bluuebunny/crossref_metadata_2025 huggingface dataset:
Systolic myocardial function measured by echocardiographic speckle-tracking and peak oxygen consumption in pediatric childhood cancer survivors—a PACCS study
Authors: Engan Britt , Diab Simone , Brun Henrik , Raastad Truls , Torsvik Ingrid Kristin , Omdal Tom Roar , Ghavidel Fatemeh Zamanzad , Greve Gottfried , Ruud Ellen , Edvardsen Elisabeth , Leirgul Elisabeth
Published: July 2023

Background

Cancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors.

Methods

In this sub-study of the international study “Physical Activity and fitness in Childhood Cancer Survivors” (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9–18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function.

Results

Mean LV-GLS was reduced in the childhood cancer survivors compared to the controls, −19.7% [95% confidence interval (CI) −20.1% to −19.3%] vs. −21.3% (95% CI: −22.2% to −20.3%) (p = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z-score. Mean RV-LS was similar in the childhood cancer survivors and the controls, −23.2% (95% CI: −23.7% to −22.6%) vs. −23.3% (95% CI: −24.6% to −22.0%) (p = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient (r) = −0.3 for LV-GLS]. Higher doses of anthracyclines (r = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment (r = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function.

Conclusions

Left ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk.
Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models
Authors: Dehdari Ebrahimi Niloofar , Sadeghi Alireza , Ala Moein , Ebrahimi Fatemeh , Pakbaz Sara , Azarpira Negar
Published: July 2023

Background

Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility.

Material and methods

We systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen’s d) and 95% confidence interval.

Results

24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high‐fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen’s testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress.

Conclusions

Melatonin can reduce damage to male rodents’ gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.
Chestnut polysaccharide rescues the damaged spermatogenesis process of asthenozoospermia-model mice by upregulating the level of palmitic acid
Authors: Han Baoquan , Guo Jiachen , Zhou Bo , Li Chunxiao , Qiao Tian , Hua Lei , Jiang Yinuo , Mai Zihang , Yu Shuai , Tian Yu , Zhang Xiaoyuan , Lu Dongliang , Wang Bin , Sun Zhongyi , Li Lan
Published: July 2023

Introduction

In recent years, the quality of male semen has been decreasing, and the number of male infertilities caused by asthenozoospermia is increasing year by year, and the diagnosis and treatment of patients with asthenozoospermia are gradually receiving the attention of the whole society. Due to the unknown etiology and complex pathogenesis, there is no specific treatment for asthenozoospermia. Our previous study found that the administration of chestnut polysaccharide could alter the intestinal microbiota and thus improve the testicular microenvironment, and rescue the impaired spermatogenesis process by enhancing the expression of reproduction-related genes, but its exact metabolome-related repairment mechanism of chestnut polysaccharide is still unclear.

Methods and results

In this study, we studied the blood metabolomic changes of busulfan-induced asthenozoospermia-model mice before and after oral administration of chestnut polysaccharide with the help of metabolome, and screened two key differential metabolites (hydrogen carbonate and palmitic acid) from the set of metabolomic changes; we then analyzed the correlation between several metabolites and between different metabolites and intestinal flora by correlation analysis, and found that palmitic acid in the blood serum of mice after oral administration of chestnut polysaccharide had different degrees of correlation with various metabolites, and palmitic acid level had a significant positive correlation with the abundance of Verrucomicrobia; finally, we verified the role of palmitic acid in rescuing the damaged spermatogenesis process by using asthenozoospermia-model mice, and screened the key target gene for palmitic acid to play the rescuing effect by integrating the analysis of multiple databases.

Discussion

In conclusion, this study found that chestnut polysaccharide rescued the damaged spermatogenesis in asthenozoospermia-model mice by upregulating palmitic acid level, which will provide theoretical basis and technical support for the use of chestnut polysaccharide in the treatment of asthenozoospermia.
A study on the multi-objective optimization method and characteristic analysis of installation locations of submersible mixer for sewage
Authors: Tian Fei , Yang Chen , Zhang Erfeng , Sun Dehua , Shi Weidong , Chen Yonghua
Published: July 2023

