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Abstract Ferroptosis, a regulated form of cell death dependent on reactive oxygen species (ROS), is characterized by iron accumulation and lethal lipid peroxidation. Mitochondria serve as the primary source of ROS and thus play a crucial role in ferroptosis initiation and execution. This study highlights the role of mitochondrial ROS and the significance of voltage-dependent anion channel 1 (VDAC1) oligomerization in ferroptosis induced by cysteine deprivation or ferroptosis-inducer RSL3. Our results demonstrate that the mitochondria-targeted antioxidants MitoQ and MitoT effectively block ferroptosis induction and that dysfunction of complex III of the mitochondrial electron transport chain contributes to ferroptosis induction. Pharmacological inhibitors that target VDAC1 oligomerization have emerged as potent suppressors of ferroptosis that reduce mitochondrial ROS production. These findings underscore the critical involvement of mitochondrial ROS production via complex III of the electron transport chain and the essential role of VDAC1 oligomerization in ferroptosis induced by cysteine deprivation or RSL3. This study deepens our understanding of the intricate molecular networks governing ferroptosis and provides insights into the development of novel therapeutic strategies targeting dysregulated cell death pathways.

A fire in a marine energy storage system (ESS) has a high risk because of the special situation of the sea compared with land systems. To mitigate serious damage in the event of a fire in marine ESSs, initial suppression of the fire is extremely important. In this study, a unit module-based fire extinguishing system was constructed for the initial suppression of an ESS fire, and a unit module fire suppression test was conducted. In addition, multiple modules were constructed to evaluate the impact of unit module fire suppression on adjacent modules. Novec 1230 and F-500, which are adaptable to ESS fire control, were used as extinguishing agents. The fire suppression test results showed that both extinguishing agents could effectively suppress the ESS fire in the initial stage using the proposed fire extinguishing system. The results of this study will contribute to the development of maritime safety protocols and practical measures for reinforcing preparation for ESS-related fire accidents.

Abstract Amino acid availability is sensed by various signaling molecules, including general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1). However, it is unclear how these sensors are associated with cancer cell survival under low amino acid availability. In the present study, we investigated AKT activation in non-small cell lung cancer (NSCLC) cells deprived of each one of 20 amino acids. Among the 20 amino acids, deprivation of glutamine, arginine, methionine, and lysine induced AKT activation. AKT activation was induced by GCN2/ATF4/REDD1 axis-mediated mTORC2 activation under amino acid deprivation. In CRISPR-Cas9-mediated REDD1-knockout cells, AKT activation was not induced by amino acid deprivation, indicating that REDD1 plays a major role in AKT activation under amino acid deprivation. Knockout of REDD1 sensitized cells cultured under glutamine deprivation conditions to radiotherapy. Taken together, GCN2/ATF4/REDD1 axis induced by amino acid deprivation promotes cell survival signal, which might be a potential target for cancer therapy.

Abstract Background Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood. Methods To investigate the molecular mechanisms underlying the effect of metformin on the mTORC1 inhibition, MTT assay, RT-PCR, and western blot analysis were performed. Results Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity. Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment. Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation. Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib. Conclusions ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.

