bluuebunny/crossref_metadata_2025 huggingface dataset:
HbA1c control in type 2 diabetes mellitus patients with coronary artery disease: a retrospective study in a tertiary hospital in South Africa
Authors: Mhlaba Lona , Mpanya Dineo , Tsabedze Nqoba
Published: October 2023

Background

Type 2 diabetes mellitus (T2DM) patients with coronary artery disease (CAD) have an increased risk of recurrent cardiovascular events. These patients require optimal glucose control to prevent the progression of atherosclerotic cardiovascular disease (ASCVD). Contemporary guidelines recommend an HbA1c ≤7% to mitigate this risk. The aim of this study was to evaluate HbA1c control in T2DM patients with angiographically proven ASCVD.

Methods

We conducted a cross-sectional, retrospective study on consecutive T2DM patients with acute and chronic coronary syndromes managed in a tertiary academic hospital in South Africa. Glycaemic control was assessed by evaluating the glycated haemoglobin (HbA1c) level measured at index presentation with acute and chronic coronary syndromes and during the most recent follow-up visit.

Results

The study population comprised 262 T2DM patients with a mean age of 61.3 ± 10.4 years. At index presentation, 110 (42.0%) T2DM patients presented with ST-segment elevation myocardial infarction, 69 (26.3%) had non-ST-segment elevation myocardial infarction, 43 (16.4%) had unstable angina, and 40 (15.3%) had stable angina. After a median duration of 16.5 months (IQR: 7-29), 28.7% of the study participants had an HbA1c ≤7%. On multivariable logistic regression analysis, females were less likely to have poor glycaemic control (HbA1c above 7%) [odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.95, p=0.038]. Also, T2DM patients prescribed metformin monotherapy (OR: 0.34, 95% CI: 0.14-0.82, p=0.017) and patients with ST-segment depression on the electrocardiogram (OR: 0.39, 95% CI: 0.16-0.96, p=0.041) were less likely to have poor glycaemic control.

Conclusion

After a median duration of 16.5 months, only 28.7% of T2DM patients with CAD had an HbA1c ≤7%. This finding underscores the substantial unmet need for optimal diabetes control in this very high-risk group.
Knockdown of Y-box binding protein 1 induces autophagy in early porcine embryos
Authors: Jiang Wen-Jie , Lee Song-Hee , Heo Geun , Chung Hak Jae , Cho Eun Seok , Sa Soo Jin , Hochi Shinichi , Cui Xiang-Shun
Published: October 2023

Y-box binding protein 1 (YBX1) plays important roles in RNA stabilization, translation, transcriptional regulation, and mitophagy. However, its effects on porcine preimplantation embryos remain unclear. In this study, we knocked down YBX1 in the one-cell (1C) stage embryo via small interfering RNA microinjection to determine its function in porcine embryo development. The mRNA level of YBX1 was found to be highly expressed at the four-cell (4C) stage in porcine embryos compared with one-cell (1C) and two-cell (2C) stages. The number of blastocysts was reduced following YBX1 knockdown. Notably, YBX1 knockdown decreased the phosphatase and tensin homolog-induced kinase 1 (PINK1) and parkin RBR E3 ubiquitin protein ligase (PRKN) mRNA levels. YBX1 knockdown also decreased PINK1, active mitochondria, and sirtuin 1 levels, indicating reduced mitophagy and mitochondrial biogenesis. Furthermore, YBX1 knockdown increased the levels of glucose-regulated protein 78 (GRP78) and calnexin, leading to endoplasmic reticulum (ER) stress. Additionally, YBX1 knockdown increased autophagy and apoptosis. In conclusion, knockdown of YBX1 decreases mitochondrial function, while increasing ER stress and autophagy during embryonic development.
EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitro
Authors: Tertel Tobias , Dittrich Robin , Arsène Pierre , Jensen Arne , Giebel Bernd
Published: October 2023

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in diverse clinical settings, largely due to their ability to produce extracellular vesicles (EVs). These EVs play a pivotal role in modulating immune responses, transforming pro-inflammatory cues into regulatory signals that foster a pro-regenerative milieu. Our previous studies identified the variability in the immunomodulatory effects of EVs sourced from primary human bone marrow MSCs as a consistent challenge. Given the limited proliferation of primary MSCs, protocols were advanced to derive MSCs from GMP-compliant induced pluripotent stem cells (iPSCs), producing iPSC-derived MSCs (iMSCs) that satisfied rigorous MSC criteria and exhibited enhanced expansion potential. Intriguingly, even though obtained iMSCs contained the potential to release immunomodulatory active EVs, the iMSC-EV products displayed batch-to-batch functional inconsistencies, mirroring those from bone marrow counterparts. We also discerned variances in EV-specific protein profiles among independent iMSC-EV preparations. Our results underscore that while iMSCs present an expansive growth advantage, they do not overcome the persistent challenge of functional variability of resulting MSC-EV products. Once more, our findings accentuate the crucial need for batch-to-batch functional testing, ensuring discrimination of effective and ineffective MSC-EV products for considered downstream applications.
Recommender systems for sustainability: overview and research issues
Authors: Felfernig Alexander , Wundara Manfred , Tran Thi Ngoc Trang , Polat-Erdeniz Seda , Lubos Sebastian , El Mansi Merfat , Garber Damian , Le Viet-Man
Published: October 2023

