bluuebunny/crossref_metadata_2025 huggingface dataset:
PHACTR1, a coronary artery disease risk gene, mediates endothelial dysfunction
Authors: Ma Xiaoxuan , Su Meiming , He Qingze , Zhang Zhidan , Zhang Fanshun , Liu Zhenghong , Sun Lu , Weng Jianping , Xu Suowen
Published: August 2022

Genome-wide association studies (GWAS) have recently identified phosphatase and actin regulator-1 (PHACTR1) as a critical risk gene associated with polyvascular diseases. However, it remains largely unclear how PHACTR1 is involved in endothelial dysfunction. Here, by mining published datasets of human stable and vulnerable/ruptured plaque tissues, we observed upregulated expression of PHACTR1 in vulnerable/ruptured plaques. Congruent with these data, we demonstrated increased Phactr1 gene expression in aortic endothelium from ApoE-/- mice fed a western type diet compared with that in normal C57BL/6J mice. Relevantly, PHACTR1 gene expression was upregulated by pro-inflammatory and pro-atherogenic stimuli, including TNF-α, IL-1β and oxidized LDL (oxLDL). By employing next-generation RNA sequencing, we demonstrate that PHACTR1 overexpression disrupts pathways associated with endothelial homeostasis. Cell biological studies unravel that PHACTR1 mediates endothelial inflammation and monocyte adhesion by activating NF-κB dependent intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) expression. In addition, overexpression of PHACTR1 also reduces the generation of nitric oxide (NO) by inhibiting Akt/eNOS activation. In-house compound screening of vasoprotective drugs identifies several drugs, including lipid-lowering statins, decreases PHACTR1 gene expression. However, PHACTR1 gene expression was not affected by another lipid-lowering drug-fenofibrate. We also performed a proteomic study to reveal PHACTR1 interacting proteins and validated that PHACTR1 can interact with heat shock protein A8 (HSPA8) which was reported to be associated with coronary artery disease and eNOS degradation. Further studies are warranted to confirm the precise mechanism of PHACTR1 in driving endothelial dysfunction. In conclusion, by using systems biology approach and molecular validation, we disclose the deleterious effects of PHACTR1 on endothelial function by inducing endothelial inflammation and reducing NO production, highlighting the potential to prevent endothelial dysfunction and atherosclerosis by targeting PHACTR1 expression. The precise role of endothelial cell PHACTR1 in polyvascular diseases remains to be validated in diseased conditions.
The miR-15a/16-1 and miR-15b/16-2 clusters regulate early B cell development by limiting IL-7 receptor expression
Authors: Hutter Katharina , Rülicke Thomas , Szabo Tamas G. , Andersen Lill , Villunger Andreas , Herzog Sebastian
Published: August 2022

MicroRNAs are small non-coding RNAs that have emerged as post-transcriptional regulators involved in development and function of different types of immune cells, and aberrant miRNA expression has often been linked to cancer. One prominent miRNA family in the latter setting is the miR-15 family, consisting of the three clusters miR-15a/16-1, miR-15b/16-2 and miR-497/195, which is best known for its prominent tumor suppressive role in chronic lymphocytic leukemia (CLL). However, little is known about the physiological role of the miR-15 family. In this study, we provide a comprehensivein vivoanalysis of the physiological functions of miR-15a/16-1 and miR-15b/16-2, both of which are highly expressed in immune cells, in early B cell development. In particular, we report a previously unrecognized physiological function of the miR-15 family in restraining progenitor B cell expansion, as loss of both clusters induces an increase of the pro-B as well as pre-B cell compartments. Mechanistically, we find that the miR-15 family mediates its function through repression of at least two different types of target genes: First, we confirm that the miR-15 family suppresses several prominent cell cycle regulators such asCcne1,Ccnd3andCdc25aalsoin vivo, thereby limiting the proliferation of progenitor B cells. Second, this is complemented by direct repression of theIl7rgene, which encodes the alpha chain of the IL-7 receptor (IL7R), one of the most critical growth factor receptors for early B cell development. In consequence, deletion of the miR-15a/16-1 and miR-15b/16-2 clusters stabilizesIl7rtranscripts, resulting in enhanced IL7R surface expression. Consistently, our data show an increased activation of PI3K/AKT, a key signaling pathway downstream of the IL7R, which likely drives the progenitor B cell expansion we describe here. Thus, by deregulating a target gene network of cell cycle and signaling mediators, loss of the miR-15 family establishes a pro-proliferative milieu that manifests in an enlarged progenitor B cell pool.
Liver sinusoidal endothelial cell expressed vascular cell adhesion molecule 1 promotes liver fibrosis
Authors: Guo Qianqian , Furuta Kunimaro , Islam Shahidul , Caporarello Nunzia , Kostallari Enis , Dielis Kobe , Tschumperlin Daniel J. , Hirsova Petra , Ibrahim Samar H.
Published: August 2022

Background

During liver injury, liver sinusoidal endothelial cells (LSECs) dysfunction and capillarization promote liver fibrosis. We have previously reported that the LSEC vascular cell adhesion molecule 1 (VCAM1) plays a key role in liver inflammation in nonalcoholic steatohepatitis (NASH) and we now aim to uncover its role in LSEC capillarization and liver fibrosis.

