bluuebunny/crossref_metadata_2025 huggingface dataset:
Smart home load scheduling system with solar photovoltaic generation and demand response in the smart grid
Authors: Hua Lyu-Guang , Ali Shah S. Haseeb , Alghamdi Baheej , Hafeez Ghulam , Ullah Safeer , Murawwat Sadia , Ali Sajjad , Khan Muhammad Iftikhar
Published: August 2024

This study introduces a smart home load scheduling system that aims to address concerns related to energy conservation and environmental preservation. A comprehensive demand response (DR) model is proposed, which includes an energy consumption scheduler (ECS) designed to optimize the operation of smart appliances. The ECS utilizes various optimization algorithms, including particle swarm optimization (PSO), genetic optimization algorithm (GOA), wind-driven optimization (WDO), and the hybrid genetic wind-driven optimization (HGWDO) algorithm. These algorithms work together to schedule smart home appliance operations effectively under real-time price-based demand response (RTPDR). The efficient integration of renewable energy into smart grids (SGs) is challenging due to its time-varying and intermittent nature. To address this, batteries were used in this study to mitigate the fluctuations in renewable generation. The simulation results validate the effectiveness of our proposed approach in optimally addressing the smart home load scheduling problem with photovoltaic generation and DR. The system achieves the minimization of utility bills, pollutant emissions, and the peak-to-average demand ratio (PADR) compared to existing models. Through this study, we provide a practical and effective solution to enhance the efficiency of smart home energy management, contributing to sustainable practices and reducing environmental impact.
Medium-voltage feeder blocks division method considering source-load uncertainty and characteristics complementary clustering
Authors: Zheng Jieyun , Zhang Zhanghuang , Shi Ying , Chen Zhuolin
Published: August 2024

Existing feeder block division methods fail to consider the complementary characteristics and uncertainty between power sources and loads, which result in excessive feeder blocks, low inter-block balance, and significant disparity in net load peak-valley difference. To address these issues, a medium-voltage feeder block division method that considers the uncertainty and complementary characteristics of sources and loads is proposed. Firstly, based on the probability density characteristics of sources and loads, an uncertainty model of DG output and load demand is established. Secondly, considering the constraints of block maximum load rate and feeder non-crossing, a feeder block division model is established. Additionally, a set of center circles is defined, and based on this, an improved K-means clustering algorithm is proposed. The initial clustering centers based on the center circles is set, and the clustering centers based on the arcs of the center circles corrected. And the weighted distances between power sources and clustering centers are calculated. An algorithm flow for improved K-means clustering feeder block division is designed accordingly. Finally, the case studies show that the result of block division is improved.
A policy analysis of China’s sustainable rural revitalization: integrating environmental, social and economic dimensions
Authors: Guo Yi , Li Shengchao
Published: August 2024

Rural decline has become a global challenge threatening sustainable development. Many countries have explored rural revitalization strategies, but systematic research on policy mechanisms and optimization paths is lacking. This study collected 74 rural revitalization policy texts in China from 2018 to 2024 through stratified sampling. Combining qualitative coding and quantitative modeling, including grounded theory, LDA topic model, sentiment analysis and semantic network analysis, this study constructed an integrated analytical framework to examine policy themes, emotional expression and logical relationships. The results identified the “Five Revitalizations” framework focusing on industrial, talent, cultural, ecological and organizational revitalization, as well as the “Four Supports” of institutional innovation, input guarantee, technological support and legal protection. The policy texts exhibit an increasingly optimistic tone, with traditional themes of deepening rural reform and increasing agricultural investment coexisting with emerging themes of urban-rural integration and digital countryside construction. Semantic network analysis further revealed the intrinsic linkages among policy themes. Comparative analysis with international rural revitalization cases yielded the following optimization paths: improving urban-rural integration mechanisms, strengthening diversified input guarantee, enhancing technological and talent support, and innovating rural governance models. This study enriches the theoretical understanding and practical guidance for sustainable rural revitalization from a global perspective.
Is oxidative stress - antioxidants imbalance the physiopathogenic core in pediatric obesity?
Authors: Lupu Ancuta , Fotea Silvia , Jechel Elena , Starcea Iuliana Magdalena , Ioniuc Ileana , Knieling Anton , Salaru Delia Lidia , Sasaran Maria Oana , Cirstea Olga , Revenco Ninel , Mihai Cristina Maria , Lupu Vasile Valeriu , Nedelcu Alin Horatiu
Published: August 2024

