bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaching and recycling of NdFeB permanent magnets using ionic non-toxic hydrotropes instead of extractants
Authors: El Maangar Asmae , Fleury Clément , Pellet-Rostaing Stéphane , Zemb Thomas
Published: September 2024

We show hereby that recycling of NdFeB permanent magnets by selective leaching and precipitation is possible, using an electrolyte as hydrotrope, thus avoiding the need of any specific extractant molecules. We analyse the yield of the extractant-free process and show that the non toxic formulation of Sodium Salicylate and ethylacetate used as diluent and choosing the optimal tie-line in a ternary phase diagram allows extraction using any type of acid in the aqueous phase. Iron is well separated from rare earths and the product can be recovered directly form the fluid used in separation by oxalic acid precipitation.
Case report: Personalized triple phage-antibiotic combination therapy to rescue necrotizing fasciitis caused by Panton-Valentine leukocidin-producing MRSA in a 12-year-old boy
Authors: Van Nieuwenhuyse Brieuc , Balcaen Mathilde , Chatzis Olga , Haenecour Astrid , Derycke Emilien , Detaille Thierry , Clément de Cléty Stéphan , Boulanger Cécile , Belkhir Leïla , Yombi Jean-Cyr , De Greef Julien , Cornu Olivier , Docquier Pierre-Louis , Lentini Audrey , Menten Renaud , Rodriguez-Villalobos Hector , Verroken Alexia , Djebara Sarah , Merabishvili Maya , Griselain Johann , Pirnay Jean-Paul , Houtekie Laurent , Van der Linden Dimitri
Published: September 2024

Maximal standard-of-care (SOC) management could not stop the life-threatening progression of a necrotizing fasciitis induced by Panton-Valentine Leukocidin-producing Methicillin-Resistant Staphylococcus aureus (MRSA) in a 12-year-old boy. Multi-route phage therapy was initiated along with antibiotics against Staphylococcus aureus, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, eventually leading to full recovery with no reported adverse events.
Governance of carbon dioxide removal: an AI-enhanced systematic map of the scientific literature
Authors: Lück Sarah , Mohn Anna , Lamb William F.
Published: September 2024

Introduction

For limiting global warming to well below 2°C rapid and stringent GHG emissions reductions are required. In addition, we also need to actively remove CO2 from the atmosphere via carbon dioxide removal (CDR). This will require advances in policymaking and governance to incentivise, coordinate and regulate CDR, including strict monitoring to ensure durable, additional removals that do not compete with emission reduction efforts. While it is critical to learn from the existing evidence on CDR policy and governance, there is no overview of this dispersed body of literature right now. IPCC and other science assessments have therefore treated the subject very selectively. This work addresses this lack of overview by systematically mapping the literature assessing policy and governance dimensions of CDR.

Methods

Systematic mapping provides a comprehensive view of a research field by analysing the state of evidence, i.e. how much research is available at any point in time on which topics and geographies studied by whom, when and where. We use an AI-enhanced approach to systematic mapping, trimming down an initial set of about 30,000 documents on CDR to a set of 876 that deal with governance and policy issues.

Results

Our findings show sharply growing attention to CDR policies and governance issues over time, but with limited coverage of the Global South. Long established conventional CDR methods such as afforestation dominate the literatureparticularly in ex-post studies -with little coverage of many novel CDR methods, such as biochar or direct air carbon capture and storage. We observe a shift from an initial discussion on CDR in international agreements towards the planning and implementation phase of national and sub-national policies.

Discussion

Our map can help to inform upcoming science assessments with critical information around CDR policies and governance and might serve as a starting point for generating a rigorous knowledge base on the topic in the future.
Pediatric RVOT reconstruction with ePTFE trileaflet valved conduits: a dual-center Chinese study
Authors: Luo Kai , Zhang Qi-Liang , Zhang Xiao-Yang , Zhou Zi-Jie , Pan Yan-Jun , Zhu Zhong-Qun , Chen Qiang , Zheng Jing-Hao , He Xiao-Min , Zhang Wei
Published: September 2024

Objective

This study aims to assess the early to mid-term clinical efficacy of expanded polytetrafluoroethylene (ePTFE) trileaflet valved conduits in pediatric right ventricular outflow tract reconstruction for congenital heart disease.

Methods

We conducted a retrospective analysis of pediatric patients who underwent right ventricular outflow tract (RVOT) reconstruction using ePTFE trileaflet valved conduits at two cardiac centers in China, between January 2017 and June 2023. The main assessment criterion was the functionality of the prosthetic pulmonary valve conduit.

Results

A total of 162 pediatric patients were included, with follow-up periods ranging from 0.1 to 5 years post-discharge, and a median follow-up duration of 1 year (interquartile range: 1, 2). Three patients (1.9%) required re-operation due to conduit obstruction. During follow-up, pulmonary valve flow velocities were recorded as <3 m/s in 134 patients (82.7%), between 3 and 4 m/s in 24 patients (14.8%), and >4 m/s in 4 patient (2.5%). Mild pulmonary valve regurgitation was noted in 148 patients (91.4%), and moderate pulmonary valve regurgitation was noted in 14 patients (8.6%), with no instances of more than moderate pulmonary valve regurgitation.

