bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a multienzyme isothermal and lateral flow dipstick combination assay for the rapid detection of goose astrovirus II
Authors: Zhu Yinchu , Chen Liu , Xu Xin , Ye Weicheng , Ni Zheng , Huo Suxin , Hua Jionggang , Yun Tao , Yao Huochun , Wang Hongyu , Zhang Cun
Published: August 2024

Introduction

Goose astrovirus (GAstV) is a newly emerging pathogen that is currently widespread among geese, causing visceral gout and leading to substantial gosling mortalities, posing a severe threat to the waterfowl industry. GAstV II is the predominant epidemic strain, characterized by its high morbidity and mortality rate. Consequently, there is an urgent necessity to develop an effective diagnostic approach to control the dissemination of GAstV II, particularly in clinical farms with limited laboratory resources.

Methods

In this study, a novel multi-enzyme isothermal rapid amplification (MIRA) and lateral flow dipstick (LFD) combined assay was developed. Different primers designed specific targeting a highly conserved region within the viral RdRp gene for the detection of GAstV II. Primers optimized and MIRA-LFD assay analyzed its performance regarding limits of detection, specificity, and efficiency of detection.

Results

The developed MIRA amplification is conducted at a constant temperature and accomplished within 10 minutes. Subsequent naked-eye observation of the LFD strips merely takes 5 minutes. The established MIRA-LFD method exhibits high specificity, with no cross-reaction with other pathogens and attains a detection sensitivity of 1 copy/μl, which is consistent with the reverse transcription quantitative PCR (RT-qPCR) assay. Further evaluation with clinical samples indicates that the accuracy of this MIRA-LFD method correlates well with RT-qPCR for the detection of GAstV II.

Conclusion

In summary, the convenience, sensitivity, and rapidity of this newly developed detection method offer a significant advantage for on-site diagnosis of GAstV II.
Exploring extracellular vesicles in zoonotic helminth biology: implications for diagnosis, therapeutic and delivery
Authors: Qadeer Abdul , Wajid Abdul , Rafey Hafiz Abdul , Nawaz Saqib , Khan Sawar , Rahman Sajid Ur , Alzahrani Khalid J. , Khan Muhammad Zahoor , Alsabi Mohammad Nafi Solaiman , Ullah Hanif , Safi Sher Zaman , Xia Zanxian , Zahoor Muhammad
Published: August 2024

Extracellular vesicles (EVs) have emerged as key intercellular communication and pathogenesis mediators. Parasitic organisms’ helminths, cause widespread infections with significant health impacts worldwide. Recent research has shed light on the role of EVs in the lifecycle, immune evasion, and disease progression of these parasitic organisms. These tiny membrane-bound organelles including microvesicles and exosomes, facilitate the transfer of proteins, lipids, mRNAs, and microRNAs between cells. EVs have been isolated from various bodily fluids, offering a potential diagnostic and therapeutic avenue for combating infectious agents. According to recent research, EVs from helminths hold great promise in the diagnosis of parasitic infections due to their specificity, early detection capabilities, accessibility, and the potential for staging and monitoring infections, promote intercellular communication, and are a viable therapeutic tool for the treatment of infectious agents. Exploring host-parasite interactions has identified promising new targets for diagnostic, therapy, and vaccine development against helminths. This literature review delves into EVS’s origin, nature, biogenesis, and composition in these parasitic organisms. It also highlights the proteins and miRNAs involved in EV release, providing a comprehensive summary of the latest findings on the significance of EVs in the biology of helminths, promising targets for therapeutic and diagnostic biomarkers.
Effect of astragalus injection on left ventricular remodeling in HFmrEF: a systematic review and meta-analysis
Authors: Han Xu , Huang Lumei , Li Geng , Mou Xinglang , Cheng Caihong
Published: August 2024

Objectives

The aim of this meta-analysis is to evaluate the effect of astragalus injection (AI) on left ventricular remodeling (LVR) in patients with heart failure with mildly reduced ejection fraction (HFmrEF).

Methods

The randomized controlled trials (RCTs) of AI in treating HFmrEF were retrieved from 8 major English and Chinese electronic databases, up until November 30, 2023. To evaluate the methodological quality of the included studies, the Cochrane bias risk tool and the Modified Jadad Scale were employed. Stata 17.0 software was utilized for statistical analysis, sensitivity analysis, and assessment of publication bias.

Results

Ten RCTs with 995 patients (562 males and 433 females) were identified. Meta-analysis indicated that compared to conventional treatment (CT), AI significantly improved LVR, specifically increasing left ventricular ejection fraction (LVEF, MD = 4.56, 95% CI: 3.68–5.44, p < 0.00001), decreasing left ventricular end-diastolic volume (LVEDV, MD = −7.89, 95% CI: −11.13 to −4.64, p < 0.00001), left ventricular end-diastolic diameter (LVEDD, MD = −4.18, 95% CI: −5.79 to −2.56, p < 0.00001), left ventricular end-systolic volume (LVESV, MD = −8.11, 95% CI: −11.79 to −4.43, p < 0.00001), and left ventricular end-systolic diameter (LVESD, MD = −3.42, 95% CI: −4.90 to −1.93, p < 0.00001). AI also improved clinical efficacy (RR = 4.62, 95% CI: 3.11–6.88, p < 0.00001), reduced N-terminal pro-brain natriuretic peptide (NT-pro BNP, MD = −27.94, 95% CI: −43.3 to −12.36) level, without increasing the incidence of adverse reactions (RR = 1.60, 95% CI: 0.59–4.29, p = 0.35). Sensitivity analysis confirmed the reliability of the merged results, and Begg's and Egger's tests showed no significant publication bias.

