bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast and accurate variant identification tool for sequencing-based studies
Authors: Gaston Jeffry M. , Alm Eric J. , Zhang An-Ni
Published: April 2024

Background

Accurate identification of genetic variants, such as point mutations and insertions/deletions (indels), is crucial for various genetic studies into epidemic tracking, population genetics, and disease diagnosis. Genetic studies into microbiomes often require processing numerous sequencing datasets, necessitating variant identifiers with high speed, accuracy, and robustness.

Results

We present QuickVariants, a bioinformatics tool that effectively summarizes variant information from read alignments and identifies variants. When tested on diverse bacterial sequencing data, QuickVariants demonstrates a ninefold higher median speed than bcftools, a widely used variant identifier, with higher accuracy in identifying both point mutations and indels. This accuracy extends to variant identification in virus samples, including SARS-CoV-2, particularly with significantly fewer false negative indels than bcftools. The high accuracy of QuickVariants is further demonstrated by its detection of a greater number of Omicron-specific indels (5 versus 0) and point mutations (61 versus 48–54) than bcftools in sewage metagenomes predominated by Omicron variants. Much of the reduced accuracy of bcftools was attributable to its misinterpretation of indels, often producing false negative indels and false positive point mutations at the same locations.

Conclusions

We introduce QuickVariants, a fast, accurate, and robust bioinformatics tool designed for identifying genetic variants for microbial studies. QuickVariants is available at https://github.com/caozhichongchong/QuickVariants.
Single-cell RNA sequencing reveals cellular and molecular landscape of fetal cystic hygroma
Authors: Fu Fang , Yang Xin , Li Ru , Li Yingsi , Zhou Hang , Cheng Ken , Huang Ruibin , Wang You , Guo Fei , Zhang Lina , Pan Min , Han Jin , Zhen Li , Li Lushan , Lei Tingying , Li Dongzhi , Liao Can
Published: April 2024

Background

The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients.

Methods

Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted.

Results

The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation.

Conclusion

Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator.

Simple summary

The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.
T cell expressions of aberrant gene signatures and Co-inhibitory receptors (Co-IRs) as predictors of renal damage and lupus disease activity
Authors: Wang Chin-Man , Jan Wu Yeong-Jian , Zheng Jian-Wen , Huang Li Yu , Tan Keng Poo , Chen Ji-Yih
Published: April 2024

Background

Systemic lupus erythematosus (SLE) is distinguished by an extensive range of clinical heterogeneity with unpredictable disease flares and organ damage. This research investigates the potential of aberrant signatures on T cell genes, soluble Co-IRs/ligands, and Co-IRs expression on T cells as biomarkers for lupus disease parameters.

Methods

Comparative transcriptome profiling analysis of non-renal and end-stage renal disease (ESRD) phenotypes of SLE was performed using CD4 + and CD8 + cDNA microarrays of sorted T cells. Comparing the expression of Co-IRs on T cells and serum soluble mediators among healthy and SLE phenotypes.

Results

SLE patients with ESRD were downregulated CD38, PLEK, interferon-γ, CX3CR1, FGFBP2, and SLCO4C1 transcripts on CD4 + and CD8 + T cells simultaneously and NKG7, FCRL6, GZMB/H, FcγRIII, ITGAM, Fas ligand, TBX21, LYN, granulysin, CCL4L1, CMKLR1, HLA-DRβ, KIR2DL3, and KLRD1 in CD8 T cells. Pathway enrichment and PPI network analyses revealed that the overwhelming majority of Differentially Expressed Genes (DEGs) have been affiliated with novel cytotoxic, antigen presentation, and chemokine-cell migration signature pathways. CD8 + GZMK + T cells that are varied in nature, including CD161 + Mucosal-associated invariant T (MAIT) cells and CD161- aged-associated T (Taa) cells and CD161-GZMK + GZMB + T cells might account for a higher level of GZMK in CD8 + T cells associated with ESRD. SLE patients have higher TIGIT + , PD1 + , and lower CD127 + cell percentages on CD4 + T cells, higher TIM3 + , TIGIT + , HLA-DR + cell frequency, and lower MFI expression of CD127, CD160 in CD8 T cells. Co-IRs expression in T cells was correlated with soluble PD-1, PDL-2, and TIM3 levels, as well as SLE disease activity, clinical phenotypes, and immune-therapy responses.

