bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Basal Ganglia Modulatory Effective Connectivity Observed in Resting-State fMRI in Individuals With Parkinson’s Disease
Authors: Wapstra Nicholas J. , Ketola Micah , Thompson Shelby , Lee Adel , Madhyastha Tara , Grabowski Thomas J. , Stocco Andrea
Published: March 2022

Alterations to interactions between networked brain regions underlie cognitive impairment in many neurodegenerative diseases, providing an important physiological link between brain structure and cognitive function. Previous attempts to characterize the effects of Parkinson’s disease (PD) on network functioning using resting-state functional magnetic resonance imaging (rs-fMRI), however, have yielded inconsistent and contradictory results. Potential problems with prior work arise in the specifics of how the area targeted by the diseases (the basal ganglia) interacts with other brain regions. Specifically, current computational models point to the fact that the basal ganglia contributions should be captured with modulatory (i.e., second-order) rather than direct (i.e., first-order) functional connectivity measures. Following this hypothesis, a principled but manageable large-scale brain architecture, the Common Model of Cognition, was used to identify differences in basal ganglia connectivity in PD by analyzing resting-state fMRI data from 111 participants (70 patients with PD; 41 healthy controls) using Dynamic Causal Modeling (DCM). Specifically, the functional connectivity of the basal ganglia was modeled as two second-level, modulatory connections that control projections from sensory cortices to the prefrontal cortex, and from the hippocampus and medial temporal lobe to the prefrontal cortex. We then examined group differences between patients with PD and healthy controls in estimated modulatory effective connectivity in these connections. The Modulatory variant of the Common Model of Cognition outperformed the Direct model across all subjects. It was also found that these second-level modulatory connections had higher estimates of effective connectivity in the PD group compared to the control group, and that differences in effective connectivity were observed for all direct connections between the PD and control groups.We make the case that accounting for modulatory effective connectivity better captures the effects of PD on network functioning and influences the interpretation of the directionality of the between-group results. Limitations include that the PD group was scanned on dopaminergic medication, results were derived from a reasonable but small number of individuals and the ratio of PD to healthy control participants was relatively unbalanced. Future research will examine if the observed effect holds for individuals with PD scanned off their typical dopaminergic medications.
Higher Burden of Cerebral Small Vascular Disease Predicts Major Adverse Cardiac and Cerebrovascular Events and Is Related to Abnormal Blood Pressure Variability Pattern in Hypertension Patients
Authors: Xu Xiaomeng , Huang Shu , Zeng YuE , Feng Yulan , Yue Dongqi , Shen Fanxia , Gao Yang , Zhang Bei , Yang Yang , Gu Lin , Fu Yi
Published: March 2022

Background and Objectives

The study aims to test the hypotheses that a higher burden of cerebral small vascular disease (CSVD) predicts major adverse cardiac and cerebrovascular events (MACCE) in patients with hypertension (HTN) and that abnormal blood pressure variability (BPV) pattern aggravates total CSVD burden.

Methods

We retrospectively reviewed patients with HTN prospectively selected between February 2015 and February 2019 from three participating centers. Patients were included if they had HTN for over 1 year and had at least one MRI feature of CSVD. Independent predictors were found using multivariate logistic regression.

Results

Among the 908 patients who finally enrolled in the study, the number of CSVD markers (OR = 1.940; 95% CI = 1.393–2.703; P < 0.001) independently predicted MACCE with acceptable predictive value (C-statistic = 0.730; 95% CI = 0.669–0.791; P < 0.001). An abnormal BPV pattern was identified as an independent risk factor for increased CSVD burden. Among them, reverse-dipper subtype demonstrated the most significant relationship (OR = 1.725; 95% CI = 1.129–2.633; P = 0.012).

Conclusion

Total CSVD burden predicts an increased risk of composite MACCE independently. An abnormal BPV pattern is associated with a higher burden of CSVD.
Impact of Voluntary Muscle Activation on Stretch Reflex Excitability in Individuals With Hemiparetic Stroke
Authors: Patterson Jacqueline R. , Dewald Julius P. A. , Drogos Justin M. , Gurari Netta
Published: March 2022

Objective

To characterize how, following a stretch-induced attenuation, volitional muscle activation impacts stretch reflex activity in individuals with stroke.

Methods

A robotic device rotated the paretic elbow of individuals with hemiparetic stroke from 70° to 150°, and then back to 70° elbow flexion at an angular speed of 120°/s. This stretching sequence was repeated 20 times. Subsequently, participants volitionally activated their elbow musculature or rested. Finally, the stretching sequence was repeated another 20 times. The flexors' stretch reflex activity was quantified as the net torque measured at 135°.

Results

Data from 15 participants indicated that the stretching sequence attenuated the flexion torque (p < 0.001) and resting sustained the attenuation (p = 1.000). Contrastingly, based on data from 14 participants, voluntary muscle activation increased the flexion torque (p < 0.001) to an initial pre-stretch torque magnitude (p = 1.000).

Conclusions

Stretch reflex attenuation induced by repeated fast stretches may be nullified when individuals post-stroke volitionally activate their muscles. In contrast, resting may enable a sustained reflex attenuation if the individual remains relaxed.

Significance

Stretching is commonly implemented to reduce hyperactive stretch reflexes following a stroke. These findings suggest that stretch reflex accommodation arising from repeated fast stretching may be reversed once an individual volitionally moves their paretic arm.
The Impact of Mean Arterial Pressure and Volume Contraction in With Acute Ischemic Stroke
Authors: Bahouth Mona N. , Saylor Deanna , Hillis Argye E. , Gottesman Rebecca F.
Published: March 2022

Background and Purpose

Hydration at the time of stroke may impact functional outcomes. We sought to investigate the relationship between blood pressure, hydration status, and stroke severity in patients with acute ischemic stroke (AIS).

