bluuebunny/crossref_metadata_2025 huggingface dataset:
A snapshot of the prevalence of dihydropteroate synthase-431V mutation and other sulfadoxine-pyrimethamine resistance markers in Plasmodium falciparum isolates in Nigeria
Authors: Adegbola Adebanjo J. , Ijarotimi Omotade A. , Ubom Akaninyene E. , Adesoji Bukola A. , Babalola Olajide E. , Hocke Emma F. , Hansson Helle , Mousa Andria , Bolaji Oluseye O. , Alifrangis Michael , Roper Cally
Published: March 2023

Background

Malaria is a major public health issue with substantial risks among vulnerable populations. Currently, the World Health Organization (WHO) recommends SP-IPTp in the second and third trimesters. However, the efficacy of SP-IPTp is threatened by the emergence of sulfadoxine-pyrimethamine resistant malaria parasites due to single nucleotide polymorphisms in the Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthetase genes. This study aimed to assess the current prevalence of Pfdhfr/Pfdhps mutations in P. falciparum isolates collected from individuals residing in Ile-Ife, Nigeria, and also present maps of the prevalence of Pfdhps 431V and 581G within Nigeria and surrounding countries.

Methods

Between October 2020 and April 2021, samples were collected as dried blood spots among 188 participants who showed malaria positivity with a histidine-rich-protein-based rapid diagnostic test (RDT). Nested PCR assays were used to confirm falciparum in the samples with RDT positivity, and to amplify fragments of the Pfdhfr/Pfdhps genes followed by targeted amplicon sequencing. Published data since 2007 on the prevalence of the Pfdhps genotypes in Nigeria and the neighbouring countries were used to produce maps to show the distribution of the mutant genotypes.

Results

Only 74 and 61 samples were successfully amplified for the Pfdhfr and Pfdhps genes, respectively. At codons resulting in N51I, C59R, and S108N, Pfdhfr carried mutant alleles of 97.3% (72/74), 97.3% (72/74) and 98.6% (73/74), respectively. The Pfdhps gene carried mutations at codons resulting in amino acid changes at 431–436-437–540-581–613; I431V [45.9%, (28/61)], A581G [31.1% (19/61)] and A613S [49.2% (30/61)]. Constructed haplotypes were mainly the triple Pfdhfr mutant 51I-59R-108N (95.9%), and the most common haplotypes observed for the Pfdhps gene were the ISGKAA (32.8%), ISGKGS (8.2%), VAGKAA (14.8%), VAGKAS (9.8%) and VAGKGS (14.8%). In the context of the previously published data, a high prevalence of 431V/581G mutations was found in the study population. It seems quite evident that the Pfdhps 431V, 581G and 613S often co-occur as Pfdhps-VAGKGS haplotype.

Conclusion

This study showed that the prevalence of VAGKGS haplotype seems to be increasing in prevalence. If this is similar in effect to the emergence of 581G in East Africa, the efficacy of SP-IPTp in the presence of these novel Pfdhps mutants should be re-assessed.
Identifying individual, household and environmental risk factors for malaria infection on Bioko Island to inform interventions
Authors: García Guillermo A. , Janko Mark , Hergott Dianna E. B. , Donfack Olivier T. , Smith Jordan M. , Mba Eyono Jeremías Nzamío , DeBoer Kylie R. , Nguema Avue Restituto Mba , Phiri Wonder P. , Aldrich Edward M. , Schwabe Christopher , Stabler Thomas C. , Rivas Matilde Riloha , Cameron Ewan , Guerra Carlos A. , Cook Jackie , Kleinschmidt Immo , Bradley John
Published: March 2023

Background

Since 2004, malaria transmission on Bioko Island has declined significantly as a result of the scaling-up of control interventions. The aim of eliminating malaria from the Island remains elusive, however, underscoring the need to adapt control to the local context. Understanding the factors driving the risk of malaria infection is critical to inform optimal suits of interventions in this adaptive approach.

Methods

This study used individual and household-level data from the 2015 and 2018 annual malaria indicator surveys on Bioko Island, as well as remotely-sensed environmental data in multilevel logistic regression models to quantify the odds of malaria infection. The analyses were stratified by urban and rural settings and by survey year.

Results

Malaria prevalence was higher in 10–14-year-old children and similar between female and male individuals. After adjusting for demographic factors and other covariates, many of the variables investigated showed no significant association with malaria infection. The factor most strongly associated was history of travel to mainland Equatorial Guinea (mEG), which increased the odds significantly both in urban and rural settings (people who travelled had 4 times the odds of infection). Sleeping under a long-lasting insecticidal net decreased significantly the odds of malaria across urban and rural settings and survey years (net users had around 30% less odds of infection), highlighting their contribution to malaria control on the Island. Improved housing conditions indicated some protection, though this was not consistent across settings and survey year.

Conclusions

Malaria risk on Bioko Island is heterogeneous and determined by a combination of factors interacting with local mosquito ecology. These interactions grant further investigation in order to better adapt control according to need. The single most important risk factor identified was travel to mEG, in line with previous investigations, and represents a great challenge for the success of malaria control on the Island.
LncRNA-BC069792 suppresses tumor progression by targeting KCNQ4 in breast cancer
Authors: Zhang Yunxiang , Dong Xiaotong , Guo Xiangyu , Li Chunsen , Fan Yanping , Liu Pengju , Yuan Dawei , Ma Xialin , Wang Jingru , Zheng Jie , Li Hongli , Gao Peng
Published: March 2023

Background

Breast cancer is the most common malignant tumor that threatens women's health. Attention has been paid on the study of long- non-coding RNA (lncRNA) in breast cancer. However, the specific mechanism remains not clear.

