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A new system for the determination of nucleic acid by rare earth metallic porphyrin of [tetra-(3-methoxy-4-hydroxyphenyl)]-Tb3+ [T(3-MO-4HP)-Tb3+] porphyrin as fluorescence spectral probe has been developed in this paper. Nucleic acid can enhance the fluorescence intensity of the T(3-MO-4HP)-Tb3+ porphyrin in the presence of bis(2-ethylhexyl)sulfosuccinate sodium salt(AOT) micelle. In pH 8.00 Tris-HCl buffer solution, under optimum conditions, the enhanced fluorescence intensity is in proportion to the concentration of nucleic acids in the range of 0.05-3.00 µg mL−1 for calf thymus DNA (ct DNA) and 0.03-4.80 µg mL−1 for fish sperm DNA(fs DNA). Their detection limits are 0.03 and 0.01 µg mL−1, respectively. In addition, the binding interaction mechanism between T(3-MO-4HP)-Tb3+ porphyrin and ct DNA is also investigated by resonance scattering and fluorescence spectra. The maximum binding number is calculated by molar ratio method. The new system can be used for the determination of nucleic acid in pig liver, yielding satisfactory results. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The modular structure can reflect the activity pattern of the brain, and exploring it may help us understand the pathogenesis of major depressive disorder (MDD). However, little is known about how to build a stable modular structure in MDD patients and how modules are separated and integrated., Method: We used four independent resting state Electroencephalography (EEG) datasets. Different coupling methods, window lengths, and optimized community detection algorithms were used to find a reliable and robust modular structure, and the module differences of MDD were analyzed from the perspectives of global module attributes and local topology in multiple frequency bands., Results: The combination of the Phase Lag Index (PLI) and the Louvain algorithm can achieve better results and can achieve stability at smaller window lengths. Compared with Healthy Controls (HC), MDD had higher Modularity (Q) values and the number of modules in low-frequency bands. In addition, MDD showed significant structural changes in the frontal and parietal-occipital lobes, which were confirmed by further correlation analysis., Conclusion: Our results provided a reliable validation of the modular structure construction method in MDD patients and contributed strong evidence for the changes in emotional cognition and visual system function in MDD patients from a new perspective. These results would afford valuable insights for further exploration of the pathogenesis of MDD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve "target-and-release" drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis., (© 2023. West China School of Stomatology Sichuan University.)

Music can effectively induce specific emotion and usually be used in clinical treatment or intervention. The electroencephalogram can help reflect the impact of music. Previous studies showed that the existing methods achieved relatively good performance in predicting emotion response to music. However, these methods tend to be time consuming and expensive due to their complexity. To this end, this study proposes a grey wolf optimiser-based method to predict the induced emotion through fusing electroencephalogram features and music features. Experimental results show that, the proposed method can reach a promising performance for predicting emotional response to music and outperform the alternative method. In addition, we analyse the relationship between the music features and electroencephalogram features and the results demonstrate that, musical timbre features are significantly related to the electroencephalogram features.Clinical relevance- This study targets the automatic prediction of the human response to music. It further explores the correlation between EEG features and music features aiming to provide the basis for the extension to the application of music. The grey wolf optimiser-based method proposed in this study could supply a promising avenue for the emotion prediction as induced by music.

Depression is a heterogeneous syndrome with certain individual differences among subjects. Exploring a feature selection method that can effectively mine the commonness intra-groups and the differences inter-groups in depression recognition is therefore of great significance. This study proposed a new clustering-fusion feature selection method. Hierarchical clustering (HC) algorithm was used to capture the heterogeneity distribution of subjects. Average and similarity network fusion (SNF) algorithms were adopted to characterize the brain network atlas of different populations. Differences analysis was also utilized to obtain the features with discriminant performance. Experiments showed that compared with traditional feature selection methods, HCSNF method yielded the optimal classification results of depression recognition in both sensor and source layers of electroencephalography (EEG) data. Especially in the beta band of EEG data at sensor layer, the classification performance was improved by more than 6%. Moreover, the long-distance connections between parietal-occipital lobe and other brain regions not only have high discriminative power, but also significantly correlate with depressive symptoms, indicating the important role of these features in depression recognition. Therefore, this study may provide methodological guidance for the discovery of reproducible electrophysiological biomarkers and new insights into common neuropathological mechanisms of heterogeneous depression diseases.

