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Azithromycin-resistant Salmonella enterica Typhi with AcrB R717L/Q mutations in the United States.

BACKGROUND AND OBJECTIVES: Azithromycin is a critical oral treatment for typhoid fever caused by Salmonella enterica serovar Typhi (Salmonella Typhi), since XDR has rendered other first-line treatment options ineffective. Azithromycin resistance conferred by amino acid changes in AcrB, an AcrAB-TolC efflux pump component, represents an emerging public health concern. Leveraging phenotypic and genotypic data from U.S. Salmonella Typhi surveillance systems, this study describes the prevalence, phenotype and genomic epidemiology of Salmonella Typhi with AcrB mutations in U.S. patients since the first detection in 2015. METHODS: AST and WGS data of >3000 Salmonella Typhi isolates were used to identify all cases with an AcrB mutation in the United States (2015-2025). We calculated annual prevalence and MIC ranges. Phylogenetic analysis was used to contextualize U.S. cases of Salmonella Typhi with an AcrB mutation within all globally reported cases. RESULTS: While the prevalence of AcrB mutations in the United States is low (1.5%), it has risen significantly in recent years, from 0.2% in 2016-2022 to 2.2% in 2023-2025. This increase is predominantly driven by clonal expansion of existing strains circulating in South Asia. AcrB mutations do not reliably confer resistance to azithromycin (MIC ≥ 32 mg/L), complicating clinical interpretation. CONCLUSIONS: The prevalence of AcrB mutations in Salmonella Typhi is increasing in the United States, and likely globally, given that U.S. data function as an informal proxy for regions without routine surveillance infrastructure. Clinical outcomes data are needed to inform Salmonella Typhi treatment guidelines and potentially amend clinical breakpoints for azithromycin.

Journal Article

Angiography-Based Index of Microcirculatory Resistance in Assessing the MVO and Infarct Size in STEMI Patients.

OBJECTIVES: To evaluate angiography-based index of microcirculatory resistance (angio-IMR) in assessing microvascular obstruction (MVO) and infarct size (IS) in ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The effect of thrombolysis on post-percutaneous coronary intervention (PCI) angio-IMR, and its associations with MVO and IS remains unclear. METHODS: One hundred twenty-three STEMI patients randomized to receive 5&#x2009;mg intravenous bolus of recombinant staphylokinase (r-SAK) or normal saline (NS) before PCI were recruited. Angio-IMR was computed in infarct-related arteries. MVO and IS were detected by cardiac magnetic resonance imaging. RESULTS: Compared with NS group, r-SAK group exhibited numerically lower post-PCI angio-IMR (39.12 U vs. 42.57 U; p&#x2009;=&#x2009;0.567), MVO (54.0% vs. 70.9%; p&#x2009;=&#x2009;0.059), MVO extent (0.70% vs. 1.90%; p&#x2009;=&#x2009;0.101) and IS (21.30% vs. 24.50%; p&#x2009;=&#x2009;0.079). Post-PCI angio-IMR was positively correlated with MVO extent (&#x3c1;&#x2009;=&#x2009;0.347; p&#x2009;<&#x2009;0.001) and IS (&#x3c1;&#x2009;=&#x2009;0.324; p&#x2009;<&#x2009;0.001). Receiver operating characteristic analyses showed moderate diagnostic performance of angio-IMR for MVO (area under the curve [AUC] = 0.750; p&#x2009;<&#x2009;0.001), MVO&#x2009;>&#x2009;2.6% (AUC&#x2009;=&#x2009;0.735; p&#x2009;<&#x2009;0.001) and IS&#x2009;>&#x2009;25% (AUC&#x2009;=&#x2009;0.712; p&#x2009;<&#x2009;0.001). The exploratory optimal cut-off values for these endpoints were approximately 40&#x2009;U. CONCLUSIONS: In STEMI patients, a single bolus of r-SAK before PCI was associated with numeric reductions in post-PCI angio-IMR, MVO, MVO extent and IS. Additionally, angio-IMR exhibited a significantly positive correlation with both MVO extent and IS, demonstrating the diagnostic value of this wire-free method for assessing microvascular injury.

Humans

Oliceridine used for patient-controlled analgesia on postoperative quality of recovery in patients undergoing laparoscopic gynecological tumour resection: a randomized clinical trial.

