bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating molecular, biochemical, and immunohistochemical features as predictors of hepatocellular carcinoma drug response using machine-learning algorithms
Authors: Matboli Marwa , Al-Amodi Hiba S. , Khaled Abdelrahman , Khaled Radwa , Ali Marwa , Kamel Hala F. M. , Hamid Manal S. Abd EL , ELsawi Hind A. , Habib Eman K. , Youssef Ibrahim
Published: October 2024

Introduction

Liver cancer, particularly Hepatocellular carcinoma (HCC), remains a significant global health concern due to its high prevalence and heterogeneous nature. Despite the existence of approved drugs for HCC treatment, the scarcity of predictive biomarkers limits their effective utilization. Integrating diverse data types to revolutionize drug response prediction, ultimately enabling personalized HCC management.

Method

In this study, we developed multiple supervised machine learning models to predict treatment response. These models utilized classifiers such as logistic regression (LR), k-nearest neighbors (kNN), neural networks (NN), support vector machines (SVM), and random forests (RF) using a comprehensive set of molecular, biochemical, and immunohistochemical features as targets of three drugs: Pantoprazole, Cyanidin 3-glycoside (Cyan), and Hesperidin. A set of performance metrics for the complete and reduced models were reported including accuracy, precision, recall (sensitivity), specificity, and the Matthews Correlation Coefficient (MCC).

Results and Discussion

Notably, (NN) achieved the best prediction accuracy where the combined model using molecular and biochemical features exhibited exceptional predictive power, achieving solid accuracy of 0.9693 ∓ 0.0105 and average area under the ROC curve (AUC) of 0.94 ∓ 0.06 coming from three cross-validation iterations. Also, found seven molecular features, seven biochemical features, and one immunohistochemistry feature as promising biomarkers of treatment response. This comprehensive method has the potential to significantly advance personalized HCC therapy by allowing for more precise drug response estimation and assisting in the identification of effective treatment strategies.
A novel animal model of spontaneous epilepsy: Cdk5 knockout in pericyte-specific mice
Authors: Lin Lin , Hu Xiaofei , Hong Weijun , Pan Tengwei , Wang Zhiren , Wang En , Wu Gang
Published: October 2024

Changes in neurovascular unit components and their interactions play a crucial role in epileptogenesis and the pathological process of epilepsy. Currently, there is a lack of animal models that can accurately reflect the etiological impact of cerebrovascular lesions on epilepsy. In this study, we constructed cyclin-dependent kinase 5 conditional knockout mice in Cspg4 (pericyte marker)-positive cells using the Cre-LoxP system. The results revealed that this strain of mice exhibited significant seizure behaviors and epileptiform brain waves, loss of hippocampal and amygdala neurons, astrogliosis, decreased pericyte coverage, and reduced AQP4 polar distribution. Herein, we have developed a novel mouse model of spontaneous epilepsy, providing a critical animal model for studying the involvement of neurovascular unit factors in the development and progression of epilepsy.
Identification of middle cerebral artery stenosis in transcranial Doppler using a modified VGG-16
Authors: Xu Dong , Li Hao , Su Fanghui , Qiu Sizheng , Tong Huixia , Huang Meifeng , Yao Jianzhong
Published: October 2024

Objectives

The diagnosis of intracranial atherosclerotic stenosis (ICAS) is of great significance for the prevention of stroke. Deep learning (DL)-based artificial intelligence techniques may aid in the diagnosis. The study aimed to identify ICAS in the middle cerebral artery (MCA) based on a modified DL model.

Methods

This retrospective study included two datasets. Dataset1 consisted of 3,068 transcranial Doppler (TCD) images of the MCA from 1,729 patients, which were assessed as normal or stenosis by three physicians with varying levels of experience, in conjunction with other medical imaging data. The data were used to improve and train the VGG16 models. Dataset2 consisted of TCD images of 90 people who underwent physical examination, which were used to verify the robustness of the model and compare the consistency between the model and human physicians.

Results

The accuracy, precision, specificity, sensitivity, and area under curve (AUC) of the best model VGG16 + Squeeze-and-Excitation (SE) + skip connection (SC) on dataset1 reached 85.67 ± 0.43(%),87.23 ± 1.17(%),87.73 ± 1.47(%),83.60 ± 1.60(%), and 0.857 ± 0.004, while those of dataset2 were 93.70 ± 2.80(%),62.65 ± 11.27(%),93.00 ± 3.11(%),100.00 ± 0.00(%), and 0.965 ± 0.016. The kappa coefficient showed that it reached the recognition level of senior doctors.

Conclusion

The improved DL model has a good diagnostic effect for MCV stenosis in TCD images and is expected to help in ICAS screening.
Effect of non-invasive brain stimulation on post-stroke cognitive impairment: a meta-analysis
Authors: Zhao Jing , Meng Qian , Qi Shuo , Zhao Hongfei , Xia Ling
Published: October 2024

Background

Previous studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may be an effective and safe alternative treatment for post-stroke cognitive impairment (PSCI). Similarly, the application of transcranial direct current stimulation (tDCS) during stroke rehabilitation has been shown to improve cognitive function in PSCI patients. However, there have been conflicting results from some studies. Therefore, this study aims to conduct a meta-analysis to evaluate the effects of tDCS and rTMS on PSCI.

