bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Radial Extracorporeal Shock Wave Therapy on Flexor Spasticity of the Upper Limb in Post-stroke Patients: Study Protocol for a Randomized Controlled Trial
Authors: Fan Tao , Zhou Xiangying , He Peichen , Zhan Xiaojia , Zheng Peng , Chen Rong , Li Rongdong , Li Rihui , Wei Mingyang , Zhang Xue , Huang Guozhi
Published: September 2021

Background:Flexor spasticity of the upper limb is common in poststroke patients and seriously affects the recovery of upper limb function. However, there are no standard management protocols for this condition. Radial extracorporeal shock wave therapy (rESWT) is widely used for various diseases, some studies reported the effects of ESWT on reducing spasticity, but the mechanism of ESWT to reduce spasticity by affecting the excitability of stretch reflex or non-neural rheological components in spastic muscles or both is not yet clear. A large randomized controlled trial with comprehensive evaluation indicators is still needed. The study is to observe the effect of rESWT on flexor spasticity of the upper limb after stroke and explore its mechanism.

Methods:A prospective, randomized, double-blind controlled trial is to be performed. One hundred participants will be recruited from the Inpatient Department of Zhujiang Hospital. Eligible patients will be randomly allocated to either receive three sessions of active rESWT (group A) or sham-placebo rESWT (group B) with 3-day intervals between each session. Assessment will be performed at baseline and at 24 h after each rESWT (t1, t2, and t3). The primary assessment outcome will be the Modified Ashworth Scale, and other assessments include surface electromyography, MyotonPRO digital muscle function evaluation, and infrared thermal imaging. All data will be analyzed using intention-to-treat principles. Multiple imputation by chained equations will be used to address missing data caused by loss to follow-up and nonresponses. Per protocol, analyses will also be performed on the participants who complete other assessments. Statistical analysis will be performed using SPSS software (version 20.0) and the significance level set atp< 0.05.

Discussion:This trial aims to analyze the application of rESWT for the management of spasticity after strokeviaappropriate assessments. We hypothesized that after receiving active rESWT, patients would show greater improvement of upper limb muscles compared with patients within the sham-placebo group. The rESWT would be an alternative to traditional methods, and the results of this study may provide support for the further study of potential mechanisms.

Clinical Trial Registration:www.chictr.org.cn, identifier: ChiCTR1800016144.
Evidence-Based Updates to Thrombectomy: Targets, New Techniques, and Devices
Authors: Yeo Leonard L. L. , Jing Mingxue , Bhogal Pervinder , Tu Tianming , Gopinathan Anil , Yang Cunli , Tan Benjamin Y. Q. , Arnberg Fabian , Sia Ching-Hui , Holmin Staffan , Andersson Tommy
Published: September 2021

Endovascular thrombectomy (EVT) has been validated in several randomized controlled trials in recent years for its efficacy in the treatment of acute ischemic strokes (AIS) and is now the standard of care according to international guidelines. However, in about 20% of EVT procedures, recanalization is not achieved, and over 50% of patients who undergo EVT still do not have good functional outcome. In this article, we provide an extensive review of the latest evidence and developments in the field of EVT, with particular focus on the factors that improve patient outcomes. These factors include new and adjunctive techniques such as combination of direct aspiration and stent retriever, intra-arterial urokinase or 2b/3a inhibitors, rescue stenting, as well as novel devices including balloon guide catheters and the newer generations of aspiration catheters and stent retrievers. We also examined the latest notion of using first-pass effect (FPE) as the target to achieve during EVT, which has been associated with an improved functional outcome. While the field of EVT has been rapidly evolving, further research is required in specific AIS patient populations such as those with large ischemic core, late presentation beyond 24 h, posterior circulation strokes, and with distal medium vessel occlusion or tandem lesions to better assess its efficacy and safety.
Increased Sodium Concentration in Substantia Nigra in Early Parkinson's Disease: A Preliminary Study With Ultra-High Field (7T) MRI
Authors: Grimaldi Stephan , El Mendili Mohamed Mounir , Zaaraoui Wafaa , Ranjeva Jean-Philippe , Azulay Jean-Philippe , Eusebio Alexandre , Guye Maxime
Published: September 2021

Pathophysiology of idiopathic Parkinson's disease (iPD) is complex and still misunderstood. At a time when treatments with disease-modifying potential are being developed, identification of early markers of neurodegeneration is essential. Intracerebral sodium accumulation could be one of them. Indeed, it may be in relation to the mitochondrial dysfunction that early exists in iPD. For the first time, we used brain sodium (23Na) MRI to explore sodium concentration changes that have already been reported to be related to neurodegeneration in other diseases. We prospectively included 10 iPD patients (mean age 52.2 ± 5.9 years-old) with motor symptoms that started <36 months before inclusion and 12 healthy subjects (mean age 53 ± 6.4 years-old). Patients were scanned in OFF medication state by using proton (1H) and 23Na MRI at 7T. We then extracted quantitative Total Sodium Concentration (TSC) from five regions of interest known to be early impaired in iPD [substantia nigra (SN), putamen, caudate nucleus, pallidum, thalamus] and in one region supposed to be relatively spared in the first stages of the disease [cortical gray matter (neocortex)]. Potential atrophy in these structures was also investigated with 1H MRI. Relative to healthy subjects, iPD patients showed higher TSC in the SN (43.73 ± 4.64 vs. 37.72 ± 5.62, p = 0.006 after Bonferroni correction). A trend of increase in sodium concentrations was found within the pallidum (45.80 ± 4.19 vs. 41.07 ± 4.94, p = 0.017), putamen (48.65 ± 4.58 vs. 43.66 ± 5.04, p = 0.041) and the cortical gray matter (56.34 ± 3.92 vs. 50.81 ± 5.50, p = 0.021). No significant brain atrophy was found in patients compared to controls. Thus, alteration of sodium homeostasis in the SN in the absence of atrophy could be considered as a potential early marker of cellular dysfunction in iPD.
Phase–Amplitude Coupling and Epileptogenic Zone Localization of Frontal Epilepsy Based on Intracranial EEG
Authors: Ma Huijuan , Wang Zeyu , Li Chunsheng , Chen Jia , Wang Yuping
Published: September 2021

Objective: This study aimed to explore the characteristics of phase-amplitude coupling in patients with frontal epilepsy based on their electrocorticography data, in order to identify the localization of epileptic regions and further guide clinical resection surgery.

