bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSF and Serum Levels of Inflammatory Markers in PD: Sparse Correlation, Sex Differences and Association With Neurodegenerative Biomarkers
Authors: Lerche Stefanie , Zimmermann Milan , Wurster Isabel , Roeben Benjamin , Fries Franca Laura , Deuschle Christian , Waniek Katharina , Lachmann Ingolf , Gasser Thomas , Jakobi Meike , Joos Thomas O. , Schneiderhan-Marra Nicole , Brockmann Kathrin 
Published: February 2022

BackgroundAn involvement of the central-nervous and peripheral, innate and adaptive immune system in the pathogenesis of Parkinson's disease (PD) is nowadays well established.ObjectivesWe face several open questions in preparation of clinical trials aiming at disease-modification by targeting the immune system: Do peripheral (blood) inflammatory profiles reflect central (CSF) inflammatory processes? Are blood/CSF inflammatory markers associated with CSF levels of neurodegenerative/PD-specific biomarkers?MethodsUsing a multiplex assay we assessed 41 inflammatory markers in CSF/serum pairs in 453 sporadic PD patients. We analyzed CSF/serum correlation as well as associations of inflammatory markers with clinical outcome measures (UPDRS-III, H&amp;Y, MoCA) and with CSF levels of α-synuclein, Aβ1−42, t-Tau, p181-Tau and NFL. All analyses were stratified by sex as the immune system shows relevant sex-specific differences.ResultsCorrelations between CSF and serum were sparse and detected in only 25% (9 out of 36) of the analysable inflammatory markers in male PD patients and in only 38% (12 out of 32) of female PD patients. The most important pro-inflammatory mediators associated with motor and cognitive decline as well as with neurodegenerative/PD-specific biomarkers were FABP, ICAM-1, IL-8, MCP-1, MIP-1-beta, and SCF. Results were more robust for CSF than for serum.InterpretationLevels of central-nervous and peripheral inflammatory markers might be regulated independently of each other with CSF inflammatory markers reflecting CNS pathology more accurately than peripheral markers. These findings along with sex-specific characteristics have to be considered when designing clinical trials aiming at disease-modification by targeting the immune system.
An Automated Tongue Tracker for Quantifying Bulbar Function in ALS
Authors: Northall Alicia , Mukhopadhyay Budhaditya , Weber Miriam , Petri Susanne , Prudlo Johannes , Vielhaber Stefan , Schreiber Stefanie , Kuehn Esther 
Published: February 2022

IntroductionBulbar symptoms, including difficulty swallowing and speaking, are common in amyotrophic lateral sclerosis (ALS) and other neurological disorders, such as stroke. The presence of bulbar symptoms provides important information regarding clinical outcomes, such as survival time after diagnosis. Nevertheless, there are currently no easily accessible, quantitative methods to measure bulbar function in patients.MethodsWe developed an open-source tool called Tongue Tracker (TT) to quantify bulbar function by training a neural network to track kinematic tongue features of short video clips of lateral tongue movements. We tested 16 healthy controls and ten patients with ALS, of whom two patients were clinically diagnosed with bulbar-onset type and eight patients were clinically diagnosed with limb-onset type. Of the limb-onset patients, five patients also showed symptoms of bulbar impairment.ResultsWe validated TT by comparing the results with manual delineation of tongue movements in the clips. We demonstrate an early-stage bulbar-onset patient who showed fewer and slower tongue sweeps compared to healthy controls and limb-onset patients and we show that five bulbar-impaired limb-onset patients have a different tongue kinematic profile compared to healthy controls.DiscussionTT may serve to detect quantitative markers of bulbar dysfunction in ALS and other motor disorders, such as stroke, by identifying signatures of spasticity or muscle weakness that affects tongue movement speed and/or tongue movement topography.
Brain Atrophy and Clinical Characterization of Adults With Mild Cognitive Impairment and Different Cerebrospinal Fluid Biomarker Profiles According to the AT(N) Research Framework of Alzheimer’s Disease
Authors: Rivas-Fernández Miguel Ángel , Lindín Mónica , Zurrón Montserrat , Díaz Fernando , Aldrey-Vázquez José Manuel , Pías-Peleteiro Juan Manuel , Vázquez-Vázquez Laura , Pereiro Arturo Xosé , Lojo-Seoane Cristina , Nieto-Vieites Ana , Galdo-Álvarez Santiago 
Published: February 2022

