High-grade serous ovarian carcinoma (HGSC) demonstrates poor prognosis with approximately 80% recurrence rates and significant chemotherapy resistance. Conventional checkpoint inhibitors show limited efficacy (10-15%), necessitating alternative immunotherapeutic approaches. Engineered T lymphocytes, particularly CAR-T and TCR-T cells, have emerged as promising strategies for HGSC. This literature review examines the promising role of engineered T lymphocytes in immunotherapy for HGSC. A comprehensive literature search was conducted across PubMed, Scopus, and Cochrane Library databases for peer-reviewed studies published between 2015 and 2025. Search terms included "engineered T lymphocytes," "CAR-T cells," "TCR-T cells," "ovarian cancer immunotherapy". CAR-T cells demonstrate promising preclinical antitumor activity in HGSC, with high-avidity T-cell clones showing robust efficacy. Engineered T lymphocytes demonstrate promising approaches across disease contexts. In high-grade serous ovarian carcinoma, Engineered T lymphocytes orchestrate tumor cell apoptosis through coordinated granzyme/perforin and Fas/FasL signaling, enabling rapid cytotoxic elimination of multiple tumor targets.
We sought to determine the suitability of a semi-validated quantitative PCR (qPCR) assay for assessing the prevalence and density of Ichthyophonus sp. infections in Yukon River Chinook Salmon Oncorhynchus tshawytscha, representing a new species and location for the assay's application. Ichthyophonus sp. causes severe disease that has been implicated in the en route prespawning mortality of this Chinook Salmon stock. The reduced survival of these fish has caused many hardships for the people who rely on them. We assessed a modified qPCR assay with stage 1 and partial stage 2 validation per World Organisation for Animal Health criteria for Ichthyophonus sp. surveillance in Yukon River Chinook Salmon. Cohen's kappa tests were used to compare qPCR results of infection status (infected/uninfected) with those of explant culture-the current reference standard. Linear regressions were used to interrogate qPCR results of parasite gene copies per milligram for infection density with parasite counts per cubic millimeter from the reference standard of histopathology. We found that the prevalence of Ichthyophonus sp. DNA by qPCR did not significantly differ from that of the reference standard for explant culture of the parasite. The qPCR demonstrated high analytical sensitivity and estimated diagnostic performance. Gene copies per milligram by qPCR were correlated to the number of schizonts per cubic millimeter with an R2 value of 0.40-0.41, but the R2 increased to 0.92 after we accounted for parasite size in the 2023-2024 data set. The results from this qPCR with our modifications were equivalent to the prevalences and densities determined by reference standards and fit our purpose for a rapid Ichthyophonus sp. surveillance assay. This could be used in-season to inform fishery managers about disease and mortality associated with Ichthyophonus sp. infections in high-risk regions like the Yukon River, where en route prespawning mortality associated with this parasite occurs periodically. The DNA test detected and quantified material of the fungal-like parasite Ichthyophonus sp. as well as the gold standards. It will allow for rapid monitoring of infections in Yukon River Chinook Salmon to better inform management of this stock, whose decline has caused severe hardships for people that rely on these iconic fish.
Neuromodulation technology, an interdisciplinary field integrating neuroscience, engineering, and clinical medicine, offers novel therapeutic paradigms for numerous intractable diseases. In pain medicine, it modulates nervous system function through electrical or chemical signals, emerging as a core approach for managing refractory pain. However, the rapid advancement of this technology has coincided with a persistent underappreciation of the core value and multidimensional roles of pain physicians. This paper systematically elucidates the essence and scope of neuromodulation technology, analyzes its unique advantages in addressing the diagnostic and therapeutic challenges of refractory pain, and reviews its rapid developmental trajectory. It critically highlights the indispensable, yet often underestimated, role of pain physicians in driving the high-quality advancement of this field. Furthermore, this paper explores safety concerns in clinical applications and highlights the need to establish robust monitoring, evaluation, and education systems. Finally, future directions for pain specialists in leading the evolution of neuromodulation are outlined.