Methods

Wild-type C57BL/6J mice were fed either chow or high fat, fructose and cholesterol diet to induce NASH and treated with either anti-VCAM1 neutralizing antibody or control isotype antibody. Inducible endothelial cell-specific Vcam1 deleted mice (Vcam1Δend) and control mice (Vcam1fl/fl) were fed choline-deficient high-fat diet (CD-HFD) to induce NASH or injected with carbon tetrachloride to induce liver fibrosis. LSECs isolated from Vcam1fl/fl or Vcam1Δend and hepatic stellate cells (HSCs) isolated from wild-type mice were cocultured in a 3-D system or a μ-Slide 2 well co-culture system.

Results

Immunostaining for Lyve1 (marker of differentiated LSECs) was reduced in Vcam1fl/fl mice and restored in Vcam1Δend mice in both NASH and liver fibrosis models. Co-immunostaining showed increased α-smooth muscle actin in the livers of Vcam1fl/fl mice in areas lacking Lyve1. Furthermore, scanning electron microscopy showed reduced LSEC fenestrae in the Vcam1fl/fl mice but not Vcam1Δend mice in both injury models, suggesting that VCAM1 promotes LSEC capillarization during liver injury. HSCs profibrogenic markers were reduced when cocultured with LSECs from CD-HFD fed Vcam1Δend mice compared to Vcam1fl/fl mice. Furthermore, recombinant VCAM1 activated the Yes-associated protein 1 pathway and induced a fibrogenic phenotype in HSCs in vitro, supporting the profibrogenic role of LSEC VCAM1.

Conclusion

VCAM1 is not just a scaffold for leukocyte adhesion during liver injury, but also a modulator of LSEC capillarization and liver fibrosis.
Effects of abundance, water temperature and light on the turbulence and mixing generated by fish schools of different sizes in quiescent water in a laboratory
Authors: Ahani Sana , Khorsandi Babak
Published: August 2022

The turbulence and mixing generated by schools of three fish species, namely koi, pangasius, and goldfish, were quantified in a series of controlled laboratory experiments. The effects of fish abundance, light, and water temperature on the turbulence parameters of the flow produced by the three fish species in a quiescent background were investigated by measuring the velocity field using acoustic Doppler velocimetry. It was observed that the turbulent flow was approximately homogeneous and isotropic and had low-mean velocities. The results show that increasing fish abundance and body size, dimming the ambient light, and increasing the water temperature increase the root-mean-square velocity, the integral time scale, and the rate of dissipation of turbulent kinetic energy. Consequently, fish abundance and body size, as well as environmental parameters, can influence fish-generated turbulence. To further quantify turbulent mixing, the dissipation rate, the mixing efficiency, and the vertical eddy diffusivity were extrapolated for the three fish species at their natural abundances. The dissipation rate of O(10-7-10-6) W/kg, the mixing efficiency of O(10-2-10-1), and the vertical eddy diffusivity of O(10-4) m2/s were estimated. These values are within the range of those of the physical sources. This demonstrates that the contribution of aquatic animals to the turbulent mixing of water environments may be significant, at least locally" to the end of the sentence so that it reads: "mixing of water environments may be significant, at least locally. Furthermore, the dissipation rate and eddy diffusivity are found to increase with the Reynolds numbers of aquatic species.
Mechanical interaction of the egg parasitoid Anastatus bifasciatus (Hymenoptera: Eupelmidae) with artificial substrates and its host egg
Authors: Rebora Manuela , Salerno Gianandrea , Piersanti Silvana , Saitta Valerio , Gorb Elena , Gorb Stanislav N.
Published: August 2022

Egg parasitoids play an important role in biological control of pest species attacking and killing their hosts at an early stage of their development. During the antagonistic coevolution with their hosts, egg parasitoids have developed a great ability to locate their host using chemical cues. A considerable amount of literature is available on this topic, while nothing is known about a possible adaptation of egg parasitoids to topography and mechanical properties of egg surface features and its shape when attaching to the host egg for oviposition. In the present investigation, the attachment ability of adults of both sexes of the egg parasitoid Anastatus bifasciatus (Hymenoptera: Eupelmidae) to artificial (polishing paper, flat glass, glass beads as dummies of the host egg) and natural surfaces (eggs of Halyomorpha halys and Nezara viridula, both Heteroptera: Pentatomidae), with different roughness and wettability, was measured using centrifugal force tester and traction force experiments. The parasitoid attachment devices and the egg surfaces were examined under cryo scanning electron microscope, wettability and roughness of natural and artificial substrates were characterised. We detected differences in the attachment devices and attachment ability of the two sexes. The collected data revealed a special ability of the female to attach to the eggs of the host species, thus suggesting an adaptation of the A. bifasciatus female to the surface features of the eggs during oviposition.
Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats
Authors: Arozal Wawaimuli , Monayo Edwina Rogayah , Barinda Agian Jeffilano , Perkasa Dian Pribadi , Soetikno Vivian , Nafrialdi Nafrialdi , Louisa Melva
Published: August 2022

Background

Silver nanoparticles (AgNPs) are widely used in the medical field, including cardiovascular. However, limited research has investigated the effect of AgNPs on the protection of myocardial infarction (MI).

Objectives

Isoproterenol (Iso)-induced MI and the cardiac protection offered by AgNPs were investigated in the present study. Additionally, we characterized the profile of Ag in the form of nanoparticles.

