The cap-proximal RNA secondary structure inhibits preinitiation complex formation on HAC1 mRNA.

Translation of HAC1 mRNA in the budding yeast Saccharomyces cerevisiae is derepressed when RNase Ire1 removes its intron via nonconventional cytosolic splicing in response to accumulation of unfolded proteins inside the endoplasmic reticulum. The spliced HAC1 mRNA is translated into a transcription factor that changes the cellular gene expression patterns to increase the protein folding capacity of cells. Previously, we showed that a segment of the intronic sequence interacts with the 5'-UTR of the unspliced mRNA, resulting in repression of HAC1 translation at the initiation stage. However, the exact mechanism of translational derepression is not clear. Here, we show that at least 11-base-pairing interactions between the 5'-UTR and intron (UI) are sufficient to repress HAC1 translation. We also show that overexpression of the helicase eukaryotic initiation factor 4A derepressed translation of an unspliced HAC1 mRNA containing only 11-bp interactions between the 5'-UTR and intronic sequences. In addition, our genetic screen identifies that single mutations in the UI interaction site could derepress translation of the unspliced HAC1 mRNA. Furthermore, we show that the addition of 24 RNA bases between the mRNA 5'-cap and the UI interaction site derepressed translation of the unspliced HAC1 mRNA. Together, our data provide a mechanistic explanation for why the cap-proximal UI-RNA duplex inhibits the recruitment of translating ribosomes to HAC1 mRNA, thus keeping mRNA translationally repressed.

Generative Adversarial Network (GAN) for Simulating Electroencephalography.

Electroencephalographs record the electrical activity of your brain through the scalp. Electroencephalography is difficult to obtain due to its sensitivity and variability. Applications of electroencephalography such as for diagnosis, education, brain-computer interfaces require large samples of electroencephalography recording, however, it is often difficult to obtain the required datasets. Generative adversarial networks are robust deep learning framework which have proven themselves to be capable of synthesizing data. The robust nature of a generative adversarial network was used to generate multi-channel electroencephalography data in order to see if generative adversarial networks could reconstruct the spatio-temporal aspects of multi-channel electroencephalography signals. We were able to find that the synthetic electroencephalography data was able to replicate fine details of electroencephalography data and could potentially help us to generate large sample synthetic resting-state electroencephalography data for use in simulation testing of neuroimaging analyses. Generative adversarial networks (GANs) are robust deep-learning frameworks that can be trained to be convincing replicants of real data GANs were capable of generating "fake" EEG data that replicated fine details and topographies of "real" resting-state EEG data.

Behind the Wheel: Unraveling the Impact of Experience Over Age Over the First 18 Months of Licensure.

OBJECTIVE: This study examined how driving attention develops with age and driving. METHODS: In this observational longitudinal study, 190 adolescents (53% female, 73% Black) were enrolled across four groups: 16- and 18-year olds with and without driving experience. They underwent driving simulation with eye-tracking technology seven times over 18 months. By using a combination of factorial and longitudinal designs, the study examined the individual and combined effects of age and driving experience on driving attention over time. RESULTS: Licensed participants had higher odds of glancing at safety-critical events initially (OR = 15.01, 95% CI: 1.36-165.53), but these odds decreased at higher driving speeds (b = -0.17, p<.01). Average glance length decreased over time (b = -0.26, p=.01), but less so in licensed participants (b=0.14, p=.01). Several visual behaviors were influenced by environmental and driving factors. CONCLUSIONS: Motor vehicle crashes (MVCs) are burdensome and costly to society. This study focused on the role of inattention in MVCs, particularly during the risky period of adolescence. Findings indicated that driving experience, as determined by licensure, had a considerable impact on visual behavior in both the short term (within two weeks of obtaining a license) and over the first 18 months of independent driving. Overall, these findings suggest that licensed adolescents are more likely to identify potential hazards on the road and navigate safely. To ensure effective guidance, pediatric psychologists and other professionals should consider the unique circumstances, needs, and concerns of individual patients.

White matter integrity, duration of untreated psychosis, and antipsychotic treatment response in medication-naïve first-episode psychosis patients.