Methods: We adopted the modulation index based on the Kullback-Leibler distance, phase-amplitude coupling co-modulogram, and time-varying phase-amplitude modulogram to explore the temporal-spatial patterns and characterization of PAC strength during the period from inter- seizure to post-seizure. Taking the resected area as the gold standard, the epileptogenic zone was located based on MI values of 7 different seizure periods, and the accuracy of localization was measured by the area under the receiver operating curve.

Results: (1) The PAC in the inter- and pre-seizure periods was weak and paroxysmal, but strong PAC channels were confined more to the seizure-onset zone and resection region. PAC during the seizure period was intense and persistent, but gradually deviated from the seizure-onset zone. (2) The characteristics of coupling strength of the inter- and pre-seizure EEG can be used to accurately locate the epileptogenic zone, which is better than that in periods after the beginning of a seizure. (3) In an epileptic seizure, the preferred phases of coupling were usually in the rising branches at the pre- and early-seizure stages, while those in the middle- and terminal-seizure were usually in the falling branch. We thus speculate that the coupling occurred in the rising branch can promote the recruitment of abnormal discharge, while the coupling occurred in the falling branch can inhibit the abnormal discharge.

Conclusion: The findings suggest that the phase-amplitude coupling during inter- and pre-seizure is a promising marker of epileptic focus location. The preferred phase of coupling changed regularly with the time of epileptic seizure, suggesting that the surge and suppression of abnormal discharges are related to different phases.
Physical and Psychological Factors Associated With Walking Capacity in Patients With Lumbar Spinal Stenosis With Neurogenic Claudication: A Systematic Scoping Review
Authors: Houle Mariève , Bonneau Jean-Daniel , Marchand Andrée-Anne , Descarreaux Martin
Published: September 2021

Objective: The purpose of this study was to evaluate the current state of scientific knowledge regarding physical and psychological factors associated with walking capacity in patients with lumbar spinal stenosis (LSS) with neurogenic claudication.

Design: Systematic scoping review.

Literature Search: We searched CINAHL (Cumulative Index to Nursing and Allied Health Literature), MEDLINE, Cochrane, PsycINFO, and SPORTDiscus databases.

Study Selection Criteria: Cohorts and cross-sectional studies reporting on associations between physical or psychological factors and impaired walking capacity in patients with symptomatic LSS were included.

Data Synthesis: Data were synthetized to identify associations between physical or psychological factors and either walking capacity, gait pattern characteristics, or functional tasks.

Results: Twenty-four studies were included. Walking capacity was significantly correlated with several pain outcomes, disability, estimated walking distance, and cross-sectional area of the lumbar spine. Gait pattern characteristics such as speed and stride were strongly and positively correlated with disability outcomes. Functional tasks were significantly correlated with lower back and upper limb disability, lower limb endurance strength, ranges of motion, and speed. Associations with psychological factors were mostly conflicting except for the Rasch-based Depression Screener and the Pain Anxiety Symptom Scale (PASS-20) questionnaire that were associated with a decreased performance in functional tasks.

Conclusion: Physical and psychological factors that are associated with walking capacity in patients with symptomatic LSS were identified. However, many associations reported between physical or psychological factors and walking capacity were conflicting, even more so when correlated with walking capacity specifically.
The Effect of Intraventricular Hemorrhage on Brain Development in Premature Infants: A Synthetic MRI Study
Authors: Zhang Chunxiang , Zhao Xin , Cheng Meiying , Wang Kaiyu , Zhang Xiaoan
Published: September 2021

Objectives: Synthetic MRI can obtain multiple parameters in one scan, including T1 and T2 relaxation time, proton density (PD), brain volume, etc. This study aimed to investigate the parameter values T1 and T2 relaxation time, PD, and volume characteristics of intraventricular hemorrhage (IVH) newborn brain, and the ability of synthetic MRI parameters T1 and T2 relaxation time and PD to diagnose IVH.

Materials and methods: The study included 50 premature babies scanned with conventional and synthetic MRI. Premature infants were allocated to the case group (n = 15) and NON IVH (n = 35). The T1, T2, PD values, and brain volume were obtained by synthetic MRI. Then we assessed the impact of IVH on these parameters.

Results: In the posterior limbs of the internal capsule (PLIC), genu of the corpus callosum (GCC), central white matter (CWM), frontal white matter (FWM), and cerebellum (each p < 0.05), the T1 and T2 relaxation times of the IVH group were significantly prolonged. There were significant differences also in PD. The brain volume in many parts were also significantly reduced, which was best illustrated in gray matter (GM), cerebrospinal fluid and intracranial volume, and brain parenchymal fraction (BPF) (each p < 0.001, t = −5.232 to 4.596). The differential diagnosis ability of these quantitative values was found to be excellent in PLIC, CWM, and cerebellum (AUC 0.700–0.837, p < 0.05).

