bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-stack seismic inversion based on model-constrained generative adversarial network
Authors: Zhang Guangzhi , Song Sirui , Zhang Haihang , Chang Dekuan
Published: June 2024

Pre-stack seismic inversion usually uses various traditional algorithms to estimate elastic parameters such as P-wave velocity, S-wave velocity, and density. It is hard to derive accurate elastic parameters due to their non-uniqueness and high dimensionality between elastic parameters and seismic data, the calculation of elastic parameters is inaccurate. Convolutional Neural Networks (CNNs) have high-dimensional feature space mapping capabilities, which are utilized to establish mapping relationships between seismic data and elasticity parameters. However, their effectiveness is greatly affected by label data, and at the same time, due to the lack of enough label data, resulting in a low degree of fitting between prediction results and real data. In addition, conventional seismic inversion methods based on CNNs lack physical model constraints, resulting in low accuracy and poor interpretability of prediction results. We propose a Cycle-consistent Generative Adversarial Network based on a geophysical mechanism (SeisInv-CycleGAN). Deterministic inversion results and labeled data are combined into hybrid geophysical data as a training set of SeisInv-CycleGAN with geophysical constraints. At the same time, the residual (seismic loss) between the seismic data synthesized by forward modeling and the actual data is used as part of the loss function. The SeisInv-CycleGAN does not require building an initial model, and it can achieve higher accuracy in prediction results with a small amount of labeled data.
Molecular storytelling: a conceptual framework for teaching and learning with molecular case studies
Authors: Trujillo Caleb M. , Dutta Shuchismita
Published: June 2024

Molecular case studies (MCSs) provide educational opportunities to explore biomolecular structure and function using data from public bioinformatics resources. The conceptual basis for the design of MCSs has yet to be fully discussed in the literature, so we present molecular storytelling as a conceptual framework for teaching with case studies. Whether the case study aims to understand the biology of a specific disease and design its treatments or track the evolution of a biosynthetic pathway, vast amounts of structural and functional data, freely available in public bioinformatics resources, can facilitate rich explorations in atomic detail. To help biology and chemistry educators use these resources for instruction, a community of scholars collaborated to create the Molecular CaseNet. This community uses storytelling to explore biomolecular structure and function while teaching biology and chemistry. In this article, we define the structure of an MCS and present an example. Then, we articulate the evolution of a conceptual framework for developing and using MCSs. Finally, we related our framework to the development of technological, pedagogical, and content knowledge (TPCK) for educators in the Molecular CaseNet. The report conceptualizes an interdisciplinary framework for teaching about the molecular world and informs lesson design and education research.
Causal relationship between T2DM microvascular complications and gut microbiota: a Mendelian randomization study
Authors: Zhang Junping , Yu Zilu , Li Shanshan , Zhang Qingfang , Chen Wen , Wang Jingying , He Shasha , Liu Ying , Chen Shen , Xu Jixiong
Published: June 2024

Background

Gowing number of studies have demonstrated the association between gut microbiome and T2DM microvascular complications, however the causal relationship remains unclear. Therefore, we using the Mendelian randomization (MR) approach to investigate this causal relation.

Methods

Using gut microbiome data from the International MiBioGen Consortium genome-wide association study (GWAS) and T2DM microvascular complications data from the FinnGen Consortium GWAS to perform MR analyses. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), the inverse variance weighting (IVW) method was used as the primary analysis method, and the results were tested for heterogeneity and horizontal pleiotropy.

Results

Our research identified that there are 5 known microbial species and 2 unknown microbial species in the gut microbiome that were causally related to T2DM retinopathy. Besides, three and seven known microbial species causal relationships between the gut microbiome and T2DM neuropathy and T2DM nephropathy, respectively.

Conclusions

Using MR methods, we demonstrated the causal relationship between gut microbiome and microvascular complications in T2DM, providing a new strategy for the prevention and treatment of it.
Mediation effect of cognitive impairment for the relationship of type 2 diabetes mellitus with mortality among elderly individuals
Authors: Wei Boyang , He Jun
Published: June 2024

Objectives

To investigate the potential mediating role of cognitive impairment on the link between type 2 diabetes mellitus (T2DM) and mortality among elderly individuals using data from the National Health and Nutrition Examination Survey (NHANES) database.

Methods

Totally, 1,891 individuals from the NHANES database were included in this cohort study. All-cause mortality was considered study endpoint. Cognitive impairment was assessed by digit symbol substitution test (DSST). Adopted weighted logistic regression analyses to explore the relationship of T2DM with cognitive impairment. Constructed weighted Cox proportional hazard models to investigate the relationship of T2DM with all-cause mortality. We employed distribution-of-the-product method to investigate the mediating effect. RMediation software package was used to calculate the 95% confidence interval (CI) of the distribution-of-the-product. If CI does not contain 0, it suggests a significant mediation effect.

