bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-dependent effect of sublethal copper concentrations on de novo cholesterol synthesis in astrocytes and their possible links to variations in cholesterol and amyloid precursor protein levels in neuronal membranes
Authors: Zubillaga Marlene , Tau Julia , Rosa Diana , Bellini M. José , Arnal Nathalie
Published: January 2024

Background

Cholesterol (Cho) is an essential lipophilic molecule in cells; however, both its decrease and its increase may favor the development of neurological diseases such as Alzheimer’s disease (AD). Although copper (Cu) is an essential trace metal for cells, the increased plasma concentration of its free form has been linked with AD development and severity. AD affects aged people, but its prevalence and severity are higher in women than in men. We have previously shown that Cu promotes Cho de novo synthesis in immature neurons as well as increased Cho in membrane rafts and Aβ levels in culture medium, but there are no results yet regarding sex differences in the effects of sublethal Cu exposure on Cho de novo synthesis.

Methods

We examined the potential sex-specific impact of sublethal Cu concentrations on de novo Cho synthesis in primary cultures of male and female astrocytes. We also explored whether this had any correlation with variations in Cho and APP levels within neuronal membrane rafts.

Results

Flow cytometry analysis demonstrated that Cu treatment leads to a greater increase in ROS levels in female astrocytes than in males. Furthermore, through RT-PCR analysis, we observed an upregulation of SREBP-2 and HMGCR. Consistently, we observed an increase in de novo Cho synthesis. Finally, western blot analysis indicated that the levels of ABCA1 increase after Cu treatment, accompanied by a higher release of radiolabeled Cho and an elevation in Cho and APP levels in neuronal membrane rafts. Importantly, all these results were significantly more pronounced in female astrocytes than in males.

Conclusions

Our findings confirm that Cu stimulates Cho synthesis in astrocytes, both in a ROS-dependent and -independent manner. Moreover, female astrocytes displayed elevated levels of HMGCR, and de novo Cho synthesis compared to males following TBH and Cu treatments. This corresponds with higher levels of Cho released into the culture medium and a more significant Cho and APP rise within neuronal rafts. We consider that the increased risk of AD in females partly arises from sex-specific responses to metals and/or exogenous substances, impacting key enzyme regulation in various biochemical pathways, including HMGCR.
ImmunoPET provides a novel way to visualize the CD103+ tissue-resident memory T cell to predict the response of immune checkpoint inhibitors
Authors: Fan Xiaoyu , Nijman Hans W. , de Bruyn Marco , Elsinga Philip H.
Published: January 2024

Background

Immune checkpoint inhibitors (ICIs) have made significant progress in oncotherapy improving survival of patients. However, the benefits are limited to only a small subgroup of patients who could achieve durable responses. Early prediction of response may enable treatment optimization and patient stratification. Therefore, developing appropriate biomarkers is critical to monitoring efficacy and assessing patient response to ICIs.

Main body

Herein, we first introduce a new potential biomarker, CD103, expressed on tissue-resident memory T cells, and discuss the potential application of CD103 PET imaging in predicting immune checkpoint inhibitor treatment. In addition, we describe the current targets of ImmunoPET and compare these targets with CD103. To assess the benefit of PET imaging, a comparative analysis between ImmunoPET and other imaging techniques commonly employed for tumor diagnosis was performed. Additionally, we compare ImmunoPET and immunohistochemistry (IHC), a widely utilized clinical method for biomarker identification with respect to visualizing the immune targets.

Conclusion

CD103 ImmunoPET is a promising method for determining tumor-infiltrating lymphocytes (TILs) load and response to ICIs, thereby addressing the lack of reliable biomarkers in cancer immunotherapy. Compared to general T cell markers, CD103 is a specific marker for tissue-resident memory T cells, which number increases during successful ICI therapy. ImmunoPET offers noninvasive, dynamic imaging of specific markers, complemented by detailed molecular information from immunohistochemistry (IHC). Radiomics can extract quantitative features from traditional imaging methods, while near-infrared fluorescence (NIRF) imaging aids tumor detection during surgery. In the era of precision medicine, combining such methods will offer a more comprehensive approach to cancer diagnosis and treatment.
An efficient hybrid optimization of ETL process in data warehouse of cloud architecture
Authors: Dinesh Lina , Devi K. Gayathri
Published: January 2024