Conclusion

The ePTFE trileaflet valved conduit, known for its accessibility and simplicity in manufacturing, demonstrates favorable early to mid-term clinical outcomes in pediatric RVOT reconstruction.
The user-centered design and development of a childhood and adolescent obesity Electronic Health Record tool, a mixed-methods study
Authors: Bosworth K. Taylor , Ghosh Parijat , Flowers Lauren , Proffitt Rachel , Koopman Richelle J. , Tosh Aneesh K. , Wilson Gwen , Braddock Amy S.
Published: September 2024

Background

Childhood and adolescent obesity are persistent public health issues in the United States. Childhood obesity Electronic Health Record (EHR) tools strengthen provider-patient relationships and improve outcomes, but there are currently limited EHR tools that are linked to adolescent mHealth apps. This study is part of a larger study entitled, CommitFit, which features both an adolescent-targeted mobile health application (mHealth app) and an ambulatory EHR tool. The CommitFit mHealth app was designed to be paired with the CommitFit EHR tool for integration into clinical spaces for shared decision-making with patients and clinicians.

Objectives

The objective of this sub-study was to identify the functional and design needs and preferences of healthcare clinicians and professionals for the development of the CommitFit EHR tool, specifically as it relates to childhood and adolescent obesity management.

Methods

We utilized a user-centered design process with a mixed-method approach. Focus groups were used to assess current in-clinic practices, deficits, and general beliefs and preferences regarding the management of childhood and adolescent obesity. A pre- and post-focus group survey helped assess the perception of the design and functionality of the CommitFit EHR tool and other obesity clinic needs. Iterative design development of the CommitFit EHR tool occurred throughout the process.

Results

A total of 12 healthcare providers participated throughout the three focus group sessions. Two themes emerged regarding EHR design: (1) Functional Needs, including Enhancing Clinical Practices and Workflow, and (2) Visualization, including Colors and Graphs. Responses from the surveys (n = 52) further reflect the need for Functionality and User-Interface Design by clinicians. Clinicians want the CommitFit EHR tool to enhance in-clinic adolescent lifestyle counseling, be easy to use, and presentable to adolescent patients and their caregivers. Additionally, we found that clinicians preferred colors and graphs that improved readability and usability. During each step of feedback from focus group sessions and the survey, the design of the CommitFit EHR tool was updated and co-developed by clinicians in an iterative user-centered design process.

Conclusion

More research is needed to explore clinician actual user analytics for the CommitFit EHR tool to evaluate real-time workflow, design, and function needs. The effectiveness of the CommitFit mHealth and EHR tool as a weight management intervention needs to be evaluated in the future.
Music listening in foreign language learning: perceptions, attitudes, and its impact on language anxiety
Authors: Kim Hyun-Ju , Chong Hyun Ju , Lee Mihye
Published: September 2024

The present study explored university students' perceptions and attitudes toward music listening in foreign language learning, examining its perceived supportive role in their learning process. In this study, “music listening in foreign language learning” refers to the practice of incorporating music as a background accompaniment during language study. With 200 participants from various majors, findings indicated that a majority (94.5%) frequently listened to music in general, with a preference for slow ballad, fast dance, and classical music genres for language study. Of these, 142 stated that listening to music played a beneficial role in their foreign language learning, perceiving it not just as a stress-reliever but also a valuable tool enhancing language skills. A significant correlation emerged between music listening and decreased communication apprehension from the Foreign Language Classroom Anxiety Scales (FLCAS). Hierarchical regression highlighted the individual variables like gender, age, and English proficiency as influential factors in foreign language anxiety, while frequent music listening displayed a protective, inverse relationship with such anxiety. The findings suggest foreign language proficiency demands both knowledge and emotional stability, with managing anxiety through informal practices like music listening playing a critical role. This highlights the potential for further pedagogical insights and more detailed subsequent research.
Research on the impact of digitalization on energy companies’ green transition: new insights from China
Authors: Ren Yangjun , Xia Yuening
Published: September 2024

Digitization has become a core engine for China’s energy companies to achieve green transition in a competitive marketplace. Using the panel data of China’s A-share listed energy companies, this study explores the impact of digitalization on energy companies’ green transition. The finding demonstrates that digitalization can significantly drive energy companies’ green transition. This finding remains valid following a series of robustness tests. Moreover, digitalization can indirectly enhance energy companies’ green transition by enhancing technological innovation and optimizing operational capacity. Further research demonstrates that the promoting effect of digitalization on green transition in the state-owned companies, growing and mature energy companies and companies in the east are more fully released. This research could assist policymakers and professionals in energy companies with decision-making references to promote green transition.
Establishing monarch butterfly overwintering sites for future climates: Abies religiosa upper altitudinal limit expansion by assisted migration
Authors: Sáenz-Romero Cuauhtémoc , Osuna-Vallejo Verónica , Herrejón-Calderón Patricia , Pérez-Cruz Legna A. , Joaquín-Juan M. Guadalupe , Cruzado-Vargas Ana Laura , O’Neill Gregory A. , Zacarías-Correa Ana Gabriela , Manzanilla-Quijada Gyorgy E. , Lindig-Cisneros Roberto , Blanco-García Arnulfo , Endara-Agramont Ángel R. , Lopez-Toledo Leonel
Published: September 2024

