bluuebunny/crossref_metadata_2025 huggingface dataset:
The SVZ stem cell niche–components, functions, and in vitro modelling
Authors: Eşiyok Nesil , Heide Michael
Published: December 2023

Neocortical development depends on the intrinsic ability of neural stem and progenitor cells to proliferate and differentiate to generate the different kinds of neurons in the adult brain. These progenitor cells can be distinguished into apical progenitors, which occupy a stem cell niche in the ventricular zone and basal progenitors, which occupy a stem cell niche in the subventricular zone (SVZ). During development, the stem cell niche provided in the subventricular zone enables the increased proliferation and self-renewal of basal progenitors, which likely underlie the expansion of the human neocortex. However, the components forming the SVZ stem cell niche in the developing neocortex have not yet been fully understood. In this review, we will discuss potential components of the SVZ stem cell niche, i.e., extracellular matrix composition and brain vasculature, and their possible key role in establishing and maintaining this niche during fetal neocortical development. We will also emphasize the potential role of basal progenitor morphology in maintaining their proliferative capacity within the stem cell niche of the SVZ. Finally, we will focus on the use of brain organoids to i) understand the unique features of basal progenitors, notably basal radial glia; ii) study components of the SVZ stem cell niche; and iii) provide future directions on how to improve brain organoids, notably the organoid SVZ, and make them more reliable models of human neocortical development and evolution studies.
A voyage from the ER: spatiotemporal insights into polarized protein secretion in neurons
Authors: Kersten Noortje , Farías Ginny G.
Published: December 2023

To function properly, neurons must maintain a proteome that differs in their somatodendritic and axonal domain. This requires the polarized sorting of newly synthesized secretory and transmembrane proteins into different vesicle populations as they traverse the secretory pathway. Although the trans-Golgi-network is generally considered to be the main sorting hub, this sorting process may already begin at the ER and continue through the Golgi cisternae. At each step in the sorting process, specificity is conferred by adaptors, GTPases, tethers, and SNAREs. Besides this, local synthesis and unconventional protein secretion may contribute to the polarized proteome to enable rapid responses to stimuli. For some transmembrane proteins, some of the steps in the sorting process are well-studied. These will be highlighted here. The universal rules that govern polarized protein sorting remain unresolved, therefore we emphasize the need to approach this problem in an unbiased, top-down manner. Unraveling these rules will contribute to our understanding of neuronal development and function in health and disease.
Metagenomic next-generation sequencing for detecting Aspergillosis pneumonia in immunocompromised patients: a retrospective study
Authors: Shi Yan , Peng Jin-Min , Hu Xiao-Yun , Yang Qi-Wen , Wang Yao
Published: December 2023

Purpose

The identification of Aspergillus by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary aspergillosis (IPA) in immunocompromised patients (ICP).

Methods

A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of Aspergillosis and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard

Results

mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, P < 0.001), culture (39.1%, P < 0.001), serum GM (23.9%, P < 0.001) and BALF GM (69.6%, P = 0.031). mNGS was capable of accurately distinguish strains of Aspergillus genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified A. fumigatus, A. flavus, A. terrestris, A. oryzae and Mucor spp. in culture-negative cases. The sequencing reads of Aspergillus by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, P = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with P. jirovecii and cytomegalovirus being the most common co-pathogens.

Conclusions

mNGS presents a feasible and remarkably sensitive approach for detecting Aspergillus in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS’s ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy.
Treatment of uncertainty in determining the UK's path to Net Zero
Authors: Joffe David
Published: December 2023

The Climate Change Committee (CCC) recommended the UK's 2050 Net Zero target in 2019 and then the emissions pathway to this as part of its advice on the Sixth Carbon Budget at the end of 2020. As part of this, the CCC's analysis included development of five pathways to Net Zero, incorporating a number of judgements and framings regarding uncertainty and decision points, to highlight key choices for Government and wider society on the path to Net Zero. This paper explores how the analysis, and its presentation, framed these choices and uncertainties, in order to highlight where decisions are required and what the trade-offs and potential contingency options might be. It concludes with reflections on the effectiveness of this approach and on the future challenges on decision-making and uncertainty toward Net Zero.
Criminal clickbait: a panel data analysis on the attractiveness of online advertisements offering stolen data
Authors: Madarie Renushka , de Poot Christianne , Weulen Kranenbarg Marleen
Published: December 2023

Introduction

Few studies have examined the sales of stolen account credentials on darkweb markets. In this study, we tested how advertisement characteristics affect the popularity of illicit online advertisements offering account credentials. Unlike previous criminological research, we take a novel approach by assessing the applicability of knowledge on regular consumer behaviours instead of theories explaining offender behaviour.

Methods

We scraped 1,565 unique advertisements offering credentials on a darkweb market. We used this panel data set to predict the simultaneous effects of the asking price, endorsement cues and title elements on advertisement popularity by estimating several hybrid panel data models.

Results

Most of our findings disconfirm our hypotheses. Asking price did not affect advertisement popularity. Endorsement cues, including vendor reputation and cumulative sales and views, had mixed and negative relationships, respectively, with advertisement popularity.

