bluuebunny/crossref_metadata_2025 huggingface dataset:
Community engagement and human perception in crocodile conservation: preliminary steps in Sian Ka’an Biosphere Reserve
Authors: Benítez-Moreno Javier Arturo , Cedeño-Vázquez José Rogelio , Castelblanco-Martínez Delma Nataly
Published: March 2024

Introduction

Wildlife tourism is important for the conservation of protected areas, endangered species, and to empower local communities. Nevertheless, when guidelines and practices are not clear and correctly executed, tourism may have a negative impact.

Methods

We carried out semi-open interviews (n = 34) and several workshops (n = 50) with locals and tour guides in the village of Punta Allen in Sian Ka'an Biosphere Reserve, Mexico. Data were organized in tables in Excel®, and statistical analysis was conducted with IBM® SPSS® Statistics software. A priori, exploratory data analysis was carried out to identify the general pattern of the data, and a priori data normality test (Shapiro–Wilks) and χ2 test were carried out to find out if there were differences in the frequency of a response depending on socioeconomic variables.

Results

Most respondents (69%) dedicated 2–10 min to crocodile observation, one quarter (25%) spent 11–20 min, and the remainder (6%) 21–30 min. The majority (97%) of respondents mentioned that when they see a crocodile, they approach at a 5–10 m distance and wait for the occupants of the boat to take pictures, and then leave; only one respondent (3%) said that they feed crocodiles to attract them to the boat. Most respondents (89%) said that crocodile observation does not need to be improved, and it is fine the way it is currently carried out; the remaining 11% said that it could be improved. Workshops were received positively and allowed us to share information on crocodile species, their conservation, and good tourism practices.

Discussion

It is necessary to enlighten tourism service providers about the biology and importance of crocodilian species, to promote conservation and provide services with an educational impact/focus for visitors to the reserve. There is a need to develop a communication program that provides accurate information for new service providers and renews and reinforces concepts for established providers. Additionally, we need to continuously monitor and evaluate wildlife observation activities to enhance current practices in our study area, and to determine if they are having a negative impact on crocodile behavior and biology.
Seismic isolation technology of shallow buried large section utility tunnel with soft soils in seismically vulnerable area
Authors: Wang Zhigang , Chang Lijun , Ma Huabing , Zhu Li , Cui Guangyao , Shan Hongwei , He Ziyang
Published: March 2024

Shallow utility tunnels with exceptionally large cross-sections in weak soil can face significantly more severe seismic risks compared to conventional deep tunnels in seismic hazard areas. This study investigates the seismic response and isolation technologies applied to a large section utility tunnel with 4 compartments in one layer, employing seismic simulations. The engineering context, dynamic motions, and measuring points of the numerical simulation were introduced. Subsequently, the finite element method was employed to explore the seismic behaviors of the large section utility tunnel when subjected to strong earthquake excitations under four conditions. The study explored and comparatively evaluated the seismic isolation effectiveness of three proposed schemes: the grouting scheme, the buffer layer, and the assembly of three-quarters buffer layer, cushion and grouting. The analysis included various indexes such as the deformation, the principal and shear stress, and the safety factor. The finding reveals that the assembly seismic scheme exhibits the most significant seismic effect (95.39%), followed by the buffer layer (38.82%), and the grouting scheme (25.66%). The assembly seismic scheme is recommended for the seismic design in the current large-section utility tunnels. These conclusions provide valuable scientific guidance for the seismic design of large-section utility tunnels, aiding in enhancing earthquake resilience.
GLP-1RA may have varying effects on cardiac structure in patients with ASCVD depending on BMI
Authors: Xu Ling , Zhu Dan
Published: March 2024

Background

Glucagon-like peptide-1 receptor agonist(GLP-1RA) is commonly used in patients with cardiovascular disease due to its significant improvement in the prognosis of atherosclerotic cardiovascular disease (ASCVD). However, previous studies have primarily focused on obese patients, leaving uncertainty regarding whether GLP-1RA can yield similar cardiovascular benefits in individuals with normal or low body weight.

Methods

In this study, we enrolled patients with ASCVD to establish a retrospective cohort. Patients receiving GLP-1RA treatment were assigned to the GLP-1RA group, while a control group was formed by matching age and body mass index (BMI) among patients not receiving GLP-1RA treatment. Each group was further divided into subgroups based on baseline BMI levels: normal weight, overweight, and obesity. A six-month follow-up was conducted to assess changes in patient weight, metabolic indicators, and cardiac structure and function.

Results

Among the normal weight subgroup, no significant weight change was observed after six months of GLP-1RA treatment (57.4 ± 4.8 vs. 58.7 ± 9.2, p = 0.063). However, significant weight reduction was observed in the other two subgroups (Overweight group: 70.0 ± 9.1 vs. 73.1 ± 8.2, p = 0.003, Obesity group: 90.5 ± 14.3 vs. 95.5 ± 16.6, p<0.001). Regardless of baseline BMI levels, GLP-1RA demonstrated significant glucose-lowering effects in terms of metabolic indicators. However, GLP-1RA have a more significant effect on improving blood lipids in overweight and obese patients. The effects of GLP-1RA on cardiac structure exhibited variations among patients with different baseline BMI levels. Specifically, it was observed that the improvement in atrial structure was more prominent in patients with normal body weight(LAD: 33.0 (30.3, 35.5) vs. 35.0 (32.5, 37.1), p = 0.018, LAA (18.0 (16.0, 21.5) vs. 18.5 (16.5, 20.5), p = 0.008), while the enhancement in ventricular structure was more significant in obese subjects(LEVDD: 49.8 ± 5.8 vs. 50.2 ± 5.0, p < 0.001, LVMI: 65.1 (56.2, 71.4) vs. 65.8 (58.9, 80.4), p < 0.039).

