Radical Gastrectomy After Chemotherapy May Prolong Survival in Stage IV Gastric Cancer: A Korean Multi-institutional Analysis.

ABASTRACT: BACKGROUND: Despite the development of newer treatments, the prognosis for patients with stage IV gastric cancer remains grave. This study evaluated the efficacy of gastrectomy following response to chemotherapy in patients with stage IV gastric cancer. METHODS: A total of 419 patients who were diagnosed with stage IV gastric cancer were identified from the multi-institutional Catholic Gastric Cancer Study Group database. The patients were divided into four groups: 212 were in the chemotherapy only (CTx) group, 124 were in the chemotherapy after palliative gastrectomy (G-CTx) group, 23 were in the radical gastrectomy after chemotherapy (CTx-G) group, and 60 were in the best supportive care group. To compensate for the effects of chemotherapy, cases of chemotherapy responsive were analyzed separately. To identify factors affecting survival rates, cure rates for surgery in the surgery group were analyzed. RESULTS: The 3-year survival rate of the CTx-G group was significantly higher than that of the CTx group (42.8 vs. 12.0%, p = 0.001). Moreover, the CTx-G group's 3-year survival rate was greater than that of the G-CTx group (42.8 vs. 37.1%, p = 0.207). Chemotherapy-responsive patients in the CTx-G group had a better 3-year survival rate than those in the G-CTx group (46.1 vs. 18.4%, respectively, p = 0.011). In the surgery group, R0 resection led to a significantly better 3-year survival rate than palliative gastrectomy (61.1 vs. 16.2%, p = 0.003). CONCLUSIONS: Adjuvant surgery might improve the survival rate of patients with stage IV gastric cancer, particularly in R0 resection cases.

Review of Image-Processing-Based Technology for Structural Health Monitoring of Civil Infrastructures.

The continuous monitoring of civil infrastructures is crucial for ensuring public safety and extending the lifespan of structures. In recent years, image-processing-based technologies have emerged as powerful tools for the structural health monitoring (SHM) of civil infrastructures. This review provides a comprehensive overview of the advancements, applications, and challenges associated with image processing in the field of SHM. The discussion encompasses various imaging techniques such as satellite imagery, Light Detection and Ranging (LiDAR), optical cameras, and other non-destructive testing methods. Key topics include the use of image processing for damage detection, crack identification, deformation monitoring, and overall structural assessment. This review explores the integration of artificial intelligence and machine learning techniques with image processing for enhanced automation and accuracy in SHM. By consolidating the current state of image-processing-based technology for SHM, this review aims to show the full potential of image-based approaches for researchers, engineers, and professionals involved in civil engineering, SHM, image processing, and related fields.

Characteristics of the ErmK Protein of Bacillus halodurans C-125.

Bacillus halodurans C-125 is an alkaliphilic microorganism that grows best at pH 10 to 10.5. B. halodurans C-125 harbors the erm (erythromycin resistance methylase) gene as well as the mphB (macrolide phosphotransferase) and putative mef (macrolide efflux) genes, which confer resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics. The Erm protein expressed in B. halodurans C-125 could be classified as ErmK because it shares 66.2% and 61.2% amino acid sequence identity with the closest ErmD and Erm(34), respectively. ErmK can be regarded as a dimethylase, as evidenced by reverse transcriptase analysis and the antibiotic resistance profile exhibited by E. coli expressing ermK. Although ErmK showed one-third or less in vitro methylating activity compared to ErmC', E. coli cells expressing ErmK exhibited comparable resistance to erythromycin and tylosin, and a similar dimethylation proportion of 23S rRNA due to the higher expression rate in a T7 promoter-mediated expression system. The less efficient methylation activity of ErmK might reflect an adaption to mitigate the fitness cost caused by dimethylation through the Erm protein presumably because B. halodurans C-125 has less probability to encounter the antibiotics in its favorable growth conditions and grows retardedly in neutral environments. IMPORTANCE Erm proteins confer MLSB antibiotic resistance (minimal inhibitory concentration [MIC] value up to 4,096 µg/mL) on microorganisms ranging from antibiotic producers to pathogens, imposing one of the most pressing threats to clinics. Therefore, Erm proteins have long been speculated to be plausible targets for developing inhibitor(s). In our laboratory, it has been noticed that there are variations in enzymatic activity among the Erm proteins, Erm in antibiotic producers being better than that in pathogens. In this study, it has been observed that Erm protein in B. halodurans C-125 extremophile is a novel member of Erm protein and acts more laggardly, compared to that in pathogen. While this sluggishness of Erm protein in extremophile might be evolved to reduce the fitness cost incurred by Erm activity adapting to its environments, this feature could be exploited to develop the more potent and/or efficacious drug to combat formidably problematic antibiotic-resistant pathogens.

