bluuebunny/crossref_metadata_2025 huggingface dataset:
Body mass index and partial remission in 119 children with type 1 diabetes—a 6-year observational study
Authors: Sokołowska-Gadoux Magdalena , Jarosz-Chobot Przemysława , Polanska Joanna , Kalemba Alicja , Chobot Agata
Published: September 2023

Background/objective

This long-term study aimed to analyze the associations between BMI Z-score, HbA1c, and daily insulin requirement (DIR) and the prevalence and duration of partial remission (PR) in children and adolescents with type 1 diabetes (T1D).

Methods

After retrieving retrospective data for 195 patients from their health records at 24, 48, and 72 months after T1D diagnosis, the study group was comprised of 119 (57 girls) children with a complete dataset for all 6 years. PR was defined according to the ISPAD guidelines. Analyses were carried out in the whole group and subgroups according to PR duration: no PR at all (NPR), PR lasting less than 2 years (PR < 2), and PR at least 2 years (PR ≥ 2).

Results

PR was observed in 63% of the patients (78.9% of overweight and 100% of obese patients). NPR patients showed the lowest mean initial BMI Z-score [−0.65 ± 1.29 vs. 0.02 ± 1.42, (PR < 2), p = 0.01 and vs. 0.64 ± 1.43 (PR ≥ 2), p = 0.17]. The dissimilarity in BMI across patients declined over time. Within the NPR group, the initial mean BMI Z-score significantly increased within the first 2 years (unadjusted p < 0.001) and remained constant afterward. In the PR <2 group, the highest increase in BMI Z-score occurred after 4 years (p < 0.001) and then decreased (p = 0.04). In the PR ≥2, the BMI Z-score slightly decreased within the first 2 years (p = 0.02), then increased (p = 0.03) and remained unchanged for the last 2 years. Six years after T1D started, the mean DIRs do not differ among the patient groups (ANOVA p = 0.272).

Conclusion

During 6 years of follow-up, PR occurred in almost two-thirds of the studied children including almost all overweight and obese children. We observed a gradual normalization of the BMI Z-score at the end of the follow-up. BMI Z-score increased slightly in children with no remission initially but remained later constant until the end of observation. In both remitter groups, the increase in BMI Z-score appeared later when the protective honeymoon period ended. Regardless of BMI Z-score, the β-cell destruction process progresses, and after 6 years, the DIR is similar for all patients.
Short-term PV power prediction based on the 24 traditional Chinese solar terms and adaboost-GA-BP model
Authors: Liu Yujun , Duan Shutong , He Xinrui , Wang Hongqing
Published: September 2023

High-precision, short-term power forecasting for photovoltaic systems not only reduces unnecessary energy consumption but also provides power grid security. To this end, in this paper we propose a photovoltaic short-term power forecasting model based on the division of data of the 24 traditional Chinese solar terms and the Adaboost-GA-BP model. The 24 solar terms were condensed from the laws of meteorology, phenology, and seasonal changes to adapt to agricultural times in ancient China and have become intangible cultural heritage. This article first analyzes the numerical characteristics of meteorological factors and demonstrates their close correlation with the turning points of the 24 solar terms. Second, using Standardized Euclidean Distance and Spearman’s Correlation Coefficients to analyze data similarity between the Gregorian half-months and the 24 solar terms divisions for comparative analysis purposes, it is shown that the intragroup data under the division of the 24 solar terms have a higher similarity, leading to an average decrease of 15.68%, 40.57%, 14.68%, and 14.64% in the MAE, MSE, RMSE, and WMAPE of the predicted results, respectively. Finally, based on the data derived from the 24 solar terms, the combined algorithm was compared with the Adaboost-GA-BP model and then was verified. The genetic algorithm and Adaboost were used to optimize the BP neural network algorithm in initial value assignment and neural network structure, resulting in a 23.42%, 18.12%, and 22.28% reduction in the mean values of the MAE, RMSE, and WMAPE of the predicted results, respectively. Analysis of the results show that using the Adaboost-GA-BP model based on the 24 solar terms for short-term photovoltaic power forecasting can improve the accuracy of photovoltaic power forecasting and significantly improve the predictive performance of the model.
Research on multi-timescale operation optimization of a distributed electro-hydrogen coupling system considering grid interaction
Authors: Ma Shun , Mei Shiyan , Yu Liwei
Published: September 2023

Against the backdrop of increasingly prominent environmental issues, new energy consumption issues, and energy supply and demand balance issues, the optimization of multi time scale operation of distributed electro hydrogen coupling systems has become a research focus. Based on this, this article optimizes the multi time scale operation of a distributed electric hydrogen coupling system that takes into account grid interaction. By designing a system framework for distributed electro hydrogen coupling systems, operational strategies for each system were proposed. Analyzed the uncertainty and response characteristics of wind and solar power generation units and load demand, and constructed a multiple uncertainty model for distributed electric hydrogen coupling system. At the same time, a three stage, multi time scale operation optimization model of the electric hydrogen coupling system was constructed based on the response characteristics of the distributed electric hydrogen coupling system. The construction of these models reduced scheduling costs by 12.55% and increased clean energy consumption rate by 13.50%.
Boundary green infrastructure: a green infrastructure connecting natural and artificial spaces
Authors: Yuan Jingyuan , Wu Bing , Liu Xiaoguang , Lu Ming
Published: September 2023