Despite the early recognition of obesity as an epidemic with global implications, research on its pathogenesis and therapeutic approach is still on the rise. The literature of the 21st century records an excess weight found in up to 1/3 of children. Both the determining factors and its systemic effects are multiple and variable. Regarding its involvement in the potentiation of cardio-vascular, pulmonary, digestive, metabolic, neuro-psychic or even dermatological diseases, the information is already broadly outlined. The connection between the underlying disease and the associated comorbidities seems to be partially attributable to oxidative stress. In addition to these, and in the light of the recent COVID-19 pandemic, the role played by oxidative stress in the induction, maintenance and potentiation of chronic inflammation among overweight children and adolescents becomes a topic of interest again. Thus, this review’s purpose is to update general data on obesity, with an emphasis on the physiopathological mechanisms that underlie it and involve oxidative stress. At the same time, we briefly present the latest principles of pathology diagnosis and management. Among these, we will mainly emphasize the impact played by endogenous and exogenous antioxidants in the evolutionary course of pediatric obesity. In order to achieve our objectives, we will refer to the most recent studies published in the specialized literature.
Case report: Immune response characterization of a pseudoprogression in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic NSCLC
Authors: Roussot Nicolas , Thibaudin Marion , Fumet Jean-David , Daumoine Susy , Hampe Léa , Rébé Cédric , Limagne Emeric , Lagrange Aurélie , Herreros Victor , Lecuelle Julie , Mananet Hugo , Ilie Alis , Rageot David , Boidot Romain , Goussot Vincent , Comte Anthony , Jacob Pierre , Beltjens Françoise , Bergeron Anthony , Charon-Barra Céline , Arnould Laurent , Derangère Valentin , Ladoire Sylvain , Truntzer Caroline , Ghiringhelli François
Published: August 2024

A patient with a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic non-small cell lung cancer (NSCLC) experienced a multisite radiological progression at 3 months after initiation of chemoimmunotherapy as first-line treatment for metastatic disease. After the radiological progression, while she was not undergoing treatment, the patient had spontaneous lesions shrinkage and further achieved a prolonged complete response. Genomic and transcriptomic data collected at baseline and at the time of pseudoprogression allowed us to biologically characterize this rare response pattern. We observed the presence of a tumor-specific T-cell response against tumor-specific neoantigens (TNAs). Endogenous retroviruses (ERVs) expression following chemoimmunotherapy was also observed, concurrent with biological features of an anti-viral-like innate immune response with type I IFN signaling and production of CXCR3-associated chemokines. This is the first biological characterization of a NSCLC pseudoprogression under chemoimmunotherapy followed by a prolonged complete response in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated NSCLC. These clinical and biological data underline that even patients with multiple factors of resistance to immune checkpoint inhibitors could trigger a tumor-specific immune response to tumor neoantigen, leading to complete eradication of the tumor and probably a vaccinal immune response.
X-linked severe combined immunodeficiency complicated by disseminated bacillus Calmette-Guérin disease caused by a novel pathogenic mutation in exon 3 of the IL2RG gene: a case report and literature review
Authors: Jiang Chunxue , He Yunhan , Chen Xin , Xia Fei , Shi Feng , Xu Xuewen , Sun Tingting , You Kai
Published: August 2024

X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor (IL2RG), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. The incidence of disseminated bacillus Calmette-Guérin (BCG) disease among children with SCID is much higher than in the general population. Here, we report the case of a 4-month-old male infant who presented with subcutaneous induration, fever, an unhealed BCG vaccination site, and hepatosplenomegaly. Metagenomic next-generation sequencing in blood, and the detection of gastric juice and skin nodule pus all confirmed the infection of Mycobacterium tuberculosis. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Whole-exome and Sanger sequencing revealed a novel microdeletion insertion mutation (c.316_318delinsGTGAT p.Leu106ValfsTer42) in the IL2RG gene, resulting in a rare shift in the amino acid sequence of the coding protein. Consequently, the child was diagnosed with X-SCID caused by a novel mutation in IL2RG, complicated by systemic disseminated BCG disease. Despite receiving systemic anti-infection treatment and four days of hospitalization, the patient died three days after discharge. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. In our systemic review, we outline the efficacy of systemic anti-tuberculosis therapy, hematopoietic stem cell transplantation, and gene therapy in children with SCID and BCG diseases caused by IL2RG gene mutation.
Predicting intraoperative major blood loss in microsurgery for brain arteriovenous malformations
Authors: Shi Jichun , Xu Shuangxiang , Feng Yu , Wei Wei , Zou Yichun , Xiong Wenping , Zhao Wenyuan , Zhang Tingbao , Peng Hao , Chen Jincao
Published: August 2024

Objective

Intraoperative blood loss poses a great challenge for brain arteriovenous malformation (AVM) microsurgery, although systematic researches are still lacking. This study aimed to identify factors predicting intraoperative major blood loss in brain AVM microsurgery and to investigate its impact on patient outcome. To deal with the fierce bleeding, we introduced a modified hemostatic method, bone-wax (BW) coated bipolar electrocoagulation.

Methods

The authors retrospectively analyzed the clinical data of 131 patients (50/81 in intraoperative major/non-major blood loss cohort) with brain AVMs who underwent microsurgery in our center during the period between January 2018 and April 2023. According to previous studies, major blood loss was defined as blood loss of at least 1,000 mL. The accuracy and objectivity of our grouping methodology were validated by comparing the hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding. Potential clinical and radiological predictors for intraoperative major blood loss were evaluated using a multivariate stepwise logistic regression. And outcomes of patients in the two cohorts were also compared. At last, the performance of BW coated bipolar electrocoagulation in brain AVM microsurgery was illustrated by the case presentation, histological staining and transmission electron microscopy of the coagulated nidus vessels.

Results

Hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding were significant different between the two cohorts. five independent factors predicting intraoperative major blood loss were identified: (1) clinical manifestations; (2,3) location and size of the nidus; (4) deep venous drainage; and (5) the number of draining veins. And the intraoperative major blood loss can not only adversely affect the surgical progression, but also predict poor perioperative outcomes for patients. Regarding the application of BW coated bipolar electrocoagulation, we found the novel hemostatic method exerted efficient hemostatic effect and reduced the damage to the vascular structure in brain AVM microsurgery.

