Amount Estimation Method for Food Intake Based on Color and Depth Images through Deep Learning.

In this paper, we propose an amount estimation method for food intake based on both color and depth images. Two pairs of color and depth images are captured pre- and post-meals. The pre- and post-meal color images are employed to detect food types and food existence regions using Mask R-CNN. The post-meal color image is spatially transformed to match the food region locations between the pre- and post-meal color images. The same transformation is also performed on the post-meal depth image. The pixel values of the post-meal depth image are compensated to reflect 3D position changes caused by the image transformation. In both the pre- and post-meal depth images, a space volume for each food region is calculated by dividing the space between the food surfaces and the camera into multiple tetrahedra. The food intake amounts are estimated as the difference in space volumes calculated from the pre- and post-meal depth images. From the simulation results, we verify that the proposed method estimates the food intake amount with an error of up to 2.2%.

The glacier melting process is an invisible barrier to the development of Antarctic subtidal macroalgal assemblages.

Ecological macroalgal succession in glacier-free areas has remained at the pioneer seral stage despite six decades of glacial retreat at Marian Cove, King George Island, Antarctica. With the rapid melting of glaciers in the West Antarctic Peninsula owing to global warming, a massive amount of meltwater is flowing into the coast, creating marine environmental gradients such as turbidity, water temperature, and salinity. This study examined the spatial and vertical distributions (up to a depth of 25 m) of macroalgal assemblages from nine sites in Maxwell Bay and Marian Cove. The macroalgal assemblages were analyzed for six sites located 0.2, 0.8, 1.2, 2.2, 3.6, and 4.1 km away from the glacier, including three sites where the glacial retreat history of Marian Cove could be estimated. To investigate the effects of meltwater, differences in the coastal environment were analyzed based on data collected from five stations located 0.4, 0.9, 3.0, 4.0, and 5.0 km away from the glacier. The macroalgal assemblages and marine environment were divided into two groups-inside and outside the cove-based on the region 2-3 km away from the glacier, which has been ice-free since 1956 and shows significant differences. In the three sites near the glacier front, Palmaria decipiens was dominant, and three to four species were distributed, whereas in the two sites outside the cove, nine and 14 species appeared, respectively, similar to the assemblage of the other three sites in Maxwell Bay. Palmaria decipiens, a representative opportunistic pioneer species in Antarctica, is dominant because of its physiological adaptation despite the high turbidity and low water temperature of the glacier front. This study shows that macroalgal assemblages in Antarctic fjord-like coves respond to glacial retreat and are valuable in understanding the macroalgal succession in Antarctica.

Mitochondrial peroxiredoxin 5 overexpression suppresses insulin-induced adipogenesis by downregulating the phosphorylation of p38.

Obesity is caused by the accumulation of excess lipids due to an energy imbalance. Differentiation of pre-adipocytes induces abnormal lipid accumulation, and reactive oxygen species (ROS) generated in this process promote the differentiation of pre-adipocytes through mitogen-activated protein kinase (MAPK) signaling. Peroxiredoxin (Prx) is a potent antioxidant enzyme, and peroxiredoxin 5 (Prx5), which is mainly expressed in cytosol and mitochondria, inhibits adipogenesis by regulating ROS levels. Based on previous findings, the present study was performed to investigate whether cytosolic Prx5 (CytPrx5) or mitochondrial Prx5 (MtPrx5) has a greater effect on the inhibition of adipogenesis. In this study, MtPrx5 decreased insulin-mediated ROS levels to reduce adipogenic gene expression and lipid accumulation more effectively than CytPrx5. In addition, we found that p38 MAPK mainly participates in adipogenesis. Furthermore, we verified that MtPrx5 overexpression suppressed the phosphorylation of p38 during adipogenesis. Thus, we suggest that MtPrx5 inhibits insulin-induced adipogenesis more effectively than CytPrx5.

PCNB exposure during early embryogenic development induces developmental delay and teratogenicity by altering the gene expression in Xenopus laevis.

