Working Experiences of Care Aides in Long-Term Care Institutions Following the Relaxation of COVID-19 Regulations in Taiwan: A Qualitative Study.

Care aides in long-term care (LTC) institutions care for older disabled residents at high risk for COVID-19. However, they experienced many stressors during the COVID-19 pandemic. This study aims to explore the working experiences of care aides in LTC institutions following the relaxation of COVID-19 regulations in Taiwan. This qualitative descriptive study included 20 care aides who had cared for residents with COVID-19. Data were obtained via semi-structured interviews. Caring for residents with COVID-19 and the difficulties, resources and teamwork, and impact of care aides' work on their lives were discussed. Consequently, four themes were identified. First, difficulties in care, which included physical limitations by protection, workload, and impact of work schedule on the lives of the care aides. Second, psychological impact, such as worry, social isolation, and burnout. Third, interpersonal relationships with supervisors, colleagues, residents, and their families. Fourth, infection control policy from the institution and government. When infection control policies were relaxed, care aides had difficulties in caring for residents; furthermore, their family and social lives were also affected. They were required to learn knowledge of and skills for COVID-19 management. Institutions were required to provide support in materials, care processes, environment, and management.

Precision Colorectal Cancer Fecal Immunological Test Screening With Fecal-Hemoglobin-Concentration-Guided Interscreening Intervals.

Importance: Given a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb-guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy. Objective: To demonstrate the applicability of personalized colorectal cancer (CRC) screening with f-Hb-guided screening intervals to reduce the number of FITs and colonoscopy with as equivalent efficacy as universal biennial screening equivalent efficacy as universal biennial screening. Design, Setting, and Participants: A retrospective cohort study for developing f-Hb-guided precision interscreening interval was conducted using data on a Taiwanese biennial nationwide FIT screening program that enrolled more than 3 million participants aged 50 to 74 years between 2004 and 2014. The cohort was followed up over time until 2019 to ascertain colorectal neoplasia and causes of death. A comparative study was further designed to compare the use of FIT and colonoscopy between the personalized f-Hb-guided group and the universal biennial screening group given the equivalent efficacy of reducing CRC-related outcomes. Main Outcomes and Measurements: A spectrum of f-Hb-guided intervals was determined by using the Poisson regression model given the equivalent efficacy of a universal biennial screening. The use of FIT and colonoscopy for the pragmatic f-Hb-guided interval group was measured compared with the universal biennial screening group. Data analysis was performed from September 2022 to October 2023. Results: Using data from the 3 500 250 participants (mean [SD] age, 57.8 [6.0] years) enrolled in the Taiwanese biennial nationwide FIT screening program, an incremental increase in baseline f-Hb associated with colorectal neoplasia and CRC mortality consistently was observed. Participants with different f-Hb levels were classified into distinct risk categories. Various screening intervals by different f-Hb levels were recommended. Using the proposed f-Hb-guided screening intervals, it was found that the personalized method was imputed to reduce the number of FIT tests and colonoscopies by 49% and 28%, respectively, compared with the universal biennial screening. Conclusion and Relevance: The gradient relationship between f-Hb and colorectal neoplasia and CRC mortality was used to develop personalized FIT screening with f-Hb-guided screening intervals. Such a precision interscreening interval led to the reduced use of FIT test and colonoscopy without compromising the effectiveness of universal biennial screening.

Impact of metformin on neocortical development during pregnancy: Involvement of ERK and p35/CDK5 pathways.

Metformin, the most commonly prescribed drug for the treatment of diabetes, is increasingly used during pregnancy to address various disorders such as diabetes, obesity, preeclampsia, and metabolic diseases. However, its impact on neocortex development remains unclear. Here, we investigated the direct effects of metformin on neocortex development, focusing on ERK and p35/CDK5 regulation. Using a pregnant rat model, we found that metformin treatment during pregnancy induces small for gestational age (SGA) and reduces relative cortical thickness in embryos and neonates. Additionally, we discovered that metformin inhibits neural progenitor cell proliferation in the sub-ventricular zone (SVZ)/ventricular zone (VZ) of the developing neocortex, a process possibly mediated by ERK inactivation. Furthermore, metformin induces neuronal apoptosis in the SVZ/VZ area of the developing neocortex. Moreover, metformin retards neuronal migration, cortical lamination, and differentiation, potentially through p35/CDK5 inhibition in the developing neocortex. Remarkably, compensating for p35 through in utero electroporation partially rescues metformin-impaired neuronal migration and development. In summary, our study reveals that metformin disrupts neocortex development by inhibiting neuronal progenitor proliferation, neuronal migration, cortical layering, and cortical neuron maturation, likely via ERK and p35/CDK5 inhibition. Consequently, our findings advocate for caution in metformin usage during pregnancy, given its potential adverse effects on fetal brain development.

