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Longitudinal analysis of circulating tumor DNA and CA19-9 dynamics in predicting disease relapse and monitoring treatment response in stage I-III pancreatic ductal adenocarcinoma: An interim analysis of a prospective observational study.

INTRODUCTION: Postoperative recurrence is the leading cause of mortality in resected pancreatic ductal adenocarcinoma (PDAC), yet reliable tools for early relapse detection and treatment response assessment remain lacking. METHODS: In a prospective cohort of 136 patients with resected stage I-III PDAC receiving adjuvant chemotherapy, we evaluated circulating tumor DNA (ctDNA) and CA19-9 as longitudinal biomarkers across multiple postoperative time windows. RESULTS: ctDNA consistently outperformed CA19-9 as an independent prognostic factor; ctDNA positivity at on-treatment and surveillance assessments achieved a positive predictive value of 91.7%, while persistent negativity identified the lowest-risk patients. Integrating CA19-9 with ctDNA resolved the ctDNA-alone gap in distinguishing treatment clearance from conversion, improving discrimination of responders from non-responders (HR 3.72; P = .008). A time-weighted dynamic ctDNA risk score (MinerVa-dynamic) further stratified ctDNA-negative patients into clinically distinct prognostic subgroups, achieving an area under the curve of 0.87 and 0.82 for one- and two-year disease-free survival prediction, respectively. CONCLUSIONS: These findings support a dual-biomarker longitudinal monitoring framework as a practical, individualized approach to postoperative surveillance and early therapeutic decision-making in PDAC.

CA19-9

Spatiotemporal genomic analysis and risk assessment of the plasmids carrying blaOXA-48-like genes based on a large-scale international dataset.

BACKGROUND: The spread of OXA-48-like carbapenemases represents a major public health challenge. Although previous studies have investigated OXA-48-like carbapenemases risk factors, nosocomial dissemination, and plasmid dynamics, an integrated plasmid-centered framework combining complete plasmid mining, transmission-unit analysis, phylogenetic reconstruction, and machine learning-based risk assessment remains limited. METHODS: We systematically collected 747 complete plasmid sequences carrying blaOXA-48-like genes from the NCBI database, establishing the largest collections of complete plasmid sequences to date. Using an integrative framework of population genomics, phylogenetic dating, and machine learning, this study aimed to characterize the dissemination patterns, plasmid replicon diversity, transmission units, mobile genetic elements, co-resistance profiles, and risk classification of these plasmid. RESULTS: Plasmids carrying blaOXA-48-like genes were detected across 50 countries on six continents, with blaOXA-48 predominating in Europe, blaOXA-181 in South Asia, and blaOXA-232 largely in Asia. IncL and ColKP3/IncX3 replicons, together with Tn1999.2 and other MGEs, were central drivers of plasmid maintenance and spread. Sixteen transmission units were defined, with AA068_Cluster3 estimated to have originated in the Netherlands around 2005 before expanding to Europe, the Middle East, Asia, and North America. Co-resistance analyses revealed frequent modules involving aminoglycoside and quinolone resistance, with qnrS1 and aph(3'')-Ib most prevalent. Notably, high-risk transposon structures were often identified in non-clinical environments, underscoring their cross-ecological transmission potential. Machine learning-based classification models showed good internal performance for predefined composite-risk categories, with plasmid mobility, clinical/non-clinical source composition, and host background contributing to the classification results. CONCLUSIONS: This study provides a large-scale plasmid-centered genomic analysis of publicly available complete plasmid sequences carrying blaOXA-48-like genes, integrating transmission-unit inference, phylogeographic reconstruction, mobile genetic element and co-resistance profiling, and composite genomic risk stratification. This gene-centered framework may support future One Health-oriented antimicrobial resistance surveillance and prioritization of plasmids with higher dissemination and resistance potential.

Plasmids

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans

Mutational Landscape and Clonal Dynamics in AML Undergoing PTCy Hematopoietic Cell Transplantation.

