Locational and functional characterization of PI4KB in the mouse embryo.

Phosphatidylinositol 4-kinase beta (PI4KB) is a member of the PI4K family, which is mainly enriched and functions in the Golgi apparatus. The kinase domain of PI4KB catalyzes the phosphorylation of phosphatidylinositol to form phosphatidylinositol 4-phosphate, a process that regulates various sub-cellular events, such as non-vesicular cholesterol and ceramide transport, protein glycosylation, and vesicle transport, as well as cytoplasmic division. In this study, a strain of PI4KB knockout mouse, immunofluorescence, reverse transcription polymerase chain reaction and microinjection were used to characterize the cytological location and biological function of PI4KB in the mouse embryos. we found that knocking down Pi4kb in mouse embryos resulted in embryonic lethality at around embryonic day (E) 7.5. Additionally, we observed dramatic fluctuations in PI4KB expression during the development of preimplantation embryos, with high expression in the 4-cell and morula stages. PI4KB colocalized with the Golgi marker protein TGN46 in the perinuclear and cytoplasmic regions in early blastomeres. Postimplantation, PI4KB was highly expressed in the epiblast of E7.5 embryos. Treatment of embryos with PI4KB inhibitors was found to inhibit the development of the morula into a blastocyst and the normal progression of cytoplasmic division during the formation of a 4-cell embryo. These findings suggest that PI4KB plays an important role in mouse embryogenesis by regulating various intracellular vital functions of embryonic cells.

Endocrine modulation of brain-skeleton axis driven by neural stem cell-derived perilipin 5 in the lipid metabolism homeostasis for bone regeneration.

Factors released from the nervous system always play crucial roles in modulating bone metabolism and regeneration. How the brain-driven endocrine axes maintain bone homeostasis, especially under metabolic disorders, remains obscure. Here, we found that neural stem cells (NSCs) residing in the subventricular zone participated in lipid metabolism homeostasis of regenerative bone through exosomal perilipin 5 (PLIN5). Fluorescence-labeled exosomes tracing and histological detection identified that NSC-derived exosomes (NSC-Exo) could travel from the lateral ventricle into bone injury sites. Homocysteine (Hcy) led to osteogenic and angiogenic impairment, whereas the NSC-Exo were confirmed to restore it. Mecobalamin, a clinically used neurotrophic drug, further enhanced the protective effects of NSC-Exo through increased PLIN5 expression. Mechanistically, NSC-derived PLIN5 reversed excessive Hcy-induced lipid metabolic imbalance and aberrant lipid droplet accumulation through lipophagy-dependent intracellular lipolysis. Intracerebroventricular administration of mecobalamin and/or AAV-shPlin5 confirmed the effects of PLIN5-driven endocrine modulations on new bone formation and vascular reconstruction in hyperhomocysteinemic and high-fat diet models. This study uncovered a novel brain-skeleton axis that NSCs in the mammalian brain modulated bone regeneration through PLIN5-driven lipid metabolism modulation, providing evidence for lipid- or bone-targeted medicine development.

Enhanced Bone Regeneration through Regulation of Mechanoresponsive FAK-ERK1/2 Signaling by ZINC40099027 during Distraction Osteogenesis.

Background: Focal adhesion kinase (FAK) is activated by mechanical stimulation and plays a vital role in distraction osteogenesis (DO), a well-established but lengthy procedure for repairing large bone defects. Both angiogenesis and osteogenesis contribute to bone regeneration during DO. However, the effects of ZINC40099027 (ZN27), a potent FAK activator, on angiogenesis, osteogenesis, and bone regeneration in DO remain unknown. Methods: The angiogenic potential of human umbilical vein endothelial cells (HUVECs) was evaluated using transwell migration and tube formation assays. The osteogenic activity of bone marrow mesenchymal stem cells (BMSCs) was assessed using alkaline phosphatase (ALP) and alizarin red s (ARS) staining. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence staining were used to assay angiogenic markers, osteogenic markers, and FAK-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In vivo, a rat tibia DO model was established to verify the effects of ZN27 on neovascularization and bone regeneration using radiological and histological analyses. Results: ZN27 promoted the migration and angiogenesis of HUVECs. Additionally, ZN27 facilitated the osteogenic differentiation of BMSCs, as revealed by increased ALP activity, calcium deposition, and expression of osteogenesis-specific markers. The ERK1/2-specific inhibitor PD98059 significantly hindered the effects of ZN27, suggesting the participation of FAK-ERK1/2 signaling in ZN27-enhanced angiogenesis and osteogenesis. As indicated by improved radiological and histological features, ZN27 induced active angiogenesis within the distraction area and accelerated bone regeneration in a rat DO model. Conclusion: Our results show that ZN27 targets FAK-ERK1/2 signaling to stimulate both angiogenesis and osteogenesis, and ZN27 accelerates bone regeneration in DO, suggesting the therapeutic potential of ZN27 for repairing large bone defects in the mechanobiological environment during DO.

