Aims: Tyrosine kinase inhibitors (TKIs) improve patient outcomes, but the prevalence of clinically significant TKI-associated drug–drug interaction (DDI) is unknown. We aim to assess the risk prevalence between TKIs and other drugs in cancer patients. Methods: This was a retrospective cross-sectional study conducted in three tertiary care hospitals. All medical data were collected in the computer-based medication prescription system from January 2020 to December 2020. The hazardous DDIs identification has been performed using US Food and Drug Administration-approved labels. Descriptive statistics and univariate and multivariate logistic regression analyses were applied to identify risk factors associated with potential hazardous interactions. Results: A total of 2754 patients were included in our study. 413 hazardous DDIs were identified and 387 (14.1%) patients experienced at least one DDI. Proton pump inhibitor, dexamethasone and fluoroquinolones were most frequently implicated in clinically relevant DDIs with TKIs. In a multivariate analysis, younger age, the number of drugs and lung cancer had a higher risk for the occurrence of hazardous DDIs. Conclusions: The prevalence of hazardous DDIs is relatively high in the cancer patient population receiving TKIs treatment. The awareness of potential clinically relevant DDIs can help patients reduce the probability of adverse event of drugs.

Objectives: Mental-health issues accounted for 418 million disability-adjusted life years in 2019, costing the world economy approximately US$5 trillion. Untreated hearing loss is a well-known modifiable risk factor for mental-health issues, with severe-to-profound hearing loss having the largest impact. Therefore, treatment of severe-to-profound hearing loss, namely with cochlear implantation, could help to alleviate psychological distress. However, previous studies have failed to include comprehensive measures of mental health or adequate controls. The current study thus aimed to conduct a controlled, longitudinal investigation of how cochlear implantation affects depression, anxiety, and stress levels. Participants: Participants were 87 adults assigned to conditions based on hearing status: normal hearing ( n = 44), received cochlear implant ( n = 26), or untreated hearing loss ( n = 17). Main Outcome Measures: The short-form Depression Anxiety Stress Scale was given at four timepoints (baseline, three months, six months, 12 months). Data were analysed with linear mixed-effects modelling. Results: Results showed that cochlear implants helped to stabilise anxiety and stress symptoms, while depression symptoms were observed to worsen over time despite treatment. Conclusion: Our findings suggest that treatment of severe-to-profound hearing loss with cochlear implantation can help to alleviate associated anxiety and stress symptoms; associated depressive symptoms did not benefit. Due to the current study’s non-randomised treatment allocation, future randomised controlled trials are required for confirmation. The present findings help inform clinical and societal interventions for mental-health issues associated with hearing loss.

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In degraded ecosystems, soil microbial communities (SMCs) may influence the outcomes of ecological restoration. Restoration practices can affect SMCs, though it is unclear how variation in the onset of restoration activities in woodlands affects SMCs, how those SMCs influence the performance of hard-to-establish woodland forbs, and how different woodland forbs shape SMCs. In this study, we quantified soil properties and species abundances in an oak woodland restoration chronosequence (young, intermediate, and old restorations). We measured growth of three woodland forb species when inoculated with live whole-soil from young, intermediate, or old restorations. We used DNA metabarcoding to characterize SMCs of each inoculum treatment and the soil after conditioning by each plant species. Our goals were to: 1) understand how time since onset of restoration affected soil abiotic properties, plant communities, and SMCs in a restoration chronosequence, 2) test growth-responses of three forb species to whole-soil inoculum from restoration sites, and 3) characterize changes in SMCs before and after conditioning by each forb species. Younger restored woodlands had greater fire-sensitive tree species and lower concentrations of soil phosphorous than intermediate or older restored woodlands. Bacterial and fungal soil communities varied significantly among sites. Forbs exhibited greater growth in soil from the young restoration. Each forb species developed unique soil microbial community. Our results highlight how restoration practices affect SMCs, which can in turn affect growth of hard-to-establish forb species. Our results also highlight that the choice of forb species can have major effects on SMCs, with long-term potential consequences for restoration success.

