A dynamic flow fetal membrane organ-on-a-chip system for modeling the effects of amniotic fluid motion.

Fetal membrane (amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. A previously developed amnion membrane (AM) organ-on-chip (OOC) was utilized but with dynamic flow to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48 h to mimic fluid motion. A static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control representing pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to cytokeratin 18 (CK-18) ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a dynamic flow environment is not necessary to mimic in utero physiologic cellular conditions of an amnion membrane.

Development of a Web-Based Interactive Tool for Visualizing Breast Cancer Clinical Trial Tolerability Data.

PURPOSE: Longitudinal patient tolerability data collected as part of randomized controlled trials are often summarized in a way that loses information and does not capture the treatment experience. To address this, we developed an interactive web application to empower clinicians and researchers to explore and visualize patient tolerability data. METHODS: We used adverse event (AE) data (Common Terminology Criteria for Adverse Events) and patient-reported outcomes (PROs) from the NSABP-B35 phase III clinical trial, which compared anastrozole with tamoxifen for breast cancer-free survival, to demonstrate the tools. An interactive web application was developed using R and the Shiny web application framework that generates Sankey diagrams to visualize AEs and PROs using four tools: AE Explorer, PRO Explorer, Cohort Explorer, and Custom Explorer. RESULTS: To illustrate how users can use the interactive tool, examples for each of the four applications are presented using data from the NSABP-B35 phase III trial and the NSABP-B30 trial for the Custom Explorer. In the AE and PRO explorers, users can select AEs or PROs to visualize within specified time periods and compare across treatments. In the cohort explorer, users can select a subset of patients with a specific symptom, severity, and treatment received to visualize the trajectory over time within a specified time interval. With the custom explorer, users can upload and visualize structured longitudinal toxicity and tolerability data. CONCLUSION: We have created an interactive web application and tool for clinicians and researchers to explore and visualize clinical trial tolerability data. This adaptable tool can be extended for other clinical trial data visualization and incorporated into future patient-clinician interactions regarding treatment decisions.

A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform.

Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface (FMi). The two interfaces-placenta/decidua and fetal membranes/decidua are gatekeepers of drug transport; however, testing their functions is impractical during pregnancy. Limitations of current in-vivo/in-vitro models have hampered drug development and testing during pregnancy. Hence, major complications like preterm births and maternal and neonatal mortalities remain high. Advancements in organ-on-chip (OOC) platforms to test drug kinetics and efficacy and novel extracellular vesicle-based fetal drug delivery are expected to accelerate preclinical trials related to pregnancy complications. Here we report the development and testing of a humanized multi-organ fetal membrane/placenta (fetal)-decidua (maternal) interface OOC (FMi-PLA-OOC) that contains seven cell types interconnected through microchannels to maintain intercellular interactions as seen in-utero. Cytotoxicity, propagation, mechanism of action, and efficacy of engineered extracellular vesicles containing anti-inflammatory interleukin (IL)-10 (eIL-10) were evaluated to reduce FMi inflammation associated with preterm birth. A healthy and disease model (lipopolysaccharide-infectious inflammation) of the FMi-PLA-OOC was created and co-treated with eIL-10. eIL-10 propagated from the maternal to fetal side within 72-hours, localized in all cell types, showed no cytotoxicity, activated IL-10 signaling pathways, and reduced lipopolysaccharide-induced inflammation (minimized NF-kB activation and proinflammatory cytokine production). These data recapitulated eIL-10s' ability to reduce inflammation and delay infection-associated preterm birth in mouse models, suggesting FMi-PLA-OOC as an alternative approach to using animal models. Additionally, we report the utility of eIL-10 that can traverse through FMis to reduce inflammation-associated pregnancy complications.

Thigh muscle mass evaluated by point-of-care ultrasound is associated with short-term mortality in patients with sepsis in the emergency department.