Methods

We evaluated hydration status, determined by blood urea nitrogen (BUN)/creatinine ratio, in consecutive patients with AIS from a single comprehensive stroke center. Baseline mean arterial pressure (MAP) was analyzed using a linear spline with a knot at 90 mmHg. Baseline stroke severity was defined based on admission NIH Stroke Scale scores (NIHSSS) and MRI diffusion-weighted imaging.

Results

Among 108 eligible subjects, 55 (51%) presented in a volume contracted state. In adjusted models, in the total sample, for every 10 mmHg higher MAP up to 90 mmHg, NIHSSS was 2.8 points lower (p = 0.053), without further statistically significant association between MAP above 90 and NIHSSS. This relationship was entirely driven by the individuals in a volume contracted state: MAP was not associated with NIHSSS in individuals who were euvolemic. For individuals in a volume contracted state, each 10 mmHg higher MAP, up to 90 mmHg, was associated with 6.9 points lower NIHSSS (95% CI −11.1, −2.6). MAP values above 90 mmHg were not related to NIHSSS in either dehydrated or euvolemic patients.

Conclusions

Lower MAP contributes to more severe stroke in patients who are volume contracted, but not those who are euvolemic, suggesting that hydration status and blood pressure may jointly contribute to the outcome. Hydration status should be considered when setting blood pressure goals for patients with AIS.
A Radiomics Approach to Assess High Risk Carotid Plaques: A Non-invasive Imaging Biomarker, Retrospective Study
Authors: Chen Sihan , Liu Changsheng , Chen Xixiang , Liu Weiyin Vivian , Ma Ling , Zha Yunfei
Published: March 2022

Objective

This study aimed to construct a radiomics-based MRI sequence from high-resolution magnetic resonance imaging (HRMRI), combined with clinical high-risk factors for non-invasive differentiation of the plaque of symptomatic patients from asyptomatic patients.

Methods

A total of 115 patients were retrospectively recruited. HRMRI was performed, and patients were diagnosed with symptomatic plaques (SPs) and asymptomatic plaques (ASPs). Patients were randomly divided into training and test groups in the ratio of 7:3. T2WI was used for segmentation and extraction of the texture features. Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were employed for the optimized model. Radscore was applied to construct a diagnostic model considering the T2WI texture features and patient demography to assess the power in differentiating SPs and ASPs.

Results

SPs and ASPs were seen in 75 and 40 patients, respectively. Thirty texture features were selected by mRMR, and LASSO identified a radscore of 16 radiomics features as being related to plaque vulnerability. The radscore, consisting of eight texture features, showed a better diagnostic performance than clinical information, both in the training (area under the curve [AUC], 0.923 vs. 0.713) and test groups (AUC, 0.989 vs. 0.735). The combination model of texture and clinical information had the best performance in assessing lesion vulnerability in both the training (AUC, 0.926) and test groups (AUC, 0.898).

Conclusion

This study demonstrated that HRMRI texture features provide incremental value for carotid atherosclerotic risk assessment.
Relationship Between Cortical Excitability Changes and Cortical Thickness in Subcortical Chronic Stroke
Authors: Graterol Pérez José A. , Guder Stephanie , Choe Chi-un , Gerloff Christian , Schulz Robert
Published: March 2022

Ischemic stroke leads to excitability changes of the motor network as probed by means of transcranial magnetic stimulation (TMS). There is still limited data that shows to what extent structural alterations of the motor network might be linked to excitability changes. Previous results argue that the microstructural state of specific corticofugal motor tracts such as the corticospinal tract associate with cortical excitability in chronic stroke patients. The relationship between changes of cortical anatomy after stroke, as operationalized by means of decreases or increases in local cortical thickness (CT), has scarcely been addressed. In the present study, we re-analyzed TMS data and recruitment curve properties of motor evoked potentials and CT data in a group of 14 well-recovered chronic stroke patients with isolated supratentorial subcortical lesions. CT data of the stroke patients were compared to CT data of 17 healthy controls. Whole-brain and region-of-interest based analyses were conducted to relate CT data to measures of motor cortical excitability and clinical data. We found that stroke patients exhibited significantly reduced CT not only in the ipsilesional primary motor cortex but also in numerous secondary motor and non-motor brain regions, particularly in the ipsilesional hemisphere including areas along the central sulcus, the inferior frontal sulcus, the intraparietal sulcus, and cingulate cortices. We could not detect any significant relationship between the extent of CT reduction and stroke-related excitability changes of the motor network or clinical scores.
Effects of Early-Stage Blood Pressure Variability on the Functional Outcome in Acute Ischemic Stroke Patients With Symptomatic Intracranial Artery Stenosis or Occlusion Receiving Intravenous Thrombolysis
Authors: Yao Mian-Xuan , Qiu Dong-Hai , Zheng Wei-Cheng , Zhao Jiang-Hao , Yin Han-Peng , Liu Yong-Lin , Chen Yang-Kun
Published: March 2022

Background

Studies exploring the relationship between blood pressure (BP) fluctuations and outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) are limited. We aimed to investigate the influence of blood pressure variability (BPV) during the first 24 h after IVT on early neurological deterioration (END) and 3-month outcome after IVT in terms of different stroke subtypes.