Pentachloronitrobenzene (PCNB) is an organochlorine fungicide commonly used to treat seeds against seedling infections and controlling snow mold on golf courses. PCNB has been demonstrated to be toxic to living organisms, including fish and several terrestrial organisms. However, only phenotypical deformities have been studied, and the effects of PCNB on early embryogenesis, where primary organogenesis occurs, have not been completely studied. In the current study, the developmental toxicity and teratogenicity of PCNB is evaluated by using frog embryo teratogenesis assay Xenopus (FETAX). Our results confirmed the teratogenic potential of PCNB revealing the teratogenic index of 1.29 during early embryogenesis. Morphological studies revealed tiny head, bent axis, reduced inter ocular distance, hyperpigmentation, and reduced total body lengths. Whole mount in situ hybridization and reverse transcriptase polymerase chain reaction were used to identify PCNB teratogenic effects at the gene level. The gene expression analyses revealed that PCNB was embryotoxic to the liver and heart of developing embryos. Additionally, to determine the most sensitive developmental stages to PCNB, embryos were exposed to the compound at various developmental stages, demonstrating that the most sensitive developmental stage to PCNB is primary organogenesis. Taken together, we infer that PCNB's teratogenic potential affects not just the phenotype of developing embryos but also the associated genes and involving the oxidative stress as a possible mechanism of toxicity, posing a hazard to normal embryonic growth. However, the mechanisms of teratogenesis require additional extensive investigation to be defined completely.

A Sensing-Based Visualization Method for Representing Pressure Distribution in a Multi-Zone Building by Floor.

Airflow in a multi-zone building can be a major cause of pollutant transfer, excessive energy consumption, and occupants discomfort. The key to monitoring airflows and mitigating related problems is to obtain a comprehensive understanding of pressure relationships within the buildings. This study proposes a visualization method for representing pressure distribution within a multi-zone building by using a novel pressure-sensing system. The system consists of a Master device and a couple of Slave devices that are connected with each other by a wireless sensor network. A 4-story office building and a 49-story residential building were installed with the system to detect pressure variations. The spatial and numerical mapping relationships of each zone were further determined through grid-forming and coordinate-establishing processes for the building floor plan. Lastly, 2D and 3D visualized pressure mappings of each floor were generated, illustrating the pressure difference and spatial relationship between adjacent zones. It is expected that the pressure mappings derived from this study will allow building operators to intuitively perceive the pressure variations and the spatial layouts of the zones. These mappings also make it possible for operators to diagnose the differences in pressure conditions between adjacent zones and plan a control scheme for the HVAC system more efficiently.

Significance of digestive symptoms after COVID-19 vaccination: A retrospective single-center study.

OBJECTIVE: There is insufficient research on digestive symptoms and outcomes following coronavirus disease (COVID-19) vaccination. We aimed to investigate digestive symptoms and related complications among South Koreans who were administered COVID-19 vaccines. METHODS: Forty-six patients (men: 22, women: 24) with a median age of 68 years (interquartile range:55.5, 73.8 years) who experienced digestive symptoms following COVID-19 vaccination between March 1 and July 30, 2021, were included. This retrospective single-center study collected information on clinical symptoms, laboratory tests, imaging results, comorbidities, complications, treatment type, and prognosis. RESULTS: Thirty-three (71.7%), nine (19.6%), and three (6.5%) patients were administered AZD1222 (AstraZeneca), BNT162b2 (Pfizer/BioNTech), and JNJ-78436735 (Johnson and Johnson) vaccines, respectively. Patients were classified with mild (25 patients, 54.3%), moderate (five patients, 10.9%), and severe (16 patients, 34.8%) based on disease severity. Digestive symptoms included abdominal pain, diarrhea, dyspepsia, and nausea, which usually developed within 1 day (78.3%) following the first vaccination. In total, 14 (30.4%) patients experienced only gastrointestinal symptoms, whereas 32 (69.6%) experienced non-gastrointestinal symptoms. Complications included enterocolitis (76%), acute kidney injury (9%), anaphylactoid reaction (2%), and duodenal perforation (2%). CONCLUSIONS: COVID-19 vaccines caused digestive symptoms and other complications that ranged from mild to severe. While further validation is required, our results suggest that monitoring digestive symptoms following COVID-19 vaccination can help detect rather severe complications that require medical intervention.

