Implementation difficulties and solutions for a smart-clothes assisted home nursing care program for older adults with dementia or recovering from hip fracture.

BACKGROUND: Wearable devices have the advantage of always being with individuals, enabling easy detection of their movements. Smart clothing can provide feedback to family caregivers of older adults with disabilities who require in-home care. METHODS: This study describes the process of setting up a smart technology-assisted (STA) home-nursing care program, the difficulties encountered, and strategies applied to improve the program. The STA program utilized a smart-vest, designed specifically for older persons with dementia or recovering from hip-fracture surgery. The smart-vest facilitated nurses' and family caregivers' detection of a care receiver's movements via a remote-monitoring system. Movements included getting up at night, time spent in the bathroom, duration of daytime immobility, leaving the house, and daily activity. Twelve caregivers of older adults and their care receiver participated; care receivers included persons recovering from hip fracture (n = 5) and persons living with dementia (n = 7). Data about installation of the individual STA in-home systems, monitoring, and technical difficulties encountered were obtained from researchers' reports. Qualitative data about the caregivers' and care receivers' use of the system were obtained from homecare nurses' reports, which were explored with thematic analysis. RESULTS: Compiled reports from the research team identified three areas of difficulty with the system: incompatibility with the home environment, which caused extra hours of manpower and added to the cost of set-up and maintenance; interruptions in data transmissions, due to system malfunctions; and inaccuracies in data transmissions, due to sensors on the smart-vest. These difficulties contributed to frustration experienced by caregivers and care receivers. CONCLUSIONS: The difficulties encountered impeded implementation of the STA home nursing care. Each of these difficulties had their own unique problems and strategies to resolve them. Our findings can provide a reference for future implementation of similar smart-home systems, which could facilitate ease-of-use for family caregivers.

Room temperature operation of germanium-silicon single-photon avalanche diode.

The ability to detect single photons has led to the advancement of numerous research fields1-11. Although various types of single-photon detector have been developed12, because of two main factors-that is, (1) the need for operating at cryogenic temperature13,14 and (2) the incompatibility with complementary metal-oxide-semiconductor (CMOS) fabrication processes15,16-so far, to our knowledge, only Si-based single-photon avalanche diode (SPAD)17,18 has gained mainstream success and has been used in consumer electronics. With the growing demand to shift the operation wavelength from near-infrared to short-wavelength infrared (SWIR) for better safety and performance19-21, an alternative solution is required because Si has negligible optical absorption for wavelengths beyond 1 µm. Here we report a CMOS-compatible, high-performing germanium-silicon SPAD operated at room temperature, featuring a noise-equivalent power improvement over the previous Ge-based SPADs22-28 by 2-3.5 orders of magnitude. Key parameters such as dark count rate, single-photon detection probability at 1,310 nm, timing jitter, after-pulsing characteristic time and after-pulsing probability are, respectively, measured as 19 kHz µm-2, 12%, 188 ps, ~90 ns and <1%, with a low breakdown voltage of 10.26 V and a small excess bias of 0.75 V. Three-dimensional point-cloud images are captured with direct time-of-flight technique as proof of concept. This work paves the way towards using single-photon-sensitive SWIR sensors, imagers and photonic integrated circuits in everyday life.

Design of a Completely Vertical, Polarization-Independent Two-Dimensional Grating Coupler with High Coupling Efficiency.

An efficient optical coupler to transfer the signal between an optical fiber and a silicon waveguide is essential for realizing the applications of silicon photonic integrated circuits such as optical communication and optical sensing. In this paper, we numerically demonstrate a two-dimensional grating coupler based on a silicon-on-insulator platform to obtain completely vertical and polarization-independent couplings, which potentially ease the difficulty of packaging and measurement of photonic integrated circuits. To mitigate the coupling loss induced by the second-order diffraction, two corner mirrors are respectively placed at the two orthogonal ends of the two-dimensional grating coupler to create appropriate interference conditions. Partial single-etch is assumed to form an asymmetric grating to obtain high directionalities without a bottom mirror. The two-dimensional grating coupler is optimized and verified with finite-difference time-domain simulations, achieving a high coupling efficiency of -1.53 dB and a low polarization-dependent loss of 0.015 dB when coupling to a standard single-mode fiber at approximately 1310 nm wavelength.