As a naturally-based solution (NBS), green infrastructural network constructing can improve urban ecological resilience and support sustainable urban development. However, as the Frontier of urban expansion, the boundary of built-up areas has little research on the boundary green infrastructure (BGI) connecting natural and artificial spaces. In order to make up for the shortcomings of relevant research, we propose a method for identifying BGI and analyze its landscape pattern characteristics. We selected 15 European cities as cases to extract the boundaries of built-up areas. Moreover, we used morphological pattern analysis (MSPA) to identify the ecological source and select the best distance threshold for the landscape connectivity model to identify the BGI range. Through the gradient area method and MSPA, the BGI landscape pattern characteristics of the case cities were analyzed quantitatively. The BGI scale was affected by the area of the built-up area and the threshold of GI landscape connectivity distance. Additionally, the BGI space contained a small number of large ecological sources and many scattered and small fragmented patches. The best landscape model of BGI was the surrounding pattern, followed by the aggregation pattern, which had good landscape connectivity; however, the fragmentation of the scattered pattern was high. Lastly, the ecological core area in BGI was the main landscape type; it has a high landscape connection function for the GI network inside and outside the built-up area and promotes biological exchange inside and outside the built-up area. This study proves that BGI has an important ecological significance, can guarantee the scientific nature of the NBS method, and ensures the ecological security pattern of cities.
Soil organic pollution and ecological risk assessment in brownfield soil from Northwest China: an integrated analysis of man-land interrelations
Authors: Wang Luyao , Xie Xiao , Liu Siqi , Wang Jing , Peng Biao , Sun Yingying
Published: September 2023

In general, chemical plants are accompanied by a variety of secondary production in the production process, which may have different degrees of impact on the environment. At the same time, in order to ensure the environmental safety of new urban construction land, it is necessary to conduct pollution investigation and further environmental risk assessment on potentially polluting abandoned chemical plants. This paper takes a chemical plant producing food grade fumaric acid in Northwest China as an example to investigate the pollution of organic matter in the soil in accordance with relevant standards, then analyzes the vertical pollution degree of key pollution areas. The calculation results of single factor pollution index and Nemerow pollution index show that there are 17 kinds of organic pollutants that exceed the screening value in land of Class I. Among them, benzene, 1,2,3-trichloropropane and 1,1,2,2-tetrachloroethane are most serious, and the highest exceeded the standard by 11,311 times. Moreover, the distillation zone and the reactor zone have reached the level of V pollution, and the maximum pollution depth can reach more than 6 m. The results of HERA software analysis showed that there were 18 and 10 kinds of organic pollutants with carcinogenic risk values exceeding 10−6 in the reactor and distillation area, respectively, and 25 and 11 kinds of organic pollutants with hazard quotients exceeding 1, respectively. According to relevant regulations, the contaminated areas with unacceptable regional risks must be properly repaired.
Leasing from the perspective of environmental management and its influence on business performance
Authors: Bocok Vojtech , Hinke Jana , Abrham Josef
Published: September 2023

Goals: The paper aims to analyze the current development in the field of circular economy relating to the use of lease financing as possible environemental management’s tool.

Methods: The paper contains own research conducted on companies trading on the Prague Stock Exchange from 1993 to 2019, in which the influence of lease financing on market values of companies representing investor confidence and profitability ratios are examined. The research uses a regression model of panel data.

Results: The research confirms the fact that companies using leases are able to maintain investor confidence better. There has been an increase in their market value. It has been proved that lease financing does not harm the economic performance of companies and that, on the contrary, it is a possible way of financing companies, which would be more in line with sustainable development.

Conclusion: The presented article extended further quantitative research in the field of sustainability, circular economy, environmental management and the position of leasing as one of the possible instruments of these policies. It has been confirmed that the use of leases increases the value of Tobin’s Q. However, there has been a decrease in investor confidence expressed by the negative correlation of Tobin’s Q when comparing with the situation where the company invests in increasing its tangible assets in the standard way.
Establishment of linkage phase, using Oxford Nanopore Technologies, for preimplantation genetic testing of Coffin-Lowry syndrome with a de novo RPS6KA3 mutation
Authors: Wen Xiaojun , Du Jing , Li Zhiming , Liu Nengqing , Huo Junye , Li Jieliang , Ke Wanna , Wu Jiaqi , Fang Xiaowu , Lin Xiufeng
Published: September 2023

Background: This study aimed to perform preimplantation genetic testing (PGT) for a female Coffin-Lowry Syndrome (CLS) patient with a de novo mutation (DNM) in RPS6KA3. It was challenging to establish the haplotype in this family because of the lack of information from affected family members. Hence, we explored a new and reliable strategy for the detection of the DNM in PGT, using Oxford Nanopore Technologies (ONT) and the MARSALA platform.

Methods: We performed whole-exome sequencing (WES) on the proband and confirmed the pathogenic mutation by Sanger sequencing. The proband then underwent PGT to prevent the transmission of the pathogenic mutation to her offspring. We diverged from the conventional methods and used long-read sequencing (LRS) on the ONT platform to directly detect the mutation and nearby SNPs, for construction of the haplotype in the preclinical phase of PGT. In the clinical phase of embryo diagnosis, the MARSALA method was used to detect both the SNP-based haplotype and chromosome copy number variations (CNVs), in each blastocyst. Finally, a normal embryo was selected by comparison to the haplotype of the proband and transferred into the uterus. Sanger sequencing and karyotyping were performed by amniocentesis, at 17 weeks of gestation, to confirm the accuracy of PGT.

