Search

Abstract Background Pathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases. Results in healthy human subjects are limited. Besides, most studies were performed using MRI methods with limited temporal resolution and significant partial-volume effects from blood and CSF. Methods This study employs the recently developed dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI approach to measure GBCA-distribution in the CSF immediately and 4 h after intravenous-GBCA administration in healthy subjects. With a temporal resolution of 10 s, cDSC MRI can track GBCA-induced CSF signal changes during the bolus phase, which has not been investigated previously. It employs a long echo-time (TE = 1347 ms) to suppress tissue and blood signals so that pure CSF signal is detected with minimal partial-volume effects. GBCA concentration in the CSF can be estimated from cDSC MRI. In this study, cDSC and FLAIR MRI were performed immediately and 4 h after intravenous GBCA administration in 25 healthy volunteers (age 48.9 ± 19.5 years; 14 females). Paired t-tests were used to compare pre-GBCA and post-GBCA signal changes, and their correlations with age were evaluated using Pearson-correlation-coefficients. Results At ~ 20 s post-GBCA, GBCA-induced cDSC signal changes were detected in the CSF around CP (ΔS/S = − 2.40 ± 0.30%; P

ObjectiveThe objective of this study is to examine the risk factors associated with apnea in hospitalized patients diagnosed with bronchiolitis and to develop a nomogram prediction model for the early identification of patients who are at risk of developing apnea.MethodsThe clinical data of patients diagnosed with acute bronchiolitis and hospitalized at the Children's Hospital of Nanjing Medical University between February 2018 and May 2021 were retrospectively analyzed. LASSO regression and logistic regression analysis were used to determine the risk factors for apnea in these patients. A nomogram was constructed based on variables selected through multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve and calibration curve were used to assess the accuracy and discriminative ability of the nomogram model, and decision curve analysis (DCA) was performed to evaluate the model's performance and clinical effectiveness.ResultsA retrospective analysis was conducted on 613 children hospitalized with bronchiolitis, among whom 53 (8.6%) experienced apnea. The results of Lasso regression and Logistic regression analyses showed that underlying diseases, feeding difficulties, tachypnea, WBC count, and lung consolidation were independent risk factors for apnea. A nomogram prediction model was constructed based on the five predictors mentioned above. After internal validation, the nomogram model demonstrated an AUC of 0.969 (95% CI 0.951–0.987), indicating strong predictive performance for apnea in bronchiolitis. Calibration curve analysis confirmed that the nomogram prediction model had good calibration, and the clinical decision curve analysis (DCA) indicated that the nomogram was clinically useful in estimating the net benefit to patients.ConclusionIn this study, a nomogram model was developed to predict the risk of apnea in hospitalized children with bronchiolitis. The model showed good predictive performance and clinical applicability, allowing for timely identification and intensified monitoring and treatment of high-risk patients to improve overall clinical prognosis.

H5, H7, and H9 are pivotal avian influenza virus (AIV) subtypes that cause substantial economic losses and pose potential threats to public health worldwide. In this study, a novel triplex fluorescence reverse transcription-loop-mediated isothermal amplification (TLAMP) assay was developed in which traditional LAMP techniques were combined with probes for detection. Through this innovative approach, H5, H7, and H9 subtypes of AIV can be simultaneously identified and differentiated, thereby offering crucial technical support for prevention and control efforts. Three primer sets and composite probes were designed based on conserved regions of the haemagglutinin gene for each subtype. The probes were labelled with distinct fluorophores at their 3′ ends, which were detached to release the fluorescence signal during the amplification process. The detection results were interpreted based on the colour of the TLAMP products. Then, the reaction conditions were optimized, and three primer sets and probes were combined in the same reaction system, resulting in a TLAMP detection assay for the differential diagnosis of AIV subtypes. Sensitivity testing with in vitro-transcribed RNA revealed that the detection limit of the TLAMP assay was 205 copies per reaction for H5, 360 copies for H7, and 545 copies for H9. The TLAMP assay demonstrated excellent specificity, no cross-reactivity with related avian viruses, and 100% consistency with a previously published quantitative polymerase chain reaction (qPCR) assay. Therefore, due to its simplicity, rapidity, sensitivity, and specificity, this TLAMP assay is suitable for epidemiological investigations and is a valuable tool for detecting and distinguishing H5, H7, and H9 subtypes of AIV in clinical samples.

Aims Neuroleptic malignant syndrome (NMS) is a rare, life-threatening idiosyncratic reaction to medications, specifically dopamine receptor antagonists. We report a case of a patient who initially developed extrapyramidal side effects (EPSE) and subsequently developed NMS after being treated with flupentixol depot. Methods A 64-year-old woman with an underlying recurrent depressive disorder with psychotic symptoms presented to a psychiatric hospital in June 2023. She exhibited self-neglect, low mood, paranoid delusions, and non-concordance to oral psychiatric medications. In the first week, she declined all oral medications and was subsequently started on flupentixol decanoate (Depixol) depot injection at 40 mg once every 2 weeks. While showing good improvements in her mental state, she began complaining of akathisia and dystonia since July 2023, consistent with extrapyramidal side effects secondary to flupentixol. The symptoms improved by lowering flupentixol to 30 mg every 2 weeks and adding procyclidine 5 mg twice daily and propranolol 20 mg three times daily. In early September 2023, she experienced severe restlessness, stiffness, muscle weakness and felt hot and clammy over 36 hours. Physical observations showed fever, tachycardia, and hypertension. Examination revealed diaphoresis, rigidity in both upper and lower limbs, lower limb weakness, and normal reflexes. Blood tests indicated acute kidney injury (AKI) stage 1, deranged liver function tests, and a creatinine kinase (CK) level of 9405. She was promptly admitted to the medical hospital for NMS and received extensive intravenous fluid rehydration along with oral Dantrolene. She made a complete recovery, and Depixol was discontinued. Two weeks later, she was started on quetiapine and gradually titrated to 50 mg once daily. Results EPSE and NMS are associated with dopamine receptor blockade and commonly occur during the initiation or dosage increment of neuroleptic medications. NMS is rare but life-threatening, presenting with manifestations of muscle rigidity, pyrexia, altered mental status, sympathetic nervous system lability and elevated CK. In our case, our patient, who recently started taking neuroleptic medication, experienced EPSE and later deteriorated acutely, raising a high suspicion of NMS. It is essential to consider other possible diagnoses, including serotonin syndrome, malignant hyperthermia, malignant catatonia and electrolyte disturbances. The commonly used diagnostic criteria include Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and Levenson's criteria but diagnosis of NMS remains clinical. The crucial step after identifying NMS is to immediately stop the neuroleptic agent, followed by supportive medical treatment. Conclusion Early recognition and prompt treatment of NMS in our patient led to a full recovery.

