Journal of Microbiology & Biology Education

The iTHRIV Scholars Mentored Career Development Program initiated an Internal Grant Review (IGR) program in 2020 for current and recently graduated Scholars seeking funding through K and R awards from the NIH. The IGR program is designed to replicate the NIH review process and provide Scholars the opportunity to receive valuable feedback on their applications prior to NIH submission. A key characteristic of the program is the integration of REDCap, enabling automation and year-round offering while improving tracking and reporting efforts and capabilities. Results of the program have been overall positive, both in proposal development and participant feedback. IGR is a sustainable, valuable resource for early-career faculty competing for limited resources in the pursuit to become independently funded clinical translational scientists.

The health and wellbeing of living organisms and the environment are irrevocably interconnected. Animals constantly shape the environments in which they live, and environmental factors, in turn, shape the minds and behaviours of animals. The emerging discipline of environmental neuroscience studies this reciprocal interaction and offers a unique opportunity to integrate sustainability into undergraduate training. Here, we present and evaluate Forging Sustainable Research, an interdisciplinary undergraduate course that integrates teaching of neuroscience, biology, psychology, environmental science, and sustainable development. Students explore how research in these fields can be interlinked 24 and re-oriented towards addressing emerging environmental challenges. In parallel, students learn how to measure and mitigate the environmental impact of research activities. Student feedback suggests that the course is effective at raising awareness and understanding of sustainability in research, while also enhancing student perception of their own ability to promote positive change. As climate and ecosystem change impact all sectors, sustainability awareness in academic and professional spaces is increasingly sought after. Students in the course therefore receive training in transferable skills relevant for diverse career paths. In the long term, this course may serve as model for direct integration of sustainability training into undergraduate curricula in the natural sciences.

Background: Neuroanatomy poses a significant challenge for Psychology students due to its spatial and conceptual complexity. Educational approaches that enhance the relevance and visualization of neuroanatomical content may improve students learning experiences. This study implemented a tractography-based activity focused on the virtual dissection of the arcuate fasciculus, a major white matter pathway, in undergraduate Psychology students and examined the relationships between perceived learning and students perceptions of utility, difficulty and handling, and organizational aspects of the activity. Methods: First-year undergraduate Psychology students participated in a two-session tractography-based activity combining instruction on white matter anatomy and diffusion tractography with a hands-on virtual dissection of the arcuate fasciculus using research-grade software routinely employed in neuroscience research. Following the activity, students completed an anonymous questionnaire assessing perceived learning, utility, difficulty and handling, and organizational aspects of the activity. Pearson correlations, multiple regression analyses, and relative importance analyses were performed. Results: Sixty-eight students completed the questionnaire. Students reported generally positive perceptions of the activity across the evaluated dimensions, with perceived learning receiving the highest mean score (M = 3.44, SD = .85). Perceived utility showed the strongest association with perceived learning (r = .64, p < .001). The regression model explained 41% of the variance in perceived learning (R2 = .41, adjusted R2 = .38, p < .001). Perceived utility was the only significant predictor in the model ({beta} = .59, p = .001), accounting for 67.9% of the explained variance. Conclusions: The findings support the feasibility of integrating authentic neuroimaging tools into undergraduate neuroanatomy teaching. Students who perceived the activity as more useful also reported higher perceived learning outcomes, with perceived utility emerging as the strongest predictor of perceived learning. In contrast, perceived difficulty and handling, and organizational aspects did not make significant independent contributions. These results suggest that students perceptions of educational relevance may play an important role in technology-enhanced STEM learning experiences.