Conclusion

According to the study, it was found that the administration of GLP-1RA can have different effects on cardiac structure in patients with different baseline BMI, In obese patients, improvements in ventricular remodeling may be more associated with weight loss mechanisms, while in patients with normal or low BMI, GLP-1RA may directly improve atrial remodeling through GLP-1 receptors in atrial tissue.
Two-stage robust planning method for distribution network energy storage based on load forecasting
Authors: Yuan Minghan , Zhang Hua , Ji Kunhua , Liu Yangyang , Tang Xiao , Tao Biao , Li Zichen , Mi Yang
Published: March 2024

A two-stage robust planning method for energy storage in distribution networks based on load prediction is proposed to address the uncertainty of active load in energy storage planning. First, considering the uncertainty of active load, a short-term load forecasting model combining the mutual information method and BiLSTM is established based on k-means++ clustering. Second, based on the results of load forecasting, a comprehensive norm-constrained uncertainty set is constructed, and a two-stage robust model for distribution network energy storage planning is established. The first stage aims to minimize the annual investment cost of the energy storage system, while the second stage aims to minimize the daily operating cost of the distribution network. At the same time, a second-order cone relaxation transformation model with non-convex constraints is introduced to ultimately achieve the optimal economy of the distribution network in energy storage planning. Finally, the effectiveness of the proposed method and model is validated on the IEEE 33-node distribution network model using the MATLAB platform.
Multi-scenario flexibility assessment of power systems considering renewable energy output uncertainty
Authors: Ai Qing , Xiang Jianqiang , Liu Yaolin , Qu Luguang , Cao Jinchao , Li Xiangnan , Wang Yingge
Published: March 2024

The widespread adoption of renewable energy sources presents a significant challenge to the flexibility of power system. To assess the flexibility of the power system in scenarios with uncertain renewable energy output, it is crucial to quantify it quantitatively. This evaluation plays a vital role in planning flexible regulatory resources and dispatching resources for both the energy source and load. This study introduces a novel flexibility assessment model tailored for power grids with high renewable energy penetration, specifically addressing uncertainty associated with wind and PV. By analyzing the impact of wind and PV uncertainty on system flexibility, the paper proposes an improved cohesive hierarchical cluster analysis method, incorporating reliability considerations based on the Davies-Bouldin classification reliability index. Additionally, the study develops models for flexibility resources and demands within high renewable energy power systems, along with quantitative assessment indicators across three key aspects. Through a structured flexibility assessment process accounting for wind and PV uncertainty, the effectiveness of the proposed approach is validated using real-world data from a renewable energy power grid in Shandong province. A set of typical renewable energy output scenarios with uncertainty is constructed using the improved hierarchical cluster analysis method. The study then analyses the impact of different wind and PV penetration rates and the proportion of energy storage units on system flexibility by the flexibility assessment model to validate the proposed method's effectiveness.
Onshore power supply–trends in research studies
Authors: Kizielewicz Joanna
Published: March 2024

Restrictive regulations introduced by the European Parliament and the United Nations have forced the seaport authorities to reach net zero gas emissions by 2030. An important source of pollution emitted in ports involves exhaust gas emissions from ships powered by ship engines while they are berthed in seaports. One of the ways to reduce the level of pollution and nuisance caused by ship engines is to equip ships with Onshore Power Supply (OPS). Unfortunately, still few ports can boast this type of systems at their quays. There are many publications devoted to the analysis of this phenomenon in the technical and engineering terms, but a significant part also concerns the economic, financial, logistic and organizational aspects. The aim of this research is to identify the directions of development as for research into OPS, to organize the terminology devoted to OPS, and to define scientific disciplines of research in the field of OPS. This research was conducted on the basis of the data mining method using the Scopus, EBSCO and Web of Science databases, applying the multi-stage selection of criteria. The research results may provide an interesting material for scientists to identify the gaps of research regarding OPS.
The impact of green finance on the intensity and efficiency of carbon emissions: the moderating effect of the digital economy
Authors: Liu Wenjie , Zhu Peng
Published: March 2024

