bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel investigations in retinoic-acid-induced cleft palate about the gut microbiome of pregnant mice
Authors: Wang Yijia , Chen Jing , Wang Xiaotong , Guo Cui , Peng Xia , Liu Ying , Li Tianli , Du Juan 
Published: December 2022

IntroductionCleft palate (CP) is one of the most common congenital birth defects in the craniofacial region, retinoic acid (RA) gavage is the most common method for inducing cleft palate model. Although several mechanisms have been proposed to illuminate RA-induced cleft palate during embryonic development, these findings are far from enough. Many efforts remain to be devoted to studying the etiology and pathogenesis of cleft palate. Recent research is gradually shifting the focus to the effect of retinoic acid on gut microbiota. However, few reports focus on the relationship between the occurrence of CP in embryos and gut microbiota.MethodsIn our research, we used RA to induce cleft palate model for E10.5 the feces of 5 RA-treated pregnant mice and 5 control pregnant mice were respectively metagenomics analysis.ResultsCompared with the control group, Lactobacillus in the gut microbiome the RA group was significantly increased. GO, KEGG and CAZy analysis of differentially unigenes demonstrated the most abundant metabolic pathway in different groups, lipopolysaccharide biosynthesis, and histidine metabolism.DiscussionOur findings indicated that changes in the maternal gut microbiome palatal development, which might be related to changes in Lactobacillus and These results provide a new direction in the pathogenesis of CP induced by RA.
A multicenter investigation of 2,773 cases of bloodstream infections based on China antimicrobial surveillance network (CHINET)
Authors: Hu Fupin , Yuan Lili , Yang Yang , Xu Yuanhong , Huang Ying , Hu Yunjian , Ai Xiaoman , Zhuo Chao , Su Danhong , Shan Bin , Du Yan , Yu Yunsong , Lin Jie , Sun Ziyong , Chen Zhongju , Xu Yingchun , Zhang Xiaojiang , Wang Chuanqing , He Leiyan , Ni Yuxing , Zhang Yibo , Lin Dongfang , Zhu Demei , Zhang Yingyuan 
Published: December 2022

BackgroundBloodstream infections (BSIs), especially hospital-acquired BSIs, are a major cause of morbidity and mortality. However, the details about the pathogens and antimicrobial resistance profile of BSIs across China are still lacking.MethodsAn investigation was conducted in 10 large teaching hospitals from seven geographic regions across China in 2016 based on China Antimicrobial Surveillance Network (CHINET) to profile the clinical and etiological features of BSIs.ResultsA total of 2,773 cases of BSIs were identified, a majority (97.3%) of which were monomicrobial. Overall, 38.4% (1,065/2,773) were community-acquired BSIs (CABSIs), and 61.6% (1,708/2,773) were hospital-acquired BSIs (HABSIs). Of the 2,861 pathogenic BSI isolates, 67.5% were Gram-negative bacteria, 29.6% were Gram-positive bacteria, and 2.9% were fungi. The top BSI pathogens were Escherichia coli, Klebsiella pneumoniae, coagulase-negative Staphylococci (CNS), Staphylococcus aureus, Enterococci, and Acinetobacter baumannii. Escherichia coli and K. pneumoniae isolates showed low susceptibility to penicillins, cephalosporins (except ceftazidime and cefepime), and ampicillin-sulbactam (13.1%–43.4% susceptible); moderate susceptibility (about 60% susceptible) to ceftazidime, cefepime, and aztreonam; and high susceptibility (&gt;90%) to β-lactam/β-lactamase inhibitor combinations other than ampicillin-sulbactam, except K. pneumoniae strains to piperacillin-tazobactam (59.2% susceptible). HABSIs were associated with significantly higher prevalence of carbapenem-resistant and extended-spectrum β-lactamases-producing K. pneumoniae, methicillin-resistant S. aureus, methicillin-resistant CNS, and ampicillin-resistant Enterococci than CABSIs. Overall, 42.0% of the BSI due to S. aureus strains were resistant to methicillin.ConclusionsThe findings about BSIs in teaching hospitals across China add more scientific evidence to inform the appropriate management of the disease.
The clinical significance of in-house metagenomic next-generation sequencing for bronchoalveolar lavage fluid diagnostics in patients with lower respiratory tract infections
Authors: Li Shixiao , Qin Jiajia , Zhou Peng , Peng Minfei , Qian Jiao , Cai Yingying , Shi Qingxin , Tung Tao-Hsin , Shen Bo , Yu Sufei 
Published: December 2022

