bluuebunny/crossref_metadata_2025 huggingface dataset:
Dismissal informs the priorities of endometriosis patients in New Zealand
Authors: Ellis Katherine , Munro Deborah , Wood Rachael
Published: June 2023

Introduction

Endometriosis is a common condition with average delays to diagnosis in New Zealand of almost 9 years.

Methods

In total, 50 endometriosis patients participated in anonymous, asynchronous, online group discussions about their priorities, and their experiences with the development of symptoms, seeking a diagnosis, and receiving appropriate treatment.

Results

Higher subsidy of care was the top change endometriosis patients wanted, followed by more research funding. When asked to choose whether research should be focused on improving diagnosis or improving treatment methods, the results were evenly split. Within this cohort, patients highlighted that they did not know the difference between normal menstrual discomfort and pathological endometriotic pain. If, upon seeking help, medical practitioners classified their symptoms as “normal,” these dismissals could instill doubt in patients, which made it more difficult for them to continue to seek a diagnosis and effective treatments. Patients who did not express dismissal had a significantly shorter delay from symptom onset to diagnosis of 4.6 ± 3.4 years vs. 9.0 ± 5.2 years.

Conclusion

Doubt is a frequent experience for endometriosis patients in New Zealand, which was reinforced by some medical practitioners who were dismissive of their pain and thus prolonged the patient's delay to diagnosis.
Cellulose metabolism in halo(natrono)archaea: a comparative genomics study
Authors: Elcheninov Alexander G. , Ugolkov Yaroslav A. , Elizarov Ivan M. , Klyukina Alexandra A. , Kublanov Ilya V. , Sorokin Dimitry Y.
Published: June 2023

Extremely halophilic archaea are one of the principal microbial community components in hypersaline environments. The majority of cultivated haloarchaea are aerobic heterotrophs using peptides or simple sugars as carbon and energy sources. At the same time, a number of novel metabolic capacities of these extremophiles were discovered recently among which is a capability of growing on insoluble polysaccharides such as cellulose and chitin. Still, polysaccharidolytic strains are in minority among cultivated haloarchaea and their capacities of hydrolyzing recalcitrant polysaccharides are hardly investigated. This includes the mechanisms and enzymes involved in cellulose degradation, which are well studied for bacterial species, while almost unexplored in archaea and haloarchaea in particular. To fill this gap, a comparative genomic analysis of 155 cultivated representatives of halo(natrono)archaea, including seven cellulotrophic strains belonging to the genera Natronobiforma, Natronolimnobius, Natrarchaeobius, Halosimplex, Halomicrobium and Halococcoides was performed. The analysis revealed a number of cellulases, encoded in the genomes of cellulotrophic strains but also in several haloarchaea, for which the capacity to grow on cellulose was not shown. Surprisingly, the cellulases genes, especially of GH5, GH9 and GH12 families, were significantly overrepresented in the cellulotrophic haloarchaea genomes in comparison with other cellulotrophic archaea and even cellulotrophic bacteria. Besides cellulases, the genes for GH10 and GH51 families were also abundant in the genomes of cellulotrophic haloarchaea. These results allowed to propose the genomic patterns, determining the capability of haloarchaea to grow on cellulose. The patterns helped to predict cellulotrophic capacity for several halo(natrono)archaea, and for three of them it was experimentally confirmed. Further genomic search revealed that glucose and cellooligosaccharides import occurred by means of porters and ABC (ATP-binding cassette) transporters. Intracellular glucose oxidation occurred through glycolysis or the semi-phosphorylative Entner-Dudoroff pathway which occurrence was strain-specific. Comparative analysis of CAZymes toolbox and available cultivation-based information allowed proposing two possible strategies used by haloarchaea capable of growing on cellulose: so-called specialists are more effective in degradation of cellulose while generalists are more flexible in nutrient spectra. Besides CAZymes profiles the groups differed in genome sizes, as well as in variability of mechanisms of import and central metabolism of sugars.
Prevalence, genomic characterization and antimicrobial resistance of Campylobacter spp. isolates in pets in Shenzhen, China
Authors: Ju Changyan , Ma Yanping , Zhang Bi , Zhou Guilan , Wang Hairui , Yu Muhua , He Jiaoming , Duan Yongxiang , Zhang Maojun
Published: June 2023

