bluuebunny/crossref_metadata_2025 huggingface dataset:
Enerji Santrallerinin Sosyo-Ekonomik Yararları ve Doğaya Verdiği Zararların Karşılaştırılmalı Analizi: Neom Şehir Projesi Örneği
Authors: TAGHIYEV Ali
Published: October 2023

Çalışmanın konusu, İklim değişikliği ile mücadele kapsamında sürdürülebilir enerji kaynaklarının oluşturulması ve kullanılması ile ilgili olarak iyi proje örneklerinin incelenmesidir. Bu kapsamda “NEOM Projesi” örnek alınarak genel bir incelemede bulunulmuştur. Çalışmanın amacı, yenilenebilir enerji kaynaklarının çağımız için ne kadar önemli olduğunu kısaca ortaya koymak ve yenilenebilir enerji kaynaklarının dönüştürülmekte olan ya da dönüştürülecek olan şehirler ile ve yeni kurulan akıllı şehirlere uyarlanmasının önemini ortaya koymaktır. Ayrıca çalışma ile “Neom şehir projesi neden yapıldı?”, “Neom şehir projesi neden ayna tasarımı ile inşa edilecek?” ve “Böyle bir projeye neden ihtiyaç duyulmuştur?” gibi sorulara cevaplar sunulmuştur. Neom Projesi birçok yönü ile akıllı kentler için bir rol model olma özelliğini taşımaktadır. Günümüzde teknolojinin gelişmesiyle bu şehirlere olan ilgi her geçen gün daha da artmaktadır. Bu nedenle bu şehirlerin incelenmesi ve SWOT analizinin yapılması, yeni projelerin kurgulanmasında önemli bir veri olacaktır. Çalışmanın gerçekleştirilmesinde içerik analizi yöntemi kullanılmıştır. Neom projesi için, Neom projesinin internet sitesindeki bilgilere ulaşılarak genel bilgiler sunulmuştur. Bilgilerin daha iyi anlaşılabilmesi için enerji türleri kavramına yer verilmiş ve günümüzde dünyada en çok kullanılan enerji türleri ve nükleer santrallerin yoğun olarak kullanıldığı devletlerin istatistiksel durumu açıklanmıştır. Sonuç olarak, iklim değişikliği sorunu, dünyanın geleceği için büyük için büyük tehdittir. Bu sorunun çözümü için de yenilenebilir enerji kaynakları önemli bir unsur haline gelmiştir. Bu bağlamda yeni nesil şehirlerin kurulması ve bu şehirlerinin enerji altyapısının elektrik enerjisi gibi yenilenebilir enerji kaynaklarından oluşturulması daha yararlı olacaktır.
Implementasi IoT Pada Sistem Pembayaran di Koperasi Sekolah
Authors: Silalahi Mesri , Saragih Saut Pintubipar
Published: October 2023

Information technology has been widely adopted by numerous educational institutions, both formal and informal, based on religion or non-religious, The urgency of innovative technologi which appliable to school business processes are rising rapidly  within enormous applicable internet of Things available. The research methodology in this research conducted comprehensively. Researcher will used the technolgu of Microcontroller Esp32 to help the implementation of payment in one of the department of the research object. Developing the system within the school system will need very trmendous effort to justify the system accepted by all the stakeholder. Researcher using the srum methods in software development and using the esp32 microcontroller as the thechologu to merged within, researcher hope the capablity of Background Subtraction Algorithm on ESP32, it is elucidated that the background subtraction algorithm can be implemented on the ESP32 device. This device possesses the capability to process image frames measuring 80 x 60 pixels a total of 10,000 times within a temporal span of 2,000 milliseconds (at an approximate rate of ±5,000 frames per secondThe result of this research supposedly achieve the implementation of the microcontroller technology to provide the solution in school business unit payment processes. All the visitor to the business unit are detected with the RFID card using the microcontroller to automate the identification and enabling better transaction process flow.
DFT-assisted low-dimensional carbon-based electrocatalysts design and mechanism study: a review
Authors: Han Yun , Xu Hongzhe , Li Qin , Du Aijun , Yan Xuecheng
Published: October 2023

Low-dimensional carbon-based (LDC) materials have attracted extensive research attention in electrocatalysis because of their unique advantages such as structural diversity, low cost, and chemical tolerance. They have been widely used in a broad range of electrochemical reactions to relieve environmental pollution and energy crisis. Typical examples include hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), carbon dioxide reduction reaction (CO2RR), and nitrogen reduction reaction (NRR). Traditional “trial and error” strategies greatly slowed down the rational design of electrocatalysts for these important applications. Recent studies show that the combination of density functional theory (DFT) calculations and experimental research is capable of accurately predicting the structures of electrocatalysts, thus revealing the catalytic mechanisms. Herein, current well-recognized collaboration methods of theory and practice are reviewed. The commonly used calculation methods and the basic functionals are briefly summarized. Special attention is paid to descriptors that are widely accepted as a bridge linking the structure and activity and the breakthroughs for high-volume accurate prediction of electrocatalysts. Importantly, correlated multiple descriptors are used to systematically describe the complicated interfacial electrocatalytic processes of LDC catalysts. Furthermore, machine learning and high-throughput simulations are crucial in assisting the discovery of new multiple descriptors and reaction mechanisms. This review will guide the further development of LDC electrocatalysts for extended applications from the aspect of DFT computations.
Bone marrow vasculature advanced in vitro models for cancer and cardiovascular research
Authors: Campanile Marzia , Bettinelli Leonardo , Cerutti Camilla , Spinetti Gaia
Published: October 2023