Climate change projections suggest a precarious future for the Monarch butterfly (Danaus plexippus) as the suitable climatic habitat of its exclusive overwintering host Abies religiosa (oyamel, Sacred fir, a conifer endemic to Mexico) inside the Monarch Butterfly Biosphere Reserve (MBBR) is expected to disappear by 2090. Since the upper elevation limit of A. religiosa is approximately 3,500 m and the summits of mountains within the MBBR are ca. 3,550 m, we tested the feasibility of establishing A. religiosa at four locations outside its current geographic range in the MBBR, on a geographically close volcano, Nevado de Toluca at 4000 (timberline, an extreme site), 3,800, and 3,600 m (to test species range expansion upward in elevation), and at 3400 m (a reference site, slightly lower than the upper elevation limit of A. religiosa). Using existing shrubs as nurse plants to protect the seedlings from extreme temperatures, at each site we planted five to eight populations, originating between 3,100 and 3,500 m within the MBBR. After three growing seasons in the field (6 years after sowing), we found that: (a) survival and height increment declined steeply with test site elevation; (b) even at the highest sites (3,800 and 4,000 m), survival was acceptable, at 68 and 44%, respectively, although the growth was very poor at 4000 m; (c) populations responded similarly to transfer; (d) transfer effects were best accounted for by annual dryness index; (e) to compensate for the expected 2.3°C increase in mean annual temperature or 0.009 √°Cmm−1 increase of annual dryness index from the reference period (1961–1990) to the decade centered in 2060, it would be necessary to shift populations approximately 500 m to higher elevations; and (f) upward transfers to compensate for the 2.3°C increase in mean annual temperature are expected to result in height increment and survival that are approximately 47 and 21% lower, respectively, than values expected at zero transfer distance. We conclude that the establishment of A. religiosa at 3600 and 3,800 m is feasible and that planted stands could eventually serve as overwintering sites for the Monarch butterfly under projected future climates.
Integrative multi-omics summary-based mendelian randomization identifies key oxidative stress-related genes as therapeutic targets for atrial fibrillation and flutter
Authors: Chen Shijian , Sun Junlong , Wen Wen , Chen Zhenfeng , Yu Ziheng
Published: September 2024

Background

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with substantial morbidity and mortality. Oxidative stress (OS) has been implicated in the pathogenesis of AF, suggesting that targeting OS-related genes could offer novel therapeutic opportunities. This study aimed to identify causal OS-related genes contributing to AF through a comprehensive multi-omics Summary-based Mendelian Randomization (SMR) approach.

Methods

This study integrated data from genome-wide association studies (GWAS) with methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) to explore the relationships between oxidative stress-related (OS-related) genes and AF risk. Genes associated with oxidative stress and AF were obtained from the Nielsen et al. study (discovery) and the FinnGen study (replication). The SMR analysis and HEIDI test were utilized to assess causal associations, followed by Bayesian co-localization analysis (PPH4 > 0.5) to confirm shared causal variants. Multi-omics data were employed to analyze the associations within mQTL-eQTL pathways. A two-sample MR analysis was conducted for sensitivity verification. The significance of findings was determined using a false discovery rate (FDR) < 0.05 and p_HEIDI > 0.01.

Results

At the DNA methylation level, 19 CpG sites near 7 unique genes were found to have causal effects on AF and strong co-localization evidence support (PPH4 > 0.70). At the gene expression level, six oxidative stress-related genes from eQTLGen and three from GTEx (v8), including TNFSF10, CDKN1A, ALOX15, TTN, PTK2, ALB, KCNJ5, and CASQ2, were found to have causal effects on AF in the sensitivity and co-localization analyses (PPH4 > 0.50). At the circulating protein level, both ALAD (OR 0.898, 95% CI 0.845–0.954, PPH4 = 0.67) and APOH (OR 0.896, 95% CI 0.844–0.952, PPH4 = 0.93) were associated with a lower risk of AF, and APOH was validated in the replication group. After integrating the multi-omics data between mQTL and eQTL, we identified two oxidative stress-related genes, TTN and CASQ2. The methylation of cg09915519 and cg10087519 in TTN was associated with higher expression of TTN and a lower risk of AF, which aligns with the negative effect of TTN gene expression on AF risk. TTN may play a protective role in AF.

Conclusion

This study identified several OS-related genes, particularly TTN, as having causal roles in AF, which were verified across three-omics pathways. The findings underscore the importance of these genes in AF pathogenesis and highlight their potential as therapeutic targets. The integration of multi-omics data provides a comprehensive understanding of the molecular mechanisms underlying AF, paving the way for targeted therapeutic strategies.
The potential role of purinergic signaling in cancer therapy: perspectives on anti-CD73 strategies for prostate cancer
Authors: Gardani Carla Fernanda Furtado , Diz Fernando Mendonça , Dondé Luísa Brandalise , Rockenbach Liliana , Laufer Stefan , Morrone Fernanda Bueno
Published: September 2024

