bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline immunoglobulin G and immune function in non-Hodgkin lymphoma: a retrospective analysis
Authors: Brazel Danielle , Grant Christopher , Cabal Angelo , Chen Wen-Pin , Pinter-Brown Lauren
Published: April 2024

Introduction

Non-Hodgkin’s lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin’s lymphomas, though it is not known how this applies across all B-cell lymphoid malignancies.

Methods

We conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution.

Results

Two-hundred twenty-three adults (aged = 18 years) with available pre-treatment IgG levels were selected, with hypogammaglobulinemia defined as IgG< 500 mg/mL. For this analysis, we grouped DLBCL (n=90), Primary CNS (n=5), and Burkitt lymphoma (n=1) together as high-grade, while CLL (n=52), mantle cell (n=20), marginal zone (n=25), follicular (n=21), and Waldenstrom macroglobulinemia (n=5) were low-grade. The incidence of hypogammaglobulinemia in our cohort of both high and low-grade lymphoma patients was 13.5% (n=30). Across all NHL subtypes, individuals with baseline IgG< 500 mg/dL showed an increased rate of hospitalization (4.453, CI: 1.955-10.54, p= 0.0005) and higher mortality (3.325, CI: 1.258, 8.491, p= 0.013), yet no association in number of infections when compared with those with IgG=500 mg/dL. There was a higher hospitalization rate (3.237, CI: 1.77-6.051, p=0.0017) in those with high-grade lymphoma with hypogammaglobulinemia when compared with low-grade. There was no statistically significant difference in individuals who were alive after three years in those with baseline IgG<500 mg/dL.

Discussion

Our study is the first to analyze incidence of hypogammaglobulinemia at the time of diagnosis of NHL as a potential biomarker of interest for future outcomes including hospitalization and infection.
Green tea extract suppresses airway inflammation via oxidative stress-driven MAPKs/MMP-9 signaling in asthmatic mice and human airway epithelial cells
Authors: Kim Jeong-Won , Kim Jin-Hwa , Jeong Ji-Soo , Kim Chang-Yeop , Chung Eun-Hye , Kim Sung-Hwan , Hong Eui-Ju , Kwon Hyo-Jung , Ko Je-Won , Kim Tae-Won
Published: April 2024

Introduction

The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated.

Methods

To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors.

Results

The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)‐13, IL-5, and IL‐4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase‐9 activity and protein levels.

Conclusion

GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.
Predictive biomarkers and initial analysis of maternal immune alterations in postpartum preeclampsia reveal an immune-driven pathology
Authors: Couture Camille , Brien Marie-Eve , Rechtzigel Jade , Ling SuYun , Ledezma-Soto Cecilia , Duran Bishop Gilberto , Boufaied Ines , Dal Soglio Dorothée , Rey Evelyne , McGraw Serge , Graham Charles H. , Girard Sylvie
Published: April 2024

Introduction

Postpartum preeclampsia (PPPE) is an under-diagnosed condition, developing within 48 hours to 6 weeks following an uncomplicated pregnancy. The etiology of PPPE is still unknown, leaving patients vulnerable and making the identification and treatment of patients requiring postpartum care an unmet need. We aimed to understand the immune contribution to PPPE at the time of diagnosis, as well as uncover the predictive potential of perinatal biomarkers for the early postnatal identification of high-risk patients.

Methods

Placentas were collected at delivery from uncomplicated pregnancies (CTL) and PPPE patients for immunohistochemistry analysis. In this initial study, blood samples in PPPE patients were collected at the time of PPPE diagnosis (48h-25 days postpartum; mean 7.4 days) and compared to CTL blood samples taken 24h after delivery. Single-cell transcriptomics, flow cytometry, intracellular cytokine staining, and the circulating levels of inflammatory mediators were evaluated in the blood.

Results

Placental CD163+ cells and 1st trimester blood pressures can be valuable non-invasive and predictive biomarkers of PPPE with strong clinical application prospects. Furthermore, changes in immune cell populations, as well as cytokine production by CD14+, CD4+, and CD8+ cells, suggested a dampened response with an exhausted phenotype including decreased IL1β, IL12, and IFNγ as well as elevated IL10.

Discussion

Understanding maternal immune changes at the time of diagnosis and prenatally within the placenta in our sizable cohort will serve as groundwork for pre-clinical and clinical research, as well as guiding clinical practice for example in the development of immune-targeted therapies, and early postnatal identification of patients who would benefit from more thorough follow-ups and risk education in the weeks following an uncomplicated pregnancy.
Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis
Authors: Dekeyser Cathérine , De Kesel Pieter , Cambron Melissa , Vanopdenbosch Ludo , Van Hijfte Liesbeth , Vercammen Martine , Laureys Guy
Published: April 2024

Background

Cerebrospinal fluid (CSF) kappa free light chain (κFLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal κFLC parameter for identifying MS remains a subject of ongoing debate.