BACKGROUND: Oliceridine, a novel biased &#x3bc;-opioid receptor agonist, is widely used perioperatively, yet limited data exists regarding its impact on postoperative quality of recovery. This study investigated the effect of oliceridine-based&#xa0;patient-controlled intravenous analgesia (PCIA) on postoperative quality of recovery among patients undergoing laparoscopic gynecological tumour resection. METHODS: Ninety&#x2011;four female patients scheduled for elective laparoscopic gynecological tumour resection were included. Patients were randomized to two groups: oliceridine group (loading dose 1.5&#x2009;mg, PCIA 0.55&#x2009;mg/kg) or sufentanil group (loading dose 10&#x2009;&#x3bc;g, PCIA 3&#x2009;&#x3bc;g/kg). The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. The secondary outcomes included the QoR-40 score, the numeric rating scale (NRS) pain score, the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) index and adverse events within 3 postoperative days. RESULTS: Higher QoR-40 scores were found in the oliceridine group on postoperative day 1 (182.9&#x2009;&#xb1;&#x2009;3.1 versus 177.5&#x2009;&#xb1;&#x2009;3.9, p&#x2009;<&#x2009;0.001). Compared with the sufentanil group, the oliceridine group showed better QoR-40 scores within 3&#x2009;days after operation. No significant differences were observed in NRS pain scores or HADS-A scores between the two groups (all p&#x2009;>&#x2009;0.05). However, the median FRAIL score in the oliceridine group was lower on postoperative day 2 (p&#x2009;=&#x2009;0.018). CONCLUSION: Oliceridine used in PCIA improves early postoperative recovery quality of patients undergoing laparoscopic gynecological tumour resection. It provides analgesic effect comparable to sufentanil and lowers incidences of postoperative frailty, nausea and vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR.org.cn, identifier: ChiCTR2400094271.

Humans

Healing from within: A randomized controlled trial of a novel expressive writing intervention among trans and gender expansive adults.

Transgender and gender expansive (TGE) populations in the United States experience high rates of mental health disparities. High rates of depressive and anxiety symptoms have been linked to a host of stigma-related stressors and exacerbated by decreased access to competent and affirming formalized health care supports, particularly in the face of legislation aiming to curb access. As a result, intervention strategies that can be made widely available, accessed at no cost, and address these stressors to improve mental health and well-being are needed. This study presents findings from a self-administered online mental health intervention, titled Reflections to (re)Claim an Affirmed Identity to Improve Mental Health (RECLAIM), which used an expressive writing approach to address internalized anti-TGE stigma to reduce depressive and anxiety symptoms and improve perceived community connectedness. In this randomized controlled trial, 115 TGE community adults were assigned to one of three study conditions: two RECLAIM interventions and one expressive writing active control group. Analysis of between-group effects found that all three groups experienced similar levels of improvement in mental health over time, while within-group effects of time by condition demonstrated some notable differences in the overall trajectory of treatment or control effects. Overall, results of this randomized controlled trial provide preliminary empirical support for the efficacy of RECLAIM in reducing depressive and anxiety symptoms and internalized anti-TGE stigma and improving community connectedness. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Humans

Whole genome sequencing of unusual Hepatitis C virus subtypes and drug resistance analysis during direct-acting antiviral therapy in India.

INTRODUCTION AND OBJECTIVES: Pangenotypic direct-acting antivirals (DAA) are effective against highly prevalent Hepatitis C virus (HCV) subtypes, but have been clinically validated almost exclusively in high-income countries. Unusual HCV subtypes may carry natural polymorphisms, potentially impacting DAA susceptibility. We conducted full-genome characterization and resistance analysis of unusual HCV subtypes in patients receiving DAA treatment. PATIENTS AND METHODS: In this prospective hospital-based study, eligible patients were screened for anti-HCV antibodies and active infection was confirmed by diagnostic 5'NCR-based HCV RNA detection. Genotyping was performed by core region sequencing, and viral load quantified by real-time PCR. For whole genome sequencing, multiplex primers were designed using alignments of global reference sequences. Sequencing was carried out using the Oxford Nanopore Technology platform. Phylogenetic analysis used multiple sequence alignment and the HCV-GLUE resource for resistance-associated substitution (RAS) analysis. RESULTS: Predominant genotype was genotype 3 in 64.3% (n = 45); genotype 6 in 21.4% (n = 15); and genotype 1 in 14.2% (n = 10). Unusual HCV subtype 6xa was detected in two patients and showed no NS5A resistance mutations. One genotype 3b patient relapsed at 24 weeks post-DAA treatment completion and carried NS5A resistance-associated substitutions 30 K and 31 M both at baseline and at relapse, conferring high-level resistance to NS5A inhibitors. CONCLUSION: This is the first report from India of whole genome sequencing of HCV subtype 6xa. The identification of NS5A resistance mutations in the 3b relapse case underscores challenges for global HCV elimination strategies.