Results: Using WES, we found the novel, heterozygous, pathogenic c.1496delG (p.Gly499Valfs*25) mutation of RPS6KA3 in the proband. The SNP-based haplotype that was linked to the pathogenic mutation site was successfully established in the proband, without the need for other family members to be tested with ONT. Eight blastocysts were biopsied to perform PGT and were assessed with a haplotype linkage analysis (30 SNP sites selected), to give results that were consistent with direct mutation detection using Sanger sequencing. The results of PGT showed that three of the eight blastocysts were normal, without the DNM. Moreover, the patient had a successful pregnancy, after transfer of a normal blastocyst into the uterus, and delivered a healthy baby.

Conclusion: The ONT platform, combined with the MARSALA method, can be used to perform PGT for DNM patients without the need for other samples as a reference.
Engineered CD4 T cells expressing a membrane anchored viral inhibitor restrict HIV-1 through cis and trans mechanisms
Authors: Wang Weiming , Truong Khanghy , Ye Chaobaihui , Sharma Suman , He Huan , Liu Lihong , Wen Michael , Misra Anisha , Zhou Paul , Kimata Jason T.
Published: September 2023

HIV-1 infection of target cells can occur through either cell-free virions or cell-cell transmission in a virological synapse, with the latter mechanism of infection reported to be 100- to 1,000-fold more efficient. Neutralizing antibodies and entry inhibitors effectively block cell-free HIV-1, but with few exceptions, they display much less inhibitory activity against cell-mediated HIV-1 transmission. Previously, we showed that engineering HIV-1 target cells by genetically linking single-chain variable fragments (scFvs) of antibodies to glycosyl phosphatidylinositol (GPI) potently blocks infection by cell-free virions and cell-mediated infection by immature dendritic cell (iDC)-captured HIV-1. Expression of scFvs on CD4+ cell lines by transduction with X5 derived anti-HIV-1 Env antibody linked to a GPI attachment signal directs GPI-anchored scFvs into lipid rafts of the plasma membrane. In this study, we further characterize the effect of GPI-scFv X5 on cell-cell HIV-1 transmission from DCs to target cells. We report that expression of GPI-scFv X5 in transduced CD4+ cell lines and human primary CD4+ T cells potently restricts viral replication in iDC- or mDC-captured HIV-1 in trans. Using live-cell imaging, we observed that when GPI-GFP or GPI-scFv X5 transduced T cells are co-cultured with iDCs, GPI-anchored proteins enrich in contact zones and subsequently migrate from T cells into DCs, suggesting that transferred GPI-scFv X5 interferes with HIV-1 infection of iDCs. We conclude that GPI-scFv X5 on the surface of transduced CD4+ T cells not only potently blocks cell-mediated infection by DCs, but it transfers from transduced cells to the surface of iDCs and neutralizes HIV-1 replication in iDCs. Our findings have important implications for HIV-1 antibody-based immunotherapies as they demonstrate a viral inhibitory effect that extends beyond the transduced CD4+ T cells to iDCs which can enhance HIV-1 replication.
Cell-type-specific role of P2Y2 receptor in HDM-driven model of allergic airway inflammation
Authors: Schneble Dominik , El-Gazzar Ahmed , Kargarpour Zahra , Kramer Markus , Metekol Seda , Stoshikj Slagjana , Idzko Marco
Published: September 2023

Allergic airway inflammation (AAI) is a chronic respiratory disease that is considered a severe restriction in daily life and is accompanied by a constant risk of acute aggravation. It is characterized by IgE-dependent activation of mast cells, infiltration of eosinophils, and activated T-helper cell type 2 (Th2) lymphocytes into airway mucosa. Purinergic receptor signaling is known to play a crucial role in inducing and maintaining allergic airway inflammation. Previous studies in an ovalbumin (OVA)–alum mouse model demonstrated a contribution of the P2Y2 purinergic receptor subtype (P2RY2) in allergic airway inflammation. However, conflicting data concerning the mechanism by which P2RY2 triggers AAI has been reported. Thus, we aimed at elucidating the cell-type-specific role of P2RY2 signaling in house dust mite (HDM)-driven model of allergic airway inflammation. Thereupon, HDM-driven AAI was induced in conditional knockout mice, deficient or intact for P2ry2 in either alveolar epithelial cells, hematopoietic cells, myeloid cells, helper T cells, or dendritic cells. To analyze the functional role of P2RY2 in these mice models, flow cytometry of bronchoalveolar lavage fluid (BALF), cytokine measurement of BALF, invasive lung function measurement, HDM re-stimulation of mediastinal lymph node (MLN) cells, and lung histology were performed. Mice that were subjected to an HDM-based model of allergic airway inflammation resulted in reduced signs of acute airway inflammation including eosinophilia in BALF, peribronchial inflammation, Th2 cytokine production, and bronchial hyperresponsiveness in mice deficient for P2ry2 in alveolar epithelial cells, hematopoietic cells, myeloid cells, or dendritic cells. Furthermore, the migration of bone-marrow-derived dendritic cells and bone-marrow-derived monocytes, both deficient in P2ry2, towards ATP was impaired. Additionally, we found reduced levels of MCP-1/CCL2 and IL-8 homologues in the BALF of mice deficient in P2ry2 in myeloid cells and lower concentrations of IL-33 in the lung tissue of mice deficient in P2ry2 in alveolar epithelial cells. In summary, our results show that P2RY2 contributes to HDM-induced airway inflammation by mediating proinflammatory cytokine production in airway epithelial cells, monocytes, and dendritic cells and drives the recruitment of lung dendritic cells and monocytes.
Disseminated tuberculosis in a child during the COVID-19 pandemic: a case report and literature review
Authors: Weng Taoping , Dong Yaqiong , Huang Niwen , Zhao Chenqu , Zhang Lei , Cao Shan , Tang Jing , Zhang Danni , Zhang Xianming
Published: September 2023

