bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the dry matter intake and enteric methane emissions of pre-partum dairy cows offered grass clover or grass-only silage from two different silage systems
Authors: Kennedy Michael , Lahart Ben , Herron Jonathan , Boland Tommy M. , Fleming Christina , Egan Michael
Published: October 2024

Over the winter period, the low grass growth and availability in pasture-based dairy systems results in animals being housed and predominantly fed a diet of grass silage. There is limited availability of methane (CH4) data evaluating the impact of forage type on dairy cows over the pre-partum period. The objective of the current experiment was to evaluate the impact of feeding grass clover (GC) silage and grass-only (GO) silage on the dry matter intake (DMI) and enteric CH4 emissions of dairy cows pre-partum. A complete randomised block design was utilised for the 6-week experiment over two winter periods: from December 2020 to January 2021 and from December 2021 to January 2022. In each year, 30 non-lactating pregnant dairy cows were randomly allocated to two treatments (n = 15). In both years, cows in the GC treatment were offered grass clover bale silage, while cows in the GO treatment were offered grass-only pit silage. The DMI and gaseous emissions of individual animals were monitored daily using Hokofarm RIC (roughage intake control) feed stations and the GreenFeed technology. GC silage consistently had greater (p< 0.05) organic matter (OM) digestibility and lower (p< 0.05) neutral detergent fibre (NDF) and acid detergent fibre (ADF) contents when compared with GO silage. Cows in the GC treatment had significantly greater (p< 0.05) total DMI (TDMI) compared with cows in the GO treatment. The daily CH4 emissions (in grams per day) were not affected by treatment; however, cows in the GC treatment had reduced (p< 0.05) CH4 yield (in grams per kilogram TDMI). Offering dairy cows GC silage over the pre-partum period resulted in greater DMI with reduced CH4 yield when compared with cows offered GO silage.
FixThePig: a custom 3D-printed femoral intramedullary nailing for preclinical research applications
Authors: Manon Julie , Englebert Alexandre , Evrard Robin , Schubert Thomas , Cornu Olivier
Published: October 2024

Background

Critical-size bone defects (CSBDs) pose significant challenges in clinical orthopaedics and traumatology. Developing reliable preclinical models that accurately simulate human conditions is crucial for translational research. This study addresses the need for a reliable preclinical model by evaluating the design and efficacy of a custom-made 3D-printed intramedullary nail (IMN) specifically for CSBDs in minipigs. The study aims to answer the following questions: Can a custom-made 3D-printed IMN be designed for femoral osteosynthesis in minipigs? Does the use of the custom-made IMN result in consistent and reproducible surgical procedure, particularly in the creation and fixation of CSBDs? Can the custom-made IMN effectively treat and promote bone consolidation of CSBDs?

Hypothesis

The custom-made 3D-printed IMN can be designed to effectively create, fix and treat CSBDs in minipigs, resulting in consistent surgical outcomes.

Materials and Methods

The IMN was designed based on CT scans of minipig femurs, considering factors such as femoral curvature, length, and medullary canal diameters. It was 3D-printed in titanium and evaluated through both in vitro and in vivo testing. Female Aachen minipigs underwent bilateral femoral surgeries to create and fix CSBDs using the custom-made IMN. Post-operative follow-up included X-rays and CT scans every 2 weeks, with manual examination of explanted femurs to assess consolidation and mechanical stability after 3 months.

Results

The custom-made IMN effectively fitted the minipig femoral anatomy and facilitated reproducible surgical outcomes. Symmetric double osteotomies were successfully performed, and allografts showed minimal morphological discrepancies. However, proximal fixation faced challenges, leading to non-union in several cases, while most distal osteotomy sites achieved stable consolidation.

Discussion

The custom-made 3D-printed IMN demonstrated potential in modelling and treating CSBDs in minipigs. While the design effectively supported distal bone healing, issues with proximal fixation highlight the need for further refinements. Potential improvements include better screw placement, additional mechanical support, and adaptations such as a reduction clamp or a cephalic screw to enhance stability and distribute forces more effectively.
Telomere maintenance and the DNA damage response: a paradoxical alliance
Authors: Harman Ashley , Bryan Tracy M.
Published: October 2024

Telomeres are the protective caps at the ends of linear chromosomes of eukaryotic organisms. Telomere binding proteins, including the six components of the complex known as shelterin, mediate the protective function of telomeres. They do this by suppressing many arms of the canonical DNA damage response, thereby preventing inappropriate fusion, resection and recombination of telomeres. One way this is achieved is by facilitation of DNA replication through telomeres, thus protecting against a “replication stress” response and activation of the master kinase ATR. On the other hand, DNA damage responses, including replication stress and ATR, serve a positive role at telomeres, acting as a trigger for recruitment of the telomere-elongating enzyme telomerase to counteract telomere loss. We postulate that repression of telomeric replication stress is a shared mechanism of control of telomerase recruitment and telomere length, common to several core telomere binding proteins including TRF1, POT1 and CTC1. The mechanisms by which replication stress and ATR cause recruitment of telomerase are not fully elucidated, but involve formation of nuclear actin filaments that serve as anchors for stressed telomeres. Perturbed control of telomeric replication stress by mutations in core telomere binding proteins can therefore cause the deregulation of telomere length control characteristic of diseases such as cancer and telomere biology disorders.
Mesenchymal stem cell-derived extracellular vesicles in systemic sclerosis: role and therapeutic directions
Authors: Wang Xuan , Guo Jiaying , Dai Qiangfu
Published: October 2024