Methods

The meta-analysis search for articles published from the initial availability date to 5 February 2024 in databases. The extracted study data were entered into STATA 12.0 software for statistical analysis.

Results

This meta-analysis provides evidence that both rTMS and tDCS have a positive impact on general cognitive function in PSCI patients [immediate effect of rTMS: standard mean difference (SMD) = 2.58, 95% confidence interval (CI) = 1.44 to 3.71; long-term effect of rTMS: SMD = 2.33, 95% CI = 0.87–3.78; immediate effect of tDCS: SMD = 2.22, 95% CI = 1.31–3.12]. Specifically, rTMS was found to significantly improve attention, language, memory, and visuospatial functions, while it did not show a significant therapeutic effect on executive function (attention: SMD = 3.77, 95% CI = 2.30–5.24; executive function: SMD = −0.52, 95% CI = −3.17–2.12; language: SMD = 3.43, 95% CI = 1.50–5.36; memory: SMD = 3.52, 95% CI = 1.74–5.30; visuospatial function: SMD = 4.71, 95% CI = 2.61–6.80). On the other hand, tDCS was found to significantly improve executive and visuospatial functions but did not show a significant improvement in attention function and memory (attention: SMD = 0.63, 95% CI = −0.30–1.55; executive function: SMD = 2.15, 95% CI = 0.87–3.43; memory: SMD = 0.99, 95% CI = −0.81–2.80; visuospatial function: SMD = 2.64, 95% CI = 1.04–4.23).

Conclusion

In conclusion, this meta-analysis demonstrates that both rTMS and tDCS are effective therapeutic techniques for improving cognitive function in PSCI. However, more large-scale studies are needed to further investigate the effects of these techniques on different cognitive domains in PSCI.
Effect of probiotics and paraprobiotics on patients with sleep disorders and sub-healthy sleep conditions: a meta-analysis of randomized controlled trials
Authors: Yu Bei , Wang Ke-Yi , Wang Ning-Rui , Zhang Lu , Zhang Jian-Ping
Published: October 2024

Background

The microbial-gut-brain axis has received much attention in recent years, and regulating intestinal flora can effectively improve sleep disorders, which hints the potential effects of probiotics on sleep disorders, but lack of research evidence for meta-analysis. Therefore, this study aims to quantitatively evaluate the influence of probiotics on sleep disorders and sub-healthy sleep conditions.

Methods

Up to 2023, online databases including Pubmed, Embase, Cochrane library, Web of science have been searched for studies involving adults who consume probiotics or paraprobiotics in controlled trials, during which, changes in subjective and/or objective sleep parameters and contributing factors in sleeping quality are examined. We conduct a meta-analysis of 11 clinical randomized controlled studies.

Results

Probiotic supplementation improves sleep states to some extent in adults with sleep disorders and healthy adults with condition-induced sleep disorders (−0.34 [−0.56 to −0.13]; I2 = 42.6%; p = 0.001). Meanwhile, subgroup analysis shows that the effect of probiotics on improving sleep disorders is influenced by other factors such as the health states of the subjects, the duration of the intervention, the type of strain, and the test criteria.

Conclusion

Probiotics and paraprobiotics have a significant positive effect on the sleep quality of adults with sleep disorders or sub-healthy sleep conditions. However, the therapeutic effects of probiotics on sleep problems need future additional trials.

Systematic review registration

https://inplasy.com/inplasy-2022-12-0066/, identifier 2022120066.
Effects of aging on otolith morphology and functions in mice
Authors: Ueda Keita , Imai Takao , Ito Taeko , Okayasu Tadao , Harada Shotaro , Kamakura Takefumi , Ono Kazuya , Katsuno Tatsuya , Tanaka Tatsuhide , Tatsumi Kouko , Hibino Hiroshi , Wanaka Akio , Kitahara Tadashi
Published: October 2024

Background

Increased fall risk caused by vestibular system impairment is a significant problem associated with aging. A vestibule is composed of linear acceleration-sensing otoliths and rotation-sensing semicircular canals. Otoliths, composed of utricle and saccule, detect linear accelerations. Otolithic organs partially play a role in falls due to aging. Aging possibly changes the morphology and functions of otoliths. However, the specific associations between aging and otolith changes remain unknown. Therefore, this study aimed to clarify these associations in mice.

Methods

Young C56BL/6 N (8 week old) and old (108–117 weeks old) mice were used in a micro-computed tomography (μCT) experiment for morphological analysis and a linear acceleration experiment for functional analysis. Young C56BL/6 N (8 week old) and middle-aged (50 week old) mice were used in electron microscopy experiments for morphological analysis.

Results

μCT revealed no significant differences in the otolith volume (p = 0.11) but significant differences in the otolith density (p = 0.001) between young and old mice. μCT and electron microscopy revealed significant differences in the structure of striola at the center of the otolith (μCT; p = 0.029, electron microscopy; p = 0.017). Significant differences were also observed in the amplitude of the eye movement during the vestibulo-ocular reflex induced by linear acceleration (maximum amplitude of stimulation = 1.3G [p = 0.014]; maximum amplitude of stimulation = 0.7G [p = 0.015]), indicating that the otolith function was worse in old mice than in young mice.