Enhanced Electrical Transport Properties of Molybdenum Disulfide Field-Effect Transistors by Using Alkali Metal Fluorides as Dielectric Capping Layers.

The electronic properties of 2D materials are highly influenced by the molecular activity at their interfaces. A method was proposed to address this issue by employing passivation techniques using monolayer MoS2 field-effect transistors (FETs) while preserving high performance. Herein, we have used alkali metal fluorides as dielectric capping layers, including lithium fluoride (LiF), sodium fluoride (NaF), and potassium fluoride (KF) dielectric capping layers, to mitigate the environmental impact of oxygen and water exposure. Among them, the LiF dielectric capping layer significantly improved the transistor performance, specifically in terms of enhanced field effect mobility from 74 to 137 cm2/V·s, increased current density from 17 µA/µm to 32.13 µA/µm at a drain voltage of Vd of 1 V, and decreased subthreshold swing to 0.8 V/dec The results have been analytically verified by X-ray photoelectron spectroscopy (XPS) and Raman, and photoluminescence (PL) spectroscopy, and the demonstrated technique can be extended to other transition metal dichalcogenide (TMD)-based FETs, which can become a prospect for cutting-edge electronic applications. These findings highlight certain important trade-offs and provide insight into the significance of interface control and passivation material choice on the electrical stability, performance, and enhancement of the MoS2 FET.

Physical Fitness and Risk of Mental Disorders in Children and Adolescents.

Importance: With the rising prevalence of mental disorders among children and adolescents, identifying modifiable associations is critical. Objective: To examine the association between physical fitness and mental disorder risks. Design, Setting, and Participants: This nationwide cohort study used data from the Taiwan National Student Fitness Tests and National Health Insurance Research Databases from January 1, 2009 to December 31, 2019. Participants were divided into 2 cohorts targeting anxiety and depression (1 996 633 participants) and attention-deficit/hyperactivity disorder (ADHD; 1 920 596 participants). Participants were aged 10 to 11 years at study entry and followed up for at least 3 years, had a nearly equal gender distribution, and an average follow-up of 6 years. Data were analyzed from October 2022 to February 2024. Exposures: Assessments of physical fitness included cardiorespiratory fitness (CF), muscular endurance (ME), muscular power (MP), and flexibility, measured through an 800-m run time, bent-leg curl-ups, standing broad jump, and sit-and-reach test, respectively. Main Outcomes and Measures: Kaplan-Meier method calculated the cumulative incidence of anxiety, depression, and ADHD across fitness quartiles. Additionally, multivariable Cox proportional hazards models were used that included all 4 fitness components and explored sex and income as modifiers. Results: The anxiety and depression cohort had 1 996 633 participants (1 035 411 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years), while the ADHD cohort had 1 920 596 (975 568 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years). Cumulative incidence of mental disorders was lower among participants in better-performing fitness quartiles, suggesting a dose-dependent association. Gender-specific analyses, controlling for confounders, revealed that improved CF, indicated by a 30-second decrease in run times, was associated with reduced risks of anxiety, depression, and ADHD in female participants, and lower risks of anxiety and ADHD in male participants (adjusted hazard ratio [aHR] for ADHD risk for female participants, 0.92; 95% CI, 0.90-0.94; P < .001; for male participants, 0.93; 95% CI, 0.92-0.94; P < .001). Enhanced ME, marked by an increase of 5 curl-ups per minute, was associated with decreased risks of depression and ADHD in female participants, and lower anxiety and ADHD risks in male participants (aHR for ADHD risk for female participants, 0.94; 95% CI, 0.92-0.97; P < .001; for male participants, 0.96; 95% CI, 0.95-0.97; P < .001). Improved MP, reflected by a 20-cm increase in jump distance, was associated with reduced risks of anxiety and ADHD in female participants and reduced anxiety, depression, and ADHD in male participants (aHR for ADHD risk for female participants, 0.95; 95% CI, 0.91-1.00; P = .04; for male participants, 0.96; 95% CI, 0.94-0.99; P = .001). Conclusions and Relevance: This study highlights the potential protective role of cardiorespiratory fitness, muscular endurance, and muscular power in preventing the onset of mental disorders. It warrants further investigation of the effectiveness of physical fitness programs as a preventive measure for mental disorders among children and adolescents.

