bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular autonomic modulation differences between moderate-intensity continuous and high-intensity interval aerobic training in women with PCOS: A randomized trial
Authors: Philbois Stella V. , Ribeiro Victor B. , Tank Jens , Reis Rosana Maria dos , Gerlach Darius A. , Souza Hugo C. D.
Published: November 2022

Background

Moderate-intensity continuous training (MICT) is strongly recommended for polycystic ovarian syndrome (PCOS) treatment. However, recent studies have suggested that high-intensity interval training (HIIT) would promote great benefits for cardiac autonomic control. Therefore, we investigated whether the benefits of HIIT related to cardiovascular autonomic control were greater than those of MICT in women with PCOS.

Methods

Women with PCOS were randomly allocated through a blind draw into three groups: control, MICT, and HIIT. The control group did not undergo exercise, whereas those in the MICT and HIIT groups underwent 16 weeks of aerobic physical training. All groups were evaluated before and after the 16 weeks of intervention in the following aspects: quantification of serum lipids, testosterone, fasting insulin and blood glucose; physical fitness through cardiopulmonary testing; analysis of heart rate variability (HRV) by linear (time domain and frequency domain) and non-linear (symbolic analysis) methods, analysis of blood pressure variability (BPV) and spontaneous baroreflex sensitivity (BRS).

Results

The final analysis, each group comprised 25 individuals. All groups had similar baseline parameters. After 16 weeks, intragroup comparison showed that the MICT and HIIT groups had a reduction in baseline heart rate (P < 0.001; P < 0.001, respectively) and testosterone levels P < 0.037; P < 0.012, respectively) associated with an increase in VO2peak (MICT, P < 0.001; HIIT, P < 0.001). The MICT (P < 0.36) and HIIT (P < 0.17) groups also showed an increase in cardiac vagal modulation, however only observed in the non-linear analysis. The intergroup comparison showed no differences between the MICT and HIIT groups in any of the hormonal, metabolic and autonomic parameters evaluated, including testosterone, peak oxygen uptake (VO2peak), HRV, BPV and BRS.

Conclusion

HIIT and MICT showed similar results for the different parameters evaluated. This suggests that both training protocols can be recommended for the treatment of PCOS. Brazilian Clinical Trials Registry (RBR-78qtwy).
Health-related quality of life in boys with constitutional delay of growth and puberty
Authors: Kariola Laura , Varimo Tero , Huopio Hanna , Tenhola Sirpa , Voutilainen Raimo , Kosola Silja , Toppari Jorma , Sintonen Harri , Miettinen Päivi J. , Raivio Taneli , Hero Matti
Published: November 2022

Introduction

Constitutional delay of growth and puberty (CDGP) is the most common reason for delayed puberty in healthy male adolescents. The main indication for medical treatment for this condition is psychosocial burden. However, to the best of our knowledge, no previous study has addressed the impact of puberty-promoting treatment on health-related quality of life (HRQoL) among boys with CDGP.

Methods

We investigated HRQoL in 22 boys with CDGP, who participated in a randomized controlled trial in four Finnish pediatric endocrinology outpatient clinics between 2013 and 2017. The boys were randomized to receive either aromatase inhibitor letrozole (2.5mg/day; n=11) or intramuscular testosterone (1mg/kg/every 4 weeks; n=11) for 6 months and followed up to 12 months. HRQoL was assessed with a generic self-assessment 16D© instrument developed and validated for adolescents aged 12 to 15 years. The 16D includes 16 dimensions (vitality, sight, breathing, distress, hearing, sleeping, eating, discomfort and symptoms, speech, physical appearance, school and hobbies, mobility, friends, mental function, excretion and depression). The results were compared with an age-matched reference population that included 163 boys from the Finnish capital-city area. The study protocol is registered to ClinicalTrials.gov (registration number: NCT01797718).

Results

At baseline, the mean 16D score of the CDGP boys was similar to the age-matched reference population (0.95 vs 0.96, p=0.838). However, the physical appearance score (satisfaction with general appearance, height and weight) was significantly lower in the CDGP boys (0.75 vs 0.92, p=0.004) than their peers. Twelve months after treatment, Appearance had improved significantly (0.75 vs 0.87, p=0.004) and no HRQoL dimension was inferior compared to the age-matched reference population.

Discussion

In terms of HRQoL, the main impact of delayed puberty was dissatisfaction with physical appearance. Puberty promoting therapy was associated with a positive change in perceived appearance, with no clear difference between low-dose testosterone and letrozole treatments.
Novel biomarkers and therapeutic approaches for diabetic retinopathy and nephropathy: Recent progress and future perspectives
Authors: Xie Ziyan , Xiao Xinhua
Published: November 2022

The global burden due to microvascular complications in patients with diabetes mellitus persists and even increases alarmingly, the intervention and management are now encountering many difficulties and challenges. This paper reviews the recent advancement and progress in novel biomarkers, artificial intelligence technology, therapeutic agents and approaches of diabetic retinopathy and nephropathy, providing more insights into the management of microvascular complications.
Analysis of circRNA and miRNA expression profiles in IGF3-induced ovarian maturation in spotted scat (Scatophagus argus)
Authors: Li Zhiyuan , Guo Yuwen , Ndandala Charles Brighton , Chen Huadong , Huang Chunren , Zhao Guangwen , Huang Hai , Li Guangli , Chen Huapu
Published: November 2022