The beneficial effect of social interaction in mitigating the incidence of post-stroke depression (PSD) and ameliorating depressive symptoms has been consistently demonstrated through preclinical and clinical studies. However, the underlying relationship with oxytocin requires further investigation. In light of this, the present study aimed to explore the protective effect of pair housing on the development of PSD and the potential relationship with oxytocin receptors. The PSD model was induced by middle cerebral artery occlusion (MCAO) for 50 min, followed by 4-week isolated housing and restrained stress. Subsequently, each mouse in the pair-housing group (PH) was pair-housed with an isosexual healthy partner. Another group was continuously administrated fluoxetine (10 mg/Kg, i.p, once a day) for 3 weeks. To elucidate the potential role of oxytocin, we subjected pair-housed PSD mice to treatment with an oxytocin receptor (OXTR) antagonist (L368,889) (5 mg/Kg, i.p, once a day) for 3 weeks. At 31 to 32 days after MCAO, anxiety- and depressive-like behaviors were assessed using sucrose consumption, forced swim test, and tail-suspension test. The results showed that pair housing significantly improved post-stroke depression to an extent comparable to that of fluoxetine treatment. Furthermore, pair housing significantly decreased corticosterone in serum, increasing OXT mRNA expression in the hypothalamus. Treatment with L368,889 essentially reversed the effect of pair housing, with no discernible sex differences apart from changes in body weight. Pair housing increased hippocampal serotonin (5-HT), but treatment with L368,889 had no significant impact. Additionally, pair housing effectively reduced the number of reactive astrocytes and increased Nissl's body in the cortex and hippocampal CA3 regions. Correspondingly, treatment with L368,889 significantly reversed the changes in the Nissl's body and reactive astrocytes. Moreover, pair housing downregulated mRNA levels of TNF-α, IL-1β, and IL-6 in the cortex caused by PSD, which was also reversed by treatment with L368,889. In conclusion, pair housing protects against the development of PSD depending on OXT and OXTR in the brain, with no significant divergence based on sex. These findings provide valuable insights into the potential of social interaction and oxytocin as therapeutic targets for PSD. Further research into the underlying mechanisms of these effects may contribute to the development of novel treatments for PSD.

Abstract Objective To create a nomogram for predicting the likelihood of venous thromboembolism (VTE) in colon cancer patients from China. Methods The data of colon cancer patients from Chongqing University Cancer Hospital between 2019 and 2022 were analyzed. Patients were divided into training set and internal validation set by random split‐sample method in a split ratio of 7:3. The univariable and multivariable logistic analysis gradually identified the independent risk factors for VTE. A nomogram was created using all the variables that had a significance level of p

The glymphatic system, a macroscopic waste clearance system in the brain, is crucial for maintaining neural health. It facilitates the exchange of cerebrospinal and interstitial fluid, aiding the clearance of soluble proteins and metabolites and distributing essential nutrients and signaling molecules. Emerging evidence suggests a link between glymphatic dysfunction and the pathogenesis of neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s disease. These disorders are characterized by the accumulation and propagation of misfolded or mutant proteins, a process in which the glymphatic system is likely involved. Impaired glymphatic clearance could lead to the buildup of these toxic proteins, contributing to neurodegeneration. Understanding the glymphatic system’s role in these disorders could provide insights into their pathophysiology and pave the way for new therapeutic strategies. Pharmacological enhancement of glymphatic clearance could reduce the burden of toxic proteins and slow disease progression. Neuroimaging techniques, particularly MRI-based methods, have emerged as promising tools for studying the glymphatic system in vivo. These techniques allow for the visualization of glymphatic flow, providing insights into its function under healthy and pathological conditions. This narrative review highlights current MRI-based methodologies, such as motion-sensitizing pulsed field gradient (PFG) based methods, as well as dynamic gadolinium-based and glucose-enhanced methodologies currently used in the study of neurodegenerative disorders.

Abstract In China, the prevalence of diabetic retinopathy (DR) is increasing, so it is necessary to provide convenient and effective community outreach screening programs for DR, especially in rural and remote areas. The purpose of this study was to use the results of ophthalmologists as the gold standard to evaluate the accuracy of community general practitioners' judgement and grading of DR to find a feasible and convenient DR screening method to reduce the risk of visual impairment and blindness in known diabetes patients. Retinal images of 1646 diabetic patients who underwent DR screening through teleophthalmology at Nanchang First Hospital were collected for 30 months (January 2020 to June 2022). Retinal images were collected without medication for mydriasis, stored by community general practitioner, and diagnosed by both community general practitioner and ophthalmologist of our hospital through teleophthalmology. The grading of ophthalmologist was used as a reference or gold standard for comparison with that of community general practitioner. A total of 1646 patients and 3185 eyes were examined, including 2310 eyes with DR. The evaluation by the community general practitioner had a Kappa value of 0.578, sensitivity of 80.58%, specificity of 89.94%, and accuracy of 83.38%% in 2020; a Kappa value of 0.685, sensitivity of 95.43%, specificity of 78.55%, and accuracy of 90.77% in 2021; and a Kappa value of 0.744, sensitivity of 93.99%, specificity of 88.97%, and accuracy of 92.86% in 2022. Teleophthalmology helped with large-scale screening of DR and made it possible for community general practitioner to grade images with high accuracy after appropriate training. It is possible to solve the current shortage of eye care personnel, promote the early recognition of disease and reduce the impact of diabetes-associated blindness.

Abstract We calculate the soft function using lattice QCD in the framework of large momentum effective theory incorporating the one-loop perturbative contributions. The soft function is a crucial ingredient in the lattice determination of light cone objects using transverse-momentum-dependent (TMD) factorization. It consists of a rapidity-independent part called intrinsic soft function and a rapidity-dependent part called Collins-Soper kernel. We have adopted appropriate normalization when constructing the pseudoscalar meson form factor that is needed in the determination of the intrinsic part and applied Fierz rearrangement to suppress the higher-twist effects. In the calculation of CS kernel we consider a CLS ensemble other than the MILC ensemble used in a previous study. We have also compared the applicability of determining the CS kernel using quasi TMDWFs and quasi TMDPDFs. As an example, the determined soft function is used to obtain the physical TMD wave functions (WFs) of pion and unpolarized iso-vector TMD parton distribution functions (PDFs) of proton.

Abstract We study the pion electromagnetic form factor in the modulus squared dispersion relation, and do the model independent extraction of the chiral mass embedded in the sub-leading twist light-cone distribution amplitude. The motivation of this work is the recent measurement of timelike form factor in the resonant regions, which makes up the piece lacking solid QCD-based calculation. With the perturbative QCD calculation up to next-to-leading-order of strong coupling and twist four level of meson distribution amplitudes, we obtain the chiral mass of pion meson as $$m_0^\pi (1 \, \textrm{GeV}) = 1.31^{+0.27}_{-0.30} \, \textrm{GeV}$$ m 0 π ( 1 GeV ) = 1 . 31 - 0.30 + 0.27 GeV . Due to the chiral enhancement contribution from the sub-leading twist distribution amplitudes in the perturbative QCD calculation, we can not extract the lowest Gegenbauer moments of pion from the study of electromagnetic form factor. This problem could be settled down with the foresee Belle-II and BESIII measurement of the transition form factor especially in the large momentum transfers regions.