It is becoming increasingly clear that longer duration of untreated psychosis (DUP) is associated with adverse clinical outcomes in patients with psychosis spectrum disorders. Because this association is often cited when justifying early intervention efforts, it is imperative to better understand underlying biological mechanisms. We enrolled 66 antipsychotic-naïve first-episode psychosis (FEP) patients and 45 matched healthy controls in this trial. At baseline, we used a human connectome style diffusion-weighted imaging (DWI) sequence to quantify white matter integrity in both groups. Patients then received 16 weeks of treatment with risperidone, 51 FEP completed the trial. We compared whole-brain fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity between groups. To test if structural white matter integrity mediates the relationship between longer DUP and poorer treatment response, we fit a mediator model and estimated indirect effects. We found decreased whole-brain FA and AD in medication-naive FEP compared with controls. In patients, lower FA was correlated with longer DUP (r = -0.32; p = 0.03) and poorer subsequent response to antipsychotic treatment (r = 0.40; p = 0.01). Importantly, we found a significant mediation effect for FA (indirect effect: -2.70; p = 0.03), indicating that DUP exerts its effects on treatment response through affecting white matter integrity. Our data provide empirical support to the idea the DUP may have fundamental pathogenic effects on the natural history of psychosis, suggest a biological mechanism underlying this phenomenon, and underscore the importance of early intervention efforts in this disabling neuropsychiatric syndrome.

Gender moderates the relationship between media use and sleep quality.

With high screen time and poor sleep commonly reported in adolescents, it is important to more fully understand how screen time impacts sleep. Despite similar overall screen times, male and female media preferences and usages differ, making it critical to determine if different domains of screen time differentially affect sleep quality. The present study examined whether differing amounts and domains of screen-based media vary in impact on sleep quality of 16-year-old male and female adolescents over a 3-month period. A total of 98 adolescents (mean [SD] age 16.27 [0.29] years; 51% female) completed two online surveys spaced 3 months apart and comprised of well-validated self-reported measures of sleep quality, media usage, and depressive symptoms. The various domains of media were categorised into screen-based media with little-to-no peer-to-peer interaction involved (video-only) and screen-based media with interaction a predominant component to the usage (peer-to-peer interaction-involved). Self-reported sleep quality decreased across the 3-month study period. Gender moderated the effect of interactive screen time on sleep quality 3 months later, with interactive screen time associated with better sleep quality in males, but remaining poorer in females. Screen time competes with sleep time and may do so differentially depending on the media domain. Compared to females, interactive components of screen time may lessen worsening sleep quality over time in males. Understanding the relationships among screen time, its content, age, and gender may inform guidelines for educators, parents, and adolescents to help improve sleep quality of adolescents.

Fifty years of digestive endoscopy: Successes, setbacks, solutions and the future.

Flexible endoscopes became generally available 50 years ago and created a revolution in the practice of gastroenterology. They improved diagnosis enormously, enabled quicker, less invasive, and more cost-effective surgical treatment, while endoscopic screening has prevented many cancer deaths. The new technology stimulated research leading to a better understanding of gastrointestinal pathology, identifying new diseases and clarifying the etiology of others. Better-controlled clinical trials accelerated the use of newer and more effective drugs. National and international endoscopy societies supported nursing input, encouraged research, stimulated specialist journals, and devised guidelines that encouraged audit and quality assurance. Advances in instrument design and the manufacture of new accessories enhanced endoscopic technique, diagnostic ability, patient comfort, and safety. The risk of cross-infection inherent in the use of complex labile equipment that cannot be autoclaved remains a challenge. Endoscopy societies working closely with industry have established rigid protocols for high-level disinfection that minimize the risks, but strict adherence to guidelines and continued vigilance is essential, especially with the increasing prevalence of antibiotic-resistant commensals that can give rise to opportunistic infection. Government health departments have a responsibility to encourage and support research in this area by endoscopists, instrument manufacturers, and the pharmaceutical industry. Current trends suggest that in the future, artificial intelligence will greatly improve endoscopic diagnosis, and that therapeutic endoscopy will expand, encouraging endoscopists to subspecialize.

Skeletal muscle secretion of IL-6 is muscle type specific: Ex vivo evidence.

