Copper-Based Two-Dimensional Metal-Organic Frameworks for Fenton-like Photocatalytic Degradation of Methylene Blue under UV and Sunlight Irradiation.

To efficiently degrade organic pollutants, photocatalysts must be effective under both ultraviolet (UV) radiation and sunlight. We synthesized a series of new metal-organic frameworks by using mild hydrothermal conditions. These frameworks incorporate three distinct bipyridyl ligands: pyrazine (pyr), 4,4'-bipyridine (bpy), and 1,2-bis(4-pyridyl)ethane (bpe). The resulting compounds are denoted as [Cu(pyz)(H2O)2MF6], [Cu(bpy)2(H2O)2]·MF6, and [Cu(bpe)2(H2O)2]·MF6·H2O [M = Zr (1, 3, and 5) and Hf (2, 4, and 6)]. All six compounds exhibited a two-dimensional crystal structure comprising infinitely nonintersecting linear chains. Compound 3 achieved 100% degradation of methylene blue (MB) after 8 min under UV irradiation and 100 min under natural sunlight in the presence of H2O2 as the electron acceptor. For compound 5, 100% MB degradation was achieved after 120 min under sunlight and 10 min under UV light. Moreover, reactive radical tests revealed that the dominant species involved in photocatalytic degradation are hydroxyl (•OH), superoxide radicals (•O2-), and photogenerated holes (h+). The photodegradation process followed pseudo-first-order kinetics, with photodegradation rate constants of 0.362 min-1 (0.039 min-1) for 3 and 0.316 min-1 (0.033 min-1) for 5 under UV (sunlight) irradiation. The developed photocatalysts with excellent activity and good recyclability are promising green catalysts for degrading organic pollutants during environmental decontamination.

Anticancer Effect of Hemin through ANO1 Inhibition in Human Prostate Cancer Cells.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC50 value of 0.45 µM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 µM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.

TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53.

T-LAK cell originated protein kinase (TOPK) has been shown to regulate proliferation, invasion or migration of various cancer cells. However, the role of TOPK in follicle environments remains unknown. Here we reveal that TOPK inhibits TNF-α-induced human granulosa COV434 cell apoptosis. The expression of TOPK were increased in COV434 cells in response to TNF-α. TOPK inhibition also decreased TNF-α-induced SIRT1 expression but promoted TNF-α-induced p53 acetylation and expression of PUMA or NOXA. Accordingly, TOPK inhibition attenuated TNF-α-mediated SIRT1 transcriptional activity. In addition, SIRT1 inhibition augmented acetylation of p53 or expression of PUMA and NOXA in response to TNF-α, leading to COV434 cell apoptosis. We conclude that TOPK suppresses TNF-α-induced COV434 granulosa cell apoptosis via regulation of p53/SIRT1 axis, suggesting a potential role of TOPK in regulation of ovarian follicular development.

Pharmaceutical and Immunological Evaluation of Cholera Toxin A1 Subunit as an Adjuvant of Hepatitis B Vaccine Microneedles.

PURPOSE: For successful delivery of a solid vaccine formulation into the skin using microneedles, the solubility of an adjuvant should be considered because the decrease in the dissolution rate by the addition of adjuvant decreases the delivery efficiency of the vaccine. METHODS: In this study, cholera toxin A subunit 1 (CTA1) was examined as an adjuvant to Hepatitis B vaccine (HBV) microneedles because of its good water solubility, improved safety, and positive effect as shown in intramuscular administration of a liquid vaccine. RESULTS: All solid formulations with CTA 1 dissolved in in vivo mouse skin within 30 min, and they were successfully delivered into the skin. In experiments with mice, the addition of CTA1 led to improved IgG immune response compared to the use of an aluminum hydroxide-based formulation and intramuscular administration of HBV. In addition, CTA1 induced CD8 + T cell response as much as in which the aluminum hydroxide-based formulation induced. CONCLUSIONS: CTA1 is an adjuvant that satisfies both the delivery efficiency and the immunological characteristics required for vaccine microneedles. CTA1 will be used as a potential adjuvant through vaccine microneedles.

