Exocyst stimulates multiple steps of exocytic SNARE complex assembly and vesicle fusion.

Exocyst is a large multisubunit tethering complex essential for targeting and fusion of secretory vesicles in eukaryotic cells. Although the assembled exocyst complex has been proposed to tether vesicles to the plasma membrane and activate soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) for membrane fusion, the key biochemical steps that exocyst stimulates in SNARE-mediated fusion are undetermined. Here we use a combination of single-molecule and bulk fluorescence assays to investigate the roles of purified octameric yeast exocyst complexes in a reconstituted yeast exocytic SNARE assembly and vesicle fusion system. Exocyst had stimulatory roles in multiple distinct steps ranging from SNARE protein activation to binary and ternary complex assembly. Importantly, exocyst had a downstream role in driving membrane fusion and full content mixing of vesicle lumens. Our data suggest that exocyst provides extensive chaperoning functions across the entire process of SNARE complex assembly and fusion, thereby governing exocytosis at multiple steps.

Efficacy of an Aspiration Prevention Program That Utilizes the Gugging Swallowing Screen in Older Patients.

Purpose: Older patients have a higher risk of aspiration pneumonia and mortality if they are hospitalized. We aimed to assess the effectiveness of an aspiration prevention quality improvement (QI) program that utilizes the Gugging Swallowing Screen (GUSS) in older patients. Patients and Methods: This retrospective cohort study was conducted in an acute medical care unit of a tertiary hospital in South Korea. The study used one-to-one propensity matching and included 96 patients who received the QI program and 96 who did not. All patients were aged 65 years or older and had risk factors for aspiration, including neurological and non-neurological disorders, neuromuscular disorders, impaired airway defenses, and dysphagia due to esophageal or gastrointestinal disorders. The primary outcomes included the duration of the fasting period during hospitalization, changes in nutritional status before admission and at discharge, in-hospital mortality, and readmission due to pneumonia within 90 days. Results: Fasting period, changes in weight and albumin levels upon discharge after hospitalization, and length of stay did not differ significantly between patients in the GUSS and non-GUSS groups. However, the risk of readmission within 90 days was significantly lower in patients who underwent the GUSS than in those who did not (hazard ratio, 0.085; 95% confidence interval, 0.025-0.290; p = 0.001). Conclusion: The GUSS aspiration prevention program effectively prevented readmission due to pneumonia within 90 days in older patients with acute illnesses. This implies that the adoption of efficient aspiration prevention methods in older patients with acute illnesses could play a pivotal role by enhancing patient outcomes and potentially mitigating the healthcare costs linked to readmissions.

The Impact of Real-Time Documentation of In-Hospital Medication Changes on Preventing Undocumented Discrepancies at Discharge and Improving Physician-Pharmacist Communication: A Retrospective Cohort Study and Survey.

Background: Transitional medication safety is crucial, as miscommunication about medication changes can lead to significant risks. Unclear or incomplete documentation during care transitions can result in outdated or incorrect medication lists at discharge, potentially causing medication errors, adverse drug events, and inadequate patient education. These issues are exacerbated by extended hospital stays and multiple care events, making accurate medication recall challenging at discharge. Objective: Thus, we aimed to investigate how real-time documentation of in-hospital medication changes prevents undocumented medication changes at discharge and improves physician-pharmacist communication. Methods: We conducted a retrospective cohort study in a tertiary hospital. Two pharmacists reviewed medical records of patients admitted to the acute medical unit from April to June 2020. In-hospital medication discrepancies were determined by comparing preadmission and hospitalization medication lists and it was verified whether the physician's intent of medication changes was clarified by documentation. By a documentation rate of medication changes of 100% and <100%, respectively, fully documented (FD) and partially documented (PD) groups were defined. Any undocumented medication changes at discharge were considered a "documentation error at discharge". Pharmacists' survey was conducted to assess the impact of appropriate documentation on the pharmacists. Results: After reviewing 400 medication records, patients were categorized into FD (61.3%) and PD (38.8%) groups. Documentation errors at discharge were significantly higher in the PD than in the FD group. Factors associated with documentation errors at discharge included belonging to the PD group, discharge from a non-hospitalist-managed ward, and having three or more intentional discrepancies. Pharmacists showed favorable attitudes towards physician's documentation. Conclusion: Appropriate documentation of in-hospital medication changes, facilitated by free-text communication, significantly decreased documentation errors at discharge. This analysis underlines the importance of communication between pharmacists and hospitalists in improving patient safety during transitions of care.

