bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer: a systematic review and meta-analysis
Authors: Yan Guangwei , Du Yanmin , Zhang Huanhuan , Yan Jinxiang , Liu Yixuan , Ban Zhenying , Guo Yong-Zhen , Zeng Xianxu
Published: August 2024

Background

Various trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer.

Methods

We utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR).

Results

Four trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9–36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1–70.2) for dMMR group and 33.1% (95% CI: 25.7–40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3–78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5–97.6) for the dMMR group and 76.3% (95% CI: 66.3–86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5–100.0) and 80.2% (95% CI: 59.9–100.0), respectively.

Conclusion

Lenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.
Distinct characteristics of unique immunoregulatory canine non-conventional TCRαβpos CD4negCD8αneg double-negative T cell subpopulations
Authors: Karwig Laura , Moore Peter F. , Alber Gottfried , Eschke Maria
Published: August 2024

Conventional CD4pos regulatory T (Treg) cells characterized by expression of the key transcription factor forkhead box P3 (FoxP3) are crucial to control immune responses, thereby maintaining homeostasis and self-tolerance. Within the substantial population of non-conventional T cell receptor (TCR)αβpos CD4negCD8αneg double-negative (dn) T cells of dogs, a novel FoxP3pos Treg-like subset was described that, similar to conventional CD4pos Treg cells, is characterized by high expression of CD25. Noteworthy, human and murine TCRαβpos regulatory dn T cells lack FoxP3. Immunosuppressive capacity of canine dn T cells was hypothesized based on expression of inhibitory molecules (interleukin (IL)-10, cytotoxic T-lymphocyte associated protein 4, CTLA4). Here, to verify their regulatory function, the dnCD25pos (enriched for FoxP3pos Treg-like cells) and the dnCD25neg fraction, were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells (PBMC) of Beagle dogs and analyzed in an in vitro suppression assay in comparison to conventional CD4posCD25pos Treg cells (positive control) and CD4posCD25neg T cells (negative control). Canine dnCD25pos T cells suppressed the Concanavalin A-driven proliferation of responder PBMC to a similar extent as conventional CD4posCD25pos Treg cells. Albeit to a lesser extent than FoxP3-enriched dn and CD4posCD25pos populations, even dnCD25neg T cells reduced the proliferation of responder cells. This is remarkable, as dnCD25neg T cells have a FoxP3neg phenotype comparable to non-suppressive CD4posCD25neg T cells. Both, CD25pos and CD25neg dn T cells, can mediate suppression independent of cell-cell contact and do not require additional signals from CD4posCD25neg T cells to secrete inhibitory factors in contrast to CD4posCD25pos T cells. Neutralization of IL-10 completely abrogated the suppression by dnCD25pos and CD4posCD25pos Treg cells in a Transwell™ system, while it only partially reduced suppression by dnCD25neg T cells. Taken together, unique canine non-conventional dnCD25pos FoxP3pos Treg-like cells are potent suppressor cells in vitro. Moreover, inhibition of proliferation of responder T cells by the dnCD25neg fraction indicates suppressive function of a subset of dn T cells even in the absence of FoxP3. The identification of unique immunoregulatory non-conventional dn T cell subpopulations of the dog in vitro is of high relevance, given the immunotherapeutic potential of manipulating regulatory T cell responses in vivo.
Progress of immune checkpoint inhibitors in the treatment of advanced hepatocellular carcinoma
Authors: Liu Tong , Meng Guorui , Ma Shihui , You Junqi , Yu Liang , He Risheng , Zhao Xudong , Cui Yunfu
Published: August 2024

Among primary liver cancers, hepatocellular carcinoma is the most common pathological type. Its onset is insidious, and most patients have no obvious discomfort in the early stage, so it is found late, and the opportunity for surgical radical treatment is lost, resulting in a poor prognosis. With the introduction of molecular-targeted drugs represented by sorafenib, patients with middle- and late-stage liver cancer have regained the light of day. However, their therapeutic efficacy is relatively low due to the limited target of drug action, toxic side effects, and other reasons. At this time, the emergence of immunotherapy represented by immune checkpoint inhibitors (ICIs) well breaks this embarrassing situation, which mainly achieves the anti-tumor purpose by improving the tumor immune microenvironment. Currently, ICI monotherapy, as well as combination therapy, has been widely used in the clinic, further prolonging the survival of patients with advanced hepatocellular carcinoma. This article reviews the development of monotherapy and combination therapy for ICIs in advanced hepatocellular carcinoma and the latest research progress.
Both sides now: evolutionary traits of antigens and B cells in tolerance and activation
Authors: Hong Youngjae , Kwak Kihyuck
Published: August 2024

