Harnessing the Power of Voice: A Deep Neural Network Model for Alzheimer's Disease Detection.

Background and Purpose: Voice, reflecting cerebral functions, holds potential for analyzing and understanding brain function, especially in the context of cognitive impairment (CI) and Alzheimer's disease (AD). This study used voice data to distinguish between normal cognition and CI or Alzheimer's disease dementia (ADD). Methods: This study enrolled 3 groups of subjects: 1) 52 subjects with subjective cognitive decline; 2) 110 subjects with mild CI; and 3) 59 subjects with ADD. Voice features were extracted using Mel-frequency cepstral coefficients and Chroma. Results: A deep neural network (DNN) model showed promising performance, with an accuracy of roughly 81% in 10 trials in predicting ADD, which increased to an average value of about 82.0%±1.6% when evaluated against unseen test dataset. Conclusions: Although results did not demonstrate the level of accuracy necessary for a definitive clinical tool, they provided a compelling proof-of-concept for the potential use of voice data in cognitive status assessment. DNN algorithms using voice offer a promising approach to early detection of AD. They could improve the accuracy and accessibility of diagnosis, ultimately leading to better outcomes for patients.

Macrophage transcription factor TonEBP promotes systemic lupus erythematosus and kidney injury via damage-induced signaling pathways.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases. To explore the role of TonEBP, we examined kidney biopsy samples from patients with LN. Kidney TonEBP expression was found to be elevated in these patients compared to control patients - in both kidney cells and infiltrating immune cells. Kidney TonEBP mRNA was elevated in LN and correlated with mRNAs encoding inflammatory cytokines and the degree of proteinuria. In a pristane-induced SLE model in mice, myeloid TonEBP deficiency blocked the development of SLE and LN. In macrophages, engagement of various toll-like receptors (TLRs) that respond to damage-associated molecular patterns induced TonEBP expression via stimulation of its promoter. Intracellular signaling downstream of the TLRs was dependent on TonEBP. Therefore, TonEBP can act as a transcriptional cofactor for NF-κB, and activated mTOR-IRF3/7 via protein-protein interactions. Additionally, TonEBP-deficient macrophages displayed elevated efferocytosis and animals with myeloid deficiency of TonEBP showed reduced Th1 and Th17 differentiation, consistent with macrophages defective in TLR signaling. Thus, our data show that myeloid TonEBP may be an attractive therapeutic target for SLE and LN.

Stiffness Restricts the Stemness of the Intestinal Stem Cells and Skews Their Differentiation Toward Goblet Cells.

BACKGROUND & AIMS: Fibrosis and tissue stiffening are hallmarks of inflammatory bowel disease (IBD). We have hypothesized that the increased stiffness directly contributes to the dysregulation of the epithelial cell homeostasis in IBD. Here, we aim to determine the impact of tissue stiffening on the fate and function of the intestinal stem cells (ISCs). METHODS: We developed a long-term culture system consisting of 2.5-dimensional intestinal organoids grown on a hydrogel matrix with tunable stiffness. Single-cell RNA sequencing provided stiffness-regulated transcriptional signatures of the ISCs and their differentiated progeny. YAP-knockout and YAP-overexpression mice were used to manipulate YAP expression. In addition, we analyzed colon samples from murine colitis models and human IBD samples to assess the impact of stiffness on ISCs in vivo. RESULTS: We demonstrated that increasing the stiffness potently reduced the population of LGR5+ ISCs and KI-67+-proliferating cells. Conversely, cells expressing the stem cell marker, olfactomedin-4, became dominant in the crypt-like compartments and pervaded the villus-like regions. Concomitantly, stiffening prompted the ISCs to preferentially differentiate toward goblet cells. Mechanistically, stiffening increased the expression of cytosolic YAP, driving the extension of olfactomedin-4+ cells into the villus-like regions, while it induced the nuclear translocation of YAP, leading to preferential differentiation of ISCs toward goblet cells. Furthermore, analysis of colon samples from murine colitis models and patients with IBD demonstrated cellular and molecular remodeling reminiscent of those observed in vitro. CONCLUSIONS: Collectively, our findings highlight that matrix stiffness potently regulates the stemness of ISCs and their differentiation trajectory, supporting the hypothesis that fibrosis-induced gut stiffening plays a direct role in epithelial remodeling in IBD.