Sustainability development goals (SDGs) are regarded as a universal call to action with the overall objectives of planet protection, ending of poverty, and ensuring peace and prosperity for all people. In order to achieve these objectives, different AI technologies play a major role. Specifically, recommender systems can provide support for organizations and individuals to achieve the defined goals. Recommender systems integrate AI technologies such as machine learning, explainable AI (XAI), case-based reasoning, and constraint solving in order to find and explain user-relevant alternatives from a potentially large set of options. In this article, we summarize the state of the art in applying recommender systems to support the achievement of sustainability development goals. In this context, we discuss open issues for future research.
Polycystic ovary syndrome and recurrent pregnancy loss, a review of literature
Authors: Wartena Rosa , Matjila Mushi
Published: October 2023

Objective

PCOS is a syndrome of ovarian dysfunction associated with recurrent pregnancy loss. Several correlating factors have been investigated that influence the risk of pregnancy loss in PCOS. However, uncertainty remains about their contribution to pregnancy loss and prognosis. This review of literature aims to identify what is known and what requires further investigation on the relationship between PCOS and recurrent pregnancy loss, to guide future research and optimize medical guidance throughout pregnancy.

Study design

a review of literature was performed on several search engines using the following terms; polycystic ovarian syndrome, PCOS, recurrent pregnancy loss, recurrent miscarriage, RPL, aborted fetus, abortus provocatus, miscarriage and habitual abortion.

Results

37 articles were included; 3 systematic reviews, 1 meta-analysis, 2 randomized controlled trials, 6 prospective cohort studies, 22 case-control studies and 3 case series. The main objectives investigated by studies were pregnancy complications, pregnancy loss and live birth in the PCOS population.

Conclusion

Studies that investigated the relationship between PCOS and recurrent pregnancy loss are few and inconsistent and warrant further research. Factors apt for further investigation include the extent to which PCOS phenotypes, BMI, obesity, insulin resistance, hyperandrogenemia, SHBG, hs-CRP, CTRP6, adiponectin, plasma leptin, homocysteine, AMH and thrombophilia contribute to further risk of miscarriage. Other factors requiring further exploration in relation to risk for miscarriage in PCOS patient with RPL include sOB-R, PAI-Fx and the Factor-V-Leiden mutations.
Association between MTHFR gene C677T polymorphism and gestational diabetes mellitus in Chinese population: a meta-analysis
Authors: Tan Xi , Chen Hongqin
Published: October 2023

Background and purpose

The relationship of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese population remains controversial. This study aimed to further clarify the effect of the MTHFR gene C677T polymorphism on GDM risk among Chinese pregnant women based on current evidence.

Methods

Several databases were searched up to July 29, 2023 for relevant case-control studies. The numbers of patients with and without the T allele of the MTHFR gene C677T polymorphism in the GDM and control groups were determined, and all statistical analyses were performed by RevMan 5.3 software and STATA 15.0 software. Trial sequential analysis (TSA) was performed by TSA version 0.9 beta software to determine the required information size.

Results

A total of 17 case-control studies involving 12345 Chinese participants were included. The pooled results demonstrated that the T allele of the MTHFR gene C677T polymorphism was significantly associated with an increased risk of GDM, which was manifested by the five gene models of the MTHFR C677T polymorphism [T vs. C: odds ratio (OR)=1.59, P=0.03; TT vs. CC: OR=2.24, P<0.001; TC vs. CC: OR=1.28, P=0.05; (TT+TC) vs. CC: OR=1.55, P=0.003; TT vs. (TC+CC): OR=1.89, P<0.001]. Subgroup analysis based on the regions indicated that the significant relationship between the T allele of the MTHFR gene C677T polymorphism and an increased risk of GDM was detected only among the southern population [T vs. C: OR=1.62, P=0.09; TT vs. CC: OR=2.22, P=0.004; TC vs. CC: OR=1.17, P=0.28; (TT+TC) vs. CC: OR=1.43, P=0.03; TT vs. (TC+CC): OR=1.97, P=0.006]. TSA plots showed that the information sizes for the association between the MTHFR gene C677T polymorphism and GDM risk were sufficient in the homozygote (TT vs. CC) and recessive (TT vs. TC+CC) models.

Conclusion

The MTHFR gene C677T polymorphism is closely related to susceptibility to GDM in the southern Chinese population, and the C-T mutation serves as an important genetic risk factor for GDM. More well-designed large case-control studies are needed to further confirm the above findings.
Assessment of five typical environmental endocrine disruptors and thyroid cancer risk: a meta-analysis
Authors: Yang Yuyao , Bai Xiaoyue , Lu Juan , Zou Ronghao , Ding Rui , Hua Xiaohui
Published: October 2023

Introduction

There are conflicting reports on the association between environmental endocrine disruptors (EEDs) and thyroid cancer. This meta-analysis aimed to elucidate the relationship between EEDs and thyroid cancer.

Methods

We searched for epidemiological studies on EEDs and thyroid cancer published in PubMed and Web of Science up to December 2022. We then screened the articles that could extract data on EEDs concentration levels in both thyroid cancer patients and healthy controls. We excluded articles that could not calculate effect sizes, focused on other thyroid diseases, or lacked controls. Standardized mean difference (SMD) was calculated to analyze the association between EEDs and thyroid cancer. We measured the heterogeneity among the included studies using I2, assessed publication bias by Egger’s and Begg’s test, and evaluated article quality using the Newcastle-Ottawa Quality Score (NOS). In the end, fifteen eligible case-control studies were included.

