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Uric acid (UA) is the end product of purine metabolism. Numerous studies have reported an association between serum UA levels and the risk of several solid tumors, but its association with gastric cancer (GC) remains controversial. This study aims to explore the relationship between serum uric acid (SUA) and GC, to inform GC prevention and treatment strategies. Literature searches were conducted in PubMed, Embase, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI). Mean differences (MD) with 95% confidence intervals (95% CI) were calculated using fixed or random effects models. Subgroup analysis was performed to explore heterogeneity sources. Additionally, bioinformatics analyses were carried out using publicly available datasets from the Gene Expression Omnibus (GEO), STRING, and DAVID databases to identify shared molecular pathways. Six studies met the inclusion criteria. Meta-analysis revealed significantly higher SUA levels in GC patients compared to controls (pooled MD: 48.74; 95% CI 35.23-62.25; P&#x2009;<&#x2009;0.00001; pooled SMD: 1.52, 95% CI 0.69-2.34), with extreme high heterogeneity was observed (I&#xb2; = 89%, P&#x2009;<&#x2009;0.00001; I&#xb2; = 98%, P&#x2009;<&#x2009;0.00001). Subgroup analysis based on control types presented numerical differences in pooled MD values between healthy control group (MD: 55.73; 95% CI 51.29-60.17; P&#x2009;=&#x2009;0.33) and non-healthy control group (MD: 27.82; 95% CI -&#x2009;7.87-63.51; P&#x2009;=&#x2009;0.0006), while no statistically significant difference was detected in the healthy control subgroup. No publication bias was detected (P&#x2009;=&#x2009;0.175). Bioinformatics analysis identified 188 overlapping differentially expressed genes (DEGs) between hyperuricemia and GC. Protein-protein interaction (PPI) network analysis highlighted IL6, TNF, and CXCL8 as central hub genes. Functional enrichment analysis showed enrichment trends in inflammatory pathways such as the IL-17 signaling axis, as well as interactions between viral proteins and cytokine receptors. These enrichment results provide preliminary bioinformatic clues that the correlation between SUA and GC may be associated with inflammatory response, immune microenvironment alteration and gastric mucosal barrier-related biological processes. Our findings suggest a possible correlation between elevated SUA levels and GC, with a more obvious numerical trend in studies adopting healthy population controls. Elevated SUA may correlate with GC, especially in studies using healthy controls. Inflammation and immune dysregulation pathways likely underlie this association. SUA shows preliminary potential as a GC-related biomarker, though clinical use is unconfirmed. Large-sample prospective studies and basic experiments are needed to verify the correlation and mechanisms.

Peutz-Jeghers Syndrome (PJS) is caused by germline pathogenic variants in the STK11 gene and is associated with elevated lifetime risks for several cancers, including lung cancer. Currently, no formal recommendations exist for lung cancer screening in PJS. This structured narrative review compares lung cancer risk in PJS with lung cancer risk in individuals currently eligible for screening based on age and smoking history. PubMed and Web of Science were searched from 1/1/1980 to 9/11/2023 using the terms "Peutz-Jeghers Syndrome" AND "Cancer." Studies reporting lung cancer risk in PJS were included. Reported lung cancer risks were compared to 5-year, 10-year, and lifetime lung cancer risks in the general population based on age and pack-years of smoking. Seventeen studies were included. Across the studies, the incidence of lung cancer ranged from 0.8 to 13.3%. Studies that included lung cancer risk relative to the general population reported a relative risk range of 2.9-22.9. Cumulative risk was reported in 5 studies and surpassed 5% by age 60 (range 7 to 17%). Guidelines for low-dose CT (LDCT) lung cancer screening for individuals aged 50-80 with a smoking history of at least 20 pack-years are associated with a similar or higher threshold for lung cancer risk. The lifetime lung cancer risk for individuals with PJS is similar to current guideline-based risk thresholds for screening based on age and smoking status. Given their elevated lifetime risk, individuals with PJS may be candidates for LDCT for lung cancer screening and should be formally studied to elucidate the risks, benefits, and optimal implementation in this patient population.