In this study, the performance of submersible mixers in sewage treatment was improved by optimizing the installation position parameters of the mixer. The aim was to enhance the average flow velocity and mixing efficiency in the pool. The study employed ISIGHT software, integrated with Creo Parametric 6.0 software and ANSYS Workbench 2020 software, to analyze the factors affecting mean flow velocity and completed a multi-objective optimized design using Non-dominated Sorting Genetic Algorithm (NSGA-II). The study used the ISIGHT software to analyze the factors affecting mean flow velocity in the pool. The installation position parameters of the submersible mixer were selected as design variables. The study employed Creo Parametric 6.0 software to create a three-dimensional model of the pool and the submersible mixer. ANSYS Workbench 2020 software was used to simulate fluid flow in the pool. The Non-dominated Sorting Genetic Algorithm (NSGA-II) was used for multi-objective optimization. The results of the study indicated an increase of approximately 0.021 m/s in average flow velocity and an improvement of approximately 0.47% in mixing efficiency compared to pre-optimization values. The effective axial propulsion distance and effective radial diffusion radius were significantly increased by 6.71% and 8.33%, respectively, after optimization. The fluid distribution in the pool became more uniform, and the low-speed zone was greatly reduced, resulting in an enhanced flow state of the fluid in the pool and a strengthened mixing effect. The study provides insights into the control of the submersible mixer’s installation position to improve the average flow velocity inside the pool. Automatic optimization of submersible mixer installation locations using the ISIGHT software can effectively improve mixing efficiency, overall plant operating efficiency, and economic benefits in sewage treatment plants. The multi-objective optimization platform based on the ISIGHT platform for wastewater treatment mixer installation location can be successfully applied in engineering practice.
A conceptual approach to developing biodiversity informatics as a field of science in South Africa
Authors: Parker-Allie Fatima , Gibbons Mark J. , Harebottle Douglas M.
Published: July 2023

In South Africa, as in other parts of the world, Biodiversity Informatics (BDI) has been identified as a young field of science that lies at the nexus of several disciplines, including informatics, biology and mathematics/statistics. Being such a new and dynamic field, there are challenges in the recruitment, training and retention of personnel that can support inter alia the mobilisation, management, coordination, and utilisation of biodiversity information for key conservation and biodiversity outcomes. The lack of human capital also place at risk the implementation of (e.g.) the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), and hinders attainment of the Convention on Biological Diversity post-2020 framework targets. There is a clear demand for broad efforts to build human capital in the field. Using our experiences in South Africa, we provide a framework for establishing BDI as a field of science in developing countries and look at the potential building blocks towards this broad objective, including the need and requirements for the establishment of a Centre for BDI. We explore this concept against a backdrop of the South African government’s 2019 White Paper on Science, Technology and Innovation, and the associated Decadal Plan, both developed under the auspices of the Department of Science and Innovation. We also reflect on efforts in the broader landscape to look at the establishment of BDI curricula.
PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis
Authors: Liu Mingchong , Wang Yongheng , Shi Wentao , Yang Chensong , Wang Qidong , Chen Jingyao , Li Jun , Chen Bingdi , Sun Guixin
Published: July 2023

Sarcopenia and osteoporosis, two degenerative diseases in older patients, have become severe health problems in aging societies. Muscles and bones, the most important components of the motor system, are derived from mesodermal and ectodermal mesenchymal stem cells. The adjacent anatomical relationship between them provides the basic conditions for mechanical and chemical signals, which may contribute to the co-occurrence of sarcopenia and osteoporosis. Identifying the potential common crosstalk genes between them may provide new insights for preventing and treating their development. In this study, DEG analysis, WGCNA, and machine learning algorithms were used to identify the key crosstalk genes of sarcopenia and osteoporosis; this was then validated using independent datasets and clinical samples. Finally, four crosstalk genes (ARHGEF10, PCDH7, CST6, and ROBO3) were identified, and mRNA expression and protein levels of PCDH7 in clinical samples from patients with sarcopenia, with osteoporosis, and with both sarcopenia and osteoporosis were found to be significantly higher than those from patients without sarcopenia or osteoporosis. PCDH7 seems to be a key gene related to the development of both sarcopenia and osteoporosis.
Comprehensive analysis of the progression mechanisms of CRPC and its inhibitor discovery based on machine learning algorithms
Authors: Wang Zhen , Zou Jing , Zhang Le , Liu Hongru , Jiang Bei , Liang Yi , Zhang Yuzhe
Published: July 2023

Background: Almost all patients treated with androgen deprivation therapy (ADT) eventually develop castration-resistant prostate cancer (CRPC). Our research aims to elucidate the potential biomarkers and molecular mechanisms that underlie the transformation of primary prostate cancer into CRPC.

Methods: We collected three microarray datasets (GSE32269, GSE74367, and GSE66187) from the Gene Expression Omnibus (GEO) database for CRPC. Differentially expressed genes (DEGs) in CRPC were identified for further analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Weighted gene coexpression network analysis (WGCNA) and two machine learning algorithms were employed to identify potential biomarkers for CRPC. The diagnostic efficiency of the selected biomarkers was evaluated based on gene expression level and receiver operating characteristic (ROC) curve analyses. We conducted virtual screening of drugs using AutoDock Vina. In vitro experiments were performed using the Cell Counting Kit-8 (CCK-8) assay to evaluate the inhibitory effects of the drugs on CRPC cell viability. Scratch and transwell invasion assays were employed to assess the effects of the drugs on the migration and invasion abilities of prostate cancer cells.

