bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional vitamin K status and risk of incident chronic kidney disease and microalbuminuria: a prospective general population-based cohort study
Authors: Groothof Dion , Post Adrian , Sotomayor Camilo G , Keyzer Charlotte A , Flores-Guerero Jose L , Hak Eelko , Bos Jens H J , Schurgers Leon J , Navis Gerjan J , Gans Reinold O B , Eelderink Coby , de Borst Martin H , Bakker Stephan J L , Riphagen Ineke J 
Published: November 2020

Abstract

Background
Circulating desphospho-uncarboxylated matrix γ-carboxyglutamate (Gla) protein (dp-ucMGP), a marker of vitamin K status, is associated with renal function and may serve as a potentially modifiable risk factor for incident chronic kidney disease (CKD). We aimed to assess the association between circulating dp-ucMGP and incident CKD.

Methods
We included 3969 participants with a mean age of 52.3 ± 11.6 years, of whom 48.0% were male, enrolled in the general population–based Prevention of REnal and Vascular ENd-stage Disease study. Study outcomes were incident CKD, defined as either development of an estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m2 or microalbuminuria. Associations of dp-ucMGP with these outcomes were quantified using Cox proportional hazards models and were adjusted for potential confounders.

Results
Median plasma dp-ucMGP was 363 [interquartile range (IQR) 219–532] pmol/L and mean serum creatinine- and serum cystatin C-based eGFR (eGFRSCr-SCys) was 95.4 ± 21.8 mL/min/1.73 m2. During 7.1 years of follow-up, 205 (5.4%) participants developed incident CKD and 303 (8.4%) developed microalbuminuria. For every doubling of plasma dp-ucMGP, hazard ratios for the development of incident CKD and microalbuminuria were 1.85 [95% confidence interval (CI) 1.59–2.16; P &lt; 0.001] and 1.19 (95% CI 1.07–1.32; P = 0.001), respectively. These associations lost significance after adjustment for baseline eGFRSCr-SCys [0.99 (95% CI 0.88–1.12; P = 0.86)] and baseline age [1.03 (95% CI 0.94–1.14; P = 0.50)], respectively.

Conclusions
The associations of plasma dp-ucMGP with incident CKD and microalbuminuria were driven by the respective baseline effects of renal function and age.
What is the burden of proof for tumor mutational burden in gliomas?
Authors: Khasraw Mustafa , Walsh Kyle M , Heimberger Amy B , Ashley David M 
Published: November 2020

Abstract
The treatment of patients with a variety of solid tumors has benefitted from immune checkpoint inhibition targeting the anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis. The US Food and Drug Administration (FDA) granted accelerated approval of PD-1 inhibitor, pembrolizumab, for the treatment of adult and pediatric patients with high tumor mutational burden (TMB-H), solid tumors that have progressed following prior treatment, and who have no other treatment options, including the extension to tumors of the central nervous system (CNS). In general, pan-cancer approvals are viewed positively to empower patients and clinicians. There are subsets (eg, BRAF, NTRK) for which this pathway for approval is appropriate. However, the pan-cancer FDA approval of pembrolizumab raises several concerns regarding the generalizability of the evidence to other tumor types, including managing patients with gliomas and other CNS tumors. The cutoff for TMB-H is not well defined. There are intrinsic immunological differences between gliomas and other cancers types, including the immunosuppressive glioma microenvironment, the tumor’s effects on systemic immune function, and the transformation of the T-cell populations to an exhausted phenotype in glioma. Here, we address the caveats with pan-cancer approvals concerning gliomas and complexities of the unique CNS immune environment, discuss potential predictive biomarkers, including TMB, and explain why the recent approval should be applied with caution in CNS tumors.
PATIENT SIZE INDICES AND DOSE IN FLUOROSCOPICALLY GUIDED LUMBAR DISCECTOMY AND FUSION: A PRELIMINARY STUDY
Authors: Metaxas Vasileios I , Gatzounis George D , Tzortzidis Fotios N , Panayiotakis George S 
Published: November 2020