CA125 for the Diagnosis of Advanced Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis.

BACKGROUND: Urothelial carcinoma of the bladder (UCB) is the second most common genitourinary cancer. This study aims to assess the diagnostic accuracy of CA125 in advanced UCB. METHODS: We searched prevalent studies in PubMed, the Cochrane Library, Scopus, Embase, the Web of Science China National Knowledge Infrastructure database, and Wanfang data before October 2022. Pooled sensitivity, specificity, and summary receiver operating characteristics were used to assess the diagnostic value of CA125. RESULTS: One thousand six hundred forty-one patients from 14 studies were analyzed. UCB stage T3-4N1 was defined as advanced UCB in ten studies; T2-4 was used in three studies; and N1M1 in one study. Patients' age was between 21 to 92, and 21% to 48.6% of patients were female. The pooled sensitivity was 0.695 (95% confidence interval (CI): 0.426-0.875). The pooled specificity was 0.846 (95% CI: 0.713-0.924). The diagnostic odds ratio was 8.138 (95% CI: 4.559-14.526). The AUC was 0.797. CONCLUSION: CA125 may provide significant diagnostic accuracy in identifying muscle-invasive, lymph node-involved, and distant metastatic tumors in patients with urothelial carcinoma of the bladder. Limited studies have been conducted on the prognostic role of CA125. More studies are needed for a meta-analysis on the prognostic role of CA125 in UCB.

A Semi-Analytical Method for Designing a Runner System of a Multi-Cavity Mold for Injection Molding.

Multi-cavity mold design is an efficient approach to achieving mass production and is frequently used in plastic injection applications. The runner system of a multi-cavity mold delivers molten plastic to each cavity evenly and makes the molded product from each individual cavity possess an equivalent quality. Not only the dimensions, but also the invisible quality, e.g., the internal stress of the product is of great concern in regard to molding quality. Using commercial software to find an optimal solution for the runner system may be time-consuming in respect to iterations if the engineers lack empirical rules. The H-type runner system is often used due to an inherently balanced filling in multi-cavities. However, the shear heat inducing an imbalanced flow behavior requires the H-type runner system to be improved as the number of the cavities is increased. This work develops a methodology based on the rheological concept to determine the runner system of a multi-cavity mold semi-analytically. As the relation of the viscosity with respect to shear rate is known, the runner system can be constructed step-by-step via this method. The use of the proposed method helps to focus attention on the connection between the physical situation and its related mathematical model. The influences of the melt temperature and resin type can be easily investigated. Three design examples, a 16-cavity mold with a fishbone runner system, an 8-cavity mold with an arbitrary runner layout, and the influences of melt temperature and resin type on the runner design are demonstrated and validated by the commercial software. The proposed method shows its great benefit when a new runner design project is launched in the initial design stage and then cooperates with the commercial software for further modifications.

Experiences of family caregivers of persons living with dementia with and without a smart- clothes assisted home nursing program during the heightened COVID-19 alert.

BACKGROUND: The COVID-19 pandemic has required restrictions of daily activities, which has been found to impact the lives of persons living with dementia (PLWDs) and their family caregivers, who have multiple care demands. The lack of relevant studies in Taiwan emphasized the need to explore the experiences of family caregivers of older PLWDs faced with the intensified restrictions to control the spread of COVID-19, and the impact of the availability of a smart-clothes home nursing program. METHODS: This qualitative study used semi-structured interviews with family caregivers of older PLWDs. Participants were recruited from dementia clinics of a medical center in northern Taiwan from a subset of a sample from a larger study on smart-clothes assisted home nursing care. A total of 12 family caregivers who participated in the original study were interviewed during the follow-up period; seven family caregivers of a PLWD wearing a smart-vest, which transmitted information to a home care nurse; five caregivers of a PLWD not wearing a smart-vest. Interviews were conducted by telephone because the conditions of the pandemic prevented face-to-face interviews. Recorded interviews were transcribed and analyzed using content analysis. RESULTS: Interview data showed family caregivers' felt the care recipient's health was compromised and functional conditions intensified as Covid-19-related pandemic restrictions increased. Specific concerns included a lack social interactions, decreased daily activity levels, loss of interest and lack of motivation for activities, increased mood and behavioral problems, a decline in physical function and an increase in health problems. Family caregivers were also impacted by these restrictions, with significant increases in severity of caregiver role strain, including feeling trapped, a lack of in-home support, profound powerlessness, and worries about the PLWD contracting the coronavirus. The smart-clothes assisted home nursing care program offered supplementary support to family caregivers by providing on-time interactions, helping them manage health problems, enhancing predictability of the care recipient's behaviors, and providing caregivers with emotional support. CONCLUSIONS: The findings of this study support alternative care such as implementation of technology-assisted home health services to meet caregiver needs to facilitate family caregiving of PLWDs during the necessary restrictions in activities implemented during the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Record NCT05063045.