Carbon emissions have become a global challenge that threatens human development. Governments have taken various measures to reduce carbon emissions, and green finance is an important and innovative way to realize carbon emission reductions. This paper uses data on a prefecture-level city in China to explore the impact of green finance on carbon emission intensity from both theoretical and empirical perspectives, and analyzes the mechanisms by which green finance affects carbon emission intensity. On this basis, this paper further analyzes the impact of green finance on carbon emission efficiency. In addition, this paper introduces variables related to the digital economy to perform a comprehensive examination of the moderating effect of digital economy development on the relationship between green finance and both carbon emission intensity and efficiency. The results indicate that green finance reduces carbon emission intensity and that green innovation, green total factor productivity and the transformation and upgrading of industry are important mediating mechanisms. Meanwhile, analysis shows that green finance improves carbon emission efficiency. This paper also finds that the digital economy significantly enhances the role of green finance in reducing carbon emission intensity and promoting carbon emission efficiency, and makes a positive contribution to promoting carbon emission reduction. The findings will contribute to strengthening the government’s capacity for environmental protection, developing green finance, and reducing carbon emissions.
Role of Treg cell subsets in cardiovascular disease pathogenesis and potential therapeutic targets
Authors: Xia Yuanliang , Gao Di , Wang Xu , Liu Bin , Shan Xue , Sun Yunpeng , Ma Dashi
Published: March 2024

In the genesis and progression of cardiovascular diseases involving both innate and adaptive immune responses, inflammation plays a pivotal and dual role. Studies in experimental animals indicate that certain immune responses are protective, while others exacerbate the disease. T-helper (Th) 1 cell immune responses are recognized as key drivers of inflammatory progression in cardiovascular diseases. Consequently, the CD4+CD25+FOXP3+ regulatory T cells (Tregs) are gaining increasing attention for their roles in inflammation and immune regulation. Given the critical role of Tregs in maintaining immune-inflammatory balance and homeostasis, abnormalities in their generation or function might lead to aberrant immune responses, thereby initiating pathological changes. Numerous preclinical studies and clinical trials have unveiled the central role of Tregs in cardiovascular diseases, such as atherosclerosis. Here, we review the roles and mechanisms of Treg subsets in cardiovascular conditions like atherosclerosis, hypertension, myocardial infarction and remodeling, myocarditis, dilated cardiomyopathy, and heart failure. While the precise molecular mechanisms of Tregs in cardiac protection remain elusive, therapeutic strategies targeting Tregs present a promising new direction for the prevention and treatment of cardiovascular diseases.
Comparison of SARS-CoV-2 spike-specific IgA and IgG in nasal secretions, saliva and serum
Authors: Bladh Oscar , Aguilera Katherina , Marking Ulrika , Kihlgren Martha , Greilert Norin Nina , Smed-Sörensen Anna , Sällberg Chen Margaret , Klingström Jonas , Blom Kim , Russell Michael W. , Havervall Sebastian , Thålin Charlotte , Åberg Mikael
Published: March 2024

Introduction

Several novel vaccine platforms aim at mucosal immunity in the respiratory tract to block SARS-CoV-2 transmission. Standardized methods for mucosal sample collection and quantification of mucosal antibodies are therefore urgently needed for harmonized comparisons and interpretations across mucosal vaccine trials and real-world data.

Methods

Using commercial electrochemiluminescence antibody panels, we compared SARS-CoV-2 spike-specific IgA and IgG in paired saliva, nasal secretions, and serum from 1048 healthcare workers with and without prior infection.

Results

Spike-specific IgA correlated well in nasal secretions and saliva (r>0.65, p<0.0001), but the levels were more than three-fold higher in nasal secretions as compared to in saliva (p<0.01). Correlations between the total population of spike-specific IgA and spike-specific secretory IgA (SIgA) were significantly stronger (p<0.0001) in nasal secretions (r=0.96, p<0.0001) as opposed to in saliva (r=0.77, p<0.0001), and spike-specific IgA correlated stronger (p<0.0001) between serum and saliva (r=0.73, p<0.001) as opposed to between serum and nasal secretions (r=0.54, p<0.001), suggesting transudation of monomeric spike specific IgA from the circulation to saliva. Notably, spike-specific SIgA had a markedly higher SARS-CoV-2 variant cross-binding capacity as compared to the total population of spike specific IgA and IgG in both nasal secretions, saliva and serum, (all p<0.0001), which emphasizes the importance of taking potential serum derived monomeric IgA into consideration when investigating mucosal immune responses.

Discussion

Taken together, although spike-specific IgA can be reliably measured in both nasal secretions and saliva, our findings imply an advantage of higher levels and likely also a larger proportion of SIgA in nasal secretions as compared to in saliva. We further corroborate the superior variant cross-binding capacity of SIgA in mucosal secretions, highlighting the potential protective benefits of a vaccine targeting the upper respiratory tract.
Effect of the gut microbiome, plasma metabolome, peripheral cells, and inflammatory cytokines on obesity: a bidirectional two-sample Mendelian randomization study and mediation analysis
Authors: Li Ying , Wang Xin , Zhang Zitong , Shi Lei , Cheng Liang , Zhang Xue
Published: March 2024

Background

Obesity is a metabolic and chronic inflammatory disease involving genetic and environmental factors. This study aimed to investigate the causal relationship among gut microbiota abundance, plasma metabolomics, peripheral cell (blood and immune cell) counts, inflammatory cytokines, and obesity.

Methods

Summary statistics of 191 gut microbiota traits (N = 18,340), 1,400 plasma metabolite traits (N = 8,299), 128 peripheral cell counts (blood cells, N = 408,112; immune cells, N = 3,757), 41 inflammatory cytokine traits (N = 8,293), and 6 obesity traits were obtained from publicly available genome-wide association studies. Two-sample Mendelian randomization (MR) analysis was applied to infer the causal links using inverse variance-weighted, maximum likelihood, MR-Egger, weighted median, weighted mode, and Wald ratio methods. Several sensitivity analyses were also utilized to ensure reliable MR results. Finally, we used mediation analysis to identify the pathway from gut microbiota to obesity mediated by plasma metabolites, peripheral cells, and inflammatory cytokines.

