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Although active flow control based on deep reinforcement learning (DRL) has been demonstrated extensively in numerical environments, practical implementation of real-time DRL control in experiments remains challenging, largely because of the critical time requirement imposed on data acquisition and neural-network computation. In this study, a high-speed field-programmable gate array (FPGA) -based experimental DRL (FeDRL) control framework is developed, capable of achieving a control frequency of 1–10 kHz, two orders higher than that of the existing CPU-based framework (10 Hz). The feasibility of the FeDRL framework is tested in a rather challenging case of supersonic backward-facing step flow at Mach 2, with an array of plasma synthetic jets and a hot-wire acting as the actuator and sensor, respectively. The closed-loop control law is represented by a radial basis function network and optimised by a classical value-based algorithm (i.e. deep Q-network). Results show that, with only ten seconds of training, the agent is able to find a satisfying control law that increases the mixing in the shear layer by 21.2 %. Such a high training efficiency has never been reported in previous experiments (typical time cost: hours).
This study is dedicated to achieving efficient active noise control in a supersonic underexpanded planar jet, utilizing control parameters informed by resolvent analysis. The baseline supersonic underexpanded jet exhibits complex wave structures and substantial high-amplitude noise radiations. To perform the active control, unsteady blowing and suction are applied along the nozzle inner wall close to the exit. Employing both standard and acoustic resolvent analyses, a suitable frequency and spanwise wavenumber range for the blowing and suction is identified. Within this range, the control forcing can be significantly amplified in the near field, effectively altering the original sound-producing energetic structure while minimizing far-field amplification to prevent excessive noise. A series of large-eddy simulations are further conducted to validate the control efficiency, demonstrating an over 10 dB reduction in upstream-propagated screech noise. It is identified that the present unsteady control proves more effective than steady control at the same momentum coefficient. The controlled jet flow indicates that the shock structures become more stable, and the stronger the streamwise amplification of the forcing, the more likely it is to modify the mean flow characteristics, which is beneficial for reducing far-field noise radiation. Spectral proper orthogonal decomposition analysis of the controlled flow confirms that the control redistributes energy to higher forcing frequencies and suppresses large-scale antisymmetric and symmetric modes related to screech and its harmonics. The findings of this study highlight the potential of resolvent-guided control techniques in reducing noise in supersonic underexpanded jets and provide a detailed understanding of the inherent mechanisms for effective noise reduction through active control strategies.
Microstates of an electroencephalogram (EEG) are canonical voltage topographies that remain quasi-stable for 90 ms, serving as the foundational elements of brain dynamics. Different changes in EEG microstates can be observed in psychiatric disorders like schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). However, the similarities and disparatenesses in whole-brain dynamics on a subsecond timescale among individuals diagnosed with SCZ, BD, and MDD are unclear.
Methods
This study included 1112 participants (380 individuals diagnosed with SCZ, 330 with BD, 212 with MDD, and 190 demographically matched healthy controls [HCs]). We assembled resting-state EEG data and completed a microstate analysis of all participants using a cross-sectional design.
Results
Our research indicates that SCZ, BD, and MDD exhibit distinct patterns of transition among the four EEG microstate states (A, B, C, and D). The analysis of transition probabilities showed a higher frequency of switching from microstates A to B and from B to A in each patient group compared to the HC group, and less frequent transitions from microstates A to C and from C to A in the SCZ and MDD groups compared to the HC group. And the probability of the microstate switching from C to D and D to C in the SCZ group significantly increased compared to those in the patient and HC groups.
Conclusions
Our findings provide crucial insights into the abnormalities involved in distributing neural assets and enabling proper transitions between different microstates in patients with major psychiatric disorders.
The efficacy of probiotics as a therapeutic alternative for attention-deficit hyperactivity disorder (ADHD) remain unclear.
Aims
To investigate the effectiveness of probiotics for symptoms of ADHD and identify possible factors affecting their efficacy.
