bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Analysis of Patients With Early-Onset Parkinson’s Disease in Eastern China
Authors: Hua Ping , Zhao Yuwen , Zeng Qian , Li Lanting , Ren Jingru , Guo Jifeng , Tang Beisha , Liu Weiguo
Published: May 2022

Background

Genetic factors play an important role in the pathogenesis of early-onset Parkinson’s disease (EOPD). To date, more than 20 pathogenic genes associated with Parkinson’s disease (PD) have been identified. This study aims to explore the mutation spectrum of EOPD and the clinical characteristics of mutation carriers in eastern China.

Methods

We recruited 155 unrelated EOPD patients, including 8 familial and 147 sporadic EOPD (age at onset ≤ 50 years). Overall, 24 known PD-associated genes were detected by whole exome sequencing and multiplex ligation-dependent probe amplification (MLPA) from patient samples. The genetic and clinical characteristics of pathogenic/likely pathogenic (P/LP) loci in this cohort were analyzed.

Results

Overall, 14 (9.03%) patients were detected with P/LP variants distributed in seven genes. The most frequent mutation occurred in PRKN (7/155, 4.52%), followed by LRRK2 (2/155, 1.29%), SNCA, CHCHD2, TMEM230, DNAJC13 and PLA2G6 (1/155, 0.64%, respectively). Exon rearrangement mutations accounted for 57.9% (11/19) of all mutations in PRKN. Four novel variants were detected: c.14T > C (p.M5T) in SNCA, c.297C > A (p.Y99X) in CHCHD2, c.2578C > T (p.R860C) in DNAJC13 and c.4C > T (p.Q2X) in TMEM230. We found the first case of LRRK2 c.6055G > A (p.G2019S) mutation in Chinese population. The median onset age of patients with P/LP mutations in autosomal recessive genes (PRKN and PLA2G6) was about 18.0 years earlier than patients without mutation. The proportion of patients with mutations were 63.64%, 27.03% and 9.68% when patients were stratified according to the age of onset at ≤ 30, ≤ 40 and ≤ 50 years, respectively.

Conclusion

Early-onset Parkinson’s disease patients from eastern China present a regional specific mutation spectrum. Analysis of larger patient cohorts is required to support these findings, and mechanistic studies of the four novel missense/non-sense mutations will clarify their role in the pathogenicity of EOPD.
Nomogram-Based Risk Model of Small (≤5 mm) Intracranial Aneurysm Rupture in an Eastern Asian Study
Authors: Lou Haiyan , Nie Kehui , Yang Jun , Zhang Tiesong , Wang Jincheng , Fan Weijian , Gu Chenjie , Yan Min , Chen Tao , Zhang Tingting , Min Junxia , Zhan Renya , Pan Jianwei
Published: May 2022

Background and Purpose

Risk stratification of small unruptured intracranial aneurysms (IAs) (< =5 mm) is important for clinical decision-making and management. The aim of this study was to develop an individualized rupture risk model for small IAs in an eastern Asian population.

Methods

This study retrospectively enrolled 343 patients with ruptured (n = 96) and unruptured (n = 285) small IAs. Clinical data and aneurysmal morphology were taken into consideration, regression analysis was performed to identify significant variables, and these variables were then incorporated into a predictive nomogram. The diagnostic performance of the nomogram was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot. Clinical effectiveness was validated by decision curve analysis (DCA). The PHASES score calculated for each case was used for comparison.

Results

The nomogram achieved an AUC of 0.849 (95% CI: 0.805–0.893), with a sensitivity of 86.5%, a specificity of 70.9%, and accuracy of 74.7%, which was superior to PHASES score system (AUC = 0.693, sensitivity = 83.6%, specificity = 48.8%, and accuracy = 57.5%). A good agreement between predicted rupture risk and actual rupture status in the small aneurysms was observed, and DCA illustrated the benefit of using the nomogram when decisions needed to be made clinically.

Conclusions

The nomogram based on clinical and morphological risk factors can be useful in assisting clinicians with individualized assessments and benefit-risk balancing in patients with small IAs (< =5 mm).
Nutritional Intake and Gut Microbiome Composition Predict Parkinson’s Disease
Authors: Lubomski Michal , Xu Xiangnan , Holmes Andrew J. , Muller Samuel , Yang Jean Y. H. , Davis Ryan L. , Sue Carolyn M.
Published: May 2022

Background

Models to predict Parkinson’s disease (PD) incorporating alterations of gut microbiome (GM) composition have been reported with varying success.

Objective

To assess the utility of GM compositional changes combined with macronutrient intake to develop a predictive model of PD.

Methods

We performed a cross-sectional analysis of the GM and nutritional intake in 103 PD patients and 81 household controls (HCs). GM composition was determined by 16S amplicon sequencing of the V3-V4 region of bacterial ribosomal DNA isolated from stool. To determine multivariate disease-discriminant associations, we developed two models using Random Forest and support-vector machine (SVM) methodologies.

Results

Using updated taxonomic reference, we identified significant compositional differences in the GM profiles of PD patients in association with a variety of clinical PD characteristics. Six genera were overrepresented and eight underrepresented in PD patients relative to HCs, with the largest difference being overrepresentation of Lactobacillaceae at family taxonomic level. Correlation analyses highlighted multiple associations between clinical characteristics and select taxa, whilst constipation severity, physical activity and pharmacological therapies associated with changes in beta diversity. The random forest model of PD, incorporating taxonomic data at the genus level and carbohydrate contribution to total energy demonstrated the best predictive capacity [Area under the ROC Curve (AUC) of 0.74].