Muscle mass depletion is associated with mortality and morbidity in various conditions including sepsis. However, few studies have evaluated muscle mass using point-of-care ultrasound in patients with sepsis. This study aimed to evaluate the association between thigh muscle mass, evaluated using point-of-care ultrasound with panoramic view in patients with sepsis in the emergency department, and mortality. From March 2021 to October 2022, this prospective observational study used sepsis registry. Adult patients who were diagnosed with sepsis at the emergency department and who underwent point-of-care ultrasounds for lower extremities were included. The thigh muscle mass was evaluated by the cross-sectional area of the quadriceps femoris (CSA-QF) on point-of-care ultrasound using panoramic view. The primary outcome was 28 day mortality. Multivariable Cox proportional hazard model was performed. Of 112 included patients with sepsis, mean CSA-QF was significantly lower in the non-surviving group than surviving group (49.6 [34.3-56.5] vs. 63.2 [46.9-79.6] cm2, p = 0.002). Each cm2 increase of mean CSA-QF was independently associated with decreased 28 day mortality (adjusted hazard ratio 0.961, 95% CI 0.928-0.995, p = 0.026) after adjustment for potential confounders. The result of other measurements of CSA-QF were similar. The muscle mass of the quadriceps femoris evaluated using point-of-care ultrasound with panoramic view was associated with mortality in patients with sepsis. It might be a promising tool for determining risk factors for mortality in sepsis patients in the early stages of emergency department.

Ultrasmall 2D Sn-Doped MAPbBr3 Nanoplatelets Enable Bright Pure-Blue Emission.

Synthesis of perovskites that exhibit pure-blue emission with high photoluminescence quantum yield (PLQY) in both nanocrystal solutions and nanocrystal-only films presents a significant challenge. In this work, a room-temperature method is developed to synthesize ultrasmall, monodispersed, Sn-doped methylammonium lead bromide (MAPb1- xSnxBr3) perovskite nanoplatelets (NPLs) in which the strong quantum confinement effect endows pure blue emission (460 nm) and a high quantum yield (87%). Post-treatment using n-hexylammonium bromide (HABr) repaired surface defects and thus substantially increased the stability and PLQY (80%) of the NPL films. Concurrently, high-precision patterned films (200-µm linewidth) are successfully fabricated by using cost-effective spray-coating technology. This research provides a novel perspective for the preparation of high PLQY, highly stable, and easily processable perovskite nanomaterials.

Uniform sized cancer spheroids production using hydrogel-based droplet microfluidics: a review.

Three-dimensional (3D) cell culture models have been extensively utilized in various mechanistic studies as well as for drug development studies as superior in vitro platforms than conventional two-dimensional (2D) cell culture models. This is especially the case in cancer biology, where 3D cancer models, such as spheroids or organoids, have been utilized extensively to understand the mechanisms of cancer development. Recently, many sophisticated 3D models such as organ-on-a-chip models are emerging as advanced in vitro models that can more accurately mimic the in vivo tissue functions. Despite such advancements, spheroids are still considered as a powerful 3D cancer model due to the relatively simple structure and compatibility with existing laboratory instruments, and also can provide orders of magnitude higher throughput than complex in vitro models, an extremely important aspects for drug development. However, creating well-defined spheroids remain challenging, both in terms of throughputs in generation as well as reproducibility in size and shape that can make it challenging for drug testing applications. In the past decades, droplet microfluidics utilizing hydrogels have been highlighted due to their potentials. Importantly, core-shell structured gel droplets can avoid spheroid-to-spheroid adhesion that can cause large variations in assays while also enabling long-term cultivation of spheroids with higher uniformity by protecting the core organoid area from external environment while the outer porous gel layer still allows nutrient exchange. Hence, core-shell gel droplet-based spheroid formation can improve the predictivity and reproducibility of drug screening assays. This review paper will focus on droplet microfluidics-based technologies for cancer spheroid production using various gel materials and structures. In addition, we will discuss emerging technologies that have the potential to advance the production of spheroids, prospects of such technologies, and remaining challenges.