A Water-Soluble Core for Manufacturing Hollow Injection-Molded Products.

To manufacture a complicated hollow product without any assembly process, for example, the plastic intake manifold, is difficult by the traditional injection molding method. The fusible-core technique, which uses a low-melting-point alloy as a sacrificial core, was developed to solve this problem; however, the limited selection of resin type and the huge capital investment have caused this technique to spread slowly. In this work, a novel method is established that can produce similar products without the limitation of resin type, as well as a lower-energy-consumption process. The concept of the enveloped core defined by a water-soluble core assembled with a shell is proposed herein; it provides both rigidity and toughness to resist the pressure during the injection molding process. The shape of the enveloped core equals the internal contour of the designated product. An insert molding process was introduced to cover the enveloped core with a skin layer. Cut out the end of the enveloped core and immerse it into a water bath. When the water-soluble core inside the shell is dissolved, the product with a special internal contour is accomplished. A tee-joint is presented to demonstrate how the proposed method can be utilized. The optimal ingredient of the core and processing parameters are determined by the Taguchi method. The result shows that the proposed product is molded successfully when the compressive strength of the core is larger than 2 MPa. In addition, the eccentricity measurement of internal contour of the optimal sample exhibits a 56% improvement, and the required time for the core removal is less than 154 s.

Prompts for the Future to Live Healthier: A Study of Cognition and Motivation for Healthy Behaviors.

"Aging" is a continuous phenomenon. Medically speaking, physical decline starts after the age of 25. Generally, people do not sense such a decline at a young age, but most transition to some awareness by the age of 50. To enhance the physical and mental health of elderly people and to reduce the length of time spent bedridden, the thoughts and behaviors regarding health and health care among a target group aged between 55 and 75 years were investigated in this study based on the perspective of health beliefs. A total of 300 survey questionnaires were issued and all were returned. The results indicated that after the respondents were reminded of the unhealthy implications of bedridden time, they were willing to enhance their health-promoting behaviors in their diets and regular routines.

Effectiveness of end-stage renal disease communication skills training for healthcare personnel: a single-center, single-blind, randomized study.

BACKGROUND: Given that the consequences of treatment decisions for end-stage renal disease (ESRD) patients are long-term and significant, good communication skills are indispensable for health care personnel (HCP) working in nephrology. However, HCP have busy schedules that make participation in face-to-face courses difficult. Thus, online curricula are a rising trend in medical education. This study aims to examine the effectiveness of online ESRD communication skills training (CST) concerning the truth-telling confidence and shared decision-making (SDM) ability of HCP. METHODS: For this single-center, single-blind study, 91 participants (nephrologists and nephrology nurses) were randomly assigned to two groups, the intervention group (IG) (n = 45) or the control group (CG) (n = 46), with the IG participating in ESRD CST and the CG receiving regular in-service training. Truth-telling confidence and SDM ability were measured before (T0), 2 weeks after (T1), and 4 weeks after (T2) the intervention. Group differences over the study period were analyzed by generalized estimating equations. RESULTS: IG participants exhibited significantly higher truth-telling confidence at T1 than did CG participants (t = 2.833, P = .006, Cohen's d = 0.59), while there were no significant intergroup differences in the confidence levels of participants in the two groups at T0 and T2. Concerning SDM ability, there were no significant intergroup differences at any of the three time points. However, IG participants had high levels of satisfaction (n = 43, 95%) and were willing to recommend ESRD CST to others (n = 41, 91.1%). CONCLUSIONS: ESRD CST enhanced short-term truth-telling confidence, though it is unclear whether this was due to CST content or the online delivery. However, during pandemics, when face-to-face training is unsuitable, online CST is an indispensable tool. Future CST intervention studies should carefully design interactive modules and control for method of instruction.

