bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of an optimal control strategy for a cholera disease transmission model with programs
Authors: Alemneh Haileyesus Tessema , Teklu Shewafera Wondimagegnhu , Kotola Belela Samuel , Mekonen Kassahun Getnet
Published: October 2024

Cholera is a disease of poverty affecting people with inadequate access to safe water and basic sanitation. Conflict, unplanned urbanization and climate change all increase the risk of cholera. In this article, an optimal control deterministic mathematical model of cholera disease with cost-effectiveness analysis is developed and analyzed considering both direct and indirect contact transmission pathways. The model qualitative behaviors, such as the invariant region, the existence of a positive invariant solution, the two equilibrium points (disease-free and endemic equilibrium), and their stabilities (local as well as global stability) of the model are studied. Moreover, the basic reproduction number of the model is obtained. We also performed sensitivity analysis of the basic parameters of the model. Then an optimal control problem is designed with a control functional having five controls: vaccination, treatment, environment sanitation and personal hygiene, and water quality improvement program. We examined the existence and uniqueness of the optimal controls of the system. Through the implementation of Pontryagin's maximum principle, the characterization of the optimal controls optimality system is established. The numerical simulation results the integrated control strategies demonstrated that strategy 2, 7, and 12 are effective programs to combat cholera disease from the community. Based on the local circumstances, available funds, and resources, it is recommended to the government stakeholders and policymakers to execute any one of the three integrated intervention programs.
Enhancing wound healing through innovative technologies: microneedle patches and iontophoresis
Authors: Jin Yong Xun , Ngoc Chien Pham , Thi Nga Pham , Zhang Xin Rui , Ngan Giang Nguyen , Thi Thuy Le Linh , Trinh Thuy-Tien Thi , Zhou Shu Yi , Nam Sun Young , Heo Chan Yeong
Published: October 2024

Introduction

Wound healing is a complex process involving multiple stages, including inflammation, proliferation, and remodeling. Effective wound management strategies are essential for accelerating healing and improving outcomes. The CELLADEEP patch, incorporating iontophoresis therapy and microneedle technology, was evaluated for its potential to enhance the wound healing process.

Methods

This study utilized a full-thickness skin defect model in Sprague-Dawley rats, researchers compared wound healing outcomes between rats treated with the CELLADEEP Patch and those left untreated. Various histological staining techniques were employed to examine and assess the wound healing process, such as H&E, MT and immunofluorescence staining. Furthermore, the anti-inflammatory and proliferative capabilities were further investigated using biochemical assays.

Results

Macroscopic and microscopic analyses revealed that the CELLADEEP patch significantly accelerated wound closure, reduced wound width, and increased epidermal thickness and collagen deposition compared to an untreated group. The CELLADEEP patch decreased nitric oxide and reactive oxygen species levels, as well as pro-inflammatory cytokines IL-6 and TNF-α, indicating effective modulation of the inflammatory response. Immunofluorescence staining showed reduced markers of macrophage activity (CD68, F4/80, MCP-1) in the patch group, suggesting a controlled inflammation process. Increased levels of vimentin, α-SMA, VEGF, collagen I, and TGF-β1 were observed, indicating enhanced fibroblast activity, angiogenesis, and extracellular matrix production.

Discussion

The CELLADEEP patch demonstrated potential in promoting effective wound healing by accelerating wound closure, modulating the inflammatory response, and enhancing tissue proliferation and remodeling. The CELLADEEP patch offers a promising non-invasive treatment option for improving wound healing outcomes.
Safe and favorable prognosis of thoracic endovascular aortic repair for the low-risk patients with non-acute type B aortic dissection
Authors: Nakamura Ken , Kobayashi Kimihiro , Nakai Shingo , Sho Ri , Arai Shusuke , Ishizawa Ai , Watanabe Daisuke , Hirooka Shuto , Ohba Eiichi , Mizumoto Masahiro , Kuroda Yoshinori , Kim Cholsu , Uchino Hideaki , Shimanuki Takao , Uchida Tetsuro
Published: October 2024

Objective

Preemptive thoracic endovascular aortic repair (TEVAR) has the potential to improve the prognosis of Stanford type B aortic dissection (TBAD), however it is important to determine whether it could be safely performed as a prophylactic treatment. This study aimed to determine the short- and long-term outcomes of preemptive TEVAR for uncomplicated TBAD with a small aortic aneurysm.

Design

Retrospective multicenter analysis.

Methods

We analyzed 212 patients with medically treated uncomplicated subacute TBAD between July 2004 and October 2019 in two Japanese academic centers. The short- and long-term prognosis of patients who underwent preemptive TEVAR and the changes in aortic diameter over time after TEVAR were analyzed. Aorta-related complications, aortic-related death and postoperative complications were recorded and analyzed. Analysis was performed on an intension-to-treat basis.

Results

During follow-up, patients were divided into two groups: optimal medical treatment [OMT; n = 185 (87%)] and preemptive TEVAR [n = 27 (13%)]. In all cases, aortic enlargement was the reason for therapeutic intervention in the preemptive TEVAR group. Propensity score matching yielded a cohort of 27 control patients with OMT (group A) and 27 patients who underwent preemptive TEVAR (group B). Preoperative characteristics were similar between groups. In group B, only one patient developed type A dissection at a late stage and died from aortic rupture. Freedom from aortic-related death at 1/5/10 years was 100%/92%/92% in group B. Overall growth (mm/year) of max aorta was significantly smaller in the TEVAR group than in the control group (−3.7 ± 2.9 vs. 0.4 ± 5.6, p < 0.01), and the diameter of the false lumen was reduced (−8 ± 4.8 vs. −1.3 ± 8.0, p < 0.001).