IntroductionThis study aimed to evaluate, in adults with mild cognitive impairment (MCI), the brain atrophy that may distinguish between three AT(N) biomarker-based profiles, and to determine its clinical value.MethodsStructural MRI (sMRI) was employed to evaluate the volume and cortical thickness differences in MCI patients with different AT(N) profiles, namely, A−T−(N)−: normal AD biomarkers; A+T−(N)−: AD pathologic change; and A+T+(N)+: prodromal AD. Sensitivity and specificity of these changes were also estimated.ResultsAn initial atrophy in medial temporal lobe (MTL) areas was found in the A+T−(N)− and A+T+(N)+ groups, spreading toward the parietal and frontal regions in A+T+(N)+ patients. These structural changes allowed distinguishing AT(N) profiles within the AD continuum; however, the profiles and their pattern of neurodegeneration were unsuccessful to determine the current clinical status.ConclusionsMRI is useful in the determination of the specific brain structural changes of AT(N) profiles along the AD continuum, allowing differentiation between MCI adults with or without pathological AD biomarkers.
Effectiveness of Different Methods for Baroreflex Sensitivity Assessment in Determining the Severity of Cardiovascular Autonomic Neuropathy in Patients With Parkinson’s Disease
Authors: Huang Chih-Cheng , Lai Yun-Ru , Lien Chia-Yi , Cheng Ben-Chung , Kung Chia-Te , Chiang Yi-Fang , Lu Cheng-Hsien 
Published: February 2022

BackgroundAutonomic disorders are an important non-motor feature of Parkinson’s disease (PD). Baroreflex sensitivity (BRS) is often used as an indicator of cardiovascular autonomic function, and it is clinically significant. Several different methods of BRS assessment have been described. We evaluated and compared the efficiency of several methods of BRS assessment for additional insight into the underlying physiology and the determination of its severity in patients with PD.Materials and MethodsEighty-five patients with PD underwent cardiovascular autonomic testing. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment and to define the presence of cardiovascular autonomic neuropathy (CAN). BRS was assessed using the Valsalva maneuver (BRS_VM). In addition, spontaneous BRS was computed using the sequence method and the spectral method.Results and ConclusionThere was considerable agreement between the different methods of BRS assessment. Nevertheless, BRS_VM exhibited a higher degree of correlation with cardiovascular autonomic function than spontaneous BRS indexes obtained by the sequence or spectral method. BRS_VM, rather than spontaneous BRS, also had a predictive value for the presence of CAN to the diagnostic criteria by CASS in patients with PD.
Type I Interferon Response Is Mediated by NLRX1-cGAS-STING Signaling in Brain Injury
Authors: Fritsch Lauren E. , Ju Jing , Gudenschwager Basso Erwin Kristobal , Soliman Eman , Paul Swagatika , Chen Jiang , Kaloss Alexandra M. , Kowalski Elizabeth A. , Tuhy Taylor C. , Somaiya Rachana Deven , Wang Xia , Allen Irving Coy , Theus Michelle H. , Pickrell Alicia M. 
Published: February 2022

BackgroundInflammation is a significant contributor to neuronal death and dysfunction following traumatic brain injury (TBI). Recent evidence suggests that interferons may be a key regulator of this response. Our studies evaluated the role of the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) signaling pathway in a murine model of TBI.MethodsMale, 8-week old wildtype, STING knockout (−/−), cGAS−/−, and NLRX1−/− mice were subjected to controlled cortical impact (CCI) or sham injury. Histopathological evaluation of tissue damage was assessed using non-biased stereology, which was complemented by analysis at the mRNA and protein level using qPCR and western blot analysis, respectively.ResultsWe found that STING and Type I interferon-stimulated genes were upregulated after CCI injury in a bi-phasic manner and that loss of cGAS or STING conferred neuroprotection concomitant with a blunted inflammatory response at 24 h post-injury. cGAS−/− animals showed reduced motor deficits 4 days after injury (dpi), and amelioration of tissue damage was seen in both groups of mice up to 14 dpi. Given that cGAS requires a cytosolic damage- or pathogen-associated molecular pattern (DAMP/PAMP) to prompt downstream STING signaling, we further demonstrate that mitochondrial DNA is present in the cytosol after TBI as one possible trigger for this pathway. Recent reports suggest that the immune modulator NLR containing X1 (NLRX1) may sequester STING during viral infection. Our findings show that NLRX1 may be an additional regulator that functions upstream to regulate the cGAS-STING pathway in the brain.ConclusionsThese findings suggest that the canonical cGAS-STING-mediated Type I interferon signaling axis is a critical component of neural tissue damage following TBI and that mtDNA may be a possible trigger in this response.
Impact of Overhydration on Left Ventricular Hypertrophy in Patients With Chronic Kidney Disease
Authors: Sun Lianqin , Li Qing , Sun Zhiying , Duan Suyan , Nie Guangyan , Dong Jiaxin , Zhang Chengning , Zeng Ming , Sun Bin , Yuan Yanggang , Wang Ningning , Mao Huijuan , Xing Changying , Zhang Bo 
Published: February 2022