Results

The findings from the weighted logistic regression revealed that individuals with T2DM had a significantly higher likelihood of experiencing cognitive impairment [odds ratio =1.86, 95% CI: 1.39–2.49]. The result showed that T2DM was related to an increased all-cause mortality (hazard ratio=1.37, 95%CI: 1.01–1.87). Importantly, the mediation effect of cognitive impairment on the relationship of T2DM with all-cause mortality is significant (95%CI: 0.06–0.59). The percentage of mediation effect was calculated as 16.2%.

Conclusion

Our study suggested that the presence of cognitive impairment plays a significant role in explaining the link between T2DM and all-cause mortality in older individuals.
Association between life’s essential 8 and testosterone deficiency in men: NHANES 2011–2016
Authors: Cai Min , Chen Jinzao
Published: June 2024

Background

Serum testosterone is intrinsically associated to cardiovascular disease. Our aim is to explore the relationship between the recently updated cardiovascular health measurement, known as Life’s Essential 8 (LE8), and the prevalence of testosterone deficiency (TD) in adult males in the United States.

Methods

Study data was obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. A weighted multivariate logistic regression model was applied to evaluate the correlation between LE8 and testosterone deficiency. Restricted Cubic Spline (RCS) was employed to explore its non-linear relationship. In addition, a stratified analysis was conducted.

Results

The final analysis included 2332 participants from NHANES from 2011 to 2016. After adjusting for confounding factors, the odds ratios (ORs) and 95% confidence intervals (CIs) for testosterone deficiency in participants with moderate and higher LE8 scores compared to the lowest LE8 scores were 0.59 (0.38–0.92) and 0.38 (0.19–0.76), respectively. The results of subgroup analysis showed that LE8 score was significantly associated with TD among young and middle-aged participants.

Conclusion

A lower LE8 score is related to a higher incidence of testosterone deficiency, especially in young and middle-aged men. Further research is necessary to explore the potential mechanisms between them.
18F-AlF-NOTA-octreotide PET/CT in the localization of tumor-induced osteomalacia: case series and literature review
Authors: Li Jing
Published: June 2024

Introduction

This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT).

Methods

We analyzed TIO patients who underwent 18F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed.

Results

6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent 18F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm3).

Conclusion

The implementation of whole-body 18F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of 18F-OC PET/CT in managing TIO.
LCA analysis of a roof mounted PV system: a Romanian case study
Authors: Rus Tania , Moldovan Raluca-Paula , Pardo Picazo Miguel Ángel
Published: June 2024

Using solar photovoltaic power sources has become a discussed topic in the construction and energy industry. The pressing need to reduce reliance on fossil fuels, increasing costs of traditional electricity generation, and affording photovoltaic modules has sparked a growing interest in solar photovoltaics. This study aims to optimis e the layout of solar photovoltaic systems to minimise environmental impact and building load, comparing the performing south-oriented panels with east-west-oriented panels. The comprehensive analysis performed hinges on a diverse array of determinative factors that demand thoughtful consideration before embarking upon implementing any photovoltaic installation. These salient factors, including but not limited to structural integrity, incorporating ballast for stability enhancement, integrating requisite electrical components, selecting solar panels, quantifying energy production capabilities, assessing carbon emissions, and discerning associated benefits, require thoughtful consideration before implementing any photovoltaic installation. The findings derived from this study underscore that, within the context of the given geographical location, the solar photovoltaic system configured with an East-West orientation represents the optimal choice to reduce both emissions and structural load. This study provides a scientific basis for the construction industry and the energy field and guides the future development of photovoltaic installation projects in a more economic and environmentally friendly direction.
Case report: Overlap syndrome of neuromyelitis optica spectrum disorder with anti-Argonaute antibodies
Authors: Liu Pei , Lin Xuemei , Wu Songdi
Published: June 2024

Aquaporin-4 antibodies (AQP4-Abs) are a diagnostic marker for patients with a demyelinating disease called neuromyelitis optica spectrum disorder (NMOSD). Anti-Argonaute antibodies (AGO-Abs) present as potential biomarkers of the overlap syndrome between NMOSD and other autoimmune diseases. In this paper, we present the case of an adult woman with numbness, tingling, and burning sensations in her arms and subsequent bilateral internuclear ophthalmoplegia. Brain–cervical–thoracic magnetic resonance imaging (MRI) showed T2 hyperintensities in the dorsal brainstem and around the midbrain aqueduct and longitudinally transverse myelitis with homogeneous enhancement on gadolinium-enhanced MRI. The contemporaneous detection of AQP4- and AGO-Abs led to a definite diagnosis of overlap syndrome of NMOSD with AGO-Abs. The patient was treated with immunosuppressive agents, including corticosteroids and immunoglobulins, and achieved remission. This case highlights a novel phenotype of NMOSD with AGO-Abs overlap syndrome, which presents with relapsing brainstem syndrome and longitudinally extensive myelitis with acute severe neurological involvement. The promising prognosis of the disease could serve as a distinct clinical profile. Broad screening for antibodies against central nervous system autoimmune antigens is recommended in suspected patients with limited or atypical clinical manifestations.
Pyroptosis mediates osteoporosis via the inflammation immune microenvironment
Authors: Chen Te , Jin Linyu , Li Jingyi , Liu Yikai
Published: June 2024

