bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated neurofilament light chain CSF/serum ratio indicates impaired CSF outflow in idiopathic intracranial hypertension
Authors: Engel Sinah , Halcour Johannes , Ellwardt Erik , Uphaus Timo , Steffen Falk , Zipp Frauke , Bittner Stefan , Luessi Felix 
Published: January 2023

Abstract
Background
Impaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients.

Methods
NfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry.

Results
CSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = − 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort.

Conclusions
The observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.
Geometric and dosimetric consequences of intra-fractional movement in single isocenter non-coplanar stereotactic radiosurgery
Authors: Fung Nelson Tsz Cheong , Wong Wai Lung , Lee Michael Chi Hang , Cheung Elki Sze Nga , Wu Philip Yuguang 
Published: January 2023

Abstract
Purpose
To investigate the geometric and dosimetric impacts of intra-fractional movement for patients with single or multiple brain metastasis treated using Varian Hyperarc™ mono-isocentric radiosurgery.

Methods
A total of 50 single or hypo-fractionated Hyperarc™ treatment courses (118 lesions) were included in the analysis. Intra-fractional translational and rotational movements were quantified according to the post-treatment cone-beam CT (CBCT). Geometric displacements of all targets were calculated individually based on the assessed head movement in each treatment fraction and their relationships with treatment time and target-to-isocenter distances were studied. For dosimetric analysis, only single-fraction treatments (56 lesions) were included. Re-planning was performed with 0, 1, and 2 mm planning target volume (PTV) margins. Doses were then re-calculated on rotated CT images with isocenter shifted which emulate the change in patient treatment position. Target coverage, target and normal brain doses before and after intra-fractional movement were compared.

Results
The mean 3D target displacements was 0.6 ± 0.3 (SD) mm. Target shifts for patients treated within 10 min were significantly smaller than those treated in longer sessions. No correlation was found between target shift and target-to-isocenter distance as the origin of head rotation was not located at the isocenter. Loss of target coverage and minimum Gross Tumor Volume (GTV) dose due to intra-fractional movement were apparent only when no margin was used, leading to an extra 23% of the targets violating the dose acceptance criteria, in contrast, the effects on normal brain V12Gy were negligible regardless of the margin used. The use of 1 mm PTV margin can compensate clinically significant geographical miss caused by intra-fractional movements while limiting V12Gy to within dose criteria for 88% of the cases. The plan acceptance rate (fulfillment of both target and normal brain dose criteria) after intra-fractional movement was also the highest with the 1 mm margin.

Conclusion
Although intra-fractional movements during Hyperarc™ treatments were small, there were substantial dosimetric effects due to the sharp dose fall-off near target boundaries. These effects could be mitigated by using a 1 mm PTV margin and maintaining the effective treatment time to within 10 min.
Morphometric measurement of lumbar pedicle in different regions: a systematic review
Authors: Wang Yixi , Kahaer Alafate , Shi Wenjie , Guo Hailong , Rexiti Paerhati 
Published: January 2023

Abstract
Objective
To collect the data of pedicle width and height in different areas, and to investigate the difference and variation rule of pedicle width and height.

Methods
Comprehensive search of PubMed, Ovid Medline, and Web of science databases was performed. Collected data were imported into SPSS, and one-way ANOVA test and post hoc test were used to determine whether there were statistical differences in pedicle width and height between the different regions.

Results
Oceania had the largest pedicle width and height, followed by Americans. West Asian had the largest pedicle width in Asia, followed by East and Southeast Asian, and Chinese and South Asian had similar pedicle width. Different from the variation pattern of pedicle width, the pedicle height of Chinese, East and Southeast Asian and West Asian in Asian range is similar, but the pedicle height of South Asian is significantly smaller than the first three, and has statistical significance.

Conclusions
People in different regions have similar patterns of variation in pedicle width and height even though they belong to different ethnic groups. This phenomenon is particularly prominent and pronounced in populations in geographically close areas, which may be related to inter-ethnic integration due to population movement between adjacent areas. There is a relationship between the morphological characteristics of the human lumbar pedicle and geographical location.
Genetic analysis reveals the inconsistency of amorpha-4,11-diene synthase, a key enzyme in the artemisinin synthesis pathway, in asteraceae
Authors: Chen Shiyu , Liao Baosheng , Guo Shuai , Shen Xiaofeng , Meng Ying , Liang Yu , Xu Jiang , Chen Shilin 
Published: January 2023

Abstract
Background
Amorpha-4,11-diene synthase (ADS) is a key enzyme in the artemisinin biosynthetic pathway. ADS promotes the first step of artemisinin synthesis by cyclizing faresyl pyrophosphate to synthesize the sesquiterpene product amorpha-4,11-diene. Thanks to the continuous improvement of genomic information, its evolutionary trace can be analyzed in a genome view.