Efficacy and safety of alemtuzumab in Korean multiple sclerosis patients.

BACKGROUND: Efficacy and safety profiles of alemtuzumab for relapsing-remitting multiple sclerosis (RRMS) mainly come from Western countries and have not been reported in Asian populations. The aim of this study was to report the efficacy and safety of alemtuzumab for RRMS patients in a Korean population. METHODS: We retrospectively reviewed RRMS patients treated with alemtuzumab. Study outcomes included annualized relapse rate (ARR), expanded disability status scale (EDSS) score, 6-month confirmed disability worsening (CDW), confirmed disability improvement (CDI), MRI lesion activity (new/enlarging T2 hyperintense and gadolinium-enhancing T1 lesions), no evidence of disease activity (NEDA), and adverse events. RESULTS: Nineteen patients were identified and mean follow-up was 1.5 years after alemtuzumab initiation. Mean ARR fell from 1.20 pre-treatment to 0.30 post-treatment (p < 0.001). Mean EDSS score remained stable, with a change from baseline of -0.08 at 1 year. After treatment, 16 patients (84.2%) had freedom from 6-month CDW, 3 (15.8%) had 6-month CDI, 11 (57.9%) had freedom from new/enlarging T2 hyperintense lesions, 13 (68.4%) had freedom from gadolinium-enhancing lesions, and 10 (52.6%) had NEDA. Four patients (21.1%) developed relapses after alemtuzumab therapy. CONCLUSION: Alemtuzumab efficacy and safety were similar to that reported previously in Western populations. Severe relapses can occur after alemtuzumab administration.

The Effect of Cognitive Intervention on Cognitive Improvement in Patients with Dementia.

BACKGROUND AND PURPOSE: The effect of cognitive intervention in patients with dementia is inconsistent. This study sought to find out the effect of cognitive intervention by measuring interval change between before and after intervention. METHODS: We evaluated cognitive changes according to clinical diagnostic group across Gangwon province for 940 patients with dementia diagnosed at hospital clinics and 2,975 subjects without dementia. All subjects were treated with cognitive intervention. They underwent a cognitive and mood assessment before and after intervention. We used interval change of Mini-Mental State Examination (MMSE) scores as a primary measure of interventional outcome. RESULTS: Changes in mean MMSE score were significantly different between the non-dementia group and the dementia group (p=0.016), with changes of 0.7±2.4 and 1.0±3.7 points (±standard deviation), respectively. Cognitive improvement regarding completion of session was significantly higher in the dementia group (p=0.001), with changes of 0.41±4.51 for uncompleted group and 1.30±3.22 points for completed ones. Lower initial MMSE scores, lower age, and type of intervention were found to be independent predictive factors of subsequent cognitive changes as indicated by mean MMSE scores. CONCLUSIONS: These findings suggest that cognitive intervention might be useful for patients with dementia. Their response to treatment might be related to the type of intervention.

Differential stringent responses of Streptomyces coelicolor M600 to starvation of specific nutrients.