Insulin-like growth factor 3 (IGF3) induces ovarian maturation in teleosts; however, research on its molecular regulatory mechanism remains deficient. Circular RNAs (circRNAs) and microRNAs (miRNAs) are involved in various biological processes, including reproduction. In this study, circRNAs and miRNAs involved in IGF3-induced ovarian maturation were evaluated in spotted scat (Scatophagus argus). In ovarian tissues, we identified 176 differentially expressed (DE) circRNAs and 52 DE miRNAs between IGF3 treatment and control groups. Gene Ontology (GO) enrichment analyses showed that host genes of DE circRNAs and target genes of DE miRNAs were enriched for various processes with a high degree of overlap, including cellular process, reproduction, reproductive process, biological adhesion, growth, extracellular region, cell junction, catalytic activity, and transcription factor activity. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included cell adhesion molecules, ECM–receptor interaction, regulation of actin cytoskeleton, focal adhesion, cell cycle, Hedgehog signaling pathway, phosphatidylinositol signaling system, PI3K-Akt signaling pathway, Apelin signaling pathway, Notch signaling pathway, insulin signaling pathway, and Rap1 signaling pathway. A circRNA–miRNA–mRNA regulatory network was constructed, including DE genes involved in reproduction (e.g., oocyte maturation, oocyte meiosis, and ECM remodeling), such as ccnd2, hecw2, dnm2, irs1, adam12, and cdh13. According to the regulatory network and tissue distribution, we identified one circRNA (Lachesis_group5:6245955|6270787) and three miRNAs (novel_miR_622, novel_miR_980, and novel_miR_64) that may exert regulatory effects in IGF3-induced ovarian maturation in S. argus. Taken together, this study provides a novel insight into the molecular mechanisms by which IGF3 functions in ovaries and highlights the effects of circRNAs and miRNAs in reproduction in S. argus.
Land use as a major factor of riverine nitrate in a semi-arid farming-pastoral ecotone: New insights from multiple environmental tracers and molecular signatures of DOM
Authors: Li Cai , Yue Fu-Jun , Li Si-Liang , Ge Jin-Feng , Chen Sai-Nan , Qi Yulin
Published: November 2022

The nitrogen contamination in rivers has become significant concern in arid and semiarid areas due to water resource shortage and extensive anthropogenic activities in relation to land-use changes in China. As a major nitrogen species, identifying driving factors, transformation and sources of nitrate is crucial for managing nitrogen pollution in rivers. In this study, nitrate sources and transformations were deciphered using physicochemical variables, molecular signature of dissolved organic matter and coupled isotopes of nitrate under different land use types in the Yang River, a typical farming-pastoral ecotone in the semi-arid area of North China. The results of river water showed a significant positive correlation between NO3− concentrations, δ15N-NO3− values and percentage of urban land and cropland, which confirmed the critical role of land use in the variations of riverine nitrate. The correlation between dissolved organic matter composition (aliphatic and lignin-like compounds) and NO3−/Cl− ratios as well as Cl− concentrations verified the effect of agricultural activities on nitrate source and transport. The variation in water chemical variables and dual isotopes of nitrate in river and soil extracts (δ15N-NO3− and δ18O-NO3−) was indicative of the concurrence of in-soil nitrification process and assimilation, whereas denitrification was inhibited under aerobic conditions in the semiarid area. The Bayesian model revealed that about 60% of nitrate was derived from non-point sources (manure, soil organic nitrogen and chemical fertilizer) and 36% from sewage. Although urban is not the major land-use type in the farming-pastoral ecotone, sewage contributed to about 36% of nitrate. The source identification of nitrate stresses the importance of the management of non-point pollution and demand for sewage treatment facilities in the farming-pastoral ecotone. This multiple-tracer approach will help gain deeper insights into nitrogen management in semi-arid areas with extensive human disturbance.
The effects of COVID-19 on the water sector
Authors: Ibrahim Sarah
Published: November 2022

The COVID-19 pandemic affected public health, economy, social life, and the environment. It infected and killed millions of people around the world. Most of the recent literature has focused on the medications to combat this virus, including antivirals and vaccines, but studies about its effect on the environment are still rare, particularly on the water sector. Most of the studies concentrate on the effect of water availability on COVID-19, the effect of the used medications on the water, and the probability of transmission of SARS-CoV-2 through water. Herein, we have summarized the effects of COVID-19 on the water sector from many perspectives. We show different methods to detect the effect of the pandemic on water and also methods to investigate the presence of the virus or its RNA in the water. We also show the different effects of its presence in the wastewater, the probability of transmission, the detection of different variants, and the prediction of new waves. We also show the disadvantages and advantages of the pandemic in the water sector. We finally suggest some recommendations to face this pandemic and the future pandemics for the governments and water policymakers, water treatment plants, general population, and researchers. The aim of this review is to show the different aspects of the pandemic in order to give a general idea about what must be done in order to minimize its effect and any probable pandemic in the future.
Integrating genome-wide association studies and population genomics analysis reveals the genetic architecture of growth and backfat traits in pigs
Authors: Shi Liangyu , Wang Ligang , Fang Lingzhao , Li Mianyan , Tian Jingjing , Wang Lixian , Zhao Fuping
Published: November 2022