To estimate the prevalence of breastfeeding-overall, exclusive, partial and depending on infants' age-in infants with Down syndrome, and to investigate associated factors. A systematic literature search was conducted in Medline, Cochrane Library, Web of Science, Embase, CINAHL and SciELO up to 1 August 2024. Original articles that estimated the prevalence of breastfeeding in infants with Down syndrome, written in French, English or Spanish, were included. Study quality was assessed using the Joanna Briggs Institute (JBI) scale. Meta-analyses were performed for breastfeeding outcomes and meta-regression explored heterogeneity. The review was registered in PROSPERO (CRD42021278019). Twenty-six studies (3463 infants) were included. The estimated prevalence of overall breastfeeding regardless of duration was 71.6% (95% CI [60.3; 80.7]; 25 studies, 3351 infants) with high heterogeneity, I2&#x2009;=&#x2009;94%. The estimated prevalence of exclusive breastfeeding was 38.4% (95% CI [22.4; 57.3]; 10 studies, 1099 infants). No factor assessed in meta-regression was significantly associated with overall breastfeeding. The estimated breastfeeding prevalence in infants with Down syndrome is similar to that reported in the general population, despite high heterogeneity. Further studies using standardised methodology to assess breastfeeding barriers and facilitators in the context of Down syndrome would allow us to improve support for breastfeeding.

Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence and limited systemic options in recurrent or metastatic disease. Although epidermal growth factor receptor (EGFR) inhibitors show activity in other squamous cancers, their role in ASCC remains unclear due to fragmented evidence. This systematic review and meta-analysis evaluated the efficacy and safety of EGFR inhibitors in adults with locally advanced or metastatic ASCC. PubMed/MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception to December 2025 for studies of EGFR inhibitors in ASCC. Eligible designs included randomized trials, phase II studies, prospective or retrospective cohorts, and case series. Proportional meta-analyses were performed using fixed- or random-effects models according to heterogeneity. Twelve studies including 404 patients were analyzed. Median age ranged from 47 to 65 years, and both locally advanced and metastatic settings were represented. The EGFR inhibitors cetuximab and panitumumab were administered with chemoradiotherapy in locally advanced disease or with systemic therapy in metastatic or refractory settings. The pooled objective response rate was 52% (95% CI: 36-68; I&#xb2;=84.2%, &#x3c4;&#xb2;=0.0518, p&#x2009;<&#x2009;0.0001), with a complete response rate of 37% (95% CI: 15-61; I&#xb2;=94.0%, &#x3c4;&#xb2;=0.1287, p&#x2009;<&#x2009;0.0001). Median overall survival was 11.9 months and progression-free survival 4.5 months. Grade&#x2009;&#x2265;&#x2009;3 adverse events occurred in 56% of patients; treatment discontinuation was infrequent (8%), and no treatment-related deaths were reported. EGFR inhibitors show a reproducible signal of activity in locally advanced and metastatic ASCC with manageable toxicity, though evidence is limited by nonrandomized designs and heterogeneity; prospective, biomarker-driven studies are needed.

Systemic arterial hypertension affects up to 50% of patients with obstructive sleep apnea (OSA) and represents one of the main modifiable cardiovascular risk factors. Hypoxemia is a recognized marker of OSA severity; however, it remains unclear which specific desaturation parameters during sleep, such as oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), percentage of sleep time with peripheral oxygen saturation&#x2009;<&#x2009;90% (T90%) or hypoxic burden (HB) are most consistently associated with elevated blood pressure (BP). This systematic review aims to evaluate, in patients with OSA, the impact between nocturnal desaturation parameters and elevated BP as measured by ambulatory blood pressure monitoring (ABPM). A literature search was performed in PubMed, Web of Science, Scopus and Embase databases, covering all records available up to June 2025. A total of 5,587 records were identified through database searches, and 24 studies met the inclusion criteria. The studies revealed heterogeneous results, with some showing significant associations between hypoxemia indices and hypertension, while others did not. Evidence suggests that ODI3% is commonly related to increased BP, whereas minimum SpO2, mean SpO2 and T90% yielded variable findings. HB was evaluated in only one study, suggesting a potential role in BP reduction after CPAP; however, the available evidence remains preliminary. ODI3% showed the most consistent association with increased BP across studies, whereas other hypoxemia indices yielded more variable results. Evidence regarding HB remains preliminary and warrants further investigation. These findings suggest that although ODI currently appears to be the most reliable marker, evidence from a single study indicates that composite indices such as HB may represent more informative predictors of BP outcomes and deserve further investigation in future studies.

