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Hypoxia plays a crucial role in cell physiology. Defining the oxygen level that induces cell death within 3D tissues is vital for understanding tissue hypoxia; however, obtaining accurate measurements has been technically challenging. In this study, we introduce a non-invasive, high-throughput methodology to quantify critical survival partial oxygen pressure (pO₂) with high spatial resolution within spheroids by employing a combination of controlled hypoxic conditions, semi-automated live/dead cell imaging, and computational oxygen modeling. The oxygen-permeable, micro-pyramid patterned culture plates created a precisely controlled oxygen condition around the individual spheroid. Live/dead cell imaging provided the geometric information of the live/dead boundary within spheroids. Finally, computational oxygen modeling calculated the pO₂ at the live/dead boundary within spheroids. As proof of concept, we determined the critical survival pO₂ in two types of spheroids: isolated primary pancreatic islets and tumor-derived pseudo-islets (2.43 ± 0.08 vs. 0.84 ± 0.04 mmHg), indicating higher hypoxia tolerance in pseudo-islets due to their tumorigenic origin. We also applied this method for evaluating graft survival in cell transplantations for diabetes therapy, where hypoxia is a critical barrier to successful transplantation outcomes; thus, designing oxygenation strategies is required. Based on the elucidated critical survival pO₂, 100% viability could be maintained in a typically sized primary islet under the tissue pO₂ above 14.5 mmHg. This work presents a valuable tool that is potentially instrumental for fundamental hypoxia research. It offers insights into physiological responses to hypoxia among different cell types and may refine translational research in cell therapies.

Abstract Background In patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure, approximately 10% of them are considered to be at high risk for prolonged mechanical ventilation (PMV, > 21 days). PMV have been identified as independent predictors of unfavorable outcomes. Our previous study revealed that patients aged 70 years older and COPD severity were at a significantly higher risk for PMV. We aimed to analyze the impact of comorbidities and their associated risks in patients with COPD who require PMV. Methods The data used in this study was collected from Kaohsiung Medical University Hospital Research Database. The COPD subjects were the patients first diagnosed COPD (index date) between January 1, 2012 and December 31, 2020. The exclusion criteria were the patients with age less than 40 years, PMV before the index date or incomplete records. COPD and non-COPD patients, matched controls were used by applying the propensity score matching method. Results There are 3,744 eligible patients with COPD in the study group. The study group had a rate of 1.6% (60 cases) patients with PMV. The adjusted HR of PMV was 2.21 (95% CI 1.44–3.40; P

Abstract Large‐area graphene is typically synthesized on rolled‐annealed copper foils, which require transferring to other substrates for applications. This study examines large‐area graphene growth on electrodeposited (ED) copper foils—used in lithium‐ion batteries and printed circuit boards—via plasma‐enhanced chemical vapor deposition (PECVD). It reveals that, for a set plasma power, a minimum growth time ensures full graphene coverage, leading to monolayer and then multilayer graphene, showing PECVD growth on ED copper is not self‐limited. The process also beneficially modifies the ED copper substrate, like removing the surface zinc layer and changing copper grain size and orientation, thus improving graphene growth. Additionally, the study includes high‐frequency scattering parameter (S‐parameter) measurements in a coplanar waveguide (CPW) system. This involves graphene on a sapphire substrate with a silver electrode. The S‐parameter data indicate that the CPW with graphene shows reduced insertion losses in high‐frequency circuits compared to those without graphene. This underscores graphene's role in reducing insertion losses between metallic and dielectric layers in high‐frequency settings, offering valuable insights for industrial and technological applications.