A Dynamic Flow Fetal Membrane Organ-on-a-Chip System for Modeling the Effects of Amniotic Fluid Motion.

Fetal membrane(amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. An amnion membrane (AM) organ-on-chip (OOC) was utilized to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48 hours flow culture to mimic fluid motion. Static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control for pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to CK-18 ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a flow culture environment is not necessary to mimic any in utero physiologic cellular conditions of fetal membrane-derived cells.

Enhancing Genomic Prediction Accuracy for Body Conformation Traits in Korean Holstein Cattle.

The Holstein breed is the mainstay of dairy production in Korea. In this study, we evaluated the genomic prediction accuracy for body conformation traits in Korean Holstein cattle, using a range of π levels (0.75, 0.90, 0.99, and 0.995) in Bayesian methods (BayesB and BayesC). Focusing on 24 traits, we analyzed the impact of different π levels on prediction accuracy. We observed a general increase in accuracy at higher levels for specific traits, with variations depending on the Bayesian method applied. Notably, the highest accuracy was achieved for rear teat angle when using deregressed estimated breeding values including parent average as a response variable. We further demonstrated that incorporating parent average into deregressed estimated breeding values enhances genomic prediction accuracy, showcasing the effectiveness of the model in integrating both offspring and parental genetic information. Additionally, we identified 18 significant window regions through genome-wide association studies, which are crucial for future fine mapping and discovery of causal mutations. These findings provide valuable insights into the efficiency of genomic selection for body conformation traits in Korean Holstein cattle and highlight the potential for advancements in the prediction accuracy using larger datasets and more sophisticated genomic models.

Vertically Stackable Ovonic Threshold Switch Oscillator Using Atomic Layer Deposited Ge0.6Se0.4 Film for High-Density Artificial Neural Networks.

Nanodevice oscillators (nano-oscillators) have received considerable attention to implement in neuromorphic computing as hardware because they can significantly improve the device integration density and energy efficiency compared to complementary metal oxide semiconductor circuit-based oscillators. This work demonstrates vertically stackable nano-oscillators using an ovonic threshold switch (OTS) for high-density neuromorphic hardware. A vertically stackable Ge0.6Se0.4 OTS-oscillator (VOTS-OSC) is fabricated with a vertical crossbar array structure by growing Ge0.6Se0.4 film conformally on a contact hole structure using atomic layer deposition. The VOTS-OSC can be vertically integrated onto peripheral circuits without causing thermal damage because the fabrication temperature is <400 °C. The fabricated device exhibits oscillation characteristics, which can serve as leaky integrate-and-fire neurons in spiking neural networks (SNNs) and coupled oscillators in oscillatory neural networks (ONNs). For practical applications, pattern recognition and vertex coloring are demonstrated with SNNs and ONNs, respectively, using semiempirical simulations. This structure increases the oscillator integration density significantly, enabling complex tasks with a large number of oscillators. Moreover, it can enhance the computational speed of neural networks due to its rapid switching speed.

Causal impact analysis of weir opening on cyanobacterial blooms and water quality in the Yeongsan River, Korea: A bayesian structural time-series analysis and median difference test.

The construction of weirs in Korea's Four Major Rivers Project has led to an increase in cyanobacterial blooms, posing environmental challenges. To address this, the government began opening weirs in 2017. However, interpreting experimental results has proven to be complex due to the multifaceted nature of blooms. This study aimed to assess the impact of opening the Juksan Weir on cyanobacterial blooms and water quality in the Yeongsan River. Using a median difference test (MDT) and causal impact analysis (CIA) with Bayesian structural time-series (BSTS) models, changes in cyanobacterial cell density (Cyano) and chlorophyll a concentration (Chl-a) before (January 2013 to June 2017) and after (July 2017 to December 2021) the weir-opening event were analyzed. The MDT revealed no significant change in Cyano post-weir opening (p = 0.267), but Chl-a significantly increased by 48.1 % (p < 0.01). As a result of CIA, Cyano decreased, albeit statistically insignificantly (p = 0.454), while Chl-a increased by 59.0 % (p < 0.01). These findings contradict the expectation that Cyano decrease due to the increased flow velocity resulting from weir opening. The absence of changes in Cyano and the increase in Chl-a can be attributed to several factors, including the constrained and inadequate duration of full weir opening combined with conducive conditions for the proliferation of other algae such as diatoms and green algae. These findings suggest that the effectiveness of weir opening in controlling Cyano may have been compromised by factors influencing the overall aquatic ecosystem dynamics. Further analysis revealed that factors such as elevated water temperatures (≥ 30 °C) and reduced flow rates (< 37 m3/s) contributed to the flourishing of cyanobacteria, whose concentrations exceeded 10,000 cells/mL. In analyzing causal relationships in environmental management, especially when there are complex causal interactions, the application of MDT and CIA provides valuable insights.