Methods

In this study, we explored the role of lncRNA BC069792 in breast cancer. In vitro and in vivo functional experiments were carried out in cell culture and mouse models. High-throughput next-generation sequencing technology and real-time fluorescence quantitative PCR technology were used to evaluate differentially expressed genes and mRNA expression, Western blot and immunohistochemical staining were used to detect protein expression. RNA immunoprecipitation assay and dual-luciferase activity assay were used to evaluate the competing endogenous RNAs (ceRNA), and rescue and mutation experiments were used for verification.

Results

We found that lncRNA BC069792 was expressed at a low level in breast cancer tissues, and significantly decreased in breast cancer with high pathological grade, lymph node metastasis and high Ki-67 index groups. Moreover, BC069792 inhibited the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Mechanically, BC069792 acts as a molecular sponge to adsorb hsa-miR-658 and hsa-miR-4739, to up-regulate the protein expression of Potassium Voltage-Gated Channel Q4 (KCNQ4), inhibits the activities of JAK2 and p-AKT, and plays a role in inhibiting breast cancer growth.

Conclusions

LncRNA BC069792 plays the role of tumor suppressor gene in breast cancer and is a new diagnostic index and therapeutic target in breast cancer.
An intravitreal-injectable hydrogel depot doped borneol-decorated dual-drug-coloaded microemulsions for long-lasting retina delivery and synergistic therapy of wAMD
Authors: Su Wenting , Liu Congyan , Jiang Xi , Lv Yanli , Chen Qin , Shi Jiachen , Zhang Huangqin , Ma Qiuling , Ge Chang , Kong Fei , Li Xiaoqi , Liu Yuping , Chen Yan , Qu Ding
Published: March 2023

Sustained retina drug delivery and rational drug combination are considered essential for enhancing the efficacy of therapy for wet age-related macular degeneration (wAMD) due to the conservative structure of the posterior ocular segment and the multi-factorial pathological mechanism. Designing a drug co-delivery system that can simultaneously achieve deep penetration and long-lasting retention in the vitreous is highly desired, yet remains a huge challenge. In this study, we fabricated Bor/RB-M@TRG as an intravitreal-injectable hydrogel depot for deep penetration into the posterior ocular segment and long-lasting distribution in the retinal pigment epithelium (RPE) layer. The Bor/RB-M@TRG consisted of borneol-decorated rhein and baicalein-coloaded microemulsions (Bor/RB-M, the therapy entity) and a temperature-responsive hydrogel matrix (the intravitreal depot). Bor/RB-M exhibited the strongest in vitro anti-angiogenic effects among all the groups studied, which is potentially associated with improved cellular uptake, as well as the synergism of rhein and baicalein, acting via anti-angiogenic and anti-oxidative stress pathways, respectively. Importantly, a single intravitreal (IVT) injection with Bor/RB-M@TRG displayed significant inhibition against the CNV of wAMD model mice, compared to all other groups. Particularly, coumarin-6-labeled Bor/RB-M@TRG (Bor/C6-M@TRG) could not only deeply penetrate into the retina but also stably accumulate in the RPE layer for at least 14 days. Our design integrates the advantages of borneol-decorated microemulsions and hydrogel depots, offering a promising new approach for clinically-translatable retinal drug delivery and synergistic anti-wAMD treatment.
Mutation spectrum of Kallmann syndrome: identification of five novel mutations across ANOS1 and FGFR1
Authors: Chu Guoming , Li Pingping , Zhao Qian , He Rong , Zhao Yanyan
Published: March 2023

Background

Kallmann syndrome (KS) is a common type of idiopathic hypogonadotropic hypogonadism. To date, more than 30 genes including ANOS1 and FGFR1 have been identified in different genetic models of KS without affirmatory genotype–phenotype correlation, and novel mutations have been found.

Methods

A total of 35 unrelated patients with clinical features of disorder of sex development were recruited. Custom-panel sequencing or whole-exome sequencing was performed to detect the pathogenic mutations. Sanger sequencing was performed to verify single-nucleotide variants. Copy number variation-sequencing (CNV-seq) was performed to determine CNVs. The pathogenicity of the identified variant was predicted in silico. mRNA transcript analysis and minigene reporter assay were performed to test the effect of the mutation on splicing.

Results

ANOS1 gene c.709 T > A and c.711 G > T were evaluated as pathogenic by several commonly used software, and c.1063-2 A > T was verified by transcriptional splicing assay. The c.1063-2 A > T mutation activated a cryptic splice acceptor site downstream of the original splice acceptor site and resulted in an aberrant splicing of the 24-basepair at the 5′ end of exon 8, yielding a new transcript with c.1063–1086 deletion. FRFR1 gene c.1835delA was assessed as pathogenic according to the ACMG guideline. The CNV of del(8)(p12p11.22)chr8:g.36140000_38460000del was judged as pathogenic according to the ACMG & ClinGen technical standards.