Conclusion

The notable differences in GM diversity and composition when combined with clinical measures and nutritional data enabled the development of a predictive model to identify PD. These findings support the combination of GM and nutritional data as a potentially useful biomarker of PD to improve diagnosis and guide clinical management.
Extract of Euterpe oleracea Martius Stone Presents Anticonvulsive Activity via the GABAA Receptor
Authors: Muto Nilton Akio , Hamoy Moisés , da Silva Ferreira Chryslen Brenda , Hamoy Akira Otake , Lucas David Cristian Rodrigues , de Mello Vanessa Jóia , Rogez Hervé
Published: May 2022

Epilepsy is one of the most common neurological diseases globally, resulting from a disorder in brain activity. This condition can be triggered by birth trauma, traumatic brain injury (TBI), infections of the brain and stroke. More than 70 million people suffer seizures caused by neurological abnormalities. Approximately 80% of all epileptic patients reside in low-income conditions or in developing countries, and over 75% of patients do not receive proper treatment. Our previous study found an anticonvulsant property of an extract of Euterpe oleracea stone (EEOS) that caused myorelaxation, sedation, and cardiac and respiratory depression after intraperitoneal administration. The present study investigated through electroencephalographic (EEG) profiling the anticonvulsant protective properties of EEOS in induced convulsing rats. Male Wistar rats were treated with EEOS (300 mg/kg), diazepam (DZP) (5 mg/kg), pentylenetetrazol (PTZ) (60 mg/kg) and flumazenil (FMZ) (0.1 mg/kg) by intraperitoneal (i.p.). Electrodes implanted on the dura mater provided EEG data in which EEOS suppressed seizure deflagration caused by PTZ. In addition, EEOS presented no significant difference in comparison to DZP, which has the same mechanism of action. After FMZ injection, a GABAA receptor antagonist blocked the anticonvulsive effect in both the DZP and EEOS groups, suggesting that EEOS exerts it action on the GABAA receptor at the benzodiazepine (BDZ) subunit.
The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives
Authors: Stagni Fiorenza , Bartesaghi Renata
Published: May 2022

Down syndrome (DS), also known as trisomy 21, is a genetic disorder caused by triplication of Chromosome 21. Gene triplication may compromise different body functions but invariably impairs intellectual abilities starting from infancy. Moreover, after the fourth decade of life people with DS are likely to develop Alzheimer’s disease. Neurogenesis impairment during fetal life stages and dendritic pathology emerging in early infancy are thought to be key determinants of alterations in brain functioning in DS. Although the progressive improvement in medical care has led to a notable increase in life expectancy for people with DS, there are currently no treatments for intellectual disability. Increasing evidence in mouse models of DS reveals that pharmacological interventions in the embryonic and neonatal periods may greatly benefit brain development and cognitive performance. The most striking results have been obtained with pharmacotherapies during embryonic life stages, indicating that it is possible to pharmacologically rescue the severe neurodevelopmental defects linked to the trisomic condition. These findings provide hope that similar benefits may be possible for people with DS. This review summarizes current knowledge regarding (i) the scope and timeline of neurogenesis (and dendritic) alterations in DS, in order to delineate suitable windows for treatment; (ii) the role of triplicated genes that are most likely to be the key determinants of these alterations, in order to highlight possible therapeutic targets; and (iii) prenatal and neonatal treatments that have proved to be effective in mouse models, in order to rationalize the choice of treatment for human application. Based on this body of evidence we will discuss prospects and challenges for fetal therapy in individuals with DS as a potential means of drastically counteracting the deleterious effects of gene triplication.
Influence of Hearing Rehabilitation With Active Middle Ear and Bone Conduction Implants on Postural Control
Authors: Seiwerth Ingmar , Brylok Antonia , Schwesig René , Rahne Torsten , Fröhlich Laura , Lauenroth Andreas , Hullar Timothy E. , Plontke Stefan K.
Published: May 2022

Background

As audition also seems to contribute to balance control, additionally to visual, proprioceptive, and vestibular information, we hypothesize that hearing rehabilitation with active middle ear and bone conduction implants can influence postural control.

Methods

In a prospective explorative study, the impact of hearing rehabilitation with active middle ear [Vibrant Soundbrige (VSB), MED-EL, Innsbruck, Austria] and bone conduction implants [Bonebridge (BB), MED-EL, Innsbruck, Austria] on postural control in adults was examined in three experiments. Vestibulospinal control was measured by cranio-corpography (CCG), trunk sway velocity (°/s) by the Standard Balance Deficit Test (SBDT), and postural stability with a force plate system, each time in best aided (BA) and unaided (UA) condition with frontal-noise presentation (Fastl noise, 65 dB SPL), followed by subjective evaluation, respectively.

