bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parkinson’s disease or multiple system atrophy: potential separation by quantitative susceptibility mapping
Authors: Marxreiter Franz , Lambrecht Vera , Mennecke Angelika , Hanspach Jannis , Jukic Jelena , Regensburger Martin , Herrler Juergen , German Alexander , Kassubek Jan , Grön Georg , Müller Hans-Peter , Laun Frederik B. , Dörfler Arnd , Winkler Juergen , Schmidt Manuel A. 
Published: February 2023

Background: Due to the absence of robust biomarkers, and the low sensitivity and specificity of routine imaging techniques, the differential diagnosis between Parkinson’s disease (PD) and multiple system atrophy (MSA) is challenging. High-field magnetic resonance imaging (MRI) opened up new possibilities regarding the analysis of pathological alterations associated with neurodegenerative processes. Recently, we have shown that quantitative susceptibility mapping (QSM) enables visualization and quantification of two major histopathologic hallmarks observed in MSA: reduced myelin density and iron accumulation in the basal ganglia of a transgenic murine model of MSA. It is therefore emerging as a promising imaging modality on the differential diagnosis of Parkinsonian syndromes. Objectives: To assess QSM on high-field MRI for the differential diagnosis of PD and MSA. Methods: We assessed 23 patients (nine PDs and 14 MSAs) and nine controls using QSM on 3T and 7T MRI scanners at two academic centers. Results: We observed increased susceptibility in MSA at 3T in prototypical subcortical and brainstem regions. Susceptibility measures of putamen, pallidum, and substantia nigra reached excellent diagnostic accuracy to separate both synucleinopathies. Increase toward 100% sensitivity and specificity was achieved using 7T MRI in a subset of patients. Magnetic susceptibility correlated with age in all groups, but not with disease duration in MSA. Sensitivity and specificity were particularly high for possible MSA, and reached 100% in the putamen. Conclusion: Putaminal susceptibility measures, in particular on ultra-high-field MRI, may distinguish MSA patients from both, PD and controls, allowing an early and sensitive diagnosis of MSA.
Impact of Occupation on 12-Month Outcomes After Anterior Cruciate Ligament Reconstruction in Male Patients
Authors: Kirby Julia C. , Whitehead Timothy S. , Webster Kate E. , Feller Julian A. , McClelland Jodie A. , Klemm Haydn J. , Devitt Brian M. 
Published: February 2023

Background: The impact of a physically demanding occupation on clinical outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR) is largely unknown. Purpose/Hypothesis: The purpose of this study was to assess the influence of occupation on 12-month outcomes after ACLR in male patients. It was hypothesized that patients undertaking manual work would not only have better functional outcomes in terms of strength and range of motion but also higher rates of joint effusion and greater anterior knee laxity. Study Design: Cohort study; Level of evidence, 3. Methods: From an initial cohort of 1829 patients, we identified 372 eligible patients aged 18 to 30 years who underwent primary ACLR between 2014 and 2017. Based on a preoperative self-assessment, 2 groups were established: patients engaged in heavy manual occupations and those engaged in low-impact occupations. Data were collected from a prospective database including effusion, knee range of motion (using side-to-side difference), anterior knee laxity, limb symmetry index for single hop and triple hop, International Knee Documentation Committee (IKDC) subjective score, and complications up to 12 months. Because of the significantly lower rate of female patients undertaking heavy manual occupations compared to low-impact occupations (12.5% and 40.0%, respectively), data analysis was focused on male patients. Outcome variables were assessed for normality, and statistical comparisons were made between the heavy manual and low-impact groups using either an independent-samples t test or the Mann-Whitney U test. Results: Of 230 male patients, 98 were included in the heavy manual occupation group, and 132 were included in the low-impact occupation group. Patients in the heavy manual occupation group were significantly younger than those in the low-impact occupation group (mean age, 24.1 vs 25.9 years, respectively; P < .005). There was a greater range of active and passive knee flexion in the heavy manual occupation group than in the low-impact occupation group (mean active, 3.38° vs 5.33°, respectively [ P = .021]; mean passive, 2.76° vs 5.00°, respectively [ P = .005]). There was no difference in effusion, anterior knee laxity, limb symmetry index, IKDC score, return-to-sport rate, or graft rupture rate at 12 months. Conclusion: At 12 months after primary ACLR, male patients engaged in heavy manual occupations had a greater range of knee flexion, with no difference in the effusion rate or anterior knee laxity, compared with those engaged in low-impact occupations.
Early post-endovascular treatment contrast extravasation on dual-energy CT is associated with clinical and radiological stroke outcomes: A 10-year single-centre experience
Authors: Pinckaers Florentina ME , Mentink Max MG , Boogaarts Hieronymus D , van Zwam Wim H , van Oostenbrugge Robert J , Postma Alida A 
Published: February 2023

