Treatment of adult attention-deficit hyperactivity disorder (ADHD) with transcranial direct current stimulation (tDCS): study protocol for a parallel, randomized, double-blinded, sham-controlled, multicenter trial (Stim-ADHD).

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects.Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148).

Overexpression of RAB27A in Oral Squamous Cell Carcinoma Promotes Tumor Migration and Invasion via Modulation of EGFR Membrane Stability.

Oral squamous cell carcinoma (OSCC) is the most prevalent subtype of head and neck tumors, highly prone to lymph node metastasis. This study aims to examine the expression pattern of Ras-related protein Rab-27A (RAB27A) and explore its potential implications in OSCC. The expression of RAB27A was assessed through immunohistochemical analysis utilizing tissue microarrays. In vitro experiments were conducted using RAB27A-knockdown cells to investigate its impact on OSCC tumor cells. Additionally, transcriptome sequencing was performed to elucidate potential underlying mechanisms. RAB27A was significantly overexpressed in OSCC, and particularly in metastatic lymph nodes. It was positively correlated with the clinical progression and poor survival prognosis. Silencing RAB27A notably decreased the proliferation, migration, and invasion abilities of OSCC cells in vitro. A Gene Ontology (GO) enrichment analysis indicated a strong association between RAB27A and the epidermal growth factor receptor (EGFR) signaling pathway. Further investigations revealed that RAB27A regulated the palmitoylation of EGFR via zinc finger DHHC-type containing 13 (ZDHHC13). These findings provide insights into OSCC progression and highlight RAB27A as a potential therapeutic target for combating this aggressive cancer.

Deriving vertical profiles of chlorophyll-a concentration in the upper layer of seawaters using ICESat-2 photon-counting lidar.

Chlorophyll-a concentration (chl-a) is a great indicator for estimating phytoplankton biomass and productivity levels and is also particularly useful for monitoring the water quality, biodiversity and species distribution, and harmful algal blooms. A great deal of studies investigated to estimate chl-a concentrations using ocean color remotely sensed data. With the development of photon-counting sensors, spaceborne photon-counting lidar can compensate for the shortcomings of passive optical remote sensing by enabling ocean vertical profiling in low-light conditions (e.g., at night). Using geolocated photons captured by the first spaceborne photon-counting lidar borne on ICESat-2 (Ice, Cloud, and Land Elevation Satellite-2), this research reported methods for deriving vertical profiles of chl-a concentration in the upper layer of ocean waters. This study first calculates the average numbers of backscattered subaqueous photons of ICESat-2 at different water depths, and then estimates the optical parameters in water column based on a discrete theoretical model of the expected number of received signal photons. With the estimated optical parameters, vertical profiles of chl-a concentration are calculated by two different empirical algorithms. In two study areas (mostly with Type I open ocean waters and small part of Type II coastal ocean waters), the derived chl-a concentrations are generally consistent when validated by BGC-Argo (Biogeochemical Argo) data in the vertical direction (MAPEs<15%) and compared with MODIS (Moderate Resolution Imaging Spectroradiometer) data in the along-track direction (average R2>0.86). Using globally covered ICESat-2 data, this approach can be used to obtain vertical profiles of chl-a concentration and optical parameters at a larger scale, which will be helpful to analyze impact factors of climate change and human activities on subsurface phytoplankton species and their growth state.

The role of comorbid depressive symptoms on long-range temporal correlations in resting EEG in adults with ADHD.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder, characterized by core symptoms of inattention, hyperactivity and impulsivity. Comorbid depression is commonly observed in ADHD-patients. Psychostimulants are recommended as first-line treatment for ADHD. Aberrant long-range temporal correlations (LRTCs) of neuronal activities in resting-state are known to be associated with disorganized thinking and concentrating difficulties (typical in ADHD) and with maladaptive thinking (typical in depression). It has yet to be examined whether (1) LRTC occur in ADHD-patients, and if so, (2) whether LRTC might be a competent biomarker in ADHD comorbid with current depression and (3) how depression affects psychostimulant therapy of ADHD symptoms. The present study registered and compared LRTCs in different EEG frequency bands in 85 adults with ADHD between groups with (n = 28) and without (n = 57) additional depressive symptoms at baseline. Treatment-related changes in ADHD, depressive symptoms and LRTC were investigated in the whole population and within each group. Our results revealed significant LRTCs existed in all investigated frequency bands. There were, however, no significant LRTC-differences between ADHD-patients with and without depressive symptoms at baseline and no LRTC-changes following treatment. However, depressed ADHD patients did seem to benefit more from the therapy with psychostimulant based on self-report.