Results

Our comprehensive analysis revealed that polychlorinated biphenyls (PCBs) were negatively associated with thyroid cancer{ SMD = -0.03, 95% confidence interval (CI) = (-0.05, -0.00), P = 0.03}, while polybrominated diphenyl ethers (PBDEs), phthalates (PAEs), and heavy metals were positively associated with thyroid cancer{PBDEs: SMD = 0.14, 95%CI = (0.04, 0.23), P = 0.007; PAEs: SMD = 0.30, 95%CI = (0.02, 0.58), P = 0.04; heavy metals: SMD = 0.21, 95%CI = (0.11, 0.32), P < 0.001}. We did not find a statistically significant relationship between bisphenol A (BPA) and thyroid cancer. Most of the included studies did not show publication bias, except for those on PCBs.

Discussion

Our results indicate that exposure to certain EEDs, such as PBDEs, PAEs, and heavy metals, increases the risk of thyroid cancer. However, further large-scale epidemiological studies and mechanism studies are needed to verify these potential relationships and understand the underlying biological mechanisms.
Impact of a high dietary fiber cereal meal intervention on body weight, adipose distribution, and cardiovascular risk among individuals with type 2 diabetes
Authors: Li Xiaofeng , Shi Yu , Wei Dongqin , Ni Wenyu , Zhu Na , Yan Xinyi
Published: October 2023

Objective

This study sought to examine the impacts of a high dietary fiber cereal meal in comparison to conventional dietary management for diabetes on body weight, distribution of adipose tissue, and cardiovascular risk among individuals diagnosed with type 2 diabetes (T2DM).

Methods

A cohort of 120 patients diagnosed with T2DM was enlisted as the study population and divided into two groups using a ratio of 2:1—namely, the W group (n=80) and the U group (n=40). The U group (control) received usual diet, while the W group (intervention) incorporated a high dietary fiber cereal meal in place of their regular staple food in addition to adhering to conventional diabetes dietary recommendations. The high dietary fiber cereal meal was based on whole grains, traditional Chinese medicinal foods, and prebiotics. A subsequent follow-up period of 3 months ensued, during which diverse parameters such as body mass index (BMI),waist-hip ratio (WHR), glycated hemoglobin (HbA1c),fasting blood glucose(FBG),C-peptide levels, blood pressure, blood lipids, high-sensitivity C-reactive protein (hsCRP),10-year cardiovascular disease (CVD) risk, and Lifetime CVD risk were assessed before and after the intervention.

Results

Among the participants, a total of 107 successfully completed the intervention and follow-up, including 72 individuals from the W group and 35 from the U group. Following the intervention, both cohorts exhibited decrease in BMI, WHR, HbA1c, FBG, blood pressure, and blood lipid levels in contrast to their initial measurements. Remarkably, the improvements in BMI, WHR, HbA1c, FBG, total cholesterol (TC), triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), and the ratio of 2-hour C-peptide (2hCP) to fasting C-peptide (FCP) were more marked within the W group, exhibiting statistically significant disparities (P<0.05) in comparison to the U group. Furthermore, the levels of hsCRP declined among individuals in the W group, while the U group experienced an elevation.10-year CVD risk reduction were similar in the two groups. While, Lifetime CVD risk only decreased significantly in the W group.

Conclusion

The intervention centred on a cereal-based dietary approach showcased favourable outcomes with regard to body weight, adipose distribution, and cardiovascular risk in overweight individuals grappling with T2DM.
Renewable energy consumption and business density as drivers of sustainable development
Authors: Zheng Renzhi , Osabohien Romanus , Madueke Emmanuel , Jaaffar Amar Hisham Bin
Published: October 2023

The East Asia and Pacific region have witnessed significant economic growth in recent decades, leading to improved living standards and increased energy consumption. However, this rapid development has also resulted in environmental degradation and heightened concerns about climate change. In response, countries in the region have been increasingly focusing on sustainable development, with renewable energy consumption and business density emerging as key drivers. Given this background, this research empirically examines the impact of entrepreneurship and clean technology on sustainable development in East Asia and the Pacific region. To control for endogeneity, the study applied system the Generalized Method of Moments (SGMM) for the data sourced from the World Development Indicators of the World Bank for the period 2015–2021. The finding indicates that both entrepreneurship and clean technology have an adverse significant impact on sustainable development in the East Asia-Pacific region. When the regions were analysed individually, the results revealed that both entrepreneurship and clean technology have a negative substantial effect on sustainable development in East Asia, but not in the Pacific region. The study concludes that entrepreneurship and renewable energy by themselves would not result in sustainable development, except some certain conditions are met. The positive impacts of entrepreneurship and renewable energy on sustainable development can only be attained when the nature, location, and practices of new businesses are low carbon in nature.