Tracking control of tendon-driven manipulators has become a prevalent research area. However, the existence of flexible elastic tendons generates substantial residual vibrations, resulting in difficulties for trajectory tracking control of the manipulator. This paper proposes the radial basis function neural network adaptive hierarchical sliding mode control (RBFNNA-HSMC) method, which combines the dynamic model of the elastic tendon-driven manipulator (ETDM) with radial basis neural network adaptive control and hierarchical sliding mode control technology. The aim is to achieve trajectory tracking control of ETDM even under conditions of model inaccuracy and disturbance. The Lyapunov stability theory demonstrates the stability of the proposed RBFNNA-HSM controller. In order to assess the effectiveness and adaptability of the proposed control method, simulations and experiments were performed on a two-DOF ETDM. The RBFNNA-HSM method shows superior tracking accuracy compared to traditional model-based HSM control. The experiment shows that the maximum tracking error for ETDM double-joint trajectory tracking is below 2.593×10 -3 rad and 1.624×10 -3 rad, respectively.

To the Editor,

Present analysis based upon the Marangoni convection of the nanofluid past a linearly expanding sheet with the help of convective heat transfer properties. Considering the base fluids as Ethylene glycol (C 2H 6O 2) and Water (H 2O) the γ - Al 2 O 3 nanoparticle is submerged into it to carry over the flow phenomena. The characteristics of the flow across a permeable medium under nonlinear thermal radiation, that influences the heat transport properties of nanofluid are studied. This research was motivated by the growing significance of nanofluids in numerous scientific and technical domains due to their distinctive and diverse applications and efficient thermal activities. Magnetic refrigeration, medication delivery, cancer treatment, and magnetic resonance imaging (MRI) are a few examples of potential uses for these fluids. The given flow problem is simulated using nonlinear partial differential equations (PDEs) in accordance with the laws of momentum and energy conservation. The resulting PDEs are converted into nonlinear ODEs with smaller dimensions by applying a similarity transformation. The influences of the controlling parameters on the flow model along with the rate coefficients are obtained via graphs. Significant increase in nanofluid temperature is marked in case of water-based nanofluid for the augmentation in water-base fluid further opposite impact is rendered in case of EG-based nanofluid.

Link prediction is a fundamental problem for graphs, which can reveal the potential relationships between users. Graph embedding can easily encode graph structural relations, and heterogeneous attribute features in a continuous vector space, which is effective in link prediction. However, graph embedding methods for large-scale graphs suffer high computation and space costs, and sampling enclosing subgraphs is a practical yet efficient way to obtain the most features at the least cost. Nevertheless, the existing sampling techniques may lose essential features when the random sampling number of nodes is not large, as node features are assumed to follow a uniform distribution. In this paper, we propose a novel enclosing subgraph embedding model named Weighted Sampling Enclosing-subgraph Embedding (WSEE) to resolve this issue, which maximumly preserves the structural and attribute features of enclosing subgraphs with less sampling. More specifically, we first extract the feature importance of each node in an enclosing subgraph and then take the node importance as node weight. Then, random walks node sequences are obtained by multiple weighted random walks from a target pair of nodes, generating a weighted sampling enclosing subgraph. By leveraging the weighted sampling enclosing subgraph, WSEE can scale to larger graphs with much less overhead while maintaining some essential information of the original graph. Experiments on real-world datasets demonstrate that our model can scale to larger graphs with acceptable overhead while link prediction performance is unaffected.

The Percidae family comprises many fish species of major importance for aquaculture and fisheries. Based on three new chromosome-scale assemblies in Perca fluviatilis, Perca schrenkii and Sander vitreus along with additional percid fish reference genomes, we provide an evolutionary and comparative genomic analysis of their sex-determination systems. We explored the fate of a duplicated anti-Mullerian hormone receptor type-2 gene (amhr2bY), previously suggested to be the master sex determining (MSD) gene in P. flavescens. Phylogenetically related and structurally similar amhr2 duplications (amhr2b) were found in P. schrenkii and Sander lucioperca, potentially dating this duplication event to their last common ancestor around 19-27 Mya. In P. fluviatilis and S. vitreus, this amhr2b duplicate has been lost while it was subject to amplification in S. lucioperca. Analyses of the amhr2b locus in P. schrenkii suggest that this duplication could be also male-specific as it is in P. flavescens. In P. fluviatilis, a relatively small (100 kb) non-recombinant sex-determining region (SDR) was characterized on chromosome-18 using population-genomics approaches. This SDR is characterized by many male-specific single-nucleotide variants (SNVs) and no large duplication/insertion event, suggesting that P. fluviatilis has a male heterogametic sex determination system (XX/XY), generated by allelic diversification. This SDR contains six annotated genes, including three (c18h1orf198, hsdl1, tbc1d32) with higher expression in testis than ovary. Together, our results provide a new example of the highly dynamic sex chromosome turnover in teleosts and provide new genomic resources for Percidae, including sex-genotyping tools for all three known Perca species.