Conclusions

Short- and long-term outcomes of TEVAR for uncomplicated TBAD with a small aortic aneurysm were excellent, with few postoperative complications. After TEVAR, aortic remodeling was observed in the short term, suggesting that it may contribute to the prevention of aortic-related death due to rupture.
A theoretical analysis of the logging-while-drilling dipole acoustic reflection measurement
Authors: Li Yanghu , Wang Zhenlin , Su Yuanda , Tang Xiaoming
Published: October 2024

Post-drilling wireline acoustic single-well imaging technology can now detect geological structures tens of meters away from boreholes. Further development of this single-well imaging technology in the logging-while-drilling (LWD) environment will have significant values in real-time applications such as geosteering and reservoir navigation. Based on the wireline imaging application, we propose a new method for the LWD application. In wireline imaging, the four-component (4C) dipole acoustic data are azimuthally rotated to scan the reflectors around the borehole. In LWD, azimuthal scanning is achieved by drilling rotation such that the 4C dipole system in the wireline is replaced by a one-dipole-source and two-receiver LWD system, where the two receivers are mounted on opposite sides of the drill collar. For the LWD application, we first developed the theory for LWD dipole shear-wave reflection imaging and validated the theory using 3D finite-difference waveform modeling. Using the analytical solution, we analyzed the far-field radiation directivity of an acoustic LWD dipole source and the effect of drilling rotation on the shear-wave reflection imaging using the LWD acoustic system. The LWD analysis results show that, for fast formations, the SH-wave is the dominant component for imaging, whereas for slow formations, the P-wave becomes important and can be used for imaging. Our results also indicate that the reflection data acquired by the system are affected by the speed of drilling rotation. The take-off azimuth at the wave radiation may be different from the incident azimuth at the wave reception. Knowing the rotation speed, this azimuth difference can be corrected. A further advantage of using the oppositely mounted receivers is that the reflected wave arrives earlier (later) at the front (back)-side receiver; thus, the arrival time difference between the receivers can be used to eliminate the 180°-azimuth ambiguity of dipole acoustic imaging. For reflection imaging, using the proposed LWD system configuration, we tested its azimuth sensitivity and validated its 180°-ambiguity solution using synthetic LWD and field wireline dipole data. The results of this work, therefore, provide a theoretical foundation for the development of the LWD acoustic reflection imaging system.
The inverse relationship between Life’s Essential 8 and risk of metabolic syndrome: evidence from NHANES 2005-2018
Authors: Liu Yuhang , Tang Jialing , Gao Siyao
Published: October 2024

Background

Metabolic syndrome (MetS) has a close association with cardiovascular diseases. Few studies have investigated the association of Life’s Essential 8 (LE8), the updated measurement of cardiovascular health (CVH), with MetS.

Methods

The National Health and Nutrition Examination Survey (2005–2018) data was extracted. The LE8 comprised 4 health behaviors (diet, physical activity, nicotine exposure, and sleep health) and 4 health factors [body mass index (BMI), blood lipids, blood glucose, and blood pressure (BP)]. The total LE8 score is the average of 8 metric scores (0-100), categorized into low (0–49), moderate (50–79), and high CVH (80–100) levels. Multivariable logistic regression models, restricted cubic spline models and stratified analyses were performed to examine the relationship between LE8 and MetS.

Results

In this study, a total of 21,543 participants represented 146.6 million non-institutionalized U.S. adults. Following adjustment for various potential covariates, participants who attained a moderate [adjusted odds ratio (AOR) = 0.234, 95% CI: 0.209, 0.262] or a high CVH level (AOR = 0.026, 95% CI: 0.021, 0.032) exhibited an inverse correlation with MetS risks when comparing those with a low CVH level. An inverse linear dose-response relationship between LE8 scores and MetS risks was also identified (P for nonlinearity > 0.05).

Conclusions

LE8 was inversely associated with the risk of MetS. Adhering to LE8 guidelines to sustain a higher CVH level may be beneficial for preventing MetS.
Design considerations for future affective automotive interfaces: a review of self-regulation strategies to manage affect behind the wheel
Authors: Lohani Monika , Do Amy S. , Aisa Aifara
Published: October 2024

Like inattention, dysregulated emotions can seriously distract motorists and disrupt their driving performance. The current review examined the literature on emotion regulation to find relevant strategies for managing intense emotions while driving a motor vehicle. Next, we considered whether those relevant strategies could be used to design future affective automotive interfaces. Results suggested that problem-solving, task-focused coping, mindfulness, and relaxation effectively regulate emotions while driving. These findings highlight that some strategies may be effective but costly to implement while driving (cognitive reappraisal and distraction), which need to be better understood before implementing them into automotive interfaces. Together, these findings suggest the potential benefits of embedding self-regulatory interventions in future automotive interfaces that can help maintain an optimal affective state to reduce distraction and improve safe driving.
Study of the genetic and molecular epidemiology of cystic fibrosis based on the patient registry for planning targeted therapy in Russian Federation
Authors: Kondratyeva Elena , Melyanovskaya Yuliya , Sherman Victoriya , Voronkova Anna , Zhekaite Elena , Krasovsky Stanislav , Amelina Elena , Kashirskaya Nataliya , Shadrina Vera , Polyakov Alexander , Adyan Tagui , Sсhagina Olga , Starinova Marina , Enina Elena , Vasilyev Andrey , Marakhonov Andrey , Zinchenko Rena , Kutsev Sergey
Published: October 2024

