bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoparticle-Based Lateral Flow Biosensor Integrated With Loop-Mediated Isothermal Amplification for Rapid and Visual Identification of Chlamydia trachomatis for Point-of-Care Use
Authors: Chen Xu , Zhou Qingxue , Tan Yan , Wang Ronghua , Wu Xueli , Liu Jiangli , Liu Rui , Wang Shuoshi , Dong Shilei
Published: July 2022

Chlamydial infection, caused by Chlamydia trachomatis, is the most common bacterial sexually transmitted infection and remains a major public health problem worldwide, particularly in underdeveloped regions. Developing a rapid and sensitive point-of-care (POC) testing for accurate screening of C. trachomatis infection is critical for earlier treatment to prevent transmission. In this study, a novel diagnostic assay, loop-mediated isothermal amplification integrated with gold nanoparticle-based lateral flow biosensor (LAMP-LFB), was devised and applied for diagnosis of C. trachomatis in clinical samples. A set of LAMP primers based on the ompA gene from 14 C. trachomatis serological variants (serovar A-K, L1, L2, L3) was successfully designed and used for the development of C. trachomatis-LAMP-LFB assay. The optimal reaction system can be performed at a constant temperature of 67°C for 35 min. The total assay process, including genomic DNA extraction (~15 min), LAMP reaction (35 min), and LFB readout (~2 min), could be finished within 60 min. The C. trachomatis-LAMP-LFB could detect down to 50 copies/ml, and the specificity was 100%, no cross-reactions with other pathogens were observed. Hence, our C. trachomatis-LAMP-LFB was a rapid, reliable, sensitive, cost-effective, and easy-to-operate assay, which could offer an attractive POC testing tool for chlamydial infection screening, especially in resource starvation settings.
Epidemiology and Drug Resistance of Fracture-Related Infection of the Long Bones of the Extremities: A Retrospective Study at the Largest Trauma Center in Southwest China
Authors: Zhang Zhengdong , Liu Pan , Wang Wenzhao , Wang Shanxi , Li Bohua , Li Jun , Yang Banyin , Li Mingxin , Li Qin , Yang Hai , Huang Zeyu , Liu Lei
Published: July 2022

Objective

To describe the demographic characteristics, risk factors, and bacterial resistance of fracture-related infection (FRI) of the long bones of the extremities.

Materials and Methods

This single-center study retrospectively evaluated patients with FRI of the long bones of the extremities at West China Hospital between January 2012 and December 2017, and analyzed the demographic characteristics, risk factors, distribution of pathogenic bacteria, and bacterial drug resistance.

Results

Among 9,900 patients, 535 patients (5.4%) were diagnosed with FRI. The most common site of FRI was tibiofibular (298, 55.7%), with 424 cases (79.2%) of open fractures, and 282 cases (52.7%) due to traffic injuries. The 41–50 years age group had the highest incidence of FRI with 157 (29.3%) cases. Overall, 546 strains of 52 types of bacteria were detected in FRI patients, with 105 strains of multidrug-resistant (MDR) bacteria. Methicillin-resistant Staphylococcus aureus (48, 8.8%) and extended-spectrum-β-lactamase Escherichia coli (32, 5.8%) accounted for the largest proportion. Multivariate logistic regression analysis showed that sex (odds ratio [OR] 1.813; 95% confidence interval [CI], 1.071∼3.070; P = 0.027) and fracture type (OR 3.128; 95% CI, 1.683∼5.815; P < 0.001) were independent risk factors for monomicrobial infection (MI). Female sex (OR 4.190; 95% CI, 1.212∼14.486; P = 0.024) was an independent risk factor for polymicrobial infection (PI).

Conclusion

This study clarified the infection rates, changes in the bacterial spectrum, and drug resistance characteristics, and risk factors of FRI of the long bones of the extremities in the largest trauma center in southwest China.
Antimicrobial Blue Light for Prevention and Treatment of Highly Invasive Vibrio vulnificus Burn Infection in Mice
Authors: dos Anjos Carolina , Leanse Leon G. , Liu Xiaojing , Miranda Hugo V. , Anderson R. Rox , Dai Tianhong
Published: July 2022

Vibrio vulnificus is an invasive marine bacterium that causes a variety of serious infectious diseases. With the increasing multidrug-resistant variants, treatment of V. vulnificus infections is becoming more difficult. In this study, we explored antimicrobial blue light (aBL; 405 nm wavelength) for the treatment of V. vulnificus infections. We first assessed the efficacy of aBL against five strains of V. vulnificus in vitro. Next, we identified and quantified intracellular porphyrins in V. vulnificus to provide mechanistic insights. Additionally, we measured intracellular reactive oxygen species (ROS) production and bacterial membrane permeabilization following aBL exposures. Lastly, we conducted a preclinical study to investigate the efficacy and safety of aBL for the prevention and treatment of burn infections caused by V. vulnificus in mice. We found that aBL effectively killed V. vulnificus in vitro in both planktonic and biofilm states, with up to a 5.17- and 4.57-log10 CFU reduction being achieved, respectively, following an aBL exposure of 216 J/cm2. Protoporphyrin IX and coproporphyrins were predominant in all the strains. Additionally, intracellular ROS was significantly increased following aBL exposures (P < 0.01), and there was evidence of aBL-induced permeabilization of the bacterial membrane (P < 0.0001). In the preclinical studies, we found that female mice treated with aBL 30 min after bacterial inoculation showed a survival rate of 81% following 7 days of observation, while only 28% survival was observed in untreated female mice (P < 0.001). At 6 h post-inoculation, an 86% survival was achieved in aBL-treated female mice (P = 0.0002). For male mice, 86 and 63% survival rates were achieved when aBL treatment was given 30 min and 6 h after bacterial inoculation, respectively, compared to 32% survival in the untreated mice (P = 0.0004 and P = 0.04). aBL did not reduce cellular proliferation or induce apoptosis. We found five cytokines were significantly upregulated in the males after aBL treatment, including MCSF (P < 0.001), MCP-5 (P < 0.01), TNF RII (P < 0.01), CXCL1 (P < 0.01), and TIMP-1 (P < 0.05), and one in the females (TIMP-1; P < 0.05), suggesting that aBL may induce certain inflammatory processes. In conclusion, aBL may potentially be applied to prevent and treat V. vulnificus infections.
Gut Commensal Fungi Protect Against Acetaminophen-Induced Hepatotoxicity by Reducing Cyp2a5 Expression in Mice
Authors: He Zhuoen , Zeng Yunong , Li Shuyu , Lin Lizhen , Zhou Ruisi , Wang Fangzhao , Yang Wenjiao , Wu Yuhao , Yang Junhao , Chen Ali , Wang Zhang , Yang Hong , Zhao Xiaoshan , Xiao Wei , Li Lei , Gong Shenhai
Published: July 2022

