bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guanidine modifications enhance the anti‐herpes simplex virus activity of (E,E)‐4,6‐bis(styryl)‐pyrimidine derivatives in vitro and in vivo
Authors: Wang Wei , Xu Cuijing , Zhang Jianqiang , Wang Jinpeng , Yu Rilei , Wang Dongping , Yin Ruijuan , Li Wenmiao , Jiang Tao 
Published: November 2019

Background and PurposeThe worldwide prevalence of herpes simplex virus (HSV) and shortage of efficient therapeutic strategies to counteract it are global concerns. In terms of treatment, the widely utilized anti‐HSV drugs such as acyclovir have serious limitations, for example, drug resistance and side effects. Here, we have identified the guanidine‐modified (E,E)‐4,6‐bis(styryl)‐pyrimidine (BS‐pyrimidine) derivative compound 5d as an inhibitor of HSV and further elucidated the anti‐HSV mechanisms of compound 5d both in vitro and in vivo.Experimental ApproachCytopathic effect inhibition assay, plaque assay, and immunofluorescence assay were used to evaluate the anti‐HSV effects of compound 5d in vitro. Membrane fusion assays, immunofluorescence assays, Western blotting assays, and pull‐down assays were used to explore the anti‐HSV mechanisms of compound 5d. HSV‐1‐infected mice, combined with haematoxylin–eosin staining and quantitative RT‐PCR, were used to study the anti‐HSV effects of compound 5d in vivo.Key ResultsThe guanidine‐modified compound 5d rather than the un‐modified compound 3a effectively inhibited both HSV‐1 and HSV‐2 multiplication in different cell lines, more effectively than acyclovir. Compound 5d may block virus binding and post‐binding processes such as membrane fusion, by targeting virus gB protein. In addition, compound 5d may also down‐regulate the cellular PI3K/Akt signalling pathway to interfere with HSV replication. Treatment with compound 5d also markedly improved survival and decreased viral titres in HSV‐infected mice.Conclusions and ImplicationsThus, the guanidine‐modified BS‐pyrimidine derivatives have the potential to be developed into novel anti‐HSV agents targeting both virus gB protein and cellular PI3K/Akt signalling pathways.
Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer
Authors: Li Dongbo , Ji Hongfei , Niu Xingjian , Yin Lei , Wang Yiran , Gu Yucui , Wang Jinlu , Zhou Xiaoping , Zhang Han , Zhang Qingyuan 
Published: November 2019

AbstractBreast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor‐associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine‐resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen‐sensitive (MCF7‐S) or ‐resistant (MCF7‐R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC‐chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor‐positive breast cancer. We found that macrophages cultured in the CM of MCF7‐S and MCF7‐R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P < .001), and patients with high CCL2 expression presented shorter progression‐free survival than those with low CCL2 expression (P < .05). We conclude that CCL2 secreted by TAM activates PI3K/Akt/mTOR signaling and promotes an endocrine resistance feedback loop in the TME, suggesting that CCL2 and TAM may be novel therapeutic targets for patients with endocrine‐resistant breast cancer.
Conditional survival and recurrence of remnant gastric cancer after surgical resection: A multi‐institutional study
Authors: Chen Qi‐Yue , Zhong Qing , Zhou Jun‐Feng , Qiu Xian‐Tu , Dang Xue‐Yi , Cai Li‐Sheng , Su Guo‐Qiang , Xu Dong‐Bo , Lin Guang‐Tan , Guo Kai‐Qing , Liu Zhi‐Yu , Chen Qiu‐Xian , Li Ping , Li Teng‐Wen , Xie Jian‐Wei , Lin Shuang‐Ming , Wang Jia‐Bin , Lin Jian‐Xian , Lu Jun , Cao Long‐Long , Lin Mi , Zheng Chao‐Hui , Lin Wei , He Qing‐Liang , Huang Chang‐Ming 
Published: November 2019

AbstractThe present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow‐up strategies. A total of 298 patients were analyzed for their 3‐year conditional overall survival (COS3), 3‐year conditional disease‐specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5‐year overall survival (OS) and the 5‐year disease‐specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%‐83.0%, Δ36.6% vs ≤T2: 82.4%‐85.7%, Δ3.3%; P < 0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The American Joint Committee on Cancer (AJCC) stage was the only factor that affected recurrence. Time‐dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (P > 0.05). Time‐dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P < 0.05). A postoperative follow‐up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow‐up model for RGC patients of different stages, which may affect the design of future clinical trials.
High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma
Authors: Zhou Yan , Wang Xuan , Huang Xing , Li Xu‐Dong , Cheng Kai , Yu Hao , Zhou Yu‐Jie , Lv Peng , Jiang Xiao‐Bing 
Published: November 2019

AbstractAimsTo evaluate the clinical significance of coatomer protein complex subunit beta 2 (COPB2) in patients with glioma using a bioinformatics analysis.MethodsOncomine, GEO, and The Cancer Genome Atlas databases were used to examine the COPB2 transcript levels in glioma tissues. Gene expression profiles with clinical information from low‐grade glioma and glioblastoma (GBM) projects were analyzed for associations between COPB2 expression and clinicopathologic characteristics. Kaplan‐Meier survival and Cox regression analyses were used for survival analysis. Gene set enrichment analysis (GSEA) was conducted to screen the pathways involved in COPB2 expression. Gene set variation analysis (GSVA) and correlograms were performed to verify the correlations between COPB2 and inflammatory responses. Canonical correlation analyses examined whether COPB2‐high patients have more infiltrating inflammatory and immune cells.ResultsCOPB2 was highly expressed in gliomas and high COPB2 expression correlated with shorter overall survival time and several poor clinical prognostic variables. GSEA indicated that some immune‐related pathways and other signaling pathways in cancer were associated with the COPB2‐high phenotype. The GSVA and canonical correlation analysis demonstrated that COPB2 expression was closely linked to inflammatory and immune responses, and higher immune cell infiltration.ConclusionsCOPB2 may be a potential prognostic biomarker and an immunotherapeutic target for glioma.
Management of pouch‐vaginal fistulas – experience from our institution
Authors: Sivathondan P. C. , Bloemendaal A. , Travis S. , Mortensen N. , George B. D. 
Published: November 2019

AbstractAimPouch–vaginal fistula (PVF) is an uncommon but serious complication of ileo‐anal pouch reconstruction. This study aimed to review the recent management of PVF, in particular the role of anti‐tumour necrosis factor (anti‐TNF) drugs.MethodAll patients presenting for management of PVF to our surgical service between 2007 and 2016 were studied. The median duration of follow‐up from diagnosis of PVF was 6 years. Details of the original pouch surgery, timing of presentation of PVF, management and final outcome were recorded. Primary outcome was gastrointestinal (GI) continuity (as defined by the presence or absence of a stoma).ResultsA total of 23 patients were identified (median age 45 years) of whom nine had pelvic sepsis at the time of original pouch surgery. Management included local surgical repair, defunctioning ileostomy, pouch excision and anti‐TNF therapy. GI continuity was achieved in 12 patients (52%). Healing of the PVF was achieved in 12 patients (52%). Pelvic sepsis was significantly associated with the need for a long‐term ileostomy (P = 0.009). Biological