Results: Overall, a total of 719 DEGs, consisting of 513 upregulated and 206 downregulated genes, were identified. The biological functional enrichment analysis indicated that DEGs were mainly enriched in pathways related to the cell cycle and metabolism. CCNA2 and CKS2 were identified as promising biomarkers using a combination of WGCNA, LASSO logistic regression, SVM-RFE, and Venn diagram analyses. These potential biomarkers were further validated and exhibited a strong predictive ability. The results of the virtual screening revealed Aprepitant and Dolutegravir as the optimal targeted drugs for CCNA2 and CKS2, respectively. In vitro experiments demonstrated that both Aprepitant and Dolutegravir exerted significant inhibitory effects on CRPC cells (p < 0.05), with Aprepitant displaying a superior inhibitory effect compared to Dolutegravir.

Discussion: The expression of CCNA2 and CKS2 increases with the progression of prostate cancer, which may be one of the driving factors for the progression of prostate cancer and can serve as diagnostic biomarkers and therapeutic targets for CRPC. Additionally, Aprepitant and Dolutegravir show potential as anti-tumor drugs for CRPC.
A novel murine model of pyoderma gangrenosum reveals that inflammatory skin-gut crosstalk is mediated by IL-1β-primed neutrophils
Authors: Jatana Samreen , Ponti András K. , Johnson Erin E. , Rebert Nancy A. , Smith Jordyn L. , Fulmer Clifton G. , Maytin Edward V. , Achkar Jean-Paul , Fernandez Anthony P. , McDonald Christine
Published: July 2023

Pyoderma gangrenosum (PG) is a debilitating skin condition often accompanied by inflammatory bowel disease (IBD). Strikingly, ~40% of patients that present with PG have underlying IBD, suggesting shared but unknown mechanisms of pathogenesis. Impeding the development of effective treatments for PG is the absence of an animal model that exhibits features of both skin and gut manifestations. This study describes the development of the first experimental drug-induced mouse model of PG with concomitant intestinal inflammation. Topical application of pyrimidine synthesis inhibitors on wounded mouse skin generates skin ulcers enriched in neutrophil extracellular traps (NETs) as well as pro-inflammatory cellular and soluble mediators mimicking human PG. The mice also develop spontaneous intestinal inflammation demonstrated by histologic damage. Further investigations revealed increased circulating low density IL-1β primed neutrophils that undergo enhanced NETosis at inflamed tissue sites supported by an increase in circulatory citrullinated histone 3, a marker of aberrant NET formation. Granulocyte depletion dampens the intestinal inflammation in this model, further supporting the notion that granulocytes contribute to the skin-gut crosstalk in PG mice. We anticipate that this novel murine PG model will enable researchers to probe common disease mechanisms and identify more effective targets for treatment for PG patients with IBD.
An oncolytic adenovirus coding for a variant interleukin 2 cytokine improves response to chemotherapy through enhancement of effector lymphocyte cytotoxicity, fibroblast compartment modulation and mitotic slippage
Authors: Pakola Santeri , Quixabeira Dafne C. A. , Kudling Tatiana V. , Clubb James H. A. , Grönberg-Vähä-Koskela Susanna , Basnet Saru , Jirovec Elise , Arias Victor , Haybout Lyna , Heiniö Camilla , Santos Joao M. , Cervera-Carrascon Victor , Havunen Riikka , Anttila Marjukka , Hemminki Akseli
Published: July 2023

Pancreatic ductal adenocarcinoma (PDAC) is a highly treatment-resistant cancer. Currently, the only curative treatment for PDAC is surgery, but most patients are diagnosed with metastatic disease and thus outside the scope of surgery. The majority of metastatic patients receive chemotherapy, but responses are limited. New therapeutics are thus urgently needed for PDAC. One major limitation in treating PDAC has been the highly immunosuppressive tumor microenvironment (TME) which inhibits anti-cancer immune responses. We have constructed an oncolytic adenovirus coding for a variant the interleukin 2 molecule, Ad5/3-E2F-d24-vIL2 (also known as TILT-452, and “vIL-2 virus”), with preferential binding to IL-2 receptors on the surface of effector lymphocytes over T regulatory cells (T regs). In the present study this virus was evaluated in combination with nab-paclitaxel and gemcitabine chemotherapy in Panc02 mouse model. Ad5/3-E2F-d24-vIL2 showed marked PDAC cell killing in vitro, alongside induction of mitotic slippage and immunogenic cell death in PDAC cell lines, when combined with chemotherapy. Increased survival was seen in vivo with 80% of animals surviving long term, when compared to chemotherapy alone. Moreover, combination therapy mediated enhanced tumor growth control, without observable toxicities in internal organs or external features. Survival and tumor control benefits were associated with activation of tumor infiltrating immune cells, downregulation of inhibitory signals, change in fibroblast populations in the tumors and changes in intratumoral cytokines, with increased chemokine amounts (CCL2, CCL3, CCL4) and anti-tumor cytokines (IFN-γ and TNFα). Furthermore, vIL-2 virus in combination with chemotherapy efficiently induced tumor protection upon rechallenge, that was extended to a previously non-encountered cancer cell line. In conclusion, Ad5/3-E2F-d24-vIL2 is a promising immunotherapy candidate when combined with nab-paclitaxel and gemcitabine.
CNN stability training improves robustness to scanner and IHC-based image variability for epithelium segmentation in cervical histology
Authors: Miranda Ruiz Felipe , Lahrmann Bernd , Bartels Liam , Krauthoff Alexandra , Keil Andreas , Härtel Steffen , Tao Amy S. , Ströbel Philipp , Clarke Megan A. , Wentzensen Nicolas , Grabe Niels
Published: July 2023

