bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric Cardiovascular Magnetic Resonance in Acute Myocarditis: Comparison of 2009 and 2018 Lake Louise Criteria With Endomyocardial Biopsy Confirmation
Authors: Li Shuang , Duan Xuejing , Feng Guangxun , Sirajuddin Arlene , Yin Gang , Zhuang Baiyan , He Jian , Xu Jing , Yang Wenjing , Wu Weichun , Sun Xiaoxin , Zhao Shihua , Wang Hongyue , Teng Zhongzhao , Lu Minjie 
Published: October 2021

Background: Cardiac magnetic resonance (CMR) has been shown to improve the diagnosis of myocarditis, but no systematic comparison of this technique is currently available. The purpose of this study was to compare the 2009 and 2018 Lake Louise Criteria (LLC) for the diagnosis of acute myocarditis using 3.0 T MRI with endomyocardial biopsy (EMB) as a reference and to provide the cutoff values for multiparametric CMR techniques.Methods: A total of 73 patients (32 ± 14 years, 71.2% men) with clinically suspected myocarditis undergoing EMB and CMR with 3.0 T were enrolled in the study. Patients were divided into two groups according to EMB results (EMB-positive and -negative groups). The CMR protocol consisted of cine-SSFP, T2 STIR, T2 mapping, early and late gadolinium enhancement (EGE, LGE), and pre- and post-contrast T1 mapping. Their potential diagnostic ability was assessed with receiver operating characteristic curves.Results: The myocardial T1 and T2 relaxation times were significantly higher in the EMB-positive group than in the EMB-negative group. Optimal cutoff values were 1,228 ms for T1 relaxation times and 58.5 ms for T2 relaxation times with sensitivities of 86.0 and 83.7% and specificities of 93.3 and 93.3%, respectively. The 2018 LLC had a better diagnostic performance than the 2009 LLC in terms of sensitivity, specificity, positive predictive value, and negative predictive value. T1 mapping + T2 mapping had the largest area under the curve (0.95) compared to other single or combined parameters (2018 LLC: 0.91; 2009 LLC: 0.76; T2 ratio: 0.71; EGEr: 0.67; LGE: 0.73; ). The diagnostic accuracy for the 2018 LLC was the highest (91.8%), followed by T1 mapping (89.0%) and T2 mapping (87.7%).Conclusion: Emerging technologies such as T1/ T2 mapping have significantly improved the diagnostic performance of CMR for the diagnosis of acute myocarditis. The 2018 LLC provided the overall best diagnostic performance in acute myocarditis compared to other single standard CMR parameters or combined parameters. There was no significant gain when 2018LLC is combined with the EGE sequence.
LGR4 Gene Polymorphisms Are Associated With Bone and Obesity Phenotypes in Chinese Female Nuclear Families
Authors: Shi Su-qin , Li Shan-shan , Zhang Xiao-ya , Wei Zhe , Fu Wen-zhen , He Jin-wei , Hu Yun-qiu , Li Miao , Zheng Li-li , Zhang Zhen-lin 
Published: October 2021

ObjectiveThe current study was conducted to determine whether peak bone mineral density (BMD) and obesity phenotypes are associated with certain LGR4 gene polymorphisms found in Chinese nuclear families with female children.MethodsA total of 22 single nucleotide polymorphisms (SNPs) located in and around the LGR4 gene were identified in 1,300 subjects who were members of 390 Chinese nuclear families with female children. Then, BMD readings of the femoral neck, total hip, and lumbar spine as well as measurements of the total lean mass (TLM), total fat mass (TFM), and trunk fat mass were obtained via dual-energy X-ray absorptiometry. The quantitative transmission disequilibrium test was used to analyze the associations between specific SNPs and LGR4 haplotypes and peak BMD as well as between LGR4 haplotypes and TLM, percent lean mass, TFM, percent fat mass, trunk fat mass, and body mass index (BMI).ResultsHere, rs7936621 was significantly associated with the BMD values for the total hip and lumbar spine, while rs10835171 and rs6484295 were associated with the trunk fat mass and BMI, respectively. Regarding the haplotypes, we found significant associations between GAA in block 2 and trunk fat mass and BMI, between AGCGT in block 3 and total hip BMD, between TGCTCC in block 5 and femoral neck BMD, and between TACTTC in block 5 and both lumbar spine and femoral neck BMD (all P-values &lt; 0.05).ConclusionGenetic variations of the LGR4 gene are related to peak BMD, BMI, and trunk fat mass.
Vitamin D Status in Children With Short Stature: Accurate Determination of Serum Vitamin D Components Using High-Performance Liquid Chromatography–Tandem Mass Spectrometry
Authors: Xu Bei , Feng Yue , Gan Lingling , Zhang Yamei , Jiang Wenqiang , Feng Jiafu , Yu Lin 
Published: October 2021