Results

In 26 subjects [age 55.0 ± 12.8 years; unilateral VSB/BB: n = 15; bilateral VSB/BB: n = 3, bimodal (VSB/BB + hearing aid): n = 8], CCG-analysis showed no difference between BA and UA conditions for the means of distance, angle of displacement, and angle of rotation, respectively. Trunk sway measurements revealed a relevant increase of sway in standing on foam (p = 0.01, r = 0.51) and a relevant sway reduction in walking (p = 0.026, r = 0.44, roll plane) in BA condition. Selective postural subsystem analysis revealed a relevant increase of the vestibular component in BA condition (p = 0.017, r = 0.47). As measured with the Interactive Balance System (IBS), 42% of the subjects improved stability (ST) in BA condition, 31% showed no difference, and 27% deteriorated, while no difference was seen in comparison of means. Subjectively, 4–7% of participants felt that noise improved their balance, 73–85% felt no difference, and 7–23% reported deterioration by noise. Furthermore, 46–50% reported a better task performance in BA condition; 35–46% felt no difference and 4–15% found the UA situation more helpful.

Conclusions

Subjectively, approximately half of the participants reported a benefit in task performance in BA condition. Objectively, this could only be shown in one mobile SBDT-task. Subsystem analysis of trunk sway provided insights in multisensory reweighting mechanisms.
Factors That Influence Susceptibility Vessel Sign in Patients With Acute Stroke Referred for Mechanical Thrombectomy
Authors: Dillmann Manon , Bonnet Louise , Vuillier Fabrice , Moulin Thierry , Biondi Alessandra , Charbonnier Guillaume
Published: May 2022

Background and Purpose

The presence of a Susceptibility Vessel Sign (SVS) in the acute phase of proximal occlusion ischemic stroke indicates the presence of deoxyhemoglobin in the thrombus. Thrombi composition changes over time. The aim of this study was to investigate whether the absence of SVS is associated with a shorter symptom onset to imaging time.

Methods

We retrospectively analyzed all patients referred for mechanical thrombectomy at Besançon University Hospital between 1 January 2015 and 31 December 2020 for whom readable T2*-weighted imaging was available. We compared patient characteristics according to the presence or absence of an SVS. We also studied the subgroup for whom the exact symptom onset time was known. We performed a univariate statistical analysis, then a multivariate analysis on the variables that were statistically significant in the univariate analysis.

Results

Of the 389 patients included, 309 (79.4%) were SVS+. We found no significant relationship between SVS– and the time between symptom onset and imaging in the whole cohort. In the multivariate analysis, SVS– was associated with anticoagulant treatment (p < 0.01), and SVS+ with age (p = 0.023) and carotid terminus occlusion (p = 0.042). In the known symptom onset subgroup, SVS– was significantly associated with a shorter symptom onset -imaging time (p < 0.001), and this was confirmed in the multivariate analysis (p = 0.011; OR 0.911; 95% CI [0.844; 0.972]).

Conclusion

In the acute phase of proximal occlusion ischemic stroke, absence of SVS was associated with a shorter symptom onset–imaging time for patients with a known symptom onset time.
Regularized Functional Connectivity in Schizophrenia
Authors: Salvador Raymond , Fuentes-Claramonte Paola , García-León María Ángeles , Ramiro Núria , Soler-Vidal Joan , Torres María Llanos , Salgado-Pineda Pilar , Munuera Josep , Voineskos Aristotle , Pomarol-Clotet Edith
Published: May 2022

Regularization may be used as an alternative to dimensionality reduction when the number of variables in a model is much larger than the number of available observations. In a recent study from our group regularized regression was employed to quantify brain functional connectivity in a sample of healthy controls using a brain parcellation and resting state fMRI images. Here regularization is applied to evaluate resting state connectivity abnormalities at the voxel level in a sample of patients with schizophrenia. Specifically, ridge regression is implemented with different degrees of regularization. Results are compared to those delivered by the weighted global brain connectivity method (GBC), which is based on averaged bivariate correlations and from the non-redundant connectivity method (NRC), a dimensionality reduction approach that applies supervised principal component regressions. Ridge regression is able to detect a larger set of abnormally connected regions than both GBC and NRC methods, including schizophrenia related connectivity reductions in fronto-medial, somatosensory and occipital structures. Due to its multivariate nature, the proposed method is much more sensitive to group abnormalities than the GBC, but it also outperforms the NRC, which is multivariate too. Voxel based regularized regression is a simple and sensitive alternative for quantifying brain functional connectivity.
EEG Microstate-Specific Functional Connectivity and Stroke-Related Alterations in Brain Dynamics
Authors: Hao Zexuan , Zhai Xiaoxue , Cheng Dandan , Pan Yu , Dou Weibei
Published: May 2022

The brain, as a complex dynamically distributed information processing system, involves the coordination of large-scale brain networks such as neural synchronization and fast brain state transitions, even at rest. However, the neural mechanisms underlying brain states and the impact of dysfunction following brain injury on brain dynamics remain poorly understood. To this end, we proposed a microstate-based method to explore the functional connectivity pattern associated with each microstate class. We capitalized on microstate features from eyes-closed resting-state EEG data to investigate whether microstate dynamics differ between subacute stroke patients (N= 31) and healthy populations (N= 23) and further examined the correlations between microstate features and behaviors. An important finding in this study was that each microstate class was associated with a distinct functional connectivity pattern, and it was highly consistent across different groups (including an independent dataset). Although the connectivity patterns were diminished in stroke patients, the skeleton of the patterns was retained to some extent. Nevertheless, stroke patients showed significant differences in most parameters of microstates A, B, and C compared to healthy controls. Notably, microstate C exhibited an opposite pattern of differences to microstates A and B. On the other hand, there were no significant differences in all microstate parameters for patients with left-sided vs. right-sided stroke, as well as patients before vs. after lower limb training. Moreover, support vector machine (SVM) models were developed using only microstate features and achieved moderate discrimination between patients and controls. Furthermore, significant negative correlations were observed between the microstate-wise functional connectivity and lower limb motor scores. Overall, these results suggest that the changes in microstate dynamics for stroke patients appear to be state-selective, compensatory, and related to brain dysfunction after stroke and subsequent functional reconfiguration. These findings offer new insights into understanding the neural mechanisms of microstates, uncovering stroke-related alterations in brain dynamics, and exploring new treatments for stroke patients.
Priming Engineers to Think About Sustainability: Cognitive and Neuro-Cognitive Evidence to Support the Adoption of Green Stormwater Design
Authors: Hu Mo , Shealy Tripp
Published: May 2022

