Out-of-Mold Sensor-Based Process Parameter Optimization and Adaptive Process Quality Control for Hot Runner Thin-Walled Injection-Molded Parts.

Injection molding is a highly nonlinear procedure that is easily influenced by various external factors, thereby affecting the stability of the product's quality. High-speed injection molding is required for production due to the rapid cooling characteristics of thin-walled parts, leading to increased manufacturing complexity. Consequently, establishing appropriate process parameters for maintaining quality stability in long-term production is challenging. This study selected a hot runner mold with a thin wall fitted with two external sensors, a nozzle pressure sensor and a tie-bar strain gauge, to collect data regarding the nozzle peak pressure, the timing of peak pressure, the viscosity index, and the clamping force difference value. The product weight was defined as the quality indicator, and a standardized parameter optimization process was constructed, including injection speed, V/P switchover point, packing, and clamping force. Finally, the optimized process parameters were applied to the adaptive process control experiments using the developed control system operated within the micro-controller unit (MCU). The results revealed that the control system effectively stabilized the product weight variation and standard deviation of 0.677% and 0.0178 g, respectively.

CIDE proteins and their regulatory mechanisms in lipid droplet fusion and growth.

The cell death-inducing DFF45-like effector (CIDE) proteins, including Cidea, Cideb, and Cidec/Fsp27, regulate various aspects of lipid homeostasis, including lipid storage, lipolysis, and lipid secretion. This review focuses on the physiological roles of CIDE proteins based on studies on knockout mouse models and human patients bearing CIDE mutations. The primary cellular function of CIDE proteins is to localize to lipid droplets (LDs) and to control LD fusion and growth across different cell types. We propose a four-step process of LD fusion, characterized by (a) the recruitment of CIDE proteins to the LD surface and CIDE movement, (b) the enrichment and condensate formation of CIDE proteins to form LD fusion plates at LD-LD contact sites, (c) lipid transfer through lipid-permeable passageways within the fusion plates, and (d) the completion of LD fusion. Lastly, we outline CIDE-interacting proteins as regulatory factors, as well as their contribution in LD fusion.

Digital health interventions to promote healthy lifestyle in hemodialysis patients: an interventional pilot study.

Low physical activity has been associated with poor prognosis in hemodialysis (HD) patients. Interventions to maintain healthy lifestyle in this population are important to reduce mortality. This study aimed to evaluate the effectiveness of digital health interventions (DHIs) for improving the physical activity and health-related quality of life (HRQoL) in HD patients. The 24-week prospective study enrolled 31 clinically stable HD patients. All participants were assigned home exercises and provided with wearable devices. Dietary and exercise information was uploaded to a health management platform. Suggestions about diet and exercise were provided, and a social media group was created. Physical performance testing was performed at baseline and during weeks 4, 8, 12, 16 and 24. HRQoL and nutritional status were evaluated. A total of 25 participants completed the study. After the interventions, the daily step count increased 1658 steps. The 10-time-repeated sit-to-stand test reduced by 4.4 s, the sit-to-stand transfers in 60 s increased 12 repetitions, the distance of six-minute walk test (6MWT) increased by 55.4 m. The mental health components and burden of kidney disease of the Kidney Disease Quality of Life survey, and subjective global assessment (SGA) scores improved. By Spearman correlation, the monthly step count correlated positively with 6MWT and SGA. DHIs that combined wearable devices, a health management platform, and social media could strengthen physical activity and improve the HRQoL and nutrition of maintenance HD patients. The results outline a new model to promote healthy lifestyle behaviors in HD patients.

The significance of dense fine speckled pattern in antinuclear antibody-associated rheumatic disease and coexisting autoantibodies: A propensity score-matched cohort study.

