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In July 2023, cases of highly pathogenic avian influenza (HPAI) were reported at 2 shelters for stray cats in Seoul, South Korea. The cause of infection was suspected to be improperly sterilized raw food made from domestic duck meat, which was manufactured in South Korea. All viruses isolated from cats at the shelters and from the raw food belonged to HPAI A(H5N1) clade 2.3.4.4b. The gene constellation of all viruses was most similar to that of viruses isolated in Korea in November 2022. Of note, the viruses isolated from infected cats harbored mutations E627K or D701N in polymerase basic 2, which are indicative of adaptation to mammals. Postmortem examination revealed systemic pathologic lesions and the presence of widespread virus in different tissues. Thus, consumption of raw duck meat contaminated with HPAI virus likely caused systemic symptoms and death in cats, indicating the introduction of mammal-adapted mutations of the virus.

Abstract Background Antipsychotic drugs (APDs) are used for treating mental illnesses and are also used by cancer patients. This study aimed to evaluate APD use in adult cancer patients who received radiotherapy (RT) in South Korea and assess the effects of APD use during RT on survival. Methods This retrospective cohort study utilized the National Health Insurance Service database database of Korea. We included adult cancer patients who underwent RT or chemotherapy (CTx, cisplatin, or 5-Fluorouracil) between 2010 and 2020. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine. Results Overall, 725,897 patients received RT, and 115,500 received concomitant chemo-radiotherapy (CCRT). Of them, 41,118 (5.6%) took APDs during RT, and 8,129 (7%) took APDs during CCRT. Overall, 27,789 (67.58%) patients who took APDs during RT were men, and 28,004 (68.2%) were aged ≥ 60 years. The most frequently used APD during RT was quetiapine (64.93%). Patients who took APDs during RT and during CCRT had higher mortality rates (HR: 3.45 and 1.72, p

Abstract In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer.

Abstract Recent studies on top‐emitting structure, which is designed to enhance the color purity and outcoupling efficiency of quantum‐dot light‐emitting diodes (QLEDs), employ commercially unviable methods owing to limited options for applying the hole injection layer through solution processes on the bottom electrode. In this study, all‐solution‐processable conventional top‐emitting QLEDs (TQLEDs) are successfully fabricated by introducing a polyethylenimine (PEI) interlayer, doping isopropyl alcohol (IPA) into the hole‐injection layer (poly (3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate), PEDOT:PSS), and using the dynamic spin‐coating method. The increased hole injection resulting from the tuned anode‐HIL interface by the PEI and IPA‐doped HIL, coupled with the enhanced outcoupling efficiency and full width at half maximum (FWHM) derived from the optimized cavity length through simulation, realizes a red InP QLED with high efficiency and color purity. The optimized TQLED exhibits a maximum current efficiency and FWHM of 28.04 cd A−1 and 36 nm, respectively, which are threefold higher and 8 nm narrower than those of bottom‐emitting QLEDs, marking the highest current efficiency ever reported for top‐emitting red InP QLEDs.

CRISPR prime editing (PE) requires a Cas9 nickase-reverse transcriptase fusion protein (known as PE2) and a prime editing guide RNA (pegRNA), an extended version of a standard guide RNA (gRNA) that both specifies the intended target genomic sequence and encodes the desired genetic edit. Here, we show that sequence complementarity between the 5’ and the 3’ regions of a pegRNA can negatively impact its ability to complex with Cas9, thereby potentially reducing PE efficiency. We demonstrate this limitation can be overcome by a simple pegRNA refolding procedure, which improved ribonucleoprotein-mediated PE efficiencies in zebrafish embryos by up to nearly 25-fold. Further gains in PE efficiencies of as much as sixfold could also be achieved by introducing point mutations designed to disrupt internal interactions within the pegRNA. Our work defines simple strategies that can be implemented to improve the efficiency of PE.