Cystic fibrosis (CF) is a genetically inherited disorder characterized by a wide range of clinical manifestations and genetic variations. This study focuses on the genetic and molecular epidemiology of CF in the Russian population, utilizing data from the national CF registry. The birth prevalence of CF in Russia has been analyzed over a span of years, revealing variations in frequency. The study delves into the genetic landscape of CFTR gene variants in Russian patients, showcasing a diverse spectrum with a predominance of severe variants, some of which are rare and distinct from global populations. A total of 233 variants have been documented, exhibiting frequencies ranging from 0.01% to 51.5%, with 47 of these variants remaining uncharted within international genetic databases. As of 2021, CFTR modulator therapy has been introduced for patients under 19 years, heightening the importance of genetic diagnosis. In 2023, more than 1,850 patients under 19 received CFTR modulator therapy. Notably, the impact of complex alleles on disease progression and response to targeted therapies is gaining recognition. Comparisons with European registries highlight distinctive features of the Russian population, such as differences in age distribution among patients. Additionally, the study emphasizes the need to ascertain clinical significance and pathogenicity of newly identified genetic variants, along with exploring their suitability for targeted therapies. The integration of genetic insights into the management of CF offers potential for enhanced personalized therapeutic interventions. In conclusion, this thorough analysis provides a comprehensive understanding of the genetic nuances within the Russian CF population. By illuminating the intricate relationship between genetic variations and disease manifestation, the study underscores the essential role of genetics in shaping therapeutic strategies and improving patient outcomes. Further research and ongoing genetic exploration are crucial for optimizing the care of individuals with CF in the era of evolving therapeutic options.
Computational staining of CD3/CD20 positive lymphocytes in human tissues with experimental confirmation in a genetically engineered mouse model
Authors: Li Xiang , Heirman Casey C. , Rickard Ashlyn G. , Sotolongo Gina , Castillo Rico , Adanlawo Temitayo , Everitt Jeffery I. , Hodgin Jeffery B. , Watts Tammara L. , Janowczyk Andrew , Mowery Yvonne M. , Barisoni Laura , Lafata Kyle J.
Published: October 2024

Introduction

Immune dysregulation plays a major role in cancer progression. The quantification of lymphocytic spatial inflammation may enable spatial system biology, improve understanding of therapeutic resistance, and contribute to prognostic imaging biomarkers.

Methods

In this paper, we propose a knowledge-guided deep learning framework to measure the lymphocytic spatial architecture on human H&E tissue, where the fidelity of training labels is maximized through single-cell resolution image registration of H&E to IHC. We demonstrate that such an approach enables pixel-perfect ground-truth labeling of lymphocytes on H&E as measured by IHC. We then experimentally validate our technique in a genetically engineered, immune-compromised Rag2 mouse model, where Rag2 knockout mice lacking mature lymphocytes are used as a negative experimental control. Such experimental validation moves beyond the classical statistical testing of deep learning models and demonstrates feasibility of more rigorous validation strategies that integrate computational science and basic science.

Results

Using our developed approach, we automatically annotated more than 111,000 human nuclei (45,611 CD3/CD20 positive lymphocytes) on H&E images to develop our model, which achieved an AUC of 0.78 and 0.71 on internal hold-out testing data and external testing on an independent dataset, respectively. As a measure of the global spatial architecture of the lymphocytic microenvironment, the average structural similarity between predicted lymphocytic density maps and ground truth lymphocytic density maps was 0.86 ± 0.06 on testing data. On experimental mouse model validation, we measured a lymphocytic density of 96.5 ± %1% in a Rag2+/- control mouse, compared to an average of 16.2 ± %5% in Rag2-/- immune knockout mice (p<0.0001, ANOVA-test).

Discussion

These results demonstrate that CD3/CD20 positive lymphocytes can be accurately detected and characterized on H&E by deep learning and generalized across species. Collectively, these data suggest that our understanding of complex biological systems may benefit from computationally-derived spatial analysis, as well as integration of computational science and basic science.
Hypofractionated radiotherapy with simultaneous integrated boost for localized prostate cancer patients: effects on immune system and prediction of toxicity
Authors: D’Auria Fiorella , Valvano Luciana , Calice Giovanni , D’Esposito Vittoria , Cabaro Serena , Formisano Pietro , Bianchino Gabriella , Traficante Antonio , Bianculli Antonella , Lazzari Grazia , Statuto Teodora , Rago Luciana
Published: October 2024

Background

The other side of radiotherapy (RT), in addition to the cytotoxic effect, is the ability to modulate the immune system in terms of activation or suppression, also depending on the dose and fractionation delivered. This immune RT effect can be detected both locally in the irradiated tumor site and in the peripheral blood. The aim of this study was to assess the consequence of pelvic irradiation on peripheral immune cells and cytokine secretions in localized prostate cancer (PC) patients undergoing pelvic irradiation with a simultaneous moderately hypofractionated prostate/prostate bed boost by Volumetric Modulated Arc Therapy (VMAT). Furthermore, we analyzed whether there was a correlation between these peripheral immune parameters and acute and late genitourinary (GU) and gastrointestinal (GI) toxicity.