In big data, analysis data is collected from different sources in various formats, transforming into the aspect of cleansing the data, customization, and loading it into a Data Warehouse. Extracting data in other formats and transforming it to the required format requires transformation algorithms. This transformation stage has redundancy issues and is stored across any location in the data warehouse, which increases computation costs. The main issues in big data ETL are handling high-dimensional data and maintaining similar data for effective data warehouse usage. Therefore, Extract, Transform, Load (ETL) plays a vital role in extracting meaningful information from the data warehouse and trying to retain the users. This paper proposes hybrid optimization of Swarm Intelligence with a tabu search algorithm for handling big data in a cloud-based architecture-based ETL process. This proposed work overcomes many issues related to complex data storage and retrieval in the data warehouse. Swarm Intelligence algorithms can overcome problems like high dimensional data, dynamical change of huge data and cost optimization in the transformation stage. In this work for the swarm intelligence algorithm, a Grey-Wolf Optimizer (GWO) is implemented to reduce the high dimensionality of data. Tabu Search (TS) is used for clustering the relevant data as a group. Clustering means the segregation of relevant data accurately from the data warehouse. The cluster size in the ETL process can be optimized by the proposed work of (GWO-TS). Therefore, the huge data in the warehouse can be processed within an expected latency.
Municipal heat provision experiences and expectations in Germany
Authors: Krikser Thomas , Ehlers Melf-Hinrich , Profeta Adriano
Published: January 2024

Background

Compared to other sectors, the building sector is seriously lagging in efforts to mitigate climate change. In particular, heat provision needs to move to low-carbon options at greater speed. Municipalities are essential players in the transition to low-carbon heating. However, little is known about their experiences in developing heat provision infrastructure and their expectations of low-carbon options, such as district heating based on renewable energy. To explore how the experiences and expectations of municipalities concerning low-carbon heating are related, we conducted a survey of officers responsible for heating technology in municipal authorities across Germany. The questionnaires were analysed using multiple quantitative data analysis techniques.

Results

Our findings suggest that officers in larger municipalities have more positive expectations of low-carbon heating technologies than those in smaller and medium-sized municipalities. They also have more experience with these technologies. We identified four different clusters of municipalities based on their attitudes towards heating systems. The findings suggest that attitudes and experiences have a significant influence on the desirability and expected feasibility of the expansion of district heating. Furthermore, there are differences between south, north, and east Germany.

Conclusions

Exchange of experiences and expectations between larger and smaller municipalities could facilitate the transition to low-carbon heating. Public policy could strategically provide spaces for the required exchange, but it also needs to engage with more complex questions of finance and regulation.
Exploring factors for antibiotic over-prescription in children with acute upper respiratory tract infections in Assiut, Egypt: a qualitative study
Authors: AbdEl-Aty Mahmoud Attia , Amin Mariam Taher , Ahmed Sabra Mohamed , Elsedfy Ghada Omar , El-Gazzar Amira Fathy
Published: January 2024

Background

Over-prescription of antibiotics contributes to antibiotic resistance, which is a global health threat. Egypt has alarmingly high rates of antibiotic over-prescription for acute upper respiratory tract infections (URIs) in children. To effectively address this issue, it is important to understand the various factors that influence prescription behaviors. The Teixeira antibiotic prescription behavioral model (TAPBM) offers a comprehensive framework through which these factors can be explored. This qualitative study sought to investigate the perspectives of key stakeholders involved in pediatric healthcare in Egypt, with the primary goal of identifying the underlying determinants that contributed to this problem.

Methods

This qualitative study was conducted in Assiut City, Egypt, between January and March 2023. Purposive sampling was used to select participants, including consultant pediatricians, supervisors of pediatric training programs, and specialists in infection prevention and control. Thirteen semi-structured in-depth interviews (IDIs) were conducted, audio-recorded, and transcribed. Thematic analysis was performed using MAXQDA 2020 software.

Results

Two main themes emerged from the analysis: intrinsic factors related to physicians, extrinsic factors related to patients, and nonphysician factors. Intrinsic factors encompass personal characteristics and attitudes. Prescribing decisions were influenced by factors such as fear of complications, limited follow-up visits, and competition. Knowledge and education also played a significant role. Moreover, diagnostic uncertainty in distinguishing between bacterial and viral infections posed a challenge. Extrinsic factors included patient and caregiver factors, such as parental expectations and demands for antibiotics, driven by the belief that they produced rapid results. Moreover, patients’ demographic factors, including socioeconomic status and living conditions, affected their prescribing behavior. Health system-related factors, such as the type of healthcare institution and the absence of formal national guidelines, were identified as influential factors. Additionally, this study highlighted the influence of the pharmaceutical industry. The potential impact of the COVID-19 pandemic on antibiotic prescriptions was addressed.

Conclusions

The study highlights the intricate interplay between intrinsic and extrinsic factors that shape antibiotic prescription decisions, underscoring the significance of addressing these factors in mitigating overprescribing.
Assessing causality between inflammatory bowel diseases with frailty index and sarcopenia: a bidirectional Mendelian randomization study
Authors: Wang Peng , Tao Wei , Zhang Zhiqiang , Xu Cong , Qiu Yuan , Xiao Weidong
Published: January 2024

Background

Previous studies have found that frailty and sarcopenia are commonly diagnosed in inflammatory bowel disease (IBD) patients, indicating an association between these conditions. Nonetheless, the cause‒effect connection between IBD, frailty, and sarcopenia remains unclear.

