bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Citrullination in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases
Authors: Yusuf Issa O. , Camille Webb , Thompson Paul R. , Xu Zuoshang
Published: December 2024

Protein citrullination (PC) is a posttranslational modification (PTM) that converts a peptidyl arginine into a peptidyl citrulline. Aberrant PC is a hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, prion disease, and multiple sclerosis. Common among these diseases is a dramatic increase of PC in reactive astrocytes. Some citrullinated proteins have been identified. The most prominent are astrocytic cytoskeletal proteins such as GFAP and vimentin, and myelin protein MBP. Recent investigation in ALS has revealed new changes, including a decreased PC in neurons and an association of PC with myelin protein aggregates. These findings suggest that PC contributes to protein aggregation, neuronal dysfunction, neuroinflammation, and axonal degeneration. However, how PC impact neurodegeneration remains to be understood. Further studies are needed to understand a range of questions, from how PC modulates individual protein functions to its impact on diseases. Because of the PC’s robust changes in neurodegenerative diseases, there are also prospects that this PTM may be harnessed as biomarkers, and modulation of this PTM may be an avenue for therapy. In this review, we summarize the current understanding of PC in ALS and other neurodegenerative diseases, the investigative methods for PC, and PC’s potential as a biomarker and a therapeutic target.
Protein Assembly Modulation: A New Approach to Amyotrophic Lateral Sclerosis (ALS) Therapeutics
Authors: Yu Shao Feng , Paulvannan Kumar , Solas Dennis , Lingappa Anuradha F. , Moreira Ana Raquel , Sahu Shriya , Michon Maya , Macieik Amanda , Goldsmith Danielle , DeYarman Nicholas , Mallesh Suguna , Prasad M. Dharma , Maios Claudia , Ruan Kai , Tomassy Giulio S. , Jensen Elizabeth , McGuirk Emma , Bader Verian , Mueller-Schiffmann Andreas , Reed Jonathan C. , Lingappa Jaisri R. , Asundi Vinod , Hong Shi , Jacobsen Steve , Brandon Nicholas , Ostrow Lyle , Lloyd Tom , Parker J. Alex , Staats Kim A. , Ichida Justin , Dodge James C. , Dey Debendranath , Korth Carsten , Selvarajah Suganya , Lingappa Vishwanath R. , Rosenfeld Jeffrey
Published: December 2024

Amyotrophic Lateral Sclerosis (ALS) is a devastating and progressive neurodegenerative disease with a complex, multifactorial pathophysiology, culminating in death of motor neurons. We introduce a new mechanism of ALS pathogenesis via study of a novel drug-like small molecule series that targets a subset of protein disulfide isomerase (PDI) within a previously largely unappreciated transient and energy-dependent multi-protein complex enriched for proteins of the ALS interactome. This drug, found by a novel phenotypic screen, has activity in cellular models for both familial and sporadic ALS, as well as in transgenic worms, flies, and mice bearing a diversity of human genes with ALS-associated mutations. The hit compound was initially identified as a modulator of human immunodeficiency virus (HIV) capsid assembly in cell-free protein synthesis and assembly (CFPSA) systems, with demonstrated antiviral activity against infectious HIV in cell culture. Its advancement for ALS-therapeutics, subsequent separation of activity against HIV and ALS into separate chemical subseries through structure-activity-relationship (SAR) optimization, and identification of the drug target by affinity chromatography as shown here, may provide insights into the molecular mechanisms governing pathophysiology of disordered homeostasis relevant to ALS.
Policies for accelerating sustainability transitions: Bridging insights from transition studies and policy studies
Authors: Salas-Gironés Edgar , Goedeking Nicholas , Rogge Karoline
Published: December 2024

Pressing environmental and societal challenges, such as the climate crisis and social inequality, call for policy interventions that steer and accelerate sustainability transitions. In this chapter, we foreground four key intervention areas for such transition policies: providing direction to socio-technical transitions (directionality), creating and protecting novelty (niche support), destabilizing existing technologies and practices (regime destabilization), and coordinating transition processes (coordination). For each of these four areas we outline their theoretical rationale grounded in transition studies and offer interdisciplinary reflections based on research from policy studies. We then present and discuss fifteen concrete policy interventions aimed at accelerating the transformation of our systems of production and consumption towards sustainability, building on a comprehensive review of the relevant transitions literature. We evaluate these interventions with empirical findings from work published in leading transition journals and highlight potential research avenues for scholars who are interested in the intersection of public policy and sustainability transitions. Given the persistent resistance to and intense contestations around transformational policy interventions, we ultimately hope to spark more interdisciplinary exchange and research that bridges transition and policy studies on how to accelerate sustainability transitions.
A PANEL DATA ANALYSIS OF EFFECTS OF ECONOMIC VULNERABILITY INDEX INDICATORS ON REAL EFFECTIVE EXCHANGE RATE IN DEVELOPING COUNTRIES
Authors: Arslan Burak
Published: December 2024