This study focused on the involvement of the unusual nucleotide (p)ppGpp, a stringent factor, during the morphological and physiological differentiation of Streptomyces coelicolor. Two genes, relA and rshA, were disrupted to demonstrate the roles of the stringent factor in the differentiation. The intracellular concentration of (p)ppGpp in the wild-type (M600) and disrupted mutants was measured in relation to the intentional starvation of a specific nutrient such as carbon, nitrogen, and phosphate or the in situ depletion of nutrients in a batch culture. As a result, it was found that the morphological characteristic of the deltarelA mutant was a bld phenotype forming condensed mycelia, whereas the deltarshA mutant grew fast-forming spores and straightforward mycelia. In both mutants, the production of actinorhodin (Act) was completely abolished, yet the undecylprodigiosin (Red) production was increased. Intracellular (p)ppGpp was detected in the deltarelA mutant in the case of limited phosphate, yet not with limited carbon or nitrogen sources. In contrast, (p)ppGpp was produced in the deltarshA mutant under limited carbon and nitrogen conditions. Therefore, (p)ppGpp in S. coelicolor was found to be selectively regulated by either the RelA or RshA protein, which was differentially expressed in response to the specific nutrient limitation. These results were also supported by the in situ ppGpp production during a batch culture. Furthermore, it is suggested that RelA and RshA are bifunctional proteins that possess the ability to both synthesize and hydrolyze (p)ppGpp.

Inflammatory markers associated with seizures.

Seizures can produce systemic changes, including elevated body temperature, white blood cell count, and C-reactive protein levels, which raises concern for potential infection. We describe seizure-induced inflammation-like responses and discuss how these changes may be distinguished from those associated with infection. We prospectively investigated 140 consecutive visits to the emergency room, in which patients presented with seizures. We defined elevated body temperature, white blood cell count, or C-reactive protein levels as inflammation-like responses. We investigated the occurrence of inflammation-like responses, characteristics of the seizures, neurological status at the initial visit, outcomes, and clinical findings to determine the presence of infection. We ascertained whether the patients had infection or not based on the overall information post-discharge. An inflammation-like response was observed in 56.3% of all visits and 19.3% were diagnosed with concurrent infection. Among the visits with inflammation-like response, 34.7% were shown to have an infection. Increases in body temperature and C-reactive protein levels were milder (<39°C and <6 mg/dl, respectively) in patients without infection compared to those with infection, whereas there was no difference in leukocytosis, with regard to the presence or absence of infection. Increased body temperature occurred only in cases of generalized tonic-clonic seizures, whereas leukocytosis and elevated C-reactive protein levels were reported in patients with any type of seizure. Body temperatures returned to normal within eight hours in uncomplicated cases. Seizures frequently induce an increase in body temperature, white blood cell count, or C-reactive protein levels, making it challenging to distinguish these changes from those associated with infection. Nonetheless, elevated body temperature in the absence of generalized tonic-clonic seizures, above 39̊C, or persisting for more than eight hours after recovery of consciousness, and C-reactive protein levels above 6 mg/dl warrant close observation and consideration for concurrent infection.

The complete mitochondrial genome of Grapsus tenuicrustatus (Herbst, 1783) (Decapoda, Grapsidae).

A complete mitochondrial genome was sequenced from a grapsid crab, Grapsus tenuicrustatus (Herbst 1783), which was collected from a rocky intertidal zone of Chuuk lagoon. The size of mitochondrial genome is 15,858 bp with 31.9% A, 22.8% C, 12.2% G and 33.1% T distribution. Furthermore phylogenetic relationships of the Grapsoidea evaluated due to mitochondrial protein-coding genes. As per the obtained results, the families Grapsidae and Varunidae have sister group relationship in the superfamily Grapsoidea.

Identification and use of zinc finger transcription factors that increase production of recombinant proteins in yeast and mammalian cells.

Randomized ZFP-TF libraries could induce a specific phenotype without detailed knowledge about the phenotype of interest because, theoretically, the libraries could modulate any gene in the target organism. We have developed a novel method for enhancing the efficiency of recombinant protein production in mammalian and microbial cells using combinatorial libraries of zinc finger protein transcription factors. To this end, we constructed tens of thousands of zinc finger proteins (ZFPs) with distinct DNA-binding specificities and fused these ZFPs to either a transcriptional activation or repression domain to make transcriptional activators or repressors, respectively. Expression vectors that encode these artificial transcription factors were delivered into Saccharomyces cerevisiae or HEK 293 cells along with reporter plasmids that code for human growth hormone (hGH) or SEAP (secreted alkaline phosphatase) (for yeast or HEK, respectively). Expression of the reporter genes was driven by either the cytomegalovirus (CMV) or SV40 virus promoters. After transfection, we screened the cells for increased synthesis of the reporter proteins. From these cells, we then isolated several ZFP-transcription factors (ZFP-TFs) that significantly increased hGH or SEAP synthesis and subjected these regulatory proteins to further characterization. Our results show that randomized ZFP-TF libraries are useful tools for improving the yield of heterologous recombinant protein both in yeast and mammalian cells.

