bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Excessive Intake of Oil and Salt to Prevent and Control Hypertension: A Latent Class Analysis
Authors: He Lu , Yan Yan , Wang Yuxiao , Sun Yudan , La Yuanyuan , Liu Jie , Cai Yutong , Cao Xi , Feng Qilong
Published: April 2022

Introduction

To identify health hazard behaviors and provide a basis for targeted management and intervention for patients with hypertension, we classified their health-related behaviors.

Methods

A multi-stage random sampling method was used to conduct an on-site questionnaire survey among residents aged ≥15 years in a certain urban area of Taiyuan City, Shanxi Province, China. A latent class analysis was used to classify the lifestyle behaviors of patients with hypertension. The lifestyle behavior characteristics of different types of patients with hypertension and their awareness of hypertension were assessed.

Results

The prevalence of hypertension in Taiyuan City was 19.5%. Patients with hypertension were classified into three clusters according to their lifestyle patterns: smoking and drinking (13.35%), excessive edible oil and salt intake (68.27%), and healthy behavior (18.38%). Comparing the three latent classes of lifestyle, the distribution of age, sex, marital status, and education level was different (P < 0.05). The awareness of hypertension and the rate of control among the three classes were also different (P < 0.05).

Conclusion

The lifestyle behaviors of patients with hypertension have evident classification characteristics. Approximately two-thirds of the patients with hypertension have an excessive intake of oil and salt. Therefore, targeted and precise intervention measures should be taken to control the intake of oil and salt in this cohort.
Anatomical Feasibility Study on Novel Ascending Aortic Endograft With More Proximal Landing Zone for Treatment of Type A Aortic Dissection
Authors: Li Xiaoye , Zhu Longtu , Zhang Lei , Song Chao , Zhang Hao , Xia Shibo , Guo Wenying , Jing Zaiping , Lu Qingsheng
Published: April 2022

Objective

Type A aortic dissection (TAAD) is associated with high morbidity and mortality, and open surgery is the best treatment option. Development of endovascular repair devices for TAAD will benefit patients deemed unfit for open surgery. In this study, we performed a thorough investigation of anatomical features in Asian patients with TAAD to learn about the patient eligibility of a novel ascending aortic endograft technique.

Methods

Computed tomography angiography (CTA) images of TAAD cases in our institution from January 2015 to November 2021 were reviewed, and three-dimensional reconstructions were performed with the Endosize software (Therenva, Rennes, France). Anatomic structures including length measured along centerline and greater/lesser curvature, ascending aorta/aortic root dimensions, as well as location of entry tear and extent of dissection were analyzed.

Results

A total of 158 patients were included [median age 58 years, interquartile range (IQR), 30–76 years; 115 males, 72.8%]. In 99 (62.7%) of the cases, entry tear was distal to the sinotubular junction (STJ). In 106 (67.1%) of the cases, the pathology proximally extended into the aortic root, which was intramural hematoma in 37 (23.4%) of the cases, and the aortic root was free from the pathology in 52 (32.9%) of the cases. The median distance from the STJ to the proximal edge of the ostium of the innominate artery (IA) measured along the centerline was 65 mm (IQR 58–74 mm). The median distance from the distal edge of the higher coronary ostium to the STJ was 7.95 mm (IQR 5.625–10.9 mm). The bare metal stent part was set between the edge of the higher coronary ostium and the STJ. In our series, 63 (39.9%) of the cases had this distance >10 mm. The relative difference was <20% between the STJ and the proximal edge of the ostium of the IA in 92 (58.2%) of the cases. Ascending aorta radius of curvature was 52.2 mm (IQR 43.7–63.7 mm).

Conclusions

Our study demonstrates that 56.3% of the TAAD cases would be amenable to endovascular repair by the novel ascending aortic endograft, with sufficient landing zone free of the dissected aorta.
Lack of Usefulness of Donor-Derived Cell-Free DNA as a Biomarker for Cardiac Allograft Vasculopathy: A Prospective Study
Authors: Jiménez-Blanco Bravo Marta , Pérez-Gómez Laura , Hernández-Pérez Francisco J. , Arellano-Serrano Carlos , Torres-Sanabria Mario , Gómez-Bueno Manuel , Oteo-Domínguez Juan F. , Mingo-Santos Susana , Segovia-Cubero Javier
Published: April 2022

Background

Cardiac allograft vasculopathy (CAV) remains a major cause of morbidity and mortality among long-term heart transplant recipients. There is an unmet need for a non-invasive biomarker of CAV that could obviate the need to perform surveillance coronary angiograms in these patients. Our aim was to evaluate the performance of Donor-derived Cell Free DNA (dd-cfDNA) as a biomarker of CAV.

Methods

We prospectively measured dd-cfDNA levels in all patients undergoing routine coronary angiography >1 year after heart transplant at a single center. Endpoints included the association between dd-cfDNA levels and the presence CAV, according to several prespecified criteria.

Results

We included 94 heart transplant recipients, a median of 10.9 years after transplant. Coronary angiogram revealed CAV0, CAV1, CAV2, and CAV3 in 61, 19, 14, and 6% of patients, respectively. Comparison of dd-cfDNA levels in patients with CAV0 and CAV1–2–3 (primary end-point) did not show significant differences (0.92%, IQR 0.46–2.0 vs. 0.46%, IQR 0.075–1.5, p = 0.059), nor did the comparison between patients with stable CAV (no new coronary lesions since previous angiogram, n = 77) and progressive CAV (n = 17); dd-cfDNA values 0.735% (IQR 0.195–2.0) vs. 0.9% (IQR 0.12–1.8), p = 0.76. However, we found an association between NTproBNP levels and CAV degree (p = 0.017). Dd-cfDNA levels did not correlate with NTproBNP (ρ = −0.095).