Methods

Clinical data from consecutive AIS patients who received IVT were retrospectively analyzed. The hourly systolic BP of all patients were recorded during the first 24 h following IVT. We calculated three systolic BPV parameters, including coefficient of variability (CV), standard deviation of mean BP (SD) and successive variation (SV), within the first 6, 12, and 24 h after IVT. END was defined as neurological deterioration with an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within the first 72 h after admission. Follow-up was performed at 90 days after onset, and favorable and poor outcomes were defined as a modified Rankin Scale scores (mRS) of ≤1 or ≥2, respectively.

Results

A total of 339 patients, which were divided into those with (intracranial artery stenosis or occlusion group, SIASO group) and without (non-SIASO group) SIASO, were included. Among them, 110 patients (32.4%) were with SIASO. Patients in SIASO group had higher NIHSS on admission and difference in term of mRS at 90 days compared with non-SIASO group (P < 0.001). In SIASO group, patients in favorable outcome group were younger and had lower NIHSS on admission, lower SV-24 h (14.5 ± 4.3 vs. 11.8 ± 3.2, respectively) and lower SD-24 h (12.7 ± 3.8 vs. 10.9 ± 3.3, respectively), compared with patients with poor outcome (all P < 0.05). In the multivariable logistic regression analysis, compared with the lowest SV (SV < 25% quartile), SV50−75% [odds ratio (OR) = 4.449, 95% confidence interval (CI) = 1.231–16.075, P = 0.023] and SV>75% (OR = 8.676, 95% CI = 1.892–39.775, P = 0.005) were significantly associated with poor outcome at 3 months in patients with SIASO, adjusted for age, NIHSS on admission and atrial fibrillation. No BPV parameters were associated with END in SIASO group. In non-SIASO group, there were no significant association between BPV patterns and END or 90-day outcome.

Conclusions

SV-24 h had a negative relationship with 3-month outcome in AIS patients with SIASO treated with IVT, indicating that BPV may affect the outcome of AIS.
Functional Connectivity of the Brain Across Rodents and Humans
Authors: Xu Nan , LaGrow Theodore J. , Anumba Nmachi , Lee Azalea , Zhang Xiaodi , Yousefi Behnaz , Bassil Yasmine , Clavijo Gloria P. , Khalilzad Sharghi Vahid , Maltbie Eric , Meyer-Baese Lisa , Nezafati Maysam , Pan Wen-Ju , Keilholz Shella
Published: March 2022

Resting-state functional magnetic resonance imaging (rs-fMRI), which measures the spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, is increasingly utilized for the investigation of the brain’s physiological and pathological functional activity. Rodents, as a typical animal model in neuroscience, play an important role in the studies that examine the neuronal processes that underpin the spontaneous fluctuations in the BOLD signal and the functional connectivity that results. Translating this knowledge from rodents to humans requires a basic knowledge of the similarities and differences across species in terms of both the BOLD signal fluctuations and the resulting functional connectivity. This review begins by examining similarities and differences in anatomical features, acquisition parameters, and preprocessing techniques, as factors that contribute to functional connectivity. Homologous functional networks are compared across species, and aspects of the BOLD fluctuations such as the topography of the global signal and the relationship between structural and functional connectivity are examined. Time-varying features of functional connectivity, obtained by sliding windowed approaches, quasi-periodic patterns, and coactivation patterns, are compared across species. Applications demonstrating the use of rs-fMRI as a translational tool for cross-species analysis are discussed, with an emphasis on neurological and psychiatric disorders. Finally, open questions are presented to encapsulate the future direction of the field.
Significant Structural Alterations and Functional Connectivity Alterations of Cerebellar Gray Matter in Patients With Somatic Symptom Disorder
Authors: Liang Huai-Bin , Dong Liao , Cui Yangyang , Wu Jing , Tang Wei , Du Xiaoxia , Liu Jian-Ren
Published: March 2022

Objective

Recent studies have revealed a strong association between the cerebellum and psychiatric disorders. However, the structural changes in the cerebellar regions and functional connectivity (FC) patterns in patients with somatic symptom disorder (SSD) have not been elucidated.

Methods

Thirty-seven patients with SSD (29 drug-naive and 8 medicated patients) and 37 sex- and age-matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging scans. The spatially unbiased infratentorial (SUIT) cerebellar atlas-based voxel-based morphometry was used to investigate the changes in cerebellar regional gray matter (GM). Seed-based FC was further computed to explore the pattern of abnormal FC across the whole brain. Correlations were calculated to investigate the relationship between cerebellar structural (and FC) changes and clinical characteristics.

Results

After controlling for age, sex, total intracranial volume, medication, and mean FD covariates, all patients with SSD had increased mean GM volume (GMV) in the posterior lobules of the cerebellum bilaterally when compared with HCs, specifically, in the bilateral cerebellar crura I and II. Patients with SSD showed significantly stronger FC between the right crura I and II and bilateral precuneus inferior parietal region, and postcentral gyrus, extending to the superior parietal lobe, cingulate gyrus, and the white matter subgyral. In addition to the two clusters, right lingual gyrus was also a surviving cluster with significantly higher FC. Partial correlation analysis revealed that the degree of regional GMV increases in the two significant clusters and the Hamilton Depression Scale (HAMD) score was negatively correlated. Moreover, the FC of right crura I and II with the left parietal lobe and right lingual gyrus were also negatively associated with the HAMD score.

