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Summary: Viral respiratory tract infections exacerbate airway disease and facilitate life-threatening bacterial colonization in cystic fibrosis (CF). Annual influenza vaccination is recommended and vaccines against other common respiratory viruses may further reduce pulmonary morbidity risk. Enteroviruses have been found in nasopharyngeal samples from CF patients experiencing pulmonary exacerbations. Using serology tests, we found that infections by a group of enteroviruses, Coxsackievirus Bs (CVBs), are prevalent in CF. We next showed that a CVB vaccine, currently undergoing clinical development, prevents infection and CVB-instigated lung damage in a murine model of CF. Finally, we demonstrate that individuals with CF have normal vaccine responses to a similar, commonly used enterovirus vaccine (inactivated poliovirus vaccine). Our study demonstrates that CVB infections are common in CF and provides experimental evidence indicating that CVB vaccines could be efficacious in the CF population. The role of CVB infections in contributing to pulmonary exacerbations in CF should be further studied.

Nitrite in drinking water is a potentially harmful substance for humans, and controlling nitrite formation in drinking water distribution systems (DWDSs) is highly important. The effect of natural organic matter (NOM) on the formation of nitrite in simulated distribution systems was studied. The objective was to inspect how a reduced NOM concentration affected nitrite development via nitrification, separated from the effects of disinfection. We observed that nitrite formation was noticeably sensitive to the changes in the NOM concentrations. Nitrite declined with reduced NOM (TOC 1.0 mg L-1) but increased with the normal NOM concentration of tap water (TOC 1.6 mg L-1). Ammonium oxidation was not altered by the reduced NOM, however, nitrite oxidation was enhanced significantly according to the pseudo-first order reaction rate model interpretation. The enhanced nitrite oxidation was observed with both ammonium and nitrite as the initial nitrogen source. The theoretical maximum nitrite concentrations were higher with the normal concentration of NOM than with reduced NOM. The results suggest that the role of nitrite oxidation may be quite important in nitrite formation in DWDSs and worth further studies. As a practical result, our study supported enhanced NOM removal in non-disinfected DWDSs.

RNA viruses have specific mutation rates that balance the conflicting needs of an evolutionary response to host antiviral defenses and avoidance of the error catastrophe. While most mutations are known to originate in replication errors, difficulties of capturing the underlying dynamics have left the mechanochemical basis of viral mutagenesis unresolved. Here, we use multiplexed magnetic tweezers to investigate error incorporation by the bacteriophage Φ6 RNA-dependent RNA polymerase. We extract large datasets fingerprinting real-time polymerase dynamics over four magnitudes in time, in the presence of nucleotide analogs, and under varying NTP and divalent cation concentrations and fork stability. Quantitative analysis reveals a new pause state that modulates polymerase fidelity and so ties viral polymerase pausing to the biological function of optimizing virulence. Adjusting the frequency of such pauses offers a target for therapeutics and may also reflect an evolutionary strategy for virus populations to track the gradual evolution of their hosts.

Background & Aims: For patients with short-bowel syndrome, intestinal adaptation is required to achieve enteral independence. Although adaptation has been studied extensively in animal models, little is known about this process in human intestine. We hypothesized that analysis of matched specimens with and without luminal flow could identify new potential therapeutic pathways. Methods: Fifteen paired human ileum samples were collected from children aged 2â20 months during ileostomy-reversal surgery after short-segment intestinal resection and diversion. The segment exposed to enteral feeding was denoted as fed, and the diverted segment was labeled as unfed. Morphometrics and cell differentiation were compared histologically. RNA Sequencing and Gene Ontology Enrichment Analysis identified over-represented and under-represented pathways. Immunofluorescence staining and Western blot evaluated proteins of interest. Paired data were compared with 1-tailed Wilcoxon rank-sum tests with a P value less than .05 considered significant. Results: Unfed ileum contained shorter villi, shallower crypts, and fewer Paneth cells. Genes up-regulated by the absence of mechanoluminal stimulation were involved in digestion, metabolism, and transport. Messenger RNA expression of LGR5 was significantly higher in unfed intestine, accompanied by increased levels of phosphorylated signal transducer and activator of transcription 3 protein, and CCND1 and C-MYC messenger RNA. However, decreased proliferation and fewer LGR5+, OLFM4+, and SOX9+ intestinal stem cells (ISCs) were observed in unfed ileum. Conclusions: Even with sufficient systemic caloric intake, human ileum responds to the chronic absence of mechanoluminal stimulation by up-regulating brush-border enzymes, transporters, structural genes, and ISC genes LGR5 and ASCL2. These data suggest that unfed intestine is primed to replenish the ISC population upon re-introduction of enteral feeding. Therefore, the elucidation of pathways involved in these processes may provide therapeutic targets for patients with intestinal failure. RNA sequencing data are available at Gene Expression Omnibus series GSE82147. Keywords: Intestinal Stem Cell, LGR5, Small Intestine, Calorie Restriction, Enteric Nutrition, Mechanoluminal Flow

Maternal immune activation (MIA) during pregnancy is implicated in offspring psychiatric disorders. However, it is unknown to what extent MIA affects neurodevelopment, particularly cerebrocortical anatomy, in the general population, and whether effects differ by sex. The current study used vertex-wise statistics to examine the association between maternal prenatal CRP, an archetypal systemic inflammatory marker, and offspring cortical thickness, surface area, and volume, in 2635 mother-child dyads (5.4-26.5 years) from three population-based cohorts, and one clinical cohort enriched for presence of inflammation markers. Maternal CRP within a normal physiological range (<10 mg/L) exhibited sex-specific quadratic associations with cortical morphological measures in 2 regions in males and 1 region in females at childhood. Elevated (>10 mg/L) CRP was associated with regional cortical morphology in females and in a pooled sample of sexes. Overall, MIA is associated with cortical development in a regional and sex-specific manner in studies spanning childhood to adulthood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Seasonality can influence many physiological traits requiring optimal energetic capacity for life-history stage transitions. In Atlantic salmon, high-energy status is essential for the initiation of maturation. Earlier studies have linked a genomic region encoding vgll3 to maturation age, potentially mediated via body condition. Vgll3 has also been shown to act as an inhibitor of adipogenesis in mice. Here we investigate the influence of season and vgll3 genotypes associating with early (EE) and late (LL) maturation on lipid profiles in the muscle and liver of