The gut microbiota varies along the length and cross-section of the gastrointestinal (GI) tract, influencing diseases. Direct sampling from the upper GI tract remains challenging due to anatomical constraints and low-volume genomic sequencing. Here, we report an ingestible, pill-like microdevice (7 × 2.7mm) that enables in vivo microbiome and biomarker sampling in Sprague-Dawley rats - demonstrating, for the first time, successful autonomous pyloric transit of a microdevice via oral gavage. The device comprises an enteric-coated gelatin cap that protects it in gastric pH (1-1.5) and disintegrates at intestinal pH (3-5), allowing luminal fluid via an inlet connected to activation and sampling chambers. A polyacrylate hydrogel in the activation chamber swells to seal the inlet to prevent cross-contamination. In vivo studies (n = 5) confirmed successful pyloric transit in 4/5 rats without tissue injury or inflammation. Each retrieved device yielded 13.48 ± 4.66ng genomic DNA, enabling 16S rRNA sequencing of site-specific microbiota distinct from fecal profiles. Concurrent detection of intestinal alkaline phosphatase (≈6.5µgmL-1) confirmed dual microbiome-protein biomarker capability. We demonstrate species-level microbiota identification via nanopore sequencing using an orally ingestible platform technology for longitudinal gut microbiome profiling, paving way for studies in large animals and humans.

Extracellular vesicles (EVs) are naturally secreted as non-cell-autonomous signals involved in regulating immune responses, aging, angiogenesis, and tissue injury and repair within the central nervous system (CNS). Consequently, EVs have emerged as promising therapeutic targets in CNS-related diseases. More recently, a subset of these vesicles has been found to contain mitochondria (mitoEVs), suggesting that vesicles carrying mitochondrial signatures may also function as non-cell-autonomous signals and serve as potential biomarkers for injury or recovery in CNS pathophysiology. In this mini-review, we summarize current findings highlighting the critical roles of EVs and their therapeutic potential as demonstrated in cellular, animal, and human studies related to CNS injury and disease.

The 2016 Surviving Sepsis Campaign (SSC) guidelines recommended tapering corticosteroids once vasopressors were no longer needed, while the 2021 update suggested IV hydrocortisone for patients with ongoing vasopressor needs but offered no guidance on tapering. Evidence on steroid taper duration remains limited. This study evaluates corticosteroid tapering strategies in septic shock patients. A retrospective analysis, approved by the UNC Human Research Review Committee, was conducted on adult critically ill patients with septic shock who received vasopressors and hydrocortisone between January 1, 2016, and April 1, 2024. Patients were divided into 2 groups based on the duration of their steroid taper: rapid taper (<72 hours) and prolonged taper (≥72 hours). The primary outcome was vasopressor reinitiation within 72 hours of all vasopressors being stopped. Secondary outcomes included vasopressor reinitiation within 24 hours of all vasopressors being stopped, length of stay (LOS), mortality, and adverse effects. The study was approved by the University of North Carolina Human Research Review Committee. A total of 312 patients were analyzed: 222 received a rapid taper and 90 received a prolonged taper. Vasopressor reinitiation within 72 hours occurred in 48% of the rapid taper group and 66% of the prolonged group (P = 0.006). Within 24 hours, reinitiation was 42% in the rapid group versus 56% in the prolonged group (P = 0.039). Mortality was 32% in the rapid group and 41% in the prolonged group (P = 0.185). Mean intensive care unit (ICU) LOS was 215 hours for the rapid group and 418 for the prolonged group (P < 0.001). Mean hospital LOS was 447 hours for the rapid group and 734 for the prolonged group (P < 0.001). Hypernatremia was less frequent in the rapid group (29% vs 47%, P = 0.004). Hyperglycemia was similar between groups (24% vs 21%, P = 0.327). Limitations included the retrospective design and potential for selection bias, temporal bias, and missing or inconsistently documented clinical variables. Rapid corticosteroid tapering in septic shock patients was associated with a reduced incidence of vasopressor reinitiation, shorter ICU and hospital stay, and a lower incidence of hypernatremia. These findings enhance our understanding of tapering strategies and suggest that rapid tapering (<72 hours) in septic shock may improve patient outcomes, informing future clinical guidelines.