Design and Fabrication of Interdigital Supercapacitors as Force/Acceleration Sensors.

The integrated device for energy supply and sensing (IDESS) is a potential candidate for relieving the energy and space burdens caused by the rising integration degrees of microsystems. In this article, we propose a force sensor based on an interdigital supercapacitor (IDTSC). The capacitance and internal resistance of the IDTSC change under external loads, resulting in a transient current fluctuation at a constant bias voltage, which can be used to sense external force/acceleration. The IDTSC showed a specific energy and specific power of 4.16 Wh/kg and 22.26 W/kg (at 0.1 A/g), respectively, which could maintain an essential energy supply. According to the simulation analysis, the designed IDTSC's current response exhibited good linearity with the external force. In addition, benefiting from its light weight and the applied gel electrolytes, the IDTSC showed good high-g impact sensing performance (from 9.9 × 103× g to 3.2 × 104× g). This work demonstrated the feasibility of realizing an integrated energy supply and force-sensing device by empowering energy storage devices with sensing capabilities.

Human brain arousal in the resting state: a genome-wide association study.

Arousal affects cognition, emotion, and behavior and has been implicated in the etiology of psychiatric disorders. Although environmental conditions substantially contribute to the level of arousal, stable interindividual characteristics are well-established and a genetic basis has been suggested. Here we investigated the molecular genetics of brain arousal in the resting state by conducting a genome-wide association study (GWAS). We selected N = 1877 participants from the population-based LIFE-Adult cohort. Participants underwent a 20-min eyes-closed resting state EEG, which was analyzed using the computerized VIGALL 2.1 (Vigilance Algorithm Leipzig). At the SNP-level, GWAS analyses revealed no genome-wide significant locus (p < 5E-8), although seven loci were suggestive (p < 1E-6). The strongest hit was an expression quantitative trait locus (eQTL) of TMEM159 (lead-SNP: rs79472635, p = 5.49E-8). Importantly, at the gene-level, GWAS analyses revealed significant evidence for TMEM159 (p = 0.013, Bonferroni-corrected). By mapping our SNPs to the GWAS results from the Psychiatric Genomics Consortium, we found that all corresponding markers of TMEM159 showed nominally significant associations with Major Depressive Disorder (MDD; 0.006 ≤ p ≤ 0.011). More specifically, variants associated with high arousal levels have previously been linked to an increased risk for MDD. In line with this, the MetaXcan database suggests increased expression levels of TMEM159 in MDD, as well as Autism Spectrum Disorder, and Alzheimer's Disease. Furthermore, our pathway analyses provided evidence for a role of sodium/calcium exchangers in resting state arousal. In conclusion, the present GWAS identifies TMEM159 as a novel candidate gene which may modulate the risk for psychiatric disorders through arousal mechanisms. Our results also encourage the elaboration of the previously reported interrelations between ion-channel modulators, sleep-wake behavior, and psychiatric disorders.

Brain arousal regulation and depressive symptomatology in adults with attention-deficit/hyperactivity disorder (ADHD).

BACKGROUND: The aim of the present study was to evaluate the stability of brain arousal in adult attention-deficit/hyperactivity disorder (ADHD) outpatients with and without depressive symptomatology, and its association with depressive symptom severity and absolute electroencephalogram (EEG) power in different frequency bands. METHODS: We included 31 outpatient adults (45.16% females), who were diagnosed according to DSM-IV and received no medication. Their arousal stability score (index of the steepness of arousal decline during a 15-min EEG under resting conditions), the absolute EEG power and self-reports, including depressive and ADHD-related symptoms, were analyzed. Participants were split into an unstable and stable arousal group based on the median (= 6) of the arousal stability score. RESULTS: ADHD patients in the stable group reported more severe depressive symptoms (p = 0.018) and showed reduced absolute EEG power in the delta (0.002 ≤ p ≤ 0.025) and theta (0.011 ≤ p ≤ 0.034) bands compared to those in the unstable group. There was no correlation between the arousal stability score and self-report-scales concerning ADHD-related symptoms (0.214 ≤ p ≤ 0.989), but a positive association with self-reported depressive severity (p = 0.018) and negative association with powers in the EEG delta and theta bands (0.001 ≤ p ≤ 0.033). CONCLUSIONS: In view of high comorbidity of depression and ADHD in adult patients, these findings support the assumption that brain arousal regulation could be considered as a helpful marker for the clinical differentiation between ADHD and depression.

