bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the neuroanatomical abnormalities in a phenotype of male compulsive rats
Authors: Martín-González Elena , Prados-Pardo Ángeles , Sawiak Stephen J. , Dalley Jeffrey W. , Padro Daniel , Ramos-Cabrer Pedro , Mora Santiago , Moreno-Montoya Margarita
Published: November 2023

Compulsivity is considered a transdiagnostic dimension in obsessive–compulsive and related disorders, characterized by heterogeneous cognitive and behavioral phenotypes associated with abnormalities in cortico-striatal-thalamic-cortical circuitry. The present study investigated the structural morphology of white and gray matter in rats selected for low- (LD) and high- (HD) compulsive drinking behavior on a schedule-induced polydipsia (SIP) task. Regional brain morphology was assessed using ex-vivo high-resolution magnetic resonance imaging (MRI). Voxel-based morphometry of segmented MRI images revealed larger white matter volumes in anterior commissure and corpus callosum of HD rats compared with LD rats. HD rats also showed significantly larger regional volumes of dorsolateral orbitofrontal cortex, striatum, amygdala, hippocampus, midbrain, sub-thalamic nucleus, and cerebellum. By contrast, the medial prefrontal cortex was significantly smaller in HD rats compared with LD rats with no significant group differences in whole brain, ventricular, or cerebrospinal fluid volumes. These findings show that limbic cortico-basal ganglia structures implicated in impulse control disorders are distinct in rats that are vulnerable to develop compulsive behavior. Such abnormalities may be relevant to the etiology of compulsive disorders in humans.
Semantic segmentation of plant roots from RGB (mini-) rhizotron images—generalisation potential and false positives of established methods and advanced deep-learning models
Authors: Baykalov Pavel , Bussmann Bart , Nair Richard , Smith Abraham George , Bodner Gernot , Hadar Ofer , Lazarovitch Naftali , Rewald Boris
Published: November 2023

Background

Manual analysis of (mini-)rhizotron (MR) images is tedious. Several methods have been proposed for semantic root segmentation based on homogeneous, single-source MR datasets. Recent advances in deep learning (DL) have enabled automated feature extraction, but comparisons of segmentation accuracy, false positives and transferability are virtually lacking. Here we compare six state-of-the-art methods and propose two improved DL models for semantic root segmentation using a large MR dataset with and without augmented data. We determine the performance of the methods on a homogeneous maize dataset, and a mixed dataset of > 8 species (mixtures), 6 soil types and 4 imaging systems. The generalisation potential of the derived DL models is determined on a distinct, unseen dataset.

Results

The best performance was achieved by the U-Net models; the more complex the encoder the better the accuracy and generalisation of the model. The heterogeneous mixed MR dataset was a particularly challenging for the non-U-Net techniques. Data augmentation enhanced model performance. We demonstrated the improved performance of deep meta-architectures and feature extractors, and a reduction in the number of false positives.

Conclusions

Although correction factors are still required to match human labelled root lengths, neural network architectures greatly reduce the time required to compute the root length. The more complex architectures illustrate how future improvements in root segmentation within MR images can be achieved, particularly reaching higher segmentation accuracies and model generalisation when analysing real-world datasets with artefacts—limiting the need for model retraining.
Incidence and survival of transthyretin amyloid cardiomyopathy from a French nationwide study of in- and out-patient databases
Authors: Damy Thibaud , Bourel Guillaume , Slama Michel , Algalarrondo Vincent , Lairez Olivier , Fournier Pauline , Costa Jérôme , Pelcot Françoise , Farrugia Agnès , Zaleski Isabelle Durand , Lilliu Hervé , Rault Caroline , Bartoli Mathilde , Fievez Stéphane , Granghaud Anna , Rudant Jeremie , Coste Agathe , Cosson Charlotte Noirot , Squara Pierre-Alexandre , Narbeburu Marion , De Neuville Bertrand , Charron Philippe
Published: November 2023

Background

Precise data about ATTR-CM incidence rates at national level are scarce. Consequently, this study aimed to estimate the annual incidence and survival of transthyretin amyloid cardiomyopathy (ATTR-CM) in France between 2011 and 2019 using real world data. We used the French nationwide exhaustive data (SNDS database) gathering in- and out-patient claims. As there is no specific ICD-10 marker code for ATTR-CM, diagnosis required both amyloidosis (identified by E85. ICD-10 code or a tafamidis meglumine delivery) and a cardiovascular condition (identified by ICD-10 or medical procedure codes related to either heart failure, arrhythmias, conduction disorders or cardiomyopathies), not necessarily reported at the same visit. Patients with probable AL-form of amyloidosis or probable AA-form of amyloidosis were excluded.

Results

Between 2011 and 2019, 8,950 patients with incident ATTR-CM were identified. Incidence rates increased from 0.6 / 100,000 person-years in 2011 to 3.6 / 100,000 person-years in 2019 (p < 0.001), reaching 2377 new cases in 2019. Sex ratios (M/F) increased from 1.52 in 2011 to 2.23 in 2019. In 2019, median age at diagnosis was 84.0 years (85.5 for women and 83.5 for men). Median survival after diagnosis was 41.9 months (95% CI [39.6, 44.1]).

