bluuebunny/crossref_metadata_2025 huggingface dataset:
SIRT1 haplo-insufficiency results in reduced cortical bone thickness, increased porosity and decreased estrogen receptor alpha in bone in adult 129/Sv female mice
Authors: Artsi Hanna , Cohen-Kfir Einav , Shahar Ron , Kalish-Achrai Noga , Lishinsky Natan , Dresner-Pollak Rivka
Published: December 2022

Introduction

Sirtuin 1 (SIRT1) is a key player in aging and metabolism and regulates bone mass and architecture. Sexual dimorphism in skeletal effects of SIRT1 has been reported, with an unfavorable phenotype primarily in female mice.

Methods

To investigate the mechanisms of gender differences in SIRT1 skeletal effect, we investigated femoral and vertebral cortical and cancellous bone in global Sirt1 haplo-insufficient 129/Sv mice aged 2,7,12 months lacking Sirt1 exons 5,6,7 (Sirt1+/Δ) and their wild type (WT) counterparts.

Results

In females, femoral bone mineral content, peak cortical thickness, and trabecular bone volume (BV/TV%), number and thickness were significantly lower in Sirt1+/Δ compared to WT mice. Increased femoral cortical porosity was observed in 7-month-old Sirt1+/Δ compared to WT female mice, accompanied by reduced biomechanical strength. No difference in vertebral indices was detected between Sirt1+/Δ and WT female mice. SIRT1 decreased with aging in WT female mice and was lower in vertebrae and femur in 18- and 30- versus 3-month-old 129/Sv and C57BL/6J female mice, respectively. Decreased bone estrogen receptor alpha (ERα) was observed in Sirt1+/Δ compared to WT female mice and was significantly higher in Sirt1 over-expressing C3HT101/2 murine mesenchymal stem cells. In males no difference in femoral indices was detected in Sirt1+/Δ versus WT mice, however vertebral BV/TV%, trabecular number and thickness were higher in Sirt1+/Δ vs. WT mice. No difference in androgen receptor (AR) was detected in bone in Sirt1+/Δ vs. WT male mice. Bone SIRT1 was significantly lower in male compared to female WT mice, suggesting that SIRT1 maybe more significant in female than male skeleton.

Discussion

These findings demonstrate that 50% reduction in SIRT1 is sufficient to induce the hallmarks of skeletal aging namely, decreased cortical thickness and increased porosity in female mice, highlighting the role of SIRT1 as a regulator of cortical bone quantity and quality. The effects of SIRT1 in cortical bone are likely mediated in part by its regulation of ERα. The age-associated decline in bone SIRT1 positions SIRT1 as a potential therapeutic target to ameliorate age-related cortical bone deterioration in females. The crosstalk between ERα, AR and SIRT1 in the bone microenvironment remains to be further investigated.
Diabetic cardiomyopathy: Clinical phenotype and practice
Authors: Zhao Xudong , Liu Shengwang , Wang Xiao , Chen Yibing , Pang Pai , Yang Qianjing , Lin Jingyi , Deng Shuaishuai , Wu Shentao , Fan Guanwei , Wang Bin
Published: December 2022

Diabetic cardiomyopathy (DCM) is a pathophysiological condition of cardiac structure and function changes in diabetic patients without coronary artery disease, hypertension, and other types of heart diseases. DCM is not uncommon in people with diabetes, which increases the risk of heart failure. However, the treatment is scarce, and the prognosis is poor. Since 1972, one clinical study after another on DCM has been conducted. However, the complex phenotype of DCM still has not been fully revealed. This dilemma hinders the pace of understanding the essence of DCM and makes it difficult to carry out penetrating clinical or basic research. This review summarizes the literature on DCM over the last 40 years and discusses the overall perspective of DCM, phase of progression, potential clinical indicators, diagnostic and screening criteria, and related randomized controlled trials to understand DCM better.
Bioinformatics analysis identifies immune-related gene signatures and subtypes in diabetic nephropathy
Authors: Lu Kunna , Wang Li , Fu Yan , Li Guanghong , Zhang Xinhuan , Cao Mingfeng
Published: December 2022

Background

Systemic inflammation and immune response are involved in the pathogenesis of diabetic nephropathy (DN). However, the specific immune-associated signature during DN development is unclear. Our study aimed to reveal the roles of immune-related genes during DN progression.

Methods

The GSE30529 and GSE30528 datasets were acquired from the Gene Expression Omnibus (GEO) database. Then, the intersection between differentially expressed genes (DEGs) and immune score-related genes (ISRGs) was screened. Subsequently, functional enrichment analyses were performed. The different immune phenotype-related subgroups were finally divided using unsupervised clustering. The core genes were identified by WGCNA and the protein-protein interaction (PPI) network. xCell algorithm was applied to assess the proportion of immune cell infiltration.

Results

92 immune score-related DEGs (ISRDEGs) were identified, and these genes were enriched in inflammation- and immune-associated pathways. Furthermore, two distinct immune-associated subgroups (C1 and C2) were identified, and the C1 subgroup exhibited activated immune pathways and a higher percentage of immune cells compared to the C2 subgroup. Two core genes (LCK and HCK) were identified and all up-regulated in DN, and the expressions were verified using GSE30122, GSE142025, and GSE104954 datasets. GSEA indicated the core genes were mainly enriched in immune-related pathways. Correlation analysis indicated LCK and HCK expressions were positively correlated with aDC, CD4+ Tem, CD8+T cells, CD8+ Tem, and mast cells.