Background and Aims

Drug-induced liver injury (DILI) is a common cause of acute liver failure and represents a significant global public health problem. When discussing the gut-liver axis, although a great deal of research has focused on the role of gut microbiota in regulating the progression of DILI, the gut commensal fungal component has not yet been functionally identified.

Methods

Mice were pretreated with fluconazole (FC) to deplete the gut commensal fungi and were then subject to acetaminophen (APAP) gavage. In addition, transcriptome sequencing was performed to identify differentially expressed genes (DEGs) between control and fluconazole-pretreated groups of the mice challenged with APAP.

Results

Gut commensal fungi ablation through fluconazole pretreatment predisposed mice to APAP-induced hepatotoxicity, characterized by elevated serum liver enzyme levels and more severe centrilobular necrosis, which appears to be caused by robust inflammation and oxidative stress. The 16S rDNA sequencing results indicated that Akkermansia muciniphila abundance had significantly decreased in gut fungi-depleted mice, whereas increased abundance of Helicobacter rodentium was observed. The gene interaction network between DEGs identified by the transcriptome sequencing highlighted a significant enrichment of Cyp2a5 in the liver of APAP-treated mice that were preadministrated with fluconazole. Pharmacological inhibition of Cyp2a5 by 8-methoxypsoralen (8-MOP) could significantly attenuate hepatic inflammation and oxidative stress in mice, thereby conferring resistance to acute liver injury caused by APAP administration.

Conclusion

Our data highlighted the significance of gut commensal fungi in hepatic inflammation and oxidative stress of APAP mice, shedding light on promising therapeutic strategies targeting Cyp2a5 for DILI treatment.
Sustained Biotic-Abiotic Hybrids Methanogenesis Enabled Using Metal-Free Black Phosphorus/Carbon Nitride
Authors: Hu Andong , Fu Tao , Ren Guoping , Zhuang Minghan , Yuan Weiqi , Zhong Sining , Zhou Shungui
Published: July 2022

Biotic-abiotic hybrid systems (BAHs) constructed by integrating biological methanogens with photocatalysts offer novel approaches for the effective solar-driven conversion of CO2 to CH4, providing significant inspiration for achieving carbon neutrality and alleviating the energy crisis. As metal photocatalysts would cause photocorrosion that damages microbial cells and lead to system imbalance. Therefore, exploring suitable metal-free photocatalysts is of particular importance in the search for more efficient and sustainable BAHs to improve the actual operability and applicability. Herein, black phosphorus/carbon nitride (BPCNx) as an alternative metal-free heterostructure was combined with Methanosarcina barkeri (M. barkeri) to construct M. barkeri-BPCNx hybrid systems, and their cyclic methanogenesis performance was investigated. Our results demonstrated that BPCNx promotes the separation of photogenerated charges and enhances the quantum yield, providing a sustained energy source for the cyclically driven M. barkeri reduction of CO2 to CH4 under visible light. Our system achieved a total CH4 yield of 1087.45 ± 29.14 μmol gcat–1 after three cycles, 1.96 times higher than that of M. barkeri-Ni@CdS. M. barkeri-BPCNx overcame the defects of the metal photocatalyst and kept cell permeability, achieving cyclic stability and effectively maintaining the activity of M. barkeri. These results highlight the viable role of BPCNx as a metal-free photocatalysts in the construction of BAHs for the sustained and efficient methanation of CO2, which is conducive to the development of an environmentally-friendly, low-cost, and efficient strategy for the conversion of CO2 to CH4.
Structural Requirements and Plasticity of Receptor-Binding Domain in Human Coronavirus Spike
Authors: Li Yajuan , Zheng Peiyi , Liu Tingting , Shi Cuixiao , Wang Bo , Xu Yuanhong , Jin Tengchuan
Published: July 2022