Background

In digital pathology, image properties such as color, brightness, contrast and blurriness may vary based on the scanner and sample preparation. Convolutional Neural Networks (CNNs) are sensitive to these variations and may underperform on images from a different domain than the one used for training. Robustness to these image property variations is required to enable the use of deep learning in clinical practice and large scale clinical research.

Aims

CNN Stability Training (CST) is proposed and evaluated as a method to increase CNN robustness to scanner and Immunohistochemistry (IHC)-based image variability.

Methods

CST was applied to segment epithelium in immunohistological cervical Whole Slide Images (WSIs). CST randomly distorts input tiles and factors the difference between the CNN prediction for the original and distorted inputs within the loss function. CNNs were trained using 114 p16-stained WSIs from the same scanner, and evaluated on 6 WSI test sets, each with 23 to 24 WSIs of the same tissue but different scanner/IHC combinations. Relative robustness (rAUC) was measured as the difference between the AUC on the training domain test set (i.e., baseline test set) and the remaining test sets.

Results

Across all test sets, The AUC of CST models outperformed “No CST” models (AUC: 0.940–0.989 vs. 0.905–0.986, p < 1e − 8), and obtained an improved robustness (rAUC: [−0.038, −0.003] vs. [−0.081, −0.002]). At a WSI level, CST models showed an increase in performance in 124 of the 142 WSIs. CST models also outperformed models trained with random on-the-fly data augmentation (DA) in all test sets ([0.002, 0.021], p < 1e-6).

Conclusion

CST offers a path to improve CNN performance without the need for more data and allows customizing distortions to specific use cases. A python implementation of CST is publicly available at https://github.com/TIGACenter/CST_v1.
Case report: Rudimentary uterine horn with ovarian endometriosis manifested as pelvic ectopic kidney
Authors: Yin Si-fan , Chai Jia-gui , Feng Run-lin , Yin Zhi-yuan , Zhao Shen-zhao , Zhang Tao , Ke Chang-xing
Published: July 2023

Background

Unicornuate uterus is a congenital uterine malformation. Unicornuate uterus with rudimentary horn, ovarian endometriosis, and congenital renal agenesis are rare combinations that can be easily misdiagnosed due to the lack of typical clinical manifestations.

Case summary

A 19-year-old woman with pelvic pain was admitted to the hospital after a month. Physical examination was unremarkable. B-ultrasound and CT scan both indicated pelvic ectopic kidney. In addition, renal scintigraphy revealed normal perfusion and function of the right kidney, but the perfusion and function of the left kidney were not visible. A left pelvic ectopic kidney was diagnosed by preoperative images. A laparoscopic left pelvic ectopic nephrectomy was performed after adequate surgical preparation. However, the postoperative pathological diagnosis revealed a rudimentary uterine horn with ovarian endometriosis and congenital renal agenesis. Fortunately, she got recovered and was discharged from the hospital after 5 days following the operation. Moreover, she received regular follow-ups at the gynecology clinic. To date, no right adnexal or uterine abnormalities have been detected on ultrasound during the follow-up visits.

Conclusion

Rudimentary uterine horn with ovarian endometriosis and congenital renal agenesis are rare and are easily Misdiagnosed due to the lack of typical clinical manifestations. A gynecological examination is recommended for patients who may have this disease.
Efficacy of a continuous wound infiltration system for postoperative pain management in gynecologic patients who underwent single-port access laparoscopy for adnexal disease
Authors: Kang Jun-Hyeok , Lee Kyung A , Heo Yae Rin , Kim Woo Young , Paik E Sun
Published: July 2023

Introduction

Single-port access (SPA) laparoscopy requires only one incision, unlike conventional laparoscopy. However, its umbilical incision is larger than that of conventional laparoscopy and can be vulnerable to postoperative pain. This study aimed to evaluate whether simultaneous use of a continuous wound infiltration (CWI) system and intravenous patient-controlled analgesia (IV PCA) effectively decreases surgical site pain in patients who underwent SPA laparoscopy due to gynecologic adnexal disease.

Methods

A total of 371 patients who underwent SPA laparoscopy and who received IV PCA or CWI was retrospectively reviewed (combined group [CWI + IV PCA, n = 159] vs. PCA group [IV PCA only, n = 212]). To evaluate postoperative pain management, the numeric rating scale (NRS) pain score after surgery, total amount of fentanyl administered via IV PCA, and additional pain killer consumption were collected.