Background

Disseminated tuberculosis is an uncommon but devastating form of tuberculosis, possibly developing with the immune response of patients. COVID-19 infection may produce an immunosuppressive effect with possible implications for tuberculosis dissemination.

Case presentation

A 17-year-old female patient with a history of tuberculous pleurisy presented to the hospital with a high fever and life-threatening dyspnea after contracting a COVID-19 infection. Her condition deteriorated rapidly with grand mal epilepsy and acute gastrointestinal bleeding with a grossly depressed CD4 T-cell count, which was indicative of her profoundly immunosuppressed state. After identifying Mycobacterium tuberculosis in her cerebrospinal fluid and a subcutaneous abscess in her left lower back, she was diagnosed with disseminated tuberculosis involving both lungs, the central nervous system, the terminal ileum, the liver, bilateral adnexal tissue, and subcutaneous soft tissue in accordance with the chest and abdominal CT. Empirical treatment was initiated with dexamethasone (5 mg/day) and an anti-tuberculosis regimen of isoniazid, rifampicin, pyrazinamide, amikacin, and meropenem, which was replaced with faropenem after she left the hospital. The therapeutic effect was considered satisfied in the second month of follow-up.

Conclusion

To the best of our knowledge, we report the first case report of disseminated tuberculosis after COVID-19 infection. Tuberculosis may disseminate and progress during the COVID-19 pandemic, requiring more significant studies to provide better diagnosis and treatment options for the co-infection.
Dendritic cell vaccine of gliomas: challenges from bench to bed
Authors: Zheng Ye , Ma Xiaoyu , Feng Shouchang , Zhu Hongtao , Chen Xin , Yu Xingjiang , Shu Kai , Zhang Suojun
Published: September 2023

Gliomas account for the majority of brain malignant tumors. As the most malignant subtype of glioma, glioblastoma (GBM) is barely effectively treated by traditional therapies (surgery combined with radiochemotherapy), resulting in poor prognosis. Meanwhile, due to its “cold tumor” phenotype, GBM fails to respond to multiple immunotherapies. As its capacity to prime T cell response, dendritic cells (DCs) are essential to anti-tumor immunity. In recent years, as a therapeutic method, dendritic cell vaccine (DCV) has been immensely developed. However, there have long been obstacles that limit the use of DCV yet to be tackled. As is shown in the following review, the role of DCs in anti-tumor immunity and the inhibitory effects of tumor microenvironment (TME) on DCs are described, the previous clinical trials of DCV in the treatment of GBM are summarized, and the challenges and possible development directions of DCV are analyzed.
Remarkable response to PD-1 inhibitor in a patient with extensive-stage small cell lung cancer: a case report and literature review
Authors: Yuan Ge , Liu Xiangliang , Zhang Xinwei , Song Wei , Lu Jin , Ding Zhongyang , Chen Xiao
Published: September 2023

We report a case of a 59-year-old male diagnosed with extensive-stage small cell lung cancer (SCLC). He received first-line platinum doublet chemotherapy and second-line topotecan-based regimen, but experienced disease progression after each line of therapy. He was then treated with Sintilimab, a PD-1 inhibitor, in combination with nab-paclitaxel in the third-line setting, which resulted in significant tumor shrinkage. Restaging scans showed a partial response per RECIST criteria with 62% reduction in tumor burden. This case highlights the application and efficacy of immune checkpoint inhibitors in extensive-stage SCLC.
Effect of inspiratory muscle training on hypoxemia in obese patients undergoing painless gastroscopy: protocol for a single-center, double-blind, randomized controlled trial
Authors: Yan Lijuan , Wang Xiao , Du Kairong , Liang Ying
Published: September 2023

Introduction

Obese patients who undergo painless gastroscopy are particularly prone to suffer from upper airway obstruction, respiratory depression, and subsequent hypoxemia. Despite adequate preoxygenation, the incidence of hypoxemia remains high. Recently, inspiratory muscle training (IMT) has been considered to be a promising strategy to increase respiratory muscle strength and endurance with the attendant improvement of pulmonary function. However, it remains unclear whether IMT is associated with a lower rate of hypoxemia in obese patients during this sedative procedure. This study aims to investigate the effectiveness of IMT used in obese patients who are scheduled for selective painless gastroscopy.

