PANCDR: precise medicine prediction using an adversarial network for cancer drug response.

Pharmacogenomics aims to provide personalized therapy to patients based on their genetic variability. However, accurate prediction of cancer drug response (CDR) is challenging due to genetic heterogeneity. Since clinical data are limited, most studies predicting drug response use preclinical data to train models. However, such models might not be generalizable to external clinical data due to differences between the preclinical and clinical datasets. In this study, a Precision Medicine Prediction using an Adversarial Network for Cancer Drug Response (PANCDR) model is proposed. PANCDR consists of two sub-models, an adversarial model and a CDR prediction model. The adversarial model reduces the gap between the preclinical and clinical datasets, while the CDR prediction model extracts features and predicts responses. PANCDR was trained using both preclinical data and unlabeled clinical data. Subsequently, it was tested on external clinical data, including The Cancer Genome Atlas and brain tumor patients. PANCDR outperformed other machine learning models in predicting external test data. Our results demonstrate the robustness of PANCDR and its potential in precision medicine by recommending patient-specific drug candidates. The PANCDR codes and data are available at https://github.com/DMCB-GIST/PANCDR.

Identification and characterization of structural variants related to meat quality in pigs using chromosome-level genome assemblies.

BACKGROUND: Many studies have been performed to identify various genomic loci and genes associated with the meat quality in pigs. However, the full genetic architecture of the trait still remains unclear in part because of the lack of accurate identification of related structural variations (SVs) which resulted from the shortage of target breeds, the limitations of sequencing data, and the incompleteness of genome assemblies. The recent generation of a new pig breed with superior meat quality, called Nanchukmacdon, and its chromosome-level genome assembly (the NCMD assembly) has provided new opportunities. RESULTS: By applying assembly-based SV calling approaches to various genome assemblies of pigs including Nanchukmacdon, the impact of SVs on meat quality was investigated. Especially, by checking the commonality of SVs with other pig breeds, a total of 13,819 Nanchukmacdon-specific SVs (NSVs) were identified, which have a potential effect on the unique meat quality of Nanchukmacdon. The regulatory potentials of NSVs for the expression of nearby genes were further examined using transcriptome- and epigenome-based analyses in different tissues. CONCLUSIONS: Whole-genome comparisons based on chromosome-level genome assemblies have led to the discovery of SVs affecting meat quality in pigs, and their regulatory potentials were analyzed. The identified NSVs will provide new insights regarding genetic architectures underlying the meat quality in pigs. Finally, this study confirms the utility of chromosome-level genome assemblies and multi-omics analysis to enhance the understanding of unique phenotypes.

Evaluation of Multiplex Rapid Antigen Test for the Detection of SARS-CoV-2 and Influenza A/B in Respiratory Samples.

BACKGROUND: There is little data about the performance of multiplex rapid antigen tests (RATs) on the detection of SARS-CoV-2, influenza A (Flu A), and influenza B (Flu B). This study is to evaluate the performance of Panbio COVID-19/Flu A&B rapid panel (Abbott Diagnostics, Korea) and analyze the factors influencing its sensitivity. METHODS: Nasopharyngeal swabs were collected and stored at the Korea University Anam hospital. In total, 400 residual samples from nasopharyngeal swabs were examined. The diagnostic accuracy of RAT was compared to that of RT-qPCR using the Allplex SARS-CoV-2/FluA/FluB/RSV Assay (Seegene, Seoul, South Korea). RESULTS: Panbio COVID-19/Flu A&B rapid panel showed the sensitivities of 88.0%, 92.0%, and 100% for SARS-CoV-2, Flu A, and Flu B, respectively, and specificities of 100% for all. The agreements with previously licensed single-plex RATs were shown to be high. In the analysis of variables affecting sensitivity, inappropriate sampling time after symptom onset (STASO) and high cycle threshold (Ct value) were shown to negatively affect the sensi-tivity. CONCLUSIONS: In conclusion, the multiplex RAT is useful for diagnosing SARS-CoV-2 and Flu A/B, but more clinical studies are needed.

