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Paenibacillus konkukensis sp. nov., SK3146 is a novel strain isolated from a pig feed. Here, we present complete genome sequence of SK3146. The genome consists of a single circular genome measuring 7,968,964 bp in size with an average guanine + cytosine (G+C) content of 53.4%. Genomic annotation revealed that the strain encodes 151 proteins related to hydrolases (EC3), which was higher than those in Bacillus subtilis and Escherichia coli. Diverse kinds of hydrolases including galactosidase, glucosidase, cellulase, lipase, xylanase, and protease were found in the genome of SK3146, coupled with one bacteriocin encoding gene. The complete genome sequence of P. konkukensis SK3146 indicates the immense probiotic potential of the strain with nutrient digestibility and antimicrobial activity functions.

OBJECTIVE To assess whether epilepsy is associated with increased odds of 30-day readmission due to psychiatric illness during the postpartum period. METHODS The 2014 Nationwide Readmissions Database and the International Classification of Disease, Ninth Revision, Clinical Modification codes were used to identify postpartum women up to 50 years old in the United States, including the subgroup with epilepsy. The primary outcome was 30-day readmission and was categorized as (1) readmission due to psychiatric illness, (2) readmission due to all other causes, or (3) no readmission. Secondary outcome was diagnosis at readmission. The association of the primary outcome and presence of epilepsy was examined using multinomial logistic regression. RESULTS Of 1 558 875 women with admissions for delivery identified, 6745 (.45%) had epilepsy. Thirteen of every 10 000 women had 30-day psychiatric readmissions in the epilepsy group compared to one of every 10 000 in the no-epilepsy group (p

Objective To derive and validate a comorbidity-based delirium risk index (DRI) to predict postoperative delirium. Data source/study setting Data of 506 438 hip fracture repair surgeries from 2006 to 2016 were collected to derive DRI and perform internal validation from the Premier Healthcare Database, which provided billing information on 20-25 percent of hospitalizations in the USA. Additionally, data of 1 130 569 knee arthroplasty surgeries were retrieved for external validation. Study design Thirty-six commonly seen comorbidities were evaluated by logistic regression with the outcome of postoperative delirium. The hip fracture repair surgery cohort was separated into a training dataset (60 percent) and an internal validation (40 percent) dataset. The least absolute shrinkage and selection operator (LASSO) procedure was applied for variable selection, and weights were assigned to selected comorbidities to quantify corresponding risks. The newly developed DRI was then compared to the Charlson-Deyo Index for goodness-of-fit and predictive ability, using the Akaike information criterion (AIC), Bayesian information criterion (BIC), area under the ROC curve (AUC) for goodness-of-fit, and odds ratios for predictive performance. Additional internal validation was performed by splitting the data by four regions and in 4 randomly selected hospitals. External validation was conducted in patients with knee arthroplasty surgeries. Data collection Hip fracture repair surgeries, knee arthroplasty surgeries, and comorbidities were identified by using ICD-9 codes. Postoperative delirium was defined by using ICD-9 codes and analyzing billing information for antipsychotics (specifically haloperidol, olanzapine, and quetiapine) typically recommended to treat delirium. Principal findings The derived DRI includes 14 comorbidities and assigns comorbidities weights ranging from 1 to 6. The DRI outperformed the Charlson-Deyo Comorbidity Index with better goodness-of-fit and predictive performance. Conclusions Delirium risk index is a valid comorbidity index for covariate adjustment and risk prediction in the context of postoperative delirium. Future work is needed to test its performance in different patient populations and varying definitions of delirium.

OBJECTIVE Identifying adverse outcomes and examining trends and causes of nonelective admissions among persons with epilepsy would be beneficial to optimize patient care and reduce health services utilization. We examined the association of epilepsy with discharge status, in-hospital mortality, length-of-stay, and charges. We also examined 10-year trends and causes of hospital admissions among those with and without epilepsy. METHODS Nonelective hospital admission in persons with epilepsy was identified in the 2005-2014 National Inpatient Sample (NIS) using a validated International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) case definition. The NIS is the largest US all-payer database including patient and hospital-level variables, and represents hospitalizations in the general population. Descriptive statistics on trends and causes of admissions and multivariable regression analysis summarizing the association of epilepsy with the outcomes of interest are presented. RESULTS Of 4 718 178 nonelective admissions in 2014, 3.80% (n = 179 461) were in persons with epilepsy. Admissions in persons with epilepsy increased from 14 636 to 179 461 (P

