peng Rong-mei , Xiao Ge-ge , Lin Jing , Bian Xiao-yan , Chen Tie-hong , Cheng Yan , Gu Shao-feng , Wang Hai-kun , Hong Jing
Published: May 2024

Purpose

To use artificial intelligence to establish an automatic diagnosis system for corneal endothelium diseases (CEDs).

Methods

We develop an automatic system for detecting multiple common CEDs involving an enhanced compact convolutional transformer (ECCT). Specifically, we introduce a cross-head relative position encoding scheme into a standard self-attention module to capture contextual information among different regions and employ a token-attention feed-forward network to place greater focus on valuable abnormal regions.

Results

A total of 2723 images from CED patients are used to train our system. It achieves an accuracy of 89.53%, and the area under the receiver operating characteristic curve (AUC) is 0.958 (95% CI 0.943–0.971) on images from multiple centres.

Conclusions

Our system is the first artificial intelligence-based system for diagnosing CEDs worldwide. Images can be uploaded to a specified website, and automatic diagnoses can be obtained; this system can be particularly helpful under pandemic conditions, such as those seen during the recent COVID-19 pandemic.
Multi-institutional validation of a radiomics signature for identification of postoperative progression of soft tissue sarcoma
Authors: Yu Yuan , Guo Hongwei , Zhang Meng , Hou Feng , Yang Shifeng , Huang Chencui , Duan Lisha , Wang Hexiang
Published: May 2024

Background

To develop a magnetic resonance imaging (MRI)-based radiomics signature for evaluating the risk of soft tissue sarcoma (STS) disease progression.

Methods

We retrospectively enrolled 335 patients with STS (training, validation, and The Cancer Imaging Archive sets, n = 168, n = 123, and n = 44, respectively) who underwent surgical resection. Regions of interest were manually delineated using two MRI sequences. Among 12 machine learning-predicted signatures, the best signature was selected, and its prediction score was inputted into Cox regression analysis to build the radiomics signature. A nomogram was created by combining the radiomics signature with a clinical model constructed using MRI and clinical features. Progression-free survival was analyzed in all patients. We assessed performance and clinical utility of the models with reference to the time-dependent receiver operating characteristic curve, area under the curve, concordance index, integrated Brier score, decision curve analysis.

Results

For the combined features subset, the minimum redundancy maximum relevance-least absolute shrinkage and selection operator regression algorithm + decision tree classifier had the best prediction performance. The radiomics signature based on the optimal machine learning-predicted signature, and built using Cox regression analysis, had greater prognostic capability and lower error than the nomogram and clinical model (concordance index, 0.758 and 0.812; area under the curve, 0.724 and 0.757; integrated Brier score, 0.080 and 0.143, in the validation and The Cancer Imaging Archive sets, respectively). The optimal cutoff was − 0.03 and cumulative risk rates were calculated.

Data conclusion

To assess the risk of STS progression, the radiomics signature may have better prognostic power than a nomogram/clinical model.
Novel role of LLGL2 silencing in autophagy: reversing epithelial-mesenchymal transition in prostate cancer
Authors: Hong Geum-Lan , Kim Kyung-Hyun , Kim Yae-Ji , Lee Hui-Ju , Cho Sung-Pil , Han Seung-Yun , Yang Seung Woo , Lee Jong-Soo , Kang Shin-Kwang , Lim Jae-Sung , Jung Ju-Young
Published: May 2024

Purpose

Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo.

Methods

PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model.

Results

In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition.

Conclusion

Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.
The digital transformation in pharmacy: embracing online platforms and the cosmeceutical paradigm shift
Authors: Almeman Ahmad
Published: May 2024

In the face of rapid technological advancement, the pharmacy sector is undergoing a significant digital transformation. This review explores the transformative impact of digitalization in the global pharmacy sector. We illustrated how advancements in technologies like artificial intelligence, blockchain, and online platforms are reshaping pharmacy services and education. The paper provides a comprehensive overview of the growth of online pharmacy platforms and the pivotal role of telepharmacy and telehealth during the COVID-19 pandemic. Additionally, it discusses the burgeoning cosmeceutical market within online pharmacies, the regulatory challenges faced globally, and the private sector’s influence on healthcare technology. Conclusively, the paper highlights future trends and technological innovations, underscoring the dynamic evolution of the pharmacy landscape in response to digital transformation.
Ultrasound-guided minimally invasive thread release of Guyon’s canal: initial experience in cadaveric specimens
Authors: Jengojan Suren , Sorgo Philipp , Kasprian Gregor , Streicher Johannes , Gruber Gerlinde , Moser Veith , Bodner Gerd
Published: May 2024

Objective

Guyon’s canal syndrome is caused by compression of the ulnar nerve at the wrist, occasionally requiring decompression surgery. In recent times, minimally invasive approaches have gained popularity. The aim of this study was to assess the efficacy and safety of ultrasound-guided thread release for transecting the palmar ligament in Guyon’s canal without harming surrounding structures, in a cadaveric specimen model.

