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Purpose: The neutrophil-to-lymphocyte ratio is a simple biomarker that reflects the balance between the systemic inflammatory and immunity status. Here we investigate the prognostic role of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in an Asian cohort of oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: A retrospective review of OPSCC patients from a tertiary institution was conducted. The NLR was calculated from the haematological specimen taken within a month before treatment. Survival rates were estimated via the Kaplan–Meier method, and Cox proportional hazards regression was performed for univariable and multivariable analyses. The NLR cutpoint was determined using maximally selected log-rank statistics. Results: In a cohort of 148 OPSCC patients, 43% were p16-positive and 44% were p16-negative, with a median follow-up of 24 months. The p16-positive patients were younger (median age 62 vs. 67 years) and exhibited a lower prevalence of heavy smoking (47% vs. 69%). The p16-negative cases frequently presented at an advanced disease stage (74% vs. 41%), with a history of previous radiotherapy (26% vs. 3%). The p16-negative patients displayed a higher median NLR (2.91 vs. 2.49). The 3-year disease-specific survival (DSS) in p16-positive was higher compared to p16-negative patients (89.9% vs. 41.6%). The optimal NLR cutpoint was determined as 3.56 and predicted for decreased DSS (hazard ratio [HR] 2.59, p = 0.004). Multivariable analysis revealed smoking, high NLR ≥ 3.56, and p16-negativity as independent variables associated with poorer DSS and overall survival (OS) across the cohort. Conclusion: A high NLR is independently prognostic of poorer DSS in OPSCC, independent of p16 and smoking status. A NLR of more than 3.56 was highly prognostic for poorer survival and warrants further validation in larger cohorts of OPSCC.

Introduction Self-compassion (SC) describes an emotionally positive attitude extended toward ourselves when we suffer, consisting of three main components; self-kindness, common humanity, and mindfulness (Germer & Neff, 2013). SC entails being warm and understanding towards ourselves when encountering pain or personal shortcomings, rather than ignoring them or flagellating ourselves with self-criticism. SC also involves recognizing that suffering and failure are part of the shared human experience rather than isolating. In addition, SC requires taking a mindful approach to one’s feelings and thoughts, without judgment of them. Objectives Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing depression and anxiety in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied. Methods Magnetic resonance imaging data were acquired from 71 healthy participants with measured levels of SC and its six subscales. Mirroring network as WM regions of interest were analyzed using tract-based spatial statistics (TBSS). After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed. Results We found that self-compassion scale (SCS) total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores of SCS were also negatively correlated with FA values of the same regions. The FA values of SLF related to SC were found to be negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy. Conclusions Our findings suggest that levels of SC and its self-kindness and mindfulness components may be negatively associated with DMN-related WM microstructures in healthy individuals. These less WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies. Disclosure of Interest None Declared

Early childhood caries is a severe oral disease that results in aggressive tooth decay. Particularly, a synergistic association between a fungus, Candida albicansStreptococcus mutans

Abstract Background The advent of the immunomodulatory imide drugs (IMiDs) lenalidomide and thalidomide for the treatment of patients with plasma cell myeloma (PCM), has contributed to more than a doubling of the overall survival of these individuals. As a result, PCM patients join survivors of other malignancies such as breast and prostate cancer with a relatively new clinical problem – second primary malignancies (SPMs) – many of which are a result of the treatment of the initial cancer. PCM patients have a statistically significant increased risk for acute myeloid leukemia (AML) and Kaposi sarcoma. IMiD treatment has also been associated with an increased risk of myelodysplastic syndrome (MDS), AML, and squamous cell carcinoma of the skin. However, within these overlapping groups, acute lymphoblastic leukemia (ALL) is much less common. Case presentation Herein, we describe an elderly man with PCM and a 14-year cumulative history of IMiD therapy who developed persistent pancytopenia and was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). He joins a group of 17 other patients documented in the literature who have followed a similar sequence of events starting with worsening cytopenias while on IMiD maintenance for PCM. These PCM patients were diagnosed with B-ALL after a median time of 36 months after starting IMiD therapy and at a median age of 61.5 years old. Conclusions PCM patients with subsequent B-ALL have a poorer prognosis than their de novo B-ALL counterparts, however, the very low prevalence rate of subsequent B-ALL and high efficacy of IMiD maintenance therapy in PCM should not alter physicians’ current practice. Instead, there should be a low threshold for bone marrow biopsy for unexplained cytopenias.