Conclusions

We identified two immune-related genes and two immune-associated subgroups, which might help to design more precise tailored immunotherapy for DN patients.
Techno-economic assessment of jet fuel production using the Fischer-Tropsch process from steel mill gas
Authors: Collis Jason , Duch Karsten , Schomäcker Reinhard
Published: December 2022

In order to reduce human-made global warming, the aviation industry is under pressure to reduce greenhouse gas (GHG) emissions. Production of sustainable aviation fuel (SAF) from steel mill gases could help reduce the emissions intensity of jet fuel. This study presents a simulation, techno-economic assessment, and GHG emissions assessment of a Fischer-Tropsch (FT) process using two steel mill gases (coke oven gas and blast furnace gas) as feedstock. The process was analysed both with and without carbon capture and storage (CCS) to reduce process emissions. The minimum viable selling price (MVSP) was determined to be 1,046 €/tonne for the standard scenario and 1,150 €/tonne for the CCS scenario, which is higher than the fossil-fuel-based benchmark (325–1,087 €/tonne since 2020), although similar to the lowest costs found for other SAF benchmarks. The GHG emissions intensity was found to be 49 gCO2-eq./MJ for the standard scenario and 21 gCO2-eq./MJ with CCS, far lower than the 88 gCO2-eq./MJ average for the conventional benchmark and in the mid-lower range of found emissions intensities for other SAF benchmarks. When a CO2 tax of 130 €/tonne is considered, the MVSP for the standard scenario increases to 1,320 €/tonne while the CCS scenario increases to 1,269 €/tonne, making them cost-competitive with the fossil-fuel benchmark (797–1,604 €/tonne). The studied process offers economically viable small-to-medium scale SAF plants (up to 50 kt/y SAF) at a CO2 tax of 190 €/tonne or higher for the CCS scenario and 290 €/tonne or higher for the standard scenario.
Discovering novel reproductive genes in a non-model fly using de novo GridION transcriptomics
Authors: Walter Mrinalini , Puniamoorthy Nalini
Published: December 2022

Gene discovery has important implications for investigating phenotypic trait evolution, adaptation, and speciation. Male reproductive tissues, such as accessory glands (AGs), are hotspots for recruitment of novel genes that diverge rapidly even among closely related species/populations. These genes synthesize seminal fluid proteins that often affect post-copulatory sexual selection—they can mediate male-male sperm competition, ejaculate-female interactions that modify female remating and even influence reproductive incompatibilities among diverging species/populations. Although de novo transcriptomics has facilitated gene discovery in non-model organisms, reproductive gene discovery is still challenging without a reference database as they are often novel and bear no homology to known proteins. Here, we use reference-free GridION long-read transcriptomics, from Oxford Nanopore Technologies (ONT), to discover novel AG genes and characterize their expression in the widespread dung fly, Sepsis punctum. Despite stark population differences in male reproductive traits (e.g.: Body size, testes size, and sperm length) as well as female re-mating, the male AG genes and their secretions of S. punctum are still unknown. We implement a de novo ONT transcriptome pipeline incorporating quality-filtering and rigorous error-correction procedures, and we evaluate gene sequence and gene expression results against high-quality Illumina short-read data. We discover highly-expressed reproductive genes in AG transcriptomes of S. punctum consisting of 40 high-quality and high-confidence ONT genes that cross-verify against Illumina genes, among which 26 are novel and specific to S. punctum. Novel genes account for an average of 81% of total gene expression and may be functionally relevant in seminal fluid protein production. For instance, 80% of genes encoding secretory proteins account for 74% total gene expression. In addition, median sequence similarities of ONT nucleotide and protein sequences match within-Illumina sequence similarities. Read-count based expression quantification in ONT is congruent with Illumina’s Transcript per Million (TPM), both in overall pattern and within functional categories. Rapid genomic innovation followed by recruitment of de novo genes for high expression in S. punctum AG tissue, a pattern observed in other insects, could be a likely mechanism of evolution of these genes. The study also demonstrates the feasibility of adapting ONT transcriptomics for gene discovery in non-model systems.
Characteristics of piRNAs and their comparative profiling in testes of sheep with different fertility
Authors: Di Ran , Zhang Rensen , Mwacharo Joram Mwashigadi , Wang Xiangyu , He Xiaoyun , Liu Yufang , Zhang Jinlong , Gong Yiming , Zhang Xiaosheng , Chu Mingxing
Published: December 2022

As a novel class of small RNAs, piRNAs are highly expressed in the animal gonads and their main known role is to inhibit transposon activity for ensuring the correctness and integrity of genome. In order to explore the characteristics of piRNAs in sheep testis and their possible regulatory roles on male reproduction, deep sequencing technology was used to sequence small RNAs and identify piRNAs in testes of sheep. The length of piRNAs in sheep testes showed a unimodal distribution between 26 and 31 nt, with a peak at 29 nt. These piRNAs exhibited obvious ping-pong signature and strand specificity. In the genome, they were mainly aligned to CDS, intron, repetitive sequence regions and unannotated regions. Furthermore, in transposon analysis, piRNAs were aligned predominantly to LINE, SINE, and LTR types of retrotransposon in sheep testes, and the piRNAs derived from each type showed obvious ping-pong signature. The piRNA clusters identified in sheep testes were mainly distributed on chromosomes 3, 7, 15, 17, 18 and 20. The results combining semen determination with pathway enrichment analysis implied that differentially expressed piRNAs between the testes of rams with different fertility might participate in spermatogenesis by regulating multiple pathways closely related to stabilization of blood-testis barrier and renewal and differentiation of spermatogonial stem cell. Taken together, the study provided new insights into the characteristics, origin and expression patterns of piRNAs in sheep testes tissue, which would help us better understand the role of piRNAs in sheep reproduction.
Accurate determination of causalities in gene regulatory networks by dissecting downstream target genes
Authors: Jia Zhigang , Zhang Xiujun
Published: December 2022

