Opportunistic Networks (OppNets) are characterized by intermittently connected nodes with fluctuating performance. Their dynamic topology, caused by node movement, activation, and deactivation, often relies on controlled flooding for routing, leading to significant resource consumption and network congestion. To address this challenge, we propose the Adaptive Clustering-based Routing Protocol (ACRP). This ACRP protocol uses the common member-based adaptive dynamic clustering approach to produce optimal clusters, and the OppNet is converted into a TCP/IP network. This protocol adaptively creates dynamic clusters in order to facilitate the routing by converting the network from a disjointed to a connected network. This strategy creates a persistent connection between nodes, resulting in more effective routing and enhanced network performance. It should be noted that ACRP is scalable and applicable to a variety of applications and scenarios, including smart cities, disaster management, military networks, and distant places with inadequate infrastructure. Simulation findings demonstrate that the ACRP protocol outperforms alternative clustering approaches such as kRop, QoS-OLSR, LBC, and CBVRP. The analysis of the ACRP approach reveals that it can boost packet delivery by 28% and improve average end-to-end, throughput, hop count, and reachability metrics by 42%, 45%, 44%, and 80%, respectively. Full article

Until recently, the diagnosis of feline infectious peritonitis (FIP) in cats usually led to euthanasia, but recent research has revealed that antiviral drugs, including the nucleoside analog GS-441524, have the potential to effectively cure FIP. Alpha-1-acid glycoprotein (AGP) has been suggested as a diagnostic marker for FIP. However, AGP quantification methods are not easily accessible. This study aimed to establish a Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL^TM) assay on the VetBio-1 analyzer to determine the AGP concentrations in feline serum and effusion samples. Linearity was found in serial dilutions between 1:2000 and 1:32,000; the intra-run and inter-run precision was <5% and <15%, respectively; and AGP was stable in serum stored for at least 8 days at room temperature, at 4 °C and at −20 °C. Cats with confirmed FIP had significantly higher serum AGP concentrations (median: 2954 µg/mL (range: 200–5861 µg/mL)) than those with other inflammatory diseases (median: 1734 µg/mL (305–3449 µg/mL)) and clinically healthy cats (median 235 µg/mL (range: 78–616 µg/mL); p_KW < 0.0001). The AGP concentrations were significantly higher in the effusions from cats with FIP than in those from diseased cats without FIP (p_MWU < 0.0001). The AGP concentrations in the serum of cats with FIP undergoing GS-441524 treatment showed a significant drop within the first seven days of treatment and reached normal levels after ~14 days. In conclusion, the VetBio-1 SPARCL^TM assay offers a precise, fast and cost-effective method to measure the AGP concentrations in serum and effusion samples of feline patients. The monitoring of the AGP concentration throughout FIP treatment provides a valuable marker to evaluate the treatment’s effectiveness and identify potential relapses at an early stage. Full article

Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies –with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer). Full article

Agricultural heritage includes both material and immaterial vestiges of past agricultural practices that are directly tied to human agriculture. It holds great ecological, cultural, commercial, and tourism value. There are not many historical sites available for developing agricultural heritage tourism right now, and no experience is ideal. This study used sophisticated PLS-SEM techniques and SmartPLS 3.3.9 software to carefully examine data, examine measurement and structural models, rigorously test hypotheses, determine the validity and reliability of the findings, and investigate potential moderating effects. To address the critical issue of brand loyalty in agricultural heritage tourism, this study developed and tested a comprehensive impact route, which was supported by an examination of 427 visitors’ cultural memories and brand experiences, demonstrating their critical role in influencing brand loyalty. The findings show the importance of cultural memory in shaping travelers’ brand experiences and loyalty. Furthermore, due to their unique characteristics, various groups react differently to each phase of the brand loyalty effect route. Full article

