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The science of Arabic coffee (Qahwa): from phytochemistry and nutritional profile to health benefits and safety evaluation.

Arabic coffee (Qahwa), a traditional beverage widely consumed in the Middle East, has attracted increasing scientific attention due to its distinctive phytochemical composition and associated health effects. This review provides an integrated analysis of Qahwa's nutritional profile, focusing on its key bioactive constituents, including chlorogenic acids, caffeine, diterpenes (cafestol and kahweol), and phenolic compounds. These constituents contribute to a range of biological activities, notably antioxidant, anti-inflammatory, hepatoprotective, and metabolic regulatory effects. The influence of technological variables, including roasting degree, brewing method, and bean origin, on the chemical composition and functional properties is critically examined. Safety concerns, particularly acrylamide formation and mycotoxin contamination, are also discussed. Although emerging data support Qahwa's potential as a functional beverage, further research is required to clarify dose-response relationships, synergistic interactions, and long-term health outcomes. This work highlights Qahwa as a promising candidate for food and nutraceutical applications, warranting standardized compositional profiling and toxicological evaluation.

Humans

Morphology-Encoded Colorimetric Hydrogen Sensing Using Embedded Reactive Pd Absorbers in Fabry-Perot Cavities.

Chemical reactions offer a powerful strategy for generating visible optical responses through localized changes in absorption, dielectric environment, and interfacial wetting. A palladium (Pd)-embedded Fabry-Perot cavity is introduced as a reaction-active optical platform in which structural color is governed by intracavity absorption coupled with reaction-induced dielectric perturbation. Positioning Pd within the dielectric spacer creates a spatially controllable reactive absorber whose vertical location relative to the standing-wave field dictates wavelength-selective absorption within the cavity. The morphology of the embedded Pd layer provides an additional design parameter by modulating both optical loss and interfacial wetting. Under hydrogen exposure in the presence of oxygen, catalytic water formation at the Pd/polymer interface generates localized dielectric heterogeneity and interfacial water droplets, thereby perturbing the optical path length and amplifying the visible response. As a result, the cavity exhibits pronounced, morphology-dependent color transitions that are inaccessible through dielectric-layer engineering or Pd/PdH refractive-index changes alone, enabling direct visual hydrogen sensing under ambient light, as well as flexible optical devices capable of large-area patterning. These findings establish a design framework for reaction-active optical cavities that translate localized chemistry into a colorimetric hydrogen sensing mechanism.

Fabry–Perot resonator

Elucidation of microbial community structure, small-molecule metabolic and flavor profile characteristics in Xuanwei ham under different processing techniques.

This study systematically compared the impacts of traditional (TH) and modern (MH) processing techniques on the physicochemical properties, microbial community structure, metabolome, and volatile aroma compounds of Xuanwei ham. The results showed that the TH group had higher moisture content and water activity, along with a more tender texture, whereas the MH group exhibited greater hardness and chewiness. Microbiological analysis revealed that the interior of the MH group had higher species richness of both fungi and bacteria, while the TH group maintained higher fungal diversity. Metabolomic analysis identified 112 differential metabolites, with sweet amino acids and certain lipids being more enriched in modern ham, whereas traditional ham contained higher levels of umami amino acids, polyunsaturated fatty acids, and flavor compounds such as carnosine. KEGG pathway enrichment indicated that the differences were primarily concentrated in amino acid biosynthesis and metabolism-related pathways. Volatile flavoromics analysis identified 45 odor-active compounds and screened 15 key aroma-active substances. Among them, modern processed ham was significantly enriched in fatty aldehydes such as (E)-2-nonenal, hexanal, nonanal, and octanal, whereas traditional processed ham was characterized by 1-octen-3-ol, (E,E)-2,4-decadienal, methional, acetoin, and benzeneacetaldehyde. Correlation analysis confirmed that dominant microbes in Xuanwei ham were significantly associated with differential metabolites and characteristic aroma compounds, respectively. This study provides a scientific basis for standardizing production processes, enabling precise quality control, and promoting high-quality industrial development of Xuanwei ham.