B cells are the cornerstone of our body’s defense system, producing precise antibodies and safeguarding immunological memory for future protection against pathogens. While we have a thorough understanding of how naïve B cells differentiate into plasma or memory B cells, the early B cell response to various antigens—whether self or foreign—remains a thrilling and evolving area of study. Advances in imaging have illuminated the molecular intricacies of B cell receptor (BCR) signaling, yet the dynamic nature of B cell activation continues to reveal new insights based on the nature of antigen exposure. This review explores the evolutionary journey of B cells as they adapt to the unique challenges presented by pathogens. We begin by examining the specific traits of antigens that influence their pathogenic potential, then shift our focus to the distinct characteristics of B cells that counteract these threats. From foundational discoveries to the latest cutting-edge research, we investigate how B cells are effectively activated and distinguish between self and non-self antigens, ensuring a balanced immune response that defends against pathogenic diseases but not self-antigens.
“Due regard” obligations toward nuclear wastewater discharge from the perspective of sustainable development of the marine environment
Authors: Xiao Wan
Published: August 2024

The events of the 2011 Fukushima nuclear accident in Japan have garnered global concern. Despite nuclear power plants addressing numerous energy challenges, they poses substantial risks to environmental safety. The global legal basis to fulfill due regard obligations toward nuclear wastewater discharge involves international nuclear energy and marine environmental protection laws. There is substantive scope of due regard obligations toward nuclear wastewater discharge, including fulfilling international duties, prohibiting marine environmental pollution, preventing transboundary harm, and ensuring procedural obligations. The procedural obligations encompass timely notification of nuclear pollution, scientific assessment, and active consultation and cooperation with the international community. As there are still numerous obstacles to the application of due regard in the discharge of nuclear wastewater, the international marine environment frequently suffers from nuclear pollution. Considering the potential for transboundary environmental harm owing to the discharge of nuclear wastewater, this paper proposes effective solutions to this issue from the perspective of sustainable development of the marine environment. These solutions include formulating specific normative guidelines, clarifying liability for paying transboundary harm compensation, developing unified international assessment standards, and establishing an international platform for mandatory cooperation. Such solutions reinforce the national responsibility of all countries to actively fulfill their due regard obligations and effectively resolve the issue of potential irreversible damage to the marine environment. Additionally, the paper provides suggestions regarding how the international community can address the issue of Japan’s nuclear wastewater discharge and other similar issues that may arise.
Evaluation of antibacterial and osteogenic properties of a novel Poly (acrylic acid)-calcium-zinc biomineralized hydrogel
Authors: Xie Xiaobin , Feng Xiaoxiao , Hong Lihui , Yu Xinke , Li Hongye , Zhang Hao , Liu Mingming , Wang Yimeng
Published: August 2024

Infectious bone defects are one of the thorny problems faced by orthopedists. Developing prosthetic materials with antimicrobial osteogenic features is a key solution. Biodegradable Polyacrylic acid (PAA)-based hydrogels have gained attention for their exceptional qualities. However, the influence of zinc ions on PAA-based mineralized hydrogels remains understudied. In this paper, Poly (acrylic acid)-calcium-zinc (PA-CZ) biomineralized hydrogel was prepared through ionic cross-linking and biomineralization. In vitro bacterial and cell tests demonstrated the hydrogel’s exceptional biocompatibility, antibacterial, and osteogenic traits, along with good mechanical strength. The PA-CZ mineralized hydrogel lays the foundation for developing orthopedic implants with antimicrobial osteogenic features and offers a promising approach for treating infected bone defects.
The role of methylprednisolone in severe COVID-19 patients: a meta-analysis
Authors: Xu Wanru , Zeng Yujun , Han Hedong , Lv Tangfeng , Lin Dang
Published: August 2024

Background

The purpose of this study is to assess the effectiveness of methylprednisolone in severe COVID-19.

Methods

PubMed, the Cochrane Library and Web of Science were searched for literatures comparing methylprednisolone and control treatment in severe COVID-19 patients. Statistical pooling was reported as risk ratio (RR) with corresponding 95% confidence interval (CI). The outcomes of interest in the literature survey were mortality and adverse events.

Results

A total of 13 studies were included, including 3,138 patients with severe COVID-19, of which 1,634 patients were treated with methylprednisolone and 1,504 patients were treated with control treatment. Five of the 13 studies reported severe adverse events. Our meta-analysis indicates that methylprednisolone treatment in COVID-19 patients is associated with a significant reduction in mortality (RR 0.62, 95% CI 0.46–0.85, p = 0.003) compared to control treatment, without an increased risk of adverse events (RR 1.20, 95% CI 0.92–1.56, p = 0.17). Moreover, high-dose methylprednisolone treatment (RR 0.57; 95% CI 0.40–0.82, p = 0.003) and short-course methylprednisolone treatment (RR 0.54; 95% CI 0.38–0.89, p = 0.01) found to significantly reduce mortality. Additionally, it was found that younger severe COVID-19 patients (RR 0.40; 95% CI 0.20–0.80, p = 0.01) had better outcomes to methylprednisolone than older patients.