Background and Purpose: Macrophages not only can maintain gut immune homeostasis by driving clearance of infection, but also can prevent chronic inflammation and induce tissue repair. Macrophages are a heterogenous group of cells whose characteristics are determined by tissue microenvironment and metabolism. Since macrophages play an important role in inflammatory disorders such as inflammatory bowel disease (IBD), they can be a potential therapeutic target. Experimental Approach: Here we show an IBD therapeutic candidate LMT503, a substrate which modulates NADH quinone oxidoreductase 1, which enhances NAD+ and induce anti-inflammatory macrophage polarization. To determine the anti-inflammatory effect of LMT503, a dextran sulfate sodium (DSS)-induced colitis mouse model was used in this study. Key Results: Treatment of bone marrow derived macrophages (BMDMs) with LMT503 increased IL-10 and Arg1 levels but decreased levels of TNF-α, iNOS, and IL-6. LMT503 also increased levels of SIRT1, SIRT3, and SIRT6, suggesting that macrophages were driven to an anti-inflammatory character. In a murine DSS-induced colitis model, oral treatment with LMT503 ameliorated colonic inflammation and decreased infiltrating monocytes and neutrophils. Although NAD+ enhancement did not alter CX3CR1intCD206- or CX3CR1hiCD206+ colon macrophage population, it decreased levels of TNF-α and iNOS and increased IL-10 level, with colonic macrophages showing an anti-inflammatory character shift. Depletion of CX3CR1 expressing gut resident macrophages abrogated the immune regulatory effect of LMT503 in the colon. Conclusion and Implications: These data suggest that LMT503 is a therapeutic candidate that can target macrophages to drive polarization with an immunosuppressive character and ameliorate IBD.

A Case of Ulcerative Colitis Complicated by a Simple Appendiceal OpeningXiao Liu1*, Fang Fang2，Qingfeng Luo11 Department of Gastroenterology, Beijing Hospital, National Center of Gerontology；Institute of Geriatric Medicine, Chinese Academy of Medical Sciences，P.R. China2 Department of pathology, Beijing Hospital, National Center of Gerontology；Institute of Geriatric Medicine, Chinese Academy of Medical Sciences，P.R. ChinaEmail: liuxiao3424@bjhmoh.cn

Antimicrobial Resistance (AMR) arises when microorganisms develop resistance to formerly effective medications. This poses a significant global threat, impacting healthcare systems and economies. AMR leads to severe illnesses, prolonged hospitalizations, and increased costs, with millions affected annually, particularly those with chronic conditions. It’s a pressing issue, especially exemplified by multi-drug resistant (MDR) bacteria including methicillin-resistant Staphylococcus aureus (MRSA), making treatment more challenging. Biofilms, once overlooked, now demand attention. Addressing biofilms in chronic infections is crucial. Urgent measures are needed, targeting biofilm-forming bacteria using alternative strategies due to their resistance to standard treatments. This study focused on evaluating phytocompounds from Nigella sativa against S. aureus biofilms, with a specific focus on clumping factor B (ClfB). Chlorogenic acid emerged as a lead compound based on binding energy (-8.4 kcal/mol) and binding site analysis. The analysis of molecular dynamics data affirms that chlorogenic acid formed a stable complex with the ClfB under physiological conditions. Additionally, in vitro testing validated the effectiveness of chlorogenic acid against biofilms, leading to approximately a 60% reduction in biofilm formation in S. aureus MTCC 3160. The thorough evaluation of biofilm through both light microscopy and electron microscopy revealed that chlorogenic acid treatment reduced biofilm formation and resulted in decreased bacterial colonization. Furthermore, the clustering of bacteria on the glass surface diminished in presence of chlorogenic acid. The findings of this study establish a foundation for the utilization of chlorogenic acid as an effective antibiofilm agent against S. aureus, offering a novel perspective for the development of antibacterial medications.