Methods
Phylogenetic analysis was used to identify ADS-like genes in other Asteraceae. Gene structure and motif analysis was used to analyze the structural similarity of these identified genes. Heterologous expression and GC–MS analysis were performed to determine whether the functions of ADS and Cna4666 are consistent. Validation of ADS genes evolutionary trajectories was achieved by selective pressure and synteny analysis.

Result
In this study, we extracted 8 ADS genes from the Artemisia annua L. genome annotation and 121 ADS similar genes from the genomes of Artemisia annua L. and other plants in the Asteraceae, and further exploring their evolutionary relationship. Phylogenetic analysis showed that the genes most closely related to ADS genes were found in the genome of Chrysanthemum nankingense. Among them, the gene structure and motif composition of Cna4666 is very similar to ADS, we wondered whether it has the potential to synthesize amorpha-4,11-diene. Therefore, we extracted the products of recombinant p0_ADS.1 and Cna4666 proteins by HS-SPME combined with GC–MS analysis, the results indicate that Cna4666 is an α-bisabolol synthase, which cannot synthesize amorpha-4,11-diene. Through synteny analysis, we did not find collinear blocks of ADS genes in the Helianthus annuus and C. nankingense genomes. Furthermore, Ka/Ks ratios indicated that the evolution of ADS genes from their similar genes principally underwent purifying selection, and there was a strong positive selection between ADS genes.

Conclusions
This study proved that ADS is a multi-copy gene in Artemisia annua L., and they are not widely distributed in Asteraceae. The data will increase our understanding of the evolutionary selection pressure on ADS genes. The results suggest that ADS genes are subject to strong positive selection internally, and it is possible that they are a recently evolved gene in the Artemisia.
Screening and treatment of brain metastasis from papillary thyroid carcinoma: a case series
Authors: Ha Le Ngoc , Khanh Le Quoc , Hanh Ngo Thi Minh , Seo Hyo Jung , Son Mai Hong 
Published: January 2023

AbstractBackgroundThe brain metastasis from differentiated thyroid carcinoma (DTC) is a rare condition and its prognosis is poor. The standard protocol for screening and treatment of patients with brain metastases from papillary thyroid cancer (PTC) remains controversial. This report aims to share the experience of a single center in the management of brain metastases from DTC.Material and methodsFive patients with brain metastases were identified from 5000 patients with DTC attending the department of nuclear medicine, Hospital 108 between 2016 to 2022. The statistical software Statistical Package for Social Sciences (SPSS) 20.0 (SPSS Inc., Chicago, IL, USA) was used to analyze the data.ResultsFive patients with brain metastases from DTC were revealed by MRI,18F-FDG PET/CT with contrast enhancement, and131I-SPECT/CT. The median time of overall survival (OS) was 15 months, ranging from 10 to 65 months. Two out of the five patients underwent surgery, and futher 2 patients were treated with stereotactic surgery (SRS). All patients are still alive.ConclusionsBrain metastases from DTC are rare. MRI is the preferred imaging mobility to screen brain lesions in DTC. The primary treatment modalities are surgery and SRS.
M2 macrophage-derived exosomal miR-193b-3p promotes progression and glutamine uptake of pancreatic cancer by targeting TRIM62
Authors: Zhang Ke , Li Yu-Jie , Peng Lin-Jia , Gao Hui-Feng , Liu Lu-Ming , Chen Hao 
Published: January 2023

Abstract
Background
Pancreatic cancer (PC) is a highly lethal malignancy that requires effective novel therapies. M2 macrophages are abundant in the PC microenvironment and promote cancer progression. Exosomes are emerging mediators of the crosstalk between cancer cells and the microenvironment. This study was conducted to explore the role of M2 macrophage-derived exosomes in PC.

Methods
Exosomes derived from M2 macrophages were extracted. miR-193b-3p and TRIM62 were overexpressed or silenced to examine their function in PC. Luminescence assays were used to investigate the interaction between miR-193b-3p and TRIM62. Cell proliferation was examined by EdU staining. Would healing and transwell assays were applied to evaluate cell migration and invasion. Co-immunoprecipitation was used to assess the interaction between TRIM62 and c-Myc. Gene and protein expressions were analyzed by quantitative RT-PCR and immunoblotting, respectively.