JEL Classifications: Q01, Q42, Q56
The effect of technological innovations, urbanization and economic growth on environmental quality: does governance matter?
Authors: Khan Hayat , Khan Itbar
Published: October 2023

Climate change has become a major challenge in recent decades as a result of rapid economic growth due to increased energy use and a rise in urbanization. Environmental damage induced by energy use, urbanization, and economic growth can be overcome by technological advancement and good governance. This study examines the effect of urbanization, technological innovations, and economic growth on carbon dioxide emissions in the Belt and Road initiative countries from 2002 to 2022. By using GMM model, the results show that, technological innovations and foreign direct investment raise carbon dioxide emissions however, research and development enhance environmental quality. This study also found that urbanization has a nonlinear relationship with carbon emission where effective governance exert a moderating role in this association. This study provides important policy suggestions for BRI countries.
Histological transformation into SCLC: An important resistance mechanism of NSCLC upon immunotherapy
Authors: Zeng Jiao , Ding Xinjing , Ding Jianghua , Wang Xin
Published: October 2023

The phenomenon of histological transformation has been widely reported in advanced non-small cell lung cancer (NSCLC) with EGFR mutations following the failure of EGFR-TKI treatment. Recent evidence suggests that similar histological changes can also occur in advanced NSCLC without driver gene mutations after developing resistance to immunotherapy. In this review, it was found that 66.7% of cases with immunotherapy-induced histological transformation were classified as lung squamous cell carcinoma (LSCC), while histological conversion into lung adenocarcinoma (LUAD) without EGFR or ALK gene mutations has rarely been reported. There have been sporadic reports on the occurrence of mutual transformation between LUAD and LSCC. The histological conversion from NSCLC into small cell lung cancer (SCLC) appears to be significantly underestimated, likely due to the infrequency of re-biopsy following the development of immunotherapy resistance. Several studies have reported a close association between the transformation and mutations at TP53 and the RB1 splice site, as well as the loss of an FBXW7 mutation. However, the exact mechanisms underlying this conversion remain unclear. Currently, there is a lack of guidelines for the management of transformed SCLC from NSCLC following immunotherapy, with chemotherapy being the most commonly employed treatment approach.
Respiration, phytoplankton size and the metabolic balance in the Atlantic gyres
Authors: Serret Pablo , Lozano Jose , Harris Carolyn B. , Lange Priscila K. , Tarran Glen A. , Tilstone Gavin H. , Woodward E. Malcolm S. , Zubkov Mikhail V.
Published: October 2023

The balance between plankton photosynthesis (GPP) and community respiration (CR) in the euphotic zone (net community production, NCP) is an essential driver of the biological carbon pump. Deficient datasets and a lack of knowledge of the mechanisms regulating CR cause poor empirical models and oversimplified parameterisations that maintain NCP as one of the most important unknowns for projections of the carbon pump. One important unresolved issue is the unexpected lack of empirical relationships between CR and the biomass or size-structure of the phytoplankton, which undermines the use of remotely sensed observations to predict net community metabolism. Here we analyse the spatial variation of plankton metabolism, chlorophyll a concentration (Chla), pico- and nanophytoplankton abundance and size-fractionated primary production (14CPP) along a latitudinal (49°N–46°S) transect of 73 stations across the Atlantic Ocean (AMT-22 cruise). The use of depth-weighted rates (rates integrated to the depth of 0.1% PAR, divided by the regionally varying depth of integration) markedly improved the depiction of latitudinal patterns and the significance of relationships, over volumetric or integrated rates. Depth-weighted CR showed clear and consistent latitudinal patterns with relevance for the distribution of NCP. Depth-weighted Chla and CR exhibited a significant relationship (CRZ=1.42ChlaZ-0.21, r2 = 0.69, N=37, p<0.001) with potential for the difficult prediction of CR. A general ratio of 1.42 mmolO2 mgChla-1 d-1 and a threshold Chla for net heterotrophy of ca. 0.25 mgChla m-3 can be tentatively proposed for the Atlantic, although further analyses of spatial and seasonal variation are necessary. We observed unusually positive NCP rates in the central part of the N gyre, due to a marked decrease of CR in a patch of high Synechococcus spp. abundance and high 14CPP by large phytoplankton. However, no relationship was observed between size-fractionated 14CPP and CR or the GPP : CR ratio during the cruise, contradicting the hypothesis that food web functioning is determined by the phytoplankton size structure. Such independence, together with the persistence of distinct GPP : CR and 14CPP : NCP relationships in distinct biogeographic provinces suggest a resilience of trophic dynamics and the existence of alternative ecosystem states, whose implications for projections of the metabolic state of the ocean are discussed.
Improving data reliability to support marine pollution assessment according to MSFD Descriptor 8 in the European Seas: the contribution of EMODnet Chemistry
Authors: French Megan Anne , Lipizer Marina
Published: October 2023

Introduction

According to the Marine Strategy Framework Directive (MSFD, 2008/56/EC), member states of the European Union (EU) had to develop a common approach in environmental monitoring and assessment. Regarding marine pollution assessments, large heterogeneities remain regarding sampling protocols, analytical methods, and quality assurance (QA) and quality control (QC) procedures. Further, data availability for Descriptor 8 (contaminants) was very fragmented in the first cycle of the MSFD. As one of the major EU spatial data infrastructures for providing access to marine data, EMODnet Chemistry has endeavoured to overcome data fragmentation and increase data ‘FAIRness’ (findable, accessible, interoperable, and reusable).

Methods

Aiming to improve the reliability of marine contaminant data for assessment purposes under the MSFD, detailed QA/QC information was collected using a questionnaire based on the requirements of the European Environment Agency, International Council for the Exploration of the Sea, United Nations Environment Program–Mediterranean Action Plan, and NORMAN Network. The questionnaire was distributed to institutions in 26 countries participating in EMODnet Chemistry.

Results

Information was received from 18 countries on ~90% of the substances included in EU legislation on priority substances. The results indicate an overall good level of laboratory proficiency; however, heterogeneities were observed in sampling protocols (especially for biota) and analytical methods (e.g. for metals), suggesting the potential for increased harmonisation. While laboratory proficiency and equipment depend on institutional resources that may differ among countries, it is fundamental to share detailed QA/QC information associated with data to improve data reliability and re-usability, and to support marine pollution assessment.