Orai1 is an Entotic Ca2+ Channel for Non-Apoptotic Cell Death, Entosis in Cancer Development.

Entosis is a non-apoptotic cell death process that forms characteristic cell-in-cell structures in cancers, killing invading cells. Intracellular Ca2+ dynamics are essential for cellular processes, including actomyosin contractility, migration, and autophagy. However, the significance of Ca2+ and Ca2+ channels participating in entosis is unclear. Here, it is shown that intracellular Ca2+ signaling regulates entosis via SEPTIN-Orai1-Ca2+ /CaM-MLCK-actomyosin axis. Intracellular Ca2+ oscillations in entotic cells show spatiotemporal variations during engulfment, mediated by Orai1 Ca2+ channels in plasma membranes. SEPTIN controlled polarized distribution of Orai1 for local MLCK activation, resulting in MLC phosphorylation and actomyosin contraction, leads to internalization of invasive cells. Ca2+ chelators and SEPTIN, Orai1, and MLCK inhibitors suppress entosis. This study identifies potential targets for treating entosis-associated tumors, showing that Orai1 is an entotic Ca2+ channel that provides essential Ca2+ signaling and sheds light on the molecular mechanism underlying entosis that involves SEPTIN filaments, Orai1, and MLCK.

Human coronavirus 3CL proteases cleave septins and disrupt Hedgehog signaling, causing ciliary dysfunction.

Coronaviruses target ciliate cells causing the loss of cilia, acute rhinorrheas, and other ciliopathies. The loss of ciliary function may help the virus infect, replicate, and spread. However, the molecular mechanisms by which coronaviruses cause ciliary defects are still unclear. Herein we demonstrate how coronavirus infection and severe acute respiratory syndrome coronavirus2 3CL protease induce cilia dysfunction by targeting a host protein septin that is required for the structure and function of cilia. Further, we demonstrate that coronaviruses and 3CL protease lead to the cleavage of several septin proteins (SEPT2, -6, and -9), producing cleaved obstructive fragments. Furthermore, ectopic expression of cleaved SEPT2 fragments shows defective ciliogenesis, disoriented septin filaments, and ablated Sonic Hedgehog (SHH) signaling in a protease activity-dependent manner. We present that the 3CLpro inhibitors are potent and prevent abnormal ciliary structures and SHH signaling. These results provide useful insights into the general mechanisms underlying ciliary defects caused by coronaviruses, which, in turn, facilitate virus spread and prove that preclinical and clinical 3CL protease inhibitors may prove useful as therapeutics for treating ciliary defects of coronaviruses.

Origami and Kirigami Structure for Impact Energy Absorption: Its Application to Drone Guards.

As the use of drones grows, so too does the demand for physical protection against drone damage resulting from collisions and falls. In addition, as the flight environment becomes more complicated, a shock absorption system is required, in which the protective structure can be deformed based on the circumstances. Here, we present an origami- and kirigami-based structure that provides protection from various directions. This research adds a deformation capacity to existing fixed-shape guards; by using shape memory alloys, the diameter and height of the protective structure are controlled. We present three protective modes (1: large diameter/low height; 2: small diameter/large height; and 3: lotus shaped) that mitigate drone falls and side collisions. From the result of the drop impact test, mode 2 showed a 78.2% reduction in the maximum impact force at side impact. We incorporated kirigami patterns into the origami structures in order to investigate the aerodynamic effects of the hollow patterns. Airflow experiments yielded a macro understanding of flow-through behaviors on each kirigami pattern. In the wind speed experiment, the change in airflow velocity induced by the penetration of the kirigami pattern was measured, and in the force measurement experiment, the air force applied to the structure was determined.

Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness.

Obesity increases asthma prevalence and severity. However, the underlying mechanisms are poorly understood, and consequently, therapeutic options for asthma patients with obesity remain limited. Here we report that cholecystokinin-a metabolic hormone best known for its role in signaling satiation and fat metabolism-is increased in the lungs of obese mice and that pharmacological blockade of cholecystokinin A receptor signaling reduces obesity-associated airway hyperresponsiveness. Activation of cholecystokinin A receptor by the hormone induces contraction of airway smooth muscle cells. In vivo, cholecystokinin level is elevated in the lungs of both genetically and diet-induced obese mice. Importantly, intranasal administration of cholecystokinin A receptor antagonists (proglumide and devazepide) suppresses the airway hyperresponsiveness in the obese mice. Together, our results reveal an unexpected role for cholecystokinin in the lung and support the repurposing of cholecystokinin A receptor antagonists as a potential therapy for asthma patients with obesity.