Systemic sclerosis (SSc) is a complex autoimmune disease with clinical symptoms of vascular damage, immune disorders, and fibrosis, presenting significant treatment challenges and limited therapeutic options. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been demonstrated in numerous studies as more effective than MSCs in treating autoimmune diseases. Recent studies demonstrate that MSC-EVs can significantly ameliorate the symptoms of SSc and mitigate pathological changes such as vascular injury, immune dysregulation, and fibrosis. These findings underscore the promising therapeutic potential of MSC-EVs in the treatment of SSc. MSC-EVs promote angiogenesis, modulate immune dysfunction, and combat fibrosis. This article summarizes the therapeutic applications and possible mechanisms of MSC-EVs for SSc, thereby offering a novel therapeutic direction for the treatment of SSc.
Endovascular treatment of aortic coarctation using covered balloon-expandable stents—a systematic review and meta-analysis
Authors: He Fei , Cao Zhongze , Wang Chen , Premaratne Shyamal , Starnes Benjamin W. , Shu Chang , Zhang Wayne W.
Published: October 2024

Objectives

Balloon dilation followed by balloon-expandable stent implantation is an effective treatment for improving hemodynamic status in patients with coarctation of the aorta (CoA). However, limited evidence exists regarding the safety and efficacy of covered balloon-expandable stents (CBSs) in a large cohort. In this meta-analysis, we aimed to evaluate the overall success rates, hemodynamic and anatomical benefits, complications, and mid-term results of CBSs in treating CoA.

Methods

The PubMed, Embase, and Cochrane Library databases were systemically searched for studies reporting outcomes of CBSs in treating CoA. Single-group rate meta-analyses were performed to calculate estimated pooled procedural success rates, the incidence of complications, and re-coarctation rates. A meta-analysis using standardized mean differences was conducted to compare pre- and postoperative trans-coarctation pressure gradients (PGs), coarctation diameter, and overall changes in systolic blood pressure (SBP). Subgroup analyses were performed to identify potential sources of heterogeneity.

Results

The final analysis included 12 studies with a total of 411 patients. The estimated pooled procedural success rate was 100% [95% confidence interval (CI): 98%–100%, I2 = 0, P = 0.78]. Significant decreases in trans-coarctation PGs and SBP were observed. The pooled incidences of stent-related, aortic, and access site complications were 2% (95% CI: 0%–5%, I2 = 30.4%, P = 0.15), 2% (95% CI: 0%–4%, I2 = 0%, P = 0.76), and 3% (95% CI: 1%–7%, I2 = 52.9%, P = 0.02), respectively. Subgroup analyses showed that implantation of BeGraft stents was related to a significantly higher incidence of access site complications.

Conclusion

Covered balloon-expandable stent implantation in treating CoA is safe and effective with high procedural success rates, an acceptable incidence of complications, and a low incidence of re-coarctation.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42023430356).
Recommendations for prediction models in clinical practice guidelines for cardiovascular diseases are over-optimistic: a global survey utilizing a systematic literature search
Authors: Jing Cheng-yang , Zhang Le , Feng Lin , Li Jia-chen , Liang Li-rong , Hu Jing , Liao Xing
Published: October 2024

Background

This study aimed to synthesize the recommendations for prediction models in cardiovascular clinical practice guidelines (CPGs) and assess the methodological quality of the relevant primary modeling studies.

Methods

We performed a systematic literature search of all available cardiovascular CPGs published between 2018 and 2023 that presented specific recommendations (whether in support or non-support) for at least one multivariable clinical prediction model. For the guideline-recommended models, the assessment of the methodological quality of their primary modeling studies was conducted using the Prediction model Risk Of Bias ASsessment Tool (PROBAST).

Results

In total, 46 qualified cardiovascular CPGs were included, with 69 prediction models and 80 specific recommendations. Of the 80 specific recommendations, 74 supported 57 models (53 were fully recommended and 4 were conditionally recommended) in cardiovascular practice with moderate to strong strength. Most of the guideline-recommended models were focused on predicting prognosis outcomes (53/57, 93%) in primary and tertiary prevention, focusing primarily on long-term risk stratification and prognosis management. A total of 10 conditions and 7 types of target population were involved in the 57 models, while heart failure (14/57, 25%) and a general population with or without cardiovascular risk factor(s) (12/57, 21%) received the most attention from the guidelines. The assessment of the methodological quality of 57 primary studies on the development of the guideline-recommended models revealed that only 40% of the modeling studies had a low risk of bias (ROB). The causes of high ROB were mainly in the analysis and participant domains.