Growth and fat deposition are complex traits, which can affect economical income in the pig industry. Due to the intensive artificial selection, a significant genetic improvement has been observed for growth and fat deposition in pigs. Here, we first investigated genomic-wide association studies (GWAS) and population genomics (e.g., selection signature) to explore the genetic basis of such complex traits in two Large White pig lines (n = 3,727) with the GeneSeek GGP Porcine HD array (n = 50,915 SNPs). Ten genetic variants were identified to be associated with growth and fatness traits in two Large White pig lines from different genetic backgrounds by performing both within-population GWAS and cross-population GWAS analyses. These ten significant loci represented eight candidate genes, i.e., NRG4, BATF3, IRS2, ANO1, ANO9, RNF152, KCNQ5, and EYA2. One of them, ANO1 gene was simultaneously identified for both two lines in BF100 trait. Compared to single-population GWAS, cross-population GWAS was less effective for identifying SNPs with population-specific effect, but more powerful for detecting SNPs with population-shared effects. We further detected genomic regions specifically selected in each of two populations, but did not observe a significant enrichment for the heritability of growth and backfat traits in such regions. In summary, the candidate genes will provide an insight into the understanding of the genetic architecture of growth-related traits and backfat thickness, and may have a potential use in the genomic breeding programs in pigs.
Establishment of a CRISPR/Cas9 knockout library for screening type I interferon-inducible antiviral effectors in pig cells
Authors: Dang Wen , Li Tao , Xu Fan , Wang Yannan , Yang Fan , Zheng Haixue
Published: November 2022

Diseases caused by emerging swine viruses had a great economic impact, constituting a new challenge for researchers and practicing veterinarians. Innate immune control of viral pathogen invasion is mediated by interferons (IFNs), resulting in transcriptional elevation of hundreds of IFN-stimulated genes (ISGs). However, the ISG family is vast and species-specific, and despite remarkable advancements in uncovering the breadth of IFN-induced gene expression in mouse and human, it is less characterized with respect to the repertoire of porcine ISGs and their functional annotation. Herein, with the application of RNA-sequencing (RNA-Seq) gene profiling, the breadth of IFN-induced gene expression in the context of type I IFN stimulation was explored by using IBRS-2 cell, a commonly used high-efficient cultivation system for porcine picornaviruses. By establishing inclusion criteria, a total of 359 ISGs were selected. Aiming to identify key effectors mediating type I IFN inhibition of swine viruses, a CRISPR/Cas9 knockout library of 1908 sgRNAs targeting 5’ constitutive exons of 359 ISGs with an average of 5 to 6 sgRNAs per gene was constructed. Using VSV-eGFP (vesicular stomatitis virus, fused with GFP) as a model virus, a subset of highest-ranking candidates were identified, including previously validated anti-VSV genes IRF9, IFITM3, LOC100519082 and REC8, as well as several novel hits. This approach attains a high level of feasibility and reliability, and a high rate of hit identification, providing a forward-looking platform to systematically profile the effectors of type I IFN antiviral response against porcine viruses.
Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay
Authors: Liu Hong , Varvel Stephen , Chen Ge , McConnell Joseph , Caffrey Rebecca , Galdzicka Marzena , Shabahang Shahrokh
Published: November 2022

Introduction

Neutralizing antibodies (NAbs) have been recognized as surrogates of protection against SARS-CoV-2; however, the emergence of variants/subvariants escaping neutralization suggests that laboratory assessments of NAbs against the ancestral/wild type (WT) antigens likely overestimate the degree of protection.

Methods

A novel flow cytometry-based multiplex test system was developed for the simultaneous detection of NAbs of multiple SARS-CoV-2 variants. SARS-CoV-2 antibodies (Abs) including IgG, IgM, IgA isotypes were measured in the same system. Samples from negative, convalesced, vaccinated, boosted, and breakthrough infection (BTI) populations were tested for both NAbs and Abs.

Results

NAbs induced by WT showed neutralization activity that correlated strongly to all variants (R2 > 0.85) except omicron BA.1/BA.2 (R2 <0.50). Two doses of vaccine elicited very little protective immunity against BA.1/BA.2, though a booster dose significantly improved NAbs for all variants. NAbs/Abs increased more following BTI than after a booster, suggesting that hybrid immunity (vaccination + natural immunity) was more robust to all variants including BA.1/BA.2. BTIs occurring in the omicron era led to stronger NAb responses against BA.1/BA.2 than did older BTIs. In all comparisons, the RBD antigens demonstrated greater differences between WT and BA.1/BA.2 than the spike antigens.

Discussion

Taken together, we demonstrated that both Ab and NAb against multiple SARS-CoV-2 variants/subvariants can be reliably detected on the same multiplex platform. Distinguishing NAbs to the appropriate antigenic target of prevalent variants offers the best correlate of protection and aids individual decisions about the appropriateness and cadence of vaccine boosters and other exposure mitigation strategies.
Viruses utilize ubiquitination systems to escape TLR/RLR-mediated innate immunity
Authors: Huang Shanzhi , Cheng Anchun , Wang Mingshu , Yin Zhongqiong , Huang Juan , Jia Renyong
Published: November 2022

When the viruses invade the body, they will be recognized by the host pattern recognition receptors (PRRs) such as Toll like receptor (TLR) or retinoic acid-induced gene-I like receptor (RLR), thus causing the activation of downstream antiviral signals to resist the virus invasion. The cross action between ubiquitination and proteins in these signal cascades enhances the antiviral signal. On the contrary, more and more viruses have also been found to use the ubiquitination system to inhibit TLR/RLR mediated innate immunity. Therefore, this review summarizes how the ubiquitination system plays a regulatory role in TLR/RLR mediated innate immunity, and how viruses use the ubiquitination system to complete immune escape.
Platelet signaling at the nexus of innate immunity and rheumatoid arthritis
Authors: Jiang Steven Z. , To Jeffrey L. , Hughes Michael R. , McNagny Kelly M. , Kim Hugh
Published: November 2022

Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation of the synovial tissues and progressive destruction of bone and cartilage. The inflammatory response and subsequent tissue degradation are orchestrated by complex signaling networks between immune cells and their products in the blood, vascular endothelia and the connective tissue cells residing in the joints. Platelets are recognized as immune-competent cells with an important role in chronic inflammatory diseases such as RA. Here we review the specific aspects of platelet function relevant to arthritic disease, including current knowledge of the molecular crosstalk between platelets and other innate immune cells that modulate RA pathogenesis.
Integrated profiling uncovers prognostic, immunological, and pharmacogenomic features of ferroptosis in triple-negative breast cancer
Authors: Fang Kun , Xu Zhengjie , Jiang Suxiao , Yan Changsheng , Tang Desheng , Huang Yan
Published: November 2022

Objective

Ferroptosis is an iron-dependent type of regulated cell death triggered by the toxic buildup of lipid peroxides on cell membranes. Nonetheless, the implication of ferroptosis in triple‐negative breast cancer (TNBC), which is the most aggressive subtype of breast carcinoma, remains unexplored.

Methods

Three TNBC cohorts—TCGA-TNBC, GSE58812, and METABRIC—were adopted. Consensus molecular subtyping on prognostic ferroptosis-related genes was implemented across TNBC. Ferroptosis classification-relevant genes were selected through weighted co-expression network analysis (WGCNA), and a ferroptosis-relevant scoring system was proposed through the LASSO approach. Prognostic and immunological traits, transcriptional and post-transcriptional modulation, therapeutic response, and prediction of potential small-molecule agents were conducted.

Results

Three disparate ferroptosis patterns were identified across TNBC, with prognostic and immunological traits in each pattern. The ferroptosis-relevant scoring system was proposed, with poorer overall survival in high-risk patients. This risk score was strongly linked to transcriptional and post-transcriptional mechanisms. The high-risk group had a higher response to anti-PD-1 blockade or sunitinib, and the low-risk group had higher sensitivity to cisplatin. High relationships of risk score with immunological features were observed across pan-cancer. Two Cancer Therapeutics Response Portal (CTRP)-derived agents (SNX-2112 and brefeldin A) and PRISM-derived agents (MEK162, PD-0325901, PD-318088, Ro-4987655, and SAR131675) were predicted, which were intended for high-risk patients.

Conclusion

Altogether, our findings unveil prognostic, immunological, and pharmacogenomic features of ferroptosis in TNBC, highlighting the potential clinical utility of ferroptosis in TNBC therapy.
Development of a pressure-retaining separation and transfer system for sediment and overlying seawater
Authors: Guo Jin , Zhou Qixiao , Ge Yongqiang , Li Haonan , Gao Qiaoling , Wang Ying , Lin Yuan , Chen Jiawang
Published: November 2022

Methane leakage at the interface between sediment and overlying seawater is an important basis for gas hydrate exploration. Therefore, a transfer device with working pressure of 30MPa and corresponding scheme are proposed to separate and transfer the sediment and overlying water inside the sampler under the condition of pressure-retaining. Based on the pressure relief valve with adjustable threshold pressure, the device transfers the overlying water by compressing the internal volume and transfers the sediment by secondary sampling. The performance of transfer device is studied by simulation and experiment. Based on the coupled Eulerian-Lagrangian approach in the Abaqus, the secondary sampling was investigated, and the penetration resistance and coring rate of the secondary sampling tube are 141N and 86.2%, respectively. By using the hydraulic simulation software AMESim, the pressure fluctuation caused by the movement of the mechanism during the transfer process was studied, and the pressure fluctuation amplitude is within 0.89 MPa. Furthermore, the laboratory transfer tests were carried out under high pressure conditions, and meantime, the simulation results are verified. Under the working condition of 30MPa, the device can maintain a pressure loss of no more than 8.0% (2.4MPa) within two hours, maintain pressure fluctuations during the transfer process within 4.8% (1.44MPa), and ensure that the pressure in the culture kettle decreases by 4.7% relative to the pressure in the sampler after the transfer, which shows the feasibility of the device application.
A novel approach for fibrous dysplasia assessment using combined planar and quantitative SPECT/CT analysis of Tc-99m-diphosphonate bone scan in correlation with biological bone turnover markers of disease activity
Authors: Jreige Mario , Hall Nicolas , Becce Fabio , Aubry-Rozier Bérengère , Gonzalez Rodriguez Elena , Schaefer Niklaus , Prior John O. , Nicod Lalonde Marie
Published: November 2022

Purpose

To investigate the emerging role of Tc-99m-labeled diphosphonate (Tc-99m-DPD) uptake quantification by SPECT/CT in fibrous dysplasia (FD) bone lesions and its correlation with biological bone turnover markers (BTMs) of disease activity.

Materials and methods

Seven patients (49 ± 16 years) with a confirmed diagnosis of FD were included in this retrospective study. Bone scans with Tc-99m-DPD and quantitative SPECT/CT (xSPECT/CT) were performed. SUVmax (maximum standard unit value) and SUVmean (mean standard unit value) were measured in all FD bone lesions. The skeletal burden score (SBS) was assessed on planar scintigraphy and multiplied by mean SUVmax and SUVmean to generate two new parameters, SBS_SUVmax and SBS_SUVmean, respectively. Planar and xSPECT/CT quantitative measures were correlated with biological BTMs of disease activity, including fibroblast growth factor 23 (FGF-23), alkaline phosphatase (ALP), procollagen 1 intact N-terminal propeptide (P1NP) and C-terminal telopeptide (CTX), as well as scoliosis angle measured on radiographs. Statistical significance was evaluated with Spearman’s correlations.