Emerging evidence indicates that skeletal muscle possesses endocrine function to secret myokines. Interleukin 6 (IL-6) is a well-characterized myokine that is involved in regulation of metabolism and muscle function. Metabolism type and contractile dynamics vary in different muscle types. It is not clear, however, if IL-6 secretion differs in different muscle types. In this study, we first established an ex vivo approach to test the inducible muscle secretion. Freshly isolated muscles were incubated in Krebs solution at 37 °C with oxygen supply. Secreted IL-6 in the incubation media was measure using Western blot and ELISA assay. We first confirmed that the IL-6 release was inducible by treating the incubated muscle with a cytokine stimulant. We demonstrated that physiological temperature (37 °C) and O2 supply were essential for the induction of IL-6 release from the incubated muscle, suggesting it is a controlled secretion rather than a spontaneous leak. Using this approach, we found that IL-6 release was only inducible from soleus muscle but not EDL muscle. We further showed that IL-6 protein level was higher in slow oxidative muscle fibers. Moreover, we showed that EDL, although lacks of IL-6 release, surely has inducible secretory function that had different secretory pattern from soleus.

A novel family of proline/serine-rich proteins, which are phospho-targets of stress-related mitogen-activated protein kinases, differentially regulates growth and pathogen defense in Arabidopsis thaliana.

The molecular actions of mitogen-activated protein kinases (MAPKs) are ultimately accomplished by the substrate proteins where phosphorylation affects their molecular properties and function(s), but knowledge regarding plant MAPK substrates is currently still fragmentary. Here, we uncovered a previously uncharacterized protein family consisting of three proline/serine-rich proteins (PRPs) that are substrates of stress-related MAPKs. We demonstrated the importance of a MAPK docking domain necessary for protein-protein interaction with MAPKs and consequently also for phosphorylation. The main phosphorylated site was mapped to a residue conserved between all three proteins, which when mutated to a non-phosphorylatable form, differentially affected their protein stability. Together with their distinct gene expression patterns, this differential accumulation of the three proteins upon phosphorylation probably contributes to their distinct function(s). Transgenic over-expression of PRP, the founding member, led to plants with enhanced resistance to Pseudomonas syringae pv. tomato DC3000. Older plants of the over-expressing lines have curly leaves and were generally smaller in stature. This growth phenotype was lost in plants expressing the phosphosite variant, suggesting a phosphorylation-dependent effect. Thus, this novel family of PRPs may be involved in MAPK regulation of plant development and / or pathogen resistance responses. As datamining associates PRP expression profiles with hypoxia or oxidative stress and PRP-overexpressing plants have elevated levels of reactive oxygen species, PRP may connect MAPK and oxidative stress signaling.

High-Intensity Exercise Acutely Increases Substantia Nigra and Prefrontal Brain Activity in Parkinson's Disease.

BACKGROUND Pathologic alterations in resting-state brain activity patterns exist among individuals with Parkinson's disease (PD). Since physical exercise alters resting-state brain activity in non-PD populations and improves PD symptoms, we assessed the acute effect of exercise on resting-state brain activity in exercise-trained individuals with PD. MATERIAL AND METHODS Resting-state functional magnetic resonance imaging (fMRI) was collected twice for 17 PD participants at the conclusion of an exercise intervention. The acute effect of exercise was examined for PD participants using the amplitude of low frequency fluctuation (ALFF) before and after a single bout of exercise. Correlations of clinical variables (i.e., PDQ-39 quality of life and MDS-UPDRS) with ALFF values were examined for the exercise-trained PD participants. RESULTS An effect of acute exercise was observed as an increased ALFF signal within the right ventromedial prefrontal cortex (PFC), left ventrolateral PFC, and bilaterally within the substantia nigra (SN). Quality of life was positively correlated with ALFF values within the vmPFC and vlPFC. CONCLUSIONS Given the role of the SN and PFC in motor and non-motor symptoms in PD, the acute increases in brain activity within these regions, if repeated frequently over time (i.e., exercise training), may serve as a potential mechanism underlying exercise-induced PD-specific clinical benefits.

Learning to play against any mixture of opponents.

Intuitively, experience playing against one mixture of opponents in a given domain should be relevant for a different mixture in the same domain. If the mixture changes, ideally we would not have to train from scratch, but rather could transfer what we have learned to construct a policy to play against the new mixture. We propose a transfer learning method, Q-Mixing, that starts by learning Q-values against each pure-strategy opponent. Then a Q-value for any distribution of opponent strategies is approximated by appropriately averaging the separately learned Q-values. From these components, we construct policies against all opponent mixtures without any further training. We empirically validate Q-Mixing in two environments: a simple grid-world soccer environment, and a social dilemma game. Our experiments find that Q-Mixing can successfully transfer knowledge across any mixture of opponents. Next, we consider the use of observations during play to update the believed distribution of opponents. We introduce an opponent policy classifier-trained reusing Q-learning data-and use the classifier results to refine the mixing of Q-values. Q-Mixing augmented with the opponent policy classifier performs better, with higher variance, than training directly against a mixed-strategy opponent.