Phosphorylation of EIF2S1 (eukaryotic translation initiation factor 2 subunit alpha) is indispensable for nuclear translocation of TFEB and TFE3 during ER stress.

There are diverse links between macroautophagy/autophagy pathways and unfolded protein response (UPR) pathways under endoplasmic reticulum (ER) stress conditions to restore ER homeostasis. Phosphorylation of EIF2S1/eIF2α is an important mechanism that can regulate all three UPR pathways through transcriptional and translational reprogramming to maintain cellular homeostasis and overcome cellular stresses. In this study, to investigate the roles of EIF2S1 phosphorylation in regulation of autophagy during ER stress, we used EIF2S1 phosphorylation-deficient (A/A) cells in which residue 51 was mutated from serine to alanine. A/A cells exhibited defects in several steps of autophagic processes (such as autophagosome and autolysosome formation) that are regulated by the transcriptional activities of the autophagy master transcription factors TFEB and TFE3 under ER stress conditions. EIF2S1 phosphorylation was required for nuclear translocation of TFEB and TFE3 during ER stress. In addition, EIF2AK3/PERK, PPP3/calcineurin-mediated dephosphorylation of TFEB and TFE3, and YWHA/14-3-3 dissociation were required for their nuclear translocation, but were insufficient to induce their nuclear retention during ER stress. Overexpression of the activated ATF6/ATF6α form, XBP1s, and ATF4 differentially rescued defects of TFEB and TFE3 nuclear translocation in A/A cells during ER stress. Consequently, overexpression of the activated ATF6 or TFEB form more efficiently rescued autophagic defects, although XBP1s and ATF4 also displayed an ability to restore autophagy in A/A cells during ER stress. Our results suggest that EIF2S1 phosphorylation is important for autophagy and UPR pathways, to restore ER homeostasis and reveal how EIF2S1 phosphorylation connects UPR pathways to autophagy.Abbreviations: A/A: EIF2S1 phosphorylation-deficient; ACTB: actin beta; Ad-: adenovirus-; ATF6: activating transcription factor 6; ATZ: SERPINA1/α1-antitrypsin with an E342K (Z) mutation; Baf A1: bafilomycin A1; BSA: bovine serum albumin; CDK4: cyclin dependent kinase 4; CDK6: cyclin dependent kinase 6; CHX: cycloheximide; CLEAR: coordinated lysosomal expression and regulation; Co-IP: coimmunoprecipitation; CTSB: cathepsin B; CTSD: cathepsin D; CTSL: cathepsin L; DAPI: 4',6-diamidino-2-phenylindole dihydrochloride; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; DTT: dithiothreitol; EBSS: Earle's Balanced Salt Solution; EGFP: enhanced green fluorescent protein; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 subunit alpha; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERAD: endoplasmic reticulum-associated degradation; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FBS: fetal bovine serum; gRNA: guide RNA; GSK3B/GSK3ß: glycogen synthase kinase 3 beta; HA: hemagglutinin; Hep: immortalized hepatocyte; IF: immunofluorescence; IRES: internal ribosome entry site; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LMB: leptomycin B; LPS: lipopolysaccharide; MAP1LC3A/B/LC3A/B: microtubule associated protein 1 light chain 3 alpha/beta; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEFs: mouse embryonic fibroblasts; MFI: mean fluorescence intensity; MTORC1: mechanistic target of rapamycin kinase complex 1; NES: nuclear export signal; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; OE: overexpression; PBS: phosphate-buffered saline; PLA: proximity ligation assay; PPP3/calcineurin: protein phosphatase 3; PTM: post-translational modification; SDS: sodium dodecyl sulfate; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SEM: standard error of the mean; TEM: transmission electron microscopy; TFE3: transcription factor E3; TFEB: transcription factor EB; TFs: transcription factors; Tg: thapsigargin; Tm: tunicamycin; UPR: unfolded protein response; WB: western blot; WT: wild-type; Xbp1s: spliced Xbp1; XPO1/CRM1: exportin 1.

Strengthening deep-learning models for intracranial hemorrhage detection: strongly annotated computed tomography images and model ensembles.

