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Aims Methods Results Conclusions Hydroxychloroquine (HCQ) is recommended for the long‐term treatment of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Given the complex process of HCQ metabolism and individual physiological differences, the metabolic profile of HCQ after long‐term administration is unknown. This study aimed to establish a population pharmacokinetic model for long‐term HCQ treatment in patients with rheumatic diseases and to identify the factors influencing HCQ metabolism.This study included 274 HCQ whole‐blood trough concentration data points from 203 patients with rheumatic diseases, all of whom had taken HCQ for more than 6 months, with a median duration of 36 months. A nonlinear mixed‐effects model was derived to establish a population pharmacokinetic model, and potential influencing factors were investigated. Different covariates were used to simulate the optimal dose.The final model describing the HCQ blood concentration–time profile was a compartmental model with first‐order absorption. The estimated values for apparent clearance and volume of distribution were 16.4 L/h and 1220 L, respectively. The clearance of HCQ gradually increased with increasing dosing regimens and weight gain. Monte Carlo simulations were used to determine the optimal dosage regimens for patients with different body weights and drug durations. The simulation results revealed that an initial dose of 5 mg/kg was appropriate.We developed a population pharmacokinetic model for long‐term HCQ therapy in patients with rheumatic diseases. HCQ clearance from whole blood increased progressively with increasing duration of drug administration. [ABSTRACT FROM AUTHOR]

Labeled hyperspectral image (HSI) information is commonly difficult to acquire, so the lack of valid labeled data becomes a major puzzle for HSI classification. Semi-supervised methods can efficiently exploit unlabeled and labeled data for classification, which is highly valuable. Graph-based semi-supervised methods only focus on HSI local or global data and cannot fully utilize spatial–spectral information; this significantly limits the performance of classification models. To solve this problem, we propose an adaptive global–local feature fusion (AGLFF) method. First, the global high-order and local graphs are adaptively fused, and their weight parameters are automatically learned in an adaptive manner to extract the consistency features. The class probability structure is then used to express the relationship between the fused feature and the categories and to calculate their corresponding pseudo-labels. Finally, the fused features are imported into the broad learning system as weights, and the broad expansion of the fused features is performed with the weighted broad network to calculate the model output weights. Experimental results from three datasets demonstrate that AGLFF outperforms other methods. [ABSTRACT FROM AUTHOR]

Background: Chronic neck pain (CNP) is a common public health problem that affects daily living activities and quality of life. There is biomechanical interdependence between the neck and scapula. Studies have shown that shoulder blade function might be related to chronic neck pain. We therefore evaluated the effects of scapular targeted therapy on neck pain and function in patients with CNP. Methods: Databases, including MEDLINE (via PubMed), EMBASE (via Ovid), Ovid, Web of Science, and Scopus, were systematically searched for randomized controlled trials published in English investigating treatment of the scapula for CNP before July 16, 2023. Results: A total of 313 participants were included from 8 RCTs. Compared with those in the control group, the intervention in the scapular treatment group exhibited greater improvement in pain intensity (standardized mean difference (SMD) = 2.55; 95% CI = 0.97 to 4.13; P = 0.002), with moderate evidence. Subgroup analysis for pain intensity revealed a significant difference between the sexes, with only the female population (SMD = 6.23, 95% CI = 4.80 to 7.65) showing better outcomes than those with both sexes (SMD = 1.07, 95% CI = 0.57 to 1.56) (p < 0.00001). However, moderate evidence demonstrated no improvement in neck disability after scapular treatment (SMD of 0.24[-0.14, 0.62] of Neck Disability Index or Northwick Park Neck Pain Questionnaire). No effect of scapular treatment was shown on the pressure pain threshold (PPT). The cervical range of motion (CROM) and electromyographic activity of neck muscles could not be conclusively evaluated due to limited support in the articles, and further study was needed. However, the patient's head forward posture appeared to be corrected after scapular treatment. Conclusion: Scapular therapy was beneficial for relieving pain intensity in patients with CNP, especially in women. Head forward posture might also be corrected with scapular therapy. However, scapular therapy may have no effect on the PPT or neck disability. However, whether scapular therapy could improve CROM and cervical muscle activation in patients with CNPs had not been determined and needed further study. [ABSTRACT FROM AUTHOR]