Methods

We sourced the genetic variants for the exposures and outcomes from publicly accessible, extensive genome-wide association studies (GWAS). Specifically, we obtained IBD data from the International IBD Genetics Consortium, frailty index (FI) data from the United Kingdom Biobank and Swedish TwinGene, and sarcopenia data from a recent GWAS meta-analysis. Five methods, including inverse variance weighted (IVW), simple mode, MR-Egger, weighted mode, and the weighted median, were used to proceed with MR estimates. We also performed heterogeneity and horizontal pleiotropy tests.

Results

Our results indicated a positive causal relationship between ulcerative colitis (UC) (IVW: β = 0.014, 95% CI, 0.006 to 0.021, p = 0.001) and Crohn's disease (CD) (IVW: β = 0.012; 95% CI, 0.006 to 0.018, p = 2e−04) with the FI. However, we uncovered no proof of a cause-and-effect relationship between UC (IVW: β = 0.001, 95% CI, −0.015 to 0.017, p = 0.344) or CD (IVW: β = 0.003, 95% CI, −0.009 to 0.015, p = 0.214) and sarcopenia. Additionally, in the inverse order, we also discovered no cause-and-effect connection between FI or sarcopenia on UC or CD in this study.

Conclusion

The MR analysis showed a positive causal association between IBD and FI, indicating that IBD patients may exhibit aging-related characteristics. Therefore, frailty assessments should be conducted as early as possible in IBD patients.
Prognostic, diagnostic and clinicopathological roles of tsRNAs: a meta-analysis in breast cancer
Authors: Gao Lu-Jue , Zhu Si-Xun , Wei Ying-Yi , Meng Hua-Wei , Gu Jing , Zhang Hao , Dai Li-Juan
Published: January 2024

Breast cancer (BC) is one of the most common malignancies in women and the leading cause of cancer-related death in women. The newly emerged non-coding RNAs tsRNAs (tRNA-derived small RNAs) play an important role in the occurrence and development of BC. The purpose of this study was to comprehensively evaluate the prognostic, diagnostic and clinicopathological roles of tsRNAs in BC. Through literature screening, a total of 13 BC-related tsRNA studies were included in this meta-analysis, all of which passed quality assessment. Prognostic studies showed upregulated tsRNAs to be associated with poor survival outcomes (HR = 1.64, 95%CI 1.51–1.77) and downregulated tsRNAs to be associated with better outcomes (HR = 0.58, 95%CI 0.50–0.68). Results of diagnostic studies showed a combined sensitivity of 72% (95%CI 68–76%) and combined specificity of 64% (95%CI 61–67%); the AUC was 0.72 (95%CI 0.68–0.75) and the DOR 4.62 (95%CI 3.76–5.68). Finally, correlation analysis of clinicopathological features showed that downregulation of tsRNAs correlated significantly with age, TNM stage and lymphatic metastasis. Sensitivity analysis and publication bias showed no significant difference. In conclusion, BC-associated tsRNAs are closely related to the prognosis and clinicopathological features of patients with this disease and can be used to assist in early diagnosis of BC. Therefore, tsRNAs are potential targets for the diagnosis and treatment of BC.
Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease
Authors: Qi Xiu-Hong , Chen Peng , Wang Yue-Ju , Zhou Zhe-Ping , Liu Xue-Chun , Fang Hui , Wang Chen-Wei , Liu Ji , Liu Rong-Yu , Liu Han-Kui , Zhang Zhen-Xin , Zhou Jiang-Ning
Published: January 2024

Background

Microglia-mediated neuroinflammation in Alzheimer’s disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD.

Methods

Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining.

Results

A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aβ plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD.

Conclusions

The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD.
Individualized microbiotas dictate the impact of dietary fiber on colitis sensitivity
Authors: Bonazzi Erica , Bretin Alexis , Vigué Lucile , Hao Fuhua , Patterson Andrew D. , Gewirtz Andrew T. , Chassaing Benoit
Published: January 2024

Background

The observation that the intestinal microbiota is  central in the development of IBD suggests that dietary fiber, the microbiota’s primary source of nourishment, could play a central role in these diseases. Accordingly, enriching diets with specific soluble fibers remodels microbiota and modulates colitis sensitivity. In humans, a recent study suggests that the microbiota of select IBD patients might influence the impacts they would experience upon fiber exposure. We sought here to define the extent to which individual microbiotas varied in their responsiveness to purified soluble fiber inulin and psyllium. Moreover, the extent to which such variance might impact proneness to colitis.

Results

We observed a high level of inter-individual variation in microbiota responsiveness to fiber inulin and psyllium: while microbiotas from select donors exhibited stark fiber-induced modulation in composition, pro-inflammatory potential, and metabolomic profile, others were only minimally impacted. Mice transplanted with fiber-sensitive microbiomes exhibited colitis highly modulated by soluble fiber consumption, while mice receiving fiber-resistant microbiotas displayed colitis severity irrespective of fiber exposure.