The prevalence of Campylobacter spp.in pets is a potential concern for human health. However, little is known about the pet-related Campylobacter spp. in China. A total of 325 fecal samples were collected from dogs, cats, and pet foxes. Campylobacter spp. were isolated by culture, and MALDI-TOF MS was used to identify 110 Campylobacter spp. isolates in total. C. upsaliensis (30.2%, 98/325), C. helveticus (2.5%, 8/325), and C. jejuni (1.2%, 4/325) were the three found species. In dogs and cats, the prevalence of Campylobacter spp. was 35.0% and 30.1%, respectively. A panel of 11 antimicrobials was used to evaluate the antimicrobial susceptibility by the agar dilution method. Among C. upsaliensis isolates, ciprofloxacin had the highest rate of resistance (94.9%), followed by nalidixic acid (77.6%) and streptomycin (60.2%). Multidrug resistance (MDR) was found in 55.1% (54/98) of the C. upsaliensis isolates. Moreover, 100 isolates, including 88 C. upsaliensis, 8 C. helveticus, and 4 C. jejuni, had their whole genomes sequenced. By blasting the sequence against the VFDB database, virulence factors were identified. In total, 100% of C. upsaliensis isolates carried the cadF, porA, pebA, cdtA, cdtB, and cdtC genes. The flaA gene was present in only 13.6% (12/88) of the isolates, while the flaB gene was absent. By analyzing the sequence against the CARD database, we found that 89.8% (79/88) of C. upsaliensis isolates had antibiotic target alteration in the gyrA gene conferring resistance to fluoroquinolone, 36.4% (32/88) had the aminoglycoside resistance gene, and 19.3% (17/88) had the tetracycline resistance gene. The phylogenetic analysis using the K-mer tree method obtained two major clades among the C. upsaliensis isolates. All eight isolates in subclade 1 possessed the gyrA gene mutation, the aminoglycoside and tetracycline resistance genes, and were phenotypically resistant to six classes of antimicrobials. It has been established that pets are a significant source of Campylobacter spp. strains and a reservoir for them. This study is the first to have documented the presence of Campylobacter spp. in pets in Shenzhen, China. In this study, C. upsaliensis of subclade 1 required additional attention due to its broad MDR phenotype and relatively high flaA gene prevalence.
Glomerular endothelial glycocalyx-derived heparan sulfate inhibits glomerular leukocyte influx and attenuates experimental glomerulonephritis
Authors: Maciej-Hulme Marissa L. , Van Gemst Jasper J. , Sanderson Patience , Rops Angelique L. W. M. M. , Berden Jo H. , Smeets Bart , Amster I. Jonathan , Rabelink Ton J. , Van Der Vlag Johan
Published: June 2023

Proliferative forms of glomerulonephritis are characterized by the influx of leukocytes, albuminuria, and loss of kidney function. The glomerular endothelial glycocalyx is a thick carbohydrate layer that covers the endothelium and is comprised of heparan sulfate (HS), which plays a pivotal role in glomerular inflammation by facilitating endothelial-leukocyte trafficking. We hypothesize that the exogenous glomerular glycocalyx may reduce the glomerular influx of inflammatory cells during glomerulonephritis. Indeed, administration of mouse glomerular endothelial cell (mGEnC)-derived glycocalyx constituents, or the low-molecular-weight heparin enoxaparin, reduced proteinuria in mice with experimental glomerulonephritis. Glomerular influx of granulocytes and macrophages, as well as glomerular fibrin deposition, was reduced by the administration of mGEnC-derived glycocalyx constituents, thereby explaining the improved clinical outcome. HSglx also inhibited granulocyte adhesion to human glomerular endothelial cells in vitro. Notably, a specific HSglx fraction inhibited both CD11b and L-selectin binding to activated mGEnCs. Mass spectrometry analysis of this specific fraction revealed six HS oligosaccharides, ranging from tetra- to hexasaccharides with 2–7 sulfates. In summary, we demonstrate that exogenous HSglx reduces albuminuria during glomerulonephritis, which is possibly mediated via multiple mechanisms. Our results justify the further development of structurally defined HS-based therapeutics for patients with (acute) inflammatory glomerular diseases, which may be applicable to non-renal inflammatory diseases as well.
Identification of key signaling pathways and hub genes related to immune infiltration in Kawasaki disease with resistance to intravenous immunoglobulin based on weighted gene co-expression network analysis
Authors: Wang Yue , Cao Yinyin , Li Yang , Yuan Meifen , Xu Jin , Li Jian
Published: June 2023

Background: Kawasaki disease (KD) is an acute vasculitis, that is, the leading cause of acquired heart disease in children, with approximately 10%–20% of patients with KD suffering intravenous immunoglobulin (IVIG) resistance. Although the underlying mechanism of this phenomenon remains unclear, recent studies have revealed that immune cell infiltration may associate with its occurrence.

Methods: In this study, we downloaded the expression profiles from the GSE48498 and GSE16797 datasets in the Gene Expression Omnibus database, analyzed differentially expressed genes (DEGs), and intersected the DEGs with the immune-related genes downloaded from the ImmPort database to obtain differentially expressed immune-related genes (DEIGs). Then CIBERSORT algorithm was used to calculate the immune cell compositions, followed by the WGCNA analysis to identify the module genes associated with immune cell infiltration. Next, we took the intersection of the selected module genes and DEIGs, then performed GO and KEGG enrichment analysis. Moreover, ROC curve validation, Spearman analysis with immune cells, TF, and miRNA regulation network, and potential drug prediction were implemented for the finally obtained hub genes.

Results: The CIBERSORT algorithm showed that neutrophil expression was significantly higher in IVIG-resistant patients compared to IVIG-responsive patients. Next, we got differentially expressed neutrophil-related genes by intersecting DEIGs with neutrophil-related module genes obtained by WGCNA, for further analysis. Enrichment analysis revealed that these genes were associated with immune pathways, such as cytokine-cytokine receptor interaction and neutrophil extracellular trap formation. Then we combined the PPI network in the STRING database with the MCODE plugin in Cytoscape and identified 6 hub genes (TLR8, AQP9, CXCR1, FPR2, HCK, and IL1R2), which had good diagnostic performance in IVIG resistance according to ROC analysis. Furthermore, Spearman’s correlation analysis confirmed that these genes were closely related to neutrophils. Finally, TFs, miRNAs, and potential drugs targeting the hub genes were predicted, and TF-, miRNA-, and drug-gene networks were constructed.