Animals

Are there any common effects in preclinical models of micro- and nanoplastic (MNP) exposure? A systematic review.

Micro- and nanoplastics (MNPs) are emerging contaminants detected in food sources and the marine food chain, raising concerns about human health. Although no causal relationship has been established between MNP exposure and specific diseases, growing evidence suggests adverse developmental, behavioral, cognitive and biochemical effects. This systematic review synthesized evidence from common preclinical neurotoxicology models, including C. elegans, D. rerio, D. melanogaster, in vitro systems and rodents, to identify convergent developmental, behavioral and biochemical outcomes. The protocol was preregistered in OSF, followed PRISMA-P guidelines, applied PICOS criteria, and assessed methodological quality using the European Commission's ToxRTool. Overall, 185 studies were included. Consistent findings showed impaired survival and disrupted development across all models. Behavioral alterations affecting anxiety, memory, learning, sociability and locomotor activity were also consistently reported. In addition, numerous studies identified disruptions in the serotonergic (5-HT) system, including changes in neurotransmitter levels, transporters and metabolic enzymes. Despite methodological heterogeneity, these findings indicate that MNP exposure produces reproducible neurodevelopmental and neurochemical alterations across experimental models. Future studies should improve methodological harmonization, strengthen cross-model comparability and identify robust biomarkers and key mechanisms underlying MNP-induced neurotoxicity, facilitating translation to human health risk assessment frameworks.

Animals

Biomimetic mesoporous silica nanosphere ameliorate experimental autoimmune uveitis by delivering sCD83.

Autoimmune uveitis (AU) is an autoimmune disease that may lead to blindness, but there are currently no precise targeted therapies for its prevention and treatment. Dendritic cell (DC) is key cell involved in the pathogenesis of AU, and specific regulation of their state can help improve AU. In this work, mesoporous silica nanospheres were loaded with the immunomodulator soluble CD83 (sCD83) and subsequently camouflaged with dendritic cell (DC) membranes to fabricate the nanocarrier DCM@MSN/sCD83 for treating experimental autoimmune uveitis (EAU). Research results show that DCM@MSN/sCD83 effectively alleviated the symptoms of uveitis in EAU, reduced the proportion of CD4+CD25-T cell/CD4+CD25+T cell and the percentage of DC in the eyes and cervical lymph nodes. It also decreased the expression of STING in Müller cell. Furthermore, the efficacy of DCM@MSN/sCD83 was found to be primarily targeting DC, and promoted the expression of IL-10 and TGF-β1 in DC by activating the phosphorylated HIF/STAT3 pathway, to induce the production of CD4+CD25+ T. This effect is superior to nanomedicine loaded with dexamethasone. Moreover,DCM enabled the nanocarriers to efficiently cross the blood-eye barrier and reach cervical lymph nodes, thereby regulating peripheral immunity. This research indicate that cell membrane-modified nanoparticles targeting homologous cells can effectively improve treatment efficiency and duration, which is potential therapy strategy for uveitis.

Animals

Effectiveness of high-power laser use in the removal of esthetic restorations: a systematic review.

This systematic review aimed to evaluate the effectiveness of high-power lasers in the removal of esthetic restorations compared with conventional methods. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in PROSPERO (registration number: CRD420251055736). A comprehensive electronic search was performed in MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Library. Study selection, data extraction, and methodological quality assessment were independently performed by four reviewers using QUIN tool for in vitro studies. A total of 2.384 records were identified, of which 19 in vitro studies conducted on extracted human permanent teeth met the eligibility criteria and were included in the qualitative synthesis. The included studies evaluated different high-power laser systems, predominantly Er: YAG and Er, Cr: YSGG lasers, as well as CO₂ lasers. Five studies were classified as high quality, whereas the remaining fourteen studies were classified as moderate quality. Available laboratory evidence suggests that laser-assisted techniques may represent a potential alternative approach for removing esthetic restorations, with advantages including conservative tissue removal, reduced damage to underlying tooth structures, and intrapulpal temperature increases within acceptable limits. The Er: YAG laser was the most frequently investigated system, with power settings ranging from 1.5 to 5.9 W, showing particularly favorable laboratorial performance in the removal of lithium disilicate restorations, especially in thinner substrates. Within the limitations of the available evidence, high-power lasers appear to be a promising and minimally invasive alternative to conventional methods for the removal of esthetic restorations. However, the predominance of in vitro studies highlights the need for well-designed clinical trials to confirm these findings and support their clinical application.