Results

A total of 76 FD bone lesions were analyzed, showing an average SUVmax and SUVmean (g/mL) of 13 ± 7.3 and 8 ± 4.5, respectively. SBS, SBS_SUVmax and SBS_SUVmean values were 30.8 ± 25.6, 358 ± 267 and 220.1 ± 164.5, respectively. Mean measured values of FGF-23 (pg/mL), ALP (U/L), P1NP (μg/L) and CTX (pg/mL) were 98.4 (22–175), 283.5 (46–735), 283.1 (31–1,161) and 494 (360–609), respectively. Mean scoliosis angle was 15.7 (7–22) degrees. We found a very strong positive correlation between planar-derived SBS and CTX (r = 0.96, p = 0.010), but no significant correlation between SUVmax or SUVmean and biological BTMs. SBS_SUVmax showed a strong to very strong positive correlation with CTX (ρ = 0.99, p = 0.002), FGF-23 (ρ = 0.91, p = 0.010), ALP (ρ = 0.82, p = 0.020), and P1NP (ρ = 0.78, p = 0.039), respectively.

Conclusion

This study showed that biological BTMs are significantly correlated with diphosphonate uptake on bone scan, quantified by a new parameter combining information from both planar and quantitative SPECT/CT. Further analysis of bone scan quantitative SPECT/CT data in a larger patient population might help better characterize the skeletal disease burden in FD, and guide treatment and follow-up.
Evaluation of the use of video consultation in German rheumatology care before and during the COVID-19 pandemic
Authors: Richter Jutta G. , Chehab Gamal , Reiter Joana , Aries Peer , Muehlensiepen Felix , Welcker Martin , Acar Hasan , Voormann Anna , Schneider Matthias , Specker Christof
Published: November 2022

Background

The COVID-19 pandemic led to transformations in healthcare infrastructures and increased use of (innovative) telemedicine (TM) tools. Comparison of the use of video consultation (VC) in rheumatology in the pre-pandemic period and during the pandemic might allow for evaluating this new form of consultancy in healthcare due to changing conditions and possibilities.

Materials and methods

Cross-sectional nationwide online survey among German rheumatologists and rheumatologists in training between March and May 2021 promoted by newsletters and Twitter posts.

Results

Results refer to 205 participants. The majority was male (59%), older than 40 years (90%). Thirty-eight percent stated to have employed TM before (“digital users”), 27% were using VC as part of their TM expertise (“VC-users”), 10% stated to have experience with TM but not VC (“TM-users”). Those negating the use of any TM (62%) were designated as “digital non-users.” TM-Knowledge was self-rated as 4 [median on a Likert Scale 1 (very high) to 6 (very low)] with a significant difference between digital users (VC-user 2.7 ± 1.2, TM-user 3.2 ± 1.1) and digital non-users (4.4 ± 1.3). The reported significant increase of VC use during the lockdown periods and between the lockdowns compared to the pre-pandemic phase was regarded as a proxy for VC acceptance in the pandemic. Reasons for VC non-use were administrative/technical efforts (21%), lack of technical equipment (15%), time constraints (12%), time required for individual VC sessions (12%), inadequate reimbursement (11%), lack of demand from patients (11%), data security concerns (9%), poor internet connection (8%), and lack of scientific evaluation/evidence (5%). Physicians considered the following clinical situations to be particularly suitable for VC: follow-up visits (VC-user 79%, TM-user 62%, digital non-user 47%), emergency consultations (VC-user 20%, TM-user 33%, digital non-user 20%), and patients presenting for the first time (VC-user 11%, TM-user 19%, digital non-user 8%).

Conclusion

Even though the pandemic situation, with social distancing and several lockdowns, provides an ideal environment for the implementation of new remote care forms as VC, its use and acceptance remained comparatively low due to multiple reasons. This analysis may help identify hurdles in employing innovative digital care models for rheumatologic healthcare.
Predictors of use of direct oral anticoagulants in patients with venous thromboembolism: Findings from the Registro Informatizado Enfermedad Tromboembólica registry
Authors: Lorenzo Alicia , Beroiz Patricia , Ortiz Salvador , del Toro Jorge , Mazzolai Lucia , Bura-Riviere Alessandra , Visonà Adriana , Verhamme Peter , Di Micco Pierpaolo , Camporese Giuseppe , Sancho Bueso Teresa , Monreal Manuel ,   the RIETE Investigators
Published: November 2022

Background

Current guidelines recommend the use of direct oral anticoagulants (DOACs) for patients with venous thromboembolism (VTE). However little is known about the use of DOACs in daily practice.

Methods

We used the RIETE registry to identify predictors of use of DOACs for initial and/or long-term therapy of VTE based on patient-related factors, institution-related factors or over time.