Biological subtypes have been strongly correlated with loco-regional recurrence after definitive treatment for localized breast cancer. Brain metastases (BM) occur in 15% of patient diagnosed with breast cancer (BC). Therefore, we sought to determine whether biologic subtype is predictive of local control (LC) in BC patients with BM treated with stereotactic radiosurgery (SRS). This is a single-center retrospective study conducted with Institutional Review Board approval for the period January 1, 2004–December 31, 2018. Eligibility criteria included (1) histopathologic proven BC with documented biologic subtype, (2) presence of BM treated with SRS (single fraction), (3) follow-up MRIs, and (4) clinical follow-up. Patients were subdivided into three biologic subtypes: ER+/HER2- (“luminal”), HER2+, and ER-/PR-/HER2 (TN). All patients were treated with LINAC-based SRS with dose according to published guidelines. Cox proportional hazard model and Kaplan-Meier were used for statistical analysis of LC and overall survival (OS). With a median follow-up of 11.1 months, 17 BC BM in 50 consecutive patients were included in this study. The median disease-specific GPA was 2.0, and all patients received systemic chemotherapy and/or hormonal therapy. The 12-month LC rates for the entire cohort were 85%, 87%, and 49% for luminal, HER2+, and TN, respectively, with a significantly shorter time to local failure for the TN subtype (p = 0.014). The 12-month OS rates were 83%, 88%, and 80% for luminal, HER2+, and TN, respectively, with a trend toward shorter OS in the TN group. This study shows that in BC patients with BM treated with SRS, biologic subtype affects LC. Consideration of radiation treatment intensification or altered fractionation to improve LC may be indicated for the TN subtype. Further multicenter studies are necessary to corroborate our results.

Background Currently, there are no recognized or validated biomarkers to identify hepatocellular carcinoma patients (HCC) likely to benefit from anti–PD‐1 therapy. We evaluated the relationship between neutrophil‐lymphocyte ratio (NLR) and platelet‐lymphocyte ratio (PLR) and survival outcomes, pretreatment and after three doses (posttreatment) of nivolumab in HCC patients. Methods Medical records of HCC patients treated with nivolumab between June 2016 and July 2018 were reviewed. Kaplan‐Meier analysis and the log‐rank test were used to calculate and compare overall survival between NLR, In this study evaluating 103 patients with advanced hepatocellular carcinoma, lower neutrophil‐lymphocyte ratio (NLR) and platelet‐lymphocyte ratio (PLR) were both strongly predictive of improved survival after three cycles of nivolumab. Baseline NLR was not associated with survival. An elevated NLR and PLR in the posttreatment setting may be an early sign of treatment failure and may warrant consideration for early change in therapy.

The National Lung Screening Trial (NLST) found that low-dose computed tomography (LDCT) screening provided lung cancer (LC) mortality benefit compared to chest radiography (CXR). Considerable research concerns identifying the differential treatment effects that may exist in certain subpopulations. We shed light on several important issues in existing research and highlight the need for further investigation of the heterogeneous comparative effect of LDCT versus CXR, using more flexible and rigorous statistical approaches. We used a high-performance Bayesian machine learning approach designed for censored survival data, accelerated failure time Bayesian additive regression trees model (AFT-BART), to flexibly capture the relationships between the failure time and predictors. We then used the counterfactual framework to draw Markov chain Monte Carlo samples of the individual treatment effect for each participant. Using these posterior samples, we explored the possible treatment effect heterogeneity via a stepwise binary tree approach. When re-analyzed with AFT-BART, LDCT did not have a statistically significant LC or overall mortality benefit compared to CXR. The Asian and Black (particularly those with pack-year ≥ 37 years and without emphysema) NLST population were shown to have enhanced overall mortality benefit from LDCT than the population average. Although inconclusive for LC mortality benefit, Asians, Blacks and Whites with history of chronic obstructive pulmonary disease showed a small trend towards benefit from LDCT. Causal inference with flexible machine learning modeling can provide valuable knowledge for informing treatment decision and planning targeted clinical trials emphasizing personalized medicine approaches.

AIMS: The aim of this study was to improve medication reconciliation and reduce the occurrence of duplicate prescriptions by pharmacists and physicians within 72 hours of hospital admission using an intelligent prescription system combined with the National Health Insurance PharmaCloud system to integrate the database with the medical institution computerized physician order entry (CPOE) system. METHODS: This 2‐year intervention study was implemented in the geriatric ward of a hospital in Taiwan. We developed an integrated CPOE system linked with the PharmaCloud database and established an electronic platform for coordinated communication with all healthcare professionals. Patients provided written informed consent to access their PharmaCloud records. We compared the intervention effectiveness within 72 hours of admission for improvement in pharmacist medication reconciliation, increased at‐home medications documentation and decreased costs from duplicated at‐home prescriptions. RESULTS: The medication reconciliation rate within 72 hours of admission increased from 44.0% preintervention to 86.8% postintervention (relative risk = 1.97, 95% confidence interval [CI]: 1.69–2.31; P