Background and purpose: Multiple attempts at intracranial hemorrhage (ICH) detection using deep-learning techniques have been plagued by clinical failures. We aimed to compare the performance of a deep-learning algorithm for ICH detection trained on strongly and weakly annotated datasets, and to assess whether a weighted ensemble model that integrates separate models trained using datasets with different ICH improves performance. Methods: We used brain CT scans from the Radiological Society of North America (27,861 CT scans, 3,528 ICHs) and AI-Hub (53,045 CT scans, 7,013 ICHs) for training. DenseNet121, InceptionResNetV2, MobileNetV2, and VGG19 were trained on strongly and weakly annotated datasets and compared using independent external test datasets. We then developed a weighted ensemble model combining separate models trained on all ICH, subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), and small-lesion ICH cases. The final weighted ensemble model was compared to four well-known deep-learning models. After external testing, six neurologists reviewed 91 ICH cases difficult for AI and humans. Results: InceptionResNetV2, MobileNetV2, and VGG19 models outperformed when trained on strongly annotated datasets. A weighted ensemble model combining models trained on SDH, SAH, and small-lesion ICH had a higher AUC, compared with a model trained on all ICH cases only. This model outperformed four deep-learning models (AUC [95% C.I.]: Ensemble model, 0.953[0.938-0.965]; InceptionResNetV2, 0.852[0.828-0.873]; DenseNet121, 0.875[0.852-0.895]; VGG19, 0.796[0.770-0.821]; MobileNetV2, 0.650[0.620-0.680]; p < 0.0001). In addition, the case review showed that a better understanding and management of difficult cases may facilitate clinical use of ICH detection algorithms. Conclusion: We propose a weighted ensemble model for ICH detection, trained on large-scale, strongly annotated CT scans, as no model can capture all aspects of complex tasks.

Electrochemical Gene Amplification Signal Detection of Disposable Biochips Using Electrodes.

Real-time Polymerase Chain Reaction (RT-PCR), a molecular diagnostic technology, is spotlighted as one of the quickest and fastest diagnostic methods for the actual coronavirus (SARS-CoV-2). However, the fluorescent label-based technology of the RT-PCR technique requires expensive equipment and a sample pretreatment process for analysis. Therefore, this paper proposes a biochip based on Electrochemical Impedance Spectroscopy (EIS). In this paper, it was possible to see the change according to the concentration by measuring the impedance with a chip made of two electrodes with different shapes of sample DNA.

Compact Camera Fluorescence Detector for Parallel-Light Lens-Based Real-Time PCR System.

The polymerase chain reaction is an important technique in biological research. However, it is time consuming and has a number of disadvantages. Therefore, real-time PCR technology that can be used in real-time monitoring has emerged, and many studies are being conducted regarding its use. Real-time PCR requires many optical components and imaging devices such as expensive, high-performance cameras. Therefore, its cost and assembly process are limitations to its use. Currently, due to the development of smart camera devices, small, inexpensive cameras and various lenses are being developed. In this paper, we present a Compact Camera Fluorescence Detector for use in parallel-light lens-based real-time PCR devices. The proposed system has a simple optical structure, the system cost can be reduced, and the size can be miniaturized. This system only incorporates Fresnel lenses without additional optics in order for the same field of view to be achieved for 25 tubes. In the center of the Fresnel lens, one LED and a complementary metal-oxide semiconductor camera were placed in directions that were as similar as possible. In addition, to achieve the accurate analysis of the results, image processing was used to correct them. As a result of an experiment using a reference fluorescent substance and double-distilled water, it was confirmed that stable fluorescence detection was possible.

Effects of a Fluoroscopy Agent on Radio Opacity and Steering Performance of Pressure-Driven Steerable Micro Guidewire.

This paper presents experimental results of effects of a fluoroscopy agent on the radio opacity and steering performance of the steerable micro guidewire. The guidewire is driven by internal pressure, and made of the silicone polymer mixed with the barium sulfate, BaSO4, masterbatch. Steerable distal tips with different BaSO4 densities up to 30 % are fabricated. The radio opacity is measured by comparing CT (computed tomography) numbers of the steerable distal tips. The steering performance is measured by the bending angle at particular internal pressures while being bent up to 180 0. Experiment results show that the radio opacity improves while the bending stiffness decreases as the concentration of the barium sulfate increases.