To improve risk stratification, we performed targeted NGS at diagnosis in 191 patients with AML undergoing myeloablative allogeneic HCT with PTCy-based prophylaxis. We also investigated clonal evolution using paired diagnostic and relapse samples from 39 individuals. A total of 610 mutations were detected in 184 patients (96%), most commonly in FLT3 (26%), DNMT3A (25%), RUNX1 (24%), and NPM1 (19%). Sixteen unique fusion genes were identified in 35 patients, with KMT2A (43%) and core binding factor rearrangements (23%) being the most frequent. TP53 and WT1 mutations were strongly associated with adverse outcomes, whereas NPM1 retained favorable significance. RUNX1 co-mutations with SF3B1 or NRAS were associated with inferior survival. In an exploratory allelic analysis, multi-hit TP53 alterations, but not single-hit mutations, were associated with distinctly poorer OS, EFS, and relapse risk. Relapse involved mutational shifts in ∼70% of cases, with significant enrichment of WT1 and more modest increases in TP53, KRAS, ASXL1, NF1, and MECOM, while DNMT3A, TET2, and ASXL1 persisted stably. Neither acute nor chronic graft-versus-host disease was associated with molecular remodeling at relapse. Incorporating TP53 and WT1 into risk models, recognizing context-dependent effects of DNMT3A and RUNX1, and applying longitudinal genomic monitoring may help guide personalized strategies to prevent relapse. Extended abstract BACKGROUND Relapse remains the leading cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML), yet the genetic mechanisms underlying post-transplant relapse remain poorly understood, particularly in the era of post-transplant cyclophosphamide (PTCy). Characterizing the mutational landscape at diagnosis and the clonal evolution leading to relapse may improve post-transplant risk stratification and identify opportunities for personalized surveillance and intervention. OBJECTIVES To characterize the diagnostic mutational landscape, evaluate its prognostic significance, and investigate clonal evolution from diagnosis to relapse in AML patients undergoing myeloablative HCT with PTCy-based graft-versus-host disease prophylaxis. STUDY DESIGN We performed targeted next-generation sequencing (NGS) at diagnosis in 191 consecutive AML patients undergoing myeloablative allogeneic HCT with PTCy-based prophylaxis. Paired diagnostic and relapse samples were available for 39 patients to evaluate clonal evolution. RESULTS A total of 610 mutations were detected in 184 patients (96%), most commonly in FLT3 (26%), DNMT3A (25%), RUNX1 (24%), and NPM1 (19%). Sixteen unique fusion genes were identified in 35 patients, with KMT2A (43%) and core binding factor rearrangements (23%) being the most frequent. TP53 and WT1 mutations were strongly associated with adverse outcomes, whereas NPM1 retained favorable significance. RUNX1 co-mutations with SF3B1 or NRAS were associated with inferior survival. In an exploratory allelic analysis, multi-hit TP53 alterations, but not single-hit mutations, were associated with distinctly poorer OS, EFS, and relapse risk. Relapse involved mutational shifts in ∼70% of cases, with significant enrichment of WT1 and more modest increases in TP53, KRAS, ASXL1, NF1, and MECOM, while DNMT3A, TET2, and ASXL1 persisted stably. Neither acute nor chronic graft-versus-host disease was associated with molecular remodeling at relapse. CONCLUSIONS This study provides a comprehensive characterization of the mutational landscape and clonal evolution of AML undergoing contemporary PTCy-based allogeneic HCT. TP53 and WT1 identify patients at particularly high risk of post-transplant relapse, whereas NPM1 retains favorable prognostic significance. The frequent acquisition of new genetic lesions at relapse underscores the dynamic nature of post-transplant clonal evolution and supports longitudinal molecular monitoring together with genomically informed post-transplant surveillance and relapse-prevention strategies.

Clonal Dynamics

Defining and managing high-risk acute myeloid leukemia (AML) in 2026.

Acute myeloid leukemia (AML) remains a highly heterogeneous malignancy in which outcomes are particularly poor for patients classified as having high-risk disease. Traditionally, high-risk AML has been defined by adverse baseline genetic features, including complex cytogenetics, TP53 alterations, and mutations associated with secondary or therapy-related disease. However, this static, genetics-centered definition is increasingly insufficient in the modern therapeutic era. Emerging evidence supports a more dynamic and context-dependent model in which risk is shaped not only by molecular architecture but also by treatment intensity, patient fitness, measurable residual disease (MRD), and evolving resistance mechanisms. Advances in genomic profiling have refined risk stratification frameworks, including ELN 2022 for intensively treated patients and the ELN 2024 classification for those receiving less-intensive therapies. In parallel, MRD has emerged as a powerful biomarker that reclassifies patients during treatment, identifying those with persistent, therapy-resistant disease despite morphologic remission. Biologically, high-risk AML is driven by the interplay of clonal evolution, epigenetic plasticity, leukemic stem cell persistence, and protective microenvironmental and immune interactions, all of which contribute to relapse. Therapeutically, the landscape has expanded to include targeted agents, venetoclax-based combinations, and transplantation strategies, yet outcomes remain limited in key high-risk subsets, particularly TP53-mutated disease and post-venetoclax relapse. Accordingly, current strategies emphasize rational combination therapies, MRD-guided treatment adaptation, and approaches targeting both leukemic cells and their supportive niches. In 2026, high-risk AML is best understood as a dynamic, treatment-context-dependent state. Improving outcomes will require integration of precision diagnostics, biologically informed therapy, and adaptive strategies designed to anticipate and overcome resistance.