Conclusion

The extent to which select soluble fibers alter proneness to colitis is highly influenced by an individual's microbiota composition and further investigation of individual microbiota responsiveness toward specific dietary fiber could pave the way to personalized fiber-based intervention, both in IBD patients and healthy individuals.
In-depth metaproteomics analysis of tongue coating for gastric cancer: a multicenter diagnostic research study
Authors: Chen Jiahui , Sun Yingying , Li Jie , Lyu Mengge , Yuan Li , Sun Jiancheng , Chen Shangqi , Hu Can , Wei Qing , Xu Zhiyuan , Guo Tiannan , Cheng Xiangdong
Published: January 2024

Background

Our previous study revealed marked differences in tongue images between individuals with gastric cancer and those without gastric cancer. However, the biological mechanism of tongue images as a disease indicator remains unclear. Tongue coating, a major factor in tongue appearance, is the visible layer on the tongue dorsum that provides a vital environment for oral microorganisms. While oral microorganisms are associated with gastric and intestinal diseases, the comprehensive function profiles of oral microbiota remain incompletely understood. Metaproteomics has unique strength in revealing functional profiles of microbiota that aid in comprehending the mechanism behind specific tongue coating formation and its role as an indicator of gastric cancer.

Methods

We employed pressure cycling technology and data-independent acquisition (PCT-DIA) mass spectrometry to extract and identify tongue-coating proteins from 180 gastric cancer patients and 185 non-gastric cancer patients across 5 independent research centers in China. Additionally, we investigated the temporal stability of tongue-coating proteins based on a time-series cohort. Finally, we constructed a machine learning model using the stochastic gradient boosting algorithm to identify individuals at high risk of gastric cancer based on tongue-coating microbial proteins.

Results

We measured 1432 human-derived proteins and 13,780 microbial proteins from 345 tongue-coating samples. The abundance of tongue-coating proteins exhibited high temporal stability within an individual. Notably, we observed the downregulation of human keratins KRT2 and KRT9 on the tongue surface, as well as the downregulation of ABC transporter COG1136 in microbiota, in gastric cancer patients. This suggests a decline in the defense capacity of the lingual mucosa. Finally, we established a machine learning model that employs 50 microbial proteins of tongue coating to identify individuals at a high risk of gastric cancer, achieving an area under the curve (AUC) of 0.91 in the independent validation cohort.

Conclusions

We characterized the alterations in tongue-coating proteins among gastric cancer patients and constructed a gastric cancer screening model based on microbial-derived tongue-coating proteins. Tongue-coating proteins are shown as a promising indicator for identifying high-risk groups for gastric cancer.
A comparative effectiveness study of the Breaking the Cycle and Maxxine Wright intervention programs for substance-involved mothers and their children: study protocol
Authors: Racine Nicole , Barriault Sophie , Motz Mary , Leslie Margaret , Poole Nancy , Premji Shainur , Andrews Naomi C. Z. , Penaloza Denise , Pepler Debra
Published: January 2024

Background

Children of substance-involved mothers are at especially high risk for exposure to adverse childhood experiences (ACEs) and poor mental health and development. Early interventions that support mothers, children, and the mother-child relationship have the greatest potential to reduce exposure to early adversity and the mental health problems associated with these exposures. Currently, there is a lack of evidence from the real-world setting demonstrating effectiveness and return on investment for intervention programs that focus on the mother-child relationship in children of substance-involved mothers.

Methods

One hundred substance-involved pregnant and/or parenting women with children between the ages of 0–6 years old will be recruited through the Breaking the Cycle and Maxxine Wright intervention programs, in Toronto, Ontario, Canada and Surrey, British Columbia, Canada, respectively. Children’s socioemotional development and exposure to risk and protective factors, mothers’ mental health and history of ACEs, and mother-child relationship quality will be assessed in both intervention programs. Assessments will occur at three time points: pre-intervention, 12-, and 24-months after engagement in the intervention program.

Discussion

There is a pressing need to identify interventions that promote the mental health of infants and young children exposed to early adversity. Bringing together an inter-disciplinary research team and community partners, this study aligns with national strategies to establish strong evidence for infant mental health interventions that reduce child exposure to ACEs and support the mother-child relationship. This study was registered with clinicaltrials.gov (NCT05768815) on March 14, 2023.
Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways
Authors: Liu Dequan , Che Xiangyu , Wu Guangzhen
Published: January 2024