Portable high-efficiency particulate air (HEPA) filters effectively remove airborne microbes. To investigate whether HEPA filters reduce respiratory infection episodes in care home residents. This 2-arm cluster randomized clinical trial included care homes for older adults in England, with or without nursing and dementia care provision, and capacity for 20 or more residents in individual bedrooms. Data were collected between September 2021 and May 2024, with each care home participating for 1 winter. Up to 5 HEPA filters for communal areas (clean air delivery rate set at 160 m3/h) and up to 16 filters for bedrooms (clean air delivery rate set at 60 m3/h). Both groups continued usual infection prevention and control measures. The primary outcome was respiratory infection rate per winter per bedroom resident (exposed to bedroom and communal room filters). Secondary outcomes included staff absenteeism. All outcomes were also explored for residents exposed only to communal room filters. During the study period, 91 care homes were randomized, 47 to receive communal room filters, with 569 bedroom residents (median [IQR] age, 87 [81-92] years; 398 [70.0%] female), and 44 without communal room filters, with 589 residents without bedroom filters (median [IQR] age, 88 [82-92] years; 23 [71.8%] female). There was no evidence of a difference in the number of respiratory infections per winter per intervention vs control bedroom residents (0.99 vs 1.04; adjusted incident rate ratio, 0.92; 95% CI, 0.64-1.33; P = .67). There was also no evidence of a difference in the rates of staff absenteeism (adjusted incident rate ratio, 0.80 95% CI, 0.55-1.16; P = .24). Results were similar for the residents exposed only to communal room HEPA filters. In this cluster randomized clinical trial, there was no difference in resident respiratory infection rates in care homes with HEPA filters in communal areas and bedrooms. Care homes should continue existing recommended prevention measures to control respiratory and other infections. isrctn.org Identifier: ISRCTN63437172.
Hard carbon (HC) anodes are promising for sodium-ion batteries, yet achieving high initial Coulombic efficiency (ICE), large plateau contribution, and fast charge-transfer kinetics remains challenging due to insufficient control of micro-nanostructure and interphase chemistry. Here, we present a precursor-level molecular engineering strategy that simultaneously regulates sodium desolvation and interphase chemistry in HC. An iodine-mediated oxidative cross-linking process converts starch into spherical HC with uniformly distributed ultramicropores and carbonyl-rich surfaces. These nanoconfined pores are proposed to act as molecular sieves, preferentially excluding bulky solvent molecules while allowing PF6--coordinated Na+ access, thereby favoring anion-enriched electrolyte structures under confinement. Surface carbonyls exhibit strong PF6- affinity, which may promote fluorine-rich inorganic interphases on pore surfaces. The synergistic effects of anion-selective adsorption and confined desolvation are suggested to favor thin and robust NaF-rich interphases at external surfaces and within nanoconfined pore regions, contributing to reversible interfacial reactions and rapid Na+ storage kinetics. Consequently, the HC delivers an ICE of 88.4%, a reversible capacity of 352.9 mAh g-1 at 0.1C, excellent rate capability (288.9 mAh g-1 at 5C), and 95.6% capacity retention over 200 cycles. This work offers a molecular-level design paradigm integrating efficiency, capacity, and kinetics in HC anodes.
Pembrolizumab monotherapy improves survival in advanced non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 50%. However, survival in randomised trials may not fully reflect outcomes in routine practice, with implications for economic evaluation. To evaluate the cost-effectiveness of pembrolizumab monotherapy compared with platinum-based chemotherapy from an Australian health-payer perspective, integrating both randomised controlled trial (RCT) and real-world evidence (RWE). A semi-Markov model with three health states (progression-free, progressed disease, death) was developed over a 3-year horizon. Clinical inputs were derived from KEYNOTE-024 for the RCT scenario and from nationwide Australian real-world data for the RWE scenario, with chemotherapy outcomes retained from the pivotal trials in both scenarios. Direct medical costs (2024 AU$) and quality-adjusted life years (QALYs) were estimated. Incremental cost-effectiveness ratios (ICERs) were calculated, probabilistic and deterministic sensitivity analyses conducted. Compared with chemotherapy, pembrolizumab monotherapy was associated with incremental costs of AU$87,399 (RCT-based) and AU$75,935 (RWE-based), and incremental QALY gains of 0.23 and 0.11, respectively. Corresponding ICERs were AU$385,561/QALY (RCT) and AU$705,729/QALY (RWE). At a AU$75,000/QALY willingness-to-pay (WTP) threshold, the probability of cost-effectiveness was < 1% in both scenarios. Differences in overall survival between trial and real-world cohorts likely contributed to the variation in ICERs. At current pricing and Australian WTP thresholds, pembrolizumab monotherapy is unlikely to be cost-effective, with RWE-informed scenarios yielding less favourable cost-effectiveness estimates than from trial data. These findings highlight that cost-effectiveness estimates may be sensitive to differences between trial-based and real-world effectiveness inputs.
