bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioimpedance Phase Angle as a Prognostic Tool in Late-Onset Pompe Disease: A Single-Centre Prospective Study With a 15-year Follow-Up
Authors: Ravaglia Sabrina , de Giuseppe Rachele , Carlucci Annalisa , Jehne Susan , Crescimanno Grazia , Ahmad Lara , Paoletti Matteo , Clemente Gabriele , Pichiecchio Anna , Bazzano Rosella , Cirio Serena , Valente Enza Maria , Danesino Cesare , De Filippi Paola , Tartara Alice , Cena Hellas 
Published: February 2022

Background: Late-onset Pompe disease (LOPD) is an autosomal-recessive metabolic myopathy caused by deficiency of the lysosomal enzyme Acid Alpha—Glucosidase (GAA), leading to glycogen accumulation in proximal and axial muscles, and in the diaphragm. Enzyme Replacement Therapy (ERT) with recombinant GAA became available in 2006. Since then, several outcome measures have been investigated for the adequate follow-up of disease progression and treatment response, usually focusing on respiratory and motor function. Prognostic factors predicting outcome have not been identified till now.Methods: In this single Centre, prospective study, we evaluate the response to enzyme replacement therapy in 15 patients (7 males) with LOPD in different stages of disease, aged 49.4 ± 16.1, followed-up for 15 years. Treatment response was measured by the 6-min walking test, vital capacity in supine and upright position, respiratory muscle strength, muscle MRI, manual muscle testing. We investigated the usefulness of Body Impedance Vectorial Analysis for serial body composition assessment.Results: Although most patients with LOPD benefit from long-term treatment, some secondary decline may occur after the first 3–5 years. Some nutritional (lower body mass index, higher fat free mass, higher phase angle) and disease parameters (higher creatinine and shorter disease duration at the beginning of treatment) seem to predict a better motor outcome. Lower Phase Angle, possibly reflecting loss of integrity of skeletal muscle membranes and thus treatment mis-targeting, seems to correlate with worse treatment response on long-term follow-up.Conclusion: Body Impedance Vectorial Analysis is a fast, easily performed and cheap tool that may be able to predict long-term treatment response in patients with LOPD. Low Phase angle may serve as a marker of muscle quality and may be used to predict the response to a muscle-targeted intervention such as ERT, thus improving the identification of patients needing a closer follow-up due to higher fragility and risk of deterioration.
PSRC1 May Affect Coronary Artery Disease Risk by Altering CELSR2, PSRC1, and SORT1 Gene Expression and Circulating Granulin and Apolipoprotein B Protein Levels
Authors: Chai Tianci , Wang Zhisheng , Yang Xiaojie , Qiu Zhihuang , Chen Liangwan 
Published: February 2022

ObjectiveThe aim of the study was to identify additional factors that contributed to coronary artery disease (CAD).MethodsWe conducted integrative analysis on publicly available data from genome-wide association studies and quantitative trait locus studies by employing Mendelian randomization methods to examine the associations of gene expression in liver cells and circulating protein levels with LDL-C and CAD.ResultsWe found that the mRNA expression levels of CELSR2, PSRC1, SORT1, SYPL2, RHD, RHCE, ANGPTL3, ATXN7L2, DNAH11, FADS3, ST3GAL4, NYNRIN, CETP, EFCAB13, and SPTLC3 were significantly associated with LDL-C. The expression levels of SORT1, PSRC1, and CELSR2 in liver cells were significantly associated with CAD. Higher expression levels of SORT1, PSRC1, and CELSR2 in the liver were significantly associated with lower circulating LDL-C levels and CAD risk. PSRC1 variants were strongly associated with SORT1, PSRC1, and CELSR2 gene expression in liver cells. Higher circulating granulin and apolipoprotein B levels, which were strongly affected by PSRC1 variants, were significantly associated with higher LDL-C levels and CAD risk, with odds ratios of 1.15 (1.10–1.19) and 1.45 (1.21–1.74), respectively.ConclusionThis study showed that regulatory SNPs in PSRC1 may affect CAD risk by altering CELSR2, PSRC1, and SORT1 gene expression in liver cells and circulating granulins and apolipoprotein B proteins.
Risk Factors and Nomogram for Predicting Relapse Risk in Pediatric Neuromyelitis Optica Spectrum Disorders
Authors: Zhang Shanchao , Qiao Shan , Li Haiyun , Zhang Ranran , Wang Meiling , Han Tao , Liu Xuewu , Wang Yunshan 
Published: February 2022