Nitrous oxide has rapid antidepressant effects in patients with treatment-resistant depression (TRD), but its underlying mechanisms of therapeutic actions are not well understood. Moreover, most of the current studies lack objective biological indicators to evaluate the changes of nitrous oxide-induced brain function for TRD. Therefore, this study assessed the effect of nitrous oxide on brain function for TRD based on event-related potential (ERP) components and functional connectivity networks (FCNs) methods. In this randomized, longitudinal, placebo-controlled trial, all TRD participants were divided into two groups to receive either a 1-hour inhalation of nitrous oxide or a placebo treatment, and they took part in the same task-state electroencephalogram (EEG) experiment before and after treatment. The experimental results showed that nitrous oxide improved depressive symptoms better than placebo in terms of 17-Hamilton Depression Rating Scale score (HAMD-17). Statistical analysis based on ERP components showed that nitrous oxide-induced significant differences in amplitude and latency of N1, P1, N2, P2. In addition, increased brain functional connectivity was found after nitrous oxide treatment. And the change of network metrics has a significant correlation with decreased depressive symptoms. These findings may suggest that nitrous oxide improves depression symptoms for TRD by modifying brain function., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Objective . Brain connectivity network is a vital tool to reveal the interaction between different brain regions. Currently, most functional connectivity methods can only capture pairs of information to construct brain networks which ignored the high-order correlations between brain regions. Approach . Therefore, this study proposed a weighted connectivity hyper-network based on resting-state EEG data, and then applied to depression identification and analysis. The hyper-network model was build based on least absolute shrinkage and selection operator sparse regression method to effectively represent the higher-order relationships of brain regions. On this basis, by integrating the correlation-based weighted hyper-edge information, the weighted hyper-network is constructed, and the topological features of the network are extracted for classification. Main results . The experimental results obtained an optimal accuracy compared to the traditional coupling methods. The statistical results on network metrics proved that there were significant differences between depressive patients and normal controls. In addition, some brain regions and electrodes were found and discussed to highly correlate with depression by analyzing of the critical nodes and hyper-edges. Significance . These may help discover disease-related biomarkers important for depression diagnosis., (© 2023 IOP Publishing Ltd.)

Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.

Introduction: Aging brings with an increased risk of chronic diseases among older adults, which could affect health outcomes. Evidence has showed that health literacy is associated with health outcomes. However, limited studies explore the underlying mechanism between health literacy and health outcomes. Hence, this study aimed to determine whether self-efficacy for managing chronic disease mediates the relationship between health literacy and health outcomes among older patients with chronic diseases, and to explore whether disease duration moderates the relationship between health literacy, self-efficacy for managing chronic disease, and health outcomes., Methods: Participants were recruited from tertiary hospitals in Zhejiang Province, China from May 2019 to June 2020 using a convenience sampling method. A total of 471 older patients with chronic diseases completed questionnaires measuring demographics, disease-related information, health literacy, self-efficacy for managing chronic disease, and health outcomes. The mediation effect was examined using the structural equation model method, based on the bias-corrected bootstrapping method. The moderation effect was tested by the multiple-group analysis., Results: A good fit model suggested that self-efficacy for managing chronic disease partially mediated the relationships between health literacy and health outcomes. In addition, disease duration moderated the relationships between health literacy, self-efficacy for managing chronic disease, and health outcomes., Discussion: The findings highlight that adequate health literacy improved health outcomes among older patients with chronic diseases, which was further promoted by self-efficacy for managing chronic diseases. Moreover, a long disease duration could enhance the effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lu, Sun, Gu, Li, Fang, Zhu and Xu.)