Conclusion

In this study, dd-cfDNA did not perform as a useful biomarker to avoid surveillance coronary angiograms for CAV diagnosis.

Clinical Trial Notation

Potential Role of Donor-derived Cell Free DNA as a Biomarker in Cardiac Allograft Vasculopathy, NCT 04791852.
Long Term Results of the Modified Bentall Procedure With Mechanical and Biological Composite Valve Grafts
Authors: Werner Paul , Gritsch Jasmin , Kaider Alexandra , Coti Iuliana , Osorio Emilio , Mahr Stephane , Stelzmueller Marie-Elisabeth , Kocher Alfred , Laufer Günther , Andreas Martin , Ehrlich Marek
Published: April 2022

Objectives

Despite the evident shift toward biological prostheses, the optimal choice of valve remains controversial in composite valve graft (CVG) replacement. We investigated long-term morbidity and mortality after CVG implantation in an all-comer cohort with a subgroup analysis of patients aged 50–70 years stratified after valve type.

Methods

A total of 507 patients underwent the Bentall procedure with either a mechanical (MCVG, n = 299) or a biological (BCVG n = 208) CVG replacement between 2000 and 2020. A single-center analysis comprising clinical and telephone follow-up was conducted to investigate late mortality and morbidity

Results

The 30-day mortality in all patients [age 56 ± 14 years, 78.1% male, EuroSCORE II 3.12 (1.7; 7.1)] was 5.9%. Patients who were electively operated on had a 30-day mortality of 1.5% (n = 5) while it remained higher in urgent/emergent procedures (n = 25, 15.4%). Survival at 10 and 15 years was 78.19 ± 2.26% and 72.6 ± 3.2%, respectively. In patients aged 50–70 years (n = 261; MCVG = 151, BCVG = 110), survival did not differ significantly between the valve groups (p = 0.419). Multivariable analysis showed no significant impact of valve type on survival (p = 0.069). A time-varying relation with survival was notable, showing a higher risk in the MCVG group in the early postoperative phase, which declined compared to the BCVG group in the course of follow-up.

Conclusions

The Bentall technique presents with excellent mortality when performed electively. The type of valve prosthesis showed no statistically significant effect on mortality in patients aged 50–70 years. However, a time-varying relation showing an initially higher risk with MCVG which decreased compared to BCVG at long-term follow-up was notable. Further studies with even longer follow-up of BCVGs will clarify the ideal choice of prosthesis in this patient subset.
Biomarker Records From Eocene Lacustrine Sequence in the Eastern Tibet Plateau and Its Implication for Organic Matter Sources
Authors: Wei Jingyi , Wang Yongli , Wang Gen , Wei Zhifu , He Wei , Zhang Ting , Ma Xueyun , Zhang Pengyuan , Ma He , Yu Xiaoli , Li Shangkun , Li Lun
Published: April 2022

The Eocene is the initial stage of the Cenozoic global cooling. Compared with the abundant marine records, the continental records of Eocene are scarce. Throughout the Eocene, a series of continuous deposition of gypsum and volcanic tuff-bearing red clastic sediments have developed in the Nangqian Basin (NB). In this work, representative sediments were collected from the NB, and lipid biomarkers and compound-specific carbon isotopes of n-alkanes were analyzed. Based on the robust paleomagnetic age–depth model, from the early to the late Eocene, the compound-specific carbon isotopic compositions (δ13C23 and δ13C25) increased with the sedimentary facies changed. At the same time, the relative proportion of mid-chain length to the long-chain length homologs (Paq) decreased, and the peak carbon number (Cmax) shifted from nC21, nC22 or nC23 to nC16, nC25, nC27, or nC31. We ascribed these variations to the climate drying and water level turning high as indicated by the lithology change from fluvial to lacustrine facies and the terrestrial inputs from neighboring mountain belts in the middle–late Eocene. Moreover, we compared our n-alkane results with other records from the TP and the global sea level and marine benthic δ18O. We found that a nearly synchronous deformation and drying of the eastern TP caused by the India–Asia collision in the early Eocene was closely related to the arid conditions and topographically changed in the northern TP. The climate variations in the Eocene in the NB were mainly controlled by the global climate change and the uplift of the TP and affected by the Paratethys Sea on a long scale.
Influence of Swelling on Shear Strength of Expansive Soil and Slope Stability
Authors: Lan Tian , Zhang Rui , Yang Biyu , Meng Xiong
Published: April 2022