Objectives: Long-acting bronchodilators are important treatments for chronic obstructive pulmonary disease (COPD) and adequate medication adherence decreases COPD exacerbations, especially in reducing the hazard of influenza infection. Therefore, the study aim was to evaluate adherence of long-acting bronchodilator treatment and the risk of influenza in patients with COPD. Methods: This retrospective nested case-control study included patients with newly diagnosed COPD from 2012 to 2018. Cases with influenza infection were defined and matched to 2 randomly selected controls. The influenza infection date was the index date. Conditional logistic regressions were used to estimate odds ratios of influenza from proportion of days covered (PDC) of long-acting bronchodilators measured in one year before the index date. Adherence was divided into high adherence (PDC ≥80 %) and low adherence (PDC

Abstract Background This study examines incidence, mortality, medical expenditure and prescription patterns for asthma on a national scale, particularly in Asian countries for asthma is limited. Our aim is to investigate incidence, mortality, prescription patterns and provide a comprehensive overview of healthcare utilization trends for asthma from 2009 to 2018. Methods We included patients diagnosed with asthma between 2009 and 2018. We excluded patients with missing demographic data. Our analysis covered comorbidities, including diabetes mellitus, hypertension, allergic rhinitis, eczema, atopic dermatitis, coronary artery disease, congestive heart failure, chronic kidney disease, chronic hepatitis, stroke, and cancer. Investigated medications comprised oral and intravenous steroids, short-acting beta-agonists, inhaled corticosteroids (ICS), combinations of ICS and long-acting beta-agonists, long-acting muscarinic antagonists, and leukotriene receptor antagonists montelukast. We also assessed the number of outpatient visits, emergency visits, and hospitalizations per year, as well as the average length of hospitalization and average medical costs. Results The study included a final count of 88,244 subjects from 1,998,311 randomly selected samples between 2000 and 2019. Over the past decade, there was a gradual decline in newly diagnosed asthma patients per year, from 10,140 to 6,487. The mean age annually increased from 47.59 in 2009 to 53.41 in 2018. Over 55% of the patients were female. Eczema was diagnosed in over 55% of the patients. Around 90% of the patients used oral steroids, with a peak of 97.29% in 2018, while the usage of ICS varied between 86.20% and 91.75%. Intravenous steroids use rose from 40.94% in 2009 to 54.14% in 2018. The average annual hospital stay ranged from 9 to 12 days, with a maximum of 12.26 days in 2013. Lastly, the average medical expenses per year ranged from New Taiwan dollars 5558 to 7921. Conclusions In summary, both asthma incidence and all-cause mortality rates decreased in Taiwan from 2009 to 2018. Further analysis of medical expenses in patients with asthma who required multiple hospitalizations annually revealed an increase in outpatient and emergency visits and hospitalizations, along with longer hospital stays and higher medical costs.

Abstract Objective The healthcare challenge driven by an aging population and rising demand is one of the most pressing issues leading to emergency department (ED) overcrowding. An emerging solution lies in machine learning’s potential to predict ED dispositions, thus leading to promising substantial benefits. This study’s objective is to create a predictive model for ED patient dispositions by employing ensemble learning. It harnesses diverse data types, including structured and unstructured information gathered during ED visits to address the evolving needs of localized healthcare systems. Methods In this cross-sectional study, 80,073 ED patient records were amassed from a major southern Taiwan hospital in 2018–2019. An ensemble model incorporated structured (demographics, vital signs) and pre-processed unstructured data (chief complaints, preliminary diagnoses) using bag-of-words (BOW) and term frequency-inverse document frequency (TF-IDF). Two random forest base-learners for structured and unstructured data were employed and then complemented by a multi-layer perceptron meta-learner. Results The ensemble model demonstrates strong predictive performance for ED dispositions, achieving an area under the receiver operating characteristic curve of 0.94. The models based on unstructured data encoded with BOW and TF-IDF yield similar performance results. Among the structured features, the top five most crucial factors are age, pulse rate, systolic blood pressure, temperature, and acuity level. In contrast, the top five most important unstructured features are pneumonia, fracture, failure, suspect, and sepsis. Conclusions Findings indicate that utilizing ensemble learning with a blend of structured and unstructured data proves to be a predictive method for determining ED dispositions.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic condition characterized by progressive, partially reversible airflow obstruction. Osteoporosis represents a significant comorbidity in individuals with COPD. However, the incidence and prevalence of osteoporosis among the COPD population remain unclear in Taiwan. Therefore, our objective is to investigate the incidence and prevalence of osteoporosis in patients with COPD. Methods In this cross-sectional study, we enrolled a COPD population retrieved from the Taiwan National Health Insurance Research Database (NHIRD) spanning the years 2003 to 2016. Osteoporosis patients were identified using diagnosis codes. The study included newly diagnosed COPD patients from 2003 to 2016. The case group comprised patients who developed osteoporosis or osteoporotic fractures after their COPD diagnosis. We calculated the prevalence and incidence of osteoporosis in individuals with COPD and conducted trend tests. Results A total of 1,297,579 COPD patients were identified during the period from 2003 to 2016, with 275,233 of them in the osteoporosis group. The average prevalence of osteoporosis among individuals with COPD was 21.21% from 2003 to 2016 in Taiwan. The number of osteoporosis cases increased from 6,727 in 2003 to 24,184 in 2016. The prevalence of osteoporosis among COPD patients increased from 3.62% in 2003 to 18.72% in 2016. The number of osteoporosis cases among individuals with COPD continued to rise over the years, reaching its highest point in 2016 with 24,184 new cases. The incidence of osteoporosis fluctuated during the study period but generally remained around 3,000 cases per 100,000 person-years. Notably, there was a significant upward trend in incidence from 2003 to 2006, after which the trend stabilized and remained relatively constant. Conclusions Our study highlights an increase in both the prevalence and incidence of osteoporosis in individuals with COPD. Given the significant medical, economic, and social implications associated with osteoporosis, a comprehensive and robust assessment of its healthcare burden can offer valuable insights for healthcare system planning and policymaking.

