An Intelligent Thermal Compensation System Using Edge Computing for Machine Tools.

This paper focuses on the use of smart manufacturing in lathe-cutting tool machines, which can experience thermal deformation during long-term processing, leading to displacement errors in the cutting head and damage to the final product. This study uses time-series thermal compensation to develop a predictive system for thermal displacement in machine tools, which is applicable in the industry using edge computing technology. Two experiments were carried out to optimize the temperature prediction models and predict the displacement of five axes at the temperature points. First, an examination is conducted to determine possible variances in time-series data. This analysis is based on the data obtained for the changes in time, speed, torque, and temperature at various locations of the machine tool. Using the viable machine-learning models determined, the study then examines various cutting settings, temperature points, and machine speeds to forecast the future five-axis displacement. Second, to verify the precision of the models created in the initial phase, other time-series models are examined and trained in the subsequent phase, and their effectiveness is compared to the models acquired in the first phase. This work also included training seven models of WNN, LSTNet, TPA-LSTM, XGBoost, BiLSTM, CNN, and GA-LSTM. The study found that the GA-LSTM model outperforms the other three best models of the LSTM, GRU, and XGBoost models with an average precision greater than 90%. Based on the analysis of training time and model precision, the study concluded that a system using LSTM, GRU, and XGBoost should be designed and applied for thermal compensation using edge devices such as the Raspberry Pi.

Telomerase is essential for cardiac differentiation and sustained metabolism of human cardiomyocytes.

Telomeres as the protective ends of linear chromosomes, are synthesized by the enzyme telomerase (TERT). Critically short telomeres essentially contribute to aging-related diseases and are associated with a broad spectrum of disorders known as telomeropathies. In cardiomyocytes, telomere length is strongly correlated with cardiomyopathies but it remains ambiguous whether short telomeres are the cause or the result of the disease. In this study, we employed an inducible CRISPRi human induced pluripotent stem cell (hiPSC) line to silence TERT expression enabling the generation of hiPSCs and hiPSC-derived cardiomyocytes with long and short telomeres. Reduced telomerase activity and shorter telomere lengths of hiPSCs induced global transcriptomic changes associated with cardiac developmental pathways. Consequently, the differentiation potential towards cardiomyocytes was strongly impaired and single cell RNA sequencing revealed a shift towards a more smooth muscle cell like identity in the cells with the shortest telomeres. Poor cardiomyocyte function and increased sensitivity to stress directly correlated with the extent of telomere shortening. Collectively our data demonstrates a TERT dependent cardiomyogenic differentiation defect, highlighting the CRISPRi TERT hiPSCs model as a powerful platform to study the mechanisms and consequences of short telomeres in the heart and also in the context of telomeropathies.

Meta-analysis of the effectiveness of heparin in suppressing physiological myocardial FDG uptake in PET/CT.

BACKGROUND: The present meta-analysis aims to investigate the effectiveness of heparin administration in suppressing physiological myocardial 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT), as its role in this regard has not been well investigated. METHODS: PRISMA guidelines were used to interrogate the PubMed, Embase, Cochrane library, Web of Knowledge, and www.clinicaltrail.gov databases from the earliest records to March 2023. The final analysis included five randomized controlled trials (RCTs). Meta-analysis was conducted to compare the effectiveness of unfractionated heparin (UFH) administration versus non-UFH administration, and subgroup analysis based on fixed and variable fasting durations was conducted. Effect sizes were pooled using a random-effects model, and the pooled odds ratios (ORs) were calculated. RESULTS: Five eligible RCTs with a total of 910 patients (550 with heparin, 360 without heparin) were included. The forest plot analysis initially indicated no significant difference in the suppression of myocardial FDG uptake between the UFH and non-UFH groups (OR 2.279, 95% CI 0.593 to 8.755, p = 0.23), with a high degree of statistical heterogeneity (I2 = 91.16%). Further subgroup analysis showed that the fixed fasting duration group with UFH administration had statistically significant suppression of myocardial FDG uptake (OR 4.452, 95% CI 1.221 to 16.233, p = 0.024), while the varying fasting duration group did not show a significant effect. CONCLUSIONS: According to the findings of our meta-analysis, we suggest that intravenous administration of UFH can be considered as a supplementary approach to suppress myocardial FDG uptake.

Effective suppression of myocardial glucose uptake using predesigned low-carbohydrate boxed meals.