Methods

Twenty-four male Wistar rats were randomly divided into four groups as follows: normal, Iso, Iso + AgNO3, and Iso + AgNP groups. AgNPs and silver ion (AgNO3) were administered intraperitoneally at 2.5 mg/kg BW for 14 days. Iso induction was performed using two doses of 85 mg/kg BW given subcutaneously on days 13 and 14. Blood and cardiac tissue samples were taken 24 h after the last dose of Iso and checked for Creatine Kinase-MB (CK-MB), lactate dehydrogenase in plasma along with oxidative stress parameters, mitochondria biogenesis markers, and inflammation representative genes in cardiac tissue. Additionally, we analyzed the histopathological features in cardiac tissue.

Results

The silver was confirmed in the form of nanoparticles by its size at intervals of 8.72–37.84 nm. Both AgNO3 and AgNPs showed similar cardioprotective effects, as shown by the decrease in biochemical markers of cardiac toxicity, namely, CK-MB. Additionally, AgNPs group have better efficacy compared with AgNO3 group in ameliorating Iso-mediated oxidative stress production, as evidenced by the significant decrease in malondialdehyde level and increased superoxide dismutase activity (P < 0.0001 and P < 0.01, respectively) in cardiac tissue compared with the Iso group. Mechanistically, AgNPs, but not AgNO3, enhanced the expression levels of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha in post-MI heart and reduced the protein expression of nuclear factor-kappa B (NF-κB) assessed by western blot analysis. Furthermore, these results were confirmed with the histopathological evaluation of cardiac tissue. Nevertheless, pretreatment with either AgNO3 or AgNPs improved the aspartate aminotransferase level.

Conclusion

These results suggested that AgNPs have more superior cardioprotective effect compared with AgNO3 against Iso-induced MI, at least in part through amelioration of NF-κB expression level induced by oxidative stress overproduction.
Nociception monitors vs. standard practice for titration of opioid administration in general anesthesia: A meta-analysis of randomized controlled trials
Authors: Ma Dandan , Ma Jiahui , Chen Huayong , Mu Dongliang , Kong Hao , Yu Lingzhi
Published: August 2022

Background

Nociception monitors are being increasingly used during surgery, but their effectiveness in guiding intraoperative opioid administration is still uncertain. This meta-analysis of randomized controlled trials (RCTs) aimed to compare the effectiveness of nociception monitors vs. standard practice for opioid administration titration during general anesthesia.

Methods

We searched the electronic databases of PubMed, EMBASE, Cochrane Library, Clinical Trial, and Web of Science from inception up to August 1, 2021, to identify relevant articles, and extracted the relevant data. Intraoperative opioid administration, extubation time, postoperative pain score, postoperative opioid consumption and postoperative nausea and vomiting (PONV) were compared between patients receiving nociception monitoring guidance and patients receiving standard management. The standardized mean difference (SMD), with 95% confidence interval (CI), was used to assess the significance of differences. The risk ratio (RR), with 95% CI, was used to assess the difference in incidence of PONV. Heterogeneity among the included trials was evaluated by the I2 test. RevMan 5.3 software was used for statistical analysis.

Results

A total of 21 RCTs (with 1957 patients) were included in the meta-analysis. Intraoperative opioid administration was significantly lower in patients receiving nociception monitor-guided analgesia than in patients receiving standard management (SMD, −0.71; 95% CI, −1.07 to −0.36; P < 0.001). However, pain scores and postoperative opioid consumption were not significantly higher in the former group. Considerable heterogeneity was found among the studies (92%). Extubation time was significantly shorter (SMD, −0.22; 95% CI, −0.41 to −0.03; P = 0.02) and the incidence of PONV significantly lower (RR, 0.78; 95% CI, 0.61 to 1.00; P = 0.05) in patients receiving nociception monitoring guidance.

Conclusions

Intraoperative nociception monitoring guidance may reduce intraoperative opioid administration and appears to be a viable strategy for intraoperative titration of opioids.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273619, identifier: CRD42019129776.
Preserving plant samples from remote locations for detection of RNA and DNA viruses
Authors: Hamim Islam , Suzuki Jon Y. , Borth Wayne B. , Melzer Michael J. , Wall Marisa M. , Hu John S.
Published: August 2022

Viral diseases in plants have a significant impact on agricultural productivity. Effective detection is needed to facilitate accurate diagnosis and characterization of virus infections essential for crop protection and disease management. For sensitive polymerase chain reaction (PCR)-based methods, it is important to preserve the integrity of nucleic acids in plant tissue samples. This is especially critical when samples are collected from isolated areas, regions distant from a laboratory, or in developing countries that lack appropriate facilities or equipment for diagnostic analyses. RNAlater® provides effective, reliable sample storage by stabilizing both RNA and DNA in plant tissue samples. Our work indicated that total RNA or DNA extracted from virus-infected leaf samples preserved in RNAlater® was suitable for reverse transcription polymerase chain reaction (RT-PCR), PCR, Sanger sequencing, high-throughput sequencing (HTS), and enzyme-linked immunosorbent assay (ELISA)-based diagnostic analyses. We demonstrated the effectiveness of this technology using leaf tissue samples from plants with virus symptoms grown in farmers’ fields in Bangladesh. The results revealed that RNAlater® technology was effective for detection and characterization of viruses from samples collected from remote areas and stored for extended periods. Adoption of this technology by developing countries with limited laboratory facilities could greatly increase their capacity to detect and diagnose viral infections in crop plants using modern analytical techniques.
Effect of dietary peNDF levels on digestibility and rumen fermentation, and microbial community in growing goats
Authors: Zhou Jia , Xue Benchu , Hu Anhai , Yue Shuangming , Wu Mei , Hong Qionghua , Wu Yuhan , Wang Zhisheng , Wang Lizhi , Peng Quanhui , Xue Bai
Published: August 2022