Humans

Elastic tape as an add-on strategy to potentiate pulmonary rehabilitation outcomes in nonobese males with moderate-to-very severe COPD: A randomised clinical trial.

BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation (PR) improves exercise capacity but has limited effects on ventilatory constraints in severe COPD. Application of elastic tape (ET) is a potential adjunctive strategy that improves ventilatory efficiency, but its effects during PR remain un lear. This study investigated whether ET potentiates PR benefits on exercise capacity, health status, psychological symptoms, and health-related quality of life (HRQoL) in individuals with COPD. METHODS: Forty-two nonobese men with moderate-to-very severe COPD were randomised to ET or Sham groups during an 8-week PR programme. The primary outcome was endurance shuttle walk test (ESWT) time; secondary outcomes included COPD Assessment Test (CAT), Chronic Respiratory Questionnaire (CRQ), and Hospital Anxiety and Depression Scale (HADS). RESULTS: ESWT improved by +329s in the ET group, exceeding the MCID. Greater CAT improvements (p&#x2009;=&#x2009;0.02), and a higher proportion achieving minimal clinically important difference (MCID) (48% vs. 29%; p&#x2009;=&#x2009;0.02) were observed in the ET group. Only ET group achieved MCIDs for depression (p&#x2009;=&#x2009;0.003) and anxiety (p&#x2009;=&#x2009;0.02). HRQoL improved similarly in both groups. The only outcome with a significant time&#x2009;&#xd7;&#x2009;group interaction was HADS-D (p&#x2009;=&#x2009;0.001), improved by ET. Only This study was performed in accordance with the Declaration of Helsinki. This human study was approved by Ethics Committee for Analysis of Research Projects (CAPPesq) of School of Medicine of the University of S&#xe3;o Paulo - Hospital das Cl&#xed;nicas (approval 55 617 321.20000.0068). All adult participants provided written informed consent to participate in this study. Clinical Trial Registration number NCT05939999 (https://clinicaltrials.gov), registered on October 26th, 2025.ET group presented moderate-to-large effect sizes for ESWT (d&#x2009;=&#x2009;0.89), HADS-A (d&#x2009;=&#x2009;0.51) and HADS-D (d&#x2009;=&#x2009;1.02). CONCLUSIONS: ET potentiates PR benefits on exercise capacity, health status, and psychological symptoms in individuals with moderate-to-very severe COPD.

Humans

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n&#xa0;=&#xa0;75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p&#xa0;=&#xa0;0.02 to p&#xa0;<&#xa0;0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans

Cannabis and cannabinoids for the treatment of mental and substance use disorders and symptoms: A systematic review and meta-analysis of experimental and observational studies.

BACKGROUND: Interest in cannabinoids for mental and substance use disorders is increasing. We examined experimental and observational evidence for treating these disorders and their symptoms. METHODS: Systematic review and meta-analysis (PROSPERO CRD42023467536). We searched CENTRAL, MEDLINE, Embase and PsycINFO to May 2025 for studies of cannabinoids in adults (&#x2265;18 years) with ADHD, anxiety, depression, PTSD, psychosis or Tourette syndrome, or alcohol, cannabis, opioid or tobacco use disorders. Two reviewers screened, extracted and assessed quality using a risk-of-bias tool and GRADE. RESULTS: We included 82 experimental and 118 observational studies. In RCTs, cannabinoids reduced anxiety symptoms (SMD=-0.40; 95% CI: -0.57, -0.23; I&#xb2;=90%) and, in one small trial, PTSD symptoms (SMD=-2.60; 95% CI: -4.58, -0.62; n=20), with trivial-to-no effect on depression (SMD=-0.20; 95% CI: -0.43, 0.04; I&#xb2;=91.6%), ADHD, psychosis and Tourette syndrome. Much anxiety and depression evidence came from symptoms measured as secondary outcomes in other primary conditions. Cannabinoids worsened cannabis use disorder severity in one RCT (SMD=2.35; 95% CI: 1.49, 3.21), with no effect on craving or withdrawal; evidence for alcohol, opioid and tobacco use disorders was very limited. Observational studies suggested improvements but had high risk of bias. The only significant safety finding was increased withdrawals due to adverse events with THC (OR=2.78; 95% CI: 1.66, 4.65). Certainty was predominantly very low. DISCUSSION: The evidence base shows very low certainty, high heterogeneity and methodological limitations, and is insufficient to support cannabinoids as first-line treatment. Signals for anxiety and PTSD are limited by indirectness and low certainty; no benefit was evident for depression; THC-related safety signals warrant careful consideration.