Rainfall is the main factor leading to the landslide of expansive soil slope. To deeply understand the instability mechanism of expansive soil slope under rainfall conditions, it is necessary to clarify the strength attenuation mechanism of expansive soil caused by water absorption and swelling. Therefore, the improved constant volume direct shear test was used in this study to compare with the conventional test, focusing on the variation of effective shear strength parameters with dry density (volume). The micromechanism of expansive soil strength attenuation is further studied, and the influence of expansive soil on slope stability is analyzed by numerical calculation. The results show that the improved direct shear apparatus and method can keep the volume of expansive soil specimens unchanged before and after shear and obtain the real effective shear strength parameter of soil. Under the same conditions, the shear strength parameter of the improved direct shear test is lower than that of the conventional direct shear test. The rapid thickening of the lamellar structure of montmorillonite in expansive soil will lead to the fragmentation and dispersion of clay particles, which is one of the fundamental reasons for the strength difference between expansive soil and ordinary clay. In slope stability analysis, the effect of swelling on the shear strength of slope cannot be ignored and should be considered in engineering design.
Seasonally Evolving Impacts of Multiyear La Niña on Precipitation in Southern China
Authors: Huang Guansheng , Wang Run , Liu Jingpeng , Gao Li , Liu Minghong , Chen Quanliang
Published: April 2022

The multiyear La Niña (MYLN) is characterized by longer duration, bimodal feature, more continuous circulation anomaly, and different climate impacts compared to the canonical single-peak La Niña. In this study, we focus on the evolving impacts of the MYLN on precipitation in southern China, which mainly occur in boreal winter and summer and correspond to significantly less precipitation and frequency of extreme rainfall. Results show that such impacts have remarkable differences between the first and second half of the MYLN lifecycle. In the first boreal winter when the MYLN reaches its first peak, the precipitation in southern China decreases significantly, while it tends to be insignificantly anomalous in the next winter. In the summer after its first peak, the MYLN has no apparent impact on precipitation in southern China, but when it basically disappears in the next summer, precipitation decreases significantly in southern China. Such seasonally evolving features in the impacts of the MYLN on precipitation in southern China can be mainly interpreted by the patterns of the anomalous cyclonic circulation in northwestern subtropical Pacific during the first peak winter and the decaying summer of the MYLN, which favors an anomalous reduction of moisture supply over southern China.
The Invisible Curriculum’s Influence on Youth’s Self-Identity and Self-Esteem Development
Authors: Nyamai Dinah K.
Published: April 2022

This article sought to determine the role played by the invisible curriculum on young people’s view of self-including their self-identity and self-esteem. This comes against a backdrop of accusations and counter accusations regarding, on whose doorstep should the blame on young people’s vulnerability to risk behavior should be placed on, yet limited research, especially in Kenya, has given due consideration to the invisible curriculum. The invisible curriculum accounts for more than 90% of all Students’ learning experiences including their self-conception or self-identity formation and people tend to behave in ways coherent with the view they have about themselves (self-identity). To fill this gap, a sequential explanatory research design was employed to answer one main questions:what role does accidental lessons arising from learning institutions’ social atmosphere play in young peoples’ self-identity and self-esteem development?The target population was 1,246 and Yamane’s sample size calculation formular was used to determine the sample size which was 486. Stratified random sampling was used in selecting the respondents. A self-report questionnaire with 60-closed ended questions and an interview guide with 14 open-ended questions were used in data collection. The results confirmed that accidental lessons arising from invisible curriculum elements shape young people’s self-concept or self-identity and self-esteem.
Clarifying the Relation Between Epistemic Emotions and Learning by Using Experience Sampling Method and Pre-posttest Design
Authors: Vilhunen Elisa , Turkkila Miikka , Lavonen Jari , Salmela-Aro Katariina , Juuti Kalle
Published: April 2022

Epistemic emotions (surprise, curiosity, enjoyment, confusion, anxiety, frustration and boredom) have an object focus on knowledge or knowledge construction and are thus hypothesized to affect learning outcomes. In the context of upper secondary school science, the present study clarifies this relation by examining the students’ pre- and posttest performance (n = 148 students) and their experiences of situational epistemic emotions (n = 1801 experience sampling method observations). As expected, epistemic emotions correlated with both pre- and posttest performance: curiosity and enjoyment correlated positively, and frustration and boredom correlated negatively with the performance. However, based on structural equation modeling, after controlling for the pretest performance, only boredom was found to have a significant negative effect on posttest performance. The findings underline the complexity of the interplay between emotions and learning. Thus, the state versus trait nature of epistemic emotions, and the implications for research and practice are being discussed.
Reproductive Outcome After GnRH Agonist Triggering With Co-Administration of 1500 IU hCG on the Day of Oocyte Retrieval in High Responders: A Long-Term Retrospective Cohort Study
Authors: Abdulkhalikova Dzhamilyat , Bokal Eda Vrtacnik , Stimpfel Martin , Ciglar Primoz , Korosec Sara
Published: April 2022

While triggering oocyte maturation with GnRH agonist (GnRHa) seems to be safe and effective in terms of the risk of developing OHSS and the number of metaphase II oocytes, it nevertheless results in luteal phase deficiency. To date, strategies have been developed in order to rescue defective luteal phase of GnRHa triggered cycles. Our study aimed to assess the reproductive outcome of GnRHa triggered cycles combined with modified luteal support (1500 IU hCG at the day of oocyte retrieval) in women with high ovarian response and to compare the outcome with hCG triggered cycles in GnRH antagonist IVF-ICSI procedures. A retrospective cohort database review of the results of GnRH antagonist IVF-ICSI cycles was conducted at a tertiary-care IVF center in Ljubljana, Slovenia. A total of 6126 cycles, performed from January 1, 2014, to December 31, 2020, were included in the final analysis. Final oocyte maturation was performed with either 5000, 6500, or 10,000 IU hCG (women with normal ovarian response) or 0.6 mg GnRHa (buserelin), supplemented with 1500 IU hCG on the day of oocyte retrieval (in women with high ovarian response). In cases of excessive ovarian response and/or high risk of OHSS luteal support was not introduced and all good quality blastocysts were frozen. According to significant differences in patients’ age and the number of oocytes in the two groups, matching by age and number of oocytes was performed. No significant differences were observed regarding pregnancy rate per embryo transfer, rate of early pregnancy loss, and livebirth rate per pregnancy between the GnRHa and hCG trigger groups, respectively. A significant difference in the number of developed embryos and blastocysts, as well as the number of frozen blastocysts, was seen in favor of the GnRHa trigger. However, the birth weight in the GnRHa trigger group was significantly lower.

