bluuebunny/crossref_metadata_2025 huggingface dataset:
Low dose ATG-Fresenius for GVHD prophylaxis: a comparative study with ATG-Thymoglobulin
Authors: Falicovich Itai , Nachmias Boaz , Elias Shlomo , Zimran Eran , Shaulov Adir , Stepensky Polina , Avni Batia , Grisariu Sigal
Published: January 2025

Background

Anti-Thymocyte Globulin (ATG) is commonly used to prevent graft-versus-host disease (GVHD), but the optimal dosage and type of ATG remains to be determined.

Objective

We compared retrospectively the safety and efficacy outcomes of allogeneic transplantation using low-dose ATG-Fresenius (15mg/kg) and ATG-Thymoglobulin (10mg/kg) for GVHD prevention.

Study design

Ninety-eight patients were included, with 46 in the ATG-T group and 52 in the ATG-F group. The median age was 48 years in the ATG-T group (range 20-71) and 50 years in the ATG-F group (range 18-73). Baseline characteristics were similar, with slightly more HLA mismatched donors and single-agent cyclosporine GVHD prophylaxis use in the ATG-T group. Additionally, the ATG-F group had more myeloid leukemia and myelodysplastic syndrome patients, while the ATG-T group had more lymphoma patients.

Results

The cumulative incidence of acute GVHD (aGVHD) grade II-IV and chronic GVHD (cGVHD) showed no significant differences. Multivariate analysis indicated that donor HLA mismatch influenced aGVHD risk significantly (p=0.005), and myeloablative conditioning increased cGVHD risk. Bacteremia and CMV reactivation rates were similar, but EBV DNA viremia was higher in the ATG-T group (22% vs. 8%, p=0.047), with one case of Post-Transplant Lymphoproliferative Disorder (PTLD) in the ATG-T group. Cumulative incidence of overall survival (OS), relapse incidence, non-relapse mortality (NRM) and GVHD free, Relapse free Survival (GRFS) did not significantly differ.

Conclusions

This study highlights the safety and efficacy of low-dose ATG-F compared to a relatively high dose ATG-T. Prospective studies are necessary to validate the safety and efficacy of low dose ATG-F for GVHD prevention.
Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy
Authors: Huang Jian , Song Shuangna , Yin Yihua , He Yinyan , Wang Huimin , Gu Ye , He Laman , Wang Xintao , Miao Xiaocao , Zhang Zhigang , Zhang Xueli , Li Yiran
Published: January 2025

Background

Immunotherapy, especially with the use of immune checkpoint inhibitors, has demonstrated efficacy for a variety of malignant tumors. However, the potential of immunotherapy for endometrial cancer (EC) with POLE mutations remains underexplored.

Methods

We utilized multiple databases and clinical specimens to investigate the immunogenicity profiles of EC patients carrying POLE mutations. One particular hotspot mutation POLEP286R was identified and further studied. Consequently, by constructing human leukocyte antigen (HLA) tetramers and incubating them with patients’ peripheral blood mononuclear cells (PBMCs), T cells capable of recognizing the POLEP286R mutation were sorted for further transcriptomic, proteomic and T-cell receptor (TCR) sequencing analyses and for an organoid EC model.

Results

Tumor- and immune-related pathways were shown to be activated in the POLEP286R mutant group. Importantly, by using an organoid model of EC, we further confirmed the antitumor potential of T cells that were specific to the POLEP286R mutation.

Conclusions

Our study uncovers the pronounced immunogenicity of POLE-mutant EC and characterizes neoantigens that are unique to the POLEP286R mutation, thus providing a promising new immunotherapeutic strategy for EC.
Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth
Authors: Ezcurra-Hualde Miriam , Zalba Sara , Bella Ángela , Arrizabalaga Leire , Risson Aline , García-Fuentes Román , Gomar Celia , Ardaiz Nuria , Belsue Virginia , Ruiz-Guillamon David , Serrano-Alcaide Alejandro , Salgado Ainara , Aranda Fernando , Garrido Maria J. , Berraondo Pedro
Published: January 2025

Introduction

Vitamin D3 (cholecalciferol) has demonstrated potential anticancer properties, but its clinical application is limited by associated toxicity at effective doses. This study investigated the use of liposomal encapsulation to increase the therapeutic efficacy of vitamin D3 while mitigating its toxicity.

Methods

Liposomal vitamin D3 (VD-LP) was prepared via the film-hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and long-term stability. In vitro gene expression modulation was evaluated in monocytic THP-1 cells, and antiproliferative effects were assessed in HT29 (colorectal), BT474 (breast), and TRAMP-C1 (prostate) cancer cell lines. In vivo antitumor efficacy and toxicity were tested in a mouse model with subcutaneously implanted MC38 tumors. Tumor growth, survival rates, and serum calcium and phosphate levels were analyzed.

Results

VD-LP demonstrated high encapsulation efficiency and stability over 90 days, with a consistent particle size of approximately 83 nm. VD-LP modulated immune-related and metabolic gene expression in THP-1 cells, including upregulation of antimicrobial peptides and vitamin D receptor genes. VD-LP showed superior antiproliferative effects compared to free vitamin D3 in all tested cancer cell lines. In vivo, VD-LP delayed tumor growth and improved survival without causing hypercalcemia, highlighting its favorable toxicity profile.

