bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Very Low-Level Somatic Mosaic COL4A5 Splicing Variant in Asymptomatic Female Using Droplet Digital PCR
Authors: Deng Haiyue , Zhang Yanqin , Ding Jie , Wang Fang 
Published: March 2022

BackgroundAlport syndrome is a hereditary glomerulopathy featured by haematuria, proteinuria, and progressive renal failure. X-linked Alport syndrome (XLAS) due to COL4A5 disease-causing variants is the most common form. In the case of XLAS resulting from 10–18% presumed de novo COL4A5 disease-causing variants, there are only a few studies for mosaicism in the probands or parents. Very low-level (&lt;1.0%) somatic mosaicism for COL4A5 disease-causing variants has not been published.Materials and MethodsChinese XLAS families with suspected parental mosaicism were enrolled in the present study to evaluate the forms of mosaicism, to offer more appropriate genetic counseling. PCR and direct sequencing were used to detect COL4A5 disease-causing variants harbored by the affected probands in parental multi-tissue DNAs (peripheral blood, urine sediments, saliva, hair), and droplet digital PCR (ddPCR) was used to quantify the mutant COL4A5 allelic fractions in parental different samples such as peripheral blood, saliva, and urine sediments.ResultsA Chinese asymptomatic female with suspected somatic and germline mosaicism was enrolled in the present study. She gave birth to two boys with XLAS caused by a hemizygous disease-causing variant c. 2245-1G&gt;A in COL4A5 (NM_033380) intron 28, whereas this disease-causing variant was not detected in genomic DNA extracted from peripheral blood leukocytes in the woman using Sanger sequencing. She had multiple normal urine test results, and continuous linear immunofluorescence staining of α2 (IV) and α5 (IV) chains of skin tissue. Sanger sequencing demonstrated that COL4A5 disease-causing variant c. 2245-1G&gt;A was not detected in her genomic DNAs isolated from urine sediments, saliva, and hair roots. Using ddPCR, the wild-type and mutant-type (c.2245-1G&gt;A) COL4A5 was identified in the female's genomic DNAs isolated from peripheral blood, saliva, and urine sediments. The mutant allelic fractions in these tissues were 0.26% (peripheral blood), 0.73% (saliva), and 1.39% (urine), respectively.ConclusionsGermline and very low-level somatic mosaicism for a COL4A5 splicing variant was detected in an asymptomatic female, which highlights that parental mosaicism should be excluded when a COL4A5 presumed de novo disease-causing variant is detected.
Lung Ventilation/Perfusion Scintigraphy for the Screening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Which Criteria to Use?
Authors: Le Pennec Romain , Tromeur Cécile , Orione Charles , Robin Philippe , Le Mao Raphaël , De Moreuil Claire , Jevnikar Mitja , Hoffman Clément , Savale Laurent , Couturaud Francis , Sitbon Olivier , Montani David , Jaïs Xavier , Le Gal Grégoire , Salaün Pierre Yves , Humbert Marc , Le Roux Pierre Yves 
Published: March 2022

ObjectiveThe diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is a major challenge as it is a curable cause of pulmonary hypertension (PH). Ventilation/Perfusion (V/Q) lung scintigraphy is the imaging modality of choice for the screening of CTEPH. However, there is no consensus on the criteria to use for interpretation. The aim of this study was to assess the accuracy of various interpretation criteria of planar V/Q scintigraphy for the screening of CTEPH in patients with PH.MethodsThe eligible study population consisted of consecutive patients with newly diagnosed PH in the Brest University Hospital, France. Final diagnosis (CTEPH or non-CTEPH) was established in a referential center on the management of PH, based on the ESC/ERS guidelines and a minimum follow-up of 3 years. A retrospective central review of planar V/Q scintigraphy was performed by three nuclear physicians blinded to clinical findings and to final diagnosis. The number, extent (sub-segmental or segmental) and type (matched or mismatched) of perfusion defects were reported. Sensitivity and specificity were evaluated for various criteria based on the number of mismatched perfusion defects and the number of perfusion defects (regardless of ventilation). Receiver operating characteristic (ROC) curves were generated and areas under the curve (AUC) were calculated for both.ResultsA total of 226 patients with newly diagnosed PH were analyzed. Fifty six (24.8%) were diagnosed with CTEPH while 170 patients (75.2%) were diagnosed with non-CTEPH. The optimal threshold was 2.5 segmental mismatched perfusion defects, providing a sensitivity of 100 % (95% CI 93.6–100%) and a specificity of 94.7% (95%CI 90.3–97.2%). Lower diagnostic cut-offs of mismatched perfusion defects provided similar sensitivity but lower specificity. Ninety five percent of patients with CTEPH had more than 4 segmental mismatched defects. An interpretation only based on perfusion provided similar sensitivity but a specificity of 81.8% (95%CI 75.3–86.9%).ConclusionOur study confirmed the high diagnostic performance of planar V/Q scintigraphy for the screening of CTEPH in patients with PH. The optimal diagnostic cut-off for interpretation was 2.5 segmental mismatched perfusion defects. An interpretation only based on perfusion defects provided similar sensitivity but lower specificity.
Concurrent Training Increases Serum Brain-Derived Neurotrophic Factor in Older Adults Regardless of the Exercise Frequency
Authors: Canton-Martínez Ermilo , Rentería Iván , García-Suárez Patricia C. , Moncada-Jiménez José , Machado-Parra Juan Pablo , Lira Fabio Santos , Johnson David K. , Jiménez-Maldonado Alberto 
Published: March 2022