Discussion

Enriching data with required metadata and detailed QA/QC is part of the data curation process, which is still an overlooked aspect of the overall scientific research process and is crucial to support a reliable assessment of marine pollution, and ultimately better management of the marine environment.
A concept for multi-winner tenders for medicinal products with balancing between efficient prices, long-term competition and sustainability of supply
Authors: Németh Gergely , Mágó Mánuel László , Kaló Zoltán , Lám Judit , Balogh Tamás , Brodszky Valentin
Published: October 2023

Achieving price efficiency via tenders, the sustainability of competition, and the prevention of shortages are hot topics in the debates about shaping the pharmaceutical markets. Single-winner tenders receive growing criticism for concentrating on achieving low prices at the expense of the long-term maintenance of a competitive pharmaceutical industry, the security of continuous supply, and disregarding the therapeutic needs of patient populations with specific conditions. This paper aims at drafting a concept to assist the design of multi-winner tenders for medicinal products with a focus on supply and sales guarantees, price efficiency, and equity in access. The concept shall be generally applicable to all kinds of medicinal products including generics, biosimilars, and on-patent products in the out- and in-patient sector. Principles for multi-winner tenders for medicinal products are set and a number of delimitations are made in order to get rid of factors that prevent clairvoyance amid the various pricing and reimbursement systems when designing a concept. The steps to plan and implement a multi-winner tendering procedure are drafted on the basis of the defined principles. The tender should consist of planning, bidding, preparation, sales, and evaluation phases. Pharmaceutical companies shall make bids with price and quantity pairs, which shall be ranked by prices and if applicable then taking into account other factors. The tenderer shall predefine market shares to the various places of the ranking. A double ceiling shall be applicable for the sales of the winners: their sales must not exceed their quantity offer and the predefined market share applicable to their place in the ranking. The implementation of the concept will require the careful adjustment of the tender conditions to the specificities of the pharmaceutical market concerned on the one hand and to the local pricing and reimbursement system on the other hand.
A targeted strategic peer support intervention to increase adherence to video teletherapy exposure and response prevention treatment for obsessive-compulsive disorder: a retrospective observational analysis
Authors: Murphy Christopher E. , Rhode Andreas , Kreyling Jeremy , Appel Scott , Heintz Jonathan , Osborn Kerry , Lucas Kyle , Mohideen Reza , Trusky Larry , Smith Stephen , Feusner Jamie D.
Published: October 2023

Exposure and response prevention (ERP) therapy, a form of cognitive-behavioral therapy, is a first-line, evidence-based treatment for obsessive-compulsive disorder (OCD) for adults and children. It is effective for the majority of those who engage in it, but treatment adherence can be challenging for some due to the stress involved in the treatment as well as different life circumstances that arise. To help improve treatment adherence, NOCD, a provider of video teletherapy ERP, identifies those at risk of non-adherence using a prediction algorithm trained on a data set of N = 13,809 and provides targeted peer support interventions by individuals (“Member Advocates”) who successfully completed ERP treatment for OCD. Member Advocates, using lived OCD experience as well as experience with ERP, engage at-risk patients through digital messaging to engage, educate, and encourage patients in the early stages of treatment. From June 2022 to August 2022, N = 815 patients deemed at risk were reached out to and n = 251 responded and engaged with the Member Advocates. In the at-risk patients who engaged, the intervention resulted in a significant mean 30.4% more therapy hours completed compared to those who did not engage. Additionally, engaged patients had greater reductions in OCD severity. These results have implications for how data science, digital interventions, and strategic peer-to-peer communication and support can be combined to enhance the effectiveness of treatment.
Identification ferroptosis-related hub genes and diagnostic model in Alzheimer’s disease
Authors: Zhao Huabin , Wang Jiawei , Li Zhongzheng , Wang Shenghui , Yu Guoying , Wang Lan
Published: October 2023

Background

Ferroptosis is a newly defined form of programmed cell death and plays an important role in Alzheimer’s disease (AD) pathology. This study aimed to integrate bioinformatics techniques to explore biomarkers to support the correlation between ferroptosis and AD. In addition, further investigation of ferroptosis-related biomarkers was conducted on the transcriptome characteristics in the asymptomatic AD (AsymAD).

Methods

The microarray datasets GSE118553, GSE132903, GSE33000, and GSE157239 on AD were downloaded from the GEO database. The list of ferroptosis-related genes was extracted from the FerrDb website. Differentially expressed genes (DEGs) were identified by R “limma” package and used to screen ferroptosis-related hub genes. The random forest algorithm was used to construct the diagnostic model through hub genes. The immune cell infiltration was also analyzed by CIBERSORTx. The miRNet and DGIdb database were used to identify microRNAs (miRNAs) and drugs which targeting hub genes.

Results

We identified 18 ferroptosis-related hub genes anomalously expressed in AD, and consistent expression trends had been observed in both AsymAD The random forest diagnosis model had good prediction results in both training set (AUC = 0.824) and validation set (AUC = 0.734). Immune cell infiltration was analyzed and the results showed that CD4+ T cells resting memory, macrophages M2 and neutrophils were significantly higher in AD. A significant correlation of hub genes with immune infiltration was observed, such as DDIT4 showed strong positive correlation with CD4+ T cells memory resting and AKR1C2 had positive correlation with Macrophages M2. Additionally, the microRNAs (miRNAs) and drugs which targeting hub genes were screened.