Neddylation is a post-translational modification process, similar to ubiquitination, that controls several biological processes. Notably, it is often aberrantly activated in neoplasms and plays a critical role in the intricate dynamics of the tumor microenvironment (TME). This regulatory influence of neddylation permeates extensively and profoundly within the TME, affecting the behavior of tumor cells, immune cells, angiogenesis, and the extracellular matrix. Usually, neddylation promotes tumor progression towards increased malignancy. In this review, we highlight the latest understanding of the intricate molecular mechanisms that target neddylation to modulate the TME by affecting various signaling pathways. There is emerging evidence that the targeted disruption of the neddylation modification process, specifically the inhibition of cullin-RING ligases (CRLs) functionality, presents a promising avenue for targeted therapy. MLN4924, a small-molecule inhibitor of the neddylation pathway, precisely targets the neural precursor cell-expressed developmentally downregulated protein 8 activating enzyme (NAE). In recent years, significant advancements have been made in the field of neddylation modification therapy, particularly the integration of MLN4924 with chemotherapy or targeted therapy. This combined approach has demonstrated notable success in the treatment of a variety of hematological and solid tumors. Here, we investigated the inhibitory effects of MLN4924 on neddylation and summarized the current therapeutic outcomes of MLN4924 against various tumors. In conclusion, this review provides a comprehensive, up-to-date, and thorough overview of neddylation modifications, and offers insight into the critical importance of this cellular process in tumorigenesis.
Nanomaterial-encapsulated STING agonists for immune modulation in cancer therapy
Authors: Chen Xi , Xu Zhijie , Li Tongfei , Thakur Abhimanyu , Wen Yu , Zhang Kui , Liu Yuanhong , Liang Qiuju , Liu Wangrui , Qin Jiang-Jiang , Yan Yuanliang
Published: January 2024

The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing a crucial role in improving antitumor immunity through immune effector responses. Targeting the cGAS-STING pathway holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective tumor elimination. However, systemic administration of current STING agonists faces challenges related to low bioavailability and potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed to modulate TMEs for robust immunotherapeutic responses. The encapsulation and delivery of STING agonists within nanoparticles (STING-NPs) present an attractive avenue for antitumor immunotherapy. This review explores a range of nanoparticles designed to encapsulate STING agonists, highlighting their benefits, including favorable biocompatibility, improved tumor penetration, and efficient intracellular delivery of STING agonists. The review also summarizes the immunomodulatory impacts of STING-NPs on the TME, including enhanced secretion of pro-inflammatory cytokines and chemokines, dendritic cell activation, cytotoxic T cell priming, macrophage re-education, and vasculature normalization. Furthermore, the review offers insights into co-delivered nanoplatforms involving STING agonists alongside antitumor agents such as chemotherapeutic compounds, immune checkpoint inhibitors, antigen peptides, and other immune adjuvants. These platforms demonstrate remarkable versatility in inducing immunogenic responses within the TME, ultimately amplifying the potential for antitumor immunotherapy.
Chromatographic analysis of natural dyes in mediaeval Islamic paper
Authors: Ebeid Hassan , Di Gianvincenzo Fabiana , Kralj Cigić Irena , Strlič Matija
Published: January 2024

Numerous natural dyes were used to dye mediaeval Islamic paper from the tenth to the nineteenth century, using a variety of techniques. The objective of this research is to develop an analytical method using high performance liquid chromatography with diode array detection (HPLC–DAD) to identify natural dyes in forty historical Islamic paper manuscripts from two collections. In addition, novel information was obtained from original treatises containing recipes for dyeing paper and the chronological use of dyes in dyeing mediaeval Islamic paper between the tenth and seventeenth centuries. The results show that thirty-four of the forty manuscripts examined contained dyes. Six natural dyes were detected, including henna, madder, lac, safflower, turmeric, and weld. This is the first study aimed at developing a method for determining various natural dyes in Islamic paper from a wide historical and geographical range in the mediaeval time and to fill significant gaps in the technical and historical knowledge of papermaking.
Three-dimensional velocity structure models in and around the Kathmandu Valley, Central Nepal
Authors: Koketsu Kazuki , Suzuki Haruhiko , Guo Yujia
Published: January 2024

We analyzed observations of microtremors and seismic ground motion to determine the depths of sedimentary interfaces and basement surface in the Kathmandu Valley. The results of these analyses and a reflection survey were combined to produce a data set of seismic depths for sedimentary interfaces and basement surface in the valley. Moreover, we introduced a data set of gravimetric depths, which had been produced for the basement surface from gravity observations. Because both sets of data differ in accuracy and number, we adopt the Sequential Gaussian Co-Simulation to generate the depth distributions of the sedimentary interfaces and basement surface. This method includes the cokriging approach, wherein the seismic and gravimetric depths are used as primary and secondary data, respectively. A three-dimensional velocity structure model of the Kathmandu Valley was constructed from the obtained depth distributions, which showed that the sedimentation in the valley is mainly related to the Paleo-Kathmandu Lake. Subsequently, we incorporated this model into a previous regional-scale model, and revised the latter to solve the issues of the extension of the underthrusting lithosphere and the S-wave velocity in its adjacent area.