Smart clothes-assisted home-nursing care program for family caregivers of older persons with dementia and hip fracture: a mixed-methods study.

BACKGROUND: The purpose of this preliminary study was to explore whether a smart clothes-assisted home-nursing care program could benefit family caregivers and their care recipients. METHODS: Family caregivers in charge of a care recipient's living situation participated in this convergent parallel, mixed methods study. We recruited older persons with dementia (n = 7) and those discharged following hip-fracture surgery (n = 6) from neurological clinics and surgical wards of a medical center, respectively, along with their family caregivers: three spouses, eight sons, one daughter, and one daughter-in-law. Care recipients were asked to wear a smart vest at least 4 days/week for 6 months, which contained a coin-size monitor hidden in an inner pocket. Sensors installed in bedrooms and living areas received signals from the smart clothing, which were transmitted to a mobile phone app of homecare nurses, who provided caregivers with transmitted information regarding activities, emergency situations and suggestions for caregiving activities. Outcomes included changes from baseline in caregivers' preparedness and depressive symptoms collected at 1- and 3-months, which were analyzed with Friedman's non-parametric test of repeated measures with post-hoc analysis. Transcripts of face-to-face semi-structured interview data about caregivers' experiences were analyzed to identify descriptive, interpretative, and pattern codes. RESULTS: Preparedness did not change from baseline at either 1- or 3-months for family caregivers of persons with dementia. However, depressive symptoms decreased significantly at 1-month and 3-months compared with baseline, but not between 1-months and 3-months. Analysis of the interview data revealed the smart clothes program increased family caregivers' knowledge of the care recipient's situation and condition, informed healthcare providers of the care recipient's physical health and cognitive status, helped homecare nurses provide timely interventions, balanced the care recipient's exercise and safety, motivated recipients to exercise, helped family caregivers balance work and caregiving, and provided guidance for caregiving activities. CONCLUSIONS: Experiences with the smart clothes-assisted home-nursing care program directly benefited family caregivers, which provided indirect benefits to the care recipients due to the timely interventions and caregiving guidance from homecare nurses. These benefits suggest a smart-clothes-assisted program might be beneficial for all family caregivers.

Reduced mitochondria membrane potential and lysosomal acidification are associated with decreased oligomeric Aß degradation induced by hyperglycemia: A study of mixed glia cultures.

Diabetes is a risk factor for Alzheimer's disease (AD), a chronic neurodegenerative disease. We and others have shown prediabetes, including hyperglycemia and obesity induced by high fat and high sucrose diets, is associated with exacerbated amyloid beta (Aß) accumulation and cognitive impairment in AD transgenic mice. However, whether hyperglycemia reduce glial clearance of oligomeric amyloid-ß (oAß), the most neurotoxic Aß aggregate, remains unclear. Mixed glial cultures simulating the coexistence of astrocytes and microglia in the neural microenvironment were established to investigate glial clearance of oAß under normoglycemia and chronic hyperglycemia. Ramified microglia and low IL-1ß release were observed in mixed glia cultures. In contrast, amoeboid-like microglia and higher IL-1ß release were observed in primary microglia cultures. APPswe/PS1dE9 transgenic mice are a commonly used AD mouse model. Microglia close to senile plaques in APPswe/PS1dE9 transgenic mice exposed to normoglycemia or chronic hyperglycemia exhibited an amoeboid-like morphology; other microglia were ramified. Therefore, mixed glia cultures reproduce the in vivo ramified microglial morphology. To investigate the impact of sustained high-glucose conditions on glial oAß clearance, mixed glia were cultured in media containing 5.5 mM glucose (normal glucose, NG) or 25 mM glucose (high glucose, HG) for 16 days. Compared to NG, HG reduced the steady-state level of oAß puncta internalized by microglia and astrocytes and decreased oAß degradation kinetics. Furthermore, the lysosomal acidification and lysosomal hydrolysis activity of microglia and astrocytes were lower in HG with and without oAß treatment than NG. Moreover, HG reduced mitochondrial membrane potential and ATP levels in mixed glia, which can lead to reduced lysosomal function. Overall, continuous high glucose reduces microglial and astrocytic ATP production and lysosome activity which may lead to decreased glial oAß degradation. Our study reveals diabetes-induced hyperglycemia hinders glial oAß clearance and contributes to oAß accumulation in AD pathogenesis.