Objectives

The aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods.

Methods

Paired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite®-Optilite (Sint-Jan Bruges hospital) and N Latex®-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis.

Results

A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite®-Optilite: 7.7; N Latex®-BNII: 4.71), κIgG index (Freelite®-Optilite: 14.15, N Latex®-BNII: 12.19), and CSF κFLC/IgG ratio (Freelite®-Optilite: 2.27; N Latex®-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite®-Optilite) versus 94.6% (N Latex®-BNII) for the κFLC index, 91% (Freelite®-Optilite) versus 92.2% (N Latex®-BNII) for the κIgG index, and 81.3% (Freelite®-Optilite) versus 91.4% (N Latex®-BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite®-Optilite and 90.5% for N Latex®-BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite®-Optilite: 0.924; N Latex®-BNII: 0.962] and κIgG index (AUC Freelite®-Optilite: 0.929; N Latex®-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%).

Conclusions

The κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures.
Adverse events associated with immune checkpoint inhibitors in non-small cell lung cancer: a safety analysis of clinical trials and FDA pharmacovigilance system
Authors: Liang Xueyan , Xiao Hewei , Li Huijuan , Chen Xiaoyu , Li Yan
Published: April 2024

Objectives

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). This study was to evaluate both the irAEs and trAEs of different ICI strategies for NSCLC based on randomized clinical trials (RCTs). The study also examined real-world pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) regarding claimed ICI-associated AEs in clinical practice.

Methods

Based on Pubmed, Embase, Medline, and the Cochrane CENTRAL, we retrieved RCTs comparing ICIs with chemotherapy drugs or with different ICI regimens for the treatment of NSCLC up to October 20, 2023. Bayesian network meta-analysis (NMA) was performed using odds ratios (ORs) with 95% credible intervals (95%CrI). Separately, a retrospective pharmacovigilance study was performed based on FAERS database, extracting ICI-associated AEs in NSCLC patients between the first quarter (Q1) of 2004 and Q4 of 2023. The proportional reports reporting odds ratio was calculated to analyze the disproportionality.

Results

The NMA included 51 RCTs that involved a total of 26,958 patients with NSCLC. Based on the lowest risk of any trAEs, cemiplimab, tislelizumab, and durvalumab were ranked as the best. Among the agents associated with the lowest risk of grades 3-5 trAEs, tislelizumab, avelumab, and nivolumab were most likely to rank highest. As far as any or grades 3-5 irAEs are concerned, atezolizumab plus bevacizumab plus chemotherapy is considered the most safety option. However, it is associated with a high risk of grades 3-5 trAEs. As a result of FAERS pharmacovigilance data analysis, 9,420 AEs cases have been identified in 7,339 NSCLC patients treated with ICIs, and ICIs were related to statistically significant positive signal with 311 preferred terms (PTs), and comprehensively investigated and identified those AEs highly associated with ICIs. In total, 152 significant signals were associated with Nivolumab, with malignant neoplasm progression, death, and hypothyroidism being the most frequent PTs.

Conclusion

These findings revealed that ICIs differed in their safety profile. ICI treatment strategies can be improved and preventive methods can be developed for NSCLC patients based on our results.
Bioremoval of Co(II) by a novel halotolerant microalgae Dunaliella sp. FACHB-558 from saltwater
Authors: Liu Chenglong , Wen Xueer , Pan Huiqiao , Luo Ying , Zhou Junyang , Wu Yuzhe , Zeng Zhiyong , Sun Ting , Chen Jun , Hu Zhangli , Lou Sulin , Li Hui
Published: April 2024

Cobalt pollution is harmful to both the aquatic ecosystem and human health. As the primary producer of aquatic ecosystems in hypersaline environments, unicellular planktonic Dunaliella microalgae is considered to be a low-energy and eco-friendly biosorbent that removes excess cobalt and enhances the vitality of coastal and marine ecosystems. In this study, we found that the halotolerant microalga named Dunaliella sp. FACHB-558 could grow under a salinity condition with 0.5–4.5 M NaCl. A phylogenetic analysis based on the rbcL gene revealed that Dunaliella sp. FACHB-558 is a close relative of Dunaliella primolecta TS-3. At lab-scale culture, Dunaliella sp. FACHB-558 exhibited high tolerance to heavy metal stresses, including cobalt, nickel, and cadmium. Treatment with 60 μM cobalt delayed its stationary phase but ultimately led to a higher population density. Furthermore, Dunaliella sp. FACHB-558 has the ability to adsorb the cobalt ions in the aquatic environment, which was evidenced by the decreased amount of cobalt in the culture medium. In addition, the tolerance of Dunaliella sp. FACHB-558 to cobalt stress was correlated with enhanced nitric oxide content and peroxidase activity. The autophagy inhibitor 3-MA enhanced nitric oxide burst, increased peroxidase activity, and accelerated the bioremoval of cobalt, suggesting that the autophagy pathway played a negative role in response to cobalt stress in Dunaliella sp. FACHB-558. In summary, our study identified a novel microalga possessing high cobalt tolerance and provided a promising natural biosorbent for the research and application of heavy metal bioremediation technology.
DTDNet: Dynamic Target Driven Network for pedestrian trajectory prediction
Authors: Liu Shaohua , Sun Jingkai , Yao Pengfei , Zhu Yinglong , Mao Tianlu , Wang Zhaoqi
Published: April 2024