Enhancement of target specificity of CRISPR-Cas12a by using a chimeric DNA-RNA guide.

The CRISPR-Cas9 system is widely used for target-specific genome engineering. CRISPR-Cas12a (Cpf1) is one of the CRISPR effectors that controls target genes by recognizing thymine-rich protospacer adjacent motif (PAM) sequences. Cas12a has a higher sensitivity to mismatches in the guide RNA than does Cas9; therefore, off-target sequence recognition and cleavage are lower. However, it tolerates mismatches in regions distant from the PAM sequence (TTTN or TTN) in the protospacer, and off-target cleavage issues may become more problematic when Cas12a activity is improved for therapeutic purposes. Therefore, we investigated off-target cleavage by Cas12a and modified the Cas12a (cr)RNA to address the off-target cleavage issue. We developed a CRISPR-Cas12a that can induce mutations in target DNA sequences in a highly specific and effective manner by partially substituting the (cr)RNA with DNA to change the energy potential of base pairing to the target DNA. A model to explain how chimeric (cr)RNA guided CRISPR-Cas12a and SpCas9 nickase effectively work in the intracellular genome is suggested. Chimeric guide-based CRISPR- Cas12a genome editing with reduced off-target cleavage, and the resultant, increased safety has potential for therapeutic applications in incurable diseases caused by genetic mutations.

Intra Prediction Method for Depth Video Coding by Block Clustering through Deep Learning.

In this paper, we propose an intra-picture prediction method for depth video by a block clustering through a neural network. The proposed method solves a problem that the block that has two or more clusters drops the prediction performance of the intra prediction for depth video. The proposed neural network consists of both a spatial feature prediction network and a clustering network. The spatial feature prediction network utilizes spatial features in vertical and horizontal directions. The network contains a 1D CNN layer and a fully connected layer. The 1D CNN layer extracts the spatial features for a vertical direction and a horizontal direction from a top block and a left block of the reference pixels, respectively. 1D CNN is designed to handle time-series data, but it can also be applied to find the spatial features by regarding a pixel order in a certain direction as a timestamp. The fully connected layer predicts the spatial features of the block to be coded through the extracted features. The clustering network finds clusters from the spatial features which are the outputs of the spatial feature prediction network. The network consists of 4 CNN layers. The first 3 CNN layers combine two spatial features in the vertical and horizontal directions. The last layer outputs the probabilities that pixels belong to the clusters. The pixels of the block are predicted by the representative values of the clusters that are the average of the reference pixels belonging to the clusters. For the intra prediction for various block sizes, the block is scaled to the size of the network input. The prediction result through the proposed network is scaled back to the original size. In network training, the mean square error is used as a loss function between the original block and the predicted block. A penalty for output values far from both ends is introduced to the loss function for clear network clustering. In the simulation results, the bit rate is saved by up to 12.45% under the same distortion condition compared with the latest video coding standard.

Major modifications to minimize thoracic esophago-gastric leak and eradicate esophageal stricture after Ivor Lewis esophagectomy.

BACKGROUND: The Ivor Lewis esophagectomy (ILE) remains the procedure of choice for localized middle or lower esophageal carcinoma. Nevertheless, anastomotic leak remains a common complication with rates from 3% to 25% and a stricture rate as high as 40%. The frequency of these complications suggests that the procedure itself may have inherent limitations including the use of potentially ischemic tissue for the esophagogastric anastomosis. We introduce a modified technique that reduces operative steps, preserves blood supply, and uses a modified esophagogastric anastomosis. METHODS: All consecutive patients undergoing ILE with the described modified technique were identified. An esophagram was performed on postoperative day six or seven. To ensure that all cases were identified, anastomotic leaks were defined as any radiographic evidence of contrast extravasation. RESULTS: A total of 110 patients underwent the modified esophagectomy with 2 anastomotic leaks (1.82%) and zero strictures. There was 1 late death but no early deaths (<30 or 90 days) or early re-admissions (<30 days). The average number of risk factors was 2.12, and 98 patients (90%) had at least 1 risk factor in their medical history. CONCLUSIONS: The modifications proposed simplify procedural steps, limit unnecessary dissection and introduce a technique that ends the practice of connecting ischemic tissue. We believe this technique contributes to surgical durability and reduces the rate of postoperative leak and eliminates stricture.