Accurate determination of causalities between genes is a challenge in the inference of gene regulatory networks (GRNs) from the gene expression profile. Although many methods have been developed for the reconstruction of GRNs, most of them are insufficient in determining causalities or regulatory directions. In this work, we present a novel method, namely, DDTG, to improve the accuracy of causality determination in GRN inference by dissecting downstream target genes. In the proposed method, the topology and hierarchy of GRNs are determined by mutual information and conditional mutual information, and the regulatory directions of GRNs are determined by Taylor formula-based regression. In addition, indirect interactions are removed with the sparseness of the network topology to improve the accuracy of network inference. The method is validated on the benchmark GRNs from DREAM3 and DREAM4 challenges. The results demonstrate the superior performance of the DDTG method on causality determination of GRNs compared to some popular GRN inference methods. This work provides a useful tool to infer the causal gene regulatory network.
Different local, innate and adaptive immune responses are induced by two commercial Mycoplasma hyopneumoniae bacterins and an adjuvant alone
Authors: Beuckelaere Lisa , Haspeslagh Maarten , Biebaut Evelien , Boyen Filip , Haesebrouck Freddy , Krejci Roman , Meyer Evelyne , Gleerup David , De Spiegelaere Ward , Devriendt Bert , Maes Dominiek
Published: December 2022

Introduction

Enzootic pneumonia still causes major economic losses to the intensive pig production. Vaccination against its primary pathogen, Mycoplasma hyopneumoniae, is carried out worldwide to control the disease and minimize clinical signs and performance losses. Nonetheless, the effects of both infection with, and vaccination against Mycoplasma hyopneumoniae on the innate and adaptive immune responses remain largely unknown. Therefore, we conducted a study in which piglets were injected once with a commercial bacterin V1 or V2, or the adjuvant of V1 (A) to investigate their effect on local, innate and adaptive immune responses.

Methods

Three weeks after vaccination, piglets were challenge infected with M. hyopneumoniae and euthanized four weeks later to assess vaccine efficacy via macroscopic and microscopic evaluation of lung lesions. Blood and broncho-alveolar lavage fluid (BAL) samples were collected to measure antibody responses, cellular immunity, BAL cytokine levels and BAL M. hyopneumoniae DNA load as well as cytokine secretion by monocytes.

Results

After vaccination, proliferation of antigen-specific CD3+ T cells and a higher percentage of TNF-α+ CD8+, and TNF-α+ and TNF-α+IFN-γ+ CD4+CD8+ T cells was seen in V1, while proliferation of or a significant increase in cytokine production by different T cell subsets could not be observed for animals from V2. Interestingly, LPS-stimulated blood monocytes from V1 and A secreted less IL-10 on D7. After challenge, higher levels of IgA, more IL-10 and less IL-1β was detected in BAL from V1, which was not observed in V2. Animals from A had significantly more IL-17A in BAL. The macroscopic lung lesion score and the M. hyopneumoniae DNA load at euthanasia was lower in V1, but the microscopic lung lesion score was lower in both vaccinated groups.

Discussion

In conclusion, these results indicate that the two commercial bacterins induced different local and adaptive immune responses, that the adjuvant alone can reduce anti-inflammatory innate immune responses, and that both vaccines had a different efficacy to reduce Mycoplasma-like lung lesions and M. hyopneumoniae DNA load in the lung.
Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers
Authors: Martin-Gayo Enrique , Gao Ce , Calvet-Mirabent Marta , Ouyang Zhengyu , Lichterfeld Mathias , Yu Xu G.
Published: December 2022

Introduction

Spontaneous control of HIV-1 replication in the absence of anti-retroviral therapy (ART) naturally occurs in a small proportion of HIV-1-infected individuals known as elite controllers (EC), likely as a result of improved innate and adaptive immune mechanisms. Previous studies suggest that enhanced cytosolic immune recognition of HIV-1 reverse transcripts in conventional dendritic cells (mDC) from EC enables effective induction of antiviral effector T cell responses. However, the specific molecular circuits responsible for such improved innate recognition of HIV-1 in mDC from these individuals remain unknown.

Results and methods

Here, we identified a subpopulation of EC whose mDC displayed higher baseline abilities to respond to intracellular HIV-1 dsDNA stimulation. A computational analysis of transcriptional signatures from such high responder EC, combined with functional studies, suggested cytosolic recognition of HIV-1 dsDNA by cGAS, combined with sensing of viral mRNA by RIG-I after polymerase III-mediated HIV-1 DNA transcription.