Unraveling the Structural Instability of Li(Ni0.80 Co0.15 Al0.05 )O2 as a Cathode Material Due to Operating a Li-ion Battery.

The change of the crystal structure for Li(Ni0.80 Co0.15 Al0.05 )O2 as a cathode material in a Li-ion battery is traced. During charging and discharging, the crystallographic change of Lix (Ni0.80 Co0.15 Al0.05 )O2 (x ≈ 1.0-0.25) is confirmed with in situ X-ray diffraction, an electrochemical measurement, and the density functional theory calculation. Li atoms after cycling do not completely return to the initial state and defects in the Li-layer generate about 5%. The effect of defects in the Li-layer reveals the transformation of crystal structure and the change of lattice constants. Upon increasing the temperature, the instability of Li0.95 (Ni0.80 Co0.15 Al0.05 )O2 is clearly shown as the movement of transition metals using X-ray and neutron diffraction. The crystallographic values dramatically change upon increasing from 373 to 423 K, but linearly vary upon decreasing temperature. Furthermore, the result of the calculation demonstrates that the possible atom for mixing is Ni. The evolution of magnetic properties explicitly certifies the atomic movement that gives rise to a spin-glass state through the induction of ferromagnetism. In conclusion, defects are created in crystal structure during operation of the Li-ion battery and generate structural instability. The results provide the cause and mechanism of the degradation of cathode material in a Li-ion battery.

The Relationship between the Drug Delivery Properties of a Formulation of Teriparatide Microneedles and the Pharmacokinetic Evaluation of Teriparatide Administration in Rats.

PURPOSE: Teriparatide is an effective drug for the treatment of osteoporosis. This study examines the relationship between the drug delivery properties of the solid formulation with teriparatide and the pharmacokinetic properties of teriparatide in vivo. METHODS: Teriparatide microneedles with different dissolution rates were prepared using sucrose and carboxymethylcellulose (CMC). There were three aspects of this study: (1) The dissolution rate of teriparatide from both formulations (sucrose and CMC) was measured in vitro. (2) After administration into porcine skin ex vivo, the diffusion rate of FITC-dextran was observed using a confocal microscope. (3) Pharmacokinetic studies were performed in rats and pharmacokinetic data compared with the release rate and the diffusion pattern. RESULTS: In the in vitro dissolution experiment, 80% of teriparatide was released within 30 min from the CMC MNs, whereas 80% of teriparatide was released within 10 min from the sucrose MNs. After 30 min, the fluorescence intensity on the surface of the MNs was 40% of the initial intensity for sucrose MNs and 90% for CMC MNs. In the pharmacokinetic study, the Cmax values of the CMC and sucrose MNs were 868 pg/mL and 6809 pg/mL, respectively, and the AUClast values were 6771 pg*hr/mL for the CMC MNs and 17,171 pg*hr/mL for the sucrose MNs. CONCLUSIONS: When teriparatide is delivered into the skin using microneedles, the release rate from the solid formulation determines the drug's pharmacokinetic properties. The diffusion pattern of fluorescence into the skin can be used to anticipate the pharmacokinetic properties of the drug.

TOPK mediates hypoxia-induced epithelial-mesenchymal transition and the invasion of nonsmall-cell lung cancer cells via the HIF-1α/snail axis.

Hypoxia has been suggested to induce epithelial-mesenchymal transition (EMT) in various cancer types via the transcription factor hypoxia-inducible factor-1 alpha (HIF-1α). Here, we demonstrated that TOPK upregulates EMT and the invasion of H460 nonsmall-cell lung cancer cells through the induction of the HIF-1α/Snail axis and hypoxic signaling. The expression of endogenous TOPK, phosphorylated TOPK, HIF-1α and Snail was significantly increased upon hypoxia exposure, but TOPK depletion markedly abrogated the induced mRNA and protein levels of HIF-1α and Snail. Interestingly, TOPK knockdown restored the hypoxia-induced suppression of E-cadherin and diminished hypoxia-induced N-cadherin expression. In addition, Snail depletion suppressed hypoxia-induced N-cadherin expression, which was attenuated by TOPK knockdown. Moreover, knockdown of Snail decreased hypoxia-induced nonsmall-cell lung cancer cell migration and invasion, which were suppressed by TOPK depletion. In summary, we conclude that TOPK positively regulates HIF-1α expression through hypoxia signaling and thereby promotes Snail expression, leading to EMT and the invasion of nonsmall-cell lung cancer cells. These findings suggest that TOPK plays a critical role as a novel mediator of hypoxia signaling that regulates nonsmall-cell lung cancer development.