Conclusion

The results of our study support the use of GnRHa for final oocyte maturation in GnRH antagonist IVF cycles in women with high ovarian response. Luteal phase rescue was performed by co-administration of 1500 IU hCG on the day of oocyte retrieval and estradiol and progesterone supplementation. In our experience, such an approach results in a comparable reproductive outcome with hCG trigger group.
Expression and Role of INSL3 in the Fetal Testis
Authors: Ivell Richard , Mamsen Linn Salto , Andersen Claus Yding , Anand-Ivell Ravinder
Published: April 2022

Insulin-like peptide 3 (INSL3) is a small peptide hormone of the insulin-relaxin family which is produced and secreted by the fetal Leydig cells in the testes only. It appears to be undetectable in female fetuses. In the human fetus INSL3 synthesis begins immediately following gonadal sex determination at weeks 7 to 8 post coitum and the peptide can be detected in amniotic fluid 1 to 2 weeks later. INSL3 acts through a unique G-protein-coupled receptor, called RelaXin-like Family Peptide receptor 2 (RXFP2), which is expressed by the mesenchymal cells of the gubernacular ligament linking the testes to the inguinal wall. The role of INSL3 in the male fetus is to cause a thickening of the gubernaculum which then retains the testes in the inguinal region, while the remainder of the abdominal organs grow away in an antero-dorsal direction. This represents the first phase of testis descent and is followed later in pregnancy by the second inguino-scrotal phase whereby the testes pass into the scrotum through the inguinal canal. INSL3 acts as a significant biomarker for Leydig cell differentiation in the fetus and may be reduced by maternal exposure to endocrine disrupting chemicals, such as xenoestrogens or phthalates, leading to cryptorchidism. INSL3 may have other roles within the fetus, but as a Leydig cell biomarker its reduction acts also as a surrogate for anti-androgen action.
Environmental Risk and Management of Herbal-Extraction Residues Induced by the Composition and Metal Binding Properties of DOM
Authors: Yuan Donghai , Cui Yanqi , Kou Yingying , Guo Xujing , Chen Bin
Published: April 2022

As the consumption of Chinese medicine resources increases, the waste of traditional Chinese medicine extraction cannot be disposed of reasonably, which has a serious impact on the environment. Dissolved organic matter (DOM), a crucial fraction in herbal extraction residue, can bond to heavy metals (HMs), creating a potential environmental risk. This study investigated the binding property of herbal extraction residue DOM with Cu(II) via two-dimensional Fourier transform infrared (FTIR) and synchronous fluorescence correlation spectroscopy (2D-COS) in conjunction with parallel factor (PARAFAC) modeling. Through PARAFAC analysis, three kinds of protein components and one kind of fulvic acid can be obtained, and protein-like substances are dominant in the residual DOM of Chinese medicine extracts, becoming the main factor of water quality deterioration. A fluorescence quenching experiment shows that protein-like materials provide the primary binding sites with Cu(II). During the detection, the long-wavelength low-intensity signal will be obscured. The 2D-COS obtained by the 1/9th power transformation can enhance the fluorescence signal so as to get even more information about the binding sites and heterogeneity of DOM and heavy metal ion ligands. The N−H of amine in the protein-like materials could prioritize combining with Cu(II). This study urges that continuous and effective attention be paid to the impact of the herbal extraction residue on the geochemical behavior of HMs.
Characterization of Plasma Extrachromosomal Circular DNA in Gouty Arthritis
Authors: Pang Jingyuan , Pan Xiaoguang , Lin Ling , Li Lei , Yuan Shuai , Han Peng , Ji Xiaopeng , Li Hailong , Wang Can , Chu Zhaobin , Wu Haoru , Fan Guangyi , Du Xiao , Ji Aichang
Published: April 2022

Objective: Extrachromosomal circular DNA elements (eccDNAs) are known for their broad existence in cells and plasma, which may potentially play important roles in many biological processes. Our aim was to identify potentially functional or marked eccDNAs in gout patients.

Methods: The Circle-Seq approach was applied for eccDNA detection from plasma in acute gout patients and healthy controls. Further analysis was performed on the distribution of genomic elements and eccDNA gene annotations in two groups.

Results: We detected 57,216 and 109,683 eccDNAs from the acute gout and healthy control plasma, respectively. EccDNAs were mapped to the reference genome to identify diverse classes of genomic elements and there was no significant difference of eccDNAs on genomic element annotation between gout and control group. A total of 256 eccDNA-associated genes were detected as gout unique eccDNA genes, including COL1A1 and EPB42, which potentially contribute to hyperuricemia and gout, and a couple of genes involved in inflammation or immune response. Enrichment analysis showed that these eccDNA genes were highly correlated with defense response, stress response, and immune and inflammatory responses, including T cell receptor signaling pathway, Fc epsilon RI signaling pathway, and JAK-STAT signaling pathway.