Investigation of droplets released during digestive endoscopy using a high-speed camera (with video): a pilot study.

BACKGROUND: A large release of droplets is often expected around the periphery of the digestive endoscope insertion site. Therefore, a sense of alarm over infection because of droplets that may be released during digestive endoscopy examination is increasing. This study aimed to investigate the droplets released during digestive endoscopy using a high-speed camera. METHODS: We utilized a high-speed camera (FASTCAM SA-3, Photron Limited) capable of recording small, transparent droplets with a black background and high-brightness lighting. The obtained video files were analyzed using post-processing software. We divided the 20 models into the control (a spray bottle model and a cough model) and experimental groups (digestive endoscopy models). The sedative, proficiency of digestive endoscopy and the amount of gas injected were modulated to change the level of released droplets. RESULTS: For the control groups, droplets were clearly observed using a high-speed camera. However, no droplet larger than 10 µm in size was observed in the experimental groups. Furthermore, the changes in the sedative, proficiency of digestive endoscopy, and amount of gas injected did not affect droplet formation. CONCLUSIONS: Based on high-speed camera photography, the risk of droplet generation during digestive endoscopy was not higher than that during violent expiratory events, such as coughing and sneezing.

Amyloid-beta oligomers induce Parkin-mediated mitophagy by reducing Miro1.

Alzheimer's disease (AD) is a neurodegenerative disease associated with the accumulation of amyloid-beta oligomers (AßO). Recent studies have demonstrated that mitochondria-specific autophagy (mitophagy) contributes to mitochondrial quality control by selectively eliminating the dysfunctional mitochondria. Mitochondria motility, which is regulated by Miro1, is also associated with neuronal cell functions. However, the role played by Miro1 in the mitophagy mechanism, especially relative to AßO and neurodegenerative disorders, remains unknown. In this study, AßO induced mitochondrial dysfunction, enhanced Parkin-mediated mitophagy, and reduced mitochondrial quantities in hippocampal neuronal cells (HT-22 cells). We demonstrated that AßO-induced mitochondrial fragmentation could be rescued to the elongated mitochondrial form and that mitophagy could be mitigated by the stable overexpression of Miro1 or by pretreatment with N-acetylcysteine (NAC)-a reactive oxygen species (ROS) scavenger-as assessed by immunocytochemistry. Moreover, using time-lapse imaging, under live cell-conditions, we verified that mitochondrial motility was rescued by the Miro1 overexpression. Finally, in hippocampus from amyloid precursor protein (APP)/presenilin 1 (PS1)/Tau triple-transgenic mice, we noted that the co-localization between mitochondria and LC3B puncta was increased. Taken together, these results indicated that up-regulated ROS, induced by AßO, increased the degree of mitophagy and decreased the Miro1 expression levels. In contrast, the Miro1 overexpression ameliorated AßO-mediated mitophagy and increased the mitochondrial motility. In AD model mice, AßO induced mitophagy in the hippocampus. Thus, our results would improve our understanding of the role of mitophagy in AD toward facilitating the development of novel therapeutic agents for the treatment of AßO-mediated diseases.

Dieckol Ameliorates Aß Production via PI3K/Akt/GSK-3ß Regulated APP Processing in SweAPP N2a Cell.

The proteolytic processing of amyloid precursor protein (APP) by ß-secretase (BACE1) and γ-secretase releases amyloid-ß peptide (Aß), which deposits in amyloid plaques and contributes to the initial causative events of Alzheimer's disease (AD). In the present study, the regulatory mechanism of APP processing of three phlorotannins was elucidated in Swedish mutant APP overexpressed N2a (SweAPP N2a) cells. Among the tested compounds, dieckol exhibited the highest inhibitory effect on both intra- and extracellular Aß accumulation. In addition, dieckol regulated the APP processing enzymes, such as α-secretase (ADAM10), ß-secretase, and γ-secretase, presenilin-1 (PS1), and their proteolytic products, sAPPα and sAPPß, implying that the compound acts on both the amyloidogenic and non-amyloidogenic pathways. In addition, dieckol increased the phosphorylation of protein kinase B (Akt) at Ser473 and GSK-3ß at Ser9, suggesting dieckol induced the activation of Akt, which phosphorylated GSK-3ß. The specific phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 triggered GSK-3ß activation and Aß expression. In addition, co-treatment with LY294002 noticeably blocked the effect of dieckol on Aß production, demonstrating that dieckol promoted the PI3K/Akt signaling pathway, which in turn inactivated GSK-3ß, resulting in the reduction in Aß levels.