Physically effective neutral detergent fiber (peNDF) is a concept that accounts for the particle length of NDF in diets, sustaining the normal chewing behavior and rumen fermentation of ruminants. Specifically, peNDF>1.18 is the commonest one that is calculated from NDF and the percentage of feed dry matter left on the 1.18, 8.00, and 19.00 mm sieves. This study aimed to investigate the effects of different levels of peNDF>1.18 on the rumen microbiome and its correlation with nutrient digestibility and rumen fermentation in goats. A total of 30 Lezhi black goats were randomized and blocked to five dietary treatments (n = 6). All the diets were identical in composition but varied in hay lengths, leading to the different peNDF>1.18 content of the diets: 32.97, 29.93, 28.14, 26.48, and 24.75%. The results revealed that the nutrient digestibility increased when dietary peNDF>1.18 levels decreased from 32.97% to 28.14%, with the highest digestibility at 28.14% peNDF>1.18 treatment, after which nutrient digestibility decreased with the decreasing of dietary peNDF levels. Ruminal NH3-N concentrations in the 29.93% and 28.14% groups were higher than that in the 24.75% group (p < 0.05). Ruminal microbial protein concentration was the highest in the 32.97% group (p < 0.05). Daily CH4 production in the 32.97% and 24.75% peNDF>1.18 treatments was lower than that in the 26.48% group (p < 0.05) and no differences were observed among other groups. The relative abundance of rumen fungi at the phylum and genus levels and archaea at the species were affected by dietary peNDF>1.18 content. In conclusion, decreasing dietary peNDF>1.18 levels within a certain range can improve nutrient digestibility and change the rumen microbial community structure of goats. Dietary peNDF>1.18 level should be 28.14% (roughage length around 1 cm) among the five levels for 4 months Lezhi black goats with the purpose of optimal nutrient digestibility.
Antifungal action and induction of resistance by Bacillus sp. strain YYC 155 against Colletotrichum fructicola for control of anthracnose disease in Camellia oleifera
Authors: Zhou Aiting , Wang Fang , Yin Jiabi , Peng Ruiqi , Deng Jia , Shen Dezhou , Wu Jianrong , Liu Xiaoyun , Ma Huancheng
Published: August 2022

Anthracnose disease caused by Colletotrichum fructicola is a serious disease that can afflict Camellia oleifera. Biological control is a rapidly growing approach for the management of plant diseases. In this study, we investigated the bio-control efficiency and the defense responses of an endophytic Bacillus tequilensis strain YYC 155, which was isolated from the root nodules of the Crotalaria pallida against anthracnose disease, caused by C. fructicola in C. oleifera. B. tequilensis YYC 155 exhibited significant inhibitory activity against anthracnose disease, caused by C. fructicola in C. oleifera. YYC 155 can secrete extracellular hydrolases, such as chitinase and β-1, 3-glucanase, which produce lipopeptides that are antimicrobial and forms strong biofilms. In addition, in treatment with YYC 155, the cell membranes of C. fructicola were injured and the leakage of cell contents from the mycelia of the pathogen was increased. Spraying 1 × 107 cells mL–1 bacterial suspension of YYC 155 on C. oleifera leaves enhanced the activity of key enzymes in C. oleifera associated with the phenylpropanoid pathway and increased the content of phenolic compounds and flavonoids. Results of our study indicate that B. tequilensis YYC 155 may potentially represent an effective biocontrol agent against anthracnose disease in C. oleifera.
Effects of epiphytic and exogenous lactic acid bacteria on fermentation quality and microbial community compositions of paper mulberry silage
Authors: Cheng Qiming , Li Maoya , Fan Xueying , Chen Yulian , Sun Hong , Xie Yixiao , Zheng Yulong , Chen Chao , Li Ping
Published: August 2022

This study aimed to isolate, characterize, and identify lactic acid bacteria (LAB) strains from various sources and evaluate their effects on the nutritional quality, fermentation characteristics, and microbial compositions of paper mulberry (PM) after 60 days of ensiling. Forty-nine LAB strains were isolated from Phalaris arundinacea silage, pickle, and fresh PM leaves; three of these strains (Lactiplantibacillus plantarum, YC1; Levilactobacillus brevis, PC3; and Lactiplantibacillus plantarum, BP17) and one commercial inoculant Gaofuji (GFJ) were subsequently used. Compared with other treatments, PC3 and BP17 increased (P < 0.05) the LAB count and crude protein content and decreased (P < 0.05) the molds and coliform bacteria counts, pH, and ammonia-N content of PM silages. BP17 and PC3 increased the relative Lactiplantibacillus abundance and decreased that of Lelliottia and Cladosporium, improving PM silage quality. Therefore, PC3 and BP17 can improve the fermentation quality of PM silage and could be used as silage starter cultures.
A statistical optimization by response surface methodology for the enhanced production of riboflavin from Lactobacillus plantarum–HDS27: A strain isolated from bovine milk
Authors: Hemalatha M. , Subathra Devi C.
Published: August 2022