B cell receptors (BCRs) denote antigen specificity, while corresponding cell subsets indicate B cell functionality. Since each B cell uniquely encodes this combination, physical isolation and subsequent processing of individual B cells become indispensable to identify both attributes. However, this approach accompanies high costs and inevitable information loss, hindering high-throughput investigation of B cell populations. Here, we present BCR-SORT, a deep learning model that predicts cell subsets from their corresponding BCR sequences by leveraging B cell activation and maturation signatures encoded within BCR sequences. Subsequently, BCR-SORT is demonstrated to improve reconstruction of BCR phylogenetic trees, and reproduce results consistent with those verified using physical isolation-based methods or prior knowledge. Notably, when applied to BCR sequences from COVID-19 vaccine recipients, it revealed inter-individual heterogeneity of evolutionary trajectories towards Omicron-binding memory B cells. Overall, BCR-SORT offers great potential to improve our understanding of B cell responses.

This paper assesses trending AI foundation models, especially emerging computer vision foundation models and their performance in natural landscape feature segmentation. While the term foundation model has quickly garnered interest from the geospatial domain, its definition remains vague. Hence, this paper will first introduce AI foundation models and their defining characteristics. Built upon the tremendous success achieved by Large Language Models (LLMs) as the foundation models for language tasks, this paper discusses the challenges of building foundation models for geospatial artificial intelligence (GeoAI) vision tasks. To evaluate the performance of large AI vision models, especially Meta’s Segment Anything Model (SAM), we implemented different instance segmentation pipelines that minimize the changes to SAM to leverage its power as a foundation model. A series of prompt strategies were developed to test SAM’s performance regarding its theoretical upper bound of predictive accuracy, zero-shot performance, and domain adaptability through fine-tuning. The analysis used two permafrost feature datasets, ice-wedge polygons and retrogressive thaw slumps because (1) these landform features are more challenging to segment than man-made features due to their complicated formation mechanisms, diverse forms, and vague boundaries; (2) their presence and changes are important indicators for Arctic warming and climate change. The results show that although promising, SAM still has room for improvement to support AI-augmented terrain mapping. The spatial and domain generalizability of this finding is further validated using a more general dataset EuroCrops for agricultural field mapping. Finally, we discuss future research directions that strengthen SAM’s applicability in challenging geospatial domains.

B cells recognize antigens via membrane‐expressed B‐cell receptors (BCR) and antibodies. Similar human BCR sequences are frequently found at a significantly higher frequency than that theoretically calculated. Patients infected with SARS‐CoV2 and HIV or with autoimmune diseases share very similar BCRs. Therefore, in silico reconstitution of BCR repertoires and identification of stereotypical BCR sequences related to human pathology have diagnostic potential. Furthermore, monitoring changes of clinically significant BCR sequences and isotype conversion has prognostic potential. For BCR repertoire analysis, peripheral blood (PB) is the most convenient source. However, the optimal human PB volume for in silico reconstitution of the BCR repertoire has not been studied in detail. Here, we sampled 5, 10, and 20 mL PB from the left arm and 40 mL PB from the right arm of two volunteers, reconstituted in silico PB BCR repertoires, and compared their composition. In both volunteers, PB sampling over 20 mL resulted in slight increases in functional unique sequences (FUSs) or almost no increase in repertoire diversity. All FUSs with a frequency above 0.08% or 0.03% in the 40 mL PB BCR repertoire were detected even in the 5 mL PB BCR repertoire from each volunteer. FUSs with a higher frequency were more likely to be found in BCR repertoires from reduced PB volume, and those coexisting in two repertoires showed a statistically significant correlation in frequency irrespective of sampled anatomical site. The correlation was more significant in higher‐frequency FUSs. These observations support the potential of BCR repertoire analysis for diagnosis.

Abstract This study investigates the impacts of Lake Baikal, the largest by volume and the deepest freshwater lake in the world, on its nearby precipitation climate. Satellite observations and a reanalysis data set reveal that summertime precipitation amount is smaller over Lake Baikal than around it. A 15‐year regional climate simulation at a cloud‐resolving scale supports the smaller precipitation, and another simulation in which the lake is replaced by forest shows that the lake reduces summertime precipitation over it by 15%. The lake decreases daytime near‐surface air temperature, resulting in more convectively stable atmosphere over the lake. Latent heat flux is reduced along with the weakened convection, and the lower‐level moisture convergence and upper‐level moisture divergence over the lake are weakened.