Background/purposeLeptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report an assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE).MethodsThis was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR).ResultsLME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008).Conclusion7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.

Abstract We recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel CD46-targeted alpha therapy based on YS5. We conjugated 212Pb, an in vivo generator of alpha-emitting 212Bi and 212Po, to YS5 through the chelator TCMC to create the radioimmunoconjugate, 212Pb-TCMC-YS5. We characterized 212Pb-TCMC-YS5 in vitro and established a safe dose in vivo. We next studied therapeutic efficacy of a single dose of 212Pb-TCMC-YS5 using three prostate cancer small animal models: a subcutaneous mCRPC cell line-derived xenograft (CDX) model (subcu-CDX), an orthotopically grafted mCRPC CDX model (ortho-CDX), and a prostate cancer patient-derived xenograft model (PDX). In all three models, a single dose of 0.74 MBq (20 µCi) 212Pb-TCMC-YS5 was well tolerated and caused potent and sustained inhibition of established tumors, with significant increases of survival in treated animals. A lower dose (0.37 MBq or 10 µCi 212Pb-TCMC-YS5) was also studied on the PDX model, which also showed a significant effect on tumor growth inhibition and prolongation of animal survival. These results demonstrate that 212Pb-TCMC-YS5 has an excellent therapeutic window in preclinical models including PDXs, opening a direct path for clinical translation of this novel CD46-targeted alpha radioimmunotherapy for mCRPC treatment.

This paper presents a comprehensive study on fall recognition and forecasting for reconfigurable stair-accessing robots by leveraging deep learning techniques. The proposed framework integrates machine learning algorithms and recurrent neural networks (RNNs), specifically Long Short-Term Memory (LSTM) and Bidirectional LSTM (BiLSTM), for fall detection of service robots on staircases. The reconfigurable stair-accessing robot sTetro serves as the platform, and the fall data required for training models are generated in a simulation environment. The two machine learning algorithms are compared and their effectiveness on the fall recognition task is reported. The results indicate that the BiLSTM model effectively classifies falls with a median categorical accuracy of 94.10% in simulation and 90.02% with limited experiments. Additionally, the BiLSTM model can be used for forecasting, which is practically valuable for making decisions well before the onset of a free fall. This study contributes insights into the design and implementation of fall detection systems for service robots used to navigate staircases through deep learning approaches. Our experimental and simulation data, along with the simulation steps, are available for reference and analysis via the shared link.

Abstract Background Methane (CH4) and brassinosteroids (BRs) are important signaling molecules involved in a variety of biological processes in plants. Results Here, marigold (Tagetes erecta L. ‘Marvel’) was used to investigate the role and relationship between CH4 and BRs during adventitious root (AR) formation. The results showed a dose-dependent effect of CH4 and BRs on rooting, with the greatest biological effects of methane-rich water (MRW, CH4 donor) and 2,4-epibrassinolide (EBL) at 20% and 1 μmol L− 1, respectively. The positive effect of MRW on AR formation was blocked by brassinoazole (Brz, a synthetic inhibitor of EBL), indicating that BRs might be involved in MRW-regulated AR formation. MRW promoted EBL accumulation during rooting by up-regulating the content of campestanol (CN), cathasterone (CT), and castasterone (CS) and the activity of Steroid 5α-reductase (DET2), 22α-hydroxylase (DWF4), and BR-6-oxidase (BR6ox), indicating that CH4 could induce endogenous brassinolide (BR) production during rooting. Further results showed that MRW and EBL significantly down-regulated the content of cellulose, hemicellulose and lignin during rooting and significantly up-regulated the hydrolase activity, i.e. cmcase, xylanase and laccase. In addition, MRW and EBL also significantly promoted the activity of two major cell wall relaxing factors, xyloglucan endotransglucosylase/hydrolase (XTH) and peroxidase, which in turn promoted AR formation. While, Brz inhibited the role of MRW on these substances. Conclusions BR might be involved in CH4-promoted AR formation by increasing cell wall relaxation.

Abstract Particle gluing operating parameters in particleboard (PB) production have an important influence on the mechanical properties of PBs. This study developed a multi-objective optimization model based on support vector regression (SVR) optimized by the non-dominated sorted genetic algorithm-II (NSGA2) to realize the multi-objective accurate prediction of PB mechanical properties (modulus of elasticity (MOE), modulus of rupture (MOR), and internal bonding (IB) strength) by adjusting particle gluing operating parameters. The NSGA2-SVR multi-objective prediction model was trained by 496 groups of experimental data of particle gluing operating parameters and PB mechanical properties. The prediction results of the NSGA2-SVR multi-objective prediction model were evaluated by 124 groups of experimental data and compared with the prediction results of the back propagation neural network (BPNN) model, general regression neural network (GRNN) model, and SVR model. The mean absolute percentage errors (MAPEs) of the NSGA2-SVR model were 49.11%, 33.64%, and 24.20% lower than that of the BPNN model, GRNN model, and SVR model, respectively. The Theil’s inequality coefficients (TICs) of the NSGA2-SVR model were 40.93%, 27.39%, and 18.58% lower than that of the BPNN model, GRNN model, and SVR model, respectively. The results showed that the multi-objective prediction model based on NSGA2-SVR has a superior fitting and higher prediction accuracy for the prediction performance of particle gluing operating parameters, and the NSGA2-SVR model can be applied to the multi-objective synchronous prediction of particle gluing operating parameters in the PB production line.

Abstract 7‐Tesla (T) magnetic resonance imaging may allow for higher resolution images but may produce greater acoustic noise than 1.5‐ and 3‐T scanners. We sought to characterize the intensity of acoustic noise from 7‐ versus 3‐T scanners. A‐weighted sound pressure levels from 5 types of pulse sequences used for brain and inner ear imaging in 3‐ and 7‐T scanners were measured. Time‐averaged sound level and maximum sound levels generated for each sequence were compared. Time‐averaged sound levels exceeded 95 dB and reached maximums above 105 dB on the majority of 3‐ and 7‐T scans. The mean time‐averaged sound level and maximum sound level across pulse sequences were greater in 7‐ than 3‐T (105.6 vs 91.4, P = .01; 114.0 vs. 96.5 dB, P

Abstract Purpose External ventricular drains (EVD) are commonly used in aneurysmal subarachnoid hemorrhage (aSAH) patients and can be life-saving by diverting cerebrospinal fluid. However, the overall relationship between EVD use and outcome is poorly understood. Methods In an exploratory analysis of an aSAH patient cohort, we examined EVD use in relation to modified Rankin Scale (mRS) at hospital discharge and at 6 months (unfavorable outcome = mRS > 2) using univariable and multivariable analyses. Results EVDs were placed in 31 of 56 (55.4%) patients and more often in women than men (66.7% vs 35.0%, p = 0.022) despite similar rates of hydrocephalus. Women had greater ICU [18 (13.5–25) vs 11.5 (6.5–18.5) days, p = 0.014] and hospital lengths of stay (LOS) [20.5 (16.5–34) vs 13.5 (10.5–27) days, p = 0.015] than men and greater mRS at discharge [4 (3–5) vs 3 (2–3.5), p = 0.011] although mRS at 6 months was similar. Patients with EVDs had longer ICU and hospital LOS and greater mRS at discharge [5 (3–6) vs 2 (2–3), p

