bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of Paternal Effects on Telomere Length Increases in Early Life
Authors: Bennett Sophie , Girndt Antje , Sánchez-Tójar Alfredo , Burke Terry , Simons Mirre , Schroeder Julia 
Published: May 2022

Offspring of older parents in many species have decreased longevity, a faster ageing rate and lower fecundity than offspring born to younger parents. Biomarkers of ageing, such as telomeres, that tend to shorten as individuals age, may provide insight into the mechanisms of such parental age effects. Parental age may be associated with offspring telomere length either directly through inheritance of shortened telomeres or indirectly, for example, through changes in parental care in older parents affecting offspring telomere length. Across the literature there is considerable variation in estimates of the heritability of telomere length, and in the direction and extent of parental age effects on telomere length. To address this, we experimentally tested how parental age is associated with the early-life telomere dynamics of chicks at two time points in a captive population of house sparrows Passer domesticus. We experimentally separated parental age from sex effects, and removed effects of age-assortative mating, by allowing the parent birds to only mate with young, or old partners. The effect of parental age was dependent on the sex of the parent and the chicks, and was found in the father-daughter relationship only; older fathers produced daughters with longer telomere lengths post-fledging. Overall we found that chick telomere length increased between the age of 0.5 and 3 months at the population and individual level. This finding is unusual in birds with such increases more commonly associated with non-avian taxa. Our results suggest parental age effects on telomere length are sex-specific either through indirect or direct inheritance. The study of similar patterns in different species and taxa will help us further understand variation in telomere length and its evolution.
Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis
Authors: Miano Maurizio , Guardo Daniela , Grossi Alice , Palmisani Elena , Fioredda Francesca , Terranova Paola , Cappelli Enrico , Lupia Michela , Traverso Monica , Dell’Orso Gianluca , Corsolini Fabio , Beccaria Andrea , Lanciotti Marina , Ceccherini Isabella , Dufour Carlo 
Published: May 2022

BackgroundEvans syndrome (ES) is a rare disorder classically defined as the simultaneous or sequential presence of autoimmune haemolytic anaemia and immune thrombocytopenia, but it has also been described as the presence of at least two autoimmune cytopenias. Recent reports have shown that ES is often a manifestation of an underlying inborn error of immunity (IEI) that can benefit from specific treatments.AimsThe aim of this study is to investigate the clinical and immunological characteristics and the underlying genetic background of a single-centre cohort of patients with ES.MethodsData were obtained from a retrospective chart review of patients with a diagnosis of ES followed in our centre. Genetic studies were performed with NGS analysis of 315 genes related to both haematological and immunological disorders, in particular IEI.ResultsBetween 1985 and 2020, 40 patients (23 men, 17 women) with a median age at onset of 6 years (range 0–16) were studied. ES was concomitant and sequential in 18 (45%) and 22 (55%) patients, respectively. Nine of the 40 (8%) patients had a positive family history of autoimmunity. Other abnormal immunological features and signs of lymphoproliferation were present in 24/40 (60%) and 27/40 (67%) of cases, respectively. Seventeen out of 40 (42%) children fit the ALPS diagnostic criteria. The remaining 21 (42%) and 2 (5%) were classified as having an ALPS-like and an idiopathic disease, respectively. Eighteen patients (45%) were found to have an underlying genetic defect on genes FAS, CASP10, TNFSF13B, LRBA, CTLA4, STAT3, IKBGK, CARD11, ADA2, and LIG4. No significant differences were noted between patients with or without variant and between subjects with classical ES and the ones with other forms of multilineage cytopenias.ConclusionsThis study shows that nearly half of patients with ES have a genetic background being in most cases secondary to IEI, and therefore, a molecular evaluation should be offered to all patients.
Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index for Detecting Liver Fibrosis in Patients With Autoimmune Hepatitis: A Meta-Analysis
Authors: Dong Bingtian , Chen Yuping , Lyu Guorong , Yang Xiaocen 
Published: May 2022

BackgroundAspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are the two most widely studied noninvasive markers of liver fibrosis. We aimed to assess the diagnostic accuracy of APRI and FIB-4 for liver fibrosis in patients with autoimmune hepatitis (AIH) using liver biopsy as the reference standard.MethodsPubMed, EMBASE, Cochrane Library and Web of Science databases were searched for studies (published as of May 1st, 2021) that assessed the diagnostic performance of APRI and FIB-4 for liver fibrosis in AIH. The summary area under receiver operating characteristics curve (AUROC), sensitivity, specificity, diagnostic odds ratios were used to assess the diagnostic accuracy of APRI and FIB-4 for detecting liver fibrosis.ResultsFourteen studies (including 1015 patients) were selected with 13 studies each evaluating the use of APRI and FIB-4 for detecting different stages of fibrosis in AIH. For prediction of significant fibrosis, advanced fibrosis, and cirrhosis, the summary AUROC value was 0.66 [95% confidence interval (CI): 0.61–0.70], 0.71 (95% CI: 0.67–0.75), and 0.75 (95% CI: 0.71–0.79) for APRI, and the summary AUROC value was 0.75 (95% CI: 0.71–0.79), 0.73 (95% CI: 0.69–0.77) and 0.79 (95% CI: 0.75–0.82) for FIB-4, respectively. The summary sensitivity and specificity for diagnosis of significant fibrosis, advanced fibrosis, and cirrhosis were 90% and 36%, 78% and 55%, and 77% and 61% for APRI, and 70% and 70%, 65% and 70%, and 78% and 65% for FIB-4, respectively.ConclusionsAPRI and FIB-4 showed suboptimal diagnostic performance for identifying liver fibrosis in AIH with mediocre sensitivity and specificity.
Detection of Five Types of HPV Genotypes Causing Anogenital Warts (Condyloma Acuminatum) Using PCR-Tm Analysis Technology
Authors: Wu Lixia , Wang Weifeng , Zhang Jie , Wu Xuan , Chen Yan , Gu Xiaoping , Shao Huaqing , Li Hongsheng , Liu Weiwei 
Published: May 2022

ObjectivesCondyloma acuminatum (CA) is a common sexually transmitted disease caused by human papillomavirus (HPV) infection. We established a high-throughput, simple, low-cost, and accurate HPV-typing assay (polymerase chain reaction-melting temperature [PCR-Tm] analysis) to detect HPV in CA.Materials and MethodsWe detected 280 cervical scraping samples, including positive samples of HPV-6 (26), HPV-11 (12), HPV-16 (22), HPV-42 (18), HPV-43 (25), HPV-multiple (19), HPV- other type (58), and HPV-negative samples (100). All samples were compared by PCR-Tm analysis and a flow fluorescence hybridization assay. Sequencing was used to confirm the results of the PCR-Tm analysis.ResultsPCR-Tm analysis was specific for each genotype (HPV-6, HPV-11, HPV-16, HPV-42, and HPV-43). The sensitivity of the PCR-Tm analysis assay for each genotype was 103, 103, 103, 103, and 102 copies/reaction, respectively. Most of the 158 samples, including 58 HPV-other type positive and 100 HPV-negative samples tested by the flow fluorescence hybridization assay, were tested negative by PCR-Tm analysis. For the 122 remaining samples, 26 HPV-6, 12 HPV-11, 22 HPV-16, 18 HPV-42, 25 HPV-43, and 19 multiple HPV infections were detected through PCR-Tm analysis. In total, 25 HPV-6, 12 HPV-11, 21 HPV-16, 18 HPV-42, 25 HPV-43, and only 10 multiple HPV infections were detected by the flow fluorescence hybridization assay. The kappa coefficient for the analysis of PCR-Tm analysis and flow fluorescence hybridization assay was 0.940 (P &lt; 0.0001), and the 95% confidence interval of the kappa coefficient was 90.3–97.7%.ConclusionPCR-Tm analysis enabled the detection of HPV-6, HPV-11, HPV-16, HPV-42, and HPV-43, including single and multiple infections.
Potential Embolic Sources Differ in Patients With Embolic Stroke of Undetermined Source According to Age: A 15-Year Study
Authors: Hou Yan , Elmashad Ahmed , Staff Ilene , Alberts Mark , Nouh Amre 
Published: May 2022

