Machine learning based prediction of recurrence after curative resection for rectal cancer.

PURPOSE: Patients with rectal cancer without distant metastases are typically treated with radical surgery. Post curative resection, several factors can affect tumor recurrence. This study aimed to analyze factors related to rectal cancer recurrence after curative resection using different machine learning techniques. METHODS: Consecutive patients who underwent curative surgery for rectal cancer between 2004 and 2018 at Gil Medical Center were included. Patients with stage IV disease, colon cancer, anal cancer, other recurrent cancer, emergency surgery, or hereditary malignancies were excluded from the study. The Synthetic Minority Oversampling Technique with Tomek link (SMOTETomek) technique was used to compensate for data imbalance between recurrent and no-recurrent groups. Four machine learning methods, logistic regression (LR), support vector machine (SVM), random forest (RF), and Extreme gradient boosting (XGBoost), were used to identify significant factors. To overfit and improve the model performance, feature importance was calculated using the permutation importance technique. RESULTS: A total of 3320 patients were included in the study. After exclusion, the total sample size of the study was 961 patients. The median follow-up period was 60.8 months (range:1.2-192.4). The recurrence rate during follow-up was 13.2% (n = 127). After applying the SMOTETomek method, the number of patients in both groups, recurrent and non-recurrent group were equalized to 667 patients. After analyzing for 16 variables, the top eight ranked variables {pathologic Tumor stage (pT), sex, concurrent chemoradiotherapy, pathologic Node stage (pN), age, postoperative chemotherapy, pathologic Tumor-Node-Metastasis stage (pTNM), and perineural invasion} were selected based on the order of permutational importance. The highest area under the curve (AUC) was for the SVM method (0.831). The sensitivity, specificity, and accuracy were found to be 0.692, 0.814, and 0.798, respectively. The lowest AUC was obtained for the XGBoost method (0.804), with a sensitivity, specificity, and accuracy of 0.308, 0.928, and 0.845, respectively. The variable with highest importance was pT as assessed through SVM, RF, and XGBoost (0.06, 0.12, and 0.13, respectively), whereas pTNM had the highest importance when assessed by LR (0.05). CONCLUSIONS: In the current study, SVM showed the best AUC, and the most influential factor across all machine learning methods except LR was found to be pT. The rectal cancer patients who have a high pT stage during postoperative follow-up are need to be more close surveillance.

Peripheral Microneedle Patch for First-Aid Hemostasis.

Despite the minimized puncture sizes and high efficiency, microneedle (MN) patches have not been used to inject hemostatic drugs into bleeding wounds because they easily destroy capillaries when a tissue is pierced. In this study, a shelf-stable dissolving MN patch is developed to prevent rebleeding during an emergency treatment. A minimally and site-selectively invasive hemostatic drug delivery system is established by using a peripheral MN (p-MN) patch that does not directly intrude the wound site but enables topical drug absorption in the damaged capillaries. The invasiveness of MNs is histologically examined by using a bleeding liver of a Sprague-Dawley (SD) rat as an extreme wound model in vivo. The skin penetration force is quantified to demonstrate that the administration of the p-MN patch is milder than that of the conventional MN patch. Hemostatic performance is systematically studied by analyzing bleeding weight and time and comparing them with that of conventional hemostasis methods. The superior performance of a p-MN for the heparin-pretreated SD rat model is demonstrated by intravenous injection in vivo.

Comparison of Long-Term Oncologic Outcomes Between Surgical T4 and T3 in Patients Diagnosed With Pathologic Stage IIA Right Colon Cancer.