Methods

Thirty-eight PC patients were treated with pelvis irradiation (dose per fraction 1.8 Gy) and simultaneous hypofractionated (median dose per fraction: 2.7 Gy) prostate/prostate bed boost. A longitudinal analysis was performed for 12 months on peripheral blood to assess changes in 9 different lymphocyte subpopulations by flow cytometry and 10 circulating cytokines by Multiplex Luminex assay and ELISA.

Results

Our analysis revealed that basal IFN-γ serum values were significantly lower in the definitive (curative intent for patients with prostate) patient group respect to the post-operative one. All the lymphocyte subsets and IFN-α, IFN-β and Il-2 peripheral concentrations displayed significant variations between the different time points considered. The immune cell population that suffers the greatest RT toxicity in the blood was B lymphocyte. We found an interesting correlation between basal TGF-β1 and late GU toxicity. In particular, TGF-β1 concentrations before RT were significantly higher in patients that experienced grade 2-3 of late GU toxicity, respect to grade 0-1. Exploring possible correlations between some clinical/biological findings and radiation planning parameters, we found no statistical significance.

Conclusions

Our study analyzed, in the context of hypofractionated radiotherapy in prostate cancer, different parameters of the peripheral immune system. We have highlighted longitudinally the peripheral behavior of the different lymphocyte subpopulations and of a group of 10 cytokines during the first year after RT. One of the analyzed cytokines, such as TGF-β1, has proven to be promising predictive factor of severe late GU toxicity.
Delayed macrophage targeting by clodronate liposomes worsens the progression of cytokine storm syndrome
Authors: Khanna Kunjan , Eul Emily , Yan Hui , Faccio Roberta
Published: October 2024

Excessive macrophage activation and production of pro-inflammatory cytokines are hallmarks of the Cytokine Storm Syndrome (CSS), a lethal condition triggered by sepsis, autoimmune disorders, and cancer immunotherapies. While depletion of macrophages at disease onset protects from lethality in an infection-induced CSS murine model, patients are rarely diagnosed early, hence the need to characterize macrophage populations during CSS progression and assess the therapeutic implications of macrophage targeting after disease onset. In this study, we identified MHCII+F4/80+Tim4- macrophages as the primary contributors to the pro-inflammatory environment in CSS, while CD206+F4/80+Tim4+ macrophages, with an anti-inflammatory profile, become outnumbered. Additionally, we observed an expansion of Tim4- macrophages coinciding with increased hematopoietic stem progenitor cells and reduction of committed myeloid progenitors in bone marrow and spleen. Critically, macrophage targeting with clodronate liposomes at disease onset prolonged survival, while their targeting in mice with established CSS exacerbated disease severity, leading to a more dramatic loss of Tim4+ macrophages and an imbalance in pro- versus anti-inflammatory Tim4− macrophage ratio. Our findings highlight the significance of timing in macrophage-targeted interventions for effective management of CSS and suggest potential therapeutic strategies for diseases characterized by uncontrolled inflammation, such as sepsis.
Frost resistance and improvement techniques of recycled concrete: a comprehensive review
Authors: Ma Quan , Duan Zhenhua , Wang Jun , Yin Gang , Li Xi
Published: October 2024

In the pursuit of sustainable construction practices, the utilization of recycled concrete has emerged as a pivotal strategy, distinguished by its commitment to resource conservation and environmental stewardship. Nevertheless, the inherent micro-porosity and micro-cracking within the old mortar of recycled concrete may lead to weak bonding performance at the interfacial transition zone, culminating in diminished strength, reduced density, and elevated water absorption rates compared to conventional concrete, which critically impairs its performance in cold climates subjected to freeze-thaw cycles. Consequently, this paper provides a structured examination of the frost resistance properties of recycled concrete subjected to freeze-thaw cycling. Initially, the study delineates the mechanisms of frost-induced damage in recycled concrete by synthesizing the degradation pathways observed in both conventional and recycled concrete during freeze-thaw exposure. Subsequently, a detailed analysis is conducted to identify the pivotal factors affecting frost resistance, encompassing the proportion and moisture affinity of recycled aggregates, the addition of silica fume and fly ash, the water-to-cement ratio, and the degree of water saturation. In the final segment, the study compiles and reviews the strategies for bolstering the frost resistance of recycled concrete, including the incorporation of air-entraining admixtures, fiber reinforcement, and aggregate modification approaches. The objective of this research is to offer a thorough comprehension of recycled concrete, with a concentration on the mechanisms of frost damage, the critical determinants of frost resistance, and interventions to augment its resilience against freezing conditions. On this basis, the present paper, in conjunction with the characteristics and current research status of recycled concrete, proposes recommendations for the application of recycled concrete in cold regions. This review is anticipated to facilitate researchers in gaining a comprehensive understanding of the freeze-thaw characteristics of recycled concrete and the measures to enhance its frost resistance. Furthermore, it aims to assist engineering and technical personnel in selecting appropriate treatment methods to improve the frost resistance of recycled concrete in cold regions, thereby promoting the practical engineering application of recycled concrete in such areas.
Orbital decompression improves visual function and macular blood perfusion status in patients with thyroid-related eye disease
Authors: Wu Bingxuan , Zhu Min , Zhang Feng , Cao Jiamin , Xie Bingyu , Zhu Ziyi , Xiong Wei
Published: October 2024

Background

Orbital decompression surgery is a treatment option for Thyroid-associated Ophthalmopathy (TAO). However, its effects on visual function and macular perfusion status remain unclear. This study examined how orbital decompression surgery affects visual acuity and macular blood flow in TAO patients and the variation between these two factors.