Humans

Antibody-drug conjugates against multidrug-resistant cancers: Biomarker-guided patient selection, payload engineering, linker chemistry, and bystander effects.

Antibody-drug conjugates (ADCs) are one of the most significant advancements in modern cancer therapeutics. Combining the target selectivity of monoclonal antibodies with the cytotoxic potential of payloads, ADCs effectively kill cancer cells and offer hope to patients with even refractory cancer types. Beyond simply increasing the number of therapeutic options available for cancer patients, ADCs have become a powerful frontline agent in overcoming multidrug resistance (MDR). As one of the most challenging obstacles to effective cancer care, MDR is mediated by ATP-binding cassette (ABC) transporter-mediated drug efflux, target-based mutations, and dysregulated apoptosis. The clinical success of ADCs specifically engineered to overcome MDR, including in heterogeneous tumors and cancer cells that exhibit bypass signaling, is well established. This is especially evident with trastuzumab deruxtecan (T-DXd) in HER2-low, HER2-positive, and HER2-mutant cancers; sacituzumab govitecan (SG) in TROP2-expressing triple-negative breast cancer (TNBC) and urothelial carcinoma; and enfortumab vedotin in Nectin-4-positive bladder cancer. By overcoming MDR, ADCs have enabled more effective treatment algorithms across multiple malignancies. Most importantly, the clinical application of ADCs has become inextricably linked to cancer genomics. HER2 testing has evolved from a two-tiered system to a continuous spectrum including HER2-ultralow, HER2-low, HER2-positive, and ERBB2-mutant categories. Each of these categories exhibits different eligibility guidelines for ADC patient selection. As cancer cells continue to evolve and develop resistance to even ADCs through mutations and variants, researchers and clinicians have used pharmacogenomics to predict ADC response and resistance. To define the genomic architecture of ADC-resistant tumor subpopulations, single-cell transcriptomic studies and liquid biopsy approaches are being used to enable real-time examination of the tumor genome during ADC therapy, thereby optimizing treatment and circumventing resistance driven by emerging mutations and variants. This review provides a comprehensive analysis of the molecular structure of ADCs, the pharmacological principles underlying their potent cytotoxic activity against MDR cancer cells, the genomic and transcriptomic biomarkers that guide ADC patient selection, and the emerging resistance mechanisms that will shape the next generation of promising ADC development.

Humans

Digital Mindfulness Intervention for Pregnant Women With Affective Disorders and Acute Stress Reactions: Prespecified Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Pregnant women with ICD-10 (International Statistical Classification of Diseases, Tenth Revision) affective or stress-related disorders face an elevated risk of perinatal depression and anxiety, yet evidence on digital nonpharmacologic interventions for this population remains limited. OBJECTIVE: This study evaluated the effectiveness of an 8-week digital mindfulness-based intervention (eMBI) compared with treatment as usual (TAU) among pregnant women with ICD-10 affective or stress-related disorders participating in a randomized controlled trial (RCT). METHODS: This prespecified secondary analysis was conducted within a multicenter RCT in Baden-W&#xfc;rttemberg, Germany. Pregnant women aged 18 years and older with elevated depressive symptoms (Edinburgh Postnatal Depression Scale [EPDS]>9) and ICD-10-diagnosed affective or stress-related disorders were randomized 1:1 to eMBI or TAU. The intervention consisted of 8 weekly app-based mindfulness sessions (45 min each) delivered during gestational weeks 29-36, with no direct therapist contact. The primary outcome was continuous depressive symptom severity measured with the EPDS at 4-6 weeks post partum. Secondary outcomes included the EPDS at 6 months post partum, generalized anxiety (State-Trait Anxiety Inventory-State [STAI-S], State-Trait Anxiety Inventory-Trait [STAI-T]), and Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R). Analyses followed the intention-to-treat (ITT) principle, using mixed models for repeated measures and multiple imputation. RESULTS: Of the 5299 screened women, 147 met the inclusion criteria for this subgroup analysis (intervention group [IG] had n=73 women and control group had n=74 women). Groups were comparable at baseline. The IG showed significantly greater reductions in EPDS scores at gestational week 34 (&#x394;=-2.21, P=.01), week 36 (&#x394;=-3.25, P=.01), and 4-6 weeks post partum (&#x394;=-4.81, P=.007). Treatment effects remained robust under conservative missing-data assumptions. At 4-6 weeks post partum, a higher proportion of participants in the IG achieved clinically meaningful improvement (31/73, 42.5% vs 21/74, 28.4%; adjusted odds ratio 1.56, 95% CI 1.19-2.05; P=.001). Anxiety outcomes followed a similar pattern, whereas pregnancy-related anxiety did not differ between groups. CONCLUSIONS: In this prespecified subgroup of pregnant women with ICD-10 affective or stress-related disorders, the eMBI was associated with clinically meaningful reductions in depressive symptoms from late pregnancy to 4-6 weeks post partum. Effects at 6 months post partum were attenuated and less stable across missing-data assumptions. These findings support eMBIs as a scalable, nonpharmacological adjunct to perinatal mental health care for women with affective or stress-related disorders, while confirmation in adequately powered trials with strategies to reduce postpartum attrition is warranted.

