bluuebunny/crossref_metadata_2025 huggingface dataset:
PD-L1 has a heterogeneous and dynamic expression in gastric cancer with implications for immunoPET
Authors: Ibrahim Dina , Simó Cristina , Brown Emma L. , Shmuel Shayla , Panikar Sandeep Surendra , Benton Alex , DeWeerd Rachel , Dehdashti Farrokh , Park Haeseong , Pereira Patrícia M. R.
Published: June 2024

Introduction

This study aimed to investigate the dynamics of programmed death-ligand 1 (PD-L1) expression, spatial heterogeneity, and binding affinity of FDA-approved anti-PD-L1 antibodies (avelumab and atezolizumab) in gastric cancer. Additionally, we determined how PD-L1 glycosylation impacts antibody accumulation in gastric cancer cells.

Methods

Dynamic PD-L1 expression was examined in NCIN87 gastric cancer cells. Comparative binding studies of avelumab and atezolizumab were conducted in gastric cancer models, both in vitro and in vivo. Antibody uptake in tumors was visualized through positron emission tomography (PET) imaging. PD-L1 glycosylation status was determined via Western blot analyses before and after PNGase F treatment.

Results

Consistent findings revealed time-dependent PD-L1 induction in NCIN87 gastric cancer cells and spatial heterogeneity in tumors, as shown by PET imaging and immunofluorescence. Avelumab displayed superior binding affinity to NCIN87 cells compared to atezolizumab, confirmed by in vivo PET imaging and ex vivo biodistribution analyses. Notably, PD-L1 glycosylation at approximately 50 kDa was observed, with PNGase F treatment inducing a shift to 35 kDa in molecular weight. Tissue samples from patient-derived xenografts (PDXs) validated the presence of both glycosylated and deglycosylated PD-L1 (degPD-L1) forms in gastric cancer. Immunofluorescence microscopy and binding assays demonstrated enhanced avelumab binding post-deglycosylation.

Discussion

This study provides an understanding of dynamic and spatially heterogeneous PD-L1 expression in gastric cancer. Anti-PD-L1 immunoPET was able to visualize gastric tumors, and PD-L1 glycosylation has significant implications for antibody recognition. These insights contribute to demonstrating the complexities of PD-L1 in gastric cancer, holding relevance for refining PD-L1 imaging-based approaches.
T cell-related ubiquitination genes as prognostic indicators in hepatocellular carcinoma
Authors: Chen Chaobo , Chen Zheng , Zhou Zheyu , Ye Hui , Xiong Shaohui , Hu Weidong , Xu Zipeng , Ge Chen , Zhao Chunlong , Yu Decai , Shen Jiapei
Published: June 2024

Background

T lymphocytes, integral to the adaptive immune system, wield pivotal influence in bolstering anti-tumor responses, and are strictly regulated by ubiquitination modification. The objective of this investigation was to devise a novel prognostic and immunotherapeutic efficacy predictor for hepatocellular carcinoma patients utilizing T cell-related ubiquitination genes (TCRUG).

Method

The single-cell RNA sequencing (scRNA-seq) data and bulk RNA data of HCC patients are derived from the GEO database and TCGA database. Based on the processing of scRNA-seq, T cell marker genes are obtained and TCRUG is obtained. Further combined with WGCNA, differential analysis, univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis to filter and screen TCRUG. Finally construct a riskscore for predicting the prognosis of HCC patients, the predictive effect of which is validated in the GEO dataset. In addition, we also studied the correlation between riskscore and immunotherapy efficacy. Finally, the oncogenic role of UBE2E1 in HCC was explored through various in vitro experiments.

Result

Based on patients’ scRNA-seq data, we finally obtained 3050 T cell marker genes. Combined with bulk RNA data and clinical data from the TCGA database, we constructed a riskscore that accurately predicts the prognosis of HCC patients. This riskscore is an independent prognostic factor for HCC and is used to construct a convenient column chart. In addition, we found that the high-risk group is more suitable for immunotherapy. Finally, the proliferation, migration, and invasion abilities of HCC cells significantly decreased after UBE2E1 expression reduction.

Conclusion

This study developed a riskscore based on TCRUG that can accurately and stably predict the prognosis of HCC patients. This riskscore is also effective in predicting the immune therapy response of HCC patients.
Numerical modeling of bamboo fences with various infill porosities deployed for mangrove restoration
Authors: Shu Anping , Zhang Ziru , Cui Baoshan , Zhuo Yiyuan , Zhang Xin , Pi Chengling , Zhu Fuyang , Christian Huarez
Published: June 2024