Abstract Background Acute infectious conjunctivitis is a common condition most frequently caused by viruses or bacteria. Clinical outcome assessments have been used to assess signs and symptoms of bacterial and viral conjunctivitis, but have not been evaluated for content validity. We aimed to develop content-valid patient- (PRO) and observer-reported outcome (ObsRO) instruments to assess symptoms of ocular discomfort associated with viral or bacterial conjunctivitis in adult and pediatric patients. Methods Draft items were developed from a previous review of published studies from 2001 to 2015. Patients and caregivers of patients with a diagnosis of viral or bacterial conjunctivitis within the past 6 months were recruited. Concept elicitation with open-ended questions explored signs and symptoms, followed by cognitive interviewing to assess clarity and relevance of the draft items. Patients aged ≥8 years were interviewed for the PRO; parents/caregivers of children aged 1–10 years were interviewed for the ObsRO. Interviews were conducted in three rounds to allow changes. Concept saturation was documented using a saturation grid. Cognitive interview data were analyzed iteratively and focused on clarity, relevance and inconsistent interpretation of the instrument’s content. Results Overall, 23 patients or parents/caregivers participated (round 1, n = 10; round 2, n = 6; round 3, n = 7). Data saturation was reached by the 16th interview. The most frequent spontaneously reported signs/symptoms were: discharge, red/pink eyes, itchiness, swelling/puffiness, watery eyes, pain, burning and foreign body sensation. Itching, pain/burning/stinging and foreign body sensation were most commonly reported as the top three most bothersome symptoms. Interview results indicated that items on pain, itching and foreign body sensation for the PRO and pain or discomfort for the ObsRO were relevant to the patients’ experience of conjunctivitis and were clear and easy to understand. Conclusions PRO and ObsRO items were found to be clear, relevant and appropriate in assessing key viral and bacterial conjunctivitis symptoms in adult and pediatric patients.

Despite representing 30% to 40% of newly diagnosed cases of adult non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL) rarely presents (1) in the leukemic phase (2) with dysregulation of the TP53 tumor suppressor gene and (3) an elevated serum lactic acid level. In this case report and literature review, we highlight this unfortunate triad of poor prognostic features associated with an aggressive and fatal clinical course in a 53-year-old man with recrudescent DLBCL. A leukemic presentation of de novo or relapsed DLBCL is rare and may be related to differential expressions of adhesion molecules on cell surfaces. In addition, TP53 gene mutations are present in approximately 20% to 25% of DLBCL cases and foreshadow worse clinical outcomes. Finally, an elevated serum lactic acid level in DLBCL that is not clearly associated with sepsis syndrome is a poor prognostic factor for survival and manifests as type B lactic acidosis through the Warburg effect.

Abstract Germline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a two‐phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome‐wide genotypes at 246 173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazard regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta‐analysis of all samples (n = 5553) confirms that the presence of rs1131636‐T, located in the 3′‐UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20–1.47, P = 6.31 × 10−8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promotes the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR‐1253 is identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

Purpose: To report two cases of patients with late extrusion following uneventful implantation of intrastromal corneal ring segments (ICRS) for myopia. Observations: Two patients with previously implanted ICRS for low myopia presented with spontaneous onset of extrusion of their ICRS, one at 7 years post-operatively and the other at 17 and 20 years. Both cases underwent explantation and maintained excellent best-corrected visual acuity. These cases represent the longest reported intervals between implantation of the ICRS and subsequent extrusion. Conclusions and importance: Late extrusion can occur many years following implantation of ICRS, even in eyes without pre-existing thinning or ectasia. The technique for explantation described herein can result in favorable clinical outcomes in such cases. These cases demonstrate the importance of long-term follow up of eyes that have undergone ICRS implantation.

Treatment response in patient-derived models may serve as a biomarker for response in the clinic. Here, the authors use paired patient-derived mouse xenografts and patient-derived primary culture models from head and neck squamous cell carcinomas, including metastasis, as models for high-throughput screening of anti-cancer drugs.