On 21 May 2021, an earthquake of moment magnitude (Mw) 7.4 occurred near Maduo county in Qinghai Province China. This is the first major earthquake that occurred in the interior of the Bayan Har block in the Tibetan Plateau over the past 70 decades. Focusing on this event, we conducted a study on three-dimensional (3D) coseismic displacement reconstruction and its tectonic implication. We acquired both Synthetic Aperture Radar (SAR) and optical imaging satellite imagery, including SAR images from Sentinel-1 and Advanced Land Observation Satellite-2 (ALOS-2) as well as the multi-spectrum images from the Sentinel-2 (S2) satellite. We applied the Interferometric SAR (InSAR) and pixel-offset tracking (POT) techniques to coseismic SAR data pairs and reconstructed two dimensional displacements. With the constructed displacement fields in multiple viewing directions, we resolved the 3D coseismic displacements (north-south, east-west, and up components) by integrating the regional strain model with variance components estimation (SM-VCE). We recommend using the standard deviation value at each grid cell, which can be calculated in the resampling, as the initial weight. Based on the resolved 3D coseismic displacements, we further estimated the dip angles for the two segments (F4 and F5) in the east of the rupture zone. The associated moment magnitude is about Mw7.4, which corresponds to the released energy of ∼ 1.74×1020 Nm.

T2-prepared (T2prep) blood oxygenation level dependent (BOLD) functional MRI (fMRI) is an alternative fMRI approach developed to mitigate the susceptibility artifacts that are typically observed in brain regions near air-filled cavities, bleeding and calcification, and metallic objects in echo-planar-imaging (EPI) based fMRI images. Here, T2prep BOLD fMRI was evaluated in an event-related paradigm for the first time. Functional experiments were performed using gradient-echo (GRE) EPI, spin-echo (SE) EPI, and T2prep BOLD fMRI during an event-related visual task in 10 healthy human subjects. Each fMRI method was performed with a low (3.4 × 3.4 × 4 mm3) and a high (1.5 mm isotropic) spatial resolution on 3T and a high resolution (1.5 mm isotropic) on 7T. Robust activation were detected in the visual cortex with all three fMRI methods. In each group of fMRI scans (3T low resolution, 3T high resolution, and 7T high resolution), GRE EPI showed the highest signal change (ΔS/S), largest full-width-at-half-maximum (FWHM) and longest time-to-peak (TTP) extracted from the hemodynamic response functions (HRF), indicating substantial signal contribution from large draining veins which have longer response times than microvessels. In contrast, T2prep BOLD showed the lowest ΔS/S, smallest FWHM, and shortest TTP, suggesting that T2prep BOLD may have a purer T2-weighted BOLD contrast that is more sensitive to microvessels compared to GRE/SE EPI BOLD. This trend was more obvious in fMRI scans performed with a lower spatial resolution on a lower field (3T with a 3.4 × 3.4 × 4 mm3 voxel). Scan-rescan reproducibility in the same subjects was comparable among the three fMRI methods. The results from the current study are expected to be useful to establish T2prep BOLD as a useful alternative fMRI approach for event-related fMRI in brain regions with large susceptibility artifacts.

Abstract Background Human granulocytic anaplasmosis is a tick-borne zoonotic disease caused by Anaplasma phagocytophilum. Coinfections with A. phagocytophilum and other tick-borne pathogens are reported frequently, whereas the relationship between A. phagocytophilum and flea-borne Yersnia pestis is rarely concerned. Results A. phagocytophilum and Yersnia pestis were discovered within a Marmota himalayana found dead in the environment, as determined by 16S ribosomal rRNA sequencing. Comparative genomic analyses of marmot-derived A. phagocytophilum isolate demonstrated its similarities and a geographic isolation from other global strains. The 16S rRNA gene and GroEL amino acid sequence identity rates between marmot-derived A. phagocytophilum (JAHLEX000000000) and reference strain HZ (CP000235.1) are 99.73% (1490/1494) and 99.82% (549/550), respectively. 16S rRNA and groESL gene screenings show that A. phagocytophilum is widely distributed in marmots; the bacterium was more common in marmots found dead (24.59%, 15/61) than in captured marmots (19.21%, 29/151). We found a higher Y. pestis isolation rate in dead marmots harboring A. phagocytophilum than in those without it (2 = 4.047, p

Abstract The particleboard (PB) production is an extremely complex process, many operating parameters affecting panel quality. It is a big challenge to optimize the PB production parameters. The production parameters of particle gluing have an important influence on the internal bond (IB) strength of PB. In this study, using grey relation analysis (GRA) and support vector regression (SVR) algorithm, a prediction model was developed to accurately predict IB of PB through particle gluing processing parameters in a PB production line. GRA was used to analyze the grey relational grade between the particle gluing processing parameters and IB of PB, and the variables were screened. The SVR algorithm was used to train 724 groups of particle gluing sample data between six particle gluing processing parameters and IB. The SVR model was tested with 181 sets of experimental data. The SVR model was verified by 181 sets of experimental data, and the values of mean absolute error (MAE), mean relative error (MRE), root mean square error (RMSE), and Theil’s inequality coefficient (TIC) of the model were 0.008, 0.017, 0.013, and 0.014, respectively. The results showed that the prediction performance of the nonlinear regression prediction model based on GRA–SVR is superior, and the GRA–SVR prediction model can be used to real-time predict the IB in the PB production line.

Abstract Background SERPINB1 is involved in the development of a variety of diseases. The purpose of this study was to explore the effect of SERPINB1 on acute myocardial infarction (AMI). Methods Serum SERPINB1 level of AMI patients was measured for receiver operating characteristic curve analysis. The AMI rat model was constructed to observe myocardial damage, and the H9C2 cell oxygen glucose deprivation (OGD) model was constructed to detect cell viability. Transthoracic echocardiography was used to assess the cardiac function. TTC staining and HE staining were used to detect pathologic changes of myocardial tissues. The apoptosis of myocardial tissues and cells were measured by TUNLE staining and flow cytometry assay. CCK-8 assay to measure cell viability. SERPINB1 expression was measured by qRT-PCR. Protein expression was measured by western blot. Results The serum SERPINB1 level was down-regulated in AMI patients. AMI modeling reduced the SERPINB1 expression level, induced inflammatory cells infiltrated, and myocardial apoptosis. OGD treatment inhibited cell viability and promoted apoptosis. The AMPK/mTOR pathway was inhibited in AMI rats and OGD-treated H9C2 cells. Overexpression of SERPINB1 reduced infarct size and myocardial apoptosis of AMI rats, inhibited apoptosis of H9C2 cells, and activated AMPK/mTOR pathway. However, AMPK inhibitor Dorsomorphin reversed the protective effect of SERPINB1 on myocardial cells. Conclusion SERPINB1 overexpression relieved myocardial damage induced by AMI via AMPK/mTOR pathway.