Results

MR revealed a causal effect of 44 gut microbiota taxa, 281 plasma metabolites, 27 peripheral cells, and 8 inflammatory cytokines on obesity. Among them, five shared causal gut microbiota taxa belonged to the phylum Actinobacteria, order Bifidobacteriales, family Bifidobacteriaceae, genus Lachnospiraceae UCG008, and species Eubacterium nodatum group. Furthermore, we screened 42 shared causal metabolites, 7 shared causal peripheral cells, and 1 shared causal inflammatory cytokine. Based on known causal metabolites, we observed that the metabolic pathways of D-arginine, D-ornithine, linoleic acid, and glycerophospholipid metabolism were closely related to obesity. Finally, mediation analysis revealed 20 mediation relationships, including the causal pathway from gut microbiota to obesity, mediated by 17 metabolites, 2 peripheral cells, and 1 inflammatory cytokine. Sensitivity analysis represented no heterogeneity or pleiotropy in this study.

Conclusion

Our findings support a causal relationship among gut microbiota, plasma metabolites, peripheral cells, inflammatory cytokines, and obesity. These biomarkers provide new insights into the mechanisms underlying obesity and contribute to its prevention, diagnosis, and treatment.
Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives
Authors: Levstek Lucija , Janžič Larisa , Ihan Alojz , Kopitar Andreja Nataša
Published: March 2024

Chimeric antigen receptor (CAR) T cell therapy holds enormous potential for the treatment of hematologic malignancies. Despite its benefits, it is still used as a second line of therapy, mainly because of its severe side effects and patient unresponsiveness. Numerous researchers worldwide have attempted to identify effective predictive biomarkers for early prediction of treatment outcomes and adverse effects in CAR T cell therapy, albeit so far only with limited success. This review provides a comprehensive overview of the current state of predictive biomarkers. Although existing predictive metrics correlate to some extent with treatment outcomes, they fail to encapsulate the complexity of the immune system dynamics. The aim of this review is to identify six major groups of predictive biomarkers and propose their use in developing improved and efficient prediction models. These groups include changes in mitochondrial dynamics, endothelial activation, central nervous system impairment, immune system markers, extracellular vesicles, and the inhibitory tumor microenvironment. A comprehensive understanding of the multiple factors that influence therapeutic efficacy has the potential to significantly improve the course of CAR T cell therapy and patient care, thereby making this advanced immunotherapy more appealing and the course of therapy more convenient and favorable for patients.
Utilizing residual networks for remote sensing estimation of total nitrogen concentration in Shandong offshore areas
Authors: Zheng Hongxia , Wu Yulin , Han Haifeng , Wang Juan , Liu Shanwei , Xu Mingming , Cui Jianyong , Yasir Muhammad
Published: March 2024

Nitrogen is one of the critical factors in water pollution and eutrophication, so applying the deep learning method in remote sensing inversion of nitrogen can provide basic information for environmental management. This paper proposes a two-step feature extraction method to solve the problem that the number of bands in water quality inversion is insufficient and the deep learning method cannot be fully exploited. Firstly, manual feature extraction is completed through the fusion between bands to obtain a set of high-latitude shallow factors, which make the features rich and diverse. Then, a one-dimensional convolutional residual network (ResNet-1D) is constructed, and the deep features are automatically extracted through convolution operations of the model, where the residual learning is used to reduce the training difficulty. The full connection is established through depth features. The comparison of models shows that the Mean Relative Error (MRE) is decreased by at least 10% in both test and validation datasets. Finally, the spatiotemporal distribution of total nitrogen concentration (TNC) in the coastal waters of Shandong is explored. In general, the spatial distribution is that the concentration near the coast is higher than the far. The temporal variation is that the monthly mean of the TNC is low in March, moderate in May and August, and high in October; the annual average value of TNC is 0.3mg/L, which has decreased slightly year by year since 2014.
Bee chitosan nanoparticles loaded with apitoxin as a novel approach to eradication of common human bacterial, fungal pathogens and treating cancer
Authors: Sharaf Mohamed , Zahra Abdullah A. , Alharbi Maha , Mekky Alsayed E. , Shehata Abdelrazeq M. , Alkhudhayri Abdulsalam , Ali Ahmed M. , Al Suhaimi Ebtesam A. , Zakai Shadi A. , Al Harthi Norah , Liu Chen-Guang
Published: March 2024