Conclusion: This study found that the 6 hub genes (TLR8, AQP9, CXCR1, FPR2, HCK, and IL1R2) were significantly associated with neutrophil cell infiltration, which played an important role in IVIG resistance. In a word, this work rendered potential diagnostic biomarkers and prospective therapeutic targets for IVIG-resistant patients.
An update on mobile applications collecting data among subjects with or at risk of Alzheimer's disease
Authors: Piendel Lydia , Vališ Martin , Hort Jakub
Published: June 2023

Smart mobile phone use is increasing worldwide, as is the ability of mobile devices to monitor daily routines, behaviors, and even cognitive changes. There is a growing opportunity for users to share the data collected with their medical providers which may serve as an accessible cognitive impairment screening tool. Data logged or tracked in an app and analyzed with machine learning (ML) could identify subtle cognitive changes and lead to more timely diagnoses on an individual and population level. This review comments on existing evidence of mobile device applications designed to passively and/or actively collect data on cognition relevant for early detection and diagnosis of Alzheimer's disease (AD). The PubMed database was searched to identify existing literature on apps related to dementia and cognitive health data collection. The initial search deadline was December 1, 2022. Additional literature published in 2023 was accounted for with a follow-up search prior to publication. Criteria for inclusion was limited to articles in English which referenced data collection via mobile app from adults 50+ concerned, at risk of, or diagnosed with AD dementia. We identified relevant literature (n = 25) which fit our criteria. Many publications were excluded because they focused on apps which fail to collect data and simply provide users with cognitive health information. We found that although data collecting cognition-related apps have existed for years, the use of these apps as screening tools remains underdeveloped; however, it may serve as proof of concept and feasibility as there is much supporting evidence on their predictive utility. Concerns about the validity of mobile apps for cognitive screening and privacy issues remain prevalent. Mobile applications and use of ML is widely considered a financially and socially viable method of compiling symptomatic data but currently this large potential dataset, screening tool, and research resource is still largely untapped.
Effects of liraglutide on astrocyte polarization and neuroinflammation in db/db mice: focus on iron overload and oxidative stress
Authors: An Ji-Ren , Liu Jun-Tong , Gao Xiao-Meng , Wang Qing-Feng , Sun Gui-Yan , Su Jia-Nan , Zhang Chi , Yu Jia-Xiang , Yang Yu-Feng , Shi Yan
Published: June 2023

Neuroinflammation plays a crucial role in the occurrence and development of cognitive impairment in type 2 diabetes mellitus (T2DM), but the specific injury mechanism is not fully understood. Astrocyte polarization has attracted new attention and has been shown to be directly and indirectly involved in neuroinflammation. Liraglutide has been shown to have beneficial effects on neurons and astrocytes. However, the specific protection mechanism still needs to be clarified. In this study, we assessed the levels of neuroinflammation and A1/A2-responsive astrocytes in the hippocampus of db/db mice and examined their relationships with iron overload and oxidative stress. First, in db/db mice, liraglutide alleviated the disturbance of glucose and lipid metabolism, increased the postsynaptic density, regulated the expression of NeuN and BDNF, and partially restored impaired cognitive function. Second, liraglutide upregulated the expression of S100A10 and downregulated the expression of GFAP and C3, and decreased the secretion of IL-1β, IL-18, and TNF-α, which may confirm that it regulates the proliferation of reactive astrocytes and A1/A2 phenotypes polarize and attenuate neuroinflammation. In addition, liraglutide reduced iron deposition in the hippocampus by reducing the expression of TfR1 and DMT1 and increasing the expression of FPN1; at the same time, liraglutide by up-regulating the levels of SOD, GSH, and SOD2 expression, as well as downregulation of MDA levels and NOX2 and NOX4 expression to reduce oxidative stress and lipid peroxidation. The above may attenuate A1 astrocyte activation. This study preliminarily explored the effect of liraglutide on the activation of different astrocyte phenotypes and neuroinflammation in the hippocampus of a T2DM model and further revealed its intervention effect on cognitive impairment in diabetes. Focusing on the pathological consequences of astrocytes may have important implications for the treatment of diabetic cognitive impairment.
Resensitization of TRPV1 channels after the P2 receptor activation in sensory neurons of spinal ganglia in rats
Authors: Petrushenko Olena A. , Stratiievska Anastasiiya O. , Petrushenko Mariia O. , Lukyanetz Elena A.
Published: June 2023

Introduction

TRPV1 channels are responsible for detecting noxious stimuli such as heat (>43°C), acid, and capsaicin. P2 receptors are involved in numerous functions of the nervous system, including its modulation and specific response to the application of ATP. In our experiments, we investigated the dynamics of calcium transients in DRG neurons associated with TRPV1 channel desensitization and the effect of activation of P2 receptors on this process.