Conclusion

These results suggest that ferroptosis-related hub genes we screened played a part in the pathological progression of AD. We explored the potential of these genes as diagnostic markers and their relevance to immune cells which will help in understanding the development of AD. Targeting miRNAs and drugs provides new research clues for preventing the development of AD.
PDGF, NGF, and EGF as main contributors to tumorigenesis in high-risk retinoblastoma
Authors: Al-Ghazzawi Karim , Wessolly Michael , Dalbah Sami , Ketteler Petra , Kiefer Tobias , Bechrakis Nikolaos , Leyla Jabbarli , Ting Saskia , Biewald Eva , Mairinger Fabian D.
Published: October 2023

Retinoblastoma (RB) is the most common form of eye cancer experienced in childhood. Its aggressive malignancy is associated with excellent survival rates in high-income countries; however, the prognosis in third-world countries is less favorable. Early diagnosis can maximize the patient’s visual outcomes and their survival rate. Therapy should be conducted in highly specialized treatment centers. Intravenous chemotherapy (IVC) in bilaterally affected children currently forms the majority of therapy. Local destructive procedures and local chemotherapies such as intra-arterial chemotherapy (IAC) or intravitreal chemotherapy can be taken into consideration depending on the extent and size of the tumor. Nonetheless, children and parents remain under constant stress, revisiting doctors for medical treatment and fearing vision loss and even enucleation of the eye. Adequate molecular patient stratification to improve targeted therapy is still lacking. This retrospective study analyzed formalin-fixed paraffin-embedded specimens from a cohort of 21 RB samples. A total of 11 of those samples showed undifferentiated retinoblastoma (URB) histopathological risk features, and the other 10 showed differentiated retinoblastoma (DRB) histopathological grading. RNA from all samples was isolated and analyzed via digital gene expression patterns. Conductors of cell survival and DNA repair were dominant in the DRB samples. In contrast, the agents responsible for cell–cycle progression and apoptosis were overexpressed in URB samples. Our work reveals the importance of molecular mechanisms within the immune system subjected to histologic subtypes of RB, providing more detailed background on their genetic behavior. This is of great interest for therapeutic strategies, such as targeted immune- and gene-based therapies, for retinoblastoma.
Analysis of redox status and HDL subclasses in patients with lymphoma and the associations with FDG-PET/CT findings
Authors: Mirjanic-Azaric Bosa , Stankovic Sinisa , Nezic Lana , Radic Savic Zana , Malcic- Zanic Dragana , Skrbic Ranko , Kotur-Stevuljevic Jelena , Bogavac-Stanojevic Natasa
Published: October 2023

Newer research points to alterations in the plasma redox status and the HDL subclass distributions in cancer. We aimed to assess the redox status and the HDL subclass distributions, lipids, and inflammatory markers in lymphoma patients in order to determine whether they were correlated with changes in FDG-PET/CT scans. At the beginning of this study, redox status, HDL subclasses, lipids, and inflammation biomarkers were determined in 58 patients with lymphoma (Hodgkin lymphoma, n=11 and non-Hodgkin lymphoma, n=47), and these same measurements were reassessed during their ensuing treatment (in 25 patients). Initially, the total oxidation status (TOS), the prooxidant–antioxidant balance (PAB), the OS index (OSI), the total protein sulfhydryl groups (SH-groups), and the advanced oxidation protein products (AOPP) were significantly higher in lymphoma patients as compared to healthy subjects, but the total antioxidant status (TAS) was significantly reduced. The PAB had a strong correlation with the CRP and interleukin-6 (rho=0.726, p<0.001; rho=0.386, p=0.003). The correlations between these parameters and the maximum standardized uptake values (SUVmax) were: PAB, rho=0.335 and p=0.010; SH-groups, rho=0.265 and p=0.044; CRP, rho=0.391 and p=0.002; HDL3b, rho=0.283 and p=0.031; HDL2b, rho= -0.294 and p=0.025; and HDL size, rho= -0.295 and p=0.024. The reductions in SUVmax between two follow-up points were associated with increases in the OSI, TOS, and SH-groups, as well as a reduction in the PAB and TAS. In conclusion, the redox parameters in patients with lymphoma were consistent with FDG-PET/CT findings. Targeting the redox status parameters and the HDL subclasses could be potential strategies in the molecular fight against lymphoma.
Retrospective analysis of outcomes for pediatric acute lymphoblastic leukemia in South American centers
Authors: Duffy Caitlyn , Graetz Dylan E. , Lopez Arturo M. Zapata , Carrillo Angela K. , Job Godwin , Chen Yichen , Devidas Meenakshi , Leon Sandra Alarcón , Bonzi Sol Aponte , Flores Pedro Cardona , Torres Lizeth Escobar , Broncano Eddy Hernández , Jaramillo Soledad Jiménez , Zelada Ma Ofelia , Novoa Romulo Reaño , Samudio Angelica , Sánchez-Fernandez Gissela , Villanueva Erika , Metzger Monika L. , Friedrich Paola , Jeha Sima
Published: October 2023

Introduction

Acute lymphoblastic Leukemia (ALL) is the most common pediatric malignancy. While the survival rate for childhood ALL exceeds 90% in high-income countries, the estimated survival in low-and middle-income countries ranges from 22-79%, depending on the region and local resources.