AIM: To investigate the relationship between the prevalence of antinuclear antibody (ANA) -associated rheumatic diseases (AARD) and the presence of dense fine speckled (DFS) and homogeneous patterns in ANA tests. METHODS: This retrospective study enrolled adult patients with either a DFS or homogeneous pattern in their ANA test. A mixed pattern was defined as the presence of more than one pattern reported in the test. The presence of anti-DFS70 antibodies and other common autoantibodies were detected using EUROLINE ANA Profile 23. A 1:2 propensity score matching was applied to control for demographic and other interfering factors. RESULTS: A total of 59 patients with a DFS pattern were enrolled and compared with a matched homogeneous group. The DFS group had a significantly lower prevalence of AARD (3.4% vs. 16.9%, p = .008) and the subgroup with anti-DFS70 antibodies showed an even lower prevalence (2% vs. 20%, p = .002). Among the 33 patients with monospecific anti-DFS70 antibodies, five had a mixed pattern, and all patients with common autoantibodies had an isolated DFS pattern. CONCLUSIONS: The findings of this study suggest that patients with a DFS pattern in their ANA test may have a lower prevalence of AARD compared with those with a homogeneous pattern. However, an isolated DFS pattern in ANA testing does not necessarily indicate the presence of monospecific anti-DFS70 antibodies or AARD. Confirmatory testing for the monospecific anti-DFS70 antibody is mandatory to exclude AARD.

Optimize Injection-Molding Process Parameters and Build an Adaptive Process Control System Based on Nozzle Pressure Profile and Clamping Force.

The injection-molding process is a non-linear process, and the product quality and long-term production stability are affected by several factors. To stabilize the product quality effected by these factors, this research establishes a standard process parameter setup procedure and an adaptive process control system based on the data collected by a nozzle pressure sensor and a tie-bar strain gauge to achieve this goal. In this research, process parameters such as the V/P switchover point, injection speed, packing pressure, and clamping force are sequentially optimized based on the characteristics of the pressure profile. After the optimization process, this research defines the standard quality characteristics through the optimized process parameters and combines it with the adaptive process control system in order to achieve the purpose of automatic adjustment of the machine and maintain high-quality production. Finally, three different viscosity materials are used to verify the effectiveness of the optimization procedure and the adaptive process control system. With the system, the variation of product weight was reduced to 0.106%, 0.092%, and 0.079%, respectively.

Serum Mediators in Patients with Both Type 2 Diabetes Mellitus and Pruritus.

Chronic pruritus is an unpleasant sensory perception that negatively affects quality of life and is common among patients with type 2 diabetes mellitus. Current antipruritic therapies are insufficiently effective. Thus, the mediation of diabetic pruritus by histamine-independent pathways is likely. The aim of this study was to identify possible mediators responsible for diabetic pruritus. A total of 87 patients with type 2 diabetes mellitus were analysed, of whom 59 had pruritus and 28 did not. The 2 groups were assessed for baseline demographics, serum biochemistry parameters, cytokines, and chemokines. This study also investigated the associations of these factors with the severity of itching. Neither haemoglobin A1c nor serum creatinine levels were correlated with severity of itching. Significantly higher levels of interleukin-4 (p = 0.004), interleukin-13 (p = 0.006), granulocyte-macrophage colony-stimulating factor (p < 0.001) and C-X-C motif chemokine ligand 10 (p = 0.028) were observed in the patients with pruritus than in those without pruritus. Moreover, the levels of these mediators were positively correlated with the severity of itching. Thus, novel antipruritic drugs can be developed to target these molecules. This is the first study to compare inflammatory mediators comprehensively in patients with diabetes mellitus with pruritus vs those without pruritus.

CLSTN3ß enforces adipocyte multilocularity to facilitate lipid utilization.

Multilocular adipocytes are a hallmark of thermogenic adipose tissue1,2, but the factors that enforce this cellular phenotype are largely unknown. Here, we show that an adipocyte-selective product of the Clstn3 locus (CLSTN3ß) present in only placental mammals facilitates the efficient use of stored triglyceride by limiting lipid droplet (LD) expansion. CLSTN3ß is an integral endoplasmic reticulum (ER) membrane protein that localizes to ER-LD contact sites through a conserved hairpin-like domain. Mice lacking CLSTN3ß have abnormal LD morphology and altered substrate use in brown adipose tissue, and are more susceptible to cold-induced hypothermia despite having no defect in adrenergic signalling. Conversely, forced expression of CLSTN3ß is sufficient to enforce a multilocular LD phenotype in cultured cells and adipose tissue. CLSTN3ß associates with cell death-inducing DFFA-like effector proteins and impairs their ability to transfer lipid between LDs, thereby restricting LD fusion and expansion. Functionally, increased LD surface area in CLSTN3ß-expressing adipocytes promotes engagement of the lipolytic machinery and facilitates fatty acid oxidation. In human fat, CLSTN3B is a selective marker of multilocular adipocytes. These findings define a molecular mechanism that regulates LD form and function to facilitate lipid utilization in thermogenic adipocytes.