Predicting the trajectories of pedestrians is an important and difficult task for many applications, such as robot navigation and autonomous driving. Most of the existing methods believe that an accurate prediction of the pedestrian intention can improve the prediction quality. These works tend to predict a fixed destination coordinate as the agent intention and predict the future trajectory accordingly. However, in the process of moving, the intention of a pedestrian could be a definite location or a general direction and area, and may change dynamically with the changes of surrounding. Thus, regarding the agent intention as a fixed 2-d coordinate is insufficient to improve the future trajectory prediction. To address this problem, we propose Dynamic Target Driven Network for pedestrian trajectory prediction (DTDNet), which employs a multi-precision pedestrian intention analysis module to capture this dynamic. To ensure that this extracted feature contains comprehensive intention information, we design three sub-tasks: predicting coarse-precision endpoint coordinate, predicting fine-precision endpoint coordinate and scoring scene sub-regions. In addition, we propose a original multi-precision trajectory data extraction method to achieve multi-resolution representation of future intention and make it easier to extract local scene information. We compare our model with previous methods on two publicly available datasets (ETH-UCY and Stanford Drone Dataset). The experimental results show that our DTDNet achieves better trajectory prediction performance, and conducts better pedestrian intention feature representation.
Non-motor symptoms associated with progressive loss of dopaminergic neurons in a mouse model of Parkinson’s disease
Authors: Radlicka-Borysewska Anna , Jabłońska Judyta , Lenarczyk Michał , Szumiec Łukasz , Harda Zofia , Bagińska Monika , Barut Justyna , Pera Joanna , Kreiner Grzegorz , Wójcik Daniel K. , Rodriguez Parkitna Jan
Published: April 2024

Parkinson’s disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse non-motor symptoms that may develop in parallel or precede motor dysfunctions, ranging from autonomic system dysfunctions and impaired sensory perception to cognitive deficits and depression. Here, we examine the role of the progressive loss of dopaminergic transmission in behaviors related to the non-motor symptoms of PD in a mouse model of the disease (the TIF-IADATCreERT2 strain). We found that in the period from 5 to 12 weeks after the induction of a gradual loss of dopaminergic neurons, mild motor symptoms became detectable, including changes in the distance between paws while standing as well as the swing speed and step sequence. Male mutant mice showed no apparent changes in olfactory acuity, no anhedonia-like behaviors, and normal learning in an instrumental task; however, a pronounced increase in the number of operant responses performed was noted. Similarly, female mice with progressive dopaminergic neuron degeneration showed normal learning in the probabilistic reversal learning task and no loss of sweet-taste preference, but again, a robustly higher number of choices were performed in the task. In both males and females, the higher number of instrumental responses did not affect the accuracy or the fraction of rewarded responses. Taken together, these data reveal discrete, dopamine-dependent non-motor symptoms that emerge in the early stages of dopaminergic neuron degeneration.
Large-scale production of non-conventional edible plants for biodiverse school meals
Authors: Ranieri Guilherme Reis , Madeira Nuno Rodrigo , Slater Betzabeth , de Toledo Marchesi Mariana , Delgado de Oliveira Maria Angela , Badue Ana Flávia Borges , Mauad Thais
Published: April 2024

Introduction

School feeding programs are important for ensuring food security and promoting child health and development, particularly in low-income countries. In view of this importance, it is possible to increase the quality of these meals by diversifying the vegetables offered and incorporating underutilized plants to improve dietary diversity and nutritional quality into school meals.

Methods

This study was carried out using the action research methodology following the implementation and development of the “Inova na Horta” project in the city of Jundiaí, São Paulo, Brazil. The project was based on the existing and functioning physical and organizational structure of a municipal organic farm. Vegetables were selected from among 210 non-conventional species and varieties, which were further selected for continuous production based on 8 nutritional, culinary and cultivation criteria.

Results

Thirty-four vegetables were selected for continuous cultivation and provisions to the school kitchens. Nine tons of vegetables were produced and provided to 90 municipal schools from 2020–2023. Leafy vegetables accounted for most the production, with a total weight of 6441 kg corresponding to 71.6% of the total harvest. Kitchen teams were trained throughout the project duration.