Conclusion

The signature of dysfunctional pathways defines a distinct immunity pattern in LN ESRD patients. Expression levels of Co-IRs in peripheral blood T cells and serum levels of soluble PD1/PDL-2/TIM3 can serve as biomarkers for evaluating clinical parameters and therapeutic responses.
Nursing labor supply in Iran: a survey in Shiraz public hospitals in 2022
Authors: Keshavarzi Ali , Delavari Sajad , Lotfi Farhad , Goudarzi Zahra , Bashiri Faezeh , Bayati Mohsen
Published: April 2024

Background

The labor supply of nurses, as one of the main healthcare workers, is an important issue in health human resources planning in all health systems. Finding the factors affecting it, could help policymakers to solve the shortage of nursing work supply. The present study aimed to investigating the quantity and factors affecting the nurses' labor supply in Iran.

Method

In this cross-sectional study, a sample of 598 nurses working in public hospitals of Shiraz (Iran) were selected via proportionate stratified random sampling method. The required data was collected using a structured questionnaire which asked working hours and other related factors. To analyze the data, descriptive statistics, univariate analysis and multivariate linear regression were performed using STATA 15. The multivariate labor supply model was estimated separately for married and single nurses. 

Results

The average weekly working hours of nurses was 54.65 h in all medical centers and 50.28 h in the main hospital. The regression results showed that the labor supply of nurses with work experience (β = − 0.368, P = 0.014), satisfaction with work shift arrangement (β = − 2.473, P = 0.001), income between 60-89 million rial (β = − 14.046, P = 0.002), income between  90-119 million rial(β = − 12.073, P = 0.012), and working in the emergency department (β = − 5.043, P = 0.017) had negative and significant relationship; But there was a positive and significant relationship with satisfaction of the work environment (β = 1.86, P = 0.011), workload at work (β = 1.951, P = 0.023) and employment status (contractual employees) (β = 4.704, P = 0.004).

Conclusion

The labor supply function of nurses is affected by demographic, economic and non-economic factors. The most contributing factors were related to non-economic variables. It seems that the non-financial cost and benefits related to the job as well as internal factors have more important role on the nurses' labor supply.
Interleukin-4 protects retinal ganglion cells and promotes axon regeneration
Authors: Zuo Zhaoyang , Fan Bin , Zhang Ziyuan , Liang Yang , Chi Jing , Li Guangyu
Published: April 2024

Background

The preservation of retinal ganglion cells (RGCs) and the facilitation of axon regeneration are crucial considerations in the management of various vision-threatening disorders. Therefore, we investigate the efficacy of interleukin-4 (IL-4), a potential therapeutic agent, in promoting neuroprotection and axon regeneration of retinal ganglion cells (RGCs) as identified through whole transcriptome sequencing in an in vitro axon growth model.

Methods

A low concentration of staurosporine (STS) was employed to induce in vitro axon growth. Whole transcriptome sequencing was utilized to identify key target factors involved in the molecular mechanism underlying axon growth. The efficacy of recombinant IL-4 protein on promoting RGC axon growth was validated through in vitro experiments. The protective effect of recombinant IL-4 protein on somas of RGCs was assessed using RBPMS-specific immunofluorescent staining in mouse models with optic nerve crush (ONC) and N-methyl-D-aspartic acid (NMDA) injury. The protective effect on RGC axons was evaluated by anterograde labeling of cholera toxin subunit B (CTB), while the promotion of RGC axon regeneration was assessed through both anterograde labeling of CTB and immunofluorescent staining for growth associated protein-43 (GAP43).

Results

Whole-transcriptome sequencing of staurosporine-treated 661 W cells revealed a significant upregulation in intracellular IL-4 transcription levels during the process of axon regeneration. In vitro experiments demonstrated that recombinant IL-4 protein effectively stimulated axon outgrowth. Subsequent immunostaining with RBPMS revealed a significantly higher survival rate of RGCs in the rIL-4 group compared to the vehicle group in both NMDA and ONC injury models. Axonal tracing with CTB confirmed that recombinant IL-4 protein preserved long-distance projection of RGC axons, and there was a notably higher number of surviving axons in the rIL-4 group compared to the vehicle group following NMDA-induced injury. Moreover, intravitreal delivery of recombinant IL-4 protein substantially facilitated RGC axon regeneration after ONC injury.

Conclusion

The recombinant IL-4 protein exhibits the potential to enhance the survival rate of RGCs, protect RGC axons against NMDA-induced injury, and facilitate axon regeneration following ONC. This study provides an experimental foundation for further investigation and development of therapeutic agents aimed at protecting the optic nerve and promoting axon regeneration.
Pathological high intraocular pressure induces glial cell reactive proliferation contributing to neuroinflammation of the blood-retinal barrier via the NOX2/ET-1 axis-controlled ERK1/2 pathway
Authors: Shi Xin , Li Panpan , Herb Marc , Liu Hanhan , Wang Maoren , Wang Xiaosha , Feng Yuan , van Beers Tim , Xia Ning , Li Huige , Prokosch Verena
Published: April 2024

Background

NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat.