Background: Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in patients with temporal lobe epilepsy (TLE). However, alterations in the topological properties of the WM structural network in patients with TLE remain unclear. Graph theoretical analysis provides a new perspective for evaluating the connectivity of WM structural networks. Methods: DTI was used to map the structural networks of 18 patients with TLE (10 males and 8 females) and 29 (17 males and 12 females) age‐ and gender‐matched normal controls (NC). Graph theory was used to analyze the whole‐brain networks and their topological properties between the two groups. Finally, partial correlation analyses were performed on the weighted network properties and clinical characteristics, namely, duration of epilepsy, verbal intelligence quotient (IQ), and performance IQ. Results: Patients with TLE exhibited reduced global efficiency and increased characteristic path length. A total of 31 regions with nodal efficiency alterations were detected in the fractional anisotropy_ weighted network of the patients. Communication hubs, such as the middle temporal gyrus, right inferior temporal gyrus, left calcarine, and right superior parietal gyrus, were also differently distributed in the patients compared with the NC. Several node regions showed close relationships with duration of epilepsy, verbal IQ, and performance IQ. Conclusions: Our results demonstrate the disruption of the WM structural network in TLE patients. This study may contribute to the further understanding of the pathological mechanism of TLE. [ABSTRACT FROM AUTHOR]

Simple Summary: Cytokines are small molecules that modify the response of the human body to external signals. Tumor Necrosis Factor was found in 1975 and its main activity was assumed to be lethal for cancer cells and to be able to kill tumors, hence the name. Research over the last 35 years has shown that this is not really the case. This review illuminates what caused this misunderstanding and answers the question if there is any connection at all between the cytokine Tumor Necrosis Factor and cancer. Tumor Necrosis Factor was one of the first cytokines described in the literature as a soluble mediator of cytotoxicity to tumors. Over the years, more extensive research that tried to employ Tumor Necrosis Factor in cancer treatments showed nevertheless that it mainly functioned as a proinflammatory cytokine. However, this did not stop the search for the holy grail of cancer research: A cytokine that could act as a one-stop treatment for solid tumors and lymphomas. This review will summarize the long experimental history of Tumor Necrosis Factor that caused the initial observations of a tumor necrotizing cytokine that could serve as a potential cancer treatment and discuss the current state of research into this side of the activities of Tumor Necrosis Factor. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) has become a major worldwide public health concern, given its global prevalence. It has clear links with multiple comorbidities and mortality. Cognitive impairment is one related comorbidity causing great pressure on individuals and society. The clinical manifestations of cognitive impairment in OSAS include decline in attention/vigilance, verbal–visual memory loss, visuospatial/structural ability impairment, and executive dysfunction. It has been proven that chronic intermittent hypoxia (CIH) may be a main cause of cognitive impairment in OSAS. Inflammation plays important roles in CIH-induced cognitive dysfunction. Furthermore, the nuclear factor kappa B and hypoxia-inducible factor 1 alpha pathways play significant roles in this inflammatory mechanism. Continuous positive airway pressure is an effective therapy for OSAS; however, its effect on cognitive impairment is suboptimal. Therefore, in this review, we address the role inflammation plays in the development of neuro-impairment in OSAS and the association between OSAS and cognitive impairment to provide an overview of its pathophysiology. We believe that furthering the understanding of the inflammatory mechanisms involved in OSAS-associated cognitive impairment could lead to the development of appropriate and effective therapy. [ABSTRACT FROM AUTHOR]

Antibiosis and resource competition are major drivers shaping the assembly, diversity and functioning of microbial communities. While it is recognized that competition is sensitive to environmental conditions, it is unclear to what extent this mediated by the availability of different carbon resources.Here, we used a model laboratory system to directly test this by exploring how carbon resource richness and identity shape resource competition and antibiosis between plant probiotic Bacillus amyloliquefaciens and phytopathogenic Ralstonia solanacearum bacteria. We found that while sugars typically promoted B. amyloliquefaciens growth, organic and amino acids increased the production of both bacillaene and macrolactin antibiotics and the direct inhibition of R. solanacearum. In contrast, when multiple different carbon resources were available, B. amyloliquefaciens could efficiently grow and produce antibiotics at the same time.Together, these results suggest that high carbon resource richness allows concurrent expression of growth‐ and antibiosis‐related traits, potentially altering bacterial competitive dynamics and plant growth promotion in microbial communities. A plain language summary is available for this article. [ABSTRACT FROM AUTHOR]