Methods

We used DRG neurons from rats P7–8 after 1–2 days of culture to measure calcium transients by microfluorescence calcimetry using the fluorescent dye Fura-2 AM.

Results

We have shown that DRG neurons of small (d < 22 μm) and medium (d = 24–35 μm) sizes differ in TRPV1 expression. Thus, TRPV1 channels are mainly present in small nociceptive neurons (59% of the studied neurons). Short-term sequential application of the TRPV1 channel agonist capsaicin (100nM) leads to the desensitization of TRPV1 channels by the type of tachyphylaxis. We identified three types of sensory neurons based on responses to capsaicin: (1) desensitized 37.5%, (2) non-desensitized 34.4%, and (3) insensitive 23.4% to capsaicin. It has also been shown that P2 receptors are present in all types of neurons according to their size. So, the responses to ATP were different in different-sized neurons. Applying ATP (0.1 mM) to the intact cell membrane after the onset of tachyphylaxis caused recovery of calcium transients in response to the addition of capsaicin in these neurons. The amplitude of the capsaicin response after reconstitution with ATP was 161% of the previous minimal calcium transient in response to capsaicin.

Discussion

Significantly, the restoration of the amplitude of calcium transients under the ATP application is not associated with changes in the cytoplasmic pool of ATP because this molecule does not cross the intact cell membrane, thus, our results show the interaction between TRPV1 channels and P2 receptors. It is important to note that the restoration of the amplitude of calcium transients through TRPV1 channels after application of ATP was observed mainly in cells of 1–2 days of cultivation. Thus, the resensitization of capsaicin transients following P2 receptor activation may be associated with the regulation of the sensitivity of sensory neurons.
Spontaneous Necker-cube reversals may not be that spontaneous
Authors: Wilson Mareike , Hecker Lukas , Joos Ellen , Aertsen Ad , Tebartz van Elst Ludger , Kornmeier Jürgen
Published: June 2023

Introduction

During observation of the ambiguous Necker cube, our perception suddenly reverses between two about equally possible 3D interpretations. During passive observation, perceptual reversals seem to be sudden and spontaneous. A number of theoretical approaches postulate destabilization of neural representations as a pre-condition for reversals of ambiguous figures. In the current study, we focused on possible Electroencephalogram (EEG) correlates of perceptual destabilization, that may allow prediction of an upcoming perceptual reversal.

Methods

We presented ambiguous Necker cube stimuli in an onset-paradigm and investigated the neural processes underlying endogenous reversals as compared to perceptual stability across two consecutive stimulus presentations. In a separate experimental condition, disambiguated cube variants were alternated randomly, to exogenously induce perceptual reversals. We compared the EEG immediately before and during endogenous Necker cube reversals with corresponding time windows during exogenously induced perceptual reversals of disambiguated cube variants.

Results

For the ambiguous Necker cube stimuli, we found the earliest differences in the EEG between reversal trials and stability trials already 1 s before a reversal occurred, at bilateral parietal electrodes. The traces remained similar until approximately 1100 ms before a perceived reversal, became maximally different at around 890 ms (p = 7.59 × 10–6, Cohen’s d = 1.35) and remained different until shortly before offset of the stimulus preceding the reversal. No such patterns were found in the case of disambiguated cube variants.

Discussion

The identified EEG effects may reflect destabilized states of neural representations, related to destabilized perceptual states preceding a perceptual reversal. They further indicate that spontaneous Necker cube reversals are most probably not as spontaneous as generally thought. Rather, the destabilization may occur over a longer time scale, at least 1 s before a reversal event, despite the reversal event as such being perceived as spontaneous by the viewer.
Current knowledge on the effects of environmental contaminants in early life nutrition
Authors: Street Maria E. , Shulhai Anna-Mariia , Rotondo Roberta , Giannì Giuliana , Caffarelli Carlo
Published: June 2023

Breast milk represents the optimal source of feeding for newborns, in terms of nutritional compounds and as it provides immunological, metabolic, organic, and neurological well-being. As a complex biological fluid, it consists not only of nutritional compounds but also contains environmental contaminants. Formulas through production, contact with bottles and cups, and complementary feeding can also be contaminated. The current review focuses on endocrine-disrupting chemicals, and made-man xenoestrogens present in the environment and both commonly present in food sources, agricultural practices, packaging, consumer products, industry, and medical care. These contaminants are transferred by passive diffusion to breast milk and are delivered during breastfeeding. They mainly act by activating or antagonizing hormonal receptors. We summarize the effects on the immune system, gut microbiota, and metabolism. Exposure to endocrine-disrupting chemicals and indirect food additives may induce tissue inflammation and polarize lymphocytes, increase proinflammatory cytokines, promote allergic sensitization, and microbial dysbiosis, activate nuclear receptors and increase the incidence of allergic, autoimmune, and metabolic diseases. Breast milk is the most important optimal source in early life. This mini-review summarizes current knowledge on environmental contaminants and paves the way for strategies to prevent milk contamination and limit maternal and infant exposure during pregnancy and the first months of life.
Metaproteomics profiling of the microbial communities in fermentation starters (Daqu) during multi-round production of Chinese liquor
Authors: Zhao Jinzhi , Yang Yi , Teng Mengjing , Zheng Jianxujie , Wang Bing , Mallawaarachchi Vijini , Lin Yu , Fang Ziyu , Shen Chengpin , Yu Shaoning , Yang Fan , Qiao Liang , Wang Li
Published: June 2023

Introduction

The special flavor and fragrance of Chinese liquor are closely related to microorganisms in the fermentation starter Daqu. The changes of microbial community can affect the stability of liquor yield and quality.