Background Melatonin, a neurohormone, maybe involved in physiological processes, such as antioxidation, anti-inflammation, and hair growth. In the present study, we investigated the effects of melatonin on proliferation and intracellular signaling in DP cells using a three-dimensional (3D) spheroid culture system that mimics the in vivo hair follicle system. Methods DP cells were incubated in monolayer (2D) and 3D spheroid culture systems. The expression levels of melatonin receptors in DP cells were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. The effect of melatonin on the hair-inductive property of DP cells was analyzed using a WST-1-based proliferation assay, determination of DP spheroid size, expression analysis of DP signature genes, and determination of β-catenin stabilization in DP cells. The AKT/GSK3β/β-catenin signaling pathway associated with melatonin-induced β-catenin stabilization in DP cells was investigated by analyzing changes in upstream regulator proteins, including AKT, GSK3β, and their phosphorylated forms. Results The expression levels of the melatonin receptors were higher in human DP cells than in human epidermal keratinocytes and human dermal fibroblast cells. Comparing the expression level according to the human DP cell culture condition, melatonin receptor expression was upregulated in the 3D culture system compared to the traditional two-dimensional monolayer culture system. Cell viability analysis showed that melatonin concentrations up to 1 mM did not affect cell viability. Moreover, melatonin increased the diameter of DP cell 3D spheroids in a dose-dependent manner. Immunoblotting and qRT-PCR analysis revealed that melatonin upregulated the expression of hair growth-related genes, including alkaline phosphatase, bone morphogenetic protein 2, versican, and wingless-int 5A, in a melatonin receptor-dependent manner. Cell fractionation analysis showed that melatonin increased the nuclear localization of β-catenin. This result correlated with the increased transcriptional activation of T-cell factor/lymphoid enhancer factor-responsive luciferase induced by melatonin treatment. Interestingly, melatonin induced the phosphorylation of protein kinase B/AKT at serine 473 residue and GSK-3β at serine 9 residue. To determine whether AKT phosphorylation at serine 473 induced β-catenin nuclear translocation through GSK3β phosphorylation at serine 9, the PI3K/AKT inhibitor LY294002 was cotreated with melatonin. Immunoblotting showed that LY294002 inhibited melatonin-induced phosphorylation of GSK3β at serine 9 residue and β-catenin activation. Conclusion Collectively, this report suggests that melatonin promotes growth properties by activating the AKT/GSK3β/β-catenin signaling pathway through melatonin receptors.

As part of the environmentally friendly policy of ships, active research is being conducted on energy storage systems (ESS) for ships. This ESS has a major influence on determining the propulsion and operation system of the ship in the future. A separate space must be provided for the ESS, but small and medium-sized ships often require it to be located at the bottom of the ship to make use of the available space. If the ESS is located at the bottom of the ship, the slamming impact load should be considered, and a study of the vibrations generated during the slamming impact is required. Ships are subjected to various environmental effects while sailing. Among them, the risk factor caused by waves is one of the direct risk factors for the operation of the ship. This slamming phenomenon affects not only ships but also offshore structures, and is a risk factor that can cause structural damage as well as damage to human life. Therefore, it is necessary to study the slamming load, and a method is needed to address it with a dynamic load instead of a static load. In order to reflect the slamming load in the design as a dynamic load rather than the equivalent hydrostatic pressure, which is a static load, it is necessary to study the elastic effect of the structure. The plate thickness is calculated by considering the equivalent design pressure based on the measured slamming pressure peak, and several experimental and theoretical studies have been conducted to estimate the exact value of the peak pressure. However, according to recent studies, structural damage is affected not only by the peak pressure but also by the peak width in the time interval of the peak pressure. Research on slamming has been ongoing for a long time, but structural damage due to slamming is still being reported steadily. In order to understand the slamming phenomenon and reflect it in the structural design formula, high-quality experimental results are required. The slamming phenomenon occurs in a very short time. In order to obtain high-quality experimental results for this slamming phenomenon, numerous experimental variables such as experimental equipment setting, appropriate sensor selection, and data measurement and storage capability must be carefully considered. Normally the slamming load can be expressed in terms of peak pressure, peak width, and duration of the pressure, and the maximum pressure and the idealized pressure value (impulse) are applied to the structure. This slamming pressure is affected by the shape and natural period of the structure and shows the largest pressure value when the dead-rise angle is 3° to 10°. In this study, the test was performed by repeatedly dropping into the water using structural bottom angles of 0°, 3°, 10°, and 20° to the free surface of the water. The peak pressure, peak width, impulse, pressure coefficient, and traveling velocity of peak pressure obtained from the repeated tests are estimated with mean and coefficient of variation.