Discussion

Together, our work identifies collaborative networks of innate sensing pathways that enhance cell-intrinsic abilities of mDC to induce antiviral innate responses against HIV-1; these observations might be useful for the therapeutic induction of effective antiviral immune responses.
Dengue induces iNOS expression and nitric oxide synthesis in platelets through IL-1R
Authors: Pinheiro Mariana Brandi Mendonça , Rozini Stephane Vicente , Quirino-Teixeira Anna Cecíllia , Barbosa-Lima Giselle , Lopes Juliana F. , Sacramento Carolina Q. , Bozza Fernando A. , Bozza Patrícia T. , Hottz Eugenio D.
Published: December 2022

Introduction

Dengue is an arthropod-born disease caused by dengue virus (DENV), that may manifest as a mild illness or severe form, characterized by hemorrhagic fever and shock. Nitric oxide (NO) is a vasodilator signaling molecule and an inhibitor of platelet aggregation known to be increased in platelets from dengue patients. However, the mechanisms underlying NO synthesis by platelets during dengue are not yet elucidated. IL-1β is a pro-inflammatory cytokine able to induce iNOS expression in leukocytes and present in dengue patients at high levels. Nevertheless, the role of IL-1β in platelet activation, especially regarding iNOS expression, are not clear.

Methods

We prospectively followed a cohort of 28 dengue-infected patients to study NO synthesis in platelets and its relationship with disease outcomes. We used in vitro infection and stimulation models to gain insights on the mechanisms.

Results and Discussion

We confirmed that platelets from dengue patients express iNOS and produce higher levels of NO during the acute phase compared to healthy volunteers, returning to normal levels after recovery. Platelet NO production during acute dengue infection was associated with the presence of warning signs, hypoalbuminemia and hemorrhagic manifestations, suggesting a role in dengue pathophysiology. By investigating the mechanisms, we evidenced increased iNOS expression in platelets stimulated with dengue patients´ plasma, indicating induction by circulating inflammatory mediators. We then investigated possible factors able to induce platelet iNOS expression and observed higher levels of IL-1β in plasma from patients with dengue, which were correlated with NO production by platelets. Since platelets can synthesize and respond to IL-1β, we investigated whether IL-1β induces iNOS expression and NO synthesis in platelets. We observed that recombinant human IL-1β enhanced iNOS expression and dose-dependently increased NO synthesis by platelets. Finally, platelet infection with DENV in vitro induced iNOS expression and NO production, besides the secretion of both IL-1α and IL-1β. Importantly, treatment with IL-1 receptor antagonist or a combination of anti-IL-1α and anti-IL-1β antibodies prevented DENV-induced iNOS expression and NO synthesis. Our data show that DENV induces iNOS expression and NO production in platelets through mechanisms depending on IL-1 receptor signaling.
Circulatory levels of alarmins in patients with non-segmental vitiligo: Potential biomarkers for disease diagnosis and activity/severity assessment
Authors: He Kaiqiao , Wu Wei , Wang Xinju , Dai Wei , Wang Sijia , Li Chunying , Li Shuli
Published: December 2022

Background

Non-segmental vitiligo (NSV) is an autoimmune skin disorder that is difficult to determine disease activity/severity and thus to treat. Alarmins have emerged as promising biomarkers in various diseases, so further confirmation of their potential roles in NSV would be of considerable value. With the present work, we aimed to determine the serum levels of alarmins in patients with NSV, correlate these alarmins with disease activity and severity, and analyze the predictive value of the combination of these markers.

Methods

104 NSV patients and 56 healthy controls were enrolled at the Xijing Hospital of Fourth Military Medical University between September 1, 2018, and June 30, 2019. The serum levels of alarmins (including IL-33, IL-1α, S100A9, S100A12, S100B, and HMGB1) were measured with enzyme-linked immunosorbent assays. The predictive performance of these biomarkers was evaluated with the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and other representative statistics.

Results

A total of 104 patients with NSV (mean [SD] age, 34.2 [13.0] years; 62 [59.6%] male) and 56 healthy controls (mean [SD] age, 34.8 [13.5] years; 34 [60.7%] male) were enrolled. For vitiligo diagnosis, S100B had the highest sensitivity (92.31%), whereas HMGB1 had the highest specificity (85.71%); the combination of IL-1α, S100B, S100A9, and HMGB1 increased the AUC value to 0.925, with a sensitivity of 87.50% and a specificity of 85.71%. Multivariate logistic regression analysis showed S100B (OR, 1.019; 95% CI, 1.002-1.038; P =0.03), S100A9 (OR, 1.002; 95% CI, 1.001-1.003; P<0.001), and HMGB1 (OR, 1.915; 95% CI, 1.186-3.091; P =0.008) were significantly associated with vitiligo activity. S100A9 had the highest accuracy in discriminating patients at the active stage from the stable stage, with an AUC value of 0.827. The combination of these alarmins had an AUC value of 0.860 to assess disease activity, with a sensitivity of 90.00% and a specificity of 72.97%. Furthermore, S100B (r=0.61, P <0.001), S100A9 (r=0.33, P <0.001), and HMGB1 (r = 0.51, P <0.001) levels were positively correlated with the affected body surface area (BSA) in NSV patients.

Conclusions

Serum S100B, S100A9, and HMGB1 might be biomarkers for diagnosing and assessing the activity/severity of NSV, either used alone or in combination.
Impacts of short-term feeding by spotted lanternfly (Lycorma delicatula) on ecophysiology of young hardwood trees in a common garden
Authors: Lavely Emily , Iavorivska Lidiia , Uyi Osariyekemwen , Eissenstat David M. , Walsh Brian , Primka Edward J. , Harper Jeremy , Hoover Kelli
Published: December 2022