Conclusion

The systematic review and meta-analysis revealed that combining AI with CT improves LVR without increasing adverse events in HFmrEF patients. However, caution is needed in interpreting the results due to limited evidence. Future high-quality RCTs are needed to support these conclusions.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42022347248].
Multifractal analysis of heart rate variability in pregnancy during sleep
Authors: Mendez Martin O. , Bianchi Anna M. , Recker Florian , Strizek Brigitte , Murguía J. S. , Reali Pierluigi , Jimenez-Cruz Jorge
Published: August 2024

Understanding the complex dynamics of heart rate variability (HRV) during pregnancy is crucial for monitoring both maternal well-being and fetal health. In this study, we use the Multifractal Detrended Fluctuations Analysis approach to investigate HRV patterns in pregnant individuals during sleep based on RR interval maxima (MM fluctuations). In addition, we study the type of multifractality within MM fluctuations, that is, if it arises from a broad probability density function or from varying long-range correlations. Furthermore, to provide a comprehensive view of HRV changes during sleep in pregnancy, classical temporal and spectral HRV indices were calculated at quarterly intervals during sleep. Our study population consists of 21 recordings from nonpregnant women, 18 from the first trimester (early-pregnancy) and 18 from the second trimester (middle-pregnancy) of pregnancy. Results. There are statistically significant differences (p-value < 0.05) in mean heart rate, rms heart rate, mean MM fluctuations, and standard deviation of MM fluctuations, particularly in the third and fourth quarter of sleep between pregnant and non-pregnant states. In addition, the early-pregnancy group shows significant differences (p-value < 0.05) in spectral indices during the first and fourth quarter of sleep compared to the non-pregnancy group. Furthermore, the results of our research show striking similarities in the average multifractal structure of MM fluctuations between pregnant and non-pregnant states during normal sleep. These results highlight the influence of different long-range correlations within the MM fluctuations, which could be primarily associated with the emergence of sleep cycles on multifractality during sleep. Finally, we performed a separability analysis between groups using temporal and spectral HRV indices as features per sleep quarter. Employing only three features after Principal Component Analysis (PCA) to the original feature set, achieving complete separability among all groups appears feasible. Using multifractal analysis, our study provides a comprehensive understanding of the complex HRV patterns during pregnancy, which holds promise for maternal and fetal health monitoring. The separability analysis also provides valuable insights into the potential for group differentiation using simple measures such as mean heart rate, rms heart rate, and mean MM fluctuations or in the transformed feature space based on PCA.
Can heart failure phenotypes be predicted by cardiac remodelling peripartum or postpartum?
Authors: Agarwal Megha , Leeson Paul , Kitt Jamie
Published: August 2024

Hypertension during pregnancy affects up to 10% of pregnancies and is associated with significant cardiovascular morbidity and mortality. In the short-term it can result in pre-eclampsia, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, or even hypertension associated acute heart failure, all of which may necessitate pre-term delivery to prevent maternal or neonatal death. In the long term, a history of gestational hypertension and pre-eclampsia significantly increases the risk of future cardiovascular disease including chronic hypertension, coronary artery disease, heart failure and stroke. This review explores our current level of knowledge of the phenotypes of heart failure, paying particular attention to those specific to women, and the role of pregnancy and non-pregnancy related risk factors in the development of this condition. We discuss why women with hypertensive pregnancy may be disproportionately affected by heart failure with preserved ejection fraction (HFpEF) and whether a unique phenotype of heart failure unique to hypertensive pregnancy exists. Finally, we explore how future cardiovascular risk may be predicted based on cardiac remodelling during or after pregnancy and suggest potential areas of further research in the field.
Application of gene expression programing in predicting the concentration of PM2.5 and PM10 in Xi’an, China: a preliminary study
Authors: Wang Xu , Zhang Kai , Han Peishan , Wang Meijia , Li Xianjun , Zhang Yaqiong , Pan Qiong
Published: August 2024

Introduction: Traditional statistical methods cannot find quantitative relationship from environmental data.

Methods: We selected gene expression programming (GEP) to study the relationship between pollutant gas and PM2.5 (PM10). They were used to construct the relationship between pollutant gas and PM2.5 (PM10) with environmental monitoring data of Xi’an, China. GEP could construct a formula to express the relationship between pollutant gas and PM2.5 (PM10), which is more explainable. Back Propagation neural networks (BPNN) was used as the baseline method. Relevant data from January 1st 2021 to April 26th 2021 were used to train and validate the performance of the models from GEP and BPNN.

