bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features of anti-SAE1 antibody-positive myositis and interstitial lung disease: a multicenter, retrospective study in Taiwan
Authors: Hsiao Chao-Yang , Tseng Shu-Chi , Hsu Chung-Yuan , Chiu Li-Chung , Su Li-Jen , Chan Tien-Ming
Published: November 2024

Introduction

The clinical characteristics of patients positive for anti-small ubiquitin-like modifier 1-activating enzyme subunit 1 (SAE1) antibodies and diagnosed with idiopathic inflammatory myopathies (IIMs) vary across different cohorts and ethnicities, particularly concerning interstitial lung disease (ILD). We aimed to assess the clinical utility of the line immunoblot assay (LIA) in detecting anti-SAE1 autoantibodies and evaluate the clinical relevance and chronology of ILD development in relation to SAE1 autoantibody positivity among Taiwanese patients.

Methods

We retrospectively conducted a population-based cohort analysis involving 6,496 patients who visited Chang Gung Memorial Health System across Taiwan from May 2018 to December 2021. Patients were assayed for myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) using the LIA method, and the antinuclear antibody (ANA) indirect immunofluorescence (IIF) method was used to evaluate ANA patterns. Of these, 70 SAE1-positive patients (1.08%) were included and followed up until December 2023. Associations with clinical characteristics and final diagnosis, particularly ILD, were assessed.

Results

Among the 70 SAE1-positive patients, 10 (14.3%) were strongly positive and 60 (85.7%) were weakly positive. In the strong positive group, 70% (7/10) were diagnosed with IIM, with most (5/7) showing a concordant ANA IIF pattern (speckled type). Six patients presented ILD either before (1/6) or after (5/6) IIM diagnosis; the majority (4/6) were classified as organizing pneumonia. The remaining 30.0% (3/10) had connective tissue disease (CTD) other than IIM without detectable ILD during follow-up, and none demonstrated a concordant ANA IIF pattern. In the weakly positive group, only 5.0% (3/60) had IIM and 3.3% (2/60) had ILD. The positive predictive value for strong positive SAE1 autoantibodies in diagnosing IIM was significantly higher than for weak positives (70.0% vs. 5.0%; p < 0.001).

Conclusions

The study suggests that strong positive SAE1 autoantibodies detected via LIA are more closely associated with IIM compared to weak positive results. A high prevalence of ILD was observed among strong positive Taiwanese patients, indicating the need for prompt screening. Patients with weak positive or discordant ANA IIF results may represent false positives with a lower ILD risk.
Integrated analysis of single-cell, spatial and bulk RNA-sequencing identifies a cell-death signature for predicting the outcomes of head and neck cancer
Authors: Pan Yue , Fei Lei , Wang Shihua , Chen Hua , Jiang Changqing , Li Hong , Wang Changsong , Yang Yao , Zhang Qinggao , Chen Yongwen
Published: November 2024

Background

Cell death plays an essential role in carcinogenesis, but its function in the recurrence and postoperative prognosis of head and neck cancer (HNC), which ranks as the 7th most common malignancy globally, remains unclear.

Methods

Data from five main subtypes of HNC related single-cell RNA sequencing (scRNA-seq) were recruited to establish a single-cell atlas, and the distribution of cell death models (CDMs) across different tissues as well as cell subtypes were analyzed. Bulk RNA-seq from the Cancer Genome Atlas Program (TCGA) dataset was subjected to a machine learning-based integrative procedure for constructing a consensus cell death-related signature risk score (CDRscore) model and validated by external data. The biofunctions including different expression analysis, immune cell infiltration, genomic mutations, enrichment analysis as well as cellchat analysis were compared between the high- and low- risk score groups categorized by this CDRscore model. Finally, samples from laryngeal squamous cell cancer (LSCC) were conducted by spatial transcriptomics (ST) to further validate the results of CDRscore model.

Results

T cells from HNC patients manifested the highest levels of cell death while HPV infection attenuates malignant cell death based on single-cell atlas. CDMs are positively correlated with the tumor-cell stemness, immune-related score and T cells are infiltrated. A CDRscore model was established based on the transcription of ten cell death prognostic genes (MRPL10, DDX19A, NDFIP1, PCMT1, HPRT1, SLC2A3, EFNB2, HK1, BTG3 and MAP2K7). It functions as an independent prognostic factor for overall survival in HNC and displays stable and powerful performance validated by GSE41613 and GSE65858 datasets. Patients in high CDRscore manifested worse overall survival, more active of epithelial mesenchymal transition, TGF-β-related pathways and hypoxia, higher transcription of T cell exhausted markers, and stronger TP53 mutation. ST from LSCC showed that spots with high-risk scores were colocalized with TGF-β and the proliferating malignant cells, additionally, the risk scores have a negative correlation with TCR signaling but positive association with LAG3 transcription.

Conclusion

The CDRscore model could be utilized as a powerful prognostic indicator for HNC.
ZNF350 gene polymorphisms promote the response to Peg-IFNα therapy through JAK-STAT signaling pathway in patients with chronic hepatitis B
Authors: Guo Jianhui , Guo Shaoying , Chen Tianbin , Zeng Yongbin , Fu Ya , Ou Qishui
Published: November 2024

Background

The varying individual responses to Pegylated interferon-α (Peg-IFNα) in patients with chronic hepatitis B (CHB) pose significant hurdles in treatment optimization, and the underlying mechanisms remain unclear.