Discussion

This study demonstrated the decline in otolith function with age caused by age-related morphological changes. Specifically, when otolith density decreased, inertial force acting on the hair cells decreased, and when the structure of striola collapsed, the function of cross-striolar inhibition decreased, thereby causing a decline in the overall otolith function.
Diffusion tensor imaging in cerebral small vessel disease applications: opportunities and challenges
Authors: Yang Siyu , Zhou Yihao , Wang Feng , He Xuesong , Cui Xuan , Cai Shaojie , Zhu Xingyan , Wang Dongyan
Published: October 2024

Cerebral small vessel disease (CSVD) is a syndrome of pathology, imaging, and clinical manifestations caused primarily by a variety of functional or structural lesions in the small blood vessels of the brain. CSVD contributes to approximately 45% of dementia and 25% of ischemic strokes worldwide and is one of the most important causes of disability. The disease progresses insidiously, and patients often have no typical symptoms in the early stages, but have an increased risk of stroke, death, and poor long-term prognosis. Therefore, early diagnosis of CSVD is particularly important. Neuroimaging is the most important diagnostic tool used for CSVD. Therefore, it is important to explore the imaging mechanisms of CSVD for its early diagnosis and precise treatment. In this article, we review the principles and analysis methods of DTI, analyze the latest DTI studies on CSVD, clarify the disease-lesion mapping relationships between cerebral white matter (WM) microstructural damage and CSVD, explore the pathogenic mechanisms and preclinical imaging features of CSVD, and summarize the latest research directions of CSVD and research methods to provide a comprehensive and objective imaging basis for the diagnosis and treatment of CSVD.
Predicting immune risk in treatment-naïve HIV patients using a machine learning algorithm: a decision tree algorithm based on micronutrients and inversion of the CD4/CD8 ratio
Authors: Nayak Saurav , Singh Arvind , Mangaraj Manaswini , Saharia Gautom Kumar
Published: October 2024

Introduction

Micronutrients have significant functional implications for the human immune response, and the quality of food is a major factor affecting the severity and mortality caused by HIV in individuals undergoing antiretroviral therapy. A decrease in CD4 lymphocyte count and an increase in CD8 lymphocyte count are the hallmarks of HIV infection, which causes the CD4/CD8 ratio to invert from a normal value of >1.6 to <1.0. In this study, we tried to analyze whether the nutritional status of HIV-positive patients has an impact on the CD4/CD8 ratio inversion by utilizing a machine learning (ML) algorithm.

Methods

In this study, 55 confirmed HIV-positive patients who had not started their anti-retroviral therapy were included after obtaining their informed, written consent. Moreover, 55 age-and sex-matched relatives and caregivers of the patients who tested negative in the screening were enrolled as controls. All individual patient data points were analyzed for model development with an 80–20 train–test split. Four trace elements, zinc (Zn), phosphate (P), magnesium (Mg), and calcium (Ca), were utilized by implementing a random forest classifier. The target of the study was the inverted CD4/CD8 ratio.

Results

The data of 110 participants were included in the analysis. The algorithm thus generated had a sensitivity of 80% and a specificity of 83%, with a likelihood ratio (LR+) of 4.8 and LR-of 0.24. The utilization of the ML algorithm adds to the limited evidence that currently exists regarding the role of micronutrients, especially trace elements, in the causation of immune risk. Our inherent strength lies in the fact that this study is one of the first studies to utilize an ML-based decision tree algorithm to classify immune risk in HIV patients.

Conclusion

Our study uniquely corroborated the nutritional data to the immune risk in treatment-naïve HIV patients through the utilization of a decision tree ML algorithm. This could subsequently be an important classification and prognostic tool in the hands of clinicians.
Effect of probiotic supplementation combined with bismuth-containing quadruple therapy on gut microbiota during Helicobacter pylori eradication: a randomized, double-blind, placebo-controlled trial
Authors: Han Zhongxue , Li Yueyue , Nan Xueping , Zhou Tao , Li Lixiang , Li Yanqing
Published: October 2024

Background

Helicobacter pylori (H. pylori) eradication has been reported to affect gut microbiota distribution. This study aimed to evaluate the effect of probiotic supplementation on the gastrointestinal microbiota during eradication and the efficacy of bismuth-containing quadruple therapy.

Methods

One hundred treatment-naïve H. pylori-positive patients were randomly assigned 1:1 to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, and clarithromycin) combined with the probiotic (Bifidobacterium animalism subsp. lactis BLa80) or placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was completed before and after treatment. Stool samples were collected for 16S rRNA gene sequencing at weeks 0, 2, and 10.

Results

No significant difference in the eradication rate was observed between the two groups. The incidence of adverse events, especially nausea (p = 0.029), was lower in the probiotic group. After treatment, the GSRS score decreased significantly in the probiotic group (p = 0.039). The gut microbiota underwent considerable changes immediately following eradication treatment, predominantly characterized by an increase in Proteobacteria at the expense of commensal Firmicutes and Bacteroidota, but gradually returned to baseline after eight weeks. By week 10, beneficial genera such as Lachnoclostridium, Parasutterella, Hungatella, and Akkermansia were notably enriched in the probiotic group. Additionally, the correlation networks in the probiotic group were closer to their initial levels at week 10 compared to the placebo group.