Antecedents and consequences of shared decision making for patients with chronic kidney diseases: A cross-sectional survey.

BACKGROUND: Chronic kidney disease (CKD) has a strong negative impact on patients. Finding ways to improve CKD patients' conditions by shared decision-making is receiving much attention. However, little attention has been paid to influencing antecedents and effects of shared decision-making. Meanwhile, as advanced technologies bring in new communication devices, effects of different types of communications used in shared decision-making need to be addressed. OBJECTIVE: This study proposes a research framework to determine the influencing antecedents of shared decision-making, and to evaluate the effects of shared decision-making on patient outcomes when they are computer-mediated and when the decision-makers communicate face-to-face. METHODS: A cross-section survey was conducted and a total of 48 valid samples were obtained. The participants were CKD Stage III, IV, or V patients who had received medical treatment in a hospital in Taiwan. The collected data were subjected to an independent t-test and partial least squares analysis to validate the research framework. RESULTS: Doctor-patient communication (DPC) and doctor-patient relationship (DPR) have no significant direct impact on patient outcomes. Nevertheless, both DPC and DPR significantly impact shared decision-making which in turn impacts patient outcomes. Moreover, patients who use computer-mediated communication were found to have significantly higher perceptions of shared decision-making than those who did not. CONCLUSIONS: The incidence and prevalence of end-stage renal disease in Taiwan are among the highest in the world. The results of this study can serve as a reference for hospitals to improve CKD patients' outcomes. Meanwhile, during the COVID-19 pandemic, this study suggested hospitals should encourage shared decision-making with computer-mediated communication to ensure that patients receive proper treatment and have the desired outcomes.

PITPNC1 promotes the thermogenesis of brown adipose tissue under acute cold exposure.

Brown adipose tissue (BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) is identified as a lipid transporter that reciprocally transfers phospholipids between intracellular membrane structures. However, the physiological significance of PITPNC1 and its regulatory mechanism remain unclear. Here, we demonstrate that PITPNC1 is a key player in thermogenesis of BAT. While Pitpnc1-/- mice do not differ with wildtype mice in body weight and insulin sensitivity on either chow or high-fat diet, they develop hypothermia when subjected to acute cold exposure at 4°C. The Pitpnc1-/- brown adipocytes exhibit defective ß-oxidation and abnormal thermogenesis-related metabolism pathways in mitochondria. The deficiency of lipid mobilization in Pitpnc1-/- brown adipocytes might be the result of excessive accumulation of phosphatidylcholine and a reduction of phosphatidic acid. Our findings have uncovered significant roles of PITPNC1 in mitochondrial phospholipid homeostasis and BAT thermogenesis.

The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis.

BACKGROUND: Hereditary neuromuscular diseases (NMDs) are a group of rare disorders, and the diagnosis of these diseases is a substantial burden for referral centers. Although next-generation sequencing (NGS) has identified a large number of genes associated with hereditary NMDs, the diagnostic rates still vary across centers. METHODS: Patients with a suspected hereditary NMD were referred to neuromuscular specialists at the National Taiwan University Hospital. Molecular diagnoses were performed by employing a capture panel containing 194 genes associated with NMDs. RESULTS: Among the 50 patients referred, 43 had a suspicion of myopathy, and seven had polyneuropathy. The overall diagnostic rate was 58%. Pathogenic variants in 19 genes were observed; the most frequent pathogenic variant found in this cohort (DYSF) was observed in only four patients, and 10 pathogenic variants were observed in one patient each. One case of motor neuron disease was clinically mistaken for myopathy. A positive family history increased the diagnostic rate (positive: 72.7% vs. negative: 56.3%). Fourteen patients with elevated plasma creatine kinase levels remained without a diagnosis. CONCLUSION: The application of NGS in this single-center study proves the great diversity of hereditary NMDs. A capture panel is essential, but high-quality clinical and laboratory evaluations of patients are also indispensable.