Diagnostic accuracy of a three-protein signature in women with suspicious breast lesions: a multicenter prospective trial.

BACKGROUND: Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. FINDINGS: This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. CONCLUSIONS: The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( https://cris.nih.go.kr ).

HPLC-MS/MS Method Validation for Antifungal Agents in Human Serum in Clinical Application.

BACKGROUND: Therapeutic drug monitoring (TDM) of antifungal drugs is recommended. LC-MS/MS outperforms bioassay and high-performance liquid chromatography (HPLC) for TDM. In this study, we validated TDM for voriconazole, posaconazole, and itraconazole using HPLC-MS/MS with the multiple reaction monitoring (MRM) method. METHODS: For the validation of LC-MS/MS for antifungal TDM, accuracy, precision, linearity, carryover, lower limit of quantitation (LLOQ), ion suppression, and sample stability tests were performed according to the guidelines of the United States Food and Drug Administration (FDA) and the Clinical and Laboratory Standards Institute (CLSI). RESULTS: The LC-MS/MS triazole method showed that all analytes had biases less than 8.9% and coefficients of variation (CV) less than 7.7%. The linearity was validated over the ranges of 0.20 to 5.86 mg/L for voriconazole, 0.12 to 4.96 mg/L for posaconazole, 0.09 to 1.85 mg/L for itraconazole, and 0.12 to 2.38 mg/L for OH-itraconazole. Ion suppression and carryover were negligible. The lower limits of quantitation (LLOQs) for voriconazole, posaconazole, itraconazole, and OH-itraconazole were 0.114 mg/L, 0.206 mg/L, 0.118 mg/L, and 0.065 mg/L, respectively. Voriconazole, posaconazole, itraconazole, and OH-itraconazole can be stored at 4℃ for 4 - 7 days, according to sample stability. Sample preparation took < 15 minutes per batch, and analytical run time was 5 minutes per sample. CONCLUSIONS: We developed and validated a simple, reliable, and quick LC-MS/MS method for triazole antifungal agents TDM suitable for routine hospital practice.

Organic waste derived bioethanol supply chain network: Multiobjective snapshot model with a real-Korea case study.

Bioethanol, a promising biofuel gasoline additive, was recently produced by a new technology using acetic acid derived from organic waste. This study develops a multiobjective mathematical model with two competing minimization objectives: economy and environmental impact. The formulation is based on a mixed integer linear programming approach. The configuration of the organic-waste (OW)-based bioethanol supply chain network is optimized in terms of the number and locations of bioethanol refineries. The flows of acetic acid and bioethanol between the geographical nodes must meet the bioethanol regional demand. The model is validated in three real-scenario case studies with different OW utilization rates (30%, 50%, and 70%) in South Korea in the near future (2030). The multiobjective problem is solved using the ε-constraint method and the selected Pareto solutions balance the trade-off between the economic and environmental objectives. At the "best-choice" solution points, increasing the OW utilization rate from 30% to 70% decreased the total annual cost from 904.2 to 707.3 million $/yr and the total greenhouse emissions from 1087.2 to -15.7 CO2 equiv./yr.

Interactive description to enhance accessibility and experience of deaf and hard-of-hearing individuals in museums.

Text descriptions in museums provide detailed and rich information about artifacts that broadens museum visitors' knowledge and enriches their experience. However, since deaf and hard-of-hearing (DHH) individuals have low literacy compared to hearing people and communicate through sign language, museum descriptions are considerably limited in delivering a stimulating and informative environment for understanding and enjoying exhibits. To improve DHH individuals' museum experience, we investigated the potential of three interactive description prototypes: active-linked, graph-based, and chatbot-based. A comparative study with 20 DHH participants confirmed that our interaction-based prototypes improve information accessibility and provide an enhanced experience compared to conventional museum descriptions. Most participants preferred the graph-based prototype, while post-interviews suggested that each prototype has potential benefits and limitations according to DHH individuals' particular literacy skills and preferences. Text descriptions can be enlivened for DHH visitors by adding a simple interaction functionality, e.g., clicking, which can lead to a better museum experience.