Discussion

Our results might suggest that account credentials are not simply regular products, but high-risk commodities that, paradoxically, become less attractive as they gain popularity. This study highlights the necessity of a deeper understanding of illicit online market dynamics to improve theories on illicit consumer behaviours and assist cybersecurity experts in disrupting criminal business models more effectively. We propose several avenues for future experimental research to gain further insights into these illicit processes.
Power of narrative: a case study about documenting private insightful experiences while dealing with pain and associated disability
Authors: Lakha S. F. , Sohail S. F. , Holtzman C. B. , Akkok Z. A. , Khandwala A. , Suhanic W. , Pennefather P. , Fels D. I.
Published: December 2023

Objective

People adjusting to living with a chronic disability, such as chronic pain, seek support and resources from societal systems, including health systems, to help them cope with this reality. This case study describes the use of a digital health platform designed to help in that quest.

Method

MyHealthMyRecord (MHMR), is being developed to record, register and curate personal private experiences of a chronic condition. MHMR allows users to record and log short (30–90s) personal and private audio-videos of their accommodation-seeking journey in a way that can be encrypted, registered, curated and shared privately. This case study describes the use of a prototype version of the platform by a participant co-designer who experienced a sudden onset of a chronic pain condition, of undetermined origin. System use began three months after the onset of the condition and just after being discharged from several months of hospitalization without any definitive diagnosis.

Result

During a three-month period, 65 short unstructured contributions were authored and logged. This paper presents a qualitative analysis of that content. The clips used various communication styles that documented experiences, concerns, issues, positive and negative interactions and pain episodes. Using thematic analysis with open coding, three domains (person-facing, accessibility and system-facing) and eight themes (pain, joy, therapy, environmental, recommendations, technical, culture and communication) were identified. Comments about pain, stress, etc., were the most common and occurred in 75% of all videos while technical and therapy/physio related comments were the fewest and occurred in 3 and 9% of the videos, respectively.

Conclusion

We conclude that it is possible to create recordings of events, thoughts, reflections and issues on different aspects affecting an individual's health and well-being impact, including effects of the chronic condition as well as tangential outcomes such as accessibility (or lack of it), using MHMR over a longer period of time. The next steps will be to develop functionality to annotate the recordings, automatically analyze and summarize collections of recordings to make them consumable, useful and understandable to the individual and others, and then to share those analyses and summaries with others. In addition, evaluate this functionality longitudinally with more users.
Allopregnanolone pleiotropic action in neurons and astrocytes: calcium signaling as a unifying mechanism
Authors: Wang Tian , Chen Shuhua , Mao Zisu , Shang Yuan , Brinton Roberta Diaz
Published: December 2023

Objective

Allopregnanolone (Allo) is a neurosteroid with pleiotropic action in the brain that includes neurogenesis, oligogenesis, human and rodent neural stem cell regeneration, increased glucose metabolism, mitochondrial respiration and biogenesis, improved cognitive function, and reduction of both inflammation and Alzheimer’s disease (AD) pathology. Because the breadth of Allo-induced responses requires activation of multiple systems of biology in the absence of an Allo-specific nuclear receptor, analyses were conducted in both neurons and astrocytes to identify unifying systems and signaling pathways.

Methods

Mechanisms of Allo action were investigated in embryonic hippocampal neurons and astrocytes cultured in an Aging Model (AM) media. Cellular morphology, mitochondrial function, and transcriptomics were investigated followed by mechanistic pathway analyses.

Results

In hippocampal neurons, Allo significantly increased neurite outgrowth and synaptic protein expression, which were paralleled by upregulated synaptogenesis and long-term potentiation gene expression profiles. Mechanistically, Allo induced Ca2+/CREB signaling cascades. In parallel, Allo significantly increased maximal mitochondrial respiration, mitochondrial membrane potential, and Complex IV activity while reducing oxidative stress, which required both the GABAA and L-type Ca2+ channels. In astrocytes, Allo increased ATP generation, mitochondrial function and dynamics while reducing oxidative stress, inflammasome indicators, and apoptotic signaling. Mechanistically, Allo regulation of astrocytic mitochondrial function required both the GABAA and L-type Ca2+ channels. Furthermore, Allo activated NRF1-TFAM signaling and increased the DRP1/OPA1 protein ratio, which led to increased mitochondrial biogenesis and dynamics.

Conclusion

Collectively, the cellular, mitochondrial, transcriptional, and pharmacological profiles provide evidence in support of calcium signaling as a unifying mechanism for Allo pleiotropic actions in the brain.
Circadian clock and lipid metabolism disorders: a potential therapeutic strategy for cancer
Authors: Liu Mengsi , Zhang Zhen , Chen Yating , Feng Ting , Zhou Qing , Tian Xuefei
Published: December 2023