Methods and analysis

This prospective, randomized controlled trial (RCT) will enroll 232 obese patients with a body mass index (BMI) of 35–39.9 kg·m−2 who undergo painless gastroscopy at the First Affiliated Hospital of Xiamen University. Subjects will be randomly assigned to two groups with a 1:1 ratio. Participants in both groups will receive IMT for 4 weeks prior to gastroscopy. The intervention group will receive IMT with a load of 30% of the maximal inspiratory pressure (Pi(max)) in the first week, with an increase of 10% per week since the following week, while the counterparts in the control group will not receive any load during the 4-week IMT. The primary outcome is the incidence of hypoxemia during painless gastroscopy. Secondary outcomes include the need for airway maneuvers, blood pressure changes, sleep quality assessment, pro-inflammatory cytokines levels, and monitoring of adverse events.

Discussions

The outcomes of this study will offer invaluable guidance for the clinical implementation of IMT as a potential non-invasive preventive measure. Additionally, it stands to enrich our comprehension of anesthesia management and airway-related challenges in obese patients undergoing procedural sedation, which we anticipate will further contribute to addressing the turnaround concerns within high-volume, swiftly paced ambulatory endoscopy centers.

Ethics and dissemination

This study has been approved by the Ethics Committee of the First Affiliated Hospital of Xiamen University (2022, No.091). The results will be submitted for publication in peer-reviewed journals.

Trial registration number

China Clinical Trial Center (ChiCTR2200067041).
True prevalence of long COVID in children: a narrative review
Authors: Esposito Susanna , Deolmi Michela , Ramundo Greta , Puntoni Matteo , Caminiti Caterina , Principi Nicola
Published: September 2023

Contrary to what is true for adults, little is known about pediatric long COVID (LC). Studies enrolling children are relatively few and extremely heterogeneous. This does not allow to draw definitive conclusions on the frequency and pathogenesis of pediatric LC and limits the development of appropriate and effective measures to contain the clinical, social and economic impact of this condition on the pediatric population. Depending on the methods used to collect and analyze data, studies have found that the incidence rate of pediatric LC may vary from about 25% to less than 5%. However, despite true prevalence of pediatric LC cannot be exactly defined, studies comparing children with previous COVID-19 and uninfected controls have shown that most of the clinical manifestations detected in infected children, mainly mood symptoms, mental health disorders and heart abnormalities could be diagnosed with similar frequency and severity in uninfected subjects also. This seems to indicate that SARS-CoV-2 is the cause of pediatric LC only in a part of children and other factors play a relevant role in this regard. Pandemic itself with the persistent disruption of child lives may have caused persistent stress in all the pediatric population causing mood symptoms, mental health disorders or several organ and body system functional alterations, regardless SARS-CoV-2 infection. These suppositions suggest the need for long-term physical control of all the children after COVID-19 especially when they were already suffering from an underlying disease or have had a severe disease. Moreover, attention should be paid to the assessment of change in children’s emotional and behavioral functioning in order to assure adequate interventions for the best emotional and behavioral well being. However, whatever its origin, it seems highly likely that the prevalence of the pediatric LC is set to decline in the future. Preliminary observations seem to suggest that recently developed SARS-CoV-2 variants are associated with less severe COVID-19. This suggests that, as already seen in adults, a lower number of pediatric virus-associated LC cases should occur. Furthermore, the use of COVID-19 vaccines, reducing incidence and severity of SARS-CoV-2 infection, may reduce risk of LC development. Finally, elimination of restrictive measures should significantly reduce mood symptoms and mental health disorders.
Causality of anti-Helicobacter pylori IgG levels on myocardial infarction and potential pathogenesis: a Mendelian randomization study
Authors: Wang Qiubo , Liu Yingbo , Xu Zhenxing , Wang Zhimiao , Xue Mei , Li Xinran , Wang Ye
Published: September 2023

Background

Previous observational studies have shown that a potential relationship between anti-Helicobacter pylori (H. pylori) IgG levels and Myocardial Infarction (MI). Nevertheless, the evidence for the causal inferences remains disputable. To further clarify the relationship between anti-H. pylori IgG levels and MI and explore its pathogenesis, we conducted a Mendelian randomization (MR) analysis.

Methods

In this study, we used two-sample Mendelian Randomization (MR) to assess the causality of anti-H. pylori IgG levels on MI and potential pathogenesis, 12 single nucleotide polymorphisms (SNPs) related to anti-H. pylori IgG levels were obtained from the European Bioinformatics Institute (EBI). Summary data from a large-scale GWAS meta-analysis of MI was utilized as the outcome dataset. Summary data of mediators was obtained from the FinnGen database, the UK Biobank, the EBI database, MRC-IEU database, the International Consortium of Blood Pressure, the Consortium of Within family GWAS. Inverse variance weighted (IVW) analysis under the fixed effect model was identified as our main method. To ensure the reliability of the findings, many sensitivity analyses were performed.

Results

Our study revealed that increases of anti-H. pylori IgG levels were significantly related to an increased risk of MI (OR, 1.104; 95% CI,1.042–1.169; p = 7.084 × 10−4) and decreases in HDL cholesterol levels (β, −0.016; 95% CI, −0.026 to −0.006; p = 2.02 × 10−3). In addition, there was no heterogeneity or pleiotropy in our findings.