In the present study, Lactobacillus plantarum-HDS27 strain isolated from bovine milk was used for the enhanced production of riboflavin. Production medium was optimized by one factor at a time with different parameters. Statistical optimization by Response surface methodology (RSM), central composite design was used to optimize variables such as pH, temperature, glucose, and yeast extract. The present study reveals the maximum riboflavin production by one factor at a time was obtained under the culture conditions; glucose, yeast extract, pH 6, the temperature at 40°C, and 3% of inoculum size. In RSM, analysis of variance for the responses was calculated. Among the tested variables, pH, yeast extract, and temperature showed significant impact on riboflavin production. Maximum amount of yeast extract in production medium resulted in increased riboflavin production. The riboflavin production after 24 h with the optimal condition was found to be 12.33 mg/L. It was found proximate to the expected value (12.29 mg/L) achieved by the RSM model. The yield of riboflavin was increased to 3.66-fold after 24 h with the optimized parameters. The current research, emphasizes that the Lactobacillus plantarum–HDS27 could be an excellent strain for the large-scale industrial production of riboflavin.
Multisensory visual-vestibular training improves visual heading estimation in younger and older adults
Authors: Gabriel Grace A. , Harris Laurence R. , Henriques Denise Y. P. , Pandi Maryam , Campos Jennifer L.
Published: August 2022

Self-motion perception (e.g., when walking/driving) relies on the integration of multiple sensory cues including visual, vestibular, and proprioceptive signals. Changes in the efficacy of multisensory integration have been observed in older adults (OA), which can sometimes lead to errors in perceptual judgments and have been associated with functional declines such as increased falls risk. The objectives of this study were to determine whether passive, visual-vestibular self-motion heading perception could be improved by providing feedback during multisensory training, and whether training-related effects might be more apparent in OAs vs. younger adults (YA). We also investigated the extent to which training might transfer to improved standing-balance. OAs and YAs were passively translated and asked to judge their direction of heading relative to straight-ahead (left/right). Each participant completed three conditions: (1) vestibular-only (passive physical motion in the dark), (2) visual-only (cloud-of-dots display), and (3) bimodal (congruent vestibular and visual stimulation). Measures of heading precision and bias were obtained for each condition. Over the course of 3 days, participants were asked to make bimodal heading judgments and were provided with feedback (“correct”/“incorrect”) on 900 training trials. Post-training, participants’ biases, and precision in all three sensory conditions (vestibular, visual, bimodal), and their standing-balance performance, were assessed. Results demonstrated improved overall precision (i.e., reduced JNDs) in heading perception after training. Pre- vs. post-training difference scores showed that improvements in JNDs were only found in the visual-only condition. Particularly notable is that 27% of OAs initially could not discriminate their heading at all in the visual-only condition pre-training, but subsequently obtained thresholds in the visual-only condition post-training that were similar to those of the other participants. While OAs seemed to show optimal integration pre- and post-training (i.e., did not show significant differences between predicted and observed JNDs), YAs only showed optimal integration post-training. There were no significant effects of training for bimodal or vestibular-only heading estimates, nor standing-balance performance. These results indicate that it may be possible to improve unimodal (visual) heading perception using a multisensory (visual-vestibular) training paradigm. The results may also help to inform interventions targeting tasks for which effective self-motion perception is important.
Cortical neuroanatomical changes related to specific language impairments in primary progressive aphasia
Authors: Kang Sung Hoon , Park Yu Hyun , Shin Jiho , Kim Hang-Rai , Yun Jihwan , Jang Hyemin , Kim Hee Jin , Koh Seong-Beom , Na Duk L. , Suh Mee Kyung , Seo Sang Won
Published: August 2022

Objective

Language function test-specific neural substrates in Korean patients with primary progressive aphasia (PPA) might differ from those in other causes of dementia and English-speaking PPA patients. We investigated the correlation between language performance tests and cortical thickness to determine neural substrates in Korean patients with PPA.

Materials and methods

Ninety-six patients with PPA were recruited from the memory clinic. To acquire neural substrates, we performed linear regression using the scores of each language test as a predictor, cortical thickness as an outcome and age, sex, years of education, and intracranial volume as confounders.

Results

Poor performance in each language function test was associated with lower cortical thickness in specific cortical regions: (1) object naming and the bilateral anterior to mid-portion of the lateral temporal and basal temporal regions; (2) semantic generative naming and the bilateral anterior to mid-portion of the lateral temporal and basal temporal regions; (3) phonemic generative naming and the left prefrontal and inferior parietal regions; and (4) comprehension and the left posterior portion of the superior and middle temporal regions. In particular, the neural substrates of the semantic generative naming test in PPA patients, left anterior to mid-portion of the lateral and basal temporal regions, quite differed from those in patients with other causes of dementia.