BackgroundNeuromyelitis optica spectrum disorders (NMOSDs) are attack-relapsing autoimmune inflammatory diseases of the central nervous system, which are characterized by the presence of serological aquaporin-4 (AQP4) antibody. However, this disorder is uncommon in children, and AQP4 antibody was often found to be seronegative. However, some pediatric patients diagnosed with NMOSDs were tested to be positive for myelin oligodendrocyte glycoprotein (MOG) antibody. The previous investigations of pediatric NMOSDs were usually focused on the clinical presentation, treatment responses, and long-term prognoses, but little is known about the risk factors predicting NMOSD relapse attacks in a shorter time, especially, for Chinese children.MethodsWe retrospectively identified 64 Chinese pediatric patients, including 39 positive for AQP4 antibody, 12 positive for MOG antibody, and the rest negative for AQP4 and MOG antibodies. Independent risk factors predicting relapse in 1-year follow-up were extracted by multivariate regression analysis to establish a risk score model, its performance evaluation was analyzed using receiver operating characteristic (ROC) curve, and the independent risk factors related to relapse manifestation were also explored through multivariate logistic analysis. A nomogram was generated to assess relapse attacks in 1-year follow-up. Thirty-five patients from 3 other centers formed an external cohort to validate this nomogram.ResultsFour independent relapsed factors included discharge Expanded Disability Status Scale (EDSS) (p = 0.017), mixed-lesion onset (p = 0.010), counts (≧1) of concomitant autoantibodies (p = 0.015), and maintenance therapy (tapering steroid with mycophenolate mofetil (MMF), p = 0.009; tapering steroid with acetazolamide (AZA), p = 0.045; and tapering steroid only, p = 0.025). The risk score modeled with these four factors was correlated with the likelihood of relapse in the primary cohort (AUC of 0.912) and the validation cohort (AUC of 0.846). Also, our nomogram exhibited accurate relapse estimate in the primary cohort, the validation cohort, and the whole cohort, but also in the cohorts with positive/negative AQP4 antibody, and noticeably, it performed predictive risk improvement better than other factors in the concordance index (C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).ConclusionsThe risk score and nomogram could facilitate accurate prognosis of relapse risk in 1-year follow-up for pediatric NMOSDs and help clinicians provide personalized treatment to decrease the chance of relapse.
High PIRCHE Scores May Allow Risk Stratification of Borderline Rejection in Kidney Transplant Recipients
Authors: Lezoeva Ekaterina , Nilsson Jakob , Wüthrich Rudolf , Mueller Thomas F. , Schachtner Thomas 
Published: February 2022

BackgroundThe diagnosis of borderline rejection (BLR) ranges from mild inflammation to clinically significant TCMR and is associated with an increased risk of allograft dysfunction. Currently, there is no consensus regarding its treatment due in part to a lack of biomarkers to identify cases with increased risk for immune-mediated injury.MethodsWe identified 60 of 924 kidney transplant recipients (KTRs) with isolated and untreated BLR. We analyzed the impact of predicted indirectly recognizable HLA epitopes (PIRCHE) score on future rejection, de novo DSA development, and recovery to baseline allograft function. Additionally, we compared the outcomes of different Banff rejection phenotypes.ResultsTotal PIRCHE scores were significantly higher in KTRs with BLR compared to the entire study population (p=0.016). Among KTRs with BLR total PIRCHE scores were significantly higher in KTRs who developed TCMR/ABMR in follow-up biopsies (p=0.029). Notably, the most significant difference was found in PIRCHE scores for the HLA-A locus (p=0.010). PIRCHE scores were not associated with the development of de novo DSA or recovery to baseline allograft function among KTRs with BLR (p&gt;0.05). However, KTRs under cyclosporine-based immunosuppression were more likely to develop de novo DSA (p=0.033) than those with tacrolimus, whereas KTRs undergoing retransplantation were less likely to recover to baseline allograft function (p=0.003).ConclusionsHigh PIRCHE scores put KTRs with BLR at an increased risk for future TCMR/ABMR and contribute to improved immunological risk stratification. The benefit of anti-rejection treatment, however, needs to be evaluated in future studies.
Role of a Urinary Biomarker in the Common Mechanism of Physical Performance and Cognitive Function
Authors: Jiang Shan , Cui Ju , Zhang Li-Qun , Liu Zhen , Zhang Yan , Shi Yuan , Cai Jian-Ping 
Published: February 2022