Methods

In this study, we used data-independent acquisition mass spectrometry (DIA-MS) for cohort study of the microbial communities of a total of 42 Daqu samples in six production cycles at different times of a year. The DIA MS data were searched against a protein database constructed by metagenomic sequencing.

Results

The microbial composition and its changes across production cycles were revealed. Functional analysis of the differential proteins was carried out and the metabolic pathways related to the differential proteins were explored. These metabolic pathways were related to the saccharification process in liquor fermentation and the synthesis of secondary metabolites to form the unique flavor and aroma in the Chinese liquor.

Discussion

We expect that the metaproteome profiling of Daqu from different production cycles will serve as a guide for the control of fermentation process of Chinese liquor in the future.
Associations of timing of food intake with energy intake, eating behaviour traits and psychosocial factors in adults with overweight and obesity
Authors: Jacob Raphaëlle , Tremblay Angelo , Provencher Véronique , Panahi Shirin , Mathieu Marie-Ève , Drapeau Vicky
Published: June 2023

Introduction

Whether a late distribution of food intake impacts obesity through increased energy intake remains uncertain and the behavioural characterization of late eating needs to be further investigated. The first objective of this study was to assess the associations between late eating and body mass index (BMI) and total energy intake (TEI), and whether TEI mediates the association between late eating and BMI. The second objective was to assess the associations between late eating and eating behaviour traits or psychosocial factors and whether eating behaviour traits mediate the association between late eating and TEI.

Methods

Baseline data from 301 individuals (56% women, age = 38.7 ± 8.5 years; BMI = 33.2 ± 3.4 kg/m2), who participated in four weight loss studies were used in this cross-sectional study. Total energy intake was assessed using a three-day food record from which the percentage of TEI after 17:00 and after 20:00 was calculated. Eating behaviour traits and psychosocial factors were assessed with questionnaires. Pearson correlations and mediation analyses adjusted for age, sex, underreporting of energy intake, sleep duration and bedtime were performed.

Results

Percent TEI after 17:00 and after 20:00 were associated with TEI (r = 0.13, p = 0.03 for both), and TEI mediated the association between percent TEI after 17:00 and BMI (β = 0.01 ± 0.01, 95% CI: 0.001, 0.02). Percent TEI after 17:00 was associated with disinhibition (r = 0.13, p = 0.03) and percent TEI after 20:00 was associated with susceptibility to hunger (r = 0.13, p = 0.03), stress (r = 0.24, p = 0.002) and anxiety (r = 0.28, p = 0.0004). In women, disinhibition mediated the association between percent TEI after 17:00 and TEI (β = 3.41 ± 1.43, 95% CI: 0.92, 6.47). Susceptibility to hunger mediated the association between percent TEI after 20:00 and TEI (β = 0.96 ± 0.59, 95% CI: 0.02, 2.34) in men and women.

Conclusion

Late eating is associated with TEI and suboptimal eating behaviours which could contribute to explaining the association between timing of food intake and obesity.
Developing a 3-D computational model of neurons in the central amygdala to understand pharmacological targets for pain
Authors: Miller Neilan Rachael , Reith Carley , Anandan Iniya , Kraeuter Kayla , Allen Heather N. , Kolber Benedict J.
Published: June 2023

Neuropathic and nociplastic pain are major causes of pain and involve brain areas such as the central nucleus of the amygdala (CeA). Within the CeA, neurons expressing protein kinase c-delta (PKCδ) or somatostatin (SST) have opposing roles in pain-like modulation. In this manuscript, we describe our progress towards developing a 3-D computational model of PKCδ and SST neurons in the CeA and the use of this model to explore the pharmacological targeting of these two neural populations in modulating nociception. Our 3-D model expands upon our existing 2-D computational framework by including a realistic 3-D spatial representation of the CeA and its subnuclei and a network of directed links that preserves morphological properties of PKCδ and SST neurons. The model consists of 13,000 neurons with cell-type specific properties and behaviors estimated from laboratory data. During each model time step, neuron firing rates are updated based on an external stimulus, inhibitory signals are transmitted between neurons via the network, and a measure of nociceptive output from the CeA is calculated as the difference in firing rates of pro-nociceptive PKCδ neurons and anti-nociceptive SST neurons. Model simulations were conducted to explore differences in output for three different spatial distributions of PKCδ and SST neurons. Our results show that the localization of these neuron populations within CeA subnuclei is a key parameter in identifying spatial and cell-type pharmacological targets for pain.
Direct healthcare cost of pediatric systemic lupus erythematosus in the Philippines
Authors: Yee Maria Kathryn Ramirez , Collante Ma Theresa Moreno , Bernal Christine Bea
Published: June 2023

Background

Pediatric rheumatic diseases are chronic illnesses that pose a huge economic burden to children and their families; one of the most common is pediatric systemic lupus erythematosus (pSLE). The direct cost of pSLE has been studied in other countries. In the Philippines, this was only studied in the adult population. This study aimed to determine the direct cost of pSLE in the Philippines and its cost predictors.