Abstract
Patient dose values varied significantly during interventional procedures, mainly due to the patient size, operators’ choices and clinical complexity. In this study, the effect of applying a previously described and validated size-correction method to normalise kerma-area product (KAP) and average KAP rate values of the whole procedure (KAP rate) and isolate variations in dose due to the patient size and complexity, during lumbar discectomy and fusion (LDF) procedures, was investigated. Fluoroscopy time (FT), KAP, KAP rate and patient size data (weight, height and equivalent diameter) were recorded, for 96 patients who underwent single or multilevel LDF procedures by three senior neurosurgeons, defining three different patient groups (surgeon 1, surgeon 2, surgeon 3). Simple linear regression and coefficients of determination were used to investigate the relationship between uncorrected and corrected KAP and KAP rate values and patient size indices in these groups. The results showed that the size correction decreased the influence of patient size and could contribute to the isolation of the variations in patient dose due to the patient size. From this point of view, dose surveys during lumbar spine interventions may include dosimetric data from all patients independently of their body size and not only for standard-sized patients, providing the advantage of accessible data collection for the establishment of local dose reference levels and optimisation purposes, within the framework of the radiation protection program in the Neurosurgery Department.
Importance of the Primary Motor Cortex in Development of Human Hand/Finger Dexterity
Authors: Naito Eiichi , Morita Tomoyo , Asada Minoru 
Published: November 2020

Abstract
Hand/finger dexterity is well-developed in humans, and the primary motor cortex (M1) is believed to play a particularly important role in it. Here, we show that efficient recruitment of the contralateral M1 and neuronal inhibition of the ipsilateral M1 identified by simple hand motor and proprioceptive tasks are related to hand/finger dexterity and its ontogenetic development. We recruited healthy, right-handed children (n = 21, aged 8–11 years) and adults (n = 23, aged 20–26 years) and measured their brain activity using functional magnetic resonance imaging during active and passive right-hand extension–flexion tasks. We calculated individual active control-related activity (active–passive) to evaluate efficient brain activity recruitment and individual task-related deactivation (neuronal inhibition) during both tasks. Outside the scanner, participants performed 2 right-hand dexterous motor tasks, and we calculated the hand/finger dexterity index (HDI) based on their individual performance. Participants with a higher HDI exhibited less active control-related activity in the contralateral M1 defined by the active and passive tasks, independent of age. Only children with a higher HDI exhibited greater ipsilateral M1 deactivation identified by these tasks. The results imply that hand/finger dexterity can be predicted by recruitment and inhibition styles of the M1 during simple hand sensory–motor tasks.
Seasonal variations and public search interests in Toxoplasma: a 16-year retrospective analysis of big data on Google Trends
Authors: Liu Lei , Wang Peng , Jiang Su-Qin , Zhong Zi-Rong , Zhan Ting-Zheng , Yang Zi-Yin , Zhang Ya-Nan , Li Chen , Xu Jing , Xia Chao-Ming 
Published: November 2020

Abstract

Background
This study aims to understand whether there is a seasonal change in the internet search interest for Toxoplasma by using the data derived from Google Trends (GT).

Methods
The present study searched for the relative search volume (RSV) for the search term ‘Toxoplasma’ in GT within six major English-speaking countries (Australia, New Zealand [Southern Hemisphere] and Canada, Ireland, the UK and the USA [Northern Hemisphere] from 1 January 2004 to 31 December 2019, utilizing the category of ‘health’. Data regarding the RSV of Toxoplasma was obtained and further statistical analysis was performed in R software using the ‘season’ package.

Results
There were significantly seasonal patterns for the RSV of the search term ‘Toxoplasma’ in five countries (all p&lt;0.05), except for the UK. A peak in December–March and a trough in July–September (Canada, Ireland, the UK and the USA) were observed, while a peak in June/August and a trough in December/February (Australia, New Zealand) were also found. Moreover, the presence of seasonal patterns regarding RSV for ‘Toxoplasma’ between the Southern and Northern Hemispheres was also found (both p&lt;0.05), with a reversed meteorological month.

Conclusions
Overall, our study revealed the seasonal variation for Toxoplasma in using internet search data from GT, providing additional evidence on seasonal patterns in Toxoplasma.
The Role of Biological Fusion and Anterior Column Support in a Long Lumbopelvic Spinal Fixation and Its Effect on the S1 Screw—An In Silico Biomechanics Analysis
Authors: Cho Woojin , Wang Wenhai , Bucklen Brandon , Ramos Rafael De la Garza , Yassari Reza 
Published: November 2020

Study Design.
Finite element analysis.

Objective.
The aim of this study was to determine the role of biological fusion and anterior column support in a long lumbopelvic spinal fixation.

Summary of Background Data.
Retrospective studies have shown that adding anterior column support is not sensitive to construct failure, highlighting that posterior fusion quality may be a more important factor.