Objective

We aimed to identify genetic polymorphisms influencing the efficacy of Peg-IFNα in patients with HBeAg-positive CHB, with the goal to predict Peg-IFNα response before treatment.

Methods

We employed an Asian Screening Array analysis involving 124 HBeAg-positive CHB patients treated with Peg-IFNα. We conducted assessment of immunological markers and mRNA expression of pivotal genes, establishing correlations with SNPs, functional genes of SNPs, and efficacy of Peg-IFNα therapy. In vitro experiments were performed to verify the functional involvement of the candidate SNPs.

Results

The G allele presented in rs2278420 and rs6509607 were significantly more common in patients who achieved a complete response (CR) compared to those who had a suboptimal response (SR), and linked to an increased rates of HBeAg loss following Peg-IFNα treatment (all p < 0.05). Additionally, the mRNA level of ZNF350 varied notably across different genotypes of both SNPs as determined by eQTL analysis, and showed higher expression in patients achieved a SR (all p < 0.05). In vitro investigations with IFNα stimulation showed that the mRNA level of SOCS3 was elevated in patients with rs2278420 genotype AA, similarly, mRNA levels of PKR, STAT2, SOCS1, SOCS3, PIAS1, PTPN6 and TRIM8 were heightened in patients with rs6509607 genotype AA compared to those with genotypes (AG+GG) (all p < 0.05).

Conclusion

The G allele of rs2278420 and rs6509607 were associated with mRNA level of ZNF350, with an increased probability of Peg-IFNα response in HBeAg-positive CHB patients, likely through the modulation of JAK-STAT signaling pathway.
Research progress of CD80 in the development of immunotherapy drugs
Authors: Li Lanying , Yang Lei , Jiang DePeng
Published: November 2024

CD80 is a molecule that plays an important role in the immune system, especially during T-cell activation, and its ligands are mainly CD28, PD-L1, and CTLA-4. CD80 is expressed on the surface of tumor cells, and it can be used as a molecular target in the process of T-cell anti-tumor immune response. In autoimmune diseases, CD80 can also regulate autoimmune diseases by modulating immunity. This review mainly focus on the role of CD80 in the immune system, as well as the research progress on the application of CD80-related immunopharmaceuticals in the treatment of tumors and autoimmune diseases.
Enhancing Water depth inversion accuracy in turbid coastal environments using random forest and coordinate attention mechanisms
Authors: Fang Siwen , Wu Zhongqiang , Wu Shulei , Chen Zhixing , Shen Wei , Mao Zhihua
Published: November 2024

This study introduces an innovative water depth estimation method for complex coastal environments, focusing on Yantian Port. By combining Random Forest algorithms with a Coordinate Attention mechanism, we address limitations of traditional bathymetric techniques in turbid waters. Our approach incorporates geographical coordinates, enhancing spatial accuracy and predictive capabilities of conventional models. The Random Forest Lon./Lat. model demonstrated exceptional performance, particularly in shallow water depth estimation, achieving superior accuracy metrics among all evaluated models. It boasted the lowest Root Mean Square Error (RMSE) and highest coefficient of determination (R²), outperforming standard techniques like Stumpf and Log-Linear approaches. These findings highlight the potential of advanced machine learning in revolutionizing bathymetric mapping for intricate coastal zones, opening new possibilities for port management, coastal engineering, and environmental monitoring of coastal ecosystems. We recommend extending this research to diverse coastal regions to validate its broader applicability. Additionally, exploring the integration of additional geospatial features could further refine the model’s accuracy and computational efficiency. This study marks a significant advancement in bathymetric technology, offering improved solutions for accurate water depth estimation in challenging aquatic environments. As we continue to push boundaries in this field, the potential for enhanced coastal management and environmental stewardship grows, paving the way for more sustainable and informed decision-making in coastal zones worldwide.
Clinical study on the safety and efficacy of remimazolam in hysteroscopic surgery under general anesthesia in elderly patients
Authors: Xie Manjie , Zeng Fanrui , Tian Qiao , Deng Huiwei , Tao Shanqing
Published: November 2024

Objective

To evaluate the safety and efficacy of remimazolam in hysteroscopic surgery in elderly patients.

Methods

Following hysteroscopic surgery under selected general anesthesia, 60 elderly patients ASA (American Society of Anesthesiologists) class II–III, >65 years old were randomly assigned to one of two groups: the R group (remimazolam) or the C group (propofol), each with 30 patients. Sufentanil 0.1 μg/kg was given 5 min before the operation, remimazolam 0.2 mg/kg intravenously in Group R, then 0.5~1 mg/(kg.h) by pump, propofol 2 mg/kg intravenously in group B, and then 4~8 mg/(kg.h) by pump. Maintain BIS (Bispectral index) 40~70, add remimazolam 0.05 mg/kg or propofol 0.5 mg/kg when the patient is in motion, and stop the administration at the end of the operation. Record the patients' HR, MAP, RR, SpO2, PETCO2, and BIS values at entry (T0), before induction administration (T1), 1 min after administration (T2), 5 min after administration (T3), when stopping administration (T4), when awakening (T5), and 1 min after awakening (T6), as well as the onset time after administration, the awakening time, the success rate of sedation, and the number and dose of additional medications. Reactions are adverse (hypotension, hypertension, respiratory depression incidence, injection pain, nausea and vomiting following surgery, etc.).