Conclusion: Our discovery reveals the novel potential biological roles of plasma eccDNAs in gouty arthritis.
Topical Application of Tetrandrine Nanoemulsion Promotes the Expansion of CD4+Foxp3+ Regulatory T Cells and Alleviates Imiquimod-Induced Psoriasis in Mice
Authors: Chen Shaokui , Lin Zibei , He Tianzhen , Islam Md Sahidul , Xi Long , Liao Ping , Yang Yang , Zheng Ying , Chen Xin
Published: April 2022

There is compelling evidence that CD4+Foxp3+ regulatory T cells (Tregs) are indispensable in the inhibition of autoimmune inflammatory responses, including psoriasis. Recently, we showed that systemically treatment with tetrandrine (TET), a two-pore channel inhibitor identified from the Chinese herb Stephania tetrandra S. Moor, could promote the proliferative expansion of Tregs in mice through stimulation of TNF-TNFR2 interaction. We thus hypothesized that topical administration of TET might also expand Tregs and consequently inhibit psoriasis. To this end, we developed a TET nanoemulsion and examined its effect on the expansion of Tregs after topical administration on mouse psoriasis induced by imiquimod. The result of our experiment showed that topical treatment with TET nanoemulsion markedly increased the proportion and number of Tregs in the spleen, as well as TNFR2 and Ki-67 expression by Tregs, in WT and TNFR1 KO mice, but not in TNFR2 KO mice. Consequently, TET nanoemulsion potently inhibited IL-17-expressing cells in the spleen and lymph nodes of imiquimod-treated WT mice, accompanied by decreased serum levels of IL-17A, INF-γ, and TNF and their mRNA levels in the flamed lesion. Importantly, TET nanoemulsion treatment markedly inhibited the development of psoriasis-like disease in WT and TNFR1 KO mice but not in TNFR2 KO mice. Therefore, our study indicates that the topical administration of TET could also stimulate the expansion of Tregs through the TNF-TNFR2 pathway. This effect of TET and its analogs may be useful in the treatment of inflammatory skin diseases such as psoriasis.
Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination
Authors: Hernández-Luis Pablo , Aguilar Ruth , Pelegrin-Pérez Judit , Ruiz-Olalla Gemma , García-Basteiro Alberto L. , Tortajada Marta , Moncunill Gemma , Dobaño Carlota , Angulo Ana , Engel Pablo
Published: April 2022

The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerging variants raises concerns about their capacity to evade immune protection provided by natural infection or vaccination. The receptor-binding domain (RBD) of the viral spike protein is the major target of neutralizing antibodies, and viral variants accumulate mutations in this region. In this study, we determined the antibody neutralization capacity against the RBD of SARS-CoV-2 variants Alpha (B.1.1.7), Gamma (P.1), Epsilon (B.1.427), Kappa (B.1.617.1), and Delta (B.1.617.2) in a cohort of healthcare workers naturally infected or receiving COVID-19 mRNA vaccines from Moderna or Pfizer-BioNTech. We show that the five RBD variants displayed an augmented binding to ACE2 compared to the original Wuhan strain. The most significant increase was observed in variants Epsilon and Delta, containing mutation L452R. Using a flow cytometry cell-based assay, we found that SARS-CoV-2-infected subjects presented low levels of RBD-specific neutralizing antibodies against all variants analyzed, except Alpha. However, the neutralizing activity incremented considerably after a subsequent mRNA-vaccine dose, to levels significantly higher than those in naïve individuals receiving two vaccine doses. Importantly, we observed partially impaired neutralizing responses against most variants in fully vaccinated individuals. Variants Gamma and Kappa encompassing RBD E484K/Q mutations presented the highest neutralizing resistance. Furthermore, a wide heterogeneity in the magnitude of RBD-specific neutralizing responses against all tested SARS-CoV-2 variants following both mRNA vaccines was detected. Altogether, our findings provide important knowledge regarding SARS-CoV-2 vaccine-induced immunity, and should be very useful to guide future vaccination regimens and personalized vaccine approaches.
Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis
Authors: Jiang Jie , Zhan Xinli , Qu Haishun , Liang Tuo , Li Hao , Chen Liyi , Huang Shengsheng , Sun Xuhua , Jiang Wenyong , Chen Jiarui , Chen Tianyou , Yao Yuanlin , Wu Shaofeng , Zhu Jichong , Liu Chong
Published: April 2022

Introduction

The specific pathogenesis of ankylosing spondylitis (AS) remains unclear, and our study aimed to investigate the possible pathogenesis of AS.

Materials and Methods

Two datasets were downloaded from the GEO database to perform differentially expressed gene analysis, GO enrichment analysis, KEGG pathway analysis, DO enrichment analysis, GSEA analysis of differentially expressed genes, and construction of diagnostic genes using SVM and WGCNA along with Hypoxia-related genes. Also, drug sensitivity analysis was performed on diagnostic genes. To identify the differentially expressed immune genes in the AS and control groups, we analyzed the composition of immune cells between them. Then, we examined differentially expressed genes in three AS interspinous ligament specimens and three Degenerative lumbar spine specimens using high-throughput sequencing while the immune cells were examined using the neutrophil count data from routine blood tests of 1770 HLA-B27-positive samples and 7939 HLA-B27-negative samples. To assess the relationship between ANXA3 and SORL1 and disease activity, we took the neutrophil counts of the first 50 patients with above-average BASDAI scores and the last 50 patients with below-average BASDAI scores for statistical analysis. We used immunohistochemistry to verify the expression of ANXA3 and SORL1 in AS and in controls.