Anatomic versus Low Tibial Tunnel in Double-Bundle Posterior Cruciate Ligament Reconstruction: Clinical and Radiologic Outcomes with a Minimum 2-Year Follow-Up.

There is currently no consensus on the optimal placement of the tibial tunnel for double-bundle posterior cruciate ligament (PCL) reconstruction. The purpose of this study was to compare the clinical and radiologic outcomes of double-bundle PCL reconstruction utilizing anatomic versus low tibial tunnels. We conducted a retrospective cohort study involving patients who underwent double-bundle PCL reconstruction between Jan 2019 and Jan 2022, with a minimum follow-up of 2 years (n = 36). Based on the tibial tunnel position on postoperative computed tomography, patients were categorized into two groups: anatomic placement (group A; n = 18) and low tunnel placement (group L; n = 18). We compared the range of motion, stability test, complications, and side-to-side differences in tibial posterior translation using kneeling stress radiography between the two groups. There were no significant differences between the groups regarding clinical outcomes or complication rates. No significant differences in the posterior drawer test and side-to-side difference on kneeling stress radiography (2.5 ± 1.2 mm in group A vs. 3.7 ± 2.0 mm in group L; p = 0.346). In conclusion, the main findings of this study indicate that both anatomic tunnel and low tibial tunnel placements in double-bundle PCL reconstruction demonstrated comparable and satisfactory clinical and radiologic outcomes, with similar overall complication rates at the 2-year follow-up.

Feasibility estimation of injected hydrodissection before definitive radiotherapy of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however, no study has discussed which patients are suitable for the procedure. METHODS: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk. RESULTS: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for 1 patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images. CONCLUSION: Our results suggested that about half of the patients could have benefited from hydrodissection before radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control.

A Precarious Path to Partnership? The Moderating Effects of Labour Market Regulations on the Relationship Between Unstable Employment and Union Formation in Europe.

Rising employment uncertainty featured by higher risks of being temporarily employed or unemployed is often seen as the driving force behind delayed and declined partnering in Western countries. However, such an employment-partnering relationship is contextualized by labour market institutions and thus could diverge across countries over time. This paper aims to investigate how country-level variations in labour market regulations moderate individual-level effects of unstable employment on union formation, including the transitions into marriage or cohabitation unions. Using comparative panel data for 26 countries from the European Union Statistics on Income and Living Conditions (the years 2010-2019), our multilevel fixed effects models showed that temporary employment and unemployment negatively affected the probability of union formation for single women and men in Europe. Moreover, the negative relationship between unstable employment and union formation was reinforced when labour market reforms were stimulating insider-outsider segregations or decreasing welfare provisions. Specifically, stricter employment protection legislations and higher coverage rates of collective bargaining agreements could reinforce the negative effects of temporary employment and unemployment on union formation, while more generous provisions of unemployment benefits could buffer such negative effects.

New insights into three trajectories of omicron-related all-cause death reduced by COVID-19 booster vaccination.