Graphical Abstract
Performance of the double-thin-shell approach for studying nighttime medium-scale traveling ionospheric disturbances using two dense GNSS observation networks in Japan
Authors: Fu Weizheng , Otsuka Yuichi , Shinbori Atsuki , Nishioka Michi , Perwitasari Septi
Published: January 2024

Electrodynamic coupling between the ionospheric E and F regions is widely recognized as the underlying mechanism for generating medium-scale traveling ionospheric disturbances (MSTIDs) during nighttime at midlatitudes. Recently, the double-thin-shell approach has proven to be a useful tool for studying the E–F coupling. By using total electron content (TEC) measurements, this approach enables the simultaneous reconstruction of electron density perturbations in both the E and F regions with broad and continuous coverage. However, the current reconstruction performance is limited when using only GPS-TEC measurements from GEONET, a dense network of ground-based Global Navigation Satellite System (GNSS) receivers over Japan. The expansion of available data sources and the integration of multi-GNSS observation data are considered important to enhance the double-thin-shell model. Fortunately, SoftBank Corp., a Japanese telecommunications provider, has recently developed a dense independent GNSS observation network to improve positioning services. In this paper, we analyze the potential of the improved double-thin-shell approach and emphasize the importance of incorporating multi-GNSS observation data from both GEONET and SoftBank networks. The solvability analysis, simulation, and observation results collectively indicate a substantial improvement in the spatiotemporal resolution. Specifically, the longitudinal and latitudinal resolution is improved from 0.15° to 0.1° in the E region, and from 0.5° to 0.3° in the F region. The temporal resolution is also improved from 2 to 1 min. In addition, significant improvements have been achieved in the reconstruction performance, particularly for the E region under complex background conditions. Based on these assessments, we conclude that the incorporation of GEONET and SoftBank GNSS observation data holds significant potential for improving the double-thin-shell model and advancing our understanding of MSTIDs.

Graphical abstract
Enhancing child dietary diversity through cooking demonstration and nutritional education in rural Lao PDR
Authors: Sato Yu , Khamphithoun Somboun , Saiyachak Khamphanavanh , Ando Hisao , Ishizuka Takaaki , Saeki Shinjiro , Miyoshi Miki
Published: January 2024

Background

Efforts to prevent malnutrition in children under five are crucial for both short-term and long-term impact, especially in resource-constrained low- and middle-income countries, where ensuring minimal food diversity remains an urgent challenge. Our organization implemented initiatives to improve dietary diversity among children under five in rural areas of Lao People’s Democratic Republic (Lao PDR).

Methods

We carried out educational and awareness programs directed at caregivers of children aged 6–59 months. These programs were delivered by healthcare professionals and trained community volunteers in specific areas of Xaybouathong District, Khammouane Province. To evaluate the impact of our interventions, we conducted surveys both at the beginning and end of the project. We designated the Individual Dietary Diversity Score IDDS as the objective variable, serving as an indicator of child dietary diversity. Using sociodemographic and economic indicators as explanatory variables, we assessed the impact of the intervention through multivariate analysis with a generalized linear model as well as a bivariate analysis.

Results

The comparison between 210 children at baseline and 205 children at endline revealed a significant increase in IDDS among children aged 6–23 months (from 3.36 to 4.22) and children aged 24–59 months (from 3.29 to 3.83). Multivariate analysis indicated a significant association between the intervention effect (baseline vs. endline) and the village of residence. Furthermore, significant improvements were observed in each food group that constitute IDDS, including vegetables and fruits, eggs, and legumes and nuts.

Conclusions

Even in resource-limited settings, such as rural areas of Lao PDR, it is possible to improve child dietary diversity through educational approaches that encourage the utilization of locally available foods.
The gut-liver axis in hepatobiliary diseases
Authors: Ichikawa Masataka , Okada Haruka , Nakamoto Nobuhiro , Taniki Nobuhito , Chu Po-Sung , Kanai Takanori
Published: January 2024

Recent advances in the analysis of intestinal bacteria have led to reports of variations in intestinal bacterial levels among hepatobiliary diseases. The mechanisms behind the changes in intestinal bacteria in various hepatobiliary diseases include the abnormal composition of intestinal bacteria, weakening of the intestinal barrier, and bacterial translocation outside the intestinal tract, along with their metabolites, but many aspects remain unresolved. Further research employing clinical studies and animal models is expected to clarify the direct relationship between intestinal bacteria and hepatobiliary diseases and to validate the utility of intestinal bacteria as a diagnostic biomarker and potential therapeutic target. This review summarizes the involvement of the microbiota in the pathogenesis of hepatobiliary diseases via the gut-liver axis.
Early versus late diagnosis of LAMA2 congenital muscular dystrophy: a distinct consequence
Authors: Lin Chien-Heng , Lin Sheng-Shing , Hong Syuan-Yu , Chen Chieh-Ho , Chou I-Ching
Published: January 2024

Background

Laminin subunit alpha 2 (LAMA2)-related muscular dystrophy (LAMA2 MD) is caused by homozygous or compound heterozygous mutations in LAMA2 (OMIM#156225), located on chromosome 6q22.

Case presentation

We describe two patients with LAMA2 MD treated at a Taiwanese hospital. Both presented with gradual hypotonia starting in early infancy. A targeted muscular dystrophy/myopathy panel and whole-exome sequencing were used as diagnostic tools in both patients. In Patient 1, a maternally inherited variant (NM_000426.3:c.7525_7528dupCTCA/ p.Ser2510ThrfsTer3) and a paternally inherited variant (c.112 + 2 T > C) were revealed. In Patient 2, compound heterozygote mutations in LAMA2 were identified: 1) c.1583dupA(p.S529Efs*18) in exon 11, inherited paternally, and 2) c.A6931T:p.K2311X in exon 49, inherited maternally. The discovery of these four mutations enriches the genetic spectrum of LAMA2 MD.