Results

ANXA3 and SORL1 were identified as new diagnostic genes for AS. These two genes showed a significant differential expression between AS and controls, along with showing a significant positive correlation with the neutrophil count. The results of high-throughput sequencing verified that these two gene deletions were indeed differentially expressed in AS versus controls. Data from a total of 9707 routine blood tests showed that the neutrophil count was significantly higher in AS patients than in controls (p < 0.001). Patients with AS with a high BASDAI score had a much higher neutrophil count than those with a low score, and the difference was statistically significant (p < 0.001). The results of immunohistochemistry showed that the expression of ANXA3 and SORL1 in AS was significantly higher than that in the control group.

Conclusion

Upregulated of ANXA3, SORL1, and neutrophils may be a key factor in the progression of Ankylosing spondylitis.
18F-Prostate-Specific Membrane Antigen and 18F-Fluorodeoxyglucose PET/CT Unmasked the Characteristics of Prostate Lymphoma: A Case Report and Literature Review
Authors: Jiang Fan , Fan Junjie , Liang Hua , Duan XiaoYi , He Dalin , Wu Kaijie
Published: April 2022

Prostate lymphoma (PL) is rarely observed and may be concurrently presented with prostate adenocarcinoma. Moreover, the appearance of PL on conventional imaging is similar with prostate adenocarcinoma. Thus, most of PL is diagnosed through prostate biopsy, or accidentally found in the specimens of surgery. Prostate-specific membrane antigen (PSMA) PET/CT has improved the management of prostate adenocarcinoma. While, the question regarding whether it benefits the discovery of the characteristics of PL is unknown. A 32-year-old man presented with worsening dysuria for 1 month, and the prostate-specific antigen (PSA) concentration was normal. While the pelvic MRI showed a mass in the prostate and multiple enlarged lymph nodes in the bilateral inguinal area. Then, the diagnosis of prostate adenocarcinoma was considered, but the serum PSA was normal and he was younger than most patients. So, 18F-PSMA PET/CT was then performed to further reveal the characteristics of the lesion and guide biopsy. However, there was no abnormal PSMA uptake in the lesion of the prostate and lymph nodes of the pelvic cavity and bilateral inguinal area. These lesions presented with increased glucose metabolism on fluorodeoxyglucose (FDG) PET/CT, and the prostate biopsy was then performed. PL was confirmed based on the results of the histopathologic examination, and the patient subsequently received systemic chemotherapy plus radiotherapy. Fortunately, the symptoms and the lesions completely disappeared after radiotherapy. The clinical symptoms of PL are atypical, and PL and adenocarcinoma may be concurrently presented. Moreover, distinguishing PL from prostate adenocarcinoma based on the appearance of conventional imaging is difficult. As opposed to prostate adenocarcinoma, a high FDG-avidity and low PSMA uptake by lymphoma either in the prostate or metastases are seen. So, PSMA PET/CT combined with FDG PET/CT can non-invasively identify the characteristics and origin of PL.
The Risk of Hearing Impairment From Ambient Air Pollution and the Moderating Effect of a Healthy Diet: Findings From the United Kingdom Biobank
Authors: Yuan Lanlai , Li Dankang , Tian Yaohua , Sun Yu
Published: April 2022

The link between hearing impairment and air pollution has not been established, and the moderating effect of a healthy diet has never been investigated before. The purpose of this study was to investigate the association between air pollution and hearing impairment in British adults aged 37–73 years, and whether the association was modified by a healthy diet. We performed a cross-sectional population-based study with 158,811 participants who provided data from United Kingdom Biobank. A multivariate logistic regression model was used to investigate the link between air pollution and hearing impairment. Subgroup and effect modification analyses were carried out according to healthy diet scores, gender, and age. In the fully adjusted model, we found that exposure to PM10, NOX, and NO2 was associated with hearing impairment [PM10: odds ratio (OR) = 1.15, 95% confidence interval (95% CI) 1.02–1.30, P = 0.023; NOX: OR = 1.02, 95% CI 1.00–1.03, P = 0.040; NO2: OR = 1.03, 95% CI 1.01–1.06, P = 0.044], while PM2.5 and PM2.5 absorbance did not show similar associations. We discovered an interactive effect of age and air pollution on hearing impairment, but a healthy diet did not. The findings suggested that exposure to PM10, NOX and NO2 was linked to hearing impairment in British adults, whereas PM2.5 and PM2.5 absorbance did not show similar associations. These may help researchers focus more on the impact of air pollution on hearing impairment and provide a basis for developing effective prevention strategies.
Origin of Multisynaptic Corticospinal Pathway to Forelimb Segments in Macaques and Its Reorganization After Spinal Cord Injury
Authors: Ninomiya Taihei , Nakagawa Hiroshi , Inoue Ken-ichi , Nishimura Yukio , Oishi Takao , Yamashita Toshihide , Takada Masahiko
Published: April 2022