Over recent decades, historians, communities, and museum professionals have worked to share and understand stories of Indigenous Australian military service. This article posits that ephemera from the Australian War Memorial’s National Collection offer a tangible way to engage with personal stories and enrich the narrative(s) of Indigenous service in the Second World War. While many experiences were shared by the thousands of men and women who enlisted and served during the war, surviving ephemera and the related personal stories reveal the cultural, linguistic, and experiential diversity of the individuals who served. Using five case studies from the Australian War Memorial’s National Collection, this article explores the link between ephemera and stories of service and suggests that sharing these links with a wider audience can serve to broaden understandings of Indigenous service and sacrifice. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting individuals worldwide and characterized by deficits in social interaction along with the presence of restricted interest and repetitive behaviors. Despite decades of behavioral research, little is known about the brain mechanisms that influence social behaviors among children with ASD. This, in part, is due to limitations of traditional imaging techniques specifically targeting pediatric populations. As a portable and scalable optical brain monitoring technology, functional near infrared spectroscopy (fNIRS) provides a measure of cerebral hemodynamics related to sensory, motor, or cognitive function. Here, we utilized fNIRS to investigate the prefrontal cortex (PFC) activity of young children with ASD and with typical development while they watched social and nonsocial video clips. The PFC activity of ASD children was significantly higher for social stimuli at medial PFC, which is implicated in social cognition/processing. Moreover, this activity was also consistently correlated with clinical measures, and higher activation of the same brain area only during social video viewing was associated with more ASD symptoms. This is the first study to implement a neuroergonomics approach to investigate cognitive load in response to realistic, complex, and dynamic audiovisual social stimuli for young children with and without autism. Our results further confirm that new generation of portable fNIRS neuroimaging can be used for ecologically valid measurements of the brain function of toddlers and preschool children with ASD. Full article

The Bosniak classification of renal cysts aims to provide a probabilistic risk assessment indicating the likelihood of malignancy from imaging findings. Originally designed to classify adult renal cysts based on computed tomography findings, the Bosniak classification has been extended to pediatric patients, with some adjustments made with the aim of accommodating magnetic resonance imaging (MRI) and ultrasonography (US). Bosniak IV lesions are rare in adolescents, indicating localized renal cell carcinoma and requiring surgical intervention. In contrast, Bosniak III lesions can be treated conservatively, although there is a lack of specific guidelines on their management. We present a case of a 14-year-old boy with a Bosniak III lesion, which was incidentally detected during the US evaluation of a left varicocele. After a 12-month follow-up, MRI revealed progression to a Bosniak IV cyst. Robot-assisted tumor enucleation was performed with selective artery clamping when the patient was 15. Histopathology showed tubulocystic renal cell carcinoma without adverse features. Immunocytochemistry supported a favorable prognosis of this rare tumor (<1% of renal tumor), thus obviating the need for adjuvant treatment. At the 18-month follow-up, no recurrence or distant metastasis were observed. This case highlights the importance of an aggressive treatment in persistent Bosniak III and Bosniak IV renal cysts in children and adolescents and the necessity to offer a nephron-sparing surgery. Full article

This study aims to investigate the geopolymerization reaction of geopolymer foams produced with three different foaming agents: aluminum powder, zinc powder, and hydrogen peroxide. The geopolymerization reaction of geopolymer foam was monitored using the ²⁷Al and ²⁹Si magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy technique. ²⁷Al MAS-NMR was used to monitor the reaction at an early stage, while ²⁹Si and ²⁷Al MAS-NMR analyses were employed at specific time intervals of 3, 6, 10, 15, and 28 days to examine the changes that occurred in the formed gel over time. We discussed in detail how the type of foaming agent used and the duration of the reaction both influence the quantity of gel formed and the amount of remnant fly ash. Our findings indicate that the type of foaming agent used affects the formation and structure of the gel, with aluminum powder leading to the highest gel formation. Additionally, the duration of the reaction plays a significant role in determining the quantity of remnant fly ash, with longer reaction times resulting in decreased fly ash content. This study sheds light on the relevance of understanding the role of foaming agents in the geopolymerization reactions of geopolymer foams and the influence of reaction time on the formed gel properties. Full article

To modify the structure of thermal barrier coatings and improve their high-temperature resistance, induction plasma spheroidization (IPS) technology was applied to regulate the structure of YSZ powders in this study. The surface morphology, particle size distribution, phase composition, and internal microstructure of the conventional agglomerated and spheroidized powders were characterized using scanning electron microscopy and focused ion beam analysis methods. The results showed that the microstructure of the powders presented uneven evolution in the induction plasma stream. Due to the existence of the temperature gradient along the radial direction of the powders, the IPS powders consisted of outer dense shells and internal porous cores. The mechanical property of such shell–core structure was analyzed by using the finite elemental simulation method. In addition, coatings were prepared using the IPS powders and the agglomerated powders. The IPS coating showed improved water-cooling thermal cycling resistance compared to the conventional coating. Full article