Conclusion

Methylprednisolone was correlated with lower mortality compared with control treatment in severe COVID-19 patients without increasing serious adverse reactions. Furthermore, high-doses and short-term of methylprednisolone treatment were linked with better younger COVID-19 reported higher benefit from methylprednisolone than older COVID-19 patients.
Efficacy of percutaneous microwave ablation guided by contrast-enhanced and two-dimensional ultrasound for in hepatic alveolar echinococcosis in difficult/dangerous locations
Authors: Huang Wangxing , Hu Zhipeng , Qi Lina , Zhang Xiaoyan , Li Min , Yu Mingan , Hua Guoyong
Published: August 2024

Background

Ultrasound-guided microwave ablation (MWA) has become a popular method for treating malignant liver tumors. However, few studies have investigated its use in the treatment of hepatoalveolar echinococcosis (HAE). This study aimed to explore the effectiveness and safety of contrast-enhanced ultrasound combined with two-dimensional ultrasound-guided MWA for the treatment of HAE in difficult/dangerous locations.

Methods

Data from 81 patients, who were diagnosed with hepatic alveolar hydatid disease in difficult/dangerous locations between January 2018 and January 2023, and underwent contrast-enhanced ultrasonography combined with two-dimensional ultrasound-guided MWA, were analyzed. After undergoing MWA, patients were followed up to determine whether the lesions recurred and to evaluate the therapeutic effect of MWA. Preoperatively, individualized strategies were designed for lesions in different locations, and different auxiliary ablation technologies were used for contrast-enhanced ultrasound combined with two-dimensional ultrasound-guided MWA to achieve complete inactivation of lesions in difficult/dangerous locations.

Results

MWA was performed on 89 HAE lesions in 81 patients. The median diameter of the lesions was 2.86 cm (interquartile range [IQR] 2.36–3.49 cm). The complete ablation rate after surgery was 100%, with a recurrence rate of 11.11%, and median follow-up of 24 months (IQR 12–48 months). The incidence of minor complications was 14.81%; no serious complications or deaths occurred. Compared with before surgery, TB, DB, alanine aminotransferase, and aspartate aminotransferase levels increased (p < 0.001), albumin platelets and activated partial thromboplastin time decreased (p < 0.05), with no statistical difference in prothrombin time (p > 0.05).

Conclusion

MWA may be a safe and effective method for treating HAE in difficult/dangerous locations, and may represent a new and alternative option for this patient population.
Association between serum vitamin D and the risk of diabetic kidney disease in patients with type 2 diabetes
Authors: Wang Yujie , Hu Chenggang , Li Ying , Liu Qi , Gao Lichao , Zhang Dongmei , Cao Ling
Published: August 2024

Aims

This investigation explored the potential correlation between serum vitamin D concentration and diabetic kidney disease (DKD) among patients with type 2 diabetes mellitus (T2DM).

Methods

This cross-sectional study assessed 4,570 patients with T2DM drawn from the National Health and Nutrition Examination Survey (NHANES) dataset. Restricted cubic splines were utilized to examine the dose–response relationship between serum vitamin D levels and the risk of DKD in patients with T2DM. Serum vitamin D concentrations were divided into quartiles for multivariable logistic regression analysis to evaluate the association between varying serum vitamin D levels and DKD risk in patients with T2DM. Additionally, sex-stratified analyses were conducted to determine consistency of the results. The influence of vitamin D concentrations on mortality risk was assessed using a Cox regression model.

Results

Of the patients with T2DM, 33% were diagnosed with DKD. Restricted cubic spline plots revealed a U-shaped relationship between vitamin D levels and DKD risk, with a protective effect noted in the mid-range, indicating optimal serum vitamin D concentrations between 59.6 nmol/L and 84.3 nmol/L. The multivariate Cox regression analysis suggested that higher VID levels were associated with a reduced mortality risk, particularly in male patients.

Conclusion

The regulation and monitoring of serum vitamin D levels within an optimal range may play a pivotal role in the prevention of DKD in patients with T2DM. Public health strategies should emphasize the regular monitoring of vitamin D levels, especially among populations at elevated risk, to mitigate the progression of DKD and decrease the associated mortality rates.
Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system
Authors: Shera Simer , Katzka William , Yang Julianne C. , Chang Candace , Arias-Jayo Nerea , Lagishetty Venu , Balioukova Anna , Chen Yijun , Dutson Erik , Li Zhaoping , Mayer Emeran A. , Pisegna Joseph R. , Sanmiguel Claudia , Pawar Shrey , Zhang David , Leitman Madelaine , Hernandez Laura , Jacobs Jonathan P. , Dong Tien S.
Published: August 2024

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly 25% of the population and is the leading cause for liver-related mortality. Bariatric surgery is a well-known treatment for MASLD and obesity. Understanding the fundamental mechanisms by which bariatric surgery can alter MASLD can lead to new avenues of therapy and research. Previous studies have identified the microbiome’s role in bariatric surgery and in inflammatory immune cell populations. The host innate immune system modulates hepatic inflammation and fibrosis, and thus the progression of MASLD. The precise role of immune cell types in the pathogenesis of MASLD remains an active area of investigation. The aim of this study was to understand the interplay between microbiota composition post-bariatric surgery and the immune system in MASLD.