A deep learning-based precision and automatic kidney segmentation system using efficient feature pyramid networks in computed tomography images.

This paper proposes an encoder-decoder architecture for kidney segmentation. A hyperparameter optimization process is implemented, including the development of a model architecture, selecting a windowing method and a loss function, and data augmentation. The model consists of EfficientNet-B5 as the encoder and a feature pyramid network as the decoder that yields the best performance with a Dice score of 0.969 on the 2019 Kidney and Kidney Tumor Segmentation Challenge dataset. The proposed model is tested with different voxel spacing, anatomical planes, and kidney and tumor volumes. Moreover, case studies are conducted to analyze segmentation outliers. Finally, five-fold cross-validation and the 3D-IRCAD-01 dataset are used to evaluate the developed model in terms of the following evaluation metrics: the Dice score, recall, precision, and the Intersection over Union score. A new development and application of artificial intelligence algorithms to solve image analysis and interpretation will be demonstrated in this paper. Overall, our experiment results show that the proposed kidney segmentation solutions in CT images can be significantly applied to clinical needs to assist surgeons in surgical planning. It enables the calculation of the total kidney volume for kidney function estimation in ADPKD and supports radiologists or doctors in disease diagnoses and disease progression.

A deep learning-based precision volume calculation approach for kidney and tumor segmentation on computed tomography images.

Previously, doctors interpreted computed tomography (CT) images based on their experience in diagnosing kidney diseases. However, with the rapid increase in CT images, such interpretations were required considerable time and effort, producing inconsistent results. Several novel neural network models were proposed to automatically identify kidney or tumor areas in CT images for solving this problem. In most of these models, only the neural network structure was modified to improve accuracy. However, data pre-processing was also a crucial step in improving the results. This study systematically discussed the necessary pre-processing methods before processing medical images in a neural network model. The experimental results were shown that the proposed pre-processing methods or models significantly improve the accuracy rate compared with the case without data pre-processing. Specifically, the dice score was improved from 0.9436 to 0.9648 for kidney segmentation and 0.7294 for all types of tumor detections. The performance was suitable for clinical applications with lower computational resources based on the proposed medical image processing methods and deep learning models. The cost efficiency and effectiveness were also achieved for automatic kidney volume calculation and tumor detection accurately.

Development of an Online Quality Control System for Injection Molding Process.

This research developed an adaptive control system for injection molding process. The purpose of this control system is to adaptively maintain the consistency of product quality by minimize the mass variation of injection molded parts. The adaptive control system works with the information collected through two sensors installed in the machine only-the injection nozzle pressure sensor and the temperature sensor. In this research, preliminary experiments are purposed to find master pressure curve that relates to product quality. Viscosity index, peak pressure, and timing of the peak pressure are used to characterize the pressure curve. The correlation between product quality and parameters such as switchover position and injection speed were used to produce a training data for back propagation neural network (BPNN) to compute weight and bias which are applied on the adaptive control system. By using this system, the variation of part weight is maintained to be as low as 0.14%.

Serum neutrophil gelatinase-associated lipocalin as a potential biomarker of diabetic kidney disease in patients with childhood-onset type 1 diabetes.