Removal of the monosynaptic corticospinal pathway (CSP) terminating within the forelimb segments severely impairs manual dexterity. Functional recovery from the monosynaptic CSP lesion can be achieved through the remaining multisynaptic CSP toward the forelimb segments. In the present study, we applied retrograde transsynaptic labeling with rabies virus to a monkey model of spinal cord injury. By injecting the virus into the spinal forelimb segments immediately after the monosynaptic CSP lesion, we showed that the contralateral primary motor cortex (M1), especially its caudal and bank region (so-called “new” M1), was the principal origin of the CSP linking the motor cortex to the spinal forelimb segments disynaptically (disynaptic CSP). This forms a striking contrast to the architecture of the monosynaptic CSP that involves extensively other motor-related areas, together with M1. Next, the rabies injections were made at the recovery period of 3 months after the monosynaptic CSP lesion. The second-order labeled neurons were located in the ipsilateral as well as in the contralateral “new” M1. This indicates that the disynaptic CSP input from the ipsilateral “new” M1 is recruited during the motor recovery from the monosynaptic CSP lesion. Our results suggest that the disynaptic CSP is reorganized to connect the ipsilateral “new” M1 to the forelimb motoneurons for functional compensation after the monosynaptic CSP lesion.
Elevated Serum Lactate Dehydrogenase Predicts Unfavorable Outcomes After rt-PA Thrombolysis in Ischemic Stroke Patients
Authors: Jin Huijuan , Bi Rentang , Hu Jichuan , Xu Da , Su Ying , Huang Ming , Peng Qiwei , Li Zhifang , Chen Shengcai , Hu Bo
Published: April 2022

Background and Purpose

Currently, acute ischemic stroke (AIS) is one of the most common and serious diseases in the world and is associated with very high mortality and morbidity even after thrombolysis therapy. This study aims to research the relationship between lactic dehydrogenase (LDH) and prognosis in AIS patients treated with intravenous rtPA.

Method

This study (a Multicenter Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke, TRAIS) included 527 AIS patients in 5 cooperative medical institutions in China from January 2018 to February 2021. The primary outcome was major disability and death within 3 months (mRS score of 3–6), and the secondary outcomes were early neurological improvement (ENI), early neurological deterioration (END), moderate-severe cerebral edema (CE), and symptomatic intracranial hemorrhage (sICH).

Results

The mean age of the 527 patients was 65.6 ± 11.7 years, and the median baseline NIHSS score was 4 (interquartile range, 2–7). The median serum LDH level was 184 U/L (interquartile range, 163–212 U/L). In total, 287 (54.5%) patients acquired ENI, 68 (13.0%) patients suffered END, 53 (12.1%) patients were observed with moderate-severe CE, and 28 (6.2%) patients showed sICH. Within 3 months, 127 (25.15%) patients experienced the primary outcome and 42 (8.3%) patients died. Serum LDH levels before thrombolysis showed an independent association with the risk of primary outcome [adjusted odds ratio, 3.787; (95% CI, 1.525–9.404); P = 0.014]. When log-transformed LDH increased each standard deviation, the risk of primary outcome was raised by 80.1% (95% CI, 28.9–251.7%). A positive linear dependence between the risk of primary outcome and serum LDH levels (P of linearity = 0.0248, P of non-linearity = 0.8284) was shown in multivariable-adjusted spline regression models. Pre-thrombolysis LDH quartile also provided a conventional risk model and significant improvement of the prediction for clinical outcomes, with a net reclassification improvement index (NRI) = 41.86% (P < 0.001) and integrated discrimination improvement (IDI) = 4.68% (P < 0.001).

Conclusions

Elevated serum LDH levels predicted unfavorable clinical outcomes after intravenous thrombolysis in AIS patients.
Evaluating the Modulation of the Acoustic Startle Reflex in Children and Adolescents via Vertical EOG and EEG: Sex, Age, and Behavioral Effects
Authors: Giannopoulos Anastasios E. , Zioga Ioanna , Papageorgiou Panos , Pervanidou Panagiota , Makris Gerasimos , Chrousos George P. , Stachtea Xanthi , Capsalis Christos , Papageorgiou Charalabos
Published: April 2022

Acoustic startle reflex (ASR) constitutes a reliable, cross-species indicator of sensorimotor and inhibitory mechanisms, showing distinct signature in cognitive aging, sex, and psychopathological characterization. ASR can be modulated by the prepulse inhibition (PPI) paradigm, which comprises the suppression of reactivity to a startling stimulus (pulse) following a weak prepulse (30- to 500-ms time difference), being widely linked to inhibitory capabilities of the sensorimotor system. If the prepulse–pulse tones are more clearly separated (500–2,000 ms), ASR amplitude is enhanced, termed as prepulse facilitation (PPF), reflecting sustained or selective attention. Our study aimed to investigate early-life sensorimotor sex/age differences using Electroencephalographic recordings to measure muscular and neural ASR in a healthy young population. Sixty-three children and adolescents aged 6.2–16.7 years (31 females) took part in the experiment. Neural ASR was assessed by two different analyses, namely, event-related potentials (ERPs) and first-derivative potentials (FDPs). As expected, PPF showed enhanced responses compared with PPI, as indicated by eyeblink, ERP and FDP measures, confirming the gating effect hypothesis. Sex-related differences were reflected in FDPs, with females showing higher ASR than males, suggesting increased levels of poststartle excitability. Intragroup age effects were evaluated via multipredictor regression models, noticing positive correlation between age versus eyeblink and ERP responses. Attention-related ERPs (N100 and P200) showed distinct patterns in PPI versus PPF, potentially indicative for alternative attentional allocation and block-out of sensory overload. Screening measures of participants’ neurodevelopmental (assessed by Wechsler Intelligence Scale for Children) and behavioral (assessed by Child Behavior Checklist) markers were also associated with increased N100/P200 responses, presumably indexing synergy between perceptual consistency, personality profiling, and inhibitory performance. Conclusively, modulation of ASR by PPI and PPF is associated with biological sex and internal/external personality traits in childhood and adolescence, potentially useful to guide symptomatology and prevention of psychopathology.
Functional and Nutraceutical Compounds of Tomatoes as Affected by Agronomic Practices, Postharvest Management, and Processing Methods: A Mini Review
Authors: Lima Giuseppina Pace Pereira , Gómez Héctor Alonzo Gómez , Seabra Junior Santino , Maraschin Marcelo , Tecchio Marco Antonio , Borges Cristine Vanz
Published: April 2022