In this study, a novel phthalonitrile derivative (2) bearing a coumarin side group and its corresponding Zn(II) phthalocyanine complex (3) were successfully synthesized and structurally characterized using FT-IR, NMR, UV-vis, MALDI-TOF MS, and X-ray crystallography. Optical studies revealed that ZnPc (3) exhibits characteristic Q-band absorption in the visible region along with fluorescence emission, indicating its suitability for photonic applications. DFT calculations showed a significant reduction in the HOMO-LUMO gap from compound 1 to compound 3, with ZnPc (3) displaying the lowest band gap (2.16 eV), strong &#x3c0;-conjugation, and pronounced intramolecular charge transfer (ICT). MEP analysis further confirmed enhanced charge separation and donor-acceptor character. Electrochemical results supported these findings, revealing improved electron transfer and a narrow band gap (1.64 eV) for ZnPc (3). Al/p-Si/compound 2/Al and Al/p-Si/ZnPc 3/Al Schottky diodes exhibited rectifying behavior; however, ZnPc (3) showed superior performance with higher barrier height (0.68 eV), lower ideality factor (3.20), and higher rectification ratio (RR = 1702). Moreover, the increasing photocurrent under reverse bias with illumination confirmed that ZnPc acts as an efficient photoactive material. Overall, the results demonstrate that the ZnPc derivative, owing to its favorable electronic structure, strong ICT behavior, and enhanced charge transport properties, is a promising candidate for photodiode and optoelectronic applications.

Watermelon mosaic virus (species Potyvirus citrulli, WMV) poses a significant threat to various cucurbit species worldwide. In Poland, the virus has been consistently recorded in Cucurbita pepo var. giromontiina crops since 2008. To analyse the genetic diversity and population structure of WMV in Poland, comprehensive surveys were conducted in two major agricultural regions, Greater Poland and Kuyavian-Pomeranian Voivodeships (west-central and mid-northern regions of Poland, respectively). To better understand the WMV occurrence, over 1,800 leaf samples were randomly collected from symptomatic and asymptomatic zucchini and weed plants. Moreover, aphids were also analysed for the presence of the virus. In this study, 154 complete coat protein gene sequences of WMV isolates collected between 2013 and 2024 were obtained using Sanger or high-throughput sequencing. The sequence identity of the Polish WMV isolates ranged from 92.8 to 100% and 95.4 to 100% for nucleotide and amino acid sequences, respectively. Unique mutations were identified in the isolates originating from the Kuyavian-Pomeranian region. Moreover, a novel KEET motif was identified in nine isolates, which has not been reported in previous studies. Most CP codons undergo negative selection; however, eight positively selected sites were detected. Phylogenetic analysis revealed that the Polish isolates were grouped in both classical and emergent main phylogenetic clades. The population analyses indicated limited or no gene flow between WMV subpopulations, suggesting that genetic drift may be considered an important evolutionary force shaping the viral diversity.