Conclusions

Global cardiovascular CPGs presented an unduly positive appraisal of the existing prediction models in terms of ROB, leading to stronger recommendations than were warranted. Future cardiovascular practice may benefit from well-established clinical prediction models with better methodological quality and extensive external validation.
Practices of social justice-oriented teacher education: a review of the literature
Authors: Hosseini Nina , Leijgraaf Monique , Gaikhorst Lisa , Volman Monique
Published: October 2024

Social justice-oriented teacher education has emerged as a critical area of inquiry within the field of education. Drawing on 60 empirical papers, this scoping review examines what shared principles can be distinguished in how teacher educators shape their social justice-oriented teacher education practices. Social justice-oriented teacher education practices are characterized by their focus on identifying structural inequities and disrupting unjust hierarchies, for example, in which knowledge and perspectives are undervalued or marginalized. Social justice-oriented teacher education actively engages with the context and communities in which teaching takes place. In their curriculum and pedagogical approach, teacher educators pay attention to unequal power relations and centralizing marginalized perspectives. The papers included in this review further emphasize the importance of critical reflection and enacting shared principles in ways that fit the local context and power dynamics.
Associations of thyroid hormones with chronic diarrhea and constipation in euthyroid individuals
Authors: Zeng Weiwei , Wang Yanjun , Zhang Luofang
Published: October 2024

Background

Abnormalities in thyroid function affect bowel health. However, the relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation remain unclear. Thus, the aim of this study was to investigate the relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation in euthyroid US adults.

Methods

The data for this population-based study were taken from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 datasets. The relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation were examined via multivariate regression. Smoothed curve fitting and threshold effects analysis were used to test for nonlinear relationships and inflection points.

Results

This study involved 4999 participants ranging in age from 20 to 80 years. Multivariate logistic regression analysis revealed a significant positive correlation between FT3 concentrations and the risk of developing chronic diarrhea [1.37 (1.00, 1.88), P=0.049]. Multivariate linear regression analysis revealed a significant positive correlation between FT3 concentrations and the number of bowel movements [0.84 (0.39, 1.28), P<0.001]. Using smoothed curve fitting and the two-stage regression model, we found a nonlinear relationship between FT4 concentrations and chronic diarrhea, with a breakpoint of 0.79 ng/dl.

Conclusions

There were associations between thyroid hormone concentrations and abnormal bowel habits, particularly between FT3 concentrations and the risk of developing chronic diarrhea. A higher FT3 level was associated with an increased risk of developing chronic diarrhea and more frequent bowel movements. To validate our results, further large-scale prospective studies are needed.
TSH enhances neurite outgrowth
Authors: Mansoori Maryam , Latif Rauf , Morshed Syed A. , Zaidi Mone , Davies Terry F.
Published: October 2024

Extra-thyroidal effects of TSH have been reported in various tissues expressing the TSH receptor (TSHR) including several areas of the brain. However, the influence of TSH on neuronal phenotypes has not been examined. Using a well-characterized human neuroblastoma cell line (SH-SY5Y), we have examined TSH signaling effects on the phenotype of these cells after their neuronal differentiation. Following an 18-day differentiation protocol, we successfully redifferentiated the SH-SY5Y cells into ~100% neuronal cells as indicated by the development of extensive neurofilaments with SMI-31 expression. Furthermore, using absolute digital PCR, we quantified TSHR mRNA, and also TSHR protein expression, in the redifferentiated cells and found that the neuronal cells expressed high quantities of both TSHR message and protein at baseline. Exposure to TSH induced primary, secondary, and tertiary neurite outgrowths, which are essential for cell–cell communication. Quantitative analysis of neurites using ImageJ showed a dose-dependent increase in neurites. The addition of TSH up to 1 mU/ml resulted in a ~2.5-fold increase in primary, and ~1.5-fold in secondary and tertiary neurites. The lengths of the neurites remained unaffected with the dosage of TSH treatment. Furthermore, TSHR signaling in the differentiated cells resulted in enhanced generation of cAMP, pPI3K, pAKT, and pNFkB pathways and suppression of pMAPK suggesting an influence of these signals in driving neurite outgrowth. These data showed that the TSH/TSHR axis in neurons may contribute to enhanced neurite outgrowth. The potential pathophysiological effects of TSH on the induction of neurite outgrowth and its relationship to neurodegenerative diseases remain to be explored.
Aging, senescence, and cutaneous wound healing—a complex relationship
Authors: O’Reilly Steven , Markiewicz Ewa , Idowu Olusola C.
Published: October 2024