juvenile Atlantic salmon. We reared Atlantic salmon for two years from fertilization and sampled muscle and liver during the spring and autumn of the second year (at which time some males were sexually mature). We found no seasonal or genotype effect in the muscle lipid profiles of immature males or females. However, in the liver we detected a triacylglycerol enrichment and a genotype specific direction of change in membrane lipids, phosphatidylcholine and phosphatidylethanolamine, from spring to autumn. Specifically, from spring to autumn membrane lipid concentrations increased in vgll3*EE individuals but decreased in vgll3*LL individuals. This could be explained by 1) a seasonally more stable capacity of endoplasmic reticulum (ER) functions in vgll3*EE individuals compared to vgll3*LL individuals or 2) vgll3*LL individuals storing larger lipid droplets from spring to autumn in the liver compared to vgll3*EE individuals at the expense of ER capacity. This genotype specific seasonal direction of change in membrane lipid concentrations provides more indirect evidence of a potential mechanism linking vgll3 with lipid metabolism and storage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Avian coccidiosis, caused by protozoan parasites of the genus Eimeria, is a globally prevalent and highly pathogenic disease that poses a serious threat to the poultry industry, resulting in significant economic losses. However, the mechanism by which Eimeria species invade host cells remains unclear. Previous studies have identified rhoptry neck protein 2 (RON2) from Eimeria tenella as a critical factor in host cell invasion, but a comprehensive understanding of the role of EtRON2 in host cell invasion and its relationship with E. tenella invasion is lacking. To address this gap, this study focused on the secreted protein EtRON2 from E. tenella and its interaction with host cell receptors. The receptor interacting with the EtRON2 protein was identified through a GST pull-down assay, followed by mass spectrometry, and the interaction was further validated through subcellular co-localization analysis. Furthermore, sporozoites and host cells were treated with a specific antibody targeting the EtRON2/annexin A2 interaction, and the invasion rate of E. tenella was assessed using RT-qPCR to analyze the effect of inhibiting this interaction on host cell invasion by E. tenella. Annexin A2 protein, located on the surface of the host cell membrane, was screened, and the results of the sporozoite invasion assay revealed that inhibiting the interaction between these two proteins reduced F-actin aggregation. Understanding the interaction between the EtRON2 protein and its receptor during parasite invasion could help elucidate the function of the EtRON2 receptor and provide a theoretical foundation for further studies on the invasion mechanisms of E. tenella and the prevention and control of avian coccidiosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025. Published by Elsevier Inc.)

Aims: The human Inhibitor of Differentiation-2 (hID2) protein is a promising candidate for the treatment of colitis. However, its relatively low molecular weight limits its clinical application. To extend the therapeutic half-life, an albumin-binding domain (ABD), known for its high affinity for human serum albumin (HSA), was fused to hID2, resulting in a recombinant ABD-hID2. The anti-colitis bioactivity of ABD-hID2 than that of hID2 was evaluated in this study., Main Methods: Western blotting, size-exclusion high-performance chromatography, HSA binding assay, and pharmacokinetic studies were used to characterise ABD-hID2, which was induced by dextran sulfate sodium salt (DSS), Citrobacter rodentium (CR), and ABD-hID2 and hID2. The Disease Activity Index, histological pathologies, inflammatory response, Alcian blue or tuft cell staining, and tight junction proteins were determined. Alterations in the intestinal microbiota after ABD-hID2 treatment were analysed via 16S rRNA gene sequencing., Key Findings: Compared with hID2, ABD-hID2 exhibited a decreased dimer complex, bound to HSA with high affinity, and demonstrated an extended blood retention time in vivo. Consequently, ABD-hID2 exhibited increased therapeutic efficacy in both DSS- and CR-induced colitis mouse models, as evidenced by the alleviation of colitis symptoms, preservation of goblet and tuft cell functions, restoration of the intestinal mucus barrier, and suppression of abnormal immune-inflammatory responses. Additionally, the modulation of the gut microbiota may play a role in the protective effects of ABD-hID2 in mice with CR-induced ulcerative colitis., Significance: ABD-hID2 enhances the bioactivity of hID2 and has the potential for further development as a treatment for colitis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Brown carbon (BrC) is an organic aerosol (OA) component that possesses light-absorbing properties in the UV-Vis spectrum, impacting climate. However, the current understanding of climate repercussions stemming from BrC emissions remains insufficient due to a lack of comprehensive knowledge regarding its chemical makeup, light-absorption, and the role of atmospheric aging in shaping BrC properties. This study investigates BrC in PM 1 (particulate matter <1μm) during winter in Helsinki, Finland, in a street canyon and a residential area with wood combustion. The aim was to ascertain BrC sources, chemical composition, and contribution to UV-Vis light absorption. The study utilized a seven-wavelength aethalometer (AE33) to measure black carbon (BC) and BrC light absorptions, and a soot particle aerosol mass spectrometer (SP-AMS) to determine OA composition. An OA source apportionment using positive matrix factorization followed by a multiple regression analysis between BrC absorption and each factor was performed to determine the mass absorption coefficients of BrC (MAC BrC ) and light absorption contributions of distinct sources across 370-660 nm wavelengths. The BrC UV-Vis absorption relative to the one of BC was higher at 370 nm, with a median contribution of 20.1 % in the residential area and 18.2 % at the traffic site. Residential BrC absorption showed sporadic peaks, while street canyon absorption was lower but consistent. MAC BrC was higher for biomass burning organic aerosol but still significant for long-range transported (LRT) and traffic-related aerosols. Hydrocarbon-like organic aerosol exhibited higher MAC BrC at 470 nm than at 370 nm. Combined with particulate mass concentrations, biomass burning and LRT contributed the most to light absorption. Uncertainties regarding MAC BrC were evaluated. The chemical composition analysis revealed stronger correlations between BrC absorption and SP-AMS-measured ions, especially in residential areas and for polycyclic aromatic hydrocarbons and oxidized aromatics. The study emphasizes the importance of anthropogenic sources in BrC light absorption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Self-assembly of fenugreek polysaccharides FS60 (a natural macromolecular material) with curcuminoid has been proved to improve curcumin (Cur) water dispersion in preliminary studies. This study further explored the effect of FS60 on Cur bioavailability in vivo to assess the significance of this delivery method. In this study, we optimized the formulation parameters of FS60-curcuminoid aggregates (FC) and studied their effects on Cur pharmacokinetics in rats. Results showed that the optimized