RORα contributes to the maintenance of genome ploidy in the liver of mice with diet-induced nonalcoholic steatohepatitis.

Hepatic polyploidization is closely linked to the progression of nonalcoholic fatty liver disease (NAFLD); however, the underlying molecular mechanism is not clearly understood. In this study, we demonstrated the role of retinoic acid-related orphan receptor α (RORα) in the maintenance of genomic integrity, particularly in the pathogenesis of NAFLD, using the high-fat diet (HFD)-fed liver-specific RORα knockout (RORα-LKO) mouse model. First, we observed that the loss of hepatic retinoic acid receptor-related orphan receptor α (RORα) accelerated hepatocyte nuclear polyploidization after HFD feeding. In 70% partial hepatectomy experiments, enrichment of hepatocyte polyploidy was more obvious in the RORα-LKO animals, which was accompanied by early progression to the S phase and blockade of the G2/M transition, suggesting a potential role of RORα in suppressing hepatocyte polyploidization in the regenerating liver. An analysis of a publicly available RNA sequencing (RNA-seq) and chromatin immunoprecipitation-seq dataset, together with the Search Tool of the Retrieval of Interacting Genes/Proteins database resource, revealed that DNA endoreplication was the top-enriched biological process Gene Ontology term. Furthermore, we found that E2f7 and E2f8, which encode key transcription factors for DNA endoreplication, were the downstream targets of RORα-induced transcriptional repression. Finally, we showed that the administration of JC1-40, an RORα activator (5 mg/kg body wt), significantly reduced hepatic nuclear polyploidization in the HFD-fed mice. Together, our observations suggest that the RORα-induced suppression of hepatic polyploidization may provide new insights into the pathological polyploidy of NAFLD and may contribute to the development of therapeutic strategies for the treatment of NAFLD.NEW & NOTEWORTHY It has been reported that hepatic polyploidization is closely linked to the progression of NAFLD. Here, we showed that the genetic depletion of hepatic RORα in mice accelerated hepatocyte polyploidization after high-fat diet feeding. The mechanism could be the RORα-mediated repression of E2f7 and E2f8, key transcription factors for DNA endoreplication. Thus, preservation of genome integrity by RORα could provide a new insight for developing therapeutics against the disease.

AGS3-dependent trans-Golgi network membrane trafficking is essential for compaction in mouse embryos.

Activator of G-protein signaling 3 (AGS3, also known as GPSM1) regulates the trans-Golgi network. The AGS3 GoLoco motif binds to Gαi and thereby regulates the transport of proteins to the plasma membrane. Compaction of early embryos is based on the accumulation of E-cadherin (Cdh1) at cell-contacted membranes. However, how AGS3 regulates the transport of Cdh1 to the plasma membrane remains undetermined. To investigate this, AGS3 was knocked out using the Cas9-sgRNA system. Both trans-Golgi network protein 46 (TGN46, also known as TGOLN2) and transmembrane p24-trafficking protein 7 (TMED7) were tracked in early mouse embryos by tagging these proteins with a fluorescent protein label. We observed that the majority of the AGS3-edited embryos were developmentally arrested and were fragmented after the four-cell stage, exhibiting decreased accumulation of Cdh1 at the membrane. The trans-Golgi network and TMED7-positive vesicles were also dispersed and were not polarized near the membrane. Additionally, increased Gαi1 (encoded by GNAI1) expression could rescue AGS3-overexpressed embryos. In conclusion, AGS3 reinforces the dynamics of the trans-Golgi network and the transport of TMED7-positive cargo containing Cdh1 to the cell-contact surface during early mouse embryo development.

A Microfluidic Device to Fabricate One-Step Cell Bead-Laden Hydrogel Struts for Tissue Engineering.