Humans

Application of musculoskeletal ultrasound in postoperative rehabilitation assessment and monitoring after rotator cuff repair: A systematic review.

BACKGROUND: The development of rehabilitation protocols after rotator cuff repair has long lacked objective benchmarks. Traditional time‑based regimens are limited by considerable inter‑individual variability and an increased risk of re‑tear. Musculoskeletal ultrasound allows dynamic assessment of tendon healing and muscle morphology, yet evidence for directly linking its use to rehabilitation decisions remains scarce. OBJECTIVE: To systematically synthesize the evidence on the use of musculoskeletal ultrasound monitoring to inform rehabilitation decision‑making after rotator cuff repair. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines, we searched PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data from January 2020 to April 2026. Original studies were included if they involved patients who had undergone rotator cuff repair, used musculoskeletal ultrasound (including gray‑scale ultrasound, elastography, etc.) to evaluate the rotator cuff tendons or shoulder muscles, and reported at least one parameter related to rehabilitation decision-making or functional outcomes. RESULTS: Eleven studies were included. Shear wave velocity (SWV), cross‑sectional area (CSA), and echo intensity (EI) were the most frequently reported ultrasound parameters. Available evidence indicated that SWV increased progressively after surgery, with an overall increase of approximately 22% to 25% from one week to 12 months postoperatively. This dynamic trajectory may serve as a reference baseline for judging rehabilitation progress. An abnormally elevated SWV in the early postoperative period was associated with an increased risk of re‑tear, suggesting that a more conservative rehabilitation strategy should be adopted. Tendon stiffness measured at 12 weeks after surgery independently predicted long‑term return to sport. Regarding muscle parameters, changes in CSA and EI were positively correlated with shoulder function scores, and the combination of these two parameters effectively identified patients with rehabilitation bottlenecks. CONCLUSION: Musculoskeletal ultrasound parameters are associated with the initiation of active movement, adjustment of exercise load, prediction of return‑to‑sport prognosis, and identification of retear risk. Among these, SWV shows particular promise as an objective monitoring parameter for supporting rehabilitation assessment after rotator cuff repair. Future randomized controlled trials are needed to determine whether ultrasound-informed assessment can improve rehabilitation outcomes compared with traditional time-based regimens, and to establish standardized measurement protocols and clinically applicable reference values. Key findings of this review are summarized in S1 File.

Humans

Effect of submaximal exercise on vulnerability to fibrillation in the canine ventricle.

The risk of instantaneous death due to ventricular fibrillation was compared in resting and exercised dogs. Three weeks before testing, all dogs had bipolar left ventricular stimulating electrodes implanted and a reversible snare was placed around the anterior descending coronary artery. The dogs were randomly assigned to either an exercise (13 dogs) or a control (12 dogs) group. We measured ventricular fibrillation thresholds (VFTs) in all dogs before and after inducing ischemia by tightening the snare while the dogs stood at rest. The next day, nonischemic and ischemic VFTs were redetermined for control dogs at rest and for the exercise group during a treadmill run. No statistically significant changes were noted within and between groups in nonischemic or in ischemic VFTs at rest. In five exercise dogs, spontaneous ventricular fibrillation occurred during the first 8 minutes of the ischemic run, For the eight other exercise dogs, running increased the mean drop in VFTs during coronary occlusion by 23% (p less than 0.01). These data suggest that moderate dynamic exercise may greatly enhance the risk of ventricular fibrillation and sudden death in the presence of myocardial ischemia. In the absence of ischemia, exercise does not appear to increase vulnerability to ventricular fibrillation.