Conclusions

SSD exhibited significant microstructural changes and changes in FC pattern in the posterior cerebellar lobe. These results shed new light on the psychological and neural substrates of SSD and may serve as a potential treatment target for SSD based on the cerebellar area.
Polygenic Risk Score Effectively Predicts Depression Onset in Alzheimer’s Disease Based on Major Depressive Disorder Risk Variants
Authors: Upadhya Suraj , Liu Hongliang , Luo Sheng , Lutz Michael W. , Chiba-Falek Ornit
Published: March 2022

Introduction

Depression is a common, though heterogenous, comorbidity in late-onset Alzheimer’s Disease (LOAD) patients. In addition, individuals with depression are at greater risk to develop LOAD. In previous work, we demonstrated shared genetic etiology between depression and LOAD. Collectively, these previous studies suggested interactions between depression and LOAD. However, the underpinning genetic heterogeneity of depression co-occurrence with LOAD, and the various genetic etiologies predisposing depression in LOAD, are largely unknown.

Methods

Major Depressive Disorder (MDD) genome-wide association study (GWAS) summary statistics were used to create polygenic risk scores (PRS). The Religious Orders Society and Rush Memory and Aging Project (ROSMAP, n = 1,708) and National Alzheimer’s Coordinating Center (NACC, n = 10,256) datasets served as discovery and validation cohorts, respectively, to assess the PRS performance in predicting depression onset in LOAD patients.

Results

The PRS showed marginal results in standalone models for predicting depression onset in both ROSMAP (AUC = 0.540) and NACC (AUC = 0.527). Full models, with baseline age, sex, education, and APOEε4 allele count, showed improved prediction of depression onset (ROSMAP AUC: 0.606, NACC AUC: 0.581). In time-to-event analysis, standalone PRS models showed significant effects in ROSMAP (P = 0.0051), but not in NACC cohort. Full models showed significant performance in predicting depression in LOAD for both datasets (P < 0.001 for all).

Conclusion

This study provided new insights into the genetic factors contributing to depression onset in LOAD and advanced our knowledge of the genetics underlying the heterogeneity of depression in LOAD. The developed PRS accurately predicted LOAD patients with depressive symptoms, thus, has clinical implications including, diagnosis of LOAD patients at high-risk to develop depression for early anti-depressant treatment.
Role of Semaphorins in Ischemic Stroke
Authors: Du Huaping , Xu Yuan , Zhu Li
Published: March 2022

Ischemic stroke is one of the major causes of neurological morbidity and mortality in the world. Although the management of ischemic stroke has been improved significantly, it still imposes a huge burden on the health and property. The integrity of the neurovascular unit (NVU) is closely related with the prognosis of ischemic stroke. Growing evidence has shown that semaphorins, a family of axon guidance cues, play a pivotal role in multiple pathophysiological processes in NVU after ischemia, such as regulating the immune system, angiogenesis, and neuroprotection. Modulating the NVU function via semaphorin signaling has a potential to develop a novel therapeutic strategy for ischemic stroke. We, therefore, review recent progresses on the role of semphorin family members in neurons, glial cells and vasculature after ischemic stroke.
Is the Use of Glyphosate in Modern Agriculture Resulting in Increased Neuropsychiatric Conditions Through Modulation of the Gut-brain-microbiome Axis?
Authors: Barnett Jacqueline A. , Bandy Maya L. , Gibson Deanna L.
Published: March 2022

Environmental exposure to glyphosate and glyphosate-based herbicides has the potential to negatively influence neurodevelopment and behavior across generations indirectly through the gut-brain-microbiome axis. Potential mechanisms by which glyphosate may elicit these effects are through the disruption of the normally symbiotic relationship of the host and the gut microbiome. Given glyphosate can kill commensal members of the microbiome like Lactobacillus spp., Ruminococaeae and Butyricoccus spp., resulting in reductions in key microbial metabolites that act through the gut-brain-microbiome axis including indoles, L-glutamate and SCFAs. Glyphosate- resistant microbes in the gut have the potential to increase the production of pro-inflammatory cytokines and reactive oxygen species which may result in increased HPA activation, resulting in increased production of glucocorticoids which have implications on neurodevelopment. In addition, maternal transfer of the gut microbiome can affect immune and neurodevelopment, across generations. This perspective article weighs the evidence for chronic glyphosate exposure on the gut microbiome and the potential consequences on the gut-brain axis correlated with increased incidence of neuropsychiatric conditions.
Moderate Sun Exposure Is the Complementor in Insufficient Vitamin D Consumers
Authors: Wu Shou-En , Chen Wei-Liang
Published: March 2022

Background and Aims

Vitamin (Vit) D plays a vital role in human health, and the prevalence of Vit D deficiency worldwide has been a rising concern. This study investigates the serum 25-hydroxy-Vit D [25(OH)D] status in healthy US civilians and identifies how the two main sources, sun exposure and dietary Vit D intake, determine the final 25(OH)D levels in individuals.

Methods

A total of 2,360 of participants from The National Health and Nutrition Examination Survey (NHANES) 2009–2014 were analyzed. We divided the levels of sun exposure and dietary Vit D intake of all subjects into 10 strata and gave a score ranging from 1 to 10 points, respectively. Scores 1–5 in sun exposure and dietary intake were considered as relatively low exposure groups, whereas scores 6–10 were considered as relatively high exposure groups. Serum Vit D inadequacy was defined as <50 nmol/L. Linear and logistic regression analyses were used to examine the associations between sources of Vit D and serum 25(OH)D levels.