Border-associated macrophages (BAMs) represent a specialized population of tissue-resident immune cells strategically positioned at the critical interfaces between the central nervous system (CNS) and peripheral circulation, including the meninges, choroid plexus, and perivascular spaces. As frontline sentinels of the neuroimmune system, BAMs perform essential functions in immune surveillance, barrier integrity maintenance, and homeostatic regulation, yet their unique biology and disease-associated roles remain incompletely characterized compared to parenchymal microglia. This review aims to synthesize current knowledge on BAM ontogenetic origins, compartment-specific heterogeneity, transcriptional programs, and functional outputs in both health and neurological disorders. We conducted a comprehensive literature analysis integrating findings from lineage tracing studies, single-cell RNA sequencing, spatial transcriptomics, and functional interrogation in animal models of disease. The results reveal that BAMs exhibit remarkable cellular diversity shaped by distinct ontogenetic origins-primarily yolk sac-derived erythro-myeloid progenitors with variable contributions from fetal liver and postnatal monocytes depending on anatomical compartment. Compartment-specific marker combinations (CD206, LYVE1, CD163, MHCII) define functionally distinct subsets, and core transcriptional regulators including PU.1 and IRF8 maintain BAM identity while CSF-1/IL-34-CSF1R signaling governs survival and renewal. In neurological disorders including ischemic stroke, Alzheimer's disease, multiple sclerosis, and brain tumors, BAMs display pronounced double-edged roles, transitioning from protective homeostatic guardians to pathogenic drivers depending on disease stage and microenvironmental context. This comprehensive analysis establishes a unified framework for understanding BAM biology and identifies critical opportunities for developing subset-specific therapeutic strategies targeting these interface macrophages in neurological diseases.

Few studies have assessed longitudinal pulmonary function outcomes in post-infectious bronchiolitis obliterans (PIBO). This study analyzes pulmonary function changes from patients with PIBO at a single center with respect to time and inciting respiratory pathogen. Patients with PIBO were identified via retrospective observation using the Research Derivative at Vanderbilt University Medical Center. Serial spirometry was analyzed by generalized mixed-effects models. An exploratory analysis was performed to test interactions with pathogen, age at sentinel infection, and systemic corticosteroid exposure. Fifteen patients were diagnosed with PIBO from 1998 to 2023. Twelve (80%) were male. Median age of infection was 3.0 years (IQR: 1.3-6.5 years). Commonly identified pathogens were adenovirus (n&#x2009;=&#x2009;8/15) and Mycoplasma pneumoniae (n&#x2009;=&#x2009;4/15). Patients with M. pneumoniae were older at infection (p&#x2009;=&#x2009;0.02). Eleven (73%) patients performed a median of 14 pulmonary function tests per patient (IQR: 6.5-23). Median z-scores at initial spirometry were forced expiratory volume in 1&#x2009;second (FEV1) -3.83, forced vital capacity (FVC) -2.92, and FEV1/FVC ratio -2.61. FEV1, FVC, and FEV1/FVC z-scores changed by 0.008, 0.185, and -0.143/year, respectively (p&#x2009;=&#x2009;0.69, 0.003, 0.004). Four of 9 (44%) patients tested were bronchodilator responsive. The rate of annual FVC z-scores improved more in adenovirus-infected patients than in those with other pathogens (p < 0.001). Patients with PIBO demonstrate non-linear dysanaptic lung growth with stagnant FEV1 growth with respect to time. Subjects infected with adenovirus demonstrated lower FVC initially but accelerated FVC growth than those infected with other pathogens. Future research is needed on how severe respiratory infections contribute to non-linear dysanaptic lung growth in susceptible children.

In recent years, artificial intelligence (AI) has ushered in a promising era in medicine, particularly in medical education. However, studies assessing the knowledge, attitudes, and practices related to AI among medical students in Vietnam remain limited. This study aimed to evaluate AI knowledge, attitudes, and practices among Vietnamese medical students in learning and research, and to identify factors associated with their AI practices. A cross-sectional study was conducted among medical students at Thai Binh University of Medicine and Pharmacy from November to December 2025. Data were collected using an online structured questionnaire covering demographic characteristics and AI knowledge, attitudes, and practices. The main outcome of interest was AI practices in learning and research. Descriptive statistics and multivariable linear regression were used to examine associated factors. Regression coefficients (&#x3b2;), 95% CIs, and P values are reported. A total of 1002 medical students (mean age 21.00, IQR 19.00-23.00 years; n=596, 59.5% female) were included. The median percentage of maximum possible (POMP) score of AI knowledge was 66.67 (IQR 33.33-83.33), with a high level of familiarity with common tools (n=798, 79.6%). AI attitudes were generally positive (median POMP score 70.00, IQR 53.33-76.67). AI-related practices were lower (median POMP score 50.00, IQR 46.88-71.88), with AI being used primarily for information retrieval and literature research support. In the multivariable analysis, knowledge POMP score (&#x3b2;=0.12, 95% CI 0.08-0.16) and attitudes POMP score (&#x3b2;=0.42, 95% CI 0.34-0.51) were significantly associated with AI practices POMP score (P<.001). Age, gender, major, grade point average classification, and having participated in an AI seminar or training were not associated with AI practices. Medical students showed favorable knowledge and positive attitudes, but their AI practices remained limited. Integrating AI into medical curricula, including fundamentals, applications, and ethical aspects, is essential to prepare future physicians for AI-driven health care.