Antimicrobial resistance is one of the largest medical challenges because of the rising frequency of opportunistic human microbial infections across the globe. This study aimed to extract chitosan from the exoskeletons of dead bees and load it with bee venom (commercially available as Apitoxin [Api]). Then, the ionotropic gelation method would be used to form nanoparticles that could be a novel drug-delivery system that might eradicate eight common human pathogens (i.e., two fungal and six bacteria strains). It might also be used to treat the human colon cancer cell line (Caco2 ATCC ATP-37) and human liver cancer cell line (HepG2ATCC HB-8065) cancer cell lines. The x-ray diffraction (XRD), Fourier transform infrared (FTIR), and dynamic light scattering (DLS) properties, ζ-potentials, and surface appearances of the nanoparticles were evaluated by transmission electron microscopy (TEM). FTIR and XRD validated that the Api was successfully encapsulated in the chitosan nanoparticles (ChB NPs). According to the TEM, the ChB NPs and the ChB NPs loaded with Apitoxin (Api@ChB NPs) had a spherical shape and uniform size distribution, with non-aggregation, for an average size of approximately 182 and 274 ± 3.8 nm, respectively, and their Zeta potential values were 37.8 ± 1.2 mV and − 10.9 mV, respectively. The Api@ChB NPs had the greatest inhibitory effect against all tested strains compared with the ChB NPs and Api alone. The minimum inhibitory concentrations (MICs) of the Api, ChB NPs, and Api@ChB NPs were evaluated against the offer mentioned colony forming units (CFU/mL), and their lowest MIC values were 30, 25, and 12.5 μg mL−1, respectively, against Enterococcus faecalis. Identifiable morphological features of apoptosis were observed by 3 T3 Phototox software after Api@ChB NPs had been used to treat the normal Vero ATCC CCL-81, Caco2 ATCC ATP-37, and HepG2 ATCC HB-8065 cancer cell lines for 24 h. The morphological changes were clear in a concentration-dependent manner, and the ability of the cells was 250 to 500 μg mL−1. These results revealed that Api@ChB NPs may be a promising natural nanotreatment for common human pathogens.
Matrine reverses the resistance of Haemophilus parasuis to cefaclor by inhibiting the mutations in penicillin-binding protein genes (ftsI and mrcA)
Authors: Zhao JingChao , Yang Wen , Deng Hui , Li Dong , Wang QianYong , Yi LingXian , Kuang QiHong , Xu Rui , Li Di , Li RuoNan , Yu DaoJin , Yang Bo
Published: March 2024

Introduction

Matrine (MT) is a potential resistance reversal agent. However, it remains unclear whether MT can reverse the resistance of Haemophilus parasuis (H. parasuis) to β-lactams, and, if so, by what mechanism MT works.

Methods

We screened one cefaclor (CEC)-resistant strain (clinical strain C7) from eight clinical (H. parasuis) strains and determined the underlying resistance mechanism. Then, we investigated the reversal effect of MTon the resistance of this strain to CEC.

Results and Discussion

The production of β-lactamase, overexpression of AcrAB-TolC system, and formation of biofilm might not be responsible for the resistance of clinical strain C7 to CEC. Fourteen mutation sites were found in four PBP genes (ftsI, pbp1B, mrcA, and prcS) of clinical strain C7, among which the mutation sites located in ftsI (Y103D and L517R) and mrcA (A639V) genes triggered the resistance to CEC. The minimum inhibitory concentration (MIC) of CEC against clinical strain C7 was reduced by two to eight folds after MT treatment, accompanied by the significant down-regulated expression of mutated ftsI and mrcA genes. Based on such results, we believed that MT could reverse the resistance of H. parasuis to CEC by inhibiting the mutations in ftsI and mrcA genes. Our research would provide useful information for restoring the antimicrobial activity of β-lactams and improving the therapeutic efficacy of Glässer’s disease.
Efficacy of botulinum toxin A combined with extracorporeal shockwave therapy in post-stroke spasticity: a systematic review
Authors: Du Ya-nan , Li Yang , Zhang Ting-yu , Jiang Nan , Wei Ying , Cheng Shi-huan , Li He , Duan Hao-yang
Published: March 2024

Objectives

In recent years, there has been an increase in the number of randomized clinical trials of BTX-A combined with ESWT for the treatment of post-stroke spasticity. This has made it possible to observe the benefits of combination therapy in clinical practice. Therefore, this paper reviews the effectiveness of BTX-A in combination with ESWT for the treatment of post-stroke spasticity.

Methods

By October 2023, a systematic review was conducted in the databases PubMed, Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, China Biology Medicine disc and China Science and Technology Journal Database were systematically searched. We included randomized controlled trials that reported outcome metrics such as MAS, FMA, and MBI score. Studies were excluded if MAS was not reported. The quality of the included studies was assessed by the Cochrane Collaboration’s tool for assessing risk of bias, and the AMSTAR quality rating scale was selected for self-assessment.

Results

A total of 70 articles were included in the initial search, and six were ultimately included. The results of the included studies showed that the combination therapy was effective in reducing MAS scores and improving FMA and MBI scores in patients with spasticity compared to the control group. Combination therapy has also been shown to improve joint mobility and reduce pain in spastic limbs.

Conclusion

Cumulative evidence from clinical randomized controlled trial studies suggests that the combination therapy is effective in reducing lower limb spasticity and improving mobility after stroke. However, more clinical trials are still needed to corroborate the evidence regarding the efficacy of BTX-A combined with shockwave therapy.

