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Neutrophil-to-lymphocyte ratio (NLR), may predict treatment response and outcomes in some human malignancies. However, NLR has rarely been examined in older patients with head and neck squamous cell carcinoma (HNSCC). This study evaluated factors, including pre-treatment evaluation tests, predictive of mortality in older patients with HNSCC.This study prospectively enrolled 233 consecutive HNSCC patients aged 65 years or older. Pre-treatment evaluations included patient demographics, comorbidity, body weight loss, voice handicap index, dysphagia, Beck's depression inventory, comprehensive geriatric assessment, and circulating biomarkers. Cumulative incidence and cause-specific hazard functions were used to analyse the risk factors for overall mortality (OM), cancer mortality (CM), and non-cancer mortality (NCM).Multivariate analyses showed that age, performance scale, NLR, and nodal stage were independent predictors of OM and CM (all P .05). Age, body weight loss, frailty, and NLR were independent predictors of NCM (all P .05). Older age ≥ 75 years and NLR showed strong association with all OM, CM, and NCM (all P .05). NLR2.5 was related to a higher risk of OM (hazard ratio [HR] = 1.77, 95% confidence interval [CI]: 1.05-2.97, P = .031), CM (HR = 1.89, 95% CI: 1.09-3.29, P = .023), and NCM (HR = 6.29, 95% CI: 2.16-18.37, P = .001).Cancer and non-cancer mortalities among older patients with HNSCC may be predicted by several clinical and haematological data. NLR might be used as a circulating prognostic marker for mortality in older patients with HNSCC.

Background Gender-related factors might play an important role in the development of reflux esophagitis (RE) and symptomatic gastro-esophageal reflux disease (GERD). We aimed to evaluate the prevalence and risk factors for RE and symptomatic GERD and determine whether gender specific differences exist. Methods This study was conducted on a health cohort consisting of 10,158 participants who underwent comprehensive health screening. Lifestyles and gastrointestinal symptoms were investigated using a self-reported structured questionnaire. Questionnaires about menstrual status were added for the women. Results The prevalence of RE in men was significantly higher than that in women (10.6% vs. 2.0%, P < 0.001); however, symptomatic GERD showed predominance in women (6.2% vs. 2.5%, P < 0.001). Although the prevalence of RE gradually increased with the duration of menopause stratified by decade (P = 0.007), that of symptomatic GERD rapidly increased across the menopausal transit in women. Apart from common risk factors of obesity and current smoking for RE, over 70 years of age in women and hiatal hernia and hypertriglyceridemia in men were significant risk factors. In symptomatic GERD, high somatization was a common risk factor. Excessive alcohol drinking was a significant risk factor in men, but not in women. Conclusion This study showed a predominance of RE in men, but a predominance of symptomatic GERD in women. In women, dynamic increase in the prevalence of GERD is closely related to the menopause conditions and its duration. There are specific risk factors for RE and symptomatic GERD according to gender differences., Graphical Abstract

Background: To explore the effect of radiation on metastatic lymph nodes (LNs) after neoadjuvant chemo-radiation therapy (nCRT), we examined the metastatic features of LNs according to their inclusion in the ra-diation field. Methods: The patient group included 88 men and 2 women, with a mean age of 61.1±8.1 years, who underwent esophagectomy and lymphadenectomy after nCRT. Dissected LNs were compared in terms of clinical suspicion of metastasis, nodal station, and inclusion in the radiation field. Results: LN pos-itivity did not differ between LNs that were inside (in-field [IF]) and outside (out-field [OF]) of the radiation field (IF: 40 of 465 [9%], OF: 40 of 420 [10%]; p=0.313). In clinical N+ nodal stations, IF stations had a lower incidence of metastasis than OF stations (IF/cN+: 16 of 142 [11%], OF/cN+: 9/30 [30%]; p=0.010). However, in clinical N- nodal stations, pathological positivity was not affected by whether the nodal stations were included in the radiation field (IF/cN-: 24 of 323 [7%], OF/cN-: 31 of 390 [8%]; p=0.447). Conclusion: Radiation therapy for nCRT could downstage clinically suspected nodal metastasis. However, such therapy was ineffective when used to treat nodes that were not suspicious for metastasis. Because significant num-bers of residual metastases were identified irrespective of coverage by the radiation field, lymphadenectomy should be performed to ensure complete removal of residual nodal metastases after nCRT.

// Kyung Eun Kim 1,2 , Sungryung Kim 2 , Sunyoung Park 2 , Younkyung Houh 2 , Yoolhee Yang 3 , Seung Beom Park 4 , Sangyoon Kim 4 , Daejin Kim 5 , Dae Young Hur 5 , Seonghan Kim 5 , Hyun Jeong Park 6,* , Sa Ik Bang 3,* and Daeho Cho 1,2,* 1 Department of Cosmetic Sciences, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul, Republic of Korea 2 Department of Biological Sciences, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul, Republic of Korea 3 Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, Republic of Korea 4 Biotech. Team, Cent’l Res. Inst. Ilyang Pharm. Co., Ltd., Gyeonggi-do, Republic of Korea 5 Department of Anatomy, Inje University College of Medicine, Busan, Republic of Korea 6 Department of Dermatology, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea * These authors have contributed equally to this work Correspondence to: Daeho Cho, email: // Sa Ik Bang, email: // Hyun Jeong Park, email: // Keywords : erythroid differentiation regulator 1 (Erdr1), rheumatoid arthritis, inflammation, interleukin-18 (IL-18), synovial fibroblast migration, Immunology and Microbiology Section, Immune response, Immunity Received : August 25, 2016 Accepted : October 28, 2016 Published : November 03, 2016 Abstract Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and multiple inflammatory cytokines are involved in RA pathogenesis. Interleukin (IL)-18, in particular, has a significant positive correlation with RA. In this study, we investigated the effect of erythroid differentiation regulator 1 (Erdr1), which is negatively regulated by IL-18, in an animal model of inflammatory arthritis, collagen-induced arthritis (CIA) in DBA/1J mice. Treatment of mice with recombinant (r)Erdr1 significantly suppressed the severity of arthritis, histologic features of arthritic tissue, and serum levels of anti-collagen autoantibodies (IgG, IgG1, IgG2a and IgM) in CIA. In addition, IL-18 expression was reduced in the affected synovium of rErdr1-treated mice. Interestingly, Erdr1 treatment suppressed migration in contrast to the pro-migratory effect of IL-18, indicating the therapeutic effects of Erdr1 on CIA through inhibiting synovial fibroblast migration. In addition, Erdr1 inhibited activation of ERK1/2, a key signaling pathway in migration of various cell types. Taken together, these data show that rErdr1 exerts therapeutic effects on RA by inhibiting synovial fibroblast migration, suggesting that rErdr1 treatment might be an effective therapeutic approach for RA.