Purines and pyrimidines are signaling molecules in the tumor microenvironment that affect cancer immunity. The purinergic signaling pathways have been shown to play an important role in the development and progression of cancer. CD39 and CD73 are ectonucleotidases responsible for breaking down ATP or ADP into adenosine, which regulates immunosuppression in various types of cancer. These enzymes have been studied as a potential therapeutic target in immunotherapy, and recent research suggests a correlation between ectonucleotidases and clinical outcomes in cancer.Prostate cancer is the most diagnosed cancer in men, after non-melanoma skin tumors, and is the second leading cause of death in men in the world. Despite having long survival periods, patients often receive excessive or insufficient treatment. Within this complex landscape, the adenosine/CD73 pathway plays a crucial role. Therefore, this review aims to highlight new findings on the potential role of purinergic signaling in cancer treatment and emphasizes the importance of anti-CD73 as a pharmacological strategy for prostate cancer therapy.
Cell-bound complement activation products in antiphospholipid antibody-positive patients without other systemic autoimmune rheumatic diseases
Authors: Erkan Doruk , Vega Joann , O’Malley Tyler , Concoff Andrew
Published: September 2024

The objective of this study was to analyze complement activation in antiphospholipid antibody (aPL)-positive patients without other systemic autoimmune rheumatic diseases, using C3/C4 and cell-bound complement activation products (CB-CAPs) (B-lymphocytes [BC4d], erythrocytes [EC4d], and platelets [PC4d]). Persistently aPL-positive patients with or without aPL-related clinical manifestations (thrombotic APS [TAPS], microvascular APS [MAPS], obstetric APS, thrombocytopenia [TP], and/or hemolytic anemia [HA]) were enrolled in a single center study. Blood and clinical data were collected at baseline; a subgroup of patients completed 6- or 12-month follow-up. At baseline, 4/31 (13%) patients had decreased C3/C4, while 7/29 (24%) had elevated BC4d, 11/33 (33%) EC4d, and 12/32 (38%) PC4d. Based on different aPL profiles, all patients with decreased C3/C4 or elevated BC4d, EC4d, and PC4d had triple aPL or isolated lupus anticoagulant positivity. Based on different aPL clinical phenotypes, the number of patients with strongly positive EC4d and PC4d were proportionally higher in those with MAPS/TP/HA, compared to TAPS or no APS. Compared to baseline, the frequencies of BC4d, EC4d, and PC4d positivity were not significantly different in the subgroup of patients during their 6- or 12-month follow-up. There was a weak correlation between C3/C4 and CB-CAPs, especially for PC4d. In summary, complement activation in aPL-positive patients varies based on aPL profiles and clinical phenotypes. Given the higher percentage of aPL-positive patients with abnormal CB-CAPs, compared to C3/C4, and the poor inverse correlation between CB-CAPs and C3/C4, our study generates the hypothesis that CB-CAPs have a role in assessing disease activity and thrombosis risk in aPL-positive patients.
From single-cell to spatial transcriptomics: decoding the glioma stem cell niche and its clinical implications
Authors: Cao Lei , Lu Xu , Wang Xia , Wu Hao , Miao Xiaye
Published: September 2024

Background

Gliomas are aggressive brain tumors associated with a poor prognosis. Cancer stem cells (CSCs) play a significant role in tumor recurrence and resistance to therapy. This study aimed to identify and characterize glioma stem cells (GSCs), analyze their interactions with various cell types, and develop a prognostic signature.

Methods

Single-cell RNA sequencing data from 44 primary glioma samples were analyzed to identify GSC populations. Spatial transcriptomics and gene regulatory network analyses were performed to investigate GSC localization and transcription factor activity. CellChat analysis was conducted to infer cell-cell communication patterns. A GSC signature (GSCS) was developed using machine learning algorithms applied to bulk RNA sequencing data from multiple cohorts. In vitro and in vivo experiments were conducted to validate the role of TUBA1C, a key gene within the signature.

Results

A distinct GSC population was identified, characterized by high proliferative potential and an enrichment of E2F1, E2F2, E2F7, and BRCA1 regulons. GSCs exhibited spatial proximity to myeloid-derived suppressor cells (MDSCs). CellChat analysis revealed an active MIF signaling pathway between GSCs and MDSCs. A 26-gene GSCS demonstrated superior performance compared to existing prognostic models. Knockdown of TUBA1C significantly inhibited glioma cell migration, and invasion in vitro, and reduced tumor growth in vivo.

Conclusion

This study offers a comprehensive characterization of GSCs and their interactions with MDSCs, while presenting a robust GSCS. The findings offer new insights into glioma biology and identify potential therapeutic targets, particularly TUBA1C, aimed at improving patient outcomes.
Effects of temperature and storage duration on quality of an insect artificial diet
Authors: Ho Khanh-Van , Hibbard Bruce E. , Vella Michael G. , Shelby Kent S. , Huynh Man P.
Published: September 2024