Work pattern of neurology nurses in a Chinese hospital: A time and motion study.

AIM: To investigate nursing work patterns in a neurology department in a Chinese hospital. BACKGROUND: Knowledge of nursing work patterns is important for nursing management and work design, and for the evaluation of organizational process change associated with the introduction of an innovation. METHODS: A time-and-motion method was used to observe 14 registered nurses' (RNs') work patterns in a neurology department in a Chinese hospital. RESULTS: There were 147 hr of observation. Overall, the most time-consuming activities were verbal communication (28.5%) and documentation (28.3%), followed by indirect care (14.6%) and direct care (14%). Compared to support RNs, charge RNs spent 20% more time on documentation and 11% more time on verbal communication. Two-thirds of the observed activities had a duration of less than 40 s. CONCLUSIONS: Communication, in verbal and written forms, consumed more than half of the nursing time. Conversely, nurses only spent about a quarter of their worktime on preparation for care provision and direct care provision. This reflects the significant role and resource-consuming nature of communication to provide safe and quality care. IMPLICATIONS FOR NURSING MANAGEMENT: Communication methods need to be enhanced to improve nursing productivity. This may be achieved through the introduction of more effective nursing documentation methods.

Impact of brain arousal and time-on-task on autonomic nervous system activity in the wake-sleep transition.

BACKGROUND: Autonomic nervous system (ANS) activity has been shown to vary with the state of brain arousal. In a previous study, this association of ANS activity with distinct states of brain arousal was demonstrated using 15-min EEG data, but without directly controlling for possible time-on-task effects. In the current study we examine ANS-activity in fine-graded EEG-vigilance stages (indicating states of brain arousal) during two conditions of a 2-h oddball task while controlling for time-on-task. In addition, we analyze the effect of time-on-task on ANS-activity while holding the level of brain arousal constant. METHODS: Heart rate and skin conductance level of healthy participants were recorded during a 2-h EEG with eyes closed under simultaneous presentation of stimuli in an ignored (N = 39) and attended (N = 39) oddball condition. EEG-vigilance stages were classified using the Vigilance Algorithm Leipzig (VIGALL 2.1). The time-on-task effect was tested by dividing the EEG into four 30-min consecutive time blocks. ANS-activity was compared between EEG-vigilance stages across the entire 2 h and within each time block. RESULTS: We found a coherent decline of ANS-activity with declining brain arousal states, over the 2-h recording and in most cases within each 30-min block in both conditions. Furthermore, we found a significant time-on-task effect on heart rate, even when arousal was kept constant. It was most pronounced between the first and all subsequent blocks and could have been a consequence of postural change at the beginning of the experiment. CONCLUSION: Our findings contribute to the validation of VIGALL 2.1 using ANS parameters in 2-h EEG recording under oddball conditions.

Pyramiding of nine transgenes in maize generates high-level resistance against necrotrophic maize pathogens.

Key message Nine transgenes from different categories, viz. plant defense response genes and anti-apoptosis genes, played combined roles in maize to inhibit the necrotrophic pathogens Rhizoctonia solani and Bipolaris maydis. Maize sheath blight and southern corn leaf blight are major global threats to maize production. The management of these necrotrophic pathogens has encountered limited success due to the characteristics of their lifestyle. Here, we presented a transgenic pyramiding breeding strategy to achieve nine different resistance genes integrated in one transgenic maize line to combat different aspects of necrotrophic pathogens. These nine genes, selected from two different categories, plant defense response genes (Chi, Glu, Ace-AMP1, Tlp, Rs-AFP2, ZmPROPEP1 and Pti4), and anti-apoptosis genes (Iap and p35), were successfully transferred into maize and further implicated in resistance against the necrotrophic pathogens Rhizoctonia solani and Bipolaris maydis. Furthermore, the transgenic maize line 910, with high expression levels of the nine integrated genes, was selected from 49 lines. Under greenhouse and field trial conditions, line 910 showed significant resistance against maize sheath blight and southern corn leaf blight diseases. Higher-level resistance was obtained after the pyramiding of more resistance transgenes from different categories that function via different mechanisms. The present study provides a successful strategy for the management of necrotrophic pathogens.