College students' physical education plays an important role in physical activity and cultivates the concept of independent health management. At present, what kind of learning attitude do Taiwan college students face in physical education? What motivation does the student influence the attitude of the physical education? What is the relevance? All of the above are the purpose of this study. The research method adopts the questionnaire survey method, and the survey data adopts descriptive statistical analysis, independent sample t test, single factor variance analysis, LSD post hoc comparison method, and typical correlation analysis. Research results: 1. The different background variables of Taiwanese college students are that the main motivation factor of physical education is to obtain good health fitness for "physical health". 2. Taiwanese college students have different background variables. They all think that the "cognitive learning" of physical education is the main factor of attitude, that is, the knowledge about health care and sports skills. 3. There is a positive correlation between learning motivation and learning attitude (ρ=.90). Learning motivation is one of the important factors affecting learning attitude. Research conclusions: 1. The factors of Taiwanese male and female college students' motivation for learning in physical education are mainly based on "physical health". 2. Freshmen have higher motivations and learning attitudes in physical education than second-grade to fourth-grade. 3. Taiwan female college students average 1 or 2 times per week, male college students have the most athletes 2 to 3 times per week, more than 90% of college students like sports. 4. There is a positive correlation between learning motivation and learning attitude, indicating that the stronger the attribute of learning motivation "physical health", the higher the student's learning attitude. 5. Satisfying students' motivation for learning helps students to learn positively. 6. Another important task of the college physical education class is to prepare students for future lifelong sports.

Age-related macular degeneration (AMD), especially neovascular AMD with choroidal neovascularization (CNV), is the leading cause of blindness in the elderly. Although matrix metalloproteinases (MMPs) are involved in pathological ocular angiogenesis, including CNV, the cellular origin of MMPs in AMD remains unknown. The present study investigated the role of microglial MMPs in CNV. MMP activities were analyzed by gelatin zymography in aqueous humor samples from patients with CNV and laser-induced CNV mice. Active MMP-9 was increased in the aqueous humor samples from neovascular AMD patients compared with control subjects. In the retinal pigment epithelium (RPE)/choroid from CNV mice, active MMP-9 increased, beginning 1 h post-CNV induction, and remained upregulated until Day 7. In RPE/choroid from CNV mice, active MMP-9 was suppressed by minocycline, a known microglial inhibitor, at 6 h and 1-day post-CNV induction. Flow cytometry revealed that the proportion of activated microglia increased very early, beginning at 1 h post-CNV induction, and was maintained until Day 7. Similarly, immunohistochemistry revealed increased microglial activation and MMP-9 expression on CNV lesions at 6 h and 1-day post-CNV induction. SB-3CT, an MMP inhibitor, decreased vascular leakage and lesion size in laser-induced CNV mice. These findings indicated nearly immediate recruitment of activated microglia and very early MMP-9 activation in the RPE/choroid. The present study newly identified a potential role for early microglial MMP-9 expression in CNV, and furthermore that modulating microglial MMP expression is a novel putative therapeutic for CNV.

Background Previous studies have found that Black patients with multiple myeloma undergo autologous stem-cell transplantation (ASCT) less frequently than their white counterparts, although the factors leading to decreased access and utilization have not been fully elucidated. Patients and Methods To identify whether racial differences in transplantation timing played a role in these disparities, we retrospectively analyzed 410 Black and white patients who received their first transplant at The Mount Sinai Hospital between 2011 and 2016 (260 white and 150 Black patients). We compared the time from initial diagnosis to stem-cell collection and the time from collection to transplantation between the 2 races while controlling for age, socioeconomic status, and functional status. Results Between Blacks and whites, time from diagnosis to collection was higher in Black patients (median 238, vs. 195 days, respectively, P = .051). Functional status, socioeconomic status, and age were also significantly associated with time to collection, and after controlling for these covariates, the effect of race was not significant (P = .0625). Conversely, time from collection to transplantation was increased in white patients compared to Black. Conclusion Increased time from diagnosis to stem-cell collection for Black patients was driven in part by socioeconomic status and baseline functional status.

Purpose To assess the therapeutic effects of fursultiamine on choroidal neovascularization (CNV) through its modulation of inflammation and metabolic reprogramming in the retinal pigment epithelium (RPE). Methods The anti-angiogenic effects of fursultiamine were assessed by measuring vascular leakage and CNV lesion size in the laser-induced CNV mouse model. Inflammatory responses were evaluated by quantitative polymerase chain reaction, western blot, and ELISA in both CNV eye tissues and in vitro cell cultures using ARPE-19 cells or primary human RPE (hRPE) cells under lipopolysaccharide (LPS) treatment or hypoxia. Mitochondrial respiration was assessed by measuring oxygen consumption in ARPE-19 cells treated with LPS with or without fursultiamine, and lactate production was measured in ARPE-19 cells subjected to hypoxia with or without fursultiamine. Results In laser-induced CNV, fursultiamine significantly decreased vascular leakage and lesion size, as well as the numbers of both choroidal and retinal inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α. In LPS-treated ARPE-19 cells, fursultiamine decreased proinflammatory cytokine secretion and nuclear factor kappa B phosphorylation. Furthermore, fursultiamine suppressed LPS-induced upregulation of IL-6, IL-8, and monocyte chemoattractant protein-1 in a dose-dependent and time-dependent manner in primary hRPE cells. Interestingly, fursultiamine significantly enhanced mitochondrial respiration in the LPS-treated ARPE-19 cells. Additionally, fursultiamine attenuated hypoxia-induced aberrations, including lactate production and inhibitory phosphorylation of pyruvate dehydrogenase. Furthermore, fursultiamine attenuated hypoxia-induced VEGF secretion and mitochondrial fission in primary hRPE cells that were replicated in ARPE-19 cells. Conclusions Our findings show that fursultiamine is a viable putative therapeutic for neovascular age-related macular degeneration by modulating the inflammatory response and metabolic reprogramming by enhancing mitochondrial respiration in the RPE.