Methods

Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2−/− mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O2-) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study.

Results

We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst.

Conclusions

Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management.
The potency of mesenchymal stem/stromal cells: does donor sex matter?
Authors: Maged Ghada , Abdelsamed Menna A. , Wang Hongjun , Lotfy Ahmed
Published: April 2024

Mesenchymal stem/stromal cells (MSCs) are a promising therapeutic tool in cell therapy and tissue engineering because of their multi-lineage differentiation capacity, immunomodulatory effects, and tissue protective potential. To achieve optimal results as a therapeutic tool, factors affecting MSC potency, including but not limited to cell source, donor age, and cell batch, have been investigated. Although the sex of the donor has been attributed as a potential factor that can influence MSC potency and efficacy, the impact of donor sex on MSC characteristics has not been carefully investigated. In this review, we summarize published studies demonstrating donor-sex-related MSC heterogeneity and emphasize the importance of disclosing donor sex as a key factor affecting MSC potency in cell therapy.
RecSOI: recommending research directions using statements of ignorance
Authors: Bibal Adrien , Salem Nourah M. , Cardon Rémi , White Elizabeth K. , Acuna Daniel E. , Burke Robin , Hunter Lawrence E.
Published: April 2024

The more science advances, the more questions are asked. This compounding growth can make it difficult to keep up with current research directions. Furthermore, this difficulty is exacerbated for junior researchers who enter fields with already large bases of potentially fruitful research avenues. In this paper, we propose a novel task and a recommender system for research directions, RecSOI, that draws from statements of ignorance (SOIs) found in the research literature. By building researchers’ profiles based on textual elements, RecSOI generates personalized recommendations of potential research directions tailored to their interests. In addition, RecSOI provides context for the recommended SOIs, so that users can quickly evaluate how relevant the research direction is for them. In this paper, we provide an overview of RecSOI’s functioning, implementation, and evaluation, demonstrating its effectiveness in guiding researchers through the vast landscape of potential research directions.
Interruptible demyelination in avian riboflavin deficient neuropathy
Authors: Cai Zhao
Published: April 2024

Background and aims

The evolution of demyelination in individual internodes remains unclear although it has been noticed the paranodal demyelination precedes internodal demyelination in neuropathies with diverse aetiologies. For therapeutic purpose, it is fundamental to know whether the demyelinating procedure in affected internodes can be interrupted. This study aimed to delineate the development of demyelination in individual internodes in avian riboflavin deficient neuropathy.

Methods

Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin, a riboflavin deficient diet containing 1.8 mg/kg riboflavin, or initially a riboflavin deficient diet for 11 days and then routine diet plus riboflavin repletion from day 12. Evolution of demyelination in individual internodes was analyzed by teased nerve fibre studies from day 11 to 21.

Results

In riboflavin deficient chickens, demyelination was the predominant feature: it was mainly confined to the paranodal region at day 11; extended into internodal region, but less than half of the internodal length in most affected internodes at day 16; involved more than half or whole internode at day 21. In the internode undergoing demyelination, myelin degeneration of varying degrees was noticed in the cytoplasm of the Schwann cell wrapping the internode. Two days after riboflavin repletion, co-existence of remyelination and active demyelination within individual internodes was noticed. Remyelination together with preserved short original internodes was the characteristic feature 4 and 9 days after riboflavin repletion.

Conclusion

Riboflavin repletion interrupts the progression from paranodal to internodal demyelination in riboflavin deficient chickens and promotes remyelination before complete internodal demyelination.
Childhood migration experience and adult health: evidence from China’s rural migrants
Authors: Li Xiaohong , Qiao Shiyan , Zhang Dongying
Published: April 2024

Background

Place of residence plays an influential role in shaping individual development, and studies have established links between Childhood migration experience (CME) and health outcomes through maturity. Over the past three decades, China has undergone one of the largest rural-to-urban migrations, however, little is known about the effect of CME on rural migrants’ adult health in China.

Methods

Data from 7035 members of the 2016 and 2018 China Labor-force Dynamics Survey were analyzed. CME was measured by whether the place of residence and place of birth changed at the age of 14 years. Three measures of health (self-assessed health, BMI, and mental health scale) were obtained. Causal inferential analysis was performed, using the Probit model, the OLS model and the Propensity Score Matching (PSM) method, to explore the impact of CME on the adult health of rural migrants.