Methods

Eighteen morbidly obese females undergoing sleeve gastrectomy were followed pre-and post-surgery. Stool from four patients, showing resolved MASLD post-surgery with sustained weight loss, was transplanted into antibiotic treated mice. Mice received pre-or post-surgery stool and were fed a standard or high-fat diet. Bodyweight, food intake, and physiological parameters were tracked weekly. Metabolic parameters were measured post-study termination.

Results

The human study revealed that bariatric surgery led to significant weight loss (p > 0.05), decreased inflammatory markers, and improved glucose levels six months post-surgery. Patients with weight loss of 20% or more showed distinct changes in blood metabolites and gut microbiome composition, notably an increase in Bacteroides. The mouse model confirmed surgery-induced microbiome changes to be a major factor in the reduction of markers and attenuation of MASLD progression. Mice receiving post-surgery fecal transplants had significantly less weight gain and liver steatosis compared to pre-surgery recipients. There was also a significant decrease in inflammatory cytokines interferon gamma, interleukin 2, interleukin 15, and mig. This was accompanied by alterations in liver immunophenotype, including an increase in natural killer T cells and reduction of Kupfer cells in the post-surgery transplant group.

Discussion

Our findings suggest surgery induced microbial changes significantly reduce inflammatory markers and fatty liver progression. The results indicate a potential causal link between the microbiome and the host immune system, possibly mediated through modulation of liver NKT and Kupffer cells.
Integrated clinical and metabolomic analysis identifies molecular signatures, biomarkers, and therapeutic targets in primary angle closure glaucoma
Authors: Kannan Vishnu , Srimadh Bhagavatham Sai Krishna , Dandamudi Rajesh Babu , Kunchala Haripriya , Challa Sivateja , Almansour Abdulrahman I. , Pargaonkar Ashish , Pulukool Sujith Kumar , Sharma Anuj , Sivaramakrishnan Venketesh
Published: August 2024

Background

Glaucoma is the leading cause of permanent blindness. Primary angle closure glaucoma (PACG) is diagnosed only after the onset of symptoms and can result in irreversible blindness despite the standard intraocular pressure (IOP) reduction therapy. The identification of potential biomarkers associated with prognosis will help improve disease management. This study aimed to identify mechanisms associated with disease progression, potential biomarkers, and therapeutic targets of PACG.

Methods

The clinical data assessment of IOP, cup/disc ratio (CDR), Retinal Nerve Fiber Layer (RNFL) thickness of control, and PACG group were collected and analyzed for significant differences. The ATP levels were estimated, and targeted metabolomic analysis was performed on aqueous humor and cytokines in plasma. The pathways obtained from the metabolomics data set were compared with those obtained for data sets from the literature. Clinical parameters were correlated with cytokine levels. Targeted metabolomic analysis of cell culture supernatant from TNFα-treated N9 microglia was carried out, and overlap analysis was performed with data obtained from PACG patients.

Results

Elevated IOP, CDR, ATP, cytokines, and reduced RNFL thickness were found in PACG compared to controls. Analysis of PACG and TNFα-treated N9 microglial cell culture supernatant shows activation of immuno-metabolites. The metabolic pathways of PACG, TNFα, and ATP-treated microglia from the literature show considerable overlap. Biomarker analysis identified clinical parameters, ATP, cytokines, and immuno-metabolites.

Conclusion

This study shows an association between elevated levels of ATP, cytokines, immuno-metabolism, and potential microglial inflammation with disease progression, rendering these levels potential biomarkers. P2 receptors, cytokines, and IDO1/2 could be potential therapeutic targets.
The other person’s smiling amount affects one’s smiling response during face-to-face conversations
Authors: Obayashi Yota , Uehara Shintaro , Yuasa Akiko , Otaka Yohei
Published: August 2024

Introduction

Smiling during conversation occurs interactively between people and is known to build good interpersonal relationships. However, whether and how much the amount that an individual smiles is influenced by the other person’s smile has remained unclear. This study aimed to quantify the amount of two individuals’ smiles during conversations and investigate the dependency of one’s smile amount (i.e., intensity and frequency) on that of the other.

Method

Forty participants (20 females) engaged in three-minute face-to-face conversations as speakers with a listener (male or female), under three conditions, where the amount of smiling response by listeners was controlled as “less,” “moderate,” and “greater.” The amount of the smiles was quantified based on their facial movements through automated facial expression analysis.

Results

The results showed that the amount of smiling by the speaker changed significantly depending on the listener’s smile amount; when the listeners smiled to a greater extent, the speakers tended to smile more, especially when they were of the same gender (i.e., male–male and female–female pairs). Further analysis revealed that the smiling intensities of the two individuals changed in a temporally synchronized manner.