An analysis of emotions and the prominence of positivity in #BlackLivesMatter tweets.

Emotions are a central driving force of activism; they motivate participation in movements and encourage sustained involvement. We use natural language processing techniques to analyze emotions expressed or solicited in tweets about 2020 Black Lives Matter protests. Traditional off-the-shelf emotion analysis tools often fail to generalize to new datasets and are unable to adapt to how social movements can raise new ideas and perspectives in short time spans. Instead, we use a few-shot domain adaptation approach for measuring emotions perceived in this specific domain: tweets about protests in May 2020 following the death of George Floyd. While our analysis identifies high levels of expressed anger and disgust across overall posts, it additionally reveals the prominence of positive emotions (encompassing, e.g., pride, hope, and optimism), which are more prevalent in tweets with explicit pro-BlackLivesMatter hashtags and correlated with on the ground protests. The prevalence of positivity contradicts stereotypical portrayals of protesters as primarily perpetuating anger and outrage. Our work offers data, analyses, and methods to support investigations of online activism and the role of emotions in social movements.

Beneficial effects of gamma-irradiation of quinoa seeds on germination and growth.

Quinoa is one of the crops well-adapted to high altitude regions that can grow relatively well under drought, humid, and high UV radiation conditions. This study was performed to investigate the effects of gamma-radiation on quinoa. Seeds were treated with various doses of 50 Gy, 100 Gy, 200 Gy, 300 Gy, 400 Gy, 600 Gy, 800 Gy, and 1000 Gy. We investigated germination, as well as plant height, chlorophyll content, and normalized difference vegetation index (NDVI) at 0, 30, 44, 58, and 88 days after transplanting (DAT) and panicle weight at 88 DAT. The plants grown from the seeds treated at radiation doses greater than 200 Gy showed reduced values in most growth and physiological characteristics. The germination rate and germination speed were higher in the 50 Gy-treated seeds than in 0 Gy-treated (control) seeds. Plant height and panicle weight were highest in the plants from 50 Gy-treated seeds. Chlorophyll content was higher in all treated samples than in the controls. NDVI value showed the highest value in 0 Gy controls and plants treated with 50 Gy. The antioxidant activity was also higher in the plants from the seeds treated with 50 Gy and 100 Gy, showing a steady increase as the radiation dose increased even at 200 Gy. The plants from seeds treated with 0 Gy showed higher expression of proteins related to photorespiration and tubulin chains. The plants from seeds treated with 50 Gy induced more stress-responsive proteins.

Association of Depression With Susceptibility and Adaptation to Seasickness in the Military Seafarers.

BACKGROUND: Although depression and motion sickness are prevalent in military personnel and seafarers, the association between depression and seasickness has been not yet elucidated. We aimed to evaluate the relationship of depression with initial susceptibility and adaptation to seasickness amongst military seafarers. METHODS: This retrospective cohort enrolled Navy seafarers who started seafaring between 2017 and 2019. Three groups were established according to the Beck Depression Inventory (BDI) score: no depression (BDI score of 0), minimal depression (BDI score 1-9), and mild-to-moderate depression (BDI score 10-29). The occurrence of seasickness requiring treatment was observed as the prescription of medication for the first 30 distant seafaring days. Considering adjustment period, the two different outcomes were defined. The susceptibility to seasickness was evaluated via at least one day suffered from seasickness requiring treatment during the early period (the first 5 seafaring days), and adaptation ability to seasickness was defined by more than 10% of the ratio, calculated days suffered from seasickness requiring treatment/days of seafaring during the late period (the 6-30th seafaring days). Binary logistic regression was further evaluated to estimate the odds of BDI groups and BDI score adjusted for age and workplace whether outside visual perception was possible. RESULTS: Among the 185 recruits, 179 participants (97%) sailed for more than 5 days were included in the study. Of the participants, 36% was susceptible to seasickness in the early and 17% was poorly adapted to seasickness in the late period. Multivariable model revealed that mild-to-moderate depression had elevated risk of poor adaptation (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.31-16.98) whereas the results were not statistically significant for susceptibility to seasickness in the early period BDI score was independently associated with increased odds of poor adaptation (OR, 1.10; 95% CI, 1.04-1.18). CONCLUSION: The present study suggests that depression is associated with poor adaptation to seasickness in Navy seafarers. Depression screening tool might be helpful for providing preventable strategies for population at risk.

Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics.

The ability of a cell to regulate its mechanical properties is central to its function. Emerging evidence suggests that interactions between the cell nucleus and cytoskeleton influence cell mechanics through poorly understood mechanisms. Here we conduct quantitative confocal imaging to show that the loss of A-type lamins tends to increase nuclear and cellular volume while the loss of B-type lamins behaves in the opposite manner. We use fluorescence recovery after photobleaching, atomic force microscopy, optical tweezer microrheology, and traction force microscopy to demonstrate that A-type lamins engage with both F-actin and vimentin intermediate filaments (VIFs) through the linker of nucleoskeleton and cytoskeleton (LINC) complexes to modulate cortical and cytoplasmic stiffness as well as cellular contractility in mouse embryonic fibroblasts (MEFs). In contrast, we show that B-type lamins predominantly interact with VIFs through LINC complexes to regulate cytoplasmic stiffness and contractility. We then propose a physical model mediated by the lamin­LINC complex that explains these distinct mechanical phenotypes (mechanophenotypes). To verify this model, we use dominant negative constructs and RNA interference to disrupt the LINC complexes that facilitate the interaction of the nucleus with the F-actin and VIF cytoskeletons and show that the loss of these elements results in mechanophenotypes like those observed in MEFs that lack A- or B-type lamin isoforms. Finally, we demonstrate that the loss of each lamin isoform softens the cell nucleus and enhances constricted cell migration but in turn increases migration-induced DNA damage. Together, our findings uncover distinctive roles for each of the four major lamin isoforms in maintaining nucleocytoskeletal interactions and cellular mechanics.

Metastasis enhancer PGRMC1 boosts store-operated Ca2+ entry by uncoiling Ca2+ sensor STIM1 for focal adhesion turnover and actomyosin formation.

Progesterone receptor membrane component 1 (PGRMC1), the overexpression of which reduces survivability of cancer patients, is essential for cell migration and metastasis. However, the intracellular signaling pathways involved are largely unknown. Here, we report that PGRMC1 promotes store-operated Ca2+ entry (SOCE) as a functional interactor of stromal interaction molecule 1 (STIM1). PGRMC1 was repeatedly detected as an interactor of STIM1-Orai1 complex via complementation-dependent in situ labeling. Genetic depletion of PGRMC1 decreased SOCE and impaired activation of the nuclear factor of the activated T cell (NFAT) pathway. Mechanistically, PGRMC1 directly bound to the coiled-coil domain of STIM1, promoting STIM1 conformational switch. In breast cancer cells, PGRMC1 depletion reduced epidermal growth factor (EGF)-induced SOCE and disrupted focal adhesion turnover and actomyosin formation. These findings identify PGRMC1 as an essential regulator of Ca2+ signaling in breast cancer cells, providing a target for treating cancer metastasis and an insight for dissecting various PGRMC1/SOCE-induced biological processes.

Cost-Effective Multiplex Fluorescence Detection System for PCR Chip.

The lack of portability and high cost of multiplex real-time PCR systems limits the device to be used in POC. To overcome this issue, this paper proposes a compact and cost-effective fluorescence detection system that can be integrated to a multiplex real-time PCR equipment. An open platform camera with embedded lens was used instead of photodiodes or an industrial camera. A compact filter wheel using a sliding tape is integrated, and the excitation LEDs are fixed at a 45° angle near the PCR chip, eliminating the need of additional filter wheels. The results show precise positioning of the filter wheel with an error less than 20 µm. Fluorescence detection results using a reference dye and standard DNA amplification showed comparable performance to that of the photodiode system.

Cloud-Based Software Architecture for Fully Automated Point-of-Care Molecular Diagnostic Device.

This paper proposes a cloud-based software architecture for fully automated point-of-care molecular diagnostic devices. The target system operates a cartridge consisting of an extraction body for DNA extraction and a PCR chip for amplification and fluorescence detection. To facilitate control and monitoring via the cloud, a socket server was employed for fundamental molecular diagnostic functions such as DNA extraction, amplification, and fluorescence detection. The user interface for experimental control and monitoring was constructed with the RESTful application programming interface, allowing access from the terminal device, edge, and cloud. Furthermore, it can also be accessed through any web-based user interface on smart computing devices such as smart phones or tablets. An emulator with the proposed software architecture was fabricated to validate successful operation.