Results

The two groups' respective anesthetic success rates were comparable overall. In addition to having a higher BIS value and more extra medications than group C, group R experienced less incidence of respiratory depression, injection pain, and intraoperative hypotension.

Conclusion

Remimazolam, which is equivalent to propofol in terms of safety and efficacy for older patients undergoing hysteroscopic surgery, should be further promoted and used.
Enhanced skin cancer diagnosis through grid search algorithm-optimized deep learning models for skin lesion analysis
Authors: Pillai Rudresh , Sharma Neha , Gupta Sheifali , Gupta Deepali , Juneja Sapna , Malik Saurav , Qin Hong , Alqahtani Mohammed S. , Ksibi Amel
Published: November 2024

Skin cancer is a widespread and perilous disease that necessitates prompt and precise detection for successful treatment. This research introduces a thorough method for identifying skin lesions by utilizing sophisticated deep learning (DL) techniques. The study utilizes three convolutional neural networks (CNNs)—CNN1, CNN2, and CNN3—each assigned to a distinct categorization job. Task 1 involves binary classification to determine whether skin lesions are present or absent. Task 2 involves distinguishing between benign and malignant lesions. Task 3 involves multiclass classification of skin lesion images to identify the precise type of skin lesion from a set of seven categories. The most optimal hyperparameters for the proposed CNN models were determined using the Grid Search Optimization technique. This approach determines optimal values for architectural and fine-tuning hyperparameters, which is essential for learning. Rigorous evaluations of loss, accuracy, and confusion matrix thoroughly assessed the performance of the CNN models. Three datasets from the International Skin Imaging Collaboration (ISIC) Archive were utilized for the classification tasks. The primary objective of this study is to create a robust CNN system that can accurately diagnose skin lesions. Three separate CNN models were developed using the labeled ISIC Archive datasets. These models were designed to accurately detect skin lesions, assess the malignancy of the lesions, and classify the different types of lesions. The results indicate that the proposed CNN models possess robust capabilities in identifying and categorizing skin lesions, aiding healthcare professionals in making prompt and precise diagnostic judgments. This strategy presents an optimistic avenue for enhancing the diagnosis of skin cancer, which could potentially decrease avoidable fatalities and extend the lifespan of people diagnosed with skin cancer. This research enhances the discipline of biomedical image processing for skin lesion identification by utilizing the capabilities of DL algorithms.
Impact of fat intake on [18F]AlF-NOTA-FAPI-04 uptake in normal abdominal organs
Authors: Dai Jiashun , Zhou Wanjing , Liu Huaping , Jiang Chengzhi , Ye Hui
Published: November 2024

Purpose

[18F]AlF-NOTA-FAPI-04 demonstrates significant physiological uptake in the gallbladder and biliary tract system, representing a limitation of this positron emission tomography (PET) tracer. The aim of this study was to evaluate the impact of milk consumed prior to a PET/CT scan on [18F]AlF-NOTA-FAPI-04 uptake in normal abdominal organs.

Materials and methods

A total of 86 patients who underwent [18F]AlF-NOTA-FAPI-04 PET/CT imaging took part in this single-center retrospective clinical study at the Hunan Cancer Hospital between December 2020 and August 2021. Patients were divided into two groups according to their pre-PET scan diet: treated group, who consumed 250 mL of milk 10 ± 5 min after the tracer injection, while the control group was permitted no food intake subsequent to the radiotracer administration. The mean standardized uptake value (SUVmean) of gallbladder, liver, small intestine and pancreas were measured in 18F-FAPI and 18F-FDG PET/CT.

Results

There was a statistically significant difference in the 18F-FAPI uptake in the gallbladder between the treated group and the control group (p < 0.001). The average SUVmean in the treated group was 2.19 ± 2.01, which was significantly lower than the average SUVmean of 10.04 ± 9.66 in the control group. In the subgroup analysis of patients who underwent paired [18F]FDG and [18F]FAPI PET/CT scans, the 18F-FAPI uptake of liver and small intestine was significantly lower than the 18F-FDG uptake in both the treated group and the control group (p < 0.001).

Conclusion

This study suggests that milk consumption decreases physiological 18F-FAPI uptake in the gallbladder, potentially enhancing the diagnostic accuracy for gallbladder cancer.
Progression to kidney failure in ADPKD: the PROPKD score underestimates the risk assessed by the Mayo imaging classification
Authors: Allmer Daniela Maria , Parada Rodriguez Diego , Aigner Christof , Laccone Franco , Nagel Mato , Metz-Schimmerl Sylvia , Sunder-Plassmann Gere
Published: November 2024