As part of mangrove restoration initiatives eco-friendly fence has been implemented in eroded coastal areas in recent years. These fences provide the capacity to mitigate incoming wave energy and facilitate sediment deposition, thereby promoting the establishment and maintenance of mangrove habitats. Nevertheless, it is crucial to investigate the influence of the infill porosity on the wave dissipation performance of these fences, as the infill porosity can vary considerably across different restoration projects. The aim of this research is to explore the relationship between the infill porosity and wave dissipation effectiveness to identify more efficient designs for these eco-friendly restoration measures. The experiments involving wave interactions with fence models were conducted in a wave flume measuring 0.8 m in width and 25 m in length. Four wooden fences with distinct infill porosities ranging from 0.60 to 0.90 were strategically positioned to assess wave transmission, reflection, and dissipation phenomena under 18 distinct wave conditions. Additionally, the simulating waves till shore (SWASH)model was employed to calibrate critical bulk drag coefficient parameters and simulate the flow velocity distribution surrounding the fences under the experimental wave conditions. The findings indicated that a fence with a reduced infill porosity exhibits a higher wave transmission coefficient. However, this is accompanied by a higher reflection coefficient and lower wave energy dissipation within the fence. Both the infill porosity and incident wave conditions influence the flow velocity distribution characteristics in the vicinity of the fences. The area where the interaction between waves and fences is the most prominent is concentrated in the upper water layer immediately adjacent to the frontal section of the fences. Understanding the velocity distribution and hydrodynamic characteristics of the fence area aids in better determining the suitable porosity of fill materials for engineering applications.
Coastal resilience and shoreline dynamics: assessing the impact of a hybrid beach restoration strategy in Puducherry, India
Authors: Benhur Judha , Vendhan Mullai , Kumar Phani , Janagiraman Ramkumar
Published: June 2024

Puducherry, a Union Territory of India, has been strongly affected by severe erosion after the construction of the Puducherry port in 1989. To mitigate this cause, the National Institute of Ocean Technology, Chennai, and the Puducherry government implemented a beach restoration strategy involving a hybrid solution in 2017 for coastal protection/stabilization and the restoration of the lost beach. The strategy involved deploying a steel reef into the nearshore sea and implementing beach nourishment processes. To monitor the coastal morphological changes after implementing the coastal protection strategy, the Digital Shoreline Analysis System, was adopted to calculate the rate of shoreline change statistics for the years 2016 to 2022. It uses spatio-temporal shoreline positions from multi-temporal satellite imagery. The shorelines are extracted from the Sentinel-2A satellite images by a Normalized Differential Water Index based semi-automated model. Statistical parameters in DSAS analyze the shorelines to determine the shoreline changes in this area. The results reveal the remarkable resilience of a newly restored beach, where the linear regression rate statistics in Zone A show an average accretional rate of 2.92m/yr. Alternatively, Zone B exhibits an average erosion rate of -0.23m/yr, with intermittent sandy beaches experiencing maximum erosion rates of -1.63m/yr. The influence of longshore current direction and sediment transport on shoreline movement is evident in seasonal analysis, with shoreline development and recession primarily observed near shore protection structures. The study’s outcome provides valuable insights for coastal management, offering a reliable approach for shoreline monitoring post-implementation of mitigation projects.
Acute-on-chronic: using magnetic resonance imaging to disentangle the haemodynamic responses to acute and chronic fetal hypoxaemia
Authors: Darby Jack R. T. , Saini Brahmdeep S. , Holman Stacey L. , Hammond Sarah J. , Perumal Sunthara Rajan , Macgowan Christopher K. , Seed Mike , Morrison Janna L.
Published: June 2024

Introduction

The fetal haemodynamic response to acute episodes of hypoxaemia are well characterised. However, how these responses change when the hypoxaemia becomes more chronic in nature such as that associated with fetal growth restriction (FGR), is less well understood. Herein, we utilised a combination of clinically relevant MRI techniques to comprehensively characterize and differentiate the haemodynamic responses occurring during acute and chronic periods of fetal hypoxaemia.

Methods

Prior to conception, carunclectomy surgery was performed on non-pregnant ewes to induce FGR. At 108–110 days (d) gestational age (GA), pregnant ewes bearing control (n = 12) and FGR (n = 9) fetuses underwent fetal catheterisation surgery. At 117–119 days GA, ewes underwent MRI sessions where phase-contrast (PC) and T2 oximetry were used to measure blood flow and oxygenation, respectively, throughout the fetal circulation during a normoxia and then an acute hypoxia state.

Results

Fetal oxygen delivery (DO2) was lower in FGR fetuses than controls during the normoxia state but cerebral DO2 remained similar between fetal groups. Acute hypoxia reduced both overall fetal and cerebral DO2. FGR increased ductus venosus (DV) and foramen ovale (FO) blood flow during both the normoxia and acute hypoxia states. Pulmonary blood flow (PBF) was lower in FGR fetuses during the normoxia state but similar to controls during the acute hypoxia state when PBF in controls was decreased.

Conclusion

Despite a prevailing level of chronic hypoxaemia, the FGR fetus upregulates the preferential streaming of oxygen-rich blood via the DV-FO pathway to maintain cerebral DO2. However, this upregulation is unable to maintain cerebral DO2 during further exposure to an acute episode of hypoxaemia. The haemodynamic alterations required at the level of the liver and lung to allow the DV-FO pathway to maintain cerebral DO2, may have lasting consequences on hepatic function and pulmonary vascular regulation after birth.
Designing and implementing a training program on surgical hand scrubbing, wearing surgical cap and surgical mask, gowning, and gloving using HMD-based virtual reality technologies for nursing students: an exploration of student perceptions
Authors: Güngör Songül , Yava Ayla , Koyuncu Aynur
Published: June 2024

Objective

The aim of this study is to determine the steps of a training program utilizing Head-Mounted Display (HMD) based Virtual Reality Technology to enhance nursing students’ skills in surgical hand scrubbing, wearing surgical cap and surgical mask, gowning and gloving, and to evaluate students’ perceptions toward the program.