The volatility of exchange rates is considered to be an important measure of a country's economic vulnerability and has a direct or indirect causal relationship with a large number of macroeconomic variables. The aim of this study is to analyze the macroeconomic variables in the economic vulnerability index that affect the exchange rate for developing countries and the extent to which they affect the exchange rate, and to make policy recommendations. We conducted a panel data analysis using data from 11 developing countries between 2000 and 2022 for this purpose. We performed the analyses using the Augmented Mean Group (AMG) estimator. As a result of the analyses, it is found that there is a negative and statistically significant relationship between the real effective exchange rate and inflation, private sector credit debt/GDP and gross public debt/GDP ratio. In addition, the relationship between Real effective exchange rate and current account deficit/GDP ratio, External debt/GDP ratio and growth rate is positive and statistically insignificant. As a policy recommendation, it can be said that for stable and sustainable economic management in developing countries, the exchange rate level should be less volatile and should be compatible with reliable fiscal and monetary policies.
Injectable MXene/Ag-HA composite hydrogel for enhanced alveolar bone healing and mechanistic study
Authors: Li Jialing , Fan Zilu , Guan Zhenju , Ruan Jianping
Published: December 2024

Introduction

Alveolar bone defects pose significant challenges in dentistry. Due to the complexity of alveolar bone anatomy and insufficient repair mechanisms, large bone defects are difficult for the body to heal naturally. Clinical treatment typically involves the use of bone substitute materials. However, current substitutes often suffer from limitations such as insufficient osteoinductivity, rapid degradation, inflammatory responses, and poor mechanical properties. Additionally, the irregular morphology of alveolar bone defects complicates the application of solid bone substitutes, potentially leading to secondary damage at the repair site.

Methods

To address these challenges, this study introduces an innovative approach by integrating MXene nanomaterials into Ag-HA/GelMA hydrogels to create an injectable MXene/Ag-HA composite hydrogel. MXene nanomaterials are renowned for their excellent biocompatibility, antibacterial properties, and mechanical strength.

Results

The results indicate that the MXene/Ag-HA composite hydrogel exhibits satisfactory mechanical and biological properties. Specifically, it demonstrates excellent antibacterial, antioxidant, and osteogenic activities. Gene expression analysis further reveals that the MXene composite hydrogel promotes osteogenesis by regulating the expression of Dmp1 and Dusp1.

Discussion

The findings of this study suggest that the MXene/Ag-HA composite hydrogel is a promising candidate for alveolar bone repair and regeneration. The integration of MXene nanomaterials into the hydrogel enhances its mechanical and biological properties, making it well-suited for the treatment of irregular alveolar bone defects. Furthermore, the study underscores the vast potential of MXene nanomaterials in the biomedical field, hinting at potential applications beyond alveolar bone repair.
Artificial intelligence-assisted echocardiographic monitoring in pediatric patients on extracorporeal membrane oxygenation
Authors: Chen Weiling , Wu Jinhui , Zhang Zhenxuan , Gao Zhifan , Chen Xunyi , Zhang Yu , Lin Zhou , Tang Zijian , Yu Wei , Fan Shumin , Zhang Heye , Xia Bei
Published: December 2024

Background

Percutaneous extracorporeal membrane oxygenation (ECMO) is administered to pediatric patients with cardiogenic shock or cardiac arrest. The traditional method uses focal echocardiography to complete the left ventricular measurement. However, echocardiographic determination of the ejection fraction (EF) by manual tracing of the endocardial borders is time consuming and operator dependent. The standard visual assessment is also an inherently subjective procedure. Artificial intelligence (AI) based machine learning-enabled image analysis might provide rapid, reproducible measurements of left ventricular volumes and EF for ECMO patients.

Objectives

This study aims to evaluate the applicability of AI for monitoring cardiac function based on Echocardiography in patients with ECMO.

Materials and methods

We conducted a retrospective study involving 29 hospitalized patients who received ECMO support between January 2017 and December 2021. Echocardiogram was performed for patients with ECMO, including at pre-ECMO, during cannulation, during ECMO support, during the ECMO wean, and a follow up within 3 months after weaning. EF assessment of all patients was independently evaluated by junior physicians (junior-EF) and experts (expert-EF) using Simpson's biplane method of manual tracing. Additionally, raw data images of apical 2-chamber and 4-chamber views were utilized for EF assessment via a Pediatric ECMO Quantification machine learning-enabled AI (automated-EF).

Results

There was no statistically significant difference between the automated-EF and expert-EF for all groups (P > 0.05). However, the differences between junior-EF and automated-EF and expert-EF were statistically significant (P < 0.05). Inter-group correlation coefficients (ICC) indicated higher agreement between automated-EF and expert manual tracking (ICC: 0.983, 95% CI: 0.977∼0.987) compared to junior assessments (ICC: 0.932, 95% CI: 0.913∼0.946). Bland–Altman analysis showed good agreements among the automated-EF and the expert-EF and junior-EF assessments. There was no significant intra-observer variability for experts' manual tracking or automated measurements.

Conclusions

Automated EF measurements are feasible for pediatric ECMO echocardiography. AI-automated analysis of echocardiography for quantifying left ventricular function in critically ill children has good consistency and reproducibility with that of clinical experts. The automated echocardiographic EF method is reliable for the quantitative evaluation of different heart rates. It can fully support the course of ECMO treatment, and it can help improve the accuracy of quantitative evaluation.
Prevalence and risk factors of osteopenia in adults with short bowel syndrome: a retrospective longitudinal cohort study
Authors: Sun Guangming , Xia Yufei , Wang Haoyang , Xiao Yaqin , Zhang Li , Zhang Yupeng , Gao Xuejin , Wang Xinying
Published: December 2024

Background

Metabolic Bone Disease (MBD) is common in patients with short bowel syndrome (SBS). This study was to investigate the incidence and risk factors of osteopenia in adult SBS patients.