Background: The rapidly evolving United States (U.S.) health and science policy landscape in 2025 may have heterogeneous effects on academic medicine, biomedical research, physician workforce development and patient care. Research Question: How do academic pulmonary and critical care medicine (PCCM) physicians perceive U.S. health and science policy changes and which changes do they consider most influential on research, trainee education and clinical care? Study Design and Methods: We conducted a prospective survey from March 27, 2026 through April 29, 2026 among selected faculty at U.S. academic PCCM programs as part of the Alliance of Scholars and Professionals for Innovation, Research, and Education in Pulmonary and Critical Care Medicine (ASPIRE-PCCM). Results: Ninety-four of 99 ASPIRE-PCCM panel members completed the survey (response rate 95%), representing 18 of 19 ASPIRE-PCCM wave 1 institutions. All respondents reported the rate of changes in U.S. federal health and science policy in the first half of 2025 as 6 or higher on a scale of 1 ("typical pace of change") to 10 ("most change in my lifetime"), with 89 (96%) evaluating the changes as harmful or very harmful. Respondents identified cancellation of research grants, disruptions and changes to NIH scientific review processes, and changes to visa and immigration policies as key factors affecting early career recruitment. Reported negative effects on quality of care included increased vaccine hesitancy, changing reimbursement structures, and diminished research capacity. State-level and non-governmental efforts, including professional society advocacy, institutional bridge funding and personal advocacy efforts were identified as partially mitigating harms. Despite these concerns, 72% of respondents reported that would still pursue careers in PCCM. Interpretation: Academic pulmonary and critical care physicians reported challenges following recent U.S. health and science policy changes that may be mitigated, but not neutralized, by institutional, professional-society, and individual actions.

Funding and publishing scientific research has become increasingly competitive, highlighting a growing need for clear and accurate scientific communication. Scientific editors are professionals who help ensure that grant proposals and research manuscripts meet the standards of funding agencies and peer-reviewed journals while effectively communicating research significance to diverse audiences. However, detailed information characterizing the scientific editing profession is scarce. While some organizations have conducted salary surveys, to our knowledge, no comprehensive survey of the scientific editing field has been conducted. Here, we report findings from a 2024 comprehensive survey of 132 scientific editors. We collected data on demographics and education, career experience and current employment, skills and types of editing, and outcomes and satisfaction. Our data reveal that scientific editors have homogenous demographic characteristics but considerable variability in job titles, employment mechanisms, and career pathways. As the responsibilities of many scientific editors, including supporting proposal development, applying best practices in grantsmanship, and identifying strategies to enhance competitiveness for research funding, overlap with those of research development professionals, our findings provide considerations for further incorporating or defining the role of scientific editors within research development offices. Our results also suggest avenues for scientific editors to start or advance their careers. We anticipate that our results will serve as a foundation for discussions on the future directions of the scientific editing profession as well as areas for future research and professional development.

Currently, a significant proportion of young people are discouraged by the teaching of botany and, consequently, show little interest in preserving local biodiversity. On the other hand, with the recurrent use of digital technologies (DTs), young people have shown significant interest in virtual devices. Our project's tested the hypothesis whether plants awareness disparity in public school students was overcome through active teaching and learning. Thus, the objective was to investigate the use of active methodology in a non-formal teaching environment (e.g., sensory garden, SG) in order to stimulate learning in plant organography based on its evaluation using digital games. Our proposal was investigated at the Lagoa do Sino campus (Buri/SP, Brazil) in partnership with the Public School System of the Municipality of Campina do Monte Alegre/SP, Brazil. Furthermore, students were divided into two teams, which applied qualitative methodologies, such as that one of these (Team A) had face-to-face contact with the SG, using the Problem-Based Learning (PBL) methodology, digital game and survey. Team B, on the other hand, will only have contact with the game. After collecting the data, we verified statistically significant differences between the teams using the Wilcoxon test and based on the latent traits evaluated. Given this, the literature points out that discouraging students influences their learning and, consequently, their education. In addition, our considerations are based on the latent trait knowledge of botany and, thus, we reject our null hypothesis and accept our alternative hypothesis. On the other hand, based on the latent trait of plant perception, we cannot affirm the acceptance or rejection of the hypotheses. It is worth noting that future studies should have a larger number of participants than this research in order to better evaluate what is intended.