Humans

Clinical performance of monolithic and veneered zirconia three-unit posterior FDPs: A five-year multicenter randomized controlled trial.

AIM: This randomized controlled clinical study compared monolithic, partially veneered, and fully veneered zirconia FDPs over a 5-year period with respect to survival, technical and biological complications, and patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Sixty-four patients requiring three-unit posterior FDPs were randomly allocated to monolithic (MONO-FDP), partially veneered (PV-FDP), or fully veneered (FV-FDP) groups. All FDPs were fabricated from 4 mol% Y₂O₃ partially stabilized zirconia (4Y-TZP). Follow-up examinations were conducted at baseline, 1, 3, and 5 years. Technical parameters were evaluated using modified USPHS criteria. Periodontal measurements (PPD, BOP, PI) and patient satisfaction were assessed at all time points. RESULTS: A total of 63 FDPs were evaluated at baseline, 57 at 3 years, and 54 at 5 years. Survival at 5 years was 94.7% for MONO-FDPs, 100% for FV-FDPs and 100% for PV-FDPs. Technical complications occurred exclusively in PV-FDP (33%) and FV-FDP (38%) groups and consisted of minor, polishable chipping; no chipping or fractures were recorded in MONO-FDPs (0%) with statistically significant difference between MONO-FDP and the other two groups (p ≤ 0.014). Biological parameters remained stable across all groups, with no significant differences in PPD, BOP, or PI. PV-FDPs and FV-FDPs tended to receive more favorable professional color ratings, whereas PROMs were similar among the groups. CONCLUSIONS: All three FDP designs-monolithic, partially veneered, and fully veneered-fabricated from 4Y-TZP zirconia demonstrated excellent 5-year clinical performance. Technical complications were limited to PV- and FV-FDPs and consisted of minor chipping. Biological outcomes and patient satisfaction were similar across groups. CLINICAL SIGNIFICANCE: The five-year outcomes suggest that veneered, partially veneered, and monolithic FDPs can be used with high clinical reliability; however, restorations incorporating veneering ceramic may present an elevated risk of ceramic chipping.

Humans

Could creatine supplementation combined with physical rehabilitation accelerate return to play in athletes with patellar tendinopathy?