Currently, the majority of single image super-resolution algorithms based on convolutional neural networks presume that image degradation is always bicubic down sampling. In practice, however, the mechanism of medical image degradation is considerably more complicated than the Artificially simulated degradation. When the medical image degradation differs from the presumption, this algorithm performs significantly worse than anticipated. we use a degradation comparative learning to solve such problems. In addition, many CNN-based methods currently treat various channels equally, despite the fact that their information content is not equal, resulting in the underutilization of a great deal of information. As a result, the reconstructed SR pictures' texture features are not sufficiently rich. In order to solve these issues, this paper suggests a blind image super-resolution approach based on edge reconstruction and an image feature supplement module. This method reconstructs high-resolution images with rich texture information from low-resolution images and accomplishes excellent performance in the stable restoration of various degraded SR images. By comparing our approach to other blind SR approaches using natural picture testing datasets and medical images, we were able to show that it outperformed them. The results of the experiments demonstrate that our method is superior to the most cutting-edge ones currently in use.

Undifferentiated Pleomorphic Sarcoma of the Sigmoid Colon: A case report1,2, * Yuxia Yang, 1,2Yuchang Hu,2Mengxi He,1,2Min ChengThe First College of Clinical Medical Science, China Three Gorges University.Department of Pathology, Yichang Central People’s Hospital, Yichang, China)Corresponding author: Yuxia YangCorresponding author address:2916087819@qq.comYuxia Yang：2916087819@qq.com , Master’s DegreeYuchang Hu:huyuchang@hotmail.com, Master’s DegreeMengxi He: 452818936@qq.com, Master’s DegreeMin Cheng: 371227344@qq.com, Master’s DegreeFunding information: This study did not receive any funding in any form.Acknowledgements: Thanks to my tutor, family and colleagues.Ethics statement: Our institution does not require ethical approval for reporting individual cases or case series.Statement of informed consent: Written informed consent was obtained from the patient for their anonymized information to be published in this article.Conflict of interest statement: All authors declare that they have no competing interests.Data sharing statement: Data sharing is not applicable to this article as no new data were created or analyzed in this study.Key clinical message: Elderly patients with abdominal pain are easy to be misdiagnosed as gastrointestinal cancer. The possibility of UPS should be recognized in clinical work.Abstract: UPS is the most common soft tissue malignant tumor in the elderly. It usually occurs in the proximal limbs and retroperitoneum, and is usually manifested as a progressively enlarged painless mass. Due to its histological aggressiveness, it has a poor prognosis, with a five-year survival rate of less than 50% and frequent metastasis or recurrence. UPS in the colon is rare. Due to its special location, atypical clinical manifestations, and lack of characteristic pathological signs, the diagnosis is usually a diagnosis of exclusion. Early and complete resection of the tumor is the main treatment for UPS. Although some studies have shown that postoperative adjuvant radiotherapy and chemotherapy have a certain local control rate, the effect of radiotherapy and chemotherapy is not completely certain, and more cases are needed to further study its efficacy.Key words: Undifferentiated pleomorphic sarcoma, colon, treatment.IntroductionUndifferentiated pleomorphic sarcoma UPS is the most common soft tissue malignant tumor in the elderly. It usually occurs in the proximal limbs and retroperitoneum, and is usually manifested as a progressively enlarged painless mass[1]. Due to its histological aggressiveness, it has a poor prognosis, with a five-year survival rate of less than 50% and frequent metastasis or recurrence. UPS in the colon is rare. Due to its special location, atypical clinical manifestations, and lack of characteristic pathological signs, the diagnosis is usually a diagnosis of exclusion. Early and complete resection of the tumor is the main treatment for UPS. Although some studies have shown that postoperative adjuvant radiotherapy and chemotherapy have a certain local control rate[2], the effect of radiotherapy and chemotherapy is not completely certain, and more cases are needed to further study its efficacy.Case reportA 54-year-old man was admitted to the hospital due to left abdominal pain for 1 week. The pain was persistent and tolerable, without other accompanying symptoms. Abdominal Computed tomography (CT) scan showed a huge mass of mixed density shadow in the lower abdomen and pelvis, the size was about 16.3*6.8cm. Enhanced scan showed uneven enhancement of the lesion, and the mass was closely related to the intestine, and the boundary was not clear (Figure 1). The tumor was suspected as gastrointestinal