Objective: To determine the association between early post-endovascular treatment (EVT) contrast extravasation (CE) on dual-energy CT (DECT) and stroke outcomes. Methods: EVT records in 2010–2019 were screened. Exclusion criteria included the occurrence of immediate post-procedural intracranial haemorrhage (ICH). Hyperdense areas on iodine overlay maps were scored according to the Alberta Stroke Programme Early CT Score (ASPECTS), thus forming a CE-ASPECTS. Maximum parenchymal iodine concentration and maximum iodine concentration relative to the torcula were recorded. Follow-up imaging was reviewed for ICH. The primary outcome measure was the modified Rankin Scale (mRS) at 90 days. Results: Out of 651 records, 402 patients were included. CE was found in 318 patients (79%). Thirty-five patients developed ICH on follow-up imaging. Fourteen ICHs were symptomatic. Stroke progression occurred in 59 patients. Multivariable regression showed a significant association between decreasing CE-ASPECTS and the mRS at 90 days (adjusted (a)cOR: 1.10, 95% CI: 1.03–1.18), NIHSS at 24–48 h (aβ: 0.57, 95% CI: 0.29–0.84), stroke progression (aOR: 1.14, 95% CI: 1.03–1.26) and ICH (aOR: 1.21, 95% CI: 1.06–1.39), but not symptomatic ICH (aOR 1.19, 95% CI: 0.95–1.38). Iodine concentration was significantly associated with the mRS (acOR: 1.18, 95% CI: 1.06–1.32), NIHSS (aβ: 0.68, 95% CI: 0.30–1.06), ICH (aOR: 1.37, 95% CI: 1.04–1.81) and symptomatic ICH (aOR: 1.19, 95% CI: 1.02–1.38), but not stroke progression (aOR: 0.99, 95% CI: 0.86–1.15). Results of the analyses with relative iodine concentration were similar and did not improve prediction. Conclusions: CE-ASPECTS and iodine concentration are both associated with short- and long-term stroke outcomes. CE-ASPECTS is likely a better predictor for stroke progression.
A case of Aicardi-Goutières syndrome caused by TREX1 gene mutation
Authors: Chenhan Zheng , Jun Shao , Yang Ding , Linliang Yin , Xiaowen Gu , Chunya Ji , Xuedong Deng 
Published: February 2023

AbstractAicardi-Goutières syndrome (AGS) is a rare genetic disorder involving the central nervous system and autoimmune abnormalities, leading to severe intellectual and physical disability with poor prognosis. AGS has a phenotype similar to intrauterine viral infection, which often leads to delays in genetic counseling. In this study, we report a case with a prenatal diagnosis of AGS. The first fetal ultrasound detected bilateral lateral ventricle cystic structures, and fetal MRI was performed to identify other signs. The right parietal lobe signal showed cerebral white matter abnormalities, and fetal brain development level was lower than that of normal fetuses of the same gestational age. Whole-exome sequencing revealed that the fetus carried the TREX1:NM_033629.6:exon2:c.294dup:p. C99Mfs*3 variant, suggesting that the c.294dup mutation of the TREX1 gene was the pathogenic mutation site, and the final comprehensive diagnosis was AGS1. In this article, we also reviewed the previous literature for possible phenotypes in the fetus and found that microcephaly and intrauterine growth retardation may be the first and most important markers of the intrauterine phenotype of AGS.
Comparison of systemic inflammatory profiles in COVID-19 and community-acquired pneumonia patients: a prospective cohort study
Authors: Ibáñez-Prada Elsa D. , Fish Matthew , Fuentes Yuli V. , Bustos Ingrid G. , Serrano-Mayorga Cristian C. , Lozada Julian , Rynne Jennifer , Jennings Aislinn , Crispin Ana M. , Santos Ana Maria , Londoño John , Shankar-Hari Manu , Reyes Luis Felipe 
Published: February 2023