A green and convenient anhydrous method was developed to synthesize hydrophilic carbon dots (H-CDs) on large-scale in this work. During the whole process of preparation, toxicity materials and high pressure conditions were not used, and H-CDs can be formed in several minutes by directly putting glucose powder into hot edible oil, which can be used again. Therefore, it is a green method and very suitable for the industrial preparation of CDs on large-scale. Characterizations demonstrate the H-CDs possess excellent optical properties, higher photostability and very low cytotoxicty. Noticeably, the H-CDs exhibit a distinct pH-sensitive feature, and have been used to construct fluorescent pH sensor with a nice linear relationship in the pH range of 3.0–13.0. To the best of our knowledge, this is the broadest reported pH range based on carbon dots without heteroatom doped. The mechanism of pH-sensitive response was also discussed. The proposed pH sensor has been successfully used for the pH monitoring of environmental water samples and living cells, which demonstrates their applicability in complex matrixes. [ABSTRACT FROM AUTHOR]

Rationale: With the development of various imaging techniques, the deformation-based morphometry (DBM) method provides an objective automatic examination of the whole brain. Objectives: This study aims to assess the abnormalities in the brains of first-episode schizophrenia (FES) patients treated with quetiapine using another advanced nonrigid registration method, hierarchical attribute matching mechanism for elastic registration, through the application of DBM in the entire brain. Methods: Thirty FES patients and 30 normal controls were grouped by age and handedness and subjected to magnetic resonance imaging examination. The patients had relatively short durations of untreated psychosis (DUP; 6.4 ± 5.2 months), and only a single antipsychotic drug, quetiapine (dosage, 200 ± 75 mg), was used for treatment. Statistically significant changes in regional volume were analyzed via DBM. In addition, a voxel-wise analysis of correlations between the duration of treatment or dosage and volume was also performed. Results: Compared with control subjects, FES patients showed contracted regions located in Brodmann area (BA) 42 and BA 19. By contrast, expanded regions were observed in BA 38, BA 21, BA 6 and 8, and left cerebellum. A negative correlation was observed between dosage and volume in the hippocampus, while a positive correlation was found in the caudate. Meanwhile, a negative correlation was observed between duration of treatment and volume in BA 38. Conclusion: Both regional volume reductions and increases were detected in the brains of FES patients treated with quetiapine compared with healthy control subjects. Such differences may be partially relevant to dosage and treatment duration in clinic. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chitosan inhibited the growth of bacterial pathogen A. avenae subsp. avenae. [•] Antibacterial effect of chitosan depends on its concentration and incubation time. [•] Chitosan destroyed cell membrane, reduced biofilm and changed genes expression. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND AND PURPOSE This study aims to investigate the regional changes in the early onset of blindness using the deformation-based morphometry (DBM) method. METHODS A total of 15 early blindness and 30 gender- and age-matched sighted control subjects were recruited for the study. Statistically significant changes in regional volume were analyzed using DBM through HAMMER registration. Using this technique, changes in regional tissue volume can be detected on the basis of the deformation field derived from the warping subject to the template image. A voxelwise estimation of the morphological differences between the two groups can be acquired after applying a threshold ( P < .001, uncorrected) to the statistic maps. RESULTS Regions with enlarged volume in the brains of blind subjects are mainly localized in the left associated visual cortex, posterior cingulated cortex, and cerebellum, whereas volume reductions are primarily localized in the left early visual cortex. CONCLUSIONS DBM is an effective method for detecting entire brain structural changes in blindness. Visual deprivation actually alters the local structural organization during the early critical periods of neurodevelopment. Volume increases outside the occipital lobe detected with DBM may suggest compensatory adaptations. [ABSTRACT FROM AUTHOR]

Abstract: Root colonization by Bacillus amyloliquefaciens is directly related to bacterial growth, chemotaxis, biofilm formation, and the interaction with host plant root exudates. In this study, root exudates were collected from two tomato plant varieties that supported bacterial cell division and induced the B. amyloliquefaciens T-5 chemotactic response, even at the concentration of 10μgml−1. Root exudates also induced biofilm formation, but lower than control treatment. In addition, five organic acids were identified in the root exudates and subsequently evaluated. Malic acid, citric acid, succinic acid and fumaric acid significantly induced the chemotaxis response and swarming motility. Maximal chemotactic response and swarming motility were induced by malic acid, and all the organic acid did not have a significant effect on biofilm formation. Furthermore, these organic acids promoted the B. amyloliquefaciens T-5 recruitment under gnotobiotic conditions, increasing the rhizosphere bacterial population. This data suggested that tomato root colonization by B. amyloliquefaciens T-5 was influenced by organic acids secreted by roots. This study expands our understanding of B. amyloliquefaciens T-5 colonization on tomato roots under natural conditions and reflects the significance of B. amyloliquefaciens T-5 strain as biocontrol agent which will be useful for preparing formulations for the better control of plant wilt diseases. [Copyright &y& Elsevier]