Protein-energy malnutrition (PEM) is common in gastrointestinal (GI) cancers and may worsen inpatient outcomes. Contemporary national data describing the impact of PEM among young adults with GI malignancies are limited. We conducted a retrospective cohort study using HCUP NIS data from 2018 to 2021. We identified hospitalizations of adults aged 18 to 39 years with GI cancers using ICD 10 CM codes C15 to C26. We defined PEM using ICD-10-CM diagnosis codes recorded during the index hospitalization; therefore, PEM reflects clinically documented/coded malnutrition rather than the full burden of nutritional risk or clinically undiagnosed malnutrition. Primary outcomes were in hospital mortality and discharge disposition. Secondary outcomes were LOS and total hospital charges. We used survey weighted multivariable logistic and linear regression to estimate adjusted associations, accounting for age, sex, race or ethnicity, payer, income quartile, admission type, calendar year, and age adjusted CCI. Among 58,910 weighted hospitalizations of young adults with gastrointestinal cancers, 11,915 (20.2%) had protein-energy malnutrition (PEM). Compared with those without PEM, hospitalizations with PEM had a higher burden of advanced disease and acute illness, including a greater prevalence of metastatic disease (71.8% vs. 53.1%), and experienced worse unadjusted outcomes, including higher in-hospital mortality (8.4% vs. 3.2%), longer length of stay (10.43 vs. 5.63 days), and higher total hospital charges ($133,790 vs. $83,702). In adjusted analyses, PEM was independently associated with increased odds of in-hospital mortality (aOR 2.13, 95% CI 1.72-2.56; p < 0.001) and higher odds of non-home discharge (aOR 1.67, 95% CI 1.47-1.89; p < 0.001). PEM was also associated with substantially greater resource utilization, including an adjusted increase of 4.49 hospital days (β + 4.492; SE 0.248; p < 0.001) and $53,513 higher total hospital charges (β +$53,512.6; SE $5,527.6; p < 0.001). PEM affected one in five hospitalizations among young adults with GI cancers and was independently associated with increased mortality, non-home discharge, LOS, and hospital charges. These findings support routine inpatient nutritional assessment and early intervention in this high risk population.
Spin qubits based on electron spins are promising platforms for quantum information science due to their ability to form controllable superposition states with long coherence times. While most molecular spin qubits have focused on S = 1/2 systems, high-spin systems offer an alternative approach with access to multilevel quantum states. In particular, high-spin Mn(II) (S = 5/2) centers possess zero orbital angular momentum (L = 0), resulting in weak spin-orbit coupling that suppresses spin-lattice relaxation and prolongs phase memory times. The central transition (MS = -1/2 ↔ +1/2) behaves similarly to an S = 1/2 system, enabling robust and stable spin coherence, whereas the outer transitions (MS = ±5/2 ↔ ±3/2 and ±3/2 ↔ ±1/2) provide additional functionality through interactions with nuclear spin systems and external electric fields. Recent studies on Mn(II)-doped metal-organic frameworks and discrete Mn(II) complexes diluted in diamagnetic matrices demonstrate tunable spin relaxations, highlighting their potential as multilevel quantum units for advanced quantum operations such as Grover-type algorithms. Despite these promising features, molecular high-spin qubits remain less explored than their S = 1/2 counterparts, and further investigations into spin-vibration coupling, structural design, and external field control are required. Overall, high-spin metal complexes represent an emerging and versatile platform for next-generation spin-based quantum technologies.