Methods

A total of 100 pSLE patients were seen from November 2017 to January 2018 at the University of Santo Tomas. Informed consent and assent forms were obtained. A total of 79 patients met the inclusion criteria and parents were asked to answer a questionnaire. Data were tabulated and were subjected to statistical analysis. Cost predictors were estimated using a stepwise log linear regression.

Results

A total of 79 pediatric SLE patients, with a mean age of 14.68 ± 3.24 years, 89.9% of which were females, with a mean disease duration of 36.08 ± 23.54 months, were included in this study. A total of 65.82% had lupus nephritis and 49.37% were in flare. The mean annual direct cost for pediatric SLE patient was 162,764.81 PHP (USD 3,047.23). Majority of the expense was for medications. Regression analysis showed that the predictors of increased cost in doctor's fee in clinic visits (p-value 0.000) and IV infusion (p-value 0.01) were the higher combined income of the parents.

Conclusion

This is a preliminary study on the mean annual direct cost of pediatric SLE patients in a single center in the Philippines. Pediatric SLE patients with nephritis and other target organ damage were seen to increase the cost up to 2–3.5×. Patients in flare also had a higher cost of up to 1.6×. The overall cost driver of this study was the parent's or caregivers combined income. Further analysis showed that cost drivers in the subcategories include the age, sex and parent's/caregiver's educational attainment.
Renal C4d is a potential biomarker of disease activity and severity in pediatric lupus nephritis patients
Authors: Wang Xueyao , Fu Shaojie , Yu Jinyu , Tang Daru , Wu Hao , Xu Zhonggao
Published: June 2023

Background

Systemic lupus erythematosus (SLE), a multisystemic autoimmune disease, is very aggressive in pediatric-onset patients as they are prone to develop lupus nephritis (LN). Although renal C4d positivity is correlated with the activity of renal disease and SLE in adult-onset LN patients, available information for pediatric-onset patients is limited.

Methods

To evaluate the potential diagnostic significance of renal C4d staining in pediatric LN patients, we retrospectively detected C4d staining by immunohistochemistry on renal biopsy specimens from 58 pediatric LN patients. The clinical and laboratory data at the time of the kidney biopsy and the renal disease activity of histological injury were analyzed according to the C4d staining status.

Results

Glomerular C4d (G-C4d)-positive staining was detected in all 58 cases of LN. Patients with a G-C4d score of 2 displayed more severe proteinuria than those with a G-C4d score of 1 (24-h urinary protein: 3.40 ± 3.55 g vs. 1.36 ± 1.24 g, P < 0.05). Peritubular capillary C4d (PTC-C4d) positivity was found in 34 of 58 LN patients (58.62%). The PTC-C4d-positive patient groups (patients with a PTC-C4d score of 1 or 2) had higher serum creatinine and blood urea nitrogen levels as well as renal pathological activity index (AI) and SLE disease activity index (SLEDAI) scores; however, they had lower serum complement C3 and C4 levels compared to PTC-C4d-negative patients (P < 0.05). In addition, there was positive tubular basement membrane C4d (TBM-C4d) staining in 11 of 58 LN patients (18.96%), and a higher proportion of TBM-C4d-positive patients than TBM-C4d-negative patients (63.63% vs. 21.27%) had hypertension.

Conclusion

Our study revealed that G-C4d, PTC-C4d, and TMB-C4d were positively correlated with proteinuria, disease activity and severity, and hypertension, respectively, in pediatric LN patients. These data suggest that renal C4d is a potential biomarker for disease activity and severity in pediatric LN patients, providing insights into the development of novel identification and therapeutic approaches for pediatric-onset SLE with LN.
Research on named entity recognition of adverse drug reactions based on NLP and deep learning
Authors: Wei Jianxiang , Hu Tianling , Dai Jimin , Wang Ziren , Han Pu , Huang Weidong
Published: June 2023

Introduction: Adverse drug reactions (ADR) are directly related to public health and become the focus of public and media attention. At present, a large number of ADR events have been reported on the Internet, but the mining and utilization of such information resources is insufficient. Named entity recognition (NER) is the basic work of many natural language processing (NLP) tasks, which aims to identify entities with specific meanings from natural language texts.

Methods: In order to identify entities from ADR event data resources more effectively, so as to provide valuable health knowledge for people, this paper introduces ALBERT in the input presentation layer on the basis of the classic BiLSTM-CRF model, and proposes a method of ADR named entity recognition based on the ALBERT-BiLSTM-CRF model. The textual information about ADR on the website “Chinese medical information query platform” (https://www.dayi.org.cn) was collected by the crawler and used as research data, and the BIO method was used to label three types of entities: drug name (DRN), drug component (COM), and adverse drug reactions (ADR) to build a corpus. Then, the words were mapped to the word vector by using the ALBERT module to obtain the character level semantic information, the context coding was performed by the BiLSTM module, and the label decoding was using the CRF module to predict the real label.