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the world. To reduce the incidence of AD, it's essential to quantify the AD conversion risk of mild cognitive impaired (MCI) individuals. Here, we propose an AD conversion risk estimation system (CRES), which contains an automated MRI feature extractor, brain age estimation (BAE) module, and AD conversion risk estimation module. The CRES is trained on 634 normal controls (NC) from the public IXI and OASIS cohorts, then it is evaluated on 462 subjects (106 NC, 102 stable MCI (sMCI), 124 progressive MCI (pMCI) and 130 AD) from the ADNI dataset. Experimental results show that the MRI derived age gap (AG, chronological age subtracted from the estimated brain age) significantly distinguish NC, sMCI, pMCI and AD groups with p -value =0.000017 . Considering AG as the primary factor, incorporating gender and Minimum Mental State Examination (MMSE) for more robust Cox multi-variate hazard analysis, we concluded that each additional year in AG is associated with 4.57% greater AD conversion risk for the MCI group. Furthermore, a nomogram was drawn to describe MCI conversion risk at the individual level in the next 1 year, 3 years, 5 years and even 8 years from baseline. This work demonstrates that CRES can estimate AG based on MRI data, evaluate AD conversion risk of the MCI subjects, and identify the individuals with high AD conversion risk, which is valuable for effective intervention and diagnosis within an early period.

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but serious side effect of nitrogen-containing bisphosphonate drugs (N-BPs) frequently prescribed to reduce skeletal-related events in bone malignancies and osteoporosis. BRONJ is associated with abnormal oral wound healing after dentoalveolar surgery and tooth extraction. We previously found that N-BP chemisorbed to bone mineral hydroxyapatite was dissociated by secondary applied N-BP. This study investigated the effect of the surface equilibrium-based removal of N-BP from jawbone on tooth extraction wound healing of zoledronate (ZOL)-treated mice., Methods: A pharmacologically inactive N-BP derivative (the 4-pyridyl isomer of risedronate equipped with a near-infrared 800CW fluorescent imaging dye, 800CW-pRIS) was designed and synthesized. 800CW-pRIS was intra-orally injected or topically applied in a deformable nano-scale vesicle formulation (DNV) to the palatal tissue of mice pretreated with ZOL, a potent N-BP. The female C56BL6/J mice were subjected to maxillary molar extraction and oral wound healing was compared for 800CW-pRIS/ZOL, ZOL and untreated control groups., Results: 800CW-pRIS is confirmed to be inactive in inhibiting prenylation in cultured osteoclasts while retaining high affinity for hydroxyapatite. ZOL-injected mice exhibit delayed tooth extraction wound healing with osteonecrosis relative to the untreated controls. 800CW-pRIS applied topically to the jaw one week before tooth extraction significantly reduces gingival oral barrier inflammation, improves extraction socket bone regeneration, and prevents development of osteonecrosis in ZOL-injected mice., Conclusions: Topical pre-treatment with 800CW-RIS in DNV is a promising approach to prevent the complication of abnormal oral wound healing associated with BRONJ while retaining the anti-resorptive benefit of legacy N-BP in appendicular or vertebrate bones., Competing Interests: Competing interestsS.S. and F.H.E. hold executive positions in BioVinc LLC. S.S., F.H.E., and C.E.M. are founders and hold equity in BioVinc LLC. B.A.K. holds equity in BioVinc LLC. I.N. was a consultant of BioVinc LLC. All other authors declare no competing interests., (© The Author(s) 2022.)

According to the WHO, the number of mental disorder patients, especially depression patients, has overgrown and become a leading contributor to the global burden of disease. With the rising of tools such as artificial intelligence, using physiological data to explore new possible physiological indicators of mental disorder and creating new applications for mental disorder diagnosis has become a new research hot topic. We present a multi-modal open dataset for mental-disorder analysis. The dataset includes EEG and recordings of spoken language data from clinically depressed patients and matching normal controls, who were carefully diagnosed and selected by professional psychiatrists in hospitals. The EEG dataset includes data collected using a traditional 128-electrodes mounted elastic cap and a wearable 3-electrode EEG collector for pervasive computing applications. The 128-electrodes EEG signals of 53 participants were recorded as both in resting state and while doing the Dot probe tasks; the 3-electrode EEG signals of 55 participants were recorded in resting-state; the audio data of 52 participants were recorded during interviewing, reading, and picture description., (© 2022. The Author(s).)