Methods

The study aimed to investigate the potential applications of HMD-Based Virtual Reality Technology in Surgical Hand Scrubbing, Wearing Surgical Cap and Surgical Mask, Gowning and Gloving Program for nursing students, as well as students’ perceptions toward this technology. The research was conducted with a focus group consisting of second-year nursing students in Osmaniye/Turkey, between January and June 2022, and the training program was implemented in five stages: Analysis, Design, Development, Implementation, and Evaluation. The program was evaluated with a focus group of nursing students. Focus group discussions were conducted to provide insights into students’ experiences, feedback, and perceptions of the program.

Results

A vast majority of participants (92.5%) reported feeling fully immersed in the operating room environment during the virtual reality (VR) experience. Notably, all students acknowledged the potential of HMD-Based Virtual Reality Technology to enrich their understanding of surgical hand scrubbing, wearing surgical cap and surgical mask, gowning and gloving procedures, surpassing conventional instructional models. While many participants found the experience exhilarating (85.1%), a considerable portion reported a decline in engagement after repeated exposures (88.8%). Overall, participants welcomed the integration of VR technology into education, expressing optimism about its capacity to facilitate additional instructional modules (74.4%). Moreover, they conveyed satisfaction with the opportunity to engage with the VR application, emphasizing its significant educational value (81.4%).

Conclusion

Based on these findings, we can suggest that virtual reality technology has the potential to have an impact on nursing students’ education. The majority of students expressing a sense of presence in the operating room highlights the value of this method in education. However, the reported boredom after repeated experiences by most participants underscores the importance of diversifying the program and introducing innovative approaches to keep students engaged.
Association between volume of lung damage and endoplasmic reticulum stress expression among severe COVID-19 ICU patients
Authors: Renard Domitille , Verdalle-Cazes Mikael , Leprêtre Perrine , Bellien Jérémy , Brunel Valery , Renet Sylvanie , Tamion Fabienne , Besnier Emmanuel , Clavier Thomas
Published: June 2024

Introduction

Links have been established between SARS-CoV-2 and endoplasmic reticulum stress (ERS). However, the relationships between inflammation, ERS, and the volume of organ damage are not well known in humans. The aim of this study was to explore whether ERS explains lung damage volume (LDV) among COVID-19 patients admitted to the intensive care unit (ICU).

Materials and methods

We conducted a single-center retrospective study (ancillary analysis of a prospective cohort) including severe COVID-19 ICU patients who had a chest computed tomography (CT) scan 24 h before/after admission to assess LDV. We performed two multivariate linear regression models to identify factors associated with plasma levels of 78 kDa-Glucose-Regulated Protein (GRP78; ERS marker) and Interleukin-6 (IL-6; inflammation marker) at admission.

Results

Among 63 patients analyzed, GRP78 plasma level was associated with LDV in both multivariate models (β = 22.23 [4.08;40.38]; p = 0.0179, β = 20.47 [0.74;40.20]; p = 0.0423) but not with organ failure (Sequential Organ Failure Assessment (SOFA) score) at admission (r = 0.03 [−0.22;0.28]; p = 0.2559). GRP78 plasma level was lower among ICU survivors (1539.4 [1139.2;1941.1] vs. 1714.2 [1555.2;2579.1] pg./mL. respectively; p = 0.0297). IL-6 plasma level was associated with SOFA score at admission in both multivariate models (β = 136.60 [65.50;207.70]; p = 0.0003, β = 193.70 [116.60;270.90]; p < 0.0001) but not with LDV (r = 0.13 [−0.14;0.39]; p = 0.3219). IL-6 plasma level was not different between ICU survivors and non-survivors (12.2 [6.0;43.7] vs. 30.4 [12.9;69.7] pg./mL. respectively; p = 0.1857). There was no correlation between GRP78 and IL-6 plasma levels (r = 0.13 [−0.13;0.37]; p = 0.3106).

Conclusion

Among severe COVID-19 patients, ERS was associated with LDV but not with systemic inflammation, while systemic inflammation was associated with organ failure but not with LDV.
Protection from prior natural infection vs. vaccination against SARS-CoV-2—a statistical note to avoid biased interpretation
Authors: Weber Susanne , Hedberg Pontus , Naucler Pontus , Wolkewitz Martin
Published: June 2024

Introduction

The fight against SARS-CoV-2 has been a major task worldwide since it was first identified in December 2019. An imperative preventive measure is the availability of efficacious vaccines while there is also a significant interest in the protective effect of a previous SARS-CoV-2 infection on a subsequent infection (natural protection rate).