BACKGROUND: Dietary preparation protocols are an effective means to suppress physiological myocardial 18F-fluorodeoxyglucose (FDG) uptake. This study aimed to investigate the efficacy of various carbohydrate-restricted diets using predesigned boxed meals. METHODS: The patients were divided into four groups to undergo different preparatory protocols as follows: a minimum 15-hour fast alone, two meals of high-fat, low-carbohydrate diet (HFLCD), two meals of high-animal-protein, low-carbohydrate diet (HAPLCD), and two meals of high-plant-based-protein, low-carbohydrate diet (HPPLCD). Boxed meals were prepared to meet the required carbohydrate restrictions. Myocardial SUVmax and SUVmean were measured and the suppression rate was analyzed. RESULTS: The average myocardial SUVmax of fast alone, HFLCD, HAPLCD, and HPPLCD were 8.26 ± 5.85, 2.21 ± 1.50, 2.34 ± 1.88, and 4.10 ± 3.61, respectively, and the suppression rates were 36.6%, 93.3%, 93.3%, and 70%, respectively. The effectiveness of HFLCD, HAPLCD, and HPPLCD was all statistically superior to that of a 15-hour fast alone. SUVmax of HFLCD and HAPLCD showed no significant differences (p = 1), whereas HFLCD and HPPLCD had significant differences (p = .046). CONCLUSIONS: Using the predesigned boxed meals based on carbohydrate restriction, HFLCD, HAPLCD, and HPPLCD can be administered to patients with different dietary needs while providing a substantial reduction in physiological myocardial FDG uptake.

A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity.

AIMS: Cardiotoxicity leading to heart failure (HF) is a growing problem in many cancer survivors. As specific treatment strategies are not available, RNA discovery pipelines were employed and a new and powerful circular RNA (circRNA)-based therapy was developed for the treatment of doxorubicin-induced HF. METHODS AND RESULTS: The circRNA sequencing was applied and the highly species-conserved circRNA insulin receptor (Circ-INSR) was identified, which participates in HF processes, including those provoked by cardiotoxic anti-cancer treatments. Chemotherapy-provoked cardiotoxicity leads to the down-regulation of Circ-INSR in rodents and patients, which mechanistically contributes to cardiomyocyte cell death, cardiac dysfunction, and mitochondrial damage. In contrast, Circ-INSR overexpression prevented doxorubicin-mediated cardiotoxicity in both rodent and human cardiomyocytes in vitro and in a mouse model of chronic doxorubicin cardiotoxicity. Breast cancer type 1 susceptibility protein (Brca1) was identified as a regulator of Circ-INSR expression. Detailed transcriptomic and proteomic analyses revealed that Circ-INSR regulates apoptotic and metabolic pathways in cardiomyocytes. Circ-INSR physically interacts with the single-stranded DNA-binding protein (SSBP1) mediating its cardioprotective effects under doxorubicin stress. Importantly, in vitro transcribed and circularized Circ-INSR mimics also protected against doxorubicin-induced cardiotoxicity. CONCLUSION: Circ-INSR is a highly conserved non-coding RNA which is down-regulated during cardiotoxicity and cardiac remodelling. Adeno-associated virus and circRNA mimics-based Circ-INSR overexpression prevent and reverse doxorubicin-mediated cardiomyocyte death and improve cardiac function. The results of this study highlight a novel and translationally important Circ-INSR-based therapeutic approach for doxorubicin-induced cardiac dysfunction.

Identifying distinct oxygen diffusivity through type I pneumocyte-like cell layers using microfluidic device.

Oxygen is necessary for cellular respiration in aerobic organisms. In animals, such as human, inhaled oxygen moves from the alveoli to the blood through alveolar epithelium into pulmonary capillaries. Up to now, different studies have been reported to examine experimental oxygen diffusivity for simple membrane or single-celled organisms; however, devices capable of precisely characterizing oxygen transportation through cell layers with dimensions similar to their physiological ones have not been developed. In this study, we establish an integrated approach exploiting a multi-layer microfluidic device and relative fluorescence lifetime detection apparatus to reliably measure oxygen diffusivity through a cell layer. In the experiments, different types of cells, including A549 and 3T3 cell lines, lung stem/progenitor cells, and the differentiated type I pneumocyte-like cells, are used to form cell layers within the devices for their oxygen diffusivity evaluation. A distinct facilitated oxygen transportation behavior of the differentiated type I pneumocyte-like cells that has never been discussed before is identified using the approach. The study offered a new in vitro approach to evaluate the oxygen diffusivity across cell layers in a microfluidic device and open a door to construct more physiologically meaningful in vitro model system to study respiratory systems.

Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length.

Ageing provokes a plethora of molecular, cellular and physiological deteriorations, including heart failure, neurodegeneration, metabolic maladaptation, telomere attrition and hair loss. Interestingly, on the molecular level, the capacity to induce autophagy, a cellular recycling and cleaning process, declines with age across a large spectrum of model organisms and is thought to be responsible for a subset of age-induced changes. Here, we show that a 6-month administration of the natural autophagy inducer spermidine in the drinking water to aged mice is sufficient to significantly attenuate distinct age-associated phenotypes. These include modulation of brain glucose metabolism, suppression of distinct cardiac inflammation parameters, decreased number of pathological sights in kidney and liver and decrease of age-induced hair loss. Interestingly, spermidine-mediated age protection was associated with decreased telomere attrition, arguing in favour of a novel cellular mechanism behind the anti-ageing effects of spermidine administration.

Combined high-throughput library screening and next generation RNA sequencing uncover microRNAs controlling human cardiac fibroblast biology.

BACKGROUND: Myocardial fibrosis is a hallmark of the failing heart, contributing to the most common causes of deaths worldwide. Several microRNAs (miRNAs, miRs) controlling cardiac fibrosis were identified in recent years; however, a more global approach to identify miRNAs involved in fibrosis is missing. METHODS AND RESULTS: Functional miRNA mimic library screens were applied in human cardiac fibroblasts (HCFs) to identify annotated miRNAs inducing proliferation. In parallel, miRNA deep sequencing was performed after subjecting HCFs to proliferating and resting stimuli, additionally enabling discovery of novel miRNAs. In-depth in vitro analysis confirmed the pro-fibrotic nature of selected, highly conserved miRNAs miR-20a-5p and miR-132-3p. To determine downstream cellular pathways and their role in the fibrotic response, targets of the annotated miRNA candidates were modulated by synthetic siRNA. We here provide evidence that repression of autophagy and detoxification of reactive oxygen species by miR-20a-5p and miR-132-3p explain some of their pro-fibrotic nature on a mechanistic level. CONCLUSION: We here identified both miR-20a-5p and miR-132-3p as crucial regulators of fibrotic pathways in an in vitro model of human cardiac fibroblast biology.

Aging impairs alveolar epithelial type II cell function in acute lung injury.

Morbidity and mortality rates in acute lung injury (ALI) increase with age. As alveolar epithelial type II cells (AE2) are crucial for lung function and repair, we hypothesized that aging promotes senescence in AE2 and contributes to the severity and impaired regeneration in ALI. ALI was induced with 2.5 µg lipopolysaccharide/g body weight in young (3 mo) and old (18 mo) mice that were euthanized 24 h, 72 h, and 10 days later. Lung function, pulmonary surfactant activity, stereology, cell senescence, and single-cell RNA sequencing analyses were performed to investigate AE2 function in aging and ALI. In old mice, surfactant activity was severely impaired. A 60% mortality rate and lung function decline were observed in old, but not in young, mice with ALI. AE2 of young mice adapted to injury by increasing intracellular surfactant volume and proliferation rate. In old mice, however, this adaptive response was compromised, and AE2 of old mice showed signs of cell senescence, increased inflammatory signaling, and impaired surfactant metabolism in ALI. These findings provide evidence that ALI promotes a limited proliferation rate, increased inflammatory response, and surfactant dysfunction in old, but not in young, mice, supporting an impaired regenerative capacity and reduced survival rate in ALI with advancing age.

miR-21, Mediator, and Potential Therapeutic Target in the Cardiorenal Syndrome.