The most recent human coronaviruses including severe acute respiratory syndrome coronavirus-2 causing severe respiratory tract infection and high pathogenicity bring significant global public health concerns. Infections are initiated by recognizing host cell receptors by coronavirus spike protein S1 subunit, and then S2 mediates membrane fusion. However, human coronavirus spikes undergo frequent mutation, which may result in diverse pathogenesis and infectivity. In this review, we summarize some of these recent structural and mutational characteristics of RBD of human coronavirus spike protein and their interaction with specific human cell receptors and analyze the structural requirements and plasticity of RBD. Stability of spike protein, affinity toward receptor, virus fitness, and infectivity are the factors controlling the viral tropisms. Thus, understanding the molecular details of RBDs and their mutations is critical in deciphering virus evolution. Structural information of spike and receptors of human coronaviruses not only reveals the molecular mechanism of host–microbe interaction and pathogenesis but also helps develop effective drug to control these infectious pathogens and cope with the future emerging coronavirus outbreaks.
Association of Plasma and Electroencephalography Markers With Motor Subtypes of Parkinson’s Disease
Authors: Yang Xiaoxia , Li Zhen , Bai Lipeng , Shen Xiao , Wang Fei , Han Xiaoxuan , Zhang Rui , Li Zhuo , Zhang Jinghui , Dong Mengmeng , Wang Yanlin , Cao Tingyu , Zhao Shujun , Chu Chunguang , Liu Chen , Zhu Xiaodong
Published: July 2022

Objective

The aim of this study was to investigate the correlations of plasma neurodegenerative proteins and electroencephalography (EEG) dynamic functional network (DFN) parameters with disease progression in early Parkinson’s disease (PD) with different motor subtypes, including tremor-dominant (TD) and postural instability and gait disorder (PIGD).

Methods

In our study, 33 patients with PD (21 TD and 12 PIGD) and 33 healthy controls (HCs) were enrolled. Plasma neurofilament light chain (NfL), α-synuclein (α-syn), total-tau (t-tau), β-amyloid 42 (Aβ42), and β-amyloid 40 (Aβ40) levels were measured using an ultrasensitive single-molecule array (Simoa) immunoassay. All the patients with PD underwent EEG quantified by DFN analysis. The motor and non-motor performances were evaluated by a series of clinical assessments. Subsequently, a correlation analysis of plasma biomarkers and EEG measures with clinical scales was conducted.

Results

In the TD group, plasma NfL exhibited a significant association with MDS-UPDRS III and Montreal Cognitive Assessment (MoCA). A higher Aβ42/40 level was significantly related to a decrease in Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) in the PIGD group. In terms of the correlation between EEG characteristic parameters and clinical outcomes, trapping time (TT) delta was positively correlated with MDS-UPDRS III and MoCA scores in the TD group, especially in the prefrontal and frontal regions. For other non-motor symptoms, there were significant direct associations of kPLI theta with HAMD and HAMA, especially in the prefrontal region, and kPLI gamma was particularly correlated with Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores in the prefrontal, frontal, and parietal regions in the TD group. Furthermore, there was a significant positive correlation between plasma t-tau and kPLI, and pairwise correlations were found among plasma NfL, theta TT, and MoCA scores in the TD group.

Conclusion

These results provide evidence that plasma neurodegenerative proteins and EEG measures have great potential in predicting the disease progression of PD subtypes, especially for the TD subtype. A combination of these two kinds of markers may have a superposition effect on monitoring and estimating the prognosis of PD subtypes and deserves further research in larger, follow-up PD cohorts.
Intra-Arterial Thrombolysis Vs. Mechanical Thrombectomy in Acute Minor Ischemic Stroke Due to Large Vessel Occlusion
Authors: Sun Dapeng , Huo Xiaochuan , Raynald  , Wang Anxin , Mo Dapeng , Gao Feng , Ma Ning , Miao Zhongrong
Published: July 2022

Background

The efficacy and safety of mechanical thrombectomy (MT) in acute large vessel occlusion (LVO) patients with minor stroke (NIHSS ≤ 5) remains undetermined. We aimed to compare the efficacy and safety of intra-arterial thrombolysis (IAT) alone vs. MT for LVO patients with minor stroke.

Methods

Patients were selected from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry, a prospective multicenter registry study, and divided into MT and IAT alone groups. We compared the outcome measures between the two groups, including 90-day functional outcome evaluated by the modified Rankin Scale (mRS), the final recanalization level, intracranial hemorrhage, and mortality within 90-days by logistic regression models with adjustment. Besides the conventional multivariable analysis, we performed a sensitivity analysis by adjusting the propensity score to confirm our results. The propensity score was derived using a logistic regression model.

Results

Of the 120 patients, 63 received IAT alone and 57 received MT as the first-line treatment strategy. As compared to MT group, patients in the IAT alone group were associated with a higher chance of 90-day mRS 0-2 [93.7% vs. 71.9%, odds ratio (OR) = 4.75, 95% confidence interval (CI): 1.20–18.80, P = 0.027], a high chance of 90-day mRS 0-3 (96.8% vs. 86.7%, OR = 11.35, 95% CI: 1.93–66.86, P = 0.007), a shorter median time from puncture to recanalization (PTR) (60 min vs. 100 min, β = −63.70, 95% CI: −81.79– −45.61, P < 0.001), a lower chance of any intracranial hemorrhage (ICH) within 48 h (3.2% vs. 19.3%, OR = 0.15, 95% CI: 0.03–0.79, P = 0.025), and a lower chance of mortablity within 90 days (1.6% vs. 9.2%, OR = 0.05, 95% CI: 0.01–0.57, P = 0.016). Similarly, the sensitivity analysis showed the robustness of the primary analysis.