Conclusions

This is the first estimate of nationwide ATTR-CM incidence in France using comprehensive real-world databases. We observed an increased incidence over the study period, consistent with an improvement in ATTR-CM diagnosis in recent years.
Employment, occupation, and income in adults with neurofibromatosis 1 in Denmark: a population- and register-based cohort study
Authors: Kenborg Line , Frederiksen Line E. , Galanakis Michael , Doser Karoline , Nielsen Thomas T. , Doherty Mia Aagaard , Hove Hanne , Østergaard John R. , Handrup Mette M. , Ejerskov Cecilie , Mulvihill John J. , Winther Jeanette F.
Published: November 2023

Background

Little is known about employment status, occupation, and disposable income in adults with NF1.

Methods

From the Danish National Patient Registry and database of two national Centers for Rare Diseases, we identified 1469 adults with NF1, who were matched to 11,991 randomly selected population comparisons on sex and birth year and month. Annual information on employment, occupation and disposable income was ascertained from national registries in 1980–2019.

Results

Adults with NF1 had a lower odds ratio (OR) for employment [OR 0.71, 95% confidence interval (CI) 0.61–0.83] and higher OR for health-related unemployment (OR 2.94, 95% CI 2.16–3.96) at age 30 years than population comparisons, which persisted at age 40 and 50 years. Somatic diagnoses were associated with a higher OR for health-related unemployment in adults with NF1 than in the population comparisons. Adults with NF1 had a slightly lower disposable income, with a 14% (0.82–0.89) reduction observed among the youngest birth cohort. Furthermore, adults with NF1 were less likely to be in a high skilled occupation at ages 30, 40 and 50 years.

Conclusion

Adults with NF1 have a lower employment rate, which was mainly due to health-related reasons and a slightly lower disposable income than adults without NF1. Thus, anticipation guidance for employment should be part of the management of NF1 families.
The political economy of expedience: examining perspectives on military support to Sierra Leone’s Ebola response
Authors: Boland Samuel T. , Balabanova Dina , Mayhew Susannah
Published: November 2023

The 2013–2016 West Africa Ebola Epidemic is the largest outbreak of Ebola in history. By September, 2014 the outbreak was worsening significantly, and the international president of Médecins Sans Frontières called for military assistance. In Sierra Leone, the British and Sierra Leonean militaries intervened. They quickly established a National Ebola Response Centre and a constituent network of District Ebola Response Centres. Thereafter, these inherently militarised centres are where almost all Ebola response activities were coordinated. In order to examine perspectives on the nature of the militaries’ intervention, 110 semi-structured qualitative interviews were conducted and analysed. Military support to Sierra Leone’s Ebola response was felt by most respondents to be a valuable contribution to the overall effort to contain the outbreak, especially in light of the perceived weakness of the Ministry of Health and Sanitation to effectively do so. However, a smaller number of respondents emphasised that the military deployments facilitated various structural harms, including for how the perceived exclusion of public institutions (as above) and other local actors from Ebola response decision making was felt to prevent capacity building, and in turn, to limit resilience to future crises. The concurrent provision of life-saving assistance and rendering of structural harm resulting from the militaries’ intervention is ultimately found to be part of a vicious cycle, which this article conceptualises as the ‘political economy of expedience’, a paradox that should be considered inherent in any militarised intervention during humanitarian and public health crises.
Effect on capillary refill time of volume expansion and increase of the norepinephrine dose in patients with septic shock
Authors: Fage Nicolas , Moretto Francesca , Rosalba Daniela , Shi Rui , Lai Christopher , Teboul Jean-Louis , Monnet Xavier
Published: November 2023

Background

Capillary refill time (CRT) has been suggested as a variable to follow during the course of septic shock. We systematically investigated the effects on CRT of volume expansion and norepinephrine.

Methods

In 69 septic shock patients, we recorded mean arterial pressure (MAP), cardiac index (CI), and 5 consecutive CRT measurements (video method, standardized pressure applied on the fingertip) before and after a 500-mL saline infusion in 33 patients and before and after an increase of the norepinephrine dose in 36 different patients. Fluid responders were defined by an increase in CI ≥ 15%, and norepinephrine responders by an increase in MAP ≥ 15%.

Results

The least significant change of CRT was 23%, so that changes in CRT were considered significant if larger than 23%. With volume expansion, CRT remained unchanged on average in patients with baseline CRT < 3 s (n = 7) and in all but one patient with baseline CRT ≥ 3 s in whom fluid increased CI < 15% (n = 13 “fluid non-responders”). In fluid responders with baseline CRT ≥ 3 s (n = 13), CRT decreased in 8 patients and remained unchanged in the others, exhibiting a dissociation between CI and CRT responses. The proportion of patients included > 24 h after starting norepinephrine was higher in patients with such a dissociation than in the other ones (60% vs. 0%, respectively). Norepinephrine did not change CRT significantly (except in one patient) if baseline CRT was ≥ 3 s and the increase in MAP < 15% (n = 6). In norepinephrine responders with prolonged baseline CRT (n = 11), it increased in 4 patients and remained unchanged in the other ones, which exhibited a dissociation between MAP and CRT responses.