IntroductionHealthy aging is described as a process of developing and maintaining intrinsic abilities, including physical and cognitive functions. Although oxidative stress is a common mechanism shared by loss of muscle strength and dementia, its relationship with decreased physical performance and cognitive impairment remains unclear. We aimed to investigate the role of urinary 8-oxo-7, 8-dihydroguanosine (8-oxoGsn), a biomarker of oxidative damage to RNA, in physical and cognitive decline.MethodsThe study followed a cross-sectional design and recruited 40–94-year-old inhabitants of Beijing, China (471 men and 881 women). The physical performance of the participants was assessed using handgrip strength, walking speed, and the repeated chair stand test. The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) 5-min protocol. Urinary 8-oxoGsn levels were measured for all participants.ResultsParticipants with high urinary 8-oxoGsn levels were more likely to have low grip strength, slow walking speed, poor performance in the repeated chair stand test, and low scores on the MoCA 5-min protocol (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.52–7.76; OR 1.71, 95% CI: 1.16–2.53; OR 2.06, 95% CI: 0.92–4.63; OR 1.75, 95% CI: 1.18–2.58), after adjusting for age, sex, smoking habits, alcohol consumption, hypertension, diabetes, cerebro-cardiovascular disease, and chronic kidney disease.ConclusionElevated levels of oxidative stress are independently associated with cognitive and physical impairment. Thus, these results can help in the early identification and development of strategies for the prevention and treatment of intrinsic capacity decline.
Prognostic Value of Radiotherapy and Chemotherapy in Stage I–III Merkel Cell Carcinoma
Authors: Bi Aihong , Yang Sifu , Ding Yang , Yu Yong , Zhan Wenming , Song Tao 
Published: February 2022

PurposeMerkel cell carcinoma (MCC) is a highly malignant cancer associated with dismal survival outcomes. Surgery is the cornerstone for the management of MCC, but the benefit of radiotherapy (RT) and chemotherapy (CT) is still controversial. We aimed to investigate the prognostic value of RT and CT in the management of stage I-III MCC patients using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsPatients with a histopathological diagnosis of MCC between 2010 and 2016 were included. The primary endpoint of this study was overall survival (OS). The prognostic significance for OS was analyzed by Cox proportional hazard regression model.ResultsA total of 1,691 patients were identified in the SEER database. Over half of the patients had received RT (56.7%), and 9.8% of the patients were documented to have received CT. The median OS for the entire cohort was 66.0 months, and the 5-year OS rate was 53.8%. In the multivariate analysis, receiving RT was associated with significantly improved OS (P &lt; 0.001), while receiving CT significantly negatively impacted OS (P = 0.010). In stage III patients who underwent treatment based on surgical resection, RT was still demonstrated to be a positive factor (P = 0.002), while CT had no significant association with OS in the univariate analysis (P = 0.295).ConclusionsThe current data in the SEER database are consistent with earlier studies supporting the benefit of adjuvant RT for stage I-III MCC patients, but caution should be taken regarding the routine use of CT. For stage III MCC patients, the value of adjuvant CT needs to be confirmed in future studies.
Maternal Cigarette Smoke Exposure Exaggerates the Behavioral Defects and Neuronal Loss Caused by Hypoxic-Ischemic Brain Injury in Female Offspring
Authors: Huang Taida , Huang Xiaomin , Li Hui , Qi Junhua , Wang Nan , Xu Yi , Zeng Yunxin , Xiao Xuewen , Liu Ruide , Chan Yik Lung , Oliver Brian G. , Yi Chenju , Li Dan , Chen Hui 
Published: February 2022