Conclusions

Compared with MT, IAT may improve 90-day clinical outcomes with decreased ICH rate and mortality in LVO patients with minor stroke.
Multi-Omics Interdisciplinary Research Integration to Accelerate Dementia Biomarker Development (MIRIADE)
Authors: Mavrina Ekaterina , Kimble Leighann , Waury Katharina , Gogishvili Dea , Gómez de San José Nerea , Das Shreyasee , Coppens Salomé , Fernandes Gomes Bárbara , Mravinacová Sára , Wojdała Anna Lidia , Bolsewig Katharina , Bayoumy Sherif , Burtscher Felicia , Mohaupt Pablo , Willemse Eline , Teunissen Charlotte ,   the MIRIADE consortium
Published: July 2022

Proteomics studies have shown differential expression of numerous proteins in dementias but have rarely led to novel biomarker tests for clinical use. The Marie Curie MIRIADE project is designed to experimentally evaluate development strategies to accelerate the validation and ultimate implementation of novel biomarkers in clinical practice, using proteomics-based biomarker development for main dementias as experimental case studies. We address several knowledge gaps that have been identified in the field. First, there is the technology-translation gap of different technologies for the discovery (e.g., mass spectrometry) and the large-scale validation (e.g., immunoassays) of biomarkers. In addition, there is a limited understanding of conformational states of biomarker proteins in different matrices, which affect the selection of reagents for assay development. In this review, we aim to understand the decisions taken in the initial steps of biomarker development, which is done via an interim narrative update of the work of each ESR subproject. The results describe the decision process to shortlist biomarkers from a proteomics to develop immunoassays or mass spectrometry assays for Alzheimer's disease, Lewy body dementia, and frontotemporal dementia. In addition, we explain the approach to prepare the market implementation of novel biomarkers and assays. Moreover, we describe the development of computational protein state and interaction prediction models to support biomarker development, such as the prediction of epitopes. Lastly, we reflect upon activities involved in the biomarker development process to deduce a best-practice roadmap for biomarker development.
Low Gain Values of the Vestibulo-Ocular Reflex Can Optimize Retinal Image Slip
Authors: Glasauer Stefan , Straka Hans
Published: July 2022

The angular vestibulo-ocular reflex (aVOR) stabilizes retinal images by counter-rotating the eyes during head rotations. Perfect compensatory movements would thus rotate the eyes exactly opposite to the head, that is, eyes vs. head would exhibit a unity gain. However, in many species, but also in elderly humans or patients with a history of vestibular damage, the aVOR is far from compensatory with gains that are in part considerably lower than unity. The reason for this apparent suboptimality is unknown. Here, we propose that low VOR gain values reflect an optimal adaptation to sensory and motor signal variability. According to this hypothesis, gaze stabilization mechanisms that aim at minimizing the overall retinal image slip must consider the effects of (1) sensory and motor noise and (2) dynamic constraints of peripheral and central nervous processing. We demonstrate that a computational model for optimizing retinal image slip in the presence of such constraints of signal processing in fact predicts gain values smaller than unity. We further show specifically for tadpoles of the clawed toad, Xenopus laevis with particularly low gain values that previously reported VOR gains quantitatively correspond to the observed variability of eye movements and thus constitute an optimal adaptation mechanism. We thus hypothesize that lower VOR gain values in elderly human subjects or recovered patients with a history of vestibular damage may be the sign of an optimization given higher noise levels rather than a direct consequence of the damage, such as an inability of executing fast compensatory eye movements.
Leukocyte as an Independent Predictor of Lower-Extremity Deep Venous Thrombosis in Elderly Patients With Primary Intracerebral Hemorrhage
Authors: Wang Gang , Zhao Wenjun , Zhao Zhiyong , Wang Dengfeng , Wang Dong , Bai Ruobing , Hou Boru , Ren Haijun
Published: July 2022

Objective

Due to the interaction of leukocytes with platelets and coagulation factors, they may in turn play a role in hemostasis or the formation of thrombi. This study aimed to investigate the association of leukocytosis on admission with an increased risk of acute lower-extremity deep venous thrombosis (LEDVT) in elderly patients with primary intracerebral hemorrhage (ICH).

Methods

This was a single-center, retrospective observational study of consecutive patients observed with spontaneous ICH aged 60 years or above at Lanzhou University Second Hospital from January 2017 to September 2021. Clinical data and demographic information were collected and analyzed. Univariate and multivariate analyses were conducted to identify independent risk factors of acute LEDVT. One-to-one matching was implemented to balance important patient characteristics by the groups' propensity score matching (PSM) analysis.

Results

A total of 371 elderly patients with primary ICH fulfilled requirements for inclusion and exclusion, of whom 33 (8.89%) experienced LEDVT. Leukocyte counts were statistically higher in the LEDVT group compared to the non-LEDVT group [12.89 (8.80–14.61) × 109 cells/L vs. 8.31 (6.60–10.75) × 109 cells /L, p < 0.001]. Multivariate logistic regression models adjusted for several potential confounding factors were performed, and leukocytes were consistently a significant independent predictor of LEDVT. The optimal cut-off value of leukocyte counts calculated from the receiver operating characteristic (ROC) curve to predict LEDVT was 10.22 × 109 cells /L (area under the curve:0.714, 95%CI 0.665–0.759; the sensitivity was 72.73%; the specificity was 71.01%) in elderly patients with primary ICH. After one-to-one PSM, compared to the matched non-LEDVT group, the matched LEDVT group had significantly higher leukocyte counts [11.98 (8.40–13.94) × 109 cells/L vs. 6.12 (4.68–12.00) × 109 cells/L, p = 0.003]. After PSM, the ROC curve was plotted for leukocytes as a predictor of LEDVT, with an AUC of 0.722 (95%CI 0.593–0.828, p = 0.001; the sensitivity was 87.10%, and the specificity was 61.29%). Elevated leukocytes remained independently significant as predictors of LEDVT in elderly patients with primary ICH.