Green infrastructure is the application of nature-based solutions like bioswales, rain gardens, and permeable pavements to reduce flooding in urban areas. These systems are underutilized in the design of the built environment. A barrier to their implementation is that design engineers tend to discount the tangential benefits of these greener systems and overweigh the associated risks. This study tested whether priming engineers to think about the environmental and social sustainability benefits of green infrastructure can influence what attributes engineers consider and how they weigh these attributes during the design decision-making process. Forty engineering students trained in stormwater design were asked to evaluate the implementation of a conventional stormwater design option and a green stormwater design option. Their preferred design option was recorded and the changes in their neuro-cognition were measured using functional near infrared-spectroscopy. Half of the engineers were asked to first consider the potential outcomes of these options on the environment and the surrounding community. Priming engineers to first consider environmental and social sustainability before considering the cost and risk of each option, significantly increased the perceived benefits the engineers believed green infrastructure could provide. The priming intervention also increased the likelihood that engineers would recommend the green infrastructure option. The engineers primed to think about environmental and social sustainability exhibited significantly lower oxy-hemoglobin in their ventrolateral, dorsolateral, and medial prefrontal cortex through multiple phases of the judgment and decision-making process. The intervention appears to increase cognitive representativeness or salience of the benefits for green infrastructure when engineers evaluate design alternatives. This relatively low-cost intervention, asking engineers to consider environmental and social sustainability for each design alternative, can shift engineering decision-making and change neuro-cognition.
Altered Brain Topological Property Associated With Anxiety in Experimental Orthodontic Pain
Authors: Zhang Feifei , Li Fei , Yang Hong , Jin Yu , Lai Wenli , Kemp Graham J. , Jia Zhiyun , Gong Qiyong
Published: May 2022

Background

Orthodontic pain is orofacial pain caused by tooth movement. Anxiety is a strong predictor of the severity of such pain, but little is known about the underlying neuropsychological mechanisms of such effects. The purpose of this study was to investigate the effect of orthodontic pain on brain functional networks and to define the mediating role of anxiety in orthodontic pain and brain function.

Methods

Graph theory-based network analyses were applied to brain functional magnetic resonance imaging data from 48 healthy participants exposed to 24 h orthodontic pain stimuli and 49 healthy controls without any stimulation.

Results

In the experimental orthodontic pain stimulation, brain functional networks retained a small-world organization. At the regional level, the nodal centrality of ipsilateral brain nodes to the pain stimulus was enhanced; in contrast the nodal centrality of contralateral brain areas was decreased, especially the right mid-cingulate cortex, which is involved in pain intensity coding. Furthermore, anxiety mediated the relationship between nodal efficiency of mid-cingulate cortex and pain severity.

Conclusion

The results illuminate the neural mechanisms of orthodontic pain by revealing unbalanced hemispherical brain function related to the unilateral pain stimulation, and reveal clinically exploitable evidence that anxiety mediates the relationship between nodal function of right mid-cingulate cortex and orthodontic pain.
Gene and Cell Therapy for Epilepsy: A Mini Review
Authors: Shaimardanova Alisa A. , Chulpanova Daria S. , Mullagulova Aysilu I. , Afawi Zaid , Gamirova Rimma G. , Solovyeva Valeriya V. , Rizvanov Albert A.
Published: May 2022

Epilepsy is a chronic non-infectious disease of the brain, characterized primarily by recurrent unprovoked seizures, defined as an episode of disturbance of motor, sensory, autonomic, or mental functions resulting from excessive neuronal discharge. Despite the advances in the treatment achieved with the use of antiepileptic drugs and other non-pharmacological therapies, about 30% of patients suffer from uncontrolled seizures. This review summarizes the currently available methods of gene and cell therapy for epilepsy and discusses the development of these approaches. Currently, gene therapy for epilepsy is predominantly adeno-associated virus (AAV)-mediated delivery of genes encoding neuro-modulatory peptides, neurotrophic factors, enzymes, and potassium channels. Cell therapy for epilepsy is represented by the transplantation of several types of cells such as mesenchymal stem cells (MSCs), bone marrow mononuclear cells, neural stem cells, and MSC-derived exosomes. Another approach is encapsulated cell biodelivery, which is the transplantation of genetically modified cells placed in capsules and secreting various therapeutic agents. The use of gene and cell therapy approaches can significantly improve the condition of patient with epilepsy. Therefore, preclinical, and clinical studies have been actively conducted in recent years to prove the benefits and safety of these strategies.
Influence of Canning and Storage on Physicochemical Properties, Antioxidant Properties, and Bioactive Compounds of Apricot (Prunus armeniaca L.) Wholes, Halves, and Pulp
Authors: Jan Nusrat , Anjum Sadaf , Wani Sajad Mohd , Mir Sajad Ahmad , Malik A. R. , Wani Sajad Ahmad , Hussein Dina S. , Rasheed Rabab Ahmed , Gatasheh Mansour K.
Published: May 2022