Conclusions

Herein, we identified three novel ANOS1 mutations and two novel FGFR1 variations in Chinese KS families. In silico prediction and functional experiment evaluated the pathogenesis of ANOS1 mutations. FRFR1 c.1835delA mutation and del(8)(p12p11.22)chr8:g.36140000_38460000del were assessed as pathogenic variations. Therefore, our study expands the spectrum of mutations associated with KS and provides diagnostic evidence for patients who carry the same mutation in the future.
The relationship between psychological contract and occupational wellbeing of mother–infant care helpers in Zhejiang Province
Authors: Li Qingge , Li Yacen , Jin Ying , Feng Suwen
Published: March 2023

Background

Mother–infant care (MIC) helpers have become an indispensable part in hospital services. In order to stabilize the MIC workforce, it is essential for administrators to have a solid understanding of what may influence occupational wellbeing. This article aims to explore how demographic characteristics and psychological contract affect occupational wellbeing among MIC helpers in Zhejiang Province, China.

Methods

This is a quantitative, cross-sectional study with MIC helpers in obstetrics from 20 hospitals in Zhejiang Province. A questionnaire including demographic data, a psychological contract scale and an occupational wellbeing scale was used in this study. Multiple linear regression was conducted to investigate the relationships between demographic characteristics, psychological contract and occupational wellbeing.

Results

This study surveyed 260 MIC helpers and found out the mean score of the psychological contract was 4.38 and the mean score of the occupational wellbeing was 4.01. Monthly income and psychological contract were significant predictors of occupational wellbeing (F = 142.167, p < 0.001), which explained 62.1% of the total amount of variance in occupational wellbeing. Psychological contract was the most important predictor of occupational wellbeing.

Conclusions

Administrators should pay attention to the effect of psychological contract on occupational wellbeing of the MIC helpers in China. Focusing on the inner needs should be considered as a strategy for stabilizing the team.
Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption
Authors: Qin Zongshi , Shi Dong-Dong , Li Wenqi , Cheng Dan , Zhang Ying-Dan , Zhang Sen , Tsoi Bun , Zhao Jia , Wang Zhen , Zhang Zhang-Jin
Published: March 2023

Objectives

Neuroinflammation has been suggested that affects the processing of depression. There is renewed interest in berberine owing to its anti-inflammatory effects. Herein, we investigated whether berberine attenuate depressive-like behaviors via inhibiting NLRP3 inflammasome activation in mice model of depression.

Methods

Adult male C57BL/6N mice were administrated corticosterone (CORT, 20 mg/kg/day) for 35 days. Two doses (100 mg/kg/day and 200 mg/kg/day) of berberine were orally administrated from day 7 until day 35. Behavioral tests were performed to measure the depression-like behaviors alterations. Differentially expressed gene analysis was performed for RNA-sequencing data in the prefrontal cortex. NLRP3 inflammasome was measured by quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence labeling. The neuroplasticity and synaptic function were measured by immunofluorescence labeling, Golgi–Cox staining, transmission electron microscope, and whole-cell patch-clamp recordings.

Results

The results of behavioral tests demonstrated that berberine attenuated the depression-like behaviors induced by CORT. RNA-sequencing identified that NLRP3 was markedly upregulated after long-term CORT exposure. Berberine reversed the concentrations of peripheral and brain cytokines, NLRP3 inflammasome elicited by CORT in the prefrontal cortex and hippocampus were decreased by berberine. In addition, the lower frequency of neuronal excitation as well as the dendritic spine reduction were reversed by berberine treatment. Together, berberine increases hippocampal adult neurogenesis and synaptic plasticity induced by CORT.

Conclusion

The anti-depressants effects of berberine were accompanied by reduced the neuroinflammatory response via inhibiting the activation of NLRP3 inflammasome and rescued the neuronal deterioration via suppression of impairments in synaptic plasticity and neurogenesis.
Assembly and operation of an imaging system for long-term monitoring of bioluminescent and fluorescent reporters in plants
Authors: Sorkin Maria L. , Markham Kathleen K , Zorich Stevan , Menon Ananda , Edgeworth Kristen N. , Ricono Angela , Bryant Douglas , Bart Rebecca , Nusinow Dmitri A. , Greenham Kathleen
Published: March 2023

Background

Non-invasive reporter systems are powerful tools to query physiological and transcriptional responses in organisms. For example, fluorescent and bioluminescent reporters have revolutionized cellular and organismal assays and have been used to study plant responses to abiotic and biotic stressors. Integrated, cooled charge-coupled device (CCD) camera systems have been developed to image bioluminescent and fluorescent signals in a variety of organisms; however, these integrated long-term imaging systems are expensive.

Results

We have developed self-assembled systems for both growing and monitoring plant fluorescence and bioluminescence for long-term experiments under controlled environmental conditions. This system combines environmental growth chambers with high-sensitivity CCD cameras, multi-wavelength LEDs, open-source software, and several options for coordinating lights with imaging. This easy-to-assemble system can be used for short and long-term imaging of bioluminescent reporters, acute light-response, circadian rhythms, delayed fluorescence, and fluorescent-protein-based assays in vivo.

Conclusions

We have developed two self-assembled imaging systems that will be useful to researchers interested in continuously monitoring in vivo reporter systems in various plant species.
A radiomics model for predicting the response to methylprednisolone in brain necrosis after radiotherapy for nasopharyngeal carcinoma
Authors: Zhuo Xiaohuang , Zhao Huiying , Chen Meiwei , Mu Youqing , Li Yi , Cai Jinhua , Li Honghong , Xu Yongteng , Tang Yamei
Published: March 2023

Background

Methylprednisolone is recommended as the front-line therapy for radiation-induced brain necrosis (RN) after radiotherapy for nasopharyngeal carcinoma. However, some patients fail to benefit from methylprednisolone or even progress. This study aimed to develop and validate a radiomic model to predict the response to methylprednisolone in RN.

