bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Loss-of-Function Mutations in NPR2 Cause Acromesomelic Dysplasia, Maroteaux Type
Authors: Wu Jing , Wang Mengru , Jiao Zhouyang , Dou Binghua , Li Bo , Zhang Jianjiang , Zhang Haohao , Sun Yue , Tu Xin , Kong Xiangdong , Bai Ying 
Published: March 2022

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare skeletal dysplasia characterized by severe disproportionate short stature, short hands and feet, normal intelligence, and facial dysmorphism. Homozygous or compound heterozygous mutations in the natriuretic peptide receptor 2 (NPR2) gene produce growth-restricted phenotypes. The current study was designed to identify and characterize NPR2 loss-of-function mutations in patients with AMDM and to explore therapeutic responses to recombinant growth hormone (rhGH). NPR2 was sequenced in two Chinese patients with AMDM via next generation sequencing, and in silico structural analysis or transcript analysis of two novel variants was performed to examine putative protein changes. rhGH treatment was started for patient 1. Three NPR2 mutations were identified in two unrelated cases: two compound heterozygous mutations c.1112G&gt;A p.(Arg371Gln) and c.2887+2T&gt;C in patient 1 and a homozygous mutation c.329G&gt;A p.(Arg110His) in patient 2, yielding distinct phenotypes. RNA extracted from peripheral blood cells of patient 1 showed alternatively spliced transcripts not present in control cells. Homology modeling analyses suggested that the c.1112G&gt;A p.(Arg371Gln) mutation disrupted the binding of NPR-B homodimer to its ligand (C-type natriuretic peptide) in the extracellular domain as a result of global allosteric effects on homodimer formation. Thus, c.2887+2T&gt;C and c.1112G&gt;A p.(Arg371Gln) in NPR2 were loss-of-function mutations. Furthermore, rhGH therapy in patient 1 increased the patient’s height by 0.6SDS over 15 months without adversely affecting the trunk-leg proportion. The short-term growth-promoting effect was equivalent to that reported for idiopathic short stature. Overall, our findings broadened the genotypic spectrum of NPR2 mutations in individuals with AMDM and provided insights into the efficacy of rhGH in these patients.
HLA-B*13, B*35 and B*39 Alleles Are Closely Associated With the Lack of Response to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil
Authors: Pereira Leonn Mendes Soares , França Eliane dos Santos , Costa Iran Barros , Jorge Erika Vanessa Oliveira , Mattos Patrícia Jeanne de Souza Mendonça , Freire Amaury Bentes Cunha , Ramos Francisco Lúzio de Paula , Monteiro Talita Antonia Furtado , Macedo Olinda , Sousa Rita Catarina Medeiros , Santos Eduardo José Melo dos , Freitas Felipe Bonfim , Costa Igor Brasil , Vallinoto Antonio Carlos Rosário 
Published: March 2022

IntroductionImmune reconstitution failure after HIV treatment is a multifactorial phenomenon that may also be associated with a single polymorphism of human leukocyte antigen (HLA); however, few reports include patients from the Brazilian Amazon. Our objective was to evaluate the association of the immunogenic profile of the “classical” HLA-I and HLA-II loci with treatment nonresponse in a regional cohort monitored over 24 months since HIV diagnosis.Materials and MethodsTreatment-free participants from reference centers in the state of Pará, Brazil, were enrolled. Infection screening was performed using enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4+/CD8+ T lymphocyte quantification was performed by immunophenotyping and flow cytometry (BD Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on CD4+ T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3.ResultsOf the 270 patients monitored, 134 responded to treatment (CD4+ ≥ 500 cells/µL), and 136 did not respond to treatment (CD4+ &lt; 500 cells/µL). The allele frequencies of the loci were similar to heterogeneous populations. The allelic profile of locus B was statistically associated with treatment nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic influence. The B*13 allele had the highest risk of treatment nonresponse, and carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count less than 400 cells/µL with up to 2 years of therapy. The B*13 allele was associated with a switch in treatment regimens, preferably to efavirenz (EFZ)-based regimens, and among those who switched regimens, half had a history of coinfection with tuberculosis.ConclusionsThe allelic variants of the B locus are more associated with non-response to therapy in people living with HIV (PLHIV) from a heterogeneous population in the Brazilian Amazon.
Suicide and Accidental Death Among Women With Primary Ovarian Cancer: A Population-Based Study
Authors: Chen Ying , Yu Kaixu , Xiong Jiaqiang , Zhang Jinjin , Zhou Su , Dai Jun , Wu Meng , Wang Shixuan 
Published: March 2022