BackgroundHuman brain function declines with aging. In this sense, exercise-based interventions has a promising effect on brain plasticity for older adults. Serum brain-derived neurotrophic factor (BDNF) is a positive biomarker for brain neuroplasticity in healthy older adults also modified by exercise training. Selected features of the exercise prescription for improving brain health are missing; therefore, the aim of this study was to determine the effects of concurrent exercise training frequency on serum BDNF levels in healthy older adults.MethodsNineteen volunteers (age: 65 ± 4 year; body mass index: 28.0 ± 4.5 kg/m2) completed either a three times/week (3-t/w) (n = 8) or five times/week (5-t/w) (n = 11) concurrent exercise program. The exercise program lasted 11 weeks and all exercise sessions were performed for 50 min at moderate intensity. Serum BDNF, body composition, cardiovascular, and physical fitness variables were assessed before and after the exercise training program.ResultsRegardless of the group, the serum BDNF increased following the intervention (p &lt; 0.001), and there were no significant group (p = 0.827) or interaction (p = 0.063) effects. The maximal oxygen consumption (VO2max) increased regardless of the group (p = 0.007), with a non-significant group (p = 0.722) or interaction (p = 0.223) effects. Upper- and lower-body strength increased in both groups (p = 0.003); however, there was no effect of the training frequency (p = 0.53). For the skeletal muscle mass, there was a trend in the interaction effect (p = 0.053). Finally, the body fat percentage was unchanged.ConclusionEleven weeks of combined exercise training increased serum BDNF levels in healthy older adults, a response independent of the training frequency. The overall fitness level improved similarly in both exercise groups. These data reveal that a minimal dosage of concurrent exercise enhance functional capacity and a brain health biomarker in older adults.
Cerebral Autoregulation Indices Are Not Interchangeable in Patients With Sepsis
Authors: Caldas Juliana , Quispe-Cornejo Armin Alvaro , Crippa Ilaria Alice , Subira Carles , Creteur Jacques , Panerai Ronney , Taccone Fabio Silvio 
Published: March 2022