aggregates had an encapsulation efficiency (EE) of 88.22 % and hydrodynamic diameter (D H ) of 231.48 nm. Additionally, administering FC significantly increased curcumin glucuronide (Cur-O-Glu) levels. The C max was 51 times higher and AUC 0-12h was 19 times higher than curcuminoid alone. Moreover, FS60 intervention for seven days increased the absorption speed of Cur-O-Glu into the bloodstream. Further mechanistic studies indicated that FS60 promoted Cur ingestion, increased UGT expression, and inhibited enterocyte transporters, allowing large amounts of Cur-O-Glu to enter the bloodstream. Moreover, the gut microbiota modulated by FS60 accelerated the mutual conversion of pentose and gluconate to provide sufficient glucuronic acid for the glucuronidation of Cur in enterocytes. Consequently, the nano delivery system composed by FS60 and curcuminoid facilitated gastrointestinal Cur glucuronidation and Cur-O-Glu absorption., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: This review aims to provide a comprehensive overview of electric-scooter (E-Scooter) injuries by evaluating the incidence, common mechanisms of injury, clinical outcomes, associated costs, and effective interventions for injury prevention., Methods: A literature search using PubMed, Google Scholar, EMBASE, and ProQuest was performed to identify relevant articles published between July 10, 2014, and July 10, 2024. Outcomes of interest included epidemiologic trends of E-Scooter injuries, common mechanisms of injury, associated risk factors, clinical outcomes, and interventions to decrease E-Scooter injuries., Results: A total of 41 articles were included in this study, with 39 evaluating the epidemiologic trends of e-scooter injuries, 22 the most common mechanisms of injury, 21 assessed intoxication, 15 assessed helmet usage, 33 determined patient's clinical outcomes, and 3 assessed effective interventions for decreasing the incidence of e-scooter injuries. Falls were the most common mechanism of injury; however, collisions with motor vehicles caused more severe injuries. Additionally, studies showed that up to 74 % of all E-Scooter injuries included alcohol intoxication, and over 80 % did not use a helmet leading to severe head injuries., Conclusion: The incidence of E-Scooter related injuries rose significantly in recent years. These injuries typically result from falls and MVAs and are compounded by factors including limited helmet usage and riding while intoxicated. These contribute to the poorer clinical outcomes seen with E-Scooter injuries. However, there remains a significant paucity of literature focused on the outcomes of policies and interventions designed to reduce these injuries. Further investigation must address these gaps and discrepancies to inform future policies., Competing Interests: Declaration of competing interest Authors have nothing to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Global warming increases the risk of dangerous heat waves, which may have deleterious effects on humans and wildlife. Here, we have utilized zebrafish embryos as a model to analyze heat stress and effect of chemical compounds on responses to heat stress. The temperature adaptation limit of zebrafish embryos was 37 °C in behavioural test and 38 °C in cardiac test. Polyaromatic hydrocarbon phenanthrene completely blocked the behavioural adaptation to heat stress. Interestingly, the cardiotoxic effects of lapatinib, phenanthrene and paclitaxel were induced by heat stress. Taken together, our data indicates that motility and cardiac function of zebrafish embryos can be utilized as a model to analyze modulatory effects of compounds on heat stress., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ilkka Paatero, Katri Vaparanta, Minna Ampuja reports financial support was provided by Finnish Foundation for Cardiovascular Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In surgical training, a mentor is a more senior and experienced surgeon who guides a surgical trainee to meet personal, professional, and educational goals. Although mentorship is widely assumed to positively affect surgical residents' professional development, a more nuanced understanding of mentorship's impact is lacking and urgently needed as burnout rates among residents increase. This study aims to summarize the current literature on the effects of mentorship on surgical residents' burnout and well-being., Methods: A comprehensive literature review was performed with key terms related to "surgical resident" and "mentor" using Pubmed, Embase, and ProQuest databases for primary studies published in the United States or Canada from January 1, 2010 to December 9, 2022 that measured outcomes related to burnout and well-being. Multiple reviewers screened titles and abstracts for relevance, then full-text articles for eligibility., Results: Initial search resulted in 1,468 unique articles, and 19 articles were included after review. Only one article was a randomized controlled trial. Twelve studies described a decrease in burnout rates or in outcomes related to burnout. In contrast, 4 studies identified negative outcomes related to burnout. Six studies showed improved well-being or related outcomes. One study was not able to show a change in self-valuation between coached and noncoached residents., Conclusion: High quality mentorship can be associated with improved well-being and decreased burnout in surgical residents, but the key elements of effective and helpful mentorship remain poorly characterized. This summary highlights the importance of making mentorship accessible to surgical residents, and training faculty to be effective mentors., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The BCL2 inhibitor venetoclax has shown promise for treating acute myeloid leukemia (AML). However, identifying patients likely to respond remains a challenge, especially for those with relapsed/refractory (R/R) disease. We evaluated the utility of ex vivo venetoclax sensitivity testing to predict treatment responses to venetoclax-azacitidine in a prospective, multicenter, phase 2 trial conducted by the Finnish AML Group (VenEx, NCT04267081). The trial recruited 104 participants with previously untreated (n=48), R/R (n=39) or previously treated secondary AML (sAML) (n=17). The primary endpoint was complete remission or complete remission with incomplete hematologic recovery (CR/CRi) rate in ex vivo sensitive trial participants during the first three therapy cycles. The key secondary endpoints included the correlations between ex vivo drug sensitivity, responses, and survival. Venetoclax sensitivity was successfully assessed in 102/104 participants, with results available within a median of three days from sampling. In previously untreated AML, ex vivo sensitivity corresponded to an 85% (34/40) CR/CRi rate, with a median overall survival (OS) of 28.7 months, compared to 5.5 months for ex vivo resistant patients (p = 0.002). For R/R/sAML, ex vivo sensitivity resulted in a 62% CR/CRi rate (21/34) and median OS of 9.7 versus 3.3 months for ex vivo resistant patients (p < 0.001). In univariate and multivariate analysis, ex vivo venetoclax sensitivity was the strongest predictor for a favorable treatment response and survival. The VenEx trial demonstrates the feasibility of integrating ex vivo drug testing into clinical practice to identify AML patients, particularly in the R/R setting, who benefit from venetoclax., (Copyright © 2024 American Society of Hematology.)