A community-based computerised cognitive training program for older persons with mild dementia: A pilot study.

OBJECTIVES: Computerised cognitive training programs can improve cognitive function in patients with moderate-to-severe dementia or brain injuries and healthy older adults. However, most previous studies were not randomised controlled trials and did not examine older adults with mild dementia. The current study sought to analyse the effects of a computerised cognitive training program using a randomised controlled trial. METHODS: In a single-blinded randomised clinical trial, 30 older individuals with mild dementia were split into an experimental (n = 15) and a control (n = 15) group to analyse the effects of a computerised cognitive training program. Outcomes were assessed before and after each program session, and 1 and 3 months afterwards. RESULTS: Participants in the experimental group had better overall subjective memory, subjective retrospective memory and global quality of life, with fewer depressive symptoms than those in the control group 3 months following the program. CONCLUSIONS: Our computerised cognitive training program improved subjective memory and quality of life in patients with mild dementia and decreased their depressive symptoms. These results may be useful for health-care providers caring for people with mild dementia.

2D-GolgiTrack-a semi-automated tracking system to quantify morphological changes and dynamics of the Golgi apparatus and Golgi-derived membrane tubules.

The Golgi apparatus and membrane tubules derived from this organelle play essential roles in membrane trafficking in eukaryotic cells. High-resolution live cell imaging is one highly suitable method for studying the molecular mechanisms of dynamics of organelles during membrane trafficking events. Due to the complex morphological changes and dynamic movements of the Golgi apparatus and associated membrane tubules during membrane trafficking, it is challenging to accurately quantify them. In this study, a semi-automated 2D tracking system, 2D-GolgiTrack, has been established for quantifying morphological changes and movements of Golgi elements, specifically encompassing the Golgi apparatus and its associated tubules, the fission and fusion of Golgi tubules, and the kinetics of formation of Golgi tubules and redistribution of the Golgi-associated protein Rab6A to the endoplasmic reticulum. The Golgi apparatus and associated tubules are segmented by a combination of Otsu's method and adaptive local normalization thresholding. Curvilinear skeletons and tips of skeletons of segmented tubules are used for calculating tubule length by the Geodesic method. The k-nearest neighbor is applied to search the possible candidate objects in the next frame and link the correct objects of adjacent frames by a tracking algorithm to calculate changes in morphological features of each Golgi object or tubule, e.g., number, length, shape, branch point and position, and fission or fusion events. Tracked objects are classified into morphological subtypes, and the Track-Map function of morphological evolution visualizes events of fission and fusion. Our 2D-GolgiTrack not only provides tracking results with 95% accuracy, but also maps morphological evolution for fast visual interpretation of the fission and fusion events. Our tracking system is able to characterize key morphological and dynamic features of the Golgi apparatus and associated tubules, enabling biologists to gain a greater understanding of the molecular mechanisms of membrane traffic involving this essential organelle. Graphical Abstract Overview of the semi-automated 2D tracking system. There are two main parts to the system, namely detection and tracking. The workflow process requires a raw sequence of images (a), which is filtered by the Gaussian filter method (c), and threshold intensity (b) to segment elements of Golgi cisternae (d) and tubules (e). Post-processing outputs are binary images of the cisternae area and tubule skeletons. The tubules are classified into three lengths, namely short, medium, and long tubules (f). Outputs of segmentation are calculated as morphological features (g). The tracking processing starts by loading the segmented outputs (h) and key-inputs of direction reference (i; (DR)) and interval setting of the start ((S)) and end ((E)) frame numbers (j). A tubule of interest is selected by the user (k; (GTinterest, S) as the tubule input ((GTIN)) at the current frame ((i = S)). The tracking algorithm tracks and links the correct tubules at each subsequent frame ((i = i + 1)). The locations of tubule tips are determined for detecting tubule branches using the (DR) to identify the direction of tubule growth (l: (1); (GTtipBr, i); Golgi cisternae: white area; Golgi tubule: white skeleton; tubule tips: green dots; branched tubules: two branches due to the (DR) of growth of the simulated tubule moving from left-to-right away from the Golgi cisternae location). According to the position of the (GTIN), five candidates ((GTcandidates, i)) are searched using the k-nearest neighbor method (l: (2)). Matching of tubules between the (GTIN) and those (GTcandidates, i) uses the bounding box technique to check the amount of tubule-overlap based on the tracking conditions (l: (3)). If there is tubule-overlap, the system collects that tubule as the final output ((GTOUT, i)). By contrast, shape (see the Extent feature in Table reftab:1) and distance features are used to generate the tracked output, which has a priority of a minimum of both of these features ((MinDIST, EXTENT)); otherwise, it is from the minimum of the distance ((MinDIST)). Once a loop of the interval track to the last frame is finished ((i = E + 1)), a Track-Map is generated allowing visualization of the morphological pattern of tubule formation and movement, including identification of fission and fusion events (m). Dynamic features are calculated (n). Related outputs are saved, and all features obtained from the detection and tracking processing are exported as MS Excel files (o).