Osteoporosis represents a systemic imbalance in bone metabolism, augmenting the susceptibility to fractures among patients and emerging as a notable mortality determinant in the elderly population. It has evolved into a worldwide concern impacting the physical well-being of the elderly, imposing a substantial burden on both human society and the economy. Presently, the precise pathogenesis of osteoporosis remains inadequately characterized and necessitates further exploration. The advancement of osteoporosis is typically linked to the initiation of an inflammatory response. Cells in an inflammatory environment can cause inflammatory death including pyroptosis. Pyroptosis is a recently identified form of programmed cell death with inflammatory properties, mediated by the caspase and gasdermin families. It is regarded as the most inflammatory form of cell death in contemporary medical research. Under the influence of diverse cytokines, macrophages, and other immune cells may undergo pyroptosis, releasing inflammatory factors, such as IL-1β and IL-18. Numerous lines of evidence highlight the pivotal role of pyroptosis in the pathogenesis of inflammatory diseases, including cancer, intestinal disorders, hepatic conditions, and cutaneous ailments. Osteoporosis progression is frequently associated with inflammation; hence, pyroptosis may also play a role in the pathogenesis of osteoporosis to a certain extent, making it a potential target for treatment. This paper has provided a comprehensive summary of pertinent research concerning pyroptosis and its impact on osteoporosis. The notion proposing that pyroptosis mediates osteoporosis via the inflammatory immune microenvironment is advanced, and we subsequently investigate potential targets for treating osteoporosis through the modulation of pyroptosis.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease
Authors: Arron Hayley E. , Marsh Benjamin D. , Kell Douglas B. , Khan M. Asad , Jaeger Beate R. , Pretorius Etheresia
Published: June 2024

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available. Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease’s multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. This comprehensive model not only advances our understanding of ME/CFS’s pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease’s complexity and the multifaceted approach required for its study and management.
Predicting Kawasaki disease shock syndrome in children
Authors: Zhao Zhihui , Yuan Yue , Gao Lu , Li Qirui , Wang Ying , Zhao Shunying
Published: June 2024

Background

Kawasaki disease shock syndrome (KDSS) is a critical manifestation of Kawasaki disease (KD). In recent years, a logistic regression prediction model has been widely used to predict the occurrence probability of various diseases. This study aimed to investigate the clinical characteristics of children with KD and develop and validate an individualized logistic regression model for predicting KDSS among children with KD.

Methods

The clinical data of children diagnosed with KDSS and hospitalized between January 2021 and December 2023 were retrospectively analyzed. The best predictors were selected by logistic regression and lasso regression analyses. A logistic regression model was built of the training set (n = 162) to predict the occurrence of KDSS. The model prediction was further performed by logistic regression. A receiver operating characteristic curve was used to evaluate the performance of the logistic regression model. We built a nomogram model by visualizing the calibration curve using a 1000 bootstrap resampling program. The model was validated using an independent validation set (n = 68).

Results

In the univariate analysis, among the 24 variables that differed significantly between the KDSS and KD groups, further logistic and Lasso regression analyses found that five variables were independently related to KDSS: rash, brain natriuretic peptide, serum Na, serum P, and aspartate aminotransferase. A logistic regression model was established of the training set (area under the receiver operating characteristic curve, 0.979; sensitivity=96.2%; specificity=97.2%). The calibration curve showed good consistency between the predicted values of the logistic regression model and the actual observed values in the training and validation sets.