Conclusions

We suggest that comprehensive genetic investigations be performed as early as possible in patients with suspected muscular dystrophy to provide appropriate treatment.
Seismic expression of shallow-water carbonate structures through geologic time
Authors: Badali’ Marcello
Published: January 2024

Shallow-water carbonate structures are characterized by different shapes, sizes, and identifying features, which depend, among other factors, on the age of deposition and on the carbonate factory associated with a specific geologic period. These variations have a significant impact on the imaging of these structures in reflection seismic data. This study aims at providing an overall, albeit incomplete, picture of how the seismic expression of shallow-water carbonate structures has evolved through deep time. Here, 297 shallow-water carbonate systems of different ages, spanning from Precambrian to present, with a worldwide distribution of 159 sedimentary basins, have been studied. For each epoch, representative seismic examples of shallow-water carbonate structures are described through the assessment of a selection of discriminating seismic criteria or parameters. The thinnest structures, commonly represented by ramp systems, usually occurred after mass extinction events and are mainly recognizable in seismic data through prograding clinoform reflectors. The main diagnostic seismic features of most of the thickest structures, which are found to be Precambrian, Late Devonian, Middle-Late Triassic, Middle-Late Jurassic, some Early Cretaceous presalt systems, “middle” and Late Cretaceous, Middle-Late Miocene, and Plio-Pleistocene, are steep slopes and reefal facies. Slope-basinal resedimented seismic facies are mostly observed in thick steep-slope platforms, and they are more common, except for megabreccias, in post-Triassic structures. Seismic-scale early karst-related dissolution features are mostly observed in icehouse platform deposits. Pinnacle structures and the thickest margin rims are concentrated in a few epochs, such as Middle-Late Silurian, Middle-Late Devonian, earliest Permian, Late Triassic, Late Jurassic, Late Paleocene, Middle-Upper Miocene, and Plio-Pleistocene, which are all characterized by high-efficiency reef builders.
Maternal Serum Polyols and Its Link to Gestational Diabetes Mellitus: A Population-Based Nested Case–Control Study
Authors: Li Xiaoyong , Liu Yu , Qi Yicheng , Wu Yiming , Wang Meng , Gao Jing , Su Qing , Ma Jing , Qin Li
Published: January 2024

Context

Sugar alcohols (also called polyols) are regarded as a “healthy” sugar substitute. One of the possible reasons for their safe use in pregnant women is their natural origin and the presence of polyols in maternal and fetal samples during normal human gestation. But little is known about the association between circulating sugar alcohols levels and maternal metabolic disorders during pregnancy.

Objective

We aimed to detect the concentration of the polyols in participants with and without gestational diabetes mellitus (GDM), and to investigate the association between maternal serum levels of polyols and GDM, as well as newborn outcomes.

Methods

A nested population-based case–control study was conducted in 109 women with and without GDM. Maternal concentrations of serum erythritol, sorbitol, and xylitol in the fasting state were quantified using a time of flight mass spectrometry system.

Result

In women with GDM, serum concentrations of erythritol and sorbitol were higher, but serum concentrations of xylitol were lower than those in women without GDM. Per 1-SD increment of Box–Cox-transformed concentrations of erythritol and sorbitol were associated with the increased odds of GDM by 43% and 155% (95% CI 1.07-1.92 and 95% CI 1.77-3.69), while decreased odds were found for xylitol by 25% (95% CI 0.57-1.00). Additionally, per 1-SD increase of Box–Cox-transformed concentrations of serum sorbitol was associated with a 52% increased odds of large for gestational age newborns controlling for possible confounders (95% CI 1.00-2.30).

Conclusion

Maternal circulating sugar alcohols levels during pregnancy were significantly associated with GDM. These findings provide the potential roles of polyols on maternal metabolic health during pregnancy.
Association Between Cannabis Use and Opioid Consumption, Pain, and Respiratory Complications After Surgery: A Retrospective Cohort Analysis
Authors: Ekrami Elyad , Sari Sinem , Kopac Orkun , Wang Dong , Mascha Edward J. , Stamper Samantha , Esa Wael Ali Sakr , Nair Harsha , Ruetzler Kurt , Turan Alparslan
Published: January 2024

BACKGROUND:

Cannabis is a widely used illicit drug with effects on different pain pathways. However, interactions between cannabis and postoperative pain are unclear. Cannabis smoking also affects the lungs, but the impact of cannabis use on postoperative pulmonary complications is unknown. We hypothesized that preoperative cannabis use in adults having elective surgery is associated with higher postoperative opioid consumption. Secondarily, we tested the hypothesis that cannabis use is associated with higher pain scores, hypoxemia (oxygen saturation [Spo
2]/fraction of inspired oxygen [Fio
2] ratio), and higher postoperative pulmonary complications compared to nonuse of cannabis.