Assessing outcomes to determine whether symptoms related to hypertension justify renal artery stenting.

OBJECTIVE: The goal of the study was to determine the blood pressure (BP) response to renal artery stenting (RAS) for patients with hypertension urgency, hypertension emergency, and angina with congestive heart failure (angina/congestive heart failure [CHF]). METHODS: Patients who underwent RAS for hypertension emergencies (n = 13), hypertension urgencies (n = 25), and angina/CHF (n = 14) were included in the analysis. By convention, hypertension urgency was defined by a sustained systolic BP ≥ 180 mm Hg or diastolic BP ≥ 120 mm Hg, while the definition of hypertension emergency required the same BP parameters plus hypertension-related symptoms prompting hospitalization. Patient-specific response to RAS was defined according to modified American Heart Association reporting guidelines. RESULTS: The study cohort of 52 patients had a median age of 66 years (interquartile range 58-72). The BP response to RAS varied significantly according to the indication for RAS. Hypertension emergency provided the highest BP response rate (85%), while the response rate was significantly lower for hypertension urgency (52%) and angina/CHF (7%; P = .03). Only 1 of 14 patients with angina/CHF was a BP responder. Multivariate analysis showed that hypertension urgency or emergency were not independent predictors of BP response to RAS. Instead, the only independent predictor of a favorable BP response was the number of preoperative antihypertensive medications (odds ratio 7.5; 95% confidence interval 2.5-22.9; P = .0004), which is another indicator of the severity of hypertension. Angina/CHF was an independent predictor of failure to respond to RAS (odds ratio 118.6; 95% confidence interval 2.8-999.9; P = .013). CONCLUSIONS: Hypertension urgency and emergency are clinical manifestations of severe hypertension, but the number of preoperative antihypertensive medications proved to be a better predictor of a favorable BP response to RAS. In contrast, angina/CHF was a predictor of failure to respond to stenting, providing further evidence against the practice of incidental stenting during coronary interventions.

[Simultaneous determination of heavy metals in waste and biogas slurry of scale farm by microwave digestion/inductively coupled plasma-mass spectrometry].

A new microwave digestion/inductively coupled plasma mass spectrometry (ICP-MS) for simultaneous determination of 8 heavy metals including Zn, Cu, As, Pb, Cd, Cr, Hg and Ni in wastes of scale hoggery from livestock parks in Chongqing and its biogas slurry after anaerobic digestion, with which an all round, fast analysis of multiple heavy metals in biogas slurry was realized. From the experiment, Zn, Cu, As, Pb, Cd, Cr, Hg, and Ni were the dominating heavy metals in biogas slurry. The linear correlation coefficients for the heavy metals were between 0.999 89 and 0.999 98, indicating a good linear correlation. The determination limits were between 0.79 and 25.0 ng x L(-1), recovery adding standard between 96.5% and 107.6%, RSD between 1.06% and 4.35%. These parameters revealed that the method has good precision and accuracy, which could be applied to the heavy metals detection in biogas slurry, and provide reference for its post-use.

Designing all-pay auctions using deep learning and multi-agent simulation.

We propose a multi-agent learning approach for designing crowdsourcing contests and All-Pay auctions. Prizes in contests incentivise contestants to expend effort on their entries, with different prize allocations resulting in different incentives and bidding behaviors. In contrast to auctions designed manually by economists, our method searches the possible design space using a simulation of the multi-agent learning process, and can thus handle settings where a game-theoretic equilibrium analysis is not tractable. Our method simulates agent learning in contests and evaluates the utility of the resulting outcome for the auctioneer. Given a large contest design space, we assess through simulation many possible contest designs within the space, and fit a neural network to predict outcomes for previously untested contest designs. Finally, we apply mirror ascent to optimize the design so as to achieve more desirable outcomes. Our empirical analysis shows our approach closely matches the optimal outcomes in settings where the equilibrium is known, and can produce high quality designs in settings where the equilibrium strategies are not solvable analytically.

The emerging postural instability phenotype in idiopathic Parkinson disease.