Musical aesthetic experience can reveal students' cognitive, aesthetic, and emotional responses to music. However, how professional vocal training alters brain functions in female college students with varying levels of musicianship to promote these is unknown. Here we applied fMRI, psychological measures and Goldsmiths musical sophistication index (Gold-MSI) assessments to study 27 non-music major female college students consisting of instrument group (normal pitch accuracy with instrumental training), general group (normal pitch accuracy without instrumental training) and poor-pitch group (poor pitch accuracy and without instrumental training). After 1 year of one-on-one instructional practice, we found that professional vocal training enhanced information processing related to musical cognition and pleasure during musical aesthetic experiences across all three groups, involving improvements in motor control of vocalization, auditory feedback processing, musical memory and attention together with musical pleasure. Specifically, instrument group showed activation of reward circuits, general group exhibited activation of laryngeal motor control circuits, and poor-pitch group displayed activation of sensory/sensorimotor/motor control circuits. Both pre- and post-training, the instrument group exhibited higher connectivity than the other two groups in the left amygdala-dorsal anterior cingulate cortex (dACC) and the right posterior superior temporal gyrus (pSTG)-left insula pathway. After professional vocal training, the general group showed higher connectivity in the left amygdala-dACC, whereas the poor-pitch group demonstrated increased connectivity in the right pSTG-left insula and dACC-nucleus accumbens pathways. Surprisingly, professional vocal training activated the bed nucleus of the stria terminalis (BNST), a subcortical emotion center, and connectivity with the medial prefrontal cortex associated with musical information processing. Thus, vocal training can significantly improve musical cognition and aesthetic pleasure, and facilitates neural modulation in the brain's emotional centers.

Background Attentional control declines with normal aging, yet the role of modifiable lifestyle factors in accelerating this decline remains incompletely characterised in large, diverse populations. We examined associations between four modifiable risk factors (smoking intensity, alcohol binge drinking, social satisfaction and blood pressure) and sustained attention performance in 13,866 adults drawn from the All of Us Research Program. Methods Cognitive performance was assessed using the Gradual-Onset Continuous Performance Task (GradCPT). A composite cognitive efficiency score was derived via principal component analysis of four GradCPT metrics: d' (perceptual sensitivity), response criterion, median reaction time and reaction time variability. Associations between cognitive efficiency and each risk factor were examined using multiple linear regression adjusted for age, sex and race/ethnicity. Effect sizes were expressed as age-equivalent years of cognitive aging (age-equivalent years = regression coefficient for the risk factor divided by the regression coefficient for age) to aid clinical interpretation. Results GradCPT performance declined progressively with age (p < 0.001). Social satisfaction emerged as the strongest lifestyle predictor: low social satisfaction was associated with approximately 5.8 additional age-equivalent years of cognitive aging relative to high social satisfaction. Smoking showed a dose-response pattern, with heavy smokers (> 20 cigarettes/day) exhibiting an approximately 5-year age-equivalent deficit versus never-smokers. Stage 2 hypertension showed a modest, non-significant negative association. Binge drinking showed limited significant associations, likely complicated by survivor and abstainer biases. Bootstrapped analyses of combined exposures showed that combinations of risk factors, particularly those involving low social satisfaction, produced larger cognitive deficits than expected under an additive model. Conclusions These findings support an interactive rather than a purely additive model of lifestyle-related cognitive vulnerability and highlight the GradCPT as a subclinical measure of attention-based cognitive risk in non-clinical populations. Keywords Cognitive aging, Sustained attention, GradCPT, Modifiable risk factors, Social isolation, Smoking, Hypertension, All of Us Research Program