The bisphosphonates ((HO) 2 P(O)CR 1 R 2 P(O)(OH) 2 , BPs) were first shown to inhibit bone resorption in the 1960s, but it was not until 30 years later that a detailed molecular understanding of the relationship between their varied chemical structures and biological activity was elucidated. In the 1990s and 2000s, several potent bisphosphonates containing nitrogen in their R 2 side chains (N-BPs) were approved for clinical use including alendronate, risedronate, ibandronate, and zoledronate. These are now mostly generic drugs and remain the leading therapies for several major bone-related diseases, including osteoporosis and skeletal-related events associated with bone metastases. The early development of chemistry in this area was largely empirical and only a few common structural features related to strong binding to calcium phosphate were clear. Attempts to further develop structure-activity relationships to explain more dramatic pharmacological differences in vivo at first appeared inconclusive, and evidence for mechanisms underlying cellular effects on osteoclasts and macrophages only emerged after many years of research. The breakthrough came when the intracellular actions on the osteoclast were first shown for the simpler bisphosphonates, via the in vivo formation of P-C-P derivatives of ATP. The synthesis and biological evaluation of a large number of nitrogen-containing bisphosphonates in the 1980s and 1990s led to the key discovery that the antiresorptive effects of these more complex analogs on osteoclasts result mostly from their potency as inhibitors of the enzyme farnesyl diphosphate synthase (FDPS/FPPS). This key branch-point enzyme in the mevalonate pathway of cholesterol biosynthesis is important for the generation of isoprenoid lipids that are utilized for the post-translational modification of small GTP-binding proteins essential for osteoclast function. Since then, it has become even more clear that the overall pharmacological effects of individual bisphosphonates on bone depend upon two key properties: the affinity for bone mineral and inhibitory effects on biochemical targets within bone cells, in particular FDPS. Detailed enzyme-ligand crystal structure analysis began in the early 2000s and advances in our understanding of the structure-activity relationships, based on interactions with this target within the mevalonate pathway and related enzymes in osteoclasts and other cells have continued to be the focus of research efforts to this day. In addition, while many members of the bisphosphonate drug class share common properties, now it is more clear that chemical modifications to create variations in these properties may allow customization of BPs for different uses. Thus, as the appreciation for new potential opportunities with this drug class grows, new chemistry to allow ready access to an ever-widening variety of bisphosphonates continues to be developed. Potential new uses of the calcium phosphate binding mechanism of bisphosphonates for the targeting of other drugs to the skeleton, and effects discovered on other cellular targets, even at non-skeletal sites, continue to intrigue scientists in this research field., (Copyright © 2021. Published by Elsevier Inc.)

Background: Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive effects on human health. Due to the absence of antiviral medicine for COVID-19 thus far, there is a desperate need to develop effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, with the aim of achieving clinical efficacy and decreasing the use of antibiotics and glucocorticoids. The aim of this study was to evaluate the efficacy and safety of Baidu Jieduan granules in treating COVID-19., Methods/design: This multicentre, open-label, randomized controlled trial will be conducted in 300 patients with COVID-19. The patients will be randomly (1:1) divided into a treatment group and a control group. All patients will receive standard therapy at the same time. Patients in the experimental group will receive Baidu Jieduan granule treatment twice a day for 14 days. The outcomes will be assessed at baseline and at 3, 5, 7 and 14 days after treatment initiation. The primary outcome will be the rate of symptom (fever, fatigue and coughing) recovery. Adverse events (AEs) will be monitored throughout the trial., Discussion: The study will provide high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan granules in the treatment of moderate COVID-19, and enrich the theory and practice of TCM in treating COVID-19., Trial Registration: Chinese Clinical Trial Registry ChiCTR2000029869 . Registered on 15 February 2020., (© 2021. The Author(s).)