Results

The NRS scores at 12 h (1.90 ± 1.11 vs. 2.70 ± 1.08, p < 0.001) and 24 h (1.82 ± 0.82 vs. 2.11 ± 1.44, p = 0.026) after surgery were significantly lower in the combined group than in the PCA group. The total amount of PCA fentanyl was significantly smaller in the combined group than in the PCA group (p < 0.001). The total quantity of rescue analgesics was smaller in the combined group than in the PCA group (p < 0.05).

Conclusion

Combined use of the CWI system and IV PCA is an effective postoperative pain management strategy in patient who underwent SPA laparoscopy for adnexal disease.
The association between serum phosphorus and common carotid artery intima–media thickness in ischemic stroke patients
Authors: Du Huaping , Guo Tingting , Ye Huan , Bao Yingshi , Qiu Zhuoyin , Sun Yaming , You Shoujiang , Liu Yuan , Xu Yuan , Zhang Chunqing , Qiu Chunfang
Published: July 2023

Purpose

An elevated concentration of phosphorus is associated with an increased risk of atherosclerosis and cardiovascular diseases. Common carotid artery intima–media thickness (cIMT) is an imaging marker of atherosclerosis. However, data on the relationship between phosphorus and cIMT in ischemic stroke are scarce. We aimed to evaluate the association between serum phosphorus levels and cIMT in patients who had experienced ischemic stroke.

Patients and methods

A total of 1,450 ischemic stroke patients were enrolled. Participants were divided into four groups (quartiles) according to baseline serum phosphorus level. Carotid atherosclerosis was identified by measurement of cIMT; abnormal cIMT was defined as a maximum cIMT or mean cIMT ≥ 1 mm. Multivariable logistic regression models were used to assess the association between serum phosphorus level and the presence of abnormal cIMT.

Results

In the multivariable adjusted analysis, falling into the highest quartile for serum phosphorus (Q4) was associated with a 2.00-fold increased risk of having abnormal maximum cIMT [adjusted odds ratio (OR) 2.00; 95% confidence interval (CI) 1.44–2.79] and a 1.76-fold increased risk of having abnormal mean cIMT (adjusted OR 1.76; 95% CI 1.22–2.53) in comparison to Q1. Furthermore, the association between serum phosphorus and abnormal cIMT was confirmed in analyses treating serum phosphorus as a continuous variable and in subgroup analyses.

Conclusion

In acute ischemic stroke patients, baseline elevated serum phosphorus level was found to be independently associated with carotid atherosclerosis, as measured by cIMT.
A potential relationship between MMP-9 rs2250889 and ischemic stroke susceptibility
Authors: Ge Hanming , Ma Xiaojuan , Wang Jiachen , Zhang Xiaobo , Zhang Yu , Zhang Qi , Li Wu , Liu Jie , Duan Jinwei , Shi Wenzhen , Tian Ye
Published: July 2023

Purpose

Ischemic stroke (IS), a serious cerebrovascular disease, greatly affects people's health and life. Genetic factors are indispensable for the occurrence of IS. As a biomarker for IS, the MMP-9 gene is widely involved in the pathophysiological process of IS. This study attempts to find out the relationship between MMP-9 polymorphisms and IS susceptibility.

Methods

A total of 700 IS patients and 700 healthy controls were recruited. The single nucleotide polymorphism (SNP) markers of the MMP-9 gene were genotyped by the MassARRAY analyzer. Multifactor dimensionality reduction (MDR) was applied to generate SNP–SNP interaction. Furthermore, the relationship between genetic variations (allele and genotype) of the MMP-9 gene and IS susceptibility was analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Our results demonstrated that rs2250889 could significantly increase the susceptibility to IS in the codominant, dominant, overdominant, and log-additive models (p < 0.05). Further stratification analysis showed that compared with the control group, rs2250889 was associated with IS risk in different case groups (age, female, smoking, and non-drinking) (p < 0.05). Based on MDR analysis, rs2250889 was the best model for predicting IS risk (cross-validation consistency: 10/10, OR = 1.56 (1.26–1.94), p < 0.001).

Conclusion

Our study preliminarily confirmed that SNP rs2250889 was significantly associated with susceptibility to IS.
Disability evaluation in patients with Guillain-Barre syndrome and SARS-CoV-2 infection
Authors: Sanchez-Boluarte Sofía S. , Aguirre-Quispe Wilfor , Tacunan-Cuellar Jhon , Sanchez-Boluarte Arantxa N. , Segura-Chavez Darwin
Published: July 2023

Objective

Several cases of Guillain-Barre syndrome (GBS) associated with SARS-CoV-2 infection have been described. This study illustrated the demographic, clinical, and neurophysiological characteristics of patients with GBS and COVID-19, as well as associated factors with disability at discharge.