Methods

Hospital records from January 2010 to December 2019 were used to identify all eligible patients. Logistic regression and a nomogram were used to analyze the data.

Results

A total of 120 patients with SBS were included in this study, and 76 patients (63.3%) developed osteopenia during the 10-year observation period, The multivariate analysis using the logistic regression model demonstrated that age (OR = 1.070; 95%CI: 1.016–1.126, p = 0.010), female (OR = 5.098; 95%CI: 1.211–21.456, p = 0.026), tumor history (OR = 4.481; 95%CI: 1.125–17.854, p = 0.033), duration of SBS (OR = 1.0862; 95%CI: 1.022–1.103, p = 0.002) and remnant ileum (OR = 4.260; 95%CI: 1.210–15.002, p = 0.024) were independent risk factors for osteopenia in adults with SBS. The area under the curve (AUC) for the joint model (age, female, tumor history, duration of SBS, remnant ileum) was 0.848 and the corresponding sensitivity and specificity were 0.855 and 0.705, respectively. The C-index was 0.849 (95% CI: 0.778–0.917); thus, the predictions made by the model were close to the actual outcomes. In the decision curve analysis, the nomogram performed well and was feasible to make beneficial clinical decisions.

Conclusion

This study reveals the high prevalence of osteopenia in SBS patients and highlights the importance of early identification and treatment of osteopenia. A nomogram may provide personalized prediction and guidance for medical intervention.
The endothelial activation and stress index is a potential prognostic indicator for patients with acute pancreatitis managed in the intensive care unit: a retrospective study
Authors: Wang Jianjun , Chen Xi , Qin Chuan , Zeng Xintao , Du Xiaobo , Wang Decai
Published: December 2024

Background

The endothelial activation and stress index (EASIX) serves as a dependable and efficient surrogate marker for endothelial dysfunction, which plays an essential role in the pathophysiology of acute pancreatitis (AP). Hence, we investigated the prognostic value of EASIX in AP.

Methods

This was a retrospective study, using patient information obtained from the Medical Information Market for Intensive Care-IV (MIMIC-IV) database. EASIX was calculated using lactate dehydrogenase, serum creatinine, and platelet counts obtained during the first measurement within 24 h of admission. Patients were grouped into three cohorts based on log2-transformed EASIX. The main endpoint of the study was 28-day all-cause mortality (ACM) in AP patients, with the secondary endpoint being 90-day ACM. The relationship between EASIX and prognosis in patients with AP was evaluated using Cox proportional hazards models, Kaplan–Meier curves, restricted cubic spline (RCS) curves, and subgroup analyses. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of EASIX compared to other indicators.

Results

The study cohort comprised 620 patients in total. Multivariate Cox proportional hazards analysis indicated that an increased log2 (EASIX) was linked to a higher risk of 28-day ACM in AP patients (HR, 1.32; 95% CI: 1.14–1.52; p < 0.001). The risk of 28-day ACM was higher in Tertiles 2 and 3 compared with Tertile 1 [(HR, 2.80; 95% CI: 1.21–6.45); (HR, 3.50; 95% CI: 1.42–8.66)]. Comparable findings were noted for 90-day ACM. Kaplan–Meier curves demonstrated that patients with elevated log2 (EASIX) had lower 28- and 90-day survival rates. The RCS curves suggested a non-linear relationship between log2 (EASIX) and 28- and 90-day ACM. ROC curves indicated that log2 (EASIX) was not inferior to sequential organ failure assessment and systemic inflammatory response syndrome scores in predicting the prognosis of patients with AP. Subgroup analyses demonstrated no interaction between log2 (EASIX) and any subgroup.

Conclusion

Elevated EASIX levels were significantly correlated with a heightened risk of 28- and 90-day ACM in AP patients.
The effects of different doses of compound enzyme preparations on the production performance, meat quality and rumen microorganisms of yak were studied by metagenomics and transcriptomics
Authors: Zhang Chenyang , La YongFu , Ma Xiaoming , Zhandui Pingcuo , Wu Xiaoyun , Guo Xian , Yan Ping , Dunzhu Luosan , Liang Chunnian
Published: December 2024

Yak (Bos grunniens) is a large ruminant endemic to the Tibetan plateau. The addition of enzyme complexes to feed can significantly improve their growth performance. Therefore, studying the effects of ruminant compound enzyme preparations dosage on yak rumen microorganisms and production performance is crucial to promoting the development of the yak industry. This study aimed to determine the effects of feeding yaks with different doses of ruminant enzyme compounds on the performance, meat quality, and rumen microorganisms of yaks. Three kinds of experimental diets with doses of 0.5 g/kg (LE group), 1 g/kg (ME group), and 2 g/kg (HE group) were selected to determine the growth index, meat quality, serum biochemical indexes, rumen fluid pH and other indexes of the three experimental groups. Metagenomics studies were used to investigate the differences in rumen microbial composition and function among yak groups, and transcriptome sequencing of the longest dorsal muscle was performed to reveal the expression of differential genes among different groups. It was determined that the levels of dietary enzyme complexes significantly affected growth performance, rumen fluid pH, and serum biochemical indices. At the phylum level, the dominant phylum in all three treatment groups was Bacteroidota, Bacillota, Kiritimatiellota, and Pseudomonadota. At the genus level, Prevotella, Methanobrevibacter, Oscillibacter. Fibrobacter showed statistically significant differences in abundance (p < 0.05). CAZymes family analysis revealed significant differences in GHs, CTs, and CEs among the three groups. Genome-wide differential gene expression in the longest muscle of the yak back was analyzed by RNA-seq between the three experimental groups. Some DEGs were found to be enriched in the ECM, PI3K-Akt, PPAR, and protein digestion and absorption receptor pathways. Combined metagenomics and transcriptomics analyses revealed that some microorganisms were significantly associated with the genes COL11A1, POSTN, and PTHLH, which are involved in growth metabolism. In summary, this study investigated the effects and interrelationships of ruminant complex enzymes on yak performance, meat quality, and rumen environment. The results of this study provide a scientific basis for adding ruminant enzymes to yaks.
Contrasting responses of soil bacterial and fungal networks to photovoltaic power station
Authors: Li Teng , Lu Leilei , Kang Ziqing , Li Huijun , Wu Jihua , Du Weiguo
Published: December 2024