Discussion

Liposomal encapsulation of vitamin D3 significantly improves its anticancer efficacy while mitigating toxicity, making it a promising strategy for future cancer therapies. VD-LP shows potential for enhanced therapeutic applications with reduced adverse effects, warranting further clinical exploration.
What do pseudowords tell us about word processing? An overview
Authors: Martínez-Tomás Celia , Baciero Ana , Lázaro Miguel , Hinojosa José A.
Published: January 2025

This article provides an overview of the use of pseudowords—letter strings that resemble real words by adhering to phonotactic and orthotactic rules (e. g., fambo follows the rules of English phonology and orthography, but it does not have an actual meaning)—in written word processing research, with a focus on readers in alphabetic languages. We review how pseudowords have been used in research to isolate specific features of words to examine the cognitive mechanisms underlying various aspects of their processing, including orthographic, phonological decoding, lexical-semantic, and syntactic components, as well as to the way those empirical observations have shaped theories and models of word recognition. The overview also considers their broader applications, such as in studying non-alphabetic scripts, speech processing, and language disorders like dyslexia. By providing a focused synthesis of empirical findings, this article underscores the critical insights that research using pseudowords offers into the interconnected nature of cognitive mechanisms in language processing.
Relation among zootechnical performance, biochemical indicators, water quality, and small invertebrates (zooplankton) abundance reared in biofloc-supplemented systems
Authors: Al-Souti Ahmed Said , Zaher Marwa M. , Helal Amr M. , Meshhal Dina T. , D. H. Mansour , Al-Afify Afify D. G. , Rafaey Mohamed M. , El-Saharty Abeer , El-Haroun Ehab , Nassif Marian G. , Mansour Abdallah Tageldein , Ashour Mohamed
Published: January 2025

The present study was conducted to investigate the interaction of biofloc water supplementations and potential zooplankton abundance and structure in Nile tilapia Oreochromis niloticus-rearing systems on zootechnical performance and biochemical indicators. Nile tilapia juveniles (13.30 g and 9.50 cm) were randomly distributed into 18 fiberglass tanks (500 L/tank with a stocking density of 40 fish/tank) to start the feeding experiment for 60 days. Fish weights were recorded weekly to adjust the feeding rate at 3% of their biomass using a commercial diet. Compared to the control group (T0, zero biofloc water supplementation), the influence of five biofloc supplementation levels was applied as follows: 14.2, 28.4, 42.6, 56.8, and 71 g L−1 (T1, T2, T3, T4, and T5, respectively). The biofloc was prepared in an external fermentor fiberglass tank (300 L) and added to the fish tanks to keep the biofloc levels constant during the experiment. After 30 and 60 days of the experiment, the number of zooplankton was 46,501 and 24,537 Ind. L−1, respectively, which included four families (Rotifera, Copepoda, Cladocera, and free-living nematodes) with the domination of family Rotifera at 81.65% and 93.89%, respectively. The water quality indicated was within the standard values recommended for fish culture. Compared to those of the control group, the values of growth performance, whole-body biochemical composition, and blood biochemical indicators were significantly higher in biofloc groups than in the control group. Group T3 achieved the highest significant growth performance values. In comparison with the control group, T3 achieved the lowest number of cultures and the abundance of small invertebrate prey after 60 days of culture. The fish reared in groups T0 and T1 showed the highest significant urea content and the highest concentrations of liver function enzyme activities. Interestingly, compared to all groups, T3 achieved the best feed conversion ratio (FCR) value (1.68). Principal component analysis (PCA) and Pearson’s correlation coefficient confidence (PCCC) clarified a close positive relationship between T0 and T3 with the total individual, Rotifera abundance, and FCR. The highest PCCC value with T0 was in group T3 (0.947). In conclusion, biofloc supplementation (42.6 g L−1) showed a sustainable clean aquadiet strategy and significantly improved Nile tilapia growth and FCR with regard to the culture of small prey invertebrates for 60 days.
Effects of Enterocytozoon hepatopenaei infection on intestinal immune defense and physiological processes of Penaeus vannamei
Authors: Cao Zheng , He Chuanyu , Yin Zhipeng , Chen Caiyi , Li Fan , Yan Dongchun , Li Ting , Chang Linrui , Si Lingjun
Published: January 2025

As the main pathogen causing growth retardation, EHP is considered to be mainly parasitic in the hepatopancreas of shrimp. However, the intestines of shrimp infected with EHP frequently exhibit syndromes such as jejunum and white midgut. Therefore, the challenge experiment was carried out in this study to compare the differences in intestinal histology, digestion and absorption, immune defense and oxidative stress of P. vannamei between the control group and EHP infection group. Histological analysis showed that EHP infection significantly damaged the intestine of the shrimp, including intestinal villus rupture and outer membrane impairment. Concurrently, EHP infection can trigger intestinal immune response, and the expression of key immune genes like Toll, myeloid differentiation factor, anti-lipopolysaccharide factor, and Relish was significantly enhanced, while the expression of IMD and alkaline phosphatase was suppressed. Additionally, antioxidant genes manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and nuclear factor E2-related factor 2 were up-regulated to varying extents in EHP infection group, and the contents of lipid peroxides and malondialdehyde were heavily accumulated. Moreover, the expression levels of key genes involved in nutrient absorption, transport and synthesis, such as glucose transporter 1, Na+-K+ATPase, fatty acid synthase, acetyl-CoA carboxylase, rapamycin kinase, mTOR regulation-related protein, eukaryotic translation initiation factor 4E binding protein, ribosomal protein S6 kinase, were significantly up-regulated. However, the activities of amylase, lipase, and trypsin were inhibited in EHP infection group throughout the experiment. In summary, EHP infection damaged the intestine of P. vannamei, accompanied by immune response and oxidative stress. At the same time, nutrient transport and synthesis pathways were activated, while digestive enzyme activities were inhibited, indicating that in order to maintain survival, shrimps must accelerate material transport. Unfortunately, it remains in a state of nutrient deficiency that ultimately affects growth.
Influence of water masses and environmental variables on fish community in the south bank of Yangtze River Estuary, China
Authors: Zhang Dongrong , Xu Hengtao , Fang Xin , Huang Wei , Zhang Youzheng , Qian Jian
Published: January 2025