An Appearance-Semantic Descriptor with Coarse-to-Fine Matching for Robust VPR.

In recent years, semantic segmentation has made significant progress in visual place recognition (VPR) by using semantic information that is relatively invariant to appearance and viewpoint, demonstrating great potential. However, in some extreme scenarios, there may be semantic occlusion and semantic sparsity, which can lead to confusion when relying solely on semantic information for localization. Therefore, this paper proposes a novel VPR framework that employs a coarse-to-fine image matching strategy, combining semantic and appearance information to improve algorithm performance. First, we construct SemLook global descriptors using semantic contours, which can preliminarily screen images to enhance the accuracy and real-time performance of the algorithm. Based on this, we introduce SemLook local descriptors for fine screening, combining robust appearance information extracted by deep learning with semantic information. These local descriptors can address issues such as semantic overlap and sparsity in urban environments, further improving the accuracy of the algorithm. Through this refined screening process, we can effectively handle the challenges of complex image matching in urban environments and obtain more accurate results. The performance of SemLook descriptors is evaluated on three public datasets (Extended-CMU Season, Robot-Car Seasons v2, and SYNTHIA) and compared with six state-of-the-art VPR algorithms (HOG, CoHOG, AlexNet_VPR, Region VLAD, Patch-NetVLAD, Forest). In the experimental comparison, considering both real-time performance and evaluation metrics, the SemLook descriptors are found to outperform the other six algorithms. Evaluation metrics include the area under the curve (AUC) based on the precision-recall curve, Recall@100%Precision, and Precision@100%Recall. On the Extended-CMU Season dataset, SemLook descriptors achieve a 100% AUC value, and on the SYNTHIA dataset, they achieve a 99% AUC value, demonstrating outstanding performance. The experimental results indicate that introducing global descriptors for initial screening and utilizing local descriptors combining both semantic and appearance information for precise matching can effectively address the issue of location recognition in scenarios with semantic ambiguity or sparsity. This algorithm enhances descriptor performance, making it more accurate and robust in scenes with variations in appearance and viewpoint.

Long-term Functional Outcomes Among Older Adults Undergoing Video-assisted Versus Open Surgery for Lung Cancer: A Population-based Cohort Study.

OBJECTIVE: To examine the long-term healthcare dependency outcomes of older adults undergoing VATS compared to open lung cancer resection. SUMMARY OF BACKGROUND DATA: Although the benefits of VATS for lung cancer resection have been reported, there is a knowledge gap related to long-term functional outcomes central to decision-making for older adults. METHODS: We conducted a population-based retrospective comparative cohort study of patients ≥70 years old undergoing lung cancer resection between 2010 and 2017 using linked administrative health databases. VATS was compared to open surgery for lung cancer resection. Outcomes were receipt of homecare and high time-at-home, defined as <14 institution-days within 1 year, in 5 years after surgery. We used time-to-event analyses. Homecare was analyzed as recurrent dichotomous outcome with Andersen-Gill multivariable models, and high time-at-home with Cox multivariable models. RESULTS: Of 4974 patients, 2951 had VATS (59.3%). In the first three months postoperatively, homecare use ranged from 17.5% to 34.4% for VATS and 23.0% to 36.6% for open surgery. VATS was independently associated with lower need for postoperative homecare over 5 years (hazard ratio 0.82, 95% confidence interval 0.74-0.92). 1- and 5-year probability of high "time-at-home" were superior for VATS (74.4% vs 66.7% and 55.6% vs 45.4%, p < 0.001). VATS was independently associated with higher probability of high "time-at-home" (hazard ratio 0.81, 95% confidence interval 0.74-0.89) compared to open surgery. CONCLUSIONS: Compared to open surgery, VATS was associated with lower homecare needs and higher probability of high "time-at-home," indicating reduced long-term functional dependence. Those important patient-centered endpoints reflect the overall long-term treatment burden on mortality and morbidity that can inform surgical decision-making.