Discussion

These results provide quantitative evidence for the dependence of one’s smile on the other’s smile, and the differential effect between gender pairs.
A motion aftereffect from viewing other people's gaze
Authors: Renet Christian , Randall William , Guterstam Arvid
Published: August 2024

Recent work suggests that our brains may generate subtle, false motion signals streaming from other people to the objects of their attention, aiding social cognition. For instance, brief exposure to static images depicting other people gazing at objects made subjects slower at detecting subsequent motion in the direction of gaze, suggesting that looking at someone else's gaze caused a directional motion adaptation. Here we confirm, using a more stringent method, that viewing static images of another person gazing in a particular direction, at an object, produced motion aftereffects in the opposite direction. The aftereffect was manifested as a change in perceptual decision threshold for detecting left vs. right motion. The effect disappeared when the person was looking away from the object. These findings suggest that the attentive gaze of others is encoded as an implied agent-to-object motion that is sufficiently robust to cause genuine motion aftereffects, though subtle enough to remain subthreshold.
Customizable automated cleaning of multichannel sleep EEG in SleepTrip
Authors: Cox Roy , Weber Frederik D. , Van Someren Eus J. W.
Published: August 2024

While standard polysomnography has revealed the importance of the sleeping brain in health and disease, more specific insight into the relevant brain circuits requires high-density electroencephalography (EEG). However, identifying and handling sleep EEG artifacts becomes increasingly challenging with higher channel counts and/or volume of recordings. Whereas manual cleaning is time-consuming, subjective, and often yields data loss (e.g., complete removal of channels or epochs), automated approaches suitable and practical for overnight sleep EEG remain limited, especially when control over detection and repair behavior is desired. Here, we introduce a flexible approach for automated cleaning of multichannel sleep recordings, as part of the free Matlab-based toolbox SleepTrip. Key functionality includes 1) channel-wise detection of various artifact types encountered in sleep EEG, 2) channel- and time-resolved marking of data segments for repair through interpolation, and 3) visualization options to review and monitor performance. Functionality for Independent Component Analysis is also included. Extensive customization options allow tailoring cleaning behavior to data properties and analysis goals. By enabling computationally efficient and flexible automated data cleaning, this tool helps to facilitate fundamental and clinical sleep EEG research.
Modeling the effects of prebiotic interventions on luminal and mucosa-associated gut microbiota without and with Clostridium difficile challenge in vitro
Authors: Wiese Maria , van der Wurff Michelle , Ouwens Anita , van Leijden Bowien , Verheij Elwin R. , Heerikhuisen Margreet , van der Vossen Jos M. B. M.
Published: August 2024

Prebiotics can modulate the gut microbial community composition and function for improved (gut) health and increase resilience against infections. In vitro models of the gut facilitate the study of intervention effects on the gut microbial community relevant to health. The mucosa-associated gut microbiota, which thrives in close contact with the host plays a pivotal role in colonization resistance and health. Therefore, we here introduce the Mi-screen, an experimental approach implementing a 96-well plate equipped with a mucus agar layer for the additional culturing of mucosa-associated microbiota in vitro. In this study, we screened the effects of 2’-Fucosyllactose (2’-FL), fructooligosaccharides (FOS), and inulin within a complex microbiota without and with infection with the C. difficile strains ATCC 43599 (Ribotype 001) or ATCC BAA-1870 (Ribotype 027). We analyzed the microbial community composition and short-chain fatty acid levels after 48 h of incubation. The inclusion of an additional substrate and surface in the form of the mucus agar layer allowed us to culture a microbial richness ranging between 100–160 in Chao index, with Shannon indices of 5–6 across culture conditions, indicative of a microbial diversity of physiological relevance. The mucus agar layer stimulated the growth of characteristic mucosa-associated bacteria such as Roseburia inulinovorans. The prebiotic interventions affected luminal and mucosal microbial communities cultured in vitro and stimulated short-chain fatty acid production. FOS, inulin and 2’-FL promoted the growth of Bifidobacterium adolescentis within the mucosa-associated microbiota cultured in vitro. When spiking the untreated conditions with pathogenic C. difficile, the strains thrived within the luminal and the mucosal sample types, whereas prebiotic treatments exhibited inhibitory effects on C. difficile growth and prevented colonization. In conclusion, the Mi-screen facilitates the screening of luminal and mucosa-associated gut microbial community dynamics in vitro and therefore fills an important gap in the field of in vitro modeling.
Treatment accuracy of standard linear accelerator-based prostate SBRT: the delivered dose assessment of patients treated within two major clinical trials using an in-house position monitoring system
Authors: Arumugam Sankar , Young Tony , Jones Catherine , Pryor David , Sidhom Mark
Published: August 2024

Background and purpose

The purpose of this study was to assess the dosimetric improvements achieved in prostate stereotactic body radiotherapy (SBRT) treatment within the PROMETHEUS and NINJA trials using an in-house real-time position monitoring system, SeedTracker.

Methods and materials

This study considered a total of 127 prostate SBRT patients treated in the PROMETHEUS (ACTRN12615000223538) and NINJA (ACTRN12618001806257) clinical trials. The SeedTracker position monitoring system was utilized for real-time position monitoring with a 3-mm position tolerance. The doses delivered to the clinical target volume (CTV), rectum, and bladder were assessed by incorporating the actual target position during treatment. The dose that would have been delivered without monitoring was also assessed by incorporating the observed position deviations.