Conclusion

This study proposed a nomogram for neurosurgeons to predict intraoperative major blood loss in brain AVM microsurgery preoperatively. And intraoperative major blood loss is associated with poor patient outcomes. In addition, BW coated bipolar electrocoagulation, can be applied to control ferocious bleeding during brain AVM microsurgery, which still remains further researches.
Fabricated devices for performing bacterial-fungal interaction experiments across scales
Authors: Kelliher Julia M. , Johnson Leah Y. D. , Robinson Aaron J. , Longley Reid , Hanson Buck T. , Cailleau Guillaume , Bindschedler Saskia , Junier Pilar , Chain Patrick S. G.
Published: August 2024

Diverse and complex microbiomes are found in virtually every environment on Earth. Bacteria and fungi often co-dominate environmental microbiomes, and there is growing recognition that bacterial-fungal interactions (BFI) have significant impacts on the functioning of their associated microbiomes, environments, and hosts. Investigating BFI in vitro remains a challenge, particularly when attempting to examine interactions at multiple scales of system complexity. Fabricated devices can provide control over both biotic composition and abiotic factors within an experiment to enable the characterization of diverse BFI phenotypes such as modulation of growth rate, production of biomolecules, and alterations to physical movements. Engineered devices ranging from microfluidic chips to simulated rhizosphere systems have been and will continue to be invaluable to BFI research, and it is anticipated that such devices will continue to be developed for diverse applications in the field. This will allow researchers to address specific questions regarding the nature of BFI and how they impact larger microbiome and environmental processes such as biogeochemical cycles, plant productivity, and overall ecosystem resilience. Devices that are currently used for experimental investigations of bacteria, fungi, and BFI are discussed herein along with some of the associated challenges and several recommendations for future device design and applications.
Innovative optimization for enhancing Pb2+ biosorption from aqueous solutions using Bacillus subtilis
Authors: El-Sharkawy Reyad M. , Khairy Mohamed , Abbas Mohamed H. H. , Zaki Magdi E. A. , El-Hadary Abdalla E.
Published: August 2024

Introduction

Toxic heavy metal pollution has been considered a major ecosystem pollution source. Unceasing or rare performance of Pb2+ to the surrounding environment causes damage to the kidney, nervous, and liver systems. Microbial remediation has acquired prominence in recent decades due to its high efficiency, environment-friendliness, and cost-effectiveness.

Methods

The lead biosorption by Bacillus subtilis was optimized by two successive paradigms, namely, a definitive screening design (DSD) and an artificial neural network (ANN), to maximize the sorption process.

Results

Five physicochemical variables showed a significant influence (p < 0.05) on the Pb2+ biosorption with optimal levels of pH 6.1, temperature 30°C, glucose 1.5%, yeast extract 1.7%, and MgSO4.7H2O 0.2, resulting in a 96.12% removal rate. The Pb2+ biosorption mechanism using B. subtilis biomass was investigated by performing several analyses before and after Pb2+ biosorption. The maximum Pb2+ biosorption capacity of B. subtilis was 61.8 mg/g at a 0.3 g biosorbent dose, pH 6.0, temperature 30°C, and contact time 60 min. Langmuir’s isotherm and pseudo-second-order model with R2 of 0.991 and 0.999 were suitable for the biosorption data, predicting a monolayer adsorption and chemisorption mechanism, respectively.

Discussion

The outcome of the present research seems to be a first attempt to apply intelligence paradigms in the optimization of low-cost Pb2+ biosorption using B. subtilis biomass, justifying their promising application for enhancing the removal efficiency of heavy metal ions using biosorbents from contaminated aqueous systems.
A comparison of phage susceptibility testing with two liquid high-throughput methods
Authors: Parmar Krupa , Fackler Joseph R. , Rivas Zuriel , Mandrekar Jay , Greenwood-Quaintance Kerryl E. , Patel Robin
Published: August 2024

Phage therapy is a promising antibacterial strategy, especially given that drug-resistant bacterial infections are escalating worldwide. Because phages are not active against all strains of a given species, phages being considered for therapeutic use would ideally be tested against bacterial isolates from individual patients prior to administration. Standardized, clinically validated phage susceptibility testing (PST) methods are needed for assessing in vitro phage activity. This study compared two high-throughput liquid-based PST assays. The first, using the Biolog Omnilog™, assessed changes in microbial respiration leading to color changes based on a tetrazolium dye. The second, Agilent BioTek Cytation 7, assessed changes in optical density. Both used 96-well microtiter plate formats. A total of 55 diverse phages with activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, or Enterococcus faecalis were studied against their respective susceptible bacterial hosts and non-susceptible controls, with susceptibility defined based on plaque assay. PST was performed by both assays in replicates, with results compared in terms of hold times (time through which bacterial growth is inhibited by phage compared to controls). Coefficients of variance and interclass correlation coefficients were used to assess inter- and intra-assay reproducibility. Based on a ≤50% coefficient of variance cutpoint, 87% of Biolog and 84% of Agilent assays were considered valid for susceptible bacteria, with 100% considered valid for non-susceptible bacteria by both systems. Using a 8 h hold time cutpoint, 100% of the results matched between the two assays. The interclass correlation coefficient showed 26% excellent agreement, 35% good agreement, and 17% moderate agreement between the two assays for susceptible isolates and 100% excellent agreement for non-susceptible isolates. Overall, the assays compared provided good/fair statistical reproducibility for the assessment of phage susceptibility.
Possible immune mechanisms of gut microbiota and its metabolites in the occurrence and development of immune thrombocytopenia
Authors: Zhu Gengda , Yan Lixiang , Fang Lijun , Fan Chenyang , Sun Hui , Zhou Xinli , Zhang Yucheng , Shi Zhexin
Published: August 2024