Intermittent drainage of rice fields alters soil redox potential and contributes to the reduction of CH4 emission and thus may reduce net global warming potential (GWP) during rice cultivation. Incorporation of green biomass helps maintaining soil organic matter, but may increase CH4 emission. We investigated net ecosystem carbon budget (NECB) and net GWP under two water management regimes—continuous flooding and intermittent drainage—having four biomass incorporation levels (0, 3, 6 and 12 Mg ha−1). Water management and biomass incorporation level demonstrated significant (P

Background/aim Recurrent laryngeal cancer often shows an aggressive phenotype after radiotherapy and does not respond to conventional therapeutic strategies. In this study, we investigated the contribution of furin to cellular invasiveness in radio-resistant laryngeal cancer. Materials and methods Using previously established AMC-HN-3 and AMC-HN-8 cell lines from laryngeal carcinoma patients, recurrent laryngeal cancer models were generated by cumulative irradiation (AMC-HN-3-70Gy and AMC-HN-8-70Gy). Immunocytochemistry and western blotting were used to determine the epithelial-mesenchymal transition (EMT). Invasion capacity was assessed using an in vitro invasion assay. Zymography was used to assess metalloproteinase-2 (MMP-2) activity. Tumor xenografts were developed to compare growth rate and furin expression in vivo. Furin expression in 35 patients (45 samples) with salvage total laryngectomy after radiation-based treatment was assessed by laryngeal cancer tissue microarray. Results Both AMC-HN-3-70Gy and AMC-HN-8-70Gy cell lines underwent EMT following radiation. However, AMC-HN-3-70Gy cells showed increased cellular invasiveness, whereas AMC-HN-8-70Gy cells showed no difference. AMC-HN-3-70Gy cells also exhibited elevated furin expression with up-regulated expression of the active form of membrane type 1-matrix metalloproteinase (MT1-MMP)/MMP-2, whereas AMC-HN-8-70Gy cells did not show significant changes. After administration of a furin inhibitor (chloromethyl ketone (CMK)), AMC-HN-3-70Gy cells showed a significant decrease in MT1-MMP/MMP-2 expression and cellular invasiveness. Nine of 22 samples (40.9%) from salvage total laryngectomy and one of 13 pre-radiation samples (7.7%) had high furin expression. Post-radiation, furin expression increased in seven of 10 patients whose pre- and post-radiation samples were available; all-cancer mortality (three patients) was observed in this group. Conclusion Together with EMT, furin activity may serve as an indicator of an aggressive cancer phenotype, suggesting that furin is a potentially useful target for recurrent laryngeal cancer.

Papillary thyroid carcinoma (PTC) generally has an indolent course and favorable prognosis. However, an optimal treatment strategy for asymptomatic PTC is not clear. We compared the recurrence and survival outcomes of patients with asymptomatic and symptomatic PTC and identified the associated risk factors.Patients with previously untreated PTC of size ≤2 cm and who underwent curative surgery were included in this analysis. Asymptomatic PTC was defined as a tumor detected only by ultrasonography, computed tomography (CT), magnetic resonance imaging, and/orOut of 1419 patients, 1259 patients (88.7%) were asymptomatic. Patients with symptomatic PTC had significantly larger tumor size, palpability, extrathyroidal extension, high tumor and node stages, and were more likely to undergo treatment with radioactive iodine therapy compared with patients with asymptomatic PTC (p0.05 each). Recurrence was significantly higher in the symptomatic PTC group than in the asymptomatic group (p0.001). Asymptomatic PTC was an independent predictor of RFS and OS and had higher five-year rates than those associated with symptomatic tumors: 97.3% and 90.6% for RFS (p0.001) and 99.4% and 96.9% for OS (p0.001), respectively.Symptomatic PTC is associated with higher recurrence and lower overall survival rates than asymptomatic PTC. Symptomatic PTC may require total thyroidectomy and close posttreatment surveillance.

Extrathyroidal extension (ETE) and extranodal extension (ENE) indicate poor prognosis for patients with papillary thyroid carcinoma (PTC). The relationships among ETE, ENE, and nodal metastasis (N1) have not been thoroughly studied. In this study, we examined the relationships among the extent of ETE, N1, ENE, and posttreatment recurrence in patients with PTC. This study enrolled 1693 consecutive patients with previously untreated PTC who underwent thyroidectomy between 2006 and 2009. The extent of ETE was graded based on intraoperative and pathological findings, and central and lateral neck (N1b) nodal metastases and ENE were pathologically determined. Univariate and multivariate analyses were used to identify the association of clinicopathological factors with recurrence-free survival (RFS) and to define the relationships among the extent of ETE, N1, and ENE. Of 1693 patients, 1087 (64.2 %) had ETE and 201 (11.9 %) had ENE. Pathologically positive lymph nodes were found in 783 patients (46.2 %), of whom 236 (30.1 %) had N1b. During the median follow-up of 86 months, 90 (5.3 %) patients had recurrences. Multivariate analyses showed that multifocality, ETE, T and N classification, the risk of structural recurrence proposed by the American Thyroid Association, and ENE were independent variables for RFS (P

The landfilling of municipal solid waste is a significant source of atmospheric methane (CH4), contributing up to 20% of total anthropogenic CH4 emissions. The evapotranspiration (ET) cover system, an alternative final cover system in waste landfills, has been considered to be a promising way to mitigate CH4 emissions, as well as to prevent water infiltration using vegetation on landfill cover soils. In our previous studies, bottom ash from coal-fired power plants was selected among several industrial residues (blast furnace slag, bottom ash, construction waste, steel manufacture slag, stone powder sludge, and waste gypsum) as the best additive for ET cover systems, with the highest mechanical performance achieved for a 35% (wt wt−1) bottom ash content in soil. In this study, to evaluate the field applicability of bottom ash mixed soil as ET cover, four sets of lysimeters (height 1.2 m × width 2 m × length 6 m) were constructed in 2007, and four different treatments were installed: (i) soil + bottom ash (35% wt wt−1) (SB); (ii) soil + compost (2% wt wt−1, approximately corresponding to 40 Mg ha−1 in arable field scale) (SC); (iii) soil + bottom ash + compost (SBC); and (iv) soil only as the control (S). The effects of bottom ash mixing in ET cover soil on CH4 oxidation potential and vegetation growth were evaluated in a pilot ET cover system in the 5th year after installation by pilot experiments using the treatments. Our results showed that soil properties were significantly improved by bottom ash mixing, resulting in higher plant growth. Bottom ash addition significantly increased the CH4 oxidation potential of the ET cover soil, mainly due to improved organic matter and available copper concentration, enhancing methanotrophic abundances in soil amended with bottom ash. Conclusively, bottom ash could be a good alternative as a soil additive in the ET cover system to improve vegetation growth and mitigate CH4 emission impact in the waste landfill system.

Fertilization with urea can lead to a loss of carbon dioxide (CO2) that was fixed during the industrial production process. The extent of atmospheric CO2 removal from urea manufacturing was estimated by the Industrial Processes and Product Use sector (IPPU sector). On its basis, the Intergovernmental Panel on Climate Change (IPCC) has proposed a value of 0.2 Mg C per Mg urea (available in 2006 revised IPCC guidelines for greenhouse gas inventories), which is the mass fractions of C in urea, as the CO2 emission coefficient from urea for the agricultural sector. Notably, due to the possibility of bicarbonate leaching to waters, all C in urea might not get released as CO2 to the atmosphere. Hence, in order to provide an accurate value of the CO2 emission coefficient from applied urea in the rice ecosystem, the CO2 emission factors were characterized under different levels of 13C-urea applied paddy field in the current study. The total CO2 fluxes and rice grain yields increased significantly with increasing urea application (110–130 kg N ha−1) and thereafter, decreased. However, with increasing 13C-urea application, a significant and proportional increase of the 13CO2 C emissions from 13C-urea was also observed. From the relationships between urea application levels and 13CO2 C fluxes from 13C-urea, the CO2 C emission factor from urea was estimated to range between 0.0143 and 0.0156 Mg C per Mg urea. Thus, the CO2 C emission factor of this study is less than that of the value proposed by IPCC. Therefore, for the first time, we propose to revise the current IPCC guideline value of CO2 C emission factor from urea as 0.0143–0.0156 Mg C per Mg urea for Korean paddy soils.