Conclusion: The quantitative parameters of synthetic MRI show well the brain tissue characteristic values and brain volume changes of IVH premature infants. T1 and T2 relaxation times and PD contribute to the diagnosis and evaluation of IVH.
Repetitive Transcranial Magnetic Stimulation Target Location Methods for Depression
Authors: Zhang Min , Wang Runhua , Luo Xin , Zhang Si , Zhong Xiaomei , Ning Yuping , Zhang Bin
Published: September 2021

Major depressive disorder (MDD) is a substantial global public health problem in need of novel and effective treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and promising treatment for depression that has been approved by the U.S. Food and Drug Administration (FDA). However, the methodological weaknesses of existing work impairs the universal clinical use of rTMS. The variation of stimulated targets across the dorsolateral prefrontal cortex may account for most of the heterogeneity in the efficacy of rTMS. Many rTMS target location methods for MDD have been developed in recent decades. This review was conducted to assess this emerging field and to improve treatment outcomes in clinical practice.
Establishment of Effective Biomarkers for Depression Diagnosis With Fusion of Multiple Resting-State Connectivity Measures
Authors: Li Yanling , Dai Xin , Wu Huawang , Wang Lijie
Published: September 2021

Major depressive disorder (MDD) is a severe mental disorder and is lacking in biomarkers for clinical diagnosis. Previous studies have demonstrated that functional abnormalities of the unifying triple networks are the underlying basis of the neuropathology of depression. However, whether the functional properties of the triple network are effective biomarkers for the diagnosis of depression remains unclear. In our study, we used independent component analysis to define the triple networks, and resting-state functional connectivities (RSFCs), effective connectivities (EC) measured with dynamic causal modeling (DCM), and dynamic functional connectivity (dFC) measured with the sliding window method were applied to map the functional interactions between subcomponents of triple networks. Two-sample t-tests with p < 0.05 with Bonferroni correction were used to identify the significant differences between healthy controls (HCs) and MDD. Compared with HCs, the MDD showed significantly increased intrinsic FC between the left central executive network (CEN) and salience network (SAL), increased EC from the right CEN to left CEN, decreased EC from the right CEN to the default mode network (DMN), and decreased dFC between the right CEN and SAL, DMN. Moreover, by fusion of the changed RSFC, EC, and dFC as features, support vector classification could effectively distinguish the MDD from HCs. Our results demonstrated that fusion of the multiple functional connectivities measures of the triple networks is an effective way to reveal functional disruptions for MDD, which may facilitate establishing the clinical diagnosis biomarkers for depression.
Novel Point-of-Care Diagnostic Method for Neonatal Encephalopathy Using Purine Nucleosides
Authors: Beamer Edward , O’Dea Mary Isabel , Garvey Aisling A. , Smith Jonathon , Menéndez-Méndez Aida , Kelly Lynne , Pavel Andreea , Quinlan Sean , Alves Mariana , Jimenez-Mateos Eva M. , Tian Faming , Dempsey Eugene , Dale Nicholas , Murray Deirdre M. , Boylan Geraldine B. , Molloy Eleanor J. , Engel Tobias
Published: September 2021

Background: Evidence suggests that earlier diagnosis and initiation of treatment immediately after birth is critical for improved neurodevelopmental outcomes following neonatal encephalopathy (NE). Current diagnostic tests are, however, mainly restricted to clinical diagnosis with no molecular tests available. Purines including adenosine are released during brain injury such as hypoxia and are also present in biofluids. Whether blood purine changes can be used to diagnose NE has not been investigated to date.

Methods: Blood purines were measured in a mouse model of neonatal hypoxia and infants with NE using a novel point-of-care diagnostic technology (SMARTChip) based on the summated electrochemical detection of adenosine and adenosine metabolites in the blood.

Results: Blood purine concentrations were ∼2–3-fold elevated following hypoxia in mice [2.77 ± 0.48 μM (Control) vs. 7.57 ± 1.41 μM (post-hypoxia), p = 0.029]. Data in infants with NE had a 2–3-fold elevation when compared to healthy controls [1.63 ± 0.47 μM (Control, N = 5) vs. 4.87 ± 0.92 μM (NE, N = 21), p = 0.0155]. ROC curve analysis demonstrates a high sensitivity (81%) and specificity (80%) for our approach to identify infants with NE. Moreover, blood purine concentrations were higher in infants with NE and seizures [8.13 ± 3.23 μM (with seizures, N = 5) vs. 3.86 ± 0.56 μM (without seizures, N = 16), p = 0.044].

Conclusion: Our data provides the proof-of-concept that measurement of blood purine concentrations via SMARTChip technology may offer a low-volume bedside test to support a rapid diagnosis of NE.
The GH-IGF-1 Axis in Circadian Rhythm
Authors: Wang Weihao , Duan Xiaoye , Huang Zhengxiang , Pan Qi , Chen Chen , Guo Lixin
Published: September 2021

Organisms have developed common behavioral and physiological adaptations to the influence of the day/night cycle. The CLOCK system forms an internal circadian rhythm in the suprachiasmatic nucleus (SCN) during light/dark input. The SCN may synchronize the growth hormone (GH) secretion rhythm with the dimming cycle through somatostatin neurons, and the change of the clock system may be related to the pulsatile release of GH. The GH—insulin-like growth factor 1 (IGF-1) axis and clock system may interact further on the metabolism through regulatory pathways in peripheral organs. We have summarized the current clinical and animal evidence on the interaction of clock systems with the GH—IGF-1 axis and discussed their effects on metabolism.
Comparison Between Human and Rodent Neurons for Persistent Activity Performance: A Biologically Plausible Computational Investigation
Authors: Zhang Qian , Zeng Yi , Zhang Tielin , Yang Taoyi
Published: September 2021