Discussion

The feasibility of the production and culinary use of 34 biodiverse, nutrient-rich and underutilized food vegetables for school meals was demonstrated. The selected vegetables are nutrient-rich and contain higher amounts of minerals and proteins than the control vegetables (conventional vegetables), thus complementing several nutrients in school meals. This methodology can be replicated by municipalities of various sizes as a public policy of food and nutritional security associated with the valorization of local biodiversity.
Polysaccharides from Russula: a review on extraction, purification, and bioactivities
Authors: Cheng Yan , Gan Jian , Yan Bowen , Wang Peng , Wu Hao , Huang Caoxing
Published: April 2024

Russula, a renowned edible fungus, has gained popularity as a functional food among diverse populations due to the abundant presence of amino acids, proteins, and polysaccharides. As the primary constituents of Russula, polysaccharides exhibit a wide range of biological properties, making them an exceptional choice for incorporation into food, medicines, and diverse biotechnological applications. This review provides a summary of the recent research on the extraction, purification, and biological applications of polysaccharides from various Russula spp. Currently, there are many advanced extraction technologies, such as hot water-based extraction, alkali-based extraction, ultrasonic-assisted extraction and microwave-assisted extraction. Hence, the latest progress of extraction technologies, as well as their advantages and limitations will be discusses and summarizes in this review. The separation and purification methods of polysaccharide from Russula were introduced, including ethanol precipitation, deproteinization and gel filtration chromatography. It also focuses on exploring the diverse bioactive capabilities of Russula, including anti-oxidant, anti-tumor, immunomodulatory, anti-inflammation, and anti-bacterial properties. Hence, this review aims to foster a comprehensive understanding of the polysaccharides from various Russula spp. and pave the way for their promising and potential future applications in the medical and functional fields.
Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer
Authors: Li Zhen-Hao , Xu Ting , Zhang Ya-Juan , Jiang Jing-Hang , Mi Yu-Ze , Li Jia-Xuan , Shen Jing , Fu Yi-Rui , Qin Bo-Ying , Lin Fan , Fu Dong-Jing , Yue Mei-Jin , Ma Shu-Mei , Li Quan-Fu
Published: April 2024

Objectives

In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects.

Methods

Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health.

Results

Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group.

Conclusions

Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.
Bibliometric and visualization analyses of cancer-related fatigue research published worldwide from 2001 to 2023
Authors: Li Peijin , Wang Qian , Feng Li , Ding Zhiguo , Fan Weijing
Published: April 2024

Objective

Cancer seriously endangers human health and represents a global public health issue. Cancer-related fatigue (CRF) is a distressing and persistent sense of exhaustion caused by cancer or cancer treatment, widely prevalent among cancer patients. This study aims to summarize emerging trends and provide directions for future research of CRF through bibliometric and visualization analyses.

Methods

A systematic search in the Web of Science Core Collection database from 2001-01-01 to 2023-05-18 were conducted. Only reviews and articles written in English were considered. CiteSpace and the R were used for bibliometric and visualization analyses.

Results

The analysis revealed that 2,566 studies on CRF have been published by 1,041 institutions in 70 countries so far. The number of articles published and cited annually have been steadily increasing. Eduardo Bruera published the most articles, and Julienne E Bower is the most co-cited author. The University of Texas System is the leading institution in cancer-related fatigue research. The United States and China have the largest number of publications. Supportive Care in Cancer published the most articles, and Journal of Clinical Oncology is the most co-cited journal. “Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis”, authored by Mustian KM et al. and published in JAMA Oncology was the most co-cited document. Keyword analysis indicated that research focus had shifted from “epoetin alpha” and “anemia” to “risk factors”, “systematic review”, “acupuncture”, “anxiety”, “traditional Chinese medicine” and “guidelines”.

Conclusion

In conclusion, this analysis provides comprehensive research trends and knowledge network maps of CRF. Clinical physicians should concurrently focus on the anemia, insomnia, anxiety, and depression status of patients when assessing or managing CRF. Improvements in related risk factors also contribute to alleviating fatigue. Furthermore, it is essential to pay attention to authoritative CRF guidelines. Acupuncture and traditional Chinese medicine also have therapeutic potential, which merits further investigation. Researchers should draw attention to the crucial roles of inflammation, hypoxia, and mitochondrial dysfunction, which could be the frontiers.
In silico evaluation of anti-colorectal cancer inhibitors by Resveratrol derivatives targeting Armadillo repeats domain of APC: molecular docking and molecular dynamics simulation
Authors: Akash Shopnil , Islam Md. Rezaul , Bhuiyan Abdul Ali , Islam Mirza Nafeul , Bayıl Imren , Saleem Rasha Mohammed , Albadrani Ghadeer M. , Al-Ghadi Muath Q. , Abdel-Daim Mohamed M.
Published: April 2024