During transitions of care, communication failures among healthcare professionals can lead to medication errors. Therefore, effective sharing of information is essential, especially when intentional changes in prescription orders are made. Documenting medication changes facilitates real-time communication, potentially improving medication reconciliation and reducing discrepancies. However, inadequate documentation of medication changes is common in clinical practice. This retrospective cohort study underlines the importance of real-time documentation of in-hospital medication changes. There was a significant reduction in documentation errors at discharge in fully documented group, where real-time documentation of medication changes was more prevalent. Pharmacists showed favorable attitudes toward the physician's real-time documenting of medication changes because it provided valuable information on understanding the physician's intent and improving communication and also saved time for pharmacists. This study concludes that physicians' documentation on medication changes may reduce documentation errors at discharge, meaning that proper documentation of medication changes could enhance patient safety through effective communication.

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data.

Background/Objectives: The survival rate of patients with pancreatic cancer (PC) has improved gradually since the introduction of FOLFIRINOX (FFX) and gemcitabine + albumin-bound paclitaxel (GnP) regimens. However, the trends and outcomes of initial palliative chemotherapy before and after the advent of these regimens and their contribution to survival rates are not well understood. This study aimed to investigate this in patients with PC in Korea using claims data from the National Health Insurance Service (NHIS). Methods: Patients diagnosed with PC who underwent initial palliative chemotherapy between 2007 and 2019 were identified from the NHIS database. Patient demographics, comorbidities, chemotherapy regimens, and survival rates were analyzed using follow-up data up to 2020. Results: In total, 14,760 patients (mean age, 63.78 ± 10.18 years; men, 59.19%) were enrolled. As initial palliative chemotherapy, 3823 patients (25.90%) received gemcitabine alone; 2779 (18.83%) received gemcitabine + erlotinib; 1948 (13.20%) received FFX; and 1767 (11.97%) received GnP. The median survival values were 15.00 months for FFX; 11.04 months for GnP; 8.40 months for gemcitabine alone; and 8.51 months for gemcitabine + erlotinib. The adjusted hazard ratio (aHR) for GnP vs. FFX was 1.291 (95% CI, 1.206-1.383) in the multivariate Cox regression analysis of mortality. Radiation therapy (aHR, 0.667; 95% CI, 0.612-0.728) and second-line chemotherapy (aHR, 0.639; 95% CI, 0.597-0.684) were significantly associated with improved survival. Conclusions: Our study found that first-line chemotherapy with FFX was associated with significantly longer survival than the other regimens, although caution is needed in interpreting the results.

Use of spectroscopic process analytical technology for rapid quality evaluation during preparation of CHO cell culture media.

Media preparation parameters contribute significantly to media quality, cell culture performance, productivity, and product quality. Establishing proper media preparation procedures is critical for ensuring a robust CHO cell culture process. Process analytical technology (PAT) enables unique ways to quantify assessments and improve media quality. Here, cell culture media were prepared under a wide range of temperatures (40-80°C) and pH (7.6-10.0). Media quality profiles were compared using three real-time PATs: Fourier-transform infrared (FTIR) spectroscopy, Raman spectroscopy, and excitation-emission matrix (EEM) spectroscopy. FTIR and Raman spectroscopies identified shifts in media quality under high preparation temperature (80°C) and at differing preparation pH which negatively impacted monoclonal antibody (mAb) production. In fed-batch processes for production of three different mAbs, viable cell density (VCD) and cell viability were mostly unaffected under all media preparation temperatures, while titer and cell specific productivity of mAb decreased when cultured in basal and feed media prepared at 80°C. High feed preparation pH alone was tolerated but cell growth and productivity profiles deviated from the control condition. Further, charge variants (main, acidic, basic species) and glycosylation (G0F, afucosylation, and high mannose) were examined. Statistically significant differences were observed for one or more of these quality attributes with any shifts in media preparation. In this study, we demonstrated strong associations between media preparation conditions and cell growth, productivity, and product quality. The rapid evaluation of media by PAT implementation enabled more comprehensive understanding of different parameters on media quality and consequential effects on CHO cell culture.