Elucidating the multi-scale detailed differences between the human brain and other brains will help shed light on what makes us unique as a species. Computational models help link biochemical and anatomical properties to cognitive functions and predict key properties of the cortex. Here, we present a detailed human neocortex network, with all human neuron parameters derived from the newest Allen Brain human brain cell database. Compared with that of rodents, the human neural network maintains more complete and accurate information under the same graphic input. Unique membrane properties in human neocortical neurons enhance the human brain’s capacity for signal processing.
Hyperthermia-Induced Changes in EEG of Anesthetized Mice Subjected to Passive Heat Exposure
Authors: de Labra Carmen , Pardo-Vazquez Jose L. , Cudeiro Javier , Rivadulla Casto
Published: September 2021

Currently, the role of hypothermia in electroencephalography (EEG) is well-established. However, few studies have investigated the effect of hyperthermia on EEG, an important physiological parameter governing brain function. The aim of this work was to determine how neuronal activity in anesthetized mice is affected when the temperature rises above the physiological threshold mandatory to maintain the normal body functions. In this study, a temperature-elevation protocol, from 37 to 42°C, was applied to four female mice of 2–3 months old while EEG was recorded simultaneously. We found that hyperthermia reduces EEG amplitude by 4.36% when rising from 37 to 38 degrees and by 24.33% when it is increased to 42 degrees. Likewise, increasing the body temperature produces a very large impact on the EEG spectral parameters, reducing the frequency power at the delta, theta, alpha, and beta bands. Our results show that hyperthermia has a global effect on the EEG, being able to change the electrical activity of the brain.
Cafeteria Diet Impacts the Body Weight and Energy Expenditure of Brown Norway Rats in an Apparent Age Dependent Manner, but Has no Effect on Muscle Anabolic Sensitivity to Nutrition
Authors: El Ayadi Amina , Tapking Christian , Prasai Anesh , Rontoyanni Victoria G. , Abdelrahman Doaa R. , Cui Weihua , Fang Geping , Bhattarai Nisha , Murton Andrew J.
Published: September 2021

While obesity blunts the ability of muscle to mount a protein synthetic response to an amino acid infusion in older adults, it is unclear if this insensitivity to nutrition persists long term and in response to complete foods is unknown. To address this, young (2 months old) and old (17–20 months old) Brown Norway rats were randomized to receive either chow or a 12 wk diet of calorie-dense human foods. At wk 10 drinking water was supplemented with 2% heavy water, followed 2 weeks later by a flooding dose of [2H5]-phenylalanine and an oral leucine bolus, allowing the short and long-term effects of age and diet on muscle protein synthesis rates to be determined. The experimental diet increased energy intake in both young (7.4 ± 0.9%) and old (18.2 ± 1.8%) animals (P < 0.01), but only led to significant increases in body weight in the former (young: 10.2 ± 3.0% (P < 0.05) and old: 3.1 ± 5.1% (NS) vs. age-matched controls). Notably, energy expenditure in response to the cafeteria diet was increased in old animals only (chow: 5.1 ± 0.4; cafe: 8.2 ± 1.6 kcal.kg b.w−1.h−1; P < 0.05). Gastrocnemius protein fractional synthetic rates in response to either an acute leucine bolus or two weeks of feeding were equivalent across groups irrespective of age or diet. Rodents in old age appear capable of preventing weight gain in response to a calorie-dense diet by increasing energy expenditure while maintaining the anabolic sensitivity of muscle to nutrition; the mechanisms of which could have important implications for the aging obese human.
The Addition of Sirolimus to GVHD Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Efficacy and Safety
Authors: Chen Xiaoli , Sun Hengrui , Cassady Kaniel , Yang Shijie , Chen Ting , Wang Li , Yan Hongju , Zhang Xi , Feng Yimei
Published: September 2021

Objective

The objective of this study was to evaluate the safety and efficacy of sirolimus (SRL) in the prevention of graft-versus-host disease (GVHD) in recipients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods

Randomized controlled trials (RCTs) evaluating the safety and efficacy of SRL-based prophylaxis regimens in patients receiving allo-HSCT were obtained from PubMed, Embase, and the Cochrane database. Following specific inclusion and exclusion criteria, studies were selected and screened by two independent reviewers who subsequently extracted the study data. The Cochrane risk bias evaluation tool was used for quality evaluation, and RevMan 5.3 software was used for statistical analysis comparing the effects of SRL-based and non–SRL-based regimens on acute GVHD, chronic GVHD, overall survival (OS), relapse rate, non-relapse mortality (NRM), thrombotic microangiopathy (TMA), and veno-occlusive disease (VOD).

Results

Seven studies were included in this meta-analysis, with a total sample size of 1,673 cases, including 778 cases of patients receiving SRL-based regimens and 895 cases in which patients received non-SRL-based regimens. Our data revealed that SRL containing prophylaxis can effectively reduce the incidence of grade II–IV acute GVHD (RR = 0.75, 95% CI: 0.68∼0.82, p < 0.0001). SRL-based prophylaxis was not associated with an improvement of grade III–IV acute GVHD (RR = 0.78, 95% CI: 0.59∼1.03, p = 0.08), chronic GVHD (p = 0.89), OS (p = 0.98), and relapse rate (p = 0.16). Despite its immunosuppressant effects, SRL-based regimens did not increase bacterial (p = 0.68), fungal (p = 0.70), or CMV (p = 0.10) infections. However, patients receiving SRL-based regimens had increased TMA (p < 0.00001) and VOD (p < 0.00001).