stromal tumor. During the operation, a new tumor was found on the serosal surface of the sigmoid colon, with the size of 19cm*14cm*10cm, and no metastatic lesions were found around it (Figure 2). Gross examination showed that the tumor was encapsulated on the surface, with rich blood vessels. The cut surface was gray white and gray red, which was cystic and solid, soft in texture, containing a large amount of mucus, accompanied by necrosis and hemorrhage in some areas. Microscopically, the tumor cells were arranged disorderly, irregularly shaped, varying in size, with obvious atypia, numerous mitotic figures, prominent nucleoli, and a large number of tumor giant cells and multinucleated tumor giant cells (Figure 3). The tumor stroma was rich in blood vessels with myxoid degeneration. Immunohistochemically, the tumor cells showed a high Ki-67 proliferation index, focally positive for CD34 and S-100 (Figure 4), and a mutant expression pattern of P53. The pathological diagnosis was high-grade undifferentiated pleomorphic sarcoma with negative margins (no tumor cells in the margins). The patient did not receive any adjuvant therapy after surgery. Three months later, CT scan showed multiple mixed density shadows in the lower abdomen and pelvis, considering tumor metastasis or recurrence.DiscussionsHigh-grade undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma (MFH), is characterized by a progressively enlarged, painless mass[1]. It mainly occurs in the soft tissues of the extremities and the retroperitoneum, and rarely occurs in the digestive tract. Grossly, the tumor was a solitary nodule with a fish-like, offwhite to brown cut surface. Hemorrhage and necrosis were common[1]. UPS of the colon may originate from mesenchymal stem cells in the mesentery[3][4]. Histologically, UPS of the colon is characterized by large atypical cells with more mitoses and prominent nucleoli. The atypical cells can show different morphologies, including pleomorphic, myxoid, xantomatous, giant cell and angiomatoid types. They are broadly positive for CD68 and vimentin, and focally positive for CK and EMA. Due to its high degree of malignancy and strong invasion, it is easy to relapse and distant metastasis after surgery. Distant metastasis is most common in lung, followed by bone and liver[5][6]. Wide resection with negative resection margins (RO resection) is the main treatment for UPS, and negative resection margins help to reduce the risk of tumor recurrence. However, the recurrence rate of UPS is still high, and the 5-year survival rate is less than 50%. Tumor size, location, degree of differentiation and completeness of surgery are closely related to the prognosis of UPS[5]. The effects of postoperative adjuvant radiotherapy and chemotherapy have not been reported, but some studies have shown that compared with surgery alone, although adjuvant radiotherapy and chemotherapy can’t improve the overall survival rate, they can significantly improve the local control rate of high-grade soft tissue sarcoma[2].ConclusionsDue to the low incidence of UPS, there are few cases available for clinical study, and the effective treatment of this disease still needs further research. UPS arising from the colon is rare. For patients with abdominal pain and obvious abdominal mass, the possibility of UPS should be considered. Early and complete resection of the mass is the main treatment.Author contributions:Conceptualization: Yuchang Hu, Yuxia YangData curation: Mengxi He, Yuxia YangSupervision: Mengxi HeSoftware: Yuchang Hu, Min ChengWriting – original draft: Yuxia Yang, Mengxi He, Min ChengWriting – review & editing: Yuchang Hu, Yuxia YangAbbreviations:UPS= Undifferentiated pleomorphic sarcomaCT= Computed tomographyMFH= Malignant fibrous histiocytomaEMA= Epithelial membrane antigenReferencesKuboyama Y, Ousaka Y, Kato F, et al. Gan To Kagaku Ryoho. 2020;47(13):2180-2182.Jeon WJ, Moon JH, Pham B, Joung B, Denham L, Brothers J. Case Report: An exceptional response to neoadjuvant radiotherapy and chemotherapy in undifferentiated pleomorphic sarcoma following checkpoint inhibitor use. Front Oncol. 2023;13:1198292. Published 2023 Jun 23. doi:10.3389/fonc.2023.1198292.Han X, Zhao L, Mu Y, Liu G, Zhao G, He H, Wang S, Li J. Undifferentiated high-grade pleomorphic sarcoma of the colon: a rare case report and literature review. BMC Gastroenterol. 2022 Mar 10;22(1):115. doi: 10.1186/s12876-022-02189-x.Kodera K, Hoshino M, Takahashi S, et al. Surgical management of primary undifferentiated pleomorphic sarcoma of the rectum: a case report and review of the literature. World J Surg Oncol. 2022;20(1):199. Published 2022 Jun 13. doi:10.1186/s12957-022-02671-6.Winchester D, Lehman J, Tello T, et al. Undifferentiated pleomorphic sarcoma: Factors predictive of adverse outcomes. J Am Acad Dermatol. 2018;79(5):853-859. doi:10.1016/j.jaad.2018.05.022.Maçaneiro CH, Baptista AM, Camargo OP, Filippi RZ, Oliveira ET. UNDIFFERENTIATED PLEOMORPHIC SARCOMA: PROGNOSTIC FACTORS IN 42 EXTREMITY CASES. Acta Ortop Bras. 2023;31(2):e265942. Published 2023 May 1. doi:10.1590/1413-785220233102e265942