Estradiol is a key factor for tumorigenesis and prognosis of hormone receptor-positive breast cancer. Adipocytes are one source of estradiol in patients with breast cancer. Recent studies have shown that phosphorylated ribosomal protein S6 kinase-1 plays a critical role in adipogenesis. Therefore, estrogen depletion therapy might have beneficial effects in phosphorylated ribosomal protein S6 kinase-1-positive breast cancer. This study was conducted to evaluate the value of phosphorylated ribosomal protein S6 kinase-1 as a marker for gonadotropin-releasing hormone agonist treatment, a form of estrogen depletion therapy, for premenopausal patients with HR-positive, human epidermal growth factor receptor 2-negative breast cancer. We reviewed the medical records of 296 premenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary invasive breast cancer treated between 2008 and 2015. Phosphorylated ribosomal protein S6 kinase-1 positivity was defined by immunohistochemical staining scores of 1+, 2+ and 3+, whereas a score of 0 was considered negative. Phosphorylated ribosomal protein S6 kinase-1-positive tumors were found in 74.0% of the patients. In the phosphorylated ribosomal protein S6 kinase-1-positive group, disease-free survival of patients treated with a gonadotropin-releasing hormone agonist was significantly longer than that of patients treated without a gonadotropin-releasing hormone agonist (mean 106.7 months vs mean 91.1 months, P = 0.018). Phosphorylated ribosomal protein S6 kinase-1 is a potential biomarker for predicting the efficacy of gonadotropin-releasing hormone agonist therapy in premenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.

Ovarian cancer is a carcinoma that affects women and that has a high mortality rate. Overcoming paclitaxel resistance is important for clinical application. However, the effect of amino acid metabolism regulation on paclitaxel-resistant ovarian cancer is still unknown. In this study, the effect of an amino acid-deprived condition on paclitaxel resistance in paclitaxel-resistant SKOV3-TR cells was analyzed. We analyzed the cell viability of SKOV3-TR in culture conditions in which each of the 20 amino acids were deprived. As a result, the cell viability of the SKOV3-TR was significantly reduced in cultures deprived of arginine, glutamine, and lysine. Furthermore, we showed that the glutamine-deprived condition inhibited mTORC1/S6K signaling. The decreased cell viability and mTORC1/S6K signaling under glutamine-deprived conditions could be restored by glutamine and α-KG supplementation. Treatment with PF-4708671, a selective S6K inhibitor, and the selective glutamine transporter ASCT2 inhibitor V-9302 downregulated mTOR/S6K signaling and resensitized SKOV3-TR to paclitaxel. Immunoblotting showed the upregulation of Bcl-2 phosphorylation and a decrease in Mcl-1 expression in SKOV3-TR via the cotreatment of paclitaxel with PF-4708671 and V-9302. Collectively, this study demonstrates that the inhibition of glutamine uptake can resensitize SKOV3-TR to paclitaxel and represents a promising therapeutic target for overcoming paclitaxel resistance in ovarian cancer.

In the era of precision medicine, the prediction of ovarian function recovery from chemotherapy-induced amenorrhoea using feasible biological markers may be helpful to optimise the treatment strategy for young patients with hormone receptor-positive breast cancer. The purpose of this study was to investigate the accuracy of post-chemotherapy biological markers for predicting the recovery of ovarian function in breast cancer patients of the ASTRRA trial, with chemotherapy-induced amenorrhoea. Using data of 82 participants from a single institution in the ASTRRA trial, the post-chemotherapy serum levels of the anti-Müllerian hormone (AMH), oestradiol, inhibin B and other clinical factors associated with chemotherapy-induced amenorrhoea were evaluated. Recovery of ovarian function was defined by the resumption of menstruation manifested by vaginal bleeding. Fifty-two patients regained menstruation within 55 months after enrolment. In univariate analysis,