Peroxiredoxin 1 Controls Ovulation and Ovulated Cumulus-Oocyte Complex Activity through TLR4-Derived ERK1/2 Signaling in Mice.

Peroxiredoxins (PRDXs) are expressed in the ovary and during ovulation. PRDX1 activity related to the immuno-like response during ovulation is unknown. We investigated the roles of Prdx1 on TLR4 and ERK1/2 signaling from the ovulated cumulus-oocyte complex (COC) using Prdx1-knockout (K/O) and wild-type (WT) mice. Ovulated COCs were collected 12 and 16 h after pregnant mare serum gonadotropin/hCG injection. PRDX1 protein expression and COC secretion factors (Il-6, Tnfaip6, and Ptgs2) increased 16 h after ovulated COCs of the WT mice were obtained. We treated the ovulated COCs in mice with LPS (0.5 µg/mL) or hyaluronidase (Hya) (10 units/mL) to induce TLR4 activity. Intracellular reactive oxygen species (ROS), cumulus cell apoptosis, PRDX1, TLR4/P38/ERK1/2 protein expression, and COC secretion factors' mRNA levels increased in LPS- and Hya-treated COCs. The ERK inhibitor (U0126) and Prdx1 siRNA affected TLR4/ERK1/2 expression. The number and cumulus expansion of ovulated COCs by ROS were impaired in Prdx1 K/O mice but not in WT ones. Prdx1 gene deletion induced TLR4/P38/ERK1/2 expression and cumulus expansion genes. These results show the controlling roles of PRDX1 for TLR4/P38/ERK1/2 signaling activity in ovulated mice and the interlink of COCs with ovulation.

Poziotinib suppresses ovarian cancer stem cell growth via inhibition of HER4-mediated STAT5 pathway.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with an overall 5-year survival rate of only 30%. EOC is associated with drug resistance, frequent recurrence, and poor prognosis. A major contributor toward drug resistance might be cancer stem cells (CSCs), which may remain after chemotherapy. Here, we aimed to find therapeutic agents that target ovarian CSCs. We performed a high-throughput screening using the Clinical Compound Library with a sphere culture of A2780 EOCs. Poziotinib, a pan-human epidermal growth factor receptor (HER) inhibitor, decreased sphere formation, viability, and proliferation, and induced G1 cell cycle arrest and apoptosis in ovarian CSCs. In addition, poziotinib suppressed stemness and disrupted downstream signaling of Wnt/ß-catenin, Notch, and Hedgehog pathways, which contribute to many characteristics of CSCs. Interestingly, HER4 was overexpressed in ovarian CSCs and Poziotinib reduced the phosphorylation of STAT5, AKT, and ERK, which are regulated by HER4. Our results suggest that HER4 may be a promising therapeutic target for ovarian CSCs, and that poziotinib may be an effective therapeutic option for the prevention of ovarian cancer recurrence.

Peroxiredoxin 4 inhibits insulin-induced adipogenesis through regulation of ER stress in 3T3-L1 cells.

Obesity was originally considered a disease endemic to developed countries but has since emerged as a global health problem. Obesity is characterized by abnormal or excessive lipid accumulation (World Health Organization, WHO) resulting from pre-adipocyte differentiation (adipogenesis). The endoplasmic reticulum (ER) produces proteins and cholesterol and shuttles these compounds to their target sites. Many studies have implicated ER stress, indicative of ER dysfunction, in adipogenesis. Reactive oxygen species (ROS) are also known to be involved in pre-adipocyte differentiation. Prx4 specific to the ER lumen exhibits ROS scavenging activity, and we thereby focused on ER-specific Prx4 in tracking changes in adipocyte differentiation and lipid accumulation. Overexpression of Prx4 reduced ER stress and suppressed lipid accumulation by regulating adipogenic gene expression during adipogenesis. Our results demonstrate that Prx4 inhibits ER stress, lowers ROS levels, and attenuates pre-adipocyte differentiation. These findings suggested enhancing the activity of Prx4 may be helpful in the treatment of obesity; the data also support the development of new therapeutic approaches to obesity and obesity-related metabolic disorders.