The objective of the experiment was to investigate the effects of supplementing laying hens with purified amino acids (PAA) derived from the blood of animal slaughter house on their egg production, egg quality, and immune response. The experiment was based on completely randomized design. A total of 144 Isa Brown laying hens (56-weeks old) were randomly allotted to 4 treatments with 4 pen replications (control, T1: 0.05%, T2: 0.1%, and T3: 0.5% PAA). Each pen housed nine laying hens. The laying hens were reared under a deep litter system. Once a week, a total of 12 eggs of each treatment were collected for egg quality analysis. At the end of the experiment, blood samples were collected for biochemical analysis and cytokines profiles using ELISA kit assays. Hen day egg production and hen house egg production increased significantly (P

Abstract Background The current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response. Methods We initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS). Results The 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P

The effects of acetate and propionate in enhancing intramuscular fat (marbling) deposition in beef cattle are poorly understood. This study aimed to evaluate the effects of acetate and propionate on pre-adipocyte determination and adipocyte differentiation in stromal vascular cells (SVC) isolated from the intramuscular tissue of Hanwoo beef cattle. SVC were isolated and treated with different concentrations of acetate and propionate (0.125 to 1 mM). Pre-adipocyte determination was observed through the Zfp423 (Zinc finger protein 423) and Pref-1 (Pre-adipocyte factor-1) genes expressions, which were important transcription factors used to identify committed pre-adipocytes. Adipocyte differentiation was determined based on the lipid accumulation, triglyceride contents, and their molecular activities related to adipogenic markers. The results suggest that acetate supports pre-adipocyte determination in SVC which is observed to increase the expression of Zfp423 and Pref-1 along with the increasing acetate concentration. Propionate treatment was seen to significantly affect lipid accumulation as well as triglyceride content in SVC, compared to acetate treatment. Furthermore, propionate treatment very significantly increased the expressions of PPARγ, C/EBPα, SREBP-1c, and FABP4. In conclusion, acetate likely enhances pre-adipocyte determination, while propionate effectively promotes adipogenesis in SVC isolated from the intramuscular tissue of Hanwoo beef cattle.

The existences of protein are important to supply nutritional requirements and to support optimal growth performance in modern broiler chicken. The present experiment was conducted to evaluate the effect of purified amino acid (PAA) isolated from animal blood on growth performance and immune response. A total of one hundred of 1-day old broiler chicken were used in the experiment, following a completely randomized design of 4 groups of treatment differed in concentrations of PAA supplementation (T1: control, no PAA addition; T2: 0.05%; T3: 0.1%; and T4: 0.5%) with 4 replicates for each group. Levels of various cytokines, such as IgA, IgG, interleukin (IL)-2, IL-6, tumor necrosis factor α, and interferon γ, were analyzed using an ELISA kit. Insulin-like growth factor 1, an important growth hormone, was also examined using an ELISA kit. The present result showed feed efficiency and average daily feed intake of broiler chicken increased significantly along with increasing concentrations of PAA (P

Earlier studies have reported the formation of an exclusion zone devoid of microspheres at the interface of water with a hydrophilic surface such as Nafion® or the hydrophilic ceramic powder. We now report the formation of a 'three-dimensional cell-like structured exclusion zone' in water prepared by two different methods. In the first, the hydrophilic powder was agitated with deionized water and allowed to rest (contact method). Subsequently, the 'powder-supernatant water' was collected and termed 'contact water'. In the second method, deionized water in a closed container was kept in the close vicinity of the hydrophilic powder for an extended time-period and it was termed 'non-contact water'. The two kinds of waters were tested by standard methods for various physical properties. In addition, we carried out cryogenic scanning-electron microscopy of frozen samples of the two kinds of water. The powder-supernatant water showed a cell-like heterogeneous ice structure with the high-density exclusion-zone water forming the walls of a cell-like structure. A similar cell-like ice structure was formed for water treated with the hydrophilic powder in a non-contact manner; the unit cell size depended on the 'degree of structure' in the water. When highly structured, the unit cell size was smaller with a concurrently enhanced dielectric constant and reduced redox potential. It was found that the electrical properties are more sensitive to the change in water structure compared to other physical properties such as surface tension, density, and specific heat. Based on our findings of an electric potential difference between the heterogeneous structured water and the ordinary water, we propose a new model to explain the relationship between heterogeneous, structured water and its electrical properties.

Ieodo Ocean Research Station (IORS), a research tower (~ 40 m a.s.l.) for atmospheric and oceanographic observations, is located in the East China Sea (32.07° N, 125.10° E). The IORS is almost equidistant from South Korea, China, and Japan and, therefore, it is an ideal place to observe Asian outflows without local emission effects. The seasonal variation of ozone was distinct, with a minimum in August (37 ppbv) and two peaks in April and October (62 ppbv), and was largely affected by the seasonal wind pattern over east Asia. At IORS, six types of air masses were distinguished with different levels of O3 concentrations by the cluster analysis of backward trajectories. Marine air masses from the Pacific Ocean represent a relatively clean background air with a lowest ozone level of 32 ppbv, which was most frequently observed in summer (July–August). In spring (March–April) and winter (December–February), the influence of Chinese outflows was dominant with higher ozone concentrations of 62 and 49 ppbv, respectively. This study confirms that the influence of Chinese outflows was the main factor determining O3 levels at IORS and its extent was dependent on meteorological state, particularly at a long-term scale.