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired production, leading to an elevated bleeding tendency. Recent studies have demonstrated an important link between the gut microbiota and the onset and progression of several immune diseases in humans, emphasizing that gut microbiota-derived metabolites play a non-negligible role in autoimmune diseases. The gut microbiota and its metabolites, such as short-chain fatty acids, oxidized trimethylamine, tryptophan metabolites, secondary bile acids and lipopolysaccharides, can alter intestinal barrier permeability by modulating immune cell differentiation and cytokine secretion, which in turn affects the systemic immune function of the host. It is therefore reasonable to hypothesize that ecological dysregulation of the gut microbiota may be an entirely new factor in the triggering of ITP. This article reviews the potential immune-related mechanisms of the gut microbiota and representative metabolites in ITP, as well as the important influence of leaky gut on the development of ITP, with a view to enriching the theoretical system of ITP-related gut microecology and providing new ideas for the study of ITP.
The role of Mycobacterium tuberculosis exosomal miRNAs in host pathogen cross-talk as diagnostic and therapeutic biomarkers
Authors: Mukhtar Farwa , Guarnieri Antonio , Brancazio Natasha , Falcone Marilina , Di Naro Maria , Azeem Muhammad , Zubair Muhammad , Nicolosi Daria , Di Marco Roberto , Petronio Petronio Giulio
Published: August 2024

Tuberculosis (TB) is a global threat, affecting one-quarter of the world's population. The World Health Organization (WHO) reports that 6 million people die annually due to chronic illnesses, a statistic that includes TB-related deaths. This high mortality is attributed to factors such as the emergence of drug-resistant strains and the exceptional survival mechanisms of Mycobacterium tuberculosis (MTB). Recently, microRNAs (miRNAs) have garnered attention for their crucial role in TB pathogenesis, surpassing typical small RNAs (sRNA) in their ability to alter the host's immune response. For instance, miR-155, miR-125b, and miR-29a have been identified as key players in the immune response to MTB, particularly in modulating macrophages, T cells, and cytokine production. While sRNAs are restricted to within cells, exo-miRNAs are secreted from MTB-infected macrophages. These exo-miRNAs modify the function of surrounding cells to favor the bacterium, perpetuating the infection cycle. Another significant aspect is that the expression of these miRNAs affects specific genes and pathways involved in immune functions, suggesting their potential use in diagnosing TB and as therapeutic targets. This review compiles existing information on the immunomodulatory function of exosomal miRNAs from MTB, particularly focusing on disease progression and the scientific potential of this approach compared to existing diagnostic techniques. Thus, the aim of the study is to understand the role of exosomal miRNAs in TB and to explore their potential for developing novel diagnostic and therapeutic methods.
Association of peak expiratory flow with motoric cognitive risk syndrome among older adults
Authors: Xu Hui , Gong Xiangwen , Cui Kaiwang , Li Xuerui , Chen Long , Lu Yiyi , Liao Yangfang , Liu Jianping
Published: August 2024

Background

The association between lung function and motoric cognitive risk syndrome (MCR) is unclear. We aimed to explore the association of peak expiratory flow (PEF) with MCR using cross-sectional and longitudinal analyses.

Methods

Within the CHARLS, 5095 participants were included in the cross-sectional analysis, and 4340 MCR-free participants were included in the longitudinal analysis. The PEF was assessed with a lung peak flow meter. MCR was characterized by cognitive complaints and a slow walking speed with normal mobility and without dementia. Logistic regression, Cox regression, and Laplace regression models were employed for data analysis.

Results

In this cross-sectional study, logistic regression analyses revealed that continuous PEF was associated with MCR (odds ratio [OR], 0.998; 95% confidence interval [CI], 0.998, 0.999), and the ORs (95% CIs) of MCR prevalence were 0.857 (0.693, 1.061) for the middle tertile and 0.665 (0.524, 0.845) for the highest tertile compared to the lowest tertile. In a longitudinal cohort study, continuous PEF was dose-dependently associated with the risk of MCR. Compared with those in the lowest tertile of PEF, the hazard ratios (95% CIs) of incident MCR were 0.827 (0.661, 1,036) for the middle tertile and 0.576 (0.432, 0.767) for the highest tertile. Furthermore, compared with the lowest tertile, the highest tertile was associated with a delayed onset time of MCR of 0.484 (95% CI: 0.151, 0.817) years.