Cutaneous wound healing is a complex multi-step process that is highly controlled, ensuring efficient repair to damaged tissue and restoring tissue architecture. Multiple cell types play a critical role in wound healing, and perturbations in this can lead to non-healing wounds or scarring and fibrosis. Thus, the process is tightly regulated and controlled. Cellular senescence is defined as irreversible cell cycle arrest and is associated with various phenotypic changes and metabolic alterations and coupled to a secretory program. Its role in wound healing, at least in the acute setting, appears to help promote appropriate mechanisms leading to the complete restoration of tissue architecture. Opposing this is the role of senescence in chronic wounds where it can lead to either chronic non-healing wounds or fibrosis. Given the two opposing outcomes of wound healing in either acute or chronic settings, this has led to disparate views on the role of senescence in wound healing. This review aims to consolidate knowledge on the role of senescence and aging in wound healing, examining the nuances of the roles in the acute or chronic settings, and attempts to evaluate the modulation of this to promote efficient wound healing.
Nasopharyngeal carcinoma-associated inflammatory cytokines: ongoing biomarkers
Authors: Liang Chuwen , Kan Jun , Wang Jingli , Lu Wei , Mo Xiaoyan , Zhang Bei
Published: October 2024

Nasopharyngeal carcinoma (NPC) is a neoplasm related to inflammation; the expression of cytokines, such as CCL3, CCL4, CCL20, IL-1α, IL-1β, IL-6, IL-8, and IL-10, among others, is presumed to be associated with NPC occurrence and development. Therefore, the circulating levels of these cytokines may be potential biomarkers for assessing tumor aggressiveness, exploring cellular interactions, and monitoring tumor therapeutic responses. Numerous scholars have comprehensively explored the putative mechanisms through which these inflammatory factors affect NPC progression and therapeutic responses. Moreover, investigations have focused on elucidating the correlation between the systemic levels of these cytokines and the incidence and prognosis of NPC. This comprehensive review aims to delineate the advancements in research concerning the relationship between inflammatory factors and NPC while considering their prospective roles as novel prognostic and predictive biomarkers in the context of NPC.
Advancements in mitochondrial-targeted nanotherapeutics: overcoming biological obstacles and optimizing drug delivery
Authors: Li Yang , Li Xiao-meng , Wei Li-si , Ye Jun-feng
Published: October 2024

In recent decades, nanotechnology has significantly advanced drug delivery systems, particularly in targeting subcellular organelles, thus opening new avenues for disease treatment. Mitochondria, critical for cellular energy and health, when dysfunctional, contribute to cancer, neurodegenerative diseases, and metabolic disorders. This has propelled the development of nanomedicines aimed at precise mitochondrial targeting to modulate their function, marking a research hotspot. This review delves into the recent advancements in mitochondrial-targeted nanotherapeutics, with a comprehensive focus on targeting strategies, nanocarrier designs, and their therapeutic applications. It emphasizes nanotechnology’s role in enhancing drug delivery by overcoming biological barriers and optimizing drug design for specific mitochondrial targeting. Strategies exploiting mitochondrial membrane potential differences and specific targeting ligands improve the delivery and mitochondrial accumulation of nanomedicines. The use of diverse nanocarriers, including liposomes, polymer nanoparticles, and inorganic nanoparticles, tailored for effective mitochondrial targeting, shows promise in anti-tumor and neurodegenerative treatments. The review addresses the challenges and future directions in mitochondrial targeting nanotherapy, highlighting the need for precision, reduced toxicity, and clinical validation. Mitochondrial targeting nanotherapy stands at the forefront of therapeutic strategies, offering innovative treatment perspectives. Ongoing innovation and research are crucial for developing more precise and effective treatment modalities.
Exposure to butylparaben induces oxidative stress and apoptosis in the liver of Polypedates megacephalus tadpole
Authors: Ai Xiaoqi , Iqbal Muhammad Shahid , Lin Rui , Wu Xia , Wang Lijun , Hong Meiling
Published: October 2024

Butylparaben (BuP) is a ubiquitous preservative in cosmetics, foods, and medicine. As an emerging pollutant, it has gained wide attention in recent years. Because amphibians have both aquatic and terrestrial life stages and high skin permeability, they are sensitive to environmental changes. To assess the toxic effects of BuP on amphibians, the present study was conducted on the spot-legged tree frog (Polypedates megacephalus) tadpoles. In the present study, LC50 of BuP for 96 h exposures was 3509 µg/L. Then, the tadpoles were exposed to 0, 350 and 2100 µg/L BuP (hereafter named as CK, B1 and B2) for 12, 24 and 48 h, the oxidative stress and apoptosis in the liver were analyzed. The results showed that the content of MDA and activity of SOD and GSH-PX were increased with an increase in BuP exposure. BuP stress significantly altered the expression of Nrf2-Keap1 signal pathway genes. An increase in the expression of JAK-STAT signal pathway genes was observed with an increase in the exposure to BuP concentration at 24 and 48 h. In contrast, the expression of negative regulators of JAK-STAT signal pathway were significantly increased at 12 h and decreased at 24 and 48 h. A significant decrease in pro-apoptosis genes expression (Bax and Caspase3) were observed at 12 h but increased at 24 and 48 h, while the expression of anti-apoptosis gene (Bcl-2) decreased at 24 and 48 h. These results provide a valuable reference point for assessing the ecological and health risks associated with BuP in the environment.
Factorial-experimental investigation of LPBF regimes for VZh159 nickel superalloy grain structure and structural strength optimization
Authors: Kyarimov Rustam R. , Statnik Eugene S. , Sadykova Iuliia A. , Frantsuzov Alexander A. , Salimon Alexey I. , Korsunsky Alexander M.
Published: October 2024