IntroductionLiposarcoma, a prevalent form of soft tissue malignancy in adults, accounts for approximately 20% of all soft tissue malignancies [1]. While it commonly occurs in the retroperitoneum, trunk and extremities, its occurrence within the gastrointestinal tract is rare, with an autopsy-reported occurrence rate ranging from 0.1% to 5.8% [2]. Specifically, esophageal liposarcoma represents an extremely uncommon subset, comprising only 1.2% to 1.% of all gastrointestinal liposarcomas [2].The initial documentation of esophageal liposarcoma dates back to 1983, when Mansour first described its presence [3]. Since then, few cases of this rare condition have been reported in the available literature, with approximately 60 cases documented to date [4]. Notably, the existing literature primarily focuses on the pathological features and surgical treatment, without comprehensive exploration of the associated imaging manifestations.In this study, we present a case of giant liposarcoma of the esophagus, accompanied by detailed imaging findings. Our aim is to contribute to the limited body of knowledge surrounding the radiological features of this extremely rare entity.

The 0–2.5 Ma volcanism in Easter Island (Rapa Nui) emerges just east of the East Pacific Rise on young (Pliocene, 3–4.8 Ma) ocean floor. Here, we report the finding of mantle-derived zircon grains retrieved from Easter Island beach sands and red soils that are much older than the Easter Island volcanism and its underlying lithosphere. A large population of 0–165 Myr old zircons have coherent oxygen (δ18O(zircon) 3.8– 5.9‰) and hafnium mantle isotopic signatures (εHf(t) +3.5–+12.5). These results are consistent with the crystallization of zircon from plume-related melts. In addition, a chemically diverse population with ages as old as Precambrian was also found. We thus suggest that the Easter hotspot started at least ~165 Ma ago. A large population of ~160-164 Ma zircons could signal an intense initial massive melting phase associated with the formation of a Large Igneous Province (LIP) upon the first arrival of the plume. We use plate reconstructions to show that such a LIP would have formed on the Phoenix Plate. It would have subducted below the Antarctic Peninsula around 100-105 Ma, offering a solution for the enigmatic Palmer Land deformation event, previously proposed to result from a collision with an unknown indenter. Our findings show that asthenospheric mantle-derived xenocryst zircon cargo, as recently reported from Galápagos, may not be an exception. The here-reported “ghost” of a prolonged hotspot activity suggests that the Easter hotspot and the sub-lithospheric mantle in which it is entrained remained mantle-stationary for at least 165 Ma.

Heterogeneous chemical cycles of pyrogenic nitrogen and halides influence tropospheric ozone and affect the stratosphere during extreme pyrocumulonimbus (PyroCB) events. We report field-derived N2O5 uptake coefficients, γ(N2O5), and ClNO2 yields, φ(ClNO2), from two aircraft campaigns observing fresh smoke in the lower and mid troposphere and processed/aged smoke in the upper troposphere and lower stratosphere (UTLS). Derived φ(ClNO2) varied across the full 0–1 range but was typically < 0.5 and smallest in a PyroCB (< 0.05). Derived γ(N2O5) was low in agricultural smoke (0.2–3.6 ×10-3), extremely low in mid-tropospheric wildfire smoke (0.1 × 10-3), but larger in PyroCB processed smoke (0.7–5.0 × 10–3). Aged BB aerosol in the UTLS had a higher median γ(N2O5) of 17 × 10–3 that increased with sulfate and liquid water, but that was nevertheless 1–2 orders of magnitude lower than values for aqueous sulfuric aerosol used in stratospheric models.