Cell-laden structures are widely applied for a variety of tissue engineering applications, including tissue restoration. Cell-to-cell interactions in bioprinted structures are important for successful tissue restoration, because cell-cell signaling pathways can regulate tissue development and stem cell fate. However, the low degree of cell-cell interaction in conventional cell-laden bioprinted structures is challenging for the therapeutic application of this modality. Herein, a microfluidic device with cell-laden methacrylated gelatin (GelMa) bioink and alginate as a matrix hydrogel is used to fabricate a functional hybrid structure laden with cell-aggregated microbeads. This approach effectively increases the degree of cell-to-cell interaction to a level comparable to cell spheroids. The hybrid structure is obtained using a one-step process without the exhausting procedure. It consists of cell bead fabrication and an extrusion process for the cell-bead laden structure. Different flow rates are appropriately selected to develop cell-laden struts with homogeneously distributed cell beads for each hydrogel in the process. The hybrid struts exhibit significantly higher cellular activities than those of conventional alginate/GelMa struts, which are bioprinted using similar cell densities and bioink formulations. Furthermore, hybrid struts with adipose stem cells are implanted into mice, resulting in significantly higher myogenesis in comparison to normally bioprinted struts.

Development and Validation of a U-HPLC-MS/MS Method for the Concurrent Measurement of four Immunosuppressants in Whole Blood.

BACKGROUND: This study aimed to develop and validate a U-HPLC-MS/MS method for simultaneous determination of four immunosuppressants in human whole blood. METHODS: The method was based on the injection of 20 µL of calibrators and controls pretreated with the liquid phase extraction method for chromatography separation and mass spectrometry determination. LPE offline was performed by adding 0.1 mol/L ZnSO4 and acetonitrile, while separation of target compounds was achieved within 2.5 minutes by a Zorbax Eclipse XDB-C8 column using ammonium acetate and ACN mixed with formic acid as solvents. RESULTS: The assay offers ng/mL detection limits (from 1.1 to 12.4 ng/mL), accuracy (% deviation from -4.4% to 5.6%), precision (CV less than 15% at all QC levels), and linearity (from 23.4 to 948 ng/mL for CsA, from 2.11 to 45.5 ng/mL for TAC, SIR and EVR). The recovery and matrix results were acceptable, and the carryover was less than 1%. The results of method comparison show that IA-based methods overestimated the concentration of drugs compared with the MS-based method. Comparing our MS-based method with external LC-MS/MS showed that the results were within 2 SDs. CONCLUSIONS: We have developed a reliable assay for the analysis of CsA, TAC, SIR and EVR in whole blood using U-HPLC-MS/MS.

Regulation of the icl1 Gene Encoding the Major Isocitrate Lyase in Mycobacterium smegmatis.

Mycobacterium smegmatis has two isocitrate lyase (ICL) isozymes (MSMEG_0911 and MSMEG_3706). We demonstrated that ICL1 (MSMEG_0911) is the predominantly expressed ICL in M. smegmatis and plays a major role in growth on acetate or fatty acid as the sole carbon and energy source. Expression of the icl1 gene in M. smegmatis was demonstrated to be strongly upregulated during growth on acetate relative to that in M. smegmatis grown on glucose. Expression of icl1 was shown to be positively regulated by the RamB activator, and three RamB-binding sites (RamBS1, RamBS2, and RamBS3) were identified in the upstream region of icl1 using DNase I footprinting analysis. Succinyl coenzyme A (succinyl-CoA) was shown to increase the affinity of binding of RamB to its binding sites and enable RamB to bind to RamBS2, which is the most important site for RamB-mediated induction of icl1 expression. These results suggest that succinyl-CoA serves as a coinducer molecule for RamB. Our study also showed that cAMP receptor protein (Crp1; MSMEG_6189) represses icl1 expression in M. smegmatis grown in the presence of glucose. Therefore, the strong induction of icl1 expression during growth on acetate as the sole carbon source relative to the weak expression of icl1 during growth on glucose is likely to result from combined effects of RamB-mediated induction of icl1 in the presence of acetate and Crp-mediated repression of icl1 in the presence of glucose. IMPORTANCE Carbon flux through the glyoxylate shunt has been suggested to affect virulence, persistence, and antibiotic resistance of Mycobacterium tuberculosis. Therefore, it is important to understand the precise mechanism underlying the regulation of the icl gene encoding the key enzyme of the glyoxylate shunt. Using Mycobacterium smegmatis, this study revealed the regulation mechanism underlying induction of icl1 expression in M. smegmatis when the glyoxylate shunt is required. The conservation of the cis- and trans-acting regulatory elements related to icl1 regulation in both M. smegmatis and M. tuberculosis implies that a similar regulatory mechanism operates for the regulation of icl1 expression in M. tuberculosis.