Results

Overall, compared to individuals who did not migrate in childhood, the probability of reporting “very unhealthy”, “rather unhealthy”, and “fair” in the self-assessed health of the rural migrants with CME decreased by 0.23%, 1.55%, and 5.53%, the probability of reporting “healthy” and “very healthy” increased by 1.94% and 5.38%, the probability of BMI within the normal range was higher by 7.32%, and the mental health test scores were 0.2591 points higher significantly. Furthermore, in comparison with childhood non-migration, both cross-county and cross-city migration promoted the health status of rural migrants, but the positive effect of cross-province migration was not significant; from the gender perspective, CME could more dramatically improve rural women’s adult health than men, especially in mental health.

Conclusion

CME can significantly improve adult health, including physical and mental health, and the positive effect is more obvious among women, helping to reduce gender differences in health. For the migration distance, attention can be focused on the long-distance migrating individuals, who should get more support.
The effect of colchicine on cancer risk in patients with immune-mediated inflammatory diseases: a time-dependent study based on the Taiwan’s National Health Insurance Research Database
Authors: Yeh Jun-Jun , Liw Pei-Xuan , Wong Yi-Sin , Kao Husan-Min , Lee Chia-Hsun , Lin Cheng-Li , Kao Chia-Hung
Published: April 2024

Background

To determine the effect of colchicine on cancer risk in patients with the immune-mediated inflammatory diseases (IMIDs)-related to colchicine use.

Methods

This is a time-dependent propensity-matched general population study based on the National Health Insurance Research Database (NHIRD) of Taiwan. We identified the IMIDs patients (n = 111,644) newly diagnosed between 2000 and 2012 based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)—274,712, 135, 136.1, 279.49, 518.3, 287.0, 696.0, 696.1, 696.8, 420, 429.4, 710.0, 710.1, 710.3, 710.4, 714.0, 720, 55.0, 55.1, 55.9, 556. Inclusion criteria: aged ≧ 20 years, if a patient had at least these disease diagnosis requirements within 1 year of follow-up, and, these patients had at least two outpatient visits or an inpatient visit. After propensity-matched according to age, sex, comorbidities, medications and index date, the IMIDs patients enter into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (95% CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for smoking cessation such as nicotine replacement medicines (the nicotine patch) and pill medicines (varenicline), anti-inflammatory drugs and immunosuppressant drugs.

Results

Comparing the colchicine nonusers, all cancer risk were mildly attenuated, the (aHR (95% CI)) of all cancer is (0.84 (0.55, 0.99)). Meanwhile, the colchicine users were associated with the lower incidence of the colorectal cancer, the (aHRs (95% CI)) is (0.22 (0.19, 0.89)). Those aged < 65 years and male/female having the colchicine users were associated with lower risk the colorectal cancer also. Moreover, the colchicine > 20 days use with the lower aHR for colorectal cancer.

Conclusion

Colchicine was associated with the lower aHR of the all cancer and colorectal cancer formation in patients with the IMIDs.
Carrageenan maintains the contractile phenotype of vascular smooth muscle cells by increasing macromolecular crowding in vitro
Authors: Liu Qing , Jiang Hong-Jing , Wu Yin-Di , Li Jian-Dong , Sun Xu-Heng , Xiao Cong , Xu Jian-Yi , Lin Zhan-Yi
Published: April 2024

Background

The contractile phenotype of vascular smooth muscle cells (VSMCs) results in good diastolic and contractile capacities, and its altered function is the main pathophysiological basis for diseases such as hypertension. VSMCs exist as a synthetic phenotype in vitro, making it challenging to maintain a contractile phenotype for research. It is widely recognized that the common medium in vitro is significantly less crowded than in the in vivo environment. Additionally, VSMCs have a heightened sense for detecting changes in medium crowding. However, it is unclear whether macromolecular crowding (MMC) helps maintain the VSMCs contractile phenotype.

Purpose

This study aimed to explore the phenotypic, behavioral and gene expression changes of VSMCs after increasing the crowding degree by adding carrageenan (CR).

Methods

The degree of medium crowding was examined by a dynamic light scattering assay; VSMCs survival and activity were examined by calcein/PI cell activity and toxicity and CCK-8 assays; VSMCs phenotypes and migration were examined by WB and wound healing assays; and gene expression was examined by transcriptomic analysis and RT-qPCR.

Results

Notably, 225 μg/mL CR significantly increased the crowding degree of the medium and did not affect cell survival. Simultaneously, CR significantly promoted the contraction phenotypic marker expression in VSMCs, shortened cell length, decreased cell proliferation, and inhibited cell migration. CR significantly altered gene expression in VSMCs. Specifically, 856 genes were upregulated and 1207 genes were downregulated. These alterations primarily affect the cellular ion channel transport, microtubule movement, respiratory metabolism, amino acid transport, and extracellular matrix synthesis. The upregulated genes were primarily involved in the cytoskeleton and contraction processes of VSMCs, whereas the downregulated genes were mainly involved in extracellular matrix synthesis.