Colorectal cancer is the second leading cause of cancer-related deaths. In 2018, there were an estimated 1.8 million cases, and this number is expected to increase to 2.2 million by 2030. Despite its prevalence, the current therapeutic option has a lot of side effects and limitations. Therefore, this study was designed to employ a computational approach for the identification of anti-cancer inhibitors against colorectal cancer using Resveratrol derivatives. Initially, the pass prediction spectrum of 50 derivatives was conducted and selected top seven compounds based on the maximum pass prediction score. After that, a comprehensive analysis, including Lipinski Rule, pharmacokinetics, ADMET profile study, molecular orbitals analysis, molecular docking, molecular dynamic simulations, and MM-PBSA binding free energy calculations. The reported binding affinity ranges of Resveratrol derivatives from molecular docking were -6.1 kcal/mol to -7.9 kcal/mol against the targeted receptor of human armadillo repeats domain of adenomatous polyposis coli (APC) (PDB ID: 3NMW). Specifically, our findings reported that two compounds [(03) Resveratrol 3-beta-mono-D-glucoside, and (29) Resveratrol 3-Glucoside] displayed the highest level of effectiveness compared to all other derivatives (-7.7 kcal/mol and -7.9 kcal/mol), and favorable drug-likeness, and exceptional safety profiles. Importantly, almost all the molecules were reported as free from toxic effects. Subsequently, molecular dynamic simulations conducted over 100ns confirmed the stability of the top two ligand-protein complexes. These findings suggest that Resveratrol derivatives may be effective drug candidate to manage the colorectal cancer. However, further experimental research, such as in vitro/in vivo studies, is essential to validate these computational findings and confirm their practical value.
The clinical effect of gratitude extension-construction theory nursing program on bladder cancer patients with fear of cancer recurrence
Authors: Qian Liping , Zhang Yin , Chen Hui , Pang Yuan , Wang Chenchen , Wang Liangmei , Zhang Xiaoqing
Published: April 2024

Objective

To explore the clinical effect of bladder cancer patients with Fear of Cancer Recurrence (FCR) after applying the gratitude extension construction theory nursing program.

Methods

168 patients with bladder cancer hospitalized in the Department of Urology from December 2021 to June 2023 in a hospital are study subjects. The experimental subjects are uniformly designed as an experimental group and a control group, with 52 participants in each group. The former receives routine nursing care, while the later receives nursing interventions based on gratitude extension construction theory. The baseline data, Quality of life Questionnaire-core 30, Quality of Life Questionnaire-non Invasive Bladder Cancer 24, Fear of Progression Questionnaire-Short Form, gratitude level questionnaire, Self-Rating Depression Scale, Self-rating Anxiety Scale, patient compliance behavior score, Overall Survival, and Progression-free Survival are evaluated.

Results

The basic data revealed no statistical significance. The quality of life questionnaire-core 30 and quality of life questionnaire-noninvasive bladder cancer 24 was no significant difference before treatment and after treatment for 1 month. After 9 months, There was a significant difference in pre-treatment scores. The experimental group had no significant difference before and after treatment. For the overall survival rates, the two groups were 67.25% and 79.56%. The progression-free survival rates were 56.35% and 72.35%, respectively, with statistical difference. The compliance rates were 86.54% and 98.08%. The compliance rate of the experimental group exceeded the control group. After 3, 6, and 12 months, the gratitude level questionnaire score and the fear of progression questionnaire-short form in the experimental group were improved. After 3, 6, and 12 months, the control group had no statistically significant difference in the gratitude level questionnaire and the fear of progression questionnaire-short form scores. Compared with the control group, the scores on the gratitude level questionnaire and the fear of progression questionnaire-short form were significantly higher after 3, 6, and 12 months of intervention.

Conclusion

After applying the gratitude extension construction theory nursing program, the FCR of bladder cancer patients is significantly reduced. The quality of life and compliance rate are significantly improved, and anxiety and depression are relieved.
Beyond clinical trials: real-world impact of immunotherapy on NSCLC in Jordan
Authors: Abu Hejleh Taher , AlSawalha Karim , Abdel Hafiz Sufian , Al-Batsh Tamer , Abu Hejleh Roaa , Yaser Sameer , Abu Jazar Husam , Khader Jamal , Alnsour Anoud , Mohamad Issa , Abdel Jalil Riad , Abu-Shanab Ahmad , Gharaibeh Azza , Abu Shattal Mohammad , Alibraheem Akram , Haddad Hussam , Mahmoud Naser , Obeidat Shadi , Al-Jaghbeer Mohammed J. , Furqan Muhammad , Cortellini Alessio , Velcheti Vamsidhar , Al-rabi Kamal
Published: April 2024

Background

This study aims to evaluate real-world (rw) outcomes of immunotherapy (IO) for advanced stage NSCLC at King Hussein Cancer Center (KHCC) in Jordan.