Synergistic Effect of Atorvastatin and Folic Acid on Cardiac Function and Ventricular Remodeling in Chronic Heart Failure Patients with Hyperhomocysteinemia.

BACKGROUND At present, a constant progress in pathophysiology understanding and treatment of the chronic heart failure (CHF) is arising. Meanwhile, hyperhomocysteinemia (HHcy) has been linked to impaired left ventricular function and clinical class in patients with CHF. Atorvastatin therapy can reduce the incidence of sudden cardiac death in patients with advanced CHF. Folic acid could enhance endothelial function in vascular disease states. The present study aims to investigate the effect of atorvastatin and folic acid combined on the cardiac function and ventricular remodeling in CHF patients with HHcy. MATERIAL AND METHODS Elderly CHF patients with HHcy were divided into four groups: routine, routine + atorvastatin, routine + folic acid, and routine + atorvastatin + folic acid groups. Serum homocysteine (Hcy) level was detected using enzymatic cycling methods, and N-terminal pro brain natriuretic peptide (NT-proBNP) level by ELISA. The cardiac function indexes and left ventricular early diastolic peak flow velocity/atrial systolic peak flow velocity (E/A) ratio were evaluated. The six-minute walk test was performed to measure the six-minute walk distance (6MWD). RESULTS 6MWD increased, the serum Hcy and NT-proBNP levels decreased, and cardiac function was improved compared with before treatment, which was the most significant in the routine + atorvastatin + folic acid group, followed by the routine + atorvastatin group, then the routine + folic acid group, and lastly, the routine group. CONCLUSIONS The results indicated that the combination of atorvastatin and folic acid improved the cardiac function and inhibited ventricular remodeling of elderly CHF patients with HHcy.

Evoked potentials and behavioral performance during different states of brain arousal.

BACKGROUND: Previous studies compared evoked potentials (EPs) between several sleep stages but only one uniform wake state. However, using electroencephalography (EEG), several arousal states can be distinguished before sleep onset. Recently, the Vigilance Algorithm Leipzig (VIGALL 2.0) has been developed, which automatically attributes one out of seven EEG-vigilance stages to each 1-s EEG segment, ranging from stage 0 (associated with cognitively active wakefulness), to stages A1, A2 and A3 (associated with relaxed wakefulness), to stages B1 and B2/3 (associated with drowsiness) up to stage C (indicating sleep onset). Applying VIGALL, we specified the effects of these finely differentiated EEG-vigilance stages (indicating arousal states) on EPs (P1, N1, P2, N300, MMN and P3) and behavioral performance. Subjects underwent an ignored and attended condition of a 2-h eyes-closed oddball-task. Final analysis included 43 subjects in the ignored and 51 subjects in the attended condition. First, the effect of brain arousal states on EPs and performance parameters were analyzed between EEG-vigilance stages A (i.e. A1, A2 and A3 combined), B1 and B2/3&C (i.e. B2/3 and C combined). Then, in a second step, the effects of the finely differentiated EEG-vigilance stages were further specified. RESULTS: Comparing stages A versus B1 versus B2/3&C, a significant effect of EEG-vigilance stages on all behavioral parameters and all EPs, with exception of MMN and P3, was found. By applying VIGALL, a more detailed view of arousal effects on EP and performance was possible, such as the finding that the P2 showed no further significant increase in stages deeper than B1. Stage 0 did not differ from any of the A-stages. Within more fine-graded stages, such as the A-substages, EPs and performance only partially differed. However, these analyses were partly based on small sample sizes and future studies should take effort to get enough epochs of rare stages (such as A3 and C). CONCLUSIONS: A clear impact of arousal on EPs and behavioral performance was obtained, which emphasize the necessity to consider arousal effects when interpreting EPs.

Variability of particle size distribution with respect to inherent optical properties in Poyang Lake, China.