Methods

Sixty-six patients receiving methylprednisolone were enrolled. In total, 961 radiomic features were extracted from the pre-treatment magnetic resonance imagings of the brain. Least absolute shrinkage and selection operator regression was then applied to construct the radiomics signature. Combined with independent clinical predictors, a radiomics model was built with multivariate logistic regression analysis. Discrimination, calibration and clinical usefulness of the model were assessed. The model was internally validated using 10-fold cross-validation.

Results

The radiomics signature consisted of 16 selected features and achieved favorable discrimination performance. The radiomics model incorporating the radiomics signature and the duration between radiotherapy and RN diagnosis, yielded an AUC of 0.966 and an optimism-corrected AUC of 0.967 via 10-fold cross-validation, which also revealed good discrimination. Calibration curves showed good agreement. Decision curve analysis confirmed the clinical utility of the model.

Conclusions

The presented radiomics model can be conveniently used to facilitate individualized prediction of the response to methylprednisolone in patients with RN.
Aryl hydrocarbon receptor nuclear translocator limits the recruitment and function of regulatory neutrophils against colorectal cancer by regulating the gut microbiota
Authors: Bi Yujing , Yang Qiuli , Li Zhengchao , Wang Yuexin , Wang Yufei , Jia Anna , Pan Zhiyuan , Yang Ruifu , Liu Guangwei
Published: March 2023

Background

Although the role and mechanism of neutrophils in tumors have been widely studied, the precise effects of aryl hydrocarbon receptor nuclear translocator (ARNT) on neutrophils remain unclear. In this study, we investigated the roles of ARNT in the function of CD11b+Gr1+ neutrophils in colitis-associated colorectal cancer.

Methods

Wild-type (WT), ARNT myeloid-specific deficient mice and a colitis-associated colorectal cancer mouse model were used in this study. The level and functions of CD11b+Gr1+ cells were evaluated by flow cytometry and confocal microscopy.

Results

We found that ARNT deficiency drives neutrophils recruitment, neutrophil extracellular trap (NET) development, inflammatory cytokine secretion and suppressive activities when cells enter the periphery from bone marrow upon colorectal tumorigenesis. ARNT deficiency displays similar effects to aryl hydrocarbon receptor (AHR) deficiency in neutrophils. CXCR2 is required for NET development, cytokine production and recruitment of neutrophils but not the suppressive activities induced by Arnt−/− in colorectal cancer. The gut microbiota is essential for functional alterations in Arnt−/− neutrophils to promote colorectal cancer growth. The colorectal cancer effects of Arnt−/− neutrophils were significantly restored by mouse cohousing or antibiotic treatment. Intragastric administration of the feces of Arnt−/− mice phenocopied their colorectal cancer effects.

Conclusion

Our results defined a new role for the transcription factor ARNT in regulating neutrophils recruitment and function and the gut microbiota with implications for the future combination of gut microbiota and immunotherapy approaches in colorectal cancer.
Is the diagnostic validity of conventional radiography for Lisfranc injury acceptable?
Authors: Chen Cheng , Jiang JianTao , Wang Cheng , Zou Jian , Shi ZhongMin , Yang YunFeng
Published: March 2023

Background

Lisfranc injuries mainly involve the tarsometatarsal joint complex and are commonly misdiagnosed or missed in clinical settings. Most medical institutions prefer to use conventional radiography. However, existing studies on conventional radiographs in Lisfranc injury lack a large population‐based sample, influencing the validity of the results. We aimed to determine the diagnostic validity and reliability of conventional radiography for Lisfranc injury and whether computed tomography can alter clinical decision‐making.

Methods

This retrospective study included 307 patients with, and 100 patients without, Lisfranc injury from January 2017 to December 2019. Diagnosis was confirmed using computed tomography. A senior and junior surgeon independently completed two assessments of the same set of anonymised conventional radiographs at least 3 months apart. The surgeons were then asked to suggest one of two treatment options (surgery or conservative treatment) for each case based on the radiographs and subsequently on the CT images.

Results

All inter‐ and intra‐observer reliabilities were moderate to very good (all κ coefficients > 0.4). The mean (range) true positive rate was 81.8% (73.9%–87.0%), true negative rate was 90.0% (85.0%–94.0%), false positive rate was 10.0% (6.0%–15.0%), false negative rate was 18.2% (13.0%–26.1%), positive predictive value was 96.1% (93.8%–97.8%), negative predictive value was 62.4% (51.5%–69.7%), classification accuracy was 83.8% (76.7%–88.2%), and balanced error rate was 14.1% (10.2%–20.5%). Three‐column injuries were most likely to be recognized (mean rate, 92.1%), followed by intermediate‐lateral‐column injuries (mean rate, 81.5%). Medial‐column injuries were relatively difficult to identify (mean rate, 60.7%). The diagnostic rate for non‐displaced injuries (mean rate, 76.7%) was lower than that for displaced injuries (mean rate, 95.5%). The typical examples are given. A significant difference between the two surgeons was found in the recognition rate of non‐displaced injuries (p = 0.005). The mean alteration rate was 21.9%; the senior surgeon tended to a lower rate (15.6%) than the junior one (28.3%) (p < 0.001).