Epicutaneous Allergen Administration with Microneedles as a Novel Method of Immunotherapy for House Dust Mite (HDM) Allergic Rhinitis.

PURPOSE: Epicutaneous immunotherapy (EPIT) is being studied as a method for treating allergic rhinitis because of skin immunology, user convenience and enhanced patient compliance. However, the use of EPIT is limited because of the very low skin permeability of the allergen. In this study, the limitations of EPIT were overcome by using sophisticated delivery with microneedles. The immunological efficacy of this method was studied in a murine model of house dust mite (HDM) allergic rhinitis. METHODS: The length of the microneedles was 400 µm, and the coating formulation containing HDM was locally distributed near the end of the microneedle tips. The change of distribution of FITC-dextran in porcine skin in vitro was observed over time using a confocal microscope. The effect of immunotherapy in the allergic rhinitis model, sensitized by HDM-coated microneedles (HDM MNs), was observed according to the amount of HDM applied. RESULTS: The microneedles delivered the coating formulation with precision into the porcine skin layer, and the coated formulation on the microneedles was all dissolved in the porcine skin in vitro within 20 min of administration and then gradually diffused into the skin layer. When HDM MNs were administered to mice, a 0.1-µg dose of HDM provided the most effective immunization, and improved efficacy was shown between 0.1- and 0.5- µg doses of HDM. CONCLUSIONS: Effective immunotherapy can be achieved by precision delivery of the allergen into the skin layer, and microneedles can provide effective immunological therapy by delivering the appropriate amount of allergen.

KIn0.33IIITe0.67VITe2IVO7: Zirconolite-like Mixed-Valent Metal Oxide with a 3D Framework.

We provide the material synthesis method, crystal structure information, and characterization of a novel mixed-valent metal oxide KIn0.33IIITe0.67VITe2IVO7, closely related to zirconolite (CaZrTi2O7), a radioactive waste immobilized material, having a 3D framework. The reported metal oxide containing an alkali-metal cation (K+), main-group cation (In3+), tellurate, and tellurite has been synthesized as both single crystals and a pure polycrystalline phase through a hydrothermal synthesis method. Single-crystal X-ray diffraction indicates that KIn0.33Te2.67O7 crystallizing in the orthorhombic space group Cmcm (No. 63) reveals a 3D framework structure with a 1D channel consisting of Te/InO6 octahedra and TeO4 polyhedra. An interesting transition reaction from KIn0.33Te2.67O7 to KIn(TeO3)2 under hydrothermal conditions at 230 °C is discussed.

TOPK promotes epithelial-mesenchymal transition and invasion of breast cancer cells through upregulation of TBX3 in TGF-ß1/Smad signaling.

TOPK has been suggested to contribute to invasion of lung, prostate, gastric, pancreatic or breast cancer cells. However, how TOPK mediates TGF-ß1/Smad signaling leading to epithelial-mesenchymal transition (EMT) and invasion of breast cancer cells remains unknown. Here we report that TOPK upregulates T-box transcription factor TBX3 to enhance TGF-ß1-induced EMT and invasion of MDA-MB-231 breast cancer cells. Expression of endogenous TOPK was promoted by TGF-ß1 treatment of MDA-MB-231 cells time-dependently. In addition, knockdown of TOPK attenuated TGF-ß1-induced phosphorylation or transcriptional activity of Smad3. Meanwhile, levels of both mRNA and protein of TBX3 induced by TGF-ß1 were abolished by TOPK depletion. Also, knockdown of TBX3 inhibited TGF-ß1 induction of EMT-related genes Snail, Slug or Fibronectin. Furthermore, ablation of TOPK or TBX3 suppressed TGF-ß1-induced MDA-MB-231 cell invasion. Collectively, we conclude that TOPK positively regulates TBX3 in TGF-ß1/Smad signaling pathway, thereby enhancing EMT and invasion of breast cancer cells, implying a mechanistic role of TOPK in TGF-ß1/Smad signaling.