Conclusion

A higher PEF was related to a lower prevalence of MCR and a lower risk for MCR, and a higher PEF also prolonged the onset time of MCR.
Donepezil as a new therapeutic potential in KCNQ2- and KCNQ3-related autism
Authors: Nissenkorn Andreea , Bar Lior , Ben-Bassat Ariel , Rothstein Lynn , Abdelrahim Hoda , Sokol Riki , Gabis Lidia V. , Attali Bernard
Published: August 2024

Introduction

The KCNQ2/KCNQ3 genes encode the voltage-gated K channel underlying the neuronal M-current, regulating neuronal excitability. Loss-of-function (LoF) variants cause neonatal epilepsy, treatable with the M-current-opener retigabine, which is no longer marketed due to side effects. Gain-of-function (GoF) variants cause developmental encephalopathy and autism that could be amenable to M-current, but such therapies are not clinically available. In this translational project, we investigated whether donepezil, a cholinergic drug used in Alzheimer’s, suppresses M currents in vitro and improves cognitive symptoms in patients with GoF variants.

Methods

(1) The effect of 1 μM donepezil on the amplitude of the M-current was measured in excitatory and inhibitory neurons of mouse primary cultured hippocampal cells. M-current was measured using the standard deactivation protocol (holding at 0 mV and deactivation at −60 mV) in the voltage-clamp configuration of the whole-cell patch clamp technique. The impact of donepezil was also examined on the spontaneous firing activity of hippocampal neurons in the current-clamp configuration. (2) Four children with autism, aged 2.5–8 years, with the following GoF variants were enrolled: KCNQ2 (p. Arg144Gln) and KCNQ 3 (p.Arg227Gln, p.Arg230Cys). Patients were treated off-label with donepezil 2.5–5 mg/d for 12 months and assessed with: clinical Global Impression of Change (CGI-c), Childhood Autism Rating Scale 2 (CARS-2), Adaptive Behavior Assessment System-II (ABAS-II), and Child Development Inventory (CDI).

Results

(1) Application of donepezil for at least 6 min produced a significant inhibition of the M-current with an IC50 of 0.4 μM. At 1 μM, donepezil reduced by 67% the M-current density of excitatory neurons (2.4 ± 0.46 vs. 0.89 ± 0.15 pA/pF, p < 0.05*). In inhibitory neurons, application of 1 μM donepezil produced a lesser inhibition of 59% of the M-current density (1.39 ± 0.43 vs. 0.57 ± 0.21, p > 0.05). Donepezil (1 μM) potently increased by 2.6-fold the spontaneous firing frequency, which was prevented by the muscarinic receptor antagonist atropine (10 μM). (2) The CARS-2 decreased by 3.8 ± 4.9 points (p > 0.05), but in two patients with KCNQ3 variants, the improvement was over the 4.5 clinically relevant threshold. The global clinical change was also clinically significant in these patients (CGI-c = 1). The CDI increased by 65% (p < 0.05*), while the ABAS-II remained unchanged.

Discussion

Donepezil should be repurposed as a novel alternative treatment for GoF variants in KCNQ2/KCNQ3 encephalopathy.
Telerehabilitation and onsite rehabilitation effectively improve quality of life, fatigue, balance, and cognition in people with multiple sclerosis: an interventional study
Authors: Petracca Maria , Petsas Nikolaos , Sellitto Giovanni , Ruotolo Ilaria , Livi Chiara , Bonanno Valeria , Felicetti Federica , Ianniello Antonio , Ruggieri Serena , Borriello Giovanna , Pozzilli Carlo
Published: August 2024

Background

Telerehabilitation (TR) offers a valuable opportunity to improve access to care and has shown results comparable to onsite rehabilitation (SR) across different conditions. The present study aimed to explore the efficacy of TR and SR in improving clinically meaningful outcomes in people with multiple sclerosis (pwMS).

Materials and methods

Subjects enrolled in the study were assigned to one of two treatment arms: a 6-week TR intervention or a 6-week onsite rehabilitation (SR) intervention. Pre-and post-intervention evaluation included assessment of global wellbeing using the Multiple Sclerosis Quality of Life-54 scale (QoL), fatigue using the Fatigue Severity Status scale (FSS), cognitive status using the Symbol Digit Modalities Test (SDMT), and balance dysfunction using the Berg Balance Scale (BBS). Group-level and single-subject improvements were considered as outcome measures, with QoL as the primary endpoint. To determine significant group changes over time for the entire pwMS cohort, a paired t-test was applied to the overall QoL score, focusing on both physical and mental composites. An independent sample t-test was used to assess differences in baseline and follow-up performance, as well as changes over time between the intervention groups (TR and SR). This same analysis was repeated for the other clinical domains (FSS, BBS, and SDMT). The minimal clinically important difference (MCID) according to treatment group (TR vs. SR) was explored using logistic regression. Additionally, a multiple linear regression model was applied to evaluate the impact of baseline clinical-demographic features on the observed post-intervention modifications.

Results

A total of 51 subjects completed the study (37 women, mean age 46.3 ± 9.8, median Expanded Disability Status Scale 3.5, min. 2, max. 6.5). The entire sample benefited from the rehabilitation treatment, with significant improvements observed at both the group and individual levels across all measured domains for both intervention groups (TR vs. SR). Quality of life improved significantly (p = 0.005), as did fatigue and balance (both p < 0.001), and cognition (p = 0.003).