Background While the concept of oligometastatic disease is increasingly recognized as a distinct clinical disease state, the concept of oligoprogression is less well-characterized. Oligoprogression may be particularly relevant in the context of immune checkpoint inhibitors (CPI) given the underlying mechanism of action and insights regarding acquired resistance. In this study, we sought to characterize the incidence of oligoprogression in patients on CPI and explore the impact of local therapy. Materials and Methods We performed a retrospective analysis of all patients with advanced solid tumors (excluding glioblastoma multiforme) who received a PD-1, PD-L1, or CTLA-4 inhibitor at a single institution between 2011 and 2017. Oligoprogression was defined as progression at ≤3 metastatic lesions outside of the brain after achieving at least stable disease on CPI for 3 months. Progression-free survival (PFS) was calculated using the Kaplan-Meier method. Results Among 425 patients treated with CPI, 390 had advanced primary solid tumors outside of the central nervous system. 321 of these patients were evaluable for response, among whom 102 achieved at least stable disease. Oligoprogression was observed in 4.1% of the entire cohort and 15.7% of patients achieving at least stable disease on CPI. Among 16 patients experiencing oligoprogression, 15 received local therapy to the oligoprogressive lesions, many of whom continued CPI. At a median follow-up of 25.8 months, the median PFS for patients with oligoprogression after local therapy was 15.4 months. Conclusions Oligoprogression occurs in a subset of patients after an initial response to CPI. However, patients receiving local therapy to oligoprogressive sites may experience durable disease control. Further study is warranted. Microabstract Oligoprogression was observed in 4.1% of the entire cohort of patients on immune checkpoint inhibitors in this study and 15.7% of patients achieving at least stable disease. Among 16 patients experiencing oligoprogression, 15 received local therapy. At a median follow-up of 25.8 months, the median progression-free survival for patients with oligoprogression after local therapy was 15.4 months and zero patients had died. Oligoprogression occurs in a subset of patients after an initial response to CPI and local therapy to oligoprogressive sites may result in durable disease control.

PURPOSE Discharges against medical advice (DAMA) are associated with adverse patient outcomes among those with epilepsy. Our goal was to examine trends and factors associated with DAMA among those living with epilepsy. METHODS A retrospective cross-sectional study was performed using the 2003-2014 National Inpatient Sample database. ICD-9-CM diagnosis codes were used to identify admissions of patients with epilepsy. Following outcomes were examined among epilepsy patients: proportion and predictors of DAMA, 12-year DAMA trends and causes of admissions. RESULTS In 2014, of the 187,850 admissions in patients with epilepsy, 3783 (2.01 %) were DAMA. Male sex, Black race, younger age, lower household income, Medicaid/self-pay/other as primary payer, lower Elixhauser comorbidities index, weekend admission, non-elective admission, hospital in northeast region, and urban nonteaching hospital were all associated with DAMA. There was a significant increase in the proportion of DAMA in people with epilepsy from 2003 to 2014 (1.13 %-2.01 %, p

The inhibitory effect of fresh or dried daylilies extract on the generation of nitric oxide, and the effects of sulfur dioxide in dried daylily on nitric oxide production and DNA damage in Raw 264.7 macrophages were examined. The extracts from sulfitetreated and untreated dried daylily flowers exhibited stronger scavenging effects on nitric oxide production by sodium nitroprusside (SNP) than that of fresh flower. Fresh and untreated dried daylily flowers exhibited strong inhibitory effect on nitric oxide induced by lipopolysaccharide (LPS) in macrophages, but the sulfite-treated dried daylily did not. The scavenging effect of sulfite on nitric oxide production by SNP was dose-dependent, and sulfite also exhibited low inhibitory effect on nitric oxide induced by LPS in macrophages. Sodium hydrogen sulfite also slightly induced DNA damage in macrophages. Although sulfur dioxide in dried flowers is volatilized during heating, its residual adverse effects should still be concerned.

The tyrosine kinase inhibitor sorafenib is the only therapeutic agent approved for the treatment of advanced hepatocellular carcinoma (HCC), but acquired resistance to sorafenib is high. Here, we report metabolic reprogramming in sorafenib-resistant HCC and identify a regulatory molecule, peroxisome proliferator–activated receptor-δ (PPARδ), as a potential therapeutic target. Sorafenib-resistant HCC cells showed markedly higher glutamine metabolism and reductive glutamine carboxylation, which was accompanied by increased glucose-derived pentose phosphate pathway and glutamine-derived lipid biosynthetic pathways and resistance to oxidative stress. These glutamine-dependent metabolic alterations were attributed to PPARδ, which was upregulated in sorafenib-resistant HCC cells and human HCC tissues. Furthermore, PPARδ contributed to increased proliferative capacity and redox homeostasis in sorafenib-resistant HCC cells. Accordingly, inhibiting PPARδ activity reversed compensatory metabolic reprogramming in sorafenib-resistant HCC cells and sensitized them to sorafenib. Therefore, targeting compensatory metabolic reprogramming of glutamine metabolism in sorafenib-resistant HCC by inhibiting PPARδ constitutes a potential therapeutic strategy for overcoming sorafenib-resistance in HCC. Implications: This study provides novel insight into the mechanism underlying sorafenib resistance and a potential therapeutic strategy targeting PPARδ in advanced hepatocellular carcinoma. Mol Cancer Res; 15(9); 1230–42. ©2017 AACR.