Conclusions

This meta-analysis indicates that addition of sirolimus is an effective alternative prophylaxis strategy for II–IV aGVHD but may cause endothelial cell injury and result in secondary TMA or VOD events.
Reevaluation of Criteria and Establishment of Models for Total Thyroidectomy in Differentiated Thyroid Cancer
Authors: Wu Zhenghao , Xiao Yunxiao , Ming Jie , Xiong Yiquan , Wang Shuntao , Ruan Shengnan , Huang Tao
Published: September 2021

Introduction

After the publication of the 2015 American Thyroid Association (ATA) guidelines, the indication for total thyroidectomy (TT) was reported to be underestimated before surgery, which may lead to a substantial rate of secondary completion thyroidectomy (CTx).

Methods and Materials

We retrospectively analyzed differentiated thyroid cancer patients from Wuhan Union Hospital (WHUH). Univariate analysis was performed to evaluate all preoperative and intraoperative factors. New models were picked out by comminating and arranging all significant factors and were compared with ATA and National Comprehensive Cancer Network (NCCN) guidelines in the multicenter prospective Differentiated Thyroid Cancer in China (DTCC) cohort.

Results

A total of 5,331 patients from WHUH were included. Pre- and intraoperative criteria individually identified 906 (17.0%) and 213 (4.0%) patients eligible for TT. Among all factors, age <35 years old, clinical N1, and ultrasound reported local invasion had high positive predictive value to predict patients who should undergo TT. Accordingly, we established two new models that minorly revised ATA guidelines but performed much better. Model 1 replaced “nodule size >4 cm” with “age <35 years old” and achieved significant increase in the sensitivity (WHUH, 0.711 vs. 0.484; DTCC, 0.675 vs. 0.351). Model 2 simultaneously demands the presence of “nodule size >4 cm” and “age <35 years old,” which had a significant increase in the specificity (WHUH, 0.905 vs. 0.818; DTCC, 0.729 vs. 0.643).

Conclusion

All high-risk factors had limited predictive ability. Our model added young age as a new criterion for total thyroidectomy to get a higher diagnostic value than the guidelines.
Calculation of Apparent Diffusion Coefficients in Prostate Cancer Using Deep Learning Algorithms: A Pilot Study
Authors: Hu Lei , Zhou Da Wei , Fu Cai Xia , Benkert Thomas , Xiao Yun Feng , Wei Li Ming , Zhao Jun Gong
Published: September 2021

Background

Apparent diffusion coefficients (ADCs) obtained with diffusion-weighted imaging (DWI) are highly valuable for the detection and staging of prostate cancer and for assessing the response to treatment. However, DWI suffers from significant anatomic distortions and susceptibility artifacts, resulting in reduced accuracy and reproducibility of the ADC calculations. The current methods for improving the DWI quality are heavily dependent on software, hardware, and additional scan time. Therefore, their clinical application is limited. An accelerated ADC generation method that maintains calculation accuracy and repeatability without heavy dependence on magnetic resonance imaging scanners is of great clinical value.

Objectives

We aimed to establish and evaluate a supervised learning framework for synthesizing ADC images using generative adversarial networks.

Methods

This prospective study included 200 patients with suspected prostate cancer (training set: 150 patients; test set #1: 50 patients) and 10 healthy volunteers (test set #2) who underwent both full field-of-view (FOV) diffusion-weighted imaging (f-DWI) and zoomed-FOV DWI (z-DWI) with b-values of 50, 1,000, and 1,500 s/mm2. ADC values based on f-DWI and z-DWI (f-ADC and z-ADC) were calculated. Herein we propose an ADC synthesis method based on generative adversarial networks that uses f-DWI with a single b-value to generate synthesized ADC (s-ADC) values using z-ADC as a reference. The image quality of the s-ADC sets was evaluated using the peak signal-to-noise ratio (PSNR), root mean squared error (RMSE), structural similarity (SSIM), and feature similarity (FSIM). The distortions of each ADC set were evaluated using the T2-weighted image reference. The calculation reproducibility of the different ADC sets was compared using the intraclass correlation coefficient. The tumor detection and classification abilities of each ADC set were evaluated using a receiver operating characteristic curve analysis and a Spearman correlation coefficient.

Results

The s-ADCb1000 had a significantly lower RMSE score and higher PSNR, SSIM, and FSIM scores than the s-ADCb50 and s-ADCb1500 (all P < 0.001). Both z-ADC and s-ADCb1000 had less distortion and better quantitative ADC value reproducibility for all the evaluated tissues, and they demonstrated better tumor detection and classification performance than f-ADC.

Conclusion

The deep learning algorithm might be a feasible method for generating ADC maps, as an alternative to z-ADC maps, without depending on hardware systems and additional scan time requirements.
Radiomics Models for the Preoperative Prediction of Pelvic and Sacral Tumor Types: A Single-Center Retrospective Study of 795 Cases
Authors: Yin Ping , Zhi Xin , Sun Chao , Wang Sicong , Liu Xia , Chen Lei , Hong Nan
Published: September 2021

Purpose

To assess the performance of random forest (RF)-based radiomics approaches based on 3D computed tomography (CT) and clinical features to predict the types of pelvic and sacral tumors.