NTRODUCTION: Alzheimer's disease (AD) shows sex differences in risk, clinical progression, and biomarker profiles, but whether inherited genetic liability to modifiable risk factors contributes differently to AD susceptibility in females and males remains unclear. We evaluated whether genetic relationships between several modifiable dementia risk factors and AD differ between females and males. METHODS: We integrated polygenic risk scores (PRSs) for modifiable risk factors, genome-wide genetic correlation, and two-sample Mendelian randomization (MR) analyses. PRS associations with AD diagnosis were evaluated in the Alzheimer's Disease Genetics Consortium (n=27,751) and with AD plasma biomarkers in the Health and Aging Brain Study-Health Disparities (n=2,307-2,737, depending on the biomarker). Primary analyses evaluated female- and male-specific associations and compared sex-specific estimates. RESULTS: Educational attainment and physical activity PRSs were associated with AD in both sexes. PRS sex differences were nominal for educational attainment, total cholesterol, and LDL cholesterol, but none remained significant after FDR correction. Genetic correlation showed FDR-significant sex differences for social isolation, physical activity, LDL cholesterol, and pulse pressure. MR identified FDR-significant associations within sex strata; higher HDL cholesterol was associated with lower AD risk in females, whereas higher total cholesterol and type 2 diabetes were associated with lower and higher AD risk, respectively, in males. Sensitivity analyses provided inconsistent support, and no sex difference in MR estimates remained significant after FDR correction. In HABS-HD, type 2 diabetes PRS was associated with higher NfL, BMI PRS with higher pTau181, and the composite PRS with higher NfL among males after FDR correction. DISCUSSION: Evidence that modifiable dementia risk factors relate differently to AD by sex was limited and depended on the genetic measure examined. Sex differences in genome-wide genetic overlap were not consistently reflected in PRS or MR, indicating that shared genetic architecture does not necessarily translate into sex-specific inherited liability or causal effects

Quantifying neural health with a single measure remains a major unmet challenge. Here, we report a physiological marker based on the spatial distribution of signal-derived energy correlates in the resting brain. We hypothesize that energy organization in the healthy brain approaches an entropy-maximizing, homeostatically regulated state characterized by five properties: lognormal energy distributions, balanced spatial allocation, statistical independence between regions, low energy variance, and temporal stability. Together, these properties define an energetic profile that the Neural Health Index (NHI) summarizes as a single score, computable from (scalp/intracranial) electroencephalography, magnetoencephalography, or functional magnetic resonance imaging. Across 808 participants spanning neurological, psychiatric, neurodevelopmental, and neurodegenerative disorders, NHI distinguished healthy from clinical populations with sensitivity and specificity exceeding 95% in internal and external validation, scaled with disease severity, tracked pharmacological treatment exposure, and generalized to unseen diagnoses. These findings support NHI as a disease-agnostic, modality-invariant candidate biomarker for disease stratification and treatment monitoring.

Background Adverse childhood experiences are major determinants of mental disorders, health-risk behaviours and non-communicable diseases across the life course, but evidence from India remains limited. This study aims to estimate the prevalence and patterns of adverse childhood experiences among Indian adolescents, examine their associations with mental health and non-communicable disease risk factors, and evaluate a culturally adapted school-based intervention integrating trauma-informed care and social-emotional learning. Methods A sequential mixed-methods study will be conducted among approximately 1,632 adolescents in 16 public and private schools in Chandigarh and Mohali, India. Phase I is a cross-sectional survey of adverse childhood experiences, mental health, perceived stress, sleep, screen time and behavioural and biological risk factors for non-communicable diseases. Phase II comprises focus group discussions and key informant interviews with students, parents, teachers, counsellors and mental health professionals to inform intervention development. In Phase III, findings from both phases will guide development of the intervention using the ADDIE (Analysis, Design, Development, Implementation and Evaluation) instructional design framework. In Phase IV, adolescents reporting ACE exposure will participate in a school-based intervention delivered over 8-12 weeks by trained psychologists, comprising trauma-informed social-emotional learning sessions, individual counselling sessions for high-risk adolescents (at least six sessions), school-wide awareness activities and parental sensitization. Effectiveness will be evaluated using a quasi-experimental pre-post design. The primary outcome will be change in emotional and behavioural difficulties measured by the Strengths and Difficulties Questionnaire (SDQ). Secondary outcomes will include changes in depressive symptoms (Patient Health Questionnaire-9), perceived stress, sleep quality, school functioning, and behavioural risk factors for NCDs. Recruitment began in April 2026 and is ongoing; data collection is expected to be complete by June 2028, and no results have yet been generated.