The efficacy of current medical treatments for lichen planopilaris (LPP) and its variant, frontal fibrosing alopecia (FFA), both lymphocyte-mediated primary cicatricial alopecias, is limited. Hair regrowth from scar tissue is usually not possible. Although hair transplantation restores the hairline and increases hair density in patients with cicatricial alopecia, the timing of the transplantation is crucial. Here, we report two Chinese patients with LPP or FFA who underwent the follicular unit extraction method of hair transplantation after the diseases were stabilised with therapy, with satisfactory results for 3-4 years of follow up.

Background Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood. Objective This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging. Methods Dermal papilla cells were challenged with H 2 O 2 to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized. Its effect on epithelial-mesenchymal interaction was analyzed by co-culture in vitro and implantation of protein-coated beads in vivo . Result Dermal papilla cells were more resistant to oxidative stress-induced apoptosis than dermal fibroblasts. The surviving dermal papilla cells showed signs of senescence but still preserved key dermal papilla signature gene expression. In addition to the failure to respond to mitogenic stimulation from keratinocytes, they lost the ability to induce hair follicle neogenesis, promoted interfollicular epidermal differentiation, inhibited follicular differentiation and, importantly, suppressed clonal growth of hair follicle stem cells. They produced higher levels of multiple inflammatory cytokines, including IL-6. Functionally, IL-6 inhibited clonal keratinocyte growth in vitro and blocked the transition from telogen to anagen in vivo . Conclusion Stress-induced premature dermal papilla senescence can contribute to hair follicle aging change due to compromised epithelial-mesenchymal interaction.

We provide evidence for the effectiveness of acupuncture in an animal model of alcohol dependence., A withdrawal-associated impairment in β-endorphin neurotransmission in the arcuate nucleus (ARC) of the hypothalamus is associated with alcohol dependence characterized by a chronic relapsing disorder. Although acupuncture activates β-endorphin neurons in the ARC projecting to the nucleus accumbens (NAc), a role for ARC β-endorphin neurons in alcohol dependence and acupuncture effects has not been examined. Here, we show that acupuncture at Shenmen (HT7) points attenuates behavioral manifestation of alcohol dependence by activating endorphinergic input to the NAc from the ARC. Acupuncture attenuated ethanol withdrawal tremor, anxiety-like behaviors, and ethanol self-administration in ethanol-dependent rats, which are mimicked by local injection of β-endorphin into the NAc. Acupuncture also reversed the decreased β-endorphin levels in the NAc and a reduction of neuronal activity in the ARC during ethanol withdrawal. These results suggest that acupuncture may provide a novel, potential treatment strategy for alcohol use disorder by direct activation of the brain pathway.

Metabolic reprogramming during macrophage polarization supports the effector functions of these cells in health and disease. Here, we demonstrate that pyruvate dehydrogenase kinase (PDK), which inhibits the pyruvate dehydrogenase-mediated conversion of cytosolic pyruvate to mitochondrial acetyl-CoA, functions as a metabolic checkpoint in M1 macrophages. Polarization was not prevented by PDK2 or PDK4 deletion but was fully prevented by the combined deletion of PDK2 and PDK4; this lack of polarization was correlated with improved mitochondrial respiration and rewiring of metabolic breaks that are characterized by increased glycolytic intermediates and reduced metabolites in the TCA cycle. Genetic deletion or pharmacological inhibition of PDK2/4 prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus IFN-γ). Transplantation of PDK2/4-deficient bone marrow into irradiated wild-type mice to produce mice with PDK2/4-deficient myeloid cells prevented M1 polarization, reduced obesity-associated insulin resistance, and ameliorated adipose tissue inflammation. A novel, pharmacological PDK inhibitor, KPLH1130, improved high-fat diet-induced insulin resistance; this was correlated with a reduction in the levels of pro-inflammatory markers and improved mitochondrial function. These studies identify PDK2/4 as a metabolic checkpoint for M1 phenotype polarization of macrophages, which could potentially be exploited as a novel therapeutic target for obesity-associated metabolic disorders and other inflammatory conditions.