The need for maintaining cell-spheroid viability and function within high-density cultures is unmet for various clinical and experimental applications, including cell therapies. One immediate application is for transplantation of pancreatic islets, a clinically recognized treatment option to cure type 1 diabetes; islets are isolated from a donor for subsequent culture prior to transplantation. However, high seeding conditions cause unsolicited fusion of multiple spheroids, thereby limiting oxygen diffusion to induce hypoxic cell death. Here we introduce a culture dish incorporating a micropyramid-patterned surface to prevent the unsolicited fusion and oxygen-permeable bottom for optimal oxygen environment. A 400µm-thick, oxygen-permeable polydimethylsiloxane sheet topped with micropyramid pattern of 400µm-base and 200µm-height was fabricated to apply to the 24-well plate format. The micropyramid pattern separated the individual pancreatic islets to prevent the fusion of multiple islets. This platform supported the high oxygen demand of islets at high seeding density at 260 islet equivalents cm-2, a 2-3-fold higher seeding density compared to the conventional islet culture used in a preparation for the clinical islet transplantations, demonstrating improved islet morphology, metabolism and function in a 4 d-culture. Transplantation of these islets into immunodeficient diabetic mice exhibited significantly improved engraftment to achieve euglycemia compared to islets cultured in the conventional culture wells. Collectively, this simple design modification allows for high-density cultures of three-dimensional cell spheroids to improve the viability and function for an array of investigational and clinical replacement tissues.

Background Chronic airway diseases have been associated with an increased risk of tuberculosis (TB); however, data in patients with bronchiectasis is limited. Statins have been shown to exhibit anti-inflammatory effects by modulating the inflammatory response. This study investigated whether statin treatment could reduce the risk of TB in patients with bronchiectasis.Methods We conducted a retrospective cohort study using a nationwide population database of patients with bronchiectasis who did or did not receive statin treatment. The defined daily dose (DDD) of statin, current or past statin user and statin exposure time were measured for the impact of statin use. The primary outcome was the incidence of new-onset TB. Considering of potential immortal time bias due to stain exposure time, Cox regression models with time-dependent covariates were employed to estimate HRs with 95% CIs for TB incidence among patients with bronchiectasis.Results Patients with bronchiectasis receiving statin treatment had a decreased risk of TB. After adjusting for age, sex, income, comorbidities and Charlson Comorbidity Index, statin users had a 0.59-fold lower risk of TB incidence compared with non-statin users (95% CI 0.40 to 0.88; p=0.0087). Additionally, compared with non-statin users, statin treatment was a protective factor against TB in users with a cumulative DDD greater than 180 per year, with an HR of 0.32 (95% CI 0.12 to 0.87; p=0.0255).Conclusions Statin treatment demonstrated a dose-dependent protective effect and was associated with a reduced risk of TB in patients with bronchiectasis. These findings suggest that statins may play a role in lowering TB risk by modulating airway inflammation in this patient population.