BACKGROUND: Several dietary supplements have been proposed to positively influence the rehabilitation process following injury. However, to date, no studies have specifically examined the effects of scientifically supported ergogenic aids on recovery outcomes when combined with physical performance interventions. Therefore, the aim of this study was to analyze the ergogenic effects of creatine supplementation on neuromuscular performance, tendon thickness, pain, and body composition in athletes diagnosed with patellar tendinopathy (PT). METHODS: Using a triple-blind experimental design, 20 federated athletes (age: 33.7&#x2009;&#xb1;&#x2009;9.84 years) with PT were randomly assigned to either a creatine supplementation group (CR; n&#x2009;=&#x2009;9) or a placebo group (PLA; n&#x2009;=&#x2009;11). All participants followed a physical rehabilitation intervention that included daily eccentric training combined with stretching exercises, along with one session every 10 days of extracorporeal shock wave therapy (ESWT) and manual therapy targeting the tendon and surrounding muscle tissue. At the end of each eccentric training session, the participants ingested 3 capsules of creatine monohydrate - Creapure&#xae; (CR) or sucrose (PLA). At the beginning (PRE), after 4 weeks (MID), and after 8 weeks (POST), the pain level (Victorian Institute for Sports Assessment-Patella, VISA-P), tendon thickness (echography), body composition (bioelectrical impedance system), and neuromuscular performance using a countermovement jump test (CMJ) and a strength test (5-RM) of knee extension in the injured leg. RESULTS: A significant main effect of time was observed for VISA-P scores (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.626), indicating a reduction in pain over time in both the creatine (CR) and placebo (PLA) groups. At POST, both groups showed significant improvements compared to PRE (CR: 78.0 points [69.2-86.8] vs. 60.6 points [53.4-67.7]; p&#x2009;=&#x2009;0.002; PLA: 75.2 points [66.3-84.0] vs. 60.0 points [52.5-67.5]; p&#x2009;=&#x2009;0.003). However, only the CR group showed a statistically significant improvement in the MID compared to PRE (MID: 70.2 points [60.0-80.5]; p&#x2009;=&#x2009;0.027). A significant main effect of time was observed for both tendon thickness (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.629) and the 5-RM leg extension test (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.739), with both groups showing progressive improvements over time. Nevertheless, as trend toward a statistically significant time&#xb7;supplementation interaction was observed (p&#x2009;=&#x2009;0.099; &#x3b7;2p&#x2009;=&#x2009;0.126), with an increase in performance only in CMJ in MID vs PRE (36.8&#x2009; cm (33.8-39.7) vs 34.3&#x2009; cm (30.8-37.7); p&#x2009;=&#x2009;0.019) and POST vs MID (POST: 37.6&#x2009; cm (33.5-41.8); p&#x2009;=&#x2009;0.015). CONCLUSIONS: A physical rehabilitation program involving eccentric training, stretching, and ESWT is effective in reducing tendon thickness and increasing muscle strength. However. It seems that the addition of CR induces an earlier reduction of pain and a positive effect on CMJ performance. Therefore, CR could be considered as an ergogenic recovery aid in athletes with PT.

Humans

Effectiveness of an educational video for caregivers of children with neurogenic bladder: A randomized controlled trial.

BACKGROUND: The complexity of neurogenic bladder (NGB) management underscores the importance of caregiver education, yet high-quality education materials remain scarce. This study aims to assess the effectiveness and acceptability of an educational video designed to improve knowledge about NGB among caregivers of children with this condition. METHODS: We identified English-speaking caregivers of patients aged zero to 18 years, diagnosed with NGB, without prior major bladder reconstructive surgery, who received care at our institution from 2018 to 2022. Caregivers were randomly assigned into control or video groups using a block randomization model based on age. The control arm completed a six-item knowledge assessment before viewing the video, while the video group watched the video first. All participants rated the video's acceptability. Qualitative analysis of the open-ended responses to the acceptability questionnaire followed principles of thematic analysis. RESULTS: Of 409 eligible participants, 106 (25.9%) completed the study. Video (n = 48) and control (n = 58) groups were demographically similar. In the video group, 64.6% answered correctly all questions in the knowledge questionnaire, compared to 31% in the control group. After adjusting for patient age, caregivers in the video group were more likely to answer any question in the knowledge assessment correctly (relative probability: 1.13, 95% CI [1.06, 1.21], p < 0.01). Evidence for a difference in correct response rate among individual questions was strongest for question #1, which asked about common urological conditions for which NGB patients are at higher risk (95.8% vs. 79.3%, p = 0.01), and question #6, which asked about indications for bladder surgery (87.5% vs. 67.2%, p = 0.01), with the video group more likely to answer correctly for both questions. Qualitative analysis identified three major themes regarding parents' acceptance of the educational video: 1) attitudes towards video content and presentation, 2) usefulness of video as an educational tool, and 3) future directions. CONCLUSIONS: Our study found that an educational video about NGB effectively enhanced parental understanding of the condition and was deemed acceptable by parents as an introductory educational tool. The literature shows the benefit of using technology and visual aids to enhance health literacy for patients and caregivers, a key first step towards optimizing health outcomes for pediatric urologic patients.

Humans

Efficacy of an Adhesive Hydrocolloid Bandage on Wound Healing: Findings of a 28-Day, Single-Centre, Randomised, Controlled Study.