This study investigates the optimization of Laser Powder Bed Fusion (LPBF) process parameters to enhance the mechanical properties of the Russian Ni superalloy VZh159 (a close analogue of IN718) material that is commonly used in critical aerospace applications, and the corresponding studies of the grain structure within and near the melt pool formed by a single laser scan line. Through a factorial experimental approach, the influence of laser power and scanning speed on the tensile strength, yield strength, and ductility was determined. Metallurgically sound samples (based on hydrostatic weighing data and microscopy, with practically no pores detected) were obtained with nine combinations of power and scanning speed, showing significant variation in the tensile strength (in the 1,040–1,220 MPa range) and yield strength (in the 560–1,100 MPa range), which correlated with the cross-sectional area of the single scan line (for example, the depth of the melt pool varied in the range 410–530 µm), while the average grain size (deduced from Electron Backscatter Diffraction (EBSD) images) remained statistically unchanged. Key findings indicate that the optimal LPBF parameters are a laser power of 250 W, a scanning speed of 600 mm/s, and a hatch distance of 0.12 mm, which together yield the best combination of high tensile strength and ductility. This study provides new insights into the effects of LPBF parameters on the microstructure, particularly the formation of the γ′ strengthening phase and its correlation with mechanical performance. The research addresses a critical gap in understanding the relationship between LPBF processing conditions and the resulting microstructural and mechanical properties, offering potential improvements in manufacturing efficiency and material performance.
Gut microbiota and irritable bowel syndrome: status and prospect
Authors: Cheng Xinyu , Ren Cheng , Mei Xiaofei , Jiang Yufeng , Zhou Yafeng
Published: October 2024

Irritable bowel syndrome (IBS) is a very common gastrointestinal disease that, although not as aggressive as tumors, affects patients’ quality of life in different ways. The cause of IBS is still unclear, but more and more studies have shown that the characteristics of the gut microbiota, such as diversity, abundance, and composition, are altered in patients with IBS, compared to the healthy population, which confirms that the gut microbiota plays a crucial role in the development of IBS. This paper aims to identify the commonalities by reviewing a large body of literature. Changes in the characteristics of gut microbiota in patients with different types of IBS are discussed, relevant mechanisms are described, and the treatment modalities of gut microbiota in IBS are summarized. Although there are more clinical trials that have made good progress, more standardized, more generalized, larger-scale, multi-omics clinical studies are what is missing. Overall, gut microbiota plays a crucial role in the development of IBS, and there is even more potential for treating IBS by modulating gut microbiota.
Understanding the USMLE journey of Brazilian medical students and graduates: a narrative review
Authors: Garcia-Rosa Beatriz S. , Urmenyi Lucas G. , Santana Gabriel C. , Marques João Vitor M. , Miguez-Pinto Joao P. , Ramalho Clara , Boczar Daniel , Andrade Bruno B.
Published: October 2024

Over the past decades, advances in medical technology and research have promoted the globalization of medicine, drawing medical students and physicians worldwide into seeking for better career and financial prospects, as well as enhanced clinical and research training abroad. The medical landscape in Brazil has been marked by significant challenges over the past years, particularly within the Unified Health System (SUS). Despite the expansion of medical schools and initiatives such as the Mais Médicos program arising as efforts to improve healthcare access and decrease regional inequalities in the country, such problems as under-resourced working environments, inadequate infrastructure, and unattractive financial compensation for both physician and research careers, have risen as persisting challenges. In the pursuit of improved conditions, the United States Medical Licensing Examination (USMLE) has emerged as an increasingly common pathway for those seeking to overcome these challenges. This review explores the motivations behind Brazilians pursuing the USMLE while examining structural and financial challenges within the country’s medical education and SUS landscape.
A comprehensive review of integrated management strategies for damping-off disease in chili
Authors: Delai Chen , Muhae-Ud-Din Ghulam , Abid Rimsha , Tian Tian , Liu Ruirui , Xiong Yan , Ma Shirong , Ghorbani Abazar
Published: October 2024

Damping-off disease in chili (Capsicum annum L.) cultivation is a significant global issue, severely affecting seeds, seedlings, and young plants, regardless of the location of cultivation, whether in greenhouses or open fields. Despite chili being a widely popular vegetable used in various cuisines globally, farmers face challenges in meeting the growing demand due to the extensive damage caused by this disease, ranging from 20 to 85%. The shelf life and quality of mature pods are also severely affected. Damping-off disease is mainly caused by soil-borne fungus from the Pythium species, with additional contributions from Phytophthora, Fusarium, and Rhizoctonia species. These pathogens’ adaptability to diverse environmental conditions and resistance to synthetic fungicides make controlling damping-off on a commercial scale challenging. However, integrated disease management has shown promising results as a remedial approach. In this review, we discuss the current state of chili diseases, the nature of the pathogens causing damping-off, the epidemiology of the disease, and various control mechanisms. In this review, we broadly discuss the current state of chili diseases, the nature of the pathogens causing damping-off, the epidemiology of the disease, and various control mechanisms. Furthermore, we highlight the importance and efficacy of integrated disease management techniques, along with future prospects in unexplored areas, such as host–pathogen interaction and sustainable disease control measures. The information in this review aims to assist chili growers in understanding the epidemiology and management of damping-off in chili cultivation.
HYBRIDMINDS—summary and outlook of the 2023 international conference on the ethics and regulation of intelligent neuroprostheses
Authors: Buthut Maria , Starke Georg , Akmazoglu Tugba Basaran , Colucci Annalisa , Vermehren Mareike , van Beinum Amanda , Bublitz Christoph , Chandler Jennifer , Ienca Marcello , Soekadar Surjo R.
Published: October 2024

