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Functional-hydrogel-based electronic-skin patch for accelerated healing and monitoring of skin wounds
No full textConductive hydrogels feature reasonable electrical performance as well as tissue-like mechanical softness, thus positioning them as promising material candidates for soft bio-integrated electronics. Despite recent advances in materials and their processing technologies, however, facile patterning and monolithic integration of functional hydrogels (e.g., conductive, low-impedance, adhesive, and insulative hydrogels) for all-hydrogel-based soft bioelectronics still poses significant challenges. Here, we report material design, fabrication, and integration strategies for an electronic-skin (e-skin) patch based on functional hydrogels. The e-skin patch was fabricated by using photolithography-compatible functional hydrogels, such as poly(2-hydroxyethyl acrylate) (PHEA) hydrogel (substrate), Ag flake hydrogel (interconnection; conductivity: similar to 571.43 S/cm), poly(3,4-ethylenedioxythiophene:polystyrene) (PEDOT:PSS) hydrogel (working electrode; impedance: similar to 69.84 Omega @ 1 Hz), polydopamine (PDA) hydrogel (tissue adhesive; shear strength: similar to 725.1 kPa), and poly(vinyl alcohol) (PVA) hydrogel (encapsulation). The properties of these functional hydrogels closely resemble those of human tissues in terms of water content and Young's modulus, enabling stable tissue-device interfacing in dynamically changing physiological environments. We demonstrated the efficacy of the e-skin patch through its application to accelerated healing and monitoring of skin wounds in mouse models- efficient fibroblast migration, proliferation, and differentiation promoted by electric field (EF) stimulation and iontophoretic drug delivery, and monitoring of the accelerated healing process through impedance mapping. The all-hydrogel-based e-skin patch is expected to create new opportunities for various clinically-relevant tissue interfacing applications.N
Delayed Separation of Kaplan–Meier Curves is Commonly Observed in Studies of Advanced/Metastatic Solid Tumors Treated with Anti-PD-(L)1 Therapy: Systematic Review and Meta-Analysis
No full textBackground Immune checkpoint inhibitor (ICI) Kaplan-Meier (KM) curves often show delayed survival benefit followed by long-term survival in a subgroup of patients. Such outcomes can violate the proportional hazards assumption, leading to a loss of statistical power. Objective We aimed to determine common trends in delayed separation to inform future ICI clinical trials. Patients and Methods A literature search was performed using Trialtrove (R) to identify phase III trials of antiprogrammed cell death (ligand)-1 (anti-PD-[L]1) agents in locally advanced/metastatic solid tumors published between January 2010 and September 2021. The frequency of delayed separation of overall survival (OS) and progression-free survival (PFS) KM curves, correlation between duration of delayed separation in OS/PFS KM curves, and correlation between duration of delayed separation in OS/PFS KM curves with corresponding hazard ratios (HRs) were assessed in all-comer and PD-L1 enriched populations. Results Eighty-five studies with OS/PFS KM curves were identified. Most studies showed delayed separation of OS (> 67.9%) and PFS (> 54.5%) KM curves. The correlation between the duration of delayed separation in OS/PFS KM curves was strongest in the PD-L1 enriched population (adjusted R-2 = 0.66). No correlation was seen between the duration of delayed separation of OS KM curves and OS HR. A modest correlation was seen between the duration of delayed separation of PFS KM curves and PFS HR in all-comer and PD-L1 enriched populations (adjusted R2 = 0.24 and 0.31, respectively). Conclusions Delayed separation of KM curves was common in clinical trials of anti-PD-(L)1 agents. Understanding delayed separation is key to clinical study designs and assessing outcomes with ICIs.Y
Plain language summary: an analysis of the safety of futibatinib treatment in people with different types of cancer