A comparison of postoperative outcomes after open and laparoscopic reduction of Petersen's Hernia: a multicenter observational cohort study.

BACKGROUND: The aim of this multicenter cohort study was to compare the clinical courses between open and laparoscopic Petersen's hernia (PH) reduction. METHOD: We retrospectively collected the clinical data of patients who underwent PH repair surgery after gastrectomy for gastric cancer from 2015-2018. Forty patients underwent PH reduction operations that were performed by six surgeons at four hospitals. Among the 40 patients, 15 underwent laparoscopic PH reduction (LPH), and 25 underwent open PH reduction (OPH), including 4 patients who underwent LPH but required conversion to OPH. RESULTS: We compared the clinical factors between the LPH and OPH groups. In the clinical course, we found no differences in operation times or intraoperative bowel injury, morbidity, or mortality rates between the two groups (p > 0.05). However, the number of days on a soft fluid diet (OPH vs. LPH; 5.8 vs. 3.7 days, p = 0.03) and length of hospital stay (12.6 vs. 8.2 days, p = 0.04) were significantly less in the LPH group than the OPH group. Regarding postoperative complications, the OPH group had a case of pneumonia and sepsis with multi-organ failure, which resulted in mortality. In the LPH group, one patient experienced recurrence and required reoperation for PH. CONCLUSION: Laparoscopic PH reduction was associated with a faster postoperative recovery period than open PH reduction, with a similar incidence of complications. The laparoscopic approach should be considered an appropriate strategy for PH reduction in selected cases.

Dynamic changes of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predicts breast cancer prognosis.

BACKGROUND: We aimed to identify whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are more useful predictors after initial intention to treat than at the time of diagnosis. METHODS: We collected the medical data of 533 patients. The results of the peripheral blood sampling before the primary treatments were labeled as initial cohort, and those obtained between 24 and 36 months after initial treatment were defined as the 2nd cohort. Delayed metastasis has been defined as distant metastasis 2 years after treatment, and survival outcome was estimated and compared across groups. RESULTS: Median follow-up duration was 74 months (24-162 months), and 53 patients experienced delayed metastasis. In univariate analysis, metastasis-free survival, patient age at diagnosis, tumor size, axillary lymph node metastasis, HER-2 status, initial NLR and PLR, and 2nd NLR and PLR were found to be significantly associated with delayed metastasis. However, in multivariate analysis, only the 2nd NLR and PLR were found to be significantly associated with delayed metastasis, excluding initial NLR and PLR. Metastasis-free survival was analyzed through the pattern changes of NLR or PLR. The results revealed that patients with continued low NLR and PLR values at pre- and post-treatment (low initial values and 2nd values) showed a significantly better prognosis than those with a change in value or continued high NLR and PLR. CONCLUSIONS: We identified that patients with persistent high NLR and PLR after initial treatment have significant worse prognosis in terms of late metastasis. Therefore, these results suggest that NLR and PLR are more useful in predicting prognosis post-treatment.

Safety and efficacy of post-anastomotic intraoperative endoscopy to avoid early anastomotic complications during gastrectomy for gastric cancer.