Humans

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n&#x2009;=&#x2009;101) and a "Low Symptom Burden-Relieving (LSBR)" type (n&#x2009;=&#x2009;88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P&#x2009;<&#x2009;0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.&#xa0; CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans

A novel peptide encoded by circTLL1 drives osimertinib resistance in lung cancer by modulating the NT5C2/Ras/PI3K axis.

BACKGROUND: Acquired resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). Although circular RNAs (circRNAs) have been increasingly implicated in drug resistance, most studies have focused on their canonical role as microRNA sponges, while their capacity to encode functional micropeptides remains largely unexplored. This study aimed to identify novel circRNAs involved in osimertinib resistance and to characterize their regulatory functions at the protein level. METHODS: Osimertinib-resistant (OR) NSCLC cell lines were established and validated. High-throughput RNA sequencing was performed to compare the circRNA expression profiles between parental and OR cells. The function of the candidate circRNA was assessed through a series of in vitro and in vivo experiments, including cell viability assays, apoptosis analysis, and xenograft mouse models. Mechanistic investigations involved mass spectrometry, co-immunoprecipitation and western blotting to explore its protein-coding potential and downstream signaling pathways. RESULTS: We identified a novel circRNA, termed circTLL1, that was stably and significantly upregulated in OR-NSCLC cells. Functionally, overexpression of circTLL1 promoted osimertinib resistance, whereas its knockdown restored drug sensitivity both in vitro and in vivo. Mechanistically, we discovered that circTLL1 harbors an open reading frame (ORF) that is translated into a novel 90-amino-acid protein, which we designated circTLL1-90aa. Further investigation revealed that circTLL1-90aa directly interacts with and promotes the degradation of 5'-nucleotidase, cytosolic II (NT5C2), thereby uncoupling nucleotide metabolism from its normal regulatory constraints. The consequent downregulation of NT5C2 leads to elevated GTP levels and leading to the sustained activation of the downstream Ras/PI3K/AKT signaling pathway. CONCLUSION: Our findings unveil a previously unrecognized circRNA/micropeptide/metabolism cascade underlying osimertinib resistance. The identification of the circTLL1-90aa/NT5C2/Ras/PI3K axis not only expands the functional repertoire of the non-coding genome but also provides new insights into the complexity of drug resistance. Given its selective upregulation in resistant cells, circTLL1-90aa holds promise both as a predictive biomarker for treatment stratification and as an actionable therapeutic target, offering a novel strategy to overcome osimertinib resistance in NSCLC patients.

Pyrimidines

Molecular Diagnostics for WHO Priority Bacterial Pathogens: A Bibliometric Mapping of Diagnostic Platforms, Resistance Markers, and Antimicrobial Resistance Research Trends.