Suspended particulate matter plays a significant role in the studies of sediment fluxes, phytoplankton dynamics, and water optical properties. This study focuses on the relationships between particle size distribution (PSD), water's inherent optical properties (IOPs), and water constituents. We investigated the complex waters of Poyang Lake, the largest freshwater lake in China, in wet and dry seasons during 2008-2011. Because of the distinct temporal-spatial variation of Poyang Lake, these parameters and relationships also demonstrate seasonal and regional variability. The variation range of the concentration of suspended particulate matter is 0.32-69.08 mg/l, with a mean value of 22.21 mg/l. The median particle size in the dry season is much larger than that of the wet season. The Junge distribution fits the PSD of Poyang Lake very well in the scope of 6.21-331 µm. Furthermore, the slopes of the PSD range from 3.54 to 4.69, with a mean value of 4.11, with the steepest slopes (>4.5) occurring in the waters around Songmen Mountain Island and the northern waterway. A negative correlation was found between median particle size (Dv50) and the mass-specific absorption coefficient at 443 nm [apm(443)] for both wet and dry seasons. Identical to analogous waters, the spectral slopes of the PSD correlate well with the spectral slopes of the attenuation coefficient, but with different fitted formulas. In the dry season, the particle size can better explain the variability of the scattering coefficient, while the mass-specific scattering coefficient is better explained by the apparent density. However, no similar results were found for the wet season. In addition, the spectral slopes of the backscattering coefficient correlated well with the PSD slope, and the bulk refractive index calculated from the backscattering ratio and PSD slope can indicate the particle composition of Poyang Lake. Overall, the knowledge on the PSD and IOPs gained in this study broadens our understanding of water optics in highly turbid water columns.

Brain Arousal Regulation in Carriers of Bipolar Disorder Risk Alleles.

OBJECTIVES: Recent genome-wide association studies identified a number of chromosomal risk loci for bipolar disorder (BD, 'manic-depressive illness'). According to the vigilance regulation model, the regulation of brain arousal (referred to as 'vigilance') when assessed via EEG is an emerging biomarker linked to the pathogenesis of manic and depressive episodes. On this basis, the present study aimed to assess whether carriers of BD risk alleles differ in brain arousal regulation. METHODS: Healthy participants of the population-based Leipzig Health Care Study (LIFE) underwent a 20-min eyes-closed resting EEG paradigm. Brain arousal was assessed applying the computer-based Vigilance Algorithm Leipzig (VIGALL). The primary sample (n = 540) was genotyped for ten of the most reliable BD risk variants, of which two qualified for replication (n = 509). RESULTS: Primary sample analyses revealed Bonferroni-adjusted significance for rs1006737 in CACNA1C (encoding a calcium channel subunit), with risk allele carriers exhibiting relatively steep brain arousal declines. Further, carriers of two risk alleles of rs472913 at 1p32.1 showed generally lower brain arousal levels for the duration of the resting paradigm. However, both associations failed replication. CONCLUSION: Although our initial findings are in line with the vigilance regulation model and convincing in view of the previously reported notable role of ion channelopathies in BD, our results do not provide consistent evidence for a link between BD risk variants and brain arousal regulation. Several between-sample differences may account for this inconsistency. The molecular genetics of brain arousal regulation remain to be clarified.

[Particles size distribution and its influence on remote sensing retrieval of turbid Poyang Lake].

The suspended particle size distribution provides crucial information for the study of water environment structure and function. Based on the in-situ data from wet and dry season in 2008-2011, the paper studied suspended particle size distribution of Poyang Lake and its optical features. The suspended particle size distribution showed seasonal variation: the particle size of southern lake was larger than that of northern lake in dry season but showed little variation in wet season. The suspended particle size distribution exerted influence on particulate absorption coefficient, attenuation coefficient and scattering coefficient. The particulate absorption coefficient of northern lake was higher than that of southern lake. The negative correlation between specific absorption coefficient of total suspended particles and median particle size indicated that there was "package effect" of mineral particles in turbid Poyang Lake. The spatial and temporal distribution of particulate attenuation coefficient and scattering coefficient are similar: there were obvious regional differences in dry season but few in wet season. There were good correlations among the remote sensing reflectance, spectra slope of particle size distribution and spectra slope of particulate scattering coefficient. These correlations would provide the foundation for remote sensing retrieval of particle size and quantitative analysis of influence of suspended particle size on the optical properties. The relationship between particle size distribution, particulate back-scattering coefficient and bulk refractive index can provide information of particle composition in Poyang Lake.

Dynamic monitoring and analysis of chlorophyll-a concentrations in global lakes using Sentinel-2 images in Google Earth Engine.