Efficacy of intraoperative blood salvage and autotransfusion in living-donor liver transplantation: a retrospective cohort study.

BACKGROUND: Liver transplantation (LT) may be associated with massive blood loss and the need for allogeneic blood transfusion. Intraoperative blood salvage autotransfusion (IBSA) can reduce the need for allogeneic blood transfusion. This study aimed to investigate the effectiveness of blood salvage in LT. METHODS: Among 355 adult patients who underwent elective living-donor LT between January 1, 2019, and December 31, 2022, 59 recipients without advanced hepatocellular carcinoma received IBSA using Cell Saver (CS group). Based on sex, age, model for end-stage liver disease (MELD) score, preoperative laboratory results, and other factors, 118 of the 296 recipients who did not undergo IBSA were matched using propensity score (non-CS group). The primary outcome was the amount of intraoperative allogenic red blood cell (RBC) transfusion. Comparisons were made between the two groups regarding the amount of other blood components transfused and postoperative laboratory findings. RESULTS: The transfused allogeneic RBC for the CS group was significantly lower than that of the non-CS group (1,506.0 vs. 1,957.5 ml, P = 0.026). No significant differences in the transfused total fresh frozen plasma, platelets, cryoprecipitate, and estimated blood loss were observed between the two groups. The postoperative allogeneic RBC transfusion was significantly lower in the CS group than in the non-CS group (1,500.0 vs. 2,100.0 ml, P = 0.039). No significant differences in postoperative laboratory findings were observed at postoperative day 1 and discharge. CONCLUSIONS: Using IBSA during LT can effectively reduce the need for perioperative allogeneic blood transfusions without causing subsequent coagulopathy.

Sodium Intake Estimation in Hospital Patients Using AI-Based Imaging: Prospective Pilot Study.

BACKGROUND: Measurement of sodium intake in hospitalized patients is critical for their care. In this study, artificial intelligence (AI)-based imaging was performed to determine sodium intake in these patients. OBJECTIVE: The applicability of a diet management system was evaluated using AI-based imaging to assess the sodium content of diets prescribed for hospitalized patients. METHODS: Based on the information on the already investigated nutrients and quantity of food, consumed sodium was analyzed through photographs obtained before and after a meal. We used a hybrid model that first leveraged the capabilities of the You Only Look Once, version 4 (YOLOv4) architecture for the detection of food and dish areas in images. Following this initial detection, 2 distinct approaches were adopted for further classification: a custom ResNet-101 model and a hyperspectral imaging-based technique. These methodologies focused on accurate classification and estimation of the food quantity and sodium amount, respectively. The 24-hour urine sodium (UNa) value was measured as a reference for evaluating the sodium intake. RESULTS: Results were analyzed using complete data from 25 participants out of the total 54 enrolled individuals. The median sodium intake calculated by the AI algorithm (AI-Na) was determined to be 2022.7 mg per day/person (adjusted by administered fluids). A significant correlation was observed between AI-Na and 24-hour UNa, while there was a notable disparity between them. A regression analysis, considering patient characteristics (eg, gender, age, renal function, the use of diuretics, and administered fluids) yielded a formula accounting for the interaction between AI-Na and 24-hour UNa. Consequently, it was concluded that AI-Na holds clinical significance in estimating salt intake for hospitalized patients using images without the need for 24-hour UNa measurements. The degree of correlation between AI-Na and 24-hour UNa was found to vary depending on the use of diuretics. CONCLUSIONS: This study highlights the potential of AI-based imaging for determining sodium intake in hospitalized patients.

Covalent-Frameworked 2D Crown Ether with Chemical Multifunctionality.

Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C2O, which mainly consists of carbon and oxygen in a 2:1 molar ratio and features crown ether holes in its skeletal structure. The covalent-frameworked 2D crown ether can be synthesized on a gram-scale and exhibits fine chemical stability in various environments, including acid, base, and different organic solvents. The C2O efficiently activates KI through the strong coordination of K+ with crown ether holes in a rigid framework, which enhances the nucleophilicity of I- and significantly improves its catalytic activity for CO2 fixation with epoxides. The presence of C2O with KI results in remarkable increases in CO2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C2O possesses both electrophilic and nucleophilic sites at the edge of its framework, allowing for the customization of physicochemical properties by a diverse range of chemical modifications. Specifically, incorporating allyl glycidyl ether (AGE) as an electrophile or ethoxyethylamine (EEA) as a nucleophile into C2O enables the synthesis of C2O-AGE or C2O-EEA, respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO2 fixation with allyl glycidyl ether, outperforming unmodified C2O showing a conversion of 74.2%. This newly developed scalable, durable, and customizable covalent framework holds tremendous potential for the design and preparation of outstanding materials with versatile functionalities, rendering them highly attractive for a wide range of applications.

Influence of Cytokine Genetic Polymorphisms in Helicobacter pylori-Associated Gastric Inflammation According to Sex in South Korea.

Background/Aims: : The relationship between genetic polymorphisms and gastric inflammation remains unclear. This study aimed to evaluate the impact of genetic polymorphisms on Helicobacter pylori (HP)-associated gastritis according to sex. Methods: : Two hundred thirty-two male and 404 female subjects with current HP infection were prospectively enrolled. The genotyping of IL-1B-511 C/T, IL-1RN variable number of tandem repeats, IL-6-572 G/C, IL-8-251 A/T, IL-8-781 C/T, IL-10-1082 G/A, IL-10-592 C/A, TNF-A-308 G/A, and transforming growth factor (TGF)-B-509 C/T, was determined by polymerase chain reaction-restriction fragment length polymorphism. The degree of monocyte or neutrophil infiltration, atrophic gastritis, and intestinal metaplasia was evaluated using the updated Sydney system. Results: : Among the male subjects, moderate/severe atrophic gastritis of the corpus was higher in IL-1B-511 CC carriers than in CT and TT carriers independent of age, alcohol consumption, and HP virulence factors (26.9% vs 10.4%; adjusted hazard ratio [HR], 4.377; 95% confidence interval, 1.387 to 13.814). In females, IL-8-251 AA carriers were independently and significantly associated with moderate/severe atrophic gastritis of the corpus compared with that in AT and TT carriers (21.4% vs 6.0%, adjusted HR=3.799). In males, the IL-8-251 TT genotype was associated with moderate/severe intestinal metaplasia of the corpus compared with the AT and AA genotypes (13.4% vs 5.6%, adjusted HR=3.128), while the IL-10-592 CA and CC genotypes were associated with moderate/severe monocyte infiltration of the antrum compared with AA genotype (83.6% vs 71.8%, adjusted HR=2.227). Conclusions: : Genetic polymorphisms in cytokines play different roles in HP-associated gastritis according to sex.

Virucidal activity of Cu-doped TiO2 nanoparticles under visible light illumination: Effect of Cu oxidation state.

Copper (Cu) is an effective antimicrobial material; however, its activity is inhibited by oxidation. Titanium dioxide (TiO2) photocatalysis prevents Cu oxidation and improves its antimicrobial activity and stability. In this study, the virucidal efficacy of Cu-doped TiO2 nanoparticles (Cu-TiO2) with three different oxidation states of the Cu dopant (i.e., zero-valent Cu (Cu0), cuprous (CuI), and cupric (CuII) oxides) was evaluated for the phiX174 bacteriophage under visible light illumination (Vis/Cu-TiO2). CuI-TiO2 exhibited superior virucidal activity (5 log inactivation in 30 min) and reusability (only 11 % loss of activity in the fifth cycle) compared to Cu0-TiO2 and CuII-TiO2. Photoluminescence spectroscopy and photocurrent measurements showed that CuI-TiO2 exhibited the highest charge separation efficiency and photocurrent density (approximately 0.24 µA/cm2) among the three materials, resulting in the most active redox reactions of Cu. Viral inactivation tests under different additives and viral particle integrity analyses (i.e., protein oxidation and DNA damage analyses) revealed that different virucidal species played key roles in the three Vis/Cu-TiO2 systems; Cu(III) was responsible for the viral inactivation by Vis/CuI-TiO2. The Vis/CuI-TiO2 system exhibited substantial virucidal performance for different viral species and in different water matrices, demonstrating its potential practical applications. The findings of this study offer valuable insights into the design of effective and sustainable antiviral photocatalysts for disinfection.