Recent research has emphasized the interaction between the circadian clock and lipid metabolism, particularly in relation to tumors. This review aims to explore how the circadian clock regulates lipid metabolism and its impact on carcinogenesis. Specifically, targeting key enzymes involved in fatty acid synthesis (SREBP, ACLY, ACC, FASN, and SCD) has been identified as a potential strategy for cancer therapy. By disrupting these enzymes, it may be possible to inhibit tumor growth by interfering with lipid metabolism. Transcription factors, like SREBP play a significant role in regulating fatty acid synthesis which is influenced by circadian clock genes such as BMAL1, REV-ERB and DEC. This suggests a strong connection between fatty acid synthesis and the circadian clock. Therefore, successful combination therapy should target fatty acid synthesis in addition to considering the timing and duration of drug use. Ultimately, personalized chronotherapy can enhance drug efficacy in cancer treatment and achieve treatment goals
The role of gonadal hormones and sex chromosomes in sex-dependent effects of early nutrition on metabolic health
Authors: Christians Julian K. , Reue Karen
Published: December 2023

Early-life conditions such as prenatal nutrition can have long-term effects on metabolic health, and these effects may differ between males and females. Understanding the biological mechanisms underlying sex differences in the response to early-life environment will improve interventions, but few such mechanisms have been identified, and there is no overall framework for understanding sex differences. Biological sex differences may be due to chromosomal sex, gonadal sex, or interactions between the two. This review describes approaches to distinguish between the roles of chromosomal and gonadal sex, and summarizes findings regarding sex differences in metabolism. The Four Core Genotypes (FCG) mouse model allows dissociation of the sex chromosome genotype from gonadal type, whereas the XY* mouse model can be used to distinguish effects of X chromosome dosage vs the presence of the Y chromosome. Gonadectomy can be used to distinguish between organizational (permanent) and activational (reversible) effects of sex hormones. Baseline sex differences in a variety of metabolic traits are influenced by both activational and organizational effects of gonadal hormones, as well as sex chromosome complement. Thus far, these approaches have not been widely applied to examine sex-dependent effects of prenatal conditions, although a number of studies have found activational effects of estradiol to be protective against the development of hypertension following early-life adversity. Genes that escape X chromosome inactivation (XCI), such as Kdm5c, contribute to baseline sex-differences in metabolism, while Ogt, another XCI escapee, leads to sex-dependent responses to prenatal maternal stress. Genome-wide approaches to the study of sex differences include mapping genetic loci influencing metabolic traits in a sex-dependent manner. Seeking enrichment for binding sites of hormone receptors among genes showing sexually-dimorphic expression can elucidate the relative roles of hormones. Using the approaches described herein to identify mechanisms underlying sex-dependent effects of early nutrition on metabolic health may enable the identification of fundamental mechanisms and potential interventions.
Adolescent obesity and ANGPTL8: correlations with high sensitivity C-reactive protein, leptin, and chemerin
Authors: Hammad Maha M. , Channanath Arshad M. , Abu-Farha Mohamed , Rahman Abdur , Al Khairi Irina , Cherian Preethi , Alramah Tahani , Alam-Eldin Nada , Al-Mulla Fahd , Thanaraj Thangavel Alphonse , Abubaker Jehad
Published: December 2023

Angiopoietin-like proteins (ANGPTLs) mediate many metabolic functions. We had recently reported increased plasma levels of ANGPTL8 in obese adults of Arab ethnicity. However, data on ANGPTL8 levels in adolescent obesity is lacking. Arab population is characterized by a rapid transition, due to sudden wealth seen in the post-oil era, in lifestyle, food habits and extent of physical activity. We adopted a cross-sectional study on Arab adolescents from Kuwait to examine the role of ANGPTL8 in adolescent obesity. The study cohort included 452 adolescents, aged 11-14 years, recruited from Middle Schools across Kuwait. BMI-for-age growth charts were used to categorize adolescents as normal-weight, overweight, and obese. ELISA and bead-based multiplexing assays were used to measure plasma levels of ANGPTL8 and other inflammation and obesity-related biomarkers. Data analysis showed significant differences in the plasma levels of ANGPTL8 among the three subgroups, with a significant increase in overweight and obese children compared to normal-weight children. This observation persisted even when the analysis was stratified by sex. Multinomial logistic regression analysis illustrated that adolescents with higher levels of ANGPTL8 were 7 times more likely to become obese and twice as likely to be overweight. ANGPTL8 levels were correlated with those of hsCRP, leptin and chemerin. ANGPTL8 level had a reasonable prognostic power for obesity with an AUC of 0.703 (95%-CI=0.648-0.759). These observations relating to increased ANGPTL8 levels corresponding to increased BMI-for-age z-scores indicate that ANGPTL8, along with hsCRP, leptin and chemerin, could play a role in the early stages of obesity development in children. ANGPTL8 is a potential early marker for adolescent obesity and is associated with well-known obesity and inflammatory markers.
Lead in paint-contaminated residential soils with varying physicochemical properties from three large US cities: assessment of geochemical forms and recommendations on amendments for immobilization
Authors: Saleh Hadeer , Sarkar Dibyendu , Braida Washington , Larson Steve , Datta Rupali
Published: December 2023