Method
Randomised placebo-controlled trials were identified through searching major databases from inception to April 2023, using the main keywords ‘probiotics’ and ‘ADHD’ without limitation on languages or geographic locations. The outcome of interest included improvement in total symptoms of ADHD, symptoms of inattention and hyperactivity/impulsivity, and drop-out rate. Continuous and categorical data were expressed as effect sizes based on standardised mean differences (SMDs) and odds ratios, respectively, with 95% confidence intervals.
Results
Meta-analysis of seven trials involving 379 participants (mean age 10.37 years, range 4–18 years) showed no significant improvement in total symptoms of ADHD (SMD = 0.25; P = 0.12), symptoms of inattention (SMD = 0.14; P = 0.3) or hyperactivity/impulsivity (SMD = 0.08; P = 0.54) between the probiotic and placebo groups. Despite non-significance on subgroup analyses, there was a large difference in effect size between studies using probiotics as an adjunct to methylphenidate and those using probiotics as supplementation (SMD = 0.84 v. 0.07; P = 0.16), and a moderate difference in effect size between studies using multiple strains of probiotics and those using single-strain regimens (SMD = 0.45 v. 0.03; P = 0.19).
Conclusions
Current evidence shows no significant difference in therapeutic efficacy between probiotics and placebos for treatment of ADHD symptoms. However, albeit statistically non-significant, higher therapeutic efficacies associated with multiple-strain probiotics or combining probiotics with methylphenidate may provide direction for further research.
Placental trophoblastic cells play important roles in placental development and fetal health. However, the mechanism of trophoblastic cell fusion is still not entirely clear. The level of Tspan5 in the embryo culture medium was detected using enzyme-linked immunosorbent assay (ELISA). Fusion of BeWo cells was observed by immunofluorescence. Cell fusion-related factors and EMT-related factors were identified by qRT-PCR and western blotting. Notch protein repressor DAPT was used to verify the role of Tspan5 in BeWo cells. The expression of Tspan5 was significantly increased in embryo culture medium. The fusion of BeWo cells was observed after treatment with forskolin (FSK). Cell fusion-related factors (i.e. β-hCG and syncytin 1/2) and Tspan5 were significantly increased after FSK treatment. In addition, FSK treatment promoted EMT-related protein expression in BeWo cells. Knockdown of Tspan5 inhibited cell fusion and EMT-related protein levels. Notch-1 and Jagged-1 protein levels were significantly upregulated, and the EMT process was activated by overexpression of Tspan5 in FSK-treated BeWo cells. Interestingly, blocking the Notch pathway by the repressor DAPT had the opposite results. These results indicated that Tspan5 could promote the EMT process by activating the Notch pathway, thereby causing cell fusion. These findings contribute to a better understanding of trophoblast cell syncytialization and embryonic development. Tspan5 may be used as a therapeutic target for normal placental development.
A novel data-driven modal analysis method, reduced-order variational mode decomposition (RVMD), is proposed, inspired by the Hilbert–Huang transform and variational mode decomposition (VMD), to resolve transient or statistically non-stationary flow dynamics. First, the form of RVMD modes (referred to as an ‘elementary low-order dynamic process’, ELD) is constructed by combining low-order representation and the idea of intrinsic mode function, which enables the computed modes to characterize the non-stationary properties of space–time fluid flows. Then, the RVMD algorithm is designed based on VMD to achieve a low-redundant adaptive extraction of ELDs in flow data, with the modes computed by solving an elaborate optimization problem. Further, a combination of RVMD and Hilbert spectral analysis leads to a modal-based time-frequency analysis framework in the Hilbert view, providing a potentially powerful tool to discover, quantify and analyse the transient and non-stationary dynamics in complex flow problems. To provide a comprehensive evaluation, the computational cost and parameter dependence of RVMD are discussed, as well as the relations between RVMD and some classic modal decomposition methods. Finally, the virtues and utility of RVMD and the modal-based time-frequency analysis framework are well demonstrated via two canonical problems: the transient cylinder wake and the planar supersonic screeching jet.
Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD.
Methods
Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD.
Results
Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up.
Conclusion
Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe and life-threatening complication, characterised by multi-organ failure and high short-term mortality. However, there is limited information on the impact of various comorbidities on HBV-ACLF in a large population. This study aimed to investigate the relationship between comorbidities, complications and mortality. In this retrospective observational study, we identified 2166 cases of HBV-ACLF hospitalised from January 2010 to March 2018. Demographic data from the patients, medical history, treatment, laboratory indices, comorbidities and complications were collected. The mortality rate in our study group was 47.37%. Type 2 diabetes mellitus was the most common comorbidity, followed by alcoholic liver disease. Spontaneous bacterial peritonitis, pneumonia and hepatic encephalopathy (HE) were common in these patients. Diabetes mellitus and hyperthyroidism are risk factors for death within 90 days, together with gastrointestinal bleeding and HE at admission, HE and hepatorenal syndrome during hospitalisation. Knowledge of risk factors can help identify HBV-ACLF patients with a poor prognosis for HBV-ACLF with comorbidities and complications.
Under global warming, many glaciers worldwide are receding. However, recent studies have suggested the extension of the Karakoram Anomaly, a region of anomalous glacier mass gain, into the western Kunlun and eastern Pamir mountains. However, the eastern limit of this anomaly in the Kunlun Mountains is unclear. This study, using changes in glacier area and surface elevation, estimates the eastern limit of the Kunlun-Pamir-Karakoram anomaly at ~85°E. Over the past 50 years, glaciers west of 85°E in the Kunlun Mountains decreased in area from 8401 to 7945 km2 at a rate of −0.12 ± 0.07% a−1, showed a reduction in the rate of retreat through time and have recently gained mass, with surface elevation changes of 0.15 ± 0.35 m a−1 over the period of 2000–2013. Glaciers east of 85°E have experienced greater rates of area change (−61 ± 12 km2 and −0.43 ± 0.13% a−1) over the past 50 years, accelerated area loss in recent years and elevation change rate of −0.51 ± 0.18 m a−1 between 2000 and 2013. These patterns of elevation and area change are consistent with regional increases in summer temperature in the eastern Kunlun Mountains and slight cooling in the western Kunlun Mountains.
The orogenic process and crustal growth of the Changning–Menglian Palaeo-Tethys orogenic belt in the southeastern Tibetan Plateau is not fully understood. Triassic Caojian rhyolites and granites occur extensively in this orogenic belt and represent important constraints for this issue. This study aims to examine the relationships between the Triassic Caojian rhyolites and granites and to gain a better understanding of their possible petrogenesis. The study used zircon U–Pb geochronology, trace element analyses and Sr–Nd–Hf isotope data to better understand the relationships and possible origin of the rhyolites and granites. Recent zircon U–Pb ages indicated that the Caojian rhyolites were emplaced at 227.2 Ma, whereas age estimates for Caojian granites were slightly older (233.4–236.9 Ma). The Caojian rhyolites are enriched in large-ion lithophile elements and high-field-strength elements, with elevated FeOtot/MgO and Ga/Al ratios. However, they are significantly depleted in Ba, Sr, Eu, P and Ti. These geochemical characteristics indicate that they have an A-type affinity. Furthermore, the Caojian granites comprise biotite monzogranites and granodiorites and show unfractionated composition. Mineralogically, the Caojian granites were found to contain diagnostic I-type minerals such as hornblende. Geochemical data suggest that the petrogenesis of the Triassic Caojian rhyolites is characterized by rejuvenation of crystal mush represented by the Triassic Caojian granites. The necessary thermal input was supplied by mafic magma. This magmatic evolution was likely related to lithospheric delamination and upwelling of the asthenosphere during the Mid- to Late Triassic, forming post-collisional I-type granites and A-type volcanics in the Changning–Menglian Palaeo-Tethys orogenic belt.