Carotid atherosclerosis is an established risk factor for cognitive impairment. FDG-PET detects subtle inflammatory changes in the arterial wall that may precede plaque formation and rupture. We investigated whether carotid inflammation is associated with cognitive function and its relative importance as a predictor of concurrent cognitive function compared with other factors. : In this cross-sectional study, we recruited individuals &#x2265;40&#x200a;years with undetectable viral load at moderate-to-high cardiovascular risk. Participants underwent FDG-PET, stress and cognitive assessments. We used pairwise partial correlations to identify significant associations between arterial inflammation and cognition. We applied a machine learning analysis workflow to evaluate the ability of carotid inflammation alone, and in combination with other factors, to predict cognition. Among 47 people, carotid inflammation was independently correlated with global cognition [r&#x200a;=&#x200a;-0.405, 95% confidence interval (CI) -0.618 to -0.100, P&#x200a;=&#x200a;0.007]. In the machine learning analysis, the probability of carotid inflammation predicting cognitive function within one standard deviation of the true value was 68% (95% CI 52-80). The predictive accuracy improved marginally when individual cardiometabolic factors were added to the model (73%, 95% CI 57-84). When all potential variables were considered, predictive accuracy improved substantially (85%, 95% CI 71-93), with carotid inflammation remaining as the most important cardiometabolic predictor of cognitive function. Carotid inflammation on FDG-PET outperformed most other factors in predicting concurrent cognitive function and provided unique predictive information beyond traditional cardiometabolic risk factors. Future longitudinal studies should examine whether carotid inflammation predicts incident cognitive impairment, which would support its use as a clinical risk marker in people with HIV.

Locoregional therapies have emerged as key components in the therapeutic arsenal against gastrointestinal cancers, offering minimally invasive options with curative potential. Beyond their direct cytotoxic effects, these interventions can remodel the tumour microenvironment by inducing immunogenic cell death and initiating local and systemic immune responses, including abscopal effects. This review aims to examine how these immunomodulatory properties may support locoregional therapies as an ideal platform for intratumoural immunotherapy, positioning their combination at the core of the evolving field of interventional immuno-oncology. Recent studies demonstrate that locoregional therapies can induce immune responses through modulation of the tumour microenvironment, creating conditions that may be exploited by intratumoural immunotherapy. This review provides a comprehensive overview of current locoregional modalities, including thermal and non-thermal ablative techniques, transarterial therapies, and minimally invasive radiation methods, detailing their mechanisms of action, clinical applications, and immune-related effects. Special attention is given to emerging evidence supporting the combination of these approaches with intratumoural delivery of immunomodulatory agents, to enhance anticancer immune responses. The convergence of locoregional intervention and targeted immunomodulation represents an emerging therapeutic concept in the treatment of gastrointestinal cancers, offering the prospect of personalised, tumour-directed immune activation. This approach holds the potential to extend the benefits of immunotherapy beyond genetically defined subgroups to a broader patient population.