Studies of the potential role of bisphosphonates in dentistry date back to physical chemical research in the 1960s, and the genesis of the discovery of bisphosphonate pharmacology in part can be linked to some of this work. Since that time, parallel research on the effects of bisphosphonates on bone metabolism continued, while efforts in the dental field included studies of bisphosphonate effects on dental calculus, caries, and alveolar bone loss. While some utility of this drug class in the dental field was identified, leading to their experimental use in various dentrifice formulations and in some dental applications clinically, adverse effects of bisphosphonates in the jaws have also received attention. Most recently, certain bisphosphonates, particularly those with strong bone targeting properties, but limited biochemical effects (low potency bisphosphonates), are being studied as a local remedy for the concerns of adverse effects associated with other more potent members of this drug class. Additionally, low potency bisphosphonate analogs are under study as vectors to target active drugs to the mineral surfaces of the jawbones. These latter efforts have been devised for the prevention and treatment of oral problems, such as infections associated with oral surgery and implants. Advances in the utility and mechanistic understanding of the bisphosphonate class may enable additional oral therapeutic options for the management of multiple aspects of dental health., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Currently, coronavirus disease 2019 (COVID-19) is continuously and rapidly circulating, causing heavy damage on public health. No effective antiviral treatment has been proved thus far. Traditional Chinese medicine (TCM) has been widely applied in the treatment of a variety of infection diseases in China, hoping to produce clinical effects and reduce the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Shenhuang granule in treatment of severe COVID-19., Methods/design: This multicenter, open-label randomized controlled trial is conducted in 160 participants with severe COVID-19. The participants will be randomly (1:1) divided into treatment group or control group. All participants are given standard therapy at the same time. The experiment will receive Shenhuang granule treatment twice a day for 14 days. The clinical indicators of patients will be assessed at baseline and at 3, 5, 7, and 14 days after treatment initiation. The primary outcome is 14-day clinical outcome. Adverse events will be monitored throughout the trial., Discussion: This will be the first randomized controlled trial, which evaluate the effect of Shenhuang granule in patients with severe COVID-19 in China. The results of this trial may not only provide evidence-based recommendations to clinicians to treat severe COVID-19, but also enrich the theory and practice of TCM in treating infectious diseases., Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000029777. Registered on 13 February 2020.

The diagnosis of depression almost exclusively depends on doctor-patient communication and scale analysis, which have the obvious disadvantages such as patient denial, poor sensitivity, subjective biases and inaccuracy. An objective, automated method that predicts clinical outcomes in depression is essential for increasing the accuracy of depression recognition and treatments. This paper aims at better recognizing depression using the transformation of EEG features and machine learning methods. An experiment based on emotional face stimuli task was conducted, and twenty-eight subjects' EEG data were recorded from 128-channel HydroCel Geodesic Sensor Net (HCGSN) by Net Station software. The Mini International Neuropsychiatric Interview (MINI) was used by psychiatrists as the criterion for diagnosis of depression patients. The power spectral density and activity were respectively extracted as original features using Auto-regress model and Hjorth algorithm with different time windows. Two separate approaches processed the features: ensemble learning and deep learning. For the ensemble learning, a deep forest transformed the original features to new features that potentially improve feature engineering and a support vector machine (SVM) that was applied as classifier. For deep learning method, we added spatial information of EEG caps to both features by image conversion and adopted convolutional neural network (CNN) to recognize them. The performance of both methods was evaluated for separated and total frequency bands. As a result, the best accuracy obtained was 89.02% when we used the ensemble model and power spectral density. The best accuracy of deep learning method was 84.75% using the activity. These experimental results prove the efficiency of the proposed methods and show that EEG could be used as a reliable indicator for depression recognition, which makes it possible for EEG-based portable system design and application in auxiliary depression recognition in the future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Electroencephalography (EEG)-based studies focus on depression recognition using data mining methods, while those on mild depression are yet in infancy, especially in effective monitoring and quantitative measure aspects. Aiming at mild depression recognition, this study proposed a computer-aided detection (CAD) system using convolutional neural network (ConvNet). However, the architecture of ConvNet derived by trial and error and the CAD system used in clinical practice should be built on the basis of the local database; we therefore applied transfer learning when constructing ConvNet architecture. We also focused on the role of different aspects of EEG, i.e., spectral, spatial, and temporal information, in the recognition of mild depression and found that the spectral information of EEG played a major role and the temporal information of EEG provided a statistically significant improvement to accuracy. The proposed system provided the accuracy of 85.62% for recognition of mild depression and normal controls with 24-fold cross-validation (the training and test sets are divided based on the subjects). Thus, the system can be clinically used for the objective, accurate, and rapid diagnosis of mild depression. Graphical abstract The EEG power of theta, alpha, and beta bands is calculated separately under trial-wise and frame-wise strategies and is organized into three input forms of deep neural networks: feature vector, images without electrode location (spatial information), and images with electrode location. The role of EEG's spectral and spatial information in mild depression recognition is investigated through ConvNet, and the role of EEG's temporal information is investigated using different architectures to aggregate temporal features from multiple frames. The ConvNet and models for aggregating temporal features are transferred from the state-of-the-art model in mental load classification.