Artificial diets are widely used to produce insects for research and education programs. Completed diets, in which the diets are fully made from individual ingredients and ready to use, often have high water activity, making them vulnerable to degradation. Proper storage is critical to maintaining diet quality, yet the storage conditions are not well investigated. In this study, we characterized the effects of storage conditions (temperatures and storage duration) on the quality of a diet capable of rearing both specialist and generalist insect species. The completed diet, produced by both private industry and a USDA-Agricultural Research Service laboratory, was exposed to varying temperatures during a 24-hour transit over 1600 km. After transit, it was stored at 4°C for a total storage period of 28 days. In a separate experiment, the completed diet was stored immediately after diet production at five fixed temperatures (-20, 4, 22, 25, and 33°C) for up to 28 days. For both experiments, at 5 intervals after storage (1, 7, 14, 21, and 28 days), diet quality was accessed by life history parameters (survival, molting, and weight) of western corn rootworm (Diabrotica virgifera virgifera LeConte) larvae, the most serious maize pest in the United States. Our results showed that exposure to varying temperatures between -2°C and 27°C for 24 hours had no significant impact on diet quality. However, extended storage (beyond 24 hours) at any of the fixed temperatures negatively affected diet quality. Insects reared on diets stored for over 24 hours at fixed temperatures ranging from -20°C to 33°C had significant declines in performance. Among the tested temperatures, -20°C and 4°C were found to be the most effective for preserving diet quality. At these low temperatures, there were no significant changes in insect weight and survival for diets stored within 21 and 28 days, respectively, though molting was significantly reduced within 7 days of storage. These findings provide the base of information on the storage conditions for completed diets, supporting the production of healthy insects.
Seawater temperature drives the diversity of key cyanobacteria (Synechococcus and Prochlorococcus) in a warming sea
Authors: Coello-Camba Alexandra , Agustí Susana
Published: September 2024

The picocyanobacteria genera Prochlorococcus and Synechococcus play a significant role globally, dominating the primary production in warm and oligotrophic tropical and subtropical areas, which represent the largest oceanic ecosystem. Genomic studies have revealed high microdiversity within these genera. It is anticipated that ocean warming may cause decreased biodiversity in marine tropical areas, as increasing temperatures may lead to the development of a new thermal niche in these regions. Thus, our study aimed to characterize the microdiversity of picocyanobacteria in the Red Sea, one of the warmest oligotrophic seas on the planet, which is experiencing warming at a rate that exceeds the global average. We identified picocyanobacteria microdiversity in the open waters of the Eastern Red Sea basin, where seawater temperatures ranged from 22.2 to 32.4°C throughout the water column (from surface to 160 m depth). Both Prochlorococcus and Synechococcus populations were characterized to deep taxonomic levels, applying amplicon sequencing targeting the petB gene, revealing up to 15 different (sub)clades. Synechococcus dominated the basin, representing an average of 68.8% of the total reads assigned to both cyanobacteria. The subclade Synechococcus IIa and Prochlorococcus clade HLII were ubiquitous in the water column of the Eastern Red Sea basin, representing 73% and 56% of the Synechococcus and Prochlorococcus assigned reads, respectively. Maximum cyanobacteria richness was observed at approximately 27.5°C, declining at higher and lower temperatures (polynomial fit, R2 = 0.2, p<0.0001). Synechococcus IIa dominated in the warmest surface waters (>30°C) of the Red Sea, displacing other (sub)clades to more saline and nutrient-poor waters, thereby reducing community diversity (polynomial fit, R2 = 0.77, p<0.0001). Our study contributes to identifying changes in picocyanobacterial diversity when exposed to temperatures exceeding current oceanic thermal limits, through the analysis of Red Sea communities already inhabiting such higher-temperature niches.
Considerations on the basis of medical reasoning for the use in AI applications
Authors: Koumpis Adamantios , Graefe Adam S. L.
Published: September 2024

This study discusses the integration of artificial intelligence (AI) and machine learning (ML) in medical reasoning and decision-making, with a focus on the challenges and opportunities associated with the massive consumption of data required for training AI systems, and contrasts this with the limited data typically available to medical practitioners. We advocate for a balanced approach that includes small data and emphasize the importance of maintaining the art of clinical reasoning amid technological advancements. Finally, we highlight the potential of multidisciplinary research in addressing the complexities of medical reasoning and suggest the necessity of careful abstraction and conceptual modeling in AI applications.
Signaling pathways that activate hepatic stellate cells during liver fibrosis
Authors: Zhang Youtian , Ren Long , Tian Yinting , Guo Xiaohu , Wei Fengxian , Zhang Yawu
Published: September 2024

Liver fibrosis is a complex process driven by various factors and is a key feature of chronic liver diseases. Its essence is liver tissue remodeling caused by excessive accumulation of collagen and other extracellular matrix. Activation of hepatic stellate cells (HSCs), which are responsible for collagen production, plays a crucial role in promoting the progression of liver fibrosis. Abnormal expression of signaling pathways, such as the TGF-β/Smads pathway, contributes to HSCs activation. Recent studies have shed light on these pathways, providing valuable insights into the development of liver fibrosis. Here, we will review six signaling pathways such as TGF-β/Smads that have been studied more in recent years.
Antibacterial activity and mechanism of Stevia extract against antibiotic-resistant Escherichia coli by interfering with the permeability of the cell wall and the membrane
Authors: Chen Xu , Yi Lan-Kun , Bai Yu-Bin , Cao Ming-Ze , Wang Wei-Wei , Shang Zi-Xuan , Li Jia-Jing , Xu Mei-Li , Wu Li-Fei , Zhu Zhen , Zhang Ji-Yu
Published: September 2024