We previously found that skin tone correlates with intronic polymorphisms influencing the expression of the Joubert Syndrome (JS) ciliopathy gene TMEM138, suggesting that primary cilia might regulate pigment production in skin melanocytes. Herein, we show that many ciliary proteins regulate basal pigmentation in wild-type mouse and human melanocytes by facilitating primary cilium-dependent Melanocortin-1 receptor signaling, and downstream activation of the Microphthalmia transcription factor and melanogenic gene expression. Additionally, we identify an extra-ciliary moonlighting role for TMEM138 and other JS proteins in endolysosomal organization required for the biogenesis of melanosomes, the pigment-producing lysosome-related organelle in melanocytes. Our results provide new mechanistic insights into the physiological regulation of pigmentation and suggest that JS-specific pathology might be mediated by ciliary-independent mechanisms.

Background: Nutrition education and physical activity support are important components of type 1 diabetes mellitus (T1DM) care, but their association with body composition outcomes in routine Ugandan diabetes services remains uncertain. We evaluated a culturally tailored health promotion programme among adolescents and young adults living with T1DM. Methods: We conducted a trial study in Wakiso Health Centre IV, Uganda. Sixty participants aged 13 to 26 years were allocated through an alternating clinic-week schedule to an intervention group or usual-care control group, with 30 participants per group. The eight-week Active Hearts, Healthy Lives programme combined nutrition education, personalised dietetic counselling, physical activity support, and practical self-management activities. Anthropometric and bioelectrical impedance measurements were obtained at baseline and six months after baseline. Separate linear regression models compared follow-up outcomes, adjusting for the corresponding baseline measurement, age, and sex. Results: Participants had a mean age of 19.45 years (SD 3.02), and 33 (55.0%) were female. Compared with controls, the intervention group had lower adjusted fat mass and BMI and higher fat-free mass and muscle mass. These differences reflected modest changes among intervention participants alongside increased fat mass and decreased fat-free mass and muscle mass among controls. Conclusion: Participation in the programme was associated with differences in estimated body composition at six months. Larger randomised evaluations incorporating clinical and functional outcomes are needed to establish whether the programme provides meaningful health benefits.

The role of aberrant glycosylation in pancreatitis remains an under-investigated area of research. Here, we determined that the ST6GAL1 sialyltransferase, which adds 2-6-linked sialic acids to N-glycoproteins, was upregulated in pancreatic tissues from patients with acute (AP) and chronic (CP) pancreatitis, and in mice with experimental AP. Within these tissues, ST6GAL1 was selectively expressed in acinar cells undergoing acinar to ductal metaplasia (ADM), a process whereby injured acinar cells de-differentiate and re-enter the cell cycle to enable tissue repair. To study the functional role of ST6GAL1 in pancreatitis, we used HPNE pancreatic epithelial cells with modulated ST6GAL1 expression, along with pancreatic organoids from mice with transgenic expression of ST6GAL1 (SC mice). In these models, ST6GAL1 activity promoted the activation of EGFR (a well-known ADM-driver), ERK, and AKT. ST6GAL1-expressing cells also displayed an ERK-dependent upregulation of the anti-apoptotic proteins, Mcl-1 and Bcl-xL, and impaired apoptotic signaling by the TNFR1 and Fas death receptors. Unbiased kinomics profiling revealed that ST6GAL1 induced the activation of many receptor tyrosine kinases associated with cell survival and proliferation (e.g., EGFR, PDGFR, MET). Furthermore, ST6GAL1 enhanced the survival and proliferation of cells exposed to stress-inducing conditions such as serum withdrawal. Based on these findings, we hypothesized that the pro-survival phenotype imparted by ST6GAL1 would facilitate tissue healing following a bout of pancreatitis. Accordingly, we induced AP in wild type and SC mice via L-arginine injection and found that SC mice had more rapid and efficient tissue repair, evidenced by accelerated restoration of the acini, diminished acinar apoptosis, and reduced immune cell infiltration. Together, these findings highlight a novel glycosylation-dependent mechanism that drives cell survival, positioning ST6GAL1 as a key adaptive mediator of pancreatic regeneration.