Antimicrobial resistance (AMR) constrains effective treatment and carries implications for infection control, surveillance, and public health. The World Health Organization (WHO) priority bacterial pathogen framework has intensified the need for diagnostic innovation by redefining research priorities around organisms combining high disease burden with complex resistance profiles. Molecular diagnostics have accordingly moved beyond culture-based workflows, integrating rapid pathogen identification, resistance-marker detection, genomic surveillance, and clinical decision support. The present study conducted a bibliometric mapping of the literature on WHO priority pathogens. Rather than addressing resistance at a general level or a single pathogen or technology, it integrates priority pathogens, molecular platforms, and resistance markers within a single framework, tracing their joint thematic and temporal evolution along an explicit pathogen-platform-marker axis. Scopus-indexed articles and reviews (2000-2025) were retrieved, yielding 1746 publications after screening adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analyses used Bibliometrix/Biblioshiny, R, and VOSviewer. The literature expanded markedly after 2018, led by China and the United States. Methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, Enterococcus faecium, and the Enterobacterales-carbapenemase axis constituted the principal thematic cores, whereas conventional polymerase chain reaction (PCR)/nucleic acid amplification testing (NAAT) and whole-genome sequencing were the dominant platforms. Overall, the field has evolved from pathogen detection into an AMR-centered translational domain encompassing resistance prediction, genomic epidemiology, surveillance, and clinical decision support. Diagnostic development, stewardship, and surveillance depend on hybrid workflows coupling rapid marker-targeted assays with genome-based characterization, delivering actionable resistance within clinically meaningful timeframes, and extending coverage to underrepresented pathogens and platforms.

Humans

Genomic epidemiology of clinically critical antibiotic resistance in Salmonella enterica causing bloodstream infections across six Chinese provinces, 1994-2023.

Clinically critical antibiotic-resistant Salmonella enterica (S. enterica) causing bloodstream infections remains a public health challenge. Here, we aim to reveal the emergence and trends of clinically important antibiotic resistance in S. enterica causing bloodstream infections using 833 isolates from six Chinese provincial-level administrative areas during 1994-2023. We identified 48 serovars and 64 sequence types (STs). Overall, 8.52% of 833 isolates were resistant or had decreased susceptibility to ciprofloxacin, 4.32% and 6.84% reported resistance or decreased susceptibility to third- and fourth-generation cephalosporins (3GCs and 4GCs), 1.80% reported resistance to fosfomycin, and 2.16% reported resistance to azithromycin. Across these six regions, azithromycin and fosfomycin resistance is increasing, as is decreased susceptibility or resistance to ciprofloxacin, 3GCs, and 4GCs, especially among younger children and elderly people. Clinically prioritized antibiotic resistance also varies by region, serovar, and age group. S. Paratyphi A genotype 2.3.3 strains are mainly divided into 2 lineages distributed in Guangxi and Shanghai. Within the scope of this passive surveillance dataset, S. Typhi genotype 4.3.1.2.1 was identified as the earliest documented case among the collected isolates. Our retrospective and longitudinal genomic epidemiology study provides critical data for the formulation of treatment guidelines and policies for bloodstream infections and for the monitoring and control of antimicrobial resistance.

Humans

Depressive Symptoms and Smoking Cessation Among Adolescents and Young Adults Who Smoke: A Prospective Cohort Study.

PURPOSE: This study examined the bidirectional prospective associations between depressive symptoms and smoking cessation among adolescent and young adults who smoke. METHODS: Data on 1,151 participants aged &#x2264;25 years who smoke and receive peer-led quitline counseling in Hong Kong (2016-2022) were analyzed. Exposures included baseline depressive symptoms and smoking cessation (self-reported 7-day abstinence) at 1, 3, and 6 months; Outcome measures included smoking cessation at 1, 3, and 6 months and depressive symptoms at 6 months. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, with a score &#x2265;16 indicating at risk for depression. RESULTS: More severe baseline depressive symptoms were associated with lower odds of smoking cessation at 1, 3, and 6 months, which reversely was associated with lower depressive symptoms at 6 months (all p < .05). Similarly, being at risk for depression at baseline was associated with lower odds of smoking cessation at 1 (adjusted odds ratio [aOR] .66, 95% confidential interval [CI] .47-.93) and 3 months (aOR .71, 95% CI .52-.97). Conversely, smoking cessation at 1 (aOR .40, 95% CI .23-.69), 3 (aOR .58, 95% CI .37-.92), and 6 months (aOR .44, 95% CI .29-.69) was associated with lower odds of at risk for depression at 6 months. DISCUSSION: More severe depressive symptoms were prospectively associated with lower odds of smoking cessation, while smoking cessation was associated with lower depressive symptoms and risk for depression. Integrated interventions simultaneously addressing psychological needs and smoking are warranted, when delivered in smoking cessation programs or embedded within mental health services for youth who smoke.