Animals

A Dynamic Nomogram to Predict Metabolic Dysfunction-Associated Fatty Liver Disease in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) involves multiple metabolic disorders. This study aimed to identify high-risk populations for metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with MetS and to establish a dynamic predictive nomogram. METHODS: A total of 627 patients with MetS from six regions in Zhejiang Province were enrolled and categorized into MAFLD and non-MAFLD groups, then randomly assigned to training and validation sets at a ratio of 7:3. Independent predictors of MAFLD were identified using least absolute shrinkage and selection operator regression and multivariable logistic regression analyses. These predictors were then used to construct a dynamic nomogram. RESULTS: A total of 627 patients with MetS were included in the final analysis, of whom 77.0% (483/627) were diagnosed with MAFLD. Multivariable logistic regression analysis identified body mass index (BMI), waist circumference (WC), total cholesterol (TC), alanine aminotransferase (ALT), MetS-defined dysglycemia, and education level as independent risk factors for MAFLD. MetS-defined dysglycemia showed the highest odds ratio (OR) for MAFLD development [OR = 1.87, 95% confidence interval (CI): 1.07-3.29]. Although the number of MetS components and the metabolic syndrome score were significantly associated with MAFLD in univariate analysis, they were not independently associated with MAFLD in the multivariate model. A dynamic nomogram for predicting MAFLD risk in patients with MetS was developed and internally validated. The area under the receiver operating characteristic curve was 0.834 (95% CI: 0.787-0.880) in the training set and 0.839 (95% CI: 0.771-0.899) in the validation set, indicating strong predictive performance. Bootstrap internal validation demonstrated good agreement between predicted and observed outcomes in calibration curves. Decision curve analysis further indicated favorable clinical applicability of the nomogram. CONCLUSION: BMI, WC, TC, ALT, MetS-defined dysglycemia, and education level are independent risk factors for MAFLD. A dynamic nomogram for predicting MAFLD risk in patients with MetS was successfully developed and validated.

Humans

Integrating RNA sequencing with deep learning-based metabolic toxicity prediction: A new perspective on screening prioritized liquid crystal monomers.

Nearly 99 % of liquid crystal monomers (LCMs) toxicological data remains gaps, especially to aquatic organisms. Herein, this study proposes a rapid and high-throughput screening method for identifying priority LCMs in natural water. Using six fluorinated LCMs (LCMsF) with significant enrichment characteristics in zebrafish as examples, RNA sequencing revealed that LCMsF-induced metabolic disturbances are predominant, including 28 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway abnormalities attributed to 498 differentially expressed genes. Notably, the intricate sequencing process resulted in the inability to rapid identify additional 857 LCMsF that may induce metabolic disturbances. To address this, LCMsT-MTP, a predictive deep learning model based on RNA sequencing, was developed. This model integrates a comprehensive representation of LCMsF structures and metabolic toxicity target sequences. LCMsT-MTP improves upon traditional methods that are limited to single targets and mechanisms by facilitating the simultaneous identification of 21 metabolic toxicities induced by LCMsF. In addition, the LCMsT-MTP model was further applied to non-fluorinated LCMs (LCMsNone F) that satisfy the applicability domains test. Accordingly, a metabolic toxicity priority list of LCMs was proposed, with ∼95 % of LCMs classified as high or medium risk. Priority list validation by molecular dynamics confirmed that the interactions of LCMsF/LCMsNone F and metabolic toxicity targets in representative KEGG pathways were distinct.

Animals

Multi-strain carriage and intrahost diversity of Staphylococcus aureus among Indigenous adults in the USA.

Staphylococcus aureus (SA) is an opportunistic pathogen and human commensal that is frequently present in the upper respiratory tract, gastrointestinal tract and skin. While SA can cause diseases ranging from minor skin infections to life-threatening bacteraemia, it can also be carried asymptomatically. Indigenous individuals in the Southwest USA experience high rates of invasive SA disease. As carriage is the most significant risk factor for disease, understanding the dynamics of SA carriage, and in particular co-carriage of multiple strains, is important to develop strategies to prevent transmission in vulnerable communities. Here, we investigated SA co-carriage and intrahost evolution by sampling several colonies from multiple anatomical sites and whole-genome sequencing (WGS) on 310 SA isolates collected from 60 Indigenous adults participating in a cross-sectional carriage study. We assessed the richness and diversity of SA isolates via differences in multilocus sequence type, core-genome SNPs and genome content. Using WGS data, we identified 95 distinct SA intra-subject lineages (ISLs) among 60 participants; co-carriage was detected in 42% (25/60). Notably, two participants each carried four distinct SA ISLs. Variation in antibiotic resistance determinants among carried strains was identified among 42% (25/60) of participants. Lastly, we found unequal distribution of clonal complex by body site, suggesting that certain lineages may be adapted to specific anatomical sites. Together, these findings suggest that co-carriage may occur more frequently than previously appreciated and further our understanding of SA intrahost diversity during carriage, which has implications for surveillance activities and epidemiological investigations.