Results

In relatively low Vit D intake groups (Vit D intake score 1–5), relatively high sun exposure (sun exposure score >5) resulted in higher serum 25(OH)D levels (average 57 nmol/L) compared with relatively low sun exposure (sun exposure score <5) (average 50 nmol/L), whereas this difference became negligible in high intake groups (Vit D intake score 6–10). Moreover, the greatest slope occurred in the low Vit D intake curve (decile 3 of Vit D intake), which shows increased sun exposure time causing the greatest degree of change in serum 25(OH)D level in this group.

Conclusion

Sun exposure can significantly make up for deficiencies in subjects who consume insufficient dietary Vit D. Compared with the extra cost and time for building habits of Vit D supplementation, moderate sun exposure appears to be a simple and costless means for the public to start in daily practice.
Case Report: Free-Floating Intracoronary Thrombus: Who Is the Convict?
Authors: Mantovani Francesca , Paolini Ambra , Barbieri Andrea , Boriani Giuseppe
Published: March 2022

In young patients, especially with no traditional coronary risk factors, hypercoagulable states may always be considered as an alternative cause of acute coronary syndromes. The concomitant thrombotic and bleeding risk associated with myeloproliferative disorders complicates the decision-making, particularly regarding long-term dual antiplatelet therapy. The chosen therapy may need to be frequently revisited, depending on the patient’s bleeding complications. We reported the case of a 49-year-old woman with acute myocardial infarction with no traditional risk factors for coronary artery disease where a myeloproliferative neoplasm was diagnosed.
Identification of Novel Molecular Therapeutic Targets and Their Potential Prognostic Biomarkers Based on Cytolytic Activity in Skin Cutaneous Melanoma
Authors: Zhang Haoxue , Liu Yuyao , Hu Delin , Liu Shengxiu
Published: March 2022

Skin cutaneous melanoma (SKCM) attracts attention worldwide for its extremely high malignancy. A novel term cytolytic activity (CYT) has been introduced as a potential immunotherapy biomarker associated with counter-regulatory immune responses and enhanced prognosis in tumors. In this study, we extracted all datasets of SKCM patients, namely, RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database, conducted differential expression analysis to yield 864 differentially expressed genes (DEGs) characteristic of CYT and used non-negative matrix factorization (NMF) method to classify molecular subtypes of SKCM patients. Among all genes, 14 hub genes closely related to prognosis for SKCM were finally screen out. Based on these genes, we constructed a 14-gene prognostic risk model and its robustness and strong predictive performance were further validated. Subsequently, the underlying mechanisms in tumor pathogenesis and prognosis have been defined from a number of perspectives, namely, tumor mutation burden (TMB), copy number variation (CNV), tumor microenvironment (TME), infiltrating immune cells, gene set enrichment analysis (GSEA) and immune checkpoint inhibitors (ICIs). Furthermore, combined with GTEx database and HPA database, the expression of genes in the model was verified at the transcriptional level and protein level, and the relative importance of genes in the model was described by random forest algorithm. In addition, the model was used to predict the difference in sensitivity of SKCM patients to chemotherapy and immunotherapy. Finally, a nomogram was constructed to better aid clinical diagnosis.
Paradoxical Association Between Relative Cerebral Blood Volume Dynamics Following Chemoradiation and Increased Progression-Free Survival in Newly Diagnosed IDH Wild-Type MGMT Promoter Methylated Glioblastoma With Measurable Disease
Authors: Goldman Jodi , Hagiwara Akifumi , Yao Jingwen , Raymond Catalina , Ong Christian , Bakhti Rojin , Kwon Elizabeth , Farhat Maguy , Torres Carlo , Erickson Lily G. , Curl Brandon J. , Lee Maggie , Pope Whitney B. , Salamon Noriko , Nghiemphu Phioanh L. , Ji Matthew , Eldred Blaine S. , Liau Linda M. , Lai Albert , Cloughesy Timothy F. , Chung Caroline , Ellingson Benjamin M.
Published: March 2022

Background and Purpose

While relative cerebral blood volume (rCBV) may be diagnostic and prognostic for survival in glioblastoma (GBM), changes in rCBV during chemoradiation in the subset of newly diagnosed GBM with subtotal resection and the impact of MGMT promoter methylation status on survival have not been explored. This study aimed to investigate the association between rCBV response, MGMT methylation status, and progression-free (PFS) and overall survival (OS) in newly diagnosed GBM with measurable enhancing lesions.

Methods

1,153 newly diagnosed IDH wild-type GBM patients were screened and 53 patients (4.6%) had measurable post-surgical tumor (>1mL). rCBV was measured before and after patients underwent chemoradiation. Patients with a decrease in rCBV >10% were considered rCBV Responders, while patients with an increase or a decrease in rCBV <10% were considered rCBV Non-Responders. The association between change in enhancing tumor volume, change in rCBV, MGMT promotor methylation status, and PFS or OS were explored.

Results

A decrease in tumor volume following chemoradiation trended towards longer OS (p=0.12; median OS=26.8 vs. 16.3 months). Paradoxically, rCBV Non-Responders had a significantly improved PFS compared to Responders (p=0.047; median PFS=9.6 vs. 7.2 months). MGMT methylated rCBV Non-Responders exhibited a significantly longer PFS compared to MGMT unmethylated rCBV Non-Responders (p<0.001; median PFS=0.5 vs. 7.1 months), and MGMT methylated rCBV Non-Responders trended towards longer PFS compared to methylated rCBV Responders (p=0.089; median PFS=20.5 vs. 13.8 months).