This single-centre, randomised, controlled study assessed the wound healing efficacy of adhesive bandages in eligible healthy adults (N&#x2009;=&#x2009;36) aged 25-55 with Fitzpatrick skin types II and III using a model of laser-induced wounds. Here, we report data for wounds that were randomised to treatment with either a hydrocolloid bandage for multi-day use (BAND-AID Adhesive Bandage Hydroseal), standard of care (SoC) (BAND-AID Adhesive Bandage Tru-Stay Sheer) or an uncovered control. Primary endpoints included the time to complete healing and a composite wound healing score. Hydrocolloid bandage-treated wounds healed twice as fast as the uncovered control or SoC-treated wounds. Median time (days) to complete healing was significantly faster for the hydrocolloid bandage-treated wounds (6.9) versus SoC (11.9) and uncovered control (11.8). Hydrocolloid bandage-treated wounds had significantly better composite wound healing scores versus SoC and versus uncovered control over 2&#x2009;weeks. At Day 28, cosmesis was better with hydrocolloid bandage treatment (0.3) versus SoC (0.6) and uncovered control (2.1) (change from baseline in a composite scar score; higher score&#x2009;=&#x2009;worse outcome). Multi-day wound occlusion with a hydrocolloid bandage promoted faster healing and improved cosmesis compared with daily SoC dressings or uncovered control.

Humans

Metagenome-scale modeling to assess microbiome metabolic complementarity for precision microbiota transplantation therapies.

Fecal microbiota transplantation (FMT) holds therapeutic promise beyond recurrent Clostridioides difficile infection, but clinical outcomes remain unpredictable and donor-selection strategies remain limited, in part because the role of donor&#x2012;recipient metabolic interactions in shaping the post-FMT community remains poorly understood. Here, we leverage metagenome-scale metabolic modeling to quantify metabolic niche complementarity between donor and recipient microbiomes and predict post-FMT community composition. Using MICOM-derived metabolic models, we show that donor genomes whose metabolic flux profiles are more dissimilar from the recipient community colonize at significantly higher rates in a murine FMT model. In a human IBS trial, the same metric predicted post-FMT community composition via leave-one-out cross-validation and captured known disease-associated alterations in short-chain fatty acid, sulfur, and gas metabolism. We then performed 2,548 in silico FMT simulations between IBS-D/M patients and donors from the OpenBiome biobank to evaluate personalized donor screening, identifying super-donors characterized by high taxonomic diversity, broad metabolic niche coverage, and community interaction networks dominated by cross-feeding rather than competition. Together, these results support metabolic niche complementarity as a potential determinant of post-FMT community composition and provide a mechanistic basis for evaluating donor-recipient metabolic compatibility. This framework offers a scalable approach for generating testable hypotheses for personalized donor selection.

Fecal Microbiota Transplantation

Ictal electroencephalography and heart rate as treatment criteria in electroconvulsive therapy: a systematic review of the literature.

BACKGROUND: Decades before the emergence of precision medicine, psychiatrists raised the question of whether specific seizure characteristics could help optimize electroconvulsive therapy (ECT), as relationships between some of these characteristics and better outcomes were found. From 1990 onward, researchers focused on electroencephalography (EEG) and cardiovascular markers, which were broadly adopted by guidelines worldwide. However, the prognostic value of these markers is still controversial. Here, we provide a systematic summary of the studies on this topic. METHODS: We conducted a literature review on the use of ictal EEG and heart rate as outcome predictors in ECT using the PubMed, EMBASE, Cochrane and PsycINFO databases. RESULTS: Thirty-seven studies addressing more than 100 quality markers fulfilled our inclusion criteria. Single EEG markers were assigned to five categories (postictal inhibition, amplitude, coherence, regularity, and seizure duration). Heart rate and composite markers were considered separately. In contrast to single EEG markers, heart rate and composite markers could be consistently linked to better outcomes in patients with depression. Only a few studies on schizophrenia could be retrieved. CONCLUSION: Multiparametric markers outperformed single markers. Furthermore, changes in heart rate during seizures were related to better outcomes. Although clinical assessment remains the cornerstone of treatment guidance decisions, EEG and cardiac monitoring could help prevent insufficient seizures during the period preceding clinical improvement. Evidence on schizophrenia remains limited. More randomized trials are needed to analyze the role of composite markers as prognostic tools.