Conclusions

Both SR and TR approaches effectively improved the perception of fatigue, cognitive performance, balance, and quality of life in a population of MS patients with moderate disability.
Concept validation of separations for thorium-based radionuclide generator systems for medical application
Authors: Schacherl Bianca , Maurer Kiara , Schäfer Martin , Remde Yvonne , Geyer Frank , Fried Annika , Happel Steffen Alexander , Benešová-Schäfer Martina
Published: August 2024

Targeted alpha therapy (TαT) represents an emerging and cutting-edge treatment option for patients dealing with highly challenging metastatic cancer diseases. Critically, the limited supply of alpha-particle-emitting radionuclides, so-called alpha in vivo nanogenerators, hampers wider utilization of TαT in clinical settings. This could effectively be circumvented by alternative production routes, including straightforward purification and reformulation strategies. Radionuclide generators offering great potential in simple and robust elution strategies can be provided that still adhere to high radioisotopic, radionuclidic, and radiochemical purity criteria. This study takes a first step towards novel separation strategies by providing additional sources of alpha in vivo nanogenerators for TαT through experiments with various metal surrogates. With different systems, 232Th/natBa was used as a radionuclide generator analogue to 227Th/223Ra, and 232Th/natBa/natLa was used as a triplet analogue to 229Th/225Ra/225Ac. Three selective resins (UTEVA, TEVA, DGA-N) were evaluated for the 232Th/natBa system. Two perturbations of the best-performing resin were further evaluated using a larger diameter column and 1 week of equilibration. For the 232Th/natBa/natLa separation system, a combined column with two selective resins (TK200, TK101) was employed and evaluated. The results thus obtained pave the way for alternative separation strategies in radioactive proof-of-concept validation in the near future.
Paraneoplastic dermatomyositis and Hodgkin’s lymphoma in a 14-year-old girl: a case report and literature review
Authors: Ling Yanyan , Hu Huaiqiang , Xu Xiangyan , Feng Jianli , Li Mingzhe , Li Huan , Cheng Ming , Wang Xiaoling
Published: August 2024

Background

Juvenile dermatomyositis (JDM) is a rare autoimmune myopathy whose main clinical manifestations include a characteristic rash, symmetrical proximal muscle weakness, and elevated muscle enzymes. While approximately one-third of adult patients with dermatomyositis (DM) develop malignancies, typically within a year of diagnosis, this phenomenon is not commonly observed in patients with JDM. In this study, we present a rare case of both JDM and Hodgkin’s lymphoma (HL) diagnosed in an adolescent female patient.

Case description

A 14-year-old girl with proximal muscle weakness and myalgia for 8 weeks was admitted to the hospital and ultimately received a diagnosis of DM. A thorough physical examination revealed enlarged lymph nodes on both sides of the cervical, and a lymph node biopsy was performed to diagnose HL. After she underwent radiotherapy and chemotherapy, her symptoms of both HL and DM were alleviated.

Conclusion

The phenomenon of JDM as a paraneoplastic syndrome associated with HL is very rare. Thus, routine cancer screening for DM in adolescents is currently not recommended. The diagnosis of JDM requires a detailed physical examination, and further tumor screening is necessary for patients with unusual physical findings, such as atypical rashes, enlarged lymph nodes, and enlargement of the spleen and/or liver. Even if no malignancy is detected when JDM is diagnosed, long-term follow-up is necessary.
Factors associated with pathological complete remission after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a real-world clinical setting
Authors: Lin Minglin , Liu Junsheng , Lan Chongyuan , Qiu Ming , Huang Wei , Liao Cun , Zhang Sen
Published: August 2024

Objective

This study aims to identify factors associated with achieving a pathological complete remission (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT).

Methods

We conducted a cohort analysis of 171 LARC patients who underwent curative resection post-nCRT at the First Affiliated Hospital of Guangxi Medical University between January 2015 and December 2021. The data encompassed clinical and pathological information. Univariate and binary logistic regression multivariate analyses were employed to examine the factors influencing pCR achievement after nCRT. Kappa value tests were utilized to compare clinical staging after nCRT with postoperative pathological staging.

Results

Postoperative histopathology revealed that of the 171 patients, 40 (23.4%) achieved TRG 0 grade (pCR group), while 131 (76.6%) did not achieve pCR, comprising 36 TRG1, 42 TRG2, and 53 TRG3 cases. Univariate analysis indicated that younger age (p=0.008), reduced tumor occupation of intestinal circumference (p =0.008), specific pathological types (p=0.011), and lower pre-nCRT CEA levels (p=0.003) correlated with pCR attainment. Multivariate analysis identified these factors as independent predictors of pCR: younger age (OR=0.946, p=0.004), smaller tumor occupation of intestinal circumference (OR=2.809, p=0.046), non-mucinous adenocarcinoma pathological type (OR=10.405, p=0.029), and lower pre-nCRT serum CEA levels (OR=2.463, p=0.031). Clinical re-staging post-nCRT compared to postoperative pathological staging showed inconsistent MRI T staging (Kappa=0.012, p=0.718, consistency rate: 35.1%) and marginally consistent MRI N staging (Kappa=0.205, p=0.001, consistency rate: 59.6%).