Conclusions

This preliminary report demonstrates that in newly diagnosed IDH wild-type GBM with measurable enhancing disease after surgery (5% of patients), an enigmatic non-response in rCBV was associated with longer PFS, particularly in MGMT methylated patients.
Clinical Outcomes and Complications of Preoperative Embolization for Intracranial Giant Meningioma Tumorectomy: A Retrospective, Observational, Matched Cohort Study
Authors: Yin Yi , Li Yuhong , Jiang Zhouyang , Zhang Chao , Ge Hongfei , Chen Zhi , Hu Rong , Chen Yujie , Li Xuegang , Li Fei , Feng Hua
Published: March 2022

Objective

The potential benefits of preoperative embolization for intracranial meningiomas are still under debate. We aimed to investigate whether preoperative embolization can improve surgical and functional outcomes, based on controlling patient- and tumor-related confounding factors.

Methods

We reviewed all meningioma cases in our department from January 2016 to May 2021. Cases in the nonembolization cohort were matched to the embolization cohort by 1:1 ratio propensity score matching, through controlling patient- and tumor-related confounds. Surgical outcomes, complications, and functional outcomes were retrospectively compared between these two groups.

Results

Sixty-six cases in each group were included in our study after being matched. We did not find any significant differences of estimated blood loss (600.00 (400) vs. 500.00 (500.00) ml, p = 0.31), decrease of HGB level (30.81 ± 15.82 vs. 26.59 ± 12.90 g/L, p = 0.09), gross total resection rate (74.24% vs. 77.27%, p = 0.68), surgical time (302.50 (136) vs. 300.00 (72) min, p = 0.48), blood transfusion rates (53.03% vs. 42.42%, p = 0.35), blood transfusion volume [650.00 (657.50) vs. 535.00 (875.00) ml, p = 0.63] between the embolization group and nonembolization group. The number of patients who experience postsurgery complications were significantly higher in the nonembolization group (39.39% vs. 21.21%, p = 0.02). Patients in the nonembolization group were more likely to have a higher rate of mRS decline postsurgery (31.82% vs. 15.15%, p = 0.04).

Conclusion

Our study showed significant lower rates of surgical complications and long-term disabilities of meningioma patients treated with preoperative embolization. There were no significant differences in estimated blood loss, surgical time, and blood transfusion volume between embolization and nonembolization groups.
Conversion Surgery in Gastric Cancer Carcinomatosis
Authors: Morgagni Paolo , Solaini Leonardo , Saragoni Luca , Monti Manlio , Valgiusti Martina , Vittimberga Giovanni , Frassineti Giovanni Luca , Framarini Massimo , Ercolani Giorgio
Published: March 2022

Background

After the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer.

Methods

All patients with stage IV gastric cancer with peritoneal metastases as a single metastatic site operated at a single centre between 2005 and 2020 were included. Cases were grouped according to the treatment received.

Results

A total of 118 patients were considered, 46 were submitted to palliative gastrectomy (11 were considered M1 because of an unsuspected positive peritoneal cytology), and 20 were submitted to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) because of a <6 Peritoneal Cancer Index (PCI). The median overall survival (OS) after surgery plus HIPEC was 46.7 (95% CI 15.8–64.0). Surgery (without HIPEC) after CHT presented a median OS 14.4 (8.2–26.8) and after upfront surgery 14.7 (10.9–21.1). Patients treated with upfront surgery and considered M1 only because of a positive cytology, had a median OS of 29.2 (25.2–29.2). The OS of patients treated with surgery plus HIPEC were 60.4 months (9.2–60.4) in completely regressed cancer after chemotherapy and 31.2 (15.8–64.0) in those partially regressed (p = 0.742).

Conclusions

Conversion surgery for peritoneal carcinomatosis from gastric cancer was associated with long survival and it should always be taken into consideration in this group of patients.
A Deep-Learning Aided Diagnostic System in Assessing Developmental Dysplasia of the Hip on Pediatric Pelvic Radiographs
Authors: Xu Weize , Shu Liqi , Gong Ping , Huang Chencui , Xu Jingxu , Zhao Jingjiao , Shu Qiang , Zhu Ming , Qi Guoqiang , Zhao Guoqiang , Yu Gang
Published: March 2022

Background

Developmental dysplasia of the hip (DDH) is a common orthopedic disease in children. In clinical surgery, it is essential to quickly and accurately locate the exact position of the lesion, and there are still some controversies relating to DDH status. We adopt artificial intelligence (AI) to solve the above problems.

Methods

In this paper, automatic DDH measurements and classifications were achieved using a three-stage pipeline. In the first stage, we used Mask-RCNN to detect the local features of the image and segment the bony pelvis, including the ilium, pubis, ischium, and femoral heads. For the second stage, local image patches focused on semantically related areas for DDH landmarks were extracted by high-resolution network (HRNet). In the third stage, some radiographic results are obtained. In the above process, we used 1,265 patient x-ray samples as the training set and 133 samples from two other medical institutions as the verification set. The results of AI were compared with three orthopedic surgeons for reliability and time consumption.

Results

AI-aided diagnostic system's Tönnis and International Hip Dysplasia Institute (IHDI) classification accuracies for both hips ranged from 0.86 to 0.95. The measurements of numerical indices showed that there was no statistically significant difference between surgeons and AI. Tönnis and IHDI indicators were similar across the AI system, intermediate surgeon, and junior surgeon. Among some objective interpretation indicators, such as acetabular index and CE angle, there were good stability and consistency among the four observers. Intraclass consistency of acetabular index and CE angle among surgeons was 0.79–0.98, while AI was 1.00. The measurement time required by AI was significantly less than that of the doctors.