Results
M2 macrophage-derived exosomal miR-193b-3p promoted the proliferation, migration, invasion, and glutamine uptake of SW1990 cells. Mechanism study revealed that TRIM62 is a target of miR-193b-3p. TRIM62 inhibited the proliferation, migration, invasion, and glutamine uptake of SW1990 cells by promoting c-Myc ubiquitination. Our data also suggested that TRIM62 expression negatively correlated with miR-193b-3p and c-Myc expression. High-expression of miR-193b-3p and c-Myc predicts poor prognosis, whereas low-expression of TRIM62 predicts poor prognosis in patients with PC.

Conclusion
M2 macrophage-derived exosomal miR-193b-3p enhances the proliferation, migration, invasion, and glutamine uptake of PC cells by targeting TRIM62, resulting in the decrease of c-Myc ubiquitination. This study not only reveals the mechanism underlying the crosstalk between M2 macrophages and PC cells but also suggests a promising therapeutic target for PC.
Drugging the epigenome in the age of precision medicine
Authors: Feehley Taylor , O’Donnell Charles W. , Mendlein John , Karande Mahesh , McCauley Thomas 
Published: January 2023

Abstract
Background
Modulating the epigenome has long been considered a potential opportunity for therapeutic intervention in numerous disease areas with several approved therapies marketed, primarily for cancer. Despite the overall promise of early approaches, however, these drugs have been plagued by poor pharmacokinetic and safety/tolerability profiles due in large part to off-target effects and a lack of specificity.

Results
Recently, there has been marked progress in the field on a new generation of epigenomic therapies which address these challenges directly by targeting defined loci with highly precise, durable, and tunable approaches. Here, we review the promise and pitfalls of epigenetic drug development to date and provide an outlook on recent advances and their promise for future therapeutic applications.

Conclusions
Novel therapeutic modalities leveraging epigenetics and epigenomics with increased precision are well positioned to advance the field and treat patients across disease areas in the coming years.
Predictive models and early postoperative recurrence evaluation for hepatocellular carcinoma based on gadoxetic acid-enhanced MR imaging
Authors: Li Qian , Wei Yi , Zhang Tong , Che Feng , Yao Shan , Wang Cong , Shi Dandan , Tang Hehan , Song Bin 
Published: January 2023

Abstract
Background
The prognosis of hepatocellular carcinoma (HCC) is still poor largely due to the high incidence of recurrence. We aimed to develop and validate predictive models of early postoperative recurrence for HCC using clinical and gadoxetic acid-enhanced magnetic resonance (MR) imaging-based findings.

Methods
In this retrospective case-control study, 209 HCC patients, who underwent gadoxetic acid-enhanced MR imaging before curative-intent resection, were enrolled. Boruta algorithm and backward stepwise selection with Akaike information criterion (AIC) were used for variables selection Random forest, Gradient-Boosted decision tree and logistic regression model analysis were used for model development. The area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis were used to evaluate model’s performance.

Results
One random forest model with Boruta algorithm (RF-Boruta) was developed consisting of preoperative serum ALT and AFP levels and six MRI findings, while preoperative serum AST and AFP levels and four MRI findings were included in one logistic regression model with backward stepwise selection method (Logistic-AIC).The two predictive models demonstrated good discrimination performance in both the training set (RF-Boruta: AUC, 0.820; Logistic-AIC: AUC, 0.853), internal validation set (RF-Boruta: AUC, 0.857, Logistic-AIC: AUC, 0.812) and external validation set(RF-Boruta: AUC, 0.805, Logistic-AIC: AUC, 0.789). Besides, in both the internal validation and external validation sets, the RF-Boruta model outperformed Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.05).

Conclusions
The RF-Boruta and Logistic-AIC models with good prediction performance for early postoperative recurrence may lead to optimal and comprehensive treatment approaches, and further improve the prognosis of HCC after resection.
Alpha-gal syndrome initially misdiagnosed as chronic spontaneous urticaria in a pediatric patient: a case report and review of the literature
Authors: Bellutti Enders Felicitas , Elkuch Marius , Wörner Andreas , Scherer Hofmeier Kathrin , Hartmann Karin 
Published: January 2023

Abstract
Introduction
Delayed allergy to red meat, also termed alpha-gal syndrome, is increasingly reported in adults and African communities, while pediatric cases remain rare.