ObjectiveMetagenomic next-generation sequencing (mNGS) technology has the potential to detect a wide range of pathogenic microorganisms. However, reports on the diagnostic value and clinical significance of different platforms of mNGS for patients with lower respiratory tract infections (LRTIs) remain scarce.MethodsA total of 306 patients with suspected LRTIs were enrolled from January 2019 to December 2021. The diagnostic performance of conventional methods and mNGS on bronchoalveolar lavage fluid (BALF) were compared. BALF mNGS was performed using a commercial and an in-house laboratory. The diagnostic value and the clinical implications of mNGS for LRTIs were analyzed for the different platforms.ResultsThe positive rate of mNGS in the in-house group was higher than that in the commercial group (85.26% vs. 70.67%, p &lt; 0.001). mNGS significantly increased the pathogen detection rate compared with conventional methods [from 70.67% vs. 22.67% (p &lt; 0.001) to 85.26% vs. 30.77% (p &lt; 0.001)]. The pathogens detected using mNGS included bacteria, fungi, viruses, and atypical pathogens. The in-house platform performed well on a wider spectrum of microbial distribution. Furthermore, it showed an advantage in detecting mixed pathogens in immunocompromised patients. Among the mNGS positive cases, 34 (32.0%) cases had their antibiotics adjusted in the commercial group, while 51 (38.3%) cases had a change of treatment in the in-house group. Moreover, the turnaround time of mNGS and the time from mNGS to discharge in the in-house group were significantly shorter than those in the commercial group.ConclusionIn-house mNGS had a higher detection rate and can show a wider spectrum of pathogens, with potential benefits for the clinic by shortening the turnaround time and hospitalization, and it may be more suitable for clinical microbiology laboratories.
Predictors in language proficiency of young children with presumed developmental language disorder within the setting of early language intervention
Authors: Vermeij Bernadette A. M. , Wiefferink Carin H. , Scholte Ron H. J. , Knoors Harry 
Published: December 2022

IntroductionIn the Netherlands, early language intervention is offered to children with presumed Developmental Language Disorder (DLD). The intervention is a combination of group language intervention, individual speech and language therapy and parent-implemented language intervention. During the intervention, some children show more language progress than others. It is unclear what might explain this variation. In this study, we therefore explored to what extent child, parental, and treatment factors were predictive for receptive and expressive language outcomes of young children with presumed DLD during early language intervention.MethodsFour multiple regression analyses were conducted with four child factors [pre-test receptive syntax, behavior (internalizing and externalizing), non-verbal cognitive ability and gender], one parental factor (parental stress) and one treatment factor (treatment duration) as predictors and receptive and expressive language post-test scores as outcomes. For each language post-test, the corresponding pre-test language measure was also added. Data of 183 children with presumed DLD were included.ResultsReceptive syntax problems were an important predictor of expressive language outcomes. Findings also showed a longer treatment duration to be a predictor of progress in expressive vocabulary. Internalizing behavior, externalizing behavior, non-verbal cognitive ability, gender and parental stress did not contribute to predicting language outcomes. Lower pre-intervention language scores led to lower corresponding post-intervention language scores.ConclusionsProfessionals may need to be aware that children with receptive problems may be indicative of more pervasive impairment and that it can be more difficult to improve their language problems. In fact, children with receptive language problems may need both more and different approaches. The finding that the level of the pre-intervention score has an essential influence on language outcomes underlines the importance of early diagnosis and early intervention, to prevent language problems increasing.
Rapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy
Authors: Dillon Hayley T. , Foulkes Stephen , Horne-Okano Yuki A. , Kliman David , Dunstan David W. , Daly Robin M. , Fraser Steve F. , Avery Sharon , Kingwell Bronwyn A. , La Gerche Andre , Howden Erin J. 
Published: December 2022

IntroductionAllogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure for high-risk hematological malignancy; however, long-term survivors experience increased cardiovascular morbidity and mortality. It is unclear how allo-HCT impacts cardiovascular function in the short-term. Thus, this 3-month prospective study sought to evaluate the short-term cardiovascular impact of allo-HCT in hematological cancer patients, compared to an age-matched non-cancer control group.MethodsBefore and ~3-months following allo-HCT, 17 hematological cancer patients (45 ± 18 years) underwent cardiopulmonary exercise testing to quantify peak oxygen uptake (VO2peak)—a measure of integrative cardiovascular function. Then, to determine the degree to which changes in VO2peak are mediated by cardiac vs. non-cardiac factors, participants underwent exercise cardiac MRI (cardiac reserve), resting echocardiography (left-ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), dual-energy x-ray absorptiometry (lean [LM] and fat mass [FM]), blood pressure (BP) assessment, hemoglobin sampling, and arteriovenous oxygen difference (a-vO2diff) estimation via the Fick equation. Twelve controls (43 ± 13 years) underwent identical testing at equivalent baseline and 3-month time intervals.ResultsSignificant group-by-time interactions were observed for absolute VO2peak (p = 0.006), bodyweight-indexed VO2peak (p = 0.015), LM (p = 0.001) and cardiac reserve (p = 0.019), which were driven by 26, 24, 6, and 26% reductions in the allo-HCT group (all p ≤ 0.001), respectively, as no significant changes were observed in the age-matched control group. No significant group-by-time interactions were observed for LVEF, GLS, FM, hemoglobin, BP or a-vO2diff, though a-vO2diff declined 12% in allo-HCT (p = 0.028).ConclusionIn summary, allo-HCT severely impairs VO2peak, reflecting central and peripheral dysfunction. These results indicate allo-HCT rapidly accelerates cardiovascular aging and reinforces the need for early preventive cardiovascular intervention in this high-risk group.
Challenges in the treatment of late-identified untreated congenital adrenal hyperplasia due to CYP11B1 deficiency: Lessons from a developing country
Authors: Utari Agustini , Faradz Sultana M. H. , Ediati Annastasia , Rinne Tuula , Ariani Mahayu Dewi , Juniarto Achmad Zulfa , Drop Stenvert L. S. , van Herwaarden Antonius E. , Claahsen-van der Grinten Hedi L. 
Published: December 2022

BackgroundCongenital Adrenal Hyperplasia (CAH) due to CYP11B1 is a rare autosomal recessive adrenal disorder that causes a decrease in cortisol production and accumulation of adrenal androgens and steroid precursors with mineralocorticoid activity. Clinical manifestations include cortisol deficiency, ambiguous genitalia in females (differences of sex development (DSD)), and hypertension. Medical treatment recommendations are well defined, consisting of glucocorticoid treatment to substitute glucocorticoid deficiency and consequently normalize adrenal androgen and precursors levels. Current guidelines also emphasize the need for specialized multidisciplinary DSD teams and psychosocial support. In many developing countries, care for DSD patients, especially when caused by an adrenal disease, is challenging due to the lack of infrastructure, knowledge, and medication.ObjectiveThe study aims to report the conflicting decision-making process of medical treatment and sex assignment in late-identified CAH patients in developing countries.MethodsWe describe the clinical and biochemical findings and the psychological assessment of five affected but untreated family members with CAH due to CYP11B1 deficiency.ResultsAll patients had a 46,XX karyotype, ambiguous genitalia, low cortisol levels, and hypertension. Two identified as males, two as females, and one had undecided gender. The patients were counselled that refusing treatment will lead to infertility and the potential risk of developing Addisonian crisis and severe hypertension. However, all 46,XX CAH males refused treatment with glucocorticoids due to the expected lowering of adrenal androgens as their main source of testosterone. None of the patients developed Addisonian crisis, probably due to some residual cortisol activity and glucocorticoid activity of elevated adrenal steroid precursors.ConclusionMedical treatment and sex assignment in late-identified 46,XX CAH patients in Indonesia may often depend on local and cultural factors. The management of DSD conditions may have to be individualized and integrated into the psychological and social context of the affected family.
The elevated visceral adiposity index increases the risk of hyperuricemia in Chinese hypertensive patients: A cross-sectional study
Authors: Song XiaoLi , Liu Hui , Zhu Jian , Zhou Wei , Wang Tao , Yu Chao , Zhu Lingjuan , Cheng Xiaoshu , Bao Huihui 
Published: December 2022