This study aimed to determine the risk factors for chronic diseases and to identify the potential influencing mechanisms from the perspectives of lifestyle and dietary factors. The findings could provide updated and innovative evidence for the prevention and control of chronic diseases.
Design:
A cross-sectional study.
Setting:
Shanghai, China.
Participants:
1005 adults from Yangpu district of Shanghai participated in the study, and responded to questions on dietary habits, lifestyle and health status.
Results:
Residents suffering from chronic diseases accounted for about 34·99 % of the respondents. Logistic regression analysis showed that age, diet quality, amount of exercise and tea drinking were related to chronic diseases. Age > 60 and overeating (Diet Balance Index total score > 0) had negative additive interaction on the occurrence of chronic disease, while overexercise (Physical Activity Index > 17·1) and tea drinking had negative multiplicative interaction and negative additive interaction on the occurrence of chronic disease. Diet quality, physical activity and tea drinking were incomplete mediators of the relationship between types of medical insurance residents participating in and chronic diseases.
Conclusions:
The residents in Yangpu District of Shanghai have a high prevalence of chronic diseases. Strengthening access of residents to health education and interventions to prevent chronic diseases and cultivating healthy eating and exercise habits of residents are crucial. The nutritional environment of the elderly population should be considered, and the reimbursement level of different types of medical insurance should be designed reasonably to improve the accessibility of medical and health services and reduce the risk of chronic diseases.
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (Pinteraction = 0·017 for NASH and Pinteraction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.
To investigate the safety and feasibility of midazolam for conscious sedation in transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography.
Methods:
A retrospective analysis was performed on 55 patients who underwent transcatheter device closure of atrial septal defects from October, 2019 to May, 2020. All patients received intravenous midazolam and local anesthesia with lidocaine to maintain sedation. A group of previous patients with unpublished data who underwent the same procedure with general anesthesia was set as the control group. The relevant clinical parameters, the Ramsay sedation scores, the numerical rating scale, and the post-operative satisfaction questionnaire were recorded and analyzed.
Results:
In the midazolam group, the success rate of atrial septal defect closure was 98.2%. Hemodynamic stability was observed during the procedure. None of the patients needed additional endotracheal intubation for general anesthesia. Compared with the control group, the midazolam group had no statistically significant differences in the Ramsay sedation score and numerical rating scale scores. Patients in the midazolam group experienced more post-operative satisfaction than those in the control group.
Conclusions:
Conscious sedation using midazolam is a safe and effective anesthetic technique for transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
Perceived loneliness, an increasingly prevalent social issue, is closely associated with major depressive disorder (MDD). However, the neural mechanisms previously implicated in key cognitive and affective processes in loneliness and MDD still remain unclear. Such understanding is critical for delineating the psychobiological basis of the relationship between loneliness and MDD.
Methods
We isolated the unique and interactive cognitive and neural substrates of loneliness and MDD among 27 MDD patients (mean age = 51.85 years, 20 females), and 25 matched healthy controls (HCs; mean age = 48.72 years, 19 females). We assessed participants' behavioral performance and neural regional and network functions on a Stroop color-word task, and their resting-state neural connectivity.
Results
Behaviorally, we found greater incongruence-related accuracy cost in MDD patients, but reduced incongruence effect on reaction time in lonelier individuals. When performing the Stroop task, loneliness positively predicted prefrontal-anterior cingulate-parietal connectivity across all participants, whereas MDD patients showed a decrease in connectivity compared to controls. Furthermore, loneliness negatively predicted parietal and cerebellar activities in MDD patients, but positively predicted the same activities in HCs. During resting state, MDD patients showed reduced parietal-anterior cingulate connectivity, which again positively correlated with loneliness in this group.
Conclusions
We speculate the distinct neurocognitive profile of loneliness might indicate increase in both bottom-up attention and top-down executive control functions. However, the upregulated cognitive control processes in lonely individuals may eventually become exhausted, which may in turn predispose to MDD onset.