ObjectiveHypoxic-ischemic encephalopathy affects ∼6 in 1,000 preterm neonates, leading to significant neurological sequela (e.g., cognitive deficits and cerebral palsy). Maternal smoke exposure (SE) is one of the common causes of neurological disorders; however, female offspring seems to be less affected than males in our previous study. We also showed that maternal SE exaggerated neurological disorders caused by neonatal hypoxic-ischemic brain injury in adolescent male offspring. Here, we aimed to examine whether female littermates of these males are protected from such insult.MethodsBALB/c dams were exposed to cigarette smoke generated from 2 cigarettes twice daily for 6 weeks before mating, during gestation and lactation. To induce hypoxic-ischemic brain injury, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen) at postnatal day (P) 10. Behavioral tests were performed at P40–44, and brain tissues were collected at P45.ResultsMaternal SE worsened the defects in short-term memory and motor function in females with hypoxic-ischemic injury; however, reduced anxiety due to injury was observed in the control offspring, but not the SE offspring. Both hypoxic-ischemic injury and maternal SE caused significant loss of neuronal cells and synaptic proteins, along with increased oxidative stress and inflammatory responses.ConclusionOxidative stress and inflammatory response due to maternal SE may be the mechanism of worsened neurological outcomes by hypoxic-ischemic brain injury in females, which was similar to their male littermates shown in our previous study.
Muscular Function as an Alternative to Identify Cognitive Impairment: A Secondary Analysis From SABE Colombia
Authors: Garcia-Cifuentes Elkin , Botero-Rodríguez Felipe , Ramirez Velandia Felipe , Iragorri Angela , Marquez Isabel , Gelvis-Ortiz Geronimo , Acosta María-Fernanda , Jaramillo-Jimenez Alberto , Lopera Francisco , Cano-Gutiérrez Carlos Alberto 
Published: February 2022

BackgroundIdentification of cognitive impairment is based traditionally on the neuropsychological tests and biomarkers that are not available widely. This study aimed to establish the association between motor function (gait speed and handgrip strength) and cognitive performance in the Mini-Mental State Examination, globally and by domains. A secondary goal was calculating a cut-off point for gait speed and handgrip strength to classify older adults as cognitively impaired.MethodsThis is a secondary analysis of SABE Colombia (Salud, Bienestar &amp; Envejecimiento), a survey that was conducted in 2015 on health, wellbeing, and aging in Colombia. This study used linear regression models to search for an association between motor function and cognitive performance. The accuracy of motor function measurements in identifying cognitive impairment was assessed with receiver operating characteristic (ROC) curves. This study also analyzed other clinical and sociodemographical variables.ResultsGait speed was associated with orientation (r2 = 0.16), language (r2 = 0.15), recall memory (r2 = 0.14), and counting (r2 = 0.08). Similarly, handgrip strength was associated with orientation (r2 = 0.175), language (r2 = 0.164), recall memory (r2 = 0.137), and counting (r2 = 0.08). To differentiate older adults with and without cognitive impairment, a gait speed cut-off point of 0.59 m/s had an area under the curve (AUC) of 0.629 (0.613–0.646), and a weak handgrip (strength below 17.5 kg) had an AUC of 0.653 (0.645-0.661). The cut-off points for handgrip strength and gait speed were significantly higher in male participants.ConclusionsGait speed and handgrip strength are similarly associated with the cognitive performance, exhibiting the most extensive association with orientation and language domains of the Mini-Mental State Examination. Gait speed and handgrip strength can easily be measured by any clinician, and they prove to be useful screening tools to detect cognitive impairment.
Inhaled Nitric Oxide Treatment for Aneurysmal SAH Patients With Delayed Cerebral Ischemia
Authors: Fung Christian , Z'Graggen Werner J. , Jakob Stephan M. , Gralla Jan , Haenggi Matthias , Rothen Hans-Ulrich , Mordasini Pasquale , Lensch Michael , Söll Nicole , Terpolilli Nicole , Feiler Sergej , Oertel Markus F. , Raabe Andreas , Plesnila Nikolaus , Takala Jukka , Beck Jürgen 
Published: February 2022

BackgroundWe demonstrated experimentally that inhaled nitric oxide (iNO) dilates hypoperfused arterioles, increases tissue perfusion, and improves neurological outcome following subarachnoid hemorrhage (SAH) in mice. We performed a prospective pilot study to evaluate iNO in patients with delayed cerebral ischemia after SAH.MethodsSAH patients with delayed cerebral ischemia and hypoperfusion despite conservative treatment were included. iNO was administered at a maximum dose of 40 ppm. The response to iNO was considered positive if: cerebral artery diameter increased by 10% in digital subtraction angiography (DSA), or tissue oxygen partial pressure (PtiO2) increased by &gt; 5 mmHg, or transcranial doppler (TCD) values decreased more than 30 cm/sec, or mean transit time (MTT) decreased below 6.5 secs in CT perfusion (CTP). Patient outcome was assessed at 6 months with the modified Rankin Scale (mRS).ResultsSeven patients were enrolled between February 2013 and September 2016. Median duration of iNO administration was 23 h. The primary endpoint was reached in all patients (five out of 17 DSA examinations, 19 out of 29 PtiO2 time points, nine out of 26 TCD examinations, three out of five CTP examinations). No adverse events necessitating the cessation of iNO were observed. At 6 months, three patients presented with a mRS score of 0, one patient each with an mRS score of 2 and 3, and two patients had died.ConclusionAdministration of iNO in SAH patients is safe. These results call for a larger prospective evaluation.
Response and Disease Dynamics in Untreated Metastatic Colorectal Cancer With Bevacizumab-Based Sequential vs. Combination Chemotherapy—Analysis of the Phase 3 XELAVIRI Trial
Authors: Kurreck Annika , Heinemann Volker , Fischer von Weikersthal Ludwig , Decker Thomas , Kaiser Florian , Uhlig Jens , Schenk Michael , Freiberg-Richter Jens , Peuser Bettina , Denzlinger Claudio , Graeven Ullrich , Heinrich Kathrin , Held Swantje , Stahler Arndt , Alig Annabel Helga Sophie , Jelas Ivan , von Einem Jobst C. , Stintzing Sebastian , Giessen-Jung Clemens , Modest Dominik P. 
Published: February 2022