BackgroundUncertainty still remained about the relationship between visceral adiposity index (VAI) and hyperuricemia. The aim of this study was to investigate whether VAI was an independent risk factor for hyperuricemia in hypertensive Chinese patients.MethodsA cross-sectional study including 13176 hypertensive participants (6478 males) recruited from Wuyuan County, Jiangxi province, was conducted. All patients received anthropometric measurements, completed questionnaires and provided blood samples for biochemical testing. VAI was calculated by waist circumference, BMI, triglyceride and high-density lipoprotein cholesterol. Hyperuricemia was defined as serum uric acid ≥ 7 mg/dL in men and ≥ 6 mg/dL in women.ResultsOverall, the average level of uric acid was 7.8 ± 2.0 mg/dL in males and 6.34 ± 1.78 in females and prevalence of hyperuricemia was 61.4% and 51.30%, respectively. In multivariate logistic regression analysis, the risk of hyperuricemia increased 1.77 times and 1.88 times with the increase of ln VAI in males (OR:1.77, 95% CI: 1.62, 1.94) and females (OR:1.88, 95% CI: 1.73, 2.04). For males, compared to quartile 1, the risk of hyperuricemia in the second, third and the forth quartile of visceral adiposity index were 1.34 (95% CI: 1.14, 1.57),1.82(95% CI: 1.54, 2.14) and 2.97 (95% CI: 2.48, 3.57). For females, compared to quartile 1, the risk of hyperuricemia in the second, third and the forth quartile of visceral adiposity index were 1.48 (95% CI: 1.28, 1.72), 1.99 (95% CI: 1.71, 2.32) and 2.92 (95% CI: 2.50, 3.42).ConclusionsThis study found that VAI was an independent risk factor for hyperuricemia among hypertensive patients, which may provide some strategies for reducing the level of uric acid.
Construction of novel hypoxia-related gene model for prognosis and tumor microenvironment in endometrial carcinoma
Authors: Chen Junfeng , Wang Guocheng , Zhang Donghai , Luo Xiaomei , Zhang Da , Zhang Yongli 
Published: December 2022

IntroductionEndometrial cancer is currently one of the three most common female reproductive cancers, which seriously threatens women’s lives and health. Hypoxia disrupts the tumor microenvironment, thereby affecting tumor progression and drug resistance.MethodsWe established hypoxia-related gene model to predict patient prognosis and 1-, 3-, and 5-year overall survival rates. Then, the expression level of hypoxia-related genes and survival data were extracted for comprehensive analysis by Cox regression analysis, and the model was established.ResultsWe analyzed the survival and prognosis of patients in the high and low-risk groups. The Kaplan-Meier curve showed that the low-risk group is associated with a better survival rate. The 1-, 3-, and 5-year AUC values of the model were 0.680, 0.698, and 0.687, respectively. Finally, we found that LAG3 may be a potential immune checkpoint for endometrial cancer.ConclusionWe found four hypoxia-related genes (ANXA2, AKAP12, NR3C1, and GPI) associated with prognosis. The hypoxia-related gene model can also predict prognosis and tumor microenvironment in endometrial cancer.
Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort
Authors: Lv Zhengtao , Cui Jiarui , Zhang Jiaming 
Published: December 2022

ObjectiveHyperuricemia and gout have become gradually more common. The effect of serum urate on organism aging and systematic inflammation is not determined. This study aims to evaluate whether serum urate is causally associated with cellular aging markers and serum inflammation markers.MethodsA Mendelian randomization study was performed on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with a genome-wide significance level were selected as instrumental variables for leukocyte telomere length (LTL), and serum soluble makers of inflammation (CRP, IL-6, TNF-α, and IGF-1). Standard inverse variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods were used for sensitivity analysis.ResultsAn inverse causal association of genetically predicted serum urate levels and LTL was found using IVW method (OR: 0.96, 95%CI 0.95, 0.97; β=-0.040; SE=0.0072; P=4.37×10-8). The association was also supported by MR results using MR-Egger method and weighted median method. The MR-PRESSO analysis and leave-one-out sensitivity analysis supported the robustness of the combined results. In terms of other aging-related serum biomarkers, there was no evidence supporting a causal effect of serum urate on CRP, IL-6, TNF-α, or IGF-1 levels.ConclusionsSerum urate levels are negatively associated with telomere length but are not associated with serum soluble indicators of inflammation. Telomere length may be a critical marker that reflects urate-related organismal aging and may be a mechanism in the age-related pathologies and mortality caused by hyperuricemia.
Immunoproteasome inhibition attenuates experimental psoriasis
Authors: del Rio Oliva Marta , Mellett Mark , Basler Michael 
Published: December 2022