A novel probability distribution, the Generalized Alpha Power Inverted Weibull (GAPIW) distribution, is derived from the generalization of the -power family and compounded with the inverted Weibull distribution. The researchers have extensively explored various sub-models and established essential properties of the GAPIW distribution, including the quintile function, median, mode, moments, mean residual lifetime, and stress-strength reliability. The estimation of distribution parameters was carried out through maximum likelihood estimation methods. To gain insights into the characteristics of the GAPIW distribution, the study applied it to the analysis of air pollution data, specifically PM2.5, PM10, and TSP data from multiple stations in the Kathmandu Valley, including Bhaktapur, Bhaisepati, Kirtipur, and Ratna Park. Notably, the findings indicate that air quality in these areas was significantly worse during winter than in other seasons. Also, the ratio (PM2.5/PM10) of particulate matter is higher, indicating air pollution from anthropogenesis particles in the Valley. The results demonstrate that the GAPIW distribution is validated through different diagrammatic representations, such as P-P plots, Q-Q plots, and mathematical calculations like the K-S test. The findings reveal that, on average, only three days per month or one month per year predict air pollution levels below the threshold in the Kathmandu Valley. Furthermore, compared to others -power family of distribution available in the literature, the proposed GAPIW distribution stands as a viable alternative model for assessing and understanding air pollution data and related environmental data. This research has the potential to make valuable contributions to the field of environmental science and air quality monitoring.

Long-Term Retention of a Large Intraconal Stick Associated with a Discharging Fistula and Optic Nerve Granuloma

Half of patients with renal cell carcinoma (RCC) will develop metastases. The disease is likely to be curable at early stages but incurable when metastatic. New and non-invasive biomarkers are needed for the diagnosis of RCC. Extracellular vesicles (EVs) are considered promising new biomarker targets for the diagnosis of various diseases. Our study aimed to develop an EV-based assay for the detection of RCC using a highly sensitive nanoparticle-aided time-resolved fluorescence immunoassay (NP-TRFIA). To confirm that the tetraspanins were located on EVs, we used size exclusion chromatography to separate EV- and PE (protein-enriched)-fractions from RCC4 and 786-O RCC cancer cell lines and HEK293. EV- and PE-fractions were quantified using NP-TRFIA assays established for tetraspanins CD9, CD63, CD81, and CD151. Tetraspanin biomarkers were further measured from RCC cell culture medium as well as serum samples of RCC (n=14), benign (n=17), and healthy (n=9) individuals. Among the tetraspanins, CD63 showed 3-5-fold higher expression on EVs derived from RCC4 and 786-O cell lines compared to those from the HEK293. A sandwich CD63-CD63 assay demonstrated significant discrimination of RCC patients from benign (p=0.0003), and healthy (p= 0.005) individuals, respectively. Similarly, the CD81-CD81 assay also enabled significant separation of RCC patients compared to benign (p=0.014), and healthy (p= 0.003) controls, respectively. This result suggests that RCC cell lines and serum of RCC patients show higher amounts of CD63- and CD81-enriched EVs compared to controls. Detection of these tetraspanin-enriched EVs using our NP-TRFIA approach may play a vital role in the detection of RCC.

Background: Cellular migration is important for physiological and pathological processes. As such, angiogenesis and regenerative wound healing are reliant on the promotion of distinct endothelial cell phenotypes exhibiting increased migratory capacity. Functional monitoring of these hallmark events in vitro is invaluable for discovering novel therapeutics. However, while respective methods are usually simple and economic, they often lack a high-throughput character or accurate analysis tools, which are essential for effective screening suitability. Experimental approach: We stained nuclei of confluent human umbilical vein endothelial cells with Hoechst33342 prior to induction of an artificial scratch wound. Treatments with various growth factors and several concentrations of nintedanib were performed to evaluate impacts on wound closure. Images were taken frequently over 24 h to achieve high time-resolution. We developed an ImageJ macro and a Python script for automated analysis of these image sets. Utilizing cell-free area measuring or cellular density evaluation, respectively, cellular migration behavior was assessed well-wise for each time point. Key results: We proved the functionality of our novel tools and identified pro-migratory effects of interleukin 1β as well as inhibitory actions of nintedanib. Hoechst33342 staining allowed for cell counting which could be excluded as a contributing factor to wound closure in our assay. Conclusion: We herein developed a cost-effective, high-throughput pipeline that allows to monitor endothelial cell migration in vitro. We believe that our protocol will significantly accelerate pre-clinical screenings not only for medications targeting angiogenic processes but also drug discovery research in a broad range of diseases with altered vascularization.