Humans

[Dynamic and plastic expression as a method of accident prevention during infancy (author's transl)].

Authors review the importance of fostering suitable methods at infancy, as a prophylaxis of accidents at such stage in life. They propose the use of plastic expression handed-out as a sequence of pictures, ordered in the form of a story or tale, rigorously studied from the psychological point of view and which limelights the most frequent risks. Likewise they value the importance of dynamic methods of expression and summarise their experience with puppet theatres. A prototype show is described and psychological result evaluation analized.

Accident Prevention

Mitral valve replacement in infective endocarditis as prophylaxis against embolism. Identification of patients at risk by 2-dimensional echocardiography.

A 36-yr-old woman and a 46-yr-old man had infective endocarditis of the mitral valve. Examination by 2-dimensional dynamic echocardiography demonstrated large mobile vegetations in both patients, and the display pointed to an ominous risk of embolism. Heart surgery with valve replacement was performed, the main indication being prophylaxis against embolism; the operative findings seemed to justify the assumption of imminent risk of embolism. It is suggested that the display of dynamic morphology of valvular vegetations by 2-dimensional echocardiography can be useful in identifying a subset of patients at high risk of embolism during infective endocarditis. However, more experience is needed before definite conclusions can be drawn regarding the role of early operation as prophylaxis against impending embolism.

Adult

A social-psychological perspective on successful community control of high blood pressure: a review.

This review brings together studies dealing with factors that affect participation in screening, referral, and treatment for high blood pressure (HBP). Community-based screening programs are examined first, in order to describe the changing and the current distribution of hypertensives as "unaware," untreated, treated but uncontrolled, and controlled by treatment. Factors influencing this distribution are examined. Next, data on referral, acceptance of treatment, and staying in treatment are discussed, with a special reference to intervention studies. The review then brings in the broader social science literature on the psychosocial dynamics of health-maintaining and risk-reducing behaviors. The article concludes with an interpretive summary and some suggestions for further action.

Attitude to Health

Osteoarthritis Year in Review 2026: Genetics, genomics and epigenetics.

OBJECTIVE: The purpose of this narrative review is to highlight advances made over the past 12 months in the field of osteoarthritis (OA) genetics, genomics and epigenomics, with a particular focus on the interpretation of OA risk loci through functional genomic and regulatory approaches. DESIGN: PubMed and Europe PMC were searched to identify studies relevant to OA genetics, genomics and epigenomics published between 1st March 2025 and 30th April 2026. Searches used combinations of terms relating to genetics, genomics, epigenomics, functional genomics, molecular quantitative trait loci, chromatin accessibility and enhancer biology. Studies were limited to human subjects and English-language publications, with additional articles identified through citation screening and expert knowledge of the field. RESULTS: Over the past year, the field has continued to transition from large-scale locus discovery towards biological interpretation of OA genetic risk. Major advances included the largest OA genome-wide association study to date, further development of polygenic risk score approaches, and increasing integration of molecular quantitative trait loci, chromatin accessibility, and enhancer biology datasets to prioritise effector genes and elucidate regulatory mechanisms. Several studies highlighted the highly context-dependent nature of OA genetic risk mechanisms, demonstrating that distinct tissues, cell types, and regulatory layers can identify different candidate effector genes at the same locus. Additional developments included increasing application of singlecell and multi-omic technologies to study OA-relevant tissues. CONCLUSION: Recent advances in OA genetics have shifted the field from locus discovery towards mechanistic interpretation. Emerging evidence demonstrates that the biological consequences of genetic variation are highly dependent upon tissue, cell state and disease context, with different functional genomic approaches often prioritising distinct candidate genes and regulatory mechanisms at the same susceptibility locus. Together, these findings suggest that OA risk loci should increasingly be viewed as dynamic regulatory systems rather than simple variant-to-gene relationships, providing a framework for future studies aimed at resolving causal mechanisms, defining disease endotypes, and identifying therapeutic targets.