Results: After the models of GEP and BPNN constructed, coefficient of determination and RMSE (Root Mean Squared Error) are used to evaluate the fitting degree and measure the effect power of pollutant gas on PM2.5 (PM10). GEP achieved RMSE of [8.7365–14.6438] for PM2.5; RMSE of [13.2739–45.8769] for PM10, and BP neural networks achieved average RMSE of [13.8741–34.7682] for PM2.5; RMSE of [29.7327–52.8653] for PM10. Additionally, experimental results show that the influence power of pollutant gas on PM2.5 (PM10) situates between −0.0704 and 0.6359 (between −0.3231 and 0.2242), and the formulas are obtained with GEP so that further analysis become possible. Then linear regression was employed to study which pollutant gas is more relevant to PM2.5 (PM10), the result demonstrates CO (SO2, NO2) are more related to PM2.5 (PM10).

Discussion: The formulas produced by GEP can also provide a direct relationship between pollutant gas and PM2.5 (PM10). Besides, GEP could model the trend of PM2.5 and PM10 (increase and decrease). All results show that GEP can be applied smoothly in environmental modelling.
Deciphering breast cancer prognosis: a novel machine learning-driven model for vascular mimicry signature prediction
Authors: Li Xue , Li Xukui , Yang Bin , Sun Songyang , Wang Shu , Yu Fuxun , Wang Tao
Published: August 2024

Background

In the ongoing battle against breast cancer, a leading cause of cancer-related mortality among women globally, the urgent need for innovative prognostic markers and therapeutic targets is undeniable. This study pioneers an advanced methodology by integrating machine learning techniques to unveil a vascular mimicry signature, offering predictive insights into breast cancer outcomes. Vascular mimicry refers to the phenomenon where cancer cells mimic blood vessel formation absent of endothelial cells, a trait associated with heightened tumor aggression and diminished response to conventional treatments.

Methods

The study’s comprehensive analysis spanned data from over 6,000 breast cancer patients across 12 distinct datasets, incorporating both proprietary clinical data and single-cell data from 7 patients, accounting for a total of 43,095 cells. By employing an integrative strategy that utilized 10 machine learning algorithms across 108 unique combinations, the research scrutinized 100 existing breast cancer signatures. Empirical validation was sought through immunohistochemistry assays, alongside explorations into potential immunotherapeutic and chemotherapeutic avenues.

Results

The investigation successfully identified six genes related to vascular mimicry from multi-center cohorts, laying the groundwork for a novel predictive model. This model outstripped the prognostic accuracy of traditional clinical and molecular indicators in forecasting recurrence and mortality risks. High-risk individuals identified by our model faced worse outcomes. Further validation through IHC assays in 30 patients underscored the model’s extensive applicability. Notably, the model unveiled varying therapeutic responses; low-risk patients might achieve greater benefits from immunotherapy, whereas high-risk patients demonstrated a particular sensitivity to certain chemotherapies, such as ispinesib.

Conclusions

This model marks a significant step forward in the precise evaluation of breast cancer prognosis and therapeutic responses across different patient groups. It heralds the possibility of refining patient outcomes through tailored treatment strategies, accentuating the potential of machine learning in revolutionizing cancer prognosis and management.
Live imaging of center of calcification formation during septum development in primary polyps of Acropora digitifera
Authors: Ohno Yoshikazu , Takahashi Anan , Tsutsumi Motosuke , Kubota Azusa , Iguchi Akira , Iijima Mariko , Mizusawa Nanami , Nakamura Takashi , Suzuki Atsushi , Suzuki Michio , Yasumoto Jun , Watabe Shugo , Sakai Kazuhiko , Nemoto Tomomi , Yasumoto Ko
Published: August 2024

Recent studies have revealed that stony corals create their extracellular skeletons via biologically controlled calcification, in which amorphous calcium carbonate (ACC), regarded as precursors of aragonite crystals, have been observed at nanoscale using electron microscopy. However, the exact mechanism by which ACC is generated, and how it contributes to skeletal growth in coral calcifying tissue, remains enigmatic. The septal skeleton of an individual polyp is composed of radially aligned plates extending upward from the aboral calcifying tissue. This structure includes microstructure known as the centers of calcification (CoC). However, despite its importance, direct in vivo observation of septal growth has not been reported. Observations under transmitted illumination using polarized light microscopy on calcifying tissue of young Acropora digitifera revealed small crystals, a few micrometers in size, that accompany subtle movements and that emerge exclusively on the inner wall of the pocket in extracellular calcifying fluid (ECF). Crystal growth initiated from small, scattered crystals on a glass plate resembles this phenomenon observed in coral skeletons. Time-lapse photographs of 12 individuals in early primary polyp settlement revealed this process in three individuals, documenting 13 of these crystal events. This phenomenon occurred solely at the bases of subsequently formed septa. These crystals differ notably from fusiform crystals and from dumbbell-like or rod-like crystals growing individually. Upright two-photon microscopy captured movement of sub-micron-sized fluorescent calcein-accumulating particles, emphasizing their presence on the surface of the growing fronts of septa. Methodological advances that facilitate comprehensive in vivo observation of sub-micron-sized structures, calcein-accumulating particles to the skeleton, are needed to develop a more detailed understanding of coral skeletal growth.
Isolation of seawater microplastics from biologically rich samples using an alkaline K2S2O8 method
Authors: Gao Nan , Kong Xiangfeng , Zhang Yanmin , Gao Yang , Zhang Yuanbiao , Liu Yan
Published: August 2024