METHODS:

In this retrospective study, we included adult patients who had elective surgeries at Cleveland Clinic Main Campus between January 2010 and December 2020. The exposure was use of cannabis within 30 days before surgery, and the control group never used cannabis. Patients who had regional anesthesia or chronic pain diagnosis were excluded. The primary outcome was postoperative opioid consumption; 3 secondary outcomes were time-weighted average (TWA) postoperative pain score, TWA Spo
2/Fio
2 ratio, and composite of pulmonary complications after surgery. We assessed the association between cannabis use and opioid consumption during the first 24 postoperative hours using linear regression on log-transformed opioid consumption with a propensity score–based method (inverse probability of treatment weighting [IPTW]) adjusting for confounders. We further adjusted for imbalanced confounding variables after IPTW was applied.

RESULTS:

In total, 1683 of 34,521 patients were identified as cannabis users. Cannabis use was associated with increased opioid consumption, with an adjusted ratio of geometric means (95% confidence interval [CI]) of 1.30 (1.22–1.38; P < .0001) for cannabis users versus nonusers. Secondarily, (1) cannabis use was associated with increased TWA pain score, with a difference in means of 0.57 (95% CI, 0.46–0.67; P < .0001); (2) cannabis use was not associated with TWA Spo
2/Fio
2, with an adjusted difference in means of 0.5 (95% CI, −3.1 to 4.2; P = .76); and (3) cannabis use was not associated with a collapsed composite of pulmonary complications, with estimated odds ratio of 0.90 (95% CI, 0.71–1.13; P = .34).

CONCLUSIONS:

Adult cannabis users undergoing surgeries were found to have significantly higher postoperative opioid consumption and pain scores than nonusers. Cannabis use did not have a clinically meaningful association with hypoxia or composite pulmonary complications.
What Is the Role of a Periarticular Injection for Knee Arthroplasty Patients Receiving a Multimodal Analgesia Regimen Incorporating Adductor Canal and Infiltration Between the Popliteal Artery and Capsule of the Knee Blocks? A Randomized Blinded Placebo-Controlled Noninferiority Trial
Authors: YaDeau Jacques T. , Cushner Fred D. , Westrich Geoffrey , Lauzadis Justas , Kahn Richard L. , Lin Yi , Goytizolo Enrique A. , Mayman David J. , Jules-Elysee Kethy M. , Gbaje Ejiro , Padgett Douglas E.
Published: January 2024

BACKGROUND:

Optimal analgesic protocols for total knee arthroplasty (TKA) patients remain controversial. Multimodal analgesia is advocated, often including peripheral nerve blocks and/or periarticular injections (PAIs). If 2 blocks (adductor canal block [ACB] plus infiltration between the popliteal artery and capsule of the knee [IPACK]) are used, also performing PAI may not be necessary. This noninferiority trial hypothesized that TKA patients with ACB + IPACK + saline PAI (sham infiltration) would have pain scores that were no worse than those of patients with ACB + IPACK + active PAI with local anesthetic.

METHODS:

A multimodal analgesic protocol of spinal anesthesia, ACB and IPACK blocks, intraoperative ketamine and ketorolac, postoperative ketorolac followed by meloxicam, acetaminophen, duloxetine, and oral opioids was used. Patients undergoing primary unilateral TKA were randomized to receive either active PAI or control PAI. The active PAI included a deep injection, performed before cementation, of bupivacaine 0.25% with epinephrine, 30 mL; morphine; methylprednisolone; cefazolin; with normal saline to bring total volume to 64 mL. A superficial injection of 20 mL bupivacaine, 0.25%, was administered before closure. Control injections were normal saline injected with the same injection technique and volumes. The primary outcome was numeric rating scale pain with ambulation on postoperative day 1. A noninferiority margin of 1.0 was used.

RESULTS:

Ninety-four patients were randomized. NRS pain with ambulation at POD1 in the ACB + IPACK + saline PAI group was not found to be noninferior to that of the ACB + IPACK + active PAI group (difference = 0.3, 95% confidence interval [CI], [−0.9 to 1.5], P = .120). Pain scores at rest did not differ significantly among groups. No significant difference was observed in opioid consumption between groups. Cumulative oral morphine equivalents through postoperative day 2 were 89 ± 40 mg (mean ± standard deviation), saline PAI, vs 73 ± 52, active PAI, P = .1. No significant differences were observed for worst pain, fraction of time in severe pain, pain interference, side-effects (nausea, drowsiness, itching, dizziness), quality of recovery, satisfaction, length of stay, chronic pain, and orthopedic outcomes.

CONCLUSIONS:

For TKA patients given a comprehensive analgesic protocol, use of saline PAI did not demonstrate noninferiority compared to active PAI. Neither the primary nor any secondary outcomes demonstrated superiority for active PAI, however. As we cannot claim either technique to be better or worse, there remains flexibility for use of either technique.