High-resolution Diffusion-weighted Imaging to Detect Changes in Tumor Size and ADC, and Predict Adverse Biopsy Histology during Prostate Cancer Active Surveillance.

PURPOSE: Majority of men with low-risk prostate cancer can be managed with active surveillance (AS). This study evaluates a high-resolution diffusion-weighted imaging (HR-DWI) technique to predict adverse biopsy histology (AH), defined as Gleason score ≥7 on any biopsy or ≥3 increase in number of positive biopsy cores on systematic biopsies. We test the hypothesis that high-grade disease and progressing disease undergo subtle changes during even short intervals that can be detected by HR-DWI. EXPERIMENTAL DESIGN: In a prospective clinical trial, serial multiparametric MRIs, incorporating HR-DWI and standard DWI (S-DWI) were performed approximately 12 months apart prior to prostate biopsy (n = 59). HR-DWI, which uses reduced field-of-view and motion compensation techniques, was compared with S-DWI. RESULTS: HR-DWI had a 3-fold improvement in spacial resolution compared with S-DWI as confirmed using imaging phantoms. For detecting AH, multiparametric MRI using HR-DWI had a sensitivity of 75% and specificity of 83.9%, and MRI using S-DWI had a sensitivity of 71.4% and specificity of 54.8%. The AUC for HR-DWI was significantly higher (0.794 vs. 0.631, P = 0.014). Secondary analyses of univariable predictors of AH showed tumor size increase [OR 16.8; 95% confidence interval (CI): 4.06-69.48; P < 0.001] and apparent diffusion coefficient (ADC) decrease (OR 5.06; 95% CI: 1.39-18.38; P = 0.014) on HR-DWI were significant predictors of AH. CONCLUSION: HR-DWI outperforms S-DWI in predicting AH. Patient with AH have tumors that change in size and ADC that could be detected using HR-DWI. Future studies with longer follow-up should assess HR-DWI for predicting disease progression during AS. SIGNIFICANCE: We report on a prospective clinical trial using a MRI that has three times the resolution of standard MRI. During AS for prostate cancer, two high-resolution MRIs performed approximately a year apart can detect tumor changes that predict the presence of aggressive cancers that should be considered for curative therapy such as prostatectomy or radiation.

Predicting septic shock in patients with sepsis at emergency department triage using systolic and diastolic shock index.

INTRODUCTION: Identifying patients with at a high risk of progressing to septic shock is essential. Due to systemic vasodilation in the pathophysiology of septic shock, the use of diastolic blood pressure (DBP) has emerged. We hypothesized that the initial shock index (SI) and diastolic SI (DSI) at the emergency department (ED) triage can predict septic shock. METHOD: This observational study used the prospectively collected sepsis registry. The primary outcome was progression to septic shock. Secondary outcomes were the time to vasopressor requirement, vasopressor dose, and severity according to SI and DSI. Patients were classified by tertiles according to the first principal component of shock index and diastolic shock index. RESULTS: A total of 1267 patients were included in the analysis. The area under the receiver operating characteristic curve (AUC) for predicting progression to septic shock for DSI was 0.717, while that for SI was 0.707. The AUC for predicting progression to septic shock for DSI and SI were significantly higher than those for conventional early warning scores. Middle tertile showed adjusted Odd ratio (aOR) of 1.448 (95% CI 1.074-1.953), and that of upper tertile showed 3.704 (95% CI 2.299-4.111). CONCLUSION: The SI and DSI were significant predictors of progression to septic shock. Our findings suggest an association between DSI and vasopressor requirement. We propose stratifying lower tertile as being at low risk, middle tertile as being at intermediate risk, and upper tertile as being at high risk of progression to septic shock. This system can be applied simply at the ED triage.