Conclusion

Disturbances in the gut microbiota following H. pylori treatment appeared to be temporary, and probiotic supplementation could mitigate antibiotic-induced alterations in the gut microbiota. This study also provided evidence supporting the effectiveness of probiotics in alleviating gastrointestinal symptoms.
Case report: Pancreatic metastasis from small-cell lung cancer appears as primary G2 pancreatic neuroendocrine tumor on combined contrast PET imaging with three probes
Authors: Zhang Huimin , Gao Jie , Cong Xiaofeng , Chen Chen , Yin Jiaxin , Xiong Wenji , Liu Ziling
Published: October 2024

Pancreatic metastasis is a rare malignant tumor; when it comes to multiple cancers, it may be a challenge to identify the primary lesion of new pancreatic metastases. With the continuous advancement of imaging technology, the PET/computed tomography (CT) has been widely used because of its high diagnostic accuracy and non-invasiveness. However, in the present case, the patient had history of limited small-cell lung carcinoma and prostatic cancer; the combined application of the three kinds of PET/CT was used to identify the new metastases of pancreatic and bone metastases, which suggested a high probability of primary G2 pancreatic neuroendocrine tumor with bone metastases. After the needle biopsy, samples were confirmed by diagnostic pathology as small-cell lung cancer metastasizing to the pancreas and bone. The results of our case suggests the irreplaceability of pathology and possibility of misdiagnosis by PET/CT; moreover, it also supplements clinical data for second primary cancers after small-cell lung cancer.
Risk factors of renal function deterioration after radical nephroureterectomy for upper tract urothelial carcinoma
Authors: Li Qinghui , Chen Tan , Zhu Anli , Zhou Jie , Zhu Jiawei , Li Hailong , Wen Rumin
Published: October 2024

Background and objectives

To investigate the risk factors of renal function deterioration after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

Methods

A total of 153 patients with UTUC who underwent radical surgery at a high-volume center in China from January 2015 to December 2019 were included in this study. The renal function of all patients was evaluated during follow-up. Besides, these patients were grouped according to postoperative renal function. The risk factors of renal function deterioration included age, sex, body mass index (BMI), T stage, tumor location and size, lymph node invasion, lymph node dissection (LND), surgical margin, tumor histology, lymphovascular invasion (LVI), hypertension, diabetes, hematuria, blood transfusion, hydronephrosis on the affected side, urine specific gravity, creatinine, uric acid, and preoperative glomerular filtration rate (GFR) on the healthy and affected sides. The correlation between risk factors and inclusion indexes was analyzed using univariate and multivariate analyses.

Results

A total of 153 patients were enrolled in this study, and the follow-up continued for 14 (11, 24) months. Acute kidney injury (AKI) was diagnosed in 65 patients in the short-term follow-up after RNU, and renal function deterioration was diagnosed in 52 patients in the long-term follow-up after RNU. The univariate analysis of 65 patients with short-term AKI revealed that there were statistically significant differences in preoperative hydronephrosis, hypertension, urinary protein, tumor size, preoperative Hb, preoperative creatinine, blood transfusion, and preoperative GFR of the healthy kidney. The multivariate Logistic regression analysis results showed that preoperative creatinine, GFR of the healthy kidney, and blood transfusion were independent risk factors for AKI. Moreover, The multivariate Logistic regression analysis of 52 patients with long-term renal insufficiency after surgery indicated that there were statistically significant differences in preoperative hydronephrosis, tumor size, preoperative GFR of the healthy kidney, and postoperative AKI.

Conclusion

For patients with UTUC, the preoperative creatinine level is high, blood transfusion was given during or after procedure and the GFR of the healthy kidney is low, it is easy to have AKI in the short term after operation. In addition, there was no hydronephrosis before operation, the tumor size was small, the GFR of the healthy kidney was low before operation, AKI occurred after operation, the renal function was easy to deteriorate for a long time after operation. The above risk factors may aggravate renal function deterioration of these patients after surgery, resulting in the loss of the opportunity to continue treatment.
Antitumor activity of PAbs generated by immunization with a novel HER3-targeting protein-based vaccine candidate in preclinical models
Authors: Bermúdez-Abreut Ernesto , Bergado Báez Gretchen , Martínez Pestano Melissa , Attanasio Giuseppe , Gonzales Castillo Carlos Yordan , Hernández Fernández Diana Rosa , Alvarez-Arzola Rydell , Alimonti Andrea , Sánchez-Ramírez Belinda
Published: October 2024

Despite the cumulative evidence supporting HER3 as a target for antitumor therapies, no agents targeting HER3 have been approved for cancer treatment. Most of the agents evaluated in preclinical and clinical trials have been specific monoclonal antibodies (MAbs), with few examples of active immunotherapy directed against this receptor. However, some cancer vaccine formats may generate polyclonal antibodies (PAbs) that replicate the diverse effector mechanisms of MAbs, including ligand neutralization and receptor degradation. In this study, we developed a protein subunit-based monovalent vaccine candidate targeting the extracellular domain (ECD) of HER3. Immunization of mice with a formulation targeting murine ErbB3-ECD successfully overcome tolerance to this self-antigen, inducing high titers of ErbB3-specific PAbs. The antitumor potential of this formulation and the induced PAbs was demonstrated in vivo and in vitro in an ErbB3-overexpressing 3LL-D122-derived tumor model. The immunogenicity of the HER3-ECD-based vaccine candidate was confirmed by the induction of high titers of HER3-specific PAbs. Consistent with the initial results, HER3-ECD-targeting PAbs were cytotoxic in several human epithelial tumor cell lines and exerted antitumor effects in vivo. These results support the value of HER3 as a tumor antigen and the effector mechanisms of HER3-specific therapeutic MAbs, while suggesting the potential of the proposed vaccine candidate for the treatment of HER3-expressing carcinomas.
The impact of diurnal variations on emergence delirium following general anesthesia and surgery in children
Authors: Wei Wei , Xie Haihang , Xu Yingyi , Qin Jingwen , Guo Xinying , Song Xingrong , Yu Gaofeng , Zhang Na , Ma Daqing , Tan Yonghong , Zhao Tianyun
Published: October 2024