A novel method for the management of proximal segment using computer assisted simulation surgery: correct condyle head positioning and better proximal segment placement.

Computer Assisted Simulation Surgery (CASS) is a reliable method that permits oral and maxillofacial surgeons to visualize the position of the maxilla and the mandible as observed in the patient. The purpose of this report was to introduce a newly developed strategy for proximal segment management according to Balanced Orthognathic Surgery (BOS) protocol which is a type of CASS, and to establish the clinical feasibility of the BOS protocol in the treatment of complex maxillo-facial deformities. The BOS protocol consists of the following 4 phases: 1) Planning and simulation phase, 2) Modeling phase, 3) Surgical phase, and 4) Evaluation phase. The surgical interventions in 80 consecutive patients were planned and executed by the BOS protocol. The BOS protocol ensures accuracy during surgery, thereby facilitating the completion of procedures without any complications. The BOS protocol may be a complete solution that enables an orthognatic surgeon to perform accurate surgery based on a surgical plan, making real outcomes as close to pre-planned outcomes as possible.

A case of anisakiasis invading the stomach and the colon at the same time after eating anchovies.

Anisakiasis of the gastrointestinal tract is caused by the ingestion of raw fish or uncooked food infested with Anisakis larvae. A large number of cases of gastric anisakiasis have been reported in countries where the eating of raw fish is customary. However, there have been few reports of anisakiasis of the colon confirmed by colonoscopy and also very few reports of endoscopic ultrasonographic findings of anisakiasis. A 47-year-old man had epigastric pain with nausea after eating raw anchovies. Endoscopy found a living tubular structure penetrating into the lesser curvature of the stomach and the midtranseverse colon area. It was withdrawn with biopsy forceps. We report a case of anisakiasis simultaneously invading the stomach and the colon confirmed by endosopic utrasonographic findings and biopsy findings.

Overexpression of OsRDCP1, a rice RING domain-containing E3 ubiquitin ligase, increased tolerance to drought stress in rice (Oryza sativa L.).

CaRma1H1 was previously identified as a hot pepper drought-induced RING E3 Ub ligase. We have identified five putative proteins that display a significant sequence identity with CaRma1H1 in the rice genome database (http://signal.salk.edu/cgi-bin/RiceGE). These five rice paralogs possess a single RING motif in their N-terminal regions, consistent with the notion that RING proteins are encoded by a multi-gene family. Therefore, these proteins were named OsRDCPs (Oryza sativa RING domain-containing proteins). Among these paralogs, OsRDCP1 was induced by drought stress, whereas the other OsRDCP members were constitutively expressed, with OsRDCP4 transcripts expressed at the highest level in rice seedlings. osrdcp1 loss-of-function knockout mutant and OsRDCP1-overexpressing transgenic rice plants were developed. Phenotypic analysis showed that wild-type plants and the homozygous osrdcp1 G2 mutant line displayed similar phenotypes under normal growth conditions and in response to drought stress. This may be due to complementation by other OsRDCP paralogs. In contrast, 35S:OsRDCP1 T2 transgenic rice plants exhibited improved tolerance to severe water deficits. Although the physiological function of OsRDCP1 remains unclear, there are several possible mechanisms for its involvement in a subset of physiological responses to counteract dehydration stress in rice plants.

Langerhans cell histiocytosis presenting as brown lichenoid patches.

Langerhans cell histiocytosis (LCH) is related diseases characterized by proliferation of Langerhans cell with involvement of bone, skin, lung and other organs. LCH usually occurs in childhood and are presented as multiple small papules or eczematoid lesion mostly. We report a 50-year-old man with 3 brown lichenoid patches on left dorsal foot. He was diagnosed pulmonary LCH 5 years ago. Typical LC cells on skin lesion and CD1 complex positive staining confirm the diagnosis of LCH. We consider brown lichenoid patches may be a previously unreported cutaneous presentation in cutaneous or multisystem LCH.

The RpoS-mediated regulation of isocitrate dehydrogenase gene expression in Escherichia coli.