Nearly all bone fractures in humans can deteriorate into a non-union fracture, often due to formation of fibrotic tissue. Cranial allogeneic bone grafts present a striking example: although seemingly attractive for craniofacial reconstructions, they often fail due to fibrosis at the host-graft junction, which physically prevents the desired bridging of bone between the host and graft and revitalization of the latter. In the present study we show that intermittent treatment with recombinant parathyroid hormone-analogue (teriparatide) modulates neovascularization feeding in the graft surroundings, consequently reducing fibrosis and scar tissue formation and facilitates osteogenesis. Longitudinal inspection of the vascular tree feeding the allograft has revealed that teriparatide induces formation of small-diameter vessels in the 1st week after surgery; by the 2nd week, abundant formation of small-diameter blood vessels was detected in untreated control animals, but far less in teriparatide-treated mice, although in total, more blood capillaries were detected in the animals that were given teriparatide. By that time point we observed expression of the profibrogenic mediator TGF-β in untreated animals, but negligible expression in the teriparatide-treated mice. To evaluate the formation of scar tissue, we utilized a magnetization transfer contrast MRI protocol to differentiate osteoid tissue from scar tissue, based on the characterization of collagen fibers. Using this method we found that significantly more bone matrix was formed in animals given teriparatide than in control animals. Altogether, our findings show how teriparatide diminishes scarring, ultimately leading to superior bone graft integration., (Copyright © 2017. Published by Elsevier Inc.)

Background and Objective: Depression has become a major health burden worldwide, and effectively detection of such disorder is a great challenge which requires latest technological tool, such as Electroencephalography (EEG). This EEG-based research seeks to find prominent frequency band and brain regions that are most related to mild depression, as well as an optimal combination of classification algorithms and feature selection methods which can be used in future mild depression detection., Methods: An experiment based on facial expression viewing task (Emo_block and Neu_block) was conducted, and EEG data of 37 university students were collected using a 128 channel HydroCel Geodesic Sensor Net (HCGSN). For discriminating mild depressive patients and normal controls, BayesNet (BN), Support Vector Machine (SVM), Logistic Regression (LR), k-nearest neighbor (KNN) and RandomForest (RF) classifiers were used. And BestFirst (BF), GreedyStepwise (GSW), GeneticSearch (GS), LinearForwordSelection (LFS) and RankSearch (RS) based on Correlation Features Selection (CFS) were applied for linear and non-linear EEG features selection. Independent Samples T-test with Bonferroni correction was used to find the significantly discriminant electrodes and features., Results: Data mining results indicate that optimal performance is achieved using a combination of feature selection method GSW based on CFS and classifier KNN for beta frequency band. Accuracies achieved 92.00% and 98.00%, and AUC achieved 0.957 and 0.997, for Emo_block and Neu_block beta band data respectively. T-test results validate the effectiveness of selected features by search method GSW. Simplified EEG system with only FP1, FP2, F3, O2, T3 electrodes was also explored with linear features, which yielded accuracies of 91.70% and 96.00%, AUC of 0.952 and 0.972, for Emo_block and Neu_block respectively., Conclusions: Classification results obtained by GSW + KNN are encouraging and better than previously published results. In the spatial distribution of features, we find that left parietotemporal lobe in beta EEG frequency band has greater effect on mild depression detection. And fewer EEG channels (FP1, FP2, F3, O2 and T3) combined with linear features may be good candidates for usage in portable systems for mild depression detection., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study is to establish osteoclasts as key immune effectors capable of activating the function of Natural Killer (NK) cells, and expanding their numbers, and to determine in vivo and in vitro effect of bisphosphonates (BPs) during NK cell interaction with osteoclasts and on systemic and local immune function. The profiles of 27 cytokines, chemokines and growth factors released from osteoclasts were found to be different from dendritic cells and M1 macrophages but resembling to untreated monocytes and M2 macrophages. Nitrogen-containing BPs Zoledronate (ZOL) and Alendronate (ALN), but not non-nitrogen-containing BPs Etidronate (ETI), triggered increased release of pro-inflammatory mediators from osteoclasts while all three BPs decreased pit formation by osteoclasts. ZOL and ALN mediated significant release of IL-6, TNF-` and IL-1β, whereas they inhibited IL-10 secretion by osteoclasts. Treatment of osteoclasts with ZOL inhibited NK cell mediated cytotoxicity whereas it induced significant secretion of cytokines and chemokines. NK cells lysed osteoclasts much more than their precursor cells monocytes, and this correlated with the decreased expression of MHC class I expression on osteoclasts. Intravenous injection of ZOL in mice induced pro-inflammatory microenvironment in bone marrow and demonstrated significant immune activation. By contrast, tooth extraction wound of gingival tissues exhibited profound immune suppressive microenvironment associated with dysregulated wound healing to the effect of ZOL which could potentially be responsible for the pathogenesis of Osteonecrosis of the Jaw (ONJ). Finally, based on the data obtained in this paper we demonstrate that osteoclasts can be used as targets for the expansion of NK cells with superior function for immunotherapy of cancer.