Systematic Review Registration

The system review can be searched in the PROSPERO database (CRD42023476654).
Safety and efficacy of acupuncture for mild cognitive impairment: a study protocol for clinical study
Authors: Kim Jae-Hong , Shin Jeong-Cheol , Kim Ae-Ran , Seo Bok-Nam , Park Gwang-Cheon , Kang Byoung-Kab , Lee Jeong-Soon
Published: March 2024

Background

Mild cognitive impairment (MCI) is an intermediary condition between typical cognitive decline that occurs owing to aging and dementia. It is necessary to implement an intervention to slow the progression from MCI to Alzheimer’s disease. This manuscript reports the protocol for a clinical trial on the effect of acupuncture in patients with MCI.

Methods

The trial will be a randomized, prospective, parallel-arm, active-controlled trial. Sixty-four patients with MCI will be randomized to the Rehacom or acupuncture group (n = 32 each). The participants in the acupuncture group will receive electroacupuncture at GV24 (Shenting) and GV20 (Baihui) and acupuncture at EX-HN1 (Sishencong) once (30 min) a day, twice per week for 12 weeks. The patients in the Rehacom group will receive computerized cognitive rehabilitation using RehaCom software once (30 min) daily, twice weekly for 12 weeks. The primary outcome measure is the change in the Montreal Cognitive Assessment Scale score. The secondary outcome measures are the Geriatric Depression Scale, Alzheimer’s Disease Assessment Scale-Korean version-cognitive subscale-3 scores, and European Quality of Life Five Dimensions Five Level Scale. The safety outcomes will include the incidence of adverse events, blood pressure, blood chemistry parameters, and pulse rate. The efficacy outcome will be assessed at baseline and at six weeks, 13 weeks, and 24 weeks after baseline.

Discussion

The findings of this protocol will provide information regarding the effects of acupuncture on MCI.

Clinical trial registration

https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=M&pageSize=10&page=undefined&seq=25579&status=5&seq_group=25579, KCT0008861.
Automated analysis and detection of epileptic seizures in video recordings using artificial intelligence
Authors: Rai Pragya , Knight Andrew , Hiillos Matias , Kertész Csaba , Morales Elizabeth , Terney Daniella , Larsen Sidsel Armand , Østerkjerhuus Tim , Peltola Jukka , Beniczky Sándor
Published: March 2024

Introduction

Automated seizure detection promises to aid in the prevention of SUDEP and improve the quality of care by assisting in epilepsy diagnosis and treatment adjustment.

Methods

In this phase 2 exploratory study, the performance of a contactless, marker-free, video-based motor seizure detection system is assessed, considering video recordings of patients (age 0–80 years), in terms of sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves, with respect to video-electroencephalographic monitoring (VEM) as the medical gold standard. Detection performances of five categories of motor epileptic seizures (tonic–clonic, hyperkinetic, tonic, unclassified motor, automatisms) and psychogenic non-epileptic seizures (PNES) with a motor behavioral component lasting for >10 s were assessed independently at different detection thresholds (rather than as a categorical classification problem). A total of 230 patients were recruited in the study, of which 334 in-scope (>10 s) motor seizures (out of 1,114 total seizures) were identified by VEM reported from 81 patients. We analyzed both daytime and nocturnal recordings. The control threshold was evaluated at a range of values to compare the sensitivity (n = 81 subjects with seizures) and false detection rate (FDR) (n = all 230 subjects).

Results

At optimal thresholds, the performance of seizure groups in terms of sensitivity (CI) and FDR/h (CI): tonic–clonic- 95.2% (82.4, 100%); 0.09 (0.077, 0.103), hyperkinetic- 92.9% (68.5, 98.7%); 0.64 (0.59, 0.69), tonic- 78.3% (64.4, 87.7%); 5.87 (5.51, 6.23), automatism- 86.7% (73.5, 97.7%); 3.34 (3.12, 3.58), unclassified motor seizures- 78% (65.4, 90.4%); 4.81 (4.50, 5.14), and PNES- 97.7% (97.7, 100%); 1.73 (1.61, 1.86). A generic threshold recommended for all motor seizures under study asserted 88% sensitivity and 6.48 FDR/h.

Discussion

These results indicate an achievable performance for major motor seizure detection that is clinically applicable for use as a seizure screening solution in diagnostic workflows.
Contralateral acupuncture for migraine without aura: a randomized trial protocol with multimodal MRI
Authors: Chen Ziwen , Li Qifu , Lu Yi , Huang Gaoyangzi , Huang Ya , Pei Xianmei , Gong Yi , Zhang Bingkui , Tang Xin , Liu Zili , Guo Taipin , Liang Fanrong
Published: March 2024

Introduction

Migraine is a common clinical disorder, ranks as the second most disabling disease worldwide, and often manifests with unilateral onset. Contralateral acupuncture (CAT), as a classical acupuncture method, has been proven to be effective in the treatment of migraine without aura (MWoA). However, its neural mechanisms have not been investigated using multimodal magnetic resonance imaging (MRI).

Methods and analysis

In this multimodal neuroimaging randomized trial, a total of 96 female MWoA participants and 30 female healthy controls (HCs) will be recruited. The 96 female MWoA participants will be randomized into three groups: Group A (CAT group), Group B [ipsilateral acupuncture (IAT) group], and Group C (sham CAT group) in a 1:1:1 allocation ratio. Each group will receive 30 min of treatment every other day, three times a week, for 8 weeks, followed by an 8-week follow-up period. The primary outcome is the intensity of the migraine attack. Data will be collected at baseline (week 0), at the end of the 8-week treatment period (weeks 1–8), and during the 8-week follow-up (weeks 9–16). Adverse events will be recorded. Multimodal MRI scans will be conducted at baseline and after 8-week treatment.