Fish play a crucial role in the estuarine ecosystem due to their ecological and commercial significance. Consequently, it is essential to study the characteristics of fish communities and their impacts within the estuary. In this study, we employed a single-boat bottom trawl to conduct four fishery resource surveys in April (spring), August (summer), October (autumn), and December (winter) of 2020 at ten sampling sites along the south bank of the Yangtze River Estuary (SBYRE). The primary objective was to assess the influence of water masses and environmental variables on the spatial and temporal distribution and diversity of fish communities in the SBYRE. The results indicated that fish biomass and abundance during summer were significantly higher than those observed in the other three seasons. High-value areas were predominantly located on the nearshore of the SBYRE and the north bank of Hangzhou Bay, a finding also corroborated by the cluster heat map results. Furthermore, the environmental variables in summer differed significantly from those in the other seasons, suggesting that the temporal and spatial distribution of fish was substantially influenced by these variables during the summer months. Mantel test and redundancy analysis demonstrated a positive correlation between the biomass and abundance of fish in summer and the factors of temperature and salinity. The seasonal alternation of dominant fish species contributes significantly to the heterogeneity observed in the temporal and spatial distribution of their communities. The reduced biomass and abundance of fish in spring were attributed to the lower influx of freshwater from the upstream. Seasonal variations in the fronts created by the confluence of multiple water masses in the study area, which play a crucial role in influencing the temporal and spatial distribution of fish communities. Furthermore, the presence of these fronts provides suitable habitats for spawning, feeding, and fattening for various fish species, making them ideal environments for numerous migratory fish. This study enhances our understanding of the temporal and spatial heterogeneity of fish communities in estuarine ecosystems and the factors influencing them, offering valuable insights for the protection and restoration of estuarine marine ecosystems.
Phosphomolybdic acid boosts polyunsaturated fatty acid and neutral lipid production in Phaeodactylum tricornutum
Authors: Peng Kun-Tao , Xiong Bing-Hong , Cheng Gao , Zhong Yuan-Hong , Yu Lin
Published: January 2025

Phaeodactylum tricornutum is considered a potential lipid production platform due to its high growth rates and elevated natural neutral lipid and polyunsaturated fatty acid (PUFA) contents. Furthermore, microalgae are emerging as promising sources of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). In this study, phosphomolybdic acid (PMo12), as a photocatalyst, can enhance the synthesis of neutral lipids and PUFAs by influencing the expression of lipid metabolism-related genes and photosynthesis in P. tricornutum. We also observed the contents of EPA and PUFA in engineered microalgae nearly doubled compared to the wild type, while neutral lipid content showed a significant increase of 69.7% in engineered microalgae. Notably, the growth rate of engineered microalgae remained comparable to that of the wild type. This work presents an effective approach to enhance the production of microalgal bioproducts, suggesting that photocatalysts such as PMo12 could serve as viable alternatives to genetic engineering technology, facilitating the commercialization of microalgal biodiesel.
Assessing the approaches to nausea and vomiting in pregnancy: insights from a nationwide survey of Italian gynecologists (PURITY light)
Authors: Di Iorio Romolo , Bianchi Paola , Casolati Elena , Piccolo Elena , Mangrella Mario
Published: January 2025

Introduction

Nausea and vomiting in pregnancy (NVP) affect approximately 70–85% of pregnant women, starting between weeks 6 and 8 and often subsiding by week 20. This study evaluates the therapeutic approaches of Italian gynecologists in the treatment of NVP. In the Italian healthcare system, gynecologists play a central role in prenatal care and are the primary healthcare providers for pregnant women, unlike in other countries where midwives may have a more prominent role.

Methods

From June to September 2022, a survey of Italian gynecologists was conducted during 15 scientific conferences. The questionnaire collected demographic data and information on clinical practices to support the management of NVP. Statistical analysis assessed the effect of demographic characteristics on clinical behavior.

Results

Data from 157 participants, mainly women (72.61%) and professionals from the Public Health System (63.69%), were analyzed. 77.71% always checked NVP during the first visit, based on patients’ reports (84.71%). 54.78% prescribed medication in mild cases, mainly the doxylamine/pyridoxine combination (64.97%).