The spatial context of epitranscriptomic features in the tumour microenvironment remains poorly understood. Here, a method for transcriptomic and epitranscriptomic analysis of immunofluorescence-stained tissue, Select-seq, is applied to stem cell-like microniches in triple negative breast cancer.

The accidental spillage of flammable liquids on in-service ships and offshore installations may lead to pool fires, which are likely to spread over a particularly large area in large compartments under ship motion, resulting in extensive damage. However, the effect of the spreading extent of liquid fuel due to inclined ship motion on pool fire consequences has not been considered in the existing literature. Thus, in this study, fuel discharge experiments were conducted to investigate the spreading behaviour under different substrate inclination angles and discharge rates. The experimental results were analysed to derive closed-form expressions to predict the spreading extent of liquid fuel in large compartments. Additionally, the effects of surface inclination on fire consequences were investigated using the Fire Dynamics Simulator in terms of the heat release rate. The findings can provide guidance for effective fire safety design and establishing a realistic fire modelling methodology for ships and offshore installations.

BRASH (Bradycardia, Renal failure, Atrioventricular [AV]-node blocker medications, Shock, and Hyperkalemia), a novel syndrome, is a synergistic interaction between AV node blockers and hyperkalemia, resulting in bradycardia. We report a case of BRASH syndrome with marked bradycardia in a patient with End-Stage Renal Disease (ESRD) associated with synergistic interaction between mild hyperkalemia and AV node blockers. Anesthesiologists should be aware of these clinical features, in which ESRD patients with baseline mild hyperkalemia are particularly susceptible to bradycardia. This report will help in its early recognition as well as enable comprehensive and appropriate treatment strategies without further invasive therapy.

Pulmonary alveolar proteinosis (PAP) is an uncommon disease characterized by progressive accumulation of lipoprotein material in the lungs due to impaired surfactant clearance. Whole-lung lavage (WLL) is the current standard treatment and consists of sequential lavage of each lung to mechanically remove the residual material from the alveoli. Although WLL is considered safe, unexpected complications can occur. Moreover, due to the rarity of the disease itself, this procedure is unknown to many physicians, and management of intraoperative complications can be challenging for anesthesiologists. Lung ultrasound (LUS) provides reliable and valuable information for detecting perioperative pulmonary complications and, in particular, quantitation of lung water content. There have been reports on monitoring the different stages of controlled deaeration of the non-ventilated lung during WLL using LUS. However, it has been limited to non-ventilated lungs. Therefore, we report the use of LUS in WLL to proactively detect pulmonary edema in the ventilated lung and implement a safe and effective anesthesia strategy. Given the limited diagnostic tools available to anesthesiologists in the operating room, LUS is a reliable, fast, and noninvasive method for identifying perioperative pulmonary complications in patients with PAP undergoing WLL.

Abstract Background Tibial rotational alignment in total knee arthroplasty (TKA) is generally determined based on intra-articular structure, and can be difficult to ascertain in some cases. The aim of this study was to investigate whether the medial tangent angle of the tibia (MTAT) could be useful in determining the anteroposterior axis of the tibia. Methods This study was performed on 103 lower limbs in 53 patients who underwent primary total hip arthroplasty. The selection criteria for our study were based on the assumption that knees in patients undergoing THA exhibit fewer degenerative changes than knees in patients undergoing TKA. Using computed tomography images, the MTAT, comprising the medial tangent of the proximal tibia and the anteroposterior (AP) axis of the tibia, was measured on three horizontal planes: at the distal edge of the tibial tubercle (A), at 5 cm distally (B), and at 10 cm further distally (C). The tibial medial surface was grouped into three classes according to shape: valley type, flat type, and hill type. The percentage at which these shapes were observed in each group was also calculated. Measurement reliability was calculated using the intraclass correlation coefficient. Results The angles were 45.2° (interquartile range: IR 43.0–47.7) at A, 42.7° (IR 38.7–45.9) at B, and 42.4° (IR 38.2–45.9) at C. Intra-rater reliability and inter-rater reliability was 0.982 and 0.974 at A, 0.810 and 0.411 at B, and 0.940 and 0.811 at C, respectively. Regarding the tibial medial surface, the valley type was observed in all cases at A, and the hill type was observed in the highest percentage of cases at B and C. Conclusions The MTAT was approximately 45° at level A, and reproducibility was the highest among the three groups. The two points forming the valley on the tibial medial surface were bony ridges. Therefore, the medial tangent of the tibia at level A could be easily determined. Because the distal edge of the tibial tubercle exists at the surgical area and the extra-articular area, it can be a suitable intraoperative, extra-articular landmark in determining the tibial AP axis, even for revision TKA.