Conclusions

In septic shock patients with prolonged CRT, CRT very rarely improves with treatment when volume expansion increases cardiac output < 15% and increasing norepinephrine increases MAP < 15%. When the effects of fluid infusion on cardiac output and of norepinephrine on MAP are significant, the response of CRT is variable, as it decreases in some patients and remains stable in others which exhibit a dissociation between changes in macrohemodynamic variables and in CRT. In this regard, CRT behaves as a marker of microcirculation.

Trial registration: ClinicalTrial.gov (NCT04870892). Registered January15, 2021. Ethics committee approval CE SRLF 21-25.
The ongoing risk of Leishmania donovani transmission in eastern Nepal: an entomological investigation during the elimination era
Authors: Roy Lalita , Cloots Kristien , Uranw Surendra , Rai Keshav , Bhattarai Narayan R. , Smekens Tom , Hendrickx Rik , Caljon Guy , Hasker Epco , Das Murari L. , Van Bortel Wim
Published: November 2023

Background

Visceral leishmaniasis (VL), a life-threatening neglected tropical disease, is targeted for elimination from Nepal by the year 2026. The national VL elimination program is still confronted with many challenges including the increasingly widespread distribution of the disease over the country, local resurgence and the questionable efficacy of the key vector control activities. In this study, we assessed the status and risk of Leishmania donovani transmission based on entomological indicators including seasonality, natural Leishmania infection rate and feeding behavior of vector sand flies, Phlebotomus argentipes, in three districts that had received disease control interventions in the past several years in the context of the disease elimination effort.

Methods

We selected two epidemiologically contrasting settings in each survey district, one village with and one without reported VL cases in recent years. Adult sand flies were collected using CDC light traps and mouth aspirators in each village for 12 consecutive months from July 2017 to June 2018. Leishmania infection was assessed in gravid sand flies targeting the small-subunit ribosomal RNA gene of the parasite (SSU-rRNA) and further sequenced for species identification. A segment (~ 350 bp) of the vertebrate cytochrome b (cytb) gene was amplified from blood-fed P. argentipes from dwellings shared by both humans and cattle and sequenced to identify the preferred host.

Results

Vector abundance varied among districts and village types and peaks were observed in June, July and September to November. The estimated Leishmania infection rate in vector sand flies was 2.2% (1.1%–3.7% at 95% credible interval) and 0.6% (0.2%–1.3% at 95% credible interval) in VL and non-VL villages respectively. The common source of blood meal was humans in both VL (52.7%) and non-VL (74.2%) villages followed by cattle.

Conclusions

Our findings highlight the risk of ongoing L. donovani transmission not only in villages with VL cases but also in villages not reporting the presence of the disease over the past several years within the districts having disease elimination efforts, emphasize the remaining threats of VL re-emergence and inform the national program for critical evaluation of disease elimination strategies in Nepal.

Graphical Abstract﻿
Cell fusing agent virus isolated from Aag2 cells does not vertically transmit in Aedes aegypti via artificial infection
Authors: Zhou Ningxin , Huang Enjiong , Guo Xiaoxia , Xiong Yiping , Xie Jingwen , Cai Tong , Du Yutong , Wu Qixing , Guo Sihan , Han Wanrong , Zhang Hengduan , Xing Dan , Zhao Tongyan , Jiang Yuting
Published: November 2023

Background

Cell fusing agent virus (CFAV) was the first insect-specific virus to be characterized, and has been reported to negatively influence the growth of arboviruses such as dengue, Zika, and La Cross, making it a promising biocontrol agent for mosquito-borne disease prevention. Aedes aegypti Aag2 cells were naturally infected with CFAV. However, the ability of this virus to stably colonize an Ae. aegypti population via artificial infection and how it influences the vector competence of this mosquito have yet to be demonstrated.

Methods

CFAV used in this study was harvested from Aag2 cells and its complete genome sequence was obtained by polymerase chain reaction and rapid amplification of complementary DNA ends, followed by Sanger sequencing. Phylogenetic analysis of newly identified CFAV sequences and other sequences retrieved from GenBank was performed. CFAV stock was inoculated into Ae. aegypti by intrathoracic injection, the survival of parental mosquitoes was monitored and CFAV copies in the whole bodies, ovaries, and carcasses of the injected F0 generation and in the whole bodies of the F1 generation on different days were examined by reverse transcription-quantitative polymerase chain reaction.

Results

The virus harvested from Aag2 cells comprised a mixture of three CFAV strains. All genome sequences of CFAV derived from Aag2 cells clustered into one clade but were far from those isolated or identified from Ae. aegypti. Aag2-derived CFAV efficiently replicated in the mosquito body and did not attenuate the survival of Ae. aegypti. However, the viral load in the ovarian tissues was much lower than that in other tissues and the virus could not passage to the offspring by vertical transmission.

Conclusions

The results of this study demonstrate that Aag2-derived CFAV was not vertically transmitted in Ae. aegypti and provide valuable information on the colonization of mosquitoes by this virus.

Graphical abstract
Genetic hypogonadal mouse model reveals niche-specific influence of reproductive axis and sex on intestinal microbial communities
Authors: Sisk-Hackworth Laura , Brown Jada , Sau Lillian , Levine Andrew A. , Tam Lai Ying Ivy , Ramesh Aishwarya , Shah Reeya S. , Kelley-Thackray Evelyn T. , Wang Sophia , Nguyen Anita , Kelley Scott T. , Thackray Varykina G.
Published: November 2023

Background

The gut microbiome has been linked to many diseases with sex bias including autoimmune, metabolic, neurological, and reproductive disorders. While numerous studies report sex differences in fecal microbial communities, the role of the reproductive axis in this differentiation is unclear and it is unknown how sex differentiation affects microbial diversity in specific regions of the small and large intestine.