Background Glioblastoma (GBM), a highly malignant brain tumor, invariably recurs after therapy. Quiescent GBM cells represent a potential source of tumor recurrence, but little is known about their molecular underpinnings. Methods Patient-derived GBM cells were engineered by CRISPR/Cas9-assisted knock-in of an inducible histone2B-GFP (iH2B-GFP) reporter to track cell division history. We utilized an in vitro 3D GBM organoid approach to isolate live quiescent GBM (qGBM) cells and their proliferative counterparts (pGBM) to compare stem cell properties and therapy resistance. Gene expression programs of qGBM and pGBM cells were analyzed by RNA-Seq and NanoString platforms. Findings H2B-GFP-retaining qGBM cells exhibited comparable self-renewal capacity but higher therapy resistance relative to pGBM. Quiescent GBM cells expressed distinct gene programs that affect cell cycle control, metabolic adaptation, and extracellular matrix (ECM) interactions. Transcriptome analysis also revealed a mesenchymal shift in qGBM cells of both proneural and mesenchymal GBM subtypes. Bioinformatic analyses and functional assays in GBM organoids established hypoxia and TGFβ signaling as potential niche factors that promote quiescence in GBM. Finally, network co-expression analysis of TCGA glioma patient data identified gene modules that are enriched for qGBM signatures and also associated with survival rate. Interpretation Our in vitro study in 3D GBM organoids supports the presence of a quiescent cell population that displays self-renewal capacity, high therapy resistance, and mesenchymal gene signatures. It also sheds light on how GBM cells may acquire and maintain quiescence through ECM organization and interaction with niche factors such as TGFβ and hypoxia. Our findings provide a starting point for developing strategies to tackle the quiescent population of GBM. Fund National Institutes of Health (NIH) and Deutsche Forschungsgemeinschaft (DFG).

Introduction: Data-based research has rarely addressed advance directives (ADs) in community-dwelling Korean cancer survivors. The purpose of this study was to examine the relationship between AD treatment choices and decisional conflicts among low-income, home-based cancer management recipients. Method: This study uses a cross-sectional, correlational design. The cancer survivors completed the questionnaires (Korean-Advance Directive model and Decisional Conflict Scale). Results: Among the 103 participants (average age 67.92 years), 56.3% had solid cancer. Hospice care was the most desired (68.9%), followed by hemodialysis (18.4%), cardiopulmonary resuscitation/ventilation support (15.5% for each), and chemotherapy (12.6%). Patients who were older, unmarried, unemployed, or underweight/obese; lived alone; or had lower education experienced greater decisional conflicts. In the multivariate analyses, no hospice preference was associated with greater decisional conflicts ( t = −2.63, p = .01). Discussion: Early integration of AD discussion with the nurse-led, home-based service for this vulnerable population could serve as a liaison for quality and continuity of cancer survivorship care.

Background: Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting. Methods: We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs). Results: Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75–1.35) or multivariable analysis (HR 0.98, 95% CI 0.71–1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66–2.65) or AEs (OR 1.07, 95% CI 0.54–2.12) in multivariable analysis. Conclusions: Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.

Neutrophilic dermatosis on the site of lymphedema is a rare condition and considered as a localized and less severe variant of Sweet syndrome. Only 13 cases of this variant have been reported after mastectomy for breast cancer in the English-language published work. However, this condition has never been described on the lower limbs or from other causes of lymphedema. Herein, we report two cases of localized Sweet syndrome on the lymphedematous lower limbs: one occurred after radical hysterectomy, bilateral pelvic lymph node dissection and radiotherapy for cervical cancer; the other developed after radiotherapy for malignant melanoma on the right groin. Based on clinical and histological features, we suggest the name "lymphedema-associated neutrophilic dermatosis" for this underrecognized disease entity.

Oral diseases among older adults are prevalent and a major public health problem, but public attention regarding this matter is quite limited. Many older adults experience limited access to oral care services. The study aimed to describe characteristics of oral health conditions, perceived oral health status, and oral health practices and to examine factors related to living status and accessibility to dental health care among 9,660 low-income older adults living in a suburban city in Korea. Approximately 42% of low-income older adults lived alone; 68% perceived their oral health as either excellent or good; and 31% reported difficulty accessing dental services. Lack of accessibility to oral care services was significantly more common in older adults with low incomes, living alone, having poor oral conditions, poor self-perceived oral health, and poor tooth-brushing behavior. Strategies to promote access to dental care services for underserved older adults should be developed to prevent further oral problems and their impact on overall health conditions.

Objective Patients undergoing radiation treatment (RT) for head and neck malignancies often suffer significant disease- and treatment-related pain requiring opioids for effective management. However, the prevalence and associated risk factors of prolonged opioid use in this population remain poorly characterized. We sought to quantify the rate of prolonged opioid use among opioid naive patients receiving curative-intent RT for head and neck malignancies and to identify associated risk factors. Methods We retrospectively identified patients who had undergone RT for head and neck malignancies at our institution between Jan 2011 and Sept 2017. Our primary endpoint was persistent opioid use 6-months following completion of RT. Patients were included if they were opioid-naive, underwent curative intent RT, had adequate follow-up, and did not have residual or recurrent disease within our follow-up period. Univariable and multivariable logistic regression was utilized to identify risk factors for prolonged opioid use. Results We identified 311 patients meeting our inclusion criteria; 40 (12.9%) continued to use opioids 6-months following RT. Univariable analysis found current smoking, alcohol abuse, RT dose, treatment to the bilateral necks, induction chemotherapy, concurrent chemotherapy, PEG tube, daily milligram morphine equivalents, and adjuvant analgesic medication use to be positively associated with prolonged opioid use; prior surgery was negatively associated with prolonged opioid use. Delivery of induction chemotherapy (OR 2.86, CI (95%) 1.32–6.21) and alcohol abuse (OR 3.75, CI (95%) 1.66–8.47) remained statistically significant on multivariable analysis. Conclusion The prevalence of prolonged opioid use in previously opioid naive patients undergoing curative intent head and neck RT was just under 13%. Patients with history of alcohol abuse and those who undergo induction chemotherapy were most at risk.

