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Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors. Their size, however, complicates their isolation from mainstream tumor cell populations. Standard techniques like fluorescence-activated cell sorting (FACS) rely on fluorescent labeling, introducing potential challenges in subsequent PGCC analyses. In response, we developed the Isosceles Trapezoidal Spiral Microchannel (ITSμC), a microfluidic device optimizing the Dean drag force (FD) and exploiting uniform vortices for enhanced separation. Numerical simulations highlighted ITSμC's advantage in producing robust FD compared to rectangular and standard trapezoidal channels. Empirical results confirmed its ability to segregate larger polystyrene (PS) particles (avg. diameter: 50 μm) toward the inner wall, while directing smaller ones (avg. diameter: 23 μm) outward. Utilizing ITSμC, we efficiently isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) and patient-derived cancer (PDC) cells, achieving outstanding purity, yield, and viability rates (all greater than 90%). This precision was accomplished without fluorescent markers, and the versatility of ITSμC suggests its potential in differentiating a wide range of heterogeneous cell populations. [ABSTRACT FROM AUTHOR]

Hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-BC) is the most common type with a favorable prognosis under endocrine therapy. However, it still demonstrates unpredictable progression and recurrences influenced by high tumoral diversity and microenvironmental status. To address these heterogeneous molecular characteristics of HR+/HER2-BC, we aimed to simultaneously characterize its transcriptomic landscape and genetic architecture at the same resolution. Using advanced single-cell RNA and DNA sequencing techniques together, we defined four distinct tumor subtypes. Notably, the migratory tumor subtype was closely linked to genomic alterations of EGFR, related to the tumor-promoting behavior of IL6-positive inflammatory tumor-associated fibroblast, and contributing to poor prognosis. Our study comprehensively utilizes integrated analysis to uncover the complex dynamics of this breast cancer subtype, highlighting the pivotal role of the migratory tumor subtype in influencing surrounding cells. This sheds light on potential therapeutic targets by offering enhanced insights for HR+/HER2-BC treatment. [ABSTRACT FROM AUTHOR]

In this work, a flexible perovskite photodetector is demonstrated with a transferable TiO2 nanorod (NR) as an electron transport layer (ETL). The TiO2 NRs are grown by the hydrothermal method on Ni metal buffer layer/Si (100) substrates. During the growth process of TiO2 NRs in solution, the Ni sacrificial buffer layer is removed by hydrochloric acid in the initial stage. The resulting suspended seed layer can then sustain the growth of TiO2 NRs in both the top and bottom directions. The successfully grown TiO2 NRs are now transferred onto an ITO‐coated PET substrate as an ETL for the flexible Cs2AgBiBr6 perovskite photodetectors. The fabricated photodetector operates under a wavelength of 405 nm, and at an external bias voltage of −0.3 V, it exhibits an outstanding performance with an on/off ratio of 1.23 × 104, photoresponsivity (R) of 0.666 A W−1, and a detectivity (D*) of 9.29 × 1012 Jones. In terms of flexibility, the optoelectronic performance of each device is well kept within 5% after 300 bending test cycles with a radius of 1 cm. The suggested transferable TiO2 NRs can improve the efficiency of flexible optoelectronic devices that require synergistic electron transfer effects by using heterostructures with TiO2 nanostructures. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the association between initial fibrinogen levels and massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). Methods: This retrospective study was conducted in the ED of a university-affiliated, tertiary referral center from January 2004 to August 2023. Patients were divided into two groups: the MT group, which included those who received a transfusion of 10 or more units of packed red blood cells within the first 24 h, and the Non-MT group. Results: Out of the 364 patients included in the study, 97 (26.6%) required MT. Fibrinogen, shock index, and lactate were independently associated with MT (odds ratio [OR] 0.987; 95% confidence interval [CI] 0.983–0.991; p < 0.001, OR 7.277; 95% CI 1.856–28.535; p = 0.004, and OR 1.261; 95% CI 1.021–1.557; p = 0.031, respectively). The area under the receiver operating characteristic curve for fibrinogen, shock index, and lactate in predicting MT was 0.871 (95% CI 0.832–0.904; p < 0.001), 0.821 (95% CI 0.778–0.859; p < 0.001), and 0.784 (95% CI 0.738–0.825; p < 0.001), respectively. When the cutoff value of fibrinogen was 400 mg/dL, both the sensitivity and negative predictive values for predicting MT were 100.0%. When the cutoff value of fibrinogen was 100 mg/dL, the specificity and positive predictive values were 91.8% and 70.7%, respectively. Conclusion: The initial fibrinogen levels were independently associated with the need for MT in ED patients with primary PPH. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The timing of preoperative imaging in patients with lung cancer is a debated topic, as there are limited data on cancer progression during the interval between clinical staging by imaging and pathological staging after resection. We quantified disease progression during this interval in patients with early stage non-small-cell lung cancer (NSCLC) to better understand if its length impacts upstaging. METHODS We retrospectively reviewed our institutional database to identify patients who underwent surgery for clinically staged T1N0M0 NSCLC from January 2015 through September 2022. Tumour upstaging between chest computed tomography (CT) and surgery were analysed as a function of time (<30, 30–59, ≥60 days) for different nodule subtypes. We analysed data across 3 timeframes using Pearson's chi-squared and analysis of variance tests. RESULTS During the study period, 622 patients underwent surgery for clinically staged T1N0M0 NSCLC. CT-to-surgery interval was <30 days in 228 (36.7%), 30–59 days in 242 (38.9%) and ≥60 days in 152 (24.4%) with no differences in patient or nodule characteristics observed between these groups. T-stage increased in 346 patients (55.6%) between CT imaging and surgery. Among these patients, 126 (36.4%) had ground-glass nodules, 147 (42.5%) had part-solid nodules and 73 (21.1%) had solid nodules. CT-to-surgery interval length was not associated with upstaging of any nodule subtype (full-cohort, P  = 0.903; ground-glass, P  = 0.880; part-solid, P  = 0.858; solid, P  = 0.959). CONCLUSIONS This single-centre experience suggests no significant association between tumour upstaging and time from imaging to lung resection in patients with clinical stage IA NSCLC. Further studies are needed to better understand the risk factors for upstaging. [ABSTRACT FROM AUTHOR]