Conclusions

The in vitro study showed that VSMCs can maintain the contractile phenotype by sensing changes in the crowding of the culture environment, which can be maintained by adding CR.

Graphical Abstract
Respiratory drive: a journey from health to disease
Authors: Georgopoulos Dimitrios , Bolaki Maria , Stamatopoulou Vaia , Akoumianaki Evangelia
Published: April 2024

Respiratory drive is defined as the intensity of respiratory centers output during the breath and is primarily affected by cortical and chemical feedback mechanisms. During the involuntary act of breathing, chemical feedback, primarily mediated through CO2, is the main determinant of respiratory drive. Respiratory drive travels through neural pathways to respiratory muscles, which execute the breathing process and generate inspiratory flow (inspiratory flow-generation pathway). In a healthy state, inspiratory flow-generation pathway is intact, and thus respiratory drive is satisfied by the rate of volume increase, expressed by mean inspiratory flow, which in turn determines tidal volume. In this review, we will explain the pathophysiology of altered respiratory drive by analyzing the respiratory centers response to arterial partial pressure of CO2 (PaCO2) changes. Both high and low respiratory drive have been associated with several adverse effects in critically ill patients. Hence, it is crucial to understand what alters the respiratory drive. Changes in respiratory drive can be explained by simultaneously considering the (1) ventilatory demands, as dictated by respiratory centers activity to CO2 (brain curve); (2) actual ventilatory response to CO2 (ventilation curve); and (3) metabolic hyperbola. During critical illness, multiple mechanisms affect the brain and ventilation curves, as well as metabolic hyperbola, leading to considerable alterations in respiratory drive. In critically ill patients the inspiratory flow-generation pathway is invariably compromised at various levels. Consequently, mean inspiratory flow and tidal volume do not correspond to respiratory drive, and at a given PaCO2, the actual ventilation is less than ventilatory demands, creating a dissociation between brain and ventilation curves. Since the metabolic hyperbola is one of the two variables that determine PaCO2 (the other being the ventilation curve), its upward or downward movements increase or decrease respiratory drive, respectively. Mechanical ventilation indirectly influences respiratory drive by modifying PaCO2 levels through alterations in various parameters of the ventilation curve and metabolic hyperbola. Understanding the diverse factors that modulate respiratory drive at the bedside could enhance clinical assessment and the management of both the patient and the ventilator.
Phantom and clinical evaluation of the Bayesian penalised likelihood reconstruction algorithm Q.Clear without PSF correction in amyloid PET images
Authors: Wagatsuma Kei , Sakata Muneyuki , Miwa Kenta , Hamano Yumi , Kawakami Hirofumi , Kamitaka Yuto , Yamao Tensho , Miyaji Noriaki , Ishibashi Kenji , Tago Tetsuro , Toyohara Jun , Ishii Kenji
Published: April 2024

Purpose

Bayesian penalised likelihood (BPL) reconstruction, which incorporates point-spread-function (PSF) correction, provides higher signal-to-noise ratios and more accurate quantitation than conventional ordered subset expectation maximization (OSEM) reconstruction. However, applying PSF correction to brain PET imaging is controversial due to Gibbs artefacts that manifest as unpredicted cortical uptake enhancement. The present study aimed to validate whether BPL without PSF would be useful for amyloid PET imaging.

Methods

Images were acquired from Hoffman 3D brain and cylindrical phantoms for phantom study and 71 patients administered with [18F]flutemetamol in clinical study using a Discovery MI. All images were reconstructed using OSEM, BPL with PSF correction, and BPL without PSF correction. Count profile, %contrast, recovery coefficients (RCs), and image noise were calculated from the images acquired from the phantoms. Amyloid β deposition in patients was visually assessed by two physicians and quantified based on the standardised uptake value ratio (SUVR).

Results

The overestimated radioactivity in profile curves was eliminated using BPL without PSF correction. The %contrast and image noise decreased with increasing β values in phantom images. Image quality and RCs were better using BPL with, than without PSF correction or OSEM. An optimal β value of 600 was determined for BPL without PSF correction. Visual evaluation almost agreed perfectly (κ = 0.91–0.97), without depending on reconstruction methods. Composite SUVRs did not significantly differ between reconstruction methods.