Conclusion

Here we established a feasible and highly accurate logistic regression model to predict the occurrence of KDSS, which will enable its early identification.
Multi-criteria analysis for sustainable and cost-effective development of desalination plants in Chile
Authors: Sola Iván , Zarzo Domingo , Sánchez-Lizaso José Luis , Sáez Claudio A.
Published: June 2024

In Chile, there is an increasing demand for freshwater supply for human consumption, agriculture, and industrial activities. In this sense, the country is highly threatened by climate change, which is drastically affecting the availability of water resources in the north-central region due to desertification processes. Therefore, seawater reverse osmosis (SWRO) desalination is becoming one of the most feasible alternatives to address current and future challenges regarding water scarcity in the country. This investigation aims to evaluate potential locations for a sustainable and cost-effective installation of desalination projects; the latter, under a multi-criteria and geographic information system (GIS)-model. The model was tested in the highly water scarcity-threatened Valparaiso Region, Chile, as a case study. The model was developed integrating economic and socio-environmental criteria involved in the development and/or construction of desalination projects. The results of the multi-criteria analysis show that the Valparaıso Region presents optimal areas for developing SWRO projects. Both the northern and central areas of the Region show appropriate locations for installing SWRO plants and their freshwater distribution lines, ensuring short- and long-term water supply, especially for agriculture and population consumption. The results obtained in this study could be extrapolated as a tool to assess the desalination projects development in other world regions to make future desalination projects more viable and sustainable for addressing global water demands.
Migration patterns of the Japanese sardine in the Sea of Japan by combining the microscale stable isotope analysis of otoliths and an ocean data assimilation model
Authors: Aono Tomoya , Sakamoto Tatsuya , Ishimura Toyoho , Takahashi Motomitsu , Yasuda Tohya , Kitajima Satoshi , Nishida Kozue , Matsuura Takayoshi , Ikari Akito , Ito Shin-ichi
Published: June 2024

The Japanese sardine (Sardinops sagax melanostictus) is a small pelagic fish found in the Sea of Japan, the marginal sea of the western North Pacific. It is an important species for regional fisheries, but their dispersal and migration patterns during early life stages remain unclear. In this study, we analyzed the stable oxygen isotope ratios of otoliths of young-of-the-year (age 0) Japanese sardines collected from the northern offshore and southern coastal areas of the Sea of Japan in 2015 and 2016. The ontogenetic shifts of the geographic distribution were estimated by comparing the profiles of life-long isotope ratios and temporally varying isoscape, which was calculated using the temperature and salinity fields produced by an ocean data assimilation model. Individuals that were collected in the northern and southern areas hatched and stayed in the southern areas (west offshore of Kyushu) until late June, and thereafter, they can be distinguished into two groups: one that migrated northward at shallow layer and one that stayed around the southern area in the deep layer. A comparison of somatic growth trajectories of the two groups, which was reconstructed based on otolith microstructure analysis, suggested that individuals that migrated northward had significantly larger body lengths in late June than those that stayed in the southern area. These results indicate that young-of-the-year Japanese sardines that hatched in the southern area may have been forced to choose one of two strategies to avoid extremely high water temperatures within seasonal and geographical limits. These include migrating northward or moving to deeper layers. Our results indicate that the environmental variabilities in the southern area could critically impact sardine population dynamics in the Sea of Japan.
Preparation of kartogenin-loaded PLGA microspheres and a study of their drug release profiles
Authors: Chang Hyun-Kyung , Koh Yong-Gon , Hong Hyoung-Taek , Kang Kyoung-Tak
Published: June 2024

Introduction: Kartogenin, a potent inducer of chondrogenic differentiation in mesenchymal stem cells and a key agent in cartilage regeneration, presents a viable therapeutic strategy for osteoarthritis management. Despite the abundance of literature on therapeutic potential of kartogenin, there is a paucity of studies characterizing the formulation specifics in microsphere fabrication. This exploration is pivotal to advances in regenerative medicine, particularly in the domain of cartilage regeneration, to assure clinical efficacy and safety.

Methods: In this work, we fabricated kartogenin-loaded PLGA microspheres with diverse formulations and their particle size, size distribution, encapsulation efficiency, drug loading and release profiles were characterized. Ratio of polymer, drug, and solvent and the use of surfactant was used as variables, and in particular, the effect of surfactant on particles was investigated.

Results: The average diameter of the spheres was 16.0–31.7 μm. Morphological variations from solid to porous surface structures depending on surfactant incorporation during the emulsification process was observed. Cumulative kartogenin release from microspheres ranged from 53.8% to 80.9% on day 28, and release profiles conform predominantly to the Korsmeyer-Peppas kinetics model.