BACKGROUND: The trajectories of all-cause deaths linked to omicron infections are rarely studied, especially in relation to the efficacy of booster shots. For assessing three epidemiological death trajectories, including dying from COVID-19, dying with COVID-19, and non-COVID-19 death, we offer a new COVID-19-and-death competing risk model that deals with the primary pathway (e.g., dying from COVID-19) competing with two other pathways. METHODS: We applied this model to track three trajectories: deaths directly from COVID-19, deaths with COVID-19 as a contributing factor, and indirect non-COVID-19 deaths. The study used data from a Taiwanese cohort, covering periods of Omicron subvariants BA.2, BA.5, and BA.2.75. It focused on the effectiveness of monovalent and bivalent booster vaccines against these death trajectories. RESULTS: The highest mortality was observed during the BA.2 phase, which decreased in the BA.5 period and increased again in the BA.2.75 period. Analyzing each trajectory, we noted similar trends in deaths directly from and with COVID-19, while non-COVID-19 deaths remained stable across subvariants. Booster vaccines reduced all-cause mortality by 58% (52%-62%) for BA.2, 70% (65%-75%) for BA.5%, and 75% (70%-80%) for BA.2.75, compared to incomplete vaccination. The reduction in deaths directly from COVID-19 was 66% (61%-72%) for BA.2, 78% (72%-84%) for BA.5%, and 85% (76%-93%) for BA.2.75. For deaths with COVID-19, the figures were 46% (36%-55%), 76% (68%-84%), and 90% (86%-95%). Additionally, the booster shots decreased non-COVID-19 deaths by 64% (63%-66%) for BA.2, 38% (36%-40%) for BA.5, and 19% (17%-21%) for BA.2.75. CONCLUSION: Our competing risk analysis is effective for monitoring all-cause death trajectories amidst various Omicron infections. It provides insights into the impact of booster vaccines, especially bivalent ones, and highlights the consequences of inadequate healthcare for vulnerable groups.

Advancing screening tool for hospice needs and end-of-life decision-making process in the emergency department.

BACKGROUND: Predicting mortality in the emergency department (ED) is imperative to guide palliative care and end-of-life decisions. However, the clinical usefulness of utilizing the existing screening tools still leaves something to be desired. METHODS: We advanced the screening tool with the A-qCPR (Age, qSOFA (quick sepsis-related organ failure assessment), cancer, Performance Status Scale, and DNR (Do-Not-Resuscitate) risk score model for predicting one-year mortality in the emergency department of Taipei City Hospital of Taiwan with the potential of hospice need and evaluated its performance compared with the existing screening model. We adopted a large retrospective cohort in conjunction with in-time (the trained and the holdout validation cohort) for the development of the A-qCPR model and out-of-time validation sample for external validation and model robustness to variation with the calendar year. RESULTS: A total of 10,474 patients were enrolled in the training cohort and 33,182 patients for external validation. Significant risk scores included age (0.05 per year), qSOFA ≥ 2 (4), Cancer (5), Eastern Cooperative Oncology Group (ECOG) Performance Status score ≥ 2 (2), and DNR status (2). One-year mortality rates were 13.6% for low (score ≦ 3 points), 29.9% for medium (3 < Score ≦ 9 points), and 47.1% for high categories (Score > 9 points). The AUROC curve for the in-time validation sample was 0.76 (0.74-0.78). However, the corresponding figure was slightly shrunk to 0.69 (0.69-0.70) based on out-of-time validation. The accuracy with our newly developed A-qCPR model was better than those existing tools including 0.57 (0.56-0.57) by using SQ (surprise question), 0.54 (0.54-0.54) by using qSOFA, and 0.59 (0.59-0.59) by using ECOG performance status score. Applying the A-qCPR model to emergency departments since 2017 has led to a year-on-year increase in the proportion of patients or their families signing DNR documents, which had not been affected by the COVID-19 pandemic. CONCLUSIONS: The A-qCPR model is not only effective in predicting one-year mortality but also in identifying hospice needs. Advancing the screening tool that has been widely used for hospice in various scenarios is particularly helpful for facilitating the end-of-life decision-making process in the ED.

Working dilemmas in care for breastfed newborns: An exploratory study in a single center in Taiwan.