Oligonucleotide-based therapies are currently gaining attention as a new treatment option for relatively rare as well as common diseases such as cardiovascular disease. With the remarkable progression of new sequencing technologies, a further step towards personalized precision medicine to target a disease at a molecular level was taken. Such therapies may employ antisense oligonucleotides to modulate the expression of both protein coding and non-coding RNAs, such as microRNAs. The cardiorenal syndrome (CRS) is a complex and severe clinical condition where heart and renal dysfunction mutually affect one another. The underlying mechanisms remain largely unknown and current treatments of CRS are mainly supportive therapies which slow down the progression of the disease, but hardly improve the condition. The small non-coding RNA, microRNA-21 (miR-21), is dysregulated in various heart and kidney diseases and has been repeatedly suggested as therapeutic target for the treatment of CRS. Impressive preclinical results have been achieved by an antisense oligonucleotide-based therapy to effectively block the pro-fibrotic traits of miR-21. Since microRNA-mediated pathways are generally very well-conserved, there is considerable commercial interest with regards to clinical translation. In this review, we will summarize the role of miR-21 within the heart-kidney axis and discuss the advantages and pitfalls of miR-21 targeting therapeutic strategies in CRS.

The Long Non-coding RNA Cyrano Is Dispensable for Pluripotency of Murine and Human Pluripotent Stem Cells.

Pluripotency is tightly regulated and is crucial for stem cells and their implementation for regenerative medicine. Non-coding RNAs, especially long non-coding RNAs (lncRNAs) emerged as orchestrators of versatile (patho)-physiological processes on the transcriptional and post-transcriptional level. Cyrano, a well-conserved lncRNA, is highly expressed in stem cells suggesting an important role in pluripotency, which we aimed to investigate in loss-off-function (LOF) experiments. Cyrano was described previously to be essential for the maintenance of mouse embryonic stem cell (ESC) pluripotency. In contrast, using different genetic models, we here found Cyrano to be dispensable in murine and human iPSCs and in human ESCs. RNA sequencing revealed only a moderate influence of Cyrano on the global transcriptome. In line, Cyrano-depleted iPSCs retained the potential to differentiate into the three germ layers. In conclusion, different methods were applied for LOF studies to rule out potential off-target effects. These approaches revealed that Cyrano does not impact pluripotency.

Preclinical and Clinical Development of Noncoding RNA Therapeutics for Cardiovascular Disease.

RNA modulation has become a promising therapeutic approach for the treatment of several types of disease. The emerging field of noncoding RNA-based therapies has now come to the attention of cardiovascular research, in which it could provide valuable advancements in comparison to current pharmacotherapy such as small molecule drugs or antibodies. In this review, we focus on noncoding RNA-based studies conducted mainly in large-animal models, including pigs, rabbits, dogs, and nonhuman primates. The obstacles and promises of targeting long noncoding RNAs and circRNAs as therapeutic modalities in humans are specifically discussed. We also describe novel ex vivo methods based on human cells and tissues, such as engineered heart tissues and living myocardial slices that could help bridging the gap between in vivo models and clinical applications in the future. Finally, we summarize antisense oligonucleotide drugs that have already been approved by the Food and Drug Administration for targeting mRNAs and discuss the progress of noncoding RNA-based drugs in clinical trials. Additional factors, such as drug chemistry, drug formulations, different routes of administration, and the advantages of RNA-based drugs, are also included in the present review. Recently, first therapeutic miRNA-based inhibitory strategies have been tested in heart failure patients as well as healthy volunteers to study effects on wound healing (NCT04045405; NCT03603431). In summary, a combination of novel therapeutic RNA targets, large-animal models, ex vivo studies with human cells/tissues, and new delivery techniques will likely lead to significant progress in the development of noncoding RNA-based next-generation therapeutics for cardiovascular disease.

Using Cine-Averaged CT With the Shallow Breathing Pattern to Reduce Respiration-Induced Artifacts for Thoracic Cavity PET/CT Scans.

OBJECTIVE. PET/CT provides a fusion of both anatomic and functional information. However, because of the temporal difference of both modalities and respiratory motion of lungs, misregistration of lesions is frequently observed on thoracic PET/CT scans. The effect of cine-averaged CT (CACT) acquisition incorporated with the shallow breathing pattern of patients on the improvement of registration and quantification of lesions was investigated. MATERIALS AND METHODS. Thirty patients with cancer who underwent routine PET/CT followed by CACT of the thoracic region were enrolled. The misalignment between PET/helical CT (HCT) and PET/CACT was calculated. In addition, the PET data were attenuation-corrected by HCT and CACT images, and the maximum standardized uptake value (SUVmax) was evaluated. RESULTS. All lesions in the PET/HCT images showed misalignment larger than 5 mm, whereas only 33% of lesions in the PET/CACT images showed misalignment larger than 5 mm. The mean values of the maximum misalignment of the lesions in PET/HCT and PET/CACT images were 14.10 ± 6.26 mm and 5.92 ± 4.31 mm, respectively. Seven percent of the lesions had an increase in SUVmax of more than 20%, and 47% showed a slight increase in SUVmax of less than 5% after applying CACT. The mean percentage difference between the SUVmax of CACT and that of HCT was 12%. CONCLUSION. Using the CACT technique and the shallow breathing pattern effectively reduces misregistration of lesions and recovers the underestimated SUVmax. The CACT method can be applied in clinical practice of thoracic PET/CT for better cancer management.