This study aimed to examine the effect of canning and storage on physicochemical, mineral, and antioxidant properties and phenolic composition of apricot wholes, halves, and pulp. The findings for physicochemical properties revealed that the total soluble solids, titratable acidity, total sugars, and ascorbic acid were found higher in apricot pulp (37.15, 1.39, and 20.74% and 7.21 mg/100 g FW, respectively) followed by apricot wholes and halves throughout the storage period. The remarkable contents of potassium, phosphorous, zinc, copper, iron, and manganese were found in the apricot pulp which revealed that canning and storage slightly affected the mineral composition. Bioactive substances were identified and quantified by reversed-phase high-performance liquid chromatography, which indicated a higher presence of chlorogenic acid (34.45 mg/kg FW), quercitin-3-glucoside (16.78 mg/kg FW), neochlorogenic acid (26.52 mg/kg FW), gallic acid (5.37 mg/kg FW), kaempferol (14.22 mg/kg FW), ellagic acid (6.02 mg/kg FW), procyanidin B2 (8.80 mg/kg FW), and epicatechin (9.87 mg/kg FW) in apricot pulp followed by apricot wholes and halves throughout the storage period. The total phenolic content was found highest in apricot pulp (13.76 GAE mg/100 g FW) followed by wholes (8.09 GAE mg/100 g FW) and halves (6.48 GAE mg/100 g FW) which decreased significantly throughout the storage period. Antioxidant properties were assessed by DPPH, ABTS+, MCA, and BCBA, which were found higher in the apricot pulp (92.23 TEAC μg/g DW, 92.33 TEAC μg/g DW, 33.80 TEAC μg/g DW, and 68.40 TEAC μg/g DW, respectively) that is correlated with the higher presence of bioactive compounds. Thus, apricot pulp containing excellent sources of nutrients, minerals, phytochemicals, and antioxidant components could be used for consumption purposes that provide nutraceuticals and antioxidants globally.
Assessing Insulin Sensitivity and Postprandial Triglyceridemic Response Phenotypes With a Mixed Macronutrient Tolerance Test
Authors: Newman John W. , Krishnan Sridevi , Borkowski Kamil , Adams Sean H. , Stephensen Charles B. , Keim Nancy L.
Published: May 2022

The use of meal challenge tests to assess postprandial responses in carbohydrate and fat metabolism is well established in clinical nutrition research. However, challenge meal compositions and protocols remain a variable. Here, we validated a mixed macronutrient tolerance test (MMTT), containing 56-g palm oil, 59-g sucrose, and 26-g egg white protein for the parallel determination of insulin sensitivity and postprandial triglyceridemia in clinically healthy subjects. The MMTT was administered in two study populations. In one, women with overweight/obese BMIs (n = 43) involved in an 8-week dietary intervention were administered oral glucose tolerance tests (OGTTs) and MMTTs within 2 days of each other after 0, 2, and 8 weeks of the dietary intervention. In the other, 340 men and women between 18 and 64 years of age, with BMI from 18–40 kg/m2, completed the MMTT as part of a broad nutritional phenotyping effort. Postprandial blood collected at 0, 0.5, 3, and 6 h was used to measure glucose, insulin, and clinical lipid panels. The MMTT postprandial insulin-dependent glucose disposal was evaluated by using the Matsuda Index algorithm and the 0- and 3 h blood insulin and glucose measures. The resulting MMTT insulin sensitivity index (ISIMMTT) was strongly correlated (r = 0.77, p < 0.001) with the OGTT-dependent 2 h composite Matsuda index (ISIComposite), being related by the following equation: Log (ISIComposite) = [0.8751 x Log(ISIMMTT)] –0.2115. An area under the triglyceride excursion curve >11.15 mg/mL h–1 calculated from the 0, 3, and 6 h blood draws established mild-to-moderate triglyceridemia in agreement with ∼20% greater prevalence of hypertriglyceridemia than fasting indications. We also demonstrated that the product of the 0 to 3 h and 3 to 6 h triglyceride rate of change as a function of the triglyceride incremental area under the curve optimally stratified subjects by postprandial response patterns. Notably, ∼2% of the population showed minimal triglyceride appearance by 6 h, while ∼25% had increasing triglycerides through 6 h. Ultimately, using three blood draws, the MMTT allowed for the simultaneous determination of insulin sensitivity and postprandial triglyceridemia in individuals without clinically diagnosed disease.

Clinical Trial Registration

[https://clinicaltrials.gov/], identifier [NCT02298725; NCT02367287].
Haematococcus pluvialis Microalgae Extract Inhibits Proliferation, Invasion, and Induces Apoptosis in Breast Cancer Cells
Authors: Alateyah Nouralhuda , Ahmad Salma M. S. , Gupta Ishita , Fouzat Arij , Thaher Mahmoud Ibrahim , Das Probir , Al Moustafa Ala-Eddin , Ouhtit Allal
Published: May 2022