Methods

We used a genetic hypogonadal mouse model that does not produce sex steroids or go through puberty to investigate how sex and the reproductive axis impact bacterial diversity within the intestine. Using 16S rRNA gene sequencing, we analyzed alpha and beta diversity and taxonomic composition of fecal and intestinal communities from the lumen and mucosa of the duodenum, ileum, and cecum from adult female (n = 20) and male (n = 20) wild-type mice and female (n = 17) and male (n = 20) hypogonadal mice.

Results

Both sex and reproductive axis inactivation altered bacterial composition in an intestinal section and niche-specific manner. Hypogonadism was significantly associated with bacteria from theBacteroidaceae,Eggerthellaceae,Muribaculaceae, andRikenellaceaefamilies,which have genes for bile acid metabolism and mucin degradation. Microbial balances between males and females and between hypogonadal and wild-type mice were also intestinal section-specific. In addition, we identified 3 bacterial genera (EscherichiaShigella,Lachnoclostridium, andEggerthellaceaegenus) with higher abundance in wild-type female mice throughout the intestinal tract compared to both wild-type male and hypogonadal female mice, indicating that activation of the reproductive axis leads to female-specific differentiation of the gut microbiome. Our results also implicated factors independent of the reproductive axis (i.e., sex chromosomes) in shaping sex differences in intestinal communities. Additionally, our detailed profile of intestinal communities showed that fecal samples do not reflect bacterial diversity in the small intestine.

Conclusions

Our results indicate that sex differences in the gut microbiome are intestinal niche-specific and that sampling feces or the large intestine may miss significant sex effects in the small intestine. These results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.
Supply-side factors influencing demand for facility-based delivery in Tanzania: a multilevel analysis
Authors: Binyaruka Peter , Foss Anna , Alibrahim Abdullah , Mziray Nicholaus , Cassidy Rachel , Borghi Josephine
Published: November 2023

Background

Improving access to facility-based delivery care has the potential to reduce maternal and newborn deaths across settings. Yet, the access to a health facility for childbirth remains low especially in low-income settings. To inform evidence-based interventions, more evidence is needed especially accounting for demand- and supply-side factors influencing access to facility-based delivery care. We aimed to fill this knowledge gap using data from Tanzania.

Methods

We used data from a cross-sectional survey (conducted in January 2012) of 150 health facilities, 1494 patients and 2846 households with women who had given births in the last 12 months before the survey across 11 districts in three regions in Tanzania. The main outcome was the place of delivery (giving birth in a health facility or otherwise), while explanatory variables were measured at the individual woman and facility level. Given the hierarchical structure of the data and variance in demand across facilities, we used a multilevel mixed-effect logistic regression to explore the determinants of facility-based delivery care.

Results

Eighty-six percent of 2846 women gave birth in a health facility. Demand for facility-based delivery care was influenced more by demand-side factors (76%) than supply-side factors (24%). On demand-side factors, facility births were more common among women who were educated, Muslim, wealthier, with their first childbirth, and those who had at least four antenatal care visits. On supply-side factors, facility births were more common in facilities offering outreach services, longer consultation times and higher interpersonal quality. In contrast, facilities with longer average waiting times, longer travel times and higher chances of charging delivery fees had few facility births.

Conclusions

Policy responses should aim for strategies to improve demand like health education to raise awareness towards care seeking among less educated groups and those with higher parity, reduce financial barriers to access (including time costs to reach and access care), and policy interventions to enhance interpersonal quality in service provision.
Safety and efficacy of human ESC-derived corneal endothelial cells for corneal endothelial dysfunction
Authors: Yu Juan , Yu Nianye , Tian Yao , Fang Yifan , An Bin , Feng Guihai , Wu Jun , Wang Liu , Hao Jie , Wang Liqiang , Zhou Qi , Li Wei , Wang Yukai , Hu Baoyang
Published: November 2023

Background

Research on human pluripotent stem cells (hPSCs) has shown tremendous progress in cell-based regenerative medicine. Corneal endothelial dysfunction is associated with the loss and degeneration of corneal endothelial cells (CECs), rendering cell replacement a promising therapeutic strategy. However, comprehensive preclinical assessments of hPSC-derived CECs for this cell therapy remain a challenge.

Results

Here we defined an adapted differentiation protocol to generate induced corneal endothelial cells (iCECs) consistently and efficiently from clinical-grade human embryonic stem cells (hESCs) with xeno-free medium and manufactured cryopreserved iCECs. Cells express high levels of typical CECs markers and exhibit transendothelial potential properties in vitro typical of iCECs. After rigorous quality control measures, cells meeting all release criteria were available for in vivo studies. We found that there was no overgrowth or tumorigenicity of grafts in immunodeficient mice. After grafting into rabbit models, the surviving iCECs ameliorated edema and recovered corneal opacity.