Results

Among 41,678 patients from March 2013 to September 2021, 12,286 (29%) used DOACs: for initial therapy 6,456; for long-term therapy 12,046. On multivariable analysis, independent predictors were: age < 65 years (odds ratio [OR]: 1.30; 95% CI: 1.23–1.38), body weight <50 kg (OR: 0.54; 95% CI: 0.45–0.65) or >120 kg (OR: 0.64; 95% CI: 0.53–0.77), initial VTE presentation as pulmonary embolism (OR: 1.18; 95% CI: 1.13–1.25), recent bleeding (OR: 0.53; 95% CI: 0.45–0.63), renal insufficiency (OR: 0.44; 95% CI: 0.38–0.51), liver cirrhosis (OR: 0.32; 95% CI: 0.20–0.52), thrombocytopenia (OR: 0.40; 95% CI: 0.34–0.49), atrial fibrillation (OR: 1.58; 95% CI: 1.42–1.75) and prior VTE (OR: 1.14; 95% CI: 1.06–1.22). The DOACs were more likely used in other European countries (OR: 8.97; 95% CI: 8.49–9.49), America (OR: 6.35; 95% CI: 5.67–7.11) or in other countries of the world (OR: 2.99; 95% CI: 2.70–3.31) than in Spain, and progressively increased from 2013–2015 to 2016–2018 (OR: 2.78; 95% CI: 2.62–2.95) and 2019–2021 (OR: 6.36; 95% CI: 5.95–6.80).

Conclusion

In this large multinational VTE registry, variations were observed in the use of DOACs according to patient or country factors, and over time. The safety, costs, and influence of the DOACs on VTE-related outcomes in daily practice warrant further investigation.
Protozoan co-infections and parasite influence on the efficacy of vaccines against bacterial and viral pathogens
Authors: Akoolo Lavoisier , Rocha Sandra C. , Parveen Nikhat
Published: November 2022

A wide range of protozoan pathogens either transmitted by vectors (Plasmodium, Babesia, Leishmania and Trypanosoma), by contaminated food or water (Entamoeba and Giardia), or by sexual contact (Trichomonas) invade various organs in the body and cause prominent human diseases, such as malaria, babesiosis, leishmaniasis, trypanosomiasis, diarrhea, and trichomoniasis. Humans are frequently exposed to multiple pathogens simultaneously, or sequentially in the high-incidence regions to result in co-infections. Consequently, synergistic or antagonistic pathogenic effects could occur between microbes that also influences overall host responses and severity of diseases. The co-infecting organisms can also follow independent trajectory. In either case, co-infections change host and pathogen metabolic microenvironments, compromise the host immune status, and affect microbial pathogenicity to influence tissue colonization. Immunomodulation by protozoa often adversely affects cellular and humoral immune responses against co-infecting bacterial pathogens and promotes bacterial persistence, and result in more severe disease symptoms. Although co-infections by protozoa and viruses also occur in humans, extensive studies are not yet conducted probably because of limited animal model systems available that can be used for both groups of pathogens. Immunosuppressive effects of protozoan infections can also attenuate vaccines efficacy, weaken immunological memory development, and thus attenuate protection against co-infecting pathogens. Due to increasing occurrence of parasitic infections, roles of acute to chronic protozoan infection on immunological changes need extensive investigations to improve understanding of the mechanistic details of specific immune responses alteration. In fact, this phenomenon should be seriously considered as one cause of breakthrough infections after vaccination against both bacterial and viral pathogens, and for the emergence of drug-resistant bacterial strains. Such studies would facilitate development and implementation of effective vaccination and treatment regimens to prevent or significantly reduce breakthrough infections.
Young MSM changed temporal HIV-1 epidemic pattern in Heilongjiang Province, China
Authors: Li Qing-Hai , Wang Jia-Ye , Liu Si-Yu , Zhang Yun-Qi , Li En-Long , Wang Yi-Ru , Zhang Shu-Lei , Zhao Wen-Bo , Liu Shu-Lin , Chen Xiao-Hong , Wang Fu-Xiang
Published: November 2022

Background

Human immunodeficiency virus type 1 (HIV-1) epidemic in China is featured by geographical diversity of epidemic patterns. Understanding the characteristics of regional HIV-1 epidemic allows carrying out targeted prevention and controlling measures. This seven-year cross-sectional study was conducted in Heilongjiang, one province of Northeast China, where newly diagnosed infection is fast increasing yearly, but temporal HIV-1 epidemic trend is largely unknown.

Methods

Information of 1,006 newly diagnosed HIV-1-infected participants were collected before antiretroviral therapy during 2010–2016 in Heilongjiang province. HIV-1 genotype was identified based on the viral gag and env gene sequences. Recent infection was determined by Limiting-Antigen Avidity assays. Comparison analyses on the median ages, CD4 counts, proportions of stratified age groups and CD4 count groups, and rates of recent HIV-1 infection among different population and sampling times were performed to understand temporal HIV-1 epidemic features.

Results

Homosexual contact among men who have sex with men (MSM) was the main transmission route and CRF01_AE was the most dominant HIV-1 genotype. During 2010–2016, the HIV-1 epidemic showed three new changes: the median age continued to decline, the cases with a CD4 count more than 500 cells/μl (CD4hi cases) disproportionally expanded, and the recent HIV-1 infection rate steadily increased. MSM cases determined the temporal trend of HIV-1 epidemic here. Increase of young MSM cases (aged <30 years) made the main contribution to the younger age trend of MSM cases. These young MSM exhibited a higher median CD4 count, a higher proportion of CD4hi cases, and a higher rate of recent HIV-1 infection than cases aged 30 years and more. MSM infected by CRF01_AE virus mostly affected HIV-1 epidemic patterns among MSM population.