Heat sink effect of underwater polypectomy in a porcine colon model.

BACKGROUND: Underwater polypectomy without the need for submucosal injection has been reported. A heat-sink effect by immersing the polyp in water was proposed but no such experiment has been performed to support the claim. We compared the temperature rise on the serosal side during polypectomy between air- and water-filled colon. METHOD: Freshly harvested porcine colons were placed in a metal tray with cautery electrode pad attached to its bottom. An upper endoscope was used with a cap and a rubber band mounted to the distal end. A mucosal site was randomly selected and identified on its serosal surface with a marker while suction was applied. Suction was applied again and a ligation band was applied to create a polyp. A cautery snare grasped the artificial polyp just below the band. An assistant placed the tip of a thermometer at the marked site on the serosal surface to record the baseline temperature before cautery and the highest temperature during polypectomy. Seven polypectomies in air and underwater were performed. RESULTS: Mean (standard deviation) baseline temperature were 23.3 (0.6) °C and 23.4 (0.6) °C in the air and water groups, respectively. The maximum rise in temperature during polypectomy was 6.1 (4.5) °C and 1.4 (1.0) °C in the air and water groups, respectively (P = 0.004). CONCLUSIONS: The maximum temperature rise during polypectomy was significantly less when polypectomy was performed underwater, supporting the hypothesis that a heat-sink effect does exist during underwater polypectomy.

Clinical Implications of HBV PreS/S Mutations and the Effects of PreS2 Deletion on Mitochondria, Liver Fibrosis, and Cancer Development.