IntroductionDynamic cerebral autoregulation (dCA) is frequently altered in patients with sepsis and may be associated with sepsis-associated brain dysfunction. However, the optimal index to quantify dCA in patients with sepsis is currently unknown.ObjectiveTo assess the agreement between two validated dCA indices in patients with sepsis.MethodsRetrospective analysis of prospectively collected data in patients with sepsis; those with acute or chronic intracranial disease, arrhythmias, mechanical cardiac support, or history of supra-aortic vascular disease were excluded. Transcranial Doppler was performed on the right or left middle cerebral artery (MCA) with a 2-MHz probe, and MCA blood flow velocity (FV) and arterial pressure (BP) signals were simultaneously recorded. We calculated two indices of dCA: the mean flow index (Mxa), which is the Pearson correlation coefficient between BP and FV (MATLAB, MathWorks), and the autoregulation index (ARI), which is the transfer function analysis of spontaneous fluctuations in BP and FV (custom-written FORTRAN code). Impaired dCA was defined as Mxa &gt;0.3 or ARI ≤ 4. The agreement between the two indices was assessed by Cohen's kappa coefficient.ResultsWe included 95 patients (age 64 ± 13 years old; male 74%); ARI was 4.38 [2.83–6.04] and Mxa was 0.32 [0.14–0.59], respectively. There was no correlation between ARI and Mxa (r = −0.08; p = 0.39). dCA was altered in 40 (42%) patients according to ARI and in 50 (53%) patients according to Mxa. ARI and Mxa were concordant in classifying 23 (24%) patients as having impaired dCA and 28 (29%) patients as having intact dCA. Cohen's kappa coefficient was 0.08, suggesting poor agreement. ARI was altered more frequently in patients on mechanical ventilation than others (27/52, 52% vs. 13/43, 30%, p = 0.04), whereas Mxa did not differ between those two groups. On the contrary, Mxa was altered more frequently in patients receiving sedatives than others (23/34, 68% vs. 27/61, 44%, p = 0.03), whereas ARI did not differ between these two groups.ConclusionsAgreement between ARI and Mxa in assessing dCA in patients with sepsis was poor. The identification of specific factors influencing the dCA analysis might lead to a better selection of the adequate cerebral autoregulation (CAR) index in critically ill patients with sepsis.
Early Neurological Improvement Predicts Clinical Outcome After Thrombectomy for Distal Medium Vessel Occlusions
Authors: Wang Maud , Farouki Yousra , Hulscher Franny , Mine Benjamin , Bonnet Thomas , Elens Stephanie , Vazquez Suarez Juan , Jodaitis Lise , Ligot Noémie , Naeije Gilles , Lubicz Boris , Guenego Adrien 
Published: March 2022

Background and PurposeGood clinical outcome predictors have been established in mechanical thrombectomy (MT) for acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). An early neurological improvement (ENI), defined as a reduction of ≥8 on the National Institutes of Health Stroke Scale (NIHSS), compared with the baseline score or an NIHSS of 0 or 1 at 24 h after MT, is a strong predictor of favorable outcome. We aimed to study the impact of ENI after MT for distal medium vessel occlusions (DMVO).MethodsWe retrospectively analyzed the data of consecutive patients who underwent MT for a primary DMVO in one large academic center. We compared clinical outcomes between patients with DMVO stratified by ENI. Multivariate analyses were performed to determine the impact of ENI on good 90-day outcome (modified Rankin scale of 0–2) and identify factors contributing to ENI.ResultsBetween January 2018 and January 2021, 61 patients underwent an MT for an AIS with a primary DMVO. An ENI was seen in 24 (39%) patients (ENI+). Outcomes were significantly better in ENI+ patients, with 83% achieving a good outcome at 3 months vs. 43% for patients without ENI (ENI–; p = 0.019). ENI was an independent predictive factor of good clinical outcome even after adjusting for potential confounding factors [odds ratio 12.49 (1.49–105.01), p = 0.020]. The use of intravenous tissue plasminogen activator [IVtPA; Odds-ratio 6.59 (1.82–23.89), p = 0.004] was a positive predictor of ENI.ConclusionENI at day 1 following MT for DMVO stroke is a strong independent predictor of good to excellent 3-month clinical outcome.
Roles of GFPT2 Expression Levels on the Prognosis and Tumor Microenvironment of Colon Cancer
Authors: Ding Xiaorong , Liu Hua , Yuan Ying , Zhong Qin , Zhong Xiaomin 
Published: March 2022