Materials and methods

A retrospective analytical observational study was conducted. It included patients diagnosed with GBS admitted in a national reference center in Peru between 2019 and 2021. Epidemiological, clinical, neurophysiological, and cerebrospinal fluid data were analyzed. A multivariate analysis, using the generalized linear model, was performed, considering the presence of disability at discharge as the dependent variable.

Results

Eight-one subjects diagnosed with GBS were included. The mean age was 46.8 years (SD: 15.2), with a predominance of males (61.73%). The most frequent clinical presentation was the classic sensory-motor form in 74 cases (91.36%) with AIDP (82.35%) as the most frequent neurophysiological pattern in the group with COVID-19, while AMAN pattern predominated (59.26%) in those without COVID-19 (p = <0.000). The disability prevalence ratio at discharge between subjects with COVID-19 and those without COVID-19 was 1.89 (CI 1.06–3.34), p = 0.030, adjusted for age, sex, and neurophysiological subtype.

Conclusion

The neurophysiologic subtype AIDP, and a higher disability were associated with the presence of COVID-19.
Visual respiratory biofeedback to improve visuospatial cognition and cardiac interoception in migraineurs: a study protocol for a randomized controlled trial
Authors: Ramaswamy Krithika A. , Shetty Shivaprasad , Shetty Prashanth
Published: July 2023

Objectives

Migraine is a complex neurological disorder that typically presents with unilateral cephalgia associated with cognitive impairment and reduced interoception. These symptoms result in socio-economic repercussions due to reduced productivity, efficiency, and work performance. Therefore, along with headache management, improving cognition and interoception should also be significant therapeutic targets to effectively manage migraine. To achieve this, we propose to explore the role of a yoga-based visual respiratory biofeedback (VRB) as a possible therapeutic strategy.

Methods and analysis

At least 64 participants will be recruited for the trial after screening for eligibility criteria, using the migraine screening questionnaire and Montreal cognitive assessment test. They will be randomly allocated (1:1) to either the experimental group receiving a 20-min session of yoga-based VRB or the control group who will be asked to watch a documentary film for the same duration. Visuospatial cognition will be assessed by the Corsi block-tapping task, and cardiac interoceptive accuracy will be assessed by the heartbeat counting task at baseline and immediately after the intervention. Based on the distribution and variance of the data obtained, analysis will be conducted based on linear mixed models using SPSS version 28.0.1.0, with a two-sided p-value of < 0.05 considered to be statistically significant.

Discussion

To the best of our knowledge, this is the first study to design and assess the effects of yoga-based biofeedback therapy on cognition and cardiac interoception in migraineurs. Furthermore, we postulated that pranayama's therapeutic effects might be enhanced by using visual yogic respiratory biofeedback. Considering the socio-economic burden of migraine, if found effective, VRB investigated in the trial could be considered as a therapeutic strategy.

Clinical trial registration

ClinicalTrials.gov CTRI, CTRI/2023/03/050430.
Pilot study protocol of a randomized controlled trial for the potential effects of creatine monohydrate on persistent post-concussive symptoms
Authors: Bødker Ronni Lykke , Marcussen Michael
Published: July 2023

Background

Mild traumatic brain injury or concussion is a global public concern, with an estimated annual incidence between 48 million and 96 million worldwide. It is a socioeconomical problem, and almost one-third of individuals with concussion suffer from severe persistent post-concussive symptoms (PPCS), with an increased risk of unemployment or terminating their studies. To date, no single treatment is available with guaranteed success. Creatine monohydrate (CrM) has shown potential as a treatment for post-concussive symptoms, having a positive impact on cognitive function, chronic fatigue, depression, and anxiety. The aim of this study is to examine the effect of CrM on PPCS assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ).

Methods

The study is designed as a double-blinded randomised controlled trial. Study participants are found through neurological outpatient clinics in Denmark or through social media. They will be between 25 and 35 years of age, will have suffered from PPCS for 6–12 months prior to inclusion, and will have no comorbidities. The participants will be randomly allocated to either an intervention group (INT), placebo group (PLA), or control group (CG). Baseline data will be collected immediately after inclusion, and the study period will be 7 weeks. Follow-up data will be collected 1 week after the end of the study period. The primary outcome of the study is changes in RPQ score. Changes in weight and training status will be adjusted for as potential confounders.

Ethics and dissemination

This protocol is approved by the National Committee on Health Research (97508) and by the Danish Data Protection Agency 11.651. The investigators intend to submit their study findings for publication in peer-reviewed journals and disseminate the findings via presentation at academic meetings/conferences.