Methods.
Finite element models were created to match the average spinal-pelvic parameters of two patient cohorts reported in the literature: major failure and nonfailure. A moment load was applied at the T10 superior endplate to simulate gravimetric loading in a standing position. Effects of three factors on the biomechanical behavior of a fused spine were evaluated: sagittal alignment; posterior fusion versus no fusion; and anterior support at L4–S1 versus no anterior support.

Results.
Sagittal balance of the major failure group was positively correlated with 15% higher translation, 14% higher rotation, and 16% higher stress than in the nonfailure group. Simulated posterior fusion-only decreased motion by 32% and 29%, and alleviated rod stress by 15% and 5% and S1 screw stress by 26% and 35%, respectively, in major failure and non-failure groups. The addition of anterior fusion without posterior fusion did not help with rod stress alleviation but dramatically decreased S1 screw stress (by 57% and 41%), respectively. With both posterior fusion and anterior support, screw stress at the S1 was decreased by additional 30% and 6%, respectively.

Conclusion.
The spinopelvic parameters of the major failure group produced increased gravity load, resulting in increased stresses in comparison to the nonfailure group. Simulated posterior “solid” fusion in the lumbar region helped reduce stresses in both major failure and nonfailure patients. Anterior column support was an important factor in reducing S1 screw stress, with or without posterior fusion, and should be considered for patients with poor alignment.

Level of Evidence: N/A
Bone Morphogenetic Protein-2 Promotes Osteoclasts-mediated Osteolysis via Smad1 and p65 Signaling Pathways
Authors: Miao Xiong , Yuan Jiabin , Wu Jinhui , Zheng Jiaoyang , Zheng Weina , Wang Fei , Wang Chao , Li Xiaoming , Liu Shu , Shi Zhicai , Li Jingfeng 
Published: November 2020

Study Design.
An in vitro biological study.

Objective.
The aim of this study was to explore the role of bone morphogenetic protein-2 (BMP-2) in the regulation of osteoclast-mediated osteolysis, and the possible mechanism involving BMP-2 and nuclear factor-kappa B (NF-κB) signaling pathways.

Summary of Background Data.
Recombinant human BMP-2 (rhBMP-2) has been approved as a therapeutic agent in spinal fusion and bone defect repair. However, its efficacy and clinical application are limited by associated complications including osteoclast-mediated bone resorption. The mechanism of BMP-2-induced osteolysis remains unknown.

Methods.
Bone marrow-derived macrophages (BMMs) were isolated from C57BL/6J mice and cultured with macrophage colony-stimulating factor (M-CSF) and receptor activator for nuclear factor-κB Ligand (RANKL) to induce osteoclast differentiation. An in vitro bone resorption assay was performed by co-culturing BMMs and bone slides. The expression of BMP canonical and NF-κB signaling factors and their interaction during signal transduction were quantitated by reverse transcription polymerase chain reaction, Western blot analysis, confocal microscopy, and co-immunoprecipitation.

Results.
BMP-2 enhanced osteoclast-mediated bone resorption via inducing osteoclast differentiation in a concentration-dependent manner. In addition, a high concentration of BMP-2 significant upregulated phosphorylation of BMP signaling factors p-Smad1/5/8 and NF-κB downstream factor p65, and promoted the degeneration of IκBα. In addition, BMP-2 induced osteoclast differentiation through coupling between BMP receptor II and RANK.

Conclusion.
High concentrations of BMP-2 enhanced osteoclast-mediated bone resorption by promoting RANKL-induced pre-osteoclast differentiation, probably by mediating the cross-talk between BMP canonical and NF-κB signaling pathways.

Level of Evidence: N/A
Risk Factors for Cement Leakage in Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures
Authors: Tang Benqiang , Cui Libin , Chen Xueming , Liu Yadong 
Published: November 2020

Study Design.
Retrospective study.

Objective.
To identify risk factors for cement leakage in percutaneous vertebroplasty (PVP) using low-viscosity bone cement for osteoporotic vertebral compression fractures (OVCFs).

Summary of Background Data.
Cement leakage is the most common complication for PVP and its risk factors have been discussed. However, data in previous series were heterogeneous. Additionally, relative smaller patient sample or more types of cement leakage classified in those studies made the results conflicting.

Methods.
A total of 1090 patients who underwent PVP with low-viscosity bone cement for OVCFs in 1456 levels between January 2016 and June 2019 were retrospectively reviewed. Parameters potentially affecting the occurrence of cement leakage were assessed using univariate and multivariate analyses. Cement leakage was assessed using postoperative computed tomography scanning, and classified into two types (cortical leakage and venous leakage) considering the mechanism.