Beh&#xe7;et's disease (BD) is a chronic multisystem inflammatory disorder with diverse neurological manifestations. While central nervous system involvement is well recognized, peripheral neuropathy remains an underdiagnosed and poorly understood complication. Chemokines, particularly C-C motif chemokine ligand 21 (CCL21), play a critical role in immune-mediated neuroinflammation and have been implicated in several autoimmune diseases. This study aimed to investigate the association between selected CCL21 gene polymorphisms and BD-associated peripheral neuropathy, and to assess their relationship with disease activity. This cross-sectional observational study included 42 adult patients with BD and 20 age- and sex-matched healthy controls. All patients underwent comprehensive clinical and neurological evaluation, assessment of disease activity, and nerve conduction studies. Genotyping of CCL21 single nucleotide polymorphisms rs951005, rs2492358, and rs2812378 were performed for patients and controls. Electrophysiological evidence of peripheral neuropathy was detected in all evaluated Beh&#xe7;et's disease patients, despite only 50% reporting clinical neuropathic symptoms. Polyneuropathy was the predominant pattern, with sensory and mixed nerves more frequently affected than purely motor nerves, and greater involvement of upper limb nerves. A significant difference in the distribution of the CCL21 rs2492358 polymorphism was observed between patients and controls (p&#x2009;=&#x2009;0.001). Additionally, the rs951005 polymorphism was significantly associated with higher disease activity scores (p&#x2009;=&#x2009;0.009). Peripheral neuropathy is a frequent and often subclinical manifestation of BD. CCL21 gene polymorphisms appear to contribute to both peripheral neuropathy association and disease activity, highlighting CCL21 as a potential biomarker linking systemic inflammation to peripheral nerve involvement. Key Points &#x2022; Chemokine dysregulation previously found to play a central role in the development of neuroinflammation. &#x2022; This cross-sectional study identifies specific chemokines' gene&#xa0;of CCL21 linked to peripheral neuropathy in Behcet's disease. &#x2022; Results may guide future therapeutic strategies targeting chemokine modulation.

Metal-organic frameworks (MOFs) are a promising class of materials for the sorption and reactive elimination of toxic chemicals; however, the limited processability of MOF powders hinders their broader application in this field. High internal phase emulsion-derived polymer foams (polyHIPEs) offer a promising avenue for generating interconnected macroporous structures with highly tunable physical and chemical properties. Combining polyHIPEs with reactive MOFs offers a versatile platform for removing toxic chemical vapors and gases, but studies that investigate the effects of MOF loading on a polyHIPE and how the composite matrix influences MOF reactivity are limited. In this work, the MOF UiO-66-NH2 is used as a filler in the one-pot synthesis of polyHIPE composites. The MOF is shown to play a key role in the stabilization of the emulsion during polymerization at elevated temperatures, preventing droplet coalescence and pore collapse. The MOF filler is also shown to maintain its adsorption activity, although the overall performance of the composite is strongly influenced by temperature due to limited diffusion through the polymer matrix at reduced temperatures. Finally, cyclic compression tests indicate that increased MOF loadings cause a reduction in recoverable deformation, as indicated by a drop in the hysteresis toughness between the first and second compression cycles driven by microcrack formation and debonding at the matrix-filler interface. These experiments highlight that understanding the interactions between MOF fillers and the polymer matrix is the key to balancing the reactivity and mechanical stability of these composite systems.

Myocarditis is a heterogeneous inflammatory syndrome with aetiologies ranging from viral infection and drug hypersensitivity to systemic autoimmune/autoinflammatory disease and immune checkpoint inhibitor (ICI) therapy. In response to these triggers, the innate immune response and inflammasome activation can amplify myocardial injury via IL-1, providing a mechanistic rationale for IL-1 pathway inhibition as a targeted therapeutic strategy. This review synthesizes preclinical and clinical evidence for IL-1 blockade in myocarditis and related inflammatory cardiac syndromes. The immune system plays a central role in the pathogenesis of myocarditis, both in idiopathic/viral cases and in systemic autoimmune and autoinflammatory diseases (SAAD). Interleukin-1 (IL-1) has emerged as a key mediator linking inflammation to myocardial dysfunction, supported by experimental and translational evidence implicating activation of the NLRP3 inflammasome. Clinically, the randomized trial of anakinra in acute myocarditis (ARAMIS) did not improve outcomes in a largely low-risk cohort, but accumulating case reports and small series suggest potential benefit in fulminant/hyperinflammatory myocarditis and chronic active refractory myocarditis. In contrast, IL&#x2011;1 inhibitors have robust randomized and real-world evidence in recurrent pericarditis, supporting a myo&#x2011;pericardial inflammatory continuum and validating IL&#x2011;1 pathway engagement as an actionable target in selected inflammatory cardiac phenotypes. Together, these findings support the evolving concept of cardioimmunology. Current management of myocarditis remains largely supportive, with limited disease-modifying options. Anti-IL-1 therapies, particularly anakinra, have shown promising efficacy in selected severe and refractory cases, with a favourable safety profile. However, evidence is mainly derived from case reports and small series, and robust randomized data are lacking. Key clinical questions remain unresolved, including patient selection, timing of initiation, and treatment duration. Future studies should focus on identifying inflammatory endotypes and evaluating targeted immunomodulatory strategies, including in emerging settings such as ICI-associated myocarditis in which IL&#x2011;1 blockade remains investigational.