Spotted lanternfly (SLF; Lycorma delicatula White; Hemiptera: Fulgoridae) invaded the US from Asia and was first detected in 2014; currently, populations have established in 14 states primarily in the Northeast and Mid-Atlantic. It feeds voraciously on phloem sap from a broad range of host plants, with a preference for tree of heaven (Ailanthus altissima [Sapindales: Simaroubaceae]), grapevines (Vitis spp. [Vitales: Vitaceae]), and several common hardwood tree species. We evaluated the impacts of fourth instars and adults confined to a single branch or whole trees on gas exchange attributes (carbon assimilation [photosynthetic rate], transpiration and stomatal conductance), selected nutrients, and diameter growth using young saplings of four host tree species planted in a common garden. In general, the effects of adults on trees were greater than nymphs, although there was variation depending on tree species, pest density, and time post-infestation. Nymphs on a single branch of red maple (Acer rubrum [Sapindales: Sapindaceae]), or silver maple (Acer saccharinum [Sapindales: Sapindaceae]) at three densities (0, 15, or 30) had no significant effects on gas exchange. In contrast, 40 adults confined to a single branch of red or silver maple rapidly suppressed gas exchange and reduced nitrogen concentration in leaves; soluble sugars in branch wood were reduced in the fall for silver maple and in the following spring for red maple. Fourth instars confined to whole silver maple trees reduced soluble sugars in leaves and branch wood, and reduced tree diameter growth by >50% during the next growing season. In contrast, fourth instars in whole tree enclosures had no effects on black walnut (Juglans nigra [Fagales: Juglandaceae]). SLF enclosed on tree of heaven at 80 adults per tree suppressed gas exchange after two weeks of feeding, but did not alter non-structural carbohydrates, nitrogen concentrations, or tree growth. Results suggest that moderate to heavy feeding by SLF on young maple saplings may impair tree growth, which could have implications for production nurseries and forest managers.
Inequalities in glycemic and multifactorial cardiovascular control of type 2 diabetes: The Heart Healthy Hoods study
Authors: Ares-Blanco Sara , Polentinos-Castro Elena , Rodríguez-Cabrera Francisco , Gullón Pedro , Franco Manuel , del Cura-González Isabel
Published: December 2022

Aim

This study aimed to analyze glycemic control and multifactorial cardiovascular control targets in people with type 2 diabetes (T2DM) in primary care according to sex and socioeconomic status (SES).

Materials and methods

This is an observational, cross-sectional, and multicenter study. We analyzed all the patients with T2DMM aged between 40 and 75 years in Madrid city (113,265) through electronic health records from 01 August 2017 to 31 July 2018. SES was defined by an area-level socioeconomic index stratified by quintiles (1st quintile: more affluent).

Outcomes

Outcomes included glycemic control (HbA1c ≤ 7%), 3-factor cardiovascular control [HbA1c ≤ 7%, blood pressure (BP), < 140/90 mmHg, LDL < 100 mg/ml] and 4-factor control [HbA1c ≤ 7%, blood pressure (BP) < 140/90 mmHg, LDL < 100 mg/ml, and BMI < 30 kg/m2]. Multilevel logistic regression models analyzed factors associated with suboptimal glycemic control.

Results

In total 43.2% were women. Glycemic control was achieved by 63% of patients (women: 64.2% vs. men: 62.4%). Being more deprived was associated with suboptimal glycemic control (OR: 1.20, 95% CI: 1.10–1.32); however, sex was not related (OR: 0.97, 95% CI: 0.94–1.01). The optimal 3-factor control target was reached by 10.3% of patients (women: 9.3% vs. men: 11.2%), especially those in the 5th quintile of SES. The 4-factor control was achieved by 6.6% of the sample. In the 3-factor control target, being women was related to the suboptimal 3-factor control target (OR: 1.26, 95% CI: 1.19– 1.34) but only belonging to SES 4th quintile was related to the unachieved target (OR: 1.47, 95% CI: 1.04–2.07).

Conclusion

Suboptimal glycemic control was associated with being less affluent and suboptimal 3-factor control target was associated with being women.
The interplay between the gut microbiota and metabolism during the third trimester of pregnancy
Authors: Liang Xinyuan , Wang Rongning , Luo Huijuan , Liao Yihong , Chen Xiaowen , Xiao Xiaomin , Li Liping
Published: December 2022

The gut microbiota undergoes dynamic changes during pregnancy. The gut microbial and metabolic networks observed in pregnant women have not been systematically analyzed. The primary purpose of this study was to explore the alterations in the gut microbiota and metabolism during late pregnancy and investigate the associations between the gut microbiota and metabolism. A total of thirty healthy pregnant women were followed from 30 to 32 weeks of gestation to full term. Fecal samples were collected for microbiome analysis and untargeted metabolomic analysis. The characteristics of the gut microbiota were evaluated by 16S ribosomal RNA gene sequencing of the V3-V4 regions. The plasma samples were used for untargeted metabolomic analysis with liquid chromatography–tandem mass spectrometry. The interplay between the gut microbiota and metabolism was analyzed further by bioinformatics approaches. We found that the relative abundances of Sellimonas and Megamonas were higher at full term, whereas that of Proteobacteria was lower. The correlation network of the gut microbiota tended to exhibit weaker connections from 32 weeks of gestation to the antepartum timepoint. Changes in the gut microbiota during late pregnancy were correlated with the absorbance and metabolism of microbiota-associated metabolites, such as fatty acids and free amino acids, thereby generating a unique metabolic system for the growth of the fetus. Decreasing the concentration of specific metabolites in plasma and increasing the levels of palmitic acid and 20-hydroxyarachidonic acid may enhance the transformation of a proinflammatory immune state as pregnancy progresses.
Effects of nonsocial and circumscribed interest images on neural mechanisms of emotion regulation in autistic adults
Authors: Antezana Ligia , Coffman Marika C. , DiCriscio Antoinette Sabatino , Richey John A.
Published: December 2022

Introduction

Emotion dysregulation is commonly reported among autistic individuals. Prior work investigating the neurofunctional mechanisms of emotion regulation (ER) in autistic adults has illustrated alterations in dorsolateral prefrontal cortex (dlPFC) activity, as well as concurrent atypical patterns of activation in subcortical regions related to affect during cognitive reappraisal of social images. Whereas most research examining ER in autism has focused on regulation of negative emotions, the effects of regulating positive emotions has been generally understudied. This is surprising given the relevance of positive motivational states to understanding circumscribed interests (CI) in autism.