Lead in yard soils has been recognized as the principal source of excess lead absorption among young children. The hazard imposed by soil lead is dependent on the geochemical forms of lead in soils. Soil properties such as pH, soil organic matter, clay, and carbonate content influence the geochemical forms of lead in soil. This study was conducted to investigate the correlation between soil properties and the geochemical speciation of lead in lead paint-contaminated residential soils from three major US cities. A comprehensive field survey was conducted, involving the collection of soils from ten houses in each of the cities: Baltimore, San Antonio, and Detroit. The influence of soil properties on geochemical speciation was analyzed to identify effective immobilization amendments for each soil type. Results showed that soils collected from San Antonio were slightly alkaline, whereas those from Baltimore were slightly acidic. Soils collected from Detroit were neutral to mildly alkaline in pH. San Antonio soils had relatively high soil salinity, high clay content, moderate to high soil organic matter (SOM), and high total carbon (TC). In contrast, soils collected from Baltimore had lower salinity and clay content, low SOM, and total carbon. Soils from Detroit exhibited relatively high salinity, clay, SOM, and TC contents. The average total soil lead concentrations were as follows; San Antonio 4,073 mg/kg, Baltimore 2,706 mg/kg, and Detroit 850 mg/kg. Geochemical speciation studies revealed significant differences in lead distribution among the studied soils. San Antonio soils exhibited high carbonate-bound and organic matter-bound fractions, while Baltimore soils had elevated soluble + exchangeable fractions. Detroit soils showed substantial lead in organic matter-bound fractions. Correlation analysis showed that the soil properties influencing exchangeable lead, were pH, total Al, and total Ca for San Antonio soils; pH and total P for Baltimore soils; and SOM and total Al for Detroit soils. Correlation analysis showed that there is a significant negative correlation (p < 0.05) between exchangeable lead and total Al (r = −0.653), and total Ca (r = −0.438) for San Antonio soils; pH (r = −0.286) and total p (r = −0.314) for Baltimore soils; and SOM (r = −0.628) and total Al (r = −0.408) for Detroit soils. Based on these results, the best potential immobilization amendments for each of these cities were predicted.
The efficient degradation and mechanism of sulfamethoxazole using ZnO/ZnIn2S4 heterojunction under visible light
Authors: Gan Xinhong , Song Yang , Liu Guoqiang , Zhang Huijuan , Yang Jianhua
Published: December 2023

We hydrothermally synthesized a flower-shaped ZnO/ZnIn2S4(ZnO/ZIS) Z-scheme heterojunction, which could decompose antibiotics efficiently. Meanwhile, the photocatalysts degradation of sulfamethoxazole (SMX) as the representative pollutant by ZnO/ZIS were studied deeply. When irradiated by a xenon lamp (500 W), ZnO/ZIS (0.20 g/L) degraded SMX (2.5 mg/L) in 6.5 h with an efficiency of 74.9%. The O2− and h+ played key roles in the visible light-assisted decomposition of SMX by ZnO/ZIS, while the role of OH was supplementary. Additionally, we investigated the mechanism of the generation of active species environmentally persistent free radicals (PFRs) within the SMX degradation using ZnO/ZIS by performing computations and experimental analyses based on density functional theory. Besides, PFRs (predominantly oxygen-centered) generated during the visible light-assisted SMX degradation by ZnO/ZIS had a concentration of 1011 spin/mm3. The generation of PFRs involves two major events, i.e., chemical adsorption and electron transfer. To adsorb the precursor F9a on ZnO, the energy required was −2.03 eV, and the electrons were transferred to the ZnO/ZnIn2S4 heterojunction from the precursor F9a. The PFRs only had minor negative impacts on the SMX degradation through ZnO/ZIS.
Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator
Authors: Schaefer Noah , Lindner Holger A. , Hahn Bianka , Schefzik Roman , Velásquez Sonia Y. , Schulte Jutta , Fuderer Tanja , Centner Franz-Simon , Schoettler Jochen J. , Himmelhan Bianca S. , Sturm Timo , Thiel Manfred , Schneider-Lindner Verena , Coulibaly Anna
Published: December 2023

Background

Pneumonia develops frequently after major surgery and polytrauma and thus in the presence of systemic inflammatory response syndrome (SIRS) and organ dysfunction. Immune checkpoints balance self-tolerance and immune activation. Altered checkpoint blood levels were reported for sepsis. We analyzed associations of pneumonia incidence in the presence of SIRS during the first week of critical illness and trends in checkpoint blood levels.

Materials and methods

Patients were studied from day two to six after admission to a surgical intensive care unit (ICU). Blood was sampled and physician experts retrospectively adjudicated upon the presence of SIRS and Sepsis-1/2 every eight hours. We measured the daily levels of immune checkpoints and inflammatory markers by bead arrays for polytrauma patients developing pneumonia. Immune checkpoint time series were additionally determined for clinically highly similar polytrauma controls remaining infection-free during follow-up. We performed cluster analyses. Immune checkpoint time trends in cases and controls were compared with hierarchical linear models. For patients with surgical trauma and with and without sepsis, selected immune checkpoints were determined in study baseline samples.