Purpose: T stage plays an important role in the classification of subgroups in stage II colon cancer. Patients with pathologic T4 are at high risk of recurrence and it is recommended to include adjuvant chemotherapy in the treatment plan, while this is not necessary in pathologic T3. There is a discrepancy between the surgical T stage (sT), as determined by the surgeon in the operative field, and pathologic T stage (pT). The pathologic stage is considered a standard prognostic factor, but it has not been established whether the surgical stage has an oncologic impact. The aim of this study was to compare oncologic outcomes between sT4 and sT3 in pathologic stage IIA right colon cancer. Methods: Between January 2005 and December 2018, there were 354 patients who underwent right hemicolectomy performed by a single surgeon (JHB) at a tertiary hospital. The data from these patients were retrospectively collected and analyzed. Only those patients with pathologic stage IIA (pT3N0M0) right colon adenocarcinomas were included in this study. Patients with mucinous carcinoma, signet ring cell carcinoma, squamous cell carcinoma, or hereditary colon cancer, and who had emergent surgery were excluded. Finally, 86 patients were included in this study. The patients were categorized, according to their surgical records, into either the sT4 group (n=28) or the sT3 group (n=58). Results: There were no statistical differences between the two groups in terms of age, sex, body mass index, comorbidities, cancer location, histologic grade, lymphovascular invasion, perineural invasion, number of harvested lymph nodes, and adjuvant chemotherapy. The 5-year overall survival rate was significantly different between the sT4 and sT3 groups (92.6% vs. 97.7%, p=0.024). In addition, the 5-year disease-free survival rate was significantly different between the sT4 and sT3 groups (88.6% vs. 97.7%, p=0.017). In the multivariate Cox regression analysis, a classification of sT4 was a significant independent predictive factor for recurrence (p = 0.023). Conclusions: Long-term oncologic outcomes have shown significant differences between surgical T4 and T3 in pathologic stage IIA right colon cancer patients. Further large-scale, multicenter studies are required to verify the clinical impact of the surgical staging.

Prognostic Value of Severity Score Change for Septic Shock in the Emergency Room.

The vital signs or laboratory test results of sepsis patients may change before clinical deterioration. This study examined the differences in prognostic performance when systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA) scores, National Early Warning Score (NEWS), and lactate levels were repeatedly measured. Scores were obtained at arrival to triage, 1 h after fluid resuscitation, 1 h after vasopressor prescription, and before leaving the emergency room (ER) in 165 patients with septic shock. The relationships between score changes and in-hospital mortality, mechanical ventilation, admission to the intensive care unit, and mortality within seven days were compared using areas under receiver operating characteristic curve (AUROCs). Scores measured before leaving the ER had the highest AUROCs across all variables (SIRS score 0.827 [0.737-0.917], qSOFA score 0.754 [0.627-0.838], NEWS 0.888 [0.826-0.950], SOFA score 0.835 [0.766-0.904], and lactate 0.872 [0.805-0.939]). When combined, SIRS + lactate (0.882 [0.804-0.960]), qSOFA + lactate (0.872 [0.808-0.935]), NEWS + lactate (0.909 [0.855-0.963]), and SOFA + lactate (0.885 [0.832-0.939]) showed improved AUROCs. In patients with septic shock, scoring systems show better predictive performances at the timepoints reflecting changes in vital signs and laboratory test results than at the time of arrival, and combining them with lactate values increases their predictive powers.

The Poisoning Information Database Covers a Large Proportion of Real Poisoning Cases in Korea.

The poisoning information database (PIDB) provides clinical toxicological information on commonly encountered toxic substances in Korea. The aim of this study was to estimate the coverage rate of the PIDB by comparing the database with the distribution of toxic substances that real poisoning patients presented to 20 emergency departments. Development of the PIDB started in 2007, and the number of toxic substances increased annually from 50 to 470 substances in 2014. We retrospectively reviewed the medical records of patients with toxic exposure who visited 20 emergency departments in Korea from January to December 2013. Identified toxic substances were classified as prescription drug, agricultural chemical, household product, animal or plant, herbal drug, or other. We calculated the coverage rate of the PIDB for both the number of poisoning cases and the kinds of toxic substances. A total of 10,887 cases of intoxication among 8,145 patients was collected. The 470 substances registered in the PIDB covered 89.3% of 8,891 identified cases related to poisoning, while the same substances only covered 45.3% of the 671 kinds of identified toxic substances. According to category, 211 prescription drugs, 58 agricultural chemicals, 28 household products, and 32 animals or plants were not covered by the PIDB. This study suggested that the PIDB covered a large proportion of real poisoning cases in Korea. However, the database should be continuously extended to provide information for even rare toxic substances.

Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

The utility of the HeartSaver Sticker for maintaining correct hand position during chest compressions.