Activation of NF-κB by TOPK upregulates Snail/Slug expression in TGF-ß1 signaling to induce epithelial-mesenchymal transition and invasion of breast cancer cells.

TGF-ß1 is known to induce epithelial-mesenchymal transition (EMT), which is a prerequisite for cancer cell invasion. Here we reveal that TOPK upregulates EMT and invasion of human breast cancer MDA-MB-231 or Hs578T cells via NF-κB-dependent Snail/Slug in TGF-ß1 signaling. Endogenous TOPK expression was significantly increased in response to TGF-ß1 and TOPK knockdown mitigated TGF-ß1-induced breast cancer cell invasion. Interestingly, TOPK knockdown restored TGF-ß1 suppression of E-cadherin expression and markedly reduced N-cadherin induced by TGF-ß1. Also, NF-κB activity or expression of EMT markers Snail and Slug induced by TGF-ß1 was decreased by TOPK knockdown. Meanwhile, knockdown of Snail or TOPK attenuated TGF-ß1-induced breast cancer cell invasion. Taken, we conclude that TOPK mediates TGF-ß1-induced EMT and invasion in breast cancer cells via NF-κB/Snail signaling, suggesting novel role of TOPK as therapeutic target in TGF-ß1-mediated breast cancer development.

Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release.

AIMS: Crosslinked hyaluronic acid (X-linked HA) is not suitable for making microneedles because of the low fluidity of X-linked HA hydrogel. Microneedles were fabricated using X-linked HA nanoparticles (X-linked HA-NPs) to utilize the sustained drug delivery capability of X-linked HA-NPs and to obtain the processability advantages of X-linked HA. METHOD: The puncture performance of a microneedle array patch (MAP) made of crosslinked hyaluronic acid nanoparticles (X-linked HA-NP-MAP) was evaluated by insertion in vitro into porcine skin. After a predetermined attachment time, the remaining height of the X-linked HA-NP-MAP was measured to determine the dissolution rate. X-linked HA-NP-MAP and free HA-MAP containing Rhodamine B isothiocyanate-dextran were administered into the back skin of mice, and the relative fluorescent intensity in the back skin was measured over time. RESULTS: The puncture performance of the X-linked HA-NP-MAP was over 90%. The diameter of redispersed X-linked HA-NPs was same as that of the premolded X-linked HA-NPs. The dissolution rate was not different from that of free HA-MAP. In an in vivo experiment, X-linked HA-NP-MAP was administered into the mouse's back skin successfully and the relative fluorescent intensity of X-linked HA-NP-MAP lasted longer than that of HA-MAP. CONCLUSION: X-linked HA-NPs provide the biocompatibility, the processability of micromolding, sustained drug release, successful penetration into the skin, and relatively short insertion time for full disintegration of NPs in the skin. X-linked HA-NP-MAP can be used for various applications that require several days of sustained drug release.

Effects of early detection of peritoneal catheter migration on clinical outcomes: 15-years experiences from a single centre.