Conclusion

Our findings provide a better understanding of the different pathomechanisms for language impairments among PPA patients from those with other causes of dementia.
Multicomponent exercise program effects on fitness and cognitive function of elderlies with mild cognitive impairment: Involvement of oxidative stress and BDNF
Authors: Rondão Catarina Alexandra de Melo , Mota Maria Paula , Oliveira Maria Manuel , Peixoto Francisco , Esteves Dulce
Published: August 2022

Regular exercise has been shown to be one of the most important lifestyle influences on improving functional performance, and decreasing morbidity and all-cause mortality among older people. However, although there is some evidence on the effects of aerobic training on oxidative stress, there is little information regarding the effects of multicomponent exercise (dual-task training) and combination of exercise with cognitive stimulation on oxidative stress. In this context, the aim of this study was to verify the effects of a multicomponent exercise program on physical fitness and cognitive function in the elderly with mild cognitive impairment and determine the role of oxidative stress and brain-derived neurotrophic factor (BDNF). At baseline, 37 elderly nursing home residents with mild cognitive impairment were divided into two groups: the control group (CG, n = 12, 81.8 years) and the experimental group (EG, n = 25, 83.2 years). These elderlies followed multicomponent exercise training for 24 weeks, with two sessions per week and 45–50 min per session. The exercises included both aerobic and strength exercises, considering functional movements and light to moderate intensity. Cognitive stimulation comprehended exercises based on word games, puzzles, mathematical calculations, forward and backward counting, computer exercises, exergames, and games on a balanced platform. Physical assessments (weight, height, and body mass index), health and functional parameters (fitness tests: chair stand, arm curls, chair sit-and-reach, eight feet up-and-go, back scratch, 6-min walking, feet together, semi-tandem, and full tandem), lipid profile (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides), measures of lipid peroxidation damage, thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), and BDNF were measured in plasma, based on which analyses were performed before and after the 24 weeks of the multicomponent exercise intervention. The results showed an overall improvement in physical and functional performance. Regarding biochemical measures, multicomponent exercises lead to a significant decrease in oxidative damage. The results indicate that multicomponent exercise training induces benefits in functional capacity and reduces damage due to oxidative stress.
Maternal enrichment increases infantile spatial amnesia mediated by postnatal neurogenesis modulation
Authors: López-Oropeza Grecia , Durán Pilar , Martínez-Canabal Alonso
Published: August 2022

Infantile amnesia, the inability to form long-lasting episodic memories, is a phenomenon extensively known but with no clear understanding of its origins. However, a recent study showed that high rates of hippocampal postnatal neurogenesis degrade episodic-like memories in infants a few days after memory acquisition. Additionally, new studies indicate that exposure to an enriched environment in mice leads to high hippocampal neurogenesis in their offspring. Nevertheless, it is still unclear how this intergenerational trait affects the persistence of hippocampal memories. Therefore, we evaluated spatial memory retention in the offspring of enriched female mice after weaning to address this question. Ten days after spatial learning, we tested memory retention, observing that the offspring of enriched dams increased spatial memory failure; this finding correlates with high proliferation rates in the hippocampus. Furthermore, we evaluated the causal relationship between postnatal hippocampal neurogenesis and memory failure using the antiproliferative drug Temozolomide (TMZ), which rescued spatial memory retrieval. Finally, we evaluated neuronal activity in the hippocampus quantifying the cells expressing the immediate early gene c-Fos. This evaluation showed engram modifications between groups. This neural activity pattern indicates that the high neurogenesis rates can modify memory engrams and cognitive performance. In conclusion, the inherited increase of hippocampal neurogenesis by enriched dams leads to plastic changes that exacerbate infantile amnesia in a spatial task.
Classification of severe obstructive sleep apnea with cognitive impairment using degree centrality: A machine learning analysis
Authors: Liu Xiang , Shu Yongqiang , Yu Pengfei , Li Haijun , Duan Wenfeng , Wei Zhipeng , Li Kunyao , Xie Wei , Zeng Yaping , Peng Dechang
Published: August 2022

In this study, we aimed to use voxel-level degree centrality (DC) features in combination with machine learning methods to distinguish obstructive sleep apnea (OSA) patients with and without mild cognitive impairment (MCI). Ninety-nine OSA patients were recruited for rs-MRI scanning, including 51 MCI patients and 48 participants with no mild cognitive impairment. Based on the Automated Anatomical Labeling (AAL) brain atlas, the DC features of all participants were calculated and extracted. Ten DC features were screened out by deleting variables with high pin-correlation and minimum absolute contraction and performing selective operator lasso regression. Finally, three machine learning methods were used to establish classification models. The support vector machine method had the best classification efficiency (AUC = 0.78), followed by random forest (AUC = 0.71) and logistic regression (AUC = 0.77). These findings demonstrate an effective machine learning approach for differentiating OSA patients with and without MCI and provide potential neuroimaging evidence for cognitive impairment caused by OSA.
Novel machine learning models to predict pneumonia events in supratentorial intracerebral hemorrhage populations: An analysis of the Risa-MIS-ICH study
Authors: Zheng Yan , Lin Yuan-Xiang , He Qiu , Zhuo Ling-Yun , Huang Wei , Gao Zhu-Yu , Chen Ren-Long , Zhao Ming-Pei , Xie Ze-Feng , Ma Ke , Fang Wen-Hua , Wang Deng-Liang , Chen Jian-Cai , Kang De-Zhi , Lin Fu-Xin
Published: August 2022

Background

Stroke-associated pneumonia (SAP) contributes to high mortality rates in spontaneous intracerebral hemorrhage (sICH) populations. Accurate prediction and early intervention of SAP are associated with prognosis. None of the previously developed predictive scoring systems are widely accepted. We aimed to derive and validate novel supervised machine learning (ML) models to predict SAP events in supratentorial sICH populations.