Discussion: This study provides a foundational framework for modulating kartogenin release dynamics, a critical consideration for optimizing therapeutic efficacy and minimizing adverse effects in cartilage tissue engineering applications.
Efficient differential privacy enabled federated learning model for detecting COVID-19 disease using chest X-ray images
Authors: Ahmed Rawia , Maddikunta Praveen Kumar Reddy , Gadekallu Thippa Reddy , Alshammari Naif Khalaf , Hendaoui Fatma Ali
Published: June 2024

The rapid spread of COVID-19 pandemic across the world has not only disturbed the global economy but also raised the demand for accurate disease detection models. Although many studies have proposed effective solutions for the early detection and prediction of COVID-19 with Machine Learning (ML) and Deep learning (DL) based techniques, but these models remain vulnerable to data privacy and security breaches. To overcome the challenges of existing systems, we introduced Adaptive Differential Privacy-based Federated Learning (DPFL) model for predicting COVID-19 disease from chest X-ray images which introduces an innovative adaptive mechanism that dynamically adjusts privacy levels based on real-time data sensitivity analysis, improving the practical applicability of Federated Learning (FL) in diverse healthcare environments. We compared and analyzed the performance of this distributed learning model with a traditional centralized model. Moreover, we enhance the model by integrating a FL approach with an early stopping mechanism to achieve efficient COVID-19 prediction with minimal communication overhead. To ensure privacy without compromising model utility and accuracy, we evaluated the proposed model under various noise scales. Finally, we discussed strategies for increasing the model’s accuracy while maintaining robustness as well as privacy.
Genomic insights into an endophytic Streptomyces sp. VITGV156 for antimicrobial compounds
Authors: Veilumuthu Pattapulavar , Nagarajan T. , Magar Sharayu , Sundaresan Sasikumar , Moses Lenus Joy , Theodore Thomas , Christopher John Godwin
Published: June 2024

Endophytic Streptomyces sp. are recognized as a potential resource for valuable natural products but are less explored. This study focused on exploring endophytic Streptomyces species residing within tomato plants (Solanum lycopersicum) harboring genes for the production of a novel class of antibiotics. Our research involved the isolation and characterization of Streptomyces sp. VITGV156, a newly identified endophytic Streptomyces species that produces antimicrobial products. VITGV156 harbors a genome of 8.18 mb and codes 6,512 proteins, of which 4,993 are of known function (76.67%) and 1,519 are of unknown function (23.32%). By employing genomic analysis, we elucidate the genome landscape of this microbial strain and shed light on various BGCs responsible for producing polyketide antimicrobial compounds, with particular emphasis on the antibiotic kendomycin. We extended our study by evaluating the antibacterial properties of kendomycin. Overall, this study provides valuable insights into the genome of endophytic Streptomyces species, particularly Streptomyces sp. VITGV156, which are prolific producers of antimicrobial agents. These findings hold promise for further research and exploitation of pharmaceutical compounds, offering opportunities for the development of novel antimicrobial drugs.
Enterovirus genotype diversity with emergence of coxsackievirus A2 circulating in pediatric patients with acute gastroenteritis in Thailand, 2019–2022
Authors: Xie Zhenfeng , Khamrin Pattara , Jampanil Nutthawadee , Yodmeeklin Arpaporn , Ukarapol Nuthapong , Maneekarn Niwat , Kumthip Kattareeya
Published: June 2024

Introduction

Enteroviruses (EVs) are recognized as potential causative agents of acute gastroenteritis (AGE) in children worldwide. This study aimed to investigate the epidemiology and molecular characteristics of EV infection in children admitted to hospitals with AGE in Chiang Mai, Thailand from 2019 to 2022.

Methods

A total of 1,148 fecal samples collected from patients with AGE were screened for the presence of EV using RT-PCR. The prevalence, co-infection with common diarrheal viruses, and seasonal pattern of EV were examined. The genotypes of EV were identified based on the VP1 sequence and phylogenetic analysis.

Results

The overall prevalence of EV in AGE patients was 8.8% (101/1,148). After the COVID-19 outbreak in 2019, a significant decrease in the EV infection rate and genotype diversity was observed (p < 0.05). EV infection alone was observed in 68.3% (69/101) of cases while co-infection with other enteric viruses was 31.7% (32/101). The seasonal pattern of EV infection showed a peak prevalence during the rainy season. EV species A was the most prevalent (37.5%), followed by species B (32.3%), species C (29.2%), and species D (1.0%). Twenty-five genotypes of EV were identified with the most predominant of the coxsackievirus A2 (CV-A2) (13.5%), CV-B2 (7.3%) and CV-A24 (5.2%).