AIM: Catheter migration is an important cause of catheter malfunction in peritoneal dialysis (PD). The purpose of this study was to investigate the effect of early detection of catheter migration on clinical outcomes. METHODS: A retrospective review of 135 consecutive patients initiating PD immediately following catheter insertion from 2002 to 2017 was undertaken. In order to detect catheter migration without malfunction early, serial abdominal-pelvic radiographic examinations were performed according to a predefined protocol. Conservative management with rigorous catharsis was undertaken to correct catheter migration. A Kaplan-Meier method was used to calculate survival rate. RESULTS: Mean follow-up period was 42.8 ± 34.9 months. Catheter migration occurred in 62.4%. Among them, 85.9% occurred within the first 2 weeks after catheter insertion. There were no significant associations between catheter migration and variables such as gender, obesity, DM and type of catheter. Success rate of conservative management with rigorous catharsis was 91.1%. Catheter survival at 1 and 5 years were 91.5% and 64.6% in the migration group and 81.2% and 69.9% in the non-migration group, respectively (Log-rank test, P = 0.915). Patient survival at 1 and 5 years were 96.8% and 85.8% in the migration group and 91.9% and 82.3% in the non-migration group, respectively (P = 0.792). CONCLUSION: Early detection of PD catheter migration allowed the migrated tip to be easily corrected with conservative management. Once the migrated catheter tip was restored, catheter migration itself did not affect catheter survival. These findings suggest that early detection and correction of catheter migration is important for improving clinical outcomes.

Development of Botulinum Toxin A-Coated Microneedles for Treating Palmar Hyperhidrosis.

Hyperhidrosis is a disorder that is characterized by the production of excess amounts of sweat. The botulinum neurotoxin A (BoNT/A) has been used to treat hyperhidrosis through multiple intradermal injections at the site of the condition. However, because of BoNT/A toxicity, it is important to precisely deliver the proper dose of the toxin to the target site. In addition, the use of a conventional hypodermic needle for multiple injections in the palm makes the approach undesirable and painful. Here, we designed a BoNT/A-coated microneedle (BoNT-MN) array and tested its efficacy as a substitute pain-free method to treat hyperhidrosis. BoNT-MNs were prepared by coating polylactic acid microneedles with a BoNT/A formulation and were found to successfully penetrate into a thick skin in vitro. The coating formulations were then tested for their stability at 4, 25, and 37 °C for 24 h. BoNT-MNs were found to be much more stable than BoNT/A in a liquid state. Additionally, we carried out in vivo experiments by treating the right paws of mice with BoNT-MNs and found that the treatment induced a significant reduction in the sweating response in the mouse foot pad. Thus, BoNT/A treatment using microneedles is beneficial and may be used as a more efficient and less painful approach to treat hyperhidrosis.

Administration of a Sol-Gel Formulation of Phenylephrine Using Low-Temperature Hollow Microneedle for Treatment of Intermittent Fecal Incontinence.

PURPOSE: A low temperature hollow microneedle system was devised to deliver sol-gel transition formulation near the surface of the skin for extended release and local delivery of drug by a non-invasive method. This new system can improve treatment of intermittent fecal incontinence. METHOD: The low-temperature system was integrated with a hollow microneedle to maintain the low temperature of the sol formulation. Various sol-gel formulations using Pluronic F-127 (PF-127) and Hydroxy-propyl-methyl-cellulose (HPMC) were prepared, and their gelation temperature, flow property, and diffusion retardation were observed. Resting anal sphincter pressure in response to a phenylephrine (PE) sol-gel formulation was measured using an air-charged catheter. The biocompatibility of the sol-gel PE formulation was evaluated by observing the immunological response. RESULTS: When the PF-127 25%, HPMC 1% and PE formulation (PF25-HPMC1-PE) was injected through the peri-anal skin of the rat in vivo, the highest pressure on the anal sphincter muscle occurred at 6-8 h and anal pressure increased and lasted twice as long as with the phosphate-buffered saline (PBS)-PE formulation. There was no significant difference in the number of mast cells after administration into the rat in vivo between the PF25-HPMC1-PE formulation and the PBS-PE formulation. CONCLUSION: The combination of a low-pain hollow microneedle system and an injectable sol-gel formulation improved the efficacy of treatment of intermittent fecal incontinence. A low-temperature hollow microneedle system using a sol-gel formulation has many applications in medical treatments that require depot effect, local targeting, and pain control.

Bleomycin-Coated Microneedles for Treatment of Warts.