Fungal mycelium is emerging as a source for sustainable bio-based materials. Fungal biomass of Aspergillus oryzae was prepared by cultivation on bread waste hydrolysate to valorize this abundant food waste. Chitin-glucan-rich alkali-insoluble material (AIM) was isolated from fungal biomass, formed into hydrogels, and wet spun into monofilaments. AIM in the form of fungal microfibers containing 0.09 g polymer of glucosamine (GlcN)/g AIM was subjected to freeze-thaw and deacetylation treatments to increase the amount of GlcN. The GlcN fraction was 0.19 and 0.34 g polymer of GlcN/g AIM, for AIM subjected to deacetylation (AIM-DAC) and freeze-thaw cycles and deacetylation (AIM-FRTH-DAC), respectively. The increased GlcN fraction enabled the formation of hydrogels via the protonation of amino groups after the addition of lactic acid. Morphological differences in the hydrogels included aggregation of the fungal microfibers in the AIM-DAC hydrogel, whereas the microfibers in the AIM-FRTH-DAC hydrogel had a porous and interconnected network. Rheological assessment revealed shear thinning behavior and gel properties of the produced hydrogels. Wet spinning of the hydrogels resulted in monofilaments with tensile strengths of up to 70 MPa and 12 % elongation at break. This demonstrates promising avenues for biomaterial development from fungal cell walls containing chitin-glucan via food waste valorization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease in newborn infants, but it influences gut microbiota development. Gut microbiota composition is, in turn, associated with immune-related diseases in childhood., Objective: This study hypothesized that intrapartum antibiotic exposure is associated with immune-related diseases in childhood., Study Design: We conducted a population-based cohort study of vaginally delivered children. We retrieved data on intrapartum antibiotic exposure from structured electronic medical records and obtained outcome data on childhood autoimmune, allergic, and obstructive airway diseases from comprehensive national registers. We used Cox regression analysis with adjustment for maternal and neonatal covariates and regarded death as a competing risk in the analyses., Results: The study population comprised 45,575 vaginally born children of whom 9733 (21%) had been exposed to intrapartum antibiotics. Intrapartum antibiotic exposure was associated with an autoimmune disease diagnosis (adjusted hazard ratio, 1.28; 95% confidence interval, 1.02-1.62), which corresponds to 22% (95% confidence interval, 6-39) as a theoretical population-attributable fraction. Intrapartum antibiotic exposure was not associated with diagnoses of allergic (adjusted hazard ratio, 1.08; 95% confidence interval, 0.97-1.20) or obstructive airway diseases (adjusted hazard ratio, 1.04; 95% confidence interval, 0.96-1.14)., Conclusion: Intrapartum antibiotic exposure may be associated with an increased risk for autoimmune diseases in childhood. This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Otolaryngology is an important specialty in the field of surgery that deals with the diagnosis and treatment of the ear, nose, throat, trachea, as well as related anatomical structures. Various otolaryngological disorders are difficult to treat using established pharmacological and surgical approaches. The advent of molecular and cellular therapies led to further progress in this respect. This article reviews the therapeutic strategies of using stem cells, immune cells, and chondrocytes in otorhinolaryngology. As the most widely recognized cell derivatives, exosomes were also systematically reviewed for their therapeutic potential in head and neck cancer, otitis media, and allergic rhinitis. Finally, we summarize the limitations of stem cells, chondrocytes, and exosomes, as well as possible solutions, and provide an outlook on the future direction of cell- and derivative-based therapies in otorhinolaryngology, to offer a theoretical foundation for the clinical translation of this therapeutic modality., Competing Interests: Declaration of competing interest The authors declare no competing financial interests related to this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Robotic-assisted laparoscopy has become a widely and increasingly used modality of minimally invasive surgery in the treatment of endometrial cancer. Due to its technical advantages, robotic-assisted laparoscopic surgery offers benefits, such as a lower rate of conversions compared to conventional laparoscopy. Yet, data on long-term oncological outcomes after robotic-assisted laparoscopy is scarce and based on retrospective cohort studies only., Objective: This study aimed to assess overall survival, progression-free survival, and long-term surgical complications in patients with endometrial cancer randomly assigned to robotic-assisted or conventional laparoscopy., Study Design: This randomized controlled trial was conducted at the Department of Gynecology and Obstetrics of Tampere University Hospital, Finland. Between 2010 and 2013, 101 patients with low-grade endometrial cancer scheduled for minimally invasive surgery were randomized preoperatively 1:1 either to robotic-assisted or conventional laparoscopy. All patients underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. A total of 97 patients (49 in the robotic-assisted laparoscopy group and 48 in the conventional laparoscopy group) were followed up for a minimum of 10 years. Survival was analyzed using Kaplan-Meier curves, log-rank test, and Cox proportional hazard models. Binary logistic regression analysis was used to analyze risk factors for trocar site hernia., Results: In the multivariable regression analysis, overall survival was favorable in the robotic-assisted group (hazard ratio 0.39; 95% confidence interval [CI], 0.15-0.99, P=.047) compared to the conventional laparoscopy group. There was no difference in progression-free survival (log-rank test, P=.598). The 3-, 5-, and 10-year overall survival were 98.0% (95% CI, 94.0-100) vs 97.9% (93.8-100), 91.8% (84.2-99.4) vs 93.7% (86.8-100), and 75.5% (64.5-87.5) vs 85.4% (75.4-95.4) for the conventional laparoscopy and the robotic-assisted groups, respectively. Trocar site hernia developed