Remote estimation of Chlorophyll-a (Chl-a) has long been used to investigate the responses of aquatic ecosystems to global climate change. High-spatiotemporal-resolution Sentinel-2 satellite images make it possible to routinely monitor and trace the spatial distributions of lake Chl-a if reliable retrieval algorithms are available. In this study, Sentinel-2 images and in-situ measured data were used to develop a Chl-a retrieval algorithm based on 13 optical water types (OWTs) with a satisfying performance (R2 = 0.74, RMSE = 0.42 mg/m3, MAE = 0.33 mg/m3, and MAPE = 55.56 %). After removing the disturbance of algal blooms and other factors, the distribution of Chl-a in 3067 of the largest global lakes (≥50 km2) was mapped using the Google Earth Engine (GEE). From 2019 to 2021, the average Chl-a concentration was 16.95 ± 5.95 mg/m3 for the largest global lakes. During the COVID-19 pandemic, global lake-averaged Chl-a concentration reached its lowest value in 2020. From the perspective of spatial distribution, lakes with low Chl-a concentrations were mainly distributed in high-latitude, high-elevation, or economically underdeveloped areas. Among all the potential influencing factors, lake surface temperature had the largest contribution to Chl-a and showed a positive correlation with Chl-a in approximately 92.39 % of the lakes. Conversely, factors such as precipitation and tree cover area around the lake were negatively correlated with Chl-a concentration in nearly 61.44 % of the lakes.

Remote-sensing monitoring of colored dissolved organic matter in the Arctic Ocean.

In the Arctic Ocean, variations in the colored dissolved organic matter (CDOM) have important value and significance. This study proposed and evaluated a novel method by combining the Google Earth Engine with a multilayer back-propagation neural network to retrieve CDOM concentration. This model performed well on the testing data and independent validation data (R2 = 0.76, RMSE = 0.37 m-1, MAPD = 35.43 %), and it was applied to Moderate Resolution Imaging Spectroradiometer (MODIS) images. The CDOM distribution in the Arctic Ocean and its main sea areas was first depicted during the ice-free period from 2002 to 2021, with average CDOM concentration in the range of 0.25 and 0.31 m-1. High CDOM concentration appeared in coastal areas affected by rivers on the Siberian side. The CDOM concentration was highly correlated with salinity (r = -0.92) and discharge (r > 0.68), while melting sea ice diluted seawater and CDOM concentration.

No evidence of structural abnormality of the substantia nigra in adult attention-deficit/hyperactivity disorder: a pilot cross-sectional cohort study.

Background: Abnormal expansion of the echogenic substantia nigra (SN+) is a common observation in Parkinson's disease (PD) and considered a potential trait marker within this context. However, SN+ was also frequently detected in children diagnosed with attention-deficit/hyperactivity disorder (ADHD), where it has been discussed as a biomarker of maturational dopaminergic dysfunction. Interestingly, ADHD was recently linked to an elevated risk of PD in epidemiological studies, particularly among individuals treated with psychostimulants. Here, we investigated the potential of SN echogenicity as a disease biomarker in adults with ADHD and its relation to psychostimulant treatment. Methods: In an exploratory cross-sectional cohort study, we performed transcranial sonography of the SN in 30 adults (mean age 33.3 ± 7.6 years, 19 males/11 females) diagnosed with ADHD according to DSM-V criteria. Results and conclusions: In this pilot study, we observed no evidence of structural abnormalities of the SN among adults diagnosed with ADHD, thus questioning the potential of SN+ as a biomarker for ADHD in this population. Moreover, we found no evidence of treatment-related SN echogenicity changes that would link therapeutic psychostimulant use to alterations in the structural integrity of the SN.

PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

A histopathological image classification method for cholangiocarcinoma based on spatial-channel feature fusion convolution neural network.

Histopathological image analysis plays an important role in the diagnosis and treatment of cholangiocarcinoma. This time-consuming and complex process is currently performed manually by pathologists. To reduce the burden on pathologists, this paper proposes a histopathological image classification method for cholangiocarcinoma based on spatial-channel feature fusion convolutional neural networks. Specifically, the proposed model consists of a spatial branch and a channel branch. In the spatial branch, residual structural blocks are used to extract deep spatial features. In the channel branch, a multi-scale feature extraction module and some multi-level feature extraction modules are designed to extract channel features in order to increase the representational ability of the model. The experimental results of the Multidimensional Choledoch Database show that the proposed method performs better than other classical CNN classification methods.