Minimally Invasive Compared to Open Colorectal Cancer Resection for Older Adults: A Population-based Analysis of Long-term Functional Outcomes.

OBJECTIVE: We sought to compare long-term healthcare dependency and time-at-home between older adults undergoing minimally invasive surgery (MIS) for colorectal cancer (CRC) and those undergoing open resection. BACKGROUND: Although the benefits of MIS for CRC resection are established, data specific to older adults are lacking. Long-term functional outcomes, central to decision-making in the care for older adults, are unknown. METHODS: We performed a population-based analysis of patients ≥70years old undergoing CRC resection between 2007 to 2017 using administrative datasets. Outcomes were receipt of homecare and "high" time-at-home, which we defined as years with ≤14 institution-days, in the 5years after surgery. Homecare was analyzed using time-to-event analyses as a recurrent dichotomous outcome with Andersen-Gill multivariable models. High timeat-home was assessed using Cox multivariable models. RESULTS: Of 16,479 included patients with median follow-up of 4.3 (interquartile range 2.1-7.1) years, 7822 had MIS (47.5%). The MIS group had lower homecare use than the open group with 22.3% versus 31.6% at 6 months and 14.8% versus 19.4% at 1 year [hazard ratio 0.87,95% confidence interval (CI) 0.83-0.92]. The MIS group had higher probability ofhigh time-at-home than open surgery with 54.9% (95% CI 53.6%-56.1%) versus 41.2% (95% CI 40.1%-42.3%) at 5years (hazard ratio 0.71, 95% CI 0.68-0.75). CONCLUSIONS: Compared to open surgery, MIS for CRC resection was associated with lower homecare needs and higher probability of high time-at-home in the 5 years after surgery, indicating reduced long-term functional dependence. These are important patient-centered endpoints reflecting the overall long-term treatment burden to be taken into consideration in decision-making.

Direct nonlinear parameter estimation method for a phase generated carrier position sensor.

Phase generated carrier (PGC) is widely applied in interferometric phase estimation for distance, vibration and velocity measurements. However, traditional PGC methods suffer from nonlinear effects, causing limitations to demodulation of signal. Modified PGC methods, such as ellipse fitting algorithm (EFA), resolves these issues, but usually requires additional phase shift. With our proposed method in this paper, only one period of signal and one test point is required to attain accurate depth of phase modulation and phase. We use a photodiode to calibrate light intensity in data acquisition, and develop a Levenburg-Marquadt algorithm to estimate values of PGC parameters. An improved algorithm is also proposed to avoid local optimization based on prior information to ensure measurement stability. Less than 5 × 10-3 rad phase measurement uncertainty and over 55 dB Signal to Noise and Distortion Ratio (SINAD) is obtained in experiment.

Pro-inflammatory markers are associated with response to sequential pharmacotherapy in major depressive disorder: a CAN-BIND-1 report.

OBJECTIVE: There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD). METHODS: In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10-20 mg daily for 8 weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2-10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers-C-reactive protein, interleukin (IL)-1ß, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C-C motif ligand-2 (CCL-2)-measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response. RESULTS: Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16. CONCLUSION: Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

Association between lean muscle mass and treatment-resistant late-life depression in the IRL-GRey randomized controlled trial.