Methods

This study involved cross-sectional and longitudinal analyses of 54 TAO patients, who were categorized into a normal vision group (n = 40) and an impaired vision group (n = 14) based on the presence of visual impairment before surgery (LogMAR BCVA >0.097). Among the participants, 20 underwent orbital decompression surgery (normal vision group: n = 13, impaired vision group: n = 7). BCVA and IOP were assessed at baseline in patients with TAO, and macular retinal blood perfusion indices were measured using OCTA. One month post-operatively, changes in these indices were compared between the two groups, and the correlation between visual acuity and macular perfusion indices was analyzed.

Results

The LogMar BCVA in the visual impairment group was significantly worse than that in the normal vision group (p < 0.001), while the W-MVD was significantly lower (p = 0.01). In the visual impairment group, post-operative LogMar BCVA improved significantly (p = 0.038), and W-MVD increased significantly (p = 0.008) compared to baseline. However, there were no significant changes in LogMar BCVA, S-MVD, D-MVD, or W-MVD in the normal vision group from preoperative to postoperative assessments. A strong negative correlation was found between the changes in W-MVD and changes in LogMar BCVA in the eyes of the visual impairment group treated with orbital decompression (Pearson correlation coefficient, R = −0.812, p = 0.05).

Conclusion

This study found that TAO patients with visual impairment had lower macular blood flow perfusion than those with normal vision. Endoscopic orbital decompression surgery was found to improve both the best-corrected visual acuity and macular blood flow perfusion in TAO patients with visual impairment, and the improvement in visual acuity was correlated with the improvement in macular blood flow perfusion.
Epigenetic modulation of fungal pathogens: a focus on Magnaporthe oryzae
Authors: Aslam Hafiz Muhammad Usman , Chikh-Ali Mohamad , Zhou Xin-Gen , Zhang Shouan , Harris Steven , Chanda Ashok K. , Riaz Hasan , Hameed Akhtar , Aslam Saba , Killiny Nabil
Published: October 2024

Epigenetics has emerged as a potent field of study for understanding the factors influencing the effectiveness of human disease treatments and for identifying alternations induced by pathogens in host plants. However, there has been a paucity of research on the epigenetic control of the proliferation and pathogenicity of fungal plant pathogens. Fungal plant pathogens such as Magnaporthe oryzae, a significant threat to global rice production, provide an important model for exploring how epigenetic mechanisms govern fungal proliferation and virulence. In M. oryzae, epigenetic alterations, such as DNA methylation, histone modification, and non-coding RNAs, regulate gene expression patterns that influence the pathogen’s ability to infect its host. These modifications can enhance fungal adaptability, allowing the pathogen to survive in diverse environments and evade host immune responses. Our primary objective is to provide a comprehensive review of the existing epigenetic research on M. oryzae and shed light on how these changes influence the pathogen’s lifecycle, its ability to invade host tissues, and the overall severity of the disease. We begin by examining the epigenetic alterations occurring in M. oryzae and their contributions to the virulence and proliferation of the fungus. To advance our understanding of epigenetic mechanisms in M. oryzae and similar plant diseases, we emphasize the need to address unanswered questions and explore future research directions. This information is crucial for developing new antifungal treatments that target epigenetic pathways, which could lead to improved disease management.
Unraveling the key mechanisms of Gastrodia elata continuous cropping obstacles: soil bacteria Massilia, Burkholderia-Caballeronia-Paraburkholderia, and Dyella along with soil metabolites 4-hydroxy-benzenemethanol and N-(2-butyl)-N-octadecyl-, ethyl ester as crucial indicators
Authors: Duan Mingzheng , Yang Chengcui , Bao Liuyuan , Han Duo , He Haiyan , Zhang Yongzhi , Dong Li , Yang Shunqiang
Published: October 2024

Background

Tian-ma (Gastrodia elata) is a traditional medicinal herb found in China. It is used in healthy food and to treat various diseases, therefore cultivated extensively in southwest China. However, continuous cropping of this species has led to various obstacles, such as microbial disease and pest infestation, significantly affecting the production and development of valuable medicinal and food resources. As per the growth habit, soil is presumed to be the primary factor contributing to these obstacles, despite the known issues of continuous cropping obstacles in Gastrodia elata, such as microbial disease, there is a lack of comprehensive understanding of the specific soil bacterial communities and metabolites involved in these processes.

Methods

We analyzed soil samples collected during the year of Tian-ma cultivation (0 Year), after the Tian-ma harvest (1 Year), after two years (2 Year), and three years (3 Year) of fallowing post-cultivation using soil 16S rRNA metabarcoding sequencing by illumina platform and metabolomics (GC–MS/MS). Soil sample collected from the uncultivated field was used as the control (CK).