PURPOSE: Bleomycin-coated microneedles were devised for delivery of bleomycin into the sub-epidermal skin layer for the treatment of warts in order to provide patient convenience and reduce patient pain and fear. METHOD: Poly-lactic-acid (L-PLA) microneedles were fabricated by a molding process and then the tips were partially coated using a dip-coating method based on a microstructure well. The mechanical strength of the pre-coated polymer microneedles was observed by inserting them in porcine foot and back skin. The holes were stained with trypan blue and the mechanical failure of the microneedles was investigated using a scanning electron microscope (SEM). The initial distribution of a model drug using microneedles was compared with distribution by intralesional injection. The amount of drug leaked below the skin using microneedles was measured and compared with that leaked by intralesional injection. The pharmacokinetic properties of bleomycin-coated microneedles were studied. The bleomycin remaining on the coated microneedles after the in vivo pharmacokinetic study was measured. RESULTS: Bleomycin was successfully coated on the tips of L-PLA microneedles. More than 80% of the bleomycin dissolved into the skin in vitro within 15 min. L-PLA microneedles possessed sufficient mechanical strength to penetrate skin with a thick stratum corneum. Compared to intralesional injection, tip-coated microneedles were more effective in distributing a drug into the sub-epidermal skin layer. A pharmacokinetic study of bleomycin-coated microneedles showed 50 min of Tmax. CONCLUSIONS: Bleomycin-coated microneedles appeared to be a convenient and painless alternative to conventional intralesional injection of bleomycin. The microneedles delivered bleomycin into the targeted dermal layer regardless of body site. Bleomycin-coated microneedles therefore provide a suitable method for the treatment of warts.

Phosphorylation of IκBα at serine 32 by T-lymphokine-activated killer cell-originated protein kinase is essential for chemoresistance against doxorubicin in cervical cancer cells.

T-lymphokine-activated killer cell-originated protein kinase (TOPK) is known to be up-regulated in cancer cells and appears to contribute to cancer cell proliferation and survival. However, the molecular mechanism by which TOPK regulates cancer cell survival still remains elusive. Here we show that TOPK directly interacted with and phosphorylated IκBα at Ser-32, leading to p65 nuclear translocation and NF-κB activation. We also revealed that doxorubicin promoted the interaction between nonphosphorylated or phosphorylated TOPK and IκBα and that TOPK-mediated IκBα phosphorylation was enhanced in response to doxorubicin. Also, exogenously overexpressed TOPK augmented transcriptional activity driven by either NF-κB or inhibitor of apoptosis protein 2 (cIAP2) promoters. On the other hand, NF-κB activity including IκBα phosphorylation and p65 nuclear translocation, as well as cIAP2 gene expression, was markedly diminished in TOPK knockdown HeLa cervical cancer cells. Moreover, doxorubicin-mediated apoptosis was noticeably increased in TOPK knockdown HeLa cells, compared with control cells, which resulted from caspase-dependent signaling pathways. These results demonstrate that TOPK is a molecular target of doxorubicin and mediates doxorubicin chemoresistance of HeLa cells, suggesting a novel mechanism for TOPK barrier of doxorubicin-mediated cervical cancer cell apoptosis.

Diagnostic and Management Challenges of Esophageal Rupture with Concomitant Cervical Abscess in Chronic High Cervical Tetraplegia.

A 65-year-old with a history of spinal cord injury and previous cervical surgery presented with persistent fever despite antibiotic treatment. MRI scans revealed an abscess in the neck extending from C3 to C6, with associated osteomyelitis. After an initial discharge following antibiotic therapy, the patient was readmitted due to recurrent systemic infection symptoms and another abscess. A subsequent endoscopy showed esophageal rupture with protruding cervical fusion metal. Due to operative risks, a percutaneous endoscopic gastrostomy was performed without further infection recurrence. The absence of typical imaging signs of esophageal rupture made diagnosis difficult. The infection spread through the cervical fascia from superficial to deep cervical areas. Esophageal rupture, a rare complication of cervical surgery, presents with varying symptoms depending on its location and was particularly challenging to diagnose in this patient due to high cervical tetraplegia, which masked typical pain responses. Therefore, this case highlights the need to consider esophageal rupture in differential diagnoses for chronic ACDF patients, even when typical symptoms are absent.

Deep Learning-Based Real-Time Organ Localization and Transit Time Estimation in Wireless Capsule Endoscopy.