BACKGROUND: Anastomotic complications such as leaks, bleeding, and stricture remain the most serious complications of surgery for gastric cancer. No perfect method exists for an accurate and reliable prevention of these complications. This study investigated the safety and efficacy of post-anastomotic intraoperative endoscopy (PAIOE) for avoidance of early anastomotic complications during gastrectomy in gastric cancer. METHODS: This retrospective case-control study enrolled patients from a tertiary care, academic medical center. Routine PAIOE was performed on 319 patients undergoing gastrectomy for gastric cancer between 2015 and 2016. As controls, without PAIOE 270 patients from 2013 to 2014 were used for comparison. Early anastomotic complications and outcomes after PAIOE were determined. RESULTS: Although there were no differences between the PAIOE and non-PAIOE group in terms of overall complication rates (20.1% vs 26.7%; P > 0.05), there were fewer complications related to anastomosis (3.4% vs 8.9%; P < 0.01) in the PAIOE group. The PAIOE group had rates of 2.5% for anastomotic leakage, 0.9% for intra-luminal bleeding, and 0% for anastomotic stenosis, while the non-PAIOE group exhibited rates of 5.6%, 2.6%, and 0.7%, respectively. Thirty-one abnormalities were detected in 26 PAIOE patients (9.71%) (20 venous bleeding, 7 mucosal tearing, 2 air leaks, 1 arterial bleeding, and 1 anastomotic stricture). All abnormalities were corrected by proper interventions (13 reinforced additional suture, 13 endoscopic hemostasis, and 2 re-anastomosis). There were no morbidities associated with PAIOE. CONCLUSIONS: PAIOE appears to be a safe and reliable procedure to evaluate the stability of gastrointestinal anastomosis for gastric cancer patients. Further data collection and a well-designed prospective study are needed to confirm the validity of PAIOE.

INTERSPIA: a web application for exploring the dynamics of protein-protein interactions among multiple species.

Proteins perform biological functions through cascading interactions with each other by forming protein complexes. As a result, interactions among proteins, called protein-protein interactions (PPIs) are not completely free from selection constraint during evolution. Therefore, the identification and analysis of PPI changes during evolution can give us new insight into the evolution of functions. Although many algorithms, databases and websites have been developed to help the study of PPIs, most of them are limited to visualize the structure and features of PPIs in a chosen single species with limited functions in the visualization perspective. This leads to difficulties in the identification of different patterns of PPIs in different species and their functional consequences. To resolve these issues, we developed a web application, called INTER-Species Protein Interaction Analysis (INTERSPIA). Given a set of proteins of user's interest, INTERSPIA first discovers additional proteins that are functionally associated with the input proteins and searches for different patterns of PPIs in multiple species through a server-side pipeline, and second visualizes the dynamics of PPIs in multiple species using an easy-to-use web interface. INTERSPIA is freely available at http://bioinfo.konkuk.ac.kr/INTERSPIA/.

Analysis of differences in eating alone attitude of Koreans by dietary habits and age.

This study compares differences in eating alone attitude according to dietary habits and age in Seoul and Gyeonggi-do region in South Korea. Out of total 411 participants, 207(50.4%) were males and 204(49.6%) were females. 30 types of eating alone attitude were identified to perform a factor analysis; further these 30 types of attitudes were categorized into 8 factors termed as: 'enjoyable eating alone', 'eating alone as a daily routine', 'healthy eating alone', 'self-conscious eating alone', 'choose what I want', 'efficient eating alone', 'lonely eating alone', and 'solo dining'. Our investigation on the link between dietary habits and eating alone attitude revealed significant differences in 3 factors out of those 8 factors: healthy eating alone, solo dining, eating alone as a daily routine. The high healthy meal group was found to have less frequency of eating alone. Among people in their 20s and 30s, the low healthy meal group had more population than the high healthy meal group. There was a tendency that the population of the high healthy meal group increases as age rises. Our data indicated that the younger generation eats alone more frequently as a daily routine (p < 0.01), feels freer when eating alone, eats out alone more frequently (p < 0.01). People in their 20s were found to be more positive on eating alone and tended to be willing solo diners. The high healthy meal group did eat alone in a healthy way whereas the low healthy meal group had a negative view on eating alone. Our study aims at providing a good starting point to develop programs for healthy eating alone by finding gaps between healthy and unhealthy eating alone.

Connexin 43 Knockdown Induces Mitochondrial Dysfunction and Affects Early Developmental Competence in Porcine Embryos.