The Escherichia coli NADP(+)-dependent isocitrate dehydrogenase (IDH; EC 1.1.1.42), encoded by an icd gene, is a tricarboxylic acid (TCA) cycle enzyme responsible for the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. In order to examine how the icd gene expression is regulated, an icd-lacZ reporter fusion was constructed. While the icd gene was induced in exponential growth phase, it was repressed in stationary growth phase. Genetic inactivation of an rpoS gene, whose product is an alternative sigma factor, induced the icd gene expression approximately 4.8 times more in the stationary phase and the IDH enzyme activity in the rpoS mutant was 3.2 times higher than that in the wild type, indicating that the RpoS factor acts as a negative regulator of the icd gene expression in the stationary phase.

Perturbation of NgTRF1 expression induces apoptosis-like cell death in tobacco BY-2 cells and implicates NgTRF1 in the control of telomere length and stability.

Telomeres are specialized nucleoprotein complexes that are essential for preserving chromosome integrity in eukaryotic cells. Several potential telomere binding proteins have recently been identified in higher plants, but nothing is known about their in vivo functions. We previously identified NgTRF1 as a double-stranded telomeric repeat binding factor in tobacco (Nicotiana tabacum) and here show that the binding of NgTRF1 to telomeric repeats inhibits telomerase-mediated telomere extension. To determine whether NgTRF1 is involved in telomere length regulation, we established transgenic tobacco BY-2 cell lines that overexpress or suppress NgTRF1. Pulsed-field gel electrophoresis showed that 35S::NgTRF1 cells exhibited significantly shortened telomeres (45 to 10 kb), whereas 35S::antisense-NgTRF1 cells contained longer telomeres (80 to 25 kb) compared with wild-type and 35S::GUS control cells (65 to 15 kb), indicating that telomere length inversely correlates with the amount of functional NgTRF1 in BY-2 cells. 35S::NgTRF1 cells with shorter telomeres displayed a progressive reduction in cell viability and stopped dividing after 25 to 40 successive rounds of 12-d batch subculture, in sharp contrast with control cells, which have an unlimited capacity for division. Internucleosomal DNA fragmentation, mitochondrial release of cytochrome c, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling positive nuclei were detected in 35S::NgTRF1 cells during prolonged subculture, indicating that enhanced cell death was attributable to an apoptosis-like mechanism. 35S::antisense-NgTRF1 cells containing low levels of NgTRF1 also exhibited a progressive decrease in cell viability and apoptotic cell death, but less so than did 35S::NgTRF1 cells, suggesting that the level of NgTRF1 is critically associated with cell viability. Taken together, these data indicate that perturbation of NgTRF1 expression results in changes in telomere length and stability, which in turn causes apoptotic cell death in transgenic BY-2 cells. These results are discussed in light of the suggestion that NgTRF1 is involved in the mechanism by which telomere length and stability are maintained. We further suggest that the structural stability of telomeres, in addition to length maintenance, is essential for their function and for the immortality of BY-2 cells.

Two relA/spoT homologous genes are involved in the morphological and physiological differentiation of Streptomyces clavuligerus.

This study is focused on the involvement of the unusual nucleotide (p)ppGpp during the morphological and physiological differentiation of Streptomyces clavuligerus. In particular, the functional and structural elements of two genes encoding the proteins RelA and Rsh were identified. The relA gene encodes an 843 aa protein (RelA), while the rsh gene encodes a 738 aa protein (Rsh). The relA and rsh genes were disrupted by the insertion of a hygromycin resistance gene and an apramycin resistance gene, respectively. The synthesis of ppGpp in the relA gene-disrupted mutant was completely eliminated under conditions of starvation for amino acids, whereas synthesis persisted, but was greatly reduced in the rsh gene-disrupted mutant. The relA gene-disrupted mutant had a bald appearance on agar plate cultures and retarded growth in submerged culture, while the rsh-disrupted mutant was unchanged in growth characteristics relative to the wild-type culture. The production of both clavulanic acid and cephamycin C were completely abolished in the relA-disrupted mutant. Thus, it is concluded that the relA gene rather than rsh is essential for morphological and physiological differentiation in S. clavuligerus and that RelA primarily governs the stringent response of S. clavuligerus to starvation for amino acids.