BACKGROUND: Wireless capsule endoscopy (WCE) has significantly advanced the diagnosis of gastrointestinal (GI) diseases by allowing for the non-invasive visualization of the entire small intestine. However, machine learning-based methods for organ classification in WCE often rely on color information, leading to decreased performance when obstacles such as food debris are present. This study proposes a novel model that integrates convolutional neural networks (CNNs) and long short-term memory (LSTM) networks to analyze multiple frames and incorporate temporal information, ensuring that it performs well even when visual information is limited. METHODS: We collected data from 126 patients using PillCam™ SB3 (Medtronic, Minneapolis, MN, USA), which comprised 2,395,932 images. Our deep learning model was trained to identify organs (stomach, small intestine, and colon) using data from 44 training and 10 validation cases. We applied calibration using a Gaussian filter to enhance the accuracy of detecting organ boundaries. Additionally, we estimated the transit time of the capsule in the gastric and small intestine regions using a combination of a convolutional neural network (CNN) and a long short-term memory (LSTM) designed to be aware of the sequence information of continuous videos. Finally, we evaluated the model's performance using WCE videos from 72 patients. RESULTS: Our model demonstrated high performance in organ classification, achieving an accuracy, sensitivity, and specificity of over 95% for each organ (stomach, small intestine, and colon), with an overall accuracy and F1-score of 97.1%. The Matthews Correlation Coefficient (MCC) and Geometric Mean (G-mean) were used to evaluate the model's performance on imbalanced datasets, achieving MCC values of 0.93 for the stomach, 0.91 for the small intestine, and 0.94 for the colon, and G-mean values of 0.96 for the stomach, 0.95 for the small intestine, and 0.97 for the colon. Regarding the estimation of gastric and small intestine transit times, the mean time differences between the model predictions and ground truth were 4.3 ± 9.7 min for the stomach and 24.7 ± 33.8 min for the small intestine. Notably, the model's predictions for gastric transit times were within 15 min of the ground truth for 95.8% of the test dataset (69 out of 72 cases). The proposed model shows overall superior performance compared to a model using only CNN. CONCLUSIONS: The combination of CNN and LSTM proves to be both accurate and clinically effective for organ classification and transit time estimation in WCE. Our model's ability to integrate temporal information allows it to maintain high performance even in challenging conditions where color information alone is insufficient. Including MCC and G-mean metrics further validates the robustness of our approach in handling imbalanced datasets. These findings suggest that the proposed method can significantly improve the diagnostic accuracy and efficiency of WCE, making it a valuable tool in clinical practice for diagnosing and managing GI diseases.

Substantiation and Effectiveness of Remote Monitoring System Based on IoMT Using Portable ECG Device.

Cardiovascular disease is a major global health concern, with early detection being critical. This study assesses the effectiveness of a portable ECG device, based on Internet of Medical Things (IoMT) technology, for remote cardiovascular monitoring during daily activities. We conducted a clinical trial involving 2000 participants who wore the HiCardi device while engaging in hiking activities. The device monitored their ECG, heart rate, respiration, and body temperature in real-time. If an abnormal signal was detected while a physician was remotely monitoring the ECG at the IoMT monitoring center, he notified the clinical research coordinator (CRC) at the empirical research site, and the CRC advised the participant to visit a hospital. Follow-up calls were made to determine compliance and outcomes. Of the 2000 participants, 318 showed abnormal signals, and 182 were advised to visit a hospital. The follow-up revealed that 139 (76.37%) responded, and 30 (21.58% of those who responded) sought further medical examination. Most visits (80.00%) occurred within one month. Diagnostic approaches included ECG (56.67%), ECG and ultrasound (20.00%), ultrasound alone (16.67%), ECG and X-ray (3.33%), and general treatment (3.33%). Seven participants (23.33% of those who visited) were diagnosed with cardiovascular disease, including conditions such as arrhythmia, atrial fibrillation, and stent requirements. The portable ECG device using the patch-type electrocardiograph detected abnormal cardiovascular signals, leading to timely diagnoses and interventions, demonstrating its potential for broad applications in preventative healthcare.