Conclusion

This two-sample MR analysis revealed the causality of anti-H. pylori IgG levels on MI, which might be explained by lower HDL cholesterol levels. Further research is needed to clarify the results.
Development and validation of a nomogram for the risk prediction of malignant cerebral edema after acute large hemispheric infarction involving the anterior circulation
Authors: Xie Wei , Ma Xiaoming , Xu Geman , Wang Yumei , Huang Wendie , Liu Meng , Sheng Shiying , Yuan Jie , Wang Jing
Published: September 2023

Background

Malignant cerebral edema (MCE) is a life-threatening complication of large hemisphere infarction (LHI). Therefore, a fast, accurate, and convenient tool for predicting MCE can guide triage services and facilitate shared decision-making. In this study, we aimed to develop and validate a nomogram for the early prediction of MCE risk in acute LHI involving the anterior circulation and to understand the potential mechanism of MCE.

Methods

This retrospective study included 312 consecutive patients with LHI from 1 January 2019 to 28 February 2023. The patients were divided into MCE and non-MCE groups. MCE was defined as an obvious mass effect with ≥5 mm midline shift or basal cistern effacement. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to explore the MCE-associated factors, including medical records, laboratory data, computed tomography (CT) scans, and independent clinic risk factors. The independent factors were further incorporated to construct a nomogram for MCE prediction.

Results

Among the 312 patients with LHI, 120 developed MCE. The following eight factors were independently associated with MCE: Glasgow Coma Scale score (p = 0.007), baseline National Institutes of Health Stroke Scale score (p = 0.006), Alberta Stroke Program Early CT Score (p < 0.001), admission monocyte count (p = 0.004), white blood cell count (p = 0.002), HbA1c level (p < 0.001), history of hypertension (p = 0.027), and history of atrial fibrillation (p = 0.114). These characteristics were further used to establish a nomogram for predicting prognosis. The nomogram achieved an AUC-ROC of 0.89 (95% CI, 0.82–0.96).

Conclusion

Our nomogram based on LASSO-logistic regression is accurate and useful for the early prediction of MCE after LHI. This model can serve as a precise and practical tool for clinical decision-making in patients with LHI who may require aggressive therapeutic approaches.
A case report of a patient with primary familial brain calcification with a PDGFRB genetic variant
Authors: Al Ali Jamal , Yang Jessica , Phillips Matthew S. , Fink Joseph , Mastrianni James , Seibert Kaitlin
Published: September 2023

Fahr’s disease, or primary familial brain calcification (PFBC), is a rare genetic neurologic disease characterized by abnormal calcification of the basal ganglia, subcortical white matter and cerebellum. Common clinical features include parkinsonism, neuropsychiatric symptoms, and cognitive decline. Genes implicated in Fahr’s disease include PDGFB, PDGFRB, SLC20A2, XPR1, MYORG, and JAM2. We present the case of a 51-year-old woman who developed subacute cognitive and behavioral changes primarily affecting frontal-subcortical pathways and parkinsonism in association with extensive bilateral calcifications within the basal ganglia, subcortical white matter, and cerebellum on neuroimaging. Relevant family history included a paternal aunt with parkinsonism at age 50. Normal parathyroid hormone and calcium levels in the patient’s serum ruled out hypoparathyroidism or pseudohypoparathyroidism as causes for the intracranial calcifications. Genetic panel sequencing revealed a variant of unknown significance in the PDGFRB gene resulting in a p.Arg919Gln substitution in the tyrosine kinase domain of PDGFRB protein. To our knowledge this is the first report of a p.Arg919Gln variant in the PDGFRB gene associated with PFBC. Although co-segregation studies were not possible in this family, the location of the variant is within the tyrosine kinase domain of PDGFRB and pathogenicity calculators predict it is likely to be pathogenic. This report adds to the list of genetic variants that warrant functional analysis and could underlie the development of PFBC, which may help to further our understanding of its pathogenesis and the development of targeted therapies for this disorder.
Effect of melatonin on sleep quality and EEG features in childhood epilepsy: a possible non-conventional treatment
Authors: Dell'Isola Giovanni Battista , Tascini Giorgia , Vinti Valerio , Tulli Eleonora , Dini Gianluca , Mencaroni Elisabetta , Ferrara Pietro , Di Cara Giuseppe , Striano Pasquale , Verrotti Alberto
Published: September 2023

Background

Sleep and epilepsy are characterized by a bidirectional relationship. Indeed, epilepsy predisposes to the development of sleep disorders, while sleep deprivation may exacerbate epilepsy. In addition, antiseizure medication can disrupt normal sleep architecture. Therefore, adequate sleep hygiene could lead to improvement in seizure control. The present study aimed to evaluate the effect of melatonin on seizure frequency, EEG tracing, and sleep in children with focal idiopathic epilepsy.

Methods

This observation study evaluated the effect of 4 mg oral melatonin in ameliorating sleep–wake cycle, seizure frequency, and EEG features in children with focal idiopathic epilepsy of infancy. Twenty children were enrolled from September 2020 to August 2021. The study consisted of serial controls at enrollment (t0), at 3 months (t1), and at 6 months (t2) including neurological examination, questionnaire about sleep disturbances (CSHQ), and EEG.

Results

A significant improvement in sleep quality and daytime sleepiness was observed after melatonin supplementation. Furthermore, we observed a noteworthy improvement in EEG tracing at t2 that exhibited a significant correlation with improvements in CSHQ scores.