Results

In polytrauma patients with post-injury pneumonia, eleven immune checkpoints dominated subcluster 3 that separated subclusters 1 and 2 of myeloid markers from subcluster 4 of endothelial activation, tissue inflammation, and adaptive immunity markers. Immune checkpoint blood levels were more stable in polytrauma cases than controls, where they trended towards an increase in subcluster A and a decrease in subcluster B. Herpes virus entry mediator (HVEM) levels (subcluster A) were lower in cases throughout. In unselected surgical patients, sepsis was not associated with altered HVEM levels at the study baseline.

Conclusion

Pneumonia development after polytrauma until ICU-day six was associated with decreased blood levels of HVEM. HVEM signaling may reduce pneumonia risk by strengthening myeloid antimicrobial defense and dampening lymphoid-mediated tissue damage. Future investigations into the role of HVEM in pneumonia and sepsis development and as a predictive biomarker should consider the etiology of critical illness and the site of infection.
Inhibition of ERO1a and IDO1 improves dendritic cell infiltration into pancreatic ductal adenocarcinoma
Authors: Tay Apple Hui Min , Cinotti Riccardo , Sze Newman Sui Kwan , Lundqvist Andreas
Published: December 2023

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and treatment resistant cancers. Due to its desmoplastic and hypoxic nature along with an abundance of myeloid cell infiltration and scarce T cell infiltration, PDAC is considered a cold tumor.

Methods

Here we sought to investigate myeloid cell infiltration and composition in PDAC spheroids by targeting the hypoxia-associated pathways endoplasmic reticulum oxidoreductase 1 alpha (ERO1a) and indoleamine 2,3-dioxygenase 1 (IDO1). Using MiaPaCa2 spheroids with hypoxic core, we assessed the roles of ERO1a and IDO1 inhibition in modulating monocyte infiltration and differentiation, followed by characterizing immunomodulatory factors secreted using LC-MS/MS.

Results

Inhibition of ERO1a and IDO1 significantly improved monocyte infiltration and differentiation into dendritic cells. LC-MS/MS analysis of the PDAC spheroid secretome identified downregulation of hypoxia and PDAC pathways, and upregulation of antigen presentation pathways upon inhibition of ERO1a and IDO1. Furthermore, immunomodulatory factors involved in immune infiltration and migration including interleukin-8, lymphocyte cytosolic protein 1, and transgelin-2, were upregulated upon inhibition of ERO1a and IDO1.

Discussion

Collectively, our results show that inhibition of ERO1a and IDO1 modulates the tumor microenvironment associated with improved monocyte infiltration and differentiation into dendritic cells to potentially influence therapeutic responses in patients with PDAC.
Gemtuzumab ozogamicin for relapsed or primary refractory acute myeloid leukemia in children—the Polish Pediatric Leukemia and Lymphoma Study Group experience
Authors: Pawinska-Wasikowska Katarzyna , Czogala Malgorzata , Skoczen Szymon , Surman Marta , Rygielska Monika , Ksiazek Teofila , Pac Agnieszka , Wieczorek Aleksandra , Skalska-Sadowska Jolanta , Samborska Magdalena , Wachowiak Jacek , Chaber Radoslaw , Tomaszewska Renata , Szczepanski Tomasz , Zielezinska Karolina , Urasinski Tomasz , Moj-Hackemer Malgorzata , Kalwak Krzysztof , Kozlowska Marta , Irga-Jaworska Ninela , Balwierz Walentyna , Bukowska-Strakova Karolina
Published: December 2023

Background

Gemtuzumab ozogamicin (GO), one of the first targeted drugs used in oncology, consists of an anti-cluster of differentiation 33 (CD33) monoclonal antibody bound to a derivative of cytotoxic calicheamicin. After the drug withdrawn in 2010 due to a significantly higher rate of early deaths, GO regained approval in 2017 for the treatment of newly diagnosed, refractory, or relapsed acute myeloid leukemia (AML) in adults and children over 15 years of age. The objective of the study was a retrospective analysis of clinical characteristics, treatment outcomes, and GO toxicity profile in children with primary refractory or relapsed (R/R) AML treated in Poland from 2008 to 2022.

Methods

Data were collected through the Polish Registry of Acute Myeloid Leukemia. From January 2008 to December 2022, 35 children with R/R AML were treated with GO in seven centers of the Polish Pediatric Leukemia and Lymphoma Study Group.

Results

Most of the children (30 of 35) received only one GO cycle in combination with various chemotherapy cycles (IDA-FLA, DOXO-FLA, FLA, FLAG, and others). Eighteen children (51%) achieved complete remission (CR), 14 did not respond to treatment, and three progressed. GO therapy was followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 18 children in CR. The 5-year overall survival (OS) after GO therapy was 37.1% ± 8.7% for the total cohort. There was a trend toward a superior outcome in patients with strong expression of CD33 expression (over 50% positive cells) compared with that in patients with lower expression of CD33 (OS, 41.2% ± 11.9% versus 27.8% ± 13.2%; p = 0.5; 5-year event-free survival, 35.4% ± 11.6% versus 25.7% ± 12.3%; p = 0.5, respectively). Children under 15 years have better outcome (OS, 34.9% ± 10.4% versus 30% ± 14.5%, p = 0.3). The most common adverse events were bone marrow aplasia, fever of unknown origin, infections, and elevated liver enzyme elevation. Sinusoidal obstruction syndrome occurred in two children.