BACKGROUND: Clinical medical staff should be aware of and examine the correlation between breastfeeding and neonatal hospitalization. Additional attention should be paid to work dilemmas experienced by the nursing staff caring for newborns to avoid exposing newborns to hospitalization risk. OBJECTIVE: The present study investigated the working dilemmas by neonatal nurses caring for breastfed newborns and risk of newborn hospitalization. METHODS: This hospital-based study in Taiwan surveyed 84 neonatal nurses using a structured questionnaire entitled "Working Dilemmas in Clinical Care for Breastfed Newborns." RESULTS: Collected data were analyzed statistically (descriptive analysis, chi-square test, and t test) using Statistical Package for the Social Sciences (SPSS) software. Neonatal intensive care unit (NICU) staff noted that breastfed newborns showed a high risk of hospitalization and nursery staff highlighted a lack of manpower and time. NICU staff experienced more working dilemmas (117.460±12.260) than nursery staff (87.410±15.820) when caring for breastfed newborns (t = 1.080, P <  0.001). NICU staff reported a higher risk of hospitalization in breastfed newborns and experienced more working dilemmas caring for these patients compared with nursery staff, who reported a lack of manpower and time. CONCLUSION: Our findings highlight the working dilemmas by neonatal nurses and can serve as a foundation for further critical studies.

Novel nanocomposite-superlattices for low energy and high stability nanoscale phase-change memory.

Data-centric applications are pushing the limits of energy-efficiency in today's computing systems, including those based on phase-change memory (PCM). This technology must achieve low-power and stable operation at nanoscale dimensions to succeed in high-density memory arrays. Here we use a novel combination of phase-change material superlattices and nanocomposites (based on Ge4Sb6Te7), to achieve record-low power density ≈ 5 MW/cm2 and ≈ 0.7 V switching voltage (compatible with modern logic processors) in PCM devices with the smallest dimensions to date (≈ 40 nm) for a superlattice technology on a CMOS-compatible substrate. These devices also simultaneously exhibit low resistance drift with 8 resistance states, good endurance (≈ 2 × 108 cycles), and fast switching (≈ 40 ns). The efficient switching is enabled by strong heat confinement within the superlattice materials and the nanoscale device dimensions. The microstructural properties of the Ge4Sb6Te7 nanocomposite and its high crystallization temperature ensure the fast-switching speed and stability in our superlattice PCM devices. These results re-establish PCM technology as one of the frontrunners for energy-efficient data storage and computing.

The Aerodynamic Effect of Biomimetic Pigeon Feathered Wing on a 1-DoF Flapping Mechanism.

This study focused on designing a single-degree-of-freedom (1-DoF) mechanism emulating the wings of rock pigeons. Three wing models were created: one with REAL feathers from a pigeon, and the other two models with 3D-printed artificial remiges made using different strengths of material, PLA and PETG. Aerodynamic performance was assessed in a wind tunnel under both stationary (0 m/s) and cruising speed (16 m/s) with flapping frequencies from 3.0 to 6.0 Hz. The stiffness of remiges was examined through three-point bending tests. The artificial feathers made of PLA have greater rigidity than REAL feathers, while PETG, on the other hand, exhibits the weakest strength. At cruising speed, although the artificial feathers exhibit more noticeable feather splitting and more pronounced fluctuations in lift during the flapping process compared to REAL feathers due to the differences in weight and stiffness distribution, the PETG feathered wing showed the highest lift enhancement (28% of pigeon body weight), while the PLA feathered wing had high thrust but doubled drag, making them inefficient in cruising. The PETG feathered wing provided better propulsion efficiency than the REAL feathered wing. Despite their weight, artificial feathered wings outperformed REAL feathers in 1-DoF flapping motion. This study shows the potential for artificial feathers in improving the flight performance of Flapping Wing Micro Air Vehicles (FWMAVs).

Two-stage deep-learning-based colonoscopy polyp detection incorporating fisheye and reflection correction.