Tomatoes and their by-products are indisputable sources of substances with antioxidants properties. Several factors limit the production and influence the nutritional and antioxidant quality of tomato fruit. However, consumers can benefit from the effects of environmental factors, such as water and hydric stress, UV radiation, agronomic practices, among others, which lead to changes in the content of secondary metabolites in tomatoes. Molecules as phenolic compounds, carotenoids, and biogenic amines are often formed in response to environmental adversities. In this way, the consumption of tomato fruits or their by-products with higher levels of antioxidants may be important adjuvants in the prevention or reduction of diseases. In this mini-review, we will present how pre- and postharvest conditions may influence the content of some bioactive compounds in tomatoes. Furthermore, we will present how some heat processing methods may change the antioxidant content, as well as, the functional and nutritional properties of the final product.
Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports
Authors: Zeng Yue , Feng Yuanqing , Fu Guihua , Jiang Junlan , Liu Xiaohan , Pan Yue , Hu Chunhong , Liu Xianling , Wu Fang
Published: April 2022

The acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable and heterogeneous. The strategies to overcome acquired resistance are significant. For patients with secondary T790M-positive after early generation EGFR-TKIs, osimertinib is the standard second-line therapy. In patients resistant to prior early generation EGFR-TKIs, the acquired T790M mutation overlaps with other driver gene resistance, such as HER2-and MET amplification, accounting for 4–8%. The efficacy of osimertinib is unclear in patients with concurrent multiple driver gene resistance. We here report a patient who acquired EGFR T790M, STRN-ALK fusion, and EGFR amplification after gefitinib progression and subsequent MET amplification acquired from osimertinib. The other patient acquired EGFR T790M and MET amplification post-dacomitinib and acquired CCDC6-RET fusion after osimertinib treatment. Besides, subsequent new bypass activations were the possible resistance mechanisms to second-line osimertinib. Both patients had progression-free survival (PFS) less than 4 months and limited benefits from osimertinib second-line therapy. The T790M accompanying driver gene resistance will be a new subtype after EGFR-TKIs progression, needing effective treatment options.
Clostridium butyricum RH2 Alleviates Chronic Foot Shock Stress-Induced Behavioral Deficits in Rats via PAI-1
Authors: Zhang Wenying , Ding Tingyu , Zhang Hong , Chen Yuping , Liu Liping , Jiang Jinjin , Song Siyuan , Cheng Hao , Wu Changhao , Sun Jihu , Wu Qin
Published: April 2022

Recent investigations have demonstrated that the chronic stress-induced behavioral disorders can be ameliorated by probiotics including Clostridium butyricum (C. butyricum) via the gut-brain-axis. However, the molecular mechanisms underlying the beneficial effects of C. butyricum on brain remain largely unknown. Here, we investigated whether chronic foot shock stress (CFSS) paradigm used for a hypertensive animal model could induce mood disorders such as anxiety, depression and cognitive impairments. Then, we assessed the impact of C. butyricum RH2 on the behavior disorders and neurobiological alterations in the hippocampus. Male Sprague-Dawley (SD) rats received intermittent electric shocks for consecutive 14 days and were treated with C. butyricum RH2 for 17 days. Anxiety- or depression-like behaviors were evaluated by open field test (OFT), and elevated plus maze (EPM). The Morris water maze test (MWM) was used to evaluate the cognitive functions. CFSS intervention led to mild anxiety- or depression-like behavior or cognitive impairment and C. butyricum RH2 treatment reversed the CFSS-induced symptoms. The serum ACTH or CORT was increased following CFSS but was completely reversed by C. butyricum RH2 treatment. In the hippocampus of CFSS rats, the expressions of BDNF and TrkB were downregulated but proBDNF and P75NTR were upregulated. These expression changes were partially reversed by C. butyricum RH2, suggesting a mode of action on BDNF and proBDNF balance. CFSS exposure resulted in downregulation of tissue-type plasminogen activator (tPA) but upregulation of plasminogen activator inhibitor 1(PAI-1), which could contribute to the decrease in BDNF by reduced conversion from proBDNF to BDNF in the hippocampus. C. butyricum RH2 treatment reversed the upregulated PAI-1 but not the downregulated tPA, which was in parallel with the amelioration of behavioral abnormalities, suggesting a novel tPA independent mechanism for PAI-1 action. Our results demonstrate for the first time that C. butyricum RH2 attenuates stress-induced behavior disorders via inhibiting the expression of brain PAI-1.