Discussion

The results show varied practices influenced by demographic and professional factors. Many physicians treat only severe cases of NVP, perceiving it as a transient discomfort, which may lead to poor management. Balanced care is needed to improve the quality of life for pregnant women with NVP.
Experimental implementation of the peripheral nerve block clinical registry: an observational study
Authors: Dabbagh Ali , Madadi Firoozeh , Ebrahimi Moein , Dabir Shideh , Vosoughian Maryam , Dahi Mastaneh , Moshari Mohammadreza , Tabashi Soudeh , Ariannik Mohsen , Azizi Zahra
Published: January 2025

Background and aims

Peripheral nerve block (PNB) is commonly used, but there is a lack of data on its effectiveness and safety in the clinic. Therefore, anesthesiologists have limited insight into how they are faring in terms of both safety and efficacy. Additionally, No PNB registry is recorded in IRAN. Herein, we reveal how a hospital might use information gathered in a hospital registry of PNB outcomes to guide future quality enhancement efforts.

Method

This was an observational, prospective, and unicenter study of all peripheral nerve blocks done in the operating room since December 22, 2022. After studying the data collected by the existing registries worldwide, the anesthesiology research center at Taleghani Hospital developed a questionnaire that incorporated the varying parameters set forth by earlier research and registries. Parameters were documented for each patient.

Results

A total of 105 patients, were accrued from December 22, 2022, to July 23, 2023. The brachial plexus blocks namely axillary, infraclavicular, and popliteal blocks were the most frequently used PNBs, respectively. The indications that generated the greatest demand for PNBs were upper limb fractures, I&D, and amputation, respectively. 82.9% of blocks were conducted while patients were sedated employing systemic administration of sedatives. In this registry, there were no deaths or complications with sequelae. The median duration of hospitalization following admission to the hospital was 3 days. The mean patient satisfaction score was 9.46 out of 10.

Conclusion

Our analysis demonstrates the effectiveness, safety, and feasibility of peripheral nerve blocks in preoperative anesthesia. It is recommended to continue the registry and conduct additional studies to enhance our understanding of this procedure.
Pharmacological interventions for the management of anesthesia and sedation in patients with Duchenne muscular dystrophy: a systematic review and meta-analysis
Authors: Lian Xianghong , Jing Yang , Luo Ting , Guo Yixin , Lin Yunzhu
Published: January 2025

Background

Patients with duchenne muscular dystrophy (DMD) have an increased risk of complications when they undergo sedation or general anesthesia. However, due to improvements in cardiopulmonary therapies during anesthetic care, patients with DMD are experiencing an unprecedented duration of survival. We performed a systematic analysis to assess the benefits and risks of pharmacological interventions for the management of anesthesia and sedation in DMD patients.

Methods

We included any type of study reporting any drug intervention to manage anesthesia and sedation in participants previously diagnosed with DMD. Our primary outcomes were the onset time, recovery time, and neurodevelopmental disabilities. Seven electronic databases and three clinical trial registry platforms were searched. Data from the eligible studies were combined to calculate pooled risk ratios or standardized mean differences, and some included studies are presented in a narrative synthesis.

Results

Forty studies with 196 DMD participants were included in the analysis. Compared with those of the control group, the sensitivity of patients with DMD to neuromuscular blocking agents (NMBAs) may have resulted in a prolonged onset time [MD = −0.96, 95% CI (0.71, 2.60), I2 = 33%, P < 0.0001] and recovery time [MD = 2.22, 95% CI (1.14, 3.30), I2 = 76%, P < 0.0001] from anesthesia. The neuromuscular blocking effects showed a significant age dependence in DMD patients, and the safe use of 2 mg/kg sugammadex to antagonize deep neuromuscular blockade and rapid recovery has been reported. Furthermore, DMD patients are at risk of developing malignant hyperpyrexia with general/inhaled anesthesia, and dantrolene is often used for effective rescue. In addition, general anesthesia and central neuraxial blockade in patients with severe DMD are unsafe because respiratory depression and myocardial complications may occur after the administration of volatile anesthetics and depolarizing muscle relaxants (succinylcholine) during the induction of anesthesia.

Conclusions

Patients with DMD are more sensitive to NMBAs with delayed onset times and prolonged recovery times. Precautions for DMD patients should include quantitative neuromuscular monitoring, electrocardiographic monitoring and rapid airway protection throughout anesthesia. Compared with general anesthesia, regional anesthesia may be a relatively safe option.
Study on influencing factors of age-adjusted Charlson comorbidity index in patients with Alzheimer's disease based on machine learning model
Authors: Ding Jian , Long Zheng , Liu Yiming , Wang Min
Published: January 2025

Background

Alzheimer's disease (AD) is a widespread neurodegenerative disease, often accompanied by multiple comorbidities, significantly increasing the risk of death for patients. The age adjusted Charlson Comorbidity Index (aCCI) is an important clinical tool for measuring the burden of comorbidities in patients, closely related to mortality and prognosis. This study aims to use the MIMIC-V database and various regression and machine learning models to screen and validate features closely related to aCCI, providing a theoretical basis for personalized management of AD patients.

Methods

The research data is sourced from the MIMIC-V database, which contains detailed clinical information of AD patients. Multiple logistic regression, LASSO regression, random forest, Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost) models were used to screen for feature factors significantly correlated with aCCI. By comparing model performance, evaluating the classification ability and prediction accuracy of each method, and ultimately selecting the best model to construct a regression model and a nomogram. The model performance is evaluated through classification accuracy, net benefit, and robustness. The feature selection results were validated by regression analysis.