Conclusion

Young MSM have become a new hotspot and vulnerable group for HIV-1 transmission in Heilongjiang Province, Northeast China. The rapid increase in the number of young MSM cases, mainly those with CRF01_AE infection, changed temporal HIV-1 epidemic pattern here. Measures for prevention and control of HIV-1 infection among this population are urgently needed in the future.
Intestinal microbiota analysis and network pharmacology reveal the mechanism by which Lianhua Qingwen capsule improves the immune function of mice infected with influenza A virus
Authors: Xu Ping , Yang Zhu , Du Shuangqiu , Hong Zongyuan , Zhong Shuzhi
Published: November 2022

Objective

Lianhua Qingwen capsule (LHQW) can attenuate lung injury caused by influenza virus infection. However, it is unclear whether the intestinal microbiota plays a role in LHQW activity in ameliorating viral infectious pneumonia. This study aimed to investigate the role of intestinal microbiota in LHQW activity in ameliorating viral infectious pneumonia and its possible mechanisms.

Research design and methods

A mouse model of influenza A viral pneumonia was established by intranasal administration in BALB/c mice. Detection of influenza virus in the lungs, pathological examination of the lungs and small intestine, and biochemical detection of inflammatory indices were performed. The effects of LHQW on intestinal microbiota were evaluated by 16S rRNA gene sequencing. The key components and targets of LHQW were screened via network pharmacology and verified through molecular docking, molecular dynamics simulation, and free binding energy calculations.

Results

Body weight decreased, inflammatory factor levels were disturbed, and the lung and intestinal mucosal barriers were significantly injured in the infected group. The alpha diversity of the intestinal microbiota decreased, and the abundance of Bacteroidetes, Muribaculaceae_unclassified, and Streptococcus decreased significantly. LHQW treatment reduced the viral load in the lungs, rescued body weight and survival, alleviated lung and intestinal mucosal barrier injury, reversed the reduction in the intestinal microbiota alpha diversity, and significantly increased the abundance of Bacteroidetes and Muribaculaceae. Network pharmacological analysis showed that six active herbal medicinal compounds from LHQW could regulate the intestinal microbiota and inhibit the immune-inflammatory response through the Toll-like receptor (TLR) and nuclear factor-κB (NF-κB) signalling pathways in the lungs.

Conclusion

These results suggest that LHQW is effective for treating influenza A virus infectious pneumonia, and the mechanism is associated with the regulation of the TLR4/NF-κB signalling pathway in the lungs by restoring intestinal microbiota and repairing the intestinal wall.
Virulence factors of Mycoplasma synoviae: Three genes influencing colonization, immunogenicity, and transmissibility
Authors: Klose Sara M. , Omotainse Oluwadamilola S. , Zare Sahar , Vaz Paola K. , Armat Parisa , Shil Pollob , Wawegama Nadeeka , Kanci Condello Anna , O'Rourke Denise , Disint Jillian F. , Andrews Daniel M. , Underwood Gregory J. , Morrow Chris J. , Marenda Marc S. , Noormohammadi Amir H.
Published: November 2022

Infections caused by Mycoplasma synoviae are major welfare and economic concerns in poultry industries worldwide. These infections cause chronic respiratory disease and/or synovitis in chickens and turkeys leading to reduced production and increased mortality rates. The live attenuated vaccine strain MS-H (Vaxsafe® MS), commonly used for protection against M. synoviae infection in many countries, contains 32 single nucleotide variations compared to its wildtype parent strain, 86079/7NS. Genomic analysis of vaccine strains reisolated from flocks following the administration of MS-H has identified reversions to the original 86079/7NS sequence in the obgE, oppF and gapdh genes. Here, three MS-H field reisolates containing the 86079/7NS genotype in obgE (AS2), obgE and oppF (AB1), and obgE, oppF and gapdh (TS4), as well as the vaccine MS-H and the parental strain 86079/7NS were experimentally inoculated to chickens. The strains were assessed for their ability to infect and elicit immune responses in the recipient chickens, as well as in naïve in-contact chickens. Despite the loss of temperature sensitivity phenotype and colonization of the reisolates in the lower respiratory tract, there was no significant differences detected in the microscopic mucosal thickness of the middle or lower trachea of the inoculated chickens. Concurrent reversions in ObgE, OppF and GAPDH proteins were associated with higher gross air sac lesion scores and increased microscopic upper-tracheal mucosal thickness in chickens directly inoculated with the reisolates following intratracheal administration of a virulent strain of infectious bronchitis virus. The gross air sac lesions of the chickens in-contact with those inoculated with reisolates were not significantly different to those of chickens in-contact with MS-H inoculated chickens, suggesting that horizontal transmission of the reisolates in the poultry flock will not lead to higher pathogenicity or clinical signs. These results suggest a significant role of GAPDH and/or cumulative effect of ObgE, OppF and GAPDH on M. synoviae pathogenicity. Future experiments will be required to investigate the effect of single mutations in gapdh or oppF gene on pathogenicity of M. synoviae.
Effects of black soldier fly larvae as protein or fat sources on apparent nutrient digestibility, fecal microbiota, and metabolic profiles in beagle dogs
Authors: Jian Shiyan , Zhang Limeng , Ding Ning , Yang Kang , Xin Zhongquan , Hu Minhua , Zhou Zhidong , Zhao Zhihong , Deng Baichuan , Deng Jinping
Published: November 2022