Discussion

This study hypothesized that CAT may treat MWoA by restoring pathological alterations in brain neural activity, particularly by restoring cross-integrated functional connectivity with periaqueductal gray (PAG) as the core pathological brain region. The findings will provide scientific evidence for CAT in the treatment of MWoA.

Ethics and dissemination

The Medical Ethics Committee of the Second Affiliated Hospital of Yunnan University of Chinese Medicine has given study approval (approval no. 2022-006). This trial has been registered with the Chinese Clinical Trials Registry (registration no. ChiCTR2300069456). Peer-reviewed papers will be used to publicize the trial’s findings.

Clinical trial registration

https://clinicaltrials.gov/, identifier ChiCTR2300069456.
Clustering of small molecules: new perspectives and their impact on natural product lead discovery
Authors: Talevi Alan , Bellera Carolina L.
Published: March 2024

The clustering of small molecules is of considerable importance for computer-aided drug discovery and virtual screening applications. The structure of chemical data in appropriate subspaces of the chemical space is relevant to sample datasets in a representative manner, to generate small libraries with wide or narrow chemical coverage (depending on the specific goals), and to guide the selection of subsets of in silico hits that are submitted for experimental confirmation. In the field of natural products, identifying regions of the chemical space where bioactive compounds congregate and understanding the relationship between biosynthetic gene clusters and the molecular structure of secondary metabolites may have a direct impact on natural product discovery and engineering. Here, we briefly discuss general approximations and available resources for the clustering of small molecules, and how the clustering of small molecules can be boosted by the application of novel clustering approximations, namely subspace clustering and multi-view clustering, which represent opposite philosophies of the clustering paradigm. We present some specific applications of small molecule clustering in the field of natural products, and analyze how a chemogenomic perspective may be particularly embodied in the field of natural products.
Association of cancer diagnosis with disability status among older survivors of colorectal cancer: a population-based retrospective cohort study
Authors: Zhang Shiming , Chou Lin-Na , Swartz Michael D. , Mehta Hemalkumar B. , Goodwin James S. , Kuo Yong-Fang , Giordano Sharon Hermes , Tucker Carole A. , Basen-Engquist Karen M. , Lyons Elizabeth J. , Downer Brian , Peterson Susan K. , Cao Tru , Swartz Maria C.
Published: March 2024

Background

Older cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort.

Methods

This retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. The study cohort consisted of 13,229 survivors of CRC diagnosed between 2005 and 2013 and an age-sex-matched, non-cancer cohort of 13,225 beneficiaries. The primary outcome was poor DS, determined by Davidoff’s method, using predictors from 12 months of Medicare claims after cancer diagnosis. Multivariable Cox proportional hazards regression was used to identify risk factors associated with the development of poor DS.

Results

Among the survivors of CRC, 97% were 65 years or older. After a 9-year follow-up, 54% of survivors of CRC developed poor DS. Significant factors associated with future poor DS included: age at diagnosis (hazard ratio [HR] = 3.50 for >80 years old), female sex (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage at diagnosis (HR = 2.26 for distant metastasis), comorbidity index (HR = 2.18 for >1), and radiation therapy (HR = 1.21). Having cancer (HR = 1.07) was significantly associated with developing poor DS in the pooled cohorts; age and race/ethnicity were also significant factors.

Conclusions

Our findings suggest that a CRC diagnosis is independently associated with a small increase in the risk of developing poor DS after accounting for other known factors. The study identified risk factors for developing poor DS in CRC survivors, including Hispanic and Black race/ethnicity, age, sex, histologic stage, and comorbidities. These findings underscore the importance of consistent physical function assessments, particularly among subsets of older survivors of CRC who are at higher risk of disability, to prevent developing poor DS.
Risk factors analysis and the establishment of nomogram prediction model for PICC-related venous thrombosis in patients with lymphoma: a double-center cohort-based case-control study
Authors: Wang Xue-xing , He Yuan , Chu Jie , Xu Jin-song
Published: March 2024

Objective

The objective of this study is to examine the risk factors associated with the occurrence of PICC-Related Venous Thrombosis (PICC-RVTE) in individuals diagnosed with lymphoma, as well as to develop a predictive risk nomogram model.

Methods

A total of 215 patients with lymphoma treated at Yunnan Provincial Tumor Hospital from January 2017 to December 2020 were retrospectively evaluated as the training cohort; 90 patients with lymphoma treated at the Department of Oncology of the First People’s Hospital of Anning, Affiliated to Kunming University of Science and Technology during the January 2021 to September 2023 were evaluated as the validation cohort. Independent influencing factors were analyzed by logistic regression, a nomogram was developed and validated, and the model was evaluated using internal and external data cohorts for validation.

Results

A total of 305 lymphoma patients were selected and 35 (11.48%) PICC-RVTE occurred, the median time was 13 days. The incidence within 1-2week was 65.71%. Multivariate analysis suggested that the activity amount, thrombosis history(within the last 12 months), ATIII, Total cholesterol and D-dimer levels were independently associated with PICC-RVTE, and a nomogram was constructed based on the multivariate analysis. ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.907, 95%CI:0.850-0.964) and the testing set (AUC = 0.896, 95%CI: 0.782-1.000) for the PICC-RVTE nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms.