Activation of microglia by classical inflammatory mediators can convert astrocytes into a neurotoxic A1 phenotype in a variety of neurological diseases.sup.1,2. Development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat these diseases for which there are no disease-modifying therapies. Glucagon-like peptide-1 receptor (GLP1R) agonists have been indicated as potential neuroprotective agents for neurologic disorders such as Alzheimer's disease and Parkinson's disease.sup.3-13. The mechanisms by which GLP1R agonists are neuroprotective are not known. Here we show that a potent, brain-penetrant long-acting GLP1R agonist, NLY01, protects against the loss of dopaminergic neurons and behavioral deficits in the [alpha]-synuclein preformed fibril ([alpha]-syn PFF) mouse model of sporadic Parkinson's disease.sup.14,15. NLY01 also prolongs the life and reduces the behavioral deficits and neuropathological abnormalities in the human A53T [alpha]-synuclein (hA53T) transgenic mouse model of [alpha]-synucleinopathy-induced neurodegeneration.sup.16. We found that NLY01 is a potent GLP1R agonist with favorable properties that is neuroprotective through the direct prevention of microglial-mediated conversion of astrocytes to an A1 neurotoxic phenotype. In light of its favorable properties, NLY01 should be evaluated in the treatment of Parkinson's disease and related neurologic disorders characterized by microglial activation. Agonism of microglial glucagon-like peptide-1 receptor (GLP1R) using a brain-penetrant peptide prevents the generation of neurotoxic astrocytes and ameliorates disease progression in two rodent models of Parkinson's disease., Author(s): Seung Pil Yun [sup.1] [sup.2] [sup.3] , Tae-In Kam [sup.1] [sup.2] , Nikhil Panicker [sup.1] [sup.2] , SangMin Kim [sup.1] [sup.2] , Yumin Oh [sup.4] [sup.5] , Jong-Sung Park [...]