ObjectiveVolume overload is a frequent feature related to left ventricular hypertrophy (LVH) in dialysis patients, but its influence on patients with chronic kidney disease (CKD) not on dialysis has not been accurately uncovered. This article was to examine the relationship between overhydration (OH) and LVH in patients with CKD not yet on dialysis.MethodsA total of 302 patients with CKD stages 1–4 were included. Participants were divided into different subgroups according to occurring LVH or not, and OH tertiles. Clinical and laboratory parameters were compared among groups. Spearman correlation analyses were adopted to explore the relationships of echocardiographic findings with the clinical and laboratory characteristics. Binary logistic regression models were performed to estimate the odds ratios (ORs) for the associations between OH and LVH. Restricted cubic splines were implemented to assess the possible non-linear relationship between OH and LVH. LVH was defined as left ventricular mass index (LVMI) &gt;115 g/m2 in men and &gt;95 g/m2 in women.ResultsOf the enrolled patients with CKD, the mean age was 45.03 ± 15.14 years old, 165 (54.6%) cases were men, and 65 (21.5%) cases had LVH. Spearman correlation analyses revealed that OH was positively correlated with LVMI (r = 0.263, P &lt; 0.001). After adjustment for age, gender, diabetes, body mass index (BMI), systolic blood pressure (SBP), hemoglobin, serum albumin, estimated glomerular filtration rate (eGFR), and logarithmic transformation of urinary sodium and urinary protein, multivariate logistic regression analyses demonstrated that both the middle and highest tertile of OH was associated with increased odds of LVH [OR: 3.082 (1.170–8.114), P = 0.023; OR: 4.481 (1.332–15.078), P = 0.015, respectively], in comparison to the lowest tierce. Restricted cubic spline analyses were employed to investigate the relationship between OH and LVH, which unfolded a significant non-linear association (P for non-linear = 0.0363). Furthermore, patients were divided into two groups according to CKD stages. The multivariate logistic regression analyses uncovered that increased odds of LVH were observed in the middle and the highest tertile of OH [OR: 3.908 (0.975–15.670), P = 0.054; OR: 6.347 (1.257–32.054), P = 0.025, respectively] in patients with stages 1–2.ConclusionThese findings suggest that a higher level of OH was associated with a higher occurrence of LVH in patients with CKD not on dialysis, especially in patients with CKD stages 1–2.
Biomarker Testing Patterns and Treatment Outcomes in Patients With Advanced Non-Small Cell Lung Cancer and MET Exon 14 Skipping Mutations: A Descriptive Analysis From the US
Authors: Asad Zadeh Vosta Kolaei Fatemeh , Cai Beilei , Kanakamedala Hemanth , Kim Julia , Doban Vitalii , Zhang Shiyu , Shi Michael 
Published: February 2022