Identification of individuals at high risk for rapid progression of motor and cognitive signs in Parkinson disease (PD) is clinically significant. Postural instability and gait dysfunction (PIGD) are associated with greater motor and cognitive deterioration. We examined the relationship between baseline clinical factors and the development of postural instability using 5-year longitudinal de-novo idiopathic data (n = 301) from the Parkinson's Progressive Markers Initiative (PPMI). Logistic regression analysis revealed baseline features associated with future postural instability, and we designated this cohort the emerging postural instability (ePI) phenotype. We evaluated the resulting ePI phenotype rating scale validity in two held-out populations which showed a significantly higher risk of postural instability. Emerging PI phenotype was identified before onset of postural instability in 289 of 301 paired comparisons, with a median progression time of 972 days. Baseline cognitive performance was similar but declined more rapidly in ePI phenotype. We provide an ePI phenotype rating scale (ePIRS) for evaluation of individual risk at baseline for progression to postural instability.

Mastering the game of Stratego with model-free multiagent reinforcement learning.

We introduce DeepNash, an autonomous agent that plays the imperfect information game Stratego at a human expert level. Stratego is one of the few iconic board games that artificial intelligence (AI) has not yet mastered. It is a game characterized by a twin challenge: It requires long-term strategic thinking as in chess, but it also requires dealing with imperfect information as in poker. The technique underpinning DeepNash uses a game-theoretic, model-free deep reinforcement learning method, without search, that learns to master Stratego through self-play from scratch. DeepNash beat existing state-of-the-art AI methods in Stratego and achieved a year-to-date (2022) and all-time top-three ranking on the Gravon games platform, competing with human expert players.

Quality measurement in cancer care delivery.

During the past decade, increasing emphasis has been placed on defining and measuring the quality of health care delivery. The Outcomes Committee of the Society of Surgical Oncology (SSO) was established in 2008 to explore and promote emerging outcomes-related topics that are most relevant to society membership. In recognition of the importance of health care quality, a mini-symposium was held at the SSO's 63rd Annual Cancer Symposium in St. Louis, Missouri, in March 2010. The primary objective of the symposium was to define what constitutes quality measurement in cancer care. This article presents an overview of the symposium proceedings.

Clinical and kidney morphologic predictors of outcome for renal artery stenting: data to inform patient selection.

BACKGROUND: The purpose of the current study was to identify clinical and kidney morphologic features that predict a favorable blood pressure (BP) response to renal artery stenting (RAS). METHODS: The study cohort consisted of 149 patients who underwent primary RAS over 9 years. Patients were categorized as "responders" based on modified American Heart Association guidelines: BP <160/90 mm Hg on fewer antihypertensive medications or diastolic BP <90 mm Hg on the same medications. All other patients were deemed "nonresponders." Renal volume was estimated as kidney length × width × depth/2 based on preoperative computed tomography or magnetic resonance scans. Median follow-up was 19 months (interquartile range [IQR] 10.0-29.5 months). RESULTS: The median age of the cohort was 68 years (IQR, 60-74 years). A favorable BP response was observed in 50 of 149 patients (34%). Multivariate analysis identified three independent predictors of a positive BP response: (1) requirement for four or more medications (odds ratio, 29.9; P = .0001), (2) preoperative diastolic BP >90 mm Hg (OR, 31.4; P = .0011), and (3) preoperative clonidine use (OR, 7.3; P = .029). The BP response rate varied significantly based on the number of predictors present per patient (P < .0001). Among patients with three-drug hypertension, a larger ipsilateral kidney (volume ≥150 cm(3)) increased the BP response rate more than threefold compared with patients with smaller kidneys (63% vs 18% BP response rate; P = .018). CONCLUSIONS: The current study demonstrated that three clinical predictors (≥4 antihypertensive medications, diastolic BP ≥90 mm Hg, and clonidine use) are preoperative predictors of BP response to RAS. Kidney volume may help in discriminating responders from nonresponders among those patients with three-drug hypertension. These parameters may assist clinicians in patient selection and provide more concrete data with which to counsel patients on the likely outcomes for RAS.

Validation of the attention-related driving errors scale in novice adolescent drivers.