more often for the robotic-assisted group compared to the conventional laparoscopy group 18.2% vs 4.1% (odds ratio 5.42, 95% CI, 1.11-26.59, P=.028). The incidence of lymphocele, lymphedema, or other long-term complications did not differ between the groups., Conclusion: The results of this randomized controlled trial suggest a minor overall survival benefit in endometrial cancer after robotic-assisted laparoscopy compared to conventional laparoscopy. Hence, the use of robotic-assisted technique in the treatment of endometrial cancer seems safe, though larger randomized controlled trials are needed to confirm any potential survival benefit. No alarming safety signals were detected in the robotic-assisted group since the rate of long-term complications differed only in the incidence of trocar site hernia., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Information on Paxlovid™ effectiveness must be monitored and updated in real world scenarios. Our research question was what is the effectiveness of Paxlovid™ in adult patients with COVID-19? Therefore, we investigated the effectiveness of Paxlovid™ on reducing the incidence of pneumonia, hospitalization, and mortality in a cohort of COVID-19 positive adult patients from northeast Mexico., Methods: A retrospective cohort study of COVID-19 positive adult patients from Nuevo Leon, Mexico from December 2020 to May 2023 (after Omicron BA-5 circulation) was performed. Paxlovid™ use was authorized in September 2022. Therefore, we analyzed effectiveness in patients with confirmed diagnosis who met selection criteria between September 2022 and May 2023 (n = 20,799; 5,673 with and 15,126 without Paxlovid™)., Results: The pneumonia (0.1% vs. 0.4%, p < 0.0001), hospitalization (0.1% vs. 1.2%, p < 0.0001), and death rates (0.04% vs. 0.2%, p < 0.0001) were lower in patients with Paxlovid™ treatment independently of age, sex, comorbidity, and COVID-19 and pneumococcal vaccination history. Effectiveness was 88.2%, 95.9% y 91.9% for pneumonia, hospitalization, and death, respectively., Conclusions: Paxlovid™ reduces the presentation of pneumonia, hospitalization, and death secondary to COVID-19. It is recommended to continue monitoring Paxlovid™ effectiveness, as other SARS-CoV-2 variants continue to emerge., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed., Methods: The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed., Findings: From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%])., Interpretation: We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation., Funding: State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Silicone oil is a commonly used lubricant in pre-filled syringes (PFSs) and can migrate over time into solution in the form of silicone oil particles (SiOPs). The presence of these SiOPs can result in elevated subvisible particle counts in PFS drug products compared to other drug presentations such as vials or cartridges. Their presence in products presents analytical challenges as they complicate quantitation and characterization of other types of subvisible particles in solution. Previous studies have suggested that they can potentially act as adjuvant resulting in potential safety risks for patients. In this paper we present several analytical case studies describing the impact of the presence of SiOPs in biotherapeutics on the analysis of the drug as well as clinical case studies examining the effect of SiOPs on patient safety. The analytical case studies demonstrate that orthogonal techniques, especially flow imaging, can help differentiate SiOPs from other types of particulate matter. The clinical case studies showed no difference in the observed patient safety profile across multiple drugs, patient populations, and routes of administration, indicating that the presence of SiOPs does not impact patient safety., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Eimeria tenella is the most pathogenic and harmful intestinal parasitic protozoan. Recombinant DNA vaccines open options for promising strategies for preventing avian coccidiosis, replacing chemical drugs and live oocyst vaccines. Two important antigenic proteins, EtAMA3 (also known as SporoAMA1) and EtRON2 L2 , act together to promote the invasion of E. tenella sporozoites. In this study, a recombinant DNA vaccine, designated pcDNA3.1(+)-AR, was constructed based on EtAMA3DII, EtRON2 L2 D3, and EtRON2 L2 D4. Chickens were intramuscularly immunized with different doses (25, 50, or 100 μg) of pcDNA3.1(+)-AR to evaluate its immunoprotective effects in vivo. The chickens in the 50 μg and 100 μg groups had higher cytokine concentrations (interleukin 2, interferon-gamma, and interleukin 10), and lesion scores (81.9% and 67.57%, respectively) and relative oocyst production (47% and 19%, respectively) reduced compared with the unchallenged group, indicating partial protection against E. tenella. These results suggest that pcDNA3.1(+)-AR is a promising vaccine candidate against avian coccidiosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The essential point of current study was to investigate the effect of a Fenton-like system established by oxalic acid and Fe(II) on gas emission, organic matter decomposition and humification during composting. Branches were pretreated with Fenton reagents (0.02 M FeCl 2 ·4H 2 O + 1.5 M H 2 O 2 ) and then adding 10 % oxalic acid (OA). The treatments were marked as B1 (control), B2 (Fenton reagent), B3 (10% OA) and B4 (Fenton-like reagent). The results collected from 80 d of composting showed that adding Fenton-like reagent benefited the degradation of organic substances, as reflected by the total organic carbon and dissolved organic carbon, and the maximum decomposition rate was observed in B4. In addition, the Fenton-like reagent could improve the synthesis of humus characterized by complex and stable compounds, which was consistent with the spectral parameters (SUVA 254 , SUVA 280 , E 253 /E 203 and Fourier transform-infrared indicators) of DOC. Furthermore, the functional microbial succession performance and linear discriminant effect size analyses provided microbial evidence of humification improvement. Notably, compared with the control, the minimum value of CH 4 cumulation was