ObjectiveAs patient life expectancy has increased and people are living longer than before, the rate of mechanical ventilation among elderly patients in the intensive care unit has increased. Older patients who receive mechanical ventilation and have multiple comorbidities are more likely to have a do not resuscitate order than are younger patients with fewer comorbidities. The aim of our study was to describe the patient characteristics and predictive factors of do not resuscitate orders during hospitalization among elderly patients who received ventilation in the intensive care unit.MethodsThis was a retrospective review of the electronic medical records of patients in the intensive care unit of a teaching hospital in southern Taiwan. We enrolled patients admitted to the general intensive care unit from January 1, 2018, to September 31, 2020, and patients older than 80 years who experienced respiratory failure, were intubated and received mechanical ventilation. We analyzed patient demographics, disease severity during hospitalization and comorbidities. If a patient had multiple admissions to the intensive care unit, only the first admission was recorded.ResultsOf the 305 patients over 80 years of age with respiratory failure who were intubated and placed on a ventilator, 66 were excluded because of incomplete data, and 13 were excluded because they had already signed a do not resuscitate order prior to admission to the hospital. Ultimately, 226 patients were included in this study. A higher acute physiology and chronic health evaluation II score (>30) was also associated with an increased likelihood of a do not resuscitate order (odds ratio (OR) = 3.85, 95% CI = 1.09–13.62, p = 0.0362). Patients who had acute kidney injury or cerebrovascular accident were more likely to have a do not resuscitate order (OR = 2.74, 95% CI = 1.03–7.28, p = 0.0428 and OR = 7.32, 95% CI = 2.02–26.49, p = 0.0024, respectively).ConclusionOur study showed that older age, greater disease severity, and certain critical interventions were associated with a greater propensity for do not resuscitate orders, which is crucial for understanding patient preferences and guiding end-of-life care discussions. These findings highlight the importance of clinical severity and specific health events in predicting end-of-life care preferences in older patient groups.

Pancreatic islet transplantation is one of the clinical options for certain types of diabetes. However, difficulty in maintaining islets prior to transplantation limits the clinical expansion of islet transplantations. Our study introduces a dynamic culture platform developed specifically for primary human islets by mimicking the physiological microenvironment, including tissue fluidics and extracellular matrix support. We engineered the dynamic culture system by incorporating our distinctive microwell-patterned porous collagen scaffolds for loading isolated human islets, enabling vertical medium flow through the scaffolds. The dynamic culture system featured four 12 mm diameter islet culture chambers, each capable of accommodating 500 islet equivalents (IEQ) per chamber. This configuration calculates > five-fold higher seeding density than the conventional islet culture in flasks prior to the clinical transplantations (442 vs 86 IEQ/cm 2 ). We tested our culture platform with three separate batches of human islets isolated from deceased donors for an extended period of 2 weeks, exceeding the limits of conventional culture methods for preserving islet quality. Static cultures served as controls. The computational simulation revealed that the dynamic culture reduced the islet volume exposed to the lethal hypoxia (< 10 mmHg) to ~1/3 of the static culture. Dynamic culture ameliorated the morphological islet degradation in long-term culture and maintained islet viability, with reduced expressions of hypoxia markers. Furthermore, dynamic culture maintained the islet metabolism and insulin-secreting function over static culture in a long-term culture. Collectively, the physiological microenvironment-mimetic culture platform supported the viability and quality of isolated human islets at high-seeding density. Such a platform has a high potential for broad applications in cell therapies and tissue engineering, including extended islet culture prior to clinical islet transplantations and extended culture of stem cell-derived islets for maturation.