BACKGROUND AND AIMS: PreS mutants of HBV have been reported to be associated with HCC. We conducted a longitudinal study of the role of HBV preS mutations in the development of HCC, particularly in patients with chronic hepatitis B (CHB) having low HBV DNA or alanine aminotransferase (ALT) levels, and investigated the effects of secretion-defective preS2 deletion mutant (preS2ΔMT) on hepatocyte damage in vitro and liver fibrosis in vivo. APPROACH AND RESULTS: Association of preS mutations with HCC in 343 patients with CHB was evaluated by a retrospective case-control follow-up study. Effects of preS2ΔMT on HBsAg retention, endoplasmic reticulum (ER) stress, calcium accumulation, mitochondrial dysfunction, and liver fibrosis were examined. Multivariate analysis revealed a significant association of preS mutations with HCC (HR, 3.210; 95% CI, 1.072-9.613; P = 0.037) including cases with low HBV DNA or ALT levels (HR, 2.790; 95% CI, 1.133-6.873; P = 0.026). Antiviral therapy reduced HCC risk, including cases with preS mutations. PreS2ΔMT expression promoted HBsAg retention in the ER and unfolded protein response (UPR). Transmission electron microscopic examination, MitoTracker staining, real-time ATP assay, and calcium staining of preS2ΔMT-expressing cells revealed aberrant ER and mitochondrial ultrastructure, reduction of mitochondrial membrane potential and ATP production, and calcium overload. Serum HBV secretion levels were ~100-fold lower in preS2ΔMT-infected humanized Fah-/-/ Rag2-/-/Il2rg-/- triple knockout mice than in wild-type HBV-infected mice. PreS2ΔMT-infected mice displayed up-regulation of UPR and caspase-3 and enhanced liver fibrosis. CONCLUSIONS: PreS mutations were significantly associated with HCC development in patients with CHB, including those with low HBV DNA or ALT levels. Antiviral therapy reduced HCC occurrence in patients with CHB, including those with preS mutations. Intracellular accumulation of mutated HBsAg induced or promoted ER stress, calcium overload, mitochondrial dysfunction, impaired energy metabolism, liver fibrosis, and HCC.

Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection.

To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a humanized decoy antibody (ACE2-Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2). First, we demonstrated that ACE2-Fc could specifically abrogate virus replication by blocking the entry of SARS-CoV-2 spike-expressing pseudotyped virus into both ACE2-expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS-CoV-2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2-Fc to reduce the angiotensin II-mediated cytokine cascade. Furthermore, this Fc domain of ACE2-Fc was shown to activate NK cell degranulation after co-incubation with Spike-expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2-Fc as an effective treatment for COVID-19.

Predictive Factors of Cerebral Aneurysm Rerupture After Clipping.

BACKGROUND: We aimed to estimate the risk of rerupture after first-time aneurysmal clipping surgery, explore the possible related factors, and assess long-term physical functionality. We hypothesized that the modified Rankin scale (mRS) could serve as an effective substitute for Hunter and Hess scale. METHODS: This retrospective study included 171 patients with cerebral aneurysmal rupture who had completed aneurysmal clipping treatment and collected their demographic data and medical records. The outcome assessments include neuroimaging records, Hunter and Hess scale, and the mRS scale during hospitalization and follow-up after discharge. The mean length of follow-up was 4.28 years. RESULTS: After aneurysmal clipping treatment, 83 patients (48.5%) had subsequently ruptured aneurysms. The scores of the reruptured group on the Hunt and Hess scale and mRS were significantly higher than those of the non-reruptured group. Multiple Cox proportional-hazards regression also showed that postoperative mRS >2, smoking, and two or more aneurysms were potentially important risk factors leading to aneurysm rupture again [the corresponding hazard ratios (HRs) were 5.209, 2.109, and 2.775, respectively] in patients. In addition, the location of an aneurysm on the anterior cerebral artery (ACA) or the posterior communicating (Pcom) artery had a higher risk of rerupture (the corresponding HRs were 1.996 and 2.934, respectively). CONCLUSIONS: Nearly half of the collected participants experienced the rerupture episode, who had undergone the second-time clipping surgery. Smoking and multiple aneurysms are potential risk factors for aneurysmal rerupture. Most aneurysms are located along the ICA, but aneurysms located at the ACA or Pcom site are most likely to rerupture. As compared with the Hunter and Hess scale, the mRS scale does not have inferior predicting power in following patients' long-term functionalities.

Association of diabetes, education level, and care dependency with use of temporary vascular access in patients with chronic kidney disease.