Conclusion

Our data demonstrate a significant decrease in the prevalence and diversity of EV circulating in AGE patients during the COVID-19 pandemic and highlight the emergence of CV-A2 during this study period. These findings contribute to a better understanding of the molecular epidemiology and diversity of EV in patients with AGE and provide useful information for further investigation into the potential association between specific EV genotypes and AGE in future studies.
Recovery of terbium by Lysinibacillus sp. DW018 isolated from ionic rare earth tailings based on microbial induced calcium carbonate precipitation
Authors: Bian Zijun , Dong Wei , Ning Zhoushen , Song Yuexin , Hu Kaijian
Published: June 2024

Microbial induced calcium carbonate precipitation (MICP) is considered as an environmentally friendly microbial-based technique to remove heavy metals. However, its application in removal and recovery of rare earth from wastewaters remains limited and the process is still less understood. In this study, a urease-producing bacterial strain DW018 was isolated from the ionic rare earth tailings and identified as Lysinibacillus based on 16S rRNA gene sequencing. Its ability and possible mechanism to recover terbium was investigated by using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and fourier transform infrared spectroscopy (FTIR). The results showed that the urease activity of DW018 could meet the biomineralization requirements for the recovery of Tb3+ from wastewaters. The recovery rate was as high as 98.28% after 10 min of treatment. The optimal conditions for mineralization and recovery were determined as a bacterial concentration of OD600 = 1.0, a temperature range of 35 to 40°C, and a urea concentration of 0.5%. Notably, irrespective of CaCO3 precipitation, the strain DW018 was able to utilize MICP to promote the attachment of Tb3+ to its cell surface. Initially, Tb3+ existed in amorphous form on the bacterial surface; however, upon the addition of a calcium source, Tb3+ was encapsulated in calcite with the growth of CaCO3 at the late stage of the MICP. The recovery effect of the strain DW018 was related to the amino, hydroxyl, carboxyl, and phosphate groups on the cell surface. Overall, the MICP system is promising for the green and efficient recovery of rare earth ions from wastewaters.
The effect of feedback timing on category learning and feedback processing in younger and older adults
Authors: Nunn Kristen , Creighton Robert , Tilton-Bolowsky Victoria , Arbel Yael , Vallila-Rohter Sofia
Published: June 2024

Introduction

Corrective feedback can be received immediately after an action or with a temporal delay. Neuroimaging studies suggest that immediate and delayed feedback are processed by the striatum and medial temporal lobes (MTL), respectively. Age-related changes in the striatum and MTL may influence the efficiency of feedback-based learning in older adults. The current study leverages event-related potentials (ERPs) to evaluate age-related differences in immediate and delayed feedback processing and consequences for learning. The feedback-related negativity (FRN) captures activity in the frontostriatal circuit while the N170 is hypothesized to reflect MTL activation.

Methods

18 younger (Myears = 24.4) and 20 older (Myears = 65.5) adults completed learning tasks with immediate and delayed feedback. For each group, learning outcomes and ERP magnitudes were evaluated across timing conditions.

Results

Younger adults learned better than older adults in the immediate timing condition. This performance difference was associated with a typical FRN signature in younger but not older adults. For older adults, impaired processing of immediate feedback in the striatum may have negatively impacted learning. Conversely, learning was comparable across groups when feedback was delayed. For both groups, delayed feedback was associated with a larger magnitude N170 relative to immediate feedback, suggesting greater MTL activation.

Discussion and conclusion

Delaying feedback may increase MTL involvement and, for older adults, improve category learning. Age-related neural changes may differentially affect MTL- and striatal-dependent learning. Future research can evaluate the locus of age-related learning differences and how feedback can be manipulated to optimize learning across the lifespan.
Case report: Spontaneous regression of extruded lumbar disc herniation with acupuncture therapy
Authors: Liang Haiwen , Huang Jianhao
Published: June 2024

Most patients with lumbar disc herniation (LDH) derive benefit from conservative treatment, prompting growing global interest in non-surgical approaches. Despite being recognized as one of the effective conservative therapies, there is currently limited evidence to support the sole efficacy of acupuncture in treating patients with acute extruded LDH. Here we report the case of a 52-year-old male who presented with low back pain and persistent radiating lower limb pain and numbness. Physical examination and magnetic resonance imaging (MRI) revealed an extruded LDH at the L5/S1 level, compressing the nerve root and causing severe radiculopathy symptoms. After 23 days of continuous inpatient acupuncture treatment, followed by 5 intermittent outpatient acupuncture treatment over 2 months, patient’s pain and numbness was significantly alleviated and a followed-up MRI showed a remarkable regression of the extruded disc fragment. In this case, acupuncture as a monotherapy is safe and effective, but more conclusive evidence is needed.
The randomized study of enteral nutrition with rapid versus conventional administration in acute stroke patients; the protocol of rapid EN trial
Authors: Suzuki Kentaro , Onodera Hidetaka , Sugiyama Rie , Okubo Seiji , Kimura Naoto , Kaku Shogo , Seki Rieko , Fujita Satoshi , Nomura Koichi , Takagiwa Taiki , Katafuchi Izumi , Nakamura Homare , Kanamaru Takuya , Oda Momoyo , Kimura Shohei , Sonoda Shota , Kakita Hiroto , Otsuka Toshiaki , Kimura Kazumi
Published: June 2024

Rationale

Enteral nutrition is beneficial for stroke patients with oral intake difficulties. However, it is time consuming and may interfere with routine medical care. Therefore, there is a clinical benefit if enteral nutrition can be safely administered in a short time. Although our retrospective study showed the safety of rapid administration, it remains unclear whether rapid administration of enteral nutrition is as safe as conventional administration.