Cardiometabolic diseases and cancer are among the most common diseases worldwide and are a serious concern to the healthcare system. These conditions, apparently distant, share common molecular and cellular determinants, that can represent targets for preventive and therapeutic approaches. The bone marrow plays an important role in this context as it is the main source of cells involved in cardiovascular regeneration, and one of the main sites of liquid and solid tumor metastasis, both characterized by the cellular trafficking across the bone marrow vasculature. The bone marrow vasculature has been widely studied in animal models, however, it is clear the need for human-specific in vitro models, that resemble the bone vasculature lined by endothelial cells to study the molecular mechanisms governing cell trafficking. In this review, we summarized the current knowledge on in vitro models of bone marrow vasculature developed for cardiovascular and cancer research.
Interpretable machine learning model for shear wave estimation in a carbonate reservoir using LightGBM and SHAP: a case study in the Amu Darya right bank
Authors: Zhang Tianze , Chai Hui , Wang Hongjun , Guo Tongcui , Zhang Liangjie , Zhang Wenqi
Published: October 2023

The shear wave velocity (Vs) is significant for quantitative seismic interpretation. Although numerous studies have proved the effectiveness of the machine learning method in estimating the Vs using well-logging parameters, the real-world application is still hindered because of the black-box nature of machine learning models. With the rapid development of the interpretable machine learning (ML) technique, the drawback of ML can be overcome by various interpretation methods. This study applies the Light Gradient Boosting Machine (LightGBM) to predict the Vs of a carbonate reservoir and uses the Shapley Additive Explanations (SHAP) to interpret the model. The application of ML in Vs estimation normally involves using conventional well-log data that are highly correlated with Vs to train the model. To expand the model’s applicability in wells that lack essential logs, such as the density and neutron logs, we introduce three geologically important features, temperature, pressure, and formation, into the model. The LightGBM model is tuned by the automatic hyperparameter optimization framework; the result is compared with the Xu-Payne rock physics model and four machine learning models tuned with the same process. The results show that the LightGBM model can fit the training data and provide accurate predictions in the test well. The model outperforms the rock physics model and other ML models in both accuracy and training time. The SHAP analysis provides a detailed explanation of the contribution of each input variable to the model and demonstrates the variation of feature contribution in different reservoir conditions. Moreover, the validity of the LightGBM model is further proved by the consistency of the deduced information from feature dependency with the geological understanding of the carbonate formation. The study demonstrates that the newly added features can effectively improve model performance, and the importance of the input feature is not necessarily related to its correlation with Vs
Sestrin2 in diabetes and diabetic complications
Authors: Zhang Xiaodan , Luo Zirui , Li Jiahong , Lin Yaxuan , Li Yu , Li Wangen
Published: October 2023

Diabetes is a global health problem which is accompanied with multi-systemic complications. It is of great significance to elucidate the pathogenesis and to identify novel therapies of diabetes and diabetic complications. Sestrin2, a stress-inducible protein, is primarily involved in cellular responses to various stresses. It plays critical roles in regulating a series of cellular events, such as oxidative stress, mitochondrial function and endoplasmic reticulum stress. Researches investigating the correlations between Sestrin2, diabetes and diabetic complications are increasing in recent years. This review incorporates recent findings, demonstrates the diverse functions and regulating mechanisms of Sestrin2, and discusses the potential roles of Sestrin2 in the pathogenesis of diabetes and diabetic complications, hoping to highlight a promising therapeutic direction.
Intermuscular adipose tissue in obesity and related disorders: cellular origins, biological characteristics and regulatory mechanisms
Authors: Zhang Ting , Li Jun , Li Xi , Liu Yanjun
Published: October 2023

Intermuscular adipose tissue (IMAT) is a unique adipose depot interspersed between muscle fibers (myofibers) or muscle groups. Numerous studies have shown that IMAT is strongly associated with insulin resistance and muscular dysfunction in people with metabolic disease, such as obesity and type 2 diabetes. Moreover, IMAT aggravates obesity-related muscle metabolism disorders via secretory factors. Interestingly, researchers have discovered that intermuscular brown adipocytes in rodent models provide new hope for obesity treatment by acting on energy dissipation, which inspired researchers to explore the underlying regulation of IMAT formation. However, the molecular and cellular properties and regulatory processes of IMAT remain debated. Previous studies have suggested that muscle-derived stem/progenitor cells and other adipose tissue progenitors contribute to the development of IMAT. Adipocytes within IMAT exhibit features that are similar to either white adipocytes or uncoupling protein 1 (UCP1)-positive brown adipocytes. Additionally, given the heterogeneity of skeletal muscle, which comprises myofibers, satellite cells, and resident mesenchymal progenitors, it is plausible that interplay between these cellular components actively participate in the regulation of intermuscular adipogenesis. In this context, we review recent studies associated with IMAT to offer insights into the cellular origins, biological properties, and regulatory mechanisms of IMAT. Our aim is to provide novel ideas for the therapeutic strategy of IMAT and the development of new drugs targeting IMAT-related metabolic diseases.
GM-CSF-activated STAT5A regulates macrophage functions and inflammation in atherosclerosis
Authors: Nagenborg Jan , Jin Han , Ruder Adele V. , Temmerman Lieve , Mees Barend , Schalkwijk Casper , Müller-Klieser Daniel , Berg Thorsten , Goossens Pieter , Donners Marjo M. P. C. , Biessen Erik A. L.
Published: October 2023