Methods

In order to compare protection rates after infection and vaccination, researchers consider different effect measures such as 1 minus hazard ratio, 1 minus odds ratio, or 1 minus risk ratio. These measures differ in a setting with competing risks. Nevertheless, as there is no unique definition, these metrics are frequently used in studies examining protection rate. Comparison of protection rates via vaccination and natural infection poses several challenges. For instance many publications consider the epidemiological definition, that a reinfection after a SARS-CoV-2 infection is only possible after 90 days, whereas there is no such constraint after vaccination. Furthermore, death is more prominent as a competing event during the first 90 days after infection compared to vaccination. In this work we discuss the statistical issues that arise when investigating protection rates comparing vaccination with infection. We explore different aspects of effect measures and provide insights drawn from different analyses, distinguishing between the first and the second 90 days post-infection or vaccination.

Results

In this study, we have access to real-world data of almost two million people from Stockholm County, Sweden. For the main analysis, data of over 52.000 people is considered. The infected group is younger, includes more men, and is less morbid compared to the vaccinated group. After the first 90 days, these differences increased. Analysis of the second 90 days shows differences between analysis approaches and between age groups. There are age-related differences in mortality. Considering the outcome SARS-CoV-2 infection, the effect of vaccination versus infection varies by age, showing a disadvantage for the vaccinated in the younger population, while no significant difference was found in the elderly.

Discussion

To compare the effects of immunization through infection or vaccination, we emphasize consideration of several investigations. It is crucial to examine two observation periods: The first and second 90-day intervals following infection or vaccination. Additionally, methods to address imbalances are essential and need to be used. This approach supports fair comparisons, allows for more comprehensive conclusions and helps prevent biased interpretations.
Sex difference in the associations among hyperuricemia with self-reported peptic ulcer disease in a large Taiwanese population study
Authors: Yang Chi-Sheng , Geng Jiun-Hung , Wu Pei-Yu , Huang Jiun-Chi , Hu Huang-Ming , Chen Szu-Chia , Kuo Chao-Hung
Published: June 2024

Background

Hyperuricemia may play a role in various systemic diseases. However, few studies have investigated the relationship between hyperuricemia and the risk of peptic ulcer disease (PUD). Therefore, in this population-based study, we enrolled over 120,000 participants from the Taiwan Biobank (TWB) and examined the risk factors for self-reported PUD. In addition, we investigated sex differences in the association between hyperuricemia and self-reported PUD.

Methods

Data of 121,583 participants were obtained from the TWB. Male participants with a serum uric acid level >7 mg/dl and female participants with a serum uric acid level >6 mg/dl were classified as having hyperuricemia. Details of self-reported PUD were obtained by questionnaire. The association between hyperuricemia and self-reported PUD in the male and female participants was examined using multivariable logistic regression analysis.

Results

The overall prevalence of self-reported PUD was 14.6%, with a higher incidence in males (16.5%) compared to females (13.5%). After multivariable adjustment, male sex [vs. female sex; odds ratio (OR) = 1.139; 95% confidence interval (CI) = 1.084–1.198; p < 0.001], and hyperuricemia (OR = 0.919; 95% CI = 0.879–0.961; p < 0.001) were significantly associated with self-reported PUD. Further, a significant interaction was found between sex and hyperuricemia on self-reported PUD (p = 0.004). Hyperuricemia was associated with a low risk of self-reported PUD in males (OR = 0.890; 95% CI = 0.837–0.947; p < 0.001) but not in females (p = 0.139).

Conclusion

The prevalence of self-reported PUD was higher in the male participants than in the female participants. Hyperuricemia was associated with low prevalence of self-reported PUD in males, but not in females. Further studies are needed to clarify the mechanisms behind these observations and verify the potential protective role of hyperuricemia on the development of self-reported PUD.
Specific cultivation-independent enumeration of viable cells in probiotic products using a combination of fluorescence in situ hybridization and flow cytometry
Authors: Snaidr Laura , Mühlhahn Peter , Beimfohr Claudia , Kreuzer Christian , Richly Carolin , Snaidr Jiri
Published: June 2024

This study introduces an optimized integration of flow cytometry and fluorescence in situ hybridization (Flow-FISH) as an approach for the specific enumeration of gram-positive bacteria in probiotic products, overcoming the limitations of conventional methods. The enhanced Flow-FISH technique synergizes the rapid and automated capabilities of flow cytometry with the high specificity of FISH, facilitating the differentiation of viable cells at the species level within probiotic blends. By analyzing lyophilized samples of Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, and Bifidobacterium animalis subsp. lactis, and a commercial product, the study highlights the optimized Flow-FISH protocol’s advantages, including reduced hybridization times to 1.5 h and elimination of centrifugation steps. Comparative evaluations with the widely accepted enumeration methods plate count and Live/Dead (L/D) staining were conducted. The study revealed that Flow-FISH produces higher viable cell counts than plate count, thereby challenging the traditional “gold standard” by highlighting its predisposition to underestimate actual viable cell numbers. Against L/D staining, Flow-FISH achieved comparable results, which, despite the different foundational premises of each technique, confirms the accuracy and reliability of our method. In conclusion, the optimized Flow-FISH protocol represents a significant leap forward in probiotic research and quality control. This method provides a rapid, robust, and highly specific alternative for the enumeration of probiotic bacteria, surpassing traditional methodologies. Its ability to enable a more detailed and reliable analysis of probiotic products paves the way for precise quality control and research insights, underscoring its potential to improve the field significantly.
SS-DRPL: self-supervised deep representation pattern learning for voice-based Parkinson's disease detection
Authors: Kim Tae Hoon , Krichen Moez , Ojo Stephen , Sampedro Gabriel Avelino , Alamro Meznah A.
Published: June 2024