Conclusions

The sensitivity, specificity, and classification accuracy of conventional radiographs for Lisfranc injury were 81.8%, 90.0%, and 83.8%, respectively. Three‐column or displaced injuries were most likely to be recognized. The possibility of changing the initial treatment decision after subsequently evaluating computed tomography images was 21.9%. The diagnostic and clinical decision‐making of surgeons with different experience levels demonstrated some degree of variability. Protected weight‐bearing and a further CT scan should be considered if a Lisfranc injury is suspected and conventional radiography is negative.
Mitochondrial phylogenomics provides conclusive evidence that the family Ancyrocephalidae is deeply paraphyletic
Authors: Hao Cui-Lan , Wei Nian-Wen , Liu Yan-Jun , Shi Cai-Xia , Arken Kadirden , Yue Cheng
Published: March 2023

Background

Unresolved taxonomic classification and paraphyly pervade the flatworm class Monogenea: the class itself may be paraphyletic and split into Polyopisthocotylea and Monopisthocotylea; there are some indications that the monopisthocotylean order Dactylogyridea may also be paraphyletic; single-gene markers and some morphological traits indicate that the family Ancyrocephalidae is paraphyletic and intertwined with the family Dactylogyridae.

Methods

To attempt to study the relationships of Ancyrocephalidae and Monopisthocotylea using a phylogenetic marker with high resolution, we sequenced mitochondrial genomes of two fish ectoparasites from the family Dactylogyridae: Dactylogyrus simplex and Dactylogyrus tuba. We conducted phylogenetic analyses using three datasets and three methods. Datasets were ITS1 (nuclear) and nucleotide and amino acid sequences of almost complete mitogenomes of almost all available Monopisthocotylea mitogenomes. Methods were maximum likelihood (IQ-TREE), Bayesian inference (MrBayes) and CAT-GTR (PhyloBayes).

Results

Both mitogenomes exhibited the ancestral gene order for Neodermata, and both were compact, with few and small intergenic regions and many and large overlaps. Gene sequences were remarkably divergent for nominally congeneric species, with only trnI exhibiting an identity value > 80%. Both mitogenomes had exceptionally low A + T base content and AT skews. We found evidence of pervasive compositional heterogeneity in the dataset and indications that base composition biases cause phylogenetic artefacts. All six mitogenomic analyses produced unique topologies, but all nine analyses produced topologies that rendered Ancyrocephalidae deeply paraphyletic. Mitogenomic data consistently resolved the order Capsalidea as nested within the Dactylogyridea.

Conclusions

The analyses indicate that taxonomic revisions are needed for multiple Polyopisthocotylea lineages, from genera to orders. In combination with previous findings, these results offer conclusive evidence that Ancyrocephalidae is a paraphyletic taxon. The most parsimonious solution to resolve this is to create a catch-all Dactylogyridae sensu lato clade comprising the current Ancyrocephalidae, Ancylodiscoididae, Pseudodactylogyridae and Dactylogyridae families, but the revision needs to be confirmed by another marker with a sufficient resolution.

Graphical Abstract
Some weakly singular Volterra integral inequalities with maxima in two variables
Authors: Sun Yining , Xu Run
Published: March 2023

In this paper, we establish some new weakly singular Volterra type integral inequalities that include the maxima of the unknown function of two variables. We also use the results to research the boundedness of solutions to retarded nonlinear Volterra type integral equations.
Clinical significance of obstructive sleep apnea in patients with acute coronary syndrome with or without prior stroke: a prospective cohort study
Authors: Wang Bin , Hao Wen , Fan Jingyao , Yan Yan , Gong Wei , Zheng Wen , Que Bin , Ai Hui , Wang Xiao , Nie Shaoping
Published: March 2023

Background and objective

Whether obstructive sleep apnea (OSA) is associated with worse prognosis in patients with acute coronary syndrome (ACS) with or without prior stroke remains unclear. We investigated the association of OSA with cardiovascular events in ACS patients with or without prior stroke.

Methods

Between June 2015 and January 2020, we prospectively recruited eligible ACS patients who underwent cardiorespiratory polygraphy during hospitalization. We defined OSA as an apnea hypopnea index (AHI) ≥ 15 events/hour. The primary composite end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure.

Results

Among 1927 patients enrolled, 207 patients had prior stroke (10.7%) and 1014 had OSA (52.6%). After a mean follow-up of 2.9 years, patients with stroke had significantly higher risk of MACCEs than those without stroke (hazard ratio [HR]:1.49; 95% confidence interval [CI]: 1.12–1.98, P = 0.007). The multivariate analysis showed that patients with OSA had 2.0 times the risk of MACCEs in prior stroke group (41 events [33.9%] vs 18 events [20.9%]; HR:2.04, 95% CI:1.13–3.69, P = 0.018), but not in non-prior stroke group (186 events [20.8%] vs 144 events [17.4]; HR:1.21, 95% CI 0.96–1.52, P = 0.10). No significant interaction was noted between prior stroke and OSA for MACCE (interaction P = 0.17).

Conclusions

Among ACS patients, the presence of OSA was associated with an increased risk of cardiovascular events in patients with prior stroke. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS and prior stroke are warranted.

Trial registration Clinicaltrials.gov identifier NCT03362385.
Change of serum lipoproteins and its potential use in stratifying patients with sepsis among neonates
Authors: Guo Junfei , Lai Weiming , Wu Yongbing , Li Huan , Fu Zhenhua , Mu Xiaoping
Published: March 2023

Background

Changes of serum lipoprotein concentration during bacteremia or sepsis are observed and lipoproteins concentration facilitate the evaluation severity of sepsis in adults, but its clinical usage is still unclear. Here, we analyzed the lipoprotein concentration in neonates with sepsis and discussed its use in stratifying patients.