Pseudokinases are catalytically inactive proteins in the human genome that lack the ability to transfer phosphate from ATP to their substrates. The Tribbles family of pseudokinases contains three members: Tribbles 1, 2, and 3. Tribbles 1 has recently gained importance because of its involvement in various diseases, including cancer. It acts as a scaffolding protein that brings about the degradation of its substrate proteins, such as C/EBPα/β, MLXIPL, and RAR/RXRα, among others, via the ubiquitin proteasome system. It also serves as an adapter protein, which sequesters different protein molecules and activates their downstream signaling, leading to processes, such as cell survival, cell proliferation, and lipid metabolism. It has been implicated in cancers such as AML, prostate cancer, breast cancer, CRC, HCC, and glioma, where it activates oncogenic signaling pathways such as PI3K-AKT and MAPK and inhibits the anti-tumor function of p53. TRIB1 also causes treatment resistance in cancers such as NSCLC, breast cancer, glioma, and promyelocytic leukemia. All these effects make TRIB1 a potential drug target. However, the lack of a catalytic domain renders TRIB1 “undruggable”, but knowledge about its structure, conformational changes during substrate binding, and substrate binding sites provides an opportunity to design small-molecule inhibitors against specific TRIB1 interactions. Full article

Analysis of non-Markovian systems and memory-induced phenomena poses an everlasting challenge in the realm of physics. As a paradigmatic example, we consider a classical Brownian particle of mass M subjected to an external force and exposed to correlated thermal fluctuations. We show that the recently developed approach to this system, in which its non-Markovian dynamics given by the Generalized Langevin Equation is approximated by its memoryless counterpart but with the effective particle mass $M^{\ast }<M$, can be derived within the Markovian embedding technique. Using this method, we calculate the first- and the second-order memory correction to Markovian dynamics of the Brownian particle for the memory kernel represented as the Prony series. The second one lowers the effective mass of the system further and improves the precision of the approximation. Our work opens the door for the derivation of higher-order memory corrections to Markovian Langevin dynamics. Full article

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations—specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06–32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04–0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively). Full article

Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. Methods: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. Results: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46–1.23]) or OS (HR 0.82, 95% CI [0.46–1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26–1.10). There was no difference in OS (HR 1.11, CI 0.55–2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24–0.43). Conclusions: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs. Full article

This study investigated exercise participation, health status, and barriers to exercise in 109 individuals with spinal cord injury (SCI) using a self-report questionnaire. The responses of the exercise and non-exercise groups were statistically analyzed using t-tests or Fisher’s exact test. Significant differences were observed in the cause of injury and the American Spinal Injury Association Impairment Scale between the groups. The non-exercise group had a higher incidence of traumatic and complete injuries. Demographic factors such as gender, age, income level, and marital status did not significantly influence exercise participation. The exercise group reported lower pain scores, less inconvenience from complications, and higher activity and participation scores. However, less than half of the individuals with SCI met the recommended exercise intensity, and community facility usage was low. Barriers to exercise participation included severe disabilities, lack of time, insufficient exercise information, and lack of facility accessibility. To enhance exercise among individuals with SCI, it is essential to develop and extend exercise programs tailored to individual physical factors and a comprehensive understanding of barriers. Prioritizing community-based data management, alongside developing social systems and health policies, is crucial to overcome barriers to exercise participation for individuals with SCI. Full article

The corrosion and degradation behavior of high-strength steel wires during service directly affect the safety and usability of suspenders in steel pipe concrete arch bridges. In this study, three different types of specimens were fabricated using steel wires extracted from the suspenders of an 11-year-old in-service arch bridge and subjected to accelerated corrosion tests with acetic acid. Considering the differential diffusion processes of corrosion factors caused by varying degrees of damage to the suspender sheath, the spatial corrosion variability of steel wires at different positions within the suspender cross-section was investigated. Experimental results indicated a two-stage characteristic in the corrosion process of individual galvanized steel wire samples. In the first corrosion stage, the microstructure on the corroded steel wire surface evolved from a dense crystalline structure to a porous one. In the second corrosion stage, corrosion products accumulate on the steel wire substrate, subsequently further aggregating into sheet-like structures. The maximum pitting factor of individual steel wire samples from a specific area could be described by a Type I extreme value distribution. In the time-dependent model that was established, the location parameter and scale parameter exhibited an exponential decrease during the first corrosion stage and a linear decrease during the second corrosion stage. In the absence of sheath protection, the coefficient of variation in corrosion among adjacent steel wires in the suspender followed a normal distribution. The spatial corrosion variability of the wires inside the suspender is significantly influenced by the shape of the suspender sheath damage. As the corrosion time increased, the overall discrepancy in corrosion levels among different layers of wires diminished. Full article