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and fourth leading cause for renal replacement therapy worldwide. Disease progression is tightly linked to genotype, however, factors like genetic modifiers and environmental factors are responsible for a high phenotypic variability within- as well as between families. Individual’s risk of progression to kidney failure is assessed using prediction- or risk-assessment tools such as the predicting renal outcomes in ADPKD score (PROPKD score) and the Mayo Imaging Classification (MIC). The PROPKD score encompasses genetic and phenotypic parameters, while the MIC relies on renal imaging, height, and age of patients. Both methods categorize patients into low-risk, intermediate-risk, and high-risk for progression to kidney failure. In this retrospective, cross-sectional study, we calculated the risk of progression to kidney failure in our population and analyzed the agreement between the methods in three separate models with alternating stratification of MIC risk categories. We found a mismatch for risk assessment between the respective risk categories, indicating that the PROPKD score and MIC should not be used interchangeably. Preferably, the MIC should be used as a base for risk assessment and may be enhanced by genotypic and phenotypic information.
Accreditation of pharmacy programs and its impact on SPLE success and pharmacist readiness in Saudi Arabia
Authors: Almaghaslah Dalia
Published: November 2024

Aim

The impact of pharmacy program accreditation on the Saudi Pharmacists Licensure Examination (SPLE) pass rates and overall pharmacist readiness was investigated.

Methods

A cross-sectional retrospective study was conducted. Data on SPLE pass rates were obtained from the Saudi Commission for Health Specialties (SCFHS) 2024 report. Pharmacy colleges were categorized into five groups based on their students' average SPLE scores. Information on the national i.e., the Evaluation and Training Evaluation Center (ETEC) and international i.e., the American Council for Pharmacy Education (ACPE) and the Canadian Council for Accreditation of Pharmacy Programs (CCAPP) accreditation status of these colleges was also collected.

Results

Higher average SPLE scores (mean = 563, SE = 43.4) were observed in accredited colleges (either national or international) compared to non-accredited colleges (mean = 533, SE = 33.6), with a significant difference noted [t(22) = −2.149, p = 0.042]. Higher average SPLE scores (mean = 581.8, SE = 18.9) were also found in colleges with multiple accreditations compared to those with fewer or no accreditations (mean = 548.02, SE = 18.9), though this difference was not statistically significant [t(25) = −1.8, p = 0.086].

Discussion and conclusion

It was demonstrated that accreditation, whether national or international, is associated with higher SPLE pass rates, indicating a positive impact on exam performance. National accreditation by ETEC alone was found to be sufficient for improving SPLE scores and ensuring pharmacist readiness, whereas dual or international accreditations did not provide additional benefits in this context.
Recurrence and propagation of past functions through mineral facilitated horizontal gene transfer
Authors: Verma Taru , Hendiani Saghar , Carbajo Carlota , Andersen Sandra B. , Hammarlund Emma U. , Burmølle Mette , Sand Karina K.
Published: November 2024

Horizontal gene transfer is one of the most important drivers of bacterial evolution. Transformation by uptake of extracellular DNA is traditionally not considered to be an effective mode of gene acquisition, simply because extracellular DNA is degraded in a matter of days when it is suspended in e.g. seawater. Recently the age span of stored DNA was increased to at least 2 Ma. Here, we show that Acinetobacter baylyi can incorporate 60 bp DNA fragments adsorbed to common sedimentary minerals and that the transformation frequencies scale with mineral surface properties. Our work highlights that ancient environmental DNA can fuel the evolution of contemporary bacteria. In contrast to heritable stochastic mutations, the processes by which bacteria acquire new genomic material during times of increased stress and needs, indicate a non-random mechanism that may propel evolution in a non-stochastic manner.
The microbiome analysis of ripen grape berries supports the complex etiology of sour rot
Authors: Brischetto Chiara , Rossi Vittorio , Fedele Giorgia
Published: November 2024

Sour rot (SR) is a grapevine disease complex that is not completely understood in its etiology and epidemiology. Recently, SR has received special attention due to its increasing economic importance due to crop losses and reduced wine quality. In this study, the fungal and bacterial microbiota of healthy (i.e., without rot symptoms) and rotten (i.e., exhibiting visual and olfactory SR symptoms) ripe bunches were characterized across 47 epidemics (39 vineyards in six Italian grape-growing areas) over three years. The 16S rRNA gene, ITS high-throughput amplicon sequencing, and quantitative PCR were used to assess the relative abundance and dynamic changes of microorganisms associated with SR. The estimators of genera richness of fungal communities within samples indicated a significantly different diversity between healthy and rotten bunches. For bacterial communities, the healthy and rotten bunches significantly differed in the total number of species, but not in abundance distribution across species. The bunch status (i.e., healthy and rotten) was a significant source of diversity (p < 0.01) when the community composition between samples was evaluated, indicating that microbiome composition varied between healthy and rotten bunches. In particular, healthy and rotten bunches shared 43.1 and 54.8% of fungal and bacterial genera, respectively; 31.3% (fungal) and 26.2% (bacterial) genera were associated with rotten bunches only. The yeast genera Zygosaccharomyces, Zygoascus, Saccharomycopsis, Issatchenkia, and Pichia and the bacterial genera Orbus, Gluconobacter, Komagataeibacter, Gluconacetobacter, and Wolbachia were strongly associated with bunches showing SR symptoms based on a linear discriminant analysis. These microorganisms have been associated with Drosophila insects in literature. The relationships between the microflora associated with SR-affected bunches and the roles of Drosophila in SR development need further investigation, which may open perspectives for more effective disease control.
Synaptic plasticity and roles of orexin in distinct domains of the olfactory tubercle
Authors: Podder Sajib , Murata Yoshihiro , Taniguchi Mutsuo , Shimizu Shogo , Yamaguchi Masahiro
Published: November 2024