Introduction

Inhibition of STAT5 was recently reported to reduce murine atherosclerosis. However, the role of STAT5 isoforms, and more in particular STAT5A in macrophages in the context of human atherosclerosis remains unknown.

Methods and results

Here, we demonstrate reciprocal expression regulation of STAT5A and STAT5B in human atherosclerotic lesions. The former was highly upregulated in ruptured over stable plaque and correlated with macrophage presence, a finding that was corroborated by the high chromosomal accessibility of STAT5A but not B gene in plaque macrophages. Phosphorylated STAT5 correlated with macrophages confirming its activation status. As macrophage STAT5 is activated by GM-CSF, we studied the effects of its silencing in GM-CSF differentiated human macrophages. STAT5A knockdown blunted the immune response, phagocytosis, cholesterol metabolism, and augmented apoptosis terms on transcriptional levels. These changes could partially be confirmed at functional level, with significant increases in apoptosis and decreases in lipid uptake and IL-6, IL-8, and TNFa cytokine secretion after STAT5A knockdown. Finally, inhibition of general and isoform A specific STAT5 significantly reduced the secretion of TNFa, IL-8 and IL-10 in ex vivo tissue slices of advanced human atherosclerotic plaques.

Discussion

In summary, we identify STAT5A as an important determinant of macrophage functions and inflammation in the context of atherosclerosis and show its promise as therapeutic target in human atherosclerotic plaque inflammation.
NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells
Authors: Ibáñez-Navarro Marta , Fernández Adrián , Escudero Adela , Esteso Gloria , Campos-Silva Carmen , Navarro-Aguadero Miguel Ángel , Leivas Alejandra , Caracuel Beatriz Ruz , Rodríguez-Antolín Carlos , Ortiz Alejandra , Navarro-Zapata Alfonso , Mestre-Durán Carmen , Izquierdo Manuel , Balaguer-Pérez María , Ferreras Cristina , Martínez-López Joaquín , Valés-Gómez Mar , Pérez-Martínez Antonio , Fernández Lucía
Published: October 2023

Introduction

Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation.

Methods

In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells’ cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality.

Results

In vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells.

Discussion

The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.
Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte induction
Authors: Mizuno Satoru , Chuma Yasushi , Shibuya Yukihiro , Horibata Shigeo , Baba Tomoe , Yokokawa Emi , Matsuo Kazuhiro
Published: October 2023

Mycobacterium bovis bacilli Calmette-Guerin (BCG) is a licensed vaccine against tuberculosis. It requires attenuated live bacteria to be effective, possibly because actively secreted proteins play a critical role in inducing anti-tuberculosis immunity. BCG also functions as an effective adjuvant. Moreover, the effects of BCG components as adjuvants are not important as those of attenuated live BCG, which is used in cancer immunotherapy. However, the BCG secreted proteins have not been paid attention in anticancer immunity. To understand mycobacterial secreted proteins’ function, we investigate immune responses to BCG culture filtrate proteins (CFP). Here, CFP strongly induce both antigen-specific CD4+ T cells and specific CD8+ T cells, which may be functional cytotoxic T lymphocytes (CTLs). In this study, we clearly demonstrate that CFP acts as an adjuvant for CTL induction against specific co-administered proteins and propose CFP as a new protein adjuvant. The CTL response shows potent anticancer effects in mice. These findings could provide insight into the contribution of mycobacterial secreted proteins in both anticancer and antimycobacterial immunity.
Management procedure development in RFMOs offer lessons for strategic and impactful stakeholder engagement and collaboration
Authors: Wilson Ashley R. , Miller Shana K. , Galland Grantly R.
Published: October 2023