Abstract: Constitutive activation of Notch signaling was found in melanoma cells. Using siRNA specifically knocking down Notch co-activator MAML1 blocked Notch down stream transcriptional repressor Hey1 expression, significantly upregulated TweakR and CCL2 mRNA and protein expression in melanoma cell line M624. Exogenous Tweak stimulated high level CCL2 production in siMAML transfected M624 cells, which was critically dependent on Tweak–TweakR ligation. CCL2 produced by siMAML1 transfected M624 stimulated with exogenous Tweak was functional chemoattractant to activated monocytes. This study supports targeting Notch signaling using small siRNA in melanoma cells may increase immune cell recruitment and restore natural immune surveillance in tumor microenvironment. [Copyright &y& Elsevier]

In patients with Alzheimer's Disease (AD), the hippocampal network has been extensively investigated in previous studies; however, little is known about the morphological network associated with the hippocampus in the AD patients. A total of 68 patients with AD and another 68 gender and age matched healthy subjects were studied. Individual-level morphological hippocampal networks were constructed based on volume and texture features extracted from MRI to study the connections between bilateral hippocampus and 11 other subcortical gray matter structures. The relationship between morphological connections and Mini-Mental State Examination (MMSE) scores was also studied. Connections between bilateral hippocampus and bilateral thalamus, bilateral putamen were significant differences between the AD patients and controls (p < 0.05). There were significantly different in bilateral hippocampal connectivity, and for the left hippocampus, the connection to the right caudate were found to be statistically significant. The morphological connections between left hippocampus and bilateral thalamus (left: R = 0.371, p < 0.001; right: R = 0.411, p < 0.001), bilateral putamen (left: R = 0.383, p < 0.001; right: R = 0.348, p < 0.001), right hippocampus and bilateral thalamus (left: R = 0.370, p < 0.001; right: R = 0.387, p < 0.001), left putamen (R = 0.377, p < 0.001) were significantly positively correlated with the MMSE scores. Similar patterns were observed for left and right hippocampal connectivity and the connections highly associated with MMSE scores were also within the abnormal connections in AD patients. [ABSTRACT FROM AUTHOR]

• EasyMEG toolbox based on FieldTrip was developed. • Compared to the existing tools for MEG data analysis, EasyMEG provides a friendly GUI and allows users to complete analyses through a simple and clean interface. • EasyMEG is a highly integrated software that contains a set of functions for preprocessing, time-lock analysis, time–frequency analysis, source analysis, and plotting. • This toolbox has been released as an open-source software on GitHub under the GNU General Public License: https://tonywu2018.github.io/EasyMEG/. Magnetoencephalography (MEG) is an advanced magnetic source imaging technology that measures the magnetic fields produced by neural activities. It has been extensively used in scientific research and clinical diagnosis due to its high temporal and spatial resolution. Considering the special nature of MEG data, it needs to perform a series of processes and analysis to obtain valuable information. Therefore, the identification of data processing is a key point of MEG studies. At present, the software for MEG analysis such as FieldTrip has no Graphic User Interface (GUI) and users must write their own script to perform concrete analysis. It brings the difficulties to researchers like the doctors without experience in programming or newcomers to MEG. Thus, an open-sourced software-EasyMEG was developed. It has friendly interface with highly functions-integration. The functions of EasyMEG are developed based on MATLAB language to ensure the consistency of the user interface under different operating systems. EasyMEG is a highly integrated software that contains a set of functions for preprocessing, time-lock analysis, time–frequency analysis, source analysis, and plotting. EasyMEG provides a friendly GUI and allows users to complete analyses through a simple and clean interface. This toolbox has been released as an open-source software on GitHub under the GNU General Public License: https://tonywu2018.github.io/EasyMEG/. We hope to improve this toolbox by the power of community and wish to make EasyMEG a simple and powerful toolbox for further MEG studies. [ABSTRACT FROM AUTHOR]