Peroxiredoxin 2 deficiency reduces white adipogenesis due to the excessive ROS generation.

Reactive oxygen species (ROS) act as signaling molecules to regulate various cell functions. Numerous studies have demonstrated ROS to be essential for the differentiation of adipocytes. Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes in mammalian cells. Prx2 is present in the cytoplasm and cell membranes and demonstrates ROS scavenging activity. We focused on Prx2 involvement in regulating adipogenesis and lipid accumulation and demonstrated that Prx2 expression was upregulated during adipocyte differentiation. In addition, the silencing of Prx2 (shPrx2) inhibited adipogenesis by modulating adipogenic gene expression, and cell death was enhanced via increased ROS production in shPrx2-3T3-L1 cells. These results demonstrate that shPrx2 triggers adipocyte cell death and weakens adipocyte function via ROS production. Taken together, our data suggest the participation of Prx2 in adipocyte function and differentiation. Our results also imply that the downregulation of Prx2 activity could help prevent obesity. Overall, findings support the development of ROS-based therapeutic solutions for the treatment of obesity and obesity-related metabolic disorders.

Clinical significance of regional lymph node enlargement in patients with EGC within the expanded criteria for ESD.

BACKGROUND: Lymph node (LN) metastasis is negligible in early gastric cancer (EGC) within expanded criteria for endoscopic submucosal dissection (ESD). However, regional lymph nodes in abdominal CT scans are sometimes enlarged in patients with EGC within the expanded criteria for endoscopic submucosal dissection (ESD). In this study, we investigated the clinical significance of regional lymph node enlargement on abdominal CT scan in patients with EGC within the expanded criteria for ESD. METHODS: From December 2010 to April 2015, among 301 patients with EGC within the ESD expanded criteria, 47 patients with regional lymph node enlargement shown by abdominal CT scan were prospectively enrolled. We performed surgical resection or periodic follow-up with abdominal CT scans and upper endoscopy every 6 months to evaluate whether the enlarged lymph nodes are due to metastasis or a reactive change. RESULTS: The mean age of the 47 patients (38 males, 9 female) was 64.8 years. The enlarged lymph nodes were usually single (26/47, 44.6%) and sized as follows: 11 nodes were ≤ 5 mm, 19 were 6-10 mm, and 17 were ≥ 10 mm. Four of the 47 patients initially underwent surgical resection, and 8 patients underwent surgical resection after ESD. However, there was no lymph node metastasis in surgical specimens. Thirty-five patients received ESD and periodically followed up at a median duration of 56 months (IQR: 44-59 month). The enlarged lymph node disappeared in 12 of 35 patients, decreased in 9 patients and remained the same size in 13 patients, and increased in 1 patient. CONCLUSION: Regional lymph node enlargement on abdominal CT scan in patients within expanded criteria for ESD of ECG may be not due to metastasis but a reactive change.

Technical feasibility of a newly designed bendable forceps for difficult endoscopic tissue samplings (with video).