Conclusion

The AI-aided diagnosis system can quickly and automatically measure important parameters and improve the quality of clinical diagnosis and screening referral process with a convenient and efficient way.
Diagnosis of Neonatal Sepsis: The Role of Inflammatory Markers
Authors: Eichberger Julia , Resch Elisabeth , Resch Bernhard
Published: March 2022

This is a narrative review on the role of biomarkers in the diagnosis of neonatal sepsis. We describe the difficulties to obtain standardized definitions in neonatal sepsis and discuss the limitations of published evidence of cut-off values and their sensitivities and specificities. Maternal risk factors influence the results of inflammatory markers as do gestational age, the time of sampling, the use of either cord blood or neonatal peripheral blood, and some non-infectious causes. Current evidence suggests that the use of promising diagnostic markers such as CD11b, CD64, IL-6, IL-8, PCT, and CRP, either alone or in combination, might enable clinicians discontinuing antibiotics confidently within 24–48 h. However, none of the current diagnostic markers is sensitive and specific enough to support the decision of withholding antibiotic treatment without considering clinical findings. It therefore seems to be justified that antibiotics are often initiated in ill term and especially preterm infants. Early markers like IL-6 and later markers like CRP are helpful in the diagnosis of neonatal sepsis considering the clinical aspect of the neonate, the gestational age, maternal risk factors and the time (age of the neonate regarding early-onset sepsis) of blood sampling.
Does Learning Through Movement Improve Academic Performance in Primary Schoolchildren? A Systematic Review
Authors: Petrigna Luca , Thomas Ewan , Brusa Jessica , Rizzo Federica , Scardina Antonino , Galassi Claudia , Lo Verde Daniela , Caramazza Giovanni , Bellafiore Marianna
Published: March 2022

Physically active children have greater motor competence and a faster maturation compared with their sedentary peers. Recent research also suggests that physical activity during childhood may also promote cognitive development and therefore improve academic performance. The aim of this study was to understand if physically active academic lessons may improve academic achievement in primary schoolchildren. A systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was conducted. The search was performed on the following database: PubMed, Web of Science, Scopus, Education Resources Information Center (ERIC), and PsycINFO (APA). Studies evaluating schoolchildren aged between 3 and 11 years taking part in educational contexts that include physical activity and natural environments evaluating physical fitness and/or educational outcomes were included. A total of 54 studies (for a total sample of 29,460 schoolchildren) were considered eligible and included in the qualitative synthesis. The Effective Public Health Practice Project risk-of-bias assessment revealed a moderate quality of the included studies with only two considered weeks. Despite differences in the retrieved protocols, physically active academic lessons improve the total time engaged in physical activity, motor skills, and/or academic performance. The results of this review suggest that learning through movement is an effective, low-cost, and enjoyable strategy for elementary schoolchildren.
Dose Optimization of Teicoplanin for Critically Ill Patients With Renal Dysfunction and Continuous Renal Replacement Therapy: Experience From a Prospective Interventional Study
Authors: Shi Lu , Zhuang Zhiwei , Duan Lufen , Zhu Chenqi , Xue Hongzhi , Wang Xiao , Xu Xiaowen , Yuan Yunlong , Shi Ling , Li Jiahui , Sun Jiantong , Liu Xin , Zhou Qin , Lu Jian , Tang Lian
Published: March 2022

Background: Due to the lack of updated information on teicoplanin (TEI) for continuous renal replacement therapy (CRRT), no exact dosage regimen has been recommended. The aim of this study was to optimize the dosage regimen of TEI in renal dysfunction patients with or without CRRT, evaluate the influence factors of the eradication of Gram-positive bacteria, and evaluate the effect of CRRT on the clearance of TEI.

Methods: Patients with renal dysfunction receiving TEI treatment in the ICU were prospectively recruited and divided into CRRT and non-CRRT groups. Logistic regression analysis was used to screen the factors affecting the eradication of Gram-positive bacteria. The filtrate concentration of the CRRT group was measured at the time of TEI Cmin, and the filtration coefficient of TEI was calculated to evaluate the effect of CRRT on the clearance of TEI.

Results: A total of 106 patients were included, 40 cases in the CRRT group and 66 cases in the non-CRRT group. After giving high-loading doses of TEI, 75.8 and 70% of TEI Cmin in the non-CRRT and CRRT groups reached the range of 10–30 mg/L before the 3rd dose, respectively. The risk of G+ bacteria being uneradicated was higher while the APACHEⅡscore was higher than 22.5. The albumin level before the start of TEI administration and before the 6th–8th dose was lower than 32.8 g/L and 29.3 g/L, respectively, and Cmin before the 3rd dose and 6th–8th dose was lower than 13.2 mg/L and 17.1 mg/L, respectively, with the duration of TEI therapy shorter than 10.5 days. The correlation coefficient (r) was 0.6490 between Cmin before the 3rd dose and the albumin level (p < 0.001). The filtration coefficient of TEI was 10.7 ± 2.4% at Cmin and 11.1 ± 2.5% at Cmax. The GFR had no correlation with the filtration coefficient (r = −0.06204; r = −0.08059). The clearance of TEI in CRRT patients was negatively correlated with the albumin level (r = −0.6305, p = 0.0013).