A simple and effective method to eliminate the organic component from mussel shells is presented. It is based on the use of hot hydrogen peroxide. Mollusc shells are composite materials made of a calcium carbonate matrix with different polymorphs and numerous biomacromolecules. The described method was used on mussel shells, but it is generalisable and allows the complete removal of these organic components, without altering the inorganic part. Specimens were kept in a H₂O₂ 40% bath for few hours at 70 °C. The organic layers found on the faces of the shells were peeled away in this way, and biomacromolecules were degraded and removed. Their fragments are soluble in aqueous solution. This easily permits the chemical-physical characterisation and the study of the microstructure. The quality of calcite and aragonite microcrystals of biogenic origin is very high, superior to that of materials of geological or synthetic origin. This may suggest various industrial applications for them. Calcium carbonate is a useful precursor for cements and other building materials, and the one obtained in this way is of excellent quality and high purity. Full article

Zero-discharge and low-input aquaponics systems are a promising alternative to the intensive agricultural and aquacultural production systems currently used, ensuring high environmental sustainability. However, new approaches and management practices are needed to increase their productivity to reach the yields of classic production systems. In this context, the present study investigated for the first time the potential of two biostimulants to improve lettuce performance in aquaponics, whether coupled or decoupled, with hydroponics serving as a control. A comprehensive evaluation was conducted to assess the plant functional (focusing on the photosynthetic process evaluation) and growth responses at the whole-plant level. In addition, the nutritional state of the leaves was determined and metabolomic analysis was performed at the cellular level, the latter also for the first time in aquaponics research. The results demonstrated the limitations that coupled aquaponics poses in relation to lettuce growth, function and metabolism, which were already obvious from the 12th day of the experiment. Indicatively, the plants grown under coupled aquaponics exhibited a notable decrease in the leaf fresh weight, potassium content and nitrogen content, with reductions of 80%, 60%, and 30%, respectively, in comparison to the hydroponics control. However, the combined physiological and metabolomic data indicate that these plants down-regulate processes and metabolism to acclimate to low nutrient levels in lettuce leaves rather than experiencing damage. The application of biostimulants did not significantly optimize the plants’ performance, though one of them appeared to be effective in improving some aspects of the photochemical efficiency. The decoupled and hydroponics systems resulted in similarly high yields and efficiency in terms of plant function, without any marked contribution from the biostimulants. We conclude that the decoupled aquaponics system has been successful in achieving yields comparable to those of hydroponics, with lower chemical inputs. Future studies should focus on examining other biostimulants in this system to further improve its performance while maintaining its environmental benefits within a circular economy framework. Full article

The rising prevalence of obesity in children calls for new strategies for the provision of effective care by a multidisciplinary team. Telemedicine has overall proven to be an effective tool for promoting a healthy lifestyle. The main objective of the current paper is to present the protocol of our ongoing CardioMetabolic Prevention (CAMP) study and compare its design with published studies on telemedicine in paediatric obesity. Additionally, we analysed the preliminary anthropometric and laboratory data to test the efficacy of our 12-week intensive program that combines in-person and telemedicine support. The program demonstrated a positive impact on body mass index (BMI) and its z-scores in 21 adolescents, and BMI in 18 participating parents. However, we found no effect on body composition, waist circumference, cardiometabolic parameters, or fitness evaluated via a 6-min walk test in adolescents. In conclusion, the combination of in-person and telemedicine intensive support over 35 h delivered by a multidisciplinary team can be beneficial not only for adolescents with obesity but also for their parents. The ongoing CAMP study serves as a platform for precision medicine in future decisions regarding anti-obesity medication in adolescents with obesity. Full article

The Laparoscopic Approach to Cervical Cancer (LACC) trial was published in 2018 and demonstrated that minimally invasive surgery (MIS) yields inferior survival outcomes in early-stage cervical cancer compared to open surgery. This study investigates how the results of the LACC trial have impacted the selection of the primary treatment modality and adjuvant radiation utilization in early-stage cervical cancer. Using the National Cancer Database (NCDB), we compared patients with stage IA2-IB1 cervical cancer before (1/2016–12/2017) and after (1/2019–12/2020) the LACC trial. A total of 7930 patients were included: 4609 before and 3321 after the LACC trial. There was a decline in MIS usage from 67% pre-LACC to 35% thereafter (p < 0.001). In both the pre- and post-LACC periods, patients undergoing radical MIS more frequently had small volume disease (pre-LACC tumors ≤ 2 cm, 48% MIS vs. 41% open, p = 0.023; post-LACC stage IA2, 22% vs. 15%, p = 0.002). Pre-LACC, MIS radical hysterectomy was associated with White race (82% vs. 77%, p = 0.001) and private insurance (63% vs. 54%, p = 0.004), while there was no difference in socioeconomic factors in the post-LACC period. Although the proportion of patients treated with primary chemoradiation remained stable, the post-LACC cohort had a younger median age (52.47 vs. 56.37, p = 0.005) and more microscopic disease cases (13% vs. 5.4%, p = 0.002). There was no difference in the rate of radiation after radical hysterectomy before and after the trial (26% vs. 24%, p = 0.3). Conclusions: Post-LACC, patients were less likely to undergo MIS but received adjuvant radiation at similar rates, and primary chemoradiation patients were younger and more likely to have microscopic disease. Full article