Groundwater is the primary source of drinking water through which fluoride enters the human body. Excessive intake of fluoride-contaminated water poses serious health risks. The study aims to collect groundwater samples from various sources, investigate their spatial distribution, and assess non-carcinogenic health risks. 147 samples have been collected from various groundwater sources, including borewells, dug wells, tube wells, and hand pumps, across the Jaisalmer district, Rajasthan, during the post-monsoon season in November 2025, and analysed using an Ion Selective Electrode (ISE). The results indicate that the fluoride concentration range is 0.1 to 11.8 mg L-1, with 42 samples (29%) exceeding the World Health Organisation (WHO) permissible limit of 1.5 mg L-1. Spatial distribution mapping via ordinary kriging reveals that the highest fluoride contamination is localised in the Mohangarh block (maximum 11.8 mg L-1). Statistical evaluations were performed using the Shapiro-Wilk test for normality, followed by the nonparametric Kruskal-Wallis test. Block-wise non-carcinogenic health risk assessments calculating chronic daily intake (CDI) and hazard quotient (HQ) show a maximum mean HQ value of 4.04 for children and 1.73 for adults in the Mohangarh block, followed by 3.36 for children and 1.44 for adults in the Nachana block, indicating that approximately 70% of children across the study area are at a high risk of fluorosis. These findings highlight that the region is a high-risk zone for fluoride-related health issues and requires urgent mitigation strategies, such as implementing defluoridation techniques and providing alternative safe drinking water, to protect public health.
A rapid increase in ageing population across the globe has made it necessary for countries to focus on the health and well-being of older adults. City-level data on ageing is limited in the context of developing countries. The present study examines the associations between Bourdieu's core forms of capital (economic, cultural, and social) and self-rated health of older adults aged 60 and above, in Lucknow city, India. The study employs a multistage cluster sampling design. Face-to-face interviews were conducted with 410 respondents aged 60 years and older, between May 2023 to August 2023. Ordered logistic regression is used to assess the associations between all three forms of capital and self-rated health of older adults after controlling for their gender, caste and religious group, age group, overall fitness, and recreational participation. In the full model, high levels of social support from informal ties, and higher levels of cultural capital (higher education and cultural engagement) are associated with better self-rated health, while economic capital is not significant once social and cultural capital are accounted for. This study highlights the role of neighbourhood social capital and cultural engagement as possible intervention mechanisms for improving the health of older adults, which is key to policy and practice for achieving the goal of active ageing.
The precise contribution of basophils to cancer development and advancement remains undefined. Our research sought to delineate the immune subtypes of basophils in head and neck squamous cell carcinoma (HNSCC) and to develop a robust prognostic model. Single-cell and bulk transcriptomic data from the TCGA-HNSC and the GEO (GSE41613, GSE139324) were integrated. Basophil subtypes and their signature genes were identified. Samples were subjected to unsupervised consensus clustering based on basophil-related differentially expressed genes to define immune subtypes. A prognostic model was constructed and its performance validated in external datasets. The biological function of the key gene DHRS2 was investigated through in vitro experiments. Single-cell analysis identified heterogeneous basophil populations in HNSCC, classified into distinct subtypes. Cluster 1 displayed a low immune infiltration phenotype. Using basophil signature genes, TCGA-HNSC samples were stratified into two subtypes with significant survival differences. A 12-gene prognostic model with good predictive performance was developed. High-risk patients showed high tumor purity along with downregulated immune checkpoint and HLA gene expression, indicative of active immune evasion. Experimentally, the key model gene DHRS2 was highly expressed in HNSCC, and its knockdown suppressed cell proliferation, migration, and invasion while inducing apoptosis. The study characterizes basophil immune subtypes in HNSCC and establishes a robust basophil-related prognostic model that effectively identifies high-risk patients, suggesting the potential pro-tumorigenic gene DHRS2 as a therapeutic target in HNSCC.