Methods

Accordingly, the purpose of this study was to use fMRI with simultaneous eye-tracking and pupillometry to investigate the neural mechanisms of ER during passive viewing and cognitive reappraisal of a standardized set of nonsocial images and personalized (self-selected) CI images.

Results

The autistic group demonstrated comparatively reduced modulation of posterior cingulate cortex (PCC) activation during cognitive reappraisal of CI images compared to viewing of CI, although no eye-tracking/pupillometry differences emerged between-groups. Further, the autistic group demonstrated increased PCC connectivity with left lateral occipital and right supramarginal areas when engaging in cognitive reappraisal vs. viewing CI.

Discussion

In autistic adults, CI may be differentially modulated via PCC. Considering the documented role of the PCC as a core hub of the default mode network, we further postulate that ER of CI could potentially be related to self-referential cognition.
Automatic detection of abnormal hand gestures in patients with radial, ulnar, or median nerve injury using hand pose estimation
Authors: Gu Fanbin , Fan Jingyuan , Cai Chengfeng , Wang Zhaoyang , Liu Xiaolin , Yang Jiantao , Zhu Qingtang
Published: December 2022

Background

Radial, ulnar, or median nerve injuries are common peripheral nerve injuries. They usually present specific abnormal signs on the hands as evidence for hand surgeons to diagnose. However, without specialized knowledge, it is difficult for primary healthcare providers to recognize the clinical meaning and the potential nerve injuries through the abnormalities, often leading to misdiagnosis. Developing technologies for automatically detecting abnormal hand gestures would assist general medical service practitioners with an early diagnosis and treatment.

Methods

Based on expert experience, we selected three hand gestures with predetermined features and rules as three independent binary classification tasks for abnormal gesture detection. Images from patients with unilateral radial, ulnar, or median nerve injuries and healthy volunteers were obtained using a smartphone. The landmark coordinates were extracted using Google MediaPipe Hands to calculate the features. The receiver operating characteristic curve was employed for feature selection. We compared the performance of rule-based models with logistic regression, support vector machine and of random forest machine learning models by evaluating the accuracy, sensitivity, and specificity.

Results

The study included 1,344 images, twenty-two patients, and thirty-four volunteers. In rule-based models, eight features were finally selected. The accuracy, sensitivity, and specificity were (1) 98.2, 91.7, and 99.0% for radial nerve injury detection; (2) 97.3, 83.3, and 99.0% for ulnar nerve injury detection; and (3) 96.4, 87.5, and 97.1% for median nerve injury detection, respectively. All machine learning models had accuracy above 95% and sensitivity ranging from 37.5 to 100%.

Conclusion

Our study provides a helpful tool for detecting abnormal gestures in radial, ulnar, or median nerve injuries with satisfying accuracy, sensitivity, and specificity. It confirms that hand pose estimation could automatically analyze and detect the abnormalities from images of these patients. It has the potential to be a simple and convenient screening method for primary healthcare and telemedicine application.
Investigating neurological symptoms of infectious diseases like COVID-19 leading to a deeper understanding of neurodegenerative disorders such as Parkinson's disease
Authors: Zhang Jing
Published: December 2022

Apart from common respiratory symptoms, neurological symptoms are prevalent among patients with COVID-19. Research has shown that infection with SARS-CoV-2 accelerated alpha-synuclein aggregation, induced Lewy-body-like pathology, caused dopaminergic neuron senescence, and worsened symptoms in patients with Parkinson's disease (PD). In addition, SARS-CoV-2 infection can induce neuroinflammation and facilitate subsequent neurodegeneration in long COVID, and increase individual vulnerability to PD or parkinsonism. These findings suggest that a post-COVID-19 parkinsonism might follow the COVID-19 pandemic. In order to prevent a possible post-COVID-19 parkinsonism, this paper reviewed neurological symptoms and related findings of COVID-19 and related infectious diseases (influenza and prion disease) and neurodegenerative disorders (Alzheimer's disease, PD and amyotrophic lateral sclerosis), and discussed potential mechanisms underlying the neurological symptoms and the relationship between the infectious diseases and the neurodegenerative disorders, as well as the therapeutic and preventive implications in the neurodegenerative disorders. Infections with a relay of microbes (SARS-CoV-2, influenza A viruses, gut bacteria, etc.) and prion-like alpha-synuclein proteins over time may synergize to induce PD. Therefore, a systematic approach that targets these pathogens and the pathogen-induced neuroinflammation and neurodegeneration may provide cures for neurodegenerative disorders. Further, antiviral/antimicrobial drugs, vaccines, immunotherapies and new therapies (e.g., stem cell therapy) need to work together to treat, manage or prevent these disorders. As medical science and technology advances, it is anticipated that better vaccines for SARS-CoV-2 variants, new antiviral/antimicrobial drugs, effective immunotherapies (alpha-synuclein antibodies, vaccines for PD or parkinsonism, etc.), as well as new therapies will be developed and made available in the near future, which will help prevent a possible post-COVID-19 parkinsonism in the 21st century.
The establishment of the general microexpression recognition ability and its relevant brain activity
Authors: Zhang Jianxin , Yin Ming , Shu Deming , Liu Dianzhi
Published: December 2022