Methods

After ethical approval, thirteen ultrasound-guided thread releases of Guyon’s canal were performed on the wrists of softly embalmed anatomic specimens. Cadavers showing injuries or prior operations at the hand were excluded. Subsequently, the specimens were dissected, and the outcome of the interventions and potential damage to adjacent anatomical structures as well as ultrasound visibility were evaluated with a score from one to three.

Results

Out of 13 interventions, a complete transection was achieved in ten cases (76.9%), and a partial transection was documented in three cases (23.1%). Irrelevant lesions on the flexor tendons were observed in two cases (15.4%), and an arterial branch was damaged in one (7.7%). Ultrasound visibility varied among specimens, but essential structures were delineated in all cases.

Conclusion

Ultrasound-guided thread release of Guyon’s canal has shown promising first results in anatomic specimens. However, further studies are required to ensure the safety of the procedure.

Relevance statement

Our study showed that minimally invasive ultrasound-guided thread release of Guyon’s canal is a feasible approach in the anatomical model. The results may provide a basis for further research and refinement of this technique.

Key points

• In Guyon’s canal syndrome, the ulnar nerve is compressed at the wrist, often requiring surgical release.

• We adapted and tested a minimally invasive ultrasound-guided thread release technique in anatomic specimens.

• The technique was effective; however, in one specimen, a small anatomic branch was damaged.

Graphical Abstract
PMCT-based sex determination using posterior segment of greater sciatic notch in North Indian population
Authors: Kumari Ruchi , Pandit Jay Narayan , Panga Surya Kiran , Tyagi Swati , Yadav Abhishek , Gupta Sudhir Kumar
Published: May 2024

Background

Digital tools, which offer superior accuracy compared to manual metrics, utilize radiological images for noninvasive data collection, providing a convenient means of obtaining skeletal data. The greater sciatic notch exhibits high sexual dimorphism and resistance to damage, and therefore serves as a viable tool for sex determination in poorly preserved skeletons, particularly in scenarios involving mass disasters, highly putrefied, and skeletonized cases. In addition to the width and depth of the greater sciatic notch, the length and angle of the posterior segment are highly specific parameters. This study aims to obtain accurate and standardized values for determining sex by measuring the posterior segment of the greater sciatic notch using postmortem computed tomography with a 16-slice multidetector row computed tomography scanner.

Results

The study revealed that except for depth and the distance between the ischial spine and deepest point, all measured variables of the greater sciatic notch were greater for women than men on both sides. The length of the posterior segment and the posterior angle on both sides showed the highest positive correlation and provided highly significant differences between males and females. These findings not only reinforce the utility of the greater sciatic notch in sex determination but also highlight the potential for more accurate and noninvasive methods in forensic investigations.

Conclusions

Postmortem computed tomography accurately determines sex by measuring the posterior sciatic notch segment, achieving a 90.9% accuracy rate. This study, the first of its kind in India, utilized postmortem computed tomography ruler measurements for sex determination, specifically evaluating the role of the posterior segment dimensions of the greater sciatic notch in the North Indian population.
Cannabidiol’s cytotoxicity in pancreatic cancer is induced via an upregulation of ceramide synthase 1 and ER stress
Authors: Mangal Nagina , Reebye Vikash , Habib Nagy , Sodergren Mikael H.
Published: May 2024

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a median 5 year-survival rate of 12%. Cannabidiol (CBD) has been found to exhibit antineoplastic potential and may potentiate the anticancer effects of cytotoxic’s such as gemcitabine. CBD therapy has been linked to de novo synthesis of ceramide. The sphingolipid ceramide is a potent tumour suppressor lipid with roles in apoptosis and autophagy. One of the key players involved is ceramide synthase, an enzyme with six isoforms (CerS1-CerS6), reported to have disease prognostic value. Quantitative real time PCR was used to determine mRNA expression levels of ceramide synthase isoforms, GRP78, ATF4 and CHOP. Western blotting was used to analyze protein expression of these markers and knockdown of CerS1 and GRP78 were applied via an siRNA and confirmed by the two mentioned methods. Mice with PDAC xenografts were injected via intraperitoneal method with drugs and tumours were analysed with flow cytometry and processed using H&E and IHC staining. siRNA knockdown of ceramide synthase 1 (CerS1) and analysis point to evidence of a putative CerS1 dependent pathway driven by CBD in activating endoplasmic reticulum (ER) stress target; GRP78. Upon CBD treatment, CerS1 was upregulated and downstream this led to the GRP78/ATF4/CHOP arm of the unfolded protein response (UPR) pathway being activated. In an in vivo model of PDAC in which CerS1 was not upregulated on IHC, there was no observed improvement in survival of animals, however a reduction in tumour growth was observed in combination chemotherapy and CBD group, indicating further investigations in vivo. These findings provide evidence of a potential ceramide induced cytotoxic mechanism of action of CBD in pancreatic ductal adenocarcinoma.
Presentation of enthesitis-related arthritis and juvenile-onset spondyloarthritis: a cross-sectional study in a pediatric and adult clinic
Authors: Lanças Sean Hideo Shirata , Furlan Matheus Zanata Brufatto , Fernandes Taciana de Albuquerque Pedrosa , Drumond Sula Glaucia Lage , Magalhães Claudia Saad
Published: May 2024