Glucagon is a key regulator of amino acid metabolism, and elevated levels are frequently observed in maintenance hemodialysis (MHD) patients. Yet, the relationship between plasma glucagon levels, nutritional parameters, and prognosis in MHD patients remains unclear. We evaluated whether glucagon levels in MHD patients are associated with normalized protein catabolic rate (nPCR), glucagon-like peptide-1 (GLP-1), nutritional status, and all-cause mortality. In this prospective observational study, plasma hormone levels were measured alongside clinical, biochemical, anthropometric, bioimpedance-derived nutritional markers, and inflammatory indices. Mortality was assessed using Kaplan-Meier and Cox regression analyses. This study included 82 prevalent MHD patients. Patients were followed for 18.0 ± 4.9 months. Glucagon correlated positively with nPCR (r = 0.25, p = 0.03) and inversely with phase angle (PhA) (r =  - 0.24, p = 0.03) after adjustment. Additional correlations with GLP-1 became marginal after adjustment. The subgroup with high glucagon and low nPCR showed the lowest PhA (p = 0.03), and remained significant after multivariable adjustment. Patients with glucagon ≥ 120 pg/mL (ROC-derived cutoff) had higher mortality (log-rank p = 0.05); however, the discriminative power of this cutoff was limited (AUC 0.63). In multivariable models, the association persisted after adjustment for age and diabetes but was attenuated after further controlling for PhA, GLP-1, or MIS. Elevated glucagon in MHD patients was modestly associated with altered protein metabolism, impaired nutritional integrity, and borderline higher all-cause mortality. The independent prognostic value of glucagon remains uncertain, and a concept of a glucagon resistance phenotype is speculative.
Given the substantial disease burden of stomach adenocarcinoma (STAD)-the dominant and lethal subtype of gastric cancer-and the pivotal role of folate metabolism reprogramming in malignancy and treatment response, this study aimed to construct a prognostic model utilizing folate metabolism-related genes (FMRGs). Such a model is urgently required to supplement traditional TNM staging and to guide personalized precision medicine. Interrogation of TCGA and GEO transcriptomic profiles enabled the identification of differentially expressed FMRGs. These genes subsequently facilitated the construction of a prognostic signature via LASSO-Cox regression, which was then subjected to external validation. We further evaluated the clinical relevance of this risk signature by exploring its correlations with the tumor immune microenvironment, immunotherapy efficacy, and drug sensitivity, employing CIBERSORT and ssGSEA analytical frameworks. A five-gene prognostic model established from 220 FMRGs demonstrated moderate prognostic performance in identifying high-risk stomach adenocarcinoma patients with poorer survival. The high-risk group exhibited immunosuppressive microenvironments with stromal activation, while the low-risk group demonstrated "hot" tumor phenotypes characterized by higher immunogenicity and superior responses to immunotherapy and chemotherapy. Consequently, this model serves as a robust independent prognostic indicator. This five-gene folate metabolism signature shows moderate prognostic value in STAD and may help inform future investigations of the tumor immune microenvironment and therapeutic stratification.