BackgroundWomen with ovarian cancer had the highest suicidal rate among all patients with gynecological malignancies, but no large studies about suicide and accidental death for women with ovarian cancers in detail were conducted. We aimed to determine the relative risk of suicide and accidental death among patients with ovarian cancer to that of the general population, and to identify risk factors associated with suicide and accidental death.MethodsData are from the SEER (surveillance, epidemiology, and end results) cancer registry of women diagnosed with ovarian cancer data from 18 registries for the years 1973–2016. The study population comprised 149,204 patients after inclusion and exclusion criteria were applied. Standardized mortality ratios (SMRs) were calculated and Fine-Gray models were fitted to identify risk factors associated with suicidal and accidental death among cancer patients, with stratifications on demographic and tumor-related characteristics.ResultsWomen with ovarian cancer had a higher risk of suicide and accidental death than the cancer-free group [SMR = 1.86; 95% CI (1.54–2.25) and SMR = 1.54; 95% CI (1.39–1.71)]. Subgroup analysis indicated that only patients with type II epithelial ovarian cancer [SMR = 2.31; 95% CI (1.83–2.91)] had an increased risk of suicide, and those with type I and type II epithelial ovarian cancer [SMR = 1.65; 95% CI (1.39–1.97) and SMR = 1.49; 95% CI (1.30–1.70)] were at a higher risk of accidental death. Patients with ovarian cancer who were younger, white, diagnosed with high-grade, non-metastatic cancer and pelvic exenteration were at a higher risk of suicide. The advanced age, earlier year of diagnosis, and non-metastatic cancer were associated with a higher risk of accidental death. Additionally, pelvic exenteration increased the risk of suicide but not the risk of accidental death among women with primary ovarian cancer.ConclusionsWomen with ovarian cancer had a higher risk of suicide and accidental death compared with the general population. The findings suggested that clinicians should identify high-risk subgroups of ovarian cancer patients for suicide and accidental death as early as possible, with appropriate prevention strategies.
Machine Learning Improves Upon Clinicians' Prediction of End Stage Kidney Disease
Authors: Chuah Aaron , Walters Giles , Christiadi Daniel , Karpe Krishna , Kennard Alice , Singer Richard , Talaulikar Girish , Ge Wenbo , Suominen Hanna , Andrews T. Daniel , Jiang Simon 
Published: March 2022

Background and ObjectivesChronic kidney disease progression to ESKD is associated with a marked increase in mortality and morbidity. Its progression is highly variable and difficult to predict.MethodsThis is an observational, retrospective, single-centre study. The cohort was patients attending hospital and nephrology clinic at The Canberra Hospital from September 1996 to March 2018. Demographic data, vital signs, kidney function test, proteinuria, and serum glucose were extracted. The model was trained on the featurised time series data with XGBoost. Its performance was compared against six nephrologists and the Kidney Failure Risk Equation (KFRE).ResultsA total of 12,371 patients were included, with 2,388 were found to have an adequate density (three eGFR data points in the first 2 years) for subsequent analysis. Patients were divided into 80%/20% ratio for training and testing datasets.ML model had superior performance than nephrologist in predicting ESKD within 2 years with 93.9% accuracy, 60% sensitivity, 97.7% specificity, 75% positive predictive value. The ML model was superior in all performance metrics to the KFRE 4- and 8-variable models.eGFR and glucose were found to be highly contributing to the ESKD prediction performance.ConclusionsThe computational predictions had higher accuracy, specificity and positive predictive value, which indicates the potential integration into clinical workflows for decision support.
The Geospatial Distribution of Myositis and Its Phenotypes in the United States and Associations With Roadways: Findings From a National Myositis Patient Registry
Authors: Hossain Md M. , Wilkerson Jesse , McGrath John A. , Farhadi Payam N. , Brokamp Cole , Khan Md T. F. , Goldberg Bob , Brunner Hermine I. , Macaluso Maurizio , Miller Frederick W. , Rider Lisa G. 
Published: March 2022