Abstract
Background
Inflammatory responses contribute to tissue damage in COVID-19 and community-acquired pneumonia (CAP). Although predictive values of different inflammatory biomarkers have been reported in both, similarities and differences of inflammatory profiles between these conditions remain uncertain. Therefore, we aimed to determine the similarities and differences of the inflammatory profiles between COVID-19 and CAP, and their association with clinical outcomes.

Methods
We report a prospective observational cohort study; conducted in a reference hospital in Latin America. Patients with confirmed COVID-19 pneumonia and CAP were included. Multiplex (Luminex) cytokine assays were used to measure the plasma concentration of 14 cytokines at hospital admission. After comparing similarities and differences in the inflammatory profile between COVID-19 and CAP patients, an unsupervised classification method (i.e., hierarchical clustering) was used to identify subpopulations within COVID-19 and CAP patients.

Results
A total of 160 patients were included, 62.5% were diagnosed with COVID-19 (100/160), and 37.5% with CAP (60/160). Using the hierarchical clustering, COVID-19 and CAP patients were divided based on its inflammatory profile: pauci, moderate, and hyper-inflammatory immune response. COVID-19 hyper-inflammatory subpopulation had the highest mortality. COVID-19 hyper-inflammatory subpopulation, compared to pauci-inflammatory, had higher levels of IL-10 (median [IQR] 61.4 [42.0–109.4] vs 13.0 [5.0–24.9], P: < 0.001), IL-6 (48.1 [22.3–82.6] vs 9.1 [0.1–30.4], P: < 0.001), among others. Hyper-inflammatory vs pauci-inflammatory CAP patients were characterized by elevation of IFN2 (48.8 [29.7–110.5] vs 3.0 [1.7–10.3], P: < 0.001), TNFα (36.3 [24.8–53.4] vs 13.1 [11.3–16.9], P: < 0.001), among others. Hyper-inflammatory subpopulations in COVID-19 and CAP compared to the corresponding pauci-inflammatory subpopulations had higher MCP-1.

Conclusions
Our data highlights three distinct subpopulations in COVID-19 and CAP, with differences in inflammatory marker profiles and risks of adverse clinical outcomes.
Trial registration: This is a prospective study, therefore no health care intervention were applied to participants and trial registration is not applicable.
Preoperative serum low-density lipoprotein cholesterol is an independent prognostic factor in patients with renal cell carcinoma after nephrectomy
Authors: Cui Fan , Zhou Huiyu , Lv Dingyang , Wen Jie , Gong Qian , Rong Yi , Kang Yinbo , Jia Mohan , Shuang Weibing 
Published: February 2023

Abstract
Background
Little is known about the association between the preoperative low-density lipoprotein cholesterol (LDL-C) level and prognosis in patients with renal cell carcinoma (RCC) after nephrectomy, and its prognostic value needs to be elucidated.

Methods
The clinical and follow-up data of 737 RCC patients who underwent nephrectomy were retrospectively analyzed. The optimal cut-off LDL-C level was determined using X-tile, and then patients were divided into low and high LDL-C groups. The association between LDL-C levels and survival of RCC patients was assessed using the Kaplan-Meier method and Cox regression analysis.