In recent years, microplastics, especially marine microplastic pollution, have received global attention as a new type of environmental problem. The establishment of accurate and efficient methods for the detection of microplastics is the basis for in-depth research on the transport, transformation, fate, and ecotoxicological effects of microplastics in the environment. Microplastics in seawater frequently mix with biological tissues, resulting in challenges when identifying samples. However, commonly used pretreatment protocols for microplastics often suffer from long digestion times, inadequate digestion, and the risk of potentially damaging microplastics. This study compared the digestion efficiencies of five digestion reagents and provided further insights into two advanced oxidation methods involving Fenton’s reagent and an innovative alkaline K2S2O8 protocol based on sulfate and hydroxyl radicals. Using Raman spectroscopy, scanning electron microscopy-energy dispersive spectroscopy (SEM−EDS), and carbonyl index (CI) analyses, the status of microplastics after pretreatment was evaluated. The results revealed that the alkaline K2S2O8 method could enhance the reaction efficiency while reducing the potential for functional group damage during microplastic pretreatment. Moreover, the proposed K2S2O8 method was applied to the pretreatment of field seawater samples, and field microplastics were effectively separated from biologically rich samples. Thus, a digestion protocol based on alkaline K2S2O8 provides an effective way to isolate seawater microplastics from biologically rich samples. This study contributes to the development of efficiently microplastic monitoring and provides valuable insights into access to reliable data for fate and inventory of oceanic microplastics.
Preparation and property study of sawdust-modified cement mortar
Authors: Cheng Yu , Liu Jiatao , Wang Wentong , Jin Lu , Yan Shiying
Published: August 2024

Sawdust, a solid waste generated during stone processing, poses a serious threat to the environment with its untreated accumulation. This paper first analyzes the chemical composition and physical properties of sawdust, and discusses its mechanism of action in cement mortar. By systematically optimizing the blending ratio and modification method of sawdust, the sawdust-modified cement mortar with excellent performance was prepared. This study evaluates the key performance indicators of sawdust-modified cement mortar, such as compressive strength, flexural strength, and durability, through a series of experiments. The experimental results indicate that the incorporation of an appropriate amount of sawdust significantly enhances the mechanical properties of cement mortar, while also improving its durability, particularly in terms of freeze-thaw resistance. Microstructural analysis reveals the mechanism by which sawdust improves the pore structure of cement mortar; the active components in the sawdust react with the hydration products of cement, resulting in the formation of crystalline structures with higher strength.Therefore, the use of sawdust as a modifier in cement mortar can improve its mechanical properties and durability, while simultaneously reducing the accumulation of solid waste and promoting the sustainable development of building materials.
Design, motions, capabilities, and applications of quadruped robots: a comprehensive review
Authors: Majithia Ashish , Shah Darshita , Dave Jatin , Kumar Ajay , Rathee Sarita , Dogra Namrata , H. M. Vishwanatha , Chiniwar Dundesh S. , Hiremath Shivashankarayya
Published: August 2024

Robots are becoming integral to society and industries due to their enormous advantages. Among the various categories of mobile robots, including wheeled robot, tracked robot, and legged robots, the latter stands out as a better choice for most field applications due to their adaptability across various terrains. The purpose of this review is to study the locomotion capabilities of quadruped robots and judge their suitability for climbing applications as most unexplored applications of automation and robotics are required to climb. This review explores the locomotion capabilities of quadruped robots. It covers different aspects of quadruped robots like types of legs, leg design, gait patterns, and their mathematical formulations, and types of motions like omnidirectional motion and body sway motion. It also emphasizes its fault-tolerant gait, adaptability, and reliability. The paper also focuses on slope and stair climbing, outlining design requirements and applications. The study includes an examination of the applicability of various gaits under different conditions and the methods for increasing stability without compromising speed. Overall, the review serves as a valuable resource for future research in this field.
Measuring calf circumference in frail hospitalized older adults and prediction of in-hospital complications and post-discharge mortality
Authors: Canonico Silvia , Ottaviani Silvia , Tagliafico Luca , Casabella Andrea , Signori Alessio , Ponzano Marta , Marelli Cristina , Nencioni Alessio , Monacelli Fiammetta
Published: August 2024

Background

Sarcopenia, characterized by muscle mass, strength, and performance decline, significantly impacts outcomes in older adults. This study aims to assess the predictive value of calf circumference (CC), in conjunction with SARC-F and hand grip, concerning in-hospital complications and post-discharge mortality among hospitalized frail older adults.