Parkinson's disease (PD) is a globally significant health challenge, necessitating accurate and timely diagnostic methods to facilitate effective treatment and intervention. In recent years, self-supervised deep representation pattern learning (SS-DRPL) has emerged as a promising approach for extracting valuable representations from data, offering the potential to enhance the efficiency of voice-based PD detection. This research study focuses on investigating the utilization of SS-DRPL in conjunction with deep learning algorithms for voice-based PD classification. This study encompasses a comprehensive evaluation aimed at assessing the accuracy of various predictive models, particularly deep learning methods when combined with SS-DRPL. Two deep learning architectures, namely hybrid Long Short-Term Memory and Recurrent Neural Networks (LSTM-RNN) and Deep Neural Networks (DNN), are employed and compared in terms of their ability to detect voice-based PD cases accurately. Additionally, several traditional machine learning models are also included to establish a baseline for comparison. The findings of the study reveal that the incorporation of SS-DRPL leads to improved model performance across all experimental setups. Notably, the LSTM-RNN architecture augmented with SS-DRPL achieves the highest F1-score of 0.94, indicating its superior ability to detect PD cases using voice-based data effectively. This outcome underscores the efficacy of SS-DRPL in enabling deep learning models to learn intricate patterns and correlations within the data, thereby facilitating more accurate PD classification.
Enhancing brain tumor classification in MRI scans with a multi-layer customized convolutional neural network approach
Authors: Albalawi Eid , Thakur Arastu , Dorai D. Ramya , Bhatia Khan Surbhi , Mahesh T. R. , Almusharraf Ahlam , Aurangzeb Khursheed , Anwar Muhammad Shahid
Published: June 2024

Background

The necessity of prompt and accurate brain tumor diagnosis is unquestionable for optimizing treatment strategies and patient prognoses. Traditional reliance on Magnetic Resonance Imaging (MRI) analysis, contingent upon expert interpretation, grapples with challenges such as time-intensive processes and susceptibility to human error.

Objective

This research presents a novel Convolutional Neural Network (CNN) architecture designed to enhance the accuracy and efficiency of brain tumor detection in MRI scans.

Methods

The dataset used in the study comprises 7,023 brain MRI images from figshare, SARTAJ, and Br35H, categorized into glioma, meningioma, no tumor, and pituitary classes, with a CNN-based multi-task classification model employed for tumor detection, classification, and location identification. Our methodology focused on multi-task classification using a single CNN model for various brain MRI classification tasks, including tumor detection, classification based on grade and type, and tumor location identification.

Results

The proposed CNN model incorporates advanced feature extraction capabilities and deep learning optimization techniques, culminating in a groundbreaking paradigm shift in automated brain MRI analysis. With an exceptional tumor classification accuracy of 99%, our method surpasses current methodologies, demonstrating the remarkable potential of deep learning in medical applications.

Conclusion

This study represents a significant advancement in the early detection and treatment planning of brain tumors, offering a more efficient and accurate alternative to traditional MRI analysis methods.
Central retinal artery occlusion or retinal stroke: a neurosonologist’s perspective
Authors: Taroza Saulius , Jatužis Dalius , Matijošaitis Vaidas , Raugelė Saulius , Valaikienė Jurgita
Published: June 2024

In central retinal artery occlusion (CRAO) or retinal stroke, which is usually a vision-threatening condition, timely diagnosis is imperative to improve the chances of retinal preservation and to establish adequate secondary prevention measures. Even though retinal strokes have been traditionally assigned to the field of ophthalmology, while considering reperfusion therapy as the only way to avoid permanent vision loss, we suggest prompt evaluation of CRAO causes (primarily related to cardiovascular risk factors) performed by a well-organized interdisciplinary team (ophthalmologist and neurologist) in a neurovascular center with stroke expertise. Therefore, the most suitable adjunct method for rapidly diagnosing non-arteritic CRAO could be target transorbital ultrasound, performed by an experienced neurologist/neurosonologist in the stroke unit. Consequently, after an ophthalmological assessment, a final decision on thrombolytic therapy could be made. We accept that further research is obviously needed to determine whether transorbital ultrasound could replace ophthalmological investigation in the case of a suspected acute retinal stroke. We assert that retinal stroke requires interdisciplinary treatment in cooperation with neurologists and ophthalmologists, with an additive value for each to achieve the best results for the patient.
Application of emerging technologies in ischemic stroke: from clinical study to basic research
Authors: Chen Qiuyan , Zhang Shuxia , Liu Wenxiu , Sun Xiao , Luo Yun , Sun Xiaobo
Published: June 2024