Clinical Trial registration: NCT05562232, registered September 30, 2022.
Delayed closed-loop neurostimulation for the treatment of pathological brain rhythms in mental disorders: a computational study
Authors: Wahl Thomas , Riedinger Joséphine , Duprez Michel , Hutt Axel
Published: July 2023

Mental disorders are among the top most demanding challenges in world-wide health. A large number of mental disorders exhibit pathological rhythms, which serve as the disorders characteristic biomarkers. These rhythms are the targets for neurostimulation techniques. Open-loop neurostimulation employs stimulation protocols, which are rather independent of the patients health and brain state in the moment of treatment. Most alternative closed-loop stimulation protocols consider real-time brain activity observations but appear as adaptive open-loop protocols, where e.g., pre-defined stimulation sets in if observations fulfil pre-defined criteria. The present theoretical work proposes a fully-adaptive closed-loop neurostimulation setup, that tunes the brain activities power spectral density (PSD) according to a user-defined PSD. The utilized brain model is non-parametric and estimated from the observations via magnitude fitting in a pre-stimulus setup phase. Moreover, the algorithm takes into account possible conduction delays in the feedback connection between observation and stimulation electrode. All involved features are illustrated on pathological α- and γ-rhythms known from psychosis. To this end, we simulate numerically a linear neural population brain model and a non-linear cortico-thalamic feedback loop model recently derived to explain brain activity in psychosis.
Connectivity reveals homology between the visual systems of the human and macaque brains
Authors: Lu Xia , Wang Qianshan , Li Xiaowen , Wang Guolan , Chen Yifei , Li Xueqi , Li Haifang
Published: July 2023

The visual systems of humans and nonhuman primates share many similarities in both anatomical and functional organization. Understanding the homology and differences between the two systems can provide important insights into the neural basis of visual perception and cognition. This research aims to investigate the homology between human and macaque visual systems based on connectivity, using diffusion tensor imaging and resting-state functional magnetic resonance imaging to construct structural and functional connectivity fingerprints of the visual systems in humans and macaques, and quantitatively analyze the connectivity patterns. By integrating multimodal magnetic resonance imaging, this research explored the homology and differences between the two systems. The results showed that 9 brain regions in the macaque visual system formed highly homologous mapping relationships with 11 brain regions in the human visual system, and the related brain regions between the two species showed highly structure homologous, with their functional organization being essentially conserved across species. Finally, this research generated a homology information map of the visual system for humans and macaques, providing a new perspective for subsequent cross-species analysis.
Rare forms of cerebral amyloid angiopathy: pathogenesis, biological and clinical features of CAA-ri and iCAA
Authors: Storti Benedetta , Gabriel Maria Magdalena , Sennfält Stefan , Canavero Isabella , Rifino Nicola , Gatti Laura , Bersano Anna
Published: July 2023

Thanks to a more widespread knowledge of the disease, and improved diagnostic techniques, the clinical spectrum of cerebral amyloid angiopathy (CAA) is now broad. Sporadic CAA, hereditary CAA, CAA-related inflammation (CAA-ri) and iatrogenic CAA (iCAA) create a clinical and radiological continuum which is intriguing and only partially discovered. Despite being relatively rare, CAA-ri, an aggressive subtype of CAA with vascular inflammation, has gained growing attention also because of the therapeutic efficacy of anti-inflammatory and immunomodulating drugs. More recently, diagnostic criteria have been proposed for an unusual variant of CAA, probably related to an iatrogenic origin (iCAA), toward which there is mounting scientific interest. These atypical forms of CAA are still poorly known, and their recognition can be challenging and deserve to be pursued in specialized referral centres. The aim of this brief review is to focus current developments in the field of rare forms of CAA, its pathogenesis as well as clinical and biological features in order to increase awareness of these rare forms.
Economic evaluation of bailing capsules for patients with diabetic nephropathy in China
Authors: He Yumei , Li Wei , Zhu He , Han Sheng
Published: July 2023

Background: Diabetic nephropathy is a major microvascular complication and the main cause of end-stage renal disease in diabetic patients. The therapeutic effects of Bailing capsules for diabetic nephropathy have already been demonstrated; however, the cost-effectiveness of Bailing capsules remains controversial. This study aimed to evaluate the cost-effectiveness of Bailing capsules combined with Western medicine compared with Western medicine alone in diabetic nephropathy from a Chinese healthcare system perspective.

Methods: A Markov model was established to simulate the disease process of patients over a 20-year period. Clinical efficacy data were obtained from a meta-analysis, and transition probability was estimated based on microsimulation. Direct costs and utility values were collected from the Chinese Drug Bidding Database (https://www.shuju.menet.com.cn) and published literature. The incremental cost-effectiveness ratio (ICER) was measured, and one-way and probabilistic sensitivity analyses were performed to observe model stability.

Results: A total of 34 randomized controlled trials involving 3,444 patients with diabetic nephropathy were selected for the meta-analysis. Compared to Western medicine alone, the addition of Bailing capsules resulted in an increase of 0.39 quality-adjusted life-years (QALYs) and additional costs of Chinese Yuan (CNY) 24,721, yielding an ICER of CNY 63,001 per QALY gained. The ICER was lower than the threshold of willingness-to-pay of CNY 80,976 (The GDP per Capita in China). The reliability and stability of the results were confirmed by the sensitivity analysis.