Conclusion

Gibbs artefacts disappeared from phantom images using the BPL without PSF correction. Visual and quantitative evaluation of [18F]flutemetamol imaging was independent of the reconstruction method. The BPL without PSF correction could be the standard reconstruction method for amyloid PET imaging, despite being qualitatively inferior to BPL with PSF correction for [18F]flutemetamol amyloid PET imaging.
Noncoding RNAs in skeletal development and disorders
Authors: Yao Qing , He Tailin , Liao Jian-You , Liao Rongdong , Wu Xiaohao , Lin Lijun , Xiao Guozhi
Published: April 2024

Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as “junk DNA”. Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated. Furthermore, the gene regulation networks they form modulate gene expression in normal development and under pathological conditions. In this review, we integrate current information about the classification, biogenesis, and function of ncRNAs and how these ncRNAs support skeletal development through their regulation of critical genes and signaling pathways in vivo. We also summarize the updated knowledge of ncRNAs involved in common skeletal diseases and disorders, including but not limited to osteoporosis, osteoarthritis, rheumatoid arthritis, scoliosis, and intervertebral disc degeneration, by highlighting their roles established from in vivo, in vitro, and ex vivo studies.
Spontaneous clearance of serum HCV-RNA after splenectomy in a patient with HCV-related liver cirrhosis and portal hypertension: a case report
Authors: Ogata Toshiro , Sakai Terufumi , Shibata Sho , Kanno Hiroki , Nakane Hiroyuki , Aoyagi Takeshi , Koikawa Kazuhiro , Sadakari Yoshihiko , Hirokata Gentaro , Taniguchi Masahiko
Published: April 2024

Background

Spontaneous clearance of chronic hepatitis C virus (HCV) is rare in adults. A T-lymphocyte response is thought to be involved in HCV-RNA clearance. Splenectomy reportedly has a beneficial effect on T cell immune function in patients with cirrhosis. To the best of our knowledge, the present report is the first to describe spontaneous clearance of serum HCV-RNA within 1 year after splenectomy in a patient with cirrhosis.

Case presentation

A 55-year-old man with HCV cirrhosis was transferred to our institution with advanced pancytopenia, splenomegaly, and gastric varices. He had a 1-year history of ascites, edema, and general fatigue. The patient had a Child–Pugh score of 8 and serological type 1 HCV; the HCV-RNA level was 4.7 log IU/mL. Contrast-enhanced computed tomography showed gastric varices and marked splenomegaly (estimated spleen volume of 2175 mL). Esophagogastroduodenoscopy revealed enlarged gastric varices with no red color sign, and the varices were larger than those 1 year prior. He was diagnosed with decompensated HCV-related liver cirrhosis and portal hypertension. We considered direct-acting antiviral (DAA) therapy; however, DAA therapy was not approved in Japan for patients with decompensated cirrhosis at that time. Hand-assisted laparoscopic splenectomy was performed to improve the worsening portal hypertension. Further, we planned the initiation of DAA therapy after surgery, when such therapy would become available. DAA therapy was approved 1 year after splenectomy. At that time, we measured the HCV-RNA level before the initiation of DAA therapy; unexpectedly, however, serum HCV-RNA was not detectable, and the virus continued to disappear during the following 4 years. His liver function (total bilirubin, albumin, and prothrombin time) and pancytopenia improved during the 5 years postoperatively. The serum aspartate and alanine aminotransferase levels normalized between 1 and 5 years postoperatively. Esophagogastroduodenoscopy showed no change in the gastric varices during the 5 years after surgery. The patient remained asymptomatic and continued to do well.

Conclusions

We have presented a case of spontaneous clearance of HCV-RNA after splenectomy in a patient with cirrhosis and portal hypertension. Splenectomy may be associated with disappearance of HCV-RNA based on previous reports. More cases should be accumulated and evaluated.
The effect of maternal undernutrition on adverse obstetric outcomes among women who attend antenatal care in Gedeo zone public hospitals, cohort study design
Authors: Figa Zerihun , Temesgen Tesfaye , Mahamed Abbas Ahmed , Bekele Etaferahu
Published: April 2024

Background

Undernutrition refers to an overall deficiency of nutrients due to an inadequate intake of a well-balanced diet. Undernourishment during pregnancy is an important contributor to maternal morbidity and mortality. It remains a persistent problem in developing countries, where women usually fall behind men in having access to food, health care, and education. Despite the high prevalence of maternal undernourishment, its direct impact on obstetric outcomes has not been studied in developing countries, including Ethiopia.

Objective

This study aimed to assess the effect of maternal undernutrition on adverse obstetric outcomes in Gedeo zone public hospitals.