BackgroundLittle is known about the spatial distribution of idiopathic inflammatory myopathies (IIM) in the United States (U.S.), or their geospatial associations.MethodsWe studied a national myositis patient registry, with cases diagnosed in the contiguous U.S. from 1985–2011 and comprised of dermatomyositis (DM, n = 484), polymyositis (PM, n = 358), and inclusion body myositis (IBM, n = 318) patients. To assess the association of myositis prevalence with distance from roads, we employed log-Gaussian Cox process models, offset with population density.ResultsThe U.S. IIM case distribution demonstrated a higher concentration in the Northest. DM, IBM, and cases with lung disease were more common in the East, whereas PM cases were more common in the Southeast. One area in the West and one area in the South had a significant excess in cases of DM relative to PM and of cases with lung disease relative to those without lung disease, respectively. IIM cases tended to cluster, with between-points interactions more intense in the Northeast and less in the South. There was a trend of a higher prevalence of IIM and its major phenotypes among people living within 50 m of a roadway relative to living beyond 200 m. Demographic characteristics, rural-urban commuting area, and female percentage were significantly associated with the prevalence of IIM and with major phenotypes.ConclusionsUsing a large U.S. database to evaluate the spatial distribution of IIM and its phenotypes, this study suggests clustering in some regions of the U.S. and a possible association of proximity to roadways.
Role of TFRC as a Novel Prognostic Biomarker and in Immunotherapy for Pancreatic Carcinoma
Authors: Yang Cheng , Li Junqiang , Guo Yongdong , Gan Dongxue , Zhang Chao , Wang Ronglin , Hua Lei , Zhu Liaoliao , Ma Peixiang , Shi Jingjie , Li Shanshan , Su Haichuan 
Published: March 2022

Objective: To explore the expression of the transferrin receptor (TFRC) gene in pancreatic cancer and to analyze the pathogenesis and immunotherapy of TFRC in patients using bioinformatics methods.Methods: We used public data from the cancer genome atlas (TCGA) and gene expression omnibus databases to explore the expression level of the TFRC gene in pancreatic cancer patients. At the same time, we analyzed the correlation between the TFRC gene expression and patient survival, and further analyzed the correlation between TFRC and survival time of patients with different clinicopathological characteristics. Co-expressed genes and pathway enrichment analyses were used to analyze the mechanism of the TFRC in the occurrence and development of pancreatic cancer. Ultimately, we used the R software to examine the relationship between TFRC and immune phenotypes and immune cell infiltration using the TCGA database.Results: The results of the study showed that TFRC is highly expressed in pancreatic cancer tissue. The upregulated expression of TFRC was negatively correlated with the survival in patients with pancreatic cancer. The bioinformatics analysis showed that TFRC plays a role in the occurrence and development of pancreatic cancer mainly through signaling pathways (including cell adhesion molecule binding, condensed chromosomes, chromosome segregation, and cell cycle checkpoints). Finally, TFRC is associated with immune phenotypes and immune cell infiltration, which may influence immunotherapy.Conclusion: TFRC is significantly increased in pancreatic cancer and is associated with a poor prognosis. Moreover, research on TFRC may generate new ideas for the immunotherapy of pancreatic cancer.
TNF-α (G-308A) Polymorphism, Circulating Levels of TNF-α and IGF-1: Risk Factors for Ischemic Stroke—An Updated Meta-Analysis
Authors: Duan Ranran , Wang Na , Shang Yanan , Li Hengfen , Liu Qian , Li Li , Zhao Xiaofeng 
Published: March 2022

ObjectiveAccumulated studies have explored gene polymorphisms and circulating levels of tumor necrosis factor (TNF)-α and insulin-like growth factor (IGF)-1 in the etiology of ischemic stroke (IS). Of the numerous etiopathological factors for IS, a single-nucleotide polymorphism (SNP) rs1800629 located in the TNF-α gene promoter region and increased levels of TNF-α were found to be associated with IS in different ethnic backgrounds. However, the published results are inconsistent and inconclusive. The primary objective of this meta-analysis was to investigate the concordance between rs1800629 polymorphism and IS. A secondary aim was to explore circulating levels of TNF-α and IGF-1 with IS in different ethnic backgrounds and different sourced specimens.MethodsIn this study, we examined whether rs1800629 genetic variant and levels of TNF-α and IGF-1 were related to the etiology of IS by performing a meta-analysis. Relevant case-control studies were retrieved by database searching and systematically selected according to established inclusion criteria.ResultsA total of 47 articles were identified that explored the relationship between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS risk susceptibility. Statistical analyses revealed a significant association between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS pathogenesis.ConclusionOur findings demonstrated that the TNF-α rs1800629 polymorphism, the increased levels of TNF-α, and decreased levels of IGF-1 were involved in the etiology of IS.
The APOEε3/ε4 Genotype Drives Distinct Gene Signatures in the Cortex of Young Mice
Authors: Foley Kate E. , Hewes Amanda A. , Garceau Dylan T. , Kotredes Kevin P. , Carter Gregory W. , Sasner Michael , Howell Gareth R. 
Published: March 2022