Aim

The randomized study of Enteral Nutrition with Rapid versus conventional administration in acute stroke patients (Rapid EN trial) aims to clarify the safety of rapid feeding of enteral nutrition compared with conventional feeding.

Methods and design

This is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded end-point clinical trial. Eligible criteria include acute stroke patients who have difficulty with oral intake defined as severe altered consciousness (Japan Coma Scale 10–300) or modified water swallowing test <4. The target enrollment is 700 patients, with 350 patients receiving rapid enteral nutrition at a rate of 100 mL in 5 min (Rapid EN group) and 350 patients receiving conventional enteral nutrition at a rate of 100 mL in 30 min (Conventional EN group).

Study outcome

The primary outcome is the incidence of one or more complications of vomiting or diarrhea or pneumonia within 7 days would be non-inferior in the rapid EN group compared to the conventional EN group. Secondary outcomes were total time spent on enteral nutrition within 7 days from enteral nutrition, the incidence of vomiting, diarrhea and pneumonia within 3 or 7 days, and the rate of favorable clinical outcome.

Discussion

Since no previous reports have focused on the speed of administration, we felt it was necessary to prove the safety of rapid administration. If this study shows positive results, it will not only benefit patients, but also reduce the burden of medical care. We believe this study is novel and will be useful in clinical practice.

Clinical trial registration

https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000046610 Identifier UMIN000046610.
Modelling adult neurogenesis in the aging rodent hippocampus: a midlife crisis
Authors: Arellano Jon I. , Rakic Pasko
Published: June 2024

Contrary to humans, adult hippocampal neurogenesis in rodents is not controversial. And in the last three decades, multiple studies in rodents have deemed adult neurogenesis essential for most hippocampal functions. The functional relevance of new neurons relies on their distinct physiological properties during their maturation before they become indistinguishable from mature granule cells. Most functional studies have used very young animals with robust neurogenesis. However, this trait declines dramatically with age, questioning its functional relevance in aging animals, a caveat that has been mentioned repeatedly, but rarely analyzed quantitatively. In this meta-analysis, we use data from published studies to determine the critical functional window of new neurons and to model their numbers across age in both mice and rats. Our model shows that new neurons with distinct functional profile represent about 3% of the total granule cells in young adult 3-month-old rodents, and their number decline following a power function to reach less than 1% in middle aged animals and less than 0.5% in old mice and rats. These low ratios pose an important logical and computational caveat to the proposed essential role of new neurons in the dentate gyrus, particularly in middle aged and old animals, a factor that needs to be adequately addressed when defining the relevance of adult neurogenesis in hippocampal function.
PD-L1 expression as a potential predictor of immune checkpoint inhibitor efficacy and survival in patients with recurrent or metastatic nasopharyngeal cancer: a systematic review and meta-analysis of prospective trials
Authors: Xu Ruyu , Wong Charlene H.L. , Chan Kenneth S.K. , Chiang Chi Leung
Published: June 2024

Background

The predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains controversial. This study aimed to evaluate the optimal threshold of PD-L1 expression in predicting the efficacy of ICIs in patients with recurrent or metastatic (R/M) NPC.

Methods

A meta-analysis was performed by retrieving relevant literature from PubMed, EMBASE, and Cochrane Library databases. Data on the pooled risk ratio (RR), mean overall survival (OS), progression-free survival (PFS), overall response rate (ORR) with 95% confidence interval, and 1%, 10%, and 25% PD-L1 expression cutoff points were obtained to examine the role of PD-L1 as a biomarker in R/M NPC patients receiving immunotherapy.

Results

In total, 1,312 patients from 14 studies were included. An improvement in PFS was observed in both patients with PD-L1 ≥ 1% (RR = 0.76, 95% CI 0.62–0.92, P = 0.005) and those with PD-L1 < 1% (RR = 0.68, 95% CI: 0.35–1.32, P = 0.26) who received first-line treatment with immunotherapy, with no significant difference between these subgroups. The pooled ORR was significantly higher in patients with PD-L1 ≥ 1% (ORR = 0.37) than in those with PD-L1 < 1% (ORR = 0.22) (P < 0.01) undergoing subsequent-line treatment. However, when we used the PD-L1 cutoff values of 10% and 25%, there was no significant difference between the positive (PD-L1 expression ≥ the cutoff value) and negative (PD-L1 expression < the cutoff value) subgroups. PD-L1 ≥ 1% also tended to be associated with better PFS and OS.