A Gram-negative, aerobic, non-motile, non-spore-forming and rod-shaped bacterial strain, designated SK3863T, was isolated from rotten biji (residue remaining after making tofu). This bacterium was characterized in order to determine its taxonomic position by using the polyphasic approach. Strain SK3863T grew well at 25–37 °C on Reasoner’s 2A agar plates. On the basis of 16S rRNA gene sequence similarity, strain SK3863T belonged to the family Comamonadaceae and was related to Ottowia beijingensis GCS-AN-3T (96.5 % sequence similarity) and Ottowia pentelensis RB3-7T (96.4 %). Lower sequence similarities (96.2 %) were found to all of the other recognized members of the genus Ottowia . The G+C content of the genomic DNA was 65.8 mol%. The major respiratory lipoquinone was ubiquinone 8 and the major fatty acids were C16 : 1 ω6c/C16 : 1ω7c, C16 : 0 and C18 : 1 ω7c/C18 : 1ω6c. Strain SK3863T could be differentiated genotypically and phenotypically from the recognized species of the genus Ottowia . The isolate therefore represents a novel species, for which the name Ottowia konkukae sp. nov. is proposed, with the type strain SK3863T (=KCCM 43236T=DSM 105395T).

Zearalenone (ZEN) is a mycotoxin produced by Fusarium species, which is one of the main animal feed contaminants causing reproductive disorders in livestock. The aim of this study was to evaluate the probiotic characteristics and ZEN removal ability of a Bacillus licheniformis strain CK1. The probiotic properties, including acidic tolerance, bile salt tolerance, adherence capability, and anti-pathogenic activities of CK1 were evaluated. CK1 survived after incubation at pH 2.0 or 3.0 for 3 h, grew well in LB broth containing 0.3% oxgall, possessed adherence capability to Caco-2 cells, and inhibited the growth of Escherichia coli O157:H7 and Listeria monocytogenes. The ZEN removal ability of CK1 was compared with a mineral mycotoxin-adsorbing agent, hydrated sodium calcium aluminosilicate (HSCAS), and a well-characterized biological mycotoxin-adsorbing agent, Lactobacillus rhamnosus GG (LGG). At 37°C in phosphate-buffered saline (PBS, pH 7.0) containing 5 μg mL-1 of ZEN, the ZEN removal percentage of CK1 was 73.0%, which was significantly higher than that of HSCAS and LGG (45.9% and 48.4%, respectively). In the pH range of 2.5-8.0, CK1 removed up to 65% of ZEN. At temperatures between 4 and 42°C, CK1 removed more than 75% of ZEN. In the adsorption stability analysis, the amounts of ZEN removed by CK1 was over 30% even after five consecutive rounds of washing procedures. These findings demonstrated that CK1 displayed probiotic characteristics and removed ZEN effectively. Therefore, CK1 has a great potential for the development of feed additive to remove ZEN.

Background Currently there are no recognized or validated biomarkers to identify HCC patients(pts) likely to benefit from N. Several studies have established the inverse relationship between inflammation-based scores such as NLR, PLR and survival in other solid tumours treated with immunotherapy. We evaluated the relationship between NLR and PLR and survival outcomes in HCC pts treated with N at Mount Sinai Hospital. Methods One hundred and four HCC pts treated between June 2016 and July 2018 were identified. NLR=Absolute neutrophil count/ Absolute lymphocyte count (ALC) and was calculated pretreatment and at 6-8 weeks after 3 doses (Posttreatment) of N. PLR=Platelet count/ALC. Kaplan-Meier analysis and the log-rank test were used to calculate and compare Overall and Progression free survival (OS, PFS) between NLR Results Median age was 66 (29-89) years. Median treatment duration was 26 (2-149) weeks. Child Pugh score (CPS, N = 96) was A in 64 (66%) and B in 32 (33%) pts. Barcelona Clinic Liver Cancer (BCLC) stage was B in 21 (20%) and C in 83 (80%) pts. Median follow-up time was 17 months (95% CI (15.7, 20.7). NLR was Table . 744P Pretreatment PLR group N(%) OS (months) 36(36) 35 P = 0.0495 > = 119 & 32(31) 10 > = 224 33(33) 15 Post treatment PLR group 35(35) Not Reached P = 0.0126 > = 126 & 31(31) 19 > = 229 33(33) 10 Conclusions This study suggests that lower NLR and PLR levels may predict better survival outcomes in HCC patients treated with N. The potential role of NLR and PLR as early predictors of immunotherapy outcomes in HCC pts warrants further evaluation. Legal entity responsible for the study Mount Sinai Hospital. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