The problem of two-dimensional irregular packing involves the arrangement of objects with diverse shapes and sizes within a given area. This challenge arises across various industrial sectors, where effective packing optimization can yield cost savings, enhanced productivity, and reduced material waste. Existing methods for addressing the two-dimensional irregular packing problem encounter several challenges, such as limited computing resources, a prolonged solving time, and the propensity to converge to local optima. To address this issue, this study proposes a hybrid algorithm called the GA-LP algorithm to optimize the two-dimensional irregular packing problem in the manufacturing industry. The algorithm combines the global search capability of a genetic algorithm with the precise solving characteristics of linear programming. Matheuristics merges the advantages of metaheuristics, such as genetic algorithms, and mathematical programming, such as linear programming. The algorithm employs the no-fit-polygon technique along with the bottom-left and lowest-gravity center mixing placement strategies to acquire an initial solution via the utilization of a genetic algorithm. The algorithm then optimizes the solution obtained by the genetic algorithm using linear programming to obtain the final packing result. Experimental results, drawn from a real case involving the European Special Interest Group on Cutting and Packing (ESICUP) demonstrate that the GA-LP algorithm outperforms two hybrid algorithms from the relevant literature. Compared with recent methods, this algorithm can increase the best and average utilization rates by up to 5.89% and 4.02%, respectively, with important implications for improving work quality in areas such as packing and cutting.

Objective We aimed to develop a nomogram to predict the risk of severe influenza in previously healthy children. Methods In this retrospective cohort study, we reviewed the clinical data of 1135 previously healthy children infected with influenza who were hospitalized in the Children's Hospital of Soochow University between 1 January 2017 and 30 June 2021. Children were randomly assigned in a 7:3 ratio to a training or validation cohort. In the training cohort, univariate and multivariate logistic regression analyses were used to identify risk factors, and a nomogram was established. The validation cohort was used to evaluate the predictive ability of the model. Result Wheezing rales, neutrophils, procalcitonin > 0.25 ng/mL, Mycoplasma pneumoniae infection, fever, and albumin were selected as predictors. The areas under the curve were 0.725 (95% CI: 0.686–0.765) and 0.721 (95% CI: 0.659–0.784) for the training and validation cohorts, respectively. The calibration curve showed that the nomogram was well calibrated. Conclusion The nomogram may predict the risk of severe influenza in previously healthy children.

Abstract Background This study aimed to describe the causative organisms of neonatal late-onset sepsis (LOS) and their antimicrobial resistance in Suzhou, Southeast China over a 7-year period. Methods We performed a retrospective study on neonates with LOS from Jan1, 2011 to Dec 31, 2017. The demographic, clinical, and laboratory data of neonates with LOS were analyzed. Logistic regression was used to investigate the risk factors with mortality. Results During the study period, 202 neonates with LOS were finally identified. The most common pathogens were Escherichia coli (29.2%), followed by Klebsiella pneumoniae (19.3%), and Coagulase-negative Staphylococcus (CoNS) (16.8%). Nearly 90% of the K. pneumoniae were resistant to cefazolin and 71.8% to ceftazidime. Thirty-four patients (16.8%) died. Multivariable logistic regression showed that significant predictors of mortality were birth weight

Transient receptor potential melastatin 2 (TRPM2) is an important ion channel that represents a potential target for treating injury caused by cerebral ischemia. However, it is unclear whether reducing TRPM2 expression can help repair cerebral injury, and if so what the mechanism underlying this process involves. This study investigated the protective effect of reducing TRPM2 expression on pheochromocytoma (PC12) cells injured by oxygen-glucose deprivation (OGD). PC12 cells were transfected with plasmid encoding TRPM2 shRNAS, then subjected to OGD by incubation in glucose-free medium under hypoxic conditions for 8 hours, after which the cells were allowed to reoxygenate for 24 hours. Apoptotic cells, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels were detected using flow cytometry. The relative expression of C-X-C motif chemokine ligand 2 (CXCL2), NACHT, LRR, and PYD domain–containing protein 3 (NALP3), and caspase-1 were detected using fluorescence-based quantitative reverse transcription-polymerase chain reaction and western blotting. The rates of apoptosis, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels in the TRPM2-shRNA + OGD group were lower than those observed in the OGD group. Taken together, these results suggest that TRPM2 knockdown reduces OGD-induced neuronal injury, potentially by inhibiting apoptosis and reducing oxidative stress levels, mitochondrial membrane potentials, intracellular calcium concentrations, and NLRP3 inflammasome activation.

Based on the finite element theory, a joint-plane modeling method is employed to connect the corresponding nodes at the joint surface of the woodworking computer numerical control (CNC) machining center bed with a 2-node 12-degree-of-freedom unit. A spatial element model is established, which can show the state of the nodes between joint surfaces when they are stretched, compressed, or twisted; and it can help build a woodworking CNC machining center on a finite element model of bed with the characteristics of the joint surface. The simulated analysis is performed on the model and is compared with the result of simulated analysis on the bed model that ignores the characteristics of the joint surface and modal experiment. The comparison verifies the effectiveness of the modeling method based on the characteristics of the joint surface. The weak link of the machine bed structure is analyzed and optimized. The natural frequency of the bed is improved by2.55% ~ 11.3%. The displacement is reduced by a maximum of 19.4%, and dynamic performance of the bed is improved.

Purpose: To predict the prognosis of craniopharyngioma in children by optical coherence tomography angiography (OCTA).Methods: We evaluated if the relationship between preoperative OCTA of the choroidal capillary density (CCD) and visual outcome continued over long-term visual recovery in 38 patients undergoing craniopharyngioma resection. Patients were evaluated 3 times: 1 week before surgery (Visit1), followed-up at 6–10 weeks (Visit2), and 9–15 months (Visit3) after surgery.Results: In total 38 patients (70 eyes) with craniopharyngiomas, which included 20 (52.6%) boys and 18 (47.4%)girls, the mean age was 11.8 ± 2.7 years (range: 6–18 years). The age (p = 0.71), gender (p = 1.00), mean refractive error (p = 0.55), and axial length (p = 0.23) of 38 normal volunteers (76 eyes) were matched. After surgery, the cross-compression of patients was relieved. The average visual acuity change in the normal CCD group was 0.07 ± 0.02; the average visual acuity change in the low CCD group was 0.01 ± 0.01, p < 0.001. Preoperative CCD value is related to the preoperative BCVA (p < 0.001), and the visual function after the long-term follow-up (9–15 months) (p < 0.001). The prognosis of CCD has the same trend as the BCVA. Further correlation analysis shows that CCD and BCVA are significantly correlated (r = 0.878; p < 0.001). CCD has a weak but significant correlation both with MD (r = 0.19; p < 0.001) and PSD (r = −0.21; p

In this paper, the influence of a surface ultrasonic rolling process on the surface integrity of TC4 titanium alloy and its influence on the fatigue properties were studied. By comparing and analyzing the surface roughness, microhardness, residual stress, microstructure, and fatigue fracture, the surface strengthening and modification mechanism of TC4 titanium alloy is discussed. The results show that the surface roughness of titanium alloy is observably decreased after the suitable surface ultrasonic rolling process, and the maximum Ra value can be reduced to 0.052 μm. The axial residual stress on the specimen surface can be increased to −685 MPa. The hardening rate of the surface hardness of the sample was 35%. The residual compressive stress and hardness of the sample surface increased with the increase of static pressure. However, the increase of feed rate and rational speed was less. After surface ultrasonic rolling, the sample surface exhibited obvious grain refinement, the number of high-angle boundaries increased to include the formation of nano-equiaxed grains. The fatigue strength increased by 52% from 280 MPa to 425 MPa. Under 450 MPa, the fatigue life of samples with SUR 2 was the highest, at about 7.7 times that of the original samples. The surface integrity of titanium alloy samples after surface ultrasonic rolling treatment is greatly improved, which is the reason for the significant increase in fatigue life of the samples.