reported in B4, which decreased by 30.44 %. Concluded together, the addition of a Fenton-like reagent composed by OA and Fe(II) is a practical way to improve the humification. Furthermore, the mechanisms related to the promotion of humification should be investigated from free radicals, functional genes, and metabolic pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Our aim was to define reference limits for cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (proBNP) that would better reflect their concentrations in older people. In addition, the incidence of acute myocardial infarctions (AMIs) was studied using these reference limits in an older population with and without previous heart diseases., Materials and Methods: A population-based study with a ten-year follow-up. The reference population was formed by 763 individuals aged over 64 years, with no diagnoses of heart or kidney diseases., Results: There was a significant increase in cTnT and proBNP concentrations with age. The 99 % reference limits for cTnT were 25 ng/L, 28 ng/l, 38 ng/l, and 71 ng/l for men in five-year-intervals starting from 64 to 69 years to 80 years and older, and 18 ng/L, 22 ng/l, 26 ng/l, and 52 ng/L for women, respectively. The 97.5 % reference limits for proBNP were 272 ng/L, 287 ng/l, 373 ng/l and 686 ng/L for men, and 341 ng/L, 377 ng/l, 471 ng/l, and 794 ng/L for women, respectively. Elevated proBNP was statistically significantly associated with future AMIs in subjects with and without a previous heart disease., Conclusions: Age-specific reference limits for cTnT and proBNP are needed to better evaluate cardiac symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: This narrative review aims to evaluate the efficacy of adjunct direct peritoneal resuscitation (DPR) in the treatment of adult damage control surgery (DCS) patients both with and without hemorrhagic shock, and its impact on associated outcomes., Methods: PubMed, Google Scholar, EMBASE, ProQuest, and Cochrane were searched for relevant articles published through April 13th, 2023. Studies assessing the utilization of DPR in adult DCS patients were included. Outcomes included time to abdominal closure, intra-abdominal complications, in-hospital mortality, and ICU length of stay (ICU LOS)., Results: Five studies evaluating 437 patients were included. In patients with hemorrhagic shock, DPR was associated with reduced time to abdominal closure (DPR 4.1 days, control 5.9 days, p = 0.002), intra-abdominal complications including abscess formation (DPR 27 %, control 47 %, p = 0.04), and ICU LOS (DPR 8 days, control 11 days, p = 0.004). Findings in patients without hemorrhagic shock were conflicting. Closure times were decreased in one study (DPR 5.9 days, control 7.7 days, p < 0.02) and increased in another study (DPR 3.5 days, control 2.5 days, p = 0.02), intra-abdominal complications were decreased in one study (DPR 27 %, control 47 %, p = 0.04) and similar in another, and ICU LOS was decreased in one study (DPR 17 days, control 24 days, p < 0.002) and increased in another (DPR 13 days, control 11.4 days, p = 0.807)., Conclusion: In patients with hemorrhagic shock, adjunct DPR is associated with reduced time to abdominal closure, intra-abdominal complications such as abscesses, fistula, bleeding, anastomotic leak, and ICU LOS. Utilization of DPR in patients without hemorrhagic shock showed promising but inconsistent findings., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The reproductive cycle of equines tends to be seasonal and is influenced by factors such as light and temperature. The process and methods of regulating the mare oestrous cycle in the anestrus period are still immature. The effects of noncoding RNAs and mRNAs on the oestrous cycle have aroused much interest, but corresponding analyses of seasonal mare ovaries have not been reported. Here, we report a whole transcriptome analysis of the Mongolian horse ovarian cortex collected in anestrus and diestrus periods. In total, 1081 mRNAs, 205 lncRNAs, 54 circRNAs, and 13 miRNAs were upregulated in winter anestrus ovarian cortex (WAO), and 1261 mRNAs, 90 lncRNAs, 29 circRNAs, and 40 miRNAs were upregulated in summer diestrus ovarian cortex (SDO). The GO and KEGG enrichment analysis of differentially expressed mRNAs and target genes of differentially expressed lncRNAs, circRNAs, and miRNAs revealed some key functions and pathways that may be related to follicle and oocyte development. We found that estrogen-related pathways were enriched in different RNAs. Our data were used to generate miRNA, circRNA, lncRNA, and mRNA databases from the Mongolian horse ovary and differential expression profiles between WAO and SDO; these results provide clues for exploring methods of estrus regulation in mares during the anestrus period., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Extensive application of lead (Pb) brought about environmental pollution and toxic reactions of organisms. Selenium (Se) has the effect of antagonizing Pb poisoning in humans and animals. However, it is still unclear how Pb causes brainstem toxicity. In the present study, we wanted to investigate whether Se can alleviate Pb toxicity in chicken brainstems by reducing apoptosis. One hundred and eighty chickens were randomly divided into four groups, namely the control group, the Se group, the Pb group, and the Se/Pb group. Morphological examination, ultrastructural observation, relative mRNA expressions of genes on heat shock proteins (HSPs); selenoproteins; inflammatory cytokines; and apoptosis-related factors were investigated. The results showed that Pb exposure led to tissue damage and apoptosis in chicken brainstems. Furthermore, an atypical expression of HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90); selenoprotein family glutathione peroxidase (GPx) 1, GPx2, GPx3, and GPx4), thioredoxin reductases (Txnrd) (Txnrd1, Txnrd2, and Txnrd3), dio selenoprotein famliy (diodothyronine deiodinases (Dio)1, Dio2, and Dio3), as well as other selenoproteins (selenoprotein (Sel)T, SelK, SelS, SelH, SelM, SelU, SelI, SelO, Selpb, selenoprotein n1 (Sepn1), Sepp1, Sepx1, Sepw1, 15-kDa selenoprotein (Sep15), and selenophosphate synthetases 2 (SPS2)); inflammatory cytokines (Interleukin 2 (IL-2), IL-4, IL-6, IL-12β, IL-17, and Interferon-γ (IFN-γ)); and apoptosis-related genes (B-cell lymphoma-2 (Bcl-2), tumor protein 53 (p53), Bcl-2 Associated X (Bax), Cytochrome c (Cyt c), and Caspase-3) were identified. An inflammatory reaction and apoptosis were induced in chicken brainstems after exposure to Pb. Se alleviated the abnormal expression of HSPs, selenoproteins, inflammatory cytokines, and apoptosis in brainstem tissues of chickens treated with Pb. The results indicated that HSPs, selenoproteins, inflammatory, and apoptosis were involved in Se-resisted Pb poisoning. Overall, Se had resistance effect against Pb poisoning, and can be act as an antidote for Pb poisoning in animals., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Molecular mechanism of selenium against lead-induced apoptosis in chicken brainstem relating to heat shock protein, selenoproteins, and inflammatory cytokines”., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cr(VI) is known to be seriously toxic and carcinogenic. Hypoxia-inducible factor-1α (HIF-1α) is a crucial regulator to promote tumor development. In this study, we found that Cr(VI) significantly increased the expression of HIF-1α in A549 cells and in lung of BALB/c mice but not in HELF cells. Treatment with Lificiguat (YC-1), HIF-1α inhibitor, or CoCl 2 , HIF-1α inducer, could alter Cr(VI)-induced autophagy, glycolysis, and cell growth in A549 cells but not in HELF cells, validating the involvement of HIF-1α in these effects of Cr(VI) in A549 cells. Co-treatments of pcATG4B with YC-1, or siATG4B with CoCl 2 demonstrated the role of HIF-1α / autophagy axis in inducing glycolysis and cell growth in A549 cells. In HELF cells, however, only autophagy but not HIF-1α played a role in inducing glycolysis. The protein level of p53 was significantly lower in A549 cells than in HELF cells. RITA, a p53 inducer, attenuated Cr(VI)-induced HIF-1α and LC3-II in A549 cells, suggesting that p53 might be the mechanism underlying the different effects of Cr(VI) on HIF-1α in A549 and HELF cells. Thus, p53-dependent HIF-1α / autophagy-mediated glycolysis plays a role in facilitating Cr(VI)-induced carcinogenesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nutrition plays a vital role in shaping the intestinal microbiome. However, many hospitalized children undergo periods of fasting during medical treatment. Changes to the small intestinal microbiota in early life in the setting of enteral deprivation have not been well described., Objective: The aim of this study was to investigate the impact of enteral deprivation on the small intestinal mucosal microbiome and to identify factors that shape this interaction in infancy., Methods: Intestinal biopsies were collected from proximal (fed) and distal (unfed) small bowel at the time of ostomy closure in children with a small intestinal enterostomy. Mucosal and luminal microbiome comparisons were performed including β-diversity and differential abundance and correlations with clinical factors were analyzed. Host proteomics were compared between fed and unfed samples and correlated with microbiome parameters. Finally, microbial results were validated in another cohort of pediatric patients., Results: Samples from 13 children (median age 84 d) were collected. Mucosal microbiome communities in the fed and unfed segments were strikingly similar [paired UniFrac distance (β-diversity)], whereas luminal effluent differed significantly from fed samples (PERMANOVA, P = 0.003). Multivariate analysis revealed patient as the strongest predictor of the UniFrac distance. Environmental variables did not influence the intrapatient microbial dissimilarity. Host proteomics were similar intrapatient (paired fed-unfed Euclidian distance) and showed a correlation with the UniFrac distance (Spearman rho = 0.71, P < 0.001). Specific proteins and functional clusters were significantly different between paired samples, including lipid metabolism and intracellular trafficking, whereas no difference was seen in innate immune proteins. The microbiome results were validated in a different cohort with similar characteristics., Conclusion: We found the host to be the most dominant factor in the structure of the early life small intestinal mucosal microbiome. Nutrient deprivation was associated with specific changes in the host proteome. Further research is needed to better understand this host-microbe-nutrition interaction., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The aim of the study was to compare the stability of the virtual surgical planning (VSP) and computer-aided design accompanied by patient-specific implants (PSIs) and conventional mini-plates in mandible advancement with bilateral sagittal split osteotomy (BSSO). This retrospective study evaluates the clinical and cephalometric records of 53 patients (12 male, 41 female) treated with BSSO in Helsinki University Hospital. Subjects were divided into two groups: VSP-PSI (21 patients: 4 male and 17 female; mean age 38 years, range 25-53 years); and conventional wafer-based repositioning with mini-plate fixation (32 patients: 8 male and 24 female; mean age 39 years, range 21-56 years). The effect of the amount and direction of the advancement on the stability was also analysed individually. The standardized lateral cephalometric radiographs in three time points were analysed to compare the groups. After surgery (T2), there were no differences between groups in cephalometric variables. During follow-up (T2-T3), the cephalometric variables in both Groups A and B were stable, so there was no difference in stability between the VSP-PSI and the conventional mini-plate groups. During follow-up, the mandibles rotated clockwise or counterclockwise, relapsed towards their original direction, and the changes were statistically significant (jaw relationship; p = 0.018, soft tissue profile; p = 0.025); when the advancement of mandible was >6 mm, the increase in gonial angle compared to mandibles advanced ≤6 mm was statistically significant (p = 0.03). VSP-PSI and conventional mini-plate fixation can be considered equally stable. Large advancements with counterclockwise rotation regardless of fixation method are more susceptible to relapse. VSP-PSI alone