Sex differences in in-hospital management in patients with sepsis and septic shock: a prospective multicenter observational study.

Sex differences in the in-hospital management of sepsis exist. Previous studies either included patients with sepsis that was defined using previous definitions of sepsis or evaluated the 3-h bundle therapy. Therefore, this study sought to assess sex differences in 1-h bundle therapy and in-hospital management among patients with sepsis and septic shock, defined according to the Sepsis-3 definitions. This observational study used data from Korean Shock Society (KoSS) registry, a prospective multicenter sepsis registry. Adult patients with sepsis between June 2018 and December 2021 were included in this study. The primary outcome was adherence to 1-h bundle therapy. Propensity score matching (PSM) and multivariable logistic regression analyses were performed. Among 3264 patients with sepsis, 3129 were analyzed. PSM yielded 2380 matched patients (1190 men and 1190 women). After PSM, 1-h bundle therapy was performed less frequently in women than in men (13.0% vs. 19.2%; p < 0.001). Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently in women than in men (25.4% vs. 31.6%, p < 0.001), whereas adequate fluid resuscitation was performed more frequently in women than in men (96.8% vs. 95.0%, p = 0.029). In multivariable logistic regression analysis, 1-h bundle therapy was performed less frequently in women than in men [adjusted odds ratio (aOR) 1.559; 95% confidence interval (CI) 1.245-1.951; p < 0.001] after adjustment. Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently to women than men (aOR 1.339, 95% CI 1.118-1.605; p = 0.002), whereas adequate fluid resuscitation was performed more frequently for women than for men (aOR 0.629, 95% CI 0.413-0.959; p = 0.031). Invasive arterial blood pressure monitoring was performed less frequently in women than in men. Resuscitation fluid, vasopressor, steroid, central-line insertion, ICU admission, length of stay in the emergency department, mechanical ventilator use, and renal replacement therapy use were comparable for both the sexes. Among patients with sepsis and septic shock, 1-h bundle therapy was performed less frequently in women than in men. Continuous efforts are required to increase adherence to the 1-h bundle therapy and to decrease sex differences in the in-hospital management of patients with sepsis and septic shock.

Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies.

The effects of endocrine-disrupting compounds (EDCs) on the placenta, a critical gestational organ for xenobiotic protection, are well reported; however, models to determine the role of EDCs in placental disruption are limited. An advanced 2nd-trimester human placenta organ-on-chip model (2TPLA-OOC) was developed and validated, with six representative cells of the maternal and the fetal interface interconnected with microchannels. Various EDCs (150 ng mL-1 each of bisphenol A, bisphenol S, and polybrominated diphenyl ethers-47 and -99) were gradually propagated across the chip for 72 hours, and their various effects were determined. Cigarette smoke extract (CSE), an environmental risk factor, was used as a positive control. EDCs produced overall oxidative stress in the placental/decidual cells, induced cell-specific endocrine effects, caused limited (<10%) apoptosis/necrosis in trophoblasts and mesenchymal cells, induced localized inflammation but an overall anti-inflammatory shift, did not change immune cell migration from stroma to decidua, and did not affect placental nutrient transport. Overall, (1) the humanized 2TPLA-OOC recreated the placental organ and generated data distinct from the trophoblast and other cells studied in isolation, and (2) at doses associated with adverse pregnancies, EDCs produced limited and localized insults, and the whole organ compensated for the exposure.