Methods

Advanced stage NSCLC patients who received IO at KHCC between 2017 and 2022 were included. The data were retrospectively collected. PFS and OS were estimated for patients with ECOG performance status (ECOG PS) 0-1. Cox regression analyzed predictors of OS in first-line (1L) IO, regardless of performance status.

Results

The total number of patients included was 244. Out of those, 160 (65%), 67 (28%), and 17 (7%) patients received IO as 1L, second-line (2L), or third-line or beyond (3L or beyond), respectively. The median age for all patients was 59 years. Male were 88%, and 77% were smokers. The median follow-up time was 12.5 months. The median PFS and OS for 1L IO were 7 [95% CI 5.8 – 10.3] and 11.8 [95% CI 8.8 – 14.4], months, respectively. In the first 3 months after starting 1L IO, 34/160 (21%) patients had died. For those who survived beyond 3 months after starting 1L IO, the median PFS and OS were 11.3 [95% CI 8.3 – 16.5] and 15.4 [95% CI 13.2 – 21] months, respectively. In the Cox regression model of 1L IO patients with any performance status, ECOG PS 2 was predictive of worse OS compared to ECOG PS 0-1 (p= 0.005).

Conclusion

This real-world study of advanced-stage NSCLC patients treated with immunotherapy at KHCC reveals outcomes that fall short of those anticipated from clinical trials. The inclusion of Middle Eastern patients in lung cancer trials is essential to ensure adequate representation of various ethnicities in clinical research.
Development and verification of machine learning model based on anogenital distance, penoscrotal distance, and 2D:4D finger ratio before puberty to predict hypospadias classification
Authors: He Zirong , Yang Bo , Tang Yunman , Wang Xuejun
Published: April 2024

Objectives

To describe the anatomical abnormalities of hypospadias before puberty using current commonly used anthropometric index data and predict postoperative diagnostic classification.

Methods

Children with hypospadias before puberty who were initially treated at Sichuan Provincial People's Hospital from April 2021 to September 2022 were selected. We recorded their preoperative penoscrotal distance, anogenital distance, 2D:4D finger ratio, and postoperative hypospadias classification. The receiver operating character curve was used for univariate analysis of the diagnostic predictive value of each index for hypospadias classification in the training set. Binary logistic regression, random forest, and support vector machine models were constructed. In addition, we also prospectively collected data from October 2022 to September 2023 as a test set to verify the constructed machine learning models.

Results

This study included 389 cases, with 50 distal, 167 midshaft, and 172 proximal cases. In the validation set, the sensitivity of the binary LR, RF, and SVM was 17%, 17% and 0% for identifying the distal type, 61%, 55% and 64% for identifying the midshaft type, and 56%, 60% and 48% for identifying the proximal type, respectively. The sensitivity of the three-classification RF and SVM models was 17% and 17% for distal type, 64% and 73% for midshaft type, 60% and 60% for proximal type, respectively. In the Testing set, the sensitivity of the binary LR, RF and SVM was 6%, 0% and 0% for identifying the distal type, 64%, 55% and 66% for identifying the midshaft type, and 48%, 62% and 39% for identifying the proximal type, respectively. The sensitivity of the three-classification RF and SVM models was 12% and 0% for distal type, 57% and 77% for midshaft type, and 65% and 53% for proximal type, respectively. Compared with binary classification models, the sensitivity of the three-classification models for distal type was not improved.

Conclusion

Anogenital distance and penoscrotal distance have a favorable predictive value for midshaft and proximal hypospadias, among which AGD2, with higher test efficiency and stability, is recommended as the preferred anogenital distance indicator. The 2D:4D finger ratio (RadioL, RadioR) has little predictive value for hypospadias classification.
Necrotizing enterocolitis: a potential protective role for intestinal alkaline phosphatase as lipopolysaccharide detoxifying enzyme
Authors: Martins Raquel Dos Santos , Hulscher Jan B. F. , Timmer Albert , Kooi Elisabeth M. W. , Poelstra Klaas
Published: April 2024

Introduction

Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease. Its onset might be triggered by Toll-Like Receptor 4 (TLR4) activation via bacterial lipopolysaccharide (LPS). We hypothesize that a deficiency of intestinal alkaline phosphatase (IAP), an enzyme secreted by enterocytes that dephosphorylates LPS, may contribute to NEC development.

Methods

In this prospective pilot study, we analyzed intestinal resection specimens from surgical NEC patients, and from patients undergoing Roux-Y reconstruction for hepatobiliary disease as controls. We assessed IAP activity via enzymatic stainings and assays and explored IAP and TLR4 co-localization through immunofluorescence.