Colon Visualization on Bone Scan Due to Recto-abscess Fistula From Urinoma.

The accumulation of the bone-seeking agent in the bowel during a bone scan is rare. A 68-year-old man with colon cancer underwent bone scintigraphy for staging. Whole-body images revealed an abnormal accumulation of hot radioactivity in the abdominal cavity and the colon. Abdominal CT showed a recto-abscess fistula between the rectum and the urinoma. Incidental visualization of colonic radioactivity suggested the presence of a fistula between the bowel and the urinoma, explaining the peculiar finding of the bone-seeking agent in the bowel.

Four patients with gastrointestinal bleeding identified by a modified in vivo technique with labeled red blood cells sedimentation.

OBJECTIVE: Gastrointestinal bleeding scintigraphy (GIBS) offers the advantage of continuous monitoring of patients to localize the site of gastrointestinal bleeding. In this study, a modified in vivo labeling method with sedimentation of the labeled red blood cells (RBC) was applied to remove free technetium-99m (99mTc) and increase labeling efficiency. PATIENTS AND METHODS: Four patients were studied. A modified in vivo RBC labeling method was used. After 10 minutes of RBC sedimentation, patients' blood plasma in the upper part of the syringe was removed, and the erythrocytes labeled with 99mTc were re-administered to the patient. Serial dynamic scintiphotos were taken during the first 60 minutes. Delayed static images were acquired up to 22 hours after injection. RESULTS: The labeling efficiency of 99mTc-RBC increased up to 93%. GIBS can be performed after 20 hours post-injection and provide accurate diagnosis of gastrointestinal bleeding. No false positive findings due to free 99mTc accumulation were observed for the four patients. CONCLUSION: The modified in vivo method with sedimentation is a simple and effective way to increase the labeling efficiency and thus the diagnosis for the detection of gastrointestinal bleeding.

Visualization of an Incidental Ectopic Gallbladder Location on 99mTc-MIBI Myocardial Perfusion Imaging With SPECT/CT.

An ectopically located gallbladder is rare and unusual. In this study, we described a case of a 52-year-old woman who underwent SPECT-myocardial perfusion imaging because of exertional dyspnea and chest tightness. The rest sinograms reveal 2 substantially increased tracer uptakes in the right chest. Subsequently, a SPECT/CT scan was performed to clarify the indeterminate findings on the SPECT-myocardial perfusion imaging. The coregistered SPECT/CT images depict intense focal activity in the right chest, which corresponds to the gallbladder on the CT scan, thus explaining the peculiar ectopic gallbladder finding.

Optimization of imaging parameters for SPECT scans of [99mTc]TRODAT-1 using Taguchi analysis.

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the basal ganglia. Single photon emission computed tomography (SPECT) scans using [99mTc]TRODAT-1 can image dopamine transporters and provide valuable diagnostic information of PD. In this study, we optimized the scanning parameters for [99mTc]TRODAT-1/SPECT using the Taguchi analysis to improve image quality. SPECT scans were performed on forty-five healthy volunteers according to an L9 orthogonal array. Three parameters were considered, including the injection activity, uptake duration, and acquisition time per projection. The signal-to-noise ratio (SNR) was calculated from the striatum/occipital activity ratio as an image quality index. Ten healthy subjects and fifteen PD patients were used to verify the optimal parameters. The estimated optimal parameters were 962 MBq for [99mTc]TRODAT-1 injection, 260 min for uptake duration, and 60 s/projection for data acquisition. The uptake duration and time per projection were the two dominant factors which had an F-value of 18.638 (38%) and 25.933 (53%), respectively. Strong cross interactions existed between the injection activity/uptake duration and injection activity/time per projection. Therefore, under the consideration of as low as reasonably achievable (ALARA) for radiation protection, we can decrease the injection activity to 740 MBq. The image quality remains almost the same for clinical applications.