BACKGROUND: Biopsies with conventional forceps beyond the operating range are difficult and cumbersome. Thus, we developed a new bendable forceps for improved access to gastrointestinal lesions and evaluated its technical feasibility. METHODS: A bendable forceps was constructed with two channels and a two-stage knob. The bending motion-related structures were designed to improve the range of motion. For the evaluation of the forceps, we used 2 gastrointestinal simulators: an ex vivo porcine model, and an in vivo porcine model with some difficult endoscopic biopsy cases. All evaluations were performed by 5 expert endoscopists and an expert pathologist. RESULTS: Compared with the conventional forceps, the bendable forceps had greater efficacy in the simulator (6.2 ± 0.4 vs. 1.96 ± 0.2, p < 0.001), ex vivo porcine model (6.33 ± 0.52 vs. 4.25 ± 0.89, p < 0.001), and in vivo porcine model (6.33 ± 0.52 vs. 4.25 ± 0.89, p < 0.001); greater safety in the simulator (1.92 ± 0.13 s vs. 4.88 ± 0.50 s, p < 0.001), ex vivo porcine model (2.02 ± 0.15 s vs 4.66 ± 0.27 s, p < 0.001), and in vivo porcine model (2.02 ± 0.15 s vs. 4.08 ± 0.70 s, p = 0.002); and larger specimens in the ex vivo porcine model (3.92 ± 0.03 mm vs. 3.85 ± 0.07 mm, p = 0.020). CONCLUSIONS: This study showed that compared with the conventional forceps, the bendable forceps was effective and safe to use for accessing difficult lesions in the three models. We believe that the bendable forceps serves as a useful supplementary diagnostic tool for accessing difficult lesions. However, further validation of its usefulness in the human body is needed.

Clinical Characteristics and Mortality Predictors of COVID-19 Patients Hospitalized at Nationally-Designated Treatment Hospitals.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in December 2019 in China, and then it has disseminated worldwide. In Korea, a religious group-related super-spreading event triggered a sudden outbreak in Daegu city and Gyeongsangbuk-do in southeast Korea. This study was undertaken to document the clinical characteristics of patients hospitalized in Gyeongsangbuk-do. METHODS: Three hundred and fifty-two patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalized at Dongguk University Gyeongju Hospital or at the Andong Medical Center between February 18th and June 30th were enrolled in this study. Medical records were reviewed and demographic and clinical features, including comorbidities, symptoms, radiological and laboratory findings on admission were analyzed. In addition, we sought to identify risk factors of mortality. RESULTS: Mean age of the 352 study subjects was 56 years (range, 14-95). The mortality rate was 6.8% and mean age at death was 81 years (range, 57-91). The most common symptom was cough (31.8%) followed by a febrile sensation (28.4%), sputum (17.0%), sore throat (15.6%), and myalgia (13.1%). Eighty-one (23.0%) patients were asymptomatic, but a half of these patients exhibited pneumonic infiltration at presentation. Chest radiology showed no active lesion in 41.8% of the study subjects, bilateral pneumonia in 46.9%, and unilateral pneumonic infiltration in 11.4%. Among 24 patients that died, 18 subjects were transferred from a care facility. An age of ≥ 70 years, previous history of malignancy or diabetes, and fever (≥ 37.5°C) on admission were found to be significant risk factors of mortality. CONCLUSION: Patients aged ≥ 70 years, those with fever on admission, and patients with an underlying malignancy or diabetes were found to be more likely to succumb to COVID-19. Elderly in care facilities or hospitalized patients with an underlying disease should receive more attention and be considered for preventive quarantine.

Combined Poziotinib with Manidipine Treatment Suppresses Ovarian Cancer Stem-Cell Proliferation and Stemness.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in women worldwide, with an overall 5 year survival rate below 30%. The low survival rate is associated with the persistence of cancer stem cells (CSCs) after chemotherapy. Therefore, CSC-targeting strategies are required for successful EOC treatment. Pan-human epidermal growth factor receptor 4 (HER4) and L-type calcium channels are highly expressed in ovarian CSCs, and treatment with the pan-HER inhibitor poziotinib or calcium channel blockers (CCBs) selectively inhibits the growth of ovarian CSCs via distinct molecular mechanisms. In this study, we tested the hypothesis that combination treatment with poziotinib and CCBs can synergistically inhibit the growth of ovarian CSCs. Combined treatment with poziotinib and manidipine (an L-type CCB) synergistically suppressed ovarian CSC sphere formation and viability compared with either drug alone. Moreover, combination treatment synergistically reduced the expression of stemness markers, including CD133, KLF4, and NANOG, and stemness-related signaling molecules, such as phospho-STAT5, phospho-AKT, phospho-ERK, and Wnt/ß-catenin. Moreover, poziotinib with manidipine dramatically induced apoptosis in ovarian CSCs. Our results suggest that the combinatorial use of poziotinib with a CCB can effectively inhibit ovarian CSC survival and function.