OBJECTIVE: To investigate the relationship between lean muscle mass and treatment response in treatment-resistant late-life depression (TR-LLD). We hypothesized that lower lean muscle mass would be associated with older age, higher physical comorbidities, higher depressive symptom severity, and poorer treatment response. DESIGN: Secondary analysis of a randomized, placebo-controlled trial. SETTING: Three academic hospitals in the United States and Canada. PARTICIPANTS: Adults aged 60+ years with major depressive disorder who did not remit following open treatment with venlafaxine extended-release (XR) (n = 178). MEASUREMENTS: We estimated lean muscle mass using dual-energy X-ray absorptiometry (DEXA) scans prior to and following randomized treatment with aripiprazole or placebo added to venlafaxine XR. Multivariate regressions estimated influence of demographic and clinical factors on baseline lean muscle mass, and whether baseline lean muscle mass was associated with treatment response, adjusted for treatment arm. RESULTS: Low lean muscle mass was present in 22 (12.4%) participants. Older age and female sex, but not depressive symptom severity, were independently associated with lower lean muscle mass at baseline. Marital status, baseline depressive symptom severity, and treatment group were associated with improvement of depressive symptoms in the randomized treatment phase. Baseline lean muscle mass was not associated with improvement, regardless of treatment group. CONCLUSION: As expected, older age and female sex were associated with lower lean muscle mass in TR-LLD. However, contrary to prior results in LLD, lean muscle mass was not associated with depression severity or outcome. This suggests that aripiprazole augmentation may be useful for TR-LLD, even in the presence of anomalous body composition.clinicaltrials.gov Identifier: NCT00892047.

Vehicle Logo Recognition Using Spatial Structure Correlation and YOLO-T.

The vehicle logo contains the vehicle's identity information, so vehicle logo detection (VLD) technology has extremely important significance. Although the VLD field has been studied for many years, the detection task is still difficult due to the small size of the vehicle logo and the background interference problem. To solve these problems, this paper proposes a method of VLD based on the YOLO-T model and the correlation of the vehicle space structure. Aiming at the small size of the vehicle logo, we propose a vehicle logo detection network called YOLO-T. It integrates multiple receptive fields and establishes a multi-scale detection structure suitable for VLD tasks. In addition, we design an effective pre-training strategy to improve the detection accuracy of YOLO-T. Aiming at the background interference, we use the position correlation between the vehicle lights and the vehicle logo to extract the region of interest of the vehicle logo. This measure not only reduces the search area but also weakens the background interference. We have labeled a new vehicle logo dataset named LOGO-17, which contains 17 different categories of vehicle logos. The experimental results show that our proposed method achieves high detection accuracy and outperforms the existing vehicle logo detection methods.

Extremely Soft, Stretchable, and Self-Adhesive Silicone Conductive Elastomer Composites Enabled by a Molecular Lubricating Effect.

Softness, adhesion, stretchability, and fast recovery from large deformations are essential properties for conductive elastomers that play an important role in the development of high-performance soft electronics. However, it remains an ongoing challenge to obtain conductive elastomers that combine these properties. We have fabricated a super soft (Young's modulus 2.3-12 kPa), highly stretchable (up to 1500% strain), and underwater adhesive silicone conductive elastomer composite (SF-C-PDMS) by incorporating dimethyl silicone oil as a lubricating agent in a cross-linked molecular network. The resultant SF-C-PDMS not only exhibits superior softness but also can readily recover after a strain of 1000%. The initial resistance only decreases by 8% after 100000 cycles of tensile fatigue test (100% strain, 0.5 Hz, 15 mm/s). This multifunctional silicone conductive elastomer composite is obtained in a one-step preparation at room temperature using commercially available materials. Moreover, we illustrate the capabilities of this composite in motion sensing.

Novel Indane Derivatives with Antioxidant Activity from the Roots of Anisodus tanguticus.

Four novel indane derivatives, anisotindans A-D (1-4), were isolated from the roots of Anisodus tanguticus. Their structures were established using comprehensive spectroscopic analyses, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction analyses. Anisotindans C and D (3 and 4) are two unusual indenofuran analogs. ABTS•+ and DPPH•+ assays of radical scavenging activity reveal that all compounds (1-4) are active. Specifically, the ABTS•+ assay results show that anisotindan A (1) exhibits the best antioxidant activity with an IC50 value of 15.62 ± 1.85 µM (vitamin C, IC50 = 22.54 ± 5.18 µM).

[Mechanism of tonifying Qi by traditional Chinese medicine from mitochondrial dynamics].