CFD-based bioreactor model with proportional-integral-derivative controller functionality for dissolved oxygen and pH.

A physics-based model for predicting cell culture fluid properties inside a stirred tank bioreactor with embedded PID controller logic is presented. The model evokes a time-accurate solution to the fluid velocity field and overall volumetric mass transfer coefficient, as well as the ongoing effects of interfacial mass transfer, species mixing, and aqueous chemical reactions. The modeled system also includes a direct coupling between process variables and system control variables via embedded controller logic. Satisfactory agreement is realized between the model prediction and measured bioreactor data in terms of the steady-state operating conditions and the response to setpoint changes. Simulation runtimes are suitable for industrial research and design timescales.

Outcomes of Palliative Chemotherapy for Ampulla of Vater Adenocarcinoma: A Multicenter Cohort Study.

Background/Aims: : Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. Methods: : Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. Results: : Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. Conclusions: : While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.

Analysis of Recent Improvement of Survival Outcomes in Patients with Pancreatic Cancer Who Underwent Upfront Surgery.

Background/Aims: : Recently, patients with pancreatic cancer (PC) who underwent resection have exhibited improved survival outcomes, but comprehensive analysis is limited. We analyzed the trends of contributing factors. Methods: : Data of patients with resected PC were retrospectively collected from the Korean Health Insurance Review and Assessment Service (HIRA) database and separately at our institution. Cox regression analysis was conducted with the data from our institution a survival prediction score was calculated using the ß coefficients. Results: : Comparison between the periods 2013-2015 (n=3,255) and 2016-2018 (n=3,698) revealed a difference in the median overall survival (25.9 months vs not reached, p<0.001) when analyzed with the HIRA database which was similar to our single-center data (2013-2015 [n=119] vs 2016-2018 [n=148], 20.9 months vs 32.2 months, p=0.003). Multivariable analyses revealed six factors significantly associated with better OS, and the scores were as follows: age >70 years, 1; elevated carbohydrate antigen 19-9 at diagnosis, 1; R1 resection, 1; stage N1 and N2, 1 and 3, respectively; no adjuvant treatment, 2; FOLFIRINOX or gemcitabine plus nab-paclitaxel after recurrence, 4; and other chemotherapy or supportive care only after recurrence, 5. The rate of R0 resection (69.7% vs 80.4%), use of adjuvant treatment (63.0% vs 74.3%), and utilization of FOLFIRINOX or gemcitabine plus nab-paclitaxel (25.2% vs 47.3%) as palliative chemotherapeutic regimen, all increased between the two time periods, resulting in decreased total survival prediction score (mean: 7.32 vs 6.18, p=0.004). Conclusions: : Strict selection of surgical candidates, more use of adjuvant treatment, and adoption of the latest combination regimens for palliative chemotherapy after recurrence were identified as factors of recent improvement.

Confined growth of Ag nanogap shells emitting stable Raman label signals for SERS liquid biopsy of pancreatic cancer.

To develop a reliable surface-enhanced Raman scattering (SERS) immunoassay as a new liquid biopsy modality, SERS nanoprobes emitting strong and stable signals are necessary. However, Ag nanoparticles used as SERS nanoprobes are prone to rapid fading of SERS signals by oxidation. This has driven the development of a new strategy for Ag-based SERS nanoprobes emitting stable and strong SERS signals over time. Herein, Ag nanogap shells entrapping Raman labels are created in the confined pores of mesoporous silica nanoparticles (AgNSM) through a rapid single-step reaction for SERS liquid biopsy. Each AgNSM nanoprobe possesses multiple nanogaps of 1.58 nm to entrap Raman labels, allowing superior long-term SERS signal stability and large enhancement of 1.5 × 106. AgNSM nanoprobes conjugated with an antibody specific for carbohydrate antigen (CA)19-9 are employed in the SERS sandwich immunoassay including antibody-conjugated magnetic nanoparticles for CA19-9 detection, showing a two orders of magnitude lower limit of detection (0.025 U mL-1) than an enzyme-linked immunosorbent assay (0.3 U mL-1). The AgNSM nanoprobe immunoassay accurately quantifies CA19-9 levels from clinical serum samples of early and advanced pancreatic cancer. AgNSM nanoprobes with stable SERS signals provide a new route to SERS liquid biopsy for effective detection of blood biomarkers.