Dental caries is a highly prevalent yet preventable disease affecting more than 40% of US children, with severe early childhood caries (S-ECC) leading to serious health and economic consequences. This randomized clinical trial addresses critical evidence gaps by evaluating 38% silver diamine fluoride (SDF) effectiveness for caries arrest in young US children with S-ECC to inform US Food and Drug Administration (FDA) regulatory approval. To assess the efficacy of 38% SDF vs placebo for arresting active cavitated dentin caries lesions in the primary dentition of US children with S-ECC. This phase III, multisite, randomized, blind, placebo-controlled clinical trial with 2 parallel arms had a data collection period from October 2018 through April 2023. Analyses were completed in 2024. Three sites recruited from and treated children in a variety of settings: medical and dental clinics, and Head Start and city/state-subsidized preschool programs. Enrolled participants included 830 generally healthy children aged 12 to 71 months with S-ECC and active cavitated lesions. Children were randomized to receive either 38% SDF or placebo, applied at baseline and at 6 months. Clinical examinations were conducted at baseline, 3 months, 6 months, and 8 months. The primary outcome was the proportion of arrested lesions at 6 months after 1 application. Secondary outcomes included arrest efficacy at 3 months and after 2 applications (8 months), and pain at or before 6 months and 8 months. Of 830 enrolled children, 584 (70%) completed the study. Of those lost to follow-up (approximately 30%), 81 (9.8%) were lost due to COVID-19. Participants included 428 females (52%) and 402 males (48%) and were aged 1 to 6 years with high caries experience (mean [SD] decayed, missing, and filled teeth [dmft] (International Caries Detection and Assessment System ≥1), 11.36 [4.56]; range, 1-23). In intent-to-treat analyses, SDF arrested 57.5%, 54.0%, and 50.2% of lesions at 3 months, 6 months, and 8 months, respectively, vs placebo (18.8%, 22.5%, 17.4%, respectively). Differences (99.9% CI) in arrest rates were 38.7% (28.7%-48.6%), 31.5% (21.5%-41.6%), and 32.8% (22.3%-43.2%). There were no differences in pain. Averse events (AEs) were reported by 196 (47.3%) participants in the SDF group and 180 (43.3%) in the placebo group. Most AEs were mild to moderate in severity; 4 AEs (0.6%) were severe. Treatment-related AEs were similar between the 2 groups (SDF = 22.9%; placebo = 22.2%), as were discontinuation rates due to AEs (7.5% for both groups). In this randomized clinical trial, 38% SDF was significantly more effective than placebo for arresting dentin caries lesions in primary teeth in young children with S-ECC, providing a noninvasive treatment for young high-risk children and supporting its consideration for FDA drug approval. ClinicalTrials.gov Identifier: NCT03649659.
Melanin, a multifunctional biopigment with photoprotective, antioxidant, and therapeutic properties, is limited by scarce sustainable sources and poor aqueous solubility. In this study, melanin production from a newly isolated marine-associated Bacillus sp. EGY7 was optimized using a Box-Behnken design, achieving a yield of 0.208 g/L. The microbial melanin was subsequently hydrothermally converted into water-dispersible melanin-derived carbon dots (MCDs) with quasi-spherical morphology, particle size of 9-15 nm, and a quantum yield of 5.05 ± 0.31%. The MCDs exhibit strong UV absorption, tunable and often excitation-dependent photoluminescence (PL), high photostability, and environment-sensitive fluorescence governed by their core-shell structure and surface functional groups. MCDs exhibited moderate antioxidant activity and high cytocompatibility, maintaining > 70% viability in human skin fibroblasts. Compared with native melanin, MCDs demonstrated enhanced selective cytotoxicity against breast cancer cells (IC50: 0.25 mg/mL for MCF-7 and 0.68 mg/mL for MDA-MB-231), with selectivity indices reaching 19.6 and superior inhibition of long-term colony formation. Mechanistic investigations suggested that their anticancer activity is mediated by reactive oxygen species (ROS)-induced apoptosis coupled with efficient nanoscale cellular uptake. Complementary in silico analyses predicted interactions with multiple cancer-related targets involved in apoptosis, oxidative stress regulation, and cell cycle control, supporting their theragnostic potential. Overall, these findings establish Bacillus sp. EGY7 as a renewable melanin source and highlight MCDs as a sustainable multifunctional platform for selective anticancer and bioimaging applications.
Reliable battery operation in sub-zero environments is critical for polar exploration, military missions, and space applications. However, conventional lithium-ion batteries (LIBs) face inherent limitations at low temperatures by intrinsic hurdle of poor ionic mobility in liquid electrolytes. All-solid-state batteries (ASSBs), which replace liquid electrolytes with non-flammable and non-freezing solid electrolytes, are considered promising alternatives because these solid electrolytes provide high ionic conductivity at low temperatures, superior temperature stability, and exceptional safety. ASSBs still face practical limitations at extremely low temperatures due to degradation caused by interfacial side reactions and mechanical instabilities that increase resistance and polarization. Addressing these challenges is critical to realize the advantages of ASSBs and enable their practical deployment in low-temperature applications. This review provides an overview of historical developments, critical challenges, and recent progress in advancing the low-temperature performance of ASSBs. The key components of ASSBs, including solid electrolytes, cathodes, and anodes, are systematically investigated to develop strategies for improving ASSBs at low temperatures. By highlighting future perspectives, we emphasize both the potential and necessity of ASSBs to overcome the intrinsic limitations of LIBs and ensure reliable energy storage in harsh environments.