IntroductionRestrictions on existing APOE mouse models have impacted research toward understanding the strongest genetic risk factor contributing to Alzheimer’s disease (AD) and dementia, APOEε4, by hindering observation of a key, common genotype in humans – APOEε3/ε4. Human studies are typically underpowered to address APOEε4 allele risk as the APOEε4/ε4 genotype is rare, which leaves human and mouse research unsupported to evaluate the APOEε3/ε4 genotype on molecular and pathological risk for AD and dementia.MethodsAs a part of MODEL-AD, we created and validated new versions of humanized APOEε3/ε3 and APOEε4/ε4 mouse strains that, due to unrestricted breeding, allow for the evaluation of the APOEε3/ε4 genotype. As biometric measures are often translatable between mouse and human, we profiled circulating lipid concentrations. We also performed transcriptional profiling of the cerebral cortex at 2 and 4 months (mos), comparing APOEε3/ε4 and APOEε4/ε4 to the reference APOEε3/ε3 using linear modeling and WGCNA. Further, APOE mice were exercised and compared to litter-matched sedentary controls, to evaluate the interaction between APOEε4 and exercise at a young age.ResultsExpression of human APOE isoforms were confirmed in APOEε3/ε3, APOEε3/ε4 and APOEε4/ε4 mouse brains. At two mos, cholesterol composition was influenced by sex, but not APOE genotype. Results show that the APOEε3/ε4 and APOEε4/ε4 genotype exert differential effects on cortical gene expression. APOEε3/ε4 uniquely impacts ‘hormone regulation’ and ‘insulin signaling,’ terms absent in APOEε4/ε4 data. At four mos, cholesterol and triglyceride levels were affected by sex and activity, with only triglyceride levels influenced by APOE genotype. Linear modeling revealed APOEε3/ε4, but not APOEε4/ε4, affected ‘extracellular matrix’ and ‘blood coagulation’ related terms. We confirmed these results using WGCNA, indicating robust, yet subtle, transcriptional patterns. While there was little evidence of APOE genotype by exercise interaction on the cortical transcriptome at this young age, running was predicted to affect myelination and gliogenesis, independent of APOE genotype with few APOE genotype-specific affects identified.DiscussionAPOEε4 allele dosage-specific effects were observed in circulating lipid levels and cortical transcriptional profiles. Future studies are needed to establish how these data may contribute to therapeutic development in APOEε3/ε4 and APOEε4/ε4 dementia patients.
Activation of Dopamine 4 Receptor Subtype Enhances Gamma Oscillations in Hippocampal Slices of Aged Mice
Authors: Wang Yuan , Jin Yi-Kai , Guo Tie-Cheng , Li Zhen-Rong , Feng Bing-Yan , Han Jin-Hong , Vreugdenhil Martin , Lu Cheng-Biao 
Published: March 2022