Methods

This is a retrospective study involved 88 culture-proven septic patients. Clinical and microbiology data of involved patients were collected via inquiring databases of our institute. Patients were grouped according to blood culture results or procalcitonin level; the difference between groups were analyzed.

Results

Compared with uninfected group, there is no change of triglyceride (TG) concentrations and significant decrease of Total cholesterol (TC) concentration in septic patients. There is no significant difference between Gram-positive and Gram-negative-related septic patients in terms of serum TG and TC concentration. Other than group with procalcitonin level of 0.5–2 ng/ml, both serum TG and TC concentration were decreased while serum procalcitonin level increasing.

Conclusions

Our results indicated that serum lipoprotein concentration may be recommended to help diagnosis of bacteria and to evaluate the severity of sepsis.
Effect of replacement of soybean oil by Hermetia illucens fat on performance, digestibility, cecal microbiome, liver transcriptome and liver and plasma lipidomes of broilers
Authors: Schäfer Lea , Grundmann Sarah M. , Maheshwari Garima , Höring Marcus , Liebisch Gerhard , Most Erika , Eder Klaus , Ringseis Robert
Published: March 2023

Background

In contrast to protein-rich insect meal, the feed potential of insect fat is generally less explored and knowledge about the suitability of insect fat as a fat source specifically in broiler diets is still limited. In view of this, the present study aimed to comprehensively investigate the effect of partial (50%) and complete replacement of soybean oil with insect fat from Hermetia illucens (HI) larvae in broiler diets on performance, fat digestibility, cecal microbiome, liver transcriptome and liver and plasma lipidomes. Thus, 100 male, 1-day-old Cobb 500 broilers were randomly assigned to three groups and fed three different diets with either 0 (group HI-0, n = 30), 2.5% (group HI-2.5, n = 35) or 5.0% (HI-5.0, n = 35) Hermetia illucens (HI) larvae fat for 35 d.

Results

Body weight gain, final body weight, feed intake, and feed:gain ratio during the whole period and apparent ileal digestibility coefficient for ether extract were not different between groups. Cecal microbial diversity did not differ between groups and taxonomic analysis revealed differences in the abundance of only four low-abundance bacterial taxa among groups; the abundances of phylum Actinobacteriota, class Coriobacteriia, order Coriobacteriales and family Eggerthellaceae were lower in group HI-5.0 compared to group HI-2.5 (P < 0.05). Concentrations of total and individual short-chain fatty acids in the cecal digesta were not different between the three groups. Liver transcriptomics revealed a total of 55 and 25 transcripts to be differentially expressed between groups HI-5.0 vs. HI-0 and groups HI-2.5 vs. HI-0, respectively (P < 0.05). The concentrations of most lipid classes, with the exception of phosphatidylethanolamine, phosphatidylglycerol and lysophosphatidylcholine in the liver and cholesterylester and ceramide in plasma (P < 0.05), and of the sum of all lipid classes were not different between groups.

Conclusions

Partial and complete replacement of soybean oil with HI larvae fat in broiler diets had no effect on growth performance and only modest, but no adverse effects on the cecal microbiome and the metabolic health of broilers. This suggests that HI larvae fat can be used as an alternative fat source in broiler diets, thereby, making broiler production more sustainable.
Effect of growth stage on Italian ryegrass (Lolium multiflorum Lam.) silage fermentation from microbiological perspective
Authors: Yin Xuejing , Long Jiangyu , Zhao Jie , Wang Siran , Dong Zhihao , Li Junfeng , Shao Tao
Published: March 2023

Background

Italian ryegrass is a temperate climate crop, which is widely cultivated in the winter fallow paddy fields of subtropical China. The utilization efficiency of Italian ryegrass depends greatly on its growth stage at harvest. Previous studies have reported the optimum stage for harvesting various forage to balance their quality and quantity. However, when considering the practice condition, such as rainy or unavailability of harvest equipment, the harvest stage of forage cannot always be implemented according to the production schedules. Thus, to characterize the effect of growth stage on the silage fermentation profile, bacterial community construction and metabolisms of carbohydrates and amino acids, Italian ryegrass were naturally ensiled at the filling stage (FSN) and the dough stage (DSN), respectively. After ensiling for 1, 3, 7, 15, 30, and 60 days, triplicate silos were opened for sampling.

Results

The growth of Italian ryegrass increased the pH, dry matter, neutral, and acid detergent fiber contents, but decreased buffering capacity, crude protein and water-soluble carbohydrates contents, and the epiphytic microbiota of Italian ryegrass harvested at the filling stage was simpler than that harvested at the dough stage. During ensiling, FSN had lower pH and higher organic acid content than DSN. The bacterial succession rate in FSN was also faster than DSN, which showed that Lactobacillus becomes the dominant genus in the early stage of ensiling. The predicted metabolisms revealed that carbohydrate and amino acid metabolisms were the two main metabolisms in silage fermentation. When compared with epiphytic microbiota, ensiling enhanced carbohydrate metabolism and diminished amino acid metabolism. The difference of these two metabolisms between FSN and DSN was obvious at the early stage of ensiling.

Conclusions

Growth stage affected the chemical and microbial composition of Italian ryegrass, so as to the fermentation profile, bacterial community and its metabolisms intensity. Italian ryegrass harvested at the filling stage was prone to ferment. The complexity of epiphytic microbiota made Italian ryegrass harvested at the dough stage more difficult to ferment.