Materials and Methods

A total of 795 patients with pathologically confirmed pelvic and sacral tumors were analyzed, including metastatic tumors (n = 181), chordomas (n = 85), giant cell tumors (n =120), chondrosarcoma (n = 127), osteosarcoma (n = 106), neurogenic tumors (n = 95), and Ewing’s sarcoma (n = 81). After semi-automatic segmentation, 1316 hand-crafted radiomics features of each patient were extracted. Four radiomics models (RMs) and four clinical-RMs were built to identify these seven types of tumors. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) were used to evaluate different models.

Results

In total, 795 patients (432 males, 363 females; mean age of 42.1 ± 17.8 years) were consisted of 215 benign tumors and 580 malignant tumors. The sex, age, history of malignancy and tumor location had significant differences between benign and malignant tumors (P < 0.05). For the two-class models, clinical-RM2 (AUC = 0.928, ACC = 0.877) performed better than clinical-RM1 (AUC = 0.899, ACC = 0.854). For the three-class models, the proposed clinical-RM3 achieved AUCs between 0.923 (for chordoma) and 0.964 (for sarcoma), while the AUCs of the clinical-RM4 ranged from 0.799 (for osteosarcoma) to 0.869 (for chondrosarcoma) in the validation set.

Conclusions

The RF-based clinical-radiomics models provided high discriminatory performance in predicting pelvic and sacral tumor types, which could be used for clinical decision-making.
Transarterial Chemoembolization Combined With Radiofrequency Ablation Versus Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma After Curative Resection: A 10-Year Single-Center Comparative Study
Authors: Zheng Xin , Ren Yanqiao , Hu Hanqing , Qian Kun
Published: September 2021

Background

The purpose of this study was to compare the efficacy and safety of transarterial chemoembolization (TACE) in combination with radiofrequency ablation (RFA) (TACE-RFA) and repeat hepatectomy in the treatment of recurrent hepatocellular carcinoma (HCC) after curative resection.

Methods

This retrospective study evaluated consecutive medical records of patients who received either TACE-RFA or repeat hepatectomy between January 2010 and May 2021. Overall survival (OS), progression-free survival (PFS), and complications were compared.

Results

Of the 2672 patients who received either TACE-RFA or repeat hepatectomy, 111 eligible patients were included in our study, 63 in the TACE-RFA group and 48 in the repeat hepatectomy group. The median OS was 38 months in the TACE-RFA group and 42 months in the repeat hepatectomy group, with no statistically difference between the two groups (P=0.45). Meanwhile, there was also no statistically significant difference in PFS between the two groups (P=0.634). Although both groups achieved similar outcomes, the rate of major complications was significantly higher in the repeat hepatectomy group (P=0.003).

Conclusions

Patients with recurrent HCC in the TACE-RFA group and the repeat hepatectomy group had similar OS and PFS regardless of the patient’s tumor diameter, but the TACE-RFA group was safer and more minimally invasive.
Development and Validation of a Simple-to-Use Nomogram to Predict Early Death in Metastatic Pancreatic Adenocarcinoma
Authors: Zhang Zhong , Pu Juan , Zhang Haijun
Published: September 2021

Background

Pancreatic adenocarcinoma (PCa) is a highly aggressive malignancy with high risk of early death (survival time ≤3 months). The present study aimed to identify associated risk factors and develop a simple-to-use nomogram to predict early death in metastatic PCa patients.

Methods

Patients diagnosed with metastatic PCa between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were collected for model construction and internal validation. An independent data set was obtained from China for external validation. Independent risk variables contributed to early death were identified by logistic regression models, which were then used to construct a nomogram. Internal and external validation was performed to evaluate the nomogram using calibration curves and the receiver operating characteristic curves.

Results

A total of 19,464 patients in the SEER cohort and 67 patients in the Chinese cohort were included. Patients from the SEER database were randomly divided into the training cohort (n = 13,040) and internal validation cohort (n = 6,424). Patients in the Chinese cohort were selected for the external validation cohort. Overall, 10,484 patients experienced early death in the SEER cohort and 35 in the Chinese cohort. A reliable nomogram was constructed on the basis of 11 significant risk factors. Internal validation and external validation of the nomogram showed high accuracy in predicting early death. Decision curve analysis demonstrated that this predictive nomogram had excellent and potential clinical applicability.

Conclusion

The nomogram provided a simple-to-use tool to distinguish early death in patients with metastatic PCa, assisting clinicians in implementing individualized treatment regimens.
Racial Disparities and Sex Differences in Early- and Late-Onset Colorectal Cancer Incidence, 2001–2018
Authors: Petrick Jessica L. , Barber Lauren E. , Warren Andersen Shaneda , Florio Andrea A. , Palmer Julie R. , Rosenberg Lynn
Published: September 2021

Background

Colorectal cancer (CRC) incidence rates have increased in younger individuals worldwide. We examined the most recent early- and late-onset CRC rates for the US.

Methods

Age-standardized incidence rates (ASIR, per 100,000) of CRC were calculated using the US Cancer Statistics Database’s high-quality population-based cancer registry data from the entire US population. Results were cross-classified by age (20-49 [early-onset] and 50-74 years [late-onset]), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, American Indian/Alaskan Native, Asian/Pacific Islander), sex, anatomic location (proximal, distal, rectal), and histology (adenocarcinoma, neuroendocrine).

Results

During 2001 through 2018, early-onset CRC rates significantly increased among American Indians/Alaskan Natives, Hispanics, and Whites. Compared to Whites, early-onset CRC rates are now 21% higher in American Indians/Alaskan Natives and 6% higher in Blacks. Rates of early-onset colorectal neuroendocrine tumors have increased in Whites, Blacks, and Hispanics; early-onset colorectal neuroendocrine tumor rates are 2-times higher in Blacks compared to Whites. Late-onset colorectal adenocarcinoma rates are decreasing, while late-onset colorectal neuroendocrine tumor rates are increasing, in all racial/ethnic groups. Late-onset CRC rates remain 29% higher in Blacks and 15% higher in American Indians/Alaskan Natives compared to Whites. Overall, CRC incidence was higher in men than women, but incidence of early-onset distal colon cancer was higher in women.