International and domestic fisheries management bodies are increasingly embracing a management procedure (MP) approach to managing their living marine resources. An added advantage of an MP approach is the opportunity for strategic and impactful engagement and collaboration among resource managers, user groups, civil society and other stakeholder groups in MP development, adoption, and implementation. We consider examples from four regional fisheries bodies (i.e., RFMOs and a multi-lateral body) where stakeholders are contributing to the development of MPs for several stocks to varying degrees. These case studies highlight differing structures and processes for open and transparent stakeholder engagement in management strategy evaluation (MSE) and MP development. We identify that one important difference between sufficient and insufficient stakeholder engagement in these cases is the presence or absence of formalised structures and processes for inclusive and open stakeholder engagement, where there are key roles for stakeholder inputs and feedback during key stages of MSE and MP development. We highlight the benefits of engaging stakeholders from the outset of the MP development process, including designing processes, agreeing on the timelines and workplan for MSE and providing inputs that can lead to the successful adoption of an appropriate MP. We then consider how stakeholder engagement may be improved in other multi-lateral regional fisheries bodies, such as the NEAFC/Northeast Atlantic coastal States management forums, as well as other relevant RFMOs.
A measurement-to-modelling approach to understand catchment-to-reef processes: sediment transport in a highly turbid estuary
Authors: Xiao Ziyu , Carlin Geoffrey , Steven Andrew D. L. , Livsey Daniel N. , Song Dehai , Crosswell Joseph R.
Published: October 2023

As sediments carried by rivers enter coastal waters, fine particles can reduce the amount of light that reaches the reef through light attenuation. The Fitzroy Estuary - Keppel Bay (FE-KB), being the second-largest source of sediments to the Great Barrier Reef (GBR) poses a significant threat to the GBR ecosystem such as coral reefs and seagrass meadows, and biogeochemical cycles that influence water clarity. While monitoring and modelling capabilities for catchment and marine settings are now well-developed and operational, a remaining key gap is to better understand and model the transport, dynamics and fate of catchment derived material through tidally influenced sections of rivers that discharge into the GBR. This study aims to reveal sediment transport in the FE-KB estuary by continuously monitoring the seasonal variability over a year-long period and build a high-resolution model to predict sediment budgets under different scenarios of physical forcing and river conditions. Multiple data sources, including field surveys, historical data, and numerical modelling were used to obtain a detailed understanding of the sediment transport processes during wet (high river flow) and dry (low-to-no river flow) seasons. The use of high-resolution bathymetry and survey data for sediment model parameterization allowed for accurate mapping of the morphological changes, while numerical modeling provided insights into the hydrodynamic and sediment transport processes in the estuary. Observation and model data confirm the existence of a Turbidity Maximum Zone (TMZ) in the FE-KB (approximately 35 – 40 km from estuary head), where the topography plays a critical role in trapping sediments. By utilizing the model, a closed sediment budget was calculated under varying flow conditions and the results were used to determine the estuarine trapping coefficient that ranges from 28% (during extreme wet condition) to 100% (during dry condition) of the total catchment loads. Morphodynamic modelling demonstrated a persistent erosion pattern in the upper reach of the FE. The lower FE and southern tidal creeks serve as a large sediment storage basin during both wet and dry seasons, and sediment is exported and deposited offshore during high river flow conditions.
Binding force of extended continental shelf limits: investigating whether Article 76(8) of UNCLOS constitutes customary international law
Authors: Mao Zhengkai , Li Xiaohan , Liu Huirong , Zhang Zhijun
Published: October 2023

International custom is considered to be the oldest and the original source of public international law. However, because it is unwritten, the identification of international custom has always been a controversial issue in the context of international law. Article 76(8) of the United Nations Convention on the Law of the Sea (UNCLOS) is the core article of the international system of laws governing the continental shelf. It stipulates the basic procedure for identifying the rights of coastal states to the continental shelf beyond 200 nautical miles (extended continental shelf, ECS) The issue of whether this paragraph constitutes customary international law is actually the question of whether the binding force of the limits of the ECS, which have been delineated based on recommendations of the Commission on the Limits of the Continental Shelf, can extend to non-parties to the UNCLOS. This study starts with the “two elements” theory of traditional customary international law and then considers its new interpretation according to modern theories. Following this, the authors provide a jurisprudential and practical exploration of whether Article 76(8) of the UNCLOS constitutes customary international law from the perspectives of how treaties are used to form customary international law, and the current delineation practices of coastal states on the ECS.
Response of sound propagation characteristics to Luzon cold eddy coupled with tide in the Northern South China Sea
Authors: Liu Yu , Zhang Xuefeng , Fu Hongli , Qian Zhiwen
Published: October 2023

The northern part of the South China Sea is a complex ocean environment with a large range of tidal waves and the stable Luzon cold eddy, which significantly influence the sound propagation characteristics through their impact on sound speed. This study uses a 3D ocean-acoustic framework consisting of MITgcm and BELLHOP ray model to investigate the coupled effects of the Luzon cold eddy and tidal waves. Firstly, the model incorporates tidal assimilation to reconstruct the hydrographic field and compute the sound speed field. Subsequently, the sound propagation in a representative region in the northern South China Sea is simulated to compare the response of sound propagation characteristics to the Luzon cold eddy only, tide only, and the coupled effect of both. The results demonstrate that the cold eddy shifts the location of the convergence zone forward by over 5 km at most. Further, it also makes the acoustic energy focus on the first few arrivals and delays the arrival time of rays by about 0.1 s. The tidal waves intensify these effects, resulting in a further increase of the forward distance of the convergence zone by 2-5 km and a delay in arrival time by 0.02 s. Sound propagation in the coupled influence of these two dynamic processes is exposed to steady perturbations from the cold eddy and spatial-temporal perturbations from tidal waves. The model in this study provides valuable insight for underwater detection and positioning in the realistic ocean environment.
Integration of digital manufacturing skills in industrial design education and its impact on small and medium enterprises
Authors: Rapitsenyane Yaone , Moalosi Richie , Sealetsa Oanthata Jester , Ruele Victor , Mosepedi Thatayaone , Matake Botumile
Published: October 2023