No full textWhat is this summary about?: Researchers combined information from three separate phase 1 and 2 clinical trials, including over 400 people who had one of 33 different cancer types and who all received futibatinib in their clinical trial. This type of study is called a pooled analysis. Futibatinib is taken orally (by mouth) as a tablet and works by reducing the activity of a group of proteins called fibroblast growth factor receptors (FGFRs). FGFRs drive the growth of some cancers, especially cancer cells with changes in FGFR genes that make the proteins more active. Researchers wanted to look at how common some side effects were in people treated with futibatinib, how soon the side effects happened after taking futibatinib, and how they could be managed. Researchers also wanted to provide recommendations to other health care professionals on how to manage these side effects in people with cancer. What were the results?: In this analysis, the researchers focused on side effects that they had seen in previously completed trials of futibatinib. Overall, futibatinib was safe and tolerable. Most people (82%) had a high phosphate level in their blood (hyperphosphatemia), 27% had nail disorders, 27% had liver side effects (changes in liver-related laboratory tests), 19% had a sore mouth (stomatitis), 13% had hand-foot syndrome (palmar-plantar erythrodysesthesia syndrome), 9% had a rash, 8% developed changes in the back of the eye (retinal disorders), and 4% of people developed cataracts. Most side effects were mild/moderate and reversible. The median time it took from starting treatment to experiencing a severe side effect ranged from 9 days (hyperphosphatemia) to 125 days (cataracts). Some side effects tended to occur early, while others developed later. Only 2% of people stopped taking futibatinib due to treatment-related side effects, and futibatinib caused no deaths. What do the results mean?: The side effects from taking futibatinib were manageable and similar in people with different types of cancer. To fully understand the safety of futibatinib, researchers will need to look at what side effects are reported in people taking futibatinib over a longer time in the real-world setting (outside of clinical trials).Y
Easy and accurate protein structure prediction using ColabFold
No full textSince its public release in 2021, AlphaFold2 (AF2) has made investigating biological questions, by using predicted protein structures of single monomers or full complexes, a common practice. ColabFold-AF2 is an open-source Jupyter Notebook inside Google Colaboratory and a command-line tool that makes it easy to use AF2 while exposing its advanced options. ColabFold-AF2 shortens turnaround times of experiments because of its optimized usage of AF2's models. In this protocol, we guide the reader through ColabFold best practices by using three scenarios: (i) monomer prediction, (ii) complex prediction and (iii) conformation sampling. The first two scenarios cover classic static structure prediction and are demonstrated on the human glycosylphosphatidylinositol transamidase protein. The third scenario demonstrates an alternative use case of the AF2 models by predicting two conformations of the human alanine serine transporter 2. Users can run the protocol without computational expertise via Google Colaboratory or in a command-line environment for advanced users. Using Google Colaboratory, it takes <2 h to run each procedure. The data and code for this protocol are available at https://protocol.colabfold.com.N
Contributing factors to the length of stay and discharge destination of home health care patients: 10-year electronic health record analysis using the Donabedian model
No full textAimTo identify the factors affecting the length of stay (LOS) and discharge destination (DD) of home health care (HHC) patients in South Korea.MethodsA retrospective cross-sectional study was conducted using the electronic health records of 1769 patients from a hospital in South Korea. Data were collected from January 2013 to December 2022. We categorized the independent variables into patient context, structure, and process factors following a modification of Donabedian's model. Hierarchical and multinomial logistic regression analyses were used.ResultsThe mean length of stay was 26.41 days. Patients were discharged to the following locations: 35.0% continued HHC, 21.0% died, 19% were discharged to their homes, 17.0% were admitted, and 8.0% were sent to other locations. Patients' sex, type of insurance coverage, and primary caregiver as well as the number of nurse visits, HHC admission route, and type of nursing service were predictors of their LOS. Operation history, a high Charlson comorbidity index, the type of insurance coverage, HHC admission route, and certain nursing care services were associated with admission and death as the DD.ConclusionsProcess variables (e.g., number of nurse visits, HHC admission route, type of nursing services) have a considerable influence on determining the LOS and DD of HHC patients. This result provides new insights into the use of HHC services and care transitions out of the hospital for patients living in their home, offering evidence to reduce unnecessary readmissions and ensure more effective and efficient HHC.N
Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial
No full textHuman epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated. SGNTUC-019 is an open-label, phase 2 basket study evaluating tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2-altered solid tumors. The study included a cohort of 31 heavily pretreated female patients with HER2-mutated metastatic breast cancer who were also HER2 negative per local testing. Hormone receptor (HR)-positive patients also received fulvestrant. The overall response rate (primary endpoint) was 41.9% (90% confidence interval (CI): 26.9-58.2). Secondary endpoints of duration of response and progression-free survival were 12.6 months (90% CI: 4.7 to not estimable) and 9.5 months (90% CI: 5.4-13.8), respectively. No new safety signals were detected. Responses were observed across various HER2 mutations, including mutations in the tyrosine kinase and extracellular domains. The chemotherapy-free regimen of tucatinib and trastuzumab showed clinically meaningful antitumor activity with durable responses and favorable tolerability in heavily pretreated patients with HER2 mutations. These data support further investigation of HER2-targeted therapies in this patient population. ClinicalTrials.gov registration: NCT04579380.N
Deployable electronics with enhanced fatigue resistance for crumpling and tension
No full textHighly packable and deployable electronics offer a variety of advantages in electronics and robotics by facilitating spatial efficiency. These electronics must endure extreme folding during packaging and tension to maintain a rigid structure in the deployment state. Here, we present foldable and robustly deployable electronics inspired by Plantago, characterized by their tolerance to folding and tension due to integration of tough veins within thin leaf. The primary design approach for these electronics involves a high resistance to folding and tension, achieved through a thin multilayered electronic composite, which manages the neutral axis and incorporates tough Kevlar. The fabricated electronics can be folded up to 750,000 times without malfunctions and endure pulling an object 6667 times heavier than itself without stretching. Such robust electronics can be used as a deployable robot with sensor arrays, demonstrating practical applicability, as it maintains their mechanical and electrical properties during inflation from the packaged state.N
How Does Pacific Decadal Oscillation Modulate Extreme Heavy Rainfall Frequency Over Far East Asia?
No full textWe investigated the relationship between heavy rainfall events (HREs) and the Pacific Decadal Oscillation (PDO) occurring in Korea over Far East Asia for 40 years (1981-2020). Using K-means clustering on the low-level jet, we identified four clusters (C1-C4), with C1 being characterized by weaker synoptic conditions. Out of the four clusters, C1 represented localized extreme HREs compared with the other clusters. Interestingly, only the HRE frequency of C1 was found to have a strong negative correlation with PDO. During the negative-PDO, sea surface temperature increased above 30 degrees N, which decreased the meridional temperature gradient. This weakened the atmospheric circulation and created thermodynamic instability (i.e., weakened upper jet, increased low-level temperature, higher atmospheric water capacity), creating a favorable environment for HRE in C1. However, this negative-PDO environment provided somewhat unfavorable conditions for other clusters (C2-C4), so the PDO impact was insignificant.N
Establishment and characterization of endometrial organoids from different placental types
No full textUnderstanding molecular characteristics and metabolic processes of the mammalian endometrium is crucial for adva-ncing biological research, particularly in veterinary obstetrics and pathology. This study established and analyzed organoids from endometrial epithelial stem cells of five mammals with different placental types: cows (cotyledonary), dogs and cats (zonary), pigs (diffuse), and rats (discoid). Organoids from these five species were maintained for over 13 passages, frozen, and thawed. Pathological analysis confirmed that they retained chara-cteristics of their original tissues. Furthermore, integrative trans-criptome analysis of organoids and tissues from the five species highlighted key pathways such as PI3K-Akt signaling and extra-cellular matrix-receptor interaction known to be crucial in cancer research. Although genes associated with vascular smooth muscle contraction were downregulated, these organoids exhibited sig-nificant activities of genes involved in hormone metabolism. In conclusion, our study achieved stable establishment of endome-trial organoids from five mammals with different placental types, offering foundational data for organoid research. In the future, these organoids are suitable models for investigating uterine physiology and diseases and for developing potential therapies.N