cannot solve the relapse-related concerns in mandible osteotomy., Competing Interests: Declaration of competing interest J.S. has participated in congresses where attendance fees were in part or in total supported by DePuy Synthes or KLS Martin. Planmeca has provided materials and intelligent support for in vitro studies free of charge., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ticks are important vectors of zoonotic pathogens. Ticks are parasites that are dependent on their hosts for blood meal to develop and reproduce. The abundance of ticks is dependent on the availability of suitable breeding hosts, often medium- and large-sized mammals. So far there has been a shortage of direct methods identifying the breeding hosts for the female ticks. In this study, we introduce a stable isotope analysis (SIA) method that enables us to identify the trophic group of the breeding host, i.e. the host on which the tick mother fed, by sampling larval ticks from the field. We established a reference database on the stable isotope (SI) values (δ 13 C and δ 15 N) of the blood of potential tick host species, and of larvae from Ixodes ricinus females, which have fed on known hosts. By comparing the SI values from field collected larval ticks to our reference data, we can determine their most likely host species group. Our results show that the isotopic signatures of I. ricinus tick larvae reflect the diet of the breeding host of the mother tick. SIA proved reliable in categorizing the breeding hosts of I. ricinus into two distinguishable trophic groups; herbivores and carni-omnivores. To our knowledge, this is the first time that stable isotope analyses have been applied to detect transovarial (i.e. over-generational) traces of a blood meal in ticks. The method provides an efficient, novel tool for directly identifying tick breeding hosts by sampling field collected larvae. Ixodes ricinus is the most important vector of TBPs (tick-borne pathogens) in Europe, and to predict and mitigate against the future risks that TBPs pose, it is crucial to have detailed knowledge on the hosts that support tick reproduction in nature., Competing Interests: Declaration of Competing Interest The authors confirm no conflicts of interests., (Copyright © 2023. Published by Elsevier GmbH.)

Maleic acid functionalized boron nitride nanosheets (BNNS-MA)/Na-Alginate composite with enhanced mechanical, UV-shielding and antioxidation properties have been fabricated for the first time by solvent evaporation from a homogeneous aqueous dispersion of BNNS-MA/Na-Alginate composite solution. The composite fabrication was driven by homogenous nano-integrations and chemistry of compatibilization of BNNS-MA with Na-Alginate through H-bonding interactions between -COOH functional group of BNNS-MA and -OH, -COONa groups of Na-Alginate. The BNNS-MA/Na-Alginate composites show significant enhancement of mechanical, UV-blocking and antioxidant properties compared to the Na-Alginate. Integrating only 1 wt% BNNS-MA improved the UV-blocking, tensile strength, and antioxidant properties of Na-Alginate film by 99.1%, 73% and 60.3%, respectively. Overall, our findings of BNNS-MA integrated Na-Alginate composite films with improved physical, mechanical, UV shielding, and antioxidant functionalities is very promising to open new insight in the field of transparent UV-protected biopolymer film for consumer products, packaging, cosmetics, and engineering applications., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rama Layek reports financial support was provided by Kollin säätiö funding for biorefinery programme LUT University, Lahti campus., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cancer-associated thrombosis is a frequent complication in patients with malignancies. While factor XI (FXI)/FXIa inhibition is efficacious in preventing postoperative venous thromboembolism, its role in tumor cell-induced coagulation is less defined., Objectives: We thus aimed to provide mechanistic insights into FXI/FXIa inhibition in tumor cell-induced coagulation activation., Methods: Procoagulant activity (PCA) of 4 different tissue factor (TF) expressing tumor cell lines was analyzed by single-stage clotting and thrombin generation assay in the presence of a FXIa inhibitor, BMS-262084 (BMS), an inhibitory FXI antibody (anti-FXI), or peak and trough concentrations of rivaroxaban or tinzaparin. Further, tumor cell-induced platelet aggregation was recorded. Recombinant human TF served as positive control., Results: Although BMS and anti-FXI potently inhibited FXIa amidolytic activity, both inhibitors efficiently mitigated recombinant human TF- and tumor cell-induced fibrin clot formation and platelet aggregation only in the presence of low TF PCA. The anticoagulant effects showed an inverse correlation with the magnitude of cellular TF PCA expression. Similarly, BMS markedly interfered with tumor cell-induced thrombin generation, with the most prominent effects on peak and total thrombin. In addition, anticoagulant effects of FXIa inhibition by 10 μM BMS were in a similar range to those obtained by 600 nM rivaroxaban and 1.6 μM tinzaparin at low TF PCA levels. However, rivaroxaban and tinzaparin also exerted marked anticoagulant activity at high TF PCA levels., Conclusion: Our findings indicate that FXI/FXIa inhibition interferes with tumor cell-induced coagulation activation only at low TF PCA expression levels, a finding with potential implications for future in vivo studies., Competing Interests: Declaration of competing interests J.M., A.S., C.L., J.R., and L.B. declare no conflicts of interest relevant to the content of this article. C.C.R. has received travel support from Pfizer. M.V. declares personal fees for lectures from Bristol-Myers Squibb and travel support from Bayer, Bristol-Myers Squibb, and LEO Pharma. C.B. has received personal fees for consultancy, research support, and/or travel support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Novartis, Pfizer, Roche, and Sanofi. F.L. has received personal fees for lectures or consultancy and/or research support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, LEO Pharma, Pfizer, Sanofi, and Viatris., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)