Results

Metabarcoding sequencing showed high bacterial alpha diversity during the cultivation of Tian-ma (0 Year) and the period of deterioration of soil bacterial community. (1 Year), with decreased anaerobic bacterial abundance and increased copiotrophic bacterial abundance. Bacteria associated with sulfur metabolism also showed increased abundance during the year of cropping obstacles. Further metabolomics approach identified 4-hydroxy-benzenemethanol as an indicator of Tian-ma continuous cropping obstacles. Besides, metabolites of the carbohydrate class were found to be the most abundant during the occurrence of continuous cropping obstacles of Gastrodia elata, suggesting that regulation of soil microbial diversity may be a critical factor in addressing these obstacles. Finally, the correlation analysis indicated a positive association between the abundance of some metabolite, e.g., carbamic acid, N-(2-butyl)-N-octadecyl-, ethyl ester detected after Tian-ma cultivation and the abundance of bacteria capable of degrading toxic metabolites, such as Massilia, Burkholderia-Caballeronia-Paraburkholderia, and Dyella.

Conclusion

This study has revealed the specific soil bacteria and metabolic factors related to the continuous cropping obstacles of Gastrodia elata. These findings not only deepen our understanding of the continuous cropping issues but also pave the way for developing effective strategies to overcome them.
The golden batch-driven root cause analysis for anomalies in bioreactor fermentation process
Authors: Luo Dennis , He Meiling , Darko Justice , Ly Seymour Fatime , Maturana Francisco
Published: October 2024

Bioreactors are essential for the production of biopharmaceuticals and bioproducts, requiring continuous monitoring to ensure quality assurance. Manual processes in manufacturing plants often lead to anomalies such as out-of-trend and out-of-spec incidents, necessitating extensive root cause analysis that typically takes 2–8 weeks. This paper introduces an innovative methodology that uses the golden batch profile as a benchmark to identify deviations and root causes in subsequent industrial batches. The methodology involves normalizing the data and calculating the variances of a specified batch from the golden batch profile. By examining the contribution of each critical process parameter to these variances, the study highlights their importance in root cause analysis. The application of this methodology to the IndPenSim dataset demonstrated its effectiveness by significantly reducing false positives and negatives compared to traditional PCA-based methods. Emphasis on the deviations of critical quality attributes and critical process parameters from the specified batch compared to the golden batch profile offers valuable insights into industrial process analysis. This approach not only enhances anomaly detection accuracy but also improves the efficiency and reliability of biopharmaceutical and bioproduct manufacturing processes.
Cholecystokinin-expressing neurons of the ventromedial hypothalamic nucleus control energy homeostasis
Authors: Eftychidis Vasileios , Ellender Tommas J. , Szymanski Jacek , Minichiello Liliana
Published: October 2024

The hypothalamus is the primary center of the brain that regulates energy homeostasis. The ventromedial hypothalamus (VMH) plays a central role in maintaining energy balance by regulating food intake, energy expenditure, and glucose levels. However, the cellular and molecular mechanisms underlying its functions are still poorly understood. Cholecystokinin (CCK) is one of many genes expressed in this hypothalamic nucleus. Peripheral CCK regulates food intake, body weight, and glucose homeostasis. However, current research does not explain the function of CCK neurons in specific nuclei of the hypothalamus and their likely roles in network dynamics related to energy balance and food intake. This study uses genetic and pharmacological methods to examine the role of CCK-expressing neurons in the VMH (CCKVMH). Namely, using a previously generated BAC transgenic line expressing Cre recombinase under the CCK promoter, we performed targeted manipulations of CCKVMH neurons. Histological and transcriptomic database analysis revealed extensive distribution of these neurons in the VMH, with significant heterogeneity in gene expression related to energy balance, including co-expression with PACAP and somatostatin. Pharmacogenetic acute inhibition via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) resulted in increased food intake and altered meal patterns, characterized by higher meal frequency and shorter intermeal intervals. Furthermore, diphtheria toxin-mediated ablation of CCKVMH neurons led to significant weight gain and hyperphagia over time, increasing meal size and duration. These mice also exhibited impaired glucose tolerance, indicative of disrupted glucose homeostasis. Our findings underscore the integral role of CCKVMH neurons in modulating feeding behavior, energy homeostasis, and glucose regulation. This study enhances our understanding of the neurohormonal mechanisms underlying obesity and metabolic disorders, providing potential targets for therapeutic interventions.
Neuronal Intranuclear Inclusion Disease Presenting with Acute-Onset Dementia and Cortical Edema: A Case Report
Authors: Feng Xiao , Li Yue , Zhao Qin , Xu Shabei
Published: October 2024

Background

Neuronal Intranuclear Inclusion Disease (NIID) is a neurodegenerative disorder characterized by the formation of eosinophilic inclusions in the neurons, visceral and skin cells. The cause is associated with the GGC nucleotide repeat expansion in the NOTCH2NLC gene. The imaging hallmark of NIID is hyperintensities on diffusion-weighted imaging (DWI) at the corticomedullary junction. Clinical manifestations of NIID are highly heterogeneous. Here, we report a case of NIID presenting with acute-onset dementia and cortical edema.