Transparency of the human cornea is necessary for vision. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indication for corneal transplantation in developed countries. While the early onset, and rarer, form of FECD has been linked to COL8A2 mutations, the more common, late onset form of FECD has genetic mutations linked to only a minority of cases. Epigenetic modifications that occur in FECD are unknown. Here, we report on and compare the DNA methylation landscape of normal human corneal endothelial (CE) tissue and CE from FECD patients using the Illumina Infinium HumanMethylation450 (HM450) DNA methylation array. We show that DNA methylation profiles are distinct between control and FECD samples. Differentially methylated probes (10,961) were identified in the FECD samples compared with the control samples, with the majority of probes being hypermethylated in the FECD samples. Genes containing differentially methylated sites were disproportionately annotated to ontological categories involving cytoskeletal organization, ion transport, hematopoetic cell differentiation, and cellular metabolism. Our results suggest that altered DNA methylation patterns may contribute to loss of corneal transparency in FECD through a global accumulation of sporadic DNA methylation changes in genes critical to basic CE biological processes.

This study was aimed to examine the antibacterial and antioxidative properties of seven edible plants from Thailand to develop alternative antibiotics as feed additives. The plants include Citrus aurantifolia Swingle (Lime) fruits and its leaves, Sesbania grandiflora L. (Agati sesbania) leaves, Piper sarmentosum Roxb (Wild betal) leaves, Curcuma domestica Valeton (Turmeric) roots, Morinda citrifolia L. (Beach mulberry) leaves, Cassia siamea britt (Siamea cassia) leaves, and Cocos nucifera L. (Coconut) peels. The plants were extracted by methanol, n-hexane, chloroform, ethyl acetate, butanol and water. Antibacterial activities with minimum inhibitory concentration (MIC) were determined by agar diffusion assay against Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus parasuis, and Clostridium perfringens that were considered pathogenic strains in livestock infection. Methanol extracts of C. aurantifolia Swingle fruits and leaves showed the broadest spectrum of antibacterial activities except for C. perfringens. Butanol extract of S. grandiflora L. leaves showed the strongest activity against Burkholderia sp. with MIC, 135 μg/mL. P. sarmentosum Roxb leaves showed antibacterial activities against E. coli, Burkholderia sp. and H. parasuis. Ethyl acetate and water extracts from C. domesitca Valeton roots showed MIC of 306 μg/mL and 183 μg/mL, respectively against only C. perfringens. Antioxidative activity was determined by 2-diphenyl-2-picryl hydrazyl photometric assay. The methanol extracts of C. aurantifolia Swingle fruits and P. sarmentosum Roxb leaves showed the highest antioxidant activity among all the extracts with 3.46 mg/mL and 2.70 mg/mL effective concentration 50% (EC50) values, respectively. Total contents of phenolics and flavonoids were measured from the plant extracts. Methanol extracts of S. grandiflora L. and chloroform extracts of C. domestica Valeton were found to have the highest amount of total phenolics, 41.7 and 47.8 μg/mL, respectively. Flavonoid content of methanol extracts in S. grandiflora L. T was 22.5 μg/mL and the highest among plant extracts tested. These results indicated that C. aurantifolia Swingle, S. grandiflora L., P. sarmentosum Roxb, and C. domestica Valeton have antibacterial and antioxidant activities and can be used as alternative antibiotics or potential feed additives for the control of animal pathogenic bacteria.

Using a gravity model and the data of a panel of eight nations, we present evidence that supports the views that geographical influence on trade had increased from 1985 to 1997. In both years, linguistic influence on trade is found to exist in export but not in import. The estimated results show a positive relation between religious similarity and international trade for the year 1985 but not for the year 1997. However, there is an indication that, for 1997, the religious dissimilarity tends to discourage international trade with low-income countries and regions and to encourage international trade with high-income countries. We also find that, for low-income trade partners, religious dissimilarity retards imports more than exports; by contrast, for high-income trade partners, it encourages exports more than imports.