BackgroundMET exon 14 skipping mutation (METex14) is observed in ~3% of non-small cell lung cancer (NSCLC) cases and has been shown to be an independent poor prognostic factor associated with shorter overall disease-specific survival. Broad molecular testing can identify this biomarker in patients with advanced NSCLC (aNSCLC) and allow patients to be matched with the appropriate targeted therapy. This study examines biomarker testing patterns and clinical outcomes of chemotherapy and immuno-oncology (IO) monotherapy in aNSCLC patients with METex14.MethodsA descriptive retrospective study was conducted using the Flatiron Health–Foundation Medicine Inc. (FMI) clinico-genomic database. Patients with METex14 aNSCLC treated with systemic therapies were included in the biomarker testing analysis. The duration from specimen collection to reported results was assessed for PD-L1– and METex14-tested patients. Clinical outcomes were assessed in patients treated with chemotherapy or IO monotherapy. First-line (1L) and second-line (2L) real-world progression-free survival (rw-PFS) were estimated using Kaplan-Meier analysis.ResultsOf 91 METex14 patients eligible for the biomarker testing analysis, 77% and 60% received PD-L1 and FMI next-generation sequencing (NGS) testing within 3 months post aNSCLC diagnosis. Of those assessed for both PD-L1 and METex14 (n=9), the median duration between specimen collection and reporting was 1 week shorter for PD-L1 than for FMI NGS. Median 1L rw-PFS was 5.7 months (95% CI, 4.6-7.1) and 2.4 months (95% CI, 1.4-3.2) in patients receiving 1L chemotherapy (n=59) and IO monotherapy (n=18), with 3-month 1L rw-PFS rates of 78% and 33%. Median 2L rw-PFS was 3.5 months (95% CI, 1.9-11.1) and 4.7 months (95% CI, 2.8-12.9) in patients receiving 2L chemotherapy (n=16) and IO monotherapy (n=23), with 3-month 2L rw-PFS rates of 54% and 67%.ConclusionsThe median time from biopsy to test results appears 1 week shorter for PD-L1 than for FMI NGS. Chemotherapy and IO monotherapy were the most common regimens utilized but with limited PFS.
Evaluation of Multisource Adaptive MRI Fusion for Gross Tumor Volume Delineation of Hepatocellular Carcinoma
Authors: Cheung Andy Lai-Yin , Zhang Lei , Liu Chenyang , Li Tian , Cheung Anson Ho-Yin , Leung Chun , Leung Angus Kwong-Chuen , Lam Sai-Kit , Lee Victor Ho-Fun , Cai Jing 
Published: February 2022

PurposeTumor delineation plays a critical role in radiotherapy for hepatocellular carcinoma (HCC) patients. The incorporation of MRI might improve the ability to correctly identify tumor boundaries and delineation consistency. In this study, we evaluated a novel Multisource Adaptive MRI Fusion (MAMF) method in HCC patients for tumor delineation.MethodsTen patients with HCC were included in this study retrospectively. Contrast-enhanced T1-weighted MRI at portal-venous phase (T1WPP), contrast-enhanced T1-weighted MRI at 19-min delayed phase (T1WDP), T2-weighted (T2W), and diffusion-weighted MRI (DWI) were acquired on a 3T MRI scanner and imported to in-house-developed MAMF software to generate synthetic MR fusion images. The original multi-contrast MR image sets were registered to planning CT by deformable image registration (DIR) using MIM. Four observers independently delineated gross tumor volumes (GTVs) on the planning CT, four original MR image sets, and the fused MRI for all patients. Tumor contrast-to-noise ratio (CNR) and Dice similarity coefficient (DSC) of the GTVs between each observer and a reference observer were measured on the six image sets. Inter-observer and inter-patient mean, SD, and coefficient of variation (CV) of the DSC were evaluated.ResultsFused MRI showed the highest tumor CNR compared to planning CT and original MR sets in the ten patients. The mean ± SD tumor CNR was 0.72 ± 0.73, 3.66 ± 2.96, 4.13 ± 3.98, 4.10 ± 3.17, 5.25 ± 2.44, and 9.82 ± 4.19 for CT, T1WPP, T2W, DWI, T1WDP, and fused MRI, respectively. Fused MRI has the minimum inter-observer and inter-patient variations as compared to original MR sets and planning CT sets. GTV delineation inter-observer mean DSC across the ten patients was 0.81 ± 0.09, 0.85 ± 0.08, 0.88 ± 0.04, 0.89 ± 0.08, 0.90 ± 0.04, and 0.95 ± 0.02 for planning CT, T1WPP, T2W, DWI, T1WDP, and fused MRI, respectively. The patient mean inter-observer CV of DSC was 3.3%, 3.2%, 1.7%, 2.6%, 1.5%, and 0.9% for planning CT, T1WPP, T2W, DWI, T1WDP, and fused MRI, respectively.ConclusionThe results demonstrated that the fused MRI generated using the MAMF method can enhance tumor CNR and improve inter-observer consistency of GTV delineation in HCC as compared to planning CT and four commonly used MR image sets (T1WPP, T1WDP, T2W, and DWI). The MAMF method holds great promise in MRI applications in HCC radiotherapy treatment planning.
HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer
Authors: Huang Zhijian , Yang Jiasheng , Qiu Wenjing , Huang Jing , Chen Zhirong , Han Yuanyuan , Ye Changsheng 
Published: February 2022