Conclusions

Our work provides an efficient approach for generating iCECs and demonstrates the safety and efficacy of iCECs in disease modeling. Therefore, clinical-grade iCECs are a reliable source for future clinical treatment of corneal endothelial dysfunction.
MiR-181a targets STING to drive PARP inhibitor resistance in BRCA- mutated triple-negative breast cancer and ovarian cancer
Authors: Bustos Matias A. , Yokoe Takamichi , Shoji Yoshiaki , Kobayashi Yuta , Mizuno Shodai , Murakami Tomohiro , Zhang Xiaoqing , Sekhar Sreeja C. , Kim SooMin , Ryu Suyeon , Knarr Matthew , Vasilev Steven A. , DiFeo Analisa , Drapkin Ronny , Hoon Dave S. B.
Published: November 2023

Background

Poly (ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of BRCA-mutated breast cancer (BC), including triple-negative BC (TNBC) and ovarian cancer (OvCa). A key challenge is to identify the factors associated with PARPi resistance; although, previous studies suggest that platinum-based agents and PARPi share similar resistance mechanisms.

Methods

Olaparib-resistant (OlaR) cell lines were analyzed using HTG EdgeSeq miRNA Whole Transcriptomic Analysis (WTA). Functional assays were performed in three BRCA-mutated TNBC cell lines. In-silico analysis were performed using multiple databases including The Cancer Genome Atlas, the Genotype-Tissue Expression, The Cancer Cell Line Encyclopedia, Genomics of Drug Sensitivity in Cancer, and Gene Omnibus Expression.

Results

High miR-181a levels were identified in OlaR TNBC cell lines (p = 0.001) as well as in tumor tissues from TNBC patients (p = 0.001). We hypothesized that miR-181a downregulates the stimulator of interferon genes (STING) and the downstream proinflammatory cytokines to mediate PARPi resistance. BRCA1 mutated TNBC cell lines with miR-181a-overexpression were more resistant to olaparib and showed downregulation in STING and the downstream genes controlled by STING. Extracellular vesicles derived from PARPi-resistant TNBC cell lines horizontally transferred miR-181a to parental cells which conferred PARPi-resistance and targeted STING. In clinical settings, STING levels were positively correlated with interferon gamma (IFNG) response scores (p = 0.01). In addition, low IFNG response scores were associated with worse response to neoadjuvant treatment including PARPi for high-risk HER2 negative BC patients (p = 0.001). OlaR TNBC cell lines showed resistance to platinum-based drugs. OvCa cell lines resistant to platinum showed resistance to olaparib. Knockout of miR-181a significantly improved olaparib sensitivity in OvCa cell lines (p = 0.001).

Conclusion

miR-181a is a key factor controlling the STING pathway and driving PARPi and platinum-based drug resistance in TNBC and OvCa. The miR-181a-STING axis can be used as a potential marker for predicting PARPi responses in TNBC and OvCa tumors.
Functional responses to deforestation in fish communities inhabiting neotropical streams and rivers
Authors: Cantera Isabel , Jézéquel Céline , Dejean Tony , Murienne Jérôme , Vigouroux Régis , Valentini Alice , Brosse Sébastien
Published: November 2023

Background

Deforestation is a widespread disturbance for neotropical freshwater ecosystems. While biodiversity declines have been associated with deforestation, its functional consequences for stream and river fish faunas remain poorly understood. In this study, we explored how deforestation affects the different facets of the functional structure of fish communities inventoried using environmental DNA metabarcoding in 64 river and 35 stream sites of French Guiana. Specifically, we investigated how functional richness, divergence, evenness and identity of fish faunas are affected by deforestation.

Results

We showed that anthropogenic disturbances in French Guiana are modifying the functional diversity of freshwater fish communities. These disturbances not only affected the amount of functional traits held by the communities but also the identity of the traits and the internal structure of the functional space. Consequently, different facets of the functional diversity supported by fish assemblages were altered. In streams, deforestation did not affect the overall diversity of traits but reduced functional redundancy, underlined by a shift in functional identity towards assemblages dominated by pelagic detritivores. In contrast, river fish faunas experienced a decline in functional richness, paired with shifts in functional identity and a loss of fish species with extreme functions.

Conclusions

The response to deforestation differed between streams and rivers, but it supports the hypothesis that deforestation is linked to functional changes in fish assemblages. By diminishing the range of the functions in rivers or by jeopardizing the redundancy of functions in streams, deforestation could severely hamper the functioning and stability of neotropical freshwater ecosystems.
Both extracellular vesicles from helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles are involved in gastric/extragastric diseases
Authors: Wang Chengyao , Li Wenkun , Shao Linlin , Zhou Anni , Zhao Mengran , Li Peng , Zhang Zheng , Wu Jing
Published: November 2023