Graphical Abstract
The burden of firearm injuries on the hospital system, 2000–2020
Authors: Davoudi Anis , Woodworth Lindsey
Published: March 2023

Background

Firearm injuries are a long-running yet preventable public health concern in the USA. We analyzed national inpatient data to determine the burden of firearm injuries on the USA hospital system. For each year from 2000–2014 and 2016–2020, we calculated the annual frequency of firearm hospitalization in the USA overall and by the intent of the shooter. We also calculated the rate of firearm hospitalizations per 100,000 inpatient encounters. For each outcome, we used regression analysis to estimate the average year-over-year change. Finally, we explored the types of firearms responsible for firearm hospitalizations.

Findings

Each year during 2000–2020 (excluding 2015), there were an average of 30,428 firearm hospitalizations in the USA. On average, firearm hospitalizations represented 84 out of every 100,000 inpatient encounters each year. There was not a statistically significant year-over-year increase in firearm hospitalizations for either the periods 2000–2014 or 2016–2020. However, firearm hospitalizations were noticeably higher in 2020 than in other years. Until 2019, the most frequent intent among firearm hospitalizations was assault. Beginning in 2019, assaults were outnumbered by unintentional firearm hospitalizations. According to diagnosis codes, handguns were used more often than rifles/shotguns/larger firearms in firearm injuries that resulted in hospitalization for the intents assault (27.93% handguns; 5.87% rifles/shotguns/larger firearms), unintentional (23.94% handguns; 10.48% rifles/shotguns/larger firearms), self-harm (46.63% handguns; 14.35% rifles/shotguns/larger firearms) and undetermined (17.82% handguns; 6.21% rifles/shotguns/larger firearms). Frequently, the type of firearm responsible for the hospitalization was not recorded in the patient’s diagnosis code.

Conclusion

Firearm injuries inflict a significant burden on the hospital system in the USA. While firearm hospitalizations were unusually high in 2020, there is not strong evidence that the burden of firearm injuries on the hospital system is changing over time. The frequent non-identification of the type of firearm responsible for the injury in hospital patients’ diagnosis code complicates injury surveillance efforts.
Three-dimensional heads-up system assisted pars plana vitrectomy and subretinal recombinant tissue plasminogen activator injection for submacular hemorrhage
Authors: Zhao Xinyu , Zhao Qing , Wang Erqian , Li Ningning , Meng Lihui , Zhang Wenfei , Wang Tan , Chen Youxin , Min Hanyi
Published: March 2023

Background

To evaluate the outcomes of three-dimensional (3D) heads-up system assisted pars plana vitrectomy (PPV) and subretinal injection of recombinant tissue plasminogen activator (rt-PA) for submacular hemorrhage (SMH).

Methods

Medical records of SMH patients who underwent 3D heads-up system assisted-PPV and subretinal injection of rt-PA from June 2021 to January 2022 were reviewed. The main outcomes included best-corrected visual acuity (BCVA), SMH absorption, and perioperative complications.

Results

We finally included 18 SMH eyes, most of which happened secondary to polypoidal choroidal vasculopathy (PCV) (10, 55.56%), followed by retinal arterial microaneurysm (RAM) (5, 27.78%), traumatic retinopathy (2, 11.11%) and neovascular age-related macular degeneration (nAMD) (1, 5.56%). The greatest linear dimension (GLD) and height of SMH were 6538.17 ± 2533.11 μm and 937.36 ± 420.21 μm, respectively. After an average postoperative follow-up period of 131.06 ± 38.96 days, patients’ BCVA improved significantly from 1.85 ± 0.62 to 1.14 ± 0.82 logMAR (P < 0.05). SMH was completely and partially absorbed in 9 (50.00%) and 6 (33.33%) eyes, with no occurrence of iatrogenic retinal break. However, 4 additional PPVs were performed to manage the postoperative SMH and/or vitreous hemorrhage (VH) recurrence (2, 11.11%) and retinal detachment (RD) occurrence (2, 11.11%). Preoperative BCVA was significantly correlated with postoperative BCVA in multiple linear regression analysis (P < 0.05), and hemorrhagic pigment epithelial detachment (PED) was significantly correlated with SMH and VH recurrence in univariate binary logistic regression analysis (P < 0.05).

Conclusions

The 3D heads-up system assisted-PPV and subretinal injection of rt-PA were efficacious in eliminating SMH and improving visual prognosis with satisfactory safety profile, while caution should be taken for PCV patients with hemorrhagic PED and massive SMH.
Microglia activation and neuronal alterations in retinas from COVID-19 patients: correlation with clinical parameters
Authors: Albertos-Arranz Henar , Martínez-Gil Natalia , Sánchez-Sáez Xavier , Noailles Agustina , Monferrer Adsuara Clara , Remolí Sargues Lidia , Pérez-Santonja Juan J. , Lax Pedro , Calvo Andrés Ramón , Cuenca Nicolás
Published: March 2023

Background

Different ocular alterations have been described in patients with coronavirus disease 2019 (COVID-19). Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters.

Methods

Retinal sections and flat-mount retinas from human donors with COVID-19 (n = 16) and controls (n = 15) were immunostained. The location of angiotensin-converting enzyme 2 (ACE2) and the morphology of microglial cells, Müller cells, astrocytes, and photoreceptors were analyzed by confocal microscopy. Microglial quantification and the area occupied by them were measured. Correlations among retinal and clinical parameters were calculated.