Conclusions

The use of GO in severely pretreated children, including those under 15 years of age, with previous failure of AML treatment is a feasible and effective bridging therapy to allo-HSCT with an acceptable toxicity profile.
Current status and future challenges of CAR-T cell therapy for osteosarcoma
Authors: Li Shizhe , Zhang He , Shang Guanning
Published: December 2023

Osteosarcoma, the most common bone malignancy in children and adolescents, poses considerable challenges in terms of prognosis, especially for patients with metastatic or recurrent disease. While surgical intervention and adjuvant chemotherapy have improved survival rates, limitations such as impractical tumor removal or chemotherapy resistance hinder the treatment outcomes. Chimeric antigen receptor (CAR)-T cell therapy, an innovative immunotherapy approach that involves targeting tumor antigens and releasing immune factors, has shown significant advancements in the treatment of hematological malignancies. However, its application in solid tumors, including osteosarcoma, is constrained by factors such as low antigen specificity, limited persistence, and the complex tumor microenvironment. Research on osteosarcoma is ongoing, and some targets have shown promising results in pre-clinical studies. This review summarizes the current status of research on CAR-T cell therapy for osteosarcoma by compiling recent literature. It also proposes future research directions to enhance the treatment of osteosarcoma.
Improved prevention of female genital schistosomiasis: piloting integration of services into the national health system in Côte d’Ivoire
Authors: Preston Ashley , Vitolas Carlos Torres , Kouamin Alain Claver , Nadri Johara , Lavry Suzanne Lobohon , Dhanani Neerav , Dje Norbert , Toh Alain , Fleming Fiona M. , Meite Aboulaye
Published: December 2023

Introduction

Female genital schistosomiasis (FGS) is a neglected gynecological condition, putting women at-risk of poor sexual and reproductive health (SRH), including pregnancy complications or infertility. Early treatment of schistosomiasis with praziquantel is important to avoid disease progression to FGS as it is not always possible to reverse these symptoms. However, prevention programs with praziquantel have historically focused on school-aged children. Therefore, there is a gap to provide prevention services for young women in endemic areas, including Côte d’Ivoire.

Methods

We piloted integration of FGS prevention services into routine SRH care in seven health centers (Soubré district, Côte d’Ivoire, November 2020 to April 2021) and enrolled 56 health workers. We used mixed methods including key informant interviews, focus group discussions, and questionnaires to determine effectiveness, feasibility and acceptability of integration across health system decision makers, health workers and female patients (15 to 29 years old). For qualitative data, we used an inductive coding process to analyze themes. We used descriptive statistics to analyze quantitative data.

Results

Interviewed health workers perceived that the integrated services increased access and improved health outcomes for women (15 to 29 years old) due to the more comprehensive approach, although barriers to access included lack of transportation. Female patients surveyed at baseline (n=448) indicated there were no routine FGS prevention services. During the pilot, FGS prevention services were provided to >8500 women at-risk. Health workers interviewed at the end of the pilot indicated they could feasibly provide FGS prevention services as part of routine patient consultations, and they maintained knowledge from training on the key FGS health education points and the consultation processes to follow. The greatest challenge expressed by health workers was the high workload.

Discussion

Provision of integrated healthcare in the health center setting is an effective and acceptable way to increase access to prevention services and provide holistic care for women (15 to 29 years old) in this setting in Côte d’Ivoire. Future scale-up will require further streamlining of the strategy, building on existing platforms, whilst ensuring reduced impact on workload and consideration of how to overcome barriers to accessing health centers.
The association between research design and the perceived treatment effectiveness: a cross-sectional study
Authors: Bralić Nensi , Buljan Ivan
Published: December 2023

Objective

To evaluate the impact of research design on the perceived medical treatment effectiveness among researchers, healthcare workers (HCWs) and consumers in Croatia.

Methods

A cross-sectional study was conducted from November 2021 to February 2022 using an online survey. The participants were researchers, HCWs and consumers from Croatia. The survey had six scenarios about the same medical treatment presented within different study designs and in random order. Participants were asked to assess on a scale from 1 to 10 if the descriptions presented a sufficient level of evidence to conclude that the treatment was effective.

Results

For researchers (n = 97), as the number of participants and degree of variable control in the study design increased, the perceived level of sufficient evidence also increased significantly. Among consumers (n = 286) and HCWs (n = 201), no significant differences in scores were observed between the cross-sectional study, cohort study, RCT, and systematic review.