According to the traditional Chinese medicine(TCM) theory, Qi is the essential component maintaining life. Mitochondria are the cellular organelles that generate energy. Qi exhibits abundant common characteristics in bioenergetics compared with mitochondria which control the cellular energy through fusion and fission. Studies have proven that the qi-tonifying function of Chinese medicinal plants and their components facilitates mitochondrial fusion, therefore enhancing ATP synthesis. These studies provide a framework for deciphering the pharmacological mechanisms of Qi-tonifying herbs. This article introduces the common source and function shared by Qi and mitochondria and the regulatory effects of herbal remedies on energy from mitochondria dynamics. This review aims to interpret the connotation of tonifying qi in TCM theory based on the modern biomedical theory.

Upfront Small Bowel Resection for Small Bowel Neuroendocrine Tumors With Synchronous Metastases: A Propensity-score Matched Comparative Population-based Analysis.

OBJECTIVE: We examined the impact of upfront small bowel resection (USBR) for metastatic small bowel neuroendocrine (SB-NET) compared to nonoperative management (NOM) on long-term healthcare utilization and survival outcomes. SUMMARY OF BACKGROUND DATA: The role of early resection of the primary tumor in metastatic SB-NET remains controversial. Conflicting data exist regarding its clinical and survival benefits. METHODS: This is a population-based retrospective matched comparative cohort study of adults diagnosed with synchronous metastatic SB-NET between 2001 and 2017 in Ontario. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel-related surgery. Secondary outcome was overall survival. USBR and NOM patients were matched 2:1 using a propensity-score. We used time-to-event analyses with cumulative incidencefunctions and univariate Andersen-Gill regression for primary outcomes. E value methods assessed the potential for residual confounding. RESULTS: Of 1000 patients identified, 785 had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, P < 0.001) than those with NOM, with hazard ratio 0.72 (95% confidence interval 0.570.91). USBR was associated with lower risk of subsequent small bowel-related surgery (15.4% vs 40.3%, P < 0.001), with hazard ratio 0.44 (95% confidence interval 0.29-0.67). E -values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. CONCLUSIONS: USBR for SB-NETs in the presence of metastatic disease was associated with better patient-oriented outcomes of decreased subsequent admissions and interventions, compared to NOM. USBR should be considered for metastatic SB-NETs.

Long-term Dependency Outcomes in Older Adults Following Hepato-Pancreato-Biliary Surgery for Cancer: A Population-based Analysis.

OBJECTIVE: To evaluate healthcare dependency following hepatopancreato-biliary cancer surgery in older adults (OA). SUMMARY BACKGROUND DATA: Functional outcomes are central to decisionmaking by OA, but long-term risks of dependency have not been described beyond 1 year in this population. METHODS: All patients over age 70 undergoing hepatectomy or pancreatec-tomy for cancer between 2007 and 2017 in Ontario were analyzed. Outcomes were 1) receipt of homecare and 2) time at home. Homecare was analyzed with cumulative incidence functions, and time at home with Kaplan-Meier and Cox multivariate models. RESULTS: A total of 902 and 1283 patients underwent hepatectomy and pancreatectomy, respectively. Homecare use was highest (72.3%) in postoperative month-1, decreasing to stabilize between year-1 (25.5%) and year-5 (18.3%). Repeated receipt of homecare was associated with female sex (HR 1.18, 95% CI 1.05-1.32), receipt of adjuvant therapy (HR 1.56, 1.37-1.78), and more recent year of surgery (HR 3.80, 3.05-4.72). The ratio of home nursing care versus personal support services reversed from 68%/26% in year-1, to 29/64% in year-5. High time at home (>350 days) at 1 and 5 years were 40.6% (95% CI 38.5%-42.6%) and 28.1% (25.9%-30.3%), respectively. The ratio of institution-days in acute care versus nursing homes went from 77%/14% in year-1 to 23%/70% in year-5. Low time at home was associated with duodenal (HR 1.45, 1.15-1.70) and pancreas cancer (HR 1.20, 1.02-1.42), and with rural residence (HR 1.24, 1.04-1.48). High time at home was associated with more recent year of surgery (HR 0.84, 0.76-0.93) and perioperative cancer therapy (HR 0.88, 0.78-0.99). Increasing age was neither associated with homecare receipt nor time at home. CONCLUSIONS: Following hepatopancreatobiliary cancer surgery, there is a high rate of long-term healthcare dependency for OA. There is an immediate high need for homecare that reaches a new baseline after 6 months, and the majority of OA will have at least 1 year with low time at home, most commonly the first year. These findings can aid in preoperative preparation and transitional care planning.