Conclusions

The early-onset CRC disparity between Blacks and Whites has decreased, due to increasing rates in Whites—rates in Blacks have remained stable. However, rates of colorectal neuroendocrine tumors are increasing in Blacks. Blacks and American Indians/Alaskan Natives have the highest rates of both early- and late-onset CRC.

Impact

Ongoing prevention efforts must ensure access to and uptake of CRC screening for Blacks and American Indians/Alaskan Natives.
CD68+ Macrophage Infiltration Associates With Poor Outcome of HPV Negative Oral Squamous Carcinoma Patients Receiving Radiation: Poly(I:C) Enhances Radiosensitivity of CAL-27 Cells but Promotes Macrophage Recruitment Through HMGB1
Authors: Ai Dan , Dou Yu , Nan Zhaodi , Wang Ketao , Wang Huayang , Zhang Lin , Dong Zuoqing , Sun Jintang , Ma Chao , Tan Wanye , Gao Wenjuan , Liu Jia , Zhao Lei , Liu Shaohua , Song Bingfeng , Shao Qianqian , Qu Xun
Published: September 2021

Patients with human papillomavirus (HPV) negative oral squamous cell carcinoma (OSCC) generally have poor clinical outcomes and worse responses to radiotherapy. It is urgent to explore the underlining mechanisms of the distinct prognoses between HPV negative and HPV positive OSCC and to develop effective therapy strategy to increase the survival rate of HPV negative OSCC patients. We conducted a retrospective cohort of 99 resected OSCC patients to evaluate the prognosis of HPV negative and HPV positive OSCC patients receiving radiation or not. We further addressed the association of CD68+ macrophage infiltration with HPV status and the effects on survival of OSCC patients. We also used the TCGA-OSCC cohort for further verification. Based on the cohort study, we applied a synthetic dsRNA polymer, polyriboinosinic-polyribocytidylic acid (poly(I:C)), on CAL-27 (HPV negative OSCC cells). We co-cultured its condition medium with THP-1 derived macrophage and examined the cytokines and macrophage migration. We found that high CD68+ macrophage infiltration associated with poor overall survival in HPV negative OSCC patients receiving radiation. In vitro, poly(I:C) could induce apoptosis and enhance the radiosensitivity, but increase macrophage recruitment. Targeting HMGB1 could inhibit IL-6 induction and macrophage recruitment. Our findings indicated that CD68+ macrophage might play an important role in the outcomes of HPV negative OSCC patients receiving radiation. Our findings also suggested that radiation combined poly(I:C) might be a potential therapy strategy to increase the radiation response and prognosis of HPV negative OSCC. Notably, HMGB1 should be targeted to inhibit macrophage recruitment and enhance overall therapy effects.
A Retrospective Cohort Study: Safety and Effectiveness of Elbasvir/Grazoprevir ± Ribavirin Compared With Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir ± Ribavirin in Patients With Chronic Hepatitis C Genotype 1 Infection
Authors: Hung Hsuan-Yu , Chen Chung-Yu , Liao Yi-Hsiang
Published: September 2021

Background: The direct-acting antiviral (DAA) agents are widely used to treat hepatitis C virus (HCV) genotype (GT) 1 infection, while it may cause severe liver damage. The objectives of the study were to evaluate the incidence of drug-induced liver injury (DILI), sustained virologic response at post-treatment week 12 (SVR12), and recurrence rates in HCV GT 1 infection.

Methods: This was a retrospective cohort study that included patients diagnosed with HCV GT 1 infection, who had received intervention and treatment with elbasvir/grazoprevir (EBR/GZR) ± ribavirin (RBV) versus ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) + dasabuvir ± RBV (as control group) for 12 or 24 weeks at a regional hospital in southern Taiwan between April 2016 and August 2018. The primary outcome of the study was to compare the incidence rate ratio (IRR) of DILI via Poisson regression, and the secondary outcome was to evaluate the effectiveness of two treatment regimens expressed as a percentage.

Results: The study included 149 patients in the control group and 105 patients in the intervention group of which 99.33 and 98.1% patients, respectively, achieved SVR12. In the control group, one patient experienced relapse, whereas in the intervention group, two patients relapsed. Furthermore, in the control group, a total of nine patients developed DILI as determined during follow-up care. Of these patients, three were 55–84 years old. In the intervention group, six patients developed DILI. The IRR of DILI caused by EBR/GZR treatment was 2.84 times higher than that caused by the OBV/PTV/r treatment regimen.

Conclusion: There was no significant difference between the studied DAA regimens regarding the incidence of DILI and effectiveness during the treatment. DILI occurrence during therapy did not affect the cure rate of medication. The present study results can provide reference data for drug selection among patients with HCV.

Trial registration: The study was approved by DMF-CYCH (CYCH IRB No: 2018067).
Tele-pharmacy Anticoagulation Clinic During COVID-19 Pandemic: Patient Outcomes
Authors: Al Ammari Maha , AlThiab Khalefa , AlJohani Manal , Sultana Khizra , Maklhafi Nada , AlOnazi Hayel , Maringa Aswaq
Published: September 2021

Introduction: It is well-established that clinical pharmacist-managed anticoagulation services achieve superior anticoagulation control, with a positive impact. At King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia, the structure of anticoagulation management is a pharmacist-managed specialty service. With the current COVID-19 situation, measures were taken to assure the continuity of patient care by establishing tele-pharmacy anticoagulation clinics.