Rotaviruses are a global cause of acute paediatric gastroenteritis. They present a genome of 11 dsRNA segments that have been successfully incorporated into a plasmid-based reverse-genetics system that enables the generation of reassortant and chimeric viruses as a possible foundation for multi-virus vaccines. Studies have shown that these chimeric segments are pruned across successive passages, highlighting a need to better define the constraints that govern segment recognition and stable incorporation into mature viruses. This work leveraged the reverse-genetics system to investigate these constraints by introducing a series of modifications to a chimeric NSP1 sequence with an internally cloned GFP insert (NSP1gfp). Across ten serial passages, a pruned NSP1gfp segment emerged and eventually outcompeted the original construct, resulting in a loss of GFP expression. The removal of the entire NSP1 ORF sequence 3' of the insert resulted in prolonged GFP expression, but closer examination of rotavirus RNA suggested that these modifications were merely delaying replacement from pruned segments, rather than avoiding their emergence. A series of systematic truncations to the remaining NSP1 ORF sequence 5' of the GFP insert showed that as little as 27 nt of the original coding sequence is needed for rescue of infectious chimeric rotavirus. Despite a near-total replacement of NSP1 with GFP, pruned segments emerged and were preferentially incorporated into later passages, which was correlated with increased infectivity at the expense of GFP expression. These results suggest that factors beyond excess segment size drive pruning of chimeric sequences. Closer sequence analysis of pruned segments revealed that pruning occurred at high GC regions of the insert, suggesting an inherent incompatibility with the genome composition of rotavirus segments. These findings shed light on the requirements for rotavirus segment recognition and stability, as well as provide important considerations for the usage of this model as a potential vaccine platform.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, highly fatal hyperinflammatory syndrome characterized by an uncontrolled cytokine cascade. Traditional chemotherapy leaves 30% of patients unresponsive, and its side effects are significant. Precise targeted therapies are highly anticipated. Emapalumab is a monoclonal antibody targeting interferon-&#x3b3;, while ruxolitinib is a JAK1/2 inhibitor, and their application in HLH treatment is gaining attention. We retrospectively collected clinical data from pediatric HLH patients who received emapalumab added to conventional therapy, with or without ruxolitinib, at our hospital between June 1, 2022, and June 1, 2024. Treatment efficacy, safety, improvement in clinical parameters, and causes of death were analyzed. A total of 10 pediatric patients were included: 7 with refractory disease, 2 with relapsed disease, and 1 with newly diagnosed disease. EBV-associated HLH was observed in 6 of the 10 patients. All patients received emapalumab added to conventional therapy, and 7 patients additionally received ruxolitinib. The median follow-up duration was 164 days (range, 19-473 days). Among the 10 patients, 5 achieved remission. The response rates for fever, hypofibrinogenemia, neutropenia, hyperbilirubinemia, and elevated transaminases were 6/6, 5/5, 8/9, 4/7, and 6/10, respectively. Among patients with relapsed/refractory disease, the remission rate was 2/3 with emapalumab plus conventional therapy alone and 2/6 with the further addition of ruxolitinib. In patients with non-EBV-associated HLH, the corresponding remission rates were 1/2 and 2/2, respectively. In patients with EBV-associated HLH, the rates were 1/1 and 1/5, respectively. In this small-sample retrospective study, emapalumab showed a more pronounced trend toward alleviating fever, hypofibrinogenemia, and neutropenia than toward improving liver function among pediatric HLH patients. Adding ruxolitinib to the combination of emapalumab and conventional therapy did not demonstrate a clear additional clinical benefit, particularly in the EBV-associated HLH and relapsed/refractory subgroups. These findings are constrained by the study design and sample size and necessitate validation in larger, prospective studies.