Results

Multiple models have performed well in classifying aCCI patients, among which the model constructed using LASSO regression screening feature factors has the best performance, with the highest classification accuracy and net benefit. LASSO regression identified the following 11 features closely related to aCCI: age, respiratory rate, base excess, glucose, red blood cell distribution width (RDW), alkaline phosphatase (ALP), whole blood potassium, hematocrit (HCT), phosphate, creatinine, and mean corpuscular hemoglobin (MCH). The column chart constructed based on these feature factors enables intuitive prediction of patients with high aCCI probability, providing a convenient clinical tool.

Conclusion

The results of this study indicate that the features screened by LASSO regression have the best predictive performance and can significantly improve the predictive ability of aCCI related comorbidities in AD patients. The column chart constructed based on this feature factor provides theoretical guidance for personalized management and precise treatment of AD patients.
Early identification of macrophage activation syndrome in adult-onset Still’s disease: a case report and literature review
Authors: Long Ting , Xu Jing , Lin Bo-Zhi , Li Sheng-Guang
Published: January 2025

Background

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder characterized by high spiking fevers, evanescent rash, and polyarthritis. A serious complication of AOSD is macrophage activation syndrome (MAS), a life-threatening hyperinflammatory condition that can lead to multiorgan failure if not promptly diagnosed and treated.

Objective

This case report and literature review focus on the early identification of MAS in patients with AOSD, highlighting diagnostic challenges, differential diagnoses, and the utility of scoring systems like the HScore and MS score in clinical practice.

Case presentation

We report the case of an 80-year-old woman who presented with a complex diagnostic challenge involving AOSD complicated by MAS and concurrent cytomegalovirus (CMV) infection. Her clinical course was marked by recurrent high fevers, cytopenias, hyperferritinemia, and liver dysfunction. Despite extensive workup, initial diagnoses of infections and autoimmune conditions were considered and ruled out. The HScore and MS score were calculated to be 210 and 1.607, respectively, both indicative of MAS. The patient was treated according to the HLH-94 protocol, with high-dose dexamethasone and etoposide, alongside broad-spectrum antimicrobial and antiviral therapy. She responded well to treatment, with resolution of fever and improvement in clinical symptoms.

Discussion

The overlap between AOSD and MAS symptoms complicates early diagnosis, making scoring systems critical in differentiating MAS from other conditions. The HScore and MS score provided a structured approach to diagnosis, guiding timely intervention and improving the patient’s prognosis. Our literature review emphasizes the importance of early recognition and integration of these scoring systems into routine clinical practice to enhance outcomes.

Conclusion

This case underscores the necessity of early identification and intervention in MAS associated with AOSD. The application of diagnostic scoring systems like the HScore and MS score is essential for prompt diagnosis and effective treatment, ultimately improving patient survival rates.
Phenotypic and WGS-derived antibiotic resistance patterns of Salmonella Enteritidis isolates from retail meat and environment during 2014 to 2019 in China
Authors: Zheng Liya , Di Qiannan , Xu Xuebin , Liu Liyuan , Qu Chunbo , Bremer Phil , Zhou Xiujuan
Published: January 2025

The emergence of multidrug-resistant (MDR) Salmonella Enteritidis has highlighted the importance of regularly monitoring for the occurrence of antibiotic-resistant strains. The current study combined phenotyping analysis and whole-genome-sequencing (WGS) to investigate the associations between the antibiotic-resistant phenotypes (ARPs) and genetic characteristics determinants in 95 Salmonella Enteritidis isolates from retail meat and environmental samples in China (2014–2019). Phenotypic analyses revealed that 70 isolates (73.68%) were MDR with 12 distinct resistance patterns. Most MDR strains (81.43%) had NAL-AMP-FIS-STR ± TET profiles, showing a fluctuating trend from 2015 to 2019, likely influenced by tetracycline withdrawal management. WGS identified four types of mutations in the gyrA gene were associated with nalidixic acid resistance. The co-carrying of blaTEM, sul2 and aph(6)-Id/aph(3″)-Ib was likely mediated by an X1-type plasmid, corresponding to resistance against ampicillin, sulfisoxazole, and streptomycin. Combining phenotypic analyses and WGS data, the 31 sequenced strains were primarily divided into two clusters, with most epidemic resistant strains in the largest cluster A. Identical ARP patterns observed across different sample types, regions, and isolation years but clustering together in cluster A suggested potential cross-contamination within the retail chain. Cluster B exhibited more diverse resistance patterns and genetic characteristics. Notably, three isolates in cluster B require special mention: a monophasic strain resistant to eight antibiotics, a strain exhibiting highly heteroresistance, and a strain with additional exotoxin genes. These results highlight the importance of ongoing surveillance and the utility of WGS to track and understand antibiotic resistance in Salmonella Enteritidis.
Novel delivery systems for phages and lysins in the topical management of wound infections: a narrative review
Authors: Yang Pan , Li Jing , Ma Xiumei , Hu Nan , Song Zhangyong , Chen Bin , Li Shizhu
Published: January 2025