Humans

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5&#x202f;wt%) and increasing Sr contents (0.5, 1.0, 1.5&#x202f;wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-&#x3b1; and TGF-&#x3b2;; with an enhanced TNF-&#x3b1; secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or &#x2265;2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (&#x2265;160-179 and/or &#x2265;100-109 mmHg), and severe (&#x2265;180 and/or &#x2265;110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or &#x2265;2 blood pressures &#x2265; 140 and/or &#x2265;90 mmHg at &#x2265;20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Humans

Asthma Exacerbation Risk and School Asthma Readiness.

OBJECTIVES: School-based asthma management is a key facet of child asthma care. We aimed to describe the proportion of students whose schools have child-specific components of asthma care, derive a composite metric of these components ("school asthma readiness"), and assess its association with asthma exacerbations (asthma risk) in the preceding year. METHODS: Within a nested cohort of children enrolled in a larger randomized clinical trial, we assessed the baseline proportion of children whose school had elements of necessary asthma care. We then derived a "school asthma readiness" composite and used ordinal logistic regression to model the association between number of asthma exacerbations in the preceding year and the composite, accounting for demographic, clinical, and school characteristics. RESULTS: Of 202 participants aged 5 to 13&#xa0;years, most identified as Black (95%) and non-Hispanic (98%), and most participants (73%) had an emergency department visit for asthma in the year before enrollment. Most students' schools (79%) had awareness of the child's asthma diagnosis, whereas fewer had reliever medications and valved holding chambers (both 31%) and asthma care plans (7%). Asthma exacerbations in the prior year were associated with a significantly higher school asthma readiness in bivariate (odds ratio [OR], 1.44 [95% CI, 1.14-1.82]; P&#x2009;=&#x2009;.002) and multivariable analysis (OR, 1.31 [95% CI, 1.02-1.7]; P&#x2009;=&#x2009;.037). CONCLUSIONS: A minority of children attended schools that were equipped to manage asthma symptoms. More past exacerbations were associated with higher school readiness, suggesting that more work is needed to support proactive asthma care in schools.

Humans

Diagnostic utility of high-risk HPV polymerase chain reaction-based testing in head and neck FNA specimens with indeterminate cytomorphology.

BACKGROUND: Fine-needle aspiration (FNA) is critical in the initial diagnosis of many high-risk human papillomavirus (HR-HPV)-associated, metastatic oropharyngeal squamous cell carcinomas. Updated guidelines recommend HR-HPV-specific polymerase chain reaction (PCR) analysis over p16 immunohistochemistry on FNA specimens because p16 performs poorly on cytology material. PCR-based assays on liquid cytology material have demonstrated excellent analytic performance; however, the diagnostic utility of a positive HR-HPV PCR result in specimens with indeterminate cytomorphology remains uncharacterized. METHODS: The authors retrospectively identified 279 head and neck FNA specimens that had paired HR-HPV PCR testing on residual liquid cytology material over a 5-year period. The positive predictive value for histopathologically confirmed squamous cell carcinoma on surgical follow-up was calculated within each cytologic interpretive category. RESULTS: The HR-HPV PCR results were positive in 50.2% of specimens, negative in 40.9%, and indeterminate in 9.0%. The HR-HPV positivity rate ranged from 0% in specimens categorized as negative for malignancy to 57.3% in cytologically positive specimens, with 19.0%, 41.2%, and 50.0% positivity in the atypical, suspicious, and nondiagnostic categories, respectively. Among cytologically indeterminate specimens with positive HR-HPV PCR results (n&#xa0;=&#xa0;14), the positive predictive value was 100% (95% confidence interval, 78.5%-100.0%). Blinded slide review additionally identified 15 cytologically positive specimens in which the definitive malignant interpretation depended substantially on HR-HPV positivity; all 15 were confirmed as squamous cell carcinoma. CONCLUSIONS: A positive HR-HPV PCR result on liquid cytology material carries a positive predictive value of 100% for malignancy in cytologically indeterminate head&#xa0;and neck FNA specimens. These findings support integrating HR-HPV PCR analysis into routine cytologic interpretation with the potential to upgrade some indeterminate specimens to malignant when HR-HPV is detected, expediting definitive treatment and sparing patients additional, invasive sampling.