Neurotechnology and Artificial Intelligence (AI) have developed rapidly in recent years with an increasing number of applications and AI-enabled devices that are about to enter the market. While promising to substantially improve quality of life across various severe medical conditions, there are also concerns that the convergence of these technologies, e.g., in the form of intelligent neuroprostheses, may have undesirable consequences and compromise cognitive liberty, mental integrity, or mental privacy. Therefore, various international organizations, such as the Organization for Economic Cooperation and Development (OECD) or United Nations Educational, Scientific and Cultural Organization (UNESCO), have formed initiatives to tackle such questions and develop recommendations that mitigate risks while fostering innovation. In this context, a first international conference on the ethics and regulation of intelligent neuroprostheses was held in Berlin, Germany, in autumn 2023. The conference gathered leading experts in neuroscience, engineering, ethics, law, philosophy as well as representatives of industry, policy making and the media. Here, we summarize the highlights of the conference, underline the areas in which a broad consensus was found among participants, and provide an outlook on future challenges in development, deployment, and regulation of intelligent neuroprostheses.
Three-dimensional-printed headcap with embedded microdrive system for customizable multi-region brain recordings with neural probes
Authors: Hartner Jeremiah P. , Yi Dongyang , Zhu Harrison L. , Watson Brendon O. , Chen Lei
Published: October 2024

Electrophysiological recordings from single neurons are crucial for understanding the complex functioning of the brain and for developing eventual therapeutic interventions. For electrophysiology, the accuracy and fidelity of invasive implantations of small devices remains unmatched. This study introduces an innovative, cost-efficient, 3D-printed headcap with embedded microdrive (THEM) system designed to streamline the manual labor-intensive in-vivo electrode implantation process for efficient and precise multi-region brain neural probe implantations. A custom bregma-referenced headcap design and fabrication, embedded microdrive integration, and upper support structure for probe packaging are described. With the Sprague Dawley rat as test species and medial prefrontal cortex and CA1 of the dorsal hippocampus as targets, surgeries and electrophysiological recordings were conducted to test the capability of the THEM system as compared to conventional surgical methods. By shifting manual stereotaxic alignment work to pre-surgical preparation of a fully assembled headcap system, incorporating fully preassembled upper support framework for packaging management, and easy customization for specific experiment designs and probe types, our system significantly reduces the surgical time, simplifies multi-implant procedures, and enhances procedural accuracy and repeatability. The THEM system demonstrates a significant improvement over conventional surgical implantation methods and offers a promising tool for future neuroscience research.
Evaluation of a three-gene methylation model for correlating lymph node metastasis in postoperative early gastric cancer adjacent samples
Authors: Chen Shang , Long Shoubin , Liu Yaru , Wang Shenglong , Hu Qian , Fu Li , Luo Dixian
Published: October 2024

Background

Lymph node metastasis (LNM) has a profound impact on the treatment and prognosis of early gastric cancer (EGC), yet the existing evaluation methods lack accuracy. Recent research has underscored the role of precancerous lesions in tumor progression and metastasis. The objective of this study was to utilize the previously developed EGC LNM prediction model to further validate and extend the analysis in paired adjacent tissue samples.

Methods

We evaluated the model in a monocentric study using Methylight, a methylation-specific PCR technique, on postoperative fresh-frozen EGC samples (n = 129) and paired adjacent tissue samples (n = 129).

Results

The three-gene methylation model demonstrated remarkable efficacy in both EGC and adjacent tissues. The model demonstrated excellent performance, with areas under the curve (AUC) of 0.85 and 0.82, specificities of 85.1% and 80.5%, sensitivities of 83.3% and 73.8%, and accuracies of 84.5% and 78.3%, respectively. It is noteworthy that the model demonstrated superior performance compared to computed tomography (CT) imaging in the adjacent tissue group, with an area under the curve (AUC) of 0.86 compared to 0.64 (p < 0.001). Furthermore, the model demonstrated superior diagnostic capability in these adjacent tissues (AUC = 0.82) compared to traditional clinicopathological features, including ulceration (AUC = 0.65), invasional depth (AUC = 0.66), and lymphovascular invasion (AUC = 0.69). Additionally, it surpassed traditional models based on these features (AUC = 0.77).