BACKGROUND AND AIM: Colonoscopy is a useful method for the diagnosis and management of colorectal diseases. Many computer-aided systems have been developed to assist clinicians in detecting colorectal lesions by analyzing colonoscopy images. However, fisheye-lens distortion and light reflection in colonoscopy images can substantially affect the clarity of these images and their utility in detecting polyps. This study proposed a two-stage deep-learning model to correct distortion and reflections in colonoscopy images and thus facilitate polyp detection. METHODS: Images were collected from the PolypSet dataset, the Kvasir-SEG dataset, and one medical center's patient archiving and communication system. The training, validation, and testing datasets comprised 808, 202, and 1100 images, respectively. The first stage involved the correction of fisheye-related distortion in colonoscopy images and polyp detection, which was performed using a convolutional neural network. The second stage involved the use of generative and adversarial networks for correcting reflective colonoscopy images before the convolutional neural network was used for polyp detection. RESULTS: The model had higher accuracy when it was validated using corrected images than when it was validated using uncorrected images (96.8% vs 90.8%, P < 0.001). The model's accuracy in detecting polyps in the Kvasir-SEG dataset reached 96%, and the area under the receiver operating characteristic curve was 0.94. CONCLUSION: The proposed model can facilitate the clinical diagnosis of colorectal polyps and improve the quality of colonoscopy.

Beneficial effect of repeated participation in breast cancer screening upon survival.

OBJECTIVES: The benefit of mammography screening in reducing population mortality from breast cancer is well established. In this paper, we estimate the effect of repeated participation at scheduled screens on case survival. METHODS: We analysed incidence and survival data on 37,079 women from nine Swedish counties who had at least one to five invitation(s) to screening prior to diagnosis, and were diagnosed with breast cancer between 1992 and 2016. Of these, 4564 subsequently died of breast cancer. We estimated the association of survival with participation in up to the most recent five screens before diagnosis. We used proportional hazards regression to estimate the effect on survival of the number of scheduled screens in which subjects participated prior to the diagnosis of breast cancer. RESULTS: There was successively better survival with an increasing number of screens in which the subject participated. For a woman with five previous screening invitations who participated in all five, the hazard ratio was 0.28 (95% confidence interval (CI) 0.25-0.33, p < 0.0001) compared to a woman attending none (86.9% vs 68.9% 20-year survival). Following a conservative adjustment for potential self-selection factors, the hazard ratio was 0.34 (95% CI 0.26-0.43, p < 0.0001), an approximate three-fold reduction in the hazard of dying from breast cancer. CONCLUSION: For those women who develop breast cancer, regular prior participation in mammography screening confers significantly better survival.

High-performance monolayer MoS2nanosheet GAA transistor.

In this article, a 0.7 nm thick monolayer MoS2nanosheet gate-all-around field effect transistors (NS-GAAFETs) with conformal high-κmetal gate deposition are demonstrated. The device with 40 nm channel length exhibits a high on-state current density of ~410µAµm-1with a large on/off ratio of 6 × 108at drain voltage = 1 V. The extracted contact resistance is 0.48 ± 0.1 kΩµm in monolayer MoS2NS-GAAFETs, thereby showing the channel-dominated performance with the channel length scaling from 80 to 40 nm. The successful demonstration of device performance in this work verifies the integration potential of transition metal dichalcogenides for future logic transistor applications.

Ultrasensitive and High-Resolution Protein Spatially Decoding Framework for Tumor Extracellular Vesicles.

Proteins localized on the surface or within the lumen of tumor-derived extracellular vesicles (EVs) play distinct roles in cancer progression. However, quantifying both populations of proteins within EVs has been hampered due to the limited sensitivity of the existing protein detection methods and inefficient EV isolation techniques. In this study, the eSimoa framework, an innovative approach enabling spatial decoding of EV protein biomarkers with unmatched sensitivity and specificity is presented. Using the luminal eSimoa pipeline, the absolute concentration of luminal RAS or KRASG12D proteins is released and measured, uncovering their prevalence in pancreatic tumor-derived EVs. The pulldown eSimoa pipeline measured absolute protein concentrations from low-abundance EV subpopulations. The eSimoa assays detected EVs in both PBS and plasma samples, confirming their applicability across diverse clinical sample types. Overall, the eSimoa framework offers a valuable tool to (1) detect EVs at concentrations as low as 105 EV mL-1 in plasma, (2) quantify absolute EV protein concentrations as low as fM, and (3) decode the spatial distribution of EV proteins. This study highlights the potential of eSimoa in identifying disease-specific EV protein biomarkers in clinical samples with minimal pre-purification, thereby driving advancements in clinical translation.