Purpose: Bisphosphonates (BPs) are widely used for the management of bone diseases such as osteoporosis and bone malignancy. However, osteonecrosis of the jaws (ONJ) is a serious complication of BP treatment. ONJ lesions mainly occur after extraction of teeth deemed unrestorable or around teeth with active periodontal or periapical disease. Because socket healing or dental disease shows higher bone turnover, the authors hypothesized that preferentially high BP accumulation would be observed in these areas., Materials and Methods: The authors tested the uptake of fluorescein-labeled zoledronic acid (5-FAM-ZOL) in sites of tooth extraction or experimental periapical disease in mice. Maxillary molars were extracted or the crowns of mandibular molars were drilled to induce pulp exposure. Animals were injected with 5-FAM-ZOL 200 μg/kg at various times after intervention and fluorescence was measured at healthy versus intervention sites. Fluorescein injections were used as controls. Data were analyzed by t test and mixed effects linear models were constructed because the animals had repeated measurements over time and at the 2 sites., Results: A statistically significant (P≤.001 to .002) time-dependent uptake of 5-FAM-ZOL was detected in the areas of extraction socket and in the alveolar ridge around teeth with periapical disease compared with the healthy contralateral sites of the same animals. For the 2 conditions, the uptake reached a maximum 3 days after experimental intervention and decreased thereafter., Conclusions: These data suggest that sites with increased bone turnover, such as extraction sites or areas of periapical inflammation, are exposed to higher BP doses than the remaining alveolar ridge and could explain, at least in part, the susceptibility of such areas to ONJ., (Copyright © 2014. Published by Elsevier Inc.)

A new system for the determination of nucleic acid by rare earth metallic porphyrin of [tetra-(3-methoxy-4-hydroxyphenyl)]-Tb3+ [T(3-MO-4HP)-Tb3+] porphyrin as fluorescence spectral probe has been developed in this paper. Nucleic acid can enhance the fluorescence intensity of the T(3-MO-4HP)-Tb3+ porphyrin in the presence of bis(2-ethylhexyl)sulfosuccinate sodium salt(AOT) micelle. In pH 8.00 Tris-HCl buffer solution, under optimum conditions, the enhanced fluorescence intensity is in proportion to the concentration of nucleic acids in the range of 0.05-3.00 microg mL(-1) for calf thymus DNA (ct DNA) and 0.03-4.80 microg mL(-1) for fish sperm DNA(fs DNA). Their detection limits are 0.03 and 0.01 microg mL(-1), respectively. In addition, the binding interaction mechanism between T(3-MO-4HP)-Tb(3+) porphyrin and ct DNA is also investigated by resonance scattering and fluorescence spectra. The maximum binding number is calculated by molar ratio method. The new system can be used for the determination of nucleic acid in pig liver, yielding satisfactory results., (Copyright 2008 John Wiley & Sons, Ltd.)