IntroductionEarly tumor shrinkage (ETS), depth of response (DpR), and time to DpR represent exploratory endpoints that may serve as early efficacy parameters and predictors of long-term outcome in metastatic colorectal cancer (mCRC). We analyzed these endpoints in mCRC patients treated with first-line bevacizumab-based sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) chemotherapy within the phase 3 XELAVIRI trial.MethodsDpR (change from baseline to smallest tumor diameter), ETS (≥20% reduction in tumor diameter at first reassessment), and time to DpR (study randomization to DpR image) were analyzed. We evaluated progression-free survival and overall survival with ETS as stratification parameter according to treatment arm, molecular subgroup, and sex.ResultsIn 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; p = 0.001) and significantly greater DpR (-40.0% vs. -24.7%; p &lt; 0.001) were observed in the initial combination therapy arm. The improvement was pronounced in RAS/BRAF wild-type tumors. ETS correlated with improved survival irrespective of treatment arm (PFS: p &lt; 0.001; OS: p = 0.012) and molecular subgroup (PFS: p &lt; 0.001; OS: p &lt; 0.001). Male patients in contrast to female patients with ETS had survival benefit (PFS: p &lt; 0.001, HR 0.532; OS: p &lt; 0.001, HR 0.574 vs. PFS: p = 0.107; OS: p = 0.965).ConclusionsInitial irinotecan-based combination therapy with bevacizumab improved ETS and DpR in mCRC patients with a particularly high irinotecan sensitivity of RAS/BRAF wild-type tumors. ETS seems to be a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC. This finding was rather driven by male patients, potentially indicating that ETS might be less predictive of long-term outcome in an elderly, female population.
Case Report: Genetic Analysis of a Small Supernumerary Marker Chromosome in a Unique Case of Mosaic Turner Syndrome
Authors: Li Chao , Luo Weiyao , Xiao Tingting , Yang Xingkun , Ou Miaoling , Zhang Linghua , Huang Xiang , Zhu Xiaodan 
Published: February 2022

BackgroundThe aim of this study was to explore the source and morphology of a small supernumerary marker chromosome (sSMC) from karyotype analysis of a patient with a unique case of mosaic Turner syndrome. The study findings will provide technical reference and genetic counseling for similar cases.Case PresentationA female patient with 46,X,+mar karyotype was diagnosed by genetic karyotype analysis. Genetic methods including fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq) based on low-depth whole-genome sequencing were used to explore the source and morphology of sSMC. FISH technology showed that 56.5% of the cells were X and 43.5% of the cells were XY. CNV-seq detection found that the sSMC was chrY, implying that the patient's karyotype was mos 45,X[58.6%]/46,XY[41.4%]. Retrospective karyotype analysis indicated that the female patient's sSMC was inherited from her father's small chrY. Customized FISH probe of Yq12 microdeletion was positive, indicating that the sSMC was a del(Y)(q12). Based on the results of genetic diagnosis, the specialist doctor gave a comprehensive genetic consultation and ordered regular follow-up examinations.ConclusionsThe findings of the current study showed that the chromosome description of the unique Turner case was mos 45,X[56.5%]/46,X,del(Y)(q12)[43.5%]. FISH technology played a key role in diagnosis of mosaicism. The terminal deletion of mosaic chrY provided a scientific and an accurate explanation for masculinity failure and abnormal sexual development of the current case.