IntroductionUnderstanding the potential embolic source in young patients with ESUS may improve the diagnosis and treatment of such patients.HypothesisPotential embolic sources (PES) differ in young vs. older patients with ESUS, and, therefore, not all patients with ESUS have the same risk profile for stroke recurrence.MethodsYoung patients (age 18-49) with ESUS, who were admitted to our stroke center from 2006 to 2019, were identified retrospectively and matched with next consecutive older patients (age 50–99) with ESUS by admission date. PES were categorized as atrial cardiopathy, AFib diagnosed during follow-up, left ventricular disease (LVD), cardiac valvular disease (CVD), PFO or atrial septal aneurysm (ASA), and arterial disease. Patients, who had cancer or thrombophilia, were excluded. The type and number of PES and stroke recurrence rates were determined and compared between young and older patients.ResultsIn young patients (55.3% women, median age 39 years), the most common PES was PFO/ASA, and the rate of other PES was low (2–7%). Half of the young patients (54.1%) had a single PES, only 10% had multiple PES, and 35.3% of young patients did not have any PES identified. In older patients (41.7% women, median age 74 years), the 3 most common PES were atrial cardiopathy (38.1%), LVD (35.7%), and arterial disease (23.8%). Nearly half of older patients (42.9%) had multiple PES. The rate of stroke recurrence tended to be lower in young patients as compared to older patients (4.9 vs. 11.4%, p = 0.29). During a median follow-up of 3 years, only 3 young patients (4.9%) had a recurrent stroke, and two of them had unclosed PFO. There were no recurrent strokes among young patients with no PES identified.ConclusionsIt was noted that PES differ in patients with ESUS according to age and differences in recurrence. PFO is the only common PES in young patients with ESUS. Future studies prospectively evaluating PES in both age groups are needed.
Application of the Willis Covered Stent in the Treatment of Blood Blister-Like Aneurysms: A Single-Center Experience
Authors: Fang Wei , Yu Jia , Liu Yufeng , Sun Peng , Yang Zijian , Zhao Zhenwei , He Yue , Deng Jianping , Zhang Tao 
Published: May 2022

ObjectiveTo evaluate the effectiveness of the Willis covered stent (WCS) in the treatment of ruptured blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA).MethodThe clinical data of 16 patients consecutively treated with WCSs from December 2015 to January 2019 were retrospectively analyzed. Clinical data and angiographic findings were analyzed by two experienced neuroradiologists and neurosurgeons, including age, sex, Hunt and Hess (H&amp;H) grade at admission, modified Rankin scale (mRS) score, aneurysm size, and location, the diameter of the patent artery in proximal and distal ends, stent size, rate of aneurysm occlusion, procedure-related complications, and follow-up.ResultsAll the 16 patients (five males, 11 females) with ICA BBAs underwent WCS deployment successfully. The median age was 49 years (range, 29–72). All patients had complete aneurysm occlusion on immediate postoperative angiography. Anterior choroidal artery (AChA) was occluded in one patient accidentally while no obvious neurological dysfunction was observed. However, this patient underwent subarachnoid hemorrhage 1 day after the treatment; endoleak and aneurysm recurred, and the patient died 10 days later. Therefore, the effective rate of WCS treatment was 93.8% (15/16), and procedure-related complications rate was 6.3% (1/16). Moreover, one patient was urgently treated because of accidental aneurysm rupture after anesthesia, and external ventricular drainage was then performed postoperatively. Another patient developed coma and hemiplegia 3 days after treatment, with emergency angiography showing in-stent thrombosis and ICA occlusion which was recanalized with arterial rt-PA thrombolysis; the patient recovered completely. The clinical follow-up period was 3–30 months in 14 patients. The mRS scores were 0 in 12 patients (85.7%) and 4 in 1 case (7.1%), while 1 patient (7.1%) died 6 months postoperatively for unknown reasons. Angiographic follow-up was performed in 13 patients, and no recurrence was observed. However, ICA occlusion without neurological deficit was observed in one patient.ConclusionBased on careful preoperative evaluation, appropriate WCS size selection, and precise surgical operation, WCSs may provide an alternative and effective solution for blood BBAs via aneurysm isolation and ICA reconstruction immediately; However, further follow-up studies with larger samples are required.
Non-Invasive Diagnostic Test for Advanced Fibrosis in Adolescents With Non-Alcoholic Fatty Liver Disease
Authors: Mosca Antonella , Della Volpe Luca , Alisi Anna , Veraldi Silvio , Francalanci Paola , Maggiore Giuseppe 
Published: May 2022