Humans

Risk of stroke in SLE: a systematic review and meta-analysis.

UNLABELLED: The association between SLE and composite stroke, ischaemic stroke and haemorrhagic stroke remains incompletely understood. This meta-analysis aims to assess the risk of stroke in patients with SLE. METHODS: Data sources included PubMed, Embase, the Cochrane Library and reference lists of included studies. This meta-analysis included cohort studies evaluating whether stroke risk is associated with SLE. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Risk ratios (RRs) with 95% CIs were pooled using a random-effects model, and publication bias was assessed with funnel plots and Egger's test. RESULTS: A total of 25 cohort studies involving 5&#x2009;220&#x2009;837 individuals were included in this meta-analysis, which were published between 2001 and 2026. The pooled analysis demonstrated a significantly increased risk of stroke in patients with SLE (RR of 2.60, 95%&#x2009;CI 2.21 to 3.05, I&#xb2;=97.9%, p<0.001). The risk of composite stroke (RR of 2.83, 95%&#x2009;CI 2.25 to 3.57, I&#xb2;=98.0%, p<0.001), ischaemic stroke (RR of 2.34, 95%&#x2009;CI 1.75 to 3.12, I&#xb2;=97.6%, p<0.001) and haemorrhagic stroke (RR of 2.66, 95%&#x2009;CI 1.57 to 4.49, I&#xb2;=96.2%, p<0.001) was also increased in SLE. Despite the large heterogeneity, the sensitivity analysis indicated that the results were robust, and there was little evidence of publication bias. CONCLUSION: The risk of composite stroke, ischaemic stroke and haemorrhagic stroke is increased in SLE. PROSPERO REGISTRATION NUMBER: CRD420261294082.

Humans

Active Site Assembly by SMG5 as a Mechanism for SMG6 Endonuclease Licencing in Nonsense-mediated mRNA Decay.

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that eliminates transcripts containing premature termination codons (PTCs). Substantial progress has been made in defining the transcript features that mark aberrant translation termination for NMD activation, yet key mechanistic steps remain incompletely understood - including how recruitment of the central NMD factor UPF1 is coupled to the downstream effector phase in which targeted mRNAs are nucleolytically degraded. In metazoans, NMD employs an endonucleolytic route mediated by SMG6, a PIN-domain nuclease, alongside SMG5 and SMG7, which act downstream of PTC recognition. SMG5 has recently been proposed to licence SMG6 activity, yet the molecular basis of this licencing has remained elusive. Here, we combine AlphaFold structural predictions with biochemical assays to investigate interactions among human SMG5, SMG6, and SMG7. Structural models predict a high-confidence interface between SMG5 and SMG6 PIN domains that forms a composite active site: a conserved SMG5 aspartate (D893) complements the SMG6 acidic triad to reinstate the canonical tetrad required for PIN-domain catalysis. In vitro, SMG6 alone exhibits weak endonucleolytic activity, which is enhanced &#x223c;10-fold by the SMG5 PIN domain. Mutational analyses confirm that conserved residues from both proteins are essential for this composite configuration. Our findings reveal that the SMG5 PIN domain, previously considered catalytically inert, plays a critical role in activating SMG6 by completing its active site. This work provides mechanistic insight into the SMG5-dependent licencing step and uncovers a composite PIN nuclease architecture at the heart of the metazoan NMD effector phase.

Nonsense Mediated mRNA Decay