The rapid expansion of solar photovoltaic (PV) power generation raises concerns regarding its impact on terrestrial ecosystems. Although the influence of PV panels on soil conditions and plant biomass is acknowledged, their effects on the assembly processes and co-occurrence networks of soil microbial communities remain understudied. Clarifying this influence is crucial for understanding the effects of photovoltaic panels on soil ecosystem functions. In this study, we first explored the effects of PV panels on soil properties. Then, using amplicon sequencing, we analyzed the impact of PV panels on soil microbial diversity and function, focusing specifically on the assembly processes and co-occurrence networks of bacterial and fungal communities. Our results indicate that the installation of PV panels improved soil conditions, leading to concurrent effects on microbial community structure and function. This process appears to be deterministic, driven primarily by homogeneous selection. Notably, PV panels increased the complexity of bacterial networks while decreasing their stability. In contrast, PV panels did not affect the complexity of fungal networks despite their stability increased. These findings provide new evidence that soil bacterial networks are more sensitive to PV panels installation than fungal networks, deepening our understanding of land-use change effects on soil ecosystem functions. Moreover, our study demonstrates that higher complexity does not necessarily mean higher stability at least in soil microbial systems, challenging the notion that ecological complexity favors their stability.
Developmental deglutition and intrinsic tongue muscle maturation phenotypes in the Ts65Dn mouse model of Down syndrome
Authors: Glass Tiffany J. , Chatwin Benjamin A. , Fisher Erin H. , Hang Kabao K. , Yang Qiuyu , Brutto Riley , Waghray Rohan , Connor Nadine P.
Published: December 2024

Introduction

Down syndrome (DS) is associated with difficulties with feeding during infancy and childhood. Weaning, or transitioning from nursing to independent deglutition, requires developmental progression in tongue function. However, little is known about whether postnatal tongue muscle maturation is impacted in DS. This study tested the hypothesis that the Ts65Dn mouse model of DS has developmental delays in deglutition, comprised of differences in eating and drinking behaviors relative to euploid controls, coinciding with atypical measures of intrinsic tongue muscle microanatomy.

Methods

The Ts65Dn mouse model of DS and euploid controls were evaluated at 7 days of age (p7; nursing), p21 (weaning), and p35 (mature deglutition) (n = 13–18 mice per group). Eating behavior, drinking behavior, and body weight changes were quantified in p21 and p35 mice through the use of automated monitoring over 24 h. Intrinsic tongues of mice at all three ages were sectioned and stained to permit quantification of the sizes of the four major intrinsic tongue muscles. Transverse intrinsic tongue muscles were evaluated for myofiber size (average myofiber cross sectional area (CSA) of all fibers, MyHC2a fibers, MyHC 2b fibers, and minimum Feret fiber diameter), and percentage of MyHC isoforms (%MyHC2a + fibers, and %MyHC 2b + fibers) in anterior, middle, and posterior regions.

Results

Ts65Dn showed significant differences from euploid in deglutition measures. Compared to euploid, Ts65Dn also showed differences in intrinsic tongue muscle microanatomy and biology. Specifically, Ts65Dn intrinsic tongues had smaller transverse muscle myofiber size measures than control in the anterior and middle tongue, but not in the posterior tongue.

Conclusion

Differences in intrinsic tongue muscles coincide with feeding phenotypes in the Ts65Dn mouse model of DS.
Effectiveness and safety of acupuncture for cancer-related hiccups: a systematic review and meta-analysis
Authors: Guo Zining , Liang Ying , Liu Wenhao , Huang Bingjing , Zheng Huiyan , Cui Shaoyang , Xu Nenggui
Published: December 2024

Background

The use of acupuncture in cancer treatment is expanding. Nevertheless, the efficacy and safety of acupuncture in alleviating cancer-related hiccups remains uncertain and inconclusive.

Methods

We conducted a systematic search across eight databases: PubMed, China National Knowledge Infrastructure Database, WanFang, China Science and Technology Journal Database, SinoMed, Web of Science, Cochrane, and Embase, covering the period from their inception to July 2023. Literature was screened based on predefined PICOS inclusion and exclusion criteria, and the risk of bias was assessed using the Cochrane Risk of Bias tool. Data synthesis was performed using Review Manager 5.3 software and R studio 4.4. Additionally, we conducted a frequency analysis of acupoint usage.