Case presentation

We describe an elderly male patient who presented with sudden dementia within a day. Considering the abrupt onset and the stroke history, we initially diagnosed vascular disease. However, further imaging revealed cortical edema in the temporo-parieto-occipital lobes. Blood and cerebrospinal fluid tests ruled out immunological, metabolic, infectious, or neoplastic etiologies. Genetic testing ultimately confirmed the diagnosis of NIID. Intravenous immunoglobulin (IVIG) therapy did not improve the patient’s symptoms; However, about 1 month after treatment, spontaneous improvement was observed. It is noteworthy that 22 months before the onset of cognitive impairment, the patient’s MRI for headaches already exhibited the typical imaging lesions of this disease in the cerebellum paravermal region.

Conclusion

Patients with encephalopathy syndrome exhibiting imaging features resembling mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome or Creutzfeldt-Jakob disease should consider the NIID as differential diagnosis. Chronic headaches and symmetric lesions in the cerebellar paravermal region on MRI may be noteworthy indicators of NIID during non-episodic phases.
Case report: The first known case of male retroperitoneal mesonephric-like adenocarcinoma
Authors: Hu Baohong , Liu Ying , Tang Jingjing , Yang Ping , Sun Di
Published: October 2024

Aim

We aimed to analyze the clinico-pathological and molecular features of mesonephric-like adenocarcinoma (MLA) to enhance understanding of this tumor type.

Methods

This is the first case of MLA occurring in the retroperitoneum of a male patient. Clinico-pathological and molecular characteristics were analyzed, and the relevant literature was reviewed.

Results

A 65-year-old elderly male was admitted to the hospital with mild bilateral dull pain in the lumbar region for more than 1 month, accompanied by a feeling of dysuria. CT tomography revealed a retroperitoneal tumor. While tumor immuno-histochemistry was positive for CK, CK7, Vimentin, PAX-8, CD10, GATA-3, EMA, and CR to varying degrees, it was negative for P53, WT-1, HMB45, MelanA, CD117, DOG-1, CD34, S-100, ER, PR, AR, CEA, α-inhibin and TTF-1. Ki67 index was <10% in most areas and was approximately 30% in the hotspot areas in the glandular ductal region. Molecular detection (Next-generation sequencing method, 425-gene panel from NanjingShihe Gene Biotechnology Co., Ltd. for targeted DNA enrichment): No clinically significant variants detected. The final pathological diagnosis was a retroperitoneal malignant tumor consistent with a well-moderately differentiated MLA.

Conclusion

MLA in the retroperitoneum of men has not been reported yet. The diverse morphology and unclear molecular characteristics of this tumor mandate careful diagnosis for good clinical outcomes.
Organoids research progress in gynecological cancers: a bibliometric analysis
Authors: He Baiyun , Ma Huihao , Yu Hongbo , Li Dongmei , Zhang Li , Wang Junjie
Published: October 2024

Background

Gynecological cancers (GC) pose a severe threat to the health and safety of women’s lives, and organoids, as in-vitro research models, have demonstrated significant advantages in simulating tissue characteristics and drug screening. In recent years, there has been a rapid increase in research outcomes related to organoids in GC. However, there has been no bibliometric study concerning.

Methods

Publications related to GC and organoids from 2010-2023 were retrieved from the Web of Science Core Collection (WoSCC). We conducted a bibliometric analysis and visualization using CiteSpace, VOSviewer, and the Bibliometrix R Package. This analysis included the spatiotemporal distribution, author, sources, references, and keywords.

Results

A total of 333 publications were included. The number of annual publications indicated an explosive phase of development since 2019. The USA was the most important country in terms of cooperation, publication output, citation and centrality. University of California system ranked first in productivity among institutions, and HIPPO Y is the most relevant author in the research field. CANCERS published the most documents, and NATURE is the most cited sources. Analysis of Keywords and References, it is possible to establish the trend, and find the hotspots in the research field.

Conclusion

This bibliometric analysis delineated global landscapes and progress trends in GC organoids research. This study emphasized that organoids can effectively replicate the original tissue or tumors, providing a good in-vitro model for research on tumor-related mechanisms and showing significant advantages in drug screening and efficacy clinical prediction. Additionally, as preclinical models, they provide compelling evidence for personalized therapy and prediction of patient drug responses.
Fulminant myocarditis associated with human rhinovirus A66 infection: a case report
Authors: Han Shuaibing , Liu Jing , Feng Ziheng , Mao Yiyang , Gao Hengmiao , Xie Zhengde , Qian Suyun , Xu Lili
Published: October 2024

Background

Human rhinoviruses (HRVs) are among the most common pathogens of upper respiratory infections, and they are responsible for the common cold. An increasing number of studies have shown that HRV is associated with more severe illness. However, HRV-associated fulminant myocarditis has rarely been reported.

Patient presentation

A previously healthy 8-year-old boy developed fever, fatigue, and vomiting for 3 days, with a subsequent exacerbation accompanied by confusion lasting for 9 h. The day before admission, the patient presented with oliguria, confusion, and hypotension, and he was suspected of having myocarditis. The patient was transferred to our hospital for further diagnosis and treatment. On admission, rough and moist rales were detected, and the heart sounds were muffled, accompanied by an irregular heart rhythm and a gallop. An electrocardiogram (EKG) revealed a wide QRS complex, ST-segment depression, premature ventricular contractions, and complete right bundle branch block. Laboratory tests revealed that brain natriuretic peptide (BNP), N-terminal pro BNP (NT-pro BNP), and cardiac biomarkers, such as troponin I, creatinine kinase (CK), and creatinine kinase-MB (CK-MB) were elevated. Additionally, echocardiography revealed an ejection fraction of approximately 28%. The child developed severe cardiac dysfunction and tissue hypoperfusion, and the cardiogenic shock could not be corrected despite active drug therapy. He had indications for ECMO implantation. A rarely reported rhinovirus, namely, A66, was detected in his bronchoalveolar lavage fluid and oropharyngeal swabs via metagenomic next-generation sequencing and a PCR assay. Bacterial culture of all the samples yielded negative results.