Results.
The incidence of cortical and venous leakage were 20.3% (295/1456) and 56.2% (819/1456), respectively. Cortical disruption, basivertebral foramen were the strongest risk factors for cortical leakage (P = 0.000), venous leakage (P = 0.000), respectively. Greater cement volume is one risk factor for both cortical leakage and venous leakage. The intravertebral cleft, solid type of cement distribution were significant risk factors for cortical leakage, and they both were protective factors for venous leakage. For cortical leakage, older age and trauma were another two risk factors. For venous leakage, female was another one risk factor, and higher grade of fracture severity is the strongest protective factor.

Conclusion.
Both cortical leakage and venous leakage are prevalent. Adequate known of risk factors could help balance the incidence of two type leakage in unique vertebra and reduce the incidence of leakage in general in PVP for OVCFs.

Level of Evidence: 3
Efficacy of Intraoperative Intervention Following Transcranial Motor-evoked Potentials Alert During Posterior Decompression and Fusion Surgery for Thoracic Ossification of the Posterior Longitudinal Ligament
Authors: Kobayashi Kazuyoshi , Imagama Shiro , Yoshida Go , Ando Muneharu , Kawabata Shigenori , Yamada Kei , Kanchiku Tsukasa , Fujiwara Yasushi , Taniguchi Shinichirou , Iwasaki Hiroshi , Tadokoro Nobuaki , Takahashi Masahito , Wada Kanichiro , Yamamoto Naoya , Shigematsu Hideki , Funaba Masahiro , Yasuda Akimasa , Ushirozako Hiroki , Tani Toshikazu , Matsuyama Yukihiro 
Published: November 2020

Study Design.
Prospective, multicenter, observational study.

Objective.
The aim of this study was to investigate the efficacy of intervention after an alert in intraoperative neurophysiological monitoring (IONM) using transcranial motor-evoked potentials (Tc-MEPs) during surgery for thoracic ossification of the posterior longitudinal ligament (T-OPLL).

Summary of Background Data.
T-OPLL is commonly treated with posterior decompression and fusion with instrumentation. IONM using Tc-MEPs during surgery reduces the risk of neurological complications.

Methods.
The subjects were 79 patients with a Tc-MEP alert during posterior decompression and fusion surgery for T-OPLL. Preoperative muscle strength (manual muscle testing [MMT]), waveform derivation rate at the start of surgery (baseline), intraoperative waveform changes; and postoperative motor paralysis were examined. A reduction in MMT score of ≥1 on the day after surgery was classified as worsened postoperative motor deficit. An alert was defined as a decrease in Tc-MEP waveform amplitude of ≥70% from baseline. Alerts were recorded at key times during surgery.

Results.
The patients (35 males, 44 females; age 54.6 years) had OPLL at T1-4 (n = 27, 34%), T5-8 (n = 50, 63%), and T9-12 (n = 16, 20%). The preoperative status included sensory deficit (n = 67, 85%), motor deficit (MMT ≤4) (n = 59, 75%), and nonambulatory (n = 26, 33%). At baseline, 76 cases (96%) had a detectable Tc-MEP waveform for at least one muscle, and the abductor hallucis had the highest rate of baseline waveform detection (n = 66, 84%). Tc-MEP alerts occurred during decompression (n = 47, 60%), exposure (n = 13, 16%), rodding (n = 5, 6%), pedicle screw insertion (n = 4, 5%), posture change (n = 4, 5%), dekyphosis (n = 2, 3%), and other procedures (n = 4, 5%). After intraoperative intervention, the rescue rate (no postoperative neurological deficit) was 57% (45/79), and rescue cases had a significantly better preoperative ambulatory status and a significantly higher baseline waveform derivation rate.

Conclusion.
These results show the efficacy of intraoperative intervention following a Tc-MEP alert for prevention of neurological deficit postoperatively.

Level of Evidence: 2
Ventriculoperitoneal Shunt Malfunction, a Rare Cause of Paraplegia after Kyphosis Correction
Authors: Patel Bharat K. , Bapat Mihir R. 
Published: November 2020

Ventriculoperitoneal shunt (VPS) malfunction after kyphosis surgery in 12-year boy caused a sudden hydrocephalus which increased cerebrospinal fluid pressure within the spinal cord and decreased cord perfusion. Spinal cord at apex of deformity was vulnerable to ischemia which caused paraplegia. The ischemic event was reversible after re-insertion of the VPS.

Study Design.
Case report and literature review.