Because of serious electromagnetic pollution caused by the widespread use of radio frequency equipment, the study of electromagnetic interference (EMI) shielding materials has been a long-standing topic. Carbon fiber and graphene composites have great potential as EMI shielding materials due to their unique microstructure and electrical conductivity. In this work, a novel kind of core-shell composite is fabricated based on the pore-rich pine needles-derived carbon fibers (coded as PNCFs) core and the graphene shell. The pore-rich PNCFs are created by KOH activation, and the integration between the pore-rich PNCFs and the graphene relies on a plasma-enhanced chemical vapor deposition (PECVD) method. The conductivity of the pore-rich PNCFs@graphene core-shell composite reaches 4.97 S cm−1, and the composite has an excellent EMI shielding effectiveness (SE > 70 dB over X-band (8.2–12.4 GHz)) and achieves a maximum value of ~77 dB at 10.4 GHz, which is higher than many biobased EMI shielding materials in the recent literature. By calculation and comparison, the large absorption loss (accounting for 90.8% of total loss) contributes to reducing secondary radiation, which is quite beneficial for stealth uses. Thus, this work demonstrates a promising design method for the preparation of green high-performance composites for EMI shielding and stealth applications (such as warcrafts, missiles, and stealth wears).

Olfaction is a fundamental sense that plays a vital role in daily life in humans, and can be altered in neuropsychiatric and neurodegenerative diseases. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) using conventional echo-planar-imaging (EPI) based sequences can be challenging in brain regions important for olfactory processing, such as the olfactory bulb (OB) and orbitofrontal cortex, mainly due to the signal dropout and distortion artifacts caused by large susceptibility effects from the sinonasal cavity and temporal bone. To date, few studies have demonstrated successful fMRI in the OB in humans. T2-prepared (T2prep) BOLD fMRI is an alternative approach developed especially for performing fMRI in regions affected by large susceptibility artifacts. The purpose of this technical study is to evaluate T2prep BOLD fMRI for olfactory functional experiments in humans. Olfactory fMRI scans were performed on 7T in 14 healthy participants. T2prep BOLD showed greater sensitivity than GRE EPI BOLD in the OB, orbitofrontal cortex and the temporal pole. Functional activation was detected using T2prep BOLD in the OB and associated olfactory regions. Habituation effects and a bi-phasic pattern of fMRI signal changes during olfactory stimulation were observed in all regions. Both positively and negatively activated regions were observed during olfactory stimulation. These signal characteristics are generally consistent with literature and showed a good intra-subject reproducibility comparable to previous human BOLD fMRI studies. In conclusion, the methodology demonstrated in this study holds promise for future olfactory fMRI studies in the OB and other brain regions that suffer from large susceptibility artifacts.

The coronavirus disease-2019 (COVID-19) pandemic has had an unprecedented impact leading to novel adaptations in post-graduate medical education for cardiovascular and general internal medicine. Whilst the results of initial community COVID-19 vaccination are awaited, continuation of multimodality teaching and training that incorporates telelearning will have enduring benefit to post-graduate education and will place educational establishments in good stead to nimbly respond in future pandemic-related public health emergencies. With the rise in innovative virtual learning solutions, medical educators will have to leverage technology to develop electronic educational materials and virtual courses that facilitate adult learning. Technology-enabled virtual learning is thus a timely progression of hybrid classroom initiatives that are already adopted to varying degrees, with a need for faculty to serve as subject matter experts, to host and moderate online discussions, and to provide feedback and overall mentorship. As an extension from existing efforts, simulation-based teaching (SBT) and learning and the use of mixed reality technology should also form a greater core in the cardiovascular medicine curriculum. We highlight five foundational themes for building a successful e-learning model in cardiovascular and general post-graduate medical training: (1) digital solutions and associated infrastructure; (2) equity in access; (3) participant engagement; (4) diversity and inclusion; and (5) patient confidentiality and governance framework. With digitalisation impacting our everyday lives and now how we teach and train in medicine, these five guiding principles provide a cognitive scaffold for careful consideration of the required ecosystem in which cardiovascular and general post-graduate medical education can effectively operate. With due consideration of various e-learning options and associated infrastructure needs; and adoption of strategies for participant engagement under sound and just governance, virtual training in medicine can be effective, inclusive and equitable through the COVID-19 era and beyond.

Background: To update the efficacy and safety data of monoclonal antibodies for the treatment of neuromyelitis optica spectrum disorders (NMOSD) and explore the differences in the effect of treatment between patients seropositive and seronegative for AQP4-IgG. Methods: PubMed, Embase, and the Cochrane Library published up to July 2020 were searched for randomized controlled trials (RCTs) of monoclonal antibodies treatment (mAb) in patients with NMOSD. The primary outcome was the hazard ratio (HR) for relapse. The secondary outcomes included Expanded Disability Status Scale (EDSS) changes from baseline, adverse events (AEs), and serious adverse events (SAEs). A random-effects model was applied for the effect of heterogeneity among trials. Results: We included 603 patients (monoclonal antibody group, n=382, and control group, n=221) from seven RCTs. There were fewer relapses in the mAb group (HR=0.32, 95% CI: 0.23-0.46, p

Abstract Background POLR3-related leukodystrophy is an autosomal recessive neurodegenerative disorder characterized by onset time ranging from the neonatal period to late childhood, progressive motor decline that manifests as spasticity, ataxia, tremor, and cerebellar symptoms, as well as mild cognitive regression and hypodontia. POLR3-related leukodystrophy belongs to the family of RNA polymerase III-related leukodystrophy, which are caused by biallelic mutations in the POLR3A, POLR3B, POLRC1, or POLR3K genes. Case presentation In this study, we report a female child with POLR3-related leukodystrophy manifesting as cognitive decline, moderate dysarthria, motor decline, cerebellar syndrome, short stature, dysphagia, hypodontia, and mild delayed myelination by brain imaging. Interestingly, polytrichia and bronchodysplasia were first observed in a POLR3-related leukodystrophy patient. Medical exome sequencing with high coverage depth was employed to identify potential genetic variants in the patient. Novel compound heterozygous mutations of the POLR3A gene, c.1771-6C > G and c.2611del (p.M871Cfs*8), were detected. One of them is an uncommon splice site mutation, and this is the first report of this mutation in a Chinese family. The father was determined to be a heterozygous carrier of the c.2611del (p.M871Cfs*8) mutation and the mother a heterozygous carrier of the c.1771-6C > G mutation. Conclusion The patient’s newly emerged clinical features and mutations provide useful information for further exploration of genotype-phenotype correlations of POLR3-related leukodystrophy.