Stroke is a primary cause of noncommunicable disease-related death and disability worldwide. The most common form, ischemic stroke, is increasing in incidence resulting in a significant burden on patients and society. Urgent action is thus needed to address preventable risk factors and improve treatment methods. This review examines emerging technologies used in the management of ischemic stroke, including neuroimaging, regenerative medicine, biology, and nanomedicine, highlighting their benefits, clinical applications, and limitations. Additionally, we suggest strategies for technological development for the prevention, diagnosis, and treatment of ischemic stroke.
A mapping-knowledge-domain analysis of ERP research on language processing
Authors: Sun Yi , Luo Xiaoyang
Published: June 2024

The event-related potentials (ERPs) technique represents a newly developed methodology in cognitive neuroscience and has significantly extended the scope of linguistic studies, offering valuable insights into cognitive processes related to language. While extant literature reviews have addressed specific facets of ERP research on language processing, a comprehensive overview of this domain remains notably absent. This study aims to fill this gap by pioneering a mapping-knowledge-domain analysis of ERP research on language processing using Citespace, a visualized bibliometric software. The current study conducted a meticulous survey and evaluation of relevant literature extracted from the Web of Science core collection. Initially, this study outlines the spatial-temporal distribution within this domain. Subsequently, employing document co-citation analysis, keyword co-occurrence analysis, cluster analysis, and burst detection analysis, this study delved deeper into the research landscape. Findings reveal that key areas in ERP research on language processing predominantly focus on sentence comprehension, reading comprehension, and mismatch negativity, with notable emphasis on topics such as speech perception, temporal dynamics, and working memory. The current study advocates for future investigations to concentrate on larger linguistic units, explore the integration of ERP components and their functional significance, and scrutinize individual differences among participants. These directions are imperative for advancing the understanding of language processing mechanisms.
Hyper-brain hyper-frequency network topology dynamics when playing guitar in quartet
Authors: Müller Viktor , Lindenberger Ulman
Published: June 2024

Ensemble music performance is a highly coordinated form of social behavior requiring not only precise motor actions but also synchronization of different neural processes both within and between the brains of ensemble players. In previous analyses, which were restricted to within-frequency coupling (WFC), we showed that different frequencies participate in intra- and inter-brain coordination, exhibiting distinct network topology dynamics that underlie coordinated actions and interactions. However, many of the couplings both within and between brains are likely to operate across frequencies. Hence, to obtain a more complete picture of hyper-brain interaction when musicians play the guitar in a quartet, cross-frequency coupling (CFC) has to be considered as well. Furthermore, WFC and CFC can be used to construct hyper-brain hyper-frequency networks (HB-HFNs) integrating all the information flows between different oscillation frequencies, providing important details about ensemble interaction in terms of network topology dynamics (NTD). Here, we reanalyzed EEG (electroencephalogram) data obtained from four guitarists playing together in quartet to explore changes in HB-HFN topology dynamics and their relation to acoustic signals of the music. Our findings demonstrate that low-frequency oscillations (e.g., delta, theta, and alpha) play an integrative or pacemaker role in such complex networks and that HFN topology dynamics are specifically related to the guitar quartet playing dynamics assessed by sound properties. Simulations by link removal showed that the HB-HFN is relatively robust against loss of connections, especially when the strongest connections are preserved and when the loss of connections only affects the brain of one guitarist. We conclude that HB-HFNs capture neural mechanisms that support interpersonally coordinated action and behavioral synchrony.
Repetitive transcranial magnetic stimulation in central post-stroke pain: a meta-analysis and systematic review of randomized controlled trials
Authors: Liu Ying , Miao Runqing , Zou Hui , Hu Qian , Yin Shao , Zhu Fengya
Published: June 2024

Background

The rehabilitation of central post-stroke pain (CPSP) is a complex clinical challenge, and repetitive transcranial magnetic stimulation (rTMS) has been widely applied in the research of neurofunctional recovery following stroke. However, there is currently no reliable evidence-based medicine supporting the efficacy of rTMS in central post-stroke pain. This review aims to evaluate the effects of rTMS on central post-stroke pain.

Methods

Following the PRISMA guidelines, we conducted searches on PubMed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang Data Knowledge Service Platform. We searched for randomized controlled trials (RCTs) investigating the use of rTMS in treating central post-stroke pain, and conducted screening based on inclusion and exclusion criteria. Characteristics of the included RCTs were extracted. The heterogeneity of the trials was assessed using the I2 statistic. Meta-analysis was performed using Stata 17 software. Bias risk and methodological quality were evaluated using the Cochrane RoB 2 tool and the Pedro scale.

Results

A total of six randomized controlled trials involving 288 patients met our inclusion criteria. In our analysis, rTMS was more effective in treating patients with CPSP compared to the placebo group (SMD=-1.15, 95% CI: −1.69, −0.61, P < 0.001). Furthermore, results from subgroup analysis indicated no statistically significant difference in the improvement of pain for durations exceeding 6 months when comparing rTMS to conventional treatment (SMD=-0.80, 95% CI: −1.63, 0.03, P = 0.059).