Genetics

Dynamic scintigraphy in renal arteriovenous fistula.

Radiographic contrast aortography and radionuclide dynamic scintigraphy were used to diagnose a congenital renal arteriovenous fistula in a 33 year old woman who presented with hypertension, cardiac decompensation and abdominal bruit. Since dynamic scintigraphy is a noninvasive, nontraumatic, low risk and easily repeatable procedure, it is invaluable for the diagnosis of the fistula and for monitoring patients who are managed without surgery.

Adult

The dehydroepiandrosterone loading test. III. A possible placental function test.

The dehydroepiandrosterone loading test (DLT) has been used in a small population of normal and high-risk obstetric patients, to date, in an attempt to develop a dynamic test of placental function. In spite of its limited applications, it has shown reliability in discriminating, with statistical significance, between high-risk pregnancies that result in normally grown, undistressed infants, and high-risk pregnancies that result in infants showing signs of placental insufficiency. The present report expands the study population by presenting our data on 40 loading tests performed in 37 high-risk and normal obstetric patients. Results of 19 of these DLT's have been previously reported and are included herein for statistical analysis. The DLT utilizes an excess substrate load of dehydroepiandrosterone to assess the maximum capability of the placenta to convert it to estrogen. Although our previous report did not show false positive or negative results in the conversion rates, the present results (40 DLT's) found two (2 out of 17) false positives (12%) and two (2 out of 19) false negatives (11%). The highly significant correlation between DLT result and pregnancy outcome seen previously was preserved. In addition, the data of another five DLT's in four patients are presented. This group includes a pregnancy with a fetus with multiple congenital malformations, two patients with intrauterine fetal death, and a nonpregnant woman. The results are not included in the statistical analysis, but discussion of these results has interesting pathophysiologic implications.

Dehydroepiandrosterone

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

Post-traumatic stress (PTS) encompasses a range of psychological responses following trauma, which may lead to more severe outcomes such as post-traumatic stress disorder (PTSD). Identifying early neuroimaging biomarkers that link brain function to PTS outcomes is critical for understanding PTSD risk. This longitudinal study examines the association between brain dynamic functional network connectivity (dFNC) and current/future PTS symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.197, p corrected = 0.0079) and future (r=-0.176, p corrected = 0.0176) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.205, p corrected = 0.0079). We additionally observed that the association between the network dynamics of the inter-network and intra-network brain state with symptom severity is more pronounced in female group. Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger effect in female group, underscoring the importance of sex differences.

Journal Article

Bacteriocin-mediated intraspecies competition driven by acquired Bac41 operon in epidemic Enterococcus faecalis ST179.

Enterococcus faecalis is a common gut commensal and an opportunistic pathogen causing hospital-acquired infections. Despite its clinical importance, comprehensive global genomic and epidemiological data remain limited. Here, we analyzed 5,895 E. faecalis genomes collected between 2000 and 2020 and identified ST179, a human-derived single-operon variant of the high-risk CC16 clonal complex, as an emerging epidemic clone in China. Spot-killing assays revealed that ST179 strongly inhibited other clinical E. faecalis sequence types. Biochemical purification and proteomic analyses identified BacL1 as a key effector associated with this species-specific antibacterial activity. Functional assays confirmed its inhibitory phenotype, providing ST179 with a lineage-specific, bacteriocin-mediated competitive advantage. The high prevalence of the Bac41 operon likely contributed to the epidemiological success and ecological fitness of ST179. These findings highlight the role of bacteriocin-mediated intraspecies competition in shaping E. faecalis population dynamics and suggest that ST179 might become an emerging high-risk lineage in China.IMPORTANCEEnterococcus faecalis is a common gut bacterium and an opportunistic pathogen. We identify ST179 as an emerging epidemic clone in China and show that it outcompetes other strains via the bacteriocin Bac41. This competitive advantage helps explain its rapid spread. Our findings highlight how bacterial competition shapes population dynamics and provide insights into the emergence of high-risk E. faecalis lineages, informing strategies for monitoring and infection control.

Enterococcus faecalis