Olfactory behavior is highly plastic, and the olfactory tubercle (OT), a component of the olfactory cortex and ventral striatum, includes anteromedial (amOT) and lateral (lOT) domains with roles in attractive and aversive olfactory behavioral learning, respectively. However, the underlying properties of synaptic plasticity in these domains are incompletely understood. Synaptic plasticity is regulated by multiple signals including synaptic inputs and neuromodulators. Interestingly, the amOT domain exhibits high expression of various receptors for neuromodulators. We investigated synaptic plasticity in mouse OT slices by combining electrical stimulation and treatment with the appetite-promoting neuropeptide orexin, the receptors of which are highly expressed in the amOT. In both the amOT and lOT, one round of 2-Hz burst stimulation elicited short-term potentiation of the field excitatory postsynaptic potential, whereas three rounds of stimulation induced long-term potentiation (LTP) that persisted for 150 min. In the amOT, orexin-A induced LTP was blocked by the orexin receptor type 1 antagonist SB334867. Orexin-A also facilitated LTP induction in the amOT by one round of 2-Hz burst stimulation. By contrast, these effects were not observed in the lOT. These results highlighted the similarity and difference in synaptic plasticity between the OT domains and suggested that orexin facilitates synaptic plasticity in the amOT during olfactory learning processes such as food odor learning.
Adolescent sleep and its disruption in depression and anxiety
Authors: Chai Ruiming , Bian Wen-Jie
Published: November 2024

Adolescence is a pivotal stage during development when one’s personality, emotion, and behavioral traits are shaped to a great extent, and the underlying neural circuits undergo substantial developmental organizations. Dramatic and dynamic changes occur in sleep architecture throughout the postnatal developmental course. Insufficient sleep and disruption of sleep/wake coherence are prevalent among the adolescents worldwide, and even so in young patients with neuropsychiatric conditions. Although accumulating evidence has suggested a tight association between sleep disruption and depression/anxiety, the causal relationship remains largely unclear. More importantly, most of these studies focused on adult subjects, and little is known about the role of sleep during the development of mood and behavior. Here we review recent studies investigating the acute and chronic effects of adolescent sleep disruption on depression and anxiety both in humans and rodent models with focuses on the assessment methodology and age. By discussing the findings and unsolved problems, we hope to achieve a better understanding of the relationship between sleep and mental health in adolescents and provide insights for future research.
Toward making the field talk: assessing the relationship between digital technology and sustainable food production in agricultural regions
Authors: Khan Nawab , Xu Xuanguo , Khayyam Muhammad , Raziq Abdul
Published: November 2024

Introduction

The global food system faces numerous challenges, including population growth, pandemics, climate change, natural disasters, and economic instability. These challenges have a profound impact on agriculture, with climate change leading to unpredictable weather and more frequent extreme events that threaten crop yields and farming sustainability. Farmers are also grappling with rising input costs and market volatility, intensifying the need for improved productivity and efficiency.

Purpose

Considering these challenges, digital technology, particularly mobile internet (MI), is emerging as a key tool for achieving sustainable agriculture by enhancing productivity, efficiency, and cost-effectiveness. While much research has focused on the effects of MI on agricultural inputs, prices, and operational efficiency, there is limited understanding of its direct impact on food production outcomes. This study aims to fill this gap by examining the influence of MI usage on crop production.

Method

The study utilizes data from 660 farmers across two provinces of Pakistan. Propensity Score Matching (PSM) and linear regression models are employed to assess the impact of MI usage on food production.

Results

The analysis reveals a significant positive effect of MI usage on crop production, with MI users experiencing a 13.30% increase in crop yield compared to non-users. The heterogeneity analysis shows varying impacts among different farmer groups: young farmers see a 13.50% increase, less-educated farmers a 15.27% rise, larger-scale farmers a 23.80% boost, and those in economically developed villages a 10.50% improvement per hectare compared to non-users.

Conclusion

The study highlights the potential of MI in boosting crop production, particularly for specific farmer demographics. Policymakers should prioritize the development of MI infrastructure in rural areas and collaborate with research institutions, agricultural cooperatives, and enterprises to design interventions, such as financial support and technical assistance, that can help farmers fully leverage the benefits of digital technology.
Increased fat mass and obesity risk after elexacaftor–tezacaftor–ivacaftor therapy in young adults with cystic fibrosis
Authors: Merino Sánchez-Cañete Ana , López Cárdenes Concepción Marina , Vicente Santamaría Saioa , Gutiérrez Martínez José Ramón , Suárez González Marta , Álvarez Merino María , González Jiménez David
Published: November 2024

Background

When people with cystic fibrosis (PwCFs) are treated with cystic fibrosis transmembrane conductance regulator protein modulator (CFTRm), it leads to changes in body composition. An easy, non-invasive, and reproducible method to assess this is by means of electrical bioimpedance measurement, which complements the information provided by the already-known anthropometric parameters.

Methods

Seventeen adults with cystic fibrosis in treatment with elexacaftor–tezacaftor–ivacaftor (ETI) were recruited for a prospective, longitudinal, single-center study over 12 months. Study variables included weight, body mass index (BMI), and body composition by bioelectrical impedance analysis (BIA) [including fat mass (FM) and fat-free mass (FFM)].