IntroductionNon-alcoholic fatty liver disease (NAFLD) is a multifaceted disease that includes a wide spectrum of liver damage. The presence and the degree of fibrosis are considered important factors for the prognosis of NAFLD and in predicting the risk of developing cirrhosis. Our aim was to evaluate the usefulness of four fibrosis scores (aspartate aminotransferase/Platelet Index [APRI], FIB-4, NAFLD Fibrosis Score [NFS], and Hepamet) in predicting different degrees of fibrosis among children with biopsy-proven NAFLD.MethodsAbout 286 adolescents [mean age 14.3 years ± 2.5; 154 (53.6%) males], referred between January 2014 and December 2019, with biopsy-proven NAFLD were enrolled.ResultsAbout 173 (60.4%) patients presented fibrosis at histological analysis. In particular: 140 (49.3%) patients had F = 1, 31 (10.8%), had F = 2 and 2 (0.66%) had F = 3. APRI (AUROC 0.619, 95% CI 0.556–0.679) and Hepamet (AUROC 0.778, 95% CI 0.722–0.828) scores had significant (p &lt; 0.001) accuracy to distinguish subjects with fibrosis; while NFS and FIB-4 had not. APRI had a positive predictive value (PPV) of 62.77% (95% CI 57.96–67.35) and an negative predictive value (NPV) of 52.01% (95% CI 46.54–57.43); Hepamet a PPV of 63.24% (95% CI 59.95–66.41) and an NPV of 61.29% (52.9–69.01).ConclusionsOur study showed that Hepamet and APRI perform better than NFS and FIB-4 for identifying fibrosis in patients with NAFLD, but do not have PPVs so high to be considered diagnostic. Therefore, they cannot be employed, in children, for a certain diagnosis of fibrosis or its progression and cannot replace liver biopsy as the gold diagnostic standard. It is, therefore, necessary to continue to research and develop new markers of exclusive fibrosis.
N-Acetylcysteine for the Management of Non-Acetaminophen Drug-Induced Liver Injury in Adults: A Systematic Review
Authors: Sanabria-Cabrera Judith , Tabbai Sara , Niu Hao , Alvarez-Alvarez Ismael , Licata Anna , Björnsson Einar , Andrade Raul J. , Lucena M. Isabel 
Published: May 2022

Introduction: Idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction to drugs and other xenobiotics. DILI has different grades of severity and may lead to acute liver failure (ALF), for which there is no effective therapy. N-acetylcysteine (NAC) has been occasionally tested for the treatment of non-acetaminophen drug-induced ALF. However, limited evidence for its efficacy and safety is currently available. Our aim was to elucidate the benefit and safety of NAC in DILI and evaluate its hepatoprotective effect.Methods: We conducted a systematic review to evaluate the management and prevention focused on NAC in idiosyncratic DILI. The main outcomes included mortality due to DILI, time to normalization of liver biochemistry, transplant-free survival, and adverse events. We included clinical trials and observational studies, either prospective or retrospective.Results: A total of 11 studies were included after literature screening. All studies had different methodologies, and some of them had important risk of bias that may lead to interpreting their findings with caution. The majority of the studies proved NAC efficacy in a cohort of patients with ALF due to different etiologies, where DILI represented a subgroup. NAC seemed to improve transplant-free survival; however, its benefit was inconclusive in terms of overall survival. With regard to safety, NAC showed an adequate safety profile. In prevention studies, NAC showed a possible hepatoprotective effect; however, this finding is limited by the lack of studies and presence of bias.Conclusion: NAC treatment seems to have some benefit in non-acetaminophen drug-induced liver failure patients with acceptable safety; however, due to the lack of evidence and limitations detected across studies, its benefit must be corroborated in clinical trials with adequate methodology.
Efficacy and Safety of Apatinib in Advanced Hepatocellular Carcinoma: A Multicenter Real World Retrospective Study
Authors: Zheng Zhuangzhuang , Liu Zijing , Zhang Haifeng , Guo Xiao , Jia Xiaojing , Wang Jianfeng , Meng Lingbin , Xin Ying , Jiang Xin 
Published: May 2022