Head and neck soft tissue sarcoma (HNSTS) is a rare type of tumor with various histological presentations and clinical behaviors. 18F-FDG PET/CT is being increasingly used for staging, grading, and predicting treatment outcomes in various types of human cancers, although this modality has been rarely studied in the survival prediction of HNSTS. Here we examined the prognostic value of tumor metabolic parameters measured using 18F-FDG PET/CT in patients with HNSTS. This study included 36 consecutive patients with HNSTS who underwent 18F-FDG PET/CT scanning prior to treatment at our institution. Tumor gross total volume (GTV) was measured from pretreatment contrast-enhanced CT scans, and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using pretreatment 18F-FDG PET/CT scans. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between imaging parameters and disease-specific survival (DSS) or overall survival (OS). Univariate analyses showed that SUVmax, MTV, and TLG, but not GTV, were significantly associated with DSS and OS (all P 7.0 experienced an approximately fivefold increase in mortality in terms of DSS and OS relative to those with a tumor SUVmax

Introduction. Frailty refers to a decreased physiologic reserve in geriatric patients and its importance in terms of treatment planning and outcome prediction has been emphasized in oncologic practices for older patients with cancer. We investigated the clinical implications of a head and neck cancer (HNC)-specific frailty index suggested by prospective clinical and functional evaluations of HNC patients. Materials and Methods. We analyzed data on 165 elderly patients with HNC who were prospectively enrolled in our hospital from 2010 to 2013. Pretreatment functional evaluations were performed according to all comprehensive geriatric assessment (CGA) domains. We additionally evaluated the patients’ respiratory and swallowing functions using pulmonary function tests, voice handicap index (VHI), MD Anderson Dysphagia Inventory (MDADI), and other associated tests. Factors affecting the 2-year morbidity and mortality were also analyzed. Results. Respiratory and swallowing problems were major causes of 2-year morbidity. Pretreatment performance status, VHI ≥8, MDADI Conclusion. Pretreatment functional disabilities related to respiration and swallowing were significantly associated with early morbidity and mortality. The suggested index would be more useful for assessing frailty in elderly HNC patients.

Existence of the genomically and epigenomically diverse subclones in a tumor severely limits the therapeutic efficacy of targeted agents. To overcome such a limitation, we prepared a novel targeted prodrug, EMC-DEVD-S-DOX, which comprises two important features: radiation-induced apoptosis targeting and albumin-binding properties. In particular, the prodrug binds circulating albumin after intravenous administration and then activated by caspase-3, which is upregulated from apoptotic cells that responded to radiotherapy. The prodrug was designed to bind circulating albumin to extend half-life and facilitate tumor accumulation in order to increase the possibility of contacting caspase-3, which is only transiently upregulated during apoptosis. Our results showed that EMC-DEVD-S-DOX had a prolonged half-life with enhanced tumor accumulation, which clearly benefited the therapeutic effect of the prodrug. Also, agreeing with the in vitro studies that showed ignorable cytotoxic effect in the absence of caspase-3, the prodrug was effective only when combined with radiotherapy without any noticeable systemic toxicity in vivo. Due to the highly selective action of EMC-DEVD-S-DOX independent to the complex genomic profiles of tumor, the prodrug would overcome the limitation of current targeted therapy and potentiate radiotherapy in the clinical oncology.

Midseason drainage is regarded as a key practice to suppress methane (CH4) emission from paddy soil during rice cultivation, but it can increase carbon dioxide (CO2) and nitrous oxide (N2O) emissions. However, the influences of midseason drainage practice on the net global warming potential (GWP) and greenhouse gas intensity (GHGI) of rice cropping systems is not well documented in the East monsoon region. In this field study, the effect of a 30-day midseason drainage practice from the 28th day after transplanting (DAT) to the 57th DAT on the three major greenhouse gas (GHG) fluxes and yield properties were compared with those of a continuous flooding system during rice cultivation in 2011 and 2012. The impact of midseason drainage on changing three GHG emissions was compared using the GWP value and GHG intensity (GHGI). Midseason drainage significantly reduced the net GWP scale by 46–50% of the continuous flooding, mainly due to 50–53% reduction of seasonal CH4 fluxes. Midseason drainage significantly increased N2O flux by 20–37% over the conventional flooding, but the influence of N2O emission increase on the net GWP scale was negligible. Midseason drainage significantly decreased soil C sequestration capacity by around 60% of continuous flooding, and then increased net GWP by 0.25–0.32 Mg CO2-eq. ha−1 during rice cultivation. There was no significant difference of rice yield between two irrigation systems, and then midseason drainage can reduce GHGI by 50–56% of the continuous flooding. In conclusion, the midseason drainage practice during rice cultivation could be very useful soil management strategy to reduce GHG emission impact from lowland rice fields without impacting rice productivity.

BACKGROUND: Since bottom ash (BA) contains considerable amounts of CaO and MgO, it could be a useful amendment to increase soil pH and to immobilize cadmium (Cd). This study was conducted to evaluate effect of BA application in reducing Cd phytoavailability.METHODS AND RESULTS: Bottom ash was applied at the rate of 0, 20, 40, and 80 Mg/ha to Cd contaminated soil, and then lettuce was cultivated under field condition. soil pH and net negative charge increased slightly with increasing BA application; however, there was no statistical difference among the rates. Water soluble, exchangeable+acidic, reducible, and oxidizable fraction of Cd decreased with increasing bottom ash application rate, whereas residual fraction of Cd increased with increasing bottom ash application rate. Lettuce yield increased with rate of bottom ash up to 40 kg/ha. Visual evidences of cadmium toxicity and growth inhibition were not found during lettuce cultivation.CONCLUSION: Bottom ash was effective to reduce phytoextractability of Cd and to increase lettuce yield. Conclusively, BA could be a good soil amendment to reduce Cd phytoavailability in contaminated arable soil.

Pectus arcuatum is a rare complex chest wall deformity. A 31-year-old female presented with a severely protruding upper sternum combined with a concave lower sternum. We planned a modified Ravitch-type operation. Through vertical mid-sternal incision, chondrectomies were performed from the second to fifth costal cartilages, saving the perichondrium. Horizontal osteotomy was performed in a wedge shape on the most protruding point, and followed by an additional partial osteotomy at the most concaved point. The harvested wedge-shape bone fragments were minced and re-implanted to the latter osteotomy site. The osteotomized sternum was fixed with multiple wirings. With chondrosternoplasty, a complex chest wall deformity can be corrected successfully.

To evaluate whether contralateral neck metastasis (CNM) from previously untreated head and neck squamous cell carcinoma (HNSCC) can be accurately detected at combined computed tomography (CT)/magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and assess the prognostic value of CNM.This prospective study was approved by the institutional review board, and written informed consent was obtained from all enrolled patients. In total, 160 patients with HNSCC were preoperatively evaluated with FDG PET/CT and CT/MR imaging. Histopathologic results of neck dissection samples served as the reference standard for all cases. McNemar test and logistic regression with generalized estimating equations were used to compare the diagnostic value of FDG PET/CT and CT/MR imaging, and Cox proportional hazard modeling was used to assess the prognostic value of CNM.Of the 160 enrolled patients, 94 (58.8%) had a neck metastasis on 231 sides and with 974 levels, and 20 patients (21.3%) had a contralateral neck metastasis. FDG PET/CT was significantly more sensitive than CT/MR imaging according to per-patient (91.5% vs 73.4%; P.001), per-side (91.1% vs 69.6%; P.001), and per-level analyses (78.9% vs 53.0%; P.001). On the per-side basis, FDG PET/CT was also significantly more sensitive and accurate than CT/MR imaging when evaluating the contralateral neck (85.0% vs 45.0%, P = .008, and 91.6% vs 80.3%, P = .008, respectively). However, at univariate analysis, CNM was significantly associated only with cancer-specific death (P = .001) and overall survival (P = .015).CNM from HNSCC can be detected at FDG PET/CT with higher sensitivity and accuracy than at CT/MR imaging.