Light transmission mechanisms in a SMF-capillary fiber-SMF structure and its application to bi-directional liquid level measurement.

Capillary fiber (CF) has been extensively investigated in a singlemode fiber (SMF)-CF-SMF (SCS) sensing structure since multiple light guiding mechanisms can be easily excited by simply tuning the air core diameter (cladding diameter) and length of the CF. Understanding the light guiding principles in an SCS structure is essential for improved implementation of a CF based fiber sensor. In this work, light guiding principles in a relatively large air core diameter (≥ 20 µm) and long length of CF (> 1 mm) are investigated theoretically and experimentally. It is found that both multimode interference (MMI) and Anti-Resonant Reflecting Optical Waveguide (ARROW) light guiding mechanisms are excited in the SCS structure in the transmission configuration. However, MMI dips are not observed in the spectrum for the air core diameters of CF smaller than 50 µm in the experiment due to large transmission loss in small air core CFs. Further experimental results demonstrate that a CF with a bigger air core diameter shows a higher sensitivity to curvature, and the highest sensitivity of -16.15 nm/m-1 is achieved when an CF-100 was used. In addition, a SMF-CF-20-CF-30-SMF (SCCS) structure is proposed for high sensitivity bi-direction liquid level measurement for the first time, to the best of our knowledge. Two types of ARROW dips (Dip-20 and Dip-30) are simultaneously excited in transmission, hence both liquid level and liquid flow direction can be detected by tracing the dip strength changes of Dip-20 and Dip-30, respectively.

Impact of Integrated Care Pathways Within the Framework of Collaborative Care on Older Adults With Anxiety, Depression, or Mild Cognitive Impairment.

OBJECTIVES: To evaluate the impact of an Integrated Care Pathway (ICP) within a collaborative care framework for anxiety, depression and mild cognitive impairment (MCI) on clinical outcomes, quality of life, and time to treatment initiation. DESIGN: Prospective Cohort study. SETTING: Primary care practices in Toronto and Hamilton, Ontario, Canada. PARTICIPANTS: Patients of participating primary care practices born in the years 1950 to 1958. SAMPLE SIZE: Target 150 participants, 75 in ICP and 75 in Treatment-As-Usual (TAU) arm. INTERVENTION: ICP within a collaborative care framework and TAU. METHODS AND RESULTS: One hundred forty-five participants with anxiety, depression or MCI, from five primary care practices were enrolled: 69 were managed as per ICP and 76 as per TAU. All underwent outcome assessments at 6, 12, 18, and 24 months. Compared to TAU, ICP participants had a significantly higher rate of improvement in depression symptoms (ß = -0.620, F (1, 256) = 4.10, p = 0.044), anxiety symptoms (ß = -0.593, F (1, 223) = 4.00, p = 0.047), and quality of life (ß = 1.351, F(1, 358) = 6.58, p = 0.011). The ICP group had also a significantly higher "hazard" of treatment initiation (HR = 3.557; 95% CI: [2.228, 5.678]; p < 0.001) after controlling for age, gender and baseline severity of symptoms compared to TAU group. CONCLUSIONS: Use of an ICP within a collaborative care framework in primary care settings for anxiety, depression and MCI among older adults, results in faster reductions in clinical symptoms and improvement in quality of life compared to usual care, as well as faster access to recommended treatments.

Manipulating Conjugated Polymer Backbone Dynamics through Controlled Thermal Cleavage of Alkyl Side Chains.