Objective.
The aim of this study was to report a rare case of hydrocephalus due to ventriculoperitoneal shunt (VPS) malfunction following kyphosis correction that resulted in paraplegia in the postoperative period. The available English literature to explain the possible cause of paraplegia is reviewed.

Summary of Background Data.
Twelve-year male child presented with a severe dorsal kyphoscoliosis deformity with spastic paraparesis since 4 months. The lower extremities had grade-2 power and spasticity. The sensation was reduced below D9. The deep tendon reflexes were exaggerated with ankle clonus. Bowel-bladder had urgency and frequency. The radiographs and CT showed D6-7 hemi-vertebra with complex kyphoscoliosis deformity. magnetic resonance imaging showed a stretching cord at D6-7 due to 92° angular kyphosis. The somatosensory evoked potential showed posterior column involvement. The VPS was placed for hydrocephalus at 4 months of age. The shunt remained functioned throughout childhood.

Methods.
He underwent posterior vertebral column resection and kyphosis correction surgery. Postoperative CNS function was normal. Neurology was status quo. After 20 hours, the boy appeared irritable, confused with a headache and repetitive vomiting (Glasgow coma scale: 7-8/15). Computed tomography brain showed dilated both ventricles with left shunt in situ. Immediate re-shunting was done from right side. The CNS status improved dramatically and regained consciousness. Neurology deteriorated to grade-0 with increased spasticity and further decreased sensation below D9. The spinal causes (hematoma, implant malposition, syrinx) were ruled out.

Results.
Delayed neurological recovery was seen at 6th week after shunt surgery. The Rapid motor march was observed and became independent ambulatory at 12th week. At 6 months, he improved up-to grade4 power with grade 2 spasticity which maintained at 2 years.

Conclusion.
VPS blockage caused a sudden hydrocephalus which increased CSF pressure within the spinal cord and decreased cord perfusion. Spinal cord at apex of deformity was vulnerable to ischemia which caused paraplegia.

Level of Evidence: 5
Risk Factors for Poor Outcome of Cervical Laminoplasty
Authors: Machino Masaaki , Ando Kei , Kobayashi Kazuyoshi , Nakashima Hiroaki , Kanbara Shunsuke , Ito Sadayuki , Inoue Taro , Ito Keigo , Kato Fumihiko , Ishiguro Naoki , Imagama Shiro 
Published: November 2020

The risk factors for poor outcome after cervical laminoplasty in patients with cervical spondylotic myelopathy (CSM) were demonstrated. These findings suggest that advanced age, long-term CSM symptoms, and lower score of preoperative 10-second step test are risk factors for poor cervical laminoplasty outcomes in patients with CSM.

Study Design..
A prospective study.

Objective..
The aim of this study was to characterize the risk factors for poor outcome following cervical laminoplasty in patients with cervical spondylotic myelopathy (CSM).

Summary of Background Data..
Previous research has identified a variety of potential predictive factors that might affect outcomes after cervical laminoplasty. However, no study till date has assessed the effects of such risk factors, including internal medicine comorbidity and quantitative performance tests, on the outcome of laminoplasty in a large series of patients with CSM.

Methods..
A total of 505 consecutive patients with CSM (311 males; 194 females; mean age, 66.6 years; age range, 41–91 years) who underwent double-door laminoplasty were prospectively included. The average postoperative follow-up period was 26.5 months (range, 12–66 months). We evaluated the recovery rate (RR) on the basis of the Japanese Orthopaedic Association score. Logistic regression analysis was performed to identify the risk factors for poor outcome, which was defined as a postoperative RR of <50%. Relationship between outcome and various clinical and imaging predictors was examined.

Results..
Two hundred ninety-five patients had good outcomes with RR >50%, whereas 210 patients had poor outcomes with RR <50%. Compared with the good-outcome group, the poor-outcome group had a significantly higher prevalence of diabetes and hypertension and use of anticoagulant/antiplatelet agent and smoking history (P < 0.05). Multivariate logistic regression analysis showed independent risks associated with increased age (odds ratio [ORs]  = 1.029, 95% confidence interval [CI] = 1.004–1054, P = 0.023). Logistic regression analysis determined that symptom duration of CSM (OR = 1.017, 95% CI = 1.008–1.026, P < 0.001) and preoperative 10-second step test (OR = 0.922, 95% CI = 0.865–0.983, P = 0.013) were significant risk factors for poor outcome.

Conclusion..
These findings suggest that advanced age, long-term CSM symptoms, and lower score of preoperative 10-second step test are risk factors for poor outcome in patients with CSM.

Level of Evidence: 2