Methods

A cohort of 158 hospitalized patients aged over 65 years underwent Comprehensive Geriatric Assessment and sarcopenia screening, including CC measurement. Multivariable regression analyses, adjusted for confounders, were conducted to assess predictive associations.

Results

The study cohort, comprising 53% males with a median age of 86 years, exhibited significant sarcopenia prevalence based on SARC-F (85% indicating sarcopenia), hand grip strength (probable sarcopenia in 77% of males and 72% of females), and CC (sarcopenia in 83%). Multivariate analysis, adjusting for age, sex, Clinical Frailty Scale (CFS), and Mini Nutritional Assessment-Short Form (MNA-SF), demonstrated associations of CC and SARC-F with in-hospital complications, while CC also showed a significant association with reduced risks of in-hospital mortality (OR 0.441, 95% CI 0.257 to 0.754, p = 0.003) and 90-day mortality (OR 0.714, 95% CI 0.516 to 0.988, p = 0.043).

Conclusion

This study provides insights into the predictive accuracy of sarcopenia screening tools on mortality in real-world hospitalized older adults with frailty. Notably, CC emerges as a robust predictor of mortality outcomes. Further research is warranted to validate and elucidate the respective contributions of CC and frailty to mortality in vulnerable populations.
Trends in the market for drug delivery devices categorized as combination drugs and medical devices and regulatory challenges for autoinjectors in Japan
Authors: Mochizuki Makiko , Maeda Hideki
Published: August 2024

Background

Although a variety of drug delivery devices have been launched in recent years, few studies have comprehensively investigated the market trends of combination drugs and medical devices approved or certified in Japan and the regulatory challenges related to their approval. Among the drug delivery devices, autoinjectors are more convenient than traditional prefilled syringes and are designed with safety features to prevent needlestick accidents, allowing self-injection by patients. Therefore, autoinjectors have been incorporated into the treatment of various diseases and have shown significant growth among drug delivery devices.

Aim

This study aimed to investigate the market trends of combination drugs approved in Japan, especially those with autoinjector formulations, and to explore the challenges in the regulatory aspects of combination drugs.

Methods

Information on the number of marketed drugs and medical devices was obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) database using specific definitions. We looked at the annual changes in the number of drug delivery devices approved and certified as combination drugs or medical devices and the number of canceled certifications. We also examined the classification and main certification criteria for Japanese medical device nomenclature.

Results

The study suggested that the number of combination drugs with autoinjector formulations is increasing, replacing previously approved or certified pen-type medication injectors. Moreover, 53% of all drug products were approved for autoinjector formulations after the initial authorization approval in Japan, and more than half of them obtained approval for additional formulations for autoinjectors within five years of the initial authorization approval, with the largest number of cases obtaining approval for additional formulations two years later.

Conclusion

The lack of clear regulatory requirements for autoinjectors may lead to confusion among applicants. Furthermore, there are challenges in filing regulatory applications, thus hindering the rapid launch of combination drug-utilizing devices with superior usability.
Genome and pan-genome analysis of a new exopolysaccharide-producing bacterium Pyschrobacillus sp. isolated from iron ores deposit and insights into iron uptake
Authors: Najjari Afef , Jabberi Marwa , Chérif Saïda Fatma , Cherif Ameur , Ouzari Hadda Imene , Linares-Pastén Javier A. , Sghaier Haitham
Published: August 2024

Bacterial exopolysaccharides (EPS) have emerged as one of the key players in the field of heavy metal-contaminated environmental bioremediation. This study aimed to characterize and evaluate the metal biosorption potential of EPS produced by a novel Psychrobacillus strain, NEAU-3TGS, isolated from an iron ore deposit at Tamra iron mine, northern Tunisia. Genomic and pan-genomic analysis of NEAU-3TGS bacterium with nine validated published Psychrobacillus species was also performed. The results showed that the NEAU-3TGS genome (4.48 Mb) had a mean GC content of 36%, 4,243 coding sequences and 14 RNA genes. Phylogenomic analysis and calculation of nucleotide identity (ANI) values (less than 95% for new species with all strains) confirmed that NEAU-3TGS represents a potential new species. Pangenomic analysis revealed that Psychrobacillus genomic diversity represents an “open” pangenome model with 33,091 homologous genes, including 65 core, 3,738 shell, and 29,288 cloud genes. Structural EPS characterization by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy showed uronic acid and α-1,4-glycosidic bonds as dominant components of the EPS. X-ray diffraction (XRD) analysis revealed the presence of chitin, chitosan, and calcite CaCO3 and confirmed the amorphous nature of the EPS. Heavy metal bioabsorption assessment showed that iron and lead were more adsorbed than copper and cadmium. Notably, the optimum activity was observed at 37°C, pH=7 and after 3 h contact of EPS with each metal. Genomic insights on iron acquisition and metabolism in Psychrobacillus sp. NEAU-3TGS suggested that no genes involved in siderophore biosynthesis were found, and only the gene cluster FeuABCD and trilactone hydrolase genes involved in the uptake of siderophores, iron transporter and exporter are present. Molecular modelling and docking of FeuA (protein peptidoglycan siderophore-binding protein) and siderophores ferrienterobactine [Fe+3 (ENT)]-3 and ferribacillibactine [Fe+3 (BB)]-3 ligand revealed that [Fe+3 (ENT)]-3 binds to Phe122, Lys127, Ile100, Gln314, Arg215, Arg217, and Gln252. Almost the same for [Fe+3 (ENT)]-3 in addition to Cys222 and Tyr229, but not Ile100.To the best of our knowledge, this is the first report on the characterization of EPS and the adsorption of heavy metals by Psychrobacillus species. The heavy metal removal capabilities may be advantageous for using these organisms in metal remediation.
Artificial intelligence applications in the diagnosis and treatment of bacterial infections
Authors: Zhang Xiaoyu , Zhang Deng , Zhang Xifan , Zhang Xin
Published: August 2024