Connexin 43 (CX43) is a component of gap junctions. The lack of functional CX43 induces oxidative stress, autophagy, and apoptosis in somatic cells. However, the role of CX43 in the early development of porcine embryos is still unknown. Thus, the aim of this study was to investigate the role of CX43, and its underlying molecular mechanisms, on the developmental competence of early porcine embryos. We performed CX43 knockdown by microinjecting dsRNA into parthenogenetically activated porcine parthenotes. The blastocyst development rate and the total number of cells in the blastocysts were significantly reduced by CX43 knockdown. Results from FITC-dextran assays showed that CX43 knockdown significantly increased membrane permeability. ZO-1 protein was obliterated in CX43 knockdown blastocysts. Mitochondrial membrane potential and ATP production were significantly reduced following CX43 knockdown. Reactive oxygen species (ROS) levels were significantly increased in the CX43 knockdown group compared to those in control embryos. Moreover, CX43 knockdown induced autophagy and apoptosis. Our findings indicate that CX43 is essential for the development and preimplantation of porcine embryos and maintains mitochondrial function, cell junction structure, and cell homeostasis by regulating membrane permeability, ROS generation, autophagy, and apoptosis in early embryos.

Validation of the oncologic effect of hepatic resection for T2 gallbladder cancer: a retrospective study.

BACKGROUND: While extended cholecystectomy is recommended for T2 gallbladder cancer (GBC), the role of hepatic resection for T2 GBC is unclear. This study aimed to identify the necessity of hepatic resection in patients with T2 GBC. METHODS: Data of 81 patients with histopathologically proven T2 GBC who underwent surgical resection between January 1999 and December 2017 were enrolled from a retrospective database. Of these, 36 patients had peritoneal-side (T2a) tumors and 45 had hepatic-side (T2b) tumors. To identify the optimal surgical management method, T2 GBC patients were classified into the hepatic resection group (n = 44, T2a/T2b = 20/24) and non-hepatic resection group (n = 37, T2a/T2b = 16/21). The recurrence pattern and role of hepatic resection for T2 GBC were then investigated. RESULTS: Mean age of the patients was 69 (range 36-88) years, and the male-to-female ratio was 42:39 (male, 51.9%; female, 48.1%). Hepatic-side GBC had a higher rate of recurrence than peritoneal-side GBC (44.4% vs. 8.3%, p = 0.006). The most common type of recurrence in T2a GBC was para-aortic lymph node recurrence (n = 2, 5.6%); the most common types of recurrence in T2b GBC were para-aortic lymph node recurrence (n = 7, 15.6%) and intrahepatic metastasis (n = 6, 13.3%). Hepatic-side GBC patients had worse survival outcomes than peritoneal-side GBC patients (76.0% vs. 96.6%, p = 0.041). Hepatic resection had no significant treatment effect in T2 GBC patients (p = 0.272). Multivariate analysis showed that lymph node metastasis was the only significant prognostic factor (p = 0.002). CONCLUSIONS: Hepatic resection is not essential for curative treatment in T2 GBC, and more systemic treatments are needed for GBC patients, particularly for those with T2b GBC.

Peak Detection Algorithm for Vital Sign Detection Using Doppler Radar Sensors.

An accurate method for detecting vital signs obtained from a Doppler radar sensor is proposed. A Doppler radar sensor can remotely obtain vital signs such as heartbeat and respiration rate, but the vital signs obtained by using the sensor do not show clear peaks like in electrocardiography (ECG) because of the operating characteristics of the radar. The proposed peak detection algorithm extracts the vital signs from the raw data. The algorithm shows the mean accuracy of 96.78% compared to the peak count from the reference ECG sensor and a processing time approximately two times faster than the gradient-based algorithm. To verify whether heart rate variability (HRV) analysis similar to that with an ECG sensor is possible for a radar sensor when applying the proposed method, the continuous parameter variations of the HRV in the time domain are analyzed using data processed with the proposed peak detection algorithm. Experimental results with six subjects show that the proposed method can obtain the heart rate with high accuracy but cannot obtain the information for an HRV analysis because the proposed method cannot overcome the characteristics of the radar sensor itself.