Natural plant-derived compounds with broad-spectrum antimicrobial activity have become an effective strategy against multidrug-resistant bacteria. The present study was designed to compare the antibacterial activity of six chlorogenic acid (CA) isomers extracted from stevia and investigated the underlying antibacterial mechanisms involved. The results indicated that isochlorogenic acid C (ICAC) exhibited the strongest antibacterial activity against the tested bacteria, especially E. coli, at a 2 mg/mL minimum inhibitory concentration (MIC) and 8 mg/mL minimum bactericidal concentration (MBC). At the MBC, ICAC inhibited 72.66% of the clinical multidrug-resistant strains. Scanning electron microscopy (SEM) revealed that ICAC induced considerable morphological alterations in E. coli ATCC25922 and C4E2. The significant increase in the activity of extracellular alkaline phosphatase (AKP) indicated that ICAC damages the permeability of the bacterial cell wall. Additionally, the intracellular membrane (IM) permeability and the content of lipopolysaccharide (LPS), a main component of the outer membrane (OM), were determined. The significant decrease in LPS content and increased leakage of intracellular proteins and K+ from E. coli indicated that ICAC could induce the exfoliation of OM and disrupt IM permeability, resulting in the loss of barrier function. The uptake of propidium iodide (PI), a compromised cell membrane nucleic acid stain, and confocal laser scanning microscopy (CLSM) further demonstrated that ICAC disrupted IM integrity. Moreover, the bactericidal effect and damage to bacterial microstructural function occurred in a dose-dependent manner. These data demonstrate that ICAC has excellent antibacterial activity and is a promising approach for overcoming the antibiotic resistance of pathogenic bacteria.
Insight into the emerging insect to human pathogen Photorhabdus revealing geographic differences in immune cell tropism
Authors: Addison Max , Hapeshi Alexia , Wong Zi Xin , Connolly John E. , Waterfield Nicholas Robin
Published: September 2024

Background

Photorhabdus asymbiotica is a species of the insect pathogenic Photorhabdus genus that has been isolated as an etiological agent in human infections. Since then, multiple isolates have been identified worldwide; however, actual clinical infections have so far only been identified in North America, Australia, and Nepal. Previous research on the clinical isolates had shown that the strains differed in their behaviour when infecting cultured human cells.

Methods

In this study, we investigate the differences between the pathogenic activities of P. asymbiotica isolates from different geographic locations. Pathogenicity was analysed using infection assays with both cultured cell lines (THP-1, CHO, and HEK cells) and primary immune cells, and peripheral blood mononuclear cells (PBMCs) isolated from human blood.

Results

Here, we present the findings from the Australian (Kingscliff) and North American (ATCC43949) clinical isolates, and non-clinical soilborne nematode isolates from Thailand (PB68) and Northern Europe (HIT and JUN) of P. asymbiotica. We also show the first findings from a new clinical isolate of P. luminescens (Texas), the first non-asymbiotica species to cause a human infection, confirming its ability to infect and survive inside human immune cells.

Conclusion

Here for the first time, we show how P. asymbiotica selectively infects certain immune cells while avoiding others and that infectivity varies depending on growth temperature. We also show that the tropism varies depending on the geographic location a strain is isolated from, with only the European HIT and JUN strains lack the ability to survive within mammalian cells in tissue culture.
Multidrug-resistant tuberculosis clusters and transmission in Taiwan: a population-based cohort study
Authors: Liu Kuang-Hung , Xiao Yu-Xin , Jou Ruwen
Published: September 2024

Introduction

Multidrug-resistant tuberculosis (MDR-TB) remains a challenge in the TB program of Taiwan, where 0.5% of new cases and 2.1% of previously treated cases were resistant to at least rifampin (RIF) and isoniazid (INH). Since >80% of our MDR-TB are new cases, genotyping of MDR Mycobacterium tuberculosis is implemented to facilitate contact investigation, cluster identification, and outbreak delineation.

Methods

This is a population-based retrospective cohort study analyzing MDR-TB cases from 2019 to 2022. Whole genome sequencing (WGS) was performed using the Illumina MiSeq and analyzed using the TB Profiler. A single nucleotide polymorphism (SNP) threshold of ≤ 12 and phylogenetic methods were used to identify putative transmission clusters. An outbreak was confirmed using genomic data and epidemiologic links.

Results

Of the 297 MDR-TB cases, 246 (82.8%), 45 (15.2%), and 6 (2.0%) were simple MDR, extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), respectively. The sublineage 2.2 modern Beijing was the predominant (48.8%) MDR-TB strain in Taiwan. Phylogenetic analysis identified 25.3% isolates in 20 clusters, with cluster sizes ranging from 2 to 13 isolates. Nevertheless, only 2 clusters, one household and one community, were confirmed as outbreaks. In this study, we found that males had a higher risk of MDR-TB transmission compared to females, and those infected with the sublineage 2.1-proto-Beijing genotype isolates were at a higher risk of transmission. Furthermore, 161 (54.2%) isolates harbored compensatory mutations in the rpoC and non-rifampicin resistant determinant region (non-RRDR) of the rpoB gene. MDR-TB strains containing rpoB S450L and other compensatory mutations concurrently were significantly associated with clusters, especially the proto-Beijing genotype strains with the compensatory mutation rpoC E750D or the modern Beijing genotype strains with rpoC D485Y/rpoC E1140D.