ObjectiveVitamin D is critical for calcium and bone metabolism. Vitamin D insufficiency impairs skeletal mineralization and bone growth rate during childhood, thus affecting height and health. Vitamin D status in children with short stature is sparsely reported. The purpose of the current study was to investigate various vitamin D components by high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) to better explore vitamin D storage of short-stature childrenin vivo.MethodsSerum circulating levels of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], and 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3, C3-epi] were accurately computed using the LC-MS/MS method. Total 25(OH)D [t-25(OH)D] and ratios of 25(OH)D2/25(OH)D3 and C3-epi/25(OH)D3 were then respectively calculated. Free 25(OH)D [f-25(OH)D] was also measured.Results25(OH)D3 and f-25(OH)D levels in short-stature subgroups 2 (school age: 7~12 years old) and 3 (adolescence: 13~18 years old) were significantly lower compared with those of healthy controls. By contrast, C3-epi levels and C3-epi/25(OH)D3 ratios in all the three short-stature subgroups were markedly higher than the corresponding healthy cases. Based on cutoff values developed by Endocrine Society Recommendation (but not suitable for methods 2 and 3), sufficient storage capacities of vitamin D in short-stature subgroups 1, 2, and 3 were 42.8%, 23.8%, and 9.0% as determined by Method 3 [25(OH)D2/3+25(OH)D3], which were lower than those of 57.1%, 28.6%, and 18.2% as determined by Method 1 [25(OH)D2+25(OH)D3+C3-epi] and 45.7%, 28.5%, and 13.6% as determined by Method 2 [25(OH)D2/3+25(OH)D3+C3-epi]. Levels of 25(OH)D2 were found to be weakly negatively correlated with those of 25(OH)D3, and higher 25(OH)D3 levels were positively correlated with higher levels of C3-epi in both short-stature and healthy control cohorts. Furthermore, f-25(OH)D levels were positively associated with 25(OH)D3 and C3-epi levels in children.ConclusionsThe current LC-MS/MS technique can not only separate 25(OH)D2 from 25(OH)D3 but also distinguish C3-epi from 25(OH)D3. Measurement of t-25(OH)D [25(OH)D2+25(OH)D3] alone may overestimate vitamin D storage in children, and short-stature children had lower vitamin D levels compared with healthy subjects. Ratios of C3-epi/25(OH)D3 and 25(OH)D2/25(OH)D3 might be alternative markers for vitamin D catabolism/storage in short-stature children. Further studies are needed to explore the relationships and physiological roles of various vitamin D metabolites.
Case Report: Bilateral Epiphysiodesis Due to Extreme Tall Stature in a Girl With a De Novo DNMT3A Variant Associated With Tatton-Brown-Rahman Syndrome
Authors: Lennartsson Otto , Lodefalk Maria , Wehtje Henrik , Stattin Eva-Lena , Sävendahl Lars , Nilsson Ola 
Published: October 2021

ObjectiveTo present a rare clinical case of a patient with Tatton-Brown-Rahman syndrome and the outcome of tall stature management with bilateral epiphysiodesis surgery at the distal femur and proximal ends of tibia and fibula.Study DesignClinical case report.ResultsThis is a 20-year-old female with a history of proportional tall stature, developmental psychomotor and language delay with autism spectrum behavior and distinctive facial features. At 12 years and 2 months of age she was in early puberty and 172.5 cm tall (+ 2.8 SDS) and growing approximately 2 SDS above midparental target height of 173 cm (+ 0.9 SDS). A bone age assessment predicted an adult height of 187.1 cm (+3.4 SDS). To prevent extreme tall stature, bilateral epiphysiodesis surgery was performed at the distal femur and proximal ends of tibia and fibula at the age of 12 years and 9 months. After the surgery her height increased by 12.6 cm to 187.4 cm of which approximately 10.9 cm occurred in the spine whereas leg length increased by only 1.7 cm resulting in a modest increase of sitting height index from 50% (-1 SDS) to 53% (+ 0.5 SDS). Genetic evaluation for tall stature and intellectual disability identified a de novo nonsense variant in the DNMT3A gene previously associated with Tatton-Brown-Rahman syndrome.ConclusionTatton-Brown-Rahman syndrome should be considered in children with extreme tall stature and intellectual disability. Percutaneous epiphysiodesis surgery to mitigate extreme tall stature may be considered.
Metoidioplasty: Surgical Options and Outcomes in 813 Cases
Authors: Bordas Noemi , Stojanovic Borko , Bizic Marta , Szanto Arpad , Djordjevic Miroslav L. 
Published: October 2021