Conclusions

Our meta-analysis suggested that first-line immunotherapy could significantly improve PFS in R/M NPC patients, regardless of the PD-L1 expression levels. Positive PD-L1 expression (≥ 1%) might be a potential predictive biomarker for a better overall response to immunotherapy in R/M NPC patients in subsequent-line setting.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024495841 PROSPERO, identifier CRD42024495841.
Predictive model based on multiple immunofluorescence quantitative analysis for pathological complete response to neoadjuvant immunochemotherapy in lung squamous cell carcinoma
Authors: Xiao Meng , Tu Lili , Zhou Ting , He Ye , Li Xiaohui , Zuo Qiunan
Published: June 2024

Objective

This study aims to establish a prediction model for neoadjuvant immunochemotherapy (NICT) in lung squamous cell carcinoma to guide clinical treatment.

Methods

This retrospective study included 50 patients diagnosed with lung squamous cell carcinoma who received NICT. The patients were divided into the pathological complete response (PCR) group and the non-PCR group. HE staining and multiple immunofluorescence (mIF) techniques were utilized to analyze the differences in the immune microenvironment between these groups. LASSO regression and optimal subset regression were employed to identify the most significant variables and construct a prediction model.

Results

The PCR group showed higher densities of lymphocyte nuclei and karyorrhexis based on HE staining. Furthermore, based on mIF analysis, the PCR group showed higher cell densities of CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region, while showing lower cell densities of CD3+Foxp3+, Foxp3+, and CD163+. Logistic univariate analysis revealed CD8+PD-L1+, PD-L1+, CD8+, CD4+LAG-3+, lymphocyte nuclei, and karyorrhexis as significant factors influencing PCR. By using diverse screening methods, the three most relevant variables (CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region) were selected to establish the prediction model. The model exhibited excellent performance in both the training set (AUC=0.965) and the validation set (AUC=0.786). In the validation set, In comparison to the conventional TPS scoring criteria, the model attained superior accuracy (0.85), specificity(0.67), and sensitivity (0.92).

Conclusion

NICT treatment might induce anti-tumor effects by enriching immune cells and reactivating exhausted T cells. CD8+, PD-L1+, and CD8+PD-L1+ cell abundances within the tumor region have been closely associated with therapeutic efficacy. Incorporating these three variables into a predictive model allows accurate forecasting of treatment outcomes and provides a reliable basis for selecting NICT treatment strategies.
Avelumab first-line maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma: real-world results from a Korean expanded access program
Authors: Park Se Hoon , Shin Sang Joon , Rha Sun Young , Beom Seung-Hoon , Seo Ho Kyung , Keam Bhumsuk , Kim Miso , Hong Yoon-Hee , Yoon Shinkyo , Lee Jae-Lyun
Published: June 2024

Background

The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP).

Methods

This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice.

Results

Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died.

Conclusion

Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies.
Stimulation of hair regrowth in an animal model of androgenic alopecia using 2-deoxy-D-ribose
Authors: Anjum Muhammad Awais , Zulfiqar Saima , Chaudhary Aqif Anwar , Rehman Ihtesham Ur , Bullock Anthony J. , Yar Muhammad , MacNeil Sheila
Published: June 2024

Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our group reported that 2-deoxy-D-ribose (2dDR) is 80%–90% as effective as VEGF in the stimulation of neovascularization in in vitro models and in a chick bioassay. In this study, we aimed to assess the effect of 2dDR on hair growth. We prepared an alginate gel containing 2dDR, polypropylene glycol, and phenoxyethanol. AGA was developed in C57BL6 mice by intraperitoneally injecting testosterone (TE). A dihydrotestosterone (DHT)-treated group was used as a negative control, a minoxidil group was used as a positive control, and we included groups treated with 2dDR gel and a combination of 2dDR and minoxidil. Each treatment was applied for 20 days. Both groups treated with 2dDR gel and minoxidil stimulated the morphogenesis of hair follicles. H&E-stained skin sections of C57BL/6 mice demonstrated an increase in length, diameter, hair follicle density, anagen/telogen ratio, diameter of hair follicles, area of the hair bulb covered in melanin, and an increase in the number of blood vessels. Masson’s trichrome staining showed an increase in the area of the hair bulb covered in melanin. The effects of the FDA-approved drug (minoxidil) on hair growth were similar to those of 2dDR (80%–90%). No significant benefit were observed by applying a combination of minoxidil with 2dDR. We conclude that 2dDR gel has potential for the treatment of androgenic alopecia and possibly other alopecia conditions where stimulation of hair regrowth is desirable, such as after chemotherapy. The mechanism of activity of 2dDR remains to be established.