After the COVID-19 emergency phase, Mycoplasma pneumoniae (MP) infections surged globally, heightening concerns over macrolide-resistant M. pneumoniae (MRMP), especially in children. Early detection of MRMP is crucial for reducing morbidity and optimizing antimicrobial use, but developing reliable prediction models remains challenging. This retrospective study evaluated 458 hospitalized children with PCR-confirmed MP pneumonia during the 2024 outbreak at a South Korean university hospital. We compared demographic, clinical, laboratory, radiographic, and treatment data between macrolide-sensitive (MS) and -resistant groups. Multivariable logistic regression and ROC analyses identified independent predictors of resistance and developed a risk model. The prevalence of MRMP was profoundly high at 83.8%. Compared with MS infections, MRMP was associated with older age, higher inflammatory markers, lower MP PCR cycle threshold (Ct) values, and more pulmonary complications. Multivariable analysis identified elevated erythrocyte sedimentation rate (ESR) and lower PCR Ct as robust, independent predictors of macrolide resistance. Integrating the PCR Ct value into a baseline clinical model significantly improved prediction accuracy, increasing the area under the curve (AUC) from 0.659 to 0.806. Chest radiographic findings provided negligible incremental diagnostic value (AUC 0.808). MRMP is highly prevalent among hospitalized children during post-emergency outbreaks in East Asia. Incorporating admission PCR Ct values and ESR into early clinical assessments substantially improves prediction of macrolide resistance, enabling timely, targeted escalation to second-line therapies.
Food allergy is common, affecting up to 8% to 10% of children and adults. Treatment options include oral immunotherapy (OIT) and omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody. To compare omalizumab with OIT for the treatment of patients with multifood allergy. This was a double-blind, placebo-controlled, randomized clinical trial comparing omalizumab with omalizumab-facilitated multiallergen OIT (MOIT) in participants who completed stage 1 of the Omalizumab as Monotherapy and as Adjunct Therapy to Multiallergen OIT in Children and Adults With Food Allergy (OUTMATCH) trial, which led to the approval of omalizumab. The setting comprised 10 academic centers across the US. Included in this analysis were individuals aged 1 to 55 years with an allergy to peanuts and at least 2 other foods (milk, eggs, wheat, cashews, hazelnuts, walnuts). Eligibility was based on oral food challenge thresholds, requiring dose-limiting symptoms to cumulative doses of 144 mg or less of protein for peanuts and 444 mg or less for nonpeanut allergens. Data were analyzed from October 2024 to February 2026. Participants were randomized to receive MOIT with placebo omalizumab or omalizumab with placebo MOIT. All received 16 weeks of open-label omalizumab; at week 8, active or placebo MOIT was initiated and escalated to goal doses of 1000 mg per food. At week 16, participants transitioned to blinded omalizumab or placebo injections for 44 weeks. The primary end point was cumulative tolerated dose (CTD) of 4044 mg or greater for all 3 foods. Predefined secondary end points included CTDs of 1044, 2044, 4044, 6044, or 8044 mg for 1, 2, or all 3 foods. A total of 117 participants (median [IQR] age, 7 [1-29] years; 64 male [55%]) were randomized to receive active MOIT (n = 58) or active omalizumab (n = 59). A total of 30 participants (51%) receiving active MOIT and 51 (88%) receiving active omalizumab completed the study. In the intention-to-treat (ITT) analysis, omalizumab was superior to MOIT (21 of 58 [36%] vs 11 of 59 [19%]; odds ratio, 2.6; 95% CI, 1.1-6.3; P = .03), with no differences in per-protocol analyses. Omalizumab superiority for CTDs of 4044 mg or greater was also demonstrated for 2 or more foods and for several individual foods. More participants taking active MOIT experienced adverse events (serious adverse events in 18 of 59 [31%] vs 0%; events leading to discontinuation in 13 of 59 [22%] vs 0%; events treated with epinephrine (22 of 59 [37%] vs 4 of 58 [7%]). Although the ITT analysis found a higher rate of treatment success in those receiving omalizumab compared with MOIT, results suggest that the difference was largely driven by the high rate of study discontinuation in the participants treated with MOIT, mostly related to adverse events.