Results

A total of nine randomized controlled trials (RCTs) involving 580 patients were included in the analysis. The risk of bias assessment indicated a high risk of bias in all nine RCTs, primarily due to blinding of participants and personnel and random sequence generation (selection bias). The meta-analysis revealed that acupuncture significantly reduced the symptoms of cancer-related hiccups compared to pharmacological treatment (relative risk (RR) = 1.83, 95% confidence interval (CI) [1.53, 2.20], p < 0.001, I2 = 27%). In terms of onset time, acupuncture demonstrated a shorter duration of onset compared to pharmacological treatment (mean difference (MD) = −8.71, 95% CI [−23.32 5.89], p < 0.01, I2 = 100%). Furthermore, acupuncture exhibited a significant improvement in sleep, eating, and appetite scores compared to pharmacological treatment (MD = 0.68, 95% CI [0.07, 1.29], p = 0.03; MD = 0.68, 95% CI [0.07, 1.30], p = 0.03; MD = 0.66, 95% CI [0.08, 1.25, p = 0.03]). The frequency of acupoint usage was analyzed, with ST36 and PC6 being the most frequently used acupoints. Regarding adverse events, acupuncture exhibited favorable safety profiles compared to other control groups.

Conclusion

The meta-analysis results suggest that acupuncture has a positive effect on the efficacy rate for cancer-related hiccups, as well as improvements in quality of life and time to effect response. However, due to the high risk of bias and quality limitations of the included studies, no conclusive evidence currently supports the efficacy of acupuncture. High-quality, evidence-based research is still needed to confirm the effectiveness of acupuncture in treating cancer-related hiccups.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, CRD42023451403.
sTREM2 cerebrospinal fluid levels are a potential biomarker in amyotrophic lateral sclerosis and associate with UMN burden
Authors: Jiao Lin , Yang Jing , Wang Wenjing , Liu Xiangyi , Fu Yu , Fan Dongsheng
Published: December 2024

Objectives

The aims of this study were to investigate whether CSF sTREM2 may be a potential marker of disease monitoring for amyotrophic lateral sclerosis (ALS).

Methods

We investigated whether CSF sTREM2 levels are altered in ALS patients and are correlated with upper motor neuron (UMN) burden and disease progression.

Results

CSF sTREM2 was greater in the ALS patients than in the controls (p = 0.002). Elevated CSF sTREM2 was associated with the UMN score (r = 0.38, p = 0.009), ΔFS (r = 0.30, p = 0.04) and serum NFL (lg) (r = 0.35, p = 0.015). As the motor band sign (MBS) score increased, the CSF sTREM2 level increased (p-trend = 0.014). Furthermore, the correlations became stronger (UMN score (r = 0.50, p = 0.01) ΔFRS (r = 0.52, p = 0.008) and serum NFL (lg) (r = 0.55, p = 0.004) when estimated only among patients with a disease duration >12 months.

Conclusion

We found that CSF sTREM2 is elevated in ALS patients and may be a novel marker, probably reflecting upper motor unit severity and prognosis.
An exploratory cluster-randomized controlled trial on mindfulness yoga’s effectiveness in school-refusing children: reductions in SCAS-C physical injury fears and pulse rate
Authors: Kawazu Suguru , Amitani Marie , Suzuki Hajime , Amitani Haruka , Monuki Takako , Wada Midori , Toyohira Satomi , Hamada Kazumasa , Yamamoto Takako , Yoshimura Takuya , Mizuma Kimiko , Nishida Yuko , Watanabe Hiroko , Hirose Masayuki , Tagawa Koshiro , Ota Keiko , Asakawa Akihiro , Owaki Tetsuhiro
Published: December 2024

Introduction

School refusal is one of the serious problems with children’s mental health, and various studies have examined its prevalence and factors among students. Although many studies suggested that anxiety and depression are deeply associated with school refusal, there is little agreement as to effective interventions. The purpose of this paper is to evaluate the efficacy and safety of mindfulness yoga intervention in children with school refusal.

Method

This study is a multicenter, exploratory, open cluster-randomized controlled trial. 43 participants aged 10–15 years with school refusal were randomly assigned to a non-yoga group with treatment as usual (TAU) which includes cognitive behavioral therapy based on self-monitoring, or a yoga group (4-week mindfulness yoga program provided by video sessions + TAU). The primary outcome was symptoms of anxiety evaluated by Spence Children’s Anxiety Scale-Children (SCAS-C). Participants were assessed in four time periods: a 2-week baseline (Day −14), a baseline (Day 1), a post-test after 4 weeks of treatment (Day 29), and an 8-week follow-up (Day 85). Statistical analysis was conducted by a linear mixed effect model using SAS version 9.4.

Results

43 participants were included in the Full-analysis set (FAS) (21 in the mindfulness yoga group and 22 in the non-yoga group). The estimates of SCAS-C at post-test adjusted for baseline values in each treatment group were 39.9 in the mindfulness yoga group and 39.4 in the non-yoga group. The between-group difference for the estimates was 0.4 (80%CI −4.8 to −5.6, p = 0.54), which indicated mindfulness yoga program has no significant effect on anxiety compared with TAU. However, on an exploratory analysis of the subscale of SCAS-C, significant improvement was observed on the Physical Injury Fears subscale. The pulse rate was significantly lower in the yoga group compared to the non-yoga group.