IntroductionPsoriasis is an autoimmune skin disease associated with multiple comorbidities. The immunoproteasome is a special form of the proteasome expressed in cells of hematopoietic origin.MethodsThe therapeutic use of ONX 0914, a selective inhibitor of the immunoproteasome, was investigated in Card14ΔE138+/- mice, which spontaneously develop psoriasis-like symptoms, and in the imiquimod murine model.ResultsIn both models, treatment with ONX 0914 significantly reduced skin thickness, inflammation scores, and pathological lesions in the analyzed skin tissue. Furthermore, immunoproteasome inhibition normalized the expression of several pro-inflammatory genes in the ear and significantly reduced the inflammatory infiltrate, accompanied by a significant alteration in the αβ+ and γδ+ T cell subsets.DiscussionONX 0914 ameliorated psoriasis-like symptoms in two different murine psoriasis models, which supports the use of immunoproteasome inhibitors as a therapeutic treatment in psoriasis.
The immunological characteristics of TSPAN1 expressing B cells in autoimmune hepatitis
Authors: Ou Yiyan , Chen Ruiling , Qian Qiwei , Cui Nana , Miao Qi , Tang Ruqi , You Zhengrui , Ma Xiong , Wang Qixia 
Published: December 2022

Background and aimsTetraspanin proteins are closely related to the functional changes of B cells, including antigen presentation, production of cytokines, and transduction. We aim to explore the potential role of Tetraspanin 1 (TSPAN1) in the biological activities of B cells in AIH.Methods and resultsHerein, this study found that numbers of cells expressing TSPAN1 were significantly increased in AIH patients compared to PBC, chronic hepatitis B, and healthy control (P &lt; 0.0001). Moreover, there was a positive correlation between numbers of TSPAN1+ cells and AIH disease severity (P &lt; 0.0001). Immunofluorescence staining further confirmed that TSPAN1 was primarily expressed on CD19+ B cells. Flow-cytometric analysis showed that TSPAN1+ B cells secreted more inflammatory cytokines and expressed higher level of CD86 than TSPAN1- B cells. Furthermore, compared with TSAPN1- cells, the expression of CXCR3 on TSPAN1+ cells was also higher. Meanwhile, CXCL10, the ligand of CXCR3, was significantly elevated in the liver of AIH (P &lt; 0.01) and had positive correlation with the quantities of TSPAN1 (P &lt; 0.05). Interestingly, the numbers of TSPAN1+ B cells were decreased in AIH patients after immunosuppressive therapy.ConclusionsTSPAN1+ B cells in the liver may promote the progression of AIH via secreting cytokines and presenting antigens. The chemotactic movement of TSPAN1+ B cells toward the liver of AIH was possibly due to CXCR3 - CXCL10 interaction.
Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequelae of SARS-CoV-2 infection
Authors: Dean Logan S. , Devendra Gehan , Jiyarom Boonyanudh , Subia Natalie , Tallquist Michelle D. , Nerurkar Vivek R. , Chang Sandra P. , Chow Dominic C. , Shikuma Cecilia M.  , Park Juwon 
Published: December 2022

BackgroundLow-density granulocytes (LDGs) are a distinct subset of neutrophils whose increased abundance is associated with the severity of COVID-19. However, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on LDG levels and phenotypic alteration remain unexplored.MethodsUsing participants naïve to SARS-CoV-2 (NP), infected with SARS-CoV-2 with no residual symptoms (NRS), and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC), we compared LDG levels and their phenotype by measuring the expression of markers for activation, maturation, and neutrophil extracellular trap (NET) formation using flow cytometry.ResultsThe number of LDGs was elevated in PPASC compared to NP. Individuals infected with SARS-CoV-2 (NRS and PPASC) demonstrated increased CD10+ and CD16hi subset counts of LDGs compared to NP group. Further characterization of LDGs demonstrated that LDGs from COVID-19 convalescents (PPASC and NRS) displayed increased markers of NET forming ability and aggregation with platelets compared to LDGs from NP, but no differences were observed between PPASC and NRS.ConclusionsOur data from a small cohort study demonstrates that mature neutrophils with a heightened activation phenotype remain in circulation long after initial SARS-CoV-2 infection. Persistent elevation of markers for neutrophil activation and NET formation on LDGs, as well as an enhanced proclivity for platelet-neutrophil aggregation (PNA) formation in COVID-19 convalescent individuals may be associated with PPASC prognosis and development.