Results

The study population consisted of five NEC patients (two Bell's stage IIb and three-stage IIIb, median (IQR) gestational age 25 (24–28) weeks, postmenstrual age at diagnosis 28 (26–31) weeks) and 11 controls (unknown age). There was significantly lower IAP staining in NEC resection specimens [49 (41–50) U/g of protein] compared to controls [115 (76–144), P = 0.03]. LPS-dephosphorylating activity was also lower in NEC patients [0.06 (0–0.1)] than in controls [0.3 (0.2–0.5), P = 0.003]. Furthermore, we observed colocalization of IAP and TLR4 in NEC resection specimens.

Conclusion

This study suggests a significantly lower IAP level in resection specimens of NEC patients compared to controls. This lower IAP activity suggests a potential role of IAP as a protective agent in the gut, which needs further confirmation in larger cohorts.
Apigenin protects against ischemic stroke by increasing DNA repair
Authors: Ping Niu , Zuo Kuiyang , Cai Jiahan , Rong Chunshu , Yu Ziqiao , Zhang Xu , Wang Gaihua , Ma Chunyu , Yang Huirong , Li Jinhua , Wang Xu , Zhao Dexi
Published: April 2024

Background and Objective

Oxidative stress is an important pathological process in ischemic stroke (IS). Apigenin (APG) is a natural product with favorable antioxidative effects, and some studies have already demonstrated the antioxidative mechanism of APG in the treatment of IS. However, the mechanism of APG on DNA damage and repair after IS is not clear. The aim of this study was to investigate the mechanism of APG on DNA repair after IS.

Methods

Male Sprague-Dawley rats were used to establish a model of permanent middle cerebral artery occlusion (pMCAO) on one side, and were pre-treated with gavage of APG (30, 60, or 120 mg/kg) for 7 days. One day after pMCAO, the brain tissues were collected. Cerebral infarct volume, brain water content, HE staining and antioxidant index were analyzed to evaluated the brain damage. Molecular Docking, molecular dynamics (MD) simulation, immunohistochemistry, and Western blot were used to explore the potential proteins related to DNA damage repair.

Results

APG has a low binding score with DNA repair-related proteins. APG treatment has improved the volume of cerebral infarction and neurological deficits, reduced brain edema, and decreased parthanatos and apoptosis by inhibiting PARP1/AIF pathway. In addition, APG improved the antioxidative capacity through reducing reactive oxygen species and malondialdehyde, and increasing glutathione and superoxide dismutase. Also, APG has reduced DNA damage- and cell death-related proteins such as PARP1, γH2A.X, 53BP1, AIF, cleaved caspase3, Cytochrome c, and increased DNA repair by BRCA1 and RAD51 through homologous recombination repair, and reduced non-homologous end link repair by KU70.

Conclusion

APG can improve nerve damage after IS, and these protective effects were realized by reducing oxidative stress and DNA damage, and improving DNA repair.
Codonopsis radix: a review of resource utilisation, postharvest processing, quality assessment, and its polysaccharide composition
Authors: Liang Wei , Sun Jiachen , Bai Gang , Qiu Daiyu , Li Qian , Dong Pengbin , Chen Yuan , Guo Fengxia
Published: April 2024

Codonopsis radix is the dried root of C. pilosula (Franch.) Nannf., C. pilosula Nannf. var. modesta (Nannf.) L. T. Shen, or C. tangshen Oliv., constitutes a botanical medicine with a profound historical lineage. It encompasses an array of bioactive constituents, including polyacetylenes, phenylpropanoids, alkaloids, triterpenoids, and polysaccharides, conferring upon it substantial medicinal and edible values. Consequently, it has garnered widespread attention from numerous scholars. In recent years, driven by advancements in modern traditional Chinese medicine, considerable strides have been taken in exploring resources utilization, traditional processing, quality evaluation and polysaccharide research of Codonopsis radix. However, there is a lack of systematic and comprehensive reporting on these research results. This paper provides a summary of recent advances in Codonopsis research, identifies existing issues in Codonopsis studies, and offers insights into future research directions. The aim is to provide insights and literature support for forthcoming investigations into Codonopsis.
Generation and analysis of the chaos phenomenon in the molecular-distillation-Navier–Stokes (MDNS) nonlinear system
Authors: Qin Wei , Li Hui , Jiang Zhiyu , Luo Mingyue , Cong Shuofeng
Published: April 2024

Introduction: For the Navier-Stokes equation, one of the most essential tasks should be to study its completeness of the complex nonlinear systems. Also, its nature and physical practical applications would be depth explored. Moreover, as one of the routes to chaos, this equation with an external force has been investigated numerically in 1989. Recently, some information is worth noting that when the high symmetry was imposed on the velocity field, the complex nonlinear motions should occur even lead to the chaos phenomenon. However, most of the published papers are based on theoretical studies and rarely deal with the above results, which lost of the match between them and the integrity of the scientific system.