Background

Juvenile idiopathic arthritis (JIA) comprises a whole spectrum of chronic arthritis starting before 16 years of age. The study aims to explore the clinical and demographic descriptors, treatment, and disease progression of enthesitis-related arthritis (ERA) in comparison with juvenile-onset spondyloarthritis (SpA).

Methods

Cross-sectional analysis of consecutive patients in two dedicated clinics, with a single visit and retrospective case-notes review. Arthritis, enthesitis and sacroiliitis were evaluated by scoring disease activity and damage. Continuous variables were reported by median, interquartile range; categorical variables were reported by the frequency comparison of the two groups.

Results

Thirty-three cases were included, being 23 (69.7%) with ERA. The median age at diagnosis was 12.5 y (SpA) vs. 9 y (ERA) (p < 0.01); the time from symptom onset to diagnosis was 5.5 y (SpA) vs. 1.5 y (ERA) (p < 0.03). In both groups, the predominant presentation was a single joint or < 5 lower limb joints and asymmetric involvement, with a high frequency of enthesitis. There was a higher frequency of mid-tarsal and ankle synovitis in the ERA group and hip involvement in those with SpA. The comparison of the frequency of spine symptoms at presentation, 30% SpA vs. 21.7% ERA (p = 0.7), was not significant, and radiographic progression to spinal involvement occurred in 43.5% of ERA patients. The median time for spinal progression and age at onset was 2.2 and 12 y for ERA, and 4 and 16.5 y for SpA, respectively. Activity and damage scores were not significantly different between the groups. Treatment comparison resulted in 91.3% of ERA and 100% SpA being treated, predominantly with NSAIDs in both groups, followed by DMARDs and biologics, with a higher frequency of biologics in SpA.

Conclusion

The main differences were the late diagnoses of SpA, and the hip and spine involvement, with higher frequency of biologic treatment in juvenile-onset SpA compared to ERA.
Gut microbiota response to consumption of milks fermented with specific strains of Lactococcus lactis with hypocholesterolemic effect
Authors: Rendon-Rosales Miguel A. , Méndez-Romero José I. , Hernández-Mendoza Adrián , González-Córdova Aarón F. , Mazorra-Manzano Miguel A. , García Hugo S. , Beltrán-Barrientos Lilia M. , Estrada-Montoya María C. , Vallejo-Cordoba Belinda
Published: May 2024

The alteration of structure and function of gut microbiota (dysbiosis) appears to be a major factor associated with metabolic disorders such as dyslipidemia and subsequent development of cardiovascular diseases. However, the consumption of fermented milks is a promising strategy to enhance health and restore the function of gut microbiota; specifically, in individuals with intestinal dysbiosis and hypercholesterolemia. Therefore, the aim of the present study was to evaluate the potential association between gut microbiota and the hypocholesterolemic effect of fermented milks with Lactococcus lactis NRRL B-571 (FM-571), NRRL B-572 (FM-572) and NRRL B-600 (FM-600) in Sprague–Dawley rats. Fermented milks were administered to hypercholesterolemic Sprague–Dawley rats during seven weeks. At the end of the experimental period, fecal and colonic microbiota were characterized using 16S RNA gene sequencing. Also, the short chain fatty acids (SCFAs) content was quantified in feces. Results showed that a high-cholesterol diet (HCD) altered the bacterial community in both fecal and mucosal samples. The consumption of fermented milks, specifically FM-572 promoted changes in the structure (beta diversity) in fecal, but not in mucosal microbiota. The levels of SCFAs in feces were improved after fermented milks consumption. From all SCFAs, butyrate was negatively correlated with total cholesterol, LDL-C (p < 0.05) and positively correlated with HDL-C (p < 0.05). Furthermore, Ruminococcaceae, Lactobacillaceae, Lachnospiraceae and Oscillospiraceae families, were negatively associated with total cholesterol, LDL-C (p < 0.05) and positively associated with HDL-C (p < 0.05). The abundance of these families was increased in groups treated with fermented milks, particularly with FM-572 (p < 0.05). Thus, the in vivo hypocholesterolemic effect after the consumption of milks fermented with Lactococcus lactis strains may be related with the modulation of fecal microbiota associated with the increase of butyrate-producing bacteria. Furthermore, these associations may suggest that butyrate may influence the cholesterol metabolism, resulting in the decreasing cholesterol levels.

Graphical Abstract