Patients with chronic obstructive pulmonary disease (COPD) had higher risk of atrial fibrillation (AF). The treatment of AF includes medicines to control heart rate and reduce the risk of stroke, and procedures such as cardioversion to restore normal heart rhythm. To reduce the stroke, patients with AF may prescribe some type of antithrombotic medication (such as warfarin, one of the new non-vitamin K antagonist oral anticoagulants [NOACs] – dabigitran, apixaban, rivoraxaban, or edoxaban) or maybe aspirin. The aim of our study was to exam the prescription pattern in patients with COPD and AF. We selected COPD population in Taiwan older than 40 years and less than 90 years old with an COPD diagnosis at least two outpatient claims or at least one inpatient claim coded and also need at least one prescription of bronchodilators. We followed this COPD cohort until they have AF and their prescription pattern. We included 267,740 patients with COPD who meet the inclusion and exclusion criteria and 6,582 patients concomitant with COPD and AF. The mean age was 75 years, and about 77% of the patients were older than 70 years. Three-fourths of patients with COPD were male. The common comorbidities were hypertension (17.58%), diabetes (7.47%), ischemic heart disease (4.66%), and dyslipidemia (3.68%). we found that most patients received aspirin which accounting for 31%, followed by coumadin (8.22%) and clopidogrel. Prescribing NOAC within 30 days after AF diagnosis was low in patients with COPD and the percentage of NOAC usage was also lower than warfarin.

Background: We investigated the impacts of the standard treatment durations of and adherence to standard anti-tuberculous therapy (ATT) on recurrence after the successful completion of tuberculosis (TB) treatment. Methods: We recruited patients with TB who had received treatment for six or nine months from the 2008–2017 databases of the Taiwanese National Health Insurance Research Database. Treatment duration and adherence to standard ATT were analyzed for their impacts on recurrence within two years. Complete adherence to standard ATT was defined as daily use of ethambutol, isoniazid, pyrazinamide, and rifampin for the first two months, and daily use of isoniazid and rifampin for the first six months. Results: A total of 33,298 TB patients with new-onset TB were identified and classified into two groups by treatment duration: six months (n = 25,849, 77.63%) and nine months (n = 7449). Sex and age distributions varied between the groups. Treatment duration did not affect TB recurrence within two years (adjusted hazard ratio (AHR): 1.18, 95% confidence interval (C.I.) [0.96–1.44], p = 0.1156). Multivariable logistic regression showed that incomplete adherence to standard anti-tuberculous therapy (80–89% and 90–99% standard anti-TB therapy, AHR: 1.57, 95% C.I. [1.26–1.95], and 1.63, 95% C.I. [1.26–2.06], respectively, p

Background: Type 2 diabetes mellitus (DM) is a risk factor for mycobacterial pulmonary infections (MPI), including tuberculosis (TB) and nontuberculous mycobacterial lung disease (NTM-LD). Dipeptidyl peptidase IV inhibitor (DPP4i), a common DM medication, has an immune-modulation effect that raises concerns about developing MPI. However, there is scarce research on the topic. Methods: This retrospective study was conducted in a tertiary-referral center in Taiwan from 2009 to 2016. Patients with type 2 DM who were receiving any DM medication were enrolled. TB and NTM-LD were defined by microbiological criteria. We analyzed the risk of MPI in DPP4i users using Cox proportional hazard regression with adjusted inverse probability of treatment weighting. Results: A total of 9963 patients were included. Among them, 3931 were classified as DPP4i users, and 6032 patients were DPP4i nonusers. DPP4i users had no increase in incidences of MPI (604 vs. 768 per 100,000 person-years, p = 0.776), NTM-LD (174 vs. 255 per 100,000 person-years, p = 0.228), and TB (542 vs. 449 per 100,000 person-years, p = 0.663) relative to those of DPP4i nonusers. After adjustment, the adjusted hazard ratios for MPI (aHR: 1.07, 95% CI: 0.79–1.45), TB (aHR: 1.15, 95% CI: 0.81–1.64) and NTM-LD (aHR: 0.85, 95% CI: 0.49–1.47) were not significantly increased relative to those of nonusers. The subgroup analysis also showed that DPP4i use did not increase the risk of MPI in different DM severities and comorbidities. Conclusions: According to our large cohort study, DPP4i use is safe for patients with type 2 DM and might not increase the risk of MPI.