OBJECTIVE: Temporary vascular access (TVA) is frequently used during the first dialysis in patients with chronic kidney disease (CKD), and it is associated with an increased risk of infection, central vein stenosis, and mortality. Here, factors associated with TVA in patients with CKD were explored. METHODS: This study included patients in a single-center CKD care program who initiated long-term renal replacement therapy. The primary outcome was TVA use at first dialysis. Factors possibly associated with TVA use were analyzed using Cox regression. RESULTS: Temporary vascular access was used in 53.2% of the patients at first dialysis. In total, 73.2% (n = 865) and 26.8% (n = 317) of the patients were on hemodialysis and peritoneal dialysis, respectively. Multivariate Cox regression analysis showed that TVA use in patients with CKD was associated with diabetes (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.28-1.81, p < 0.001), lower albumin (HR 0.82, 95% CI 0.75-0.91, p < 0.001), lower education level (HR 0.75, 95% CI 0.56-1.00, p = 0.055), and total care dependency (HR 1.92, CI 1.44-3.43, p = 0.003). CONCLUSION: Diabetes, education level, and care dependency are associated with TVA at dialysis initiation in patients with CKD.

Influence of Heat Sink on the Mold Temperature of Gypsum Mold Used in Injection Molding.

Gypsum molds have been developed as an alternative for the Rapid tooling (RT) method used in injection molding. However, the poor capability of the heat delivery forces the gypsum mold to operate under a high-risk condition, and distortion of the molded part becomes apparent. The goal is to investigate the effect of a heat sink on the reduction of the gypsum mold temperature and to establish a methodology for the heat sink design. The methodology used the advantage of the electrical circuit concept to analyze the mold temperature. The heat transfer of a mold was modeled using an equivalent thermal circuit. After all the components on the circuit were determined, the heat transfer rate could then be calculated. Once the heat transfer rate was known, the mold temperature could be easily analyzed. A modified thermal circuit considering transverse heat conduction was also proposed, which estimated the mold temperature more accurately. The mold temperature was reduced by 16.8 °C when a gypsum mold was installed with a 40 mm thick heat sink in a parallel configuration. Moreover, the reduction of the mold temperature improved the deflection of the molded part from 0.78 mm to 0.54 mm. This work provides a quick approach to analyze the mold temperature based on the thermal circuit concept. As the cooling system of the mold was modularized analytically, important properties of the cooling system in the heat transfer process were revealed by analyzing the thermal circuit of the mold, for example, the heat transfer rate or the mold temperature.

Morphological control of mitochondria as the novel mechanism of Gastrodia elata in attenuating mutant huntingtin-induced protein aggregations.

BACKGROUND: According to Compendium of Materia Medica, Gastrodia elata (GE) Blume as a top grade and frequently prescribed herbal medicine has been used in treating dizziness, headaches, and epilepsy, indicating a neuroprotective effect. Because GE is capable of suppressing a hyperactive liver and thus calming endogenous wind, and because Huntington's disease (HD) can be classified as a phenomenon of disturbed liver wind, it is suggested that GE might be beneficial in treating HD. However, although current studies support GE for the prevention of diverse neurodegenerations such as HD, its detailed mechanisms remain elusive. PURPOSE: To investigate the molecular mechanism of GE in preventing HD by focusing on mitochondrial morphology, which is highly associated with HD etiology and thus proposed as a therapeutic target of neurodegenerations. STUDY DESIGN/METHODS: The overexpression of the mutant huntingtin (mHTT) gene in rat pheochromocytoma (PC12) cells was used as an in vitro cell model of HD. A filter retardation assay was applied to measure protein aggregations during HTT expression. Cotransfection with mitochondrial fusion and fission genes was used to test their relationships with HTT aggregates by monitoring with a confocal laser scanning microscope and filter retardation assay. Western blot analysis was used to estimate protein expression under different drug treatments or cotransfections with other related genes. RESULTS: The overexpression of mutant but not normal HTT genes significantly resulted in protein aggregations in PC12 cells. GE dose-dependently attenuated mHTT-induced protein aggregations and free radical formations. GE significantly reversed mHTT-induced mitochondrial fragmentation and dysregulation of mitochondrial fusion and fission molecules. The overexpression of mitochondrial fusion genes attenuated mHTT-induced protein aggregations. Further, Mdivi-1, a DRP1 fission molecule inhibitor, significantly reversed mHTT-induced protein aggregations and mitochondrial fragmentation. CONCLUSION: GE attenuated mHTT aggregations through the control of mitochondrial fusion and the fission pathway.