No-tillage (NT) is known as an effective method of soil management that has the potential to increase soil organic carbon (SOC) accumulation in arable lands. Unlike upland soils, the increase of SOC accumulation in paddy soils under continuous NT is likely to increase methane (CH 4 ) emissions during rice cultivation. However, the interaction between the SOC accumulation and CH 4 emission characteristics associated with continuous NT in rice paddies has not been well elucidated. To investigate the effects of continuous NT on SOC accumulation and CH 4 emissions, conventional tillage (CT) and NT plots were installed in a typical mono-rice paddy soil classified as a fine-silty, mixed, nonacid mesic Typic endoaquept in the southern part of the Korean peninsula in 2007. In the 1 st , 2 nd and 5 th years after installation, the CH 4 emission patterns were characterised during rice cultivation and rice grain yield and soil properties were investigated at the harvesting stage. Compared with CT (381 – 363 kg CH 4 ha -1 ), NT effectively decreased total CH 4 fluxes by approx. 20-27% in the 1 st and 2 nd years (279 – 291 kg CH 4 ha -1 ) after installation. However, a much higher CH 4 flux (approx. 36%) was observed in the NT (385 kg CH 4 ha -1 ) than the CT (287 kg CH 4 ha -1 ) plots in the 5 th year. The SOC content in the NT plots clearly increased over the study years (14.5 – 15.6 g kg -1 ) compared with that under CT (14.4 - 14.3 g kg -1 ) which did not change significantly during the study period. Similar to the increase of the SOC content observed under NT, the concentrations of labile C forms such as water-extractable C (WEC) and hot water-extractable C (HWEC) and labile C availability in the surface soil dramatically increased over the study years, which may have increased mcr A gene copies as a methanogen population abundance (5.7 × 10 6 mcr A gene copy number g -1 soil) and CH 4 production potentials in the 5 th year compared with CT (4.2 × 10 6 mcr A gene copy number g -1 soil). Rice productivity was slightly lower in the NT than the CT treatment, though this difference was not statistically significant across the study years. These findings led to the conclusion that because continuous NT can increase CH 4 emissions during rice cultivation under flooded paddy soil conditions due to the increased availability of labile forms of SOC, therefore, other soil management regimes that can decrease CH 4 emissions, such an intermittent drainage, should be introduced along with continuous no-tillage.

TodS is a sensor kinase that responds to various monoaromatic compounds, which either cause an agonistic or antagonistic effect on phosphorylation of its cognate response regulator TodT, and controls tod operon expression in Pseudomonas putida strains. We describe a molecular sensing mechanism of TodS that is activated in response to toluene. The crystal structures of the TodS Per-Arnt-Sim (PAS) 1 sensor domain (residues 43-164) and its complex with toluene (agonist) or 1,2,4-trimethylbenzene (antagonist) show a typical β2α3β3 PAS fold structure (residues 45-149), forming a hydrophobic ligand-binding site. A signal transfer region (residues 150-163) located immediately after the canonical PAS fold may be intrinsically flexible and disordered in both apo-PAS1 and antagonist-bound forms and dramatically adapt an α-helix upon toluene binding. This structural change in the signal transfer region is proposed to result in signal transmission to activate the TodS/TodT two-component signal transduction system. Site-directed mutagenesis and β-galactosidase assays using a P. putida reporter strain system verified the essential residues involved in ligand sensing and signal transfer and suggest that the Phe(46) residue acts as a ligand-specific switch.

Controlled and site-specific regulation of growth factor signaling remains a major challenge for current antiangiogenic therapies, as these antiangiogenic agents target normal vasculature as well tumor vasculature. In this article, we identified the prion-like protein doppel as a potential therapeutic target for tumor angiogenesis. We investigated the interactions between doppel and VEGFR2 and evaluated whether blocking the doppel/VEGFR2 axis suppresses the process of angiogenesis. We discovered that tumor endothelial cells (TECs), but not normal ECs, express doppel; tumors from patients and mouse xenografts expressed doppel in their vasculatures. Induced doppel overexpression in ECs enhanced vascularization, whereas doppel constitutively colocalized and complexed with VEGFR2 in TECs. Doppel inhibition depleted VEGFR2 from the cell membrane, subsequently inducing the internalization and degradation of VEGFR2 and thereby attenuating VEGFR2 signaling. We also synthesized an orally active glycosaminoglycan (LHbisD4) that specifically binds with doppel. We determined that LHbisD4 concentrates over the tumor site and that genetic loss of doppel in TECs decreases LHbisD4 binding and targeting both in vitro and in vivo. Moreover, LHbisD4 eliminated VEGFR2 from the cell membrane, prevented VEGF binding in TECs, and suppressed tumor growth. Together, our results demonstrate that blocking doppel can control VEGF signaling in TECs and selectively inhibit tumor angiogenesis.

Conclusion The application of adjuvant RT to reduce recurrence should be tailored in cases of pathologically negative node metastasis. Objectives The treatment modality following surgical resection of advanced laryngeal cancer is determined by adverse factors. Aside from lymph node metastasis (LNM) or positive margins, definite risk factors supporting adjuvant radiation therapy (RT) have not been clearly suggested. The aim of this study was to analyze the risk factors for advanced laryngeal cancer without LNM and the role of RT. Materials and methods Pathologically T3 and T4-staged laryngeal squamous cell carcinoma without LNM were reviewed. The patients were classified into RT (+) (n = 22) and RT (-) (n = 38) groups. Results Five-year overall survival (OS) of the RT (+) and RT (-) groups was 84.4% and 83.8%, respectively. Five-year disease-specific survival of the RT (+) and RT (-) groups was 88.4% and 93.9%. Five-year local control rate of the RT (+) and RT (-) groups was 94.7% and 91.3%. The factors affecting OS were smoking history and recurrence history (p = 0.02). By multivariate analysis, smoking history and recurrence history were determining factors for 5-year OS (p = 0.024 and p = 0.047, respectively).

Malnutrition and systemic lymphopenia are common in many cancers and are associated with tumor progression. The purpose of this study was to investigate the prognostic values of nutritional and hematologic markers in patients with head and neck squamous cell carcinoma (HNSCC).This prospective study included 153 patients with treatment-naïve HNSCC who underwent definitive chemoradiotherapy. Body weight, serologic and hematologic parameters were measured at baseline and after 2 months of treatment. Univariate and multivariate analyses using Cox proportional hazards model were used to identify predictors of progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS).Body weight, body mass index (BMI), serum albumin, total serum proteins, hemoglobin, and circulating neutrophil, lymphocyte, monocyte, and platelet counts significantly decreased, but neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) significantly increased after 2 months of treatment (P0.05 each). Multivariate analyses showed that pretreatment hypoalbuminemia and high NLR were independent predictors of PFS (P0.01 each). ECOG performance status, BMI18.5 kg/m(2) and NLR were independent predictors of CSS and OS (P0.01 each).Our data support the evidence that several nutritional and hematologic markers are associated with the prognosis of HNSCC.