Pedestrian tracking is a challenging task in the area of visual object tracking research and it is a vital component of various vision-based applications such as surveillance systems, human-following robots, and autonomous vehicles. In this paper, we proposed a single pedestrian tracking (SPT) framework for identifying each instance of a person across all video frames through a tracking-by-detection paradigm that combines deep learning and metric learning-based approaches. The SPT framework comprises three main modules: detection, re-identification, and tracking. Our contribution is a significant improvement in the results by designing two compact metric learning-based models using Siamese architecture in the pedestrian re-identification module and combining one of the most robust re-identification models for data associated with the pedestrian detector in the tracking module. We carried out several analyses to evaluate the performance of our SPT framework for single pedestrian tracking in the videos. The results of the re-identification module validate that our two proposed re-identification models surpass existing state-of-the-art models with increased accuracies of 79.2% and 83.9% on the large dataset and 92% and 96% on the small dataset. Moreover, the proposed SPT tracker, along with six state-of-the-art (SOTA) tracking models, has been tested on various indoor and outdoor video sequences. A qualitative analysis considering six major environmental factors verifies the effectiveness of our SPT tracker under illumination changes, appearance variations due to pose changes, changes in target position, and partial occlusions. In addition, quantitative analysis based on experimental results also demonstrates that our proposed SPT tracker outperforms the GOTURN, CSRT, KCF, and SiamFC trackers with a success rate of 79.7% while beating the DiamSiamRPN, SiamFC, CSRT, GOTURN, and SiamMask trackers with an average of 18 tracking frames per second. [ABSTRACT FROM AUTHOR]

Accurate daily peak load forecasting (DPLF) is crucial for informed decision-making in energy management. Deep neural networks (DNNs) are particularly apt for DPLF because they can analyze multiple factors, such as timestamps, weather conditions, and historical electric loads. Interpretability of machine learning models is essential for ensuring stakeholders understand and trust the decision-making process. We proposed the RAID (robust and interpretable DPLF) model, which enhances DPLF accuracy by recognizing daily peak load patterns and building separate DNN models for each day of the week. This approach was accessible for energy providers with limited computational resources, as the DNN models could be configured without a graphics processing unit (GPU). We utilized scikit-learn's MLPRegressor for streamlined implementation, Optuna for hyperparameter optimization, and the Shapley additive explanations (SHAP) method to ensure interpretability. Applied to a dataset from two commercial office buildings in Richland, Washington, RAID outperformed existing methods like recurrent neural networks, Cubist, and HYTREM, achieving the lowest mean absolute percentage error values: 14.67% for Building 1 and 12.74% for Building 2. The kernel SHAP method revealed the influence of the previous day's peak load and temperature-related variables on the prediction. The RAID model substantially improved energy management through enhanced DPLF accuracy, outperforming competing methods, providing a GPU-free configuration, and ensuring interpretable decision-making, with the potential to influence energy providers' choices and promote overall energy system sustainability. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The STS Thoracic Surgery Practice and Access Task Force - 2019 Workforce Report noted gender-based differences in the income of cardiothoracic surgeons in the United States. We analysed the 2019 Medicare payment data for thoracic and cardiac surgeons to investigate the gender-based payment gap among cardiothoracic surgeons. METHODS The 2019 Medicare Physician and Other Practitioners by Provider and Services data set merged with the Doctors and Clinicians National Downloadable File was utilized to conduct a cross-sectional analysis of gender differences in Medicare payments, numbers of services, unique billing codes, years in practice, Medicare beneficiary age, regional population density (rural-urban commuting area code) and patient panel complexity (hierarchical condition category) for providers. The providers' self-reported gender (women or men) and provider type (thoracic surgery or cardiac surgery) were binarily set according to the Center for Medicare and Medicaid Services standards. Independent analyses were performed with thoracic and cardiac surgeons. We also used the 2013 and 2016 Medicare Physician and Other Practitioners by Provider and Services data sets to analyse the trends in adjusted gender-based payment differences across 2013, 2016 and 2019. RESULTS After controlling for the covariates, women thoracic surgeons received $25,183.50 [95% confidence interval (CI) $16,307.60, $34,059.40] less than the mean Medicare payment than men thoracic surgeons. Likewise, women cardiac surgeons received $20,960 [95% confidence interval (CI) $1,014.80, $40,902.80] less than the mean adjusted Medicare payment than their men counterparts. CONCLUSIONS In 2019, women cardiothoracic surgeons received a significantly lower mean Medicare payment than men cardiothoracic surgeons after controlling for the number of services, unique billing codes, the complexity of the patient panel, years in practice and regional population density. The payment gap between women and men exhibited no statistically significant change over 2013, 2016 and 2019. Future studies are warranted to understand the association between gender representation and the pay gap. [ABSTRACT FROM AUTHOR]