Conclusion

LARC patients with younger age, presenting with smaller tumor circumferences in the intestinal lumen, lower pre-nCRT serum CEA levels, and non-mucinous adenocarcinoma are more likely to achieve pCR after nCRT. The study highlights the need for improved accuracy in clinical re-staging assessments after nCRT in LARC.
Effectiveness and safety of East Asian herbal medicine for menopausal insomnia: a systematic review and meta-analysis
Authors: Kwon Chan-Young , Lee Boram , Lee Ji-Yeon
Published: August 2024

Background: Menopausal insomnia significantly impacts the quality of life in women. East Asian herbal medicines (EAHMs) have been traditionally used in Asian countries, but their efficacy and safety require systematic evaluation. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of EAHM for treating menopausal insomnia.

Methods: A comprehensive literature search was conducted across 10 electronic databases from inception until 19 July 2023. Randomized controlled trials (RCTs) investigating EAHM for menopausal insomnia were included. Two reviewers independently screened studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. The primary outcome was sleep quality, insomnia severity, and sleep architecture. Secondary outcomes included total effective rate (TER), menopausal symptoms, and adverse effects. Meta-analysis was conducted using a random-effects model, and the results were calculated as mean differences (MDs) or risk ratios (RRs) and their 95% confidence intervals (CIs). Also, the certainty of evidence was assessed using the GRADE approach.

Results: A total of 70 RCTs involving 6,035 participants met the inclusion criteria. The most frequently used EAHMs were modified Suan Zao Ren Tang, and the most frequently used herbal component was Zizyphus jujuba Miller var. spinosa Hu ex H. F. Chou [Rhamnaceae; Zizyphi Semen]. Compared with sedative-hypnotics, EAHM significantly improved sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI) (MD –2.18, 95% CI –2.56 to −1.80), and reduced menopausal symptoms, as assessed by the Kupperman Index (MD –4.92, 95% CI –6.03 to −3.80). Similar results were seen when EAHM was added to sedative-hypnotics. When EAHM was additionally used in sedative-hypnotics, similar benefits were shown for PSQI (MD –2.46, 95% CI –3.09 to −1.82) and the Kupperman Index (MD –4.64, 95% CI –5.07 to −4.21). EAHM was generally safer than sedative-hypnotics, with significantly fewer adverse reactions (RR 0.15, 95% CI 0.07–0.34). However, the certainty of evidence was moderate to low.

Conclusion: EAHMs, alone or with sedative-hypnotics, may be effective and safe for improving sleep quality and managing menopausal symptoms. Future studies should include diverse populations, rigorous methodologies, and explore mechanisms of action to confirm these findings.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?], identifier [CRD42023446708].
Reliability of Metformin’s protective effects against doxorubicin-induced cardiotoxicity: a meta-analysis of animal studies
Authors: Sun Ming-Li , Chen Wei , Wang Xing-He
Published: August 2024

Background

The protective effects of metformin (Met) against doxorubicin (Dox)-induced cardiotoxicity via potential hypotheses of mechanisms of action with unknown reliability and credibility.

Objectives

This study aimed to investigate the protective effects of Met against Dox-induced cardiotoxicity and the underlying mechanisms of action, as well as examine their reliability and credibility.

Methods

A comprehensive search was conducted within the PubMed, Embase, Web of Science, Science Direct, Scopus, and CNKI databases from inception to 31 December 2023. Animal experiments evaluating the efficacy of Met against Dox-induced cardiotoxicity were included in this study. The primary efficacy outcomes were markers of myocardial injury. Effect size was measured using the standardized mean difference for continuous variables. Data were pooled using a random-effects model in the Stata 18 statistical software package.

Results

Twenty-one studies involving 203–208 animals treated with Dox and 271–276 animals treated with Dox and Met were included in this analysis. Quality assessment revealed high-quality scores. Pooled results favored Met treatment based on the serum lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and aspartate aminotransferase levels. Sensitivity analysis using the leave-one-out method demonstrated stable results. Funnel plots, Egger’s test, and Begg’s test confirmed potential publication bias. The oxidative stress hypothesis has been investigated extensively based on abundant evidence.

Conclusion

Met is effective and safe for protecting against Dox-induced cardiotoxicity, thus making it an appropriate drug for clinical investigation. The oxidative stress hypothesis of mechanism of action is well established with highest reliability and credibility.
Physiological analyses of swallowing changes due to chronic obstructive pulmonary disease in anesthetized male rats
Authors: Nagoya Kouta , Tsujimura Takanori , Yoshihara Midori , Watanabe Masahiro , Magara Jin , Kawasaki Katsushige , Inoue Makoto
Published: August 2024

Chronic obstructive pulmonary disease (COPD) was previously known as chronic bronchitis and emphysema. It has various main symptoms, such as dyspnea, chronic cough, and sputum, and is often accompanied by dysphagia. Although many published clinical reports have described COPD-related dysphagia, the physiological mechanisms underlying swallowing changes due to COPD remain unclear. Therefore, we analyzed how COPD affects the swallowing reflex using COPD model rats. We performed an electrophysiological study of respiration and swallowing using COPD model induced by intratracheal administration of porcine pancreatic elastase and lipopolysaccharide in Sprague-Dawley male rats. To identify the respiration and swallowing responses, electromyographic activity was recorded from the diaphragm, digastric (Dig), and thyrohyoid (TH) muscles. We confirmed COPD using micro-computed tomography analysis and hematoxylin and eosin staining of the lungs. The duty cycle was defined as the ratio of the inspiration duration to the total respiratory duration. In COPD model rats, the duty cycle was significantly higher than that in control rats. The frequency of the swallowing reflex evoked by electrical stimulation of the superior laryngeal nerve during the inspiration phase was higher in COPD model rats than in control rats. Furthermore, long-term COPD altered Dig and TH muscle activity without pathological muscle change. Our results suggest that COPD increases the frequency of swallowing initiation during the inspiration phase. Furthermore, long-term COPD affects swallowing-related muscle activity without pathological muscle changes. These physiological changes may increase the risk of developing dysphagia. Further studies are necessary to clarify the mechanisms contributing to the functional changes in respiration and swallowing in COPD.
A case for democratic pluralism instead of democratic minimalism
Authors: Sadr Omar
Published: August 2024