BACKGROUND/PURPOSE: Diabetic kidney disease (DKD) is a major complication in patients with type 1 diabetes (T1D). The aim of this study was to evaluate the role of serum neutrophil gelatinase-associated lipocalin (sNGAL) in the early detection of DKD in childhood-onset T1D patients. METHODS: A total of 116 patients (mean age, 22.3 ± 6.9 years) with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 were enrolled in this prospective cross-sectional study. Persistent albuminuria (PA) was defined as a urine albumin-to-creatinine ratio ≥ 30 mg/g for at least two consecutive years; non-albuminuria (NA) was defined otherwise. The patients were divided into the adult (Ad) (≥18 years, n = 91) and pediatric (Ped) (<18 years, n = 25) groups and further into the Ad-PA (n = 8), Ad-NA (n = 83), Ped-PA (n = 2), and Ad-NA (n = 23) subgroups. In all groups, the sNGAL level was determined. RESULTS: The mean diabetes duration was 14.2 ± 6.1 years, and 8.6% patients had PA. There was no significant difference in sNGAL levels between the PA and NA groups; notably, in adults, the sNGAL level was significantly higher in the Ad-PA than Ad-NA subgroups (P = 0.039). The sNGAL level was negatively correlated with the eGFR in adults (rho -0.41, P < 0.001). Multiple linear regression models showed that higher sNGAL levels in the adult group were independent and significant determinants of a lower eGFR (P < 0.001). CONCLUSION: An elevated sNGAL was significantly correlated with a decreased eGFR even in the range of normal to mildly decreased renal function. Thus, it is a potential biomarker of early deterioration of DKD in childhood-onset T1D.

A gel-like condensation of Cidec generates lipid-permeable plates for lipid droplet fusion.

Membrane contact between intracellular organelles is important in mediating organelle communication. However, the assembly of molecular machinery at membrane contact site and its internal organization correlating with its functional activity remain unclear. Here, we demonstrate that a gel-like condensation of Cidec, a crucial protein for obesity development by facilitating lipid droplet (LD) fusion, occurs at the LD-LD contact site (LDCS) through phase separation. The homomeric interaction between the multivalent N terminus of Cidec is sufficient to promote its phase separation both in vivo and in vitro. Interestingly, Cidec condensation at LDCSs generates highly plastic and lipid-permeable fusion plates that are geometrically constrained by donor LDs. In addition, Cidec condensates are distributed unevenly in the fusion plate generating stochastic sub-compartments that may represent unique lipid passageways during LD fusion. We have thus uncovered the organization and functional significance of geometry-constrained Cidec phase separation in mediating LD fusion and lipid homeostasis.

Impact of technological and departmental changes on incident rates in radiation oncology over a seventeen-year period.

INTRODUCTION: Advancements in technology and processes are designed to bring improvement. However, this is often achieved in parallel with increases in complexity, simultaneously presenting opportunities for new types of errors. This study aims to contextualise the impact of internal departmental changes upon radiation incidents and near misses recorded. METHODS: A timeline of events and a comprehensive incident categorisation system were applied to all radiation incidents and near misses recorded at the Princess Alexandra Hospital Radiation Oncology department from 2003 to 2019, inclusive. Descriptive statistics were performed to identify the type and number of incidents reported during the time period in relation to potential changes within the department, with a focus on the implementation of an electronic environment. RESULTS: Over the seventeen-year period, 157 incidents and 76 near misses were reported. The majority of incidents were classified as 'procedural' (78%), with 'treatment' being both the highest point of error and point of detection (49% and 85%, respectively). The largest number of incidents and near misses were reported in 2018 (n = 39) which was also a year that experienced the largest number of departmental changes (n = 16), including the move to a completely electronic planning process. CONCLUSIONS: Changes within the department were followed by an increasing number of reported incidents. Proactive measures should be undertaken prior to the implementation of major changes within the department to aid in the minimisation of incident occurrence.

TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis.

How amphipathic phospholipids are shuttled between the membrane bilayer remains an essential but elusive process, particularly at the endoplasmic reticulum (ER). One prominent phospholipid shuttling process concerns the biogenesis of APOB-containing lipoproteins within the ER lumen, which may require bulk trans-bilayer movement of phospholipids from the cytoplasmic leaflet of the ER bilayer. Here, we show that TMEM41B, present in the lipoprotein export machinery, encodes a previously conceptualized ER lipid scramblase mediating trans-bilayer shuttling of bulk phospholipids. Loss of hepatic TMEM41B eliminates plasma lipids, due to complete absence of mature lipoproteins within the ER, but paradoxically also activates lipid production. Mechanistically, scramblase deficiency triggers unique ER morphological changes and unsuppressed activation of SREBPs, which potently promotes lipid synthesis despite stalled secretion. Together, this response induces full-blown nonalcoholic hepatosteatosis in the TMEM41B-deficient mice within weeks. Collectively, our data uncovered a fundamental mechanism safe-guarding ER function and integrity, dysfunction of which disrupts lipid homeostasis.