Cardiovascular disease and cancer are leading contributors to the global disease burden. As a result of cancer therapy-related cardiotoxicities, cardiovascular disease results in significant morbidity and mortality in cancer survivors and patients with active cancer. There is an unmet need for management of cardio-oncology conditions, which is predicted to reach epidemic proportions, and better understanding of their pathophysiology and treatment is urgently required. The proposed mechanisms underlying cardiotoxicity induced by 5-fluorouracil (5-FU) are vascular endothelial damage followed by thrombus formation, ischaemia secondary to coronary artery vasospasm, direct toxicity on myocardium and thrombogenicity. In patients with angina and electrocardiographic evidence of myocardial ischaemia due to chemotherapy-related coronary artery vasospasm, termination of chemotherapy and administration of calcium channel blockers or nitrates can improve ischaemic symptoms. However, coronary artery vasospasm can reoccur with 5-FU re-administration with limited effectiveness of vasodilator prophylaxis observed. While pre-existing coronary artery disease may increase the ischaemic potential of 5-FU, cardiovascular risk factors do not appear to completely predict the development of cardiac complications. Pharmacogenomic studies and genetic profiling may help predict the occurrence and streamline the treatment of 5-FU-induced coronary artery vasospasm. Echocardiographic measures such as the Tei index may help detect subclinical 5-FU cardiotoxicity. Further research is required to explore the cardioprotective effect of agents such as coenzyme complex, GLP-1 analogues and degradation inhibitors on 5-FU-induced coronary artery vasospasm.

Objective To determine the risk factors for delayed radiographic resolution in children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and explore the most suitable time for interventional bronchoscopy. Methods This retrospective study involved 142 children with RMPP who were admitted to our hospital from 1 January 2015 to 31 December 2017. They were divided into a common resolution group and a delayed resolution group based on their chest radiograph series. Results Among the 142 patients, 67 showed common resolution on chest radiographs and 75 showed delayed resolution. Independent risk factors for delayed resolution were a clinical course of ≥11.5 days before the performance of interventional bronchoscopy, mucus plug formation, corticosteroid resistance, and atelectasis. When bronchoscopy was performed before the disease had been present for

For improving the emergency capacities during road transportation accidents of dangerous goods, this paper divides the accident emergency procedure into four subsystems: accident information processing, personnel rescue and evacuation, vehicle evacuation, and rescue materials delivery. On this basis, the causal mechanism and the loop diagrams of the emergency process are established by using the System Dynamics Method and Vensim software. First, six factors including transportation distance, the degree of mechanical modernization, delay time of personnel control, delay time of traffic information release, command level coefficient, and delay time of department arrival are selected as parameters to test the model’s sensitivity analysis. Then, the influences of the abovementioned factors on the observed value, such as the demand gap of on-site materials, number of people in safe area, number of vehicles in safe area, amount of disposal information, and the dynamic evolution behavior of the system, are analyzed. The results show that the transportation distance is shortened by half, and the time to fill the demand gap is reduced by 39%. The level of mechanical modernization is doubled, the peak inventory of materials in transit will increase by 9.2%, and the time to reach the peak will be shortened by 6.8%. If the delay time of personnel control is shortened by 480 s, the number of people to be evacuated in accident area will be reduced by 56. The delay time of traffic information release is shortened by 480 s, the number of vehicles to be evacuated is reduced by 74, and the time when the vehicle stops entering accident area is 1646 s in advance. The command level coefficient increases by 9.5%, and the speed of action execution increases by 9.6%.

Although the blood-brain barrier (BBB) is altered in most multiple sclerosis (MS) lesions, gadolinium enhancement is seen only in acute lesions. In this study, we aimed to investigate gadolinium-induced changes in T1 relaxation time in MS lesions on 7-tesla (7T) MRI as a means to quantify BBB breakdown in non-enhancing MS lesions. Forty-seven participants with MS underwent 7T MRI of the brain with a magnitude-prepared rapid acquisition of 2 gradient echoes (MP2RAGE) sequence before and after contrast. Subtraction of pre- and post-contrast T1 maps was used to measure T1 relaxation time change (ΔT1) from gadolinium. ΔT1 values were interrogated in enhancing white matter lesions (ELs), non-enhancing white matter lesions (NELs), and normal appearing white matter (NAWM) and metrics were compared to clinical data. ΔT1 was measurable in NELs (median: -0.139 (-0.304, 0.174) seconds; p < 0.001) and was negligible in NAWM (median: -0.001 (-0.036, 0.155) seconds; p = 0.516). Median ΔT1 in NELs correlated with disability as measured by Expanded Disability Status Scale (EDSS) (rho = -0.331, p = 0.026). Multiple measures of NEL ΔT1 variability also correlated with EDSS. NEL ΔT1 values were greater and more variable in patients with progressive forms of MS and greater in those not on MS treatment. Measurement of the changes in T1 relaxation time caused by contrast on 7T MP2RAGE reveals clinically relevant evidence of BBB breakdown in NELs in MS. This data suggests that NEL ΔT1 should be evaluated further as a potential biomarker of persistently disrupted BBB in MS.Although the blood-brain barrier (BBB) is altered in most multiple sclerosis (MS) lesions, gadolinium enhancement is seen only in acute lesions. In this study, we aimed to investigate gadolinium-induced changes in T1 relaxation time in MS lesions on 7-tesla (7T) MRI as a means to quantify BBB breakdown in non-enhancing MS lesions. Forty-seven participants with MS underwent 7T MRI of the brain with a magnitude-prepared rapid acquisition of 2 gradient echoes (MP2RAGE) sequence before and after contrast. Subtraction of pre- and post-contrast T1 maps was used to measure T1 relaxation time change (ΔT1) from gadolinium. ΔT1 values were interrogated in enhancing white matter lesions (ELs), non-enhancing white matter lesions (NELs), and normal appearing white matter (NAWM) and metrics were compared to clinical data. ΔT1 was measurable in NELs (median: -0.139 (-0.304, 0.174) seconds; p < 0.001) and was negligible in NAWM (median: -0.001 (-0.036, 0.155) seconds; p = 0.516). Median ΔT1 in NELs correlated with disability as measured by Expanded Disability Status Scale (EDSS) (rho = -0.331, p = 0.026). Multiple measures of NEL ΔT1 variability also correlated with EDSS. NEL ΔT1 values were greater and more variable in patients with progressive forms of MS and greater in those not on MS treatment. Measurement of the changes in T1 relaxation time caused by contrast on 7T MP2RAGE reveals clinically relevant evidence of BBB breakdown in NELs in MS. This data suggests that NEL ΔT1 should be evaluated further as a potential biomarker of persistently disrupted BBB in MS.