This case study aimed at disclosing the changing trends of amount of document delivery services (DDSs) in the Medical Library Information System (MEDLIS) of the Korean Medical Library Association (KMLA). The data from 2001 to 2014 in the MEDLIS were searched and analyzed according to year. To know outside environment of DDS, The trend in use of DDS of the Research Information Sharing Service and the journals listed in the Directory of Open Access Journal were presented. The DDS request in MEDLIS decreased year by year from 214,304 in 2001 to 50,352 in 2014 (23.4%). There was an increased number of requests a monthly average from 4,799 in 2009 to 8,157 in 2014 (170.0%) through Research Information Sharing Service. As of 2015, 10,702 journals were listed in the Directory of Open Access Journal. I can find that the continuous decreased request of DDS in MEDLIS which might be originated from the increased number of DDS service through RISS and the increased number of open access journals.

The aim of this study was to investigate both strategies for coping with stigma and the effects of participating in advocacy. The participants were childhood cancer survivors who had been diagnosed before the age of 18 years who had completed treatment. An embedded-design mixed-methods approach was used with 30 interview scripts, and 145 survey results were collected. Coping strategies for the stigma of cancer were “secrecy, avoid stereotypes, and discrimination” and “disclosure of medical history.” Participation in advocacy confirmed self-worth, helped in achievement, and promoted social skills. Quantitative analysis showed that greater advocacy participation was associated with higher levels of posttraumatic growth. This study could provide support for advocacy among childhood cancer survivors by demonstrating its positive effects.

Colorectal cancers (CRCs) are a critical health issue worldwide. Cancer stem cell (CSC) lineages are associated with tumour transformation, progression, and malignant transformation. However, how lineages are transformed and how chemoresistance is acquired by CRCs remain largely unknown. In this report, we demonstrated that the RNA-binding protein Musashi-1 enhanced the development of CD44+ colorectal CSCs and triggered the formation of anti-apoptotic stress granules (SGs). Our results indicated that CD44+ CSC lineage-specific induction of tumour malignancies was controlled by Musashi-1. In addition, Musashi-1 formed SGs when CRC cell lines were treated with 5-fluorouracil. The C-terminal domain of Musashi-1 was critical for recruitment of Musashi-1 into SGs. Intracellular Musashi-1 SGs enhanced the chemoresistance of CRCs. Analysis of clinical CRC samples indicated that Musashi-1 expression was prominent in CRC stage IIA and IIB. In summary, we demonstrated that Musashi-1, a stemness gene, is a critical modulator that promotes the development of CD44+ colorectal CSCs and also enhances CRC chemoresistance via formation of SGs. Our findings elucidated a novel mechanism of CRC chemoresistance through increased anti-apoptotic effects via Musashi-1-associated SGs.

Alopecia areata (AA) is the most common form of hair loss in children. We report the case of a child who had two episodes of AA after two different vaccines with complete hair regrowth between the episodes. This case supports the concept that vaccination might be a trigger for the development of AA in genetically predisposed children.

5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy.

Objective Dementia and epilepsy often co-occur and are associated with poor health outcomes and increased healthcare utilization. The literature on the association between readmission and co-occurrence of dementia and epilepsy is scant. Our objective was to determine if dementia in patients with epilepsy >40 years old is associated with 30-day hospital readmission, in-hospital mortality, discharge disposition, and length-of-stay. Methods This retrospective cohort study used the 2014 Nationwide Readmissions Database, containing data from hospital discharges across the US and readmissions. Epilepsy and dementia were identified using previously validated ICD-9-CM codes. Primary outcome was 30-day readmission, analyzed with univariable and multivariable logistic regressions. Secondary outcomes were discharge disposition, in-hospital mortality, and length-of-stay, analyzed with univariable multinomial logistic, univariable logistic, and univariable ordinary least squared regressions, respectively. The top ten causes of readmission in each group were compared as well. All analyses accounted for survey weights, cluster, and stratum. Results Patients with epilepsy with dementia (n = 15,588) had longer hospital stays [15% (95%CI 10–20%)], and higher odds of readmission [OR 1.11 (95%CI 1.05–1.17)], transfer to another facility [OR 2.18 (95%CI 1.93–2.46)], and in-hospital mortality [OR 1.50 (95%CI 1.25–1.79)] compared to those without dementia (n = 186,289). The top two causes of readmission were septicemia (dementia: 14.81%; no dementia: 9.45%) and epilepsy/convulsions (dementia: 5.91%; no dementia: 6.25%). Other top 10 causes of readmissions in those with epilepsy and dementia which were not present in those without dementia included delirium (5.21%), urinary tract infections (4.98%), and aspiration pneumonitis (4.29%). Significance Dementia in epilepsy is associated with worse outcomes, including higher in-hospital mortality and higher readmissions. Potentially preventable causes of readmission in those with epilepsy and dementia were identified, including septicemia, delirium, urinary tract infection, and aspiration pneumonitis. Future studies are needed to inform interventions aimed at decreasing premature mortality and reducing potentially preventable readmissions in this vulnerable population.