Currently, multidrug-resistant (MDR) bacterial wound infections (WIs) are an extremely challenging clinical problem for physicians. Recently, compared to traditional single liquid delivery drugs, the study of five novel drug delivery systems (i.e., hydrogel, liposomes, electrospun fibers, nanoparticles and nanoemulsion) for phages and their encoded lysins in WI management has become a hot topic. To assess the current landscape of these emerging technologies, we conducted a comprehensive literature search across PubMed, Scopus and Web of Science up to July 2024, using terms such as “phage,” “lysin,” “wound,” “hydrogel,” “liposomes,” “fibers,” “nanoparticles,” and “nanoemulsion.” The criteria included original studies of five novel delivery systems for phages and lysins in WI management. The findings highlighted the positive effects of the five novel delivery systems for phages and lysins in WI management, significantly reducing wound bacterial populations, and accelerating healing at the injury site. However, the available literature on novel delivery systems for phages and lysins remains limited, particularly for lysins. In conclusion, the application of novel drug delivery systems for phages and lysins showed great potential in combating MDR bacterial WIs.
Effects of pits of different ages on ethyl acetate and its metabolism-related microorganisms during strong-flavor Baijiu fermentation
Authors: Zhang Jing , Duan Yunxuan , Lin Yang , Chen Jing , Cheng Jie , Song Chuan , Zuo Jincen , Zhang Suyi , Zuo Yong
Published: January 2025

The esters are the most important flavor components in Baijiu as their species and content decide the style of Baijiu. During the formation of esters, pits play important roles. In this study, the main esters and their related microorganisms in different years of pits (5, 35 and 100 years) of strong-flavor Baijiu were comprehensively researched by headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) and amplicon sequencing. A total of 690 bacterial genera and 155 fungal genera were detected. The microbial composition of ZPs (fermented grains) from 100 years pit was the most abundant at the genus level. A total of 177 volatile flavor components were observed, including 80 esters, 42 alcohols, 21 acids, 10 ketones and 11 aldehydes. Ethyl acetate was the lowest and ethyl caproate was relatively high in 100 years pit. 15 genera, including Lactobacillus, Pichia, Issatchenkia, Saccharomyces, and Aspergillus, were positively related to the formation of four major esters and their precursors. The research demonstrated that 100 years pit was benefit for maintaining microbial diversity and controlling ethyl acetate. This study is helpful for understanding the microbial composition and succession in the fermentation process of strong-flavor Baijiu, and revealing the complex relationships between dominant genera, physicochemical properties and volatile flavor components.
Screening and identification of host signaling pathways for alleviating influenza-induced production of pro-inflammatory cytokines, IP-10, IL-8, and MCP-1, using a U937 cell-based influenza model
Authors: Chen Si , Yu Yang , Su Yue , Lian Xiaoqin , Jiang Lefang , Li Zhuogang , Zhang Mingxin , Gao Yarou , Zhang Haonan , Zhu Xingjian , Ke Jiaxin , Chen Xulin
Published: January 2025

Influenza virus infection initiates an exaggerated inflammatory response, which may culminate in a fatal cytokine storm characterized by the excessive production of pro-inflammatory cytokines. Prior research indicates that IP-10, IL-8, and MCP-1, primarily produced by monocytes and macrophages, play a crucial role in influenza-induced inflammation. The lung injury from influenza virus infection can be mitigated by suppressing or inhibiting these cytokines through knockout, knockdown, or targeted intervention approaches. To identify the key host signaling pathways responsible for producing pro-inflammatory cytokines, we utilized a U937 cell model that secretes IP-10, IL-8, and MCP-1 in response to influenza infection. This model has been previously validated in our laboratory as an appropriate system for screening anti-inflammatory agents and potential drug targets. We conducted a screening assay employing an inhibitor library consisting of 2,138 compounds that target various known pathways and host factors. Our findings indicated that inhibitors targeting protein tyrosine kinases and mitogen-activated protein kinases demonstrated superior efficacy in suppressing cytokine production induced by influenza A virus infection compared to inhibitors aimed at other host factors. Notably, a substantial proportion of the identified hits capable of inhibiting the expression of all three cytokines in the secondary screening were classified as tyrosine kinase inhibitors. Validation experiments further established that Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways, along with p38 MAPK and Raf–MEK–ERK pathways, are the principal regulators of pro-inflammatory cytokine expression in monocytes and macrophages. Moreover, our results suggest that TKIs present promising opportunities as novel therapeutic agents against influenza-induced pneumonia.
Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells
Authors: Tarczykowska Agata , Malmberg Per , Scheers Nathalie
Published: January 2025

Iron uptake in the intestinal epithelium is associated with transport of ferrous iron via the DMT1 transporter (SLC11a2; NRAMP2). In later years, uptake of iron from complex sources, such as nanoparticles, has been found to be mediated through endocytosis. Here we propose that iron from the simple salt ferrous fumarate, a common iron supplement, can be absorbed by clathrin-mediated endocytosis. We used siRNA to silence DMT1 transporter expression, pharmacological inhibition of endocytosis, and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to show that iron uptake from ferrous fumarate can be mediated by both transport via DMT1 and by clathrin-dependent endocytosis in Hutu-80 cells. Iron uptake (ferritin L) from ferrous fumarate (0.5 mM, 24 h) in DMT1 silenced cells was significantly decreased (60% ± 11%) in comparison to iron controls while a 1-h dose of ferrous fumarate (0.5 mM) significantly decreased ferritin L formation in the presence of the clathrin inhibitor chlorpromazine (61% ± 10%, in post-confluent cells and 37% ± 9% in non-confluent cells). A pilot showed a similar trend for Ferritin (H) levels (confluent cells) and for total cellular iron load (non-confluent cells). ToF-SIMS analysis revealed diminished membrane-associated iron load in endocytosis-inhibited ferrous fumarate treated cells. The reported results support a clathrin-mediated endocytosis mechanism for uptake of iron from ferrous fumarate in addition to iron uptake by DMT1. More studies are needed to understand what determines which uptake mechanism are employed and to which extent.
Long-term live-cell imaging of GFAP+ astroglia and laminin+ vessels in organotypic mouse brain slices using microcontact printing
Authors: Humpel Christian
Published: January 2025