IntroductionMetoidioplasty is a variant of phalloplasty for transmen that includes the creation of the neophallus from a hormonally enlarged clitoris, urethral lengthening and scrotoplasty. The procedure results in male appearance of genitalia, voiding in standing position and preserved sexual arousal, but without possibility for penetrative intercourse. We evaluated outcomes of metoidioplasty at our center, based on latest surgical refinements.MethodsDuring the period of 14 years (from February 2006 to April 2020), 813 transmen with mean age of 24.4 years and mean body mass index of 24.6, underwent one stage metoidioplasty. Hysterectomy was simultaneously performed in 156, and mastectomy in 58 cases. Hysterectomy, mastectomy and metoidioplasty were done as a one-stage procedure in 46 transmen. Patients are divided in 5 groups, depending on the type of urethroplasty. Postoperative questionnaires were used to evaluate cosmetic and functional outcomes, as well as patients’ satisfaction.ResultsFollow-up ranged from 16 to 180 months (mean 94 months). Mean surgery time was 170 minutes and mean hospital stay was 3 days. Length of the neophallus ranged from 4.8 cm to 10.2 cm (mean 5.6 cm). Urethroplasty was complication-free in 89.5% of cases, and ranged between 81% to 90.3% in different groups. Urethral fistula and stricture occured in 8.85% and 1.70% of cases, respectively. Other complications included testicular implant rejection in 2%, testicular displacement in 3.20% and vaginal remnant in 9.60% of cases. From 655 patients who answered the questionnaire, 79% were totally satisfied and 20% mainly satisfied with the result of surgery. All patients reported voiding in standing position and good sexual arousal of the neophallus, without possibility for penetrative intercourse due to small size of the neophallus.ConclusionMetoidioplasty has good cosmetic and functional outcomes, with low complication rate and high level of patients’ satisfaction. In transmen who request total phalloplasty after metoidioplasty, all available phalloplasty techniques are feasable.
Genetic Analysis of 28 Chinese Families With Tyrosinase-Positive Oculocutaneous Albinism
Authors: Ma Linya , Zhu Jianjian , Wang Jing , Huang Yazhou , Zhang Jibo , Wang Chao , Zhou Yuan , Peng Dan 
Published: October 2021

BackgroundTyrosinase-positive oculocutaneous albinism (OCA, type II, OCA2) is an autosomal recessive genetic disease in which the biosynthesis of melanin decreases in the skin, hair, and eyes. OCA2 disease is caused by mutations inOCA2gene. The gene product plays a role in regulating the pH of melanosomes. Up to now, hundreds ofOCA2mutations have been reported and novel variants are still being discovered.MethodsIn this study, we reviewed the records of OCA2 patients who had conducted albinism genetic testing, and then analyzed the clinical and genetic information of 28 OCA2 patients who had been genetically diagnosed by using Sanger sequencing and next-generation sequencing.ResultsIn this study, we reported 31 variants screened from 28 Chinese OCA2 families, and characterized the detailed molecular and clinical presentations. There were 12 novel variants among all detected variants, including 3 missense variants (p.G393V, p.T482A, and p.R720P), 4 frameshift variants (p.R53Gfs∗49, p.N279Kfs∗17, p.I469Lfs∗4, p.I655Nfs∗12), 2 splicing variants (c.1637-2A &gt; G, c.1951 + 1G &gt; C), 2 stopgain variants (p.L278X, p.W652X) and 1 insertion variants (p.P315LinsT). One potential cluster of missense variants was implicated indicating the important roles of the underlying domains in OCA2 pathogenesis.ConclusionOur results were beneficial for diagnosis and precision clinical management forOCA2-related disorder, and this study expanded the mutation spectrum of oculocutaneous albinism.
Influenza Vaccination Is Associated With Lower Incidental Asthma Risk in Patients With Atopic Dermatitis: A Nationwide Cohort Study
Authors: Li Kun Hong , Leong Pui-Ying , Tseng Chung-Fang , Wang Yu Hsun , Wei James Cheng-Chung 
Published: October 2021