The interaction of extracellular matrix (ECM) components with hepatic stellate cells (HSCs) is thought to perpetuate fibrosis by stimulating signaling pathways that drive HSC activation, survival and proliferation. Consequently, disrupting the interaction between ECM and HSCs is considered a therapeutical avenue although respective targets and underlying mechanisms remain to be established. Here we have interrogated the interaction between type VI collagen (CVI) and HSCs based on the observation that CVI is 10-fold upregulated during fibrosis, closely associates with HSCs in vivo and promotes cell proliferation and cell survival in cancer cell lines. We exposed primary rat HSCs and a rat hepatic stellate cell line (CFSC) to soluble CVI and determined the rate of proliferation, apoptosis and fibrogenesis in the absence of any additional growth factors. We find that CVI in nanomolar concentrations prevents serum starvation-induced apoptosis. This potent anti-apoptotic effect is accompanied by induction of proliferation and acquisition of a pronounced pro-fibrogenic phenotype characterized by increased α-smooth muscle actin, TGF-β, collagen type I and TIMP-1 expression and diminished proteolytic MMP-13 expression. The CVI-HSC interaction can be disrupted with the monomeric α2(VI) and α3(VI) chains and abrogates the activating CVI effects. Further, functional relevant α3(VI)-derived 30 amino acid peptides lead to near-complete inhibition of the CVI effect. In conclusion, CVI serves as a potent mitogen and activating factor for HSCs. The antagonistic effects of the CVI monomeric chains and peptides point to linear peptide sequences that prevent activation of CVI receptors which may allow a targeted antifibrotic therapy.

Phage display is one of the most frequently used platform technologies utilized to screen and select therapeutic antibodies, and has contributed to the development of more than 10 therapeutic antibodies used in the clinic. Despite advantages like efficiency and low cost, it has intrinsic technical limitations, such as the asymmetrical amplification of the library after each round of biopanning, which is regarded as a reason for it yielding a very limited number of antigen binders. In this study, we developed a high-throughput single-clonal screening system comprised of fluorescence immunoassays and a laser-driven clonal DNA retrieval system using microchip technology. Using this system, from a single-chain variable fragment (scFv) library displayed on phages with a complexity of 5.21 × 105 harboring random mutations at five amino acid residues, more than 70,000 clones—corresponding to ~14% of the library complexity—were screened, resulting in 78 antigen-reactive scFv sequences with mutations restricted to the randomized residues. Our results demonstrate that this system can significantly reduce the number of biopanning rounds, or even eliminate the need for this process for libraries with lower complexity, providing an opportunity to obtain more diverse clones from the library.

Comparisons between bin and bulk cloud microphysics schemes are conducted by simulating a heavy precipitation case using a bin microphysics scheme and four double-moment bulk microphysics schemes in the Weather Research and Forecasting (WRF) model. For this, we implemented an updated bin microphysics scheme in the WRF model. All of the microphysics schemes underestimate observed strong precipitation, but the bin microphysics scheme yields the result that is closest to observations. The differences among the schemes are more pronounced in terms of hydrometeor number concentration than in terms of hydrometeor mixing ratio. In this case, the bin scheme exhibits remarkably more latent heat release by deposition and riming than the bulk schemes. This causes stronger updrafts and more upward transport of water vapor, which leads to more deposition, and again, increases the latent heat release. An additional simulation using the bin scheme but excluding the riming of cloud droplets on ice crystals, which is not or poorly treated in the examined bulk schemes, shows that surface precipitation is slightly weakened and moved farther downwind compared to that of the control simulation. This implies that the more appropriate representation of microphysical processes in the bin microphysics scheme contributes to the more accurate prediction of precipitation in this case.