Results: Based on the constructed corpus, experimental comparisons were made with two classical models, namely, BiLSTM-CRF and BERT-BiLSTM-CRF. The experimental results show that the F1 of our method is 91.19% on the whole, which is 1.5% and 1.37% higher than the other two models respectively, and the performance of recognition of three types of entities is significantly improved, which proves the superiority of this method.

Discussion: The method proposed can be used effectively in NER from ADR information on the Internet, which provides a basis for the extraction of drug-related entity relationships and the construction of knowledge graph, thus playing a role in practical health systems such as intelligent diagnosis, risk reasoning and automatic question answering.
Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats
Authors: Mohammad  , Khan Urooj Ahmed , Warsi Musarrat Husain , Alkreathy Huda Mohammed , Karim Shahid , Jain Gaurav Kumar , Ali Asgar
Published: June 2023

Introduction: Cerium oxide nanoparticles (CONPs) have been investigated for their therapeutic potential in Parkinson’s disease (PD) due to their potent and regenerative antioxidant activity. In the present study, CONPs were used to ameliorate the oxidative stress caused by free radicals in haloperidol-induced PD in rats following intranasal administration.

Method: The antioxidant potential of the CONPs was evaluated in vitro using ferric reducing antioxidant power (FRAP) assay. The penetration and local toxicity of the CONPs was evaluated ex-vivo using goat nasal mucosa. The acute local toxicity of intranasal CONPs was also studied in rat. Gamma scintigraphy was used to assess the targeted brain delivery of CONPs. Acute toxicity studies were performed in rats to demonstrate safety of intranasal CONPs. Further, open field test, pole test, biochemical estimations and brain histopathology was performed to evaluate efficacy of intranasal CONPs in haloperidol-induced PD rat model.

Results: The FRAP assay revealed highest antioxidant activity of prepared CONPs at a concentration of 25 μg/mL. Confocal microscopy showed deep and homogenous distribution of CONPs in the goat nasal mucus layers. No signs of irritation or injury were seen in goat nasal membrane when treated with optimized CONPs. Scintigraphy studies in rats showed targeted brain delivery of intranasal CONPs and acute toxicity study demonstrated safety. The results of open field and pole test showed highly significant (p < 0.001) improvement in locomotor activity of rats treated with intranasal CONPs compared to untreated rats. Further, brain histopathology of treatment group rats showed reduced neurodegeneration with presence of more live cells. The amount of thiobarbituric acid reactive substances (TBARS) was reduced significantly, whereas the levels of catalase (CAT), superoxide dismutase (SOD), and GSH were increased significantly, while amounts of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) showed significant reduction after intranasal administration of CONPs. Also, the intranasal CONPs, significantly high (p < 0.001) dopamine concentration (13.93 ± 0.85 ng/mg protein) as compared to haloperidol-induced control rats (5.76 ± 0.70 ng/mg protein).

Conclusion: The overall results concluded that the intranasal CONPs could be safe and effective therapeutics for the management of PD.
Evaluating the inhibitory effect of resveratrol on the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice
Authors: El-Sayed Shimaa Abd El-Salam , El-Alfy El-Sayed , Sayed-Ahmed Mohamed Z. , Mohanta Uday Kumar , Alqahtani Saad S. , Alam Nawazish , Ahmad Sarfaraz , Ali Md Sajid , Igarashi Ikuo , Rizk Mohamed Abdo
Published: June 2023

Introduction: Histone post-translational modification is one of the most studied factors influencing epigenetic regulation of protozoan parasite gene expression, which is mediated by histone deacetylases (KDACs) and acetyltransferases (KATs).

Objective and methods: The present study investigated the role of resveratrol (RVT) as an activator of histone deacetylases in the control of various pathogenic Babesia sp. and Theileria equi in vitro, as well as B. microti infected mice in vivo using fluorescence assay. Its role in mitigating the side effects associated with the widely used antibabesial drugs diminazene aceturate (DA) and azithromycin (AZM) has also been investigated.

Results: The in vitro growth of B. bovis, B. bigemina, B. divergens, B. caballi and Theileria equi (T. equi) was significantly inhibited (P < 0.05) by RVT treatments. The estimated IC50 values revealed that RVT has the greatest inhibitory effects on B. bovis growth in vitro, with an IC50 value of 29.51 ± 2.46 µM. Reverse transcription PCR assay showed that such inhibitory activity might be attributed to resveratrol’s stimulatory effect on B. bovis KDAC3 (BbKADC3) as well as its inhibitory effect on BbKATS. RVT causes a significant decrease (P < 0.05) in cardiac troponin T (cTnT) levels in heart tissue of B. microti- infected mice, thereby indicating that RVT may play a part in reducing the cardiotoxic effects of AZM. Resveratrol showed an additive effect with imidocarb dipropionate in vivo. Treatment of B. microti-infected mice with a combined 5 mg/kg RVT and 8.5 mg/kg ID resulted in an 81.55% inhibition at day 10 postinoculation (peak of parasitemia).