AimNeural network oscillation at gamma frequency band (γ oscillation, 30–80 Hz) is synchronized synaptic potentials important for higher brain processes and altered in normal aging. Recent studies indicate that activation of dopamine 4 receptor (DR4) enhanced hippocampal γ oscillation of young mice and fully recovered the impaired hippocampal synaptic plasticity of aged mice, we determined whether this receptor is involved in aging-related modulation of hippocampal γ oscillation.MethodsWe recorded γ oscillations in the hippocampal CA3 region from young and aged C57bl6 mice and investigated the effects of dopamine and the selective dopamine receptor (DR) agonists on γ oscillation.ResultsWe first found that γ oscillation power (γ power) was reduced in aged mice compared to young mice, which was restored by exogenous application of dopamine (DA). Second, the selective agonists for different D1- and D2-type dopamine receptors increased γ power in young mice but had little or small effect in aged mice. Third, the D4 receptor (D4R) agonist PD168077 caused a large increase of γ power in aged mice but a small increase in young mice, and its effect is blocked by the highly specific D4R antagonist L-745,870 or largely reduced by a NMDAR antagonist. Fourth, D3R agonist had no effect on γ power of either young or aged mice.ConclusionThis study reveals DR subtype-mediated hippocampal γ oscillations is aging-related and DR4 activation restores the impaired γ oscillations in aged brain, and suggests that D4R is the potential target for the improvement of cognitive deficits related to the aging and aging-related diseases.
The Comparative Effectiveness of Traditional Chinese Medicine Exercise Therapies in Elderly People With Mild Cognitive Impairment: A Systematic Review and Network Meta-Analysis
Authors: Su Kaiqi , Yuan Jie , Liu Huanhuan , Luo Meng , Li Qi , Liu Sutong , Feng Xiaodong 
Published: March 2022

BackgroundMild cognitive impairment (MCI) in the elderly is a health problem worldwide. Studies have confirmed that traditional Chinese medicine (TCM) exercise therapies can improve MCI. However, which therapy is the best and their impacts on brain function remain controversial and uncertain. This study aims to compare and rank TCM exercise therapies for MCI in the elderly, and analyze their effects on brain function, in order to find an optimal intervention and provide a basis for clinical treatments decision-making.MethodsThe Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Clinical Trials, China National Knowledge Infrastructure (CNKI), Wangfang database, China Science and Technology Journal Database, and Chinese Biomedical Medicine (CBM) were searched through October 28, 2021. Two researchers reviewed all the studies and extracted the data. The ADDIS software version 1.16.8 and the Bayesian hierarchical model were used for pair-wise meta-analysis and network meta-analysis, and the STATA software version 14.0 was used to draw the network evidence plots and funnel plots.ResultsA total of 23 studies on 2282 participants were included in this study. In the pair-wise meta-analysis, TCM exercise therapies (Baduanjin exercise, Tai Chi, Liuzijue exercise and finger exercise) were superior to non-TCM exercise therapies (stretching and toning exercise, usual care, health education and routine daily activities) in terms of MMSE, MoCA and ADL outcomes. In the network meta-analysis, the MMSE outcome ranked Baduanjin exercise (78%) as the best intervention and Tai Chi (36%) as the second. The MoCA outcome ranked Baduanjin exercise (62%) as the best intervention. For the ADL outcome, Baduanjin exercise (60%) ranked the best, and followed by finger exercise (43%).ConclusionTCM exercise therapies may improve the cognitive function in elderly patients with MCI. Among the four therapies included, the Baduanjin exercise may be the preferred therapy for MCI in the elderly, and its mechanism may be related to the regulation of cognitive-related brain function and structure.Systematic Review Registrationhttps://inplasy.com, identifier: INPLASY202070006.
Evaluation of Intracranial Hypertension in Patients With Hypertensive Intracerebral Hemorrhage Using Texture Analysis
Authors: Shan Yingchi , Li Yihua , Wu Xiang , Liu Jiaqi , Zhang Guoqing , Xue Yajun , Gao Guoyi 
Published: March 2022

PurposeTexture analysis based on clinical images had been widely used in neurological diseases. This study aimed to achieve depth information of computed tomography (CT) images by texture analysis and to establish a model for noninvasive evaluation of intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage (HICH).MethodsForty-seven patients with HICH were selected. Related CT images and ICP value were collected. The morphological features of hematoma volume, midline shift, and ventriculocranial ratio were measured. Forty textural features were extracted from regions of interest. Four models were established to predict intracranial hypertension with morphological features, textural features of anterior horn, textural features of temporal lobe, and textural features of posterior horn.ResultsModel of posterior horn had the highest ability to predict intracranial hypertension (AUC = 0.90, F1 score = 0.72), followed by model of anterior horn (AUC = 0.70, F1 score = 0.53) and model of temporal lobe (AUC = 0.70, F1 score = 0.58), and model of morphological features displayed the worst performance (AUC = 0.42, F1 score = 0.38).ConclusionTexture analysis can realize interpretation of CT images in depth, which has great potential in noninvasive evaluation of intracranial hypertension.