INTRODUCTION: Motor vehicle collisions (MVCs) are a leading cause of death among adolescents. Identifying factors that contribute to adolescent MVCs is a pressing public health need. Exogenous (cell phones, passengers, music) and endogenous (stress, worry, mind-wandering) forms of driver inattention account for approximately 78% of all MVCs in the United States. Though both exogenous and endogenous distraction contribute to crash risk, prior work investigating adolescent crash risk has largely focused on exogenous distractors. The Attention-Related Driving Errors Scale (ARDES) is a promising measure assessing individual differences in endogenous driver inattention that has been validated in adult drivers. Its validation in an adolescent sample may prove useful in tailoring future interventions to decrease MVC risk in young drivers. METHODS: This study sought to validate the ARDES in novice adolescent drivers by investigating its underlying factor structure and its relations with self-reported measures of daily inattention, performance-based attention assessments, and a self-report measure of driving behavior. RESULTS: Replicating earlier work in adults, results suggested ARDES items can be classified according to their operational level of the driving. The ARDES had good internal reliability and construct validity, suggesting it is a valid self-report measure of the propensity for adolescents' attentional errors while driving. DISCUSSION: The ARDES provides a useful tool for researchers to identify adolescents at greater risk of attentional errors while driving. Future research should use the ARDES to better understand the role of driver inattention in adolescent crash risk.

Developmental trajectories of driving attention in adolescents: Preliminary findings from REACT.

OBJECTIVE: To characterize the trajectory of driving attention as a function of age and driving experience. Hypotheses. The rate of change in driving attention will be greater for 16- compared to 18-year-olds and those acquiring driving experience (vs. non-drivers). Age and driving experience will interact, with the effect of driving experience being stronger among 16- compared to 18-year-olds. METHODS: In this longitudinal study, 190 adolescents were enrolled into 4 groups: (1) 16-year-olds and (2) 18-year-olds recruited within 2 weeks of obtaining a full driver's license; (3) 16-year-olds and (4) 18-year-olds with no driving experience (no permit/license, no intention to obtain either over study period). At seven time points over 18 months, participants drove in a high-fidelity driving simulator integrated with eye tracking. Participants completed three experimental drives with three safety critical events and varying cognitive load conditions. Driving attention was measured by vertical and horizontal eye movements, number of glances, and glance length. A multilevel model using SAS PROC MIXED (SAS 9.4) will estimate the baseline intercept and slope of driving attention over time, with baseline age, driving experience, and their interaction serving as predictors of intercept and slope. RESULTS: Preliminary analyses suggest driving attention changes over time as a function of age, driving experience, and across cognitive load conditions. CONCLUSIONS: Inattention is the primary contributor to motor vehicle crashes. It is critical to gain a clear understanding of how driving attention changes during adolescence, the riskiest developmental period for drivers. Results will reveal how driving impacts attention development through practice, providing a target for intervention.

Neurite Orientation Dispersion and Density Imaging (NODDI) and Duration of Untreated Psychosis in Antipsychotic Medication-Naïve First Episode Psychosis Patients.

Background: Diffusion tensor imaging suggests that white matter alterations are already evident in first episode psychosis patients (FEP) and may become more prominent as the duration of untreated psychosis (DUP) increases. But because the tensor model lacks specificity, it remains unclear how to interpret findings on a biological level. Here, we used a biophysical diffusion model, Neurite Orientation Dispersion and Density Imaging (NODDI), to map microarchitecture in FEP, and to investigate associations between DUP and microarchitectural integrity. Methods: We scanned 78 antipsychotic medication-naïve FEP and 64 healthy controls using a multi-shell diffusion weighted sequence and used the NODDI toolbox to compute neurite density (ND), orientation dispersion index (ODI) and extracellular free water (FW) maps. AFNI's 3dttest++ was used to compare diffusion maps between groups and to perform regression analyses with DUP. Results: We found that ND was decreased in commissural and association fibers but increased in projection fibers in FEP. ODI was largely increased regardless of fiber type, and FW showed a mix of increase in decrease across fiber tracts. We also demonstrated associations between DUP and microarchitecture for all NODDI indices. Conclusions: We demonstrated that complex microarchitecture abnormalities are already evident in antipsychotic-naïve FEP. ND alterations are differentially expressed depending on fiber type, while decreased fiber complexity appears to be a uniform marker of white matter deficit in the illness. Importantly, we identified an empirical link between longer DUP and greater white matter pathology across NODDI indices, underscoring the critical importance of early intervention in this devastating illness.