Conclusion

Leukocyte at admission is an independent risk factor of LEDVT in elderly patients with primary ICH.
Association Between High Serum Anion Gap and All-Cause Mortality in Non-Traumatic Subarachnoid Hemorrhage: A Retrospective Analysis of the MIMIC-IV Database
Authors: Zhong Changli , Ye Min , Hu Liyi , Liu Jiuling
Published: July 2022

Background:

High serum anion gap (AG) on admission is often correlated with poor outcomes in critically ill patients; however, data in patients with non-traumatic subarachnoid hemorrhage (SAH) are lacking. Herein, we aimed to identify the association between serum AG and all-cause mortality in patients with non-traumatic SAH.

Methods

A retrospective analysis of data from the Medical Information Mart for Intensive Care (MIMIC-IV) database was performed on critically ill patients with non-traumatic SAH. Serum AG was collected on Intensive Care Unit (ICU) admission, and ICU and hospital all-cause mortality were analyzed. The multivariate Cox proportional hazard regression model and Kaplan-Meier survival curve analysis were used to analyze the correlation of serum AG with ICU and hospital all-cause mortality. Furthermore, interaction and subgroup analyses were evaluated for the consistency of these correlations.

Results

A total of 893 patients with non-traumatic SAH were included in this study. The all-cause mortality in ICU and hospital were 14.8% (132/893), and 18.9% (169/893), respectively. Multivariate analysis after adjusting for potential confounders indicated that high serum AG levels (≥16 mmol/L) were associated with increased risk of ICU and hospital all-cause mortality as compared to that with low serum AG levels (<16mmol/L), (hazards ratio (HR): 2.31 [95% CI: 1.58–3.38]) and HR: 1.91 [95% CI: 1.36–2.67)], respectively). Similarly, the Kaplan–Meier (K–M) survival curve also showed that patients with high serum AG levels presented with a lower survival rate. Stratified analyses further showed that depending on the variable testes, an association between higher serum AG levels and hospital all-cause mortality in different subgroups was observed.

Conclusion

Among patients with non-traumatic SAH, high serum AG level at ICU admission was associated with increased ICU and hospital all-cause mortality.
Objective Observer vs. Patient Motor State Assessments Using the PD Home Diary in Advanced Parkinson's Disease
Authors: Timpka Jonathan , Löhle Matthias , Bremer Alexander , Christiansson Sofia , Gandor Florin , Ebersbach Georg , Dahlström Örjan , Iwarsson Susanne , Nilsson Maria H. , Storch Alexander , Odin Per
Published: July 2022

Background

The Parkinson Disease (PD) Home Diary (HD) is a commonly used clinical outcome measure, but it has not been extensively compared to direct assessments by experienced observers.

Objective

Validation of patient-reported HD by investigating the agreement between motor state assessments by patients and observers.

Methods

This observational study included patients with PD and motor fluctuations. Observers were physicians or research nurses. Patients completed a screening visit, one day of diary ratings at home, and then two days of ratings on-site during which patients and observers simultaneously judged the participants' motor state.

Results

Observers and 40 patients completed 1,288 pairs of half-hourly blinded motor state assessments. There were significant differences between observer and patient ratings (P < 0.001) and the temporal agreement was poor (Cohen's κ = 0.358). The agreement between patient and observer ratings was 71.1% for observed “On without dyskinesia”, 57.3% for observed “Off”, and 49.4% for observed “On with dyskinesia”. Daily times spent in the three motor states as aggregated diary data showed fair to excellent reliability with intraclass coefficient values ranging from 0.45 to 0.52 for “On” and 0.77 for “Off”.

Conclusion

There were significant differences between observer and patient ratings. Patients and observers generally agreed on when the patients was in the “On” state (with or without dyskinesia). Patient ratings on the hour level seem to be influenced by other aspects of the patients' experience than the observed motor state, but assessment of daily time spent in the different motor state provides reasonable reliability.
A System-on-Chip Based Hybrid Neuromorphic Compute Node Architecture for Reproducible Hyper-Real-Time Simulations of Spiking Neural Networks
Authors: Trensch Guido , Morrison Abigail
Published: July 2022

Despite the great strides neuroscience has made in recent decades, the underlying principles of brain function remain largely unknown. Advancing the field strongly depends on the ability to study large-scale neural networks and perform complex simulations. In this context, simulations in hyper-real-time are of high interest, as they would enable both comprehensive parameter scans and the study of slow processes, such as learning and long-term memory. Not even the fastest supercomputer available today is able to meet the challenge of accurate and reproducible simulation with hyper-real acceleration. The development of novel neuromorphic computer architectures holds out promise, but the high costs and long development cycles for application-specific hardware solutions makes it difficult to keep pace with the rapid developments in neuroscience. However, advances in System-on-Chip (SoC) device technology and tools are now providing interesting new design possibilities for application-specific implementations. Here, we present a novel hybrid software-hardware architecture approach for a neuromorphic compute node intended to work in a multi-node cluster configuration. The node design builds on the Xilinx Zynq-7000 SoC device architecture that combines a powerful programmable logic gate array (FPGA) and a dual-core ARM Cortex-A9 processor extension on a single chip. Our proposed architecture makes use of both and takes advantage of their tight coupling. We show that available SoC device technology can be used to build smaller neuromorphic computing clusters that enable hyper-real-time simulation of networks consisting of tens of thousands of neurons, and are thus capable of meeting the high demands for modeling and simulation in neuroscience.
Omega-3 Polyunsaturated Fatty Acids Supplementation Alleviate Anxiety Rather Than Depressive Symptoms Among First-Diagnosed, Drug-Naïve Major Depressive Disorder Patients: A Randomized Clinical Trial
Authors: Yang Rong , Wang Lu , Jin Kun , Cao Song , Wu Chujun , Guo Jimin , Chen Jindong , Tang Hui , Tang Mimi
Published: July 2022

Background

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) augmentation of antidepressants has shown great potential in the prevention and treatment of major depressive disorders (MDD).