Microglia represent a highly dynamic and heterogeneous cell type that is critically implicated in states of health and pathology. Microglial morphological subgroups have been identified that correspond to functional characteristics determining health-related outcomes. The identification of states based on morphological characteristics will therefore provide invaluable insights into the microglia-specific functional mechanisms driving treatment effects. The application of clustering analyses enables the detection of groupings within samples reflecting differences in morphological features. Here we propose the application of three custom-created modules to be used within the open-source software CellProfiler. These modules enable the automated detection of clusters present within the sample of microglia, as well as the assessment of the abundance of these clusters across conditions. The application of the analysis is conducted in a highly user-friendly manner, with a user interface integrated into the pipeline, enabling the performance of the analysis with only minimal user input. The workflow thereby includes the conduction of an outlier assessment, followed by hierarchical clustering and k-means clustering and the generation of interactive graphs to determine the number of microglia states present in the sample. Bar plots displaying the abundance of the microglia states across conditions included in the sample will be created. This approach will facilitate faster and more comparable detection of microglial morphological clusters across studies.

Quiescence is a reversible proliferation arrest enabling cells to adapt to environmental changes, yet the post-transcriptional mechanisms governing its transitions remain poorly understood. Here, we map genome-wide alternative polyadenylation (APA) dynamics across 15 time points of quiescence transitions in fission yeast using 3'-end RNA sequencing. We reveal that APA undergoes extensive remodeling: driving global 3'UTR lengthening during early quiescence entry, 3' UTR shortening upon quiescence establishment, and progressive reversal to proliferative-state lengths during quiescence exit. Integrating 3' UTR dynamics with differential expression analysis, we identify candidate genes potentially regulated through APA-mediated 3' UTR mechanisms. We demonstrate that sod2, encoding mitochondrial superoxide dismutase, autoregulates its mRNA and protein levels via APA-dependent 3' UTR changes. Disrupting proximal APA site of sod2 in a mitophagy-deficient (atg43{Delta}) background exacerbates quiescence maintenance defects and mitochondrial dysfunction. We further identify Pabp as an upstream regulator of sod2 APA. This study establishes the temporal APA remodeling during quiescence transitions and reveals a Pabp-APA-sod2 regulatory axis governing post-transcriptional control of cellular quiescence.