Purpose: This study used the graph-theory approach, degree centrality (DC) to analyze whole-brain functional networks at the voxel level in children with ASD, and investigated whether DC changes were correlated with any clinical variables in ASD children. Methods: The current study included 86 children with ASD and 54 matched healthy subjects Aged 2– 5.5 years. Next, chloral hydrate induced sleeping-state functional magnetic resonance imaging (ss-fMRI) datasets were acquired from these ASD and healthy subjects. For a given voxel, the DC was calculated by calculating the number of functional connections with significantly positive correlations at the individual level. Group differences were tested using two-sample t-tests (p < 0.01, AlphaSim corrected). Finally, relationships between abnormal DCs and clinical variables were investigated via Pearson's correlation analysis. Results: Children with ASD exhibited low DC values in the right middle frontal gyrus (MFG) (p < 0.01, AlphaSim corrected). Furthermore, significantly negative correlations were established between the decreased average DC values within the right MFG in ASD children and the total ABC scores, as well as with two ABC subscales measuring highly relevant impairments in ASD (ie, stereotypes and object-use behaviors and difficulties in language). Conclusion: Taken together, the results of our ss-fMRI study suggest that abnormal DC may represent an important contribution to elucidation of the neuropathophysiological mechanisms of preschoolers with ASD. [ABSTRACT FROM AUTHOR]

Background: Optic cup is an important structure in ophthalmologic diagnosis such as glaucoma. Automatic optic cup segmentation is also a key issue in computer aided diagnosis based on digital fundus image. However, current methods didn't effectively solve the problem of edge blurring caused by blood vessels around the optic cup.Methods: In this study, an improved Bertalmio-Sapiro-Caselles-Ballester (BSCB) model was proposed to eliminate the noising induced by blood vessel. First, morphological operations were performed to get the enhanced green channel image. Then blood vessels were extracted and filled by improved BSCB model. Finally, Local Chart-Vest model was used to segment the optic cup. A total of 94 samples which included 32 glaucoma fundus images and 62 normal fundus images were experimented.Results: The evaluation parameters of F-score and the boundary distance achieved by the proposed method against the results from experts were 0.7955 ± 0.0724 and 11.42 ± 3.61, respectively. Average vertical optic cup-to-disc ratio values of the normal and glaucoma samples achieved by the proposed method were 0.4369 ± 0.1193 and 0.7156 ± 0.0698, which were also close to those by experts. In addition, 39 glaucoma images from the public dataset RIM-ONE were also used for methodology evaluation.Conclusions: The results showed that our proposed method could overcome the influence of blood vessels in some degree and was competitive to other current optic cup segmentation algorithms. This novel methodology will be expected to use in clinic in the field of glaucoma early detection. [ABSTRACT FROM AUTHOR]

In evidence theory, Dempster's rule of combination is the most commonly applied method to aggregate bodies of evidence obtained from different sources to make a decision. However, when multiple independent bodies of evidence with conflict are aggregated by Dempster's rule of combination, the counterintuitive results can be generated. Evidence discounting is proved to be an efficient way to eliminate the counterintuitive combination results. Following the discounting ideas, a new combination approach based on fuzzy discounting is put forward. Both the conflict between bodies of evidence and the uncertainty of a body of evidence itself are taken into account to determine the discounting factors. Jousselme's evidence distance is used to represent conflict between bodies of evidence, and discriminability measure is defined to represent uncertainty of a body of evidence itself. Consider that both the evidence distance and the discriminability measure are semantically fuzzy. Thus, fuzzy membership functions are defined to describe both of them, and a fuzzy reasoning rule base is constructed to derive the discounting factors. Numerical examples indicate that this new combination approach proposed can achieve fast convergence speed and is robust to disturbing evidences, i.e., it is an effective method to process conflicting evidences combination. [ABSTRACT FROM AUTHOR]