Background and Purpose: Apatinib is a novel antiangiogenic agent that can target vascular endothelial cell growth factor 2. The aim of our study was to evaluate the efficacy and safety of apatinib mesylate in the treatment of advanced hepatocellular carcinoma (HCC) in the real world.Methods: We retrospectively analyzed 178 patients with advanced HCC who had been treated with apatinib mesylate from January 2017 to March 2020. The primary outcome indexes were progression-free survival (PFS) and overall survival (OS), and the secondary outcome indexes were overall response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse reactions.Results: Univariate analysis showed that patients with third-line treatment (p &lt;0.001), alpha fetoprotein (AFP) ≥400 ng/ml (p &lt;0.05), distant metastasis (p &lt;0.05), portal vein tumor thrombus (PVTT) (p &lt;0.05), and apatinib monotherapy (p &lt;0.001) had shorter survival. Multivariate analysis confirmed that third-line drugs, PVTT, and combination therapy were independent prognostic factors for PFS in all patients. Univariate analysis showed that Eastern Cooperative Oncology Group (ECOG) scores (p &lt;0.05), line of apatinib (p &lt;0.001), AFP (p &lt;0.001), tumor progression (p &lt;0.05), PVTT (p &lt;0.05), and combination therapy (p &lt;0.001) may impact the OS. Multivariate analysis proved that AFP, PVTT, and combination therapy were independent prognostic factors for OS. The most common adverse reactions were secondary hypertension (29.21%), symptoms of fatigue (16.85%), hand and foot syndrome (16.29%), vomiting (14.04%), liver dysfunction (6.18%), and proteinuria (6.74%). Most of the adverse reactions were Grade 1 or 2.Conclusion: Apatinib mesylate is an effective treatment for advanced HCC, and its adverse reactions are relatively mild. Line of apatinib, PVTT, AFP level, and combination therapy were independent prognostic factors for patients with advanced HCC who were treated with apatinib.
Disrupted Causal Connectivity Anchored on the Right Anterior Insula in Drug-Naive First-Episode Patients With Depressive Disorder
Authors: Xie Haiyan , Guo Qinger , Duan Jinfeng , Jia Xize , Zhou Weihua , Sun Haozhe , Fang Ping , Yang Hong 
Published: May 2022

ObjectMajor depressive disorder (MDD) has been demonstrated to be associated with abnormalities in neural networks. However, few studies examined information flow in the salience network (SN). This study examined abnormalities in the causal connectivity between the SN and whole brain in drug-naive first-episode patients with MDD in the resting state.MethodsBased on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, 23 drug-naive first-episode MDD patients and 20 matched healthy individuals were recruited and underwent a resting-state magnetic resonance scan. The acquired functional image data were preprocessed using resting-state functional magnetic resonance imaging (rs-fMRI) data analysis toolkit plus (RESTplus). Then, using the data processing &amp; analysis for brain imaging (DPABI) software and a coefficient-based general component analysis method with the right anterior insula (rAI) as the region of interest (ROI), the causal connectivity of the SN with the whole brain and its correlation with cognitive and mental performance were examined in the resting state.Results(1) The MDD group showed a significantly higher Hamilton Depression Rating Scale total score and significantly higher scores for anxiety, cognitive disturbance, and block factors compared with normal controls. (2) Compared with control: from whole brain to the rAI, the MDD group showed a lower causal connectivity in the left inferior frontal gyrus; from the rAI to the whole brain, the MDD group showed a lower causal connectivity in the right cingulate gyrus, the right precuneus, and extending to paracentral lobule but higher causal connectivity in the left inferior and middle frontal gyrus. (3) In the MDD group, from rAI to the whole brain, the causal connectivity values for the right cingulate gyrus/precuneus were negatively correlated with the score of Stroop Color-Word Test A, B, and C as well as interference times.ConclusionOur results indicated disrupted causal connectivity among the default mode network (DMN), the central executive network (CEN), and SN in drug-naive first-episode MDD patients. Especially, our results suggest a unique role for rAI in the ordered or hierarchical information processing, presumed to include bottom-up and top-down reciprocal influences among the three networks in MDD.