The diagnosis and treatment of bacterial infections in the medical and public health field in the 21st century remain significantly challenging. Artificial Intelligence (AI) has emerged as a powerful new tool in diagnosing and treating bacterial infections. AI is rapidly revolutionizing epidemiological studies of infectious diseases, providing effective early warning, prevention, and control of outbreaks. Machine learning models provide a highly flexible way to simulate and predict the complex mechanisms of pathogen-host interactions, which is crucial for a comprehensive understanding of the nature of diseases. Machine learning-based pathogen identification technology and antimicrobial drug susceptibility testing break through the limitations of traditional methods, significantly shorten the time from sample collection to the determination of result, and greatly improve the speed and accuracy of laboratory testing. In addition, AI technology application in treating bacterial infections, particularly in the research and development of drugs and vaccines, and the application of innovative therapies such as bacteriophage, provides new strategies for improving therapy and curbing bacterial resistance. Although AI has a broad application prospect in diagnosing and treating bacterial infections, significant challenges remain in data quality and quantity, model interpretability, clinical integration, and patient privacy protection. To overcome these challenges and, realize widespread application in clinical practice, interdisciplinary cooperation, technology innovation, and policy support are essential components of the joint efforts required. In summary, with continuous advancements and in-depth application of AI technology, AI will enable doctors to more effectivelyaddress the challenge of bacterial infection, promoting the development of medical practice toward precision, efficiency, and personalization; optimizing the best nursing and treatment plans for patients; and providing strong support for public health safety.
RBPs: an RNA editor’s choice
Authors: Fierro-Monti Ivo
Published: August 2024

RNA-binding proteins (RBPs) play a key role in gene expression and post-transcriptional RNA regulation. As integral components of ribonucleoprotein complexes, RBPs are susceptible to genomic and RNA Editing derived amino acid substitutions, impacting functional interactions. This article explores the prevalent RNA Editing of RBPs, unravelling the complex interplay between RBPs and RNA Editing events. Emphasis is placed on their influence on single amino acid variants (SAAVs) and implications for disease development. The role of Proteogenomics in identifying SAAVs is briefly discussed, offering insights into the RBP landscape. RNA Editing within RBPs emerges as a promising target for precision medicine, reshaping our understanding of genetic and epigenetic variations in health and disease.
The association between rs6859 in NECTIN2 gene and Alzheimer’s disease is partly mediated by pTau
Authors: Rajendrakumar Aravind Lathika , Arbeev Konstantin G. , Bagley Olivia , Yashin Anatoliy I. , Ukraintseva Svetlana
Published: August 2024

Introduction

Emerging evidence suggests a connection between vulnerability to infections and Alzheimer’s disease (AD). The nectin cell adhesion molecule 2 (NECTIN2) gene coding for a membrane component of adherens junctions is involved in response to infections, and its single nucleotide polymorphism (SNP) rs6859 was significantly associated with AD risk in several human cohorts. It is unclear, however, how exactly rs6859 influences the development of AD pathology. The aggregation of hyperphosphorylated tau protein (pTau) is a key pathological feature of neurodegeneration in AD, which may be induced by infections, among other factors, and potentially influenced by genes involved in both AD and vulnerability to infections, such as NECTIN2.

Materials and methods

We conducted a causal mediation analysis (CMA) on a sample of 708 participants in the Alzheimer’s disease Neuroimaging Initiative (ADNI). The relationship between rs6859 and Alzheimer’s disease (AD), with AD (yes/no) as the outcome and pTau-181 levels in the cerebrospinal fluid (CSF) acting as a mediator in this association, was assessed. Adjusted estimates from the probit and linear regression models were used in the CMA model, where an additive model considered an increase in dosage of the rs6859 A allele (AD risk factor).

Results

The increase in dose of allele A of the SNP rs6859 resulted in about 0.144 increase per standard deviation (SD) of pTau-181 (95% CI: 0.041, 0.248, p < 0.01). When included together in the probit model, the change in A allele dose and each standard deviation change in pTau-181 predicted 6.84% and 9.79% higher probabilities for AD, respectively. In the CMA, the proportion of the average mediated effect was 17.05% and was higher for the risk allele homozygotes (AA), at 19.40% (95% CI: 6.20%, 43.00%, p < 0.01). The sensitivity analysis confirmed the evidence of a robust mediation effect.