Conclusion

The studies conducted so far to evaluate the effect of melatonin in persons with epilepsy do not lead to definitive conclusions. Despite the small population sample and the study design, we report sleep and EEG improvement after melatonin administration in our cohort. Larger studies are needed to further study the neuroprotective and anticonvulsant properties of melatonin.
Evaluation of consciousness rehabilitation via neuroimaging methods
Authors: Wang Jianyang , Gao Xinyu , Xiang Zuchao , Sun Fangfang , Yang Yong
Published: September 2023

Accurate evaluation of patients with disorders of consciousness (DoC) is crucial for personalized treatment. However, misdiagnosis remains a serious issue. Neuroimaging methods could observe the conscious activity in patients who have no evidence of consciousness in behavior, and provide objective and quantitative indexes to assist doctors in their diagnosis. In the review, we discussed the current research based on the evaluation of consciousness rehabilitation after DoC using EEG, fMRI, PET, and fNIRS, as well as the advantages and limitations of each method. Nowadays single-modal neuroimaging can no longer meet the researchers` demand. Considering both spatial and temporal resolution, recent studies have attempted to focus on the multi-modal method which can enhance the capability of neuroimaging methods in the evaluation of DoC. As neuroimaging devices become wireless, integrated, and portable, multi-modal neuroimaging methods will drive new advancements in brain science research.
An F-ratio-based method for estimating the number of active sources in MEG
Authors: Giri Amita , Mosher John C. , Adler Amir , Pantazis Dimitrios
Published: September 2023

Introduction

Magnetoencephalography (MEG) is a powerful technique for studying the human brain function. However, accurately estimating the number of sources that contribute to the MEG recordings remains a challenging problem due to the low signal-to-noise ratio (SNR), the presence of correlated sources, inaccuracies in head modeling, and variations in individual anatomy.

Methods

To address these issues, our study introduces a robust method for accurately estimating the number of active sources in the brain based on the F-ratio statistical approach, which allows for a comparison between a full model with a higher number of sources and a reduced model with fewer sources. Using this approach, we developed a formal statistical procedure that sequentially increases the number of sources in the multiple dipole localization problem until all sources are found.

Results

Our results revealed that the selection of thresholds plays a critical role in determining the method's overall performance, and appropriate thresholds needed to be adjusted for the number of sources and SNR levels, while they remained largely invariant to different inter-source correlations, translational modeling inaccuracies, and different cortical anatomies. By identifying optimal thresholds and validating our F-ratio-based method in simulated, real phantom, and human MEG data, we demonstrated the superiority of our F-ratio-based method over existing state-of-the-art statistical approaches, such as the Akaike Information Criterion (AIC) and Minimum Description Length (MDL).

Discussion

Overall, when tuned for optimal selection of thresholds, our method offers researchers a precise tool to estimate the true number of active brain sources and accurately model brain function.
Mastication stimuli regulate the heartbeat rate through rhythmic regulation by the hypothalamic-autonomic system; molecular and telemetric studies in weaning-stage rats
Authors: Lee Seonmi , Tochinai Ryota , Yasuoka Akihito , Nagai Toshitada , Saito Yoshikazu , Kuwahara Masayoshi , Abe Keiko , Asakura Tomiko
Published: September 2023

Mastication stimuli have been demonstrated to affect memory function and autonomic nerve activity; however, this process has not been well studied during weaning compared to old age. Previously, we conducted molecular analyses of the thalamus and hippocampus to elucidate the mechanisms underlying this memory-enhancing effect in weaning-stage rats. In this study, we aimed to evaluate the effect of masticatory stimuli on the regulation of heartbeat rate (HR) through the hypothalamic-autonomic system. Three-week-old male rats were administered a powdered diet (P group) or chow-diet (C group) for 10 days. Thereafter, transcriptome analysis was performed. Vasopressin, cocaine-amphetamine-regulated transcript prepropeptide, corticotropin-releasing hormone, and thyrotropin-releasing hormone, which are involved in sympathetic activation of heart rate, were downregulated in the C group. Electrocardiograms were recorded continuously for 12 days under the same condition. Interestingly, rats in the C group had a significantly lower HR than those in the P group on day 11. We checked several parameters representing the autonomic regulation of HR. The C group had higher values for the high-frequency band integration of the HR power spectrum (parasympathetic marker) and root mean square successive difference of R-wave intervals (parasympathetic marker) relative to the P group. Such findings provide a molecular and physiological basis for understanding the regulation of cardiovascular function in response to masticatory stimuli in the autonomic nervous system.
An interdisciplinary intervention for children with complex health complaints; a feasibility study of selection criteria
Authors: Elgen Irene , Lygre Ragnhild B , Årli Ånen , Heggestad Torhild
Published: September 2023

Background

There is a need for re-designing the health service for children suffering from complex and compound health complaints. Based on a previous register study, we have developed criteria to select patients with complex health complaints eligible for an Intervention with an interdisciplinary professional team. The team consists of a pediatrician, a psychologist and a physiotherapist.

Method

To identify children with complex health complaints who would benefit from this intervention, we have selected a group of patients by using a set of criteria consisting of the following criteria: multi-referred young school age children referred to both mental health service and pediatric service. This study focuses on the feasibility of these criteria by measuring participation and compliance and by gathering feedback from the team members in the interdisciplinary team.

Results

Among 677 children aged 6−12 years referred to a regional hospital, we found 32 (5%) children eligible for the interdisciplinary Intervention according to the applied criteria. Only 6% of the invited parents declined to participate in the intervention. According to the interdisciplinary team, the intervention was found suitable for 88% of the children.