Method

A cohort study design was employed in Gedeo zone public hospitals from June 30, 2022, to February 28, 2023. This study included 721 pregnant women, 237 were exposed group whereas 484 were non-exposed. A systematic random sampling technique was used to select a non-exposed group and the exposed group was selected consecutively. Both groups were followed for 7 months, from 16 weeks of gestation to 24 h of delivery. The pretested interviewer-administered questionnaire and checklist were used. EpiData 4.4.1.2.version was used for data entry and analyzed using Stata version 16 software. A modified Poisson regression model with robust standard errors was used to determine relative risk, and the statistical association was declared at a p-value ≤ 0.05. Finally, the findings were reported in figures, tables, and words.

Result

The incidence of adverse obstetrics outcomes among undernourished and normally nourished mothers was hypertensive disorder during pregnancy (HDDP) (7.49% vs. 3.19%), antepartum haemorrhage (7.49% vs. 3.19%), obstructed labor (1.53% vs. 3.49%), premature rupture of the membrane (2.5% vs. 3.33%), preterm labor (6.52% vs. 6.93%), instrumental vaginal delivery (1.8% vs. 4.3%), postpartum haemorrhage (5.95% vs. 3.88%), and sepsis (3.74% vs. 1.94%). The risk of adverse obstetric outcomes among undernourished women was hypertensive disorder during pregnancy (HDDP) (aRR) = 4.07, 95%CI: 2.53–6.55), antepartum haemorrhage (APH) (aRR = 5.0, 95% CI: 2.08–12.72), preterm labor (aRR = 1.8, 95%CI: 1.23–2.62), operative delivery (aRR = 1.24, 95%C: 0.87–1.78), postpartum haemorrhage (aRR = 3.02, 95%CI: 1.91–4.79), and sepsis/chrioaminitis (aRR = 3.55, 95%CI: 1.83–6.89) times higher than normally nourished women.

Conclusion

The incidence rates of hypertensive disorder during pregnancy (HDDP), antepartum haemorrhage, postpartum haemorrhage, and sepsis were higher among undernourished women than normally nourished women. Undernourished women during pregnancy have an increased risk of adverse obstetrics outcomes including hypertensive disorder during pregnancy, antepartum, preterm labor, operative delivery, postpartum haemorrhage, and sepsis/chorioamnionitis.
De-migranticizing as methodology: rethinking migration studies through immobility and liminality
Authors: Raghuram Parvati , Breines Markus Roos , Gunter Ashley
Published: April 2024

De-migranticization is becoming a core strategy for overcoming the fetishization of migrants in migration studies. However, this shift in perspectives raises questions about what categories to use instead. This paper contributes to these debates by considering the potential of studying immobility as a tool for de-migranticization. It looks at immobility through the lens of liminality: as a transitory phase, as a transformative stage and as one which enables epistemological subversion. In doing so, it goes beyond other border spanning terms to offer methodological insights into using immobility and liminality to de-migranticize. The paper suggests that these qualities of reading immobility through theories of liminality has implications for when, where and how to study migration. The empirical case draws on 165 semi-structured interviews with distance education students from Zimbabwe, Namibia and Nigeria studying at the University of South Africa (UNISA).
Retrospective analysis on prognosis of oral cancer patients according to surgical approaches for effective cancer ablation: swing approach versus visor approach
Authors: Kim Yun-Ho , Yang Jae-Young , Lee Dong-Min , Lee Jae-Yeol , Hwang Dae-Seok , Ryu Mi-Heon , Kim Uk-Kyu
Published: April 2024

Background

For the surgical treatment of oral cancer, it is sometimes necessary to expand intraoral access within the oral cavity. The “swing approach” that involves lip splitting of the mandible and temporary mandibular osteotomy and the “visor approach” that does not split the lower lip and mandible are mainly used. This study analyzed postoperative outcomes such as complications, recurrence rate, and survival rate by these two approaches. The goal of this study is to evaluate the surgical outcomes of patients using these two approaches, to propose effective perioperative management for oral cancer surgery, and to compare the prognosis of oral cancer patients.

Materials and methods

From 2005 to 2020, 29 patients who underwent surgery at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital for oral cancer lesions occurred in the mandible, floor of mouth, and tongue were selected for the study. Based on the surgical approach used, a chart review was conducted on various prognostic clinical factors such as the patients’ sex and age, primary site, TNM stage, histopathologic grade, recurrence and metastasis, postoperative survival rate, adjuvant chemo-radiation therapy, satisfaction with aesthetics/function/swallowing, length of hospital stay, tracheostomy and its duration, and neck dissection and its type. Statistical analysis was conducted using SPSS 25.0 (SPSS Inc., Chicago, IL) through Fisher’s exactt-test.