Conclusion

This study reported a new potential causal relationship between pTau-181 and AD. We found that the association between rs6859 in the NECTIN2 gene and AD is partly mediated by pTau-181 levels in CSF. The rest of this association may be mediated by other factors. Our finding sheds light on the complex interplay between genetic susceptibility, protein aggregation, and neurodegeneration in AD. Further research, using other biomarkers, is needed to uncover the remaining mechanisms of the association between the NECTIN2 gene and AD.
Neuroprotective and anti-inflammatory properties of proteins secreted by glial progenitor cells derived from human iPSCs
Authors: Salikhova Diana I. , Shedenkova Margarita O. , Sudina Anastasya K. , Belousova Ekaterina V. , Krasilnikova Irina A. , Nekrasova Anastasya A. , Nefedova Zlata A. , Frolov Daniil A. , Fatkhudinov Timur Kh. , Makarov Andrey V. , Surin Alexander M. , Savostyanov Kirill V. , Goldshtein Dmitry V. , Bakaeva Zanda V.
Published: August 2024

Currently, stem cells technology is an effective tool in regenerative medicine. Cell therapy is based on the use of stem/progenitor cells to repair or replace damaged tissues or organs. This approach can be used to treat various diseases, such as cardiovascular, neurological diseases, and injuries of various origins. The mechanisms of cell therapy therapeutic action are based on the integration of the graft into the damaged tissue (replacement effect) and the ability of cells to secrete biologically active molecules such as cytokines, growth factors and other signaling molecules that promote regeneration (paracrine effect). However, cell transplantation has a number of limitations due to cell transportation complexity and immune rejection. A potentially more effective therapy is using only paracrine factors released by stem cells. Secreted factors can positively affect the damaged tissue: promote forming new blood vessels, stimulate cell proliferation, and reduce inflammation and apoptosis. In this work, we have studied the anti-inflammatory and neuroprotective effects of proteins with a molecular weight below 100 kDa secreted by glial progenitor cells obtained from human induced pluripotent stem cells. Proteins secreted by glial progenitor cells exerted anti-inflammatory effects in a primary glial culture model of LPS-induced inflammation by reducing nitric oxide (NO) production through inhibition of inducible NO synthase (iNOS). At the same time, added secreted proteins neutralized the effect of glutamate, increasing the number of viable neurons to control values. This effect is a result of decreased level of intracellular calcium, which, at elevated concentrations, triggers apoptotic death of neurons. In addition, secreted proteins reduce mitochondrial depolarization caused by glutamate excitotoxicity and help maintain higher NADH levels. This therapy can be successfully introduced into clinical practice after additional preclinical studies, increasing the effectiveness of rehabilitation of patients with neurological diseases.
Open Brain AI and language assessment
Authors: Themistocleous Charalambos
Published: August 2024

Neurolinguistic assessments play a vital role in neurological examinations, revealing a wide range of language and communication impairments associated with developmental disorders and acquired neurological conditions. Yet, a thorough neurolinguistic assessment is time-consuming and laborious and takes valuable resources from other tasks. To empower clinicians, healthcare providers, and researchers, we have developed Open Brain AI (OBAI). The aim of this computational platform is twofold. First, it aims to provide advanced AI tools to facilitate spoken and written language analysis, automate the analysis process, and reduce the workload associated with time-consuming tasks. The platform currently incorporates multilingual tools for English, Danish, Dutch, Finnish, French, German, Greek, Italian, Norwegian, Polish, Portuguese, Romanian, Russian, Spanish, and Swedish. The tools involve models for (i) audio transcription, (ii) automatic translation, (iii) grammar error correction, (iv) transcription to the International Phonetic Alphabet, (v) readability scoring, (vi) phonology, morphology, syntax, semantic measures (e.g., counts and proportions), and lexical measures. Second, it aims to support clinicians in conducting their research and automating everyday tasks with “OBAI Companion,” an AI language assistant that facilitates language processing, such as structuring, summarizing, and editing texts. OBAI also provides tools for automating spelling and phonology scoring. This paper reviews OBAI’s underlying architectures and applications and shows how OBAI can help professionals focus on higher-value activities, such as therapeutic interventions.
Effects of auricular stimulation on weight- and obesity-related parameters: a systematic review and meta-analysis of randomized controlled clinical trials
Authors: Hua Kevin , Usichenko Taras , Cummings Mike , Bernatik Miriam , Willich Stefan N. , Brinkhaus Benno , Dietzel Joanna
Published: August 2024

Background

Over the last three decades, the number of randomized controlled trials (RCTs) using stimulation of auricular vagal sensory nerves by means of electrical stimulation, auricular acupuncture, or acupressure to support weight loss has increased markedly. This systematic review focuses on the effects of auricular stimulation (AS) on anthropometric parameters and obesity-related blood chemistry.