Conclusion

There is a need to implement educational courses on basic research methodology in lower levels of education and as part of Continuing Medical Education for all stakeholders in the healthcare system. Trial registration: this study has been registered on the Open Science Framework prior to study commencement (https://osf.io/t7xmf).
The prevalence of Staphylococcus aureus and the emergence of livestock-associated MRSA CC398 in pig production in eastern China
Authors: Zheng Lina , Jiang Zhongyi , Wang Zhenyu , Li Yang , Jiao Xinan , Li Qiuchun , Tang Yuanyue
Published: December 2023

Livestock-associated Staphylococcus aureus (LA-MRSA) has been of increasing concern due to its potential risk to humans. This study investigated the prevalence of MRSA in pig production in Eastern China and determined the genomic characteristics of pig-associated MRSA isolates by whole-genome sequencing (WGS). A total of 1,318 samples were collected from pig farms and pig slaughterhouses, and 150 S. aureus were identified, including 63 MRSA isolates and 87 MSSA isolates. MRSA was detected in all pig farms and pig slaughterhouses. The antimicrobial susceptibility test revealed that all MRSA isolates were multidrug-resistant. The WGS and MLST analysis demonstrated that 56 MRSA isolates belonged to clonal complex (CC) 398, and seven MRSA isolates belonged to CC9. All LA-MRSA isolates were absent of phiSa3 phage containing immune evasion cluster (IEC) and possessed an intact hlb gene. In addition, genes associated with Panton-Valentine leukocidin, typically indicative of human adaptation, were not detected. The analysis of antibiotic resistance genes (ARGs) demonstrated that all MRSA isolates contained multiple ARGs. All MRSA isolates had Plthe mecA gene and at least one tetracycline resistance gene. Both tetM and tetK were detected in all MRSA CC398 isolates, while tetL was detected in all MRSA CC9 isolates. The phenicol resistance gene fexA was detected in 51 MRSA isolates, while the linezolid resistance gene cfr was detected in 60 MRSA isolates. The emergence of LA-MRSA CC398 in four pig farms and one slaughterhouse in this study indicates the spread of this clonal complex in the pig production sector in Eastern China. Further investigations are required to understand the potential transmission routes of LA-MRSA CC398 within the pork production chain in China and to assess the potential risks to humans.
Comparison of the gut microbiota and metabolism in different regions of Red Swamp Crayfish (Procambarus clarkii)
Authors: Liu Songyi , Wang Ziyan , Wang Ze , Wu Qiaoli , Zhou Jun , Wang Rixin , Han Jiaojiao , Su Xiurong
Published: December 2023

Background

The gut microbiota is very important for maintaining the homeostasis and health of crustaceans. Many factors affect the gut microbiota of crustaceans, one of which is temperature. However, it is currently unclear how temperature affects the gut microbiota and metabolites of Procambarus clarkii.

Methods

Using metagenomic sequencing and gas chromatography–mass spectrometry (GC–MS) techniques, the gut microbiota and metabolites of P. clarkii from Hubei (HB), Jiangsu (JS), Shandong (SD), and Zhejiang (ZJ) in China were investigated.

Results

Under the impact of temperature, the gut microbiota and metabolites of P. clarkii exhibit a specific trend of change. The primary pathogenic bacteria affecting P. clarkii are Citrobacter, Enterobacterium, and Aeromonas, which are affected by temperature. Two metabolites, namely, sugars and amino acids, are regulated by temperature.

Implication

This study demonstrated that the gut microbiota and gut metabolites of P. clarkii were considerably affected by temperature. It provides a theoretical basis for the systematic study of P. clarkii and provides a basis for a healthy culture of P. clarkii.
Biocontrol ability of Bacillus velezensis T9 against Apiospora arundinis causing Apiospora mold on sugarcane
Authors: Liao Jie , Liang Xuelian , Li Huiling , Mo Leixing , Mo Renfu , Chen Wei , Wei Yuning , Wang Tianshun , Jiang Wenyan
Published: December 2023

Sugarcane (Saccharum officinarum L.) may be infected with Apiospora, which can produce the toxin 3-nitropropionic acid (3-NPA) during improper transportation and storage. The consumption of sugarcane that contains 3-NPA can lead to food poisoning. Therefore, this study sought to explore a novel biocontrol agent to prevent and control Apiospora mold. Bacteria were isolated from the soil of healthy sugarcane and identified as Bacillus velezensis T9 through colony morphological, physiological and biochemical characterization and molecular identification. The inhibitory effect of B. velezensis T9 on Apiospora mold on sugarcane was analyzed. Assays of the cell suspension of strain T9 and its cell-free supernatant showed that T9 had significant in vitro antifungal activities against Apiospora arundinis and thus, would be a likely antagonist. Scanning electron microscopy and transmission electron microscopy showed that treatment with T9 significantly distorted the A. arundinis mycelia, perforated the membrane, contracted the vesicles, and decomposed most organelles into irregular fragments. A re-isolation experiment demonstrates the ability of T9 to colonize the sugarcane stems and survive in them. This strain can produce volatile organic compounds (VOCs) that are remarkably strong inhibitors, and it can also form biofilms. Additionally, the cell-free supernatant significantly reduced the ability of A. arundinis to produce 3-NPA and completely inhibited its production at 10%. Therefore, strain T9 is effective at controlling A. arundinis and has the potential for further development as a fungal prevention agent for agricultural products.
Characterization of Rosculus vilicus sp. nov., a rhizarian amoeba interacting with Mycobacterium avium subsp. paratuberculosis
Authors: Jessu Amélie , Delafont Vincent , Moyen Jean-Louis , Biet Franck , Samba-Louaka Ascel , Héchard Yann
Published: December 2023