The use of excessive and inappropriate medications is a common problem in elderly populations. The use of polypharmacy (PP) and potentially inappropriate medication (PIM) may affect treatment-related morbidities in elderly cancer patients, which has rarely been studied in patients with head and neck cancer (HNC). Here, we evaluate the effects of PP and PIM on treatment and posttreatment courses in elderly HNC patients. This study included 229 elderly HNC patients who underwent definitive treatment. Medications were carefully recorded, and the prevalences of PP and PIM are reported. We evaluated the associations between PP, PIM, treatment, and posttreatment course in terms of comorbidities, treatment-related toxicity, prolonged hospitalization, and posttreatment noncancer health events. The prevalences of PP and PIM in our elderly HNC patients were 29.3 and 24.0 %, respectively, and frequently described PIMs include aspirin (12.2 %), calcium channel blockers (4.8 %), benzodiazepines (4.3 %), and nonsteroidal anti-inflammatory drugs (3.9 %). PP and PIM were not significantly associated with treatment-related toxicity, but were associated with modestly increased prolonged hospitalization [odds ratio [OR] 2.30 (95 % confidence interval 0.89–5.95); P = 0.080] and noncancer health events [OR 1.81 (0.99–3.31); P = 0.052], respectively. Among high-risk medications, benzodiazepine [OR 5.09 (1.21–21.5); P = 0.015] and calcium channel blockers [OR 5.69 (1.07–33.25); P = 0.031) were significantly associated with prolonged hospitalization. Neither PP nor PIM are significantly associated with treatment-related toxicity in elderly HNC patients, but these are associated with modest increases in prolonged hospitalization and noncancer health events.

Purpose Mandibular setback surgery can adversely affect the pharyngeal airway. The aim of this study was to investigate changes of the pharyngeal airway at specific intervals during a 12-month period after bilateral sagittal split ramus osteotomy (BSSO) for correction of mandibular prognathism. Materials and Methods This retrospective cohort study included patients with mandibular prognathism who underwent BSSO. The pharyngeal airway was measured at 3 different levels on lateral cephalograms: the uvula tip, the most inferior-anterior point on the body of the second cervical vertebra (low-C II), and a midanterior point on the body of the third cervical vertebra (mid-C III). The pharyngeal airway was measured preoperatively, immediately postoperatively, and 1, 3, 6, and 12 months postoperatively. The measurements at each level were compared. Multivariable analysis of variance was used to measure the changes in pharyngeal airway space over time. Results The study sample was composed of 30 patients (14 men and 16 women) who were diagnosed with mandibular prognathism. The pharyngeal airway at the uvular tip level was significantly reduced by 39% (P < .001) after surgery and was significantly improved by 26% (P < .01) from baseline at 1 month postoperatively. The pharyngeal airway at the low-C II level was significantly reduced by 27% (P < .001) after surgery and was significantly improved by 24% (P < .01) from baseline at 1 month postoperatively. The pharyngeal airway at the mid-C III level was significantly reduced by 23% (P

To determine the effectiveness of ultrasonographically (US) guided core needle biopsy (CNB) for diagnosis of small musculoskeletal soft-tissue lesions by demonstrating the noninferiority of the diagnostic yield with US-guided CNB in lesions measuring 2 cm or smaller to that for lesions larger than 2 cm.This retrospective study was institutional review board approved, and the requirement to obtain informed consent was waived. Five hundred US-guided CNBs performed for diagnosis of musculoskeletal soft-tissue lesions were included. Results of US-guided CNBs were divided into four categories, and the diagnostic yields were calculated on the basis of lesion size. A one-sided 97.5% confidence interval was calculated to determine the mean difference in diagnostic yields to test for noninferiority. In addition, the diagnostic yield with US-guided CNBs for lesions 1 cm or smaller was compared with that for lesions larger than 1 cm.A total of 500 technically successful US-guided CNBs in 494 patients with musculoskeletal soft-tissue lesions who underwent subsequent surgical excision or at least 6 months of follow-up were included. The diagnostic yields with US-guided CNB were 87% for lesions larger than 2 cm and 88% for lesions 2 cm or smaller. The lower bound of the confidence interval was -0.07, thus the noninferiority of the diagnostic yield with CNB for lesions 2 cm or smaller to that for lesions larger than 2 cm was shown. On the other hand, the diagnostic yield with US-guided CNB for lesions 1 cm or smaller was inferior to that for lesions larger than 1 cm.US-guided CNB of musculoskeletal soft-tissue lesions is effective for diagnosis and decision making, even in lesions measuring 2 cm or smaller. However, when a lesion is 1 cm or smaller, US-guided CNB is more frequently insufficient for histopathologic diagnosis.

The protective effects of Korean red ginseng (KRG; Panax ginseng Meyer) aqueous extract against doxorubicin (DOX)-induced testicular damage in rats was investigated. DOX (1 mg⋅mL −1 ⋅kg −1 ⋅week −1 ) was administrated intraperitoneally for 8 weeks and KRG extract was administrated orally for 9 weeks (100 or 200 mg/kg/day). The serum sex hormone levels, sperm kinematic parameters, histopathological parameters and protein expression levels were determined. DOX distinctly damaged the histology of the rat testes and decreased the sex hormonal levels, spermatogenesis, seminiferous tubular diameter, and testes weight. Further, the protein expression levels of peroxiredoxin, glutathione- S -transferase, nectin-2, inhibin-α, and cAMP response element binding protein were suppressed in DOX-treated rats. In contrast, KRG extract ameliorated the changes induced by DOX. Data indicated that KRG ameliorated DOX-induced testicular damage in rats by modulating the antioxidant system and hormonal imbalance. In conclusion, KRG can be used as a functional food and/or adjuvant for the prevention of reproductive damage caused by DOX.

Background We attempted to elucidate the mechanism of cell death after radiation by studying how β-catenin silencing controls the radiation sensitivity of radioresistant head and neck cancer cells. Methods The most radioresistant cancer cell line (AMC-HN-9) was selected for study. Targeted silencing of β-catenin was used on siRNAs. Sensitivity to radiation was examined using clonogenic and methylthiazol tetrazolium (MTT) assays. Results A combination of irradiation plus β-catenin silencing led to a significant reduction in the inherent radioresistance of AMC-HN-9 cells. Although expression of Ku70/80 was upregulated in AMC-HN-9 cells after irradiation, Ku70/80 was dramatically decreased in a combination of irradiation and β-catenin silencing. Interestingly, irradiation-induced Ku70/80 was completely prevented by β-catenin silencing-induced LKB1/AMP-activated protein kinase (LKB1/AMPK) signal. Conclusion The LKB1/AMPK pathway might relay the signal between the Wnt/β-catenin pathway and the Ku70/Ku80 DNA repair machinery, and play a decisive role in fine-tuning the responses of cancer cells to irradiation. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Context: As a class of angiogenesis inhibitors, heparin conjugates have shown significant effectiveness in several studies. Objectives: The purpose of our current study is to evaluate the effectiveness and safety of infusing the conjugate of low molecular weight heparin and taurocholate (LHT7), which has been developed as a potent angiogenesis inhibitor. Methods: To evaluate its safety, the method of intravenous infusion was compared with its i.v. bolus administration. Intravenous infusion was administered at a rate of 400 μl/min/kg of body weight for 30 min. Pharmacokinetic (PK) analysis, organ accumulation, and plasma concentration profiles of LHT7 were measured. The anticancer effect of LHT7 was evaluated in murine and human xenograft models, and preclinical studies were performed in SD rats and beagle dogs. Results: The results of the PK studies showed reduced organ accumulation in mice and the AUC(0–96 h) (area under the curve) was increased up to 1485 ± 125 h × μg/ml. The efficacy, at dose 1 mg/kg/2 d was higher for i.v. infusion than for i.v. bolus administration in both murine and human cancer models. The preclinical studies showed the safety dose of LHT7 is less than 20 mg/kg in SD rats and in the next safety analysis in beagle dogs showed that there were no organ-specific adverse effects in higher doses, such as, 12 mg/kg. LHT7 showed sustained effects with minimized adverse events when administered through i.v. infusion. Conclusions: LHT7 (i.v. infusion) could be safely used for further clinical development as a multi-targeting anti-angiogenic agent.