Cadmium is a highly neurotoxic heavy metal that impacts the functions of several organs through stimulating excessive oxidative stress. Polyphenols were evidenced to mitigate heavy metal-induced neurotoxicity and pulmonary toxicity. Crocin (CN) is a carotenoid compound extracted from Crocus sativus L. This study explored the protective activities of CN against Cadmium chloride (CdCl2)-induced neurotoxicity and lung injury. Thirty-two female albino Wistar rats, 6-8 weeks-old, were allocated into four groups: Negative control, CdCl2-intoxicated rats (two successive intraperitoneal doses of 1 and 3&#xa0;mg/kg body weight), CN group, and treated CdCl2 rats with CN (50&#xa0;mg/kg body weight, orally). Hanging-wire test was used to assess the muscular coordination. Biochemically, lipid peroxidation and glutathione (GSH) contents in the brain and lung homogenates, serum iron and phosphorus levels, serum Glucagon-like Peptide-1 (GLP-1) and spexin (SPX) levels were measured, along with histopathological investigation of cerebellar and pulmonary tissues. CdCl2 rats demonstrated loss of neuromuscular coordination and imbalance in the hanging-wire test. Furthermore, CdCl2 rats exhibited increased lipid peroxidation, GSH decline, disruption of iron and phosphorus levels, and reduction of GLP-1 and SPX levels. Concomitant treatment of CdCl2-rats with CN, for two weeks, restored the muscular strength, mitigated oxidative stress, regulated iron and phosphorus levels, modulated GLP-1 and SPX, and ameliorated the histopathological features in the cerebellum and the lungs. We concluded that CN exerted neuroprotective and pulmonary protective potentials against CdCl2-induced toxicity, and that GLP-1 and SPX could be regarded as biomarkers of heavy metals-associated neurotoxicity and lung toxicity.

Squamous cell carcinoma (SCC) has historically been associated with worse outcomes than adenocarcinoma (AD) in non-small cell lung cancer (NSCLC). However, the prognostic significance of histology in resectable disease remains incompletely defined and warrants re-evaluation in large contemporary cohorts. The National Cancer Database was queried for adults with resected stage I-III NSCLC diagnosed between 2004 and 2021. Histology was limited to AD and SCC using ICD-O-3 codes. Patients with in situ or occult disease, multiple primaries, death within 30 days of surgery, missing survival data, tumor size or pathologic stage, and ablative procedures were excluded. The primary outcome was 10-year overall survival. Adjusted Cox proportional hazards models were used to evaluate the association between histology and survival in the overall cohort and within pathologic stages I-III, with histology &#xd7; stage interaction testing. Among 130,731 patients, 92,598 (71%) had AD and 38,133 (29%) had SCC. Kaplan-Meier analysis demonstrated worse 10-year survival for SCC compared with AD (log-rank p&#x2009;<&#x2009;0.001). On multivariable analysis, SCC remained associated with worse 10-year survival (aHR 1.14, 95% CI 1.12-1.17; p&#x2009;<&#x2009;0.001). Stage-stratified models showed worse survival for SCC in stage I disease (aHR 1.24, 95% CI 1.21-1.28, p&#x2009;<&#x2009;0.001) but not in stage II or III disease. Histology &#xd7; stage interaction terms confirmed significant effect modification by stage (p&#x2009;<&#x2009;0.001). In resected stage I-III NSCLC, SCC remains associated with worse 10-year survival. SCC remained independently associated with worse survival in stage I disease, whereas this association was substantially attenuated in stage II and III disease.