Valley-centre tandem perovskite light-emitting diodes.

Perovskite light-emitting diodes (PeLEDs) have emerged as a promising new light source for displays. The development roadmap for commercializing PeLEDs should include a tandem device structure, specifically by stacking a thin nanocrystal PeLED unit and an organic light-emitting diode unit, which can achieve a vivid and efficient tandem display; however, simply combining light-emitting diodes with different characteristics does not guarantee both narrowband emission and high efficiency, as it may cause a broadened electroluminescence spectra and a charge imbalance. Here, by conducting optical simulations of the hybrid tandem (h-tandem) PeLED, we have discovered a crucial optical microcavity structure known as the h-tandem valley, which enables the h-tandem PeLED to emit light with a narrow bandwidth. Specifically, the centre structure of the h-tandem valley (we call it valley-centre tandem) demonstrates near-perfect charge balance and optimal microcavity effects. As a result, the h-tandem PeLED achieves a high external quantum efficiency of 37.0% and high colour purity with a narrow full-width at half-maximum of 27.3 nm (versus 64.5 nm in organic light-emitting diodes) along with a fast on-off response. These findings offer a new strategy to overcome the limitations of nanocrystal-based PeLEDs, providing valuable optical and electrical guidelines for integrating different types of light-emitting device into practical display applications.

The mortality of patients with sepsis increases in the first month of a new academic year.

OBJECTIVE: Many studies have examined the July effect. However, little is known about the July effect in sepsis. We hypothesized that the July effect would result in worse outcomes for patients with sepsis. METHODS: Data from patients with sepsis, collected prospectively between January 2018 and December 2021, were analyzed. In Korea, the new academic year starts on March 1, so the "July effect" appears in March. The primary outcome was 30-day mortality. Secondary outcomes included adherence to the Surviving Sepsis Campaign bundle. Outcomes in March were compared to other months. A multivariate Cox proportional hazard regression was performed to adjust for confounders. RESULTS: We included 843 patients. There were no significant differences in sepsis severity. The 30-day mortality in March was higher (49.0% vs. 28.5%, P<0.001). However, there was no difference in bundle adherence in March (42.2% vs. 48.0%, P=0.264). The multivariate Cox proportional hazard regression showed that the July effect was associated with 30-day mortality in patients with sepsis (adjusted hazard ratio, 1.925; 95% confidence interval, 1.405-2.638; P<0.001). CONCLUSION: The July effect was associated with 30-day mortality in patients with sepsis. However, bundle adherence did not differ. These. RESULTS: suggest that the increase in mortality during the turnover period might be related to unmeasured in-hospital management. Intensive supervision and education of residents caring for patients with sepsis is needed in the beginning of training.

A Practical Approach for Targeting Structural Variants Genome-wide in Plasma Cell-free DNA.

Interrogating plasma cell-free DNA (cfDNA) to detect cancer offers promise; however, no current tests scan structural variants (SVs) throughout the genome. Here, we report a simple molecular workflow to enrich a tumorigenic SV (DNA palindromes/fold-back inversions) that often demarcates genomic amplification and its feasibility for cancer detection by combining low-throughput next-generation sequencing with automated machine learning (Genome-wide Analysis of Palindrome Formation, GAPF-seq). Tumor DNA signal manifested as skewed chromosomal distributions of high-coverage 1-kb bins (HCBs), differentiating 39 matched breast tumor DNA from normal DNA with an average AUC of 0.9819. In a proof-of-concept liquid biopsy study, cfDNA from 0.5 mL plasma from prostate cancer patients was sufficient for binary classification against matched buffy coat DNA with an average AUC of 0.965. HCBs on the X chromosome emerged as a determinant feature and were associated with AR amplification. GAPF-seq could generate unique cancer-specific SV profiles in an agnostic liquid biopsy setting.

Toward Domain-Free Transformer for Generalized EEG Pre-Training.