Conclusion

This study indicated the safety of a mindfulness yoga intervention for children with school refusal, but the effectiveness of the intervention for anxiety was limited. Further research is needed to determine the long-term effects of yoga and how it can best be integrated with other therapies.
Chaperones vs. oxidative stress in the pathobiology of ischemic stroke
Authors: Soldatov Vladislav , Venediktov Artem , Belykh Andrei , Piavchenko Gennadii , Naimzada Mukhammad David , Ogneva Nastasya , Kartashkina Natalia , Bushueva Olga
Published: December 2024

As many proteins prioritize functionality over constancy of structure, a proteome is the shortest stave in the Liebig's barrel of cell sustainability. In this regard, both prokaryotes and eukaryotes possess abundant machinery supporting the quality of the proteome in healthy and stressful conditions. This machinery, namely chaperones, assists in folding, refolding, and the utilization of client proteins. The functions of chaperones are especially important for brain cells, which are highly sophisticated in terms of structural and functional organization. Molecular chaperones are known to exert beneficial effects in many brain diseases including one of the most threatening and widespread brain pathologies, ischemic stroke. However, whether and how they exert the antioxidant defense in stroke remains unclear. Herein, we discuss the chaperones shown to fight oxidative stress and the mechanisms of their antioxidant action. In ischemic stroke, during intense production of free radicals, molecular chaperones preserve the proteome by interacting with oxidized proteins, regulating imbalanced mitochondrial function, and directly fighting oxidative stress. For instance, cells recruit Hsp60 and Hsp70 to provide proper folding of newly synthesized proteins—these factors are required for early ischemic response and to refold damaged polypeptides. Additionally, Hsp70 upregulates some dedicated antioxidant pathways such as FOXO3 signaling. Small HSPs decrease oxidative stress via attenuation of mitochondrial function through their involvement in the regulation of Nrf- (Hsp22), Akt and Hippo (Hsp27) signaling pathways as well as mitophagy (Hsp27, Hsp22). A similar function has also been proposed for the Sigma-1 receptor, contributing to the regulation of mitochondrial function. Some chaperones can prevent excessive formation of reactive oxygen species whereas Hsp90 is suggested to be responsible for pro-oxidant effects in ischemic stroke. Finally, heat-resistant obscure proteins (Hero) are able to shield client proteins, thus preventing their possible over oxidation.
Postoperative unexplained sigmoid stenosis in a patient with rectal cancer complicated with connective tissue disease: a case report and literature review
Authors: Tong Deming , Li Jian , Gao Guangrong , Zhang Cheng
Published: December 2024

It is well established that host immunity plays a critical role in defending against colorectal cancer (CRC) progression. Connective tissue disease (CTD) encompasses a group of heterogeneous, immune-mediated disorders that present with diverse and often non-specific initial symptoms. Raynaud’s phenomenon is a common feature, complicating early diagnosis. As CTD progresses, it can damage the skin, muscles, and blood vessels and may extend to the lungs, heart, kidneys, and other abdominal organs. Several studies have reported that CTD can lead to intestinal vascular occlusion and related inflammation, but the occurrence of related complications after intestinal surgery has been reported rarely. In this study, an elderly female patient with rectal cancer complicated with CTD was found to have unexplained proximal anastomotic stenosis during an attempt at fistula restoration 3 months after laparoscopy-assisted transanal total mesorectal excision (TaTME) and preventive terminal ileostomy, resulting in fistula failure. This case study aims to serve as a reference for clinicians in their future practice.
Prediction of HIF-1α expression in endometrial carcinoma by enhanced T2∗ weighted angiography and dynamic contrast-enhanced magnetic resonance imaging
Authors: Xie Zongyuan , Lin Liangjie , Ma Changjun , Liu Ailian
Published: December 2024

Purpose

To explore the value of quantitative imaging parameters by enhanced T2* weighted angiography (ESWAN) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for evaluating the expression of Hypoxia-inducible factor-1α (HIF-1α) in endometrial carcinoma (EC).

Methods

Data from 122 patients with EC confirmed by clinical pathology were retrospectively analyzed. According to the number of positive cells stained with HIF-1α by immunohistochemistry, patients were divided into two groups: 65 cases with high expression of HIF-1α and 57 cases with low expression of HIF-1α. Clinical data included age, FIGO stage, menopausal status, abnormal uterine bleeding, and pathological type. All patients underwent preoperative 1.5T MRI scans, including ESWAN and DCE-MRI. The amplitude, phase, and R2* values derived from ESWAN and the volume transfer constant (Ktrans), rate constant (Kep), and extravascular volume fraction (Ve) values derived from DCE-MRI were measured by two observers, respectively. The intra-class correlation coefficient (ICC) was used to assess the measurement of reproducibility across observers, and the differences in imaging parameters between the two groups were compared using the independent sample t-test or Mann-Whitney U-test. Binary logistic regression analysis was used to find independent risk factors for HIF-1α expression. The efficacy of selected imaging parameters for predicting HIF-1α expression was assessed using receiver operating characteristic (ROC) curves, and the Delong test was used to compare the area under ROC curves (AUC).