Humans

Effectiveness of physical activity intervention for depression, anxiety and comorbid symptoms during the perinatal period among Chinese primiparas.

BACKGROUND: To examine the effectiveness of a physical activity (PA) programme incorporating partner support and enjoyment in preventing perinatal depression, anxiety, and comorbid anxiety and depression (CAD) among Chinese primiparas. METHODS: A total of 120 eligible primiparas were randomised into intervention or control groups. The intervention group received the 13-week PA programme and the control group received the usual care. The outcomes were depression, anxiety, and CAD assessed at baseline, post-intervention, and 6 weeks after delivery. Differences were examined using generalised linear mixed models with intention-to-treat. RESULTS: A significant group&#x2009;&#xd7;&#x2009;time interaction was observed for depression score, anxiety score, anxiety incidence, and CAD incidence (all p&#x2009;<&#x2009;0.05). However, no significant interaction was found for depression incidence. Compared to the control, the intervention substantially reduced the scores of depression (MD: -2.67 (-4.16 to -1.17); -2.63 (-4.15 to -1.11)) and anxiety (MD: -4.95 (-9.23 to -0.67); -7.33 (-11.85 to -2.82)), as well as the rates of depression (OR: 0.40 (0.18 to 0.85); 0.44 (0.21 to 0.93)) and CAD (OR: 0.35 (0.14 to 0.87); 0.26 (0.11 to 0.62)) at post-intervention and 6-week postpartum. Notably, anxiety incidence showed significant reduction only at 6-week postpartum (OR: 0.34 (0.16 to 0.74)) (all p&#x2009;<&#x2009;0.05). Within the intervention group, no significant changes occurred in most outcomes from baseline to post-intervention and 6-week postpartum, except depression scores (MD:-1.60 (-2.79 to -0.41); -1.23 (-2.44 to -0.03); p&#x2009;<&#x2009;0.05). CONCLUSIONS: The PA programme (including partner support and enjoyment) may be effective in reducing perinatal depression, anxiety and CAD among primiparas.

Adult

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p&#x2009;<&#x2009;0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62&#xa0;min, 95% CI 0.18-7.06; p&#x2009;<&#x2009;0.05) and reduced mean power output (mean difference&#x2009;-&#x2009;19.97 W, 95% CI&#x2009;-&#x2009;36.87 to&#x2009;-&#x2009;3.06; p&#x2009;<&#x2009;0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans

Intervention Without Borders - an Automated Self-Guided AI-Enhanced Psychoeducation Intervention for Dementia Caregivers: Parallel-Group Randomized Waitlist-Controlled Trial.

OBJECTIVE: To examine whether a fully automated, self-guided intervention (PDC30) could improve caregiver well-being over a 1-month waitlist control in an international sample. DESIGN: Randomized waitlist-controlled trial. SETTING: Web-based platform accessible globally. PARTICIPANTS: 441 individuals responded to study promotion on the internet, of whom 274 from 43 countries met the study criteria and were randomized. Eligible participants were adults providing &#x2265;10 care hours weekly to community-dwelling relatives with dementia, scoring &#x2265;5 on Patient Health Questionnaire-9 (PHQ-9), and without recent caregiver intervention. INTERVENTION: Available 24/7, PDC30 is a self-guided, automated intervention consisting of a Guidebook, an AI-powered counseling chatbot, and interactive applications for cognitive-behavioral techniques, relaxation, and caregiver-recipient bonding. MEASUREMENTS: At baseline and follow-ups at 1, 2, and 3 months, depression was assessed by PHQ-9. Secondary outcomes were measured with validated brief versions of anxiety, burden, and positive gains. RESULTS: Intent-to-treat analysis using mixed-effects regression showed treatment x time2 effects on all outcomes except anxiety. At 1-month follow-up, coinciding with exclusive access to PDC30, intervention caregivers showed significant improvements in depression (d = -0.37), burden (d = -0.34), and positive gains (d = 0.42). The differences mostly disappeared after control participants received the intervention, while improvements in both groups were sustained thereafter. Participants reported using the website several times weekly, were generally satisfied with it, and found the chatbot most helpful. CONCLUSIONS: The effects on depression and other outcomes were consistent with those observed for in-person programs, suggesting the viability of well-designed automated intervention. The study demonstrates the feasibility, acceptability, and potential global health impact of PDC30.

Humans