Background

Emergence delirium (ED) is a widely recognized issue that prolongs mechanical ventilation and post-anesthesia care unit (PACU) resuscitation time, consequently increasing hospital costs and mortality. Postoperative disturbance in circadian rhythms, commonly leading to sleep disorders, has been identified as a significant risk factor for ED. However, the influence of surgery timing (morning vs. afternoon) on the incidence of ED in pediatric patients undergoing general anesthesia remains unknown.

Methods

Patients aged 2–6 years who were operated on under general anesthesia with a bispectral index value between 50 and 60 were categorized based on anesthesia start time into either the morning surgery group (Group M, 8:00–12:00) or the afternoon surgery group (Group A, 13:00–17:00). The primary outcome was the post-extubation incidence of ED assessed by the Cornell Assessment of Pediatric Delirium (CAPD) score. Secondary outcomes included extubation time, duration of PACU stay, and adverse postoperative events and complications.

Results

We recruited a total of 560 patients, 280 in group M and 280 in group A. Compared to Group M, Group A exhibited a significantly higher incidence of ED (p < 0.001), elevated CAPD scores (p < 0.001), and prolonged PACU stays (p < 0.001). Notably, there was no significant difference in extubation time and anesthesia-related adverse events or other postoperative complications between the groups.

Conclusion

Our study highlights that the time of surgery significantly affects the incidence of ED, CAPD scores, and PACU stay duration in children. Further validation of these findings may guide future strategies to reduce ED.
Research hotspots in pediatrics: co-word clustering analysis based on readership in PubMed Central
Authors: Deng Fangming , Sun Wen , Guo Jiangwei , Yang Yujia
Published: October 2024

Objective

By analyzing high readership articles from the Chinese Journal of Contemporary Pediatrics (CJCP) in the PubMed Central (PMC) database, this study aims to identify research hotspots and trends in the field of pediatrics.

Methods

Articles from the CJCP ranked by annual readership in PMC from 2021 to 2023 were collected. Using word frequency analysis and co-word analysis, the thematic characteristics of these articles were explored.

Results

The word frequency analysis and co-word analysis revealed four thematic directions that were of significant interest to researchers: (1) current public health or medical events such as COVID-19 and influenza; (2) mental health issues in children and adolescents; (3) pediatric neurological diseases and neurodevelopment; (4) diseases in preterm infants and newborns.

Conclusions

This study provides pediatric researchers with a valuable perspective to understand and grasp the development dynamics and future directions in the field of pediatrics.
Decreasing brain activity caused by acute administration of ketamine and alcohol – A randomized, controlled, observer-blinded experimental study
Authors: Ferreira Luan Oliveira , Padilha da Silveira Esther , Paz Clarissa A. , Otake Hamoy Maria K. , Barbosa Gabriela B. , Santos Murilo F. , Conceição Raína M. , Amaral Anthony Lucas G. , Resende Karina Dias , Favacho Lopes Dielly Catrina , Hamoy Moisés
Published: October 2024

Introduction

Substance abuse is a major public health problem. In recent years, ketamine, which is a parenteral anesthetic, has been consumed increasingly as an illicit drug together with alcohol, although little is known of how this association alters brain activity. The present study investigated the influence of progressive doses of ketamine, associated with alcohol, on electrophysiological activity.

Methods

For this, 72 late-adolescent (8–10-week-old) male Wistar rats received either ketamine only, at low (10 mg/kg), intermediate (20 mg/kg) or high (30 mg/kg) doses via intraperitoneal injection, or alcohol (2 mL/100 g) via oral gavage followed by ketamine (at low, intermediate, and high doses). Electroencephalograms (EEG) and electromyographic recordings were obtained 5 min after the final application of the drug.

Results

When administered alone, ketamine resulted in an increase in delta, theta, beta, and gamma brainwaves, with a more pronounced effect being detected at the highest dose (30 mg/kg) in the case of the delta, beta, and gamma waves. The amplitude of the alpha brainwaves was reduced at all doses of ketamine, but less intensively at the highest dose. When administered alone, alcohol reduced all the brainwaves, with the reduction in the alpha waves being exacerbated by ketamine at all doses, and that of the theta and beta waves being boosted at the lowest dose. The intermediate dose of ketamine (20 mg/kg) reverted the alcohol-induced reduction in the theta and gamma waves, whereas the high dose increased delta, theta, beta, and gamma bandpower.