Free-living amoebae are described as potential reservoirs for pathogenic bacteria in the environment. It has been hypothesized that this might be the case for Mycobacterium avium subsp. paratuberculosis, the bacterium responsible for paratuberculosis. In a previous work, we isolated an amoeba from a water sample in the environment of infected cattle and showed that this amoeba was associated with Mycobacterium avium subsp. paratuberculosis. While a partial 18S rRNA gene has allowed us to suggest that this amoeba was Rosculus-like, at that time we were not able to sub-cultivate it. In the present study, we succeeded in cultivating this strain at 20–25°C. This amoeba is among the smallest (5–7 μm) described. The sequencing of the whole genome allowed us to extract the full 18S rRNA gene and propose this strain as a new species of the Rosculus genus, i.e., R. vilicus. Of note, the mitochondrial genome is particularly large (184,954 bp). Finally, we showed that this amoeba was able to phagocyte Mycobacterium avium subsp. paratuberculosis and that the bacterium was still observed within amoebae after at least 3 days. In conclusion, we characterized a new environmental amoeba species at the cellular and genome level that was able to interact with Mycobacterium avium subsp. paratuberculosis. As a result, R. vilicus is a potential candidate as environmental reservoir for Mycobacterium avium subsp. paratuberculosis but further experiments are needed to test this hypothesis.
Uncovering differences in the composition and function of phage communities and phage-bacterium interactions in raw soy sauce
Authors: Tan Guiliang , Qi Shaohan , Wang Yi , Li Xueyan , Li Xiangli , Li Mei , Li Lin , Zhao Lichao , Hu Min
Published: December 2023

Introduction

Although the composition and succession of microbial communities in soy sauce fermentation have been well-characterized, the understanding of phage communities in soy sauce remains limited.

Methods

This study determined the diversity, taxonomic composition, and predicted function of phage communities and the phage-host interactions in two types of raw soy sauce (Cantonese-type fermentation, NJ; Japanese-type fermentation, PJ) using shotgun metagenomics.

Results and discussion

These two raw soy sauces showed differences in phage composition (121 viral operational taxonomic units (vOTUs) in NJ and 387 vOTUs in PJ), with a higher abundance of the family Siphoviridae (58.50%) in the NJ phage community and a higher abundance of Myoviridae (33.01%) in PJ. Auxiliary metabolic functional annotation analyses showed that phages in the raw soy sauces mostly encoded genes with unknown functions (accounting for 66.33% of COG profiles), but the NJ sample contained genes mostly annotated to conventional functions related to carbohydrate metabolism (0.74%) and lipid metabolism (0.84%), while the PJ sample presented a higher level of amino acid metabolism functions (0.12%). Thirty auxiliary metabolism genes (AMGs) were identified in phage genomes, which were associated with carbohydrate utilization, cysteine and methionine metabolism, and aspartic acid biosynthesis for the host. To identify phage-host interactions, 30 host genomes (affiliated with 22 genera) were also recruited from the metagenomic dataset. The phage-host interaction analysis revealed a wide range of phage hosts, for which a total of 57 phage contigs were associated with 17 host genomes, with Shewanella fodinae and Weissella cibaria infected by the most phages. This study provides a comprehensive understanding of the phage community composition, auxiliary metabolic functions, and interactions with hosts in two different types of raw soy sauce.
Different impulse control disorder evolution patterns and white matter microstructural damage in the progression of Parkinson’s disease
Authors: Hu Ling , Lin Changfu , Lin Fabin , Wang Lingling , Li Zhenzhen , Cai Zhijun , Liu Xianghong , Ye Qinyong , Wu Yiwen , Cai Guoen
Published: December 2023

Background

The course of impulse control disorders (ICD) varies in the early stage of Parkinson’s disease (PD).

Aim

We aimed to delineate the association between the evolution pattern of ICD and the progression of PD.

Methods

A total of 321 de novo PD patients from the Parkinson’s Progression Markers Initiative database were included. Patients were followed up for a mean of 6.8 years and were classified into different groups according to the evolution patterns of ICD. Disease progression was compared among groups using survival analysis, in which the endpoint was defined as progression to Hoehn and Yahr stage 3 or higher for motor progression and progression to mild cognitive impairment for cognitive decline. In the fourth year of follow-up, four types of ICD evolution patterns were identified: (1) non-ICD-stable (68.2%), a patient who is consistently free of ICD; (2) late-ICD (14.6%), ICD developed during the follow-up of patients; (3) ICD-stable (11.5%), patients showed persistent ICD; and (4) ICD-reversion (5.6%), baseline ICD disappeared during the follow-up of patients with ICD.

Results

The ICD-reversion type shows daily life non-motor symptoms [Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) part I], daily life motor symptoms (MDS-UPDRS part II), rapid eye movement sleep behavior disorder, and anxiety symptoms has a greater impact. PD patients with different ICD evolution patterns had different changes in white matter microstructure at the onset of the disease. Those relevant brain regions are involved in ICD and non-motor functions.

Conclusion

Four early ICD evolution patterns are identified in de novo PD, with different prognoses and brain white matter microstructural damage patterns, and they may predict motor progression and cognitive decline in PD patients.