Breast cancer (BC) is the most common malignant cancer in females worldwide. Drug resistance, toxicity, and the failure of current therapies to completely cure BC has challenged conventional medicine. Consequently, complementary alternative medicine has become popular due to its safety and efficacy. Haematococcus pluvialis (H. pulvialis) is a green microalga living in fresh water, and its crude extract is rich of bioactives, including carotenoids, known to inhibit cancer cell growth. In the present study, we investigated the effects of a methanol crude extract called “T1” of H. pulvialis on cell growth and migration/invasion of the BC cell line MDA-MB-231 in comparison to the fibroblast control cells. TI significantly suppressed BC cell growth, inhibited migration and invasion and induced apoptosis. Interestingly, apoptosis was mediated by a significant loss of mutant p53 protein, and increased Bax/Bcl2 ratio. Our findings support our hypothesis that T1 exerts its anti-cancer effects by inhibiting BC invasion and inducing apoptosis mediated, at least, via the p53/Bax/Bcl2 pathway. Ongoing experiments aim to identify the molecular mechanisms underpinning T1-inhibited BC cell invasion using pre-designed metastasis gene-based array method.
Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol
Authors: Li Fang , Han Yanhui , Wu Xian , Cao Xiaoqiong , Gao Zili , Sun Yue , Wang Minqi , Xiao Hang
Published: May 2022

Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the biotransformation of RES, as its metabolites may contribute profound biological effects. After 4-week oral administration, 11 metabolites of RES were identified and quantified in mice by HPLC-MS/MS, including dihydro-resveratrol (DHR), lunularin (LUN), and conjugates (sulfates and glucuronides) of RES, DHR and LUN. Importantly, DHR, LUN, and their conjugates were much more abundantly distributed in tissues, gastrointestinal tract (GIT), and biological fluids compared to RES and its conjugates. Moreover, we established that DHR and LUN were gut bacteria-derived metabolites of RES, as indicated by their depletion in antibiotic-treated mice. Furthermore, the biological activities of RES, DHR, and LUN were determined at physiologically relevant levels. DHR and LUN exhibited stronger anti-inflammatory and anti-cancer effects than RES at the concentrations found in mouse tissues. In summary, our study profiled the tissue distribution of the metabolites of RES after its oral administration in mice and uncovered the important role of gut microbial metabolites of RES in the biological activities of RES in vivo.
DeepLN: A Multi-Task AI Tool to Predict the Imaging Characteristics, Malignancy and Pathological Subtypes in CT-Detected Pulmonary Nodules
Authors: Wang Chengdi , Shao Jun , Xu Xiuyuan , Yi Le , Wang Gang , Bai Congchen , Guo Jixiang , He Yanqi , Zhang Lei , Yi Zhang , Li Weimin
Published: May 2022

Objectives

Distinction of malignant pulmonary nodules from the benign ones based on computed tomography (CT) images can be time-consuming but significant in routine clinical management. The advent of artificial intelligence (AI) has provided an opportunity to improve the accuracy of cancer risk prediction.

Methods

A total of 8950 detected pulmonary nodules with complete pathological results were retrospectively enrolled. The different radiological manifestations were identified mainly as various nodules densities and morphological features. Then, these nodules were classified into benign and malignant groups, both of which were subdivided into finer specific pathological types. Here, we proposed a deep convolutional neural network for the assessment of lung nodules named DeepLN to identify the radiological features and predict the pathologic subtypes of pulmonary nodules.

Results

In terms of density, the area under the receiver operating characteristic curves (AUCs) of DeepLN were 0.9707 (95% confidence interval, CI: 0.9645-0.9765), 0.7789 (95%CI: 0.7569-0.7995), and 0.8950 (95%CI: 0.8822-0.9088) for the pure-ground glass opacity (pGGO), mixed-ground glass opacity (mGGO) and solid nodules. As for the morphological features, the AUCs were 0.8347 (95%CI: 0.8193-0.8499) and 0.9074 (95%CI: 0.8834-0.9314) for spiculation and lung cavity respectively. For the identification of malignant nodules, our DeepLN algorithm achieved an AUC of 0.8503 (95%CI: 0.8319-0.8681) in the test set. Pertaining to predicting the pathological subtypes in the test set, the multi-task AUCs were 0.8841 (95%CI: 0.8567-0.9083) for benign tumors, 0.8265 (95%CI: 0.8004-0.8499) for inflammation, and 0.8022 (95%CI: 0.7616-0.8445) for other benign ones, while AUCs were 0.8675 (95%CI: 0.8525-0.8813) for lung adenocarcinoma (LUAD), 0.8792 (95%CI: 0.8640-0.8950) for squamous cell carcinoma (LUSC), 0.7404 (95%CI: 0.7031-0.7782) for other malignant ones respectively in the malignant group.

Conclusions

The DeepLN based on deep learning algorithm represented a competitive performance to predict the imaging characteristics, malignancy and pathologic subtypes on the basis of non-invasive CT images, and thus had great possibility to be utilized in the routine clinical workflow.
Beyond Clinical Trials in Patients With Multiple Myeloma: A Critical Review of Real-World Results
Authors: Bertamini Luca , Bertuglia Giuseppe , Oliva Stefania
Published: May 2022