What is Known and Objective. Voriconazole (VRC) increases the blood concentration of Tacrolimus (TAC). However, the patterns of changes in TAC trough concentration (TAC C0) and dose-adjustment regimens after VRC discontinuation have not been reported. We aimed to explore the changing pattern of TAC C0 after VRC discontinuation and provide strategies for TAC dose adjustment and blood concentration monitoring in renal transplant recipients. Methods. The clinical data of 46 renal transplant patients pre- and during VRC medication and VRC discontinuation were retrospectively recorded, including doses and concentrations 0 of TAC and VRC; biochemical indicators such as liver and kidney function; and CYP3A5, CYP3A4, and CYP2C19 gene types. Results and Discussion. After discontinuing VRC for 2–4 days, 81% of the patients returned to their initial TAC dose, although TAC C0 and TAC dose-adjusted trough concentration (C/D) were 2.43-fold and 3.35-fold higher, respectively, than pre-VRC administration. After 5–7 days, TAC C0 and C/D gradually recovered. TAC C/D was significantly higher after VRC discontinuation when the VRC trough concentration (VRC C0) was greater than 2.43 mg/L; CYP3A5, CYP3A4, and CYP2C19 genotypes and the administration of erythromycin did not affect the change in TAC C/D. What is New and Conclusion. TAC C/D remains elevated 2–4 days after discontinuing VRC compared to pre-VRC administration, with gradual recovery observed 5–7 days after VRC discontinuation. To avoid excessive blood TAC C0 , the initial TAC dose should not be immediately reinstated upon VRC discontinuation for 2–4 days. VRC C0 are a critical factor influencing the change in TAC C/D ratio after VRC discontinuation. [ABSTRACT FROM AUTHOR]

Investigation of the properties and mechanisms of the interactions of root-colonizing biocontrol bacteria and plant pathogens is necessary to optimize the biocontrol strategies. In the present study, the interaction of a biocontrol strain Bacillus amyloliquefaciens T-5 tagged with a green fluorescent protein marker and a bacterial wilt pathogen Ralstonia solanacearum QL- Rs1115 tagged with red fluorescent protein marker was studied on tomato roots using different inoculation methods. The results showed that in the co-culture experiment, the population of pathogen QL-RFP was decreased by increasing the initial inoculum concentration of biocontrol strain. In the greenhouse experiment, both strains T-5-GFP and QL-RFP colonized tomato roots (root tips, root hairs, primary roots, and root junctions) and formed a biofilm on the root surfaces as determined by dilution plating and confocal laser scanning microscopy (CLSM) techniques. However, the root colonization of pathogen strain QL-RFP was almost completely suppressed in the presence of biocontrol strain T-5-GFP when both soil and plant seedlings were treated with T-5-GFP. The results of this study revealed the effectiveness of strain B. amyloliquefaciens T-5 as a biocontrol agent against tomato wilt pathogen and the significance of inoculation method used to inoculate biocontrol strain. [ABSTRACT FROM AUTHOR]

Background and Purpose: Understanding the pathogenesis of temporal lobe epilepsy (TLE) is essential for its diagnosis and treatment. The study aimed to explore regional homogeneity (ReHo) and changes in effective connectivity (EC) between brain regions in TLE patients, hoping to discover potential abnormalities in certain brain regions in TLE patients. Methods: Resting‐state functional magnetic resonance data were collected from 23 TLE patients and 32 normal controls (NC). ReHo was used as a feature of multivariate pattern analysis (MVPA) to explore the ability of its alterations in identifying TLE. Based on the results of the MVPA, certain brain regions were selected as seed points to further explore alterations in EC between brain regions using Granger causality analysis. Results: MVPA results showed that the classification accuracy for the TLE and NC groups was 87.27%, and the right posterior cerebellum lobe, right lingual gyrus (LING_R), right cuneus (CUN_R), and left superior temporal gyrus (STG_L) provided significant contributions. Moreover, the EC from STG_L to right fusiform gyrus (FFG_R) and LING_R and the EC from CUN_R to the right occipital superior gyrus (SOG_R) and right occipital middle gyrus (MOG_R) were altered compared to the NC group. Conclusion: The MVPA results indicated that ReHo abnormalities in brain regions may be an important feature in the identification of TLE. The enhanced EC from STG_L to FFG_R and LING_R indicates a shift in language processing to the right hemisphere, and the weakened EC from SOG_R and MOG_R to CUN_R may reveal an underlying mechanism of TLE. [ABSTRACT FROM AUTHOR]