Results

At 12 months, there was an increase in overweight patients (5.9% vs. 23.5%) and a statistically significant increase in BMI at 6 and 12 months. An increase in FM and FFM was observed at 12 months. The increase was greater in FM (95% CI) from a baseline of 1.77% (0.00–3.54; p = 0.050) at 6 months and 2.64% (0.48–4.81; p = 0.020) at 12 months.

Conclusion

After treatment with ETI, there was an increase in weight, BMI, and FM more than FFM in PwCF. These changes would be confirmed in long-term studies to improve nutritional management.
The effect of a low-carbohydrate diet on subcutaneous adipose tissue in females with lipedema
Authors: Lundanes Julianne , Gårseth Mari , Taylor Shannon , Crescenzi Rachelle , Pridmore Michael , Wagnild Rune , Hyldmo Åsne Ask , Martins Catia , Nymo Siren
Published: November 2024

Introduction

Lipedema is a common, yet underdiagnosed, subcutaneous adipose tissue (SAT) disorder. The main characteristics are SAT expansion in the lower extremities and arms, pain, and tenderness to palpation. It remains unknown if a low-carbohydrate diet (LCD) influences SAT in females with lipedema.

Objectives

To evaluate the effect of a LCD low-energy diet, compared to a low-fat isoenergetic control diet, on calf subcutaneous adipose tissue area, muscle area, SAT/muscle ratio, calf circumference and body composition in females with lipedema.

Subjects/methods

Adult females with obesity and lipedema were randomized to 1,200 kcal/day diets, either LCD or control (75 and 180 g/day of carbohydrates, respectively) for 8 weeks. Body composition was measured with bioelectrical impedance analysis, calf SAT area, muscle area, and circumference with magnetic resonance imaging and pain with brief pain inventory, before and after the intervention.

Results

Thirteen participants were included (five in the LCD group), with a mean age of 46 ± 12 years and a BMI of 37 ± 6 kg/m2. A significant reduction in calf SAT area, calf circumference, and pain was observed in the LCD group only. Both LCD and control groups experienced a significant reduction body weight, fat mass, fat free mass, and muscle area, with no differences between groups. No significant changes over time were found for SAT/muscle ratio.

Conclusion

A LCD has the potential to reduce SAT and pain in females with lipedema, despite a reduction in muscle mass in lipedema affected areas in both diet groups. Further studies are needed to confirm these findings and explore potential mechanisms.

Clinical trial registration

NCT04632810: Effect of ketosis on pain and quality of life in patients with lipedema (Lipodiet). https://clinicaltrials.gov/study/NCT04632810.
Spleen tyrosine kinase inhibition mitigates radiation-induced lung injury through anti-inflammatory effects and downregulation of p38 MAPK and p53
Authors: Zhang Guoxing , Sun Ni , Li Xiaohua
Published: November 2024

Background

To explore new modulatory intervention targets for radiation-induced lung injury, bioinformatics analysis technology was used to search for the core driving genes in the pathogenesis of radiation pneumonitis, and the results were verified by a radiation-induced murine lung injury model to find possible new targets for the treatment of radiation lung injury.

Method

Gene Expression Omnibus Database was used to identify differentially expressed genes in radiation pneumonitis. DAVID database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Gene Set Enrichment Analysis was used to analyze abnormal expressions. Protein–protein interaction networks were constructed using STRING and Cytoscape. Discovery Studio 4.5 software was used to find the preferred inhibitor of the specific gene. A radiation-induced lung injury model was induced in female C57BL/6N mice. The specific inhibitors were administered by intraperitoneal injection 24 h before and for 7 consecutive days after radiation. Lungs were harvested for further analysis 14 days and 10 weeks post-irradiation.

Results

We screened Syk as one of the most important driver genes of radiation pneumonitis by bioinformatics analysis and screened the preferred Syk inhibitor fostamatinib from the drug database. Syk was highly expressed in irradiated lung tissue, and fostamatinib inhibited the level of Syk expression. Syk inhibitor significantly alleviated the radiation-induced lung injury and downregulated the increased expression of p38 MAPK, p53, IL-1β, and IL-6 in lung tissue at 2 weeks after radiation. The levels of TGF-β, COL1A1, and α-SMA and degree of pulmonary fibrosis at 10 weeks after radiation were also decreased by Syk inhibitor.

Conclusion

Syk inhibitor may have a potential to be used as a targeted drug to mitigate radiation pneumonitis and inhibit radiation-induced pulmonary fibrosis.
Combination of ultrasound guided superficial cervical plexus block and local infiltration for oromaxillofacial surgeries: a case series
Authors: Zhao Hao-ran , Hao Jian-shuai , Xue Ling-fa , Zhao Jin-ze , Wang Yi-chen , Xiao Wen-lin
Published: November 2024

Introduction

When elderly patients have underlying diseases combined with oromaxillofacial diseases requiring surgical treatment, the application of conventional general anesthesia (GA) for oromaxillofacial surgical diseases has become a risk due to underlying disease reasons. The objective of this study was to evaluate the efficacy and safety of ultrasound-guided superficial cervical plexus block (SCPB) anesthesia combined with local infiltration anesthesia (LIA) for partial oral and maxillofacial surgery (OMFS) in patients who with risk for GA due to underlying disease.