Conclusion

TMS can alleviate pain in CPSP patients and improve their motor function, but its effects on depression, anxiety, and MEP-latency are not significant.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, CRD42024497530.
Traditional method of rhubarb processing optimized by combining flavor analysis with anthraquinone content determination
Authors: Liu Taotao , Yu Miao , Dai Yue , Xiao Yongqing , Li Li
Published: June 2024

Introduction

Rhubarb is a popular food that relieves constipation and aids with weight loss. The traditional method of preparation, includes steaming and sun-drying rhubarb nine times (SDR-9) to reduce its toxicity and increase efficacy.

Methods

Flavor analysis includes odor analysis by gas chromatography–ion mobility spectrometry and taste characterization using an electronic tongue.

Results

Odor analysis of the samples prepared through SDR-9 identified 61 volatile compounds, including aldehydes, esters, alcohols, ketones, acids, alkenes, and furans. Of these, 13 volatile components were the key substances associated with odor. This enabled the process to be divided into two stages: 1–5 times of steaming and sun-drying and 6–9 times. In the second stage, SDR-6 and SDR-9 were grouped together in terms of odor. Analysis using electronic tongue revealed that the most prominent taste was bitterness. A radar map indicated that the bitterness response was the highest for raw rhubarb, whereas that for processed (steamed and sun-dried) rhubarb decreased. Orthogonal partial least squares discriminant analysis (OPLS-DA) clustering results for SDR-6 and SDR-9 samples indicated that their tastes were similar. Anthraquinones were analyzed via high-performance liquid chromatography; moreover, analysis of the taste and components of the SDR samples revealed a significant correlation.

Discussion

These results indicate that there are similarities between SDR-6 and SDR-9 in terms of smell, taste, and composition, indicating that the steaming and sun-drying cycles can be conducted six times instead of nine.
Case report: Innovative treatment for one metastatic thyroid-like follicular carcinoma of the kidney with ATM and POLE mutations
Authors: Lei Jin-Ju , Rao Jie , Feng Hong-Yan , Cao De-Dong , Yan Hong-Lin , Yuan Jing-Ping , Jiang Zhen-Min , Zhang Yi-Qiao
Published: June 2024

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.
Risk score constructed with neutrophil extracellular traps-related genes predicts prognosis and immune microenvironment in multiple myeloma
Authors: Gao Gongzhizi , Liu Rui , Wu Dong , Gao Dandan , Lv Yang , Xu Xuezhu , Fu Bingjie , Lin Zujie , Wang Ting , He Aili , Bai Ju
Published: June 2024

Background

Multiple myeloma (MM) exhibits considerable heterogeneity in treatment responses and survival rates, even when standardized care is administered. Ongoing efforts are focused on developing prognostic models to predict these outcomes more accurately. Recently, neutrophil extracellular traps (NETs) have emerged as a potential factor in MM progression, sparking investigation into their role in prognostication.

Methods

In this study, a multi-gene risk scoring model was constructed using the intersection of NTEs and differentially expressed genes (DEGs), applying the least absolute shrinkage and selection operator (LASSO) Cox regression model. A nomogram was established, and the prognostic model’s effectiveness was determined via Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The ESTIMATE algorithm and immune-related single-sample gene set enrichment analysis (ssGSEA) were employed to evaluate the level of immune infiltration. The sensitivity of chemotherapy drugs was assessed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Ultimately, the presence of the detected genes was confirmed through quantitative real-time polymerase chain reaction (qRT-PCR) analysis in MM cell specimens.

Results

64 NETs-DEGs were yielded, and through univariate Cox regression and LASSO regression analysis, we constructed a risk score composed of six genes: CTSG, HSPE1, LDHA, MPO, PINK1, and VCAM1. MM patients in three independent datasets were classified into high- and low-risk groups according to the risk score. The overall survival (OS) of patients in the high-risk group was significantly reduced compared to the low-risk group. Furthermore, the risk score was an independent predictive factor for OS. In addition, interactions between the risk score, immune score, and immune cell infiltration were investigated. Further analysis indicated that patients in the high-risk group were more sensitive to a variety of chemotherapy and targeted drugs, including bortezomib. Moreover, the six genes provided insights into the progression of plasma cell disorders.

Conclusion

This study offers novel insights into the roles of NETs in prognostic prediction, immune status, and drug sensitivity in MM, serving as a valuable supplement and enhancement to existing grading systems.
Extra-abdominal growth of a large low-grade appendiceal mucinous tumour through the femoral canal–a rare case report
Authors: Kang Yan , Ma Junfeng , Li Xiaolong , Yang Zhong , Da Mingxu
Published: June 2024