Conclusion

The suggested criteria seemed feasible, in terms of identifying eligible patients for this interdisciplinary Intervention for children with complex health complaints.

Clinical Trial Registration

Retrospectively registered on www.clinicaltrials.gov, ID NCT04652154, on the 3rd of December 2020.
Differential effects of prenatal psychological distress and positive mental health on offspring socioemotional development from infancy to adolescence: a meta-analysis
Authors: Phua Desiree Y. , Chew Chermaine S. M. , Tan Yang Lik , Ng Benjamin J. K. , Lee Florence K. L. , Tham Megan M. Y.
Published: September 2023

The impact of prenatal maternal mental health on offspring socioemotional development is substantial and enduring. Existing literature primarily focuses on the effects of psychological distress during pregnancy, emphasizing adverse child outcomes. Recent studies, however, highlight the unique impact of positive maternal mental health on child outcomes. To elucidate the differential associations of maternal psychological distress and positive mental health during pregnancy with child outcomes, we conducted a systematic literature search and random-effects meta-analyses on studies investigating the associations of prenatal maternal mental health with child socioemotional development. Our analyses, comprising 74 studies with 321,966 mother-child dyads across 21 countries, revealed significant associations of prenatal psychological distress with both adverse and positive child socioemotional outcomes. Notably, the effect sizes for the association of psychological distress with positive child outcomes were smaller compared to adverse outcomes. Positive prenatal mental health, on the other hand, was significantly associated with positive socioemotional outcomes but not adverse outcomes. This meta-analysis highlights the independence of negative and positive prenatal mental health constructs and their distinct relationships with child socioemotional development. The findings underscore the importance of considering the positive spectrum of maternal mental health and developmental outcomes to enhance our understanding of prenatal influences on child development.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335227, identifier CRD42022335227.
Implementing pharmacogenetic testing in fluoropyrimidine-treated cancer patients: DPYD genotyping to guide chemotherapy dosing in Greece
Authors: Ragia Georgia , Maslarinou Anthi , Atzemian Natalia , Biziota Eirini , Koukaki Triantafyllia , Ioannou Charalampia , Balgkouranidou Ioanna , Kolios George , Kakolyris Stylianos , Xenidis Nikolaos , Amarantidis Kyriakos , Manolopoulos Vangelis G.
Published: September 2023

Introduction: Dihydropyrimidine dehydrogenase (DPD), encoded by DPYD gene, is the rate-limiting enzyme responsible for fluoropyrimidine (FP) catabolism. DPYD gene variants seriously affect DPD activity and are well validated predictors of FP-associated toxicity. DPYD variants rs3918290, rs55886062, rs67376798, and rs75017182 are currently included in FP genetic-based dosing guidelines and are recommended for genotyping by the European Medicines Agency (EMA) before treatment initiation. In Greece, however, no data exist on DPYD genotyping. The aim of the present study was to analyze prevalence of DPYD rs3918290, rs55886062, rs67376798, rs75017182, and, additionally, rs1801160 variants, and assess their association with FP-induced toxicity in Greek cancer patients.

Methods: Study group consisted of 313 FP-treated cancer patients. DPYD genotyping was conducted on QuantStudio ™ 12K Flex Real-Time PCR System (ThermoFisher Scientific) using the TaqMan® assays C__30633851_20 (rs3918290), C__11985548_10 (rs55886062), C__27530948_10 (rs67376798), C_104846637_10 (rs75017182) and C__11372171_10 (rs1801160).

Results: Any grade toxicity (1-4) was recorded in 208 patients (66.5%). Out of them, 25 patients (12%) experienced grade 3-4 toxicity. DPYD EMA recommended variants were detected in 9 patients (2.9%), all experiencing toxicity (p = 0.031, 100% specificity). This frequency was found increased in grade 3-4 toxicity cases (12%, p = 0.004, 97.9% specificity). DPYD deficiency increased the odds of grade 3-4 toxicity (OR: 6.493, p = 0.014) and of grade 1-4 gastrointestinal (OR: 13.990, p = 0.014), neurological (OR: 4.134, p = 0.040) and nutrition/metabolism (OR: 4.821, p = 0.035) toxicities. FP dose intensity was significantly reduced in DPYD deficient patients (β = −0.060, p <0.001). DPYD rs1801160 variant was not associated with FP-induced toxicity or dose intensity. Triple interaction of DPYD*TYMS*MTHFR was associated with grade 3-4 toxicity (OR: 3.725, p = 0.007).

Conclusion: Our findings confirm the clinical validity of DPYD reduced function alleles as risk factors for development of FP-associated toxicity in the Greek population. Pre-treatment DPYD genotyping should be implemented in clinical practice and guide FP dosing. DPYD*gene interactions merit further investigation as to their potential to increase the prognostic value of DPYD genotyping and improve safety of FP-based chemotherapy.
Destination integration: linking physiology, histology, and embryology content in foundational sciences
Authors: Dennis Jennifer F. , Creamer Bradley A.
Published: September 2023

Anatomy and physiology are tightly linked disciplines that complement each other, however, in medical education delivery of this content is often siloed and divided. To address this, we created combined anatomy and physiology content for the female reproductive system, and team-taught designated histology and embryology topics integrated with the physiology content. Collectively, this created a more holistic incorporation of topics for student learning. Here we describe the format and approach for this teaching innovation.