Bumblebee pollination is crucial to the production of tomato in protected cultivation. Both tomato yield and flavor play important roles in attracting attentions from growers and consumers. Compared with yield, much less work has been conducted to investigate whether and how pollination methods affect tomato flavor. In this study, the effects of bumblebee pollination, vibrator treatment, and plant growth regulator (PGR) treatment on tomato yield and flavor were tested in Gobi Desert greenhouses. Compared with vibrator or PGR treatments, bumblebee pollinated tomato had higher and more stable fruit set, heavier fruit weight, and more seed. We also found that the seed quantity positively correlated with fruit weight in both bumblebee pollinated, and vibrator treated tomato, but not in PGR treated tomato. Besides enhancing yield, bumblebee pollination improved tomato flavor. Bumblebee pollinated tomato fruits contained more fructose and glucose, but less sucrose, citric acid, and malic acid. Furthermore, the volatile organic compounds of bumblebee pollinated tomato were distinctive with vibrator or PGR treated tomato, and more consumer liking related compounds were identified in bumblebee pollinated tomato. Our findings provide new insights into the contributions of bee pollinator towards improving crop yield and quality, emphasizing the importance of bumblebee for tomato pollination.

Background. Several efforts have been made to find out a valuable marker to assist the diagnosis and differentiation of gangrenous/perforated appendicitis. We aimed to determine the diagnostic capacity of soluble B7H3 (sB7H3) in acute appendicitis (AA) and its accuracy as a predictor of the severity of appendicitis. Methods. 182 children were allocated into four groups as follows: control group (CG, 90), simple appendicitis (SA, 12), purulent appendicitis (PA, 49), and gangrenous appendicitis (GA, 31). Prior to appendectomy, blood was collected and sent for analysis of routine examination and cytokines (sB7H3 and TNF-α). We compared values of all measured parameters according to histological findings. Furthermore, we assigned AA patients into the nonperforated appendicitis group and the perforated appendicitis group. The diagnostic effects of significant markers were assessed by ROC curves. Results. Only the levels of CRP, FIB, and sB7H3 had a remarkable rising trend in AA-based groups, while differences in the levels of CRP and FIB between simple appendicitis and purulent appendicitis were not statistically significant. In addition, sB7H3 was found as the only marker in children with AA, which was markedly associated with the degree of histological findings of the appendix. Furthermore, sB7H3 had a high diagnostic value in predicting AA and complex appendicitis (PA+GA) in children. However, the diagnostic performance of sB7H3 for distinguishing PA from GA was not remarkable. Additionally, only the levels of CRP and sB7H3 were statistically different between the nonperforated appendicitis group and the perforated appendicitis group. The diagnostic performance of CRP and sB7H3 could not merely predict perforation of AA in children; however, the diagnostic performance was improved after combination. Conclusions. sB7H3 could be used as a valuable marker to predict the presence of AA and complex AA in children. However, the diagnostic value of sB7H3 to predict gangrenous/perforated appendicitis was not found to be remarkable. The combination of sB7H3 and CRP might improve the prediction of perforated appendicitis.

Objective: In view of the poor prognosis and difficulties in the diagnosis of osteosarcoma, and the functionality of microRNA-Let7A in different types of human cancers, our study aimed to explore the diagnostic and prognostic values of microRNA-Let7A for osteosarcoma. Methods: A total of 39 patients with osteosarcoma and 19 normal healthy people were included in this study. All patients received surgical resection, and tumor tissues as well as pericarcinomatous tissues were collected during surgical operation. Venous blood (2 ml) was extracted from each participant. Expression of microRNA-Let7A in tumor tissues and pericarcinomatous tissues, and expression of E2F2 and microRNA-Let7A in blood of each participant was detected by qRT-PCR. ROC analysis was performed to evaluate the diagnostic values of blood E2F2 and microRNA-Let7A for osteosarcoma, and prognostic values of microRNA-Let7A for osteosarcoma was evaluated by survival curve comparisons. Results: Expression level of microRNA-Let7A was significantly lower in tumor tissues than that in pericarcinomatous tissues. MicroRNA-Let7A expression in blood was significantly downregulated in osteosarcoma patients compared with normal control. Expression of microRNA-Let7A was negatively correlated with the expression of E2F2 in blood of osteosarcoma patients. Compared with E2F2, blood microRNA-Let7A can more effectively predict osteosarcoma. Overall survival rate of osteosarcoma patient with low blood expression level of miRNA-let-7a was significantly lower than that of patients with high blood expression level of miRNA-let-7a. Conclusion: Blood microRNA-Let7A is a promising diagnostic and prognostic biomarker for osteosarcoma. Keywords: Osteosarcoma, MicroRNA-Let7A, Venous blood, qRT-PCR, ROC, Pericarcinomatous

In this paper we calculate the next-to-leading-order (NLO) corrections to ρ-meson electromagnetic form factors by employing the kT factorization approach. We find that the NLO correction to Fi(Q2)(i=LT,TL) is around 30% of the leading-order (LO) contribution in the region Q2>2GeV2. The NLO correction to FLL(Q2) is close to 20% of the LO one in the region Q2>3GeV2. The NLO radiative corrections to the electric, magnetic, and quadruple form factors Fj(Q2)(j=1,2,3) are sizeable in magnitude and agree with those from other approaches.

Following the West, China exhibits a proactive attitude and conservative actions to developing entrepreneurial universities. This article deconstructs such a paradoxical approach by analysing the scholarly literature, policy discourses, and empirical data and their various perceptions of entrepreneurial universities in the Greater Bay Area (GBA). We conducted 71 interviews in four case universities to obtain empirical data for triangulation with the literature and policies. Our main research findings include the following: (1) there is a desire to introduce the concept of entrepreneurial universities from the West, along with their characteristics and aims; (2) China's policy discourse of excellence and pragmatism affects entrepreneurship education and technology transfer; and (3) an emerging identity of entrepreneurial universities is constrained by attitudes and barriers at the institutional level. China's perceptions and practices reflect a lack of sustainability of and fragmented approach to developing entrepreneurial universities, with strong implications for establishing entrepreneurial universities elsewhere.

Abstract Background The incidence of Alzheimer’s disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (Aβ), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk. Methods Thirty seven participants (mean (SD) age 74 (6.0) years, Mini-Mental State Examination 29.0 (1.2)) were dichotomized based on repeated neuropsychological test performance within 2 years. Cerebral Aβ was measured by 11C Pittsburgh Compound-B positron emission tomography, and iron by quantitative susceptibility mapping magnetic resonance imaging (MRI) at an ultra-high field strength of 7 Tesla (7T). Dynamic functional connectivity patterns were investigated by resting-state functional MRI at 7T and tested for interactive effects with genetic AD risk (apolipoprotein E (ApoE)-ε4 carrier status). Results A relationship between low episodic memory and a lower expression of anterior-posterior connectivity was seen (F(9,27) = 3.23, p