Methods

This study retrospectively reviewed demographic, biological, and clinical parameters of children under 18 years of age with newly diagnosed ALL presenting between 2013-2017 across five pediatric centers in 4 countries in South America. Survival analyses were estimated using the Kaplan-Meier method.

Results

Across the five centers, 752 patients were analyzed (Bolivia [N=9], Ecuador [N=221], Paraguay [N=197], Peru [N=325]) and 92.1% (n=690) patients were diagnosed with B-cell and 7.5% (n= 56) with T-cell ALL. The median age was 5.5 years old (IQR 7.29). At diagnosis, 47.8% of patients were categorized as standard and 51.9% as high risk per their institutional regimen. Advanced diagnostics availability varied between modalities. MRD was evaluated in 69.1% of patients; molecular testing was available for ETV6-RUNX, BCR-ABL1, TCF3-PBX1, and KMT2A-rearranged ALL in 75-81% of patients; however, karyotyping and evaluation for iAMP21 were only performed in 42-61% of patients. Central nervous system (CNS) involvement was evaluated at diagnosis in 57.3% (n=429) patients; of these, 93.7% (n=402) were CNS 1, 1.6% (n=7) were CNS 2, 0.7% (n=11) were CNS3, 1.9% (n=8) had cranial nerve palsy, and 2.1% (n=9) results unavailable. Chemotherapy delays >2 weeks were reported in 56.0% (n=421) patients during treatment. Delays were attributed to infection in 63.2% (n=265), drug-related toxicities in 47.3% (n=198), and resource constraints, including lack of bed availability in 23.2% (n=97) of patients. The 3-year Abandonment-sensitive EFS and OS were 61.0±1.9% and 67.2±1.8%, respectively. The 3-year EFS and OS were 71.0±1.8% and 79.6±1.7%, respectively.

Discussion

This work reveals opportunities to improve survival, including addressing severe infections, treatment interruptions, and modifications due to drug shortages. In 2018, healthcare professionals across South America established the Pediatric Oncology Latin America (POLA) group in collaboration with St. Jude Children’s Research Hospital. POLA collaborators developed an evidence-based, consensus-derived, adapted treatment guideline, informed by preliminary results of this evaluation, to serve as the new standard of care for pediatric ALL in participating institutions.
Metabolomics analysis delineates the therapeutic effects of Yinlan Tiaozhi capsule on triton WR-1339 -induced hyperlipidemia in mice
Authors: Xiao Guanlin , Xu Aili , Jiang Jieyi , Chen Zhao , Li Yangxue , Li Sumei , Chen Weitao , Zhang Jingnian , Jia Canchao , Zeng Zhihao , Bi Xiaoli
Published: October 2023

Hyperlipidemia is a disorder of lipid metabolism resulting from abnormal blood lipid metabolism and is one of the most frequent metabolic diseases that endanger people’s health. Yinlan Tiaozhi capsule (YL) is a formulated TCM widely used to treat hyperlipidemia. The purpose of this study was to discover biomarkers utilizing untargeted metabolomics techniques, as well as to analyze the mechanisms underlying the changes in metabolic pathways linked to lipid-lowering, anti-inflammation, and regulation of angiogenesis in hyperlipidemia mice. To assess the efficacy of YL, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) levels were measured. Biochemical examinations showed that YL significantly reduced the levels of TC, TG, LDL-c, Il6, Tnf-α, and Vegfa in hyperlipidemia mice (p < 0.01). YL also significantly increased the levels of HDL-c and Alb (p < 0.01). Twenty-seven potential serum biomarkers associated with hyperlipidemia were determined. These differential metabolites were related to the reduction of serum lipid levels in hyperlipidemia mice, probably through metabolic pathways such as linoleic acid metabolism, glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and D-glutamine and D-glutamate metabolism. Further correlation analysis showed that the serum lipid reduction through YL was related to the metabolites (amino acid metabolites, phospholipids metabolites, and fatty acids metabolites). The present study reveals that YL has a profound effect on alleviating triton WR-1339-induced hyperlipidemia, inflammation, and angiogenesis and that the positive effects of YL were primarily associated with the correction of metabolic abnormalities and the maintenance of metabolite dynamic balance.
Some novel concepts of interval-valued picture fuzzy graphs with applications toward the Transmission Control Protocol and social networks
Authors: Shi Xiaolong , Kosari Saeed , Khan Waheed Ahmad
Published: October 2023

The Transmission Control Protocol usually involves incomplete and imperfect network states for which sophisticated analysis is needed. Fuzzy logic could be more helpful for the analysis of network state more accurately. The interval-valued picture fuzzy set being the most generalized form of fuzzy set has more capacity to analyze the network state more intelligently. In this manuscript, we present the concepts of interval-valued picture fuzzy graphs (IVPFGs) as an extension of interval-valued fuzzy graphs and picture fuzzy graphs. Since interval-valued picture fuzzy sets are the most advanced form of fuzzy sets, IVPFGs would be a more efficient tool for handling data containing uncertainties. First, basic concepts such as degree, order, and size are discussed, followed by operations such as union, intersection, Cartesian product, composition, and the ring sum of IVPFGs. Then, we provide a few relationships between the ring sum and edge deletion of IVPFGs. Special types of IVPFGs including complete IVPFGs, regular IVPFGs, complement IVPFGs, and strong IVPFGs are introduced. Concepts such as the strength of arcs, path sequence, strength of the path, and connectedness are explored in IVPFGs. Different types of strengths of connectedness are discussed based on specific types of arcs. We also provide a few structural properties of IVPFGs through these arcs. Finally, we give a clue about the potential implementation of IVPFGs, an extension of the fuzzy logic-based Transmission Control Protocol and toward social networking.
Cloning and functional analysis of the BrCUC2 gene in Brassica rapa L
Authors: Tao Xiaolei , Zhao Yuhong , Ma Li , Wu Junyan , Zeng Rui , Jiao JinTang , Li Rong , Ma Weiming , Lian Yintao , Wang Wangtian , Pu Yuanyuan , Yang Gang , Liu Lijun , Li Xuecai , Sun Wancang
Published: October 2023