Anhedonia, characterized by a diminished reactivity to pleasurable stimuli, is a core symptom across multiple neuropsychiatric disorders, including major depressive disorder. Disruptions in dopaminergic neurotransmission and dysfunction within the mesolimbic dopaminergic circuitry are key contributors to reward processing deficits. We hypothesized that low receptor occupancy-mediated antagonism of presynaptic inhibitory D2/D3 receptors could enhance dopaminergic neurotransmission and, in turn, improve reward responsiveness, a behavioral phenotype implicated in anhedonia. For this purpose, we developed ENX-104, a highly selective and potent D2/D3 receptor antagonist with favorable CNS pharmacokinetics, characterized by high brain penetrance and rapid plasma clearance. In preclinical studies, ENX-104 produced sustained increases in dopamine levels in the nucleus accumbens in rats. In the Probabilistic Reward Task (PRT), a preclinical model of reward responsiveness reverse-translated for rats from human studies designed to objectively quantify subdomains of anhedonia, ENX-104 enhanced reward responsiveness at low doses corresponding to approximately 10-50% D2/D3 receptor occupancy. Predictably, higher doses (65-80% receptor occupancy) were associated with antipsychotic-like effects in the rat conditioned avoidance response assay, while extrapyramidal side effects, such as catalepsy, emerged only at much higher occupancies ( > 80% receptor occupancy). Our integrated pharmacokinetic-pharmacodynamic modeling suggests that a once-daily oral dosing regimen of ENX-104 could enable low D2/D3 receptor occupancies, potentially offering a novel therapeutic approach for the treatment of psychiatric conditions characterized by deficits in reward responsiveness.

Background. Obesity remains one of the most significant global health challenges. However, it may be cured thanks to the microbiota modulation, as it could affect metabolic regulation. Probiotics have emerged as a potential adjunctive strategy supporting weight management and metabolic health. Aim. The aim of the study was to evaluate the effectiveness of selected probiotic strains in obesity management, as well as to analyse the mechanisms through which these strains influence metabolic and anthropometric outcomes. Material and methods. The research was based on a literature review and comparative analysis of randomized controlled trials published before November 2025. The analysis included human studies examining body weight, BMI, waist circumference, visceral fat, and metabolic markers after 8-24 weeks of probiotic supplementation. Results. The findings indicate that certain strains, such as Lactobacillus gasseri, Lactobacillus plantarum, and Bifidobacterium animalis subsp. lactis, demonstrating clinically relevant benefits – reductions in body weight, as well as improved lipid profiles and enhanced insulin sensitivity. However, the effectiveness varies between strains, and the overall impact remains moderate. Conclusions. Probiotic therapy remains as supportive intervention in obesity management, particularly when used alongside standard weight-loss strategies. Further well-designed clinical studies are required to determine optimal strains, dosages, and long-term safety profiles.

Abstract Background CAR T cells still face numerous obstacles in treating hematologic and solid malignancies. Although gene editing technologies have improved CAR T cell therapy, there are currently no systematic reviews to broadly address preclinical and clinical outcomes of gene-edited CAR T cells. Therefore, we aimed to systematically review the preclinical and clinical studies that evaluate the outcomes of knocked-out/knocked-down (KO/KD) CAR T cells. Methods This study was submitted to international Prospective Register of Systematic Reviews (PROSPERO) with the ID CRD42022320541 and follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We searched Five databases (PubMed, EMBASE, Cochrane Library, Web of Science, and Clinicaltrials.gov) up to March 19th, 2022 for the keywords of “CAR T cell” and “knock-out/knock-down”. The retrieved records then underwent a two-step screening process based on the inclusion criteria, first title/abstract and then full-text screenings, and their data were used for qualitative synthesis. Results Our search results yielded 3780 records. Finally, a total of 241 records, including 193 animal and 52 human studies (four concurrent in both groups) that reported KO/KD genes for 105 proteins were included. The positive effects of these 105 KO/KD were categorized into five groups: (1) enabling allogeneic CAR production while limiting GVHD, (2) increasing the efficacy of CAR T cells, (3) Decreasing their side effects, (4) limiting CAR T cell fratricide, and (5) enabling the use of concurrent therapies. In the human section, solid tumors had fewer studies with less favorable outcomes compared to hematologic malignancies. Conclusions This systematic review emphasized the various mechanisms by which CAR T cell effects could be boosted. Future researchers can choose their desired genes out of the 105 mentioned candidates. We also encourage the researchers to increase their efforts on solid tumors to compensate for the lack of increased efficacy in this group.