Abstract Background Mammary gland tumors are the most common tumors in sexually intact female dogs; however, they are rare in male dogs. This study was conducted to investigate the relationship between sexual hormones and mammary gland tumors in a male dog. Case presentation A 13-year-old, intact male Cocker Spaniel presented to the Veterinary Teaching Hospital of Kangwon National University, Republic of Korea, with an acute right ruptured caudal abdominal mass. Physical examination revealed a 14 × 14 cm ruptured mass in the right caudal abdomen, as well as a 1.5 × 1.5 cm mass in the first right mammary gland. The estrogen and progesterone concentrations in serum were within normal levels. Total mastectomy was done on the right side mammary glands. Following surgery, the site was fully recovered; however, a mass that had grown to 2 × 2 cm was found in the left fifth mammary gland and a testis tumor was also found over the period of 4 months. Mastectomy was performed on the left caudal mammary gland and castration was also performed. After the final surgery, the dog fully recovered. Histopathological examination of all three masses revealed high grade mammary adenocarcinoma in the mammary gland and the testis was diagnosed as Leydig cell adenoma. Immunohistochemical analysis revealed that the estrogen and progesterone receptors were expressed on limited cells in mammary and testis tumors. Conclusion The results of this study suggest that mammary tumors and testes tumors can occur in male dogs without relationship to female sexual hormone.

Circadian oscillation is an essential process that influences many physiological and biological mechanisms and a decrease of circadian genes is associated with many diseases such as cancer. Despite many efforts to identify the detailed mechanism for decreasing circadian genes and recovering reduced circadian genes in cancer, it is still largely unknown. We found that BMAL1 was reduced in tumor hypoxia-induced acidosis, and recovered by selectively targeting acidic pH in breast cancer cell lines. Surprisingly, BMAL1 was reduced by decrease of protein stability as well as inhibition of transcription under acidosis. In addition, melatonin significantly prevented acidosis-mediated decrease of BMAL1 by inhibiting lactate dehydrogenase-A during hypoxia. Remarkably, acidosis-mediated metastasis was significantly alleviated by BMAL1 overexpression in breast cancer cells. We therefore suggest that tumor hypoxia-induced acidosis promotes metastatic potency by decreasing BMAL1, and that tumor acidosis could be a target for preventing breast cancer metastasis by sustaining BMAL1.

Case summary This report describes a rare case of crossed fused renal ectopia (CFRE) in a cat. A mature intact male Persian cat presented with bloody nasal discharge and ascites. Diagnostic studies revealed an ectopic left kidney fused with an orthotopic right kidney and a concurrent feline infectious peritonitis (FIP) infection. The FIP was responsible for clinical signs in this cat, while clinical signs associated with CFRE were not obvious. Despite receiving intensive treatment, the cat died. A post-mortem examination was not performed because the owners declined approval. Relevance and novel information To the best of our knowledge, this is the first report of L-shaped CFRE in a cat. In addition, this report describes the CT features of L-shaped CFRE in a cat.

Quercetin and genistein, plentifully present in fruits and vegetables, are flavonoid family members that have antioxidative function and plant-derived phytoestrogen activity. The antioxidative effects of quercetin and genistein on boar sperm characteristics and In Vitro development of IVF embryo were investigated. The sperm motility was increased by addition of genistein 50 μM for 6 hr incubation compared to control (p

Ionizing radiation (IR) has been widely used in the treatment of cancer. Radiation-induced DNA damage triggers the DNA damage response (DDR), which can confer radioresistance and early local recurrence by activating DNA repair pathways. Since karyopherin-α2 (KPNA2), playing an important role in nucleocytoplasmic transport, was significantly increased by IR in our previous study, we aimed to determine the function of KPNA2 with regard to DDR. Exposure to radiation upregulated KPNA2 expression in human colorectal cancer HT29 and HCT116 cells and breast carcinoma MDA-MB-231 cells together with the increased expression of DNA repair protein BRCA1. The knockdown of KPNA2 effectively increased apoptotic cell death via inhibition of BRCA1 nuclear import following IR. Therefore, we propose that KPNA2 is a potential target for overcoming radioresistance via interruption to DDR.

Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrientrich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry) zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic β-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the prevalence of cranial cruciate ligament rupture (RCCL) and the efficacy of tibial plateau angle (TPA) as a prognostic indicator in small breed dogs diagnosed with RCCL. Materials and Methods: For this study, 53 dogs with RCCL were selected based on their medical data. The Tibial plateau angle (TPA) was calculated by analyzing the radiographic images of the stifle joint region. The dogs were categorized based on their body weight, sex, age, breed, and RCCL. Subsequently, clinical outcomes of dogs were evaluated based on their pre- and postoperative TPAs. Results: The prevalence of RCCL was higher in neutered dogs, especially those neutered before 6 months of age. The preoperative TPAs of all dogs diagnosed with RCCL were lowered with TPLO. Preoperative walking time in the higher pre-operative TPA (>25°) group (13.58 ± 1.53 days) was significantly (p < 0.05) longer than the lower pre-operative TPA (=25°) group (10.09 ± 0.84). The lower pre-operative TPA (= 25°) group showed better prognoses without any more complications than the higher pre-operative TPA (> 25°) group. Furthermore, post-operative walking time in the higher post-operative TPA dogs (>10°) group (18.08 ± 2.22 days) was significantly (p < 0.05) longer than the lower post-operative TPA dogs (=10°) group (10.20 ± 0.90 days). Likewise, the TPA (=10°) group showed better prognoses with lowered complications. Conclusion: Therefore, pre- and post-operative TPA plays an important prognostic factor, and post-operative TPA should be kept at<10° to get better clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective : Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The treatment of PD aims to alleviate motor symptoms by replacing the reduced endogenous dopamine. Currently, there are no disease-modifying agents for the treatment of PD. Zebrafish (Danio rerio) have emerged as an effective tool for new drug discovery and screening in the age of translational research. The neurotoxin 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain, with corresponding Parkinsonian symptoms. L-type calcium channels (LTCCs) have been implicated in the generation of mitochondrial oxidative stress, which underlies the pathogenesis of PD. Therefore, we investigated the neuro-restorative effect of LTCC inhibition in an MPTP-induced zebrafish PD model and suggested a possible drug candidate that might modify the progression of PD. Methods : All experiments were conducted using a line of transgenic zebrafish, Tg(dat:EGFP), in which green fluorescent protein (GFP) is expressed in dopaminergic neurons. The experimental groups were exposed to 500 μmol MPTP from 1 to 3 days post fertilization (dpf). The drug candidates : levodopa 1 mmol, nifedipine 10 μmol, nimodipine 3.5 μmol, diethylstilbestrol 0.3 μmol, luteolin 100 μmol, and calcitriol 0.25 μmol were exposed from 3 to 5 dpf. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized in vivo by confocal microscopy. Results : Levodopa, nimodipine, diethylstilbestrol, and calcitriol had significant positive effects on the restoration of motor behavior, which was damaged by MPTP. Nimodipine and calcitriol have significant positive effects on the restoration of dopaminergic neurons, which were reduced by MPTP. Through locomotor analysis and dopaminergic neuron quantification, we identified the neuro-restorative effects of nimodipine and calcitriol in zebrafish MPTP-induced PD model. Conclusion : The present study identified the neuro-restorative effects of nimodipine and calcitriol in an MPTP-induced zebrafish model of PD. They restored dopaminergic neurons which were damaged due to the effects of MPTP and normalized the locomotor activity. LTCCs have potential pathological roles in neurodevelopmental and neurodegenerative disorders. Zebrafish are highly amenable to high-throughput drug screening and might, therefore, be a useful tool to work towards the identification of diseasemodifying treatment for PD. Further studies including zebrafish genetic models to elucidate the mechanism of action of the diseasemodifying candidate by investigating Ca2+ influx and mitochondrial function in dopaminergic neurons, are needed to reveal the pathogenesis of PD and develop disease-modifying treatments for PD. [ABSTRACT FROM AUTHOR]