Case presentation
Here, we report on a 7-year-old Caucasian boy presenting with recurrent wheals since the age of 5 years old. Episodes with hives occurred around every 3 weeks, mainly in the evening. One of these episodes was also associated with angioedema. No clear trigger was identified. At the first visit, after excluding an infection and autoimmune thyroiditis, chronic spontaneous urticaria was suspected and symptomatic treatment with antihistamines was prescribed. Six months later, the boy presented at the emergency room with generalized urticaria, dyspnoea, and emesis. Symptoms resolved after administration of epinephrine and antihistamines. A detailed medical history after this event revealed that he had eaten three sausages as well as jelly beans containing gelatine several hours prior to this episode. More precisely, after eating the sausages and jelly beans during the day, he had shown some hives before going to bed, and later developed the other symptoms in the middle of the night, suggesting alpha-gal syndrome. In his history, several tick bites are reported. Immunoglobulin E levels for alpha-gal were clearly elevated, confirming the diagnosis of a delayed-appearing immunoglobulin E-mediated allergic reaction to alpha-gal. Emergency medication was prescribed and avoidance of red meat and gelatine-containing foods was recommended. Under this exclusion diet, the boy remained asymptomatic, with the exception of two accidents in the follow up of 3 years, one developing during a barbecue and the second after exceptionally eating marshmallows.

Conclusion
A detailed clinical history led to the diagnosis of alpha-gal syndrome. Although alpha-gal syndrome is typically seen in adults, our case illustrates that children can also present with this potentially life-threatening allergy. Since alpha-gal syndrome is rare in Europe, the disease is not well known and often overlooked for several years, especially in children.
Atypical Kawasaki disease presenting with macroscopic hematuria in an infant: a case report
Authors: Thadchanamoorthy V. , Dayasiri Kavinda , Ragunathan I. R. 
Published: January 2023

Abstract
Background
Kawasaki disease is an acute febrile condition in children. It affects mainly children under 5 years old, and is known to cause coronary artery abnormalities if treatment is delayed. The diagnosis rests mainly on clinical criteria. However, it is also known that some infants do not have diagnostic criteria sufficient enough for the diagnosis of Kawasaki disease. Further, children may rarely present with unusual features, and this entity is recognized as “Atypical Kawasaki disease.”

Case presentation
We present the case of a 9-month-old Tamil boy who presented with sterile gross hematuria in association with prolonged fever, lymphadenopathy, and generalized maculopapular rash. He had high inflammatory markers and echocardiogram disclosed left coronary artery dilatation. The diagnosis of incomplete Kawasaki disease was confirmed based on clinical grounds supported by investigations and exclusion of differential diagnosis. The child showed a good response to intravenous immunoglobulin and aspirin.

Conclusion
Kawasaki disease is one of the important differential diagnoses of protracted fever of unknown origin in very young children. Since delayed treatment is associated with a high risk of complications, atypical Kawasaki disease needs to be suspected in children presenting with unusual features such as macroscopic hematuria that occurs in association with unexplained prolonged fever.
Prediction of survival time after terminal extubation: the balance between critical care unit utilization and hospice medicine in the COVID-19 pandemic era
Authors: Zheng Yun-Cong , Huang Yen-Min , Chen Pin-Yuan , Chiu Hsiao-Yean , Wu Huang-Pin , Chu Chien-Ming , Chen Wei-Siang , Kao Yu-Cheng , Lai Ching-Fang , Shih Ning-Yi , Lai Chien-Hong 
Published: January 2023

Abstract
Background
We established 1-h and 1-day survival models after terminal extubation to optimize ventilator use and achieve a balance between critical care for COVID-19 and hospice medicine.

Methods
Data were obtained from patients with end-of-life status at terminal extubation from 2015 to 2020. The associations between APACHE II scores and parameters with survival time were analyzed. Parameters with a p-value ≤ 0.2 in univariate analysis were included in multivariate models. Cox proportional hazards regression analysis was used for the multivariate analysis of survival time at 1 h and 1 day.

Results
Of the 140 enrolled patients, 76 (54.3%) died within 1 h and 35 (25%) survived beyond 24 h. No spontaneous breathing trial (SBT) within the past 24 h, minute ventilation (MV) ≥ 12 L/min, and APACHE II score ≥ 25 were associated with shorter survival in the 1 h regression model. Lower MV, SpO2 ≥ 96% and SBT were related to longer survival in the 1-day model. Hospice medications did not influence survival time.

Conclusion
An APACHE II score of ≥ 25 at 1 h and SpO2 ≥ 96% at 1 day were strong predictors of disposition of patients to intensivists. These factors can help to objectively tailor pathways for post-extubation transition and rapidly allocate intensive care unit resources without sacrificing the quality of palliative care in the era of COVID-19.
Trial registration They study was retrospectively registered. IRB No.: 202101929B0.