Objective

To investigate the effect of n-3 PUFAs plus venlafaxine in patients with first-diagnosed, drug-naïve depression.

Method

A total of 72 outpatients with first-diagnosed depression were recruited. The daily dose of 2.4 g/day n-3 PUFAs or placebo plus venlafaxine was used for over 12 weeks. The outcomes were assessed by the Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), Beck depression inventory (BDI), and Self-rating anxiety scale (SAS).

Results

Both groups exhibited improvement on clinical characteristics at week 4 and week 12 compared with baseline. The rate of responders for anxiety in n-3 PUFAs group (44.44%) was significantly higher than that in placebo group (21.21%) at week 4 (χ2 = 4.182, p = 0.041), while week 12 did not show a difference (χ2 = 0.900, p = 0.343). The rate of responders for depression at both week 4 (χ2 = 0.261, p = 0.609) and week 12 (χ2 = 1.443, p = 0.230) showed no significant difference between two groups. Further analysis found that Childhood Trauma Questionnaire (CTQ) had positive correlation with HAMA (r = 0.301, p = 0.012), SAS (r = 0.246, p = 0.015), HAMD (r = 0.252, p = 0.038) and BDI (r = 0.233, p = 0.022) with Pearson correlation analysis. Social Support Rating Scale (SSRS) had negative correlation with SAS (r = −0.244, p = 0.015) and BDI (r = −0.365, p = 0.000).

Conclusion

This trial found that n-3 PUFAs supplementation in favor of venlafaxine alleviated the anxiety symptoms rather than depressive symptoms at the early stage of treatment (4 weeks) for first-diagnosed, drug-naïve depressed patients. However, the advantage disappeared in long-term treatment. Furthermore, childhood abuse and social support are closely related to the clinical and biological characteristics of depression. Both childhood trauma and lack of social support might be predictors of poor prognosis in depression.

Clinical Trial Registration

[clinicaltrials.gov], identifier [NCT03295708].
Anthropometric Indicators as Predictors of Mortality in Early Life Among Low Birthweight Indian Infants
Authors: Choudhary Tarun Shankar , Kumar Mohan , Sinha Bireshwar , Shaikh Saijuddin , Mazumder Sarmila , Taneja Sunita , Bhandari Nita
Published: July 2022

Background

Low birthweight (LBW) babies (<2.5 kg) are at higher risk of mortality and weight for height z score is currently recommended for identifying infants at risk of mortality.

Objective

To compare different anthropometric measures at 28-day of age in a cohort of LBW Indian infants for predicting mortality between 28-day and 180-day of age.

Methods

We used data from an individually randomized controlled trial of LBW infants weighing between 1,500 and 2,250 g. Sensitivity, specificity, positive, and negative likelihood ratios, positive and negative predictive values, and area under receiver operating characteristics curves (AUC) were used to estimate the discrimination of mortality risk. The Cox regression was used to estimate hazard ratios and population attributable fraction for each anthropometric indicator. These estimates were calculated for individual as well as combinations of anthropometric indicators at the cut-off of –2 and –3 SD of the WHO 2006 growth standards.

Results

Severe underweight (weight-for-age z-scores [WAZ] < –3) had a sensitivity of 75.0%, specificity of 68.0% with an AUC of 0.72. The risk of death was higher (HR 6.18; 95% CI 4.29–8.90) with a population attributable fraction of 0.63 (95% CI 0.52–0.72) for infants severely underweight at 28-day of age. Combination of different anthropometric measures did not perform better than individual measures.

Conclusion

Severe underweight (WAZ < –3) better discriminated deaths among LBW infants < 6 months of age. It can be considered for diagnosis of nutritionally at-risk infants in this age group.

Clinical Trial Registration

[ClinicalTrials.gov], identifier [NCT02653534].
Biological Functions of Dillenia pentagyna Roxb. Against Pain, Inflammation, Fever, Diarrhea, and Thrombosis: Evidenced From in vitro, in vivo, and Molecular Docking Study
Authors: Sultana Nahida , Chung Hea-Jong , Emon Nazim Uddin , Alam Safaet , Taki Md. Tohidul Islam , Rudra Sajib , Tahamina Afroza , Alam Rashedul , Ahmed Firoj , Mamun Abdullah Al
Published: July 2022

Dillenia pentagyna Roxb. is traditionally used to treat cancer, wound healing, diabetes, and diarrhea in local tribes. This study was designed to evaluate the pharmacological potentiality of this plant. In vivo analgesic, anti-inflammatory, and antipyretic studies of the methanol extracts of D. pentagyna (MEDP) leaves were performed by using acetic acid-induced nociception, formalin-induced paw licking, and yeast-induced pyrexia assay methods, respectively. In vivo antidiarrheal activity was carried out in mice by following castor oil-induced diarrhea and gastrointestinal transit manner. In vitro thrombolytic experiment was performed employing the clot lysis activity. Besides, a molecular docking study was performed by executing the software (PyRx, Discovery Studio, and UCSF Chimera). In the acetic acid-induced writhing study, MEDP possesses significant writhing inhibition in a dose-dependent manner. It showed 50.86% of maximum inhibition of pain in the case of MEDP at a dose of 400 mg/kg body weight. In the anti-inflammatory study, maximum inhibition rate was observed at a value of 59.98 and 41.29% in early and late phases, respectively, at the dose of 400 mg/kg body weight. In the case of yeast-induced hyperpyrexia, MEDP reduced hyperpyrexia in a dose-dependent manner. In the antidiarrheal assay, MEDP moderately inhibited the occurrence of diarrhea in all the experiments. In the thrombolytic study, a moderate (17.76%) clot lysis potency has been yielded by MEDP. Again, the molecular docking simulation revealed strong binding affinities with almost all the targeted proteins. The present study suggests that the MEDP possesses remarkable pharmacological activity and this finding validated the ethnobotanical significance of D. pentagyna as the source of pain, fever, and diarrhea management agent.
Emerging Trends and Hot Spots in Hepatic Glycolipid Metabolism Research From 2002 to 2021: A Bibliometric Analysis
Authors: Zhou Yanyu , Lin Xiaoqi , Yin Suqing , Zhu Ling , Yang Yuting , Li Yixuan , Wang Baoshan , Jiao Yingfu , Yu Weifeng , Gao Po , Yang Liqun
Published: July 2022