In eukaryotic cells, the positive transcription elongation factor b (P-TEFb) plays a critical role in the transition of RNAPII from the paused state to actively transcribing mode. Although three different cyclin (Cyc) T (CycT1, T2a, and T2b) interact with CDK9 to form functional P-TEFb, a majority of P-TEFb complexes are comprised of the CycT1 and CDK9. To analyze the role of the CycT1 subunit of P-TEFb on cellular transcription, we established HEK293T cells lacking CycT1 proteins (CycT1-KO cells). While no apparent growth defects were observed with CYcT1-KO cells, the level of CDK9 was decreased and no compensatory over-expression of CycT2 was observed, suggesting that the reduced level of functional P-TEFb complexes is sufficient for the normal cell growth. Reporter gene assays indicate that NF-kappaB-dependent transcription induced by PMA was impaired in CycT1-KO cells although the function of NF-kappaB (P65) per se was not affected. On the other hand, AP1-dependent transactivation induced by PMA was unaffected in CycT1-KO cells. Moreover, transcription stimulated by JQ1, a strong P-TEFb inducer, was reduced in CycT1-KO cells. Data of biochemical analysis indicate that P-TEFb with CycT1 (P-TEFb (CDK9:CycT1)) was efficiently released from 7SKsnRNP by JQ1 while P-TEFb (CDK9:CycT2) was not affected by JQ1. Transcriptome analysis indicated that the lack of CycT1 had a minor effect on the steady-state transcription. However, expression of JQ1-dependent genes was severely reduced in CycT1-KO cells. Interestingly, referring to gene expression profiles of 33 different types of cancer revealed that 11 out of 13 top JQ1-dependent genes were also highly upregulated in Pancreatic Adenocarcinoma. From these results, we conclude that although many genes can be regulated by both P-TEFb (CDK9:CycT1) and P-TEFb (CDK9:CycT2), CycT1 plays a critical role in regulating highly inducible genes, which are also aberrantly regulated in a particular type of cancer.

While lysosomal lipid dysregulation is implicated in Parkinsons disease (PD), identifying the precise enzymatic drivers remains limited by the lack of subcellularly resolved metabolic mapping. Leveraging endosome-origin plasma extracellular vesicle (PsEV) lipidomics, we identified a profound bidirectional disruption of the ceramide-sphingomyelin (SM) axis in PD, driven by asymmetric upregulation of sphingomyelin phosphodiesterase 1 (SMPD1) and sphingomyelin synthase 1 (SGMS1). BODIPY-C5 SM tracking revealed that SMPD1 perturbation severely impairs lysosomal SM turnover. Crucially, this SMPD1-driven hydrolysis forces a salvage pathway collapse, bottlenecked by SPHK1/SGPL1 downregulation, which precipitates oxidative membrane damage and PINK1/Parkin-dependent mitophagy failure. We robustly validated this multi-pathway dysfunction across orthogonal in vitro, in vivo mouse, and postmortem human brain models. Furthermore, SMPD1/SGMS1 expression distinctly stratifies clinical phenotypes, marking the aggressive Postural Instability/Gait Difficulty (PIGD) subtype. Our findings establish SMPD1-mediated lysosomal impairment and ceramide-SM imbalance as a core biochemical axis in PD pathophysiology.

Primary sulcal patterns, the spatial arrangement of the earliest cortical folds, emerge prenatally and remain essentially stable after birth. Alterations are associated with cognitive outcomes and hold promise as clinical biomarkers. However, detecting abnormalities is challenging due to the high topological variability and complexity of normal individual sulcal patterns. Here, we introduce an unsupervised generative model that quantifies individual sulcal pattern deviations against a normative baseline learned from 10,349 typically developing subjects spanning early childhood through adulthood. We combine a generative reconstruction error with a discriminator trained on diffusion-generated pseudo-atypical graphs to leverage their complementary strengths in sensitivity and robustness. The discriminator captures subtle anomalies and is robust to demographic and data quality variations, whereas the generative model enables severity stratification and demonstrates cross-site generalizability. Across two clinical cohorts spanning subtle to overt sulcal abnormalities (congenital heart disease and polymicrogyria), our model captured global and localized condition-related deviations and linked them to neurodevelopmental outcomes. By enabling population-scale, individualized quantification of sulcal deviations, this framework provides a foundation for future clinical risk stratification.

Genetics shape cocaine behavior and abuse liability, but the underlying neurophysiological effects remain understudied. In male C57BL/6J, B6129SF2/J, and DO/J mice, we report conserved and divergent cocaine induced neuroplasticity in the accumbens shell following 5 days of cocaine and 10 to 14 days of abstinence.