Dermatophytic pseudomycetoma (DPM), which is a deeper dermal and/ or subcutaneous infection of dermatophytes, has been rarely reported in Domestic Korean Short Hair Cats. A 3-year-old, spayed female, domestic Korean Short Hair Cat presented with a history of crusts, nodules, and pruritus for 1 year. At the initial presentation, multifocal ulcerative nodules covered with yellowish grains were noted on her ventral thorax, abdomen, flank, and left hindlimb. Cytology of ulcerative nodules revealed degenerative neutrophils, macrophages, multinucleated giant cells, and hyphae. Histological examination of nodules revealed pyogranulomatous dermatitis with fungal plaques, and Microsporum canis and Staphylococcus aureus were identified in the culture. Therefore, the cat was diagnosed with DPM with secondary pyoderma. Oral itraconazole (10 mg/kg, once a day) was administered, but no significant improvement was observed. Therefore, intralesional (IL) injection of amphotericin B (0.6 mg/nodule) and oral administration of terbinafine (30 mg/kg, twice a day) were administered to the cat. With these medications, ulceration and the number and size of nodules decreased significantly, although large dome-shaped nodules remained. Skin lesions were treated with oral terbinafine and itraconazole administration for 5 months. However, after 6 months, recurrence of multifocal ulcerative nodules was observed, and the cat died 10 months after initial presentation. In this case, IL amphotericin B and oral terbinafine administration were partially effective in DPM treatment, suggesting that this may be an option for DPM treatment. Further studies to determine dose and frequency of IL amphotericin B in the management of DPM are warranted. [ABSTRACT FROM AUTHOR]

We investigate the relationship between CEO risk incentives and the innovation premium (IP) proposed by Forbes. We suggest that compared to traditional proxies of innovation, the IP is a comprehensive measure of a firm's overall innovation and, therefore, can measure innovation effectiveness in broader industries. We find that both option vega and vega-todelta ratio, as measures of CEO risk incentives, have a positive relationship with the IP. Additional tests reveal that the traditional patent-related outputs are also motivated by CEO risk incentives, but only in the IT industry. Overall, our findings are consistent with (1) the empirical evidence of Coles et al. (2006, Journal of Financial Economics 79, 431) that a higher vega after controlling for delta motivates managers to implement riskier policy choices and (2) the argument (Dittmann et al. 2017, Review of Finance 21, 1805) that the strength of the risk-taking incentive relative to the performance-based incentive, the vega-to-delta ratio, captures CEO risk-taking incentives more accurately. [ABSTRACT FROM AUTHOR]

Purpose: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF. Materials and Methods: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of =50.4 Gy were defined as the non-boost group, while =54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed. Results: A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211). Conclusion: Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed. [ABSTRACT FROM AUTHOR]

Background/Aims: Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole. [ABSTRACT FROM AUTHOR]

Neisseria (N.) animaloris is a common flora in animals, but its pathogenicity is rarely reported. In this case report, N. animaloris was isolated from a hospitalized cat with pneumonia. The cat was discharged after testing and treatment with appropriate antibiotics. This paper reports the first case of N. animaloris pneumonia in Korea. [ABSTRACT FROM AUTHOR]

We document sizable and robust excess return comovement between migration-flow receiving and sending states at the state-portfolio level. Migration comovement is not fully explained by economic fundamentals and strengthens with the size of the migration network. Consistent with the view that it is partially driven by correlated trading of a common investor base within migration networks, migration comovement a) increases substantially when there is an exogenous positive shock to migration flows, b) is greater with old firms in migration-sending states, and c) strengthens when retail investors display "old home" bias in addition to local bias. [ABSTRACT FROM AUTHOR]