BackgroundRecently, increasing evidence has suggested that Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) is related to carcinogenesis. However, the potential roles of GFPT2 in colon cancer still need to be fully investigated.MethodsWe examined the protein levels of GFPT2 by immunohistochemistry (IHC) in tissues collected from 83 patients with colon cancer. We further detected GFBPT2 protein levels by Western Blot assay. We checked the relationship between GFPT2 expression levels and overall survival (OS), stromal and immune scores and immune components from The Cancer Gene Atlas (TCGA) database. GFBP2-related pathways were validated in the Cancer Cell Line Encyclopedia (CCLE) database. Expression of GFPT2 in single cell subpopulations was calculated from The Tumor Immune Single Cell Center (TISCH). The levels of GFPT2 and drug sensitivity data were performed from CellMiner dataset.ResultsGFPT2 was highly expressed and correlated with poor pathological features in 83 colon cancer patients. Moreover, increased GFPT2 expression was significantly associated with poorer OS in 329 colon adenocarcinoma (COAD) patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the differentially expressed genes of GFPT2 were mostly enriched in focal adhesion, ECM receptor interaction, JAK/STAT signaling pathway and immune related pathways. In addition, GFPT2 expression was correlated with the tumor microenvironment (TME). GFPT2 expression was linked to cancer-associated fibroblasts (CAFs)-associated factors and epithelial-mesenchymal transition (EMT)-related factors. GFPT2 was positively correlated with immunosuppressive cells and regulated immunosuppressive factors and T-cell exhaustion. Finally, our data suggested that the expression of GFPT2 may be a judgment of the sensitivity of a certain class of drugs.ConclusionsOur work reveals the roles of GFPT2 in tumorigenesis, particularly in immune response, TME and drug resistance, which are crucial for the development of customized cancer therapies.
Development and Validation of Nomograms to Predict Overall Survival and Cancer-Specific Survival in Patients With Pancreatic Adenosquamous Carcinoma
Authors: Yang Zhen , Shi Guangjun , Zhang Ping 
Published: March 2022

BackgroundPancreatic adenosquamous carcinoma (PASC) is a heterogeneous group of primary pancreatic cancers characterized by the coexistence of both glandular and squamous differentiation. The aim of this study was to develop nomograms to predict survival outcomes in patients with PASC.MethodsIn this retrospective study, data on PASC, including clinicopathological characteristics, treatments, and survival outcomes, were collected from the SEER database between 2000 and 2018. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The eligible patients were randomly divided into development cohort and validation cohort in a 7:3 ratio. The nomograms for prediction of OS and CSS were constructed by the development cohort using a LASSO-Cox regression model, respectively. Besides the model performance was internally and externally validated by examining the discrimination, calibration, and clinical utility.ResultsA total of 632 consecutive patients who had been diagnosed with PASC were identified and randomly divided into development (n = 444) and validation (n = 188) cohorts. In the development cohort, the estimated median OS was 7.0 months (95% CI: 6.19–7.82) and the median CSS was 7.0 months (95% CI: 6.15–7.85). In the validation cohort, the estimated median OS was 6.0 months (95% CI: 4.46–7.54) and the median CSS was 7.0 months (95% CI: 6.25–7.75). LASSO-penalized COX regression analysis identified 8 independent predictors in the OS prediction model and 9 independent risk factors in the CSS prediction model: age at diagnosis, gender, year of diagnosis, tumor location, grade, stage, size, lymph node metastasis, combined metastasis, surgery, radiation, and chemotherapy. The Harrell C index and time-dependent AUCs manifested satisfactory discriminative capabilities of the models. Calibration plots showed that both models were well calibrated. Furthermore, decision curves indicated good utility of the nomograms for decision-making.ConclusionNomogram-based models to evaluate personalized OS and CSS in patients with PASC were developed and well validated. These easy-to-use tools will be useful methods to calculate individualized estimate of survival, assist in risk stratification, and aid clinical decision-making.
Tumor-Educated Platelets as a Promising Biomarker for Blood-Based Detection of Renal Cell Carcinoma
Authors: Xiao Ruotao , Liu Cheng , Zhang Bo , Ma Lulin 
Published: March 2022