Despite recent advancements in antibiotics, hygienic measures, and peri-operative systemic antibiotics, post-operative infections in osteosynthesis remain prevalent and continue to be among the most common surgical complications, leading to delayed fracture healing, osteomyelitis, implant loosening, and loss of function. Osteosynthesis implants are routinely utilized in veterinary medicine and the current study investigates the microbial colonization of implants following osteosynthesis in small animals, along with its incidence and influencing factors. The results are analyzed in regard to correlations between infection, patient, disease progression, and radiographic images, as well as other factors that may promote infection. Seventy-one explants from sixty-five patients were examined and evaluated for microbial colonization. Factors like body weight and age, location and type of plate and additional injuries like lung lesions, the surgeon’s experience, or the number of people present during the surgical procedure seem to influence the development of an infection. Of the animals, 60% showed osteolytic changes and 73.3% of those with dysfunctional mobility had an implant infection. Microorganisms were detected in almost 50% of the explants, but a clinically relevant infection was only present in five patients (7.3%), suggesting that the presence of microorganisms on an implant does not necessarily lead to treatment complications. Full article

Exercise reduces the risk of inflammatory diseases by modulating different tissue and cell types, including those within the gastrointestinal tract. Obtaining a more comprehensive understanding of pathophysiology requires monitoring of dynamic changes in cometabolites. This study aimed to develop a method for determining gut microbiota–host cometabolites and indoleamines in human urine. Four key gut microbiota–host cometabolites were chromatographically separated by isocratic elution, with a running time of 10 min. The linearity of this method was confirmed over different concentration ranges: 1.0–400 ng/mL for melatonin (MEL), indole-3-propionic acid (3-IPA), indole (IND), and skatole (SKT). This method was extremely sensitive and stable and hence could be successfully applied to characterize the changes in gut microbiota–host cometabolites in human before- and after-running urine. The concentrations of MEL, 3-IPA, IND, and SKT in after-running urine were 84.0 ± 9.69, 25.9 ± 3.39, 343.7 ± 36.8, and 14.6 ± 1.36 ng/mL, respectively. Moreover, the concentrations in before-running urine were 54.2 ± 5.10, 14.4 ± 1.30, 250.8 ± 14.1, and 9.43 ± 1.07 ng/mL, respectively, which showed significantly less difference in concentrations (p < 0.05) in before- than after-running urine. Overall, the established method could simultaneously monitor gut microbiota–host cometabolites and hence can be further applied to clinical and comprehensive pathophysiological studies. Full article

Severe post-partum hemorrhage (PPH) is a major cause of maternal mortality worldwide. Recombinant activated factor VII (rFVIIa) has recently been approved by the European Medicines Agency for the treatment of severe PPH if uterotonics fail to achieve hemostasis. Although large randomized controlled trials are lacking, accumulated evidence from smaller studies and international registries supports the efficacy of rFVIIa alongside extended standard treatment to control severe PPH. Because rFVIIa neither substitutes the activity of a missing coagulation factor nor bypasses a coagulation defect in this population, it is not immediately evident how it exerts its beneficial effect. Here, we discuss possible mechanistic explanations for the efficacy of rFVIIa and the published evidence in patients with severe PPH. Recombinant FVIIa may not primarily increase systemic thrombin generation, but may promote local thrombin generation through binding to activated platelets at the site of vascular wall injury. This explanation may also address safety concerns that have been raised over the administration of a procoagulant molecule in a background of increased thromboembolic risk due to both pregnancy-related hemostatic changes and the hemorrhagic state. However, the available safety data for this and other indications are reassuring and the rates of thromboembolic events do not appear to be increased in women with severe PPH treated with rFVIIa. We recommend that the administration of rFVIIa be considered before dilutional coagulopathy develops and used to support the current standard treatment in certain patients with severe PPH. Full article