Platelet-derived growth factor receptor (PDGFR) plays an essential role in the proliferation and invasion of malignant cancer cells. However, the functional role of PDGFR alpha (PDGFRA) in HER2-positive (HER2+) breast cancer has not been fully clarified yet. Thus, the objective of this study was to investigate the clinical significance of PDGFRA and the therapeutic potential of PDGFR inhibitors as part of an effort to overcome trastuzumab (TRZ) resistance. Aberrant PDGFRA expression is closely associated with decreased survival in HER2+ breast cancers. Therefore, we established BT474 trastuzumab-sensitive (TRZ_S) and trastuzumab-resistant (TRZ_R) cells to investigate the association between PDGFR signaling and TRZ resistance. We found that PDGFRA was significantly upregulated in the BT474 TRZ_R cells. In addition, IL-6 expression, which was also found to be upregulated in the TRZ_R cells, was induced by PDGFC, a ligand of PDGFR. Next, we investigated the effects of ponatinib and sunitinib, PDGFR inhibitors, on the BT474 TRZ_R and HCC1954 (TRZ-resistant cell line) cells. These inhibitors decreased cell viability and migration in a dose-dependent manner. Additionally, IL-6 expression was decreased by ponatinib in both the BT474 TRZ_R and HCC1954 cells. In contrast, IL-6 was not suppressed by TRZ, implying that the PDGFRA/STAT3/IL-6 axis is associated with resistance to TRZ. In addition, we found that STAT3 and ERK phosphorylation were increased in the BT474 TRZ_R cells. IL-6 expression was suppressed by a STAT3 inhibitor, indicating that IL-6 expression is modulated downstream of STAT3. Taken together, these results suggest that PDGFRA could serve as a therapeutic target to overcome TRZ resistance. [ABSTRACT FROM AUTHOR]

Basal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood. In the present study, mechanisms of aggressiveness of BLBC involving EGFR and/or HER2 expression and interactions between tumor and tumor-associated macrophages (TAMs) were explored. The prognosis of breast cancer patients who underwent surgery at Samsung Medical Center was analyzed. It was found that the co-expression of EGFR and HER2 was associated with a worse prognosis. Therefore, we generated EGFR-positive BLBC cells with stable HER2 overexpression and analyzed the profile of secretory cytokines. Chemokine (C-C motif) ligand 2 (CCL2) expression was increased in HER2-overexpressed BLBC cells. Recombinant human CCL2 treatment augmented the motility of TAMs. In addition, the conditioned culture media of HER2-overexpressed BLBC cells increased the motility of TAMs. Furthermore, activation of TAMs by CCL2 or the conditioned culture media of HER2-overexpressed cells resulted in the production of pro-inflammatory cytokines, such as IL-8 and IL-1β. These observations reveal that CCL2 derived from EGFR and HER2 co-expressed BLBC cells can lead to increased TAM recruitment and the induction of IL-8 and IL-1β from recruited TAMs, triggering the tumorigenesis of breast cancer with the expression of both EGFR and HER2. Our findings demonstrate that EGFR+ and HER2+ BLBC aggressiveness is partially mediated through the interaction between BLBC and TAMs recruited by CCL2. [ABSTRACT FROM AUTHOR]

Purpose of review: This review summarizes technology-based interventions for HIV in low- and middle-income countries (LMICs). We highlight potential benefits and challenges to using telehealth in LMICs and propose areas for future study. Recent findings: We identified several models for using telehealth to expand HIV health care access in LMICs, including telemedicine visits for pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) services, telementoring programs for providers, and virtual peer-support groups. Emerging data support the acceptability and feasibility of these strategies. However, further investigations are needed to determine whether these models are scalable and sustainable in the face of barriers related to cost, infrastructure, and regulatory approval. Summary: HIV telehealth interventions may be a valuable approach to addressing gaps along the HIV care cascade in LMICs. Future studies should focus on strategies for expanding existing programs to scale and for assessing long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

This study aims to investigate the methanogenic community of anaerobic mono-digestion of sewage sludge (SL-digester) and co-digestion of sewage sludge with food waste (co-digester). The volatile solids, chemical oxygen demands, organic fractions, and ions in influent wastewater of digester can affect both SL-only digester and co-digester. An increase of [NH4+] in the anaerobic digester affected organic removal efficiency and microbial diversity. Methanobrevibacter smithii (33.8 ± 14.7%), Methanoculleus receptaculi (12.3 ± 5.3%), Methanolinea mesophila (9.5 ± 4.1%), and Methanospirillum hungatei (5.5 ± 9.2%) were dominant in every digester. These methanogens had a significant correlation with physicochemical properties (VFA and NH4+) or methanogens depending on their microbial metabolic pathway such as propionate degradation or ammonia resistance. This research would be used as a guideline to solve the complexity of full-scale plants' operation and reveal the 'black-box' of anaerobic digestion. [ABSTRACT FROM AUTHOR]