BackgroundAtopic march refers to the natural history of atopic dermatitis (AD) in infancy followed by subsequent allergic rhinitis and asthma in later life. Respiratory viruses interact with allergic sensitization to promote recurrent wheezing and the development of asthma. We aimed to evaluate whether influenza vaccination reduces asthma risk in people with AD.MethodsThis cohort study was conducted retrospectively from 2000 to 2013 by the National Health Insurance Research Database (NHIRD). Patients with newly diagnosed AD (International Classification of Diseases, Ninth Revision, Clinical Modification code 691) were enrolled as the AD cohort. We matched each vaccinated patient with one non-vaccinated patient according to age and sex. We observed each participant until their first asthma event, or the end of the study on December 31, 2013, whichever came first.ResultsOur analyses included 4,414 people with a mean age of 53 years. Of these, 43.8 were male. The incidence density of asthma was 12.6 per 1,000 person-years for vaccinated patients, and 15.1 per 1000 person-years for non-vaccinated patients. The adjusted hazard ratio (aHR) of asthma in the vaccinated cohort relative to the non-vaccinated cohort was 0.69 (95% CI = 0.55–0.87). Vaccinated patients had a lower cumulative incidence of asthma than unvaccinated patients. Vaccinated participants in all age and sex groups trended toward a lower risk of asthma. People will reduce more asthma risk when taking shots every year.ConclusionInfluenza vaccination was associated with lower asthma risk in patients with AD.
Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies
Authors: Hou Jue , Wang Shuhui , Li Dan , Carpp Lindsay N. , Zhang Tong , Liu Ying , Jia Manxue , Peng Hong , Liu Chang , Wu Hao , Huang Yunda , Shao Yiming 
Published: October 2021

Both vaccine “take” and neutralizing antibody (nAb) titer are historical correlates for vaccine-induced protection from smallpox. We analyzed a subset of samples from a phase 2a trial of three DNA/HIV-1 primes and a recombinant Tiantan vaccinia virus-vectored (rTV)/HIV-1 booster and found that a proportion of participants showed no anti-vaccinia nAb response to the rTV/HIV-1 booster, despite successful vaccine “take.” Using a rich transcriptomic and vaccinia-specific immunological dataset with fine kinetic sampling, we investigated the molecular mechanisms underlying nAb response. Blood transcription module analysis revealed the downregulation of the activator protein 1 (AP-1) pathway in responders, but not in non-responders, and the upregulation of T-cell activation in responders. Furthermore, transcriptional factor network reconstruction revealed the upregulation of AP-1 core genes at hour 4 and day 1 post-rTV/HIV-1 vaccination, followed by a downregulation from day 3 until day 28 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated on day 7 in non-responders. We speculate that persistent pro-inflammatory signaling early post-rTV/HIV-1 vaccination inhibits the nAb response.
Effects of Neutrophil Extracellular Traps in Patients With Septic Coagulopathy and Their Interaction With Autophagy
Authors: Mao Jia-Yu , Zhang Jia-Hui , Cheng Wei , Chen Jian-Wei , Cui Na 
Published: October 2021

IntroductionNeutrophil extracellular traps (NETs) act as a critical trigger of inflammation and coagulation. We hypothesized that NETs are associated with septic hypercoagulability.Materials and MethodsIn total, 82 patients admitted with sepsis in the Department of Critical Care Medicine of Peking Union Medical College Hospital were enrolled between February 2017 and April 2018. Clinical and hematological parameters and thrombotic or hemorrhagic events were recorded. Blood samples were obtained to assess biomarkers of NET formation, including neutrophil elastase 2 (ELA2) and citrullinated histone H3, and endothelial-derived biomarker syndecan-1. Autophagy levels and their regulation pathway were also examined to explore their interaction with NETs.ResultSepsis patients with disseminated intravascular coagulation (DIC) showed significantly higher levels of NET formation [ELA2, 1,247 (86–625) vs. 2,039 (1,544–2,534), p &lt; 0.0001; H3, 140 (47–233) vs. 307 (199–415), p &lt; 0.0001]. NET formation was independently associated with DIC risk [ELA2, OR 1.0028, 95% CI, 1.0010–1.0045; H3, OR 1.0104, 95% CI, 1.0032–1.0176] and mortality [ELA2, HR 1.0014, 95% CI, 1.0004–1.0024; H3, HR 1.0056, 95% CI, 1.0008–1.0115]. The area under the curve value for ELA2 in predicting DIC occurrence was 0.902 (95% CI, 0.816–0.957), and that of H3 was 0.870 (95% CI, 0.778–0.934). Furthermore, biomarkers of NET formation, endothelial cells, and autophagy exhibited a significant correlation [ELA2 and Syn (r = 0.5985, p &lt; 0.0001), LC3B (r = −0.4224, p &lt; 0.0001); H3 and Syn (r = 0.6383, p &lt; 0.0001), LC3B (r = −0.3005, p = 0.0061)].ConclusionIncreased NET formation is significantly associated with sepsis-induced DIC incidence and mortality in sepsis patients, revealing a significant relationship with the autophagy pathway.Clinical Trial Registrationchictr.org.cn, identifier ChiCTR-ROC-17010750.
Immunogenomic Analyses of the Prognostic Predictive Model for Patients With Renal Cancer
Authors: Feng Tao , Zhao Jiahui , Wei Dechao , Guo Pengju , Yang Xiaobing , Li Qiankun , Fang Zhou , Wei Ziheng , Li Mingchuan , Jiang Yongguang , Luo Yong 
Published: October 2021