Discussion

Overall, then, while ketamine enhances the depressant effects of alcohol on the alpha brainwave at all doses, a low dose intensified this effect on the theta and beta 175 waves, whereas a high dose produces neuronal hyperexcitability in the theta and 176 gamma bandpower.
Family Malvaceae: a potential source of secondary metabolites with chemopreventive and anticancer activities supported with in silico pharmacokinetic and pharmacodynamic profiles
Authors: Sameh Salma , Elissawy Ahmed M. , Al-Sayed Eman , Labib Rola M. , Chang Hsueh-Wei , Yu Szu-Yin , Chang Fang-Rong , Yang Shyh-Chyun , Singab Abdel Nasser B.
Published: October 2024

Introduction

Cancer is the second most widespread cause of mortality following cardiovascular disorders, and it imposes a heavy global burden. Nowadays, herbal nutraceutical products with a plethora of bioactive metabolites represent a foundation stone for the development of promising chemopreventive and anticancer agents. Certain members of the family Malvaceae have traditionally been employed to relieve tumors. The literature concerning the chemopreventive and anticancer effects of the plant species along with the isolated cytotoxic phytometabolites was reviewed. Based on the findings, comprehensive computational modelling studies were performed to explore the pharmacokinetic and pharmacodynamic profiles of the reported cytotoxic metabolites to present basis for future plant-based anticancer drug discovery.

Methods

All the available information about the anticancer research in family Malvaceae and its cytotoxic phytometabolites were retrieved from official sources. Extensive search was carried out using the keywords Malvaceae, cancer, cytotoxicity, mechanism and signalling pathway. Pharmacokinetic study was performed on the cytotoxic metabolites using SWISS ADME model. Acute oral toxicity expressed as median lethal dose (LD50) was predicted using Pro Tox 3.0 web tool. The compounds were docked using AutoDock Vina platform against epidermal growth factor receptor (EGFR kinase enzyme) obtained from the Protein Data Bank. Molecular dynamic simulations and MMGBSA calculations were performed using GROMACS 2024.2 and gmx_MMPBSA tool v1.5.2.

Results

One hundred forty-five articles were eligible in the study. Several tested compounds showed safe pharmacokinetic properties. Also, the molecular docking study showed that the bioactive metabolites possessed agreeable binding affinities to EGFR kinase enzyme. Tiliroside (25), boehmenan (30), boehmenan H (31), and isoquercetin (22) elicited the highest binding affinity toward the enzyme with a score of −10.4, −10.4, −10.2 and −10.1 Kcal/mol compared to the reference drug erlotinib having a binding score equal to −9 Kcal/mol. Additionally, compounds 25 and 31 elicited binding free energies equal to −42.17 and −42.68 Kcal/mol, respectively, comparable to erlotinib.

Discussion

Overall, the current study presents helpful insights into the pharmacokinetic and pharmacodynamic properties of the reported cytotoxic metabolites belonging to family Malvaceae members. The molecular docking and dynamic simulations results intensify the roles of secondary metabolites from medicinal plants in fighting cancer.
Updating assembly parameters for spacecraft assembly process state changes: based on data fusion method
Authors: Liu Yue , Li Lijuan , Lin Xuezhu , Guo Lili , Sun Jing , Wang Hao
Published: October 2024

Thermal protection systems (TPSs) are important components of reusable spacecraft, and their assembly quality has a crucial impact on flight safety. Owing to the complex assembly process and variable states of spacecraft thermal protection systems, assembly parameters may vary under different assembly states. Therefore, to obtain assembly parameters accurately and efficiently under different assembly states, in this study, 3D point cloud data and fiber optic sensor data were fused to develop an assembly parameter update method for assembly process state changes. Firstly, based on the measured data of thermal protection components and load-bearing structure, the gap, flush and matching parameters solution model are proposed. Secondly, to address the deformation problem of the load-bearing structure caused by changes in assembly status, a fusion method based on laser scanning and sensor detection was devised to achieve deformation prediction of the assembly structure during the assembly process. Thirdly, based on the assembly parameter solution model and point cloud prediction model, a constraint-based assembly parameter optimisation model was established, and an improved quantum particle swarm optimisation (LQPSO) algorithm was employed to achieve assembly parameter updates oriented toward changes in assembly status. Finally, an experimental system for array-based thermal protection structure simulation was established to validate the proposed method. The results show that the proposed parameter update method can achieve ideal results for different assembly state simulation components.
Changing paradigm of malnutrition among Bangladeshi women of reproductive age and gaps in national Nutrition Policies and Action Plans to tackle the emerging challenge
Authors: Khan Shusmita , Haider M. Moinuddin , Jamil Kanta , Ahsan Karar Zunaid , Siraj Saiqa , Iqbal Afrin , Angeles Gustavo
Published: October 2024

Objective

The main objective of this paper is to document the changing paradigm of malnutrition in Bangladesh and estimating how this is creating an intergenerational risk. This paper also examines national policy responses to tackle the silent epidemic of double burden of malnutrition.

Methods

Publicly available datasets of five Bangladesh Demographic and Health Surveys were used to see the changing paradigm of malnutrition among Bangladesh women. In addition to that, four national policies concerning, maternal and child health; and nutrition were reviewed using CDC’s 2013 Policy Analytical Framework.