Mixing of autologous blood with priming volume has relatively significant effects on blood composition, especially in low-bodyweight neonates. In an effort to reduce these effects, mini-volume priming (MP) has been applied in cardiopulmonary bypass (CPB). The present study was designed to examine the effect of MP on clinical outcomes of low-bodyweight neonates undergoing open heart surgery.We retrospectively reviewed medical records of low-bodyweight (2.5 kg or less) neonates who underwent open heart surgery in our center from January 2000 to December 2014. A total of 64 patients were included. MP was introduced in 2007, and became a routine protocol in 2009. Preoperative and intraoperative characteristics included age, bodyweight, RACHS-1, priming volume, CPB time, and aortic cross-clamp time, transfusion, and hematocrit during CPB. Clinical outcomes included 30-day mortality, postoperative extracorporeal membrane oxygenation (ECMO) support, open sternum status, prolonged mechanical ventilation care (>7 days), and acute renal failure. MP was utilized in 39 patients and conventional priming (CP) was used in 25 patients. The priming volume decreased to 126.0 mL in the MP group compared with 321.6 mL in the CP group. Transfusion volume during CPB was 87.3 mL in the MP group versus 226.8 mL in the CP group, and the difference was statistically significant (P

Twenty-six-year-old Ebstein's anomaly patient, who had failed both biventricular and one-and-a-half repair, underwent right ventricle exclusion and Fontan operation. She completed pregnancy and delivery owing to the excellent long-term clinical course. Although the caesarean section was performed due to symptoms of heart failure on the gestational age of 32+6 weeks, preterm delivery was agreeable with neonatology support. In Korea, there has not yet been a case of pregnancy and delivery of functional single ventricle patient because most patients have been discouraged from getting pregnant. However, functional single ventricle patient can endure pregnancy and delivery, if valve function and ventricular contractility, status of Fontan pathway and absence of arrhythmia predict favorable outcome as presented in this case. Although the patient maintained her pregnancy without anticoagulation owing to laminar flow in the Fontan pathway and absence of thromboembolic event, anticoagulation should be considered, weighing the benefits and risks during the pregnancy.

Summary Background Human papillomavirus ( HPV) (+) tonsil squamous cell carcinoma (TSCC) responds well to concurrent chemoradiation therapy (CCRT) and demonstrates a favorable prognosis. However, cases of HPV (+) TSCC-related death remain unresolved. We evaluated the distribution and prognostic value of inflammatory cells in HPV (+) TSCC. Methods We reviewed the medical records of 53 patients who were diagnosed with TSCC. HPV (+) TSCC was confirmed using HPV DNA PCR and immunohistochemical p16 overexpression. The numbers of CD4 (+), CD8 (+), and CD68 (+) stained cells were used to evaluate peritumoral lymphocyte infiltration. Patients were divided into two groups according to the mean numbers of stained cells and the mean ratios of each cell type. Results HPV (+) was noted in 39 patients. During the follow-up period, 27 patients had no evidence of disease, 2 patients showed disease, and 10 patients died of disease. In this group, advanced T and N stages were not related to overall or disease-specific survival outcomes. The overall survival rate was affected by a high CD68 (+) (HR = 19.8; P = 0.040) and low CD8/CD4 ratio (HR = 7.7, P = 0.025). The disease-specific survival rate was affected by a high number of CD68 (+) cells (HR = 15.2; P = 0.03) and low CD8 (+)/CD4 (+) ratio (HR = 3.3; P = 0.04). Conclusions The number of CD68 (+) cells and the distribution of cytotoxic or immunosuppressive T lymphocytes could be determining factors for CCRT outcomes in HPV (+) TSCC patients.

Summary Isolation of ventricular cardiomyocytes (vCMs) has been challenging due to the lack of specific surface markers. Here we show that vCMs can be purified from differentiating mouse embryonic stem cells (mESCs) using molecular beacons (MBs) targeting specific intracellular mRNAs. We designed MBs (IRX4 MBs) to target mRNA encoding Iroquois homeobox protein 4 (Irx4), a transcription factor specific for vCMs. To purify mESC vCMs, IRX4 MBs were delivered into cardiomyogenically differentiating mESCs, and IRX4 MBs-positive cells were FACS-sorted. We found that, of the cells isolated, ∼98% displayed vCM-like action potentials by electrophysiological analyses. These MB-purified vCMs continuously maintained their CM characteristics as verified by spontaneous beating, Ca2+ transient, and expression of vCM-specific proteins. Our study shows the feasibility of isolating pure vCMs via cell sorting without modifying host genes. The homogeneous and functional ventricular CMs generated via the MB-based method can be useful for disease investigation, drug discovery, and cell-based therapies., Graphical Abstract, Highlights • Molecular beacon (MB)-based method was developed to purify ventricular CMs from ESCs • Ventricular CM-specific MBs targeting Irx4 mRNA were successfully generated • About 98% of the CMs sorted via Irx4-MB displayed ventricular CM-like phenotypes • Irx4-MB-based purified CMs continuously maintained ventricular CM characteristics, In this article, Yoon and colleagues demonstrate that vCMs can be purified from differentiating ESCs using MBs targeting mRNA encoding Irx4, a transcription factor specific for vCMs. Purified IRX4-MB-positive cells displayed vCM-like action potentials and continuously maintained their vCM characteristics. This study shows the feasibility of isolating pure vCMs via cell sorting without modifying host genes.

Objectives Pre- and post-treatment 18F-FDG PET/CT may have a prognostic role in human cancers. 18F-FDG PET/CT after primary surgery for head and neck cancer might also predict survival. Therefore, we evaluated the prognostic value of post-treatment 18F-FDG PET/CT in primary surgical patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). Materials and methods This prospective study involved 225 patients with previously untreated advanced-stage HNSCC who underwent primary surgery with or without postoperative radiotherapy or chemoradiotherapy. The patients also had 18F-FDG PET/CT scanning at a median 6 months after surgery. Post-treatment 18F-FDG PET/CT was considered positive, based on interpretation by experienced nuclear medicine physicians with integrating clinical information. Positive and negative predictive values (PPV and NPV) for positive 18F-FDG PET/CT in association with recurrence were calculated. Predictors for positive post-treatment 18F-FDG PET/CT were evaluated using binary logistic regression. Survival analysis was performed using Cox proportional hazard regression analysis. Results PPV and NPV for post-treatment PET/CT for overall recurrence were 75.8% and 98.7%, respectively. A positive post-treatment PET/CT was an independent predictive factor for overall and disease-free survival (both P Conclusions Post-treatment 18F-FDG PET/CT predicts survival and recurrence in patients undergoing curative surgery for advanced-stage HNSCC.