Results
The optimal cut-off LDL-C level was 1.93 mmol/L, and patients were divided into the low (≤ 1.93 mmol/L) and high LDL-C (> 1.93 mmol/L) groups. The Kaplan-Meier analysis showed that patients in the low LDL-C group had significantly shorter overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) than those in the high LDL-C group (P = 0.001, P = 0.001, and P = 0.003, respectively). The COX univariate analysis showed that the preoperative LDL-C level was closely associated with OS, CSS, and RFS in RCC patients (P = 0.002, P = 0.003, and P = 0.005, respectively). The multivariate analysis showed that the preoperative LDL-C level was an independent factor for predicting survival (OS, CSS and RFS) in RCC patients after nephrectomy. The low preoperative LDL-C levels predicted worse OS (hazard ratio [HR]: 2.337; 95% confidence interval [CI]: 1.192–4.581; P = 0.013), CSS (HR: 3.347; 95% CI: 1.515–7.392; P = 0.003), and RFS (HR: 2.207; 95% CI: 1.178–4.132; P = 0.013).

Conclusions
The preoperative LDL-C level is an independent factor for the prognosis of RCC patients after nephrectomy, and low preoperative LDL-C levels predict worse survival (OS, CSS, and RFS).
CT-determined sarcopenia is associated with neutropenia in patients undergoing hyperthermic intraperitoneal chemotherapy for gastrointestinal cancer
Authors: Jiang Wei , Zhan Wenli , He Fangxun , Wu Xiaolin , Wu Jing , Xu Xiangshang , Cao Zhixin 
Published: February 2023

Abstract
Background
With better patient selection and the increasing experience in patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) combined surgery, the rate of severe postoperative complications and mortality decreased significantly. However, leukopenia and neutropenia were still a particular concern, and their relation to sarcopenia was not clarified.

Methods
Data of consecutive patients who underwent HIPEC for gastrointestinal cancer were collected and analyzed retrospectively between September 2020 and August 2022. Sarcopenia was assessed using psoas muscle index (PMI) at the L3 level on preoperative computed tomography (CT).

Results
Among 103 patients enrolled, 37 (35.9%) were classified as sarcopenic. Most leukopenia and neutropenia occurred during the hospital leaving period after HIPEC and surgery. Before the first time of postoperative chemotherapy, the blood tests revealed 11 (29.73%) and 6 (9.09%) patients were diagnosed with neutropenia in sarcopenia and no sarcopenia groups, respectively. Logistic regression analysis revealed sarcopenia was independently associated with the increased risk of neutropenia (OR 5.58, 95% CI 1.70–18.29, p = 0.005). An incremental albumin level was protective against the occurrence of leukopenia and neutropenia.

Conclusions
Sarcopenia and low albumin level were significantly associated with an increased rate of delayed neutropenia after HIPEC in that disease setting and could be the preoperative risk predictors.
PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma
Authors: Fei Zhaodong , Xu Ting , Hong Huiling , Xu Yiying , Chen Jiawei , Qiu Xiufang , Ding Jianming , Huang Chaoxiong , Li Li , Liu Jing , Chen Chuanben 
Published: February 2023

Abstract
Objective
This study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC.

Methods
This retrospective study reviewed the results of EGFR expression and pretreatment 18F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan–Meier.

Results
The selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS.

Conclusion
The combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy.
Osteogenic effects of rapamycin on bone marrow mesenchymal stem cells via inducing autophagy
Authors: Xing Yifeng , Liu Chaowei , zhou Lin , Li Yan , Wu Dong 
Published: February 2023

Abstract
Background
While autophagy is essential for stem cells’ self-renewal and differentiation, its effect on bone marrow mesenchymal stem cells (BMSCs) remains unclear. This study aimed to investigate the interaction between autophagy and osteogenic differentiation using rapamycin (RAPA), a classical autophagy agonist with osteo-regulatory effects.

Methods
Rat BMSC’s autophagy was analyzed after osteoinduction (0, 7, 14, and 21 d) by western blotting, immunofluorescence, and real-time quantitative polymerase chain reaction (RT-qPCR). In addition, we evaluated osteogenic differentiation using alizarin red staining, alkaline phosphatase assays, and RT-qPCR/Western blotting quantification of bone sialoprotein, type 1 collagen, alkaline phosphatase, osteopontin, and Runt-related transcription factor 2 mRNA and protein levels.