Discussion

Routine and continuous surveillance using WGS-based analysis is recommended to warn of risks and delineate transmission clusters of MDR-TB. We proposed the use of compensatory mutations as epidemiological markers of M. tuberculosis to interrupt putative MDR-TB transmission.
Unlocking the potential of Kluyveromyces marxianus in the definition of aroma composition of cheeses
Authors: Perpetuini Giorgia , Rossetti Alessio Pio , Rapagnetta Arianna , Tofalo Rosanna
Published: September 2024

Introduction

The cheese microbiota is very complex and is made up of technologically-relevant, spoilage, opportunistic and pathogenic microorganisms. Among them lactic acid bacteria and yeasts are the main ones. One of the most interesting dairy yeasts is Kluyveromyces marxianus because of its technological properties including the ability to produce aroma compounds.

Methods

This study investigated the contribution of Kluyveromyces marxianus to the gross composition and aroma profile of cow cheeses. Experimental cheeses were prepared by inoculating a co-culture of K. marxianus FM09 and a commercial strain of Lacticaseibacillus casei and compared with cheeses obtained with only L. casei. The gross composition was determined by a FoodScan™ 2 Dairy Analyser, and free amino acids were evaluated at 507 nm after reaction with Cd-ninhydrin. The volatile organic compounds were extracted by head-space solid phase micro-extraction and analyzed by gas chromatography–mass spectrometry coupled with odor activity values. qRT-PCR was applied to determine the expression of genes involved in esters synthesis and degradation.

Results

The inoculation of K. marxianus induced an increase of pH and a reduction of protein content of cheeses, in agreement with the stronger proteolysis detected in these cheeses. K. marxianus influenced the content of aroma compounds both quantitatively and qualitatively. In particular, an increase of higher alcohols, esters and organic acids was observed. Moreover, 12 compounds were detected only in cheeses obtained with the co-culture. These differences were in agreement with the odor activity values (OAV). In fact, only 11 compounds showed OAV > 1 in cheeses obtained with the commercial strain, and 24 in those obtained with the co-culture. The qPCR analysis revealed an over expression of ATF1, EAT1, and IAH1 genes.

Conclusion

Kluyveromyces marxianus could act as an important auxiliary starter for cheese production through the development and diversification of compounds related to flavor in short-aged cow cheeses.
Sex differences in glutamate transmission and plasticity in reward related regions
Authors: Kniffin Alyssa R. , Briand Lisa A.
Published: September 2024

Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation.
Combinatorial protection of cochlear hair cells: not too little but not too much
Authors: Kurabi Arwa , Pak Kwang , Lee Eun Jung , Ryan Allen F.
Published: September 2024

Background

A number of drugs are toxic to the cochlear sensory cells known as hair cells (HCs), resulting in hearing loss. Treatment with survival-promoting growth factors, antioxidants, and inhibitors of cell death pathways or proteinases have been shown to reduce HC damage in in vivo and/or in vitro animal models. Conversely, translation to humans has often been disappointing. This may be due to the complexity of intracellular damage processes. We hypothesized that combining treatments targeting different cellular processes would be more effective.

Methods

Using an in vitro model of gentamicin ototoxicity for murine cochlear hair cells, we screened all 56 possible combinations of inhibitors targeting five different cell damage mechanisms, plus the activator of one cell survival pathway, each of which have been shown to be singly effective in preventing HC loss in experimental studies. A high dose of gentamicin (200 μM) was used over three days in culture. All compounds were added at a dosage below that required for significant protection in the assay, and only this single dose was then employed. This was done so that we could more easily detect interactive, as opposed to additive, effects.

Results

Increasing protection of hair cells was observed as combinations of compounds were increased from two to four factors, although not all combinations were equally protective. The optimal combination of four compounds consisted of an anti-oxidant, an apoptosis inhibitor, an autophagy inhibitor and a protective growth factor. Increasing the number of factors to five or six resulted in decreased protection.

Conclusion

The results support the hypothesis that targeting multiple cellular damage or survival pathways provides more an effective hair cell protection approach. The results help to identify critical interactions among the cellular processes that operate in gentamicin ototoxicity. They also suggest that inhibiting too many biological processes impairs functions critical to HC survival, resulting in decreased protection.
Association between hypertension requiring medication and postoperative 30-day mortality in adult patients with tumor craniotomy: an analysis of data using propensity score matching
Authors: Liu Yufei , Hu Haofei , Zheng Wenjian , Deng Zhong , Yang Jihu , Zhang Xiejun , Li Zongyang , Chen Lei , Chen Fanfan , Ji Nan , Huang Guodong
Published: September 2024

Background

Reliable quantification of the association between hypertension requiring medication and postoperative 30-day mortality in adult patients who undergo craniotomy for tumor resection is limited. We aimed to explore the associations between these factors.

Materials and methods

This work was a retrospective cohort study that used propensity score matching (PSM) among 18,642 participants from the American College of Surgeons National Surgical Quality Improvement Program database between 2012 and 2015. Hypertension requiring medication and postoperative 30-day mortality were the independent and dependent target variables, respectively. PSM was conducted via nonparsimonious multivariate logistic regression to balance the confounders. Robust estimation methods were used to investigate the association between hypertension requiring medication and postoperative 30-day mortality.