Glycolipid metabolic diseases, including type 2 diabetes, non-alcoholic fatty liver disease, obesity, hypertension, dyslipidemia, and atherosclerosis, which have become a major public health concern worldwide, are mainly triggered by hepatic glycolipid metabolism disorder. Bibliometric analysis has provided a comprehensive review of developments in hepatic glycolipid metabolism research and changes in research hotspots over the past 20 years. The articles regarding hepatic glycolipid metabolism from 2002 to 2021 were identified from the Science Citation Index-Expanded of Web of Science Core Collection. Acquired data were then processed by the CiteSpace software and the Online Analysis Platform of Literature Metrology to analyze trends and predict hot spots in this field. A total of 4,856 articles regarding hepatic glycolipid metabolism published from 2002 to 2021 were selected. The leading country was China. The Chinese Academy of Sciences was the most productive institution. Co-citation cluster labels revealed characteristics of ten main clusters: non-alcoholic fatty liver disease, gut microbiota, adiponectin, fructose, fgf21, fatty acid, liver x receptor, nr4a, obese mice, and bile acids. Keyword bursts analysis indicated that management, non-alcoholic fatty liver disease, and modulation were the newly emerging research hot spots. We described the overall structure of scientific research on hepatic glycolipid metabolism and presented systematic information to other researchers. The current focus on NAFLD and gut microbiota is critical to further study and will help explore effective therapeutic strategy for aberrant glycolipid metabolism in liver.
Serum Serine and the Risk of All-Cause Mortality: A Nested Case-Control Study From the China Stroke Primary Prevention Trial (CSPPT)
Authors: He Qiangqiang , Zhang Nan , Liang Qiongyue , Wang Zhuo , Chen Ping , Song Yun , Zhou Ziyi , Wei Yaping , Duan Yong , Wang Binyan , Qin Peiwu , Qin Xianhui , Xu Xiping
Published: July 2022

Background

Serine plays a key role in numerous cellular processes, the levels and metabolism is therefore of critical importance. However, few data are available to illustrate the association of serine with long-term health effects, especially, the predictive value for long-term mortality.

Objective

This study was conducted to evaluate the relationship between serum serine levels and all-cause mortality in general hypertensive patients in a longitudinal cohort, and to examine the potential effect modifiers.

Methods

A nested case-control (NCC) study was conducted utilizing 20702 hypertensive participants from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, actively controlled trial conducted from May 2008 to August 2013 in China. The current study included 291 cases of all-cause mortality and 291 controls matched on age (≤ 1 year), sex and treatment group. All-cause mortality was the main outcome in this analysis, which included death due to any reason.

Results

With the increase in serum serine levels, the risk of all-cause mortality first increased before flattening. After adjusting for related variables, the risk of mortality increased significantly with the increase of serum serine levels. Compared with group Q1, the mortality risk of group Q2, Q3 and Q4 were significantly increased [ORs, 95% CI: Q2: 2.32, (1.32–4.07); Q3: 2.59, (1.48–4.54); and Q4: 1.85, (1.07–3.22)]. In the exploratory analysis, we observed three effect modifiers, total homocysteine, 5-Methyltetrahydrofolate, and estimated glomerular filtration rate significantly modified the serum serine and all-cause mortality association.

Conclusion

Serum serine levels were significantly associated with an increased risk of all-cause mortality in hypertensive patients. Our results and findings, if confirmed further, suggest that serum serine should be considered as a marker for screening risk factors of mortality.

Clinical Trial Registration

[https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.], identifier [CSPPT, NCT00794885].
Dual-Energy Computed Tomography For Differentiation Between Osteoblastic Metastases and Bone Islands
Authors: Xu Chijie , Kong Lingling , Deng Xiaoyi
Published: July 2022

Objective

The objective of our study was to evaluate the utility of Rho/Z on dual-energy computed tomography (DECT) for the differentiation of osteoblastic metastases (OBMs) from bone islands (BIs).

Methods

DECT images of 110 patients with malignancies were collected. The effective atomic number (Z), electron density (Rho), dual energy index (DEI), and regular CT (rCT) values were measured by two observers. Independent-sample t-test was used to compare these values between OBMs and BIs. The diagnostic performance was assessed by receiver operating characteristic (ROC) analysis and the cutoff values were evaluated according to ROC curves.

Results

A total of 205 OBMs and 120 BIs were included. The mean values of Z, Rho, DEI, and rCT of OBMs were significantly lower than those of BIs, whereas the standard deviation values were higher than those of BIs (all p ≤ 0.05). ROC analysis showed that 11.86 was the optimal cutoff value for Z, rendering an area under the ROC curve (AUC) of 0.91, with a sensitivity of 91.2% and a specificity of 82.5%.