The current strategies for the treatment of multiple myeloma (MM) have improved, thanks to effective drug classes and combination therapies, for both the upfront and relapsed settings. Clinical trials for newly diagnosed transplant-ineligible patients led to the approval of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) in combination with anti-CD38 monoclonal antibodies (mAbs), to be administered during the induction phase before transplantation and during maintenance treatment, with lenalidomide recommended until relapse. In relapsed/refractory patients, the complex treatment scenario currently includes several options, such as triplets with anti-CD38 mAbs plus IMiDs or PIs, and novel targeted molecules. Comparisons among clinical trials and real-world data showed a good degree of reproducibility of some important results, particularly in terms of overall response rate, progression-free survival, and overall survival. This may help clinicians towards a proper selection of the best treatment options, particularly in real-world settings. However, as compared with the management of real-world settings, clinical trials have some pitfalls in terms of outcome and especially in terms of safety and quality of life. In fact, trials include younger and presumably healthier patients, excluding those with worst clinical conditions due to MM features (e.g., renal insufficiency or bone disease, which can impair the performance status) and comorbidities (e.g., cardiac and pulmonary disease), thus resulting in a possible lack of representativeness of data about the patients enrolled. In this review, we analyze comparable and discrepant results from clinical trials vs. real-world settings published in the last 10 years, focusing on different drugs and combinations for the treatment of MM and providing an overview of treatment choices.
Effects of Oxaliplatin on Facial Sensitivity to Cool Temperatures and TRPM8 Expressing Trigeminal Ganglion Neurons in Mice
Authors: Caudle Robert M. , Neubert John K.
Published: May 2022

The chemotherapeutic agent oxaliplatin is commonly used to treat colorectal cancer. Although effective as a chemotherapeutic, it frequently produces painful peripheral neuropathies. These neuropathies can be divided into an acute sensitivity to cool temperatures in the mouth and face, and chronic neuropathic pain in the limbs and possible numbness. The chronic neuropathy also includes sensitivity to cool temperatures. Neurons that detect cool temperatures are reported to utilize Transient Receptor Potential Cation Channel, Subfamily M, Member 8 (TRPM8). Therefore, we investigated the effects of oxaliplatin on facial nociception to cool temperatures (18°C) in mice and on TRPM8 expressing trigeminal ganglion (TRG) neurons. Paclitaxel, a chemotherapeutic that is used to treat breast cancer, was included for comparison because it produces neuropathies, but acute cool temperature sensitivity in the oral cavity or face is not typically reported. Behavioral testing of facial sensitivity to 18°C indicated no hypersensitivity either acutely or chronically following either chemotherapeutic agent. However, whole cell voltage clamp experiments in TRPM8 expressing TRG neurons indicated that both oxaliplatin and paclitaxel increased Hyperpolarization-Activated Cyclic Nucleotide-Gated channel (HCN), voltage gated sodium channel (Nav), and menthol evoked TRPM8 currents. Voltage gated potassium channel (Kv) currents were not altered. Histological examination of TRPM8 fibers in the skin of the whisker pads demonstrated that the TRPM8 expressing axons and possible Merkel cell-neurite complexes were damaged by oxaliplatin. These findings indicate that oxaliplatin induces a rapid degeneration of TRG neuron axons that express TRPM8, which prevents evoked activation of the sensitized neurons and likely leads to reduced sensitivity to touch and cool temperatures. The changes in HCN, Nav, and TRPM8 currents suggest that spontaneous firing of action potentials may be increased in the deafferented neurons within the ganglion, possibly producing spontaneously induced cooling or nociceptive sensations.
Toward Composite Pain Biomarkers of Neuropathic Pain—Focus on Peripheral Neuropathic Pain
Authors: Diaz Monica M. , Caylor Jacob , Strigo Irina , Lerman Imanuel , Henry Brook , Lopez Eduardo , Wallace Mark S. , Ellis Ronald J. , Simmons Alan N. , Keltner John R.
Published: May 2022

Chronic pain affects ~10–20% of the U.S. population with an estimated annual cost of $600 billion, the most significant economic cost of any disease to-date. Neuropathic pain is a type of chronic pain that is particularly difficult to manage and leads to significant disability and poor quality of life. Pain biomarkers offer the possibility to develop objective pain-related indicators that may help diagnose, treat, and improve the understanding of neuropathic pain pathophysiology. We review neuropathic pain mechanisms related to opiates, inflammation, and endocannabinoids with the objective of identifying composite biomarkers of neuropathic pain. In the literature, pain biomarkers typically are divided into physiological non-imaging pain biomarkers and brain imaging pain biomarkers. We review both types of biomarker types with the goal of identifying composite pain biomarkers that may improve recognition and treatment of neuropathic pain.
Potential Treat-to-Target Approach for Methamphetamine Use Disorder: A Pilot Study of Adenosine 2A Receptor Antagonist With Positron Emission Tomography
Authors: Okita Kyoji , Matsumoto Toshihiko , Funada Daisuke , Murakami Maki , Kato Koichi , Shigemoto Yoko , Sato Noriko , Matsuda Hiroshi
Published: May 2022

Introduction: The misuse of stimulant drugs such as methamphetamine is a global public health issue. One important neurochemical mechanism of methamphetamine use disorder may be altered dopaminergic neurotransmission. For instance, previous studies using positron emission tomography (PET) have consistently shown that striatal dopamine D2-type receptor availability (quantified as binding potential; BPND) is lower in methamphetamine use disorder. Further, methamphetamine use is known to induce chronic neuroinflammation through multiple physiological pathways. Upregulation of D2-type receptor and/or attenuation of neuroinflammation may therefore provide a therapeutic effect for this disorder. In vitro studies have shown that blockage of adenosine 2A (A2A) receptors may prevent D2-receptor downregulation and neuroinflammation-related brain damage. However, no study has examined this hypothesis yet.