Methods

The clinical data of 7 high risk patients with OMFS treated with SCPB anesthesia combined with LIA were retrospectively analyzed. All seven surgeries were performed on one side of the neck. All patients were given ultrasound-guided SCPB anesthesia by the same anesthesiologist, LIA by the same surgeon, and surgery was performed under continuous Electrocardiogram (ECG) monitoring.

Results

Seven patients had stable vital signs and no significant postoperative complications. The results of this study indicated that SCPB anesthesia combined with LIA is a safe and effective anesthesia technique with a high success rate and patient tolerance.

Discussion

For patients with OMFS who have a risk for GA due to underlying diseases, ultrasound-guided cervical superficial plexus block anesthesia combined with LIA is a safe and effective alternative to conventional GA.
Commissioning of a novel gantry-less proton therapy system
Authors: Feldman Jon , Pryanichnikov Alexander , Achkienasi Alejandro , Polyansky Ilya , Hillman Yair , Raskin Stas , Blumenfeld Philip , Popovtzer Aron , Marash Michael
Published: November 2024

Purpose

The focus of this article is to describe the configuration, testing, and commissioning of a novel gantry-less synchrotron-based proton therapy (PT) facility.

Materials and methods

The described PT system delivers protons with a water equivalent range between 4 and 38 cm in 1800 energy layers. The fixed beam delivery permits a maximum field size of 28 × 30 cm2. The patient positioning and imaging system includes a six-degree-of-freedom robotic arm, a convertible patient chair, a vertical 4DCT, and an orthogonal 2D X-ray imaging system.

Results

The spot positioning reproducibility was consistent within ±1 mm. The width (σ) of the beam profile at the isocenter was energy dependent and ranged from 2.8 mm to 7.7 mm. Absolute dose reproducibility was measured and deviations were found to be <0.62% for all possible beam scenarios. The built-in dose monitoring system was successfully tested for its ability to generate interlocks under specific conditions (beam spot deviation ≥2 mm, individual spot dose ≥10% or ≥0.25 Gy, spot energy deviation ≥0.5 MeV). The robot positioning exhibited a consistent reproducibility within ±1 mm. All tested scenarios achieved laser-free initial 3D/3D image-guided positioning within ±5 mm. Subsequent 2D/3D positioning showed an accuracy of ±1 mm. A single 2D/3D image registration event corrected positions in all cases. Results of gamma analysis (3%, 3 mm) demonstrated pass rates greater than 95% for head and neck, thorax, abdomen treatment plans.

Conclusions

We report on the performance of a novel single-room gantry-less PT system comprised of a compact synchrotron and an adjustable (from nearly horizontal to almost vertical) patient positioning system. The commissioning results show high accuracy and reproducibility of the main proton beam parameters and the patient positioning system. The new PT facility started patient treatments in March 2023, which were the first in Israel and the Middle Eastern region.
Efficacy and safety of Toliparibumab for the treatment of non-small cell lung cancer: a systematic review and meta-analysis
Authors: Liu Yihao , Yang Liangyu , Duan Zhixuan , Cheng Qian , Liu Minghui , Zhang HongBing , Zhao HongLin
Published: November 2024

Purpose

This research intends to investigate the treatment of non-small cell lung cancer (NSCLC) using Toripalimab, focusing on its effectiveness and safety profile. Efficacy refers to the survival prognosis, while safety pertains to the occurrence of adverse events in our study. It also aims to provide reference information for neoadjuvant and postoperative therapies.

Methods

Up to March 20, 2024, studies on randomized controlled trials and single-arm trials involving Toripalimab for NSCLC were sourced from the Cochrane Library, Embase, PubMed, and Web of Science databases. Data extraction and analysis were independently conducted by two researchers utilizing Stata 15.0 and R software.

Results

A total of 8 studies were analyzed, including 6 single-arm studies and 2 randomized controlled trials (RCTs). Toripalimab treatment in the RCTs showed an overall survival (OS) of [HR=0.67, 95% CI (0.53, 0.85); p=0.71]. The objective response rate (ORR) from single-arm studies was reported as [ES=0.59, 95% CI (0.36, 0.81); p<0.01], and progression-free survival (PFS) was [ES=4.89, 95% CI (2.65, 9.02); p<0.01]. Furthermore, observed adverse effects included Anemia [OR=0.53, 95% CI (0.26, 0.79); p<0.01], Neutropenia [OR=0.43, 95% CI (0.20, 0.68); p<0.01], and Thrombocytopenia [OR=0.28, 95% CI (0.18, 0.43); p<0.01].

Conclusions

Toripalimab, being China’s first domestically developed anti-tumor PD-1 antibody drug, shows potential advantages over traditional chemotherapy in possibly prolonging patients’ survival times. However, the limited number of studies included indicates the need for additional single-arm and RCT studies to further validate these findings.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42024519806).
Orbital granular cell tumor involving the superior rectus muscle: a case report
Authors: Wang Pei , Han Zijian , Peng Li , Li Xiuhong , Yuan Hongfeng
Published: November 2024

Objective

The aim of this case report is to assess the clinicopathological characteristics and differential diagnosis of orbital granular cell tumor (GCT).