Manufacturing has provided growth and employment opportunities to many developed countries. Digital technologies have further enhanced these opportunities and diversified manufacturing activities. However, it has not been as successful in developing countries, such as Botswana, due to the low absorptive capacity, lagging digital infrastructure, and the slow development of people who need upskilling or an entirely new skill set. The increase in access to the Internet and the extensive adoption of information and communication technologies by manufacturing companies are driving competition and disrupting the present circumstances. This study aims to assess the digital skills students acquire when studying an industrial design programme and compare them with the skills needed by digital manufacturing small and medium enterprises. A case study was adopted for this study because it can capture the relationship among the phenomena, context, and people in the lived realities of the participants. The findings indicate an alignment of the skills students acquire during their studies with those needed by digital manufacturing small and medium enterprises. However, the level at which students are exposed to these digital manufacturing skills is skewed towards basic awareness, with very few students reporting competency in digital manufacturing skills, such as using a laser cutter, plasma cutter, 3D printing, and a router machine. The emphasis could be shifted to developing digital manufacturing skills, as this is the future of manufacturing in the fourth and fifth industrial revolutions.
Screening for latent infectious disease in patients with alopecia areata before initiating JAK inhibitors therapy: a single-center real-world retrospective study
Authors: Huang Jundong , Tan Zixin , Tang Yan , Shi Wei
Published: October 2023

Introduction

Although there is growing evidence supporting the effectiveness of Janus kinase (JAK) inhibitors in treating alopecia areata, the high rate of recurrence following drug discontinuation has led to prolonged treatment courses and raised concerns about long-term safety. In clinical practice, caution should be exercised while using JAK inhibitors for various indications, and a comprehensive pre-treatment screening.

Methods

This study presents an analysis of screening data collected from real-world settings before the initiation of Janus kinase inhibitors in patients with alopecia areata. Investigators collected retrospective medical data characterizing patients’ screening data. Data on demographic and clinical data, including age, sex, disease duration, severity of alopecia tool scale, history of prior treatment, and treatment regimen were recorded.

Results

In this cohort (N = 218), JAK inhibitors were initiated for 163 of 218 (74.8%) alopecia areata patients. The numbers of patients positive for antinuclear antibodies, hepatitis B surface antigen, hepatitis C virus antibodies, human immunodeficiency virus antibody, treponema pallidum hemagglutination assay, and thyroid-stimulating hormone were 32 (32/176), 10(10/218), 0 (0/218), 0 (0/218), 3 (3/218) and 9 (9/176), respectively. The number of patients with T-cell spot positive or imaging of the chest indicating tuberculosis was 37 (37/218).

Disccusion

Our data provide additional information on the safety profile of JAK inhibitors in patients with alopecia areata. As such, it is necessary and crucial to screen for JAK inhibitors before it is used, particularly for individuals with a high risk of tuberculosis, hepatitis B, and other infections.
Association between gut microbiota and sensorineural hearing loss: a Mendelian randomization study
Authors: Yin Qiuyuan , Shi Guolin , Zhu Lei
Published: October 2023

Background

Several recent studies speculated that the gut microbiota is associated with sensorineural hearing loss (SNHL) and proposed the concept of the gut–inner ear axis. However, the causal effect of gut microbiota on SNHL is still unknown. In this study, we performed a two-sample Mendelian randomization (MR) analysis to estimate the causal effect of gut microbiota on SNHL.

Methods

Gut microbiota data were obtained from the largest available genome-wide association study (n = 18,340) conducted by the MiBioGen consortium. The summary statistics of SNHL were obtained from the FinnGen consortium R8 release data (28,310 cases and 302,750 controls). The causal effects were estimated with inverse-variance weighted, MR-Egger, and weighted median. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be associated with SNHL in forward Mendelian randomization analysis. We then performed sensitivity analyses, including Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, cML-MA-BIC, and leave-one-out analysis, to detect heterogeneity and pleiotropy.

Results

The inverse-variance weighted results suggested that Lachnospiraceae (UCG001) had a significant protective effect against SNHL (odds ratio = 0.85, 95% confidence interval: 0.78–0.93, P = 6.99 × 10−4). In addition, Intestinimonas (odds ratio = 0.89, 95% confidence interval: 0.82–0.97, P = 8.53 × 10−3) presented a suggestively protective effect on SNHL. Rikenellaceae (RC9gutgroup) (odds ratio = 1.08, 95% confidence interval: 1.02–1.15, P = 0.01) and Eubacterium (hallii group) (odds ratio = 1.12, 95% confidence interval: 1.00–1.24, P = 0.048) suggestively increase the risk of SNHL. The results of the reverse MR analysis showed that there is no significant causal effect of SNHL on the gut microbiota. No significant heterogeneity of instrumental variables or pleiotropy was detected.