Result

There was no statistically significant difference between two groups in terms of clinical and pathological findings, such as survival rate, the need for adjuvant therapies, and the local recurrence rate. Although better outcomes were observed in terms of function, aesthetics, and postoperative complications in the group with visor approach, there was still no statistically significant difference between two groups. However, the duration of hospital stay was shorter in the visor approach group.

Conclusion

There was no statistically significant difference in clinical prognostic factors between the swing approach and the visor approach. Therefore, when choosing between the two approaches for the ablation of oral cancer, it is considered to select the surgical priority approach that can be easy access based on the size and location of the lesion. The visor approach had advantages of aesthetics and healing period.
Remimazolam-based total intravenous anesthesia in a patient with a confirmed diagnosis of malignant hyperthermia: a case report
Authors: Kondo Hiroshi , Mukaida Keiko , Sasai Kurumi , Nao Yukiko , Hashimoto Ken , Miyoshi Hirotsugu , Kanzaki Rieko , Tsutsumi Yasuo M.
Published: April 2024

Background

Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and succinylcholine, leading to a hypermetabolic reaction. The pathogenic ryanodine receptor 1 (RYR1) gene variant is critical. Patients susceptible to MH should avoid triggering agents, and total intravenous anesthesia (TIVA) is preferred. Remimazolam is safe in patients with suspected MH.

Case presentation

We present the first case of remimazolam treatment in a genetically confirmed patient with MH without MH development. A 72-year-old man with a family history of MH underwent remimazolam-based TIVA. After informed consent was obtained, a muscle biopsy and genetic testing were performed. Intraoperatively and postoperatively, the patient exhibited no signs of MH. An enhanced function of the RYR1 channel into releasing calcium was indicated, and the genetic testing revealed a pathogenic variant of RYR1.

Conclusions

Remimazolam-based TIVA is safe in patients confirming the diagnosis of MH.
Current advances in serological and molecular diagnosis of Schistosoma mekongi infection
Authors: Macalanda Adrian Miki C. , Wanlop Atcharaphan , Ona Kevin Austin L. , Galon Eloiza May S. , Khieu Virak , Sayasone Somphou , Yajima Aya , Angeles Jose Ma. M. , Kawazu Shin-ichiro
Published: April 2024

Schistosomiasis, a neglected tropical disease, caused by blood flukes belonging to the genus Schistosoma; it persists as a public health problem in selected regions throughout Africa, South America, and Asia. Schistosoma mekongi, a zoonotic schistosome species endemic to the Mekong River in Laos and Cambodia, is one of the significant causes of human schistosomiasis along with S. japonicum, S. mansoni, S. haematobium and S. intercalatum. Since its discovery, S. mekongi infection has been highly prevalent in communities along the Mekong River. Although surveillance and control measures have shown success in recent years, more robust diagnostic tools are still needed to establish more efficient control and prevention strategies to achieve and sustain an elimination status. Diagnosis of S. mekongi infection still relies on copro-parasitological techniques, commonly made by Kato-Katz stool examination. Serological techniques such as enzyme-linked immunosorbent assay (ELISA) may also be applicable but in a limited setting. Targeted molecular and serological tools specific to the species, on the other hand, have been limited. This is due, in part, to the limited research and studies on the molecular biology of S. mekongi since genome information of this species has not yet been released. In this review, current advances, and gaps and limitations in the molecular and immunological diagnosis of S. mekongi are discussed.
Navigating thrombotic terrain: unveiling a novel homocystinuria mutation associated with thrombophilia in a 16 year old
Authors: Tulasi Poojitha , Veeramachaneni Amulya , Kamble Niranjan , Rangaswamy Darshan Rajatadri
Published: April 2024

Background

Thrombophilia is characterised by an abnormality of blood coagulation that increases thrombosis. Homocystinuria encompasses a group of disorders marked by increased levels of homocysteine and other amino acids detectable in the bloodstream and urine. Conversely, homocystinuria due to methylenetetrahydrofolatereductase (MTHFR) deficiency, a rarer disorder, stems from impaired folate metabolism due to deficient MTHFR enzyme.

Case presentation

A 16-year-old boy presented with walking difficulties, headaches, and thrombotic events, thrombophilia workup led to a diagnosis of homocystinuria due to a novel mutation in MTHFR gene. Anticoagulant therapy was initiated which showed clinical improvement, but financial constraints hindered follow-up.

Conclusions

This case highlights the complexities of diagnosing and treating paediatric thrombophilia, particularly in resource-limited settings. Notably, the identified homozygous autosomal recessive (AR) missense variation in the MTHFR gene (Exon 4—c582C>G) represents a novel mutation, suggesting the ongoing significance of genetic research in elucidating the underlying mechanisms of thrombotic disorders.