Results

The consistency between the two observers was good (ICC>0.75). The R2*, Ktrans, and Kep values of the HIF-1α high expression group were higher than those of the HIF-1α low expression group (14.59 ± 4.06 vs. 11.99 ± 2.84 Hz, 0.45 ± 0.18 vs. 0.36 ± 0.14/min, and 2.17 ± 1.10 vs. 1.54 ± 0.80/min) (P< 0.001, P = 0.011, and P =0.001). Binary logistic regression analysis revealed that R2* and Kep values were independent risk factors for HIF-1α expression. The AUC values of R2*, Kep, and their combination for prediction of HIF-1α expression were 0.697, 0.677, and 0.781, respectively. The diagnostic efficacy was significantly improved with combination of R2* and Kep.

Conclusions

Quantitative parameters by ESWAN and DCE-MRI showed significant differences between EC patients with low and high expression of HIF-1α, and the combination of ESWAN and DCE-MRI improves the efficacy in prediction of HIF-1α expression in EC, which has an excellent clinical application prospect.
Whole exome-seq and RNA-seq data reveal unique neoantigen profiles in Kenyan breast cancer patients
Authors: Wagutu Godfrey , Gitau John , Mwangi Kennedy , Murithi Mary , Melly Elias , Harris Alexandra R. , Sayed Shahin , Ambs Stefan , Makokha Francis
Published: December 2024

Background

The immune response against tumors relies on distinguishing between self and non-self, the basis of cancer immunotherapy. Neoantigens from somatic mutations are central to many immunotherapeutic strategies and understanding their landscape in breast cancer is crucial for targeted interventions. We aimed to profile neoantigens in Kenyan breast cancer patients using genomic DNA and total RNA from paired tumor and adjacent non-cancerous tissue samples of 23 patients.

Methods

We sequenced the genome-wide exome (WES) and RNA, from which somatic mutations were identified and their expression quantified, respectively. Neoantigen prediction focused on human leukocyte antigens (HLA) crucial to cancer, HLA type I. HLA alleles were predicted from WES data covering the adjacent non-cancerous tissue samples, identifying four alleles that were present in at least 50% of the patients. Neoantigens were deemed potentially immunogenic if their predicted median IC50 (half-maximal inhibitory concentration) binding scores were ≤500nM and were expressed [transcripts per million (TPM) >1] in tumor samples.

Results

An average of 1465 neoantigens covering 10260 genes had ≤500nM median IC50 binding score and >1 TPM in the 23 patients and their presence significantly correlated with the somatic mutations (R2 = 0.570, P=0.001). Assessing 58 genes reported in the catalog of somatic mutations in cancer (COSMIC, v99) to be commonly mutated in breast cancer, 44 (76%) produced >2 neoantigens among the 23 patients, with a mean of 10.5 ranging from 2 to 93. For the 44 genes, a total of 477 putative neoantigens were identified, predominantly derived from missense mutations (88%), indels (6%), and frameshift mutations (6%). Notably, 78% of the putative breast cancer neoantigens were patient-specific. HLA-C*06:01 allele was associated with the majority of neoantigens (194), followed by HLA-A*30:01 (131), HLA-A*02:01 (103), and HLA-B*58:01 (49). Among the genes of interest that produced putative neoantigens were MUC17, TTN, MUC16, AKAP9, NEB, RP1L1, CDH23, PCDHB10, BRCA2, TP53, TG, and RB1.

Conclusions

The unique neoantigen profiles in our patient group highlight the potential of immunotherapy in personalized breast cancer treatment as well as potential biomarkers for prognosis. The unique mutations producing these neoantigens, compared to other populations, provide an opportunity for validation in a much larger sample cohort.
Prognostic role of systemic inflammation response index (SIRI) in patients with pancreatic cancer: a meta-analysis
Authors: Shen Huifen , Zuo Fei
Published: December 2024

Background

The significance of the systemic inflammation response index (SIRI) in predicting the prognosis of patients with pancreatic cancer (PC) has been extensively explored; however, findings remain controversial. As such, this meta-analysis was performed to more precisely determine the utility of the SIRI in predicting PC prognosis.

Methods

A comprehensive literature search of the PubMed, Web of Science, Embase, and Cochrane Library databases for relevant studies, published up to June 25, 2024, was performed. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. The prognostic utility of the SIRI in predicting PC prognosis was estimated by calculating pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs).

Results

Seven studies comprising 1160 patients were included in the present meta-analysis. Pooled findings revealed that elevated SIRI was as a prominent prognostic marker of OS (HR 2.40 [95% CI 1.88–3.05]; p<0.001) and PFS (HR 1.95 [95% CI 1.19–3.21]; p=0.008) in patients diagnosed with PC. According to subgroup analysis, the SIRI remained an outstanding prognostic marker for OS, irrespective of region, sample size, study center, study design, TNM stage, cancer type, cut-off value, treatment, or survival analysis type (all p<0.05). Moreover, based on subgroup analysis, the SIRI demonstrated significant utility in predicting PFS, irrespective of region and threshold value (p<0.05).