The CUP-SHAPED COTYLEDON2 (CUC2) gene plays an important role in the formation of apical meristem and organ edges in plants. The apical meristematic tissue of Brassica rapa (B. rapa) is associated with cold resistance, however, the role of the CUC2 gene in cold resistance of B.rapa is unclear. In this study, we used bioinformatics software to analyze the structure of BrCUC2 gene, real-time fluorescence quantitative PCR to detect the expression level of BrCUC2, constructed transgenic Arabidopsis thaliana by the flower dipping method and subcellular localization for functional validation. The results showed that, we isolated a 1104 bp open reading frame of BrCUC2 from the winter B. rapa cultivar ‘Longyou 7’. The BrCUC2 contains a highly conserved domain belonging to the NAM superfamily. Its homologus CUC genes contain similar conserved motifs and are closely related to Brassica oleracea (B.oleracea), and the N-terminal of amino acid sequence contains NAC domain. BrCUC2 protein was localized in the nucleus and self-activation tests showed that pGBKT7-BrCUC2 had self-activation. Tissue-specific expression analysis and promoter β-Glucuronidase (GUS) activity showed that BrCUC2 had high expression levels in B. rapa growth points and A. thaliana leaf edges, stems and growth points. After low-temperature stress, BrCUC2 showed greater expression in ‘Longyou 7,’ which presents strong cold resistance and concave growth points, than in ‘Longyou 99,’ which presents weak cold resistance and protruding growth points. BrCUC2 promoter contains multiple elements related to stress responses. BrCUC2 overexpression revealed that the phenotype did not differ from that of the wild type during the seedling stage but showed weak growth and a dwarf phenotype during the flowering and mature stages. After low-temperature treatment, the physiological indexes and survival rate of BrCUC2-overexpression lines of Arabidopsis thaliana (A. thaliana) were better than those of the wild type within 12 h, although differences were not observed after 24 h. These results showed that BrCUC2 improved the low-temperature tolerance of transgenic A. thaliana within a short time. It can provide a foundation for the study of cold resistance in winter B. rapa.
Exogenous melatonin activates the antioxidant system and maintains postharvest organoleptic quality in Hami melon (Cucumis. melo var. inodorus Jacq.)
Authors: Wang Yue , Guo Minrui , Zhang Weida , Gao Yujie , Ma Xiaoqin , Cheng Shaobo , Chen Guogang
Published: October 2023

Hami melon is prone to postharvest perishing. Melatonin is a signaling molecule involved in a variety of physiological processes in fruit, and it improves fruit quality. We hypothesized that melatonin treatment would improve the storage quality of Hami melon by altering its respiration and reactive oxygen species (Graphical abstract). Our results indicated that optimal melatonin treatment (0.5 mmol L−1) effectively slowed the softening, weight loss, and respiratory rate of the Hami melon fruit. Furthermore, melatonin markedly improved the antioxidant capacity of the fruit and protected it from oxidative damage by decreasing its contents of superoxide anions, hydrogen peroxide, and malondialdehyde. Melatonin significantly enhanced the activities of superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase. The total phenol, total flavonoids, and ascorbic acid contents were maintained by melatonin treatment. This treatment also repressed the activities of lipase, lipoxygenase, and phospholipase D, which are related to lipid metabolism. Thus, exogenous melatonin can maintain postharvest organoleptic quality of Hami melon fruit by increasing its antioxidant activity and inhibiting reactive oxygen species production.
Comprehensive assessment of executive functioning following childhood severe traumatic brain injury: clinical utility of the child executive functions battery
Authors: Chevignard Mathilde , Guerra Amanda , Fliss Rafika , Salah Lucie , Pineau Emmanuelle , Notteghem Pauline , Roche Jeanne , Huon Caroline , Krasny Pacini Agata , Le Gall Didier , Fournet Nathalie , Roulin Jean-Luc , Roy Arnaud
Published: October 2023

Objectives

To perform a detailed description of executive functioning following moderate-to-severe childhood traumatic brain injury (TBI), and to study demographic and severity factors influencing outcome.

Methods

A convenience sample of children/adolescents aged 7–16 years, referred to a rehabilitation department after a TBI (n= 43), was compared to normative data using a newly developed neuropsychological test battery (Child Executive Functions Battery—CEF-B) and the BRIEF.

Results

Performance in the TBI group was significantly impaired in most of the CEF-B subtests, with moderate to large effect sizes. Regarding everyday life, patients were significantly impaired in most BRIEF clinical scales, either in parent or in teacher reports. Univariate correlations in the TBI group did not yield significant correlations between the CEF-B and socio-economic status, TBI severity, age at injury, or time since injury.

Conclusion

Executive functioning is severely altered following moderate-to-severe childhood TBI and is best assessed using a combination of developmentally appropriate neuropsychological tests and behavioral ratings to provide a comprehensive understanding of children’s executive functions.