Cancer is driven by genomic alterations, but the processes causing this disease are largely performed by proteins. However, proteins are harder and more expensive to measure than genes and transcripts. To catalyze developments of methods to infer protein levels from other omics measurements, we leveraged crowdsourcing via the NCI-CPTAC DREAM proteogenomic challenge. We asked for methods to predict protein and phosphorylation levels from genomic and transcriptomic data in cancer patients. The best performance was achieved by an ensemble of models, including as predictors transcript level of the corresponding genes, interaction between genes, conservation across tumor types, and phosphosite proximity for phosphorylation prediction. Proteins from metabolic pathways and complexes were the best and worst predicted, respectively. The performance of even the best-performing model was modest, suggesting that many proteins are strongly regulated through translational control and degradation. Our results set a reference for the limitations of computational inference in proteogenomics. A record of this paper's transparent peer review process is included in the Supplemental Information.

Background: Combination therapy of anti-PD-1 agents with other class of chemotherapeutic agents to improve treatment outcome is being attempted. Anthracycline-derived chemotherapeutic agents are known to activate immunogenic cell-death mechanism. Previously, we developed caspase-3 specific prodrug, MPD-1 containing doxorubicin. It is linked to peptide moiety cleavable by caspase-3 produced during apoptosis induced by radiation therapy (RT). We hypothesized that anti-PD-1 alone may activate MPD-1 by producing caspase-3 and reinforce antitumor efficacy of MPD-1 and anti-PD-1 effect. This study was designed to evaluate the antitumor effects of combined treatment of anti-PD-1 and MPD-1 in murine squamous cell carcinoma models. Methods: Murine SCC VII (squamous cell carcinoma) cells were inoculated to flank of mice, female C3H/J. We divided 6 treatment groups; control, RT, anti-PD-1, anti-PD-1 with MPD-1, RT with MPD-1, and triple therapy (anti-PD-1 + RT + MPD-1) (n = 5/each group). After tumor grew up to 100-200 mm3, treatment was initiated. Tumor size and mice weight were measured. Expression of caspase-3 was evaluated in cell lines and tumor tissues after each treatment. Distribution of CD8+, CD4+, and FoxP3+ cells was analyzed. Results: RT with MPD-1, anti-PD-1 with MPD-1, and triple treatment enhanced the synergistic antitumor activity compared to single treatment in SCC VII bearing mice. Anti-PD-1 with MPD-1 presented slightly better antitumor effect than RT with MPD-1. Caspase-3 was produced in tumor tissue of anti-PD-1 treatment group, which enhanced antitumor effect of activated MPD-1, while cell after anti-PD-1 did not enhance caspase-3 expression. Triple treatment suppressed tumor growth mostly, which was sustained more than 2 weeks even after cessation of treatment. Proportion of CD45+CD8+ T-cells in triple treatment group was increased mostly among tumor-infiltrating lymphocytes. Body weight of each treatment group was not significantly different. Conclusion: Systemic anti-PD-1 initiates apoptosis and produces caspase-3. This process activates MPD-1 and induces sequential mediated by tumor-infiltrating lymphocytes. Combined anti-PD-1 and MPD-1 treatment will be effective for the distant metastatic lesions. Citation Format: Yoon Se Lee, Minsu Kwon, In Kyung Son, Youngro Byun, Sang Yoon Kim. Robust antitumor effect of doxorubicin prodrug combined with anti-PD-1 in murine squamous cell cancer model [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B19.

Acupuncture is a well-known traditional medical procedure in Korea and is being increasingly used to treat various conditions including pain control, especially among the older generation. However, several problems related to acupuncture have been reported. A 27-year-old woman expressed that she had back pain occurring despite her posture. She received acupuncture therapy 2 months prior. We discovered a needle-shaped foreign material near the T12 vertebra body in the retroperitoneum. We extracted 2 pieces of deteriorated broken needles by laparoscopy. Postoperatively, the woman was discharged within 5 days with no complications. We report a patient that received laparoscopy with a full recovery after having severe back pain caused by a broken needle which was stuck in the retroperitoneum.

In Ivor Lewis operation, anastomosis site leakage is a critical complication. Interventional approach utilizing covered metal stent has been introduced for the management of this complication. This patient was diagnosed as esophageal cancer and underwent robot-assisted Ivor Lewis operation. Due to symptoms suggesting anastomosis site leakage, video-assisted thoracoscopic surgery exploration was performed without identification of gross leakage site. On esophagogastroduodenoscopy, anastomosis site leakage was detected and esophageal stent was placed. Four weeks later, the stent was removed, and the patient could intake all his diet orally without discomfort. Esophageal stent insertion can be an option to manage postesophagectomy leakage problem.

Background: The topological analysis of networks extracted from different types of “omics” data is a useful strategy for characterizing biologically meaningful properties of the complex systems underlying these networks. In particular, the biological significance of highly connected genes in diverse molecular networks has been previously determined using data from several model organisms and phenotypes. Despite such insights, the predictive potential of candidate hubs in gene co-expression networks in the specific context of cancer-related drug experiments remains to be deeply investigated. The examination of such associations may offer opportunities for the accurate prediction of anticancer drug responses. Methods: Here, we address this problem by: a) analyzing a co-expression network obtained from thousands of cancer cell lines, b) detecting significant network hubs, and c) assessing their capacity to predict drug sensitivity using data from thousands of drug experiments. We investigated the prediction capability of those genes using a multiple linear regression model, independent datasets, comparisons with other models and our own in vitro experiments. Results: These analyses led to the identification of 47 hub genes, which are implicated in a diverse range of cancer-relevant processes and pathways. Overall, encouraging agreements between predicted and observed drug sensitivities were observed in public datasets, as well as in our in vitro validations for four glioblastoma cell lines and four drugs. To facilitate further research, we share our hub-based drug sensitivity prediction model as an online tool. Conclusions: Our research shows that co-expression network hubs are biologically interesting and exhibit potential for predicting drug responses in vitro. These findings motivate further investigations about the relevance and application of our unbiased discovery approach in pre-clinical, translationally-oriented research.

Head and neck squamous cell carcinoma (HNSCC) is commonly associated with a high risk of malnutrition and sarcopenia, related to adverse clinical outcomes. This study evaluated the prognostic values of body composition on recurrence and survival in patients with advanced-stage HNSCC.This study prospectively enrolled 258 consecutive patients with definitive treatments for advanced-stage HNSCC. For the determination of sarcopenia, the cross-sectional area of the skeletal muscles (SMs) was measured at the level of the third lumbar vertebra on the computed tomography images of whole-bodyPretreatment and post-treatment diminished SM masses (sarcopenia) were found in 17 (6.6%) and 32 (12.4%) of 258 included patients, respectively. All values of body composition, SM index, visceral fat area, lean body mass, fat mass and body mass index significantly decreased after treatment (all P 0.05). Multivariable analyses showed that age, Charlson comorbidity index, pretreatment and post-treatment sarcopenia, pretreatment hypoalbuminaemia, p16 status and tumour site remained the independent variables predictive of DFS and OS outcomes (all P 0.05). Patients with sarcopenia before or after treatment had about threefold increased risk of overall recurrence or death.Diminished SM mass may predict recurrence and survival after definitive treatments in patients with advanced-stage HNSCC.