Background: Hydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to investigate the relationship of cytochrome P450 (CYP450) gene polymorphisms with blood concentrations of HCQ and its metabolites and adverse drug reactions (ADRs) in patients with SLE and RA. Methods: A cohort of 146 patients with SLE and RA treated with HCQ was reviewed. The ADRs of the patients were recorded. The blood concentrations of HCQ and its metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Genotyping of single nucleotide polymorphisms (SNPs) in CYP450, a metabolic enzyme involved in the HCQ metabolic pathway, was performed using a MassARRAY system. The chi-square test, T-test, and one-way analysis of variance were used to analyse data. Results: Among 29 candidate SNPs, we found that CYP3A4 (rs3735451) was significantly associated with blood levels of HCQ and its metabolites in both the unadjusted model and adjusted model (patients taking HCQ for > 10 years) (P < 0.05). For CYP3A5 (rs776746), a greater risk of skin and mucous membrane ADRs was associated with the TT genotype than with the CT + CC genotypes (P = 0.033). For CYP2C8 (rs1058932), the AG genotype carried a greater risk of abnormal renal function than the AA + GG genotype (P = 0.017); for rs10882526, the GG genotype carried a greater risk of ophthalmic ADRs than the AA + AG genotypes (P = 0.026). Conclusions: The CYP2C8 (rs1058932 and rs10882526) and CYP3A5 (rs776746) polymorphisms are likely involved in the ADRs of HCQ. Gene polymorphism analysis of CYP450 and therapeutic drug monitoring of HCQ and its metabolites might be useful to optimise HCQ administration and predict ADRs. [ABSTRACT FROM AUTHOR]

Introduction: Drug-resistant cytomegalovirus (CMV) infection remains a challenge in the management of pediatric recipients of hematopoietic stem cell transplantation (HSCT). In this study, we retrospectively reviewed the clinical data on pediatric recipients of HSCT and identified known and unknown drug-resistant CMV variants. Methods: A total of 221 children underwent allogeneic HSCT between October 2017 and November 2019 at Shenzhen Children's Hospital; of these, 35 patients were suspected of having drug-resistant CMV infections and were tested for drug-resistant mutations in the UL97 and UL54 genes by Sanger sequencing. Results: Mutations in UL97 or UL54, or in both, were detected in 11 patients. Most of these mutations have not been previously reported. The UL97 mutation (A582V) was detected in only one patient who also harbored two UL54 mutations (T760X and R876W). One patient with both the G604S and T691A mutations in the UL54 gene died of CMV pneumonia. We investigated the risk factors associated with the development of drug-resistant CMV infection. Patients in whom both the donor and recipient had positive CMV serostatuses were less likely to have drug-resistant mutations (Fisher's exact test, p < 0.05). Conclusion: Newly and previously detected CMV mutations in UL97 and UL54 may be associated with the development of drug-resistant CMV infection. The detection of these mutations may provide guidance for the management of post-transplant CMV infections. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to obtain antitumour molecules targeting to activate PKM2 through adequate computational methods combined with biological activity experiments. Methods: The structure‐based virtual screening was utilized to screen effective activator targeting PKM2 from ZINC database. Molecular dynamics simulations were performed to evaluate the stability of the small molecule‐binding PKM2 complex systems. Then, cell survival experiments, glutaraldehyde crosslinking reaction, western blot, and qPCR experiments were used to detect the effects of top hits on various cancer cells and the targeting specificity of PKM2. Results: Two small molecules in 1,5‐2H‐pyrrole‐dione were obtained after virtual screening. In vitro experiments demonstrated that ZINC08383544 specifically activated PKM2 and affected the expression of upstream and downstream genes of PKM2 during glycolysis, leading to the inhibition of tumour cell growth. These results indicate that ZINC08383544 conforms to the characteristics of PKM2 activator and is potential to be a novel PKM2 activator as antitumour drug. Discussion: This work proves that ZINC08383544 promotes the formation of PKM2 tetramer, effectively blocks PKM2 nuclear translocation, and inhibits the growth of tumour, and ZINC08383544 may be a novel activator of PKM2. This work may provide a good choice of drug or molecular fragments for the antitumour strategy targeting PKM2. Screening of targeted drugs by combination of virtual screening and bioactivity experiments is a rapid method for drug discovery. [ABSTRACT FROM AUTHOR]