We report on a high-repetition-rate, high-power continuously pumped Nd:GdVO4 regenerative amplifier. Numerical simulations successfully pinpoint the optimum working point free of bifurcation instability with simultaneous efficient energy extraction. At a repetition rate of 100 kHz, a maximum output power of 23 W was obtained with a pulse duration of 27 ps, corresponding to a pulse energy of $230~\unicode[STIX]{x03BC}\text{J}$. The system displayed an outstanding stability with a root mean square power noise as low as 0.3%. The geometry of the optical resonator and the pumping scheme enhanced output power in the $\text{TEM}_{00}$ mode with a single bulk crystal. Accordingly, nearly diffraction-limited beam quality was produced with $M^{2}\approx 1.2$ at full pump power.
Whether borderline personality disorder (BPD) and bipolar disorder are the same or different disorders lacks consistency.
Aims
To detect whether grey matter volume (GMV) and grey matter density (GMD) alterations show any similarities or differences between BPD and bipolar disorder.
Method
Web-based publication databases were searched to conduct a meta-analysis of all voxel-based studies that compared BPD or bipolar disorder with healthy controls. We included 13 BPD studies (395 patients with BPD and 415 healthy controls) and 47 bipolar disorder studies (2111 patients with bipolar disorder and 3261 healthy controls). Peak coordinates from clusters with significant group differences were extracted. Effect-size signed differential mapping meta-analysis was performed to analyse peak coordinates of clusters and thresholds (P < 0.005, uncorrected). Conjunction analyses identified regions in which disorders showed common patterns of volumetric alteration. Correlation analyses were also performed.
Results
Patients with BPD showed decreased GMV and GMD in the bilateral medial prefrontal cortex network (mPFC), bilateral amygdala and right parahippocampal gyrus; patients with bipolar disorder showed decreased GMV and GMD in the bilateral medial orbital frontal cortex (mOFC), right insula and right thalamus, and increased GMV and GMD in the right putamen. Multi-modal analysis indicated smaller volumes in both disorders in clusters in the right medial orbital frontal cortex. Decreased bilateral mPFC in BPD was partly mediated by patient age. Increased GMV and GMD of the right putamen was positively correlated with Young Mania Rating Scale scores in bipolar disorder.
Conclusions
Our results show different patterns of GMV and GMD alteration and do not support the hypothesis that bipolar disorder and BPD are on the same affective spectrum.
To revise an abbreviated version of the Silhouettes subtest of the Visual Object and Space Perception (VOSP) battery in order to recognize mild cognitive impairment (MCI) and determine the optimal cutoffs to differentiate among cognitively normal controls (NC), MCI, and Alzheimer’s Disease (AD) in the Chinese elderly.
Design:
A cross-sectional validation study.
Setting:
Huashan Hospital, Shanghai, China.
Subjects:
A total of 591 participants: Individuals with MCI (n = 211), AD (n = 139) and NC (n = 241) were recruited from the Memory Clinic, Huashan Hospital, Shanghai, China.
Methods:
Baseline neuropsychological battery (including VOSP) scores were collected from firsthand data. An abbreviated version of silhouettes test (Silhouettes-A) was revised from the original English version more suitable for the elderly, including eight silhouettes of animals and seven silhouettes of inanimate objects, with a score ranging from 0 to 15.
Results:
Silhouettes-A was an effective test to screen MCI in the Chinese elderly with good sensitivity and specificity, similar to the Montreal cognitive assessment and superior to other single tests reflecting language, spatial, or executive function. However, it had no advantage in distinguishing MCI from AD. The corresponding optimal cutoff scores of Silhouettes-A were 10 for screening MCI and 8 for AD.
Conclusion:
Silhouettes-A is a quick, simple, sensitive, and dependable cognitive test to distinguish among NC, MCI, and AD patients.