Organotypic brain slices are three-dimensional, 150-μm-thick sections derived from postnatal day 10 mice that can be cultured for several weeks in vitro. However, these slices pose challenges for live-cell imaging due to their thickness, particularly without access to expensive two-photon microscopy. In this study, we present an innovative method to label and visualize specific brain cell populations in living slices. Using microcontact printing, antibodies are applied directly onto the slices in a controlled 400-μm-diameter pattern. Astrocytes are labeled with glial fibrillary acidic protein (GFAP), and vessels are labeled with laminin. Subsequently, slices are incubated with secondary fluorescent antibodies (green fluorescent Alexa-488 or red fluorescent Alexa-546) and visualized using an inverted fluorescence microscope. This approach offers a cost-effective and detailed visualization technique for astroglia and vessels in living brain slices, enabling investigation to be conducted over several weeks.
Activity-dependent synaptic competition and dendrite pruning in developing mitral cells
Authors: Imai Takeshi
Published: January 2025

During the early postnatal period, neurons in sensory circuits dynamically remodel their connectivity to acquire discrete receptive fields. Neuronal activity is thought to play a central role in circuit remodeling during this period: Neuronal activity stabilizes some synaptic connections while eliminating others. Synaptic competition plays a central role in the binary choice between stabilization and elimination. While activity-dependent “punishment signals” propagating from winner to loser synapses have been hypothesized to drive synapse elimination, their exact nature has remained elusive. In this review, I summarize recent studies in mouse mitral cells that explain how only one dendrite is stabilized while others are eliminated, based on early postnatal spontaneous activity in the olfactory bulb. I discuss how the hypothetical punishment signals act on loser but not winner dendrites to establish only one primary dendrite per mitral cell, the anatomical basis for the odorant receptor-specific parallel information processing in the olfactory bulb.
Intravenous push administration of anti-seizure medications
Authors: Aljadeed Raniah , Gilbert Brian W. , Karaze Tallib , Rech Megan A.
Published: January 2025

Intravenous push (IVP) administration of anti-seizure medications is becoming increasingly popular among emergency departments. IVP administration eliminates the need for compounding and preparation by the pharmacy department, as well as the need to gather infusion materials or set up a patient’s tubing and pump, all of which translate to faster drug administration. This is important given the time-sensitive nature of status epilepticus treatment. This review will discuss several anti-seizure medications, including phenytoin, fosphenytoin, valproic acid, levetiracetam, brivaracetam and lacosamide, for which evidence supports the safe and efficacious use of IV push administration.
The role of SASP in ischemic stroke: a deep dive into cellular mechanisms
Authors: Xie Dong , Liu Yang , Xu Fang-Biao , Zhang Jin-Sheng
Published: January 2025

Background

The escalating incidence of ischemic stroke (IS) exerts a heavy toll on global health. Aging, a prominent risk factor, implicates the senescence-associated secretory phenotype (SASP) in IS pathogenesis. We postulated that alterations in SASP-related factor expression during IS correlate with remodeling of intercellular interaction networks and disease advancement. The present study endeavored to preliminarily dissect the SASP-IS nexus via combined bulk and single-cell transcriptome analysis.

Methods

Aggregated expression profiles from human peripheral blood bulk chips and MCAO mouse single-cell sequencing data, followed by SASP gene analysis. Executed protein interaction network and enrichment assays. Investigated immune infiltration in stroke patients, managed quality control and annotation of single-cell data, cherry-picked central cells based on SASP scores, unearthed essential genes via enrichment analysis, conducted pseudo-time and intercellular communication studies, and prognosticated drugs for hub genes. Finally, authenticated core gene expression in serum of MCAO and Sham rats using real-time fluorescent polymerase chain reaction (RT-qPCR).

Results

Fourteen hub genes were discerned. Seven cell types were annotated in MCAO mouse peripheral blood single-cell data. Basophils exhibited the highest SASP scores, with Lcp1 upregulated and Ccl3 downregulated in basophils of the MCAO group. Enrichment analysis divulged a significant association of Ccl3 with the cell apoptosis pathway and Lcp1 with immune responses. The Ccl3 gene is pivotal in basophils and basophil-neutrophil crosstalk. Additionally, we forecasted nagrestipen’s regulatory function on Ccl3. RT-qPCR demonstrated a marked elevation in Lcp1 mRNA and a pronounced reduction in Ccl3 in the MCAO group relative to the Sham group.