Microexpressions are very transitory expressions lasting about 1/25∼1/2 s, which can reveal people’s true emotions they try to hide or suppress. The PREMERT (pseudorandom ecological microexpression recognition test) could test the individual’s microexpression recognition ability with six microexpression Ms (the mean of accuracy rates of a microexpression type under six expression backgrounds), and six microexpression SDs (the standard deviation of accuracy rates of this microexpression type under six expression backgrounds), but it and other studies did not explore the general microexpression recognition ability (the GMERA) or could not test the GMERA effectively. Therefore, the current study put forward and established the GMERA with the behavioral data of the PREMERT. The spontaneous brain activity in the resting state is a stable index to measure individual cognitive characteristics. Therefore, the current study explored the relevant resting-state brain activity of the GMERA indicators to prove that GMERA is an individual cognitive characteristic from brain mechanisms with the neuroimaging data of the PREMERT. The results showed that (1) there was a three-layer hierarchical structure in human microexpression recognition ability: The GMERA (the highest layer); recognition of a type of microexpression under different expression backgrounds (the second layer); and recognition of a certain microexpression under a certain expression background (the third layer). A common factor GMERA was extracted from the six microexpression types recognition in PREMERT. Four indicators of the GMERA were calculated from six microexpression Ms and six microexpression SDs, such as GMERAL (level of GMERA), GMERAF (fluctuation of GMERA), GMERAB (background effect of GMERA), and GMERABF (fluctuation of GMERAB), which had good parallel-forms reliability, calibration validity, and ecological validity. The GMERA provided a concise and comprehensive overview of the individual’s microexpression recognition ability. The PREMERT was proved as a good test to measure the GMERA. (2) ALFFs (the amplitude of low-frequency fluctuations) in both eyes-closed and eyes-opened resting-states and ALFFs-difference could predict the four indicators of the GMERA. The relevant resting-state brain areas were some areas of the expression recognition network, the microexpression consciousness and attention network, and the motor network for the change from expression backgrounds to microexpression. (3) The relevant brain areas of the GMERA and different types of microexpression recognition belonged to the three cognitive processes, but the relevant brain areas of the GMERA were the “higher-order” areas to be more concise and critical than those of different types of microexpression recognition.
Task-based functional MRI challenges in clinical neuroscience: Choice of the best head motion correction approach in multiple sclerosis
Authors: Soares Júlia F. , Abreu Rodolfo , Lima Ana Cláudia , Sousa Lívia , Batista Sónia , Castelo-Branco Miguel , Duarte João Valente
Published: December 2022

Introduction

Functional MRI (fMRI) is commonly used for understanding brain organization and connectivity abnormalities in neurological conditions, and in particular in multiple sclerosis (MS). However, head motion degrades fMRI data quality and influences all image-derived metrics. Persistent controversies regarding the best correction strategy motivates a systematic comparison, including methods such as scrubbing and volume interpolation, to find optimal correction models, particularly in studies with clinical populations prone to characterize by high motion. Moreover, strategies for correction of motion effects gain more relevance in task-based designs, which are less explored compared to resting-state, have usually lower sample sizes, and may have a crucial role in describing the functioning of the brain and highlighting specific connectivity changes.

Methods

We acquired fMRI data from 17 early MS patients and 14 matched healthy controls (HC) during performance of a visual task, characterized motion in both groups, and quantitatively compared the most used and easy to implement methods for correction of motion effects. We compared task-activation metrics obtained from: (i) models containing 6 or 24 motion parameters (MPs) as nuisance regressors; (ii) models containing nuisance regressors for 6 or 24 MPs and motion outliers (scrubbing) detected with Framewise Displacement or Derivative or root mean square VARiance over voxelS; and (iii) models with 6 or 24 MPs and motion outliers corrected through volume interpolation. To our knowledge, volume interpolation has not been systematically compared with scrubbing, nor investigated in task fMRI clinical studies in MS.

Results

No differences in motion were found between groups, suggesting that recently diagnosed MS patients may not present problematic motion. In general, models with 6 MPs perform better than models with 24 MPs, suggesting the 6 MPs as the best trade-off between correction of motion effects and preservation of valuable information. Parsimonious models with 6 MPs and volume interpolation were the best combination for correcting motion in both groups, surpassing the scrubbing methods. A joint analysis regardless of the group further highlighted the value of volume interpolation.

Discussion

Volume interpolation of motion outliers is an easy to implement technique, which may be an alternative to other methods and may improve the accuracy of fMRI analyses, crucially in clinical studies in MS and other neurological populations.
Interaural speech asymmetry predicts bilateral speech intelligibility but not listening effort in adults with bilateral cochlear implants
Authors: Burg Emily A. , Thakkar Tanvi D. , Litovsky Ruth Y.
Published: December 2022

Introduction

Bilateral cochlear implants (BiCIs) can facilitate improved speech intelligibility in noise and sound localization abilities compared to a unilateral implant in individuals with bilateral severe to profound hearing loss. Still, many individuals with BiCIs do not benefit from binaural hearing to the same extent that normal hearing (NH) listeners do. For example, binaural redundancy, a speech intelligibility benefit derived from having access to duplicate copies of a signal, is highly variable among BiCI users. Additionally, patients with hearing loss commonly report elevated listening effort compared to NH listeners. There is some evidence to suggest that BiCIs may reduce listening effort compared to a unilateral CI, but the limited existing literature has not shown this consistently. Critically, no studies to date have investigated this question using pupillometry to quantify listening effort, where large pupil sizes indicate high effort and small pupil sizes indicate low effort. Thus, the present study aimed to build on existing literature by investigating the potential benefits of BiCIs for both speech intelligibility and listening effort.