Bacterial-derived extracellular vesicles (EVs) have emerged as crucial mediators in the cross-talk between hosts and pathogens, playing a significant role in infectious diseases and cancers. Among these pathogens, Helicobacter pylori (H. pylori) is a particularly important bacterium implicated in various gastrointestinal disorders, gastric cancers, and systemic illnesses. H. pylori achieves these effects by stimulating host cells to secrete EVs and generating internal outer membrane vesicles (OMVs). The EVs derived from H. pylori-infected host cells modulate inflammatory signaling pathways, thereby affecting cell proliferation, apoptosis, cytokine release, immune cell modification, and endothelial dysfunction, as well as disrupting cellular junctional structures and inducing cytoskeletal reorganization. In addition, OMVs isolated from H. pylori play a pivotal role in shaping subsequent immunopathological responses. These vesicles incite both inflammatory and immunosuppressive reactions within the host environment, facilitating pathogen evasion of host defenses and invasion of host cells. Despite this growing understanding, research involving H. pylori-derived EVs remains in its early stages across different domains. In this comprehensive review, we present recent advancements elucidating the contributions of EV components, such as non-coding RNAs (ncRNAs) and proteins, to the pathogenesis of gastric and extragastric diseases. Furthermore, we highlight their potential utility as biomarkers, therapeutic targets, and vehicles for targeted delivery.
decOM: similarity-based microbial source tracking of ancient oral samples using k-mer-based methods
Authors: Duitama González Camila , Vicedomini Riccardo , Lemane Téo , Rascovan Nicolas , Richard Hugues , Chikhi Rayan
Published: November 2023

Background

The analysis of ancient oral metagenomes from archaeological human and animal samples is largely confounded by contaminant DNA sequences from modern and environmental sources. Existing methods for Microbial Source Tracking (MST) estimate the proportions of environmental sources, but do not perform well on ancient metagenomes. We developed a novel method called decOM for Microbial Source Tracking and classification of ancient and modern metagenomic samples using k-mer matrices.

Results

We analysed a collection of 360 ancient oral, modern oral, sediment/soil and skin metagenomes, using stratified five-fold cross-validation. decOM estimates the contributions of these source environments in ancient oral metagenomic samples with high accuracy, outperforming two state-of-the-art methods for source tracking, FEAST and mSourceTracker.

Conclusions

decOM is a high-accuracy microbial source tracking method, suitable for ancient oral metagenomic data sets. The decOM method is generic and could also be adapted for MST of other ancient and modern types of metagenomes. We anticipate that decOM will be a valuable tool for MST of ancient metagenomic studies.
Bacterial quorum sensing orchestrates longitudinal interactions to shape microbiota assembly
Authors: Su Ying , Xu Ming-ying , Cui Ying , Chen Run-zhi , Xie Li-xiang , Zhang Jing-xiang , Chen Yong-qiu , Ding Tao
Published: November 2023

Background

The mechanism of microbiota assembly is one of the main problems in microbiome research, which is also the primary theoretical basis for precise manipulation of microbial communities. Bacterial quorum sensing (QS), as the most common means for bacteria to exchange information and interactions, is characterized by universality, specificity, and regulatory power, which therefore may influence the assembly processes of human microbiota. However, the regulating role of QS in microbiota assembly is rarely reported. In this study, we developed an optimized in vitro oral biofilm microbiota assembling (OBMA) model to simulate the time-series assembly of oral biofilm microbiota (OBM), by which to excavate the QS network and its regulating power in the process.

Results

By using the optimized OBMA model, we were able to restore the assembly process of OBM and generate time-series OBM metagenomes of each day. We discovered a total of 2291 QS protein homologues related to 21 QS pathways. Most of these pathways were newly reported and sequentially enriched during OBM assembling. These QS pathways formed a comprehensive longitudinal QS network that included successively enriched QS hubs, such as Streptococcus, Veillonella-Megasphaera group, and Prevotella-Fusobacteria group, for information delivery. Bidirectional cross-talk among the QS hubs was found to play critical role in the directional turnover of microbiota structure, which in turn, influenced the assembly process. Subsequent QS-interfering experiments accurately predicted and experimentally verified the directional shaping power of the longitudinal QS network in the assembly process. As a result, the QS-interfered OBM exhibited delayed and fragile maturity with prolonged membership of Streptococcus and impeded membership of Prevotella and Fusobacterium.

Conclusion

Our results revealed an unprecedented longitudinal QS network during OBM assembly and experimentally verified its power in predicting and manipulating the assembling process. Our work provides a new perspective to uncover underlying mechanism in natural complex microbiota assembling and a theoretical basis for ultimately precisely manipulating human microbiota through intervention in the QS network.
The influence of sociodemographic factors on students' attitudes toward AI-generated video content creation
Authors: Pellas Nikolaos
Published: November 2023

Artificial Intelligence (AI) and Machine Learning (ML) technologies offer the potential to support digital content creation and media production, providing opportunities for individuals from diverse sociodemographic backgrounds to engage in creative activities and enhance their multimedia video content. However, less attention has been paid to recent research exploring any possible relationships between AI-generated video creation and the sociodemographic variables of undergraduate students. This study aims to investigate the multifaceted relationship between AI-generated video content and sociodemographics by examining its implications for inclusivity, equity, and representation in the digital media landscape. An empirical study about the use of AI in video content creation was conducted with a diverse cohort of three hundred ninety-eighth undergraduate (n = 398) students. Participants voluntarily took part and were tasked with conceiving and crafting their AI-generated video content. All instruments used were combined into a single web-based self-report questionnaire that was delivered to all participants via email. Key research findings demonstrate that students have a favorable disposition when it comes to incorporating AI-supported learning tasks. The factors fostering this favorable attitude among students include their age, the number of devices they use, the time they dedicate to utilizing technological resources, and their level of experience. Nevertheless, it is the student’s participation in AI training courses that exerts a direct impact on students’ ML attitudes, along with their level of contentment with the reliability of these technologies. This study contributes to a more comprehensive understanding of the transformative power of AI in video content creation and underscores the importance of considering instructional contexts and policies to ensure a fair and equitable digital media platform for students from diverse sociodemographic backgrounds.
Baseline and interim [18F]FDG-PET/MRI to assess treatment response and survival in patients with M0 esophageal squamous cell carcinoma treated by curative-intent therapy
Authors: Chao Yin-Kai , Chang Chun-Bi , Chang Yu-Chuan , Chan Sheng-Chieh , Chiu Chien-Hung , Ng Shu-Hang , Hsieh Jason Chia-Hsun , Wang Jen-Hung
Published: November 2023