Background and objective This paper presents an automatic computer-aided diagnosis (CAD) system based on feature ranking for detection of Alzheimer's disease (AD) using structural magnetic resonance imaging (sMRI) data. Methods The proposed CAD system is composed of four systematic stages. First, global and local differences in the gray matter (GM) of AD patients compared to the GM of healthy controls (HCs) are analyzed using a voxel-based morphometry technique. The aim is to identify significant local differences in the volume of GM as volumes of interests (VOIs). Second, the voxel intensity values of the VOIs are extracted as raw features. Third, the raw features are ranked using a seven-feature ranking method, namely, statistical dependency (SD), mutual information (MI), information gain (IG), Pearson's correlation coefficient (PCC), t-test score (TS), Fisher's criterion (FC), and the Gini index (GI). The features with higher scores are more discriminative. To determine the number of top features, the estimated classification error based on training set made up of the AD and HC groups is calculated, with the vector size that minimized this error selected as the top discriminative feature. Fourth, the classification is performed using a support vector machine (SVM). In addition, a data fusion approach among feature ranking methods is introduced to improve the classification performance. Results The proposed method is evaluated using a data-set from ADNI (130 AD and 130 HC) with 10-fold cross-validation. The classification accuracy of the proposed automatic system for the diagnosis of AD is up to 92.48% using the sMRI data. Conclusions An automatic CAD system for the classification of AD based on feature-ranking method and classification errors is proposed. In this regard, seven-feature ranking methods (i.e., SD, MI, IG, PCC, TS, FC, and GI) are evaluated. The optimal size of top discriminative features is determined by the classification error estimation in the training phase. The experimental results indicate that the performance of the proposed system is comparative to that of state-of-the-art classification models. [ABSTRACT FROM AUTHOR]

Highlights: [•] Ethyl acetate and ethanol extracts of neem and ginger can reduce mycelial growth of Sclerotinia sclerotiorum. [•] The extracts were able to reduce severity of carrot rot as well as carpogenic germination of sclerotia. [•] The enzymatic analyses indicated that neem extracts can be considered as resistance inducers. [Copyright &y& Elsevier]

ABSTRACT BACKGROUND AND PURPOSE Small animal neuroimaging using magnetic resonance microscopy (MRM) has evolved significantly from understanding of imaging physics to widely use today as an important tool in computational neuroanatomy, while how to get optimal inhomogeneity correction for inhomogeneous mouse brain MRM has been given less attention. METHODS This present study investigates the ability of fine-tuning the nonparametric nonuniform intensity normalization (N3) technique to get optimal inhomogeneity correction of mouse brain MRM. Six mice were scanned on a 7-T scanner with a phased array surface coil of four elements. The N3 parameters such as stopping criteria, maximum iterations, down-sampling ratio, full width at half maximum, spline distance, and brain mask have been tuned to get optimal correction result. We used coefficient of variation of the white matter and joint variation to ascertain quantitatively the correction. The data were analyzed by two-way repeated measures analysis of variance and Bonferroni post hoc test. RESULTS The quantitative outcomes show that brain mask and spline distance have a significant influence on correcting performance. CONCLUSIONS The present study demonstrates the benefit of reducing the spline distance values to 25 and tighter mask. The finding can help researches to enhance precision in studies where mouse MRM need further registration or segmentation. [ABSTRACT FROM AUTHOR]

Highlights: [•] Ultrasound RF data of normal and coagulated porcine liver tissues is collected. [•] Wavelet analysis is used to compute the mean scatterer spacing (MSS) of normal and coagulated tissues. [•] Microwave-induced thermal lesions are detected by MSS differences between normal tissues and thermal lesions. [•] We propose a new method for evaluation of microwave-induced thermal lesions. [Copyright &y& Elsevier]

The temperature distribution in the region near a microwave antenna is a critical factor that affects the entire temperature field during microwave ablation of tissue. It is challenging to predict this distribution precisely, because the temperature in the near-antenna region varies greatly. The effects of water vaporisation and subsequent tissue carbonisation in an ex vivo porcine liver were therefore studied experimentally and in simulations. The enthalpy and high-temperature specific absorption rate (SAR) of liver tissues were calculated and incorporated into the simulation process. The accuracy of predictions for near-field temperatures in our simulations has reached the level where the average maximum error is less than 5°C. In addition, a modified thermal model that accounts for water vaporisation and the change in the SAR distribution pattern is proposed and validated with experiment. The results from this study may be useful in the clinical practice of microwave ablation and can be applied to predict the temperature field in surgical planning. [ABSTRACT FROM AUTHOR]