Vertebrobasilar dissecting aneurysm (VBDA) has high morbidity and mortality rates, and it is an important cause of stroke in young and middle-aged adults. Previous studies have shown that aneurysm wall inflammation is a major factor contributing to the high risk of aneurysm growth and rupture. Metformin inhibits inflammation and may be a suitable candidate drug for VBDA. Here, we report the protocol for a study designed to evaluate the ability of metformin to reduce the degree of aneurysm wall inflammation in patients with VBDA, as measured by high-resolution vessel wall imaging (HR-VWI). The study is a multicentre, prospective, randomised, controlled, and blinded clinical trial. Sixty patients with unruptured VBDA who meet the inclusion/exclusion criteria will be recruited competitively from three hospitals in China. Patient recruitment began in May 2024 and is expected to end in December 2025. The patients will be randomised (1:1) to treatment or placebo (n = 30 in each group), receiving either 250-mg metformin or placebo orally twice per day for 6months. The primary outcome will be the change in VBDA wall inflammation measured by HR-VWI. The secondary outcomes will be changes in VBDA morphology, typical imaging signs, and inflammatory biomarkers. Previous studies on metformin for the treatment of intracranial aneurysms have been performed in animals. However, prospective clinical studies in humans are lacking. Therefore, this study will provide insights into the anti-inflammatory effects of metformin in inhibiting VBDA growth and rupture and may reveal a new treatment modality for unruptured VBDA. The protocol has been approved by the Ethics Committee of Beijing Tiantan Hospital (approval no. KY2023-188-02). All patients will be required to provide written informed consent prior to participation. The results of the study will be disseminated through peer-reviewed journals and at relevant academic conferences. NCT06405971. Registered on May 9, 2024.

CAR-T cells (CAR-Ts) are genetically engineered T lymphocytes to express a receptor construct bearing an extracellular recognition domain that guides the killing specificity, a transmembrane domain, and an intracellular domain that elicits effector signaling. Upon encountering the target cell, CAR-Ts accomplish their cytolytic effector function directly via engagement of pro-apoptotic pathways and exocytosis of perforin and granzymes, or indirectly via secretion of cytokines that activate NK cells. Autologous CAR-Ts, bearing an extracellular recognition domain specific for the B-cell surface markers CD19 or BCMA, were initially approved for the treatment of late-stage hematologic malignancies. The last five years, mounting evidence from small studies in humans, employing autologous CAR-Ts targeting CD19 to selectively eliminate CD19 + cell subsets from the pool of the B-cell lineage, have revealed acceptable safety profile and encouraging efficacy in treatment-resistant systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myositis. Herein, we focus on a series of groundbreaking reports published within 2025 that enlighten the arising transformational potential and the emerging challenges of the CAR-based therapies regarding the management of life-threatening endotypes of autoimmune diseases.

Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.