Low-grade appendiceal mucinous neoplasms (LAMNs) are rare and heterogeneous diseases that, despite their increased incidence, are well differentiated, tend to be painless, and histologically lack distinctive invasive features without infiltrative growth, destructive infiltration, or associated pro-fibroproliferative responses. However, the biological behaviour of these tumours is difficult to determine preoperatively or intraoperatively, and the possibility of rupture puts patients at risk for peritoneal pseudomucinous neoplasms (PMPs).Patients with low-grade appendiceal mucinous tumours and peritoneal pseudomucinous tumours experience slow disease progression and are incurable and have a high risk of recurrence, morbidity, and ultimately death, despite the reported 5- and 10-year survival rates of 50–86% and 45–68%, respectively. In this article, we report the case of a 80-year-old male with a giant low-grade appendiceal mucinous tumour associated with a peritoneal pseudomucinous tumour, and discuss the diagnostic and management strategies for giant low-grade appendiceal mucinous tumours in the context of a literature review.
The incidence of drug-induced interstitial lung disease caused by epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors in patients with non-small cell lung cancer in presence and absence of vascular endothelial growth factor inhibitors: a systematic review
Authors: Fujiwara Yutaka , Shimomura Kazuhiro , Yamaguchi Teppei , Shimizu Junichi , Watanabe Naohiro , Matsuzawa Reiko , Murotani Kenta , Horio Yoshitsugu
Published: June 2024

Interstitial lung disease (ILD) or pneumonitis caused by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI) is a major concern in the treatment of non-small cell lung cancer (NSCLC). Whether the addition of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors can reduce the incidence of drug-induced ILD remains unclear. We conducted a systematic review to assess the incidence of ILD induced by EGFR-TKIs or ICIs in the presence or absence of VEGF/VEGFR inhibitors in relevant randomized trials between January 2009 and October 2023. The primary outcome was the odds ratio for the incidence of ILD in all patients worldwide and Asians. Secondary outcomes were the odds ratios (ORs) of the incidence at grade-3 or higher ILD in all patients worldwide and Asians. We identified 13 randomized studies, one sub-analysis in the EGFR-TKI group, and three randomized studies in the ICI group. In the EGFR-TKI group, the OR of ILD incidence at any grade with VEGF/VEGFR inhibitors was 0.54 (95% CI, 0.32–0.90; p = 0.02), which represented a significantly lower incidence than that without VEGF/VEGFR inhibitors. Contrarily, the OR of ILD incidence at grade ≥ 3 with VEGF/VEGFR inhibitors was 1.00 (95% CI, 0.43–2.36; p = 0.99). In all subjects in the ICI group, the OR of ILD incidence at any grade with VEGF/VEGFR inhibitors was 0.78 (95% CI, 0.51–1.21; p = 0.27). The systematic review demonstrated that the addition of VEGF/VEGFR inhibitors could reduce the incidence of drug-induced ILD at any grade caused by EGFR-TKI in patients with NSCLC but could not reduce that at grade ≥ 3. The ILD induced by ICIs remains undetermined owing to the limited number of randomized trials for which ILD data are available.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=409534, identifier CRD42023409534.
Monogenic Inborn Errors of Immunity with impaired IgG response to polysaccharide antigens but normal IgG levels and normal IgG response to protein antigens
Authors: Fasshauer Maria , Dinges Sarah , Staudacher Olga , Völler Mirjam , Stittrich Anna , von Bernuth Horst , Wahn Volker , Krüger Renate
Published: June 2024

In patients with severe and recurrent infections, minimal diagnostic workup to test for Inborn Errors of Immunity (IEI) includes a full blood count, IgG, IgA and IgM. Vaccine antibodies against tetanus toxoid are also frequently measured, whereas testing for anti-polysaccharide IgG antibodies and IgG subclasses is not routinely performed by primary care physicians. This basic approach may cause a significant delay in diagnosing monogenic IEI that can present with an impaired IgG response to polysaccharide antigens with or without IgG subclass deficiency at an early stage. Our article reviews genetically defined IEI, that may initially present with an impaired IgG response to polysaccharide antigens, but normal or only slightly decreased IgG levels and normal responses to protein or conjugate vaccine antigens. We summarize clinical, genetic, and immunological findings characteristic for these IEI. This review may help clinicians to identify patients that require extended immunologic and genetic evaluations despite unremarkable basic immunologic findings. We recommend the inclusion of anti-polysaccharide IgG antibodies as part of the initial routine work-up for possible IEI.
Real-time label-free three-dimensional invasion assay for anti-metastatic drug screening using impedance sensing
Authors: Ding Kai , Li Hailong , Xu Qian , Zhao Yongmei , Wang Kaikai , Liu Tianqing
Published: June 2024

Tumor metastasis presents a formidable challenge in cancer treatment, necessitating effective tools for anti-cancer drug development. Conventional 2D cell culture methods, while considered the “gold standard” for invasive studies, exhibit limitations in representing cancer hallmarks and phenotypes. This study proposes an innovative approach that combines the advantages of 3D tumor spheroid culture with impedance-based biosensing technologies to establish a high-throughput 3D cell invasion assay for anti-metastasis drug screening through multicellular tumor spheroids. In addition, the xCELLigence device is employed to monitor the time-dependent kinetics of cell behavior, including attachment and invasion out of the 3D matrix. Moreover, an iron chelator (deferoxamine) is employed to monitor the inhibition of epithelial–mesenchymal transition in 3D spheroids across different tumor cell types. The above results indicate that our integrated 3D cell invasion assay with impedance-based sensing could be a promising tool for enhancing the quality of the drug development pipeline by providing a robust platform for predicting the efficacy and safety of anti-metastatic drugs before advancing into preclinical or clinical trials.