Black soldier fly (Hermetia illucens) larvae (BSFL) act as a biological system converting organic waste into protein and fat with great potential application as pet food. To evaluate the feasibility of BSFL as a protein and fat source, 20 healthy beagle dogs were fed three dietary treatments for 65 days, including (1) a basal diet group (CON group), (2) a basal diet that replaced 20% chicken meal with defatted black soldier fly larvae protein group (DBP group), and (3) a basal diet that replaced 8% mixed oil with black soldier fly larvae fat group (BF group). This study demonstrated that the serum biochemical parameters among the three groups were within the normal range. No difference (p > 0.05) was observed in body weight, body condition score, or antioxidant capacity among the three groups. The mean IFN-γ level in the BF group was lower than that in the CON group, but there was no significant difference (p > 0.05). Compared with the CON group, the DBP group had decreasing (p < 0.05) apparent crude protein and organic matter digestibility. Furthermore, the DBP group had decreasing (p < 0.05) fecal propionate, butyrate, total short-chain fatty acids (SCFAs), isobutyrate, isovalerate, and total branched-chain fatty acids (BCFAs) and increased (p < 0.05) fecal pH. Nevertheless, there was no difference (p > 0.05) in SCFAs or BCFAs between the CON and BF groups. The fecal microbiota revealed that Lachnoclostridium, Clostridioides, Blautia, and Enterococcus were significantly enriched in the DBP group, and Terrisporobacter and Ralstonia were significantly enriched in the BF group. The fecal metabolome showed that the DBP group significantly influenced 18 metabolic pathways. Integrating biological and statistical correlation analysis on differential fecal microbiota and metabolites between the CON and DBP groups found that Lachnoclostridium, Clostridioides, and Enterococcus were positively associated with biotin. In addition, Lachnoclostridium, Clostridioides, Blautia, and Enterococcus were positively associated with niacinamide, phenylalanine acid, fumaric acid, and citrulline and negatively associated with cadavrine, putrescine, saccharopine, and butyrate. In all, 20% DBP restrained the apparent CP and OM digestibility, thereby affecting hindgut microbial metabolism. In contrast, 8% BF in the dog diet showed no adverse effects on body condition, apparent nutrient digestibility, fecal microbiota, or metabolic profiles. Our findings are conducive to opening a new avenue for the exploitation of DBP and BF as protein and fat resources in dog food.
Variational deep embedding-based active learning for the diagnosis of pneumonia
Authors: Huang Jian , Ding Wen , Zhang Jiarun , Li Zhao , Shu Ting , Kuosmanen Pekka , Zhou Guanqun , Zhou Chuan , Yu Gang
Published: November 2022

Machine learning works similar to the way humans train their brains. In general, previous experiences prepared the brain by firing specific nerve cells in the brain and increasing the weight of the links between them. Machine learning also completes the classification task by constantly changing the weights in the model through training on the training set. It can conduct a much more significant amount of training and achieve higher recognition accuracy in specific fields than the human brain. In this paper, we proposed an active learning framework called variational deep embedding-based active learning (VaDEAL) as a human-centric computing method to improve the accuracy of diagnosing pneumonia. Because active learning (AL) realizes label-efficient learning by labeling the most valuable queries, we propose a new AL strategy that incorporates clustering to improve the sampling quality. Our framework consists of a VaDE module, a task learner, and a sampling calculator. First, the VaDE performs unsupervised reduction and clustering of dimension over the entire data set. The end-to-end task learner obtains the embedding representations of the VaDE-processed sample while training the target classifier of the model. The sampling calculator will calculate the representativeness of the samples by VaDE, the uncertainty of the samples through task learning, and ensure the overall diversity of the samples by calculating the similarity constraints between the current and previous samples. With our novel design, the combination of uncertainty, representativeness, and diversity scores allows us to select the most informative samples for labeling, thus improving overall performance. With extensive experiments and evaluations performed on a large dataset, we demonstrate that our proposed method is superior to the state-of-the-art methods and has the highest accuracy in the diagnosis of pneumonia.
Prenatal exposure to antibiotics and risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis
Authors: Tao Qiuji , Shen Yajun , Li Yang , Luo Huan , Yuan Meng , Gan Jing
Published: November 2022

Background and purpose

A growing body of research suggests that inflammation and maternal infections may lead to an increased risk of neurodevelopmental problems such as attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), cerebral palsy (CP), and epilepsy in offspring. The aim of this study was to observe the connection between prenatal antibiotic exposure and the risk of these neurodevelopmental disorders in offspring.

Patients and methods

A comprehensive search was conducted in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Google Scholar, and Scopus databases for observational studies that looked into the link between prenatal exposure to antibiotics and the risk of neurodevelopmental problems in offspring, published from 1 January 1950 to 31 January 2022. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included studies. Data were analyzed using the STATA version 12 software, and an odds ratio (OR) with a 95% confidence interval (CI) was reported.

Results

A total of 15 studies were included in the meta-analysis. Prenatal antibiotic exposure was associated with the increased risk of ADHD (OR = 1.14; 95% CI = 1.13 to 1.15; I2 = 0%) and epilepsy (OR = 1.34; 95% CI = 1.02 to 1.66; I2 = 96.8%). The link between prenatal antibiotic exposure and the risk of ASD [OR = 1.09; 95 % CI = 0.88 to 1.31; I2 = 78.9%] and CP [OR = 0.99; 95% CI = 0.56 to 1.43; I2 = 91%] was found to be non-significant. In all of the included prospective cohort studies, subgroup analysis suggested a significant association between prenatal antibiotic exposure and the incidence of ASD [OR = 1.17; 95% CI = 1.03 to 1.31; I2 = 48.1%] and CP [OR = 1.18; 95% CI = 1.02 to 1.34; I2 = 0%].

Conclusion

Prenatal antibiotic exposure during pregnancy is linked to a higher incidence of ADHD and epilepsy in the offspring. Further prospective studies that compare prenatal antibiotic use and are adjusted for various confounders are needed to further assess the association of prenatal antibiotic exposure and neurological disorders in offspring.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42022306248.