BackgroundRenal cell carcinoma (RCC) is associated with poor prognostic outcomes. The current stratifying system does not predict prognostic outcomes and therapeutic benefits precisely for RCC patients. Here, we aim to construct an immune prognostic predictive model to assist clinician to predict RCC prognosis.MethodsHerein, an immune prognostic signature was developed, and its predictive ability was confirmed in the kidney renal clear cell carcinoma (KIRC) cohorts based on The Cancer Genome Atlas (TCGA) dataset. Several immunogenomic analyses were conducted to investigate the correlations between immune risk scores and immune cell infiltrations, immune checkpoints, cancer genotypes, tumor mutational burden, and responses to chemotherapy and immunotherapy.ResultsThe immune prognostic signature contained 14 immune-associated genes and was found to be an independent prognostic factor for KIRC. Furthermore, the immune risk score was established as a novel marker for predicting the overall survival outcomes for RCC. The risk score was correlated with some significant immunophenotypic factors, including T cell infiltration, antitumor immunity, antitumor response, oncogenic pathways, and immunotherapeutic and chemotherapeutic response.ConclusionsThe immune prognostic, predictive model can be effectively and efficiently used in the prediction of survival outcomes and immunotherapeutic responses of RCC patients.
Mechanically Activated Calcium Channel PIEZO1 Modulates Radiation-Induced Epithelial-Mesenchymal Transition by Forming a Positive Feedback With TGF-β1
Authors: Huang Jia-Qi , Zhang Hao , Guo Xue-Wei , Lu Yan , Wang Si-Nian , Cheng Bo , Dong Su-He , Lyu Xiao-Li , Li Feng-Sheng , Li Yong-Wang 
Published: October 2021

TGF-β-centered epithelial-mesenchymal transition (EMT) is a key process involved in radiation-induced pulmonary injury (RIPI) and pulmonary fibrosis. PIEZO1, a mechanosensitive calcium channel, is expressed in myeloid cell and has been found to play an important role in bleomycin-induced pulmonary fibrosis. Whether PIEZO1 is related with radiation-induced EMT remains elusive. Herein, we found that PIEZO1 is functional in rat primary type II epithelial cells and RLE-6TN cells. After irradiation, PIEZO1 expression was increased in rat lung alveolar type II epithelial cells and RLE-6TN cell line, which was accompanied with EMT changes evidenced by increased TGF-β1, N-cadherin, Vimentin, Fibronectin, and α-SMA expression and decreased E-cadherin expression. Addition of exogenous TGF-β1 further enhanced these phenomena in vitro. Knockdown of PIEZO1 partly reverses radiation-induced EMT in vitro. Mechanistically, we found that activation of PIEZO1 could upregulate TGF-β1 expression and promote EMT through Ca2+/HIF-1α signaling. Knockdown of HIF-1α partly reverses enhanced TGF-β1 expression caused by radiation. Meanwhile, the expression of PIEZO1 was up-regulated after TGF-β1 co-culture, and the mechanism could be traced to the inhibition of transcription factor C/EBPβ expression by TGF-β1. Irradiation also caused a decrease in C/EBPβ expression in RLE-6TN cells. Dual luciferase reporter assay and chromatin immunoprecipitation assay (ChIP) confirmed that C/EBPβ represses PIEZO1 expression by binding to the PIEZO1 promoter. Furthermore, overexpression of C/EBPβ by using the synonymous mutation to C/EBPβ siRNA could reverse siRNA-induced upregulation of PIEZO1. In summary, our research suggests a critical role of PIEZO1 signaling in radiation-induced EMT by forming positive feedback with TGF-β1.