Methods

Twelve BiCI adults were tested in three listening conditions: Better Ear, Poorer Ear, and Bilateral. Stimuli were IEEE sentences presented from a loudspeaker at 0° azimuth in quiet. Participants were asked to repeat back the sentences, and responses were scored by an experimenter while changes in pupil dilation were measured.

Results

On average, participants demonstrated similar speech intelligibility in the Better Ear and Bilateral conditions, and significantly worse speech intelligibility in the Poorer Ear condition. Despite similar speech intelligibility in the Better Ear and Bilateral conditions, pupil dilation was significantly larger in the Bilateral condition.

Discussion

These results suggest that the BiCI users tested in this study did not demonstrate binaural redundancy in quiet. The large interaural speech asymmetries demonstrated by participants may have precluded them from obtaining binaural redundancy, as shown by the inverse relationship between the two variables. Further, participants did not obtain a release from effort when listening with two ears versus their better ear only. Instead, results indicate that bilateral listening elicited increased effort compared to better ear listening, which may be due to poor integration of asymmetric inputs.
Characteristic cerebral perfusion pattern in neuronal intranuclear inclusion disease
Authors: Tai Hong-Fei , Hua Tian-Tian , Zhang Zai-Qiang , Duan Yun-Yun , Zhuo Zhi-Zheng , Wang An , Zhou Yi , Liu Shao-Cheng , Lv Shan
Published: December 2022

Background

Neuronal intranuclear inclusion disease (NIID), which pathogenesis remains largely unclear, is a neurodegenerative disease caused by GGC repeat expansion in NOTCH2NLC gene. As case studies have reported dynamic cortical perfusion changes in NIID, this study aimed to explore the cerebral perfusion pattern in NIID patients.

Materials and methods

A total of 38 NIID patients and 34 healthy controls (HCs) were recruited, and 2 NIID patients who had had episodic symptoms within 2 months were excluded. Data on demographic characteristics and clinical features were collected. All participants underwent three-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging (MRI) scanning. Voxel-based comparisons of cerebral blood flow (CBF) were conducted.

Results

NIID patients showed decreased perfusion in the cortex but increased perfusion in the deep brain regions compared with HCs. The regions with significant hypoperfusion were distributed in the bilateral frontal, temporal, parietal, and occipital gyri, with the left frontal gyrus being the most prominent. The regions with significant hyperperfusion included the bilateral basal ganglia, midbrain, pons, para-hippocampal, and parts of the bilateral cerebellum, fusiform, lingual, rectus, orbital, and cingulum anterior gyri, which were adjacent to the midline (all FDR-corrected p <0.05). When comparing the mean CBF value of the whole brain, no significant differences were observed between NIID patients and HCs (28.81 ± 10.1 vs. 27.99 ± 5.68 ml/100 g*min, p = 0.666). Voxel-based analysis showed no significant difference in cerebral perfusion between NIID patients with and without episodic symptoms. The perfusion within the bilateral middle frontal and anterior cingulate gyri showed positive correlations with MMSE and MoCA scores using age, sex, and education as covariates (p <0.005 uncorrected).

Conclusion

NIID patients exhibited characteristic cortical hypoperfusion and deep brain hyperperfusion. The perfusion in the bilateral frontal lobe and cingulate gyrus was correlated with the severity of cognitive dysfunction. Cerebral perfusion change may be involved in NIID pathophysiology and serve as a potential indicator for monitoring NIID severity and progression.
Protective effects and potential mechanisms of fermented egg-milk peptides on the damaged intestinal barrier
Authors: Lyu Siwen , Yang Qi , Duan Xuehui , Liu Xuanting , Du Zhiyang , Shang Xiaomin , Xu Menglei , Liu Jingbo , Pan Fengguang , Zhang Ting
Published: December 2022

Introduction

Fermented egg-milk peptides (FEMPs) could enhance the colon-intestinal barrier and upgrade the expression of zonula occludens-1 and mucin 2. Besides, the underlying biological mechanism and the targets FEMPs could regulate were analyzed in our study.

Methods

Herein, the immunofluorescence technique and western blot were utilized to evaluate the repair of the intestinal barrier. Network pharmacology analysis and bioinformatics methods were performed to investigate the targets and pathways affected by FEMPs.

Results and discussion

Animal experiments showed that FEMPs could restore intestinal damage and enhance the expression of two key proteins. The pharmacological results revealed that FEMPs could regulate targets related to kinase activity, such as AKT, CASP, RAF, and GSK. The above targets could interact with each other. GO analysis indicated that the targets regulated by FEMPs could participate in the kinase activity of the metabolic process. KEGG enrichment revealed that the core targets were enriched in pathways related to cell apoptosis and other important procedures. Molecular docking demonstrated that FEMPs could bind to the key target AKT via hydrogen bond interactions. Our study combined the experiment in vivo with the method in silico and investigated the interaction between peptides and targets in a pattern of multi-targets and multi-pathways, which offered a new perspective on the functional validation and potential application of bioactive peptides.