The Hospitalist-Oncologist co-ManagemEnt (HOME) system improves hospitalization outcomes of patients with cancer.

BACKGROUND: The hospitalist system has been introduced to improve the quality and safety of inpatient care. As its effectiveness has been confirmed in previous studies, the hospitalist system is spreading in various fields. However, few studies have investigated the feasibility and value of hospitalist-led care of patients with cancer in terms of quality and safety measures. This study aimed to evaluate the efficacy of the Hospitalist-Oncologist co-ManagemEnt (HOME) system. METHODS: Between January 1, 2019, and January 31, 2021, we analyzed 591 admissions before and 1068 admissions after the introduction of HOME system on January 1, 2020. We compared the length of stay and the types and frequencies of safety events between the conventional system and the HOME system, retrospectively. We also investigate rapid response system activation, cardiopulmonary resuscitation, unplanned intensive care unit transfer, all-cause in-hospital mortality, and 30-day re-admission or emergency department visits. RESULTS: The average length of stay (15.9 days vs. 12.9 days, P < 0.001), frequency of safety events (5.6% vs. 2.8%, P = 0.006), rapid response system activation (7.3% vs. 2.2%, P < 0.001) were significantly reduced after the HOME system introduction. However, there was no statistical difference in frequencies of cardiopulomonary resuscitation and intensive care unit transfer, all-cause in-hospital morality, 30-day unplanned re-admission or emergency department visits. CONCLUSIONS: The study suggests that the HOME system provides higher quality of care and safer environment compared to conventional oncologist-led team-based care, and the efficiency of the medical delivery system could be increased by reducing the hospitalization period without increase in 30-day unplanned re-admission.

Simultaneously enhancing the resolution and signal-to-background ratio in STED optical nanoscopy via differential depletion.

STED (stimulated emission depletion) far-field optical nanoscopy achieves resolution beyond the diffraction limit by depleting fluorescence at the periphery of excitation with a donut-shaped depletion laser. What is traded off with the superior resolution of STED nanoscopy is the unwanted elevation of structured background noise which hampers the quality of STED images. Here, we alleviate the background noise problem by adopting the differential stimulated emission depletion (diffSTED) approach. In diffSTED nanoscopy, signals obtained with different depletion strengths are compared and properly subtracted to remove two major background noise sources in STED nanoscopy. We show via simulations that by using diffSTED nanoscopy, background noise is significantly decreased, and the image contrast is improved. In addition, we show by simulation and analytical calculation that diffSTED improves resolution simultaneously. We assess the effect of different parameters, such as the STED beam intensity, depletion intensity ratio of two STED beams, and the subtraction factor, on the signal-to-background ratio (SBR) and the resolution of diffSTED nanoscopy. We introduce a logical algorithm to determine the optimal subtraction factor and the depletion intensity ratio. DiffSTED nanoscopy is a versatile technique that can be readily applied to any STED system without requiring any hardware modifications. We predict the wide applicability of diffSTED for its enhanced resolution, improved SBR, and easiness of implementation.

Analysis of Phase Heterogeneity in Lipid Membranes Using Single-Molecule Tracking in Live Cells.

In live cells, the plasma membrane is composed of lipid domains separated by hundreds of nanometers in dynamic equilibrium. Lipid phase separation regulates the trafficking and spatiotemporal organization of membrane molecules that promote signal transduction. However, visualizing domains with adequate spatiotemporal accuracy remains challenging because of their subdiffraction limit size and highly dynamic properties. Here, we present a single lipid-molecular motion analysis pipeline (lipid-MAP) for analyzing the phase heterogeneity of lipid membranes by detecting the instantaneous velocity change of a single lipid molecule using the excellent optical properties of nanoparticles, high spatial localization accuracy of single-molecule localization microscopy, and separation capability of the diffusion state of the hidden Markov model algorithm. Using lipid-MAP, individual lipid molecules were found to be in dynamic equilibrium between two statistically distinguishable phases, leading to the formation of small (∼170 nm), viscous (2.5× more viscous than surrounding areas), and transient domains in live cells. Moreover, our findings provide an understanding of how membrane compositional changes, i.e., cholesterol and phospholipids, affect domain formation. This imaging method can contribute to an improved understanding of spatiotemporal-controlled membrane dynamics at the molecular level.