Erratum: Update Notice: Lipid-exchange Rate Assay for Lipid Droplet Fusion in Live Cells.

[This corrects the article .].

Mobile Health App With Social Media to Support Self-Management for Patients With Chronic Kidney Disease: Prospective Randomized Controlled Study.

BACKGROUND: Chronic kidney disease (CKD) is a global health burden. Self-management plays a key role in improving modifiable risk factors. OBJECTIVE: The aim of this study was to evaluate the effectiveness of wearable devices, a health management platform, and social media at improving the self-management of CKD, with the goal of establishing a new self-management intervention model. METHODS: In a 90-day prospective experimental study, a total of 60 people with CKD at stages 1-4 were enrolled in the intervention group (n=30) and control group (n=30). All participants were provided with wearable devices that collected exercise-related data. All participants maintained dietary diaries using a smartphone app. All dietary and exercise information was then uploaded to a health management platform. Suggestions about diet and exercise were provided to the intervention group only, and a social media group was created to inspire the participants in the intervention group. Participants' self-efficacy and self-management questionnaire scores, Kidney Disease Quality of Life scores, body composition, and laboratory examinations before and after the intervention were compared between the intervention and control groups. RESULTS: A total of 49 participants completed the study (25 in the intervention group and 24 in the control group); 74% of the participants were men and the mean age was 51.22 years. There were no differences in measured baseline characteristics between the groups except for educational background. After the intervention, the intervention group showed significantly higher scores for self-efficacy (mean 171.28, SD 22.92 vs mean 142.21, SD 26.36; P<.001) and self-management (mean 54.16, SD 6.71 vs mean 47.58, SD 6.42; P=.001). Kidney Disease Quality of Life scores were also higher in the intervention group (mean 293.16, SD 34.21 vs mean 276.37, SD 32.21; P=.02). The number of steps per day increased in the intervention group (9768.56 in week 1 and 11,389.12 in week 12). The estimated glomerular filtration rate (eGFR) of the intervention group was higher than that of the control group (mean 72.47, SD 24.28 vs mean 59.69, SD 22.25 mL/min/1.73m2; P=.03) and the decline in eGFR was significantly slower in the intervention group (-0.56 vs -4.58 mL/min/1.73m2). There were no differences in body composition between groups postintervention. CONCLUSIONS: The use of wearable devices, a health management platform, and social media support not only strengthened self-efficacy and self-management but also improved quality of life and a slower eGFR decline in people with CKD at stages 1-4. These results outline a new self-management model to promote healthy lifestyle behaviors for patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04617431; https://www.clinicaltrials.gov/ct2/show/NCT04617431.

Effects of Erythropoietin Payment Policy on Cardiovascular Outcomes of Peritoneal Dialysis Patients: Observational Study.

BACKGROUND: The change in the reimbursement policy of erythropoietin administration to patients receiving peritoneal dialysis by the Taiwan National Health Insurance (NHI) system provided a natural experimental venue to examine whether cardiovascular risk differs when maintaining the hematocrit (Hct) level below or above 30%. OBJECTIVE: The aim of this study was to analyze the impact of loosening the erythropoietin payment criteria for peritoneal dialysis patients on their cardiovascular outcomes. METHODS: Two cohorts of incident peritoneal dialysis patients were identified according to the time before and after relaxation of the NHI's erythropoietin payment criteria, designated cohort 1 (n=1759) and cohort 2 (n=2981), respectively. The cohorts were matched according to propensity scores (1754 patients in each cohort) and then followed up for cardiovascular events, which were analyzed with Cox regressions. RESULTS: For the composite cardiovascular endpoint, patients in cohort 2 had a significantly lower risk than those in cohort 1. However, subgroup analysis showed that this risk reduction was observed only in patients with diabetes. CONCLUSIONS: After loosening erythropoietin payment criteria, reduced cardiovascular risks were observed, particularly for patients with diabetes. These results indicate that it is crucial to maintain an Hct level above 30% to reduce the cardiovascular risk in patients with diabetes undergoing peritoneal dialysis.