Results

Treatment with position corrections resulted in a mean (range) CTV D99 difference of −0.3 (−1.0 to 0.0) Gy between the planned and delivered dose. Without corrections, this difference would have been −0.6 (−3.7 to 0.0) Gy. Not correcting for position deviations resulted in a statistically significant difference between the planned and delivered CTV D99 (p < 0.05). The mean (range) dose difference between the planned and delivered D2cc of the rectum and bladder for treatment with position corrections was −0.1 (−3.7 to 4.7) Gy and −0.1 (−1.7 to 0.5) Gy, respectively. Without corrections, these differences would have been −0.6 (−6.1 to 4.7) Gy and −0.2 (−2.5 to 0.9) Gy.

Conclusions

SeedTracker improved clinical dose volume compliance in prostate SBRT. Without monitoring and corrections, delivered dose would significantly differ from the planned dose.
Patients’ perspectives on cancer care disparities in Central and Eastern European countries: experiencing taboos, misinformation and barriers in the healthcare system
Authors: Coppini Veronica , Ferraris Giulia , Ferrari Maria Vittoria , Dahò Margherita , Kirac Iva , Renko Ira , Monzani Dario , Grasso Roberto , Pravettoni Gabriella
Published: August 2024

Introduction

Despite the advancements in oncological medicine and research, cancer remains the second leading cause of death in Europe with Central and Eastern European countries, such as Slovakia and Croatia, showing the highest mortality rates and disparities in access to appropriate and comprehensive cancer care. Therefore, the primary aim of the current study is to investigate cancer patients’ perspectives and experiences to understand the possible underlying reasons for cancer disparities.

Methods

Croatian cancer patients (n=15) and Slovak patients (n=11) were recruited through social media platforms, patients’ organisations, and hospital websites and offered participation in online focus group discussions on perceived disparities, barriers or malfunctioning during and after their cancer journey. Transcripts of video and audio recordings of the interviews were translated and analysed using Thematic analysis.

Results

Six Croatian and five Slovak themes emerged from the focus group discussions highlighting encountered barriers and perceived disparities, as well as suggestions or unmet needs. Most of the themes are common to both groups, such as the lack of information and use of the internet, and the taboos regarding cancer or psycho-oncological support. However, some themes are specific to each group, for instance, Slovak cancer patients remarked the fact that they do not mind travelling to get treatment as long as they can be treated in the west of Slovakia, while Croatian patients highlighted the need for more information after the illness and the socioeconomic impact deriving from a cancer diagnosis.

Discussion

Urgent intervention is needed in addressing disparities in Central and Eastern Europe. Present results could inform dedicated guidelines or better resource allocation strategies to reduce disparities in cancer care and promote inclusive healthcare.
Exploratory analysis of high-dose corticosteroid therapy on epileptic encephalopathy with spike-and-wave activation in sleep
Authors: Xiaoyue Hu , Hongwei Tang , Jianbiao Wang , Jingbo Ma , Ying Hua
Published: August 2024

Objective

This study aims to evaluate the therapeutic efficacy of high-dose corticosteroid therapy in children diagnosed with epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS), investigate associated clinical indicators influencing treatment outcomes, and establish a predictive model for recurrence.

Methods

Children diagnosed with EE-SWAS who received high-dose corticosteroid therapy were categorized into responder group and non-responder group. Data on clinical parameters, electroencephalogram (EEG) features, and serum cytokine levels were collected. Six months post-treatment, the effectively treated children were further stratified into recurrence and non-recurrence groups. Risk factors for poor outcomes following corticosteroid therapy were identified using univariate analysis. Multivariate logistic regression analysis was then employed to determine independent factors influencing the recurrence of corticosteroid therapy, which facilitated the development of a predictive model.

Results

The study included 48 children, with 33 cases in the responder group (effective rate = 68.8%) and 15 cases in the non-responder group. The responder group exhibited an older onset age of electrical status epilepticus in sleep (ESES) and higher proportions of combined benzodiazepines (BZDs) use (P < 0.05). Among those responding to corticosteroid therapy, 11 cases experienced a recurrence (recurrence rate = 33.3%), while 22 cases did not. Significant differences were observed between the two groups concerning age of seizure onset, age of ESES onset, seizure frequency, atypical presentations, and concomitant frontal lobe discharges (all P < 0.05). Concomitant frontal lobe discharges and an earlier age of seizure onset were identified as risk factors for ESES recurrence following corticosteroid therapy. The predictive model was formulated as Logit(P) = 2.35 × presence of frontal lobe discharges—0.802 × age of seizure onset + 2.457. The Area Under the Curve (AUC) of Receiver Operating Characteristics (ROC) was 0.93, with sensitivity and specificity at 100% and 77.3%, respectively.