Conclusion: The early stage of the albumin level can significantly affect the initial Cmin and clinical efficacy of TEI, and also had effect on the clearance of TEI by CRRT. The filtration coefficient of TEI was stable, even with a higher ultrafiltration rate.
Cajaninstilbene Acid Ameliorates Acetaminophen-Induced Liver Injury Through Enhancing Sestrin2/AMPK-Mediated Mitochondrial Quality Control
Authors: Yan Mingzhu , Jin Suwei , Liu Yongguang , Wang Lisha , Wang Zhi , Xia Tianji , Chang Qi
Published: March 2022

Acetaminophen (APAP)-induced liver injury (AILI) is the main cause of acute liver failure in the developed countries. The present study aimed to evaluate the therapeutic efficacy of cajaninstilbene acid (CSA), a major stilbene compound derived from the leaves of pigeon pea [Cajanus cajan (L.) Millsp.], against AILI. CSA (50, 75 mg/kg, p. o.) was administered to male C57BL/6 N mice 0.5 h after a toxic dose of APAP (300 mg/kg, i. p.). The direct effect of CSA on hepatocytes was tested on primary mouse hepatocytes. Serum transaminases, hematoxylin and eosin staining, TUNEL and propidium iodide staining were used to assess hepatic damage and cell death. The results demonstrated that APAP-induced liver injury was ameliorated by CSA, as evidenced by decreased alanine aminotransferase and aspartate aminotransferase levels in the serum, and fewer necrotic and apoptotic hepatocytes in vitro and in vivo. Consequently, the inflammation in response to APAP overdose was inhibited by CSA. Without affecting APAP metabolic activation, CSA interrupted the sustained JNK-Sab-ROS activation loop and alleviated oxidative stress. Additionally, CSA promoted mitochondrial quality control, including mitochondrial biogenesis and mitophagy, as revealed by increased PGC-1α, TFAM, LC3-Ⅱ, PINK1 and mitochondrial Parkin expression and decreased p62 expression. Further mechanistic investigations showed that independent of CAMKK2, LKB1-mediated AMPK activation, which was promoted by Sestrin2, might be responsible for the protective effect of CSA. Our study demonstrates that CSA alleviates APAP-induced oxidative stress and enhanced mitochondrial quality control through Sestrin2/AMPK activation, thereby protecting against AILI,.
An Optimized Two-Herb Chinese Food as Medicine Formula Reduces Cisplatin-Induced Nephrotoxicity in the Treatment of Lung Cancer in Mice
Authors: Shi Le , Shu Yang , Hu Xiangdong , Akram Waheed , Wang Jun , Dong Shuang , Luo Biaobiao , Zhang Jiuliang , Hu Sheng , Li Xiaohua , Hu Xuebo
Published: March 2022

Chemotherapy is considered a most effective way to treat cancer. However, it is very common that chemotherapy causes unbearable mental and physical side effects to cancer patients, which ultimately reduces the patients’ confidence of overcoming diseases and compromises the treatment of chemotherapy. Cisplatin (DDP), a widely used anticancer agent for various types of cancers, also damages nontumor cells and tissues, which are mostly related to the activation of the inflammation pathway. Previously, we have discovered a few rational formulas of food as medicine materials that reduced systemic inflammation in in vitro and in vivo models. Hence, this study reports the ability of an optimized traditional Chinese anti-inflammatory formulation capable of synergizing the antitumor effect of DDP in vitro and in vivo. More significantly, by formulation of two anti-inflammatory herbal medicine, the Chrysanthemum × morifolium (Ramat.) Hemsl [Asteraceae] and Lonicera japonica Thunb [Caprifoliaceae] with a mediator Glycyrrhiza uralensis Fisch. ex DC [Fabaceae], a best formula relieved the kidney damage imposed by DDP. Treatments of various combinations of major chemical components of the three herbs also exhibited a similar trend for lowering the DDP-induced nephrotoxicity; however, contrary to that of the formula of herbal extracts, all chemical formulas could not recover the body weight and food intake of the tumor-bearing mice treated by DDP. Our findings suggested that the therapeutic index of DDP-based chemotherapy was able to be improved by minimizing toxicities from the two-herb formula to inhibit the inflammation in mouse tumor models and DDP-induced acute kidney injury mouse models.
CYT387, a JAK-Specific Inhibitor Impedes Osteoclast Activity and Oophorectomy-Induced Osteoporosis via Modulating RANKL and ROS Signaling Pathways
Authors: Li Jing , Liang Jiamin , Wu Liwei , Xu Yang , Xiao Chengxiang , Yang Xue , Sun Ran , Zhao Jinmin , Xu Jiake , Liu Qian , Zhou Bo
Published: March 2022

Osteoclasts are of hematopoietic lineage and have the ability to degrade mineralized bone tissues. Abnormalities in osteoclastic activity under certain pathological conditions are common in bone diseases such as osteoporosis, osteosclerosis, and arthritis. Although many kinds of drugs are currently used to treat osteoporosis, they have obvious adverse reactions and limitations. CYT387 is a new small-molecule Janus kinase (JAK) inhibitor involved in hematopoiesis, immune modulation, fertility, lactation, and embryonic development. However, it has remained unclear whether CYT387 functionally impacts osteoclast formation. Our study demonstrated through osteoclast formation assay in vitro, that the use of CYT387 is a potential drug candidate for treating osteoclast-associated bone disease. The effects of CYT387 on osteoclast formation, bone resorption, NFATc1 activation, and especially intracellular ROS levels were investigated in vitro. Further, we examined the preclinical prospects of CYT387 using an oophorectomy (OVX) mouse model of osteoporosis with its anti-osteoclast activity in vivo. On the whole, this study shows that CYT387 holds promise for treating osteoclast-related bone illnesses including osteoporosis.