Results

In Bangladesh, the share of ever-married women aged 15–49 who were underweight declined sharply between 2007 and 2017–2018, from 30 to 12%. In the same period, the proportion of women who were overweight or obese increased from 12 to 32%. Despite remarkable progress in reducing undernourishment among women, the share of well-nourished remained unchanged: 58% in 2007 and 56% in 2017–2018, mainly due to the shift in the dominant burden from undernutrition to overnutrition. This shift occurred around 2012–2013. Currently, in Bangladesh 0.8 million of births occur to overweight women and 0.5 million births occur to underweight women. If the current trend in malnutrition continues, pregnancies/births among overweight women will increase. Bangladesh’s existing relevant policies concerning maternal health and nutrition are inadequate and mostly address the underweight spectrum of malnutrition.

Discussion

Both forms of malnutrition pose a risk for maternal and child health. Underweight mothers are at risk of having anemia, antepartum/postpartum hemorrhage, and premature rupture of membranes. Maternal obesity increases the risk of perinatal complications, such as gestational diabetes, gestational hypertension, and cesarean deliveries. Currently, around 24% of the children are born to overweight/obese mothers and 15% to underweight mothers. Bangladesh should revise its national policies to address the double burden of malnutrition among women of reproductive age across pre-conception, pregnancy, and post-natal stages to ensure optimum maternal and child health.
Framework for responsive financing of district hospitals of India
Authors: Prinja Shankar , Jyani Gaurav , Goyal Aarti , Sharma Sameer , Kaur Tarandeep , Sundararaman Thiagarajan
Published: October 2024

Introduction

The current financing of public-sector district hospitals in India relies on historical budget allocations rather than actual utilization or healthcare needs. We utilized empirical data on healthcare delivery costs to develop the financing framework for these hospitals using a blended payment approach.

Methods

The primary data on cost of delivering services in 27 district hospitals across nine states of India was analysed along with indicators influencing the demand and supply of health services. Payment for outpatient, inpatient, and indirect services was assessed using the risk adjusted global budget, case-based bundled payment, and per-bed-global budget, respectively. Risk adjustment weights were computed by regressing the cost of outpatient care with demand and supply side factors which are likely to influence the utilization or the prices. Budget impact analysis was conducted to assess the fiscal implications of this payment approach, accounting for current care standards and two scenarios: upgrading district hospitals to Indian Public Health Standards (IPHS) or medical colleges.

Results

The average annual budget for a district hospital in India is estimated at ₹326 million (US$3.35 million), ranging from ₹66 million to ₹2.57 billion (US$0.8–31.13 million). Inpatient care comprises the largest portion (78%) of the budget. Upgrading to IPHS-compliant secondary hospitals or medical colleges would increase average budgets by 131 and 91.5%, respectively.

Conclusion

Implementing a blended payment approach would align funding with healthcare needs, enhance provider performance, and support ongoing financing reforms aimed at strategic purchasing and universal health coverage.
Novel bio-inspired soft actuators for upper-limb exoskeletons: design, fabrication and feasibility study
Authors: Zhang Haiyun , Naquila Gabrielle , Bae Junghyun , Wu Zonghuan , Hingwe Ashwin , Deshpande Ashish
Published: October 2024

Soft robots have been increasingly utilized as sophisticated tools in physical rehabilitation, particularly for assisting patients with neuromotor impairments. However, many soft robotics for rehabilitation applications are characterized by limitations such as slow response times, restricted range of motion, and low output force. There are also limited studies on the precise position and force control of wearable soft actuators. Furthermore, not many studies articulate how bellow-structured actuator designs quantitatively contribute to the robots’ capability. This study introduces a paradigm of upper limb soft actuator design. This paradigm comprises two actuators: the Lobster-Inspired Silicone Pneumatic Robot (LISPER) for the elbow and the Scallop-Shaped Pneumatic Robot (SCASPER) for the shoulder. LISPER is characterized by higher bandwidth, increased output force/torque, and high linearity. SCASPER is characterized by high output force/torque and simplified fabrication processes. Comprehensive analytical models that describe the relationship between pressure, bending angles, and output force for both actuators were presented so the geometric configuration of the actuators can be set to modify the range of motion and output forces. The preliminary test on a dummy arm is conducted to test the capability of the actuators.
Perceptions of celebrity athletes involved in social cause endorsement
Authors: Biz Manuela , Schubert Mathias
Published: October 2024

Introduction

Due to their ability to evoke unique associations in people's minds, professional athletes are considered prime ambassadors for companies, brands or organisations to add intangible values, credibility and awareness to their products or services. Based on that premise, using celebrity athletes for supporting social causes has also become a frequent practice over the past years. Empirical knowledge on how such activities are being perceived by involved athletes is scarce. Little is known about what they consider to be relevant attributes of their personal brand that make them suitable for endorsing social causes.

Methods

Based on semi-structured interviews with (n = 12) current and recently retired professional athletes from four different continents, we explore the most prominent attributes of athlete brands as well as other important features in that regard.

Results

Our results indicate that, in contrast to product endorsement, on-field attributes of the athlete brand are considered more important in relation to social causes. On-field attributes, such as career achievements and the behaviour shown during competitions, are seen as the main sources of credibility.