Conclusions

Patients should be advised to undergo color Doppler ultrasound system testing within two week after the implantation of a PICC catheter to detect PICC-RVTE at an early stage. The validated nomogram can be used to predict the risk of catheter-related thrombosis (CRT) in patients with lymphoma who received at least one chemotherapy after PICC catheterization, no bleeding tendency, no recent history of anticoagulant exposure and no severe heart, lung, renal insufficiency. This model has the potential to assist clinicians in formulating individualized treatment strategies for each patient.
Safety assessment of cenobamate: real-world adverse event analysis from the FAERS database
Authors: Chen Shihao , Fang Wenqiang , Zhao Linqian , Xu Huiqin
Published: March 2024

Objective:

This study aims to analyze adverse drug events (ADEs) associated with cenobamate from the FAERS database, covering the third quarter of 2020 to the second quarter of 2023.

Methods:

Data related to cenobamate-associated ADEs from the third quarter of 2020 to the second quarter of 2023 were collected. After standardizing the data, various signal quantification techniques, including ROR, MHRA, BCPNN, and MGPS, were employed for analysis.

Results:

Among 2535 ADE reports where cenobamate was the primary suspected drug, 94 adverse reactions involving 11 different System Organ Class (SOC) categories were identified through the application of four signal quantification techniques. More specifically, neurological disorders and injuries resultant from complications are frequent adverse reactions associated with cenobamate.

Conclusion:

Our research findings align with established results, affirming the favorable safety profile of cenobamate. Effective prevention of adverse reactions induced by cenobamate can be achieved through the establishment of efficient blood concentration monitoring and dose adjustments.
Integration of meta-analysis and network pharmacology analysis to investigate the pharmacological mechanisms of traditional Chinese medicine in the treatment of hepatocellular carcinoma
Authors: Lin Jie , Guo Huaijuan , Qin Hanjiao , Zhang Xuewen , Sheng Jiyao
Published: March 2024

Background: This study will explore the therapeutic value of traditional Chinese medicine (TCM) in Hepatocellular Carcinoma (HCC) through meta-analysis, combined with network pharmacology analysis.

Methods: The results of randomized controlled trials on TCM and HCC were retrieved and summarized from multiple databases. The effective active com-pounds and target genes of the high-frequency TCM were obtained using the TCMSP database, and disease targets of HCC were acquired through the public disease database. The network pharmacology analysis was used to get the core genes and investigate the potential oncogenic molecular mechanism.

Results: A total of 14 meta-analysis studies with 1,831 patients suggested that therapy combined TCM is associated with better clinical efficacy and survival prognosis, as well as avoiding many adverse events. A total of 156 compounds, 247 herbal target genes and 36 core genes were identified. The function analysis suggested above genes may participate development in HCC through regulating some pathways, such as HIF-1 pathway and PD-L1 immune-related pathway.

Conclusion: TCM, as a novel, safe, and effective multi-mechanism therapy, holds greater value in the treatment of HCC.
Effects of a proprietary mixture of extracts from Sabal serrulata fruits and Urtica dioica roots (WS® 1541) on prostate hyperplasia and inflammation in rats and human cells
Authors: Sens-Albert Carla , Weisenburger Sabrina , König Beatrix C. , Melcher Silas F. , Scheyhing Ulrike A. M. , Rollet Karin , Lluel Philippe , Koch Egon , Lehner Martin D. , Michel Martin C.
Published: March 2024

Introduction: Phytotherapeutics, particularly extracts from Sabal serrulata (saw palmetto) fruit or Urtica dioica (stinging nettle) root, are popular for the treatment of male lower urinary symptoms in many countries, but their mechanism of action is poorly understood. We performed in vivo and in vitro studies to obtain deeper insight into the mechanism of action of WS® 1541, a proprietary combination of a Sabal serrulata fruit and an Urtica dioica root extract (WS® 1473 and WS® 1031, respectively) and its components.

Methods: We used the sulpiride model of benign prostatic hyperplasia in rats and tested three doses of WS® 1541 in comparison to finasteride, evaluating weight of prostate and its individual lobes as well as aspects of inflammation, oxidative stress, growth and hyperplasia. In human BPH-1 cells, we studied the effect of WS® 1473, WS® 1031, WS® 1541 and finasteride on apoptosis, cell cycle progression and migrative capacity of the cells.

Results: WS® 1541 did not reduce prostate size in sulpiride treated rats but attenuated the sulpiride-induced changes in expression of most analyzed genes and of oxidized proteins and abrogated the epithelial thickening. In vitro, WS® 1473 and WS® 1031 showed distinct profiles of favorable effects in BPH-1 cells including anti-oxidative, anti-proliferative and pro-apoptotic effects, as well as inhibiting epithelial-mesenchymal-transition.

Conclusion: This data supports a beneficial effect of the clinically used WS® 1541 for the treatment of lower urinary tract symptoms associated with mild to moderate benign prostate syndrome and provides a scientific rationale for the combination of its components WS® 1473 and WS® 1031.