Conclusion

The evidence that the four genera mentioned above are associated with SNHL supports the hypothesis of a gut–inner ear axis. Our study provides microbial markers for the prevention and treatment of SNHL, and further studies are needed to explore the mechanisms of the gut microbiome–inner ear axis in health and diseases.
Elucidation of cold adaptation in Glaciimonas sp. PAMC28666 with special focus on trehalose biosynthesis
Authors: Shrestha Prasansah , Karmacharya Jayram , Han So-Ra , Lee Jun Hyuck , Oh Tae-Jin
Published: October 2023

Glaciimonas sp. PAMC28666, an extremophilic bacterium thriving in Antarctic soil and belonging to the Oxalobacteraceae family, represents the only complete genome of its genus available in the NCBI database. Its genome measures 5.2 Mb and comprises 4,476 genes (4,350 protein-coding and 72 non-coding). Phylogenetic analysis shows the strain PAMC28666 in a unique branch within the genus Glaciimonas, closely related to Glaciimonas alpine Cr9-12, supported by robust bootstrap values. In addition, strain PAMC28666 showed 77.08 and 23.3% ANI and DDH, respectively, with Glaciimonas sp. PCH181.This study focuses on how polar strain PAMC28666 responds to freeze–thaw conditions, Experimental results revealed a notable survival rate of 47.28% when subjected to a temperature of 15°C for a period of 10 days. Notably, two genes known to be responsive to cold stress, Trehalose 6-phosphate synthase (otsA) and Trehalose 6-phosphate phosphatase (otsB), exhibited increased expression levels as the temperature shifted from 25°C to 15°C. The upregulation of otsAB and the consequent synthesis of trehalose play pivotal roles in enhancing the cold resistance of strain PAMC28666, offering valuable insights into the correlation between trehalose production and adaptation to cold stress. Furthermore, research into this neglected cold-adapted variation, like Glaciimonas sp. PAMC28666, has the potential to shed light on how trehalose is produced in cold-adapted environments Additionally, there is potential to extract trehalose compounds from this strain for diverse biotechnological applications, including food and cosmetics, with ongoing research exploring its unique properties.
Time-varying information measures: an adaptive estimation of information storage with application to brain-heart interactions
Authors: Antonacci Yuri , Barà Chiara , Zaccaro Andrea , Ferri Francesca , Pernice Riccardo , Faes Luca
Published: October 2023

Network Physiology is a rapidly growing field of study that aims to understand how physiological systems interact to maintain health. Within the information theory framework the information storage (IS) allows to measure the regularity and predictability of a dynamic process under stationarity assumption. However, this assumption does not allow to track over time the transient pathways occurring in the dynamical activity of a physiological system. To address this limitation, we propose a time-varying approach based on the recursive least squares algorithm (RLS) for estimating IS at each time instant, in non-stationary conditions. We tested this approach in simulated time-varying dynamics and in the analysis of electroencephalographic (EEG) signals recorded from healthy volunteers and timed with the heartbeat to investigate brain-heart interactions. In simulations, we show that the proposed approach allows to track both abrupt and slow changes in the information stored in a physiological system. These changes are reflected in its evolution and variability over time. The analysis of brain-heart interactions reveals marked differences across the cardiac cycle phases of the variability of the time-varying IS. On the other hand, the average IS values exhibit a weak modulation over parieto-occiptal areas of the scalp. Our study highlights the importance of developing more advanced methods for measuring IS that account for non-stationarity in physiological systems. The proposed time-varying approach based on RLS represents a useful tool for identifying spatio-temporal dynamics within the neurocardiac system and can contribute to the understanding of brain-heart interactions.
Temporal and spectral analyses of EEG microstate reveals neural effects of transcranial photobiomodulation on the resting brain
Authors: Truong Nghi Cong Dung , Wang Xinlong , Liu Hanli
Published: October 2023

Introduction

The quantification of electroencephalography (EEG) microstates is an effective method for analyzing synchronous neural firing and assessing the temporal dynamics of the resting state of the human brain. Transcranial photobiomodulation (tPBM) is a safe and effective modality to improve human cognition. However, it is unclear how prefrontal tPBM neuromodulates EEG microstates both temporally and spectrally.

Methods

64-channel EEG was recorded from 45 healthy subjects in both 8-min active and sham tPBM sessions, using a 1064-nm laser applied to the right forehead of the subjects. After EEG data preprocessing, time-domain EEG microstate analysis was performed to obtain four microstate classes for both tPBM and sham sessions throughout the pre-, during-, and post-stimulation periods, followed by extraction of the respective microstate parameters. Moreover, frequency-domain analysis was performed by combining multivariate empirical mode decomposition with the Hilbert-Huang transform.

Results

Statistical analyses revealed that tPBM resulted in (1) a significant increase in the occurrence of microstates A and D and a significant decrease in the contribution of microstate C, (2) a substantial increase in the transition probabilities between microstates A and D, and (3) a substantial increase in the alpha power of microstate D.