Methods

The data of eligible supratentorial sICH individuals were extracted from the Risa-MIS-ICH database and split into training, internal validation, and external validation datasets. The primary outcome was SAP during hospitalization. Univariate and multivariate analyses were used for variable filtering, and logistic regression (LR), Gaussian naïve Bayes (GNB), random forest (RF), K-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and ensemble soft voting model (ESVM) were adopted for ML model derivations. The accuracy, sensitivity, specificity, and area under the curve (AUC) were adopted to evaluate the predictive value of each model with internal/cross-/external validations.

Results

A total of 468 individuals with sICH were included in this work. Six independent variables [nasogastric feeding, airway support, unconscious onset, surgery for external ventricular drainage (EVD), larger sICH volume, and intensive care unit (ICU) stay] for SAP were identified and selected for ML prediction model derivations and validations. The internal and cross-validations revealed the superior and robust performance of the GNB model with the highest AUC value (0.861, 95% CI: 0.793–0.930), while the LR model had the highest AUC value (0.867, 95% CI: 0.812–0.923) in external validation. The ESVM method combining the other six methods had moderate but robust abilities in both cross-validation and external validation and achieved an AUC of 0.843 (95% CI: 0.784–0.902) in external validation.

Conclusion

The ML models could effectively predict SAP in sICH populations, and our novel ensemble model demonstrated reliable robust performance outcomes despite the populational and algorithmic differences. This attempt indicated that ML application may benefit in the early identification of SAP.
Effects of aging on ocular vestibular-evoked myogenic potential using ER-3A insert earphone and B81 bone vibrator
Authors: Xu Zhuo , Wang Zhilin , Zhong Bo , Wang Minjiao , Fan Xiaoqin , Ren Cuncun , Qi Meihao , Lin Ying , Zha Dingjun
Published: August 2022

Purpose

Aging is a process associated with degeneration and dysfunction of peripheral vestibular system or apparatus. This study aimed to investigate the influence of aging on ocular vestibular-evoked myogenic potential (oVEMP) response rates and recording parameters using the B81 bone vibrator and compare them with air conduction stimuli (ACS) oVEMP response characteristics.

Methods

In 60 healthy participants aged 10–71 years (mean age 39.9; 29 male participants), the oVEMP response was elicited using a B81 bone vibrator and an ER-3A insert earphone. The effects of age and stimulus on oVEMP response rates and recording parameters were evaluated.

Results

Response rates and amplitudes declined with aging using either ACS or bone-conducted vibration (BCV) stimulation, particularly in individuals over 60 years of age, whereas thresholds increased and N1 latencies were prolonged. BCV showed fewer risks of absent oVEMP response than ACS (p = 0.002). BCV acquired higher amplitudes (p < 0.001), lower thresholds, and shorter N1 and P1 latencies (all p < 0.001) than ACS.

Conclusions

The absence of an oVEMP response may be attributed to aging rather than a concurrent vestibular disorder. B81-BCV likely produces higher mechanical drives to the vestibular hair cells at safer and non-traumatic levels compared with ACS and therefore may be more likely to evoke a response in the elderly cohort, whose vestibular function and mechanical sensitivity have declined. Thus, B81-BCV stimulation is more effective and safer to elicit oVEMPs, and it should be recommended when ACS fails in the clinic, particularly in the elderly population.
Comparative analysis of clinical and imaging data of first-attack neuromyelitis optica spectrum disorders with and without connective tissue disease
Authors: Yao Yaobing , Yang Xuan , Zhou Yongyan , Xie Haojie , Duan Ranran , Jing Lijun , Li Yanfei , Guan Wenjuan , Teng Junfang , Jia Yanjie
Published: August 2022

Background

The coexistence of neuromyelitis optica spectrum disorder (NMOSD) and connective tissue disease (CTD) is well recognized. The purpose of this study was to investigate and compare the characteristics of first attack NMOSD with and without CTD.

Methods

A total of 113 Patients with NMOSD were included and were divided into two groups based on the presence of co-occurring CTD. Their demographic, clinical, laboratory, and image characteristics were obtained through inpatient medical records and follow-ups. Kaplan–Meier survival analysis was used to analyze the effect of CTD in NMOSD patients at the time of first recurrence. The risk factors that could predict complications of NMOSD with CTD was analyzed by binary logistic regression. The ability of homocysteine (Hcy) to predict the coexistence of NMOSD and CTD was analyzed and evaluated by the receiver operating characteristic curve.

Results

The demographic data, clinical features, cerebrospinal fluid analysis, and MRI findings, except relapse events (including relapse rate, number of recurrences, and time of first recurrence), were similar between the two groups. The serum lymphocyte-to-monocyte ratio and albumin levels were lower (P < 0.05), while serum erythrocyte sedimentation rate and Hcy levels were higher in patients with NMOSD with CTD than in those without CTD (P < 0.001). Kaplan–Meier survival analysis showed that the time of first recurrence in NMOSD patients complicated with CTD was earlier than that of without CTD (log rank test P = 0.035). Logistic regression revealed that serum Hcy levels (OR 1.296, 95% CI, 1.050–1.601, P = 0.016) were independently associated with the occurrence of NMOSD with CTD. The receiver operating characteristic curve area was 0.738 (95% CI, 0.616–0.859; P < 0.001) for Hcy levels. Considering the Hcy concentration of 14.07 μmol/L as the cutoff value, the sensitivity and specificity of predicting the coexistence of first-attack NMOSD and CTD were 56 and 89.8%, respectively.