Materials and Methods: This was a prospective study with patients prescribed anticoagulation and followed up for 3 months. Since establishing the anticoagulation virtual clinic in March 2020, 270 patients were recruited in the study. The data collected included age, gender, comorbidities, indication for anticoagulation, intended duration of treatment, warfarin dose, testing of International Normalized Ratio (INR), INR target, range of INR values, time INR that was within the therapeutic range (TTR), and complications of therapy (bleeding and/or bruises). The patients were asked to complete the pharmacist satisfaction survey (PSS) after their consultation to assess patient satisfaction with the new virtual consultation system. Linguistic and cultural validation was conducted for the questionnaire.

Results: A total of 270 patients were included in the study. The mean percentage of overall INR values in the range was 59.39% ± 32.84, and the mean time with the overall INR was within the therapeutic range 57.81% ± 32.08. Thirty-one percent of the sample had good anticoagulation control (time in therapeutic range >70%). The median satisfaction score was 32 (IQR 28–36) with a maximum score of 40.

Conclusion: This is the first study to assess the tele-pharmacy anticoagulation clinic’s efficiency and patient satisfaction in Saudi Arabia during the COVID-19 pandemic. This type of consultation was as effective as face-to-face consultations. The study also highlighted that though the reduction in the cost of care was not substantial, there was a significant increase in resource (clinical pharmacist) utilization as a result of this model. The adoption of tele-pharmacy resulted in time savings for the clinical pharmacists who can be utilized in many other improvement projects in adult ambulatory clinics to ensure the delivery of better quality and safe patient care.
β-caryophyllene, an FDA-Approved Food Additive, Inhibits Methamphetamine-Taking and Methamphetamine-Seeking Behaviors Possibly via CB2 and Non-CB2 Receptor Mechanisms
Authors: He Xiang-Hu , Galaj Ewa , Bi Guo-Hua , He Yi , Hempel Briana , Wang Yan-Lin , Gardner Eliot L. , Xi Zheng-Xiong
Published: September 2021

Recent research indicates that brain cannabinoid CB2 receptors are involved in drug reward and addiction. However, it is unclear whether β-caryophyllene (BCP), a natural product with a CB2 receptor agonist profile, has therapeutic effects on methamphetamine (METH) abuse and dependence. In this study, we used animal models of self-administration, electrical brain-stimulation reward (BSR) and in vivo microdialysis to explore the effects of BCP on METH-taking and METH-seeking behavior. We found that systemic administration of BCP dose-dependently inhibited METH self-administration under both fixed-ratio and progressive-ratio reinforcement schedules in rats, indicating that BCP reduces METH reward, METH intake, and incentive motivation to seek and take METH. The attenuating effects of BCP were partially blocked by AM 630, a selective CB2 receptor antagonist. Genetic deletion of CB2 receptors in CB2-knockout (CB2-KO) mice also blocked low dose BCP-induced reduction in METH self-administration, suggesting possible involvement of a CB2 receptor mechanism. However, at high doses, BCP produced a reduction in METH self-administration in CB2-KO mice in a manner similar as in WT mice, suggesting that non-CB2 receptor mechanisms underlie high dose BCP-produced effects. In addition, BCP dose-dependently attenuated METH-enhanced electrical BSR and inhibited METH-primed and cue-induced reinstatement of drug-seeking in rats. In vivo microdialysis assays indicated that BCP alone did not produce a significant reduction in extracellular dopamine (DA) in the nucleus accumbens (NAc), while BCP pretreatment significantly reduced METH-induced increases in extracellular NAc DA in a dose-dependent manner, suggesting a DA-dependent mechanism involved in BCP action. Together, the present findings suggest that BCP might be a promising therapeutic candidate for the treatment of METH use disorder.
Factors Associated With Edoxaban Concentration Among Patients With Atrial Fibrillation
Authors: Lin Shin-Yi , Kuo Ching-Hua , Ho Li-Ting , Liu Yen-Bin , Huang Chih-Fen , Tang Sung-Chun , Jeng Jiann-Shing
Published: September 2021

Background and Purpose: Edoxaban exposure varies across different ethnicities. The purpose of our study was to examine the risk factors associated with high or low edoxaban concentrations in Asian populations.

Methods: Participants with atrial fibrillation who were undergoing edoxaban therapy were enrolled. Peak (1–4 h after edoxaban administration) and trough (24 ± 4 h from the last edoxaban dose) blood samples were collected to measure edoxaban concentrations using ultrahigh-performance liquid chromatography with tandem mass spectrometry. The edoxaban concentrations were compared to those observed in clinical trials to define a higher- or lower-than-expected range. Multivariate logistic regression was used to analyze the risk factors associated with high or low edoxaban concentrations.

Results: Eighty participants (49 men, 61.3%) were enrolled and provided 78 trough and 76 peak samples. Twenty participants (25.6%) were determined to have low trough concentrations, which was associated with higher creatinine clearance and the use of the 30 mg regimen (odds ratio [OR] and 95% confidence interval [CI], 1.06 [1.01, 1.11], p = 0.01 and 5.77 [1.34, 24.75], p = 0.02, respectively). In contrast, 21 participants (27.6%) had high peak concentrations, which was associated with an off-label overdosing regimen (OR = 4.68 [1.23, 17.70], p = 0.02).

Conclusion: Our study identified factors associated with increased or decreased edoxaban exposure. The measurement of edoxaban concentration may be recommended for patients with selected characteristics.