Background: Insomnia is the most prevalent sleep disorder, associated with impaired daytime functioning, increased risk of mental and physical illness, as well as social and economic burden. Aim: This review summarizes the current state of knowledge on insomnia disorder and assesses the clinical value of scientifically proven treatment strategies, including both pharmacological and non-pharmacological methods. Methods: A narrative literature review was conducted using PubMed/MEDLINE (January 2015- November 2025). Peer-reviewed human studies, clinical guidelines, systematic reviews, meta-analyses, and high-quality narrative reviews addressing definition and classification, epidemiology, mechanisms, consequences, diagnostic tools, or treatment outcomes were included. Results: Insomnia affects approximately 10% of the adult population and is more common in women, elderly people, individuals with chronic stress, and those with comorbid medical or psychiatric conditions. Evidence supports a multidimensional hyperarousal model as the core mechanism of insomnia pathophysiology. Insomnia is linked to a higher risk of anxiety, depression, cardiometabolic disease, cognitive impairment, accidents, and reduced quality of life. Diagnosis relies on clinical assessment supported by sleep diaries and validated questionnaires. Cognitive Behavioral Therapy for Insomnia (CBT-I) is the first-line treatment, with chronotherapy, mindfulness-based interventions, exercise, and complementary approaches as useful adjuncts. Pharmacological options, including benzodiazepines, "Z-drugs", and other medications, may be considered, but with careful monitoring of safety and potential dependence. Conclusions: Insomnia requires personalized care that prioritizes non-pharmacological strategies. Medications should be used with caution, for selected patients, and for short durations only. Early recognition, patient education, and wider access to CBT-I are essential to reduce the burden of insomnia.

Topical application of the antimuscarinic pirenzepine increased lower limb nerve fibre density in a phase 2a study in type 2 patients with diabetes with peripheral neuropathy.

Auditory gamma stimulation is a promising non-invasive neuromodulation technique for cognitive decline, with preclinical studies demonstrating therapeutic effects in Alzheimer's disease models. However, translating these findings into human trials has produced variable outcomes, suggesting a need to examine factors influencing efficacy. In a systematic review of 62 studies on healthy and cognitively impaired populations, we identified 16 characteristics that may affect the response to stimulation. Outcomes reported included improved cognition, slower progression of brain atrophy, and changes in functional connectivity. Optimal stimulation frequency varied across individuals, indicating that personalised approaches may be valuable. Importantly, animal-model findings regarding amyloid clearance and reduced neuroinflammation were not consistently replicated in human studies, nor did neurophysiological responses reliably predict cognitive or biological effects. Significant methodological diversity was evident, with 32 neurophysiological measures employed, highlighting a need for standardisation. Future research should prioritise consensus on outcome measurement and explore individualised intervention strategies to better assess therapeutic potential.

Estimating the postmortem interval (PMI) represents a major challenge in forensic science, particularly beyond the early postmortem phase. Protein degradation has become a promising molecular approach, as many proteins disintegrate in progressive and temporally distinct degradation patterns. However, decomposition is influenced by environmental and individual factors, resulting in case-specific variability that complicates the development of generally applicable PMI estimation methods. Available human reference data are limited and often derived from autopsy samples collected at a single time point postmortem, typically without precise PMI or environmental data. Longitudinal studies under monitored natural outdoor conditions are therefore essential to establish reliable reference data for protein-based PMI estimation. This study investigated postmortem protein degradation in skeletal muscle under natural outdoor conditions at the Forensic Research Outdoor Station (FROST), a human taphonomy research facility in Marquette, Michigan. Muscle samples of the M. vastus lateralis were collected over 8-day periods from five human donors during two summer field trials (2022 and 2024). In situ sampling was complemented by an extracorporeal model, in which excised muscle tissue of each individual was stored in containers placed next to the body. This setup allowed a semi-controlled investigation of proteolytic dynamics outside the body. Additionally, morphological changes were assessed using a Total Body Score (TBS). Our findings emphasize the crucial impact of environmental conditions on postmortem protein degradation. They further support previous observations that specific proteins degrade in a regular and predictable manner, as demonstrated in this study in human tissue under natural outdoor conditions. The extracorporeal model revealed reproducible trends comparable to in situ degradation and represents a promising tool for isolated investigation of extrinsic factors under standardized conditions. This work provides valuable reference data, advancing protein-based PMI estimation in forensic research.