Electroencephalography (EEG) signals are the brain signals acquired using the non-invasive approach. Owing to the high portability and practicality, EEG signals have found extensive application in monitoring human physiological states across various domains. In recent years, deep learning methodologies have been explored to decode the intricate information embedded in EEG signals. However, since EEG signals are acquired from humans, it has issues with acquiring enormous amounts of data for training the deep learning models. Therefore, previous research has attempted to develop pre-trained models that could show significant performance improvement through fine-tuning when data are scarce. Nonetheless, existing pre-trained models often struggle with constraints, such as the necessity to operate within datasets of identical configurations or the need to distort the original data to apply the pre-trained model. In this paper, we proposed the domain-free transformer, called DFformer, for generalizing the EEG pre-trained model. In addition, we presented the pre-trained model based on DFformer, which is capable of seamless integration across diverse datasets without necessitating architectural modification or data distortion. The proposed model achieved competitive performance across motor imagery and sleep stage classification datasets. Notably, even when fine-tuned on datasets distinct from the pre-training phase, DFformer demonstrated marked performance enhancements. Hence, we demonstrate the potential of DFformer to overcome the conventional limitations in pre-trained model development, offering robust applicability across a spectrum of domains.

Risk factors for delayed hemothorax in patients with rib fracture in the emergency department.

OBJECTIVES: Although rib fractures are a risk factor, not all rib fracture patients will develop delayed hemothorax. This study aimed to evaluate risk factors which can identify rib fracture patients in the emergency department who may develop delayed hemothorax. METHODS: Adult patients seen in the emergency room between January 2016 and February 2021 with rib fractures caused by blunt chest trauma were included in this retrospective observational study. Patients who underwent chest tube insertion within 2 days and those without follow-up chest radiographs within 2-30 days were excluded. We used a stepwise backward-elimination multivariable logistic regression model for analysis. RESULTS: A total of 202 patients were included in this study. The number of total (P < 0.001), lateral (P = 0.019), and displaced (P < 0.001) rib fractures were significantly associated with delayed hemothorax. Lung contusions (P = 0.002), and initial minimal hemothorax (P < 0.001) and pneumothorax (P < 0.001) were more frequently associated with delayed hemothorax. Age (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI) 1.00-1.06, P = 0.022), mechanical ventilator use (aOR 9.67, 95% CI 1.01-92.75, P = 0.049), initial hemothorax (aOR 2.21, 95% CI 1.05-4.65, P = 0.037) and pneumothorax (aOR 2.99, 95% CI 1.36-6.54, P = 0.006), and displaced rib fractures (aOR 3.51, 95% CI 1.64-7.53, P = 0.001) were independently associated with delayed hemothorax. CONCLUSIONS: Age, mechanical ventilation, initial hemo- or pneumothorax, and displaced rib fractures were risk factors for delayed hemothorax. Patients with these risk factors, and especially those with ≥2 displaced rib fractures, require close chest radiography follow-up of 2-30 days after the initial trauma.

A Practical Approach for Targeting Structural Variants Genome-wide in Plasma Cell-free DNA.

Plasma cell-free DNA (cfDNA) is a promising source of gene mutations for cancer detection by liquid biopsy. However, no current tests interrogate chromosomal structural variants (SVs) genome-wide. Here, we report a simple molecular and sequencing workflow called Genome-wide Analysis of Palindrome Formation (GAPF-seq) to probe DNA palindromes, a type of SV that often demarcates gene amplification. With low-throughput next-generation sequencing and automated machine learning, tumor DNA showed skewed chromosomal distributions of high-coverage 1-kb bins (HCBs), which differentiated 39 breast tumors from matched normal DNA with an average Area Under the Curve (AUC) of 0.9819. A proof-of-concept liquid biopsy study using cfDNA from prostate cancer patients and healthy individuals yielded an average AUC of 0.965. HCBs on the X chromosome emerged as a determinant feature and were associated with androgen receptor gene amplification. As a novel agnostic liquid biopsy approach, GAPF-seq could fill the technological gap offering unique cancer-specific SV profiles.