Methods

Clinical and imaging data of a rare case of orbital GCT involving the superior rectus muscle were collected. Its clinical characteristics, imaging, and histopathological features were observed.

Results

A 36-year-old female patient presented with a 2-year history of left eye proptosis. Magnetic resonance imaging (MRI) enhancement suggested a space-occupying lesion in the left superior rectus muscle region. On T1-weighted and T2-weighted MRI, the tumor was isointense to gray matter and significantly enhanced on the enhanced scan. Microscopic examination revealed that most tumor cells exhibited diffuse growth with unclear boundaries, and some cells were arranged in small nests. The tumor cells were large, with abundant, coarse eosinophilic granules in the cytoplasm. Occasional cells contained larger round eosinophilic droplets in the cytoplasm. Focal areas showed foamy cells, small and central round or oval nuclei with occasional nuclear enlargement and mild atypia, inconspicuous nucleoli, rare mitoses, and low proliferative activity. Immunohistochemistry results were Vimentin (+), S-100 (+), CD68 (+), Ki67 (2%+), Inhibin-a (−), CK (−), SMA (−), and Desmin (−). The pathological examination of a specimen harvested from the mass corresponded to a GCT.

Conclusion

Orbital GCT is rare and should be considered in the differential diagnosis of orbital tumors. It is essential to distinguish it from thyroid-associated ophthalmopathy, inflammatory pseudotumor, and myohemangioma. Definitive diagnosis requires a comprehensive analysis of clinical, histopathological, and immunohistochemical findings. Surgical excision is the primary treatment for orbital GCTs. For patients with incomplete tumor resection, close follow-up is necessary. Proton beam radiation therapy can be considered to prevent recurrence or metastasis if needed.
Uterine smooth muscle tumors of uncertain malignant potential: a 13-year retrospective study
Authors: Liu Liuliu , Xiao Zhendong , Li Zhiwen , Zheng Jinyu , Xu Xiaofeng , Zhou Huaijun
Published: November 2024

Objective

The primary objective of this study was to provide valuable evidence for the management of patients diagnosed with uterine smooth muscle tumors of uncertain malignant potential (STUMP), with a focus on those with reproductive aspirations.

Methods

We conducted a retrospective analysis of clinical and pathological data from the medical records and slides of STUMP patients treated at Drum Tower Hospital, affiliated with Nanjing University Medical School, from January 2009 to December 2021.

Results

Thirty-four patients were included in the study, with a median follow-up duration of 76 months (range: 13-157 months). After slide review, the diagnosis agreement rate was 77.3% (34/44 among initially considered cases). The consistency rate between our hospital’s diagnosis and those of other institutions was 75% (15/20). The accuracy rate of intraoperative frozen section diagnosis was low, at 21.4% (3/14). Half of the patients (17) underwent myomectomy, while the other half (17) received hysterectomy, including one subtotal hysterectomy. Two recurrences were observed (5.9%), one as STUMP and the other as leiomyosarcoma, with one recurrence in each surgical group. Notably, 4 of 9 patients with reproductive aspirations successfully underwent cesarean deliveries. Patients with single lesions appeared to exhibit potentially favorable fertility outcomes compared to those with multiple lesions.

Conclusion

The diagnosis of STUMP was difficult. Myomectomy potentially could serve as an alternative for patients with reproductive needs. In selected cases with single lesions, it may indicate potentially favorable fertility outcomes.
Conformal proctectomy with sphincter preservation retains acceptable defecation functions in very low rectal cancer male patients
Authors: Chen Weijie , Zhang Xiao , Qiu Xiaoyuan , Zhou Jiaolin , Lin Guole
Published: November 2024

Background

Conformal proctectomy with sphincter preservation (CPSP) is designed to preserve the rectal wall as much as possible in very low rectal cancer patients. Evaluations of anal function and quality of life outcomes are lacking.

Methods

This study included male patients with very low (≤ 5 cm from the anal verge) rectal adenocarcinoma between January 1, 2020, and January 1, 2022. A LARS score questionnaire survey and EORTC-QLQ-CR38 questionnaire survey were administered.

Results

A total of 21 very low rectal cancer patients were enrolled in follow-up. The average age of the patients was 56.7 years, the tumors were 1.9 ± 0.6 cm in size, and the distance from the anal verge was 4.8 ± 0.5 cm. All patients were followed up, and the mean follow-up period was 2.7 ± 0.5 years. The LARS score increased significantly from 4.1 ± 2.8 before surgery to 19.1 ± 6.0 at the 1st year after surgery (P < 0.001) and then decreased to 13.1 ± 4.2 (P < 0.001) at the 2nd year. The quality of life of patients was also lower at the 1st year after surgery (61.1 ± 9.6 vs. 74.2 ± 11.2, P < 0.001) and was restored at the 2nd year after surgery (80.6 ± 11.9 vs. 74.2 ± 11.2, P = 0.029). During standard follow-up at the outpatient department, no rectal tumor relapse was confirmed in these patients, although 2 patients were found to have suspected recurrence of local lymph node metastasis.

Conclusions

These results suggest that the CPSP technique preserves acceptable defecation function and is a safe and feasible option for male patients with very low rectal cancer.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR2100052094.