Subepithelial corneal haze remains a clinical risk after excimer laser-based surface ablation (ELSA), especially with deep ablations, high myopia or retreatments, with downstream effects on vision and quality of life. Mitomycin C (MMC) is widely used intraoperatively for haze prophylaxis and has multi-study support; however, its antiproliferative, anti-fibrotic action does not directly address early inflammation, epithelial barrier restoration or neuroregeneration, and use remains off-label with heterogeneous protocols. This narrative review synthesises preclinical, early clinical (non-randomised/small trials) and established clinical evidence (randomised trials/systematic reviews or guidelines) on amniotic membrane transplantation (AMT) as a complementary adjunct in ELSA. We emphasise modern, sutureless, dehydrated AMT (dAM), including vision-preserving formats suited to peri-operative workflows. Across adjacent ocular-surface indications, AMT demonstrates multi-modal properties: anti-inflammatory/immunomodulatory, antioxidant, anti-proteinase (including matrix metalloproteinase-9 suppression) and support of epithelial and nerve recovery. In ELSA-specific work, preclinical photorefractive keratectomy (PRK) models show reduced haze and faster epithelialisation with patch-AMT; one prospective laser-assisted sub-epithelial keratectomy (LASEK) human study reports faster healing and lower opacity versus standard care. By contrast, small fellow-eye studies using ring-mounted cryopreserved-AMT devices showed no superiority for routine myopic PRK, underscoring the importance of format and protocol. This review outlines a complementary paradigm: MMC targets downstream fibrosis, whilst patch-AMT acts earlier on inflammation, epithelial repair, protease imbalance (including MMP-9) and neurotrophic support. With major international guidelines now recognising sutureless patch-AMT for regeneration and inflammation/oxidative stress control in dry eye, prospective refractive-cohort trials with standardised product/placement protocols, long-term follow-up, patient-reported outcomes and embedded health-economic evaluation are warranted to define AMT's role alongside MMC in routine ELSA.

Choline supports phospholipid synthesis, membrane integrity, neurotransmission, verylowdensity lipoprotein export, and one-carbon/epigenetic pathways, yet most United States adults fall short of adequate intake. Fatty liver is now viewed as a mitochondrial-centric metabolic–inflammatory disorder; ethanol and excess linoleic acid (LA) can magnify bioenergetic stress when choline is insufficient to sustain phosphatidylcholine/phosphatidylethanolamine. This narrative review examines whether optimized choline delivery, alongside reduced exposure to mitochondrial toxicants, offers a rational therapeutic approach. Low choline intake associates with higher liver fat and aminotransferases. In rodents, choline deficiency combined with ethanol or LA lowers mitochondrial membrane potential, limits β-oxidation, and promotes steatosis and inflammation. Advanced formulations-especially citicoline-demonstrate favorable absorption and tissue choline delivery and may lessen trimethylamine-N-oxide formation versus free choline salts. Early, small human studies suggest that choline repletion, together with curtailed ethanol or dietary LA, can reduce intrahepatic triglyceride content and improve insulin sensitivity, though large randomized trials are lacking. Framing fatty liver as nutrition-modifiable mitochondrial toxicosis highlights correctable choline insufficiency when the liver is burdened by ethanol or excess LA. A dual strategy—using higher-bioavailability, gutmicrobial trimethylamineNoxide-sparing choline forms and mitigating mitochondrial toxicants-targets core bioenergetic defects, may reverse early steatosis, and warrants testing in adequately powered clinical trials.

This study discusses the asymmetric dominance effect in the context of political elections with third-party candidates. Animal and human research both show that the addition or removal of a third option influences choices between the remaining two options. The direction of sway created by the addition/removal of the 3rd option is context-dependent and unconsciously regulated. The results confirmed our hypotheses that both the timing and perceived viability of third-party candidates significantly influence voter preferences, with the strongest effects observed when third-party candidates remain present through election day. These findings suggest that the impact of third-party candidates extends beyond simple vote-splitting and is at least partly unconscious, though direct implicit measures were not employed. This study is situated in the context of U.S. presidential elections and focuses on moderate voters.