Results

A total of 18,642 participants (52.6% male and 47.4% female) met our inclusion criteria; 7,116 (38.17%) participants with hypertension required medication and had a 3.74% mortality rate versus an overall mortality rate of 2.46% in the adult cohort of patients who underwent craniotomy for tumor resection. In the PSM cohort, the risk of postoperative 30-day mortality significantly increased by 39.0% among patients with hypertension who required medication (OR = 1.390, 95% confidence interval (CI): 1.071–1.804, p = 0.01324) after adjusting for the full covariates. Compared with participants without hypertension requiring medication, those with hypertension requiring medication had a 34.0% greater risk of postoperative 30-day mortality after adjusting for the propensity score (OR = 1.340, 95% CI: 1.040–1.727, p = 0.02366) and a 37.6% greater risk of postoperative 30-day mortality in the inverse probability of treatment weights (IPTW) cohort (OR = 1.376, 95% CI: 1.202, 1.576, p < 0.00001).

Conclusion

Among U.S. adult patients undergoing craniotomy for tumor resection, hypertension requiring medication is a notable contributor to 30-day mortality after surgery, with odds ratios ranging from 1.34 to 1.39.
The examination of detrusor underactivity in multiple system atrophy
Authors: Yamamoto Tatsuya , Sakakibara Ryuji , Uchiyama Tomoyuki , Kuwabara Satoshi
Published: September 2024

Aims

The urinary dysfunction in multiple system atrophy (MSA) is characterized by large post-void residuals (PVR) due to impaired bladder contractility. However, the evaluations of bladder contractility are not well validated in MSA. Because the bladder contractility index can be generally represented as Pdet Qmax (detrusor pressure at maximum urinary flow rate) + kQmax (maximum urinary flow rate), we aim to examine which “k” value is suitable for representing bladder contractility concerning its correlations to PVR and voided percentage (VOID%).

Methods

We retrospectively reviewed 133 patients with MSA (74 males, 59 females, mean disease duration 3.2 years) who underwent an urodynamic study. We calculated bladder contractility using the formula PIPk = Pdet Qmax + kQmax by increasing the “k” value from 0.1 to 10 by increments of 0.1. We calculated the correlations between each PIPk (k = 0.1–10.0) and PVR and VOID%.

Results

The correlational coefficients between PIPk and VOID% were larger than those between PIPk and PVR. The correlational coefficients between PIPk and VOID% reached a plateau level at a “k” value >5.0 in male patients, suggesting that currently used formulas such as Pdet Qmax + 5Qmax for males might be appropriate for male MSA patients. However, the correlational coefficients between PIPk and VOID% reached a plateau level in female patients when the “k” values were >6.0, which might overestimate bladder contractility in female patients.

Conclusion

Although currently used formulas such as Pdet Qmax + 5Qmax might be appropriate for male MSA patients, formulas for female patients need further evaluation.
Undernutrition and associated factors among school-age children in Wolaita Zone, South Ethiopia: a comparative cross-sectional study
Authors: Meskele Dereje Kutafo , Abiso Temesgen Lera , Belete Tinsae Bekele , Koyira Mengistu Meskele , Dake Samson Kastro
Published: September 2024

Background

Nutritional deficiencies in school-age children are a public health concern, especially in resource-limited countries. A school feeding program involves the provision of food on-site or taken home to reduce hunger. It is implemented in several developing nations; however, little is known about the association of school feeding programs with the nutritional status of school-age children in the study area.

Objectives

The study aimed to determine the magnitudes and associated factors of undernutrition among school-age children with school feeding programs (SFPs) and non-school feeding programs (N-SFPs) in Kindo Didaye woreda, South Ethiopia.

Methods

A school-based comparative cross-sectional study was conducted in Kindo Didaye district from May to June 2023. A total of 612 participants were included in the study. The data were collected from each selected student's parents by using a structured interviewer-administered questionnaire. The weight and height of the children were measured, and a household dietary diversity assessment was conducted. The data were analyzed using SPSS version 25. A binary logistic regression analysis was carried out. A p-value of <0.05 and 95% confidence interval (CI) were used to establish a statistically significant association.

Results

The magnitude of undernutrition among the school-age children was 38.9%: 43.3% in the children from the SFP schools and 34.5% in the children from the N-SFP schools. Stunting was 24.1% among the children in the schools with SFPs and 16% among the children in the N-SFP schools, whereas thinness was 33.8% among the children in the SFP schools and 25.6% among the children in the N-SFP schools. The children who were in the older age group [adjusted odds ratio (AOR) = 4.4, 95%CI; 2.22–8.85], consumed less than three meals per day at home (AOR = 6.03; 95%CI 3.9–9.3), and did not eat breakfast at all before going to school (AOR = 3.5; 95%CI 1.15–10.76) were more likely to become undernourished. The children whose fathers received secondary and above education (AOR = 0.52; 95% CI (0.27–0.971) had lower odds of becoming underweight.

Conclusion

The magnitude of undernutrition was high in the current study. Existing interventions that work to improve the nutritional status of school-age children should be strengthened. Children should consume any type of food as breakfast at home before going to school regardless of the presence of school feeding programs and at least three times a day.