PurposeTumor-educated platelets (TEPs) are a promising liquid biopsy in many cancers. However, their role in renal cell carcinoma (RCC) is unknown. Thus, this study explored the diagnostic value of TEPs in RCC patients.MethodsPlatelets were prospectively collected from 24 RCC patients and 25 controls. RNA-seq was performed to identify the differentially expressed genes (DEGs) between RCC patients and controls. Besides, RNA-seq data of pan-cancer TEPs were downloaded and randomly divided into training and validation sets. A pan-cancer TEP model was developed in the training set using the support vector machine (SVM) and validated in the validation set and our RCC dataset. Finally, an RCC-based TEP model was developed and optimized through the SVM algorithms and recursive feature elimination (RFE) method.ResultTwo hundred three DEGs, 64 (31.5%) upregulated and 139 (68.5%) downregulated, were detected in the platelets of RCC patients compared with controls. The pan-cancer TEP model had a high accuracy in detecting cancer in the internal validation (training set, accuracy 98.8%, AUC: 0.999; validation set, accuracy 95.4%, AUC: 0.972; different tumor subtypes, accuracy 86.6%–96.1%, AUC: 0.952–1.000). However, the pan-cancer TEP model in the external validation had a scarce diagnostic value in RCC patients (accuracy 48.7%, AUC: 0.615). Therefore, to develop the RCC-based TEP model, the gene biomarkers mostly contributing to the model were selected using the RFE method. The RCC-based TEP model containing 68 gene biomarkers reached a diagnostic accuracy of 100% (AUC: 1.000) in the training set, 88.9% (AUC: 0.963) in the validation set, and 95.9% (AUC: 0.988) in the overall cohort.ConclusionTEPs could function as a minimally invasive blood biomarker in the detection of RCC.
Analysis of Gene Expression Profiles in the Liver of Rats With Intrauterine Growth Retardation
Authors: Shen Zheng , Zhu Weifen , Du Lizhong 
Published: March 2022

BackgroundIntrauterine growth restriction (IUGR) is highly associated with fetal as well as neonatal morbidity, mortality, and an increased risk metabolic disease development later in life. The mechanism involved in the increased risk has not been established. We compared differentially expressed genes between the liver of appropriate for gestational age (AGA) and IUGR rat models and identified their effects on molecular pathways involved in the metabolic syndrome.MethodsWe extracted RNA from the liver of IUGR and AGA rats and profiled gene expression by microarray analysis. GO function and KEGG pathway enrichment analyses were conducted using the Search Tool for the Retrieval of Interacting Genes database. Then, the Cytoscape software was used to visualize regulatory interaction networks of IUGR-related genes. The results were further verified via quantitative reverse transcriptase PCR analysis.ResultsIn this study, 815 genes were found to be markedly differentially expressed (fold-change &gt;1.5, p &lt; 0.05) between IUGR and AGA, with 347 genes elevated and 468 suppressed in IUGR, relative to AGA. Enrichment and protein–protein interaction network analyses of target genes revealed that core genes including Ppargc1a, Prkaa2, Slc2a1, Rxrg, and Gcgr, and pathways, including the PPAR signaling pathway and FoxO signaling pathway, had a potential association with metabolic syndrome development in IUGR. We also confirmed that at the mRNA level, five genes involved in glycometabolism were differentially expressed between IUGR and AGA.ConclusionOur findings elucidate on differential gene expression profiles in IUGR and AGA. Moreover, they elucidate on the pathogenesis of IUGR-associated metabolic syndromes. The suggested candidates are potential biomarkers and eventually intended to treat them appropriately.
Mycoplasma Pneumoniae Infection and Persistent Wheezing in Young Children: A Retrospective Case-Control Study
Authors: Sun Huiming , Li Shuxiang , Wang Ting , Chen Zhengrong 
Published: March 2022

BackgroundTo investigate the clinical characteristics of children with persistent wheezing (PW) with Mycoplasma pneumoniae (MP) DNA in bronchoalveolar lavage fluid (BALF).MethodsThis retrospective case-control study included consecutive admitted children under 3 years of age who were diagnosed with PW and had MP DNA detected in BALF. Patients with mycoplasma pneumoniae pneumonia (MPP) and foreign-body aspiration (FBA) were enrolled as controls. The clinical characteristics of the groups were compared.ResultsDuring the study period, there were 89 patients diagnosed with PW without structural anomalies of the conductive airways, and 30 of these patients (33.7%, 30/89) with MP DNA detected in the BALF were selected as the study group. We included 44 patients with MPP and 44 patients with FBA as controls. Patients with MPP were older and had a higher occurrence of fever and C-reactive protein (CRP) than patients with PW (all P &lt; 0.001). The median MP DNA copy number in patients with MPP was higher than that of patients with PW (P = 0.004). The median level of MP IgG in patients with PW was lower than that of patients with MPP and higher than that of patients with FBA (all P &lt; 0.001). MP DNA copy number positively correlated with age (r = 0.392, P = 0.001) and CRP (r = 0.235, P = 0.048).ConclusionsOur study reveals that MP was highly detected in the BALF of PW patients. In addition, young patients with a low load of MP infection showed lower amounts of antibody, and a weak inflammatory response might be associated with PW.