BACKGROUND: The importance of attaining correct hand position in cardiopulmonary resuscitation (CPR) instruction has not been emphasized as much as the significance of the compression performance. STUDY OBJECTIVES: This pilot study was performed to investigate the utility of a HeartSaver Sticker for maintaining correct hand position during chest compressions. METHODS: Fifty-one sophomore college students, training to become emergency medical technicians, were recruited. The students, having no previous experience using HeartSaver stickers, participated in this prospective, randomized simulation-based controlled study, which consisted of two groups: 1) with sticker (n=26), 2) without sticker (n=25). The 4×4-cm HeartSaver sticker marked with both vertical and horizontal center lines was used in this study. Proper sticker placement was such that the vertical line coincided with the mid-sternum of the chest, and the horizontal line aligned with the nipples. Participants performed adult basic life support by single rescuer according to the 2005 American Heart Association resuscitation guidelines. Skill assessment was also performed by these guidelines. RESULTS: Group 1 participants placed the HeartSaver sticker on the correct landmark within 10 s of approaching the model. The compression rate and depth were not significantly different between the two groups. However, significant improvement in correct hand position was noticed when using the HeartSaver sticker. Correct hand position was 97.1% ± 7.4% in group 1 and 85.9% ± 21.5% in group 2 (p=0.002). CONCLUSION: The HeartSaver sticker was useful in maintaining correct hand position during the single-rescuer CPR scenario because it provided easy recognition of that position when compressing after ventilations.

Electricity generation coupled with wastewater treatment using a microbial fuel cell composed of a modified cathode with a ceramic membrane and cellulose acetate film.

A noncompartmented microbial fuel cell (NCMFC) composed of a Mn(IV)-carbon plate and a Fe(III)-carbon plate was used for electricity generation from organic wastewater without consumption of external energy. The Fe(III)-carbon plate, coated with a porous ceramic membrane and a semipermeable cellulose acetate film, was used as a cathode, which substituted for the catholyte and cathode. The Mn(IV)-carbon plate was used as an anode without a membrane or film coating. A solar cell connected to the NCMFC activated electricity generation and bacterial consumption of organic matter contained in the wastewater. More than 99 degrees of the organic matter was biochemically oxidized during wastewater flow through the four NCMFC units. A predominant bacterium isolated from the anode surface in both the conventional and the solar cell-linked NCMFC was found to be more than 99 degrees similar to a Mn(II)-oxidizing bacterium and Burkeholderia sp., based on 16S rDNA sequence analysis. The isolate reacted electrochemically with the Mn(IV)-modified anode and produced electricity in the NCMFC. After 90 days of incubation, a bacterial species that was enriched on the Mn(IV)-modified anode surface in all of the NCMFC units was found to be very similar to the initially isolated predominant species by comparing 16S rDNA sequences.

Electrochemical and biochemical analysis of ethanol fermentation of zymomonas mobilis KCCM11336.

An electrochemical bioreactor (ECB) composed of a cathode compartment and an air anode was used in this study to characterize the ethanol fermentation of Zymomonas mobilis. The cathode and air anode were constructed of modified graphite felt with neutral red (NR) and a modified porous carbon plate with cellulose acetate and porous ceramic membrane, respectively. The air anode operates as a catalyst to generate protons and electrons from water. The growth and ethanol production of Z. mobilis were 50% higher in the ECB than were observed under anoxic nitrogen conditions. Ethanol production by growing cells and the crude enzyme of Z. mobilis were significantly lower under aerobic conditions than under other conditions. The growing cells and crude enzyme of Z. mobilis did not catalyze ethanol production from pyruvate and acetaldehyde. The membrane fraction of crude enzyme catalyzed ethanol production from glucose, but the soluble fraction did not. NADH was oxidized to NAD+ in association with H2O2 reduction, via the catalysis of crude enzyme. Our results suggested that NADH/NAD+ balance may be a critical factor for ethanol producton from glucose in the metabolism of Z. mobilis, and that the metabolic activity of both growing cells and crude enzyme for ethanol fermentation may be induced in the presence of glucose.

Symbiotic relationship between Microbacterium sp. SK0812 and Candida tropicalis SK090404.