Methods and analysis

The following databases were searched until November 2021: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Database. Data collection and analysis were conducted by two reviewers independently. Quality and risk assessment of included studies was performed using the risk of bias tool of the Cochrane Handbook, and the meta-analysis of the effect of the most frequently assessed biomarkers was conducted using the statistical software RevMan.

Results

The full texts of 1,274 studies were screened; 22 contained data on obesity-related outcomes, and 15 trials with 1,333 patients were included in the meta-analysis. The overall quality of the included trials was moderate. AS significantly reduced body mass index (BMI) (mean difference (MD) = −0.38 BMI points, 95% CI (−0.55 to −0.22), p < 0.0001), weight (MD = −0.66 kg, 95% CI (−1.12 to −0.20), p = 0.005), waist circumference (MD = −1.44 cm, 95% CI (−2.69 to −0.20), p = 0.02), leptin, insulin, and HOMA insulin resistance compared to controls. No significant reduction was found in body fat, hip circumference, ratio of waist/hip circumference, cholesterol, LDL, triglycerides, adiponectin, ghrelin, and glucose levels. The AS was safe throughout the trials, with only minor adverse reactions.

Conclusion

The study results suggest that a reduction of weight and BMI can be achieved by AS in obese patients; however, the size of the effect does not appear to be of clinical relevance. The effects might be underestimated due to active sham trials.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231885.
Association of gut microbiota with lactose intolerance and coeliac disease: a two-sample Mendelian randomization study
Authors: Han Zongze , Ran Ying , Li Jiwen , Zhang Xue , Yang Hui , Liu Jiangpeng , Dong Shijing , Jia Hao , Yang Zhen , Li Yanni , Guo Liping , Zhou Simin , Bao Suriguge , Yuan Wei , Wang Bangmao , Zhou Lu
Published: August 2024

Background and objectives

Lactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease.

Materials and methods

This study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane’s Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods.

Results

By employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study.

Conclusion

This study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.
Obesity prevalence, nutritional status, and physical activity levels in Turkish adults during the COVID-19 pandemic
Authors: Karaca Çelik Kezban Esen , Morales-Suárez-Varela María , Uçar Nazlı , Soriano Jose M. , İnce Palamutoğlu Merve , Baş Murat , Toprak Dilek , Hajhamidiasl Ladan , Erol Doğan Özge , Doğan Mert
Published: August 2024

Background

Although nutritional status is influenced by multidimensional aspects encompassing physical factors, there is limited research on this complex relationship.

Objectives

This study aimed to examine the interaction between physical activity level indicators and the nutritional status of adults in Türkiye.

Methods

A total of 3,970 individuals aged 18 years or older, residing in Afyonkarahisar (Türkiye), participated in this study. Data were obtained through face-to-face interviews with a questionnaire, using simple random sampling among adults. One-day food consumption was recorded using a 24-h dietary recall (24HDR). Physical activity levels were assessed using the International Physical Activity Questionnaire (IPAQ).

Results

This study comprised 3,970 participants: 2,087 (52.57%) men and 1,883 (47.42%) women. Among them, 32.64% smoked cigarettes, and 8.72% consumed alcohol. About 40% of adults were overweight, and 16.33% were obese. All participants had inadequate intake levels of potassium, calcium, and iron when compared to the recommended amounts. Physical activity levels showed a weak positive correlation with dietary energy, carbohydrates, protein, fat, and cholesterol, and a weak negative correlation with age, waist-to-hip ratio, and BMI of participants.

Conclusion

This study provides insights into the importance of addressing both physical activity and nutritional status. It was found that the weekly duration of physical activity for women was lower than for men. As a result of the nutritional status evaluation, it was found that the daily energy intake of men was higher than that of women.
Development and validation of a CT-based nomogram for accurate hepatocellular carcinoma detection in high risk patients
Authors: Liang Yingying , Wu Hongzhen , Wei Xinhua
Published: August 2024

Purpose

To establish and validate a CT-based nomogram for accurately detecting HCC in patients at high risk for the disease.

Methods

A total of 223 patients were divided into training (n=161) and validation (n=62) cohorts between January of 2017 and May of 2022. Logistic analysis was performed, and clinical model and radiological model were developed separately. Finally, a nomogram was established based on clinical and radiological features. All models were evaluated using the area under the curve (AUC). DeLong’s test was used to evaluate the differences among these models.

Results

In the multivariate analysis, gender (p = 0.014), increased Alpha-fetoprotein (AFP) (p = 0.017), non-rim arterial phase hyperenhancement (APHE) (p = 0.011), washout (p = 0.011), and enhancing capsule (p = 0.001) were the independent differential predictors of HCC. A nomogram was formed with well-fitted calibration curves based on these five factors. The area under the curve (AUC) of the nomogram in the training and validation cohorts was 0.961(95%CI: 0.935~0.986) and 0.979 (95% CI: 0.949~1), respectively. The nomogram outperformed the clinical and the radiological models in training and validation cohorts.

Conclusion

The nomogram incorporating clinical and CT features can be a simple and reliable tool for detecting HCC and achieving risk stratification in patients at high risk for HCC.