Methods and Analysis: Using a within-subject design, this trial will assess the effect of the selective A2A receptor antagonist, istradefylline, primarily on D2-type BPND in the striatum, and secondarily on neuroinflammation in the whole brain in individuals with methamphetamine use disorder. The research hypotheses are that istradefylline will increase striatal D2-type BPND and attenuate neuroinflammation. Twenty participants with methamphetamine use disorder, aged 20–65, will be recruited to undergo [11C]raclopride PET (for every participant) and [11C]DAA1106 PET (if applicable) once before and once after administration of 40 mg/day istradefylline for 2 weeks. Neuropsychological measurements will be performed on the same days of the PET scans.
Ab Initio Wavefunction Analysis of Electron Removal Quasi-Particle State of NdNiO2 With Fully Correlated Quantum Chemical Methods
Authors: Katukuri Vamshi M. , Bogdanov Nikolay A. , Alavi Ali
Published: May 2022

The discovery of superconductivity in hole-doped infinite-layer NdNiO2 — a transition metal (TM) oxide that is both isostructural and isoelectronic to cuprate superconductors—has lead to renewed enthusiasm in the hope of understanding the origin of unconventional superconductivity. Here, we investigate the electron-removal states in infinite-layered Ni1+ oxide, NdNiO2, which mimics hole doping, with the state-of-the-art many-body multireference quantum chemistry methods. From the analysis of the many-body wavefunction we find that the hole-doped d8 ground state of NdNiO2 is very different from the d8 ground state in isostructural cuprate analog CaCuO2, although the parent d9 ground states are for the most part identical. We show that the doped hole in NdNiO2 mainly localizes on the Ni 3dx2−y2 orbital to form a closed-shell singlet, and this singlet configuration contributes to ∼40% of the wavefunction. In contrast, in CaCuO2 the Zhang-Rice singlet configurations contribute to ∼65% of the wavefunction. With the help of the quantum information concept of entanglement entropy, we quantify the different types of electronic correlations in the nickelate and cuprate compounds, and find that the dynamic radial-type correlations within the Ni d manifold are persistent in hole-doped NdNiO2. As a result, the d8 multiplet effects are stronger and the additional hole foot-print is more three-dimensional in NdNiO2. Our analysis shows that the most commonly used three-band Hubbard model employed to express the doped scenario in cuprates represents ∼90% of the d8 wavefunction for CaCuO2, but such a model grossly approximates the d8 wavefunction for NdNiO2 as it only stands for ∼60% of the wavefunction.
A Note on Resistance Distances of Graphs
Authors: Sun Wensheng , Yang Yujun
Published: May 2022

Let G be a connected graph with vertex set V(G). The resistance distance between any two vertices u, v ∈ V(G) is the net effective resistance between them in the electric network constructed from G by replacing each edge with a unit resistor. Let S ⊂ V(G) be a set of vertices such that all the vertices in S have the same neighborhood in G − S, and let G[S] be the subgraph induced by S. In this note, by the {1}-inverse of the Laplacian matrix of G, formula for resistance distances between vertices in S is obtained. It turns out that resistance distances between vertices in S could be given in terms of elements in the inverse matrix of an auxiliary matrix of the Laplacian matrix of G[S], which derives the reduction principle obtained in [J. Phys. A: Math. Theor. 41 (2008) 445203] by algebraic method.
Social Perception Deficit as a Factor of Vulnerability to Psychosis: A Brief Proposal for a Definition
Authors: Cavieres Álvaro , López-Silva Pablo
Published: May 2022

Disturbances in social cognition are a core feature of schizophrenia. While most research in the field has focused on emotion perception, social knowledge, theory of mind, and attribution styles, the domain of social perception has received little specific attention. In this paper, we suggest that this issue can be explained by the lack of a precise and unitary definition of the concept, this leads to the existence of different competing uses of the concept and their conflation with other domains of social cognition. Relying on resources coming from the ecological approach to psychology and the phenomenological tradition in psychiatry, we propose that the concept of Social Perception should be used to refer to low-level pre-reflective processes underlying the awareness of interpersonal interactions with and between others. Clinical data suggests that people with schizophrenia have problems perceiving social situations as opportunities for social engagement, so, in order to fulfil this explanatory need, we propose that the term should be used to capture this important—yet neglected—domain of social cognition. We conclude with the discussion of some future directions for research derived from our proposal.
Artificial Intelligence-Based Family Health Education Public Service System
Authors: Zhao Jingyi , Fu Guifang
Published: May 2022

Family health education is a must for every family, so that children can be taught how to protect their own health. However, in this era of artificial intelligence, many technical operations based on artificial intelligence are born, so the purpose of this study is to apply artificial intelligence technology to family health education. This paper proposes a fusion of artificial intelligence and IoT technologies. Based on the characteristics of artificial intelligence technology, it combines ZigBee technology and RFID technology in the Internet of Things technology to design an artificial intelligence-based service system. Then it designs the theme of family health education by conducting a questionnaire on students’ family education and analyzing the results of the questionnaire. And it designs database and performance analysis experiments to improve the artificial intelligence-based family health education public service system designed in this paper. Finally, a comparative experiment between the family health education public service system based on artificial intelligence and the traditional health education method will be carried out. The experimental results show that the family health education public service system based on artificial intelligence has improved by 21.74% compared with the traditional family health education method; compared with the traditional family health education method, the health education effect of the family health education public service system based on artificial intelligence has increased by 13.89%.