This paper proposes a theory of democratic pluralism instead of democratic minimalism developed by Shadi Hamid in his book “The Problem of Democracy”. Democratic pluralism will leverage pluralism to create a possibility for reconciliation between liberalism, secularism, religion, and democracy. It presents a framework of democratic pluralism based on four key elements: (1) a conception of democracy that includes performance and political action in the public sphere beyond electoral participation; (2) recognition of diversity and intercultural dialog, alongside the agonistic dimension of pluralism; (3) moderation of individual autonomy and identity politics; and (4) pluralistic accommodation of religion. The paper critiques Hamid’s monolithic notions of liberalism, secularism, and democracy, suggesting that more nuanced approaches to these concepts are necessary. It contends that rather than abandoning liberalism and secularism, exploring compatible versions of liberalism and Islam within a pluralistic framework offers a more promising path for reforming religion and polity in the Muslim world.
Development and validation of dependence and craving measures specific to athletes who use anabolic-androgenic steroids
Authors: Zoob Carter Barnaby N. , Boardley Ian D.
Published: August 2024

Background

Anabolic-androgenic steroid (AAS) dependence affects approximately 30% of people who use AAS. Presently, measures to assess and diagnose AAS dependence are adapted from scales specific to other forms of drug misuse (e.g., alcohol), containing issues with internal consistency and breadth of construct capture. Additionally, there are no measures available to assess AAS craving, which represents a potentially important coeval factor to AAS dependence. Therefore, this study aimed to develop and provide evidence of validity for measures of AAS dependence and AAS craving.

Methods

Data were collected from male and female strength athletes who use AAS across two samples (nsample 1 = 206; nsample 2 = 224). Sample 1 completed the new measures alongside instruments assessing theoretically related constructs (Doping Moral Disengagement, Doping Self-Regulatory Efficacy Scale, craving items from the Wisconsin Smoking Withdrawal Scale, AAS adapted Diagnostic and Statistical Manual for Mental Disorder 4th Edition), whereas Sample 2 completed the new instruments.

Results

Exploratory and Confirmatory Factor Analyses (CFA) with Sample 1 data were used to finalize the item sets for both measures and determine the factorial structures of the AAS Dependence Scale (AASDS) and AAS Craving Scale (AASCS). The AASDS consists of 15-items across five first-order factors that are represented by one second-order factor. The AASCS consists of 16-items across four first-order factors that are represented by one second-order factor. Evidence supporting the concurrent, convergent and discriminant validity of scores obtained with both scales was provided through their associations with the theoretically related variables. CFA with the data from Sample 2 confirmed the factor structures for both scales.

Conclusion

The AASDS and AASCS represent valid and reliable measures of AAS dependence and AAS craving for use in research with strength athletes who use AAS.
Early psychosocial parent–infant interventions and parent–infant relationships after preterm birth–a scoping review
Authors: Leppänen Marika , Korja Riikka , Rautava Päivi , Ahlqvist-Björkroth Sari
Published: August 2024

Objective

Early psychosocial interventions for preterm infants and their parents are diverse. This study aimed to structure the knowledge on psychosocial parent–infant interventions and to identify gaps in the intervention studies.

Methods

We included studies on early (during first year of life) psychosocial parent–infant interventions with parent–infant relationship outcomes after preterm birth (< 37 weeks). We excluded studies that did not focus on preterm infants, failed to indicate the studied intervention and outcomes, were not written in English, were not controlled or peer-reviewed studies, or did not provide essential information for eligibility. The search included studies published between January 2000 and March 2024 in PubMed and PsycINFO. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in reporting. Psychosocial parent–infant intervention studies were classified adapting the International Classification of Health Interventions (ICHI) and the Template for Intervention Description and Replication (TIDieR).

Results

The included 22 studies reported data from 18 different interventions with preterm infants (< 37 weeks). Studies excluded preterm infants with health risks (19/22, 86%), with very low gestational age and/or birth weight (7/22, 32%), and/or mothers with psychosocial risks (14/22, 64%). Of the 18 interventions, 12 (67%) were classified as counseling, 3 (17%) as emotional support, 2 (11%) as psychotherapeutic, and 1 (6%) as educational. The parent–child relationship was assessed using 30 different methods and varying time points up to 18 months of age. Most studies (17/22, 77%) reported positive changes in the parent–child relationship favoring the intervention group.

Conclusion

We identified four types of interventions to influence parenting behavior; the most used was counseling. All four intervention types showed positive effects on parent–infant relationships, although the preterm populations studied were selective, the effects were evaluated using different methods, and the follow-up periods were short. These findings indicate a need for studies with standardized methods, longer follow-up, and less-restricted preterm populations to develop guidelines for all families with preterm infants.