Conclusion

The three-gene methylation prediction model for EGC LNM is highly effective in both cancerous and adjacent tissue samples in a postoperative setting, providing reliable diagnostic information. This extends its clinical utility, particularly when tumor samples are scarce, making it a valuable tool for evaluating LNM status and assisting in treatment planning.
Molecular characteristics, risk factors, and clinical outcomes of methicillin-resistant Staphylococcus aureus infections among critically ill pediatric patients in Shanghai, 2016–2021
Authors: Dai Congyi , Ji Wenting , Zhang Yufei , Huang Weichun , Wang Haiying , Wang Xing
Published: October 2024

Objective

Methicillin-resistant Staphylococcus aureus (MRSA) infection in children has been on the rise, which poses a serious threat to their health and life in China. The purpose of this study was to determine the molecular characteristics, risk factors, and clinical outcomes of MRSA infections among critically ill pediatric patients.

Methods

A retrospective case-control study was performed in the pediatric intensive care unit (PICU) of a tertiary university teaching hospital. All children infected with culture-positive S. aureus in the PICU between January 2016 and December 2021 were included. Univariate and multivariable logistic regression analyses were used to identify potential risk factors for MRSA infection and clinical outcomes of S. aureus infection. All S. aureus isolates were characterized based on antimicrobial resistance, multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing.

Results

Of 3,974 patients admitted to the PICU, 280 were diagnosed with a S. aureus infection during the 6-year study period. Among them, 43.2% (121/280) were MRSA. All MRSA isolates showed significantly higher rates of resistance to penicillin, erythromycin, clindamycin and tetracycline than MSSA strains. The MRSA strains consisted of 45 spa types and 20 sequence types (STs) (20 clonal complexes), among which the most frequently represented were ST59-t437and ST398-t034. Multivariable logistic regression revealed vaginal delivery, respiratory failure, co-infection with a virus, C-reactive protein (CRP) > 8 mg/L as significant risk factors for MRSA infection. There was no significant difference in all-cause mortality during hospitalization between the MRSA group and the MSSA group. Furthermore, independent predictors for mortality in patients with S. aureus infections were the presence of hypoproteinemia, hematopathy, septic shock, respiratory failure, fever, and white blood cell (WBC) > 15.0 × 109/L.

Conclusions

The study revealed a high proportion of MRSA infections among critically ill pediatric patients, and found significant risk factors for MRSA infection and poor prognosis of S. aureus infection. Methicillin resistance did not contribute to the mortality in the current study. These findings will provide evidence-based practices to make the strategies of prevention and rational use of antibiotics for pediatric patients with S. aureus infection in the ICU.
Clinical prognostic models in children with sepsis in low- and middle-income countries: a systematic review and meta-analysis
Authors: Jordan Jessica , Nguyen Celinie M. , Fletcher Lauren M. , Garbern Stephanie C.
Published: October 2024

Introduction

Sepsis is the leading cause of child death worldwide, with the majority of these deaths occurring in low- and middle-income countries (LMICs). The aim of this systematic review and meta-analysis was to describe clinical prognostic scores and models for pediatric sepsis outcomes and assess the performance of these scores for predicting mortality in LMICs.

Methods

Ovid Medline, CINAHL, Cochrane Library, EBSCO Global Health, and Web of Science, were searched through September 2022 for citations related to the development or validation of a clinical prognostic score or model among children with sepsis, conducted in LMIC. Titles, abstracts, and full texts were screened by two independent reviewers and data extracted included population characteristics, variables included, outcomes, and model performance. Risk of bias was assessed with the Prediction Model Risk of Bias Assessment Tool (PROBAST).

Results

4,251 titles/abstracts and 315 full-text studies were screened, with 12 studies meeting inclusion criteria. Study countries included India, China, Egypt, Indonesia, Tanzania, and a multi-site study in Latin America. Prognostic scores/models included existing scores such as PELOD-2, pSOFA, PRISM, P-MODS, refractory shock criteria. There was high risk of bias in all studies. Meta-analysis was possible for pSOFA, PELOD-2, PRISM, and P-MODS, with pooled area under the receiver-operator characteristic curve of 0.86 (95%CI 0.78–0.94), 0.83 (95% CI 0.76–0.91), respectively.

Conclusion

Relatively few clinical scores and models have been externally validated for prognostication and risk-stratification among children with sepsis in diverse LMIC settings. Notably there were no studies from low-income countries. Some potentially relevant studies were excluded due to lack of clarity regarding the presence of sepsis in the study populations. More widespread and standardized use of sepsis criteria may aid in better understanding the burden of sepsis and prognostic model performance at the bedside among children in LMICs. Further research to externally validate, implement and adapt these models is needed to account for challenges in use of these scores in resource-limited settings.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340126, PROSPERO [CRD42022340126].
Comparative analysis of the therapeutic efficacy of remimazolam tosylate and propofol in older adults undergoing painless endoscopic retrograde cholangiopancreatography
Authors: Tian Yu-quan , Chen Di-kun , Zhang He-ming , Sun Yong-mei
Published: October 2024

Objective

The aim of this study is to conduct a comparative analysis of the therapeutic outcomes associated with the administration of remimazolam and propofol during painless endoscopic retrograde cholangiopancreatography (ERCP) procedures in older adults.