Discussion

These findings confirm the neurophysiological effects of tPBM on EEG microstates of the resting brain, particularly in class D, which represents brain activation across the frontal and parietal regions. This study helps to better understand tPBM-induced dynamic alterations in EEG microstates that may be linked to the tPBM mechanism of action for the enhancement of human cognition.
Brain–computer interface treatment for gait rehabilitation in stroke patients
Authors: Sebastián-Romagosa Marc , Cho Woosang , Ortner Rupert , Sieghartsleitner Sebastian , Von Oertzen Tim J. , Kamada Kyousuke , Laureys Steven , Allison Brendan Z. , Guger Christoph
Published: October 2023

The use of Brain–Computer Interfaces (BCI) as rehabilitation tools for chronically ill neurological patients has become more widespread. BCIs combined with other techniques allow the user to restore neurological function by inducing neuroplasticity through real-time detection of motor-imagery (MI) as patients perform therapy tasks. Twenty-five stroke patients with gait disability were recruited for this study. Participants performed 25 sessions with the MI-BCI and assessment visits to track functional changes during the therapy. The results of this study demonstrated a clinically significant increase in walking speed of 0.19 m/s, 95%CI [0.13–0.25], p < 0.001. Patients also reduced spasticity and improved their range of motion and muscle contraction. The BCI treatment was effective in promoting long-lasting functional improvements in the gait speed of chronic stroke survivors. Patients have more movements in the lower limb; therefore, they can walk better and safer. This functional improvement can be explained by improved neuroplasticity in the central nervous system.
Measurement of body composition by deuterium oxide dilution technique and development of a predictive equation for body fat mass among severe neurologically impaired children
Authors: Sakamornchai Wirada , Dumrongwongsiri Oraporn , Phosuwattanakul Jeeraparn , Siwarom Sirinapa
Published: October 2023

Introduction

Neurologically impaired (NI) children are at risk of malnutrition, which consequently impacts their health and quality of life. Accurate nutrition assessment is an important step in guiding appropriate nutrition support. Conventional anthropometric measurements among NI children have some limitations. Determining body composition requires more complex equipment, which is not routinely performed. This study was conducted to evaluate the association between anthropometric parameters and body composition assessed using the deuterium dilution technique (DDT) in NI children.

Methods

A cross-sectional study enrolled severe NI children aged 1–20 years who received home enteral nutrition for at least 3 months. Weight, length, and 4-site skinfold thickness were measured. Body composition was determined using DDT following the International Atomic Energy Agency (IAEA) protocol.

Results

A total of 37 NI children (56.76% male, median age 7.2 years) were enrolled. The prevalence of underweight, stunting, and overweight were 22, 38, and 35%, respectively. Body composition analysis showed the mean (SD) of total body water (TBW) and fat mass (FM) were 10.52 (4.51) kg and 9.51 (6.04) kg, respectively. Multivariate GLM analysis showed that the factors associated with FM were age (β = 0.07 [0.05,0.08]; p < 0.001), body mass index (BMI) (β = 0.82 [0.52, 1.12]; p < 0.001), biceps skinfold thickness (BSF) (β = 0.49 [0.23,0.75]; p = 0.001), and subscapular skinfold thickness (SSF) (β = −0.24 [−0.46,0.03]; p = 0.030). A predictive equation for FM was constructed.

Conclusion

A high prevalence of malnutrition was found among severe NI children despite enteral nutrition support. Our findings showed that age, BMI, BSF, and SSF were associated with FM. The predictive equation of FM was proposed and needed to be further validated and applied to clinical practice.
The expression of Ki-67 and Glypican -3 in hepatocellular carcinoma was evaluated by comparing DWI and 18F-FDG PET/CT
Authors: Wang Xuedong , Li Lei , Wang Linjie , Chen Min
Published: October 2023

Objective

The value of DWI and 18F-FDG PET/CT in evaluating the expression of Ki-67 and GPC-3 in HCC was compared.

Materials and methods

Ninety-four patients with primary HCC confirmed by pathology were retrospectively divided into high- and low-Ki-67-expression groups and positive- and negative- GPC-3 groups. The ADC and SUVmax values of the lesions in both groups were measured. ROC curves were used to evaluate the identification efficiency of parameters with significant differences for each group of lesions, and AUCwas calculated. The combined ADC and SUVmax values were analyzed by binary logistic regression. The Delong test was used to compare the AUC values of the combined and single parameters. Pearson (in line with normal distribution) or Spearman (in line with abnormal distribution) correlation analysis was used to analyze the correlation.

Results

The ADC value of the high-Ki-67-expression group was lower than that of the low-Ki-67-expression group (P<0.05), and the SUVmax value of the high-expression group was higher than that of the low-expression group (P<0.05). The ADC value of the positive-GPC-3 group was lower than that of the negative group (P<0.0.tive group (P<0.05). The combined ADC and SUVmax values in the GPC-3 group were better than those of a single parameter (P<0.05). There was a strong negative correlation between the SUVmax value and ADC value in the Ki-67 group (R=-0.578, P<0.001) and a weak negative correlation between the SUVmax value and ADC value in the GPC-3 group (R=-0.279, P=0.006). The SUVmax value was strongly positively correlated with the Ki-67 expression index (R=0.733, P<0.001), while the ADC value was strongly negatively correlated with the Ki-67 expression index (R=-0.687, P<0.001).