Results
The BMSC’s basal autophagy level gradually decreased during osteogenic differentiation with a decrease in BECN1 level and the lipidated (LC3-II) to unlipidated (LC3-I) microtubule-associated protein 1 light chain 3 ratio and an increase in the expression of selective autophagic target p62. In contrast, it increased with increasing RAPA concentration. Furthermore, while 2 nM RAPA promoted BMSC osteogenic differentiation on days 7 and 14, 5 nM RAPA inhibited osteogenesis on days 14 and 21. Inhibition of autophagy by the inhibitor 3-methyladenine could impair RAPA’s osteogenesis-enhancing effect on BMSCs.

Conclusions
The BMSC’s basal autophagy level decreased over time during osteogenic differentiation. However, an appropriate RAPA concentration promoted BMSC osteogenic differentiation via autophagy activation.
Vitamin D status in healthy Italian school-age children: a single-center cross-sectional study
Authors: Galeazzi Tiziana , Quattrini Sara , Pjetraj Dorina , Gatti Simona , Monachesi Chiara , Franceschini Elisa , Marinelli Luisita , Catassi Giulia N. , Lionetti Elena , Catassi Carlo 
Published: February 2023

Abstract
Background
Vitamin D is involved in calcium homeostasis and bone metabolism, although its extra-skeletal actions are also well-known. Low serum 25(OH)D levels are common both in adults and children worldwide.

Methods
The purpose of this cross-sectional study was to determine the distribution of 25(OH)D levels in a cohort of healthy Italian school-age children, aged 5–10 years, in relationship to determinants of vitamin D deficiency such as season, BMI, gender, age and ethnicity.

Results
The mean serum 25(OH) D level was 28.2 ng/mL; the prevalence of 25(OH)D sufficiency (> 30 ng/mL), insufficiency (20–30 ng/mL), deficiency (10–20 ng/mL) and severe deficiency (< 10 ng/mL) was 36%, 37%, 21% and 6% of the study-group population, respectively. The lower serum 25(OH)D values were observed during winter (21.6 ng/mL) and spring (22.9 ng/mL), as compared to summer (46.7 ng/mL) (p < 0.001). Higher BMI z-scores were associated with lower 25(OH)D level while no statistical difference was observed as related to gender and age groups.

Conclusions
Healthy Italian schoolchildren show low 25(OH)D levels, particularly during winter and spring time. Seasonality, ethnicity and overweight/obesity were confirmed to influence the vitamin D status, thus indicating the need for effective initiatives to support adequate vitamin D status in this population group.
Knockdown of circ_0006872 alleviates CSE-induced human bronchial epithelial cells injury in chronic obstructive pulmonary disease
Authors: Wang Jieqiong , Li Zegeng , Zheng Lili , Tong Jiabing , Wang Chuanbo 
Published: February 2023

AbstractCircular RNAs (circRNAs) have been reported to be related to the initiation and progression of chronic obstructive pulmonary disease (COPD) by affecting the function of human bronchial epithelial cells (HBECs). Here, we aimed to investigate the function and mechanism of circ_0006872 in regulating COPD process using cigarette smoke extract (CSE)-induced 16HBEC in vitro. The results showed that circ_0006872 was increased in smokers without or with COPD, especially in smokers with COPD. Also, its expression was dose-dependently up-regulated by CSE exposure in 16HBECs. Functionally, circ_0006872 knockdown dramatically attenuated CSE-evoked proliferation arrest, apoptosis, inflammatory response and oxidative stress in 16HBECs. Mechanistically, circ_0006872/miR-485-3p/cyclin-dependent kinase inhibitor 1B (CDKN1B) formed a competitive endogenous RNA (ceRNA) network. CDKN1B was increased and miR-485-3p was decreased in COPD patients and CSE-induced 16HBECs. MiR-485-3p overexpression or CDKN1B knockdown protected 16HBEC against CSE-induced 16HBEC injury mentioned above. Moreover, rescue experiments showed that circ_0006872 regulated CSE-induced 16HBEC injury via miR-485-3p/CDKN1B axis. Circ_0006872 silencing protected against CSE-induced bronchial epithelial cell injury via miR-485-3p/CDKN1B axis, suggesting the potential application of circ_0006872 in preventing cigarette smoke-induced COPD.