Background

To investigate the value of [18F]FDG-PET/MRI in predicting treatment response and survival in patients with primary M0 esophageal squamous cell carcinoma.

Methods

Patients with esophageal squamous cell carcinoma received [18F]FDG-PET/MRI at baseline and during neoadjuvant or definitive chemoradiotherapy. The treatment response was classified according to the Response Evaluation Criteria for Solid Tumors 1.1. We used Kaplan-Meier and Cox regression analyses to assess the association between PET/MRI parameters and overall survival (OS) or progression-free survival (PFS).

Results

We included 40 M0 patients in the final analysis. The volume transfer constant (Ktrans) from baseline PET/MRI (area under the curve (AUC) = 0.688, P = 0.034) and total lesion glycolysis (TLG) from baseline PET/MRI (AUC = 0.723, P = 0.006) or interim PET/MRI (AUC = 0.853, P < 0.001) showed acceptable AUC for predicting treatment response. The TLG from interim PET/MRI (interim TLG, P < 0.001) and extracellular volume fraction (Ve) on interim PET/MRI (interim Ve, P = 0.001) were identified as independent prognostic factors for OS. Baseline Ve (P = 0.044) and interim TLG (P = 0.004) were significant predictors of PFS. The c-indices of the prognostic models combining interim TLG with Ve for predicting OS, and baseline Ve and interim TLG for predicting PFS were 0.784 and 0.699, respectively. These values were significantly higher than the corresponding c-indices of the TNM staging system (P = 0.002 and P = 0.047, respectively).

Conclusions

Combining the baseline and interim [18F]FDG-PET/MRI qualitative imaging parameters aids in predicting the prognosis of patients with M0 esophageal squamous cell carcinoma.

Trial registration

The study was registered at Clinicaltrials.gov (identifier: NCT 05855291 and NCT 05855278).
Experimental study of the behavior of square footing on reinforced sand with treated geotextile
Authors: Zamani Siavash , Lajevardi Seyed Hamid , Yarivand Akbar , Zeighami Ehsanolah
Published: November 2023

Bearing capacity of reinforced footing clearly depends on the characteristics of interface between geosynthetic and soil. A suitable solution for increasing the bearing capacity is to treat the geotextile surface by various additives. This study reported the results of plate load test on square model footing resting on reinforced sand with and without treated geotextiles to survey the effects of the treatment of geotextile on settlement and bearing capacity. The treated geotextiles were made using additives onto the surface, with a layer of sand located on the top. Geotextile sides were treated in the same way. Different additives including the lime, cement, emulsion, and the effect of the number of layers were considered. The bearing capacity ratio values (BCR), improvement ratio values (IR) and variation of load-settlement ratio obtained from the treated models were presented. The results showed that the treatment of geotextile has a great effect on the behavior of reinforced sand and thus bearing capacity. Also, the test results indicated that lime-treated geotextiles provided better improvement than other additives. The maximum improvement in the bearing capacity of square footing supported on treated geotextiles was found to be 75% compared with the pristine geotextiles.
Effect of lime-rice husk ash on geotechnical properties of loess soil in Golestan province, Iran
Authors: Zivari Amin , Siavoshnia Mehdi , Rezaei Hamed
Published: November 2023

Loess soils have always been among the most problematic soils, according to engineers. Due to the sensitivity and vulnerability of this soil type, researchers are constantly looking for different solutions to improve and stabilize this soil using different methods. In the present study, a mixture of lime and rice husk ash (LRHA) was used to modify the loess soil of the Golestan province, Iran. Lime and RHA were mixed in a ratio of 2:4 and with different contents of 2.5, 5, 7.5, 10 and 12.5% of the dry weight of the soil. To study the effect of curing on the strength properties, the samples were cured and tested for 7, 18 and 28 days. Atterberg limits, modified Proctor, unconfined compressive strength (UCS) and scanning electron microscope tests (SEM) were performed. It was found that increasing LRHA content increased the value of UCS at different curing times, such that UCS increased about five times by the addition of 5% LRHA to the loess at the end of 28 days. As the curing time increased, the optimum amount of the additive also decreased. The results showed that combining the soil with LRHA is an effective method for improving and stabilizing loess soil. According to the results of the study, the optimum value of 5% additive is economically and technically recommended.
Fabrication of a three-dimensional bone marrow niche-like acute myeloid Leukemia disease model by an automated and controlled process using a robotic multicellular bioprinting system
Authors: Alhattab Dana M. , Isaioglou Ioannis , Alshehri Salwa , Khan Zainab N. , Susapto Hepi H. , Li Yanyan , Marghani Yara , Alghuneim Arwa A. , Díaz-Rúa Rubén , Abdelrahman Sherin , AL-Bihani Shuroug , Ahmed Farid , Felimban Raed I. , Alkhatabi Heba , Alserihi Raed , Abedalthagafi Malak , AlFadel AlShaibani , Awidi Abdalla , Chaudhary Adeel Gulzar , Merzaban Jasmeen , Hauser Charlotte A. E.
Published: November 2023