Conclusion

Results of the present meta-analysis revealed that an increased SIRI significantly predicted OS and PFS in patients diagnosed with PC. Considering its cost-effectiveness and availability, the SIRI may be a promising biomarker for predicting prognosis in patients with PC.
Case report: Radiological features of a case of desmoplastic malignant mesothelioma of peritoneum
Authors: Wang Jingchao , Deng Heping
Published: December 2024

Desmoplastic malignant peritoneal mesothelioma (DMPM) is an extremely rare and aggressive subtype of sarcomatoid malignant mesothelioma, originating from the mesothelial lining of body cavities. It is characterized by significant local invasiveness and poor prognosis. The nonspecific symptoms of DMPM often result in delayed diagnosis. This case report presents the multimodality imaging findings of DMPM in a 58-year-old male, including ultrasound, CT, contrast-enhanced CT, magnetic resonance imaging (MRI), and 18-fluorodeoxy-glucose positron emission tomography combined with CT (18F-FDG PET/CT). These findings aim to enhance radiologists’ understanding of the imaging features and differential diagnosis of DMPM. In this case, the tumor was located in the right subdiaphragm and the right anterior and left medial lobes of the liver. Due to the patient’s history of alcoholic cirrhosis—a known risk factor for primary liver tumors—the initial diagnostic focus was on identifying a primary liver tumor with potential peritoneal invasion, overlooking other possible etiologies. However, histological results revealed that the liver lesion was secondary to invasion by DMPM. To the best of our knowledge, cases of DMPM invading the liver are exceedingly rare. This report underscores the importance of considering peritoneal tumors in the differential diagnosis when lesions involve both the peritoneum and adjacent organs, despite their rarity.
A real-world pharmacovigilance study of neuroleptic malignant syndrome based on FDA adverse event reporting system
Authors: Zhang Yu , Deng Wei , Wang Minjian , Luo Siying , Li Song
Published: December 2024

Background

Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening adverse drug reaction. This study aims to identify the most prevalent drugs associated with the risk of NMS according to the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.

Methods

Analyses were performed using data from the FAERS database from January 2004 to June 2024. Single-drug signals were evaluated using the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayes geometric mean (EBGM). Meanwhile, comparisons were performed with drug labels. Additionally, subgroup analysis was conducted, focusing on adverse drug reaction signals among populations of different genders and age groups.

Results

A total of 10,433 adverse event reports related to NMS were identified, with the top 50 drugs ranked by ROR mainly involving antipsychotics (18, 36%), antiparkinson drugs (10, 20%), antidepressants (7, 14%), antiepileptics (3, 6%), anxiolytics (3, 6%), as well as hypnotics and sedatives (3, 6%). NMS is more prevalent in males (5,713, 54.76%). Among the top 20 drugs with the strongest signal strength, the pediatric group showed an additional presence of benzodiazepines and antiepileptic drugs compared to the adult group.

Conclusion

The current comprehensive pharmacovigilance study identified more drugs associated with NMS and provides references to clinicians for clinical practice. Also, further research is needed to investigate the causal relationship between these drugs and NMS.
TML1 and TML2 synergistically regulate nodulation and affect arbuscular mycorrhiza in Medicago truncatula
Authors: Chaulagain Diptee , Schnabel Elise , Kappes Mikayla , Lin Erica Xinlei , Müller Lena Maria , Frugoli Julia A.
Published: December 2024

Two symbiotic processes, nodulation and arbuscular mycorrhiza, are primarily controlled by the plant’s need for nitrogen (N) and phosphorus (P), respectively. Autoregulation of nodulation (AON) and autoregulation of mycorrhizal symbiosis (AOM) both negatively regulate their respective processes and share multiple components—plants that make too many nodules usually have higher arbuscular mycorrhiza (AM) fungal root colonization. The protein TML (TOO MUCH LOVE) was shown to function in roots to maintain susceptibly to rhizobial infection under low N conditions and control nodule number through AON in Lotus japonicus. Medicago truncatula has two sequence homologs: MtTML1 and MtTML2. We report the generation of stable single and double mutants harboring multiple allelic variations in MtTML1 and MtTML2 using CRISPR–Cas9 targeted mutagenesis and screening of a transposon mutagenesis library. Plants containing single mutations in MtTML1 or MtTML2 produced two to three times the nodules of wild-type plants, whereas plants containing mutations in both genes displayed a synergistic effect, forming 20× more nodules compared to wild-type plants. Examination of expression and heterozygote effects suggests that genetic compensation may play a role in the observed synergy. Plants with mutations in both TMLs only showed mild increases in AM fungal root colonization at later timepoints in our experiments, suggesting that these genes may also play a minor role in AM symbiosis regulation. The mutants created will be useful tools to dissect the mechanism of synergistic action of MtTML1 and MtTML2 in M. truncatula symbiosis with beneficial microbes.
From concept to impact: strategic guidelines for environmental behavior change interventions
Authors: Biresselioglu Mehmet Efe , Demir Muhittin Hakan
Published: December 2024

Interventions aiming at behavioral change are common tools for assessing and stimulating environmentally friendly lifestyles. To obtain representative and scalable results from the interventions, the experimental design of the interventions is crucial. Likewise, an operational plan is significant concerning the coherence and consistency of the interventions and the comparability of the results from different interventions. Such a guideline contributes to the design, execution, and supervision of the interventions, provides standardisation and enhances collaboration with the intervention partners. Intervention guidelines also pertain to the strategic planning of data requirements and collection procedures. Based on the work conducted within the context of the EU-funded ENCHANT project, the guidelines presented in this manuscript are structured based on the key phases of planning and design, implementation, and analysis and reporting. Another key area that needs to be considered and included in the guidelines is the planning necessities for the administrative structure for the interventions. This includes allocating staff roles and responsibilities and potential challenges and obstacles that may arise during implementation. Ethical concerns are also addressed.