Introduction Patients with food allergies necessite having personalized information on their risk of reaction in “real-life” situations. This multicentric study aimed to investigate the link during accidental reactions between the nature and amount of food allergens consumed in “real life situation” and the severity of the symptoms. Methods Patients were prospectively recruited from the 1 st of December 2020 to the 31 st of December 2021 at the emergency departments in the Geneva University Hospitals and local pediatric urgent care, trough the allergology outpatient consultation, at school and daycare facilities and trough their primary care physicians. Medical history of patients presenting reactions suggestive with immediate food allergy and suspected food samples were collected. Allergy diagnostic tests were retrospectively and prospectively collected. The samples were analyzed for their allergen content. Results We recruited 147 subjects with an accidental immediate-type allergic reaction to a food. We were able to collect 115 reaction-eliciting food samples allowing to quantify the allergen amount occasioning the reaction, as well as correlating this amount to the severity of the reaction. Children represented a large part of the reactors, and most reactions were to common food allergens such as tree nuts, cow’s milk as well as peanuts and hen’s egg. Reactions were mostly to pre-packaged foods and seven were to products with Precautionary allergy labeling, or without labelling to the corresponding allergen. Reactions were of various degrees of severity, and independent to the amount of allergen ingested. Discussion The severity of reactions did not show a direct correlation with allergen quantity, emphasizing individual sensitivity. Some reactions occurred with allergen amounts significantly below the legal limit for mandatory labelling of 1 g/kg in Switzerland. The study also highlighted considerable variability in allergen concentrations in foods labeled with possible “contaminations” or “traces.” These findings raise questions about the accuracy of allergen labeling and regulations.

Aims This randomized controlled pilot study aimed to assess the differences in the frequency, type, and severity of prescribing errors made by medical students when assessed in an electronic prescribing system (EPS) compared to traditional prescribing methods (e.g., writing/typing out a prescription). Methods Fourth year medical students in the period of November 1st to July 31st, 2023, were asked to participate in this single center prospective, randomized, controlled intervention study. Participants performed a prescribing assessment in either an EPS (intervention group) or in a more traditional prescribing platform (control group). The prescriptions were checked for errors, graded, and categorized. Differences in prescribing errors, error categories, and severity were analyzed. Results Out of 334 students, 84 participated in the study. Nearly all participants (98.8%) made one or more prescribing errors, primarily involving inadequate information errors. In the intervention group, more participants made prescribing errors involving the prescribed amount (71.4% vs. 19.0%; P<0.01), but fewer involving administrative errors (2.4% vs. 19.0%; P=0.03). Prescribing-method-specific errors were identified in 4.8% and 40.5% of the intervention and control group, respectively, with significant differences in overlapping errors as well. Conclusions This study shows the importance of training electronic prescribing (e-prescribing) competencies in medical curricula, in addition to traditional prescribing methods. It identifies prescribing-method-specific prescribing errors and emphasizes the need for further research to define e-prescribing competencies. Additionally, the need for an accessible real-life-like e-prescribing environment tailored to educators and students is essential for effective learning and incorporation of e-prescribing into medical curricula.

Background: The respiratory diseases represent an important cause of morbidity and mortality in the pediatric age group, considered a public health problem and generate a great economic impact given the frequent use of the health system. The current study aims to verify the correlation of respiratory syncytial virus with the main risk factors associated with recurrent wheezing in hospitalized infants. Methods: Cross-sectional, descriptive and analytical study, carried out from May 2019 to May 2021, through the analysis of 681 electronic medical records in a secondary public hospital. The study included 105 infants aged less than 24 months, hospitalized for recurrent wheezing. The variables analyzed were subdivided into two groups according to the presence of the etiological agent: positive or negative for RSV. Results: Of the sample studied, 75.2% were RSV negative, with a predominance of males and an average age of 13 months. With respect to the risk factors analyzed, there was a higher incidence of prematurity (19.2%), heart disease (11.5%), family history of asthma (61.5%), and use of prophylaxis (73%) among those positive for RSV. Among positive for RSV, we observed greater use of mechanical ventilation (80%) and need for readmissions (65.4%), and a positive correlation was observed between the etiological agent and prematurity (p=0.009*), heart disease (p=0.026*), readmission (p=0.009*), and the use of mechanical pulmonary ventilation (p=0.007*). Conclusion: Faced with this prevalent public health pathology, there is a need to improve clinical care, with qualification and standardization of conduct by general pediatricians.