Conclusion

High-dose corticosteroid therapy for EE-SWAS exhibited a high effective rate as well as a notable recurrence rate. Onset age of ESES and combined benzodiazepines usage correlated with therapeutic efficacy. Seizure onset age and the presence of frontal lobe discharges may hold predictive value for recurrence following corticosteroid therapy.
Screening of anti-inflammatory activities components of Angelica dahurica root based on spectrum-effect relationship analysis and NF-κB pathway
Authors: Shi Huan , Wang Qianqian , Chang Yaqing , Zheng Yuguang , Zhang Dan , Zhao Yunsheng , Guo Long
Published: August 2024

Angelica dahurica root (ADR), a commonly utilized herbal medicine in China and other Asian nations, which has anti-inflammatory effects on diverse inflammatory ailments. However, the bioactive components and underlying mechanism responsible for the anti-inflammatory effect of ADR are still unclear. This work attempted to discover the anti-inflammatory bioactive compounds and explore their underlying mechanism in ADR based on spectrum-effect relationship analysis and NF-κB signaling pathway. Chromatographic fingerprints of ADR samples were established by high performance liquid chromatography with diode array detection (HPLC-DAD), and a total of eleven common peaks were selected. Then, high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) was employed for identification of eleven common peaks in ADR Meanwhile, the anti-inflammatory activities of ADR samples were assessed by inhibition of NO, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in LPS-induced RAW264.7 cells. The spectrum-effect relationships between the eleven common peaks in HPLC fingerprints and anti-inflammatory effects of ADR samples were investigated to identify the potential anti-inflammatory bioactive compounds by grey relational analysis (GRA) and partial least squares regression (PLSR). The spectrum-effect relationship analysis results indicated that six coumarin compounds, including bergapten, xanthotoxin, phellopterin, isoimperatorin, xanthotoxol and imperatorin could be potential anti-inflammatory bioactive compounds in ADR. The further validation experiments also showed that these six coumarins demonstrated significant inhibition of NO, IL-1β, IL-6, and TNF-α production in LPS-induced RAW264.7 cells. In addition, western blot analysis was conducted to explore the mechanisms of two potential anti-inflammatory bioactive compounds (phellopterin and isoimperatorin) by assessing the protein levels in the NF-κB signaling pathway. The western blot results illustrated that phellopterin and isoimperatorin could significantly down-regulate the phosphorylated NF-κB p65 (p-p65), phosphorylated IκBα (p-IκBα) and iNOS, and depress the pro-portion of p-p65/p65 and p-IκBα/IκBα, which indicated that these two coumarins in ADR could potentially exert anti-inflammatory effects by suppressing of NF-κB pathway.
A review of Phyllanthus urinaria L. in the treatment of liver disease: viral hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma
Authors: Liu Linhua , Wang Bing , Ma Yibo , Sun Kunhui , Wang Ping , Li Meifang , Dong Junlin , Qin Meirong , Li Mingshun , Wei Chunshan , Tan Ying , He Jinsong , Guo Keying , Yu Xie-an
Published: August 2024

Due to the pathological production of liver disease in utility particularly complexity, the morbidity and mortality of liver disease including viral hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma (HCC) are rapidly increasing worldwide. Considering its insidious onset, rapid progression and drug resistance, finding an effective therapy is particularly worthwhile. Phyllanthus urinaria L. (P. urinaria), an ethnic medicine, can be applied at the stages of viral hepatitis, liver fibrosis/cirrhosis and HCC, which demonstrates great potential in the treatment of liver disease. Currently, there are numerous reports on the application of P. urinaria in treating liver diseases, but a detailed analysis of its metabolites and a complete summary of its pharmacological mechanism are still scarce. In this review, the phytochemical metabolites and ethnopharmacological applications of P. urinaria are summarized. Briefly, P. urinaria mainly contains flavonoids, lignans, tannins, phenolic acids, terpenoids and other metabolites. The mechanisms of P. urinaria are mainly reflected in reducing surface antigen secretion and interfering with DNA polymerase synthesis for anti-viral hepatitis activity, reducing hepatic stellate cells activity, inflammation and oxidative stress for anti-liver fibrosis/cirrhosis activity, as well as preventing tumor proliferation, invasion and angiogenesis for anti-HCC activity via relevant signaling pathways. Accordingly, this review provides insights into the future application of natural products in the trilogy of liver diseases and will provide a scientific basis for further research and rational utilization of P. urinaria.
MiRNAs: a new target for Chinese medicine to repair the intestinal barrier in the treatment of ulcerative colitis
Authors: Sun Dajuan , Zhang Zhongtao , Xue Jingwei
Published: August 2024

Graphical Abstract

This review presents the progress of traditional Chinese medicines in the treatment of ulcerative colitis by regulating miRNAs.
Mitophagy in fibrotic diseases: molecular mechanisms and therapeutic applications
Authors: Cui Xinyan , Zhou Zekun , Tu Hua , Wu Jianjun , Zhou Jian , Yi Qiao , Liu Ousheng , Dai Xiaohan
Published: August 2024