Abstract As the field of cultural evolution marks its fiftieth anniversary, it has an opportunity not only to evolve in theory and scope, but also in ethics of practice. This theme issue contributes to that shift by showcasing projects supported by the Cultural Evolution Society’s Transformation Fund (CES-TF), which centred equity, diversity and inclusion (EDI). This opinion piece draws on our CES-TF projects, conducted across diverse cultural and geographical settings, to reflect on the challenges and possibilities of making cultural evolution—and human research more broadly—more just. We focus on three relational dimensions in which cultural evolution research can become more inclusive and equitable: fostering equitable cross-cultural research collaborations; building mutually beneficial researcher community collaborations; and cultivating supportive funding and institutional relationships. Our collective reflections, written by grant recipients and the CES-TF lead, emphasize that, while there is no universal model for ethical research, attending to positionality, power dynamics and diverse knowledge systems can foster responsible and impactful research. Striving to make the field more globally representative will enhance our capacity to critically reflect and improve, but real progress requires time, resources and structural reform, supported by institutions, funders and journals committed to embedding EDI at the core of research. This article is part of the theme issue ‘Transforming cultural evolution research and its application to global futures’.

Abstract Background: Treatment resistance in solid tumors is driven by clonal evolution, with therapies selecting for resistant subpopulations. Single-cell sequencing (SCS) and phylogenetic analyses reveal branching patterns and subclonal dynamics, but no meta-analysis has synthesized their prognostic impact. This study quantifies evolutionary drivers of resistance across solid tumors, informing adaptive therapy design. Methods: PubMed, Scopus, and Web of Science (2015–2025) were searched for cohort studies or trials reporting SCS or phylogenetic data in solid tumors (e.g., breast, lung, colorectal) with resistance endpoints (e.g., progression-free survival [PFS], clonal shifts). Inclusion: human studies, ≥10 patients, evolutionary metrics (e.g., clonal diversity, variant allele frequencies), resistance defined (HR &amp;gt;1.5 for PFS). Exclusion: non-solid tumors, reviews. Data extracted: study design, tumor type, sample size, diversity metrics (e.g., Shannon index), and outcomes (HR for PFS/OS). Risk of bias used QUADAS-2. Random-effects models in RevMan 5.4 computed standardized mean differences (SMD) for subclonal fraction and hazard ratios (HR) with 95% CIs. Heterogeneity assessed via I2; publication bias via Egger’s test. Results: From 1,247 records, 28 studies (n=2,456 patients; 58% female, mean age 62) were included: breast (n=9), lung (n=10), colorectal (n=6), other (n=3). Most used SCS (e.g., 10x Genomics) or phylogenetic tools (e.g., PyClone). Pooled subclonal fraction was higher in resistant tumors (SMD 1.82, 95% CI 1.40–2.24; I2=70%; 22 studies; P&amp;lt;0.001). Pooled HR for PFS was 2.10 (95% CI 1.66–2.65; I2=64%; 18 studies), with lung tumors showing stronger effects (HR 2.42, 95% CI 1.87–3.14) than breast (HR 1.75, 95% CI 1.30–2.36). Meta-regression linked branching evolution to worse outcomes (β=0.30, P=0.03). No publication bias (Egger’s P=0.22). Sensitivity analyses excluding high-bias studies (n=3) altered HR by &amp;lt;5%. Conclusions: Higher subclonal diversity predicts resistance (HR&amp;gt;2) across solid tumors, supporting evolutionary metrics in trial designs. This first meta-analysis of phylogenetic/SCS data resolves prior inconsistencies, aligning with AACR’s focus on tumor progression dynamics. Citation Format: Noureddine SAMAI. Meta-analysis of evolutionary drivers of treatment resistance in solid tumors: Insights from phylogenetic and single-cell sequencing studies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr A005.