To evaluate the efficacy and safety of early aspirin discontinuation followed by P2Y12 inhibitor monotherapy versus standard dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This systematic review and meta-analysis followed PRISMA 2020 guidelines and a prespecified protocol registered in PROSPERO (CRD420261293472). MEDLINE, Embase, Scopus, and CENTRAL were searched through December 2025 for randomized controlled trials comparing early aspirin discontinuation (≤ 3 months) with standard DAPT in ACS patients undergoing PCI with drug-eluting stents. Two reviewers independently conducted study selection, data extraction, and risk of bias assessment (Cochrane RoB 2.0). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model. Seven trials including 20,501 patients (10,246 early discontinuation; 10,255 standard DAPT) were analyzed. Early aspirin discontinuation significantly reduced bleeding (RR, 0.46; 95% CI, 0.36-0.60; p < 0.001; I²=21.9%). There was no significant difference in major adverse cardiovascular events (RR, 0.98; 95% CI, 0.77-1.26) or in myocardial infarction, stroke, repeat revascularization, or all-cause mortality. However, early aspirin discontinuation was associated with an increased risk of stent thrombosis (RR, 1.72; 95% CI, 1.07-2.78). In trials with aspirin discontinuation within 1 month, bleeding reduction remained substantial, with numerically higher but nonsignificant ischemic outcomes. In ACS patients undergoing PCI, early aspirin discontinuation reduces bleeding without a statistically significant increase in overall ischemic events; however, a significant increase in stent thrombosis was observed. These results support individualized decision-making, particularly favoring patients at high bleeding risk and low thrombotic risk treated with potent P2Y12 inhibitors. Further adequately powered studies focused on rare ischemic outcomes, including stent thrombosis, are warranted.
Extremely halophilic archaea are well adapted to salt-saturated environments. It was of interest to investigate their response to multiple stresses like chalcogen tolerance coupled to high salinity. In the present study, the haloarchaeon Halogeometricum borinquense E3 was evaluated for potassium tellurite tolerance, tellurite uptake, and biosynthesis of tellurium nanoparticles in hypersaline conditions. Growth and tellurite uptake assays demonstrated tolerance up to 8 mM potassium tellurite, with the removal of approximately 0.45 mM tellurite within 14 days, indicating its potential for tellurium bioremediation. Tellurite stress altered carotenoid biosynthesis, masking the characteristic pink pigmentation. The biosynthesized tellurium nanoparticles were characterized using ultraviolet-visible spectroscopy, dynamic light scattering, zeta potential analysis, electron microscopy, elemental analysis, X-ray diffraction, Fourier-transform infrared spectroscopy and Raman spectroscopy. Their antioxidant activity (DPPH and ABTS assays), antimicrobial efficacy against Gram-positive and Gram-negative bacteria, and biocompatibility towards human keratinocytes (HaCaT) cells were subsequently evaluated. Correlative electron microscopic analyses confirmed the intracellular biogenic synthesis of crystalline tellurium nanorods (50-95 nm in diameter and 160-700 nm in length) composed predominantly of elemental tellurium. The nanoparticles exhibited concentration dependent antioxidant activity (70% DPPH and 62% ABTS radical scavenging at 1 mg/mL), antibacterial activity against both Gram-negative and Gram-positive bacteria, and good biocompatibility toward HaCaT cells. These findings demonstrate that Hgm. borinquense E3 detoxifies toxic tellurite by converting it into multifunctional crystalline tellurium nanorods, highlighting its dual potential for sustainable tellurium bioremediation and nanoparticle biosynthesis with promising biomedical and environmental applications.