Conclusions

This case presents a patient with severe human rhinovirus A66 infection, which is likely responsible for fulminant myocarditis. This report facilitates prompt diagnosis and treatment of fulminant myocarditis. Clinicians should consider rhinovirus as a possible pathogen of fulminant myocarditis, especially when patients present with symptoms or signs of heart involvement.
Sequential versus concomitant treatment of androgen receptor signaling inhibitors and docetaxel for metastatic hormone-sensitive prostate cancer: an network meta-analysis
Authors: Li Chun Xing , Li Cong Ying , Wang Yu Qiao , Liu Hua , Yang Zhan Jiang , Zhang Xian , Wang Guan Chun , Wang Lei
Published: October 2024

Background

Androgen receptor signaling inhibitors (ARSis), when administered sequentially or in combination with docetaxel and androgen deprivation therapy (ADT), have been shown to enhance overall survival (OS) and progression-free survival (PFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Nonetheless, the optimal sequence for administering chemotherapy and ARSis remains to be determined.

Objective

To compare the efficacy of ARSis sequential therapy with ARSis combined therapy for mHSPC, and to evaluate the efficacy and safety of different combination regimens.

Methods

The PubMed, Embase, Cochrane Central, and ClinicalTrials.gov databases were searched from their inception through 14 July 2024, to identify eligible phase III randomized clinical trials (RCTs) evaluating the combination or sequential use of docetaxel + ADT with abiraterone, enzalutamide, apalutamide, or darolutamide. The outcomes of interest included OS, PFS, time to prostate-specific antigen (PSA) progression, grade 3–5 adverse events (AEs), and serious adverse events (SAEs).

Results

Five RCTs involving 2836 patients were included in the analysis. When comparing ARSis sequential therapy to ARSis combined therapy, no significant differences were observed in OS (Hazard Ratio (HR): 1.17, 95% Confidence Interval (CI): 0.69–1.96), PFS (HR: 1.03, 95% CI: 0.47–2.22), or time to PSA progression (HR: 0.48, 95% CI: 0.03–7.69). Within the different ARSis combined regimens, the triple therapies involving enzalutamide, abiraterone, and darolutamide demonstrated comparable efficacy and safety profiles in the overall population, and their efficacy in patients with high-volume disease or low-volume disease was also similar.

Conclusion

ARSis sequential therapy did not significantly differ from ARSis combined therapy in improving OS and PFS among patients with mHSPC, and thus can be considered as a viable treatment option.
Patients with dementia: prevalence and type of drug–drug interactions
Authors: Muñoz-Contreras María Cristina , Cerdá Begoña , López-Román Francisco Javier , Segarra Ignacio
Published: October 2024

Background

Patients with Alzheimer’s disease (AD) and other dementias are more frequently exposed to polymedication, mainly due to the presence of comorbidities, are particularly vulnerable to drug-related problems, and present greater risk of adverse effects due to drug–drug interactions (DDIs).

Purpose

To assess the prevalence of clinically relevant interactions in dementia patients using a routine database, we describe the most frequent interactions and risk factors associated with them to facilitate specific interventions and programs to prevent and minimize them.

Methods

An observational, descriptive, and cross-sectional study that included patients with AD and other types of dementia (n = 100, 64% female) was conducted to identify potential DDI in their treatment using the Lexi-Interact/Lexicomp® database.

Results

A total of 769 drugs were prescribed, involving 190 different active ingredients; 83% of the treatments included five or more drugs. DDI occurred in 87% of the patients, of which 63.2% were female. A total of 689 DDIs were found, grouped in 448 drug pairs, with a mean of 6.9 ± 7.1 (range, 0–31) DDIs per patient, and 680 DDIs were considered clinically relevant. It was observed that 89.8% of the DDIs had a moderate level of severity, 23.5% had a good level of relevance, and pharmacodynamic-based DDIs accounted for 89.5%. The drugs most frequently involved in DDIs were quetiapine (24.5%) and acetylsalicylic acid (10%). A total of 97 DDIs were detected between the acetylcholinesterase inhibitors (AChEIs), and the remaining drugs were administered concomitantly. One of the most frequent DDIs was between AChEIs and beta-blocking agents (n = 29, 4.3%). The most important factors that showed the strongest association with the presence of drug interactions were the use of AChEIs (p = 0.01) and the total number of drugs (p = 0.014) taken by the patient.

Conclusion

Patients with dementia present increased risk of DDIs. Among the most common drugs are psychotropic drugs, which are involved in pharmacodynamic interactions caused by the concomitant use of CNS-targeted drugs. The results highlight the difficulty to evaluate DDIs in clinical practice due to polymedication and variety of comorbidities. Therefore, it is important to review their treatment and consider metabolism inhibition or induction, and potentially P450 substrate overlapping.