Aerosol-cloud-precipitation interactions in deep convective clouds are investigated through numerical simulations of a heavy precipitation event over South Korea on 15⁻16 July 2017. The Weather Research and Forecasting model with a bin microphysics scheme is used, and various aerosol number concentrations in the range N0 = 50⁻12,800 cm−3 are considered. Precipitation amount changes non-monotonically with increasing aerosol loading, with a maximum near a moderate aerosol loading (N0 = 800 cm−3). Up to this optimal value, an increase in aerosol number concentration results in a greater quantity of small droplets formed by nucleation, increasing the number of ice crystals. Ice crystals grow into snow particles through deposition and riming, leading to enhanced melting and precipitation. Beyond the optimal value, a greater aerosol loading enhances generation of ice crystals while the overall growth of ice hydrometeors through deposition stagnates. Subsequently, the riming rate decreases because of the smaller size of snow particles and supercooled drops, leading to a decrease in ice melting and a slight suppression of precipitation. As aerosol loading increases, cold pool and low-level convergence strengthen monotonically, but cloud development is more strongly affected by latent heating and convection within the system that is non-monotonically reinforced.

Differential interference contrast microscopy is designed to image unstained and transparent specimens by enhancing the contrast resulting from the Nomarski prism-effected optical path difference. Retinitis pigmentosa, one of the most common inherited retinal diseases, is characterized by progressive loss of photoreceptors. In this study, Differential interference contrast microscopy was evaluated as a new and simple application for observation of the retinal photoreceptor layer and retinitis pigmentosa diagnostics and monitoring. Retinal tissues of Royal College of Surgeons rats and retinal-degeneration mice, both well-established animal models for the disease, were prepared as flatmounts and histological sections representing different elapsed times since the occurrence of the disease. Under the microscopy, the retinal flatmounts showed that the mosaic pattern of the photoreceptor layer was irregular and partly collapsed at the early stage of retinitis pigmentosa, and, by the advanced stage, amorphous. The histological sections, similarly, showed thinning of the photoreceptor layer at the early stage and loss of the outer nuclear layer by the advanced stage. To count and compare the number of photoreceptors in the normal and early-retinitis pigmentosa-stage tissues, an automated cell-counting program designed with MATLAB, a numerical computing language, using a morphological reconstruction method, was applied to the differential interference contrast microscopic images. The number of cells significantly decreased, on average, from 282 to 143 cells for the Royal College of Surgeons rats and from 255 to 170 for the retinal-degeneration mouse. We successfully demonstrated the potential of the differential interference contrast microscopy technique's application to the diagnosis and monitoring of RP.

Biomass burning plumes are frequently transported over the Southeast Atlantic stratocumulus deck during the southern African fire season (June-October). The plumes bring large amounts of absorbing aerosols as well as enhanced moisture, which can trigger a rich set of aerosol-cloud-radiation interactions with climatic consequences that are still poorly understood. We use large-eddy simulation (LES) to explore and disentangle the individual impacts of aerosols and moisture on the underlying stratocumulus clouds, the marine boundary layer (MBL) evolution and the stratocumulus to cumulus transition (SCT) for three different meteorological situations over the Southeast Atlantic during August 2017. For all three cases, our LES shows that the SCT is driven by increased sea surface temperatures and cloud-top entrainment as the air is advected towards the equator. In the LES model, aerosol indirect effects, including impacts on drizzle production, have a small influence on the modeled cloud evolution and SCT, even when aerosol concentrations are lowered to background concentrations. In contrast, local semi-direct effects, i.e aerosol absorption of solar radiation in the MBL, causes a reduction in cloud cover that can lead to a speed-up of the SCT, in particular during daytime and during broken cloud conditions, especially in highly polluted situations. The largest impact on the radiative budget comes from aerosol impacts on cloud albedo; the plume with absorbing aerosols produces a total average net radiative cooling effect between -4 and -9 Wm-2 over the three days of simulations. We find that the moisture accompanying the aerosol plume produces an additional cooling effect that is about as large as the total aerosol radiative effect. Overall, there is still a large uncertainty associated with the radiative and cloud evolution effects of biomass burning aerosols. A comparison between different models in a common framework, combined with constraints from in-situ observations, could help to reduce the uncertainty. [ABSTRACT FROM AUTHOR]