Conclusion

DWI and 18F-FDG PET/CT can be used to evaluate the expression of Ki-67 and GPC-3 in HCC, and there is a certain correlation between the ADC value and SUVmax. Combined DWI and 18F-FDG PET/CT is superior to a single technique in evaluating the expression of GPC-3 in HCC patients. However, the combined model did not benefit the Ki-67 group.
Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models
Authors: Chen Xiao , Tao Zhu , Liang Yun , Ma Meng , Adah Dickson , Ding Wenting , Chen Lili , Li Xiaofen , Dai Linglin , Fanuel Songwe , Zhao Siting , Hu Wen , Wu Donghai , Duan Ziyuan , Zhou Fang , Qin Li , Chen Xiaoping , Yang Zhaoqing
Published: October 2023

Objective

Our previous studies have demonstrated that Plasmodium immunotherapy (infection) has antitumor effects in mice. However, as a new form of immunotherapy, this therapy has a weakness: its specific killing effect on tumor cells is relatively weak. Therefore, we tested whether Plasmodium immunotherapy combined with gemcitabine (Gem), a representative chemotherapy drug, has synergistic antitumor effects.

Methods

We designed subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) models to test the antitumor effect of Plasmodium chabaudi ASS (Pc) infection in combination with Gem treatment and explored its underlying mechanisms.

Results

We found that both Pc infection alone and Gem treatment alone significantly inhibited tumor growth in the subcutaneous model, and combination therapy was more effective than either monotherapy. Monotherapy only tended to prolong the survival of tumor-bearing mice, while the combination therapy significantly extended the survival of mice, indicating a significant synergistic effect of the combination. In the mechanistic experiments, we found that the combination therapy significantly upregulated E-cadherin and downregulated Snail protein expression levels, thus inhibiting epithelial-mesenchymal transition (EMT) of tumor cells, which may be due to the blockade of CXCR2/TGF-β-mediated PI3K/Akt/GSK-3β signaling pathway.

Conclusion

The combination of Pc and Gem plays a synergistic role in inhibiting tumor growth and metastasis, and prolonging mice survival in murine lung cancer models. These effects are partially attributed to the inhibition of EMT of tumor cells, which is potentially due to the blockade of CXCR2/TGF-β-mediated PI3K/Akt/GSK-3β/Snail signaling pathway. The clinical transformation of Plasmodium immunotherapy combined with Gem for lung cancer is worthy of expectation.
Perilesional edema diameter associated with brain metastases as a predictive factor of response to radiotherapy in non-small cell lung cancer
Authors: Arrieta Oscar , Bolaño-Guerra Laura Margarita , Caballé-Pérez Enrique , Lara-Mejía Luis , Turcott Jenny G. , Gutiérrez Salvador , Lozano-Ruiz Francisco , Cabrera-Miranda Luis , Arroyave-Ramírez Andrés Mauricio , Maldonado-Magos Federico , Corrales Luis , Martín Claudio , Gómez-García Ana Pamela , Cacho-Díaz Bernardo , Cardona Andrés F.
Published: October 2023

Background

Different prognostic scales exist in patients with brain metastasis, particularly in lung cancer. The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA index) for brain metastases is a powerful prognostic tool that effectively identifies patients at different risks. However, these scales do not include perilesional edema diameter (PED) associated with brain metastasis. Current evidence suggests that PED might compromise the delivery and efficacy of radiotherapy to treat BM. This study explored the association between radiotherapy efficacy, PED extent, and gross tumor diameter (GTD).

Aim

The aim of this study was to evaluate the intracranial response (iORR), intracranial progression-free survival (iPFS), and overall survival (OS) according to the extent of PED and GT.

Methods

Out of 114 patients with BM at baseline or throughout the disease, 65 were eligible for the response assessment. The GTD and PED sum were measured at BM diagnosis and after radiotherapy treatment. According to a receiver operating characteristic (ROC) curve analysis, cutoff values were set at 27 mm and 17 mm for PED and GT, respectively.

Results

Minor PED was independently associated with a better iORR [78.8% vs. 50%, OR 3.71 (95% CI 1.26–10.99); p = 0.018] to brain radiotherapy. Median iPFS was significantly shorter in patients with major PED [6.9 vs. 11.8 months, HR 2.9 (95% CI 1.7–4.4); p < 0.001] independently of other prognostic variables like the Lung-molGPA and GTD. A major PED also negatively impacted the median OS [18.4 vs. 7.9 months, HR 2.1 (95% CI 1.4–3.3); p = 0.001].

Conclusion

Higher PED was associated with an increased risk of intracranial progression and a lesser probability of responding to brain radiotherapy in patients with metastatic lung cancer. We encourage prospective studies to confirm our findings.