Introduction: Adolescent pregnancy represents a complex public health challenge associated with biological vulnerability, socioeconomic disadvantage, and increased susceptibility to psychological distress. Early pregnancy can disrupt neurodevelopmental trajectories, intensify emotional instability, and heighten exposure to adverse childhood experiences, all of which may shape long-term maternal mental health. Objective: The main objective of this systematic review was to evaluate the impact of adolescent pregnancy on maternal psychological development and the onset or worsening of mental disorders. Secondary objectives included assessing associations with depression, anxiety, trauma-related symptoms, parenting stress, and long-term psychiatric outcomes. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ClinicalTrials.gov, and ICTRP. Eligible studies included observational or interventional research evaluating mental health outcomes in pregnant adolescents or adolescent mothers. Inclusion criteria comprised studies published in the last five years, with expansion to ten years if fewer than ten eligible articles were available. Human studies were prioritized; animal and in vitro studies were considered only for mechanistic insights. Data extraction followed PRISMA guidelines, and risk of bias was assessed through RoB 2, ROBINS-I, and QUADAS-2, with certainty of evidence evaluated using GRADE. Results and Discussion: A total of 18 studies were included in the final review. The evidence consistently showed heightened rates of depressive symptoms, anxiety disorders, trauma exposure, impaired emotional regulation, and intergenerational psychosocial stress among adolescent mothers. Neurodevelopmental immaturity, socioeconomic adversity, and limited access to support services were recurrent mediators across studies. Conclusion: Adolescent pregnancy is strongly associated with increased vulnerability to mental health disorders and impaired psychological development. The findings highlight the need for integrated screening, targeted psychosocial interventions, and multidisciplinary follow-up strategies. Improved mental health support during pregnancy and postpartum may mitigate long-term psychiatric consequences in this high-risk population.

Augmented whole-body scanning via magnifying PET (AWSM-PET) is a technology that aims to enhance the image resolution and sensitivity of the clinical PET/CT scanner for whole-body imaging. This study presents the system design, performance evaluation, and results from phantoms and initial human imaging studies. Methods: The AWSM-PET system integrates 2 high-resolution detector panels ("outserts") with a Biograph Vision PET/CT scanner (Siemens Healthineers). Positioned outside the scanner's axial field of view, each panel consists of 32 detector modules, each containing a 30 × 30 lutetium oxyorthosilicate crystal array (0.97 × 0.97 × 10 mm³ per crystal) at 1.05-mm pitch. These detectors are packaged and read out using the scanner's detector electronics assembly. Customized firmware and software were developed to establish the additional coincidence detection among the outserts and the scanner. The system acquires data simultaneously during a whole-body scan using continuous bed motion. List-mode-based image reconstruction software has been developed for AWSM-PET system using the continuous-bed-motion protocol. Performance was evaluated through sensitivity measurements, imaging of a mini-resolution phantom containing multiple groups of hot spheres, a National Electrical Manufacturers Association Image Quality (NEMA IQ) phantom study with custom small-diameter tumor inserts, and an initial human study. Results: The outsert detectors achieved an energy resolution of 11% at 511 keV. The coincidence resolving time between the outserts and between outserts and scanner was 183 and 211 ps full width at half maximum, respectively. Sensitivity increased by up to 18.4%, depending on the source location. Mini-resolution phantom images demonstrated higher peak-to-valley ratios for spheres with a diameter of 6 mm or less compared with native scanner images. In the NEMA IQ study, AWSM-PET achieved a higher contrast recovery ratio (CRC) for the smallest spheric lesion (diameter, 4.88 mm) across all CRC metrics (maximum, peak, and mean) but no improvement for larger lesions compared with high-resolution Biograph Vision images. Initial human imaging confirmed the system's compatibility with clinical workflows, achieving improved resolution in high-count regions, such as the brain. However, increased noise in low-count regions (e.g., abdomen) was observed and requires further improvement. Conclusion: The prototype AWSM-PET system demonstrated enhanced image resolution and sensitivity of a clinical PET/CT scanner without negatively impacting its performance, showing improved CRC and spatial resolution for small lesions in phantom and human imaging.