A bacterium growing inside yeast cytoplasm was observed by light microscope without staining. The bacterium was separately stained from yeast cell by a fluorescent dye, 4',6-diamidino-2-phenylindole (DAPI). The bacterium actively moved inside yeast cytoplasm and propagated in company with the yeast growth. The bacterium was separated from the yeast cytoplasm by selective disruption of yeast cells and the yeast without the intracellular bacterium (YWOB) was obtained by selective inactivation of bacterial cells. The yeast and the intracellular bacterium were identified as Candida tropicalis and Microbacterium sp., respectively. The length of Microbacterium sp. and C. tropicalis measured with SEM image was smaller than 0.5 microm and was larger than 5 microm, respectively. The yeast with the intracellular bacterium (YWIB) grew in a starch-based medium but the YWOB was not C. tropicalis has neither extracellular nor intracellular saccharification enzyme. Glucose was produced from starch by the extracellular crude enzyme (culture fluid) of Microbacterium sp. YWIB produced significantly more ethanol from glucose than YWOB but did not from starch. Conclusively, C. tropicalis is thought to catabolize starch dependent upon Microbacterium sp. growing in its cytoplasm and furnish stable habitat for the Microbacterium sp.

Characterization of exopolysaccharide (EPS) produced by Weissella hellenica SKkimchi3 isolated from kimchi.

Weissella hellenica SKkimchi3 produces the higher exopolysaccharide (EPS) on sucrose than lactose, glucose, and fructose at pH 5 and 20 degrees C. Sucrose was exclusively used to cultivate SKkimchi3 in all experiments base on the EPS production tests. The molecular mass of EPS, as determined by gel permeation chroma-tography, was 203,000. (1)H and (13)C NMR analysis indicated that the identity of EPS may be a glucan. When EPS, starch, and cellulose was treated with a-amylase, glucoamylase, glucosidase, and cellulase, glucose was produced from starch and cellulose but was not produced from EPS. Based on HPLC analysis, elemental analysis, (1)H and (13)C NMR analysis, and enzymatic hydrolysis tests, EPS was estimated to be a glucan. EPS suspension was not precipitated even by centrifugation at 10,000xg for 60 min, and EPS made the fermented milk and bacterial culture viscous.

Effect of electrochemical redox reaction on growth and metabolism of Saccharomyces cerevisiae as an environmental factor.

The effect of an electrochemically generated oxidation-reduction potential and electric pulse on ethanol production and growth of Saccharomyces cerevisiae ATCC 26603 was experimented and compared with effects of electron mediators (neutral red, benzyl viologen, and thionine), chemical oxidants (hydrogen peroxide and hypochlorite), chemical reductants (sulfite and nitrite), oxygen, and hydrogen. The oxidation (anodic) and reduction (cathodic) potential and electric pulse activated ethanol production and growth, and changed the total soluble protein pattern of the test strain. Neutral red electrochemically reduced activated ethanol production and growth of the test strain, but benzyl viologen and thionine did not. Nitrite inhibited ethanol production but did not influence growth of the test strain. Hydrogen peroxide, hypochlorite, and sulfite did not influence ethanol production and growth of the test strain. Hydrogen and oxygen also did not influence the growth and ethanol production. It shows that the test strain may perceive electrochemically generated oxidation-reduction potential and electric pulse as an environmental factor.

Metabolic characterization of lactic acid bacterium Lactococcus garvieae sk11, capable of reducing ferric iron, nitrate, and fumarate.

A lactic acid bacterium capable of anaerobic respiration was isolated from soil with ferric iron-containing glucose basal medium and identified as L. garvieae by using 16S rDNA sequence homology. The isolate reduced ferric iron, nitrate, and fumarate to ferrous iron, nitrite, and succinate, respectively, under anaerobic N2 atmosphere. Growth of the isolate was increased about 30-39% in glucose basal medium containing nitrate and fumarate, but not in the medium containing ferric iron. Specifically, metabolic reduction of nitrate and fumarate is thought to be controlled by the specific genes fnr, encoding FNR-like protein, and nir, regulating fumarate-nitrate reductase. Reduction activity of ferric iron by the isolate was estimated physiologically, enzymologically, and electrochemically. The results obtained led us to propose that the isolate metabolized nitrate and fumarate as an electron acceptor and has specific enzymes capable of reducing ferric iron in coupling with anaerobic respiration.