Background

Acute myeloid leukemia (AML) is a hematological malignancy that remains a therapeutic challenge due to the high incidence of disease relapse. To better understand resistance mechanisms and identify novel therapies, robust preclinical models mimicking the bone marrow (BM) microenvironment are needed. This study aimed to achieve an automated fabrication process of a three-dimensional (3D) AML disease model that recapitulates the 3D spatial structure of the BM microenvironment and applies to drug screening and investigational studies.

Methods

To build this model, we investigated a unique class of tetramer peptides with an innate ability to self-assemble into stable hydrogel. An automated robotic bioprinting process was established to fabricate a 3D BM (niche-like) multicellular AML disease model comprised of leukemia cells and the BM’s stromal and endothelial cellular fractions. In addition, monoculture and dual-culture models were also fabricated. Leukemia cell compatibility, functionalities (in vitro and in vivo), and drug assessment studies using our model were performed. In addition, RNAseq and gene expression analysis using TaqMan arrays were also performed on 3D cultured stromal cells and primary leukemia cells.

Results

The selected peptide hydrogel formed a highly porous network of nanofibers with mechanical properties similar to the BM extracellular matrix. The robotic bioprinter and the novel quadruple coaxial nozzle enabled the automated fabrication of a 3D BM niche-like AML disease model with controlled deposition of multiple cell types into the model. This model supported the viability and growth of primary leukemic, endothelial, and stromal cells and recapitulated cell-cell and cell-ECM interactions. In addition, AML cells in our model possessed quiescent characteristics with improved chemoresistance attributes, resembling more the native conditions as indicated by our in vivo results. Moreover, the whole transcriptome data demonstrated the effect of 3D culture on enhancing BM niche cell characteristics. We identified molecular pathways upregulated in AML cells in our 3D model that might contribute to AML drug resistance and disease relapse.

Conclusions

Our results demonstrate the importance of developing 3D biomimicry models that closely recapitulate the in vivo conditions to gain deeper insights into drug resistance mechanisms and novel therapy development. These models can also improve personalized medicine by testing patient-specific treatments.

Graphical Abstract
Correlates of non-institutional delivery to delayed initiation of breastfeeding in Nigeria: logit-decomposition and subnational analysis of population-based survey
Authors: Oyedele Oyewole K.
Published: November 2023

Background

Studies have connected newborn delivery settings and modality to optimal breastfeeding, but how it influences untimely initiation, mostly prevalent in sub-Saharan Africa is unknown. Hence, the role of home delivery on delay initiation of breastfeeding (DIBF) in Nigeria was investigated to inform evidence-based strategy for improved breastfeeding practice.

Methodology

This is a secondary analysis of births (11,469 home and 7632 facility delivery) by 19,101 reproductive age women in the 2018 NDHS. DIBF is the outcome, home birth is the exposure, and explanatory variables were classified as: socio-demographics, obstetrics and economic factors. Descriptive statistics (frequencies and percentages) were reported, and bivariate (chi-square) analysis was carried out at 20% (p < 0.20) cutoff point. Multivariable logistic regression assessed the probability and significance of the outcome per place of birth. Multivariate decomposition further evaluated the endowment and coefficient effect contribution by independent factors to the outcome. Analysis was carried out at p < 0.05 (95% confidence level) on Stata.

Results

56.6% of mothers DIBF, with 37.1% and 19.5% from home and facility delivery, respectively. Home delivery (AOR = 1.34, 95% CI 1.17–1.52) increase the chance of DIBF by 34%, while DIBF probability reduces by 26% in facility delivery (AOR = 0.74, 95% CI 0.65–0.85). DIBF is 5 times more likely in caesarian section delivery (AOR = 5.10, 95% CI 4.08–6.38) compared to virginal birth in facility delivery. Skilled antenatal provider, parity and wealth are negatively associated with DIBF in home birth, while undesired pregnancy, rural residency, partial/no skin-to-skin contact and large child size positively influence DIBF in both home and facility delivery. Skilled antenatal provider (C =  − 66.3%, p < 0.01) and skin-to-skin contact (C =  − 60.6%, p < 0.001) contributed most to reducing the negative DIBF effect with 69% and 31% overall characteristics and coefficient effect component, respectively. DIBF is more likely in Bauchi and Sokoto but less likely in Bayelsa.

Conclusions

High DIBF prevalent in Nigeria was largely due to elevated rate of home birth, positively associated with DIBF. Caesarian section delivery though heightens the chance of DIBF in facility delivery. Strengthening utilization of skilled provider and skin-to-skin contact can eliminate two-third of the adverse DIBF effect and improve early initiation rate. Adopting this strategy will bridge home-facility delivery gap to achieve optimal breastfeeding practice.