Methods: This study analyzed the molecular distillation process in detail based on the basic theory of nonlinear chaotic systems. Then, the mathematical model for the process of molecular distillation with one brushless DC motor (BLDCM) is built and named the Molecular-Distillation-Navier-Stokes (MDNS) equation. Also, its complex and potentially chaotic behaviors and chaotic processes are first discovered and demonstrated, such as chaotic attractors, chaotic co-attractors, phase portraits, time-domain waveforms, Lyapunov exponent spectrums, Poincare maps, the bifurcation diagrams, and so on.

Results: The good agreement among theoretical analysis, simulation and experimental results verifies the practicability and flexibility of the configured model.

Discussion: The related conclusions have supplemented and improved the theoretical system for the Navier Stokes equations. Also, it reflects the significance in molecular distillation processes. Meanwhile, the novel research direction for the fields of the chaotic nonlinear and complex industrial systems have been explored and discovered.
Ecophysiological responses of Phragmites australis populations to a tidal flat gradient in the Yangtze River Estuary, China
Authors: Jia Jing , Zhao Xiaochao , Jia Peng , Zhang Xin , Li Dezhi , Liu Yongfeng , Huang Liping
Published: April 2024

Phragmites australis is a prevalent species in the Chongming Dongtan wetland and is capable of thriving in various tidal flat environments, including high salinity habitats. P. australis population displays inconsistent ecological performances, highlighting the need to uncover their survival strategies and mechanisms in tidal flats with diverse soil salinities. Upon comparing functional traits of P. australis at multiple tidal flats (low, middle, and high) and their responses to soil physicochemical properties, this study aimed to clarify the salt-tolerant strategy of P. australis and the corresponding mechanisms. These results showed that leaf characteristics, such as specific leaf area and leaf dry matter content, demonstrated more robust stability to soil salinity than shoot height and dry weight. Furthermore, as salt stress intensified, the activities of superoxide dismutase (SOD), catalase (CAT) and peroxisome (POD) in P. australis leaves at low tidal flat exhibited an increased upward trend compared to those at other tidal flats. The molecular mechanism of salt tolerance in Phragmites australis across various habitats was investigated using transcriptome sequencing. Weighted correlation network analysis (WGCNA) combined with differentially expressed genes (DEGs) screened out 3 modules closely related to high salt tolerance and identified 105 core genes crucial for high salt tolerance. Further research was carried out on the few degraded populations at low tidal flat, and 25 core genes were identified by combining WGCNA and DEGs. A decrease in the activity of ferroptosis marker gonyautoxin-4 and an increase in the content of Fe3+ in the degenerated group were observed, indicating that ferroptosis might participate in degradation. Furthermore, correlation analysis indicated a possible regulatory network between salt tolerance and ferroptosis. In short, this study provided new insights into the salt tolerance mechanism of P. australis population along tidal flats.
Identification and expression profiling of GAPDH family genes involved in response to Sclerotinia sclerotiorum infection and phytohormones in Brassica napus
Authors: Xu Jing , Wang Rongbo , Zhang Xiong , Zhuang Wei , Zhang Yang , Lin Jianxin , Zhan Penglin , Chen Shanhu , Lu Heding , Wang Airong , Liao Changjian
Published: April 2024

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a crucial enzyme in glycolysis, an essential metabolic pathway for carbohydrate metabolism across all living organisms. Recent research indicates that phosphorylating GAPDH exhibits various moonlighting functions, contributing to plant growth and development, autophagy, drought tolerance, salt tolerance, and bacterial/viral diseases resistance. However, in rapeseed (Brassica napus), the role of GAPDHs in plant immune responses to fungal pathogens remains unexplored. In this study, 28 genes encoding GAPDH proteins were revealed in B. napus and classified into three distinct subclasses based on their protein structural and phylogenetic relationships. Whole-genome duplication plays a major role in the evolution of BnaGAPDHs. Synteny analyses revealed orthologous relationships, identifying 23, 26, and 26 BnaGAPDH genes with counterparts in Arabidopsis, Brassica rapa, and Brassica oleracea, respectively. The promoter regions of 12 BnaGAPDHs uncovered a spectrum of responsive elements to biotic and abiotic stresses, indicating their crucial role in plant stress resistance. Transcriptome analysis characterized the expression profiles of different BnaGAPDH genes during Sclerotinia sclerotiorum infection and hormonal treatment. Notably, BnaGAPDH17, BnaGAPDH20, BnaGAPDH21, and BnaGAPDH22 exhibited sensitivity to S. sclerotiorum infection, oxalic acid, hormone signals. Intriguingly, under standard physiological conditions, BnaGAPDH17, BnaGAPDH20, and BnaGAPDH22 are primarily localized in the cytoplasm and plasma membrane, with BnaGAPDH21 also detectable in the nucleus. Furthermore, the nuclear translocation of BnaGAPDH20 was observed under H2O2 treatment and S. sclerotiorum infection. These findings might provide a theoretical foundation for elucidating the functions of phosphorylating GAPDH.