The morphological stability of an organic photovoltaic (OPV) device is greatly affected by the dynamics of donors and acceptors occurring near the device's operational temperature. These dynamics can be quantified by the glass transition temperature (Tg ) of conjugated polymers (CPs). Because flexible side chains possess much faster dynamics, the cleavage of the alkyl side chains will reduce chain dynamics, leading to a higher Tg . In this work, the Tg s for CPs are systematically studied with controlled side chain cleavage. Isothermal annealing of polythiophenes featuring thermally cleavable side chains at 140 °C, is found to remove more than 95% of alkyl side chains in 24 h, and raise the backbone Tg from 23 to 75 °C. Coarse grain molecular dynamics simulations are used to understand the Tg dependence on side chain cleavage. X-ray scattering indicates that the relative degree of crystallization remains constantduring isothermal annealing process. The effective conjugation length is not influenced by thermal cleavage; however, the density of chromophore is doubled after the complete removal of alkyl side chains. The combined effect of enhancing Tg and conserving crystalline structures during the thermal cleavage process can provide a pathway to improving the stability of optoelectronic properties in future OPV devices.

Self-Powered Flexible Electrochromic Smart Window.

Electrochromic devices have attracted considerable interest for smart windows. However, current development suffers from the requirement of the external power sources and rigid ITO substrate, which not only causes additional energy consumption but also limits their applications in flexible devices. Inspired by galvanic cell, we demonstrate a self-powered flexible electrochromic device by integrating Ag/W18O49 nanowire film with the Al sheet. The Ag nanowire film first acted as the electrode to replace the ITO substrate, then coupled with the Al sheet to induce an open-circuit voltage of ∼0.83 V, which is high enough to drive the coloration of W18O49 nanowires. Remarkably, the flexible self-powered electrochromic device only expends ∼6.8 mg/cm2 of the Al sheet after 450 electrochromic switching cycles and the size can be easily expanded with an area of 20 × 20 cm2, offering significant potential applications for the next generation of flexible electrochromic smart window.

Province-Wide Analysis of Patient-Reported Outcomes for Stage IV Non-Small Cell Lung Cancer.

BACKGROUND: In Ontario, Canada, patient-reported outcome (PRO) evaluation through the Edmonton Symptom Assessment System (ESAS) has been integrated into clinical workflow since 2007. As stage IV non-small cell lung cancer (NSCLC) is associated with substantial disease and treatment-related morbidity, this province-wide study investigated moderate to severe symptom burden in this population. MATERIALS AND METHODS: ESAS collected from patients with stage IV NSCLC diagnosed between 2007 and 2018 linked to the Ontario provincial health care system database were studied. ESAS acquired within 12 months following diagnosis were analyzed and the proportion reporting moderate to severe scores (ESAS ≥4) in each domain was calculated. Predictors of moderate to severe scores were identified using multivariable Poisson regression models with robust error variance. RESULTS: Of 22,799 patients, 13,289 (58.3%) completed ESAS (84,373 assessments) in the year following diagnosis. Patients with older age, with high comorbidity, and not receiving active cancer therapy had lower ESAS completion. The majority (94.4%) reported at least one moderate to severe symptom. The most prevalent were tiredness (84.1%), low well-being (80.7%), low appetite (71.7%), and shortness of breath (67.8%). Most symptoms peaked at diagnosis and, while declining, remained high in the following year. On multivariable analyses, comorbidity, low income, nonimmigrants, and urban residency were associated with moderate to severe symptoms. Moderate to severe scores in all ESAS domains aside from anxiety were associated with radiotherapy within 2 weeks prior, whereas drowsiness, low appetite and well-being, nausea, and tiredness were associated with systemic therapy within 2 weeks prior. CONCLUSION: This province-wide PRO analysis showed moderate to severe symptoms were prevalent and persistent among patients with metastatic NSCLC, underscoring the need to address supportive measures in this population especially around treatments. IMPLICATIONS FOR PRACTICE: In this largest study of lung cancer patient-reported outcomes (PROs), stage IV non-small cell lung cancer patients had worse moderate-to-severe symptoms than other metastatic malignancies such as breast or gastrointestinal cancers when assessed with similar methodology. Prevalence of moderate-to-severe symptoms peaked early and remained high during the first year of follow-up. Symptom burden was associated with recent radiation and systemic treatments. Early and sustained PRO collection is important to detect actionable symptom progression, especially around treatments. Vulnerable patients (e.g., older, high comorbidity) who face barriers in attending in-person clinic visits had lower PRO completion. Virtual PRO collection may improve completion.