Discussion

Congruence and fit between endorser profiles and cause is perceived as highly relevant for successful cause endorsement activities. Our study is useful for a variety of stakeholders, such as athletes or organisations considering getting involved in social cause endorsement.
Immune Checkpoint Inhibitor Therapy for Kidney Transplant Recipients – A Review of Potential Complications and Management Strategies
Authors: Barbir Elena Bianca , Abdulmoneim Samer , Dudek Arkadiusz Z. , Kukla Aleksandra
Published: October 2024

Immune checkpoint inhibitor (ICI) therapy has enabled a paradigm shift in Oncology, with the treatment of metastatic cancer in certain tumor types becoming akin to the treatment of chronic disease. Kidney transplant recipients (KTR) are at increased risk of developing cancer compared to the general population. Historically, KTR were excluded from ICI clinical trials due to concern for allograft rejection and decreased anti-tumor efficacy. While early post-marketing data revealed an allograft rejection risk of 40%–50%, 2 recent small prospective trials have demonstrated lower rates of rejection of 0%–12%, suggesting that maintenance immunosuppression modification prior to ICI start modulates rejection risk. Moreover, objective response rates induced by ICI for the treatment of advanced or metastatic skin cancer, the most common malignancy in KTR, have been comparable to those achieved by immune intact patients. Non-invasive biomarkers may have a role in risk-stratifying patients before starting ICI, and monitoring for rejection, though allograft biopsy is required to confirm diagnosis. This clinically focused review summarizes current knowledge on complications of ICI use in KTR, including their mechanism, risk mitigation strategies, non-invasive biomarker use, approaches to treatment of rejection, and suggestions for future directions in research.
Rapid Aircraft Wake Vortex Identification Model Based on Optimized Image Object Recognition Networks
Authors: Deng Leilei , Pan Weijun , Luan Tian , Zhang Chen , Leng Yuanfei
Published: October 2024

Wake vortices generated by aircraft during near-ground operations have a significant impact on airport safety during takeoffs and landings. Identifying wake vortices in complex airspaces assists air traffic controllers in making informed decisions, ensuring the safety of aircraft operations at airports, and enhancing the intelligence level of air traffic control. Unlike traditional image recognition, identifying wake vortices using airborne LiDAR data demands a higher level of accuracy. This study proposes the IRSN-WAKE network by optimizing the Inception-ResNet-v2 network. To improve the model’s feature representation capability, we introduce the SE module into the Inception-ResNet-v2 network, which adaptively weights feature channels to enhance the network’s focus on key features. Additionally, we design and incorporate a noise suppression module to mitigate noise and enhance the robustness of feature extraction. Ablation experiments demonstrate that the introduction of the noise suppression module and the SE module significantly improves the performance of the IRSN-WAKE network in wake vortex identification tasks, achieving an accuracy rate of 98.60%. Comparative experimental results indicate that the IRSN-WAKE network has higher recognition accuracy and robustness compared to common recognition networks, achieving high-accuracy aircraft wake vortex identification and providing technical support for the safe operation of flights.
A Cooperative Control Method for Wide-Range Maneuvering of Autonomous Aerial Refueling Controllable Drogue
Authors: Bai Jinxin , Meng Zhongjie
Published: October 2024

In the realm of autonomous aerial refueling missions for unmanned aerial vehicles (UAVs), the controllable drogue represents a novel approach that significantly enhances both the safety and efficiency of aerial refueling operations. This paper delves into the issue of wide-range maneuverability control for the controllable drogue. Initially, a dynamic model for the variable-length hose–drogue system is presented. Based on this, a cooperative control framework that synergistically utilizes both the hose and the drogue is designed to achieve wide-range maneuverability of the drogue. To address the delay in hose retrieval and release, an open-loop control strategy based on neural networks is proposed. Furthermore, a closed-loop control method utilizing fuzzy approximation and adaptive error estimation is designed to tackle the challenges posed by modeling inaccuracies and uncertainties in aerodynamic parameters. Comparative simulation results show that the proposed control strategy can make the drogue maneuvering range reach more than 6 m. And it can accurately track the time-varying trajectory under the influence of model uncertainty and wind disturbance with an error of less than 0.1 m throughout. This method provides an effective means for achieving wide-range maneuverability control of the controllable drogue in autonomous aerial refueling missions.
Modeling and Performance Analysis of Solid Oxide Fuel Cell Power Generation System for Hypersonic Vehicles
Authors: Liu Yiming , Tan Jianguo , Zhang Dongdong , Kuai Zihan
Published: October 2024

Advanced airborne power generation technology represents one of the most effective solutions for meeting the electricity requirements of hypersonic vehicles during long-endurance flights. This paper proposes a power generation system that integrates a high-temperature fuel cell to tackle the challenges associated with power generation in the hypersonic field, utilizing techniques such as inlet pressurization, autothermal reforming, and anode recirculation. Firstly, the power generation system is modeled modularly. Secondly, the influence of key parameters on the system’s performance is analyzed. Thirdly, the performance of the power generation system under the design conditions is simulated and evaluated. Finally, the weight distribution and exergy loss of the system’s components under the design conditions are calculated. The results indicate that the system’s electrical efficiency increases with fuel utilization, decreases with rising current density and steam-to-carbon ratio (SCR), and initially increases before declining with increasing fuel cell operating temperature. Under the design conditions, the system’s power output is 48.08 kW, with an electrical efficiency of 51.77%. The total weight of the power generation system is 77.09 kg, with the fuel cell comprising 69.60% of this weight, resulting in a power density of 0.62 kW/kg. The exergy efficiency of the system is 55.86%, with the solid oxide fuel cell (SOFC) exhibiting the highest exergy loss, while the mixer demonstrates the greatest exergy efficiency. This study supports the application of high-temperature fuel cells in the hypersonic field.