Conclusion: Our data show that RVT is a promising antibabesial pharmacological candidate with therapeutic activities that could overcome the side effects of the currently used anti-Babesia medications.
A cyclic azapeptide ligand of the scavenger receptor CD36/SR-B2 reduces the atherosclerotic lesion progression and enhances plaque stability in apolipoprotein E-deficient mice
Authors: Gauvin Jade , Frégeau Geneviève , Elimam Hanan , Ménard Liliane , Huynh David , Lê Catherine , Ahsanullah Ahsanullah , Lubell William D. , Ong Huy , Marleau Sylvie
Published: June 2023

Atherosclerosis is a chronic inflammatory disease of the arterial walls that develops at predisposed sites. As a major risk factor for adverse cardiovascular pathology, atherosclerosis can progress to myocardial infarction and stroke, due to the rupture of unstable atherosclerotic lesions. Macrophage uptake of modified lipoproteins and metabolic dysfunction contributes significantly to the initiation and development of atherosclerotic lesions. The cluster of differentiation 36 receptor [CD36 (SR-B2)] plays a key role in atherosclerotic lesion progression and acts as an efferocytic molecule in the resolution of advanced plaque. In previous studies, linear azapeptide CD36 ligands were shown to exhibit anti-atherosclerotic properties. In the present study, a novel potent and selective macrocyclic azapeptide CD36 ligand, MPE-298, has proven effective in protecting against atherosclerosis progression. Features of greater plaque stability were observed after 8 weeks of daily injections with the cyclic azapeptide in apolipoprotein E-deficient mice fed a high-fat high-cholesterol diet.
Piezo1 channels mediate vasorelaxation of uterine arteries from pseudopregnant rats
Authors: Arishe Olufunke O. , McKenzie Jaine , Dela Justina Vanessa , Dos Anjos Moraes Raiana , Webb R. Clinton , Priviero Fernanda
Published: June 2023

Introduction: There is a great increase in uterine arterial blood flow during normal pregnancy, which is a result of the cardiovascular changes that occur in pregnancy to adapt the maternal vascular system to meet the increased metabolic needs of both the mother and the fetus. The cardiovascular changes include an increase in cardiac output and more importantly, dilation of the maternal uterine arteries. However, the exact mechanism for the vasodilation is not fully known. Piezo1 mechanosensitive channels are highly expressed in endothelial and vascular smooth muscle cells of small-diameter arteries and play a role in structural remodeling. In this study, we hypothesize that the mechanosensitive Piezo1 channel plays a role in the dilation of the uterine artery (UA) during pregnancy.

Methods: For this, 14-week-old pseudopregnant and virgin Sprague Dawley rats were used. In isolated segments of UA and mesenteric resistance arteries (MRA) mounted in a wire myograph, we investigated the effects of chemical activation of Piezo1, using Yoda 1. The mechanism of Yoda 1 induced relaxation was assessed by incubating the vessels with either vehicle or some inhibitors or in the presence of a potassium-free physiological salt solution (K+-free PSS).

Results: Our results show that concentration-dependent relaxation responses to Yoda 1 are greater in the UA of the pseudo-pregnant rats than in those from the virgin rats while no differences between groups were observed in the MRAs. In both vascular beds, either in virgin or in pseudopregnant, relaxation to Yoda 1 was at least in part nitric oxide dependent.

Discussion: Piezo1 channel mediates nitric oxide dependent relaxation, and this channel seems to contribute to the greater dilation that occurs in the uterine arteries of pseudo-pregnant rats.
Calculating sample entropy from isometric torque signals: methodological considerations and recommendations
Authors: Raffalt Peter C. , Yentes Jennifer M. , Freitas Sandro R. , Vaz João R.
Published: June 2023

We investigated the effect of different sampling frequencies, input parameters and observation times for sample entropy (SaEn) calculated on torque data recorded from a submaximal isometric contraction. Forty-six participants performed sustained isometric knee flexion at 20% of their maximal contraction level and torque data was sampled at 1,000 Hz for 180 s. Power spectral analysis was used to determine the appropriate sampling frequency. The time series were downsampled to 750, 500, 250, 100, 50, and 25 Hz to investigate the effect of different sampling frequency. Relative parameter consistency was investigated using combinations of vector lengths of two and three and tolerance limits of 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, and 0.4, and data lengths between 500 and 18,000 data points. The effect of different observations times was evaluated using Bland-Altman plot for observations times between 5 and 90 s. SaEn increased at sampling frequencies below 100 Hz and was unaltered above 250 Hz. In agreement with the power spectral analysis, this advocates for a sampling frequency between 100 and 250 Hz. Relative consistency was observed across the tested parameters and at least 30 s of observation time was required for a valid calculation of SaEn from torque data.
Clinical value of fecal calprotectin for evaluating disease activity in patients with Crohn’s disease
Authors: Li Junrong , Xu Mingyang , Qian Wei , Ling Fangmei , Chen Yidong , Li Shuang , Cheng Yiyu , Zhu Liangru
Published: June 2023

Objective: To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn’s disease (CD) and its relationship with disease location.

Methods: Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn’s disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn’s disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores.

Results: This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately–severely active disease were 41.01, 164.20, and 444.45 μg/g. These values were 26.94, 66.77, and 327.22 μg/g during endoscopic remission and mildly and moderately–severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52 μg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84 μg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD.

Conclusion: FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.