Conclusion

DECT can provide quantitative values of Z, Rho, and DEI and has good performance in differentiating between OBMs and BIs.
Low MxA Expression Predicts Better Immunotherapeutic Outcomes in Glioblastoma Patients Receiving Heat Shock Protein Peptide Complex 96 Vaccination
Authors: Wang Yi , Li Chunzhao , Chi Xiaohan , Huang Xijian , Gao Hua , Ji Nan , Zhang Yang
Published: July 2022

Heat shock protein peptide complex 96 (HSPPC-96) has been proven to be a safe and preliminarily effective therapeutic vaccine in treating newly diagnosed glioblastoma multiforme (GBM) (NCT02122822). However, the clinical outcomes were highly variable, rendering the discovery of outcome-predictive biomarkers essential for this immunotherapy. We utilized multidimensional immunofluorescence staining to detect CD4+ CD8+ and PD-1+ immune cell infiltration levels, MxA and gp96 protein expression in pre-vaccination GBM tissues of 19 patients receiving HSPPC-96 vaccination. We observed low MxA expression was associated with longer OS than high MxA expression (48 months vs. 20 months, p=0.038). Long-term survivors (LTS) exhibited significantly lower MxA expression than short-term survivors (STS) (p= 0.0328), and ROC curve analysis indicated MxA expression as a good indicator in distinguishing LTS and STS (AUC=0.7955, p=0.0318). However, we did not observe any significant impact of immune cell densities or gp96 expression on patient outcomes. Finally, we revealed the association of MxA expression with prognosis linked to a preexisting TCR clone (CDR3-2) but was independent of the peripheral tumor-specific immune response. Taken together, low MxA expression correlated with better survival in GBM patients receiving HSPPC-96 vaccination, indicating MxA as a potential biomarker for early recognition of responsive patients to this immunotherapy.

Clinical Trial Registration: ClinicalTrials.gov (NCT02122822) http://www. chictr.org.cn/enindex.aspx (ChiCTR-ONC-13003309).
The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression
Authors: Wu Qing , Shi Xintong , Pan Yating , Liao Xinyi , Xu Jiahua , Gu Xiaoqiang , Yu Wenlong , Chen Ying , Yu Guanzhen
Published: July 2022

Background

β-Elemene, an effective anticancer component isolated from the Chinese herbal medicine Rhizoma Zedoariae, has been proved to have therapeutic potential against multiple cancers by extensive clinical trials and experimental research. However, its preventive role in cholangiocarcinoma (CCA) and the mechanisms of action of β-elemene on CCA need to be further investigated.

Methods

A thioacetamide (TAA)-induced pre-CCA animal model was well-established, and a low dosage of β-elemene was intragastrically (i.g.) administered for 6 months. Livers were harvested and examined histologically by a deep-learning convolutional neural network (CNN). cDNA array was used to analyze the genetic changes of CCA cells following β-elemene treatment. Immunohistochemical methods were applied to detect β-elemene-targeted protein PCDH9 in CCA specimens, and its predictive role was analyzed. β-Elemene treatment at the cellular or animal level was performed to test the effect of this traditional Chinese medicine on CCA cells.

Results

In the rat model of pre-CCA, the ratio of cholangiolar proliferation lesions was 0.98% ± 0.72% in the control group, significantly higher than that of the β-elemene (0. 47% ± 0.30%) groups (p = 0.0471). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the top 10 pathways affected by β-elemene treatment were associated with energy metabolism, and one was associated with the cell cycle. β-Elemene inactivated a number of oncogenes and restored the expression of multiple tumor suppressors. PCDH9 is a target of β-elemene and displays an important role in predicting tumor recurrence in CCA patients.

Conclusions

These findings proved that long-term use of β-elemene has the potential to interrupt the progression of CCA and improve the life quality of rats. Moreover, β-elemene exerted its anticancer potential partially by restoring the expression of PCDH9.
Comparison of Different Machine Models Based on Multi-Phase Computed Tomography Radiomic Analysis to Differentiate Parotid Basal Cell Adenoma From Pleomorphic Adenoma
Authors: Zheng Yun-lin , Zheng Yi-neng , Li Chuan-fei , Gao Jue-ni , Zhang Xin-yu , Li Xin-yi , Zhou Di , Wen Ming
Published: July 2022

Objective

This study explored the value of different radiomic models based on multiphase computed tomography in differentiating parotid pleomorphic adenoma (PA) and basal cell tumor (BCA) concerning the predominant phase and the optimal radiomic model.

Methods

This study enrolled 173 patients with pathologically confirmed parotid tumors (training cohort: n=121; testing cohort: n=52). Radiomic features were extracted from the nonenhanced, arterial, venous, and delayed phases CT images. After dimensionality reduction and screening, logistic regression (LR), K-nearest neighbor (KNN) and support vector machine (SVM) were applied to develop radiomic models. The optimal radiomic model was selected by using ROC curve analysis. Univariate and multivariable logistic regression was performed to analyze clinical-radiological characteristics and to identify variables for developing a clinical model. A combined model was constructed by integrating clinical and radiomic features. Model performances were assessed by ROC curve analysis.

Results

A total of 1036 radiomic features were extracted from each phase of CT images. Sixteen radiomic features were considered valuable by dimensionality reduction and screening. Among radiomic models, the SVM model of the arterial and delayed phases showed superior predictive efficiency and robustness (AUC, training cohort: 0.822, 0.838; testing cohort: 0.752, 0.751). The discriminatory capability of the combined model was the best (AUC, training cohort: 0.885; testing cohort: 0.834).

Conclusions

The diagnostic performance of the arterial and delayed phases contributed more than other phases. However, the combined model demonstrated excellent ability to distinguish BCA from PA, which may provide a non-invasive and efficient method for clinical decision-making.