BackgroundBreast cancer (BRCA) has become the most frequently appearing, lethal, and aggressive cancer with increasing morbidity and mortality. Previously, it was discovered that the HAUS5 protein is involved in centrosome integrity, spindle assembly, and the completion of the cytoplasmic division process during mitosis. By encouraging chromosome misdivision and aneuploidy, HAUS5 has the potential to cause cancer. The significance of HAUS5 in BRCA and the relationship between its expression and clinical outcomes or immune infiltration remains unclear.MethodsPan-cancer was analyzed by TIMER2 web and the expression differential of HAUS5 was discovered. The prognostic value of HAUS5 for BRCA was evaluated with KM plotter and confirmed with Gene Expression Omnibus (GEO) dataset. Following that, we looked at the relationship between the high and low expression groups of HAUS5 and breast cancer clinical indications. Signaling pathways linked to HAUS5 expression were discovered using Gene Set Enrichment Analysis (GSEA). The relative immune cell infiltrations of each sample were assessed using the CIBERSORT algorithm and ESTIMATE method. We evaluated the Tumor Mutation Burden (TMB) value between the two sets of samples with high and low HAUS5 expression, as well as the differences in gene mutations between the two groups. The proliferation changes of BRCA cells after knockdown of HAUS5 were evaluated by fluorescence cell counting and colony formation assay.ResultHAUS5 is strongly expressed in most malignancies, and distinct associations exist between HAUS5 and prognosis in BRCA patients. Upregulated HAUS5 was associated with poor clinicopathological characteristics such as tumor T stage, ER, PR, and HER2 status. mitotic prometaphase, primary immunodeficiency, DNA replication, cell cycle related signaling pathways were all enriched in the presence of elevated HAUS5 expression, according to GSEA analysis. The BRCA microenvironment’s core gene, HAUS5, was shown to be related with invading immune cell subtypes and tumor cell stemness. TMB in the HAUS5-low expression group was significantly higher than that in the high expression group. The mutation frequency of 15 genes was substantially different in the high expression group compared to the low expression group. BRCA cells’ capacity to proliferate was decreased when HAUS5 was knocked down.ConclusionThese findings show that HAUS5 is a positive regulator of BRCA progression that contributes to BRCA cells proliferation. As a result, HAUS5 might be a novel prognostic indicator and therapeutic target for BRCA patients.
Effects of Enteral Nutrition on Patients With Oesophageal Carcinoma Treated With Concurrent Chemoradiotherapy: A Prospective, Multicentre, Randomised, Controlled Study
Authors: Lyu Jiahua , Shi Anhui , Li Tao , Li Jie , Zhao Ren , Zhu Shuchai , Wang Jianhua , Xing Ligang , Yang Daoke , Xie Conghua , Shen Liangfang , Zhang Hailin , Zhu Guangying , Wang Jing , Pan Wenyan , Li Fang , Lang Jinyi , Shi Hanping 
Published: February 2022

BackgroundThe oesophageal carcinoma patients show high incidence of malnutrition, which negatively affects their therapy outcome. Moreover, benefits of enteral nutrition remain to be studied in details in these patients. Therefore, we set to assess the effects of enteral nutrition on the nutritional status, treatment toxicities and survival in the oesophageal carcinoma patients treated with concurrent chemoradiotherapy (CCRT).Materials and MethodsEligible patients were randomly assigned to either the experimental or control group. The patients in the experimental group were treated with a whole-course enteral nutrition management, while the control group were provided a unsystematic nutrition without setting intake goals for energy and protein. The primary endpoint was a change in body weight, while the secondary endpoints included nutrition-related haematological indicators, toxicities, completion rate of treatment and survival.ResultsA total of 222 patients were randomised to either the experimental (n=148) or control (n=74) group. Patients in the experimental group showed significantly less decrease in body weight, serum albumin and haemoglobin levels, a lower incidence rates of grade ≥3 myelosuppression and infection, and a higher completion rate of CCRT than those in the control group. While analyses of the 2 and 3 year overall survival (OS) and progression-free survival (PFS) did not reveal differences between these groups, we observed a significantly higher OS at 1 year (83.6% vs. 70.0%). In the subgroup analysis, patients with patient-generated subjective global assessment (PG-SGA)=C were likely to have better OS and PFS with enteral nutrition.ConclusionsIn EC patients treated with CCRT, enteral nutrition conferred positive effects on the nutritional status, treatment toxicities and prognosis, which mandate its inclusion in clinical practice.Clinical Trial RegistrationThis prospective trial has been registered with www.clinicaltrials.gov as NCT02399306.