Interweaving Elastic and Hydrogen Bond-Forming Polymers into Highly Tough and Stress-Relaxable Binders for High-Performance Silicon Anode in Lithium-Ion Batteries.

A central challenge in practically using high-capacity silicon (Si) as anode materials for lithium-ion batteries is alleviating significant volume change of Si during cycling. One key to resolving the failure issues of Si is exploiting carefully designed polymer binders exhibiting mechanical robustness to retain the structural integrity of Si electrodes, while concurrently displaying elasticity and toughness to effectively dissipate external stresses exerted by the volume changes of Si. Herein, a highly elastic and tough polymer binder is proposed by interweaving polyacrylic acid (PAA) with poly(urea-urethane) (PUU) elastomer for Si anodes. By systematically tuning molecular parameters, including molecular weights of hard/soft segments and structures of hard segment components, it is demonstrated that the mechanical properties of polymer binders, such as elasticity, toughness, and stress relaxation ability, strongly affect the cycling performance of Si electrodes. This study provides new insight into the rational design of polymer binders capable of accommodating the volume changes of Si, primarily by judicious modulation of the mechanical properties of polymer binders.

Effect of Active Surgical Co-Management by Medical Hospitalists in Urology Inpatient Care: A Retrospective Cohort Study.

PURPOSE: This study aimed to evaluate the use of active surgical co-management (SCM) by medical hospitalists for urology inpatient care. MATERIALS AND METHODS: Since March 2019, a hospitalist-SCM program was implemented at a tertiary-care medical center, and a retrospective cohort study was conducted among co-managed urology inpatients. We assessed the clinical outcomes of urology inpatients who received SCM and compared passive SCM (co-management of patients by hospitalists only on request; March 2019 to June 2020) with active SCM (co-management of patients based on active screening by hospitalists; July 2020 to October 2021). We also evaluated the perceptions of patients who received SCM toward inpatient care quality, safety, and subjective satisfaction with inpatient care at discharge or when transferred to other wards. RESULTS: We assessed 525 patients. Compared with the passive SCM group (n=205), patients in the active SCM group (n=320) required co-management for a significantly shorter duration (p=0.012) and tended to have a shorter length of stay at the urology ward (p=0.062) and less frequent unplanned readmissions within 30 days of discharge (p=0.095) while triggering significantly fewer events of rapid response team activation (p=0.002). No differences were found in the proportion of patients transferred to the intensive care unit, in-hospital mortality rates, or inpatient care questionnaire scores. CONCLUSION: Active surveillance and co-management of urology inpatients by medical hospitalists can improve the quality and efficacy of inpatient care without compromising subjective inpatient satisfaction.

A Multifunctional Interlocked Binder with Synergistic In Situ Covalent and Hydrogen Bonding for High-Performance Si Anode in Li-ion Batteries.

Silicon has garnered significant attention as a promising anode material for high-energy density Li-ion batteries. However, Si can be easily pulverized during cycling, which results in the loss of electrical contact and ultimately shortens battery lifetime. Therefore, the Si anode binder is developed to dissipate the enormous mechanical stress of the Si anode with enhanced mechanical properties. However, the interfacial stability between the Si anode binder and Cu current collector should also be improved. Here, a multifunctional thiourea polymer network (TUPN) is proposed as the Si anode binder. The TUPN binder provides the structural integrity of the Si anode with excellent tensile strength and resilience due to the epoxy-amine and silanol-epoxy covalent cross-linking, while exhibiting high extensibility from the random coil chains with the hydrogen bonds of thiourea, oligoether, and isocyanurate moieties. Furthermore, the robust TUPN binder enhances the interfacial stability between the Si anode and current collector by forming a physical interaction. Finally, the facilitated Li-ion transport and improved electrolyte wettability are realized due to the polar oligoether, thiourea, and isocyanurate moieties, respectively. The concept of this work is to highlight providing directions for the design of polymer binders for next-generation batteries.