Conclusion: We found that Bailing capsules may be a cost-effective treatment choice for patients with diabetic nephropathy in the Chinese population.
Identification of novel and potent dual-targeting HDAC1/SPOP inhibitors using structure-based virtual screening, molecular dynamics simulation and evaluation of in vitro and in vivo antitumor activity
Authors: Yang Yingxue , Chen Shutong , Wang Qinghua , Niu Miao-Miao , Qu Yuanqian , Zhou Yang
Published: July 2023

Cancer is one of the important factors threatening human health. Hence, it is essential to create novel potent drugs to treat it. Due to the strong correlation among histone deacetylase1 (HDAC1), speckle-type POZ protein (SPOP) and cancers, dual inhibition of HDAC1 and SPOP may be a promising strategy for cancer treatment. In this study, we successfully identified four potential dual-targeting HDAC1/SPOP candidate compounds with structure-based virtual screening. In vitro inhibition experiments confirmed that the four compounds had dual inhibitory effects on HDAC1 and SPOP. Among them, compound HS-2 had a stronger inhibitory effect on HDAC1 and SPOP than the positive controls. Further molecular dynamics simulations indicated that HS-2 could stably bind to HDAC1 and SPOP. In addition, MTT assay indicated that HS-2 inhibited the growth of tumor cells in the micromolar range. In vivo evaluation showed that HS-2 could obviously inhibit the growth of tumor in nude mice without obvious toxicity. These findings suggest that HS-2 is a novel and potent dual-targeting HDAC1/SPOP inhibitor for cancer treatment.
Dry side of the core: a meta-analysis addressing the original nature of the ABA signalosome at the onset of seed imbibition
Authors: Née Guillaume , Krüger Thorben
Published: July 2023

The timing of seedling emergence is a major agricultural and ecological fitness trait, and seed germination is controlled by a complex molecular network including phytohormone signalling. One such phytohormone, abscisic acid (ABA), controls a large array of stress and developmental processes, and researchers have long known it plays a crucial role in repressing germination. Although the main molecular components of the ABA signalling pathway have now been identified, the molecular mechanisms through which ABA elicits specific responses in distinct organs is still enigmatic. To address the fundamental characteristics of ABA signalling during germination, we performed a meta-analysis focusing on the Arabidopsis dry seed proteome as a reflexion basis. We combined cutting-edge proteome studies, comparative functional analyses, and protein interaction information with genetic and physiological data to redefine the singular composition and operation of the ABA core signalosome from the onset of seed imbibition. In addition, we performed a literature survey to integrate peripheral regulators present in seeds that directly regulate core component function. Although this may only be the tip of the iceberg, this extended model of ABA signalling in seeds already depicts a highly flexible system able to integrate a multitude of information to fine-tune the progression of germination.
Random regression for modeling soybean plant response to irrigation changes using time-series multispectral data
Authors: Sakurai Kengo , Toda Yusuke , Hamazaki Kosuke , Ohmori Yoshihiro , Yamasaki Yuji , Takahashi Hirokazu , Takanashi Hideki , Tsuda Mai , Tsujimoto Hisashi , Kaga Akito , Nakazono Mikio , Fujiwara Toru , Iwata Hiroyoshi
Published: July 2023

Plant response to drought is an important yield-related trait under abiotic stress, but the method for measuring and modeling plant responses in a time series has not been fully established. The objective of this study was to develop a method to measure and model plant response to irrigation changes using time-series multispectral (MS) data. We evaluated 178 soybean (Glycine max (L.) Merr.) accessions under three irrigation treatments at the Arid Land Research Center, Tottori University, Japan in 2019, 2020 and 2021. The irrigation treatments included W5: watering for 5 d followed by no watering 5 d, W10: watering for 10 d followed by no watering 10 d, D10: no watering for 10 d followed by watering 10 d, and D: no watering. To capture the plant responses to irrigation changes, time-series MS data were collected by unmanned aerial vehicle during the irrigation/non-irrigation switch of each irrigation treatment. We built a random regression model (RRM) for each of combination of treatment by year using the time-series MS data. To test the accuracy of the information captured by RRM, we evaluated the coefficient of variation (CV) of fresh shoot weight of all accessions under a total of nine different drought conditions as an indicator of plant’s stability under drought stresses. We built a genomic prediction model (MTRRM model) using the genetic random regression coefficients of RRM as secondary traits and evaluated the accuracy of each model for predicting CV. In 2020 and 2021,the mean prediction accuracies of MTRRM models built in the changing irrigation treatments (r = 0.44 and 0.49, respectively) were higher than that in the continuous drought treatment (r = 0.34 and 0.44, respectively) in the same year. When the CV was predicted using the MTRRM model across 2020 and 2021 in the changing irrigation treatment, the mean prediction accuracy (r = 0.46) was 42% higher than that of the simple genomic prediction model (r =0.32). The results suggest that this RRM method using the time-series MS data can effectively capture the genetic variation of plant response to drought.