Mitophagy is a highly precise process of selective autophagy, primarily aimed at eliminating excess or damaged mitochondria to maintain the stability of both mitochondrial and cellular homeostasis. In recent years, with in-depth research into the association between mitophagy and fibrotic diseases, it has been discovered that this process may interact with crucial cellular biological processes such as oxidative stress, inflammatory responses, cellular dynamics regulation, and energy metabolism, thereby influencing the occurrence and progression of fibrotic diseases. Consequently, modulating mitophagy holds promise as a therapeutic approach for fibrosis. Currently, various methods have been identified to regulate mitophagy to prevent fibrosis, categorized into three types: natural drug therapy, biological therapy, and physical therapy. This review comprehensively summarizes the current understanding of the mechanisms of mitophagy, delves into its biological roles in fibrotic diseases, and introduces mitophagy modulators effective in fibrosis, aiming to provide new targets and theoretical basis for the investigation of fibrosis-related mechanisms and disease prevention.
It’s because of the cross-border commuters: opposing the free movement of persons in the Swiss borderlands with the European Union
Authors: Bernhard Laurent , Lauener Lukas
Published: August 2024

Scholarly work on populism and borders have largely followed separate paths so far. This article aims at bringing together these two strands by means of an empirical analysis of individual attitudes on a re-bordering policy in the context of a national-populist mobilization against the free movement of persons. Recent contributions on border regions in affluent countries have highlighted an increased opposition to European integration that is fueled by political actors from the populist radical right. We hypothesize that border residents are more opposed to the free movement of persons than non-border residents the more they are exposed to the influx of cross-border workers. The empirical analysis draws on a representative post-vote survey from the so-called “VOTO studies” on a popular initiative by the radical right that demanded Switzerland’s termination of the free movement of persons with the European Union in 2020. In line with our hypothesis, we find a significant positive interaction effect between border residence and the share of cross-border commuters on the likelihood to vote in favor of this proposition. While border residence turns out to be insufficient to foster increased re-bordering attitudes, we show that the magnitude of incoming cross-border commuters makes a difference.
Impact of sensory modality and tempo in motor timing
Authors: Jeong Jaeuk , Nam Soo Mi , Seo Hyejin
Published: August 2024

Background

Accurate motor timing requires the coordinated control of actions in response to external stimuli. Over the past few years, several studies have investigated the effect of sensory input on motor timing; however, the evidence remains conflicting. The purpose of this study was to examine the impact of sensory modality and tempo on the accuracy of timed movements and explore strategies for enhancing motor timing.

Methods

Participants (n = 30) performed synchronization and adaptation circle drawing tasks in virtual reality. In Experiment 1, participants synchronized circle drawing with repeated stimuli based on sensory modalities (auditory, visual, tactile, audio-visual, audio-tactile, and visual-tactile) and tempos (20, 30, and 60 bpm). In Experiment 2, we examined timing adaptation in circle drawing tasks under conditions of unexpected tempo changes, whether increased or decreased.

Results

A significant interaction effect between modality and tempo was observed in the comparison of timing accuracy. Tactile stimuli exhibited significantly higher timing accuracy at 60 bpm, whereas auditory stimuli demonstrated a peak accuracy at 30 bpm. The analysis revealed a significantly larger timing error when adapting to changes in the tempo-down condition compared with the tempo-up condition.

Discussion

Through Experiment 1, we found that sensory modality impacts motor timing differently depending on the tempo, with tactile modality being effective at a faster tempo and auditory modality being beneficial at a moderate tempo. Additionally, Experiment 2 revealed that adapting to changes by correcting timing errors is more challenging with decreasing tempo than with increasing tempo. Our findings suggest that motor timing is intricately influenced by sensory modality and tempo variation. Therefore, to enhance the motor timing, a comprehensive understanding of these factors and their applications is imperative.
Processing of emotional connotations in Chinese monomorphic and compound words reflected by the early posterior negativity
Authors: Zhang Kai , Li Jiaxin , Gu Feng
Published: August 2024

Writing stands as one of humanity’s most profound inventions, facilitating the efficient sharing and transmission of vast amounts of information. Similar to images and facial expressions, visual (written) words possess the ability to evoke emotional connotations. Understanding how the brain perceives these emotional nuances encoded in highly symbolic visual words is a key focus of the emerging field of “affective neurolinguistics.” At the core of this inquiry lies the examination of the early posterior negativity (EPN), an event-related potentials (ERPs) component peaking around 300 ms after stimulus onset in the occipitotemporal scalp region. EPN has consistently emerged in response to emotional stimuli, encompassing pictures, faces, and visual words. However, prior research has notably lacked observation of EPN in response to Chinese emotional words, raising questions about potential differences in emotional processing between Chinese and other languages. Given the logographic nature of the Chinese writing system and the prevalence of compound words in the Chinese lexicon, this study aims to explore whether the emotional processing of Chinese monomorphic and compound words elicits an EPN response. Two experiments were conducted: Experiment 1 utilized one-character words (monomorphic words), while Experiment 2 employed two-character words (compound words). Participants were assigned a go/no-go task, instructed to respond to unknown words (word recognition task) or blue stimuli (color decision task). Data analysis using a data-driven mass univariate approach revealed significant ERP differences between emotional and neutral words. Notably, the time course, scalp topography, and cortical generators of the difference ERP presented a characteristic EPN response in both experiments. These findings strongly support the notion that the processing of emotional connotations in both Chinese monomorphic and compound words is reflected by the EPN, paving the way for future research using EPN as an emotion-related ERP component for investigating emotional processing of Chinese words.