Methods

A total of 140 older adults who underwent elective painless ERCP were randomly assigned to two groups using the random number table method: the remimazolam group and the propofol group, each consisting of 70 patients. In the remimazolam group, anesthesia was administered using a combination of remimazolam and opioids, while in the propofol group, a combination of propofol and opioids was used. Comparative assessments between the two groups included anesthesia induction time, first induction success rate, intraoperative hemodynamics, awakening duration, stress response index, and the incidence of adverse reactions.

Results

The remimazolam group exhibited a prolonged anesthesia induction time compared to the propofol group and a lower success rate of first induction (P < 0.05). At the point of endoscope entry (T2) and 10 min post-operation (T3), patients in the remimazolam group demonstrated higher mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) values compared to those in the propofol group (P < 0.05). Furthermore, the remimazolam group had shorter durations for eye-opening, consciousness recovery, and residence in the recovery room compared to the propofol group (P < 0.05). Post-surgery levels of epinephrine (E), norepinephrine (NE), and cortisol (Cor) at 24 h were lower in the remimazolam group than in the propofol group (P < 0.05). The incidence of adverse reactions was significantly lower in the remimazolam group (18.57%) compared to the propofol group (31.43%) (P < 0.05).

Conclusion

Remimazolam exhibits a longer induction time compared to propofol in the painless diagnosis and treatment of ERCP in older adults. However, it provides a more stable circulatory state post-induction and throughout the operation, reduces stress response, enables rapid recovery, and has a lower incidence of serious adverse reactions. These attributes suggest that remimazolam has potential for widespread clinical application and adoption.

Clinical Trial Registration:

clinicaltrials.gov, identifier ChiCTR2400080926.
The effects of standardized cannabis products in healthy volunteers and patients: a systematic literature review
Authors: Leen Nadia A. , Kowal Mikael A. , Batalla Albert , Bossong Matthijs G.
Published: October 2024

Introduction

There is growing recognition of the potential of cannabis to treat various medical conditions and symptoms, such as chronic pain, spasticity, and epilepsy. However, one of the biggest challenges is the assurance of a standardized cannabis product that contains a consistent amount of its main psychoactive substances delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and which is compliant with predetermined specifications for these compounds. This is crucial not only to ensure consistent cannabis quality and dosage for patients but also to effectively translate research findings into clinical practice.

Methods

This systematic literature review provides an overview of the effects of standardized cannabis products from Bedrocan, a leading Dutch producer of pharmaceutical-quality standardized medicinal cannabis.

Results

Cannabis administration to healthy volunteers induces dose-dependent acute effects, such as rapidly rising THC and CBD blood concentrations, the subjective experience of high and anxiety, slower reaction time and impaired attention, learning and working memory. Patient studies suggest that treatment with medicinal cannabis reduces pain intensity across a broad range of chronic pain-related medical conditions. Medicinal cannabis showed a mild safety profile, with minor and transient side effects, such as feeling high, coughing and mental confusion. The strength of acute effects, the experience of side effects and the drop-out rate in patient studies may depend on cannabis dose, cannabis composition (CBD:THC ratio), and cannabis use history of participants.

Conclusion

Safety and efficacy of standardized medicinal cannabis products should be further investigated in randomized clinical trials with sufficient sample size, with particular focus on cannabis dose and composition, age and differences between males and females.
Evaluation of the role of metabolizing enzymes and transporter variants in ezetimibe pharmacokinetics
Authors: González-Iglesias Eva , Ochoa Dolores , Navares-Gómez Marcos , Zubiaur Pablo , Aldama Marina , Torre Tamara de la , Ríos-Rodríguez Marta de los , Soria-Chacartegui Paula , Rodríguez-Lopez Andrea , Abad-Santos Francisco , Novalbos Jesús
Published: October 2024

Introduction

Ezetimibe inhibits cholesterol uptake by modulation of intestinal sterol absorption. Currently, although some studies have shown alterations in ezetimibe levels caused by alterations in the ABCG5, ABCG8, NPC1L1 or UGT1A1 genes, there are no pharmacogenetic guidelines to confirm these biomarkers. The aim of this work was to evaluate the effect of 49 variants in 22 pharmacogenes related to metabolism and transport.

Methods

A total of 96 healthy volunteers from four bioequivalence clinical trials of ezetimibe as monotherapy or in combination with simvastatin were studied. Blood samples were extracted for unconjugated ezetimibe plasma quantification and genotyping.

Results and Discussion

No association of metabolizing enzyme variants with ezetimibe pharmacokinetic parameters was found. The results show some trends in the univariate analysis for ABCB1 rs2032582 or ABCC2 rs2273697 and Cmax (p univariate (puv) = 0.056 and 0.087, respectively), which finally reach significance in the multivariate analysis (p multivariate (pmv) = 0.049 and 0.048, respectively). Nevertheless, these results need to be validated in future studies.