Conclusions

When the first-attack NMOSD patients are complicated with CTD, they have a higher recurrence rate, more recurrences, earlier first recurrence, higher serum Hcy levels, and enhanced systemic inflammatory reactions. Furthermore, Hcy levels may help to screen for CTD in patients with first-attack NMOSD.
Transcranial current stimulation in epilepsy: A systematic review of the fundamental and clinical aspects
Authors: Simula Sara , Daoud Maëva , Ruffini Giulio , Biagi Maria Chiara , Bénar Christian-G. , Benquet Pascal , Wendling Fabrice , Bartolomei Fabrice
Published: August 2022

Purpose

Transcranial electrical current stimulation (tES or tCS, as it is sometimes referred to) has been proposed as non-invasive therapy for pharmacoresistant epilepsy. This technique, which includes direct current (tDCS) and alternating current (tACS) stimulation involves the application of weak currents across the cortex to change cortical excitability. Although clinical trials have demonstrated the therapeutic efficacy of tES, its specific effects on epileptic brain activity are poorly understood. We sought to summarize the clinical and fundamental effects underlying the application of tES in epilepsy.

Methods

A systematic review was performed in accordance with the PRISMA guidelines. A database search was performed in PUBMED, MEDLINE, Web of Science and Cochrane CENTRAL for articles corresponding to the keywords “epilepsy AND (transcranial current stimulation OR transcranial electrical stimulation)”.

Results

A total of 56 studies were included in this review. Through these records, we show that tDCS and tACS epileptic patients are safe and clinically relevant techniques for epilepsy. Recent articles reported changes of functional connectivity in epileptic patients after tDCS. We argue that tDCS may act by affecting brain networks, rather than simply modifying local activity in the targeted area. To explain the mechanisms of tES, various cellular effects have been identified. Among them, reduced cell loss, mossy fiber sprouting, and hippocampal BDNF protein levels. Brain modeling and human studies highlight the influence of individual brain anatomy and physiology on the electric field distribution. Computational models may optimize the stimulation parameters and bring new therapeutic perspectives.

Conclusion

Both tDCS and tACS are promising techniques for epilepsy patients. Although the clinical effects of tDCS have been repeatedly assessed, only one clinical trial has involved a consistent number of epileptic patients and little knowledge is present about the clinical outcome of tACS. To fill this gap, multicenter studies on tES in epileptic patients are needed involving novel methods such as personalized stimulation protocols based on computational modeling. Furthermore, there is a need for more in vivo studies replicating the tES parameters applied in patients. Finally, there is a lack of clinical studies investigating changes in intracranial epileptiform discharges during tES application, which could clarify the nature of tES-related local and network dynamics in epilepsy.
Impaired sharp-wave ripple coordination between the medial entorhinal cortex and hippocampal CA1 of knock-in model of Alzheimer’s disease
Authors: Funane Tsukasa , Jun Heechul , Sutoko Stephanie , Saido Takaomi C. , Kandori Akihiko , Igarashi Kei M.
Published: August 2022

Clinical evidence suggests that the entorhinal cortex is a primary brain area triggering memory impairments in Alzheimer’s disease (AD), but the underlying brain circuit mechanisms remain largely unclear. In healthy brains, sharp-wave ripples (SWRs) in the hippocampus and entorhinal cortex play a critical role in memory consolidation. We tested SWRs in the MEC layers 2/3 of awake amyloid precursor protein knock-in (APP-KI) mice, recorded simultaneously with SWRs in the hippocampal CA1. We found that MEC→CA1 coordination of SWRs, found previously in healthy brains, was disrupted in APP-KI mice even at a young age before the emergence of spatial memory impairments. Intriguingly, long-duration SWRs critical for memory consolidation were mildly diminished in CA1, although SWR density and amplitude remained intact. Our results point to SWR incoordination in the entorhinal-hippocampal circuit as an early network symptom that precedes memory impairment in AD.
Considerations for the translation of nutrient recommendations as dietary plans for infants, children, and adolescents as reported in Italian Guidelines for healthy eating
Authors: Rossi Laura , Martone Deborah , Piccinelli Raffaela , Buonocore Pasquale , Ghiselli Andrea ,   the Working Group on Pediatric Nutrition of Italian Dietary Guidelines
Published: August 2022

Healthy eating in childhood and adolescence is important for proper growth and development and to establish a healthy foundation for future dietary habits. This paper aims to describe the elaboration of dietary plans for pediatric ages highlighting critical points related to the application of the Italian nutrient recommendations. National databases on food composition data were used to compile the dietary plans. Starting from the definition of serving size for adults, the suggested portion size for pediatric ages was shaped to produce appropriate dietary plans according to the different classes of age. Items from “cereals and derivatives,” “milk,” “fruit,” “vegetables,” “olive oil,” and “water” groups were included daily. Pizza was included once a week. Sweets and snacks were gradually introduced, once a week in infants and up to five times a week in adolescents. Legumes were provided three times a week, as a source of vegetable and sustainable proteins. The main critical aspect of the dietary plans was related to the monotony, especially for snacks and breakfasts. This work demonstrated the limits of the translation of Italian nutrient recommendations into dietary plans for pediatric age groups. Keeping the protein intake in the recommended range of 8–12% of daily energy resulted in inadequate provision of calcium and iron. Other critical points were the reference values for body weight and physical activity. The proposed dietary plans are adequate with regard to food composition, the intake of energy and several nutrients, and in terms of food selection. However, their implementations require action, information, and advocacy.