Conclusion

The Ccl3 gene in basophils and its immune cell interaction is a linchpin in the IS immune microenvironment. Ccl3 and Lcp1 might potentially modulate IS progression by influencing SASP, proffering novel prospects for IS clinical diagnosis and treatment.
Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review
Authors: Cowansage Kiriana , Nair Reshmi , Lara-Ruiz Jose M. , Berman Daniel E. , Boyd Courtney C. , Milligan Tiffany L. , Kotzab Daniel , Bellanti Dawn M. , Shank Lisa M. , Morgan Maria A. , Smolenski Derek J. , Babakhanyan Ida , Skopp Nancy A. , Evatt Daniel P. , Kelber Marija S.
Published: January 2025

Background

Posttraumatic stress disorder (PTSD) commonly cooccurs with traumatic brain injury (TBI) in military populations and is a significant predictor of poor long-term outcomes; however, it is unclear to what extent specific biological variables are associated with comorbidity. This PROSPERO-registered systematic review evaluates the current body of literature on genetic and peripheral biomarkers associated with comorbid TBI and PTSD.

Methods

Searches were conducted in four databases (PubMed, PsycInfo, PTSDPubs, Scopus). We included published studies examining differences in peripheral biomarkers among civilian, military, and veteran participants with both TBI and PTSD compared to those with TBI alone as well as, in some cases, PTSD alone and healthy controls. Data were extracted from included studies and evidence quality was assessed.

Results

Our final analysis included 16 studies, the majority of which were based on data from active duty military and veteran participants. The results suggest that multiple gene variants are likely to contribute to the cumulative risk of PTSD comorbid with TBI. An elevated circulating level of the pro-inflammatory cytokine IL-6 was the most consistently replicated blood-based indicator of comorbid illness, compared to mTBI alone.

Conclusion

Several genetic and protein markers of cellular injury and inflammation appear to be promising indicators of chronic pathology in comorbid TBI and PTSD. Additional research is needed to determine how such factors indicate, predict, and contribute to comorbidity and to what extent they represent viable targets for the development of novel diagnostic tools and therapeutic interventions.
Convergent construct validity and test-retest reliability of both German versions of the original and the revised Niigata PPPD Questionnaire: NPQ and NPQ-R
Authors: Chételat Sarah , Gerber Eve-Yaël , El Khadlaoui Sarah , Behrendt Frank , Stark Michaela , Schädler Stefan , Maywald Maximilian , Fabritius Lena , Gerb Johannes , Grabova Denis , Trost Wiebke , Zwergal Andreas , Strobl Ralf , Parmar Katrin , Gerth Hans Ulrich , Bonati Leo H. , Becker-Bense Sandra , Schuster-Amft Corina
Published: January 2025

Background

Persistent Postural-Perceptual Dizziness (PPPD) is a frequent chronic functional disorder that manifests with dizziness, unsteadiness, or non-spinning vertigo present for at least 3 months. Characteristic provocation factors are moving or complex visual stimuli and exclusion of organic diseases. To assess the severity and impact of PPPD, Japanese researchers developed the Niigata PPPD Questionnaire (NPQ). The study's aim was to evaluate the concurrent construct validity and reliability [including test-retest reliability, internal consistency, standard error of measurement (SEM), and minimal detectable change (MDC)] of the German version of the NPQ (12 items) and its revised version, NPQ-R, which contains 19 items addressing additional symptoms and symptom behavior.

Methods

The Swiss Reha Rheinfelden and the German Center for Vertigo and Balance Disorders included 265 PPPD patients (mean age 50.2 ± 16.8 years, disease duration 46.3 ± 76.6 months). Patients completed the NPQ and the NPQ-R (twice), the DHI and potentially related constructs: anxiety (ABC-Scale, VSS), depression (HADS), and general health (SF-36) once. To assess the questionnaires' reliability and validity, several statistical measures were calculated, including Spearman's rank correlation coefficients, Intraclass Correlation Coefficients (ICC2, 1), Cronbach's alpha, SEM, and MDC.

Results

On average, patients scored 29.9 ± 13.2 for NPQ and 52.3 ± 19.6 for NPQ-R. Correlations between NPQ/NPQ-R and (1) disease-specific questionnaires were rs= 0.712 and rs= 0.752 (DHI), rs=0.426 and rs= 0.0.462 (VSS-V), rs= -0.500 and rs= -0.545 (ABC-Scale), (2) anxiety-specific subscales rs = 0.394 and rs = 0.430 (VSS-A) and rs= 0.354 and rs= 0.430 (HADS-A), (3) depression-related subscales rs=0.438 and rs= 0.487 (HADS-D), and (4) general health rs ranged between rs= -0.216 and −0.578 (all SF-36 subscales). Internal consistency, test-retest reliability, SEM and MDC calculated for NPQ/NPQ-R were α = 0.88/α = 0.91, ICC=0.83 (CI 0.77 to 0.0.87), SEM 5.55/8.37, and MDC 15/23 points.

Conclusion

The German versions of NPQ and NPQ-R are valid and reliable patient-reported outcome measures for assessing PPPD, demonstrating satisfactory psychometric measurement properties including convergent construct validity and reliability parameters: internal consistency, test-retest reliability, SEM, and MDC as an evaluative measure. The NPQ-R, with its additional subscales addressing associated symptoms and symptom behavior, represents both the patient and clinician perspective on PPPD-specific problems. Therefore, we recommend utilizing the NPQ-R for a comprehensive assessment of PPPD.