Results

ACE2 was mainly located in the Müller cells, outer segment of cones and retinal pigment epithelium. Cell bodies of Müller cells in COVID-19 group showed greater staining of ACE2 and cellular retinaldehyde-binding protein (CRALBP). The 81.3% of COVID-19 patients presented disorganization of honeycomb-like pattern formed by Müller cells. Gliosis was detected in 56.3% of COVID-19 patients compared to controls (40%) as well as epiretinal membranes (ERMs) or astrocytes protruding (50%). Activated or ameboid-shape microglia was the main sign in the COVID-19 group (93.8%). Microglial migration towards the vessels was greater in the COVID-19 retinas (P < 0.05) and the area occupied by microglia was also reduced (P < 0.01) compared to control group. Cone degeneration was more severe in the COVID-19 group. Duration of the disease, age and respiratory failure were the most relevant clinical data in relation with retinal degeneration.

Conclusions

The retinas of patients with COVID-19 exhibit glial activation and neuronal alterations, mostly related to the inflammation, hypoxic conditions, and age.
Development of a screening platform to discover natural products active against SARS-CoV-2 infection using lung organoid models
Authors: Lee Joo-Eun , Jeong Se Yun , Li Zijun , Kim Hyun-Yi , Kim Hyun-Woo , Yoo Min Jeong , Jang Hee Joo , Kim Do-Kyun , Cho Namki , Yoo Hee Min , Kim Ki Hyun
Published: March 2023

Background

Natural products can serve as one of the alternatives, exhibiting high potential for the treatment and prevention of COVID-19, caused by SARS-CoV-2. Herein, we report a screening platform to test the antiviral efficacy of a natural product library against SARS-CoV-2 and verify their activity using lung organoids.

Methods

Since SARS-CoV-2 is classified as a risk group 3 pathogen, the drug screening assay must be performed in a biosafety level 3 (BSL-3) laboratory. To circumvent this limitation, pseudotyped viruses (PVs) have been developed as replacements for the live SARS-CoV-2. We developed PVs containing spikes from Delta and Omicron variants of SARS-CoV-2 and improved the infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. Human induced pluripotent stem cells (hiPSCs) derived lung organoids were generated to test the SARS-CoV-2 therapeutic efficacy of natural products.

Results

Flavonoids from our natural product library had strong antiviral activity against the Delta- or Omicron-spike-containing PVs without affecting cell viability. We aimed to develop strategies to discover the dual function of either inhibiting infection at the beginning of the infection cycle or reducing spike stability following SARS-CoV-2 infection. When lung cells are already infected with the virus, the active flavonoids induced the degradation of the spike protein and exerted anti-inflammatory effects. Further experiments confirmed that the active flavonoids had strong antiviral activity in lung organoid models.

Conclusion

This screening platform will open new paths by providing a promising standard system for discovering novel drug leads against SARS-CoV-2 and help develop promising candidates for clinical investigation as potential therapeutics for COVID-19.

Graphical Abstract
Association of vascular endothelial growth factor serum levels with ankylosing spondylitis in Egyptian patients
Authors: Galal Salwa , Hassan Rasha Mohamed , Labib Hossam Salaheldin Abdelmohsen
Published: March 2023

Background

Ankylosing spondylitis (AS) is one of inflammatory rheumatic diseases which result in wide range of manifestations on the musculoskeletal system and axial joint specifically. Endothelial cell migration and proliferation, as well as subsequent neoangiogenesis and remodelling in autoimmune disorders, are pathogenic mechanisms that are fundamental to inflammation activation and angiogenesis. The development of advanced lesions is thought to involve vascular proliferation as well as vascular endothelial growth factor (VEGF), which serves a regulatory role. It was found that AS patients had increased serum levels of VEGF, which were linked to the disease activity.

Aim of the work

The purpose of this study is to measure serum VEGF levels in Egyptian AS patients and assess their relation to disease-related variables, including radiographic findings.

Results

VEGF serum levels showed a highly significant positive correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) and modified Stroke Ankylosing Spondylitis Spinal Score (MSASS) (p < 0.001); also, there was a significant correlation between the VEGF values and the Ankylosing Spondylitis Disease Activity Index (ASDAS) and the New York x-ray sacroiliac score.

Conclusions

These findings and data illustrate the strong relationship between ASDAS and VEGF and the radiographic score in AS patients. ASDAS combined with VEGF not only is considered a tool for determining the level of disease activity only but also is considered as an indicator for the assessment of the syndesmophytes formation, which performs a crucial role in the prognosis and outcome in AS patients.
Can elastic waveform inversion benefit from inverting multicomponent data?
Authors: Solano Carlos Pérez , Plessix René-Édouard
Published: March 2023

Waveform inversion aims to retrieve high-resolution earth parameter volumes. Due to its high computational cost, acoustic approaches using low to mid seismic data frequencies are often applied in velocity model building. However, in the presence of large parameter contrasts, an elastic formulation should be preferred due to wave interferences that limit the applicability of phase- and kinematics-only approaches. The benefits of elastic waveform inversion have been demonstrated with inversion of hydrophone data in marine environments. Here, we extend the approach to inversion of the vertical geophone component. We propose a weighted cost function in the waveform inversion algorithm to jointly invert multicomponent data sets, and we compare the results to the inversion of single-component data. For this study, we use an ocean-bottom-node data set from the deepwater Gulf of Mexico around a salt dome. We show that slightly different velocity models, reverse time migration images, and angle gathers are retrieved when using hydrophone or vertical geophone data, further improving either the shallow or deeper sediments. The joint inversion combines the improvements brought by the single-component inversions. Though it doubles the cost, joint elastic waveform inversion of hydrophone and vertical geophone data can help velocity model building around salt bodies.