The selective targeting of cytotoxic agents to a tumor has shown limited success by difficulties in identifying the appropriate target molecules, and more importantly, by the phenotypically dynamic nature of the tumor cells and intratumoral heterogeneity. In an attempt to overcome these issues and efficiently deliver cytotoxic drugs to the tumor, we previously reported a strategy termed radiation-induced apoptosis-targeted chemotherapy (RIATC), which utilizes the radiotherapy for intentionally triggering the caspase-3 and in situ amplification of tumor apoptosis by caspase-3 activated prodrug. Herein, we propose an advanced form of RIATC prodrug, AP1-DEVD-S-DOX, that could more actively target to the ligands of radiation-induced tumor cells, which could accumulate more prodrugs, thereby allowing more effective in situ activation and amplification of tumor apoptosis, comparing to RIATC. Indeed, AP1-DEVD-S-DOX was able to exert improved doxorubicin (DOX) delivery to the tumor and anticancer effect than the RIATC prodrug that lacks apoptotic cell-binding property but having a similar degree of off-target distribution in the other organs. Accordingly, AP1-DEVD-S-DOX could be an efficient prodrug for concurrent chemoradiotherapy by selectively delivering doxorubicin to the tumor with less systemic cytotoxicity.

Objectives: This study aimed to compare the characteristics of idiopathic unilateral vocal fold paralysis (IUVFP) in elderly versus younger patients, including the diagnostic yield of computed tomography (CT) scans for identifying the structural causes of IUVFP. Methods: We retrospectively analyzed medical records of the patients initially diagnosed with IUVFP in a single referral tertiary hospital. We compared patients’ baseline characteristics, initial symptoms, laryngoscopic findings, and prevalence of structural causes on CT scans with respect to age (younger, Results: One hundred forty-two patients were enrolled (90 younger, 52 older). Evident structural causes were more frequently found on CT in older patients than younger patients (40.4% vs 22.2%, P = .034). Among truly idiopathic cases (70 younger, 31 older), recovered vocal fold mobility was identified in 48.6% younger and 41.9% older patients ( P = .666). There was no statistically significant difference in the characteristics between unrecovered and recovered subjects of the older patients with true IUVFP (all P > .05). Conclusions: The CT scans provided significantly higher diagnostic yields in older patients than younger patients. The degrees of symptoms and complications and likelihood of natural recovery did not significantly differ between younger and older patients with IUVFP.

Despite the emergence of advanced therapeutics such as targeted therapy and immunotherapy in the modern oncology, cytotoxic chemotherapy still remains as the first-line treatment option in a wide range of cancers attributing to its potency. Many endeavors have been made to overcome the toxicity issues of cytotoxic chemotherapy by improving the specific delivery to the tumor, with active tumor targeting being one of the most popular approaches. However, such an approach has been challenged by the intratumor heterogeneity and the lack of valid molecular target in many types of cancer. Here, we introduce a novel albumin-binding prodrug MPD02 that could specifically deliver highly potent cytotoxin monomethyl auristatin E (MMAE) to the tumor as an important component of chemoradiotherapy for the treatment of triple-negative breast cancer (TNBC). MPD02 was synthesized by conjugating MMAE to the C-terminus of the KGDEVD peptide via self-eliminating linker and introducing a maleimide group to the Lys side chain of the peptide. MPD02 was able to bind albumin after administration via maleimide group for an extended circulation time and metabolized into MMAE in tumor-specific manner by reacting with the caspase-3 upregulated in tumor by radiotherapy, exerting a highly potent anticancer effect with good safety profile in two different TNBC xenograft models.

Recurrent laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC) is commonly associated with poor survival outcomes. We evaluated the prognostic role ofThis study involved 100 consecutive LHSCC patients who underwentTwo-year postsalvage PFS and OS rates were 67.9% and 74.3%, respectively. All

We are concerned about burst synchronization (BS), related to neural information processes in health and disease, in the Barab\'{a}si-Albert scale-free network (SFN) composed of inhibitory bursting Hindmarsh-Rose neurons. This inhibitory neuronal population has adaptive dynamic synaptic strengths governed by the inhibitory spike-timing-dependent plasticity (iSTDP). In previous works without considering iSTDP, BS was found to appear in a range of noise intensities for fixed synaptic inhibition strengths. In contrast, in our present work, we take into consideration iSTDP and investigate its effect on BS by varying the noise intensity. Our new main result is to find occurrence of a Matthew effect in inhibitory synaptic plasticity: good BS gets better via LTD, while bad BS get worse via LTP. This kind of Matthew effect in inhibitory synaptic plasticity is in contrast to that in excitatory synaptic plasticity where good (bad) synchronization gets better (worse) via LTP (LTD). We note that, due to inhibition, the roles of LTD and LTP in inhibitory synaptic plasticity are reversed in comparison with those in excitatory synaptic plasticity. Moreover, emergences of LTD and LTP of synaptic inhibition strengths are intensively investigated via a microscopic method based on the distributions of time delays between the pre- and the post-synaptic burst onset times. Finally, in the presence of iSTDP we investigate the effects of network architecture on BS by varying the symmetric attachment degree $l^*$ and the asymmetry parameter $\Delta l$ in the SFN., Comment: arXiv admin note: substantial text overlap with arXiv:1708.04543, arXiv:1801.01385

High-grade salivary gland carcinoma (SGC) shows a high rate of metastasis and post-treatment recurrence, resulting in poor patient survival. Therefore, we evaluated the utility of pre-treatmentThis observational study included 75 patients with previously untreated high-grade SGC who underwent pre-treatmentA total of 36 (48%) patients had neck or distant metastases at initial staging. After controlling for clinical factors, MTV ( 8.8 mL) was an independent factor for initial metastasis (adjusted odds ratio 4.80, 95% confidence interval 1.09-21.20; P = 0.039). All PET parameters of SUVMTV is useful among quantitative PET measurements for predicting initial metastasis and PFS in patients with high-grade SGC.

To examine risk factors for posttreatment recurrence in papillary thyroid carcinoma (PTC) patients with initial presentation of lateral neck metastasis (N1b).N1b PTC recurs after definitive treatment.Study subjects were 437 consecutive PTC patients who underwent total thyroidectomy and therapeutic neck dissection of central and lateral compartments and postoperative radioactive iodine ablation therapy. The patients' demographics and pathological factors, including factors related to tumors and lymph nodes (LNs), and postoperative thyroglobulin levels were reviewed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify factors associated with recurrence-free survival (RFS).During a median follow-up of 83 months (range, 32-135 months), recurrence occurred in 81 (18.1%) patients. Univariate analyses showed that male sex, tumor size, macroscopic extrathyroidal extension, perineural invasion, extranodal extension, LN involvement, LN ratio, MACIS score, and postoperative serum levels of thyroglobulin were significantly associated with RFS (P0.05). Multivariate analyses revealed that LN ratio (0.25) in the lateral compartment (adjusted hazard ratio = 2.099, 95% confidence interval = 1.278-3.448; P = 0.003), and postoperative serum levels of stimulated (5.0 ng/mL; 3.172, 1.661-6.056, P0.001) and unstimulated (0.1 ng/mL; 3.200, 1.569-6.526, P = 0.001) thyroglobulin were independent predictors of any-site RFS. Clinical and tumor factors were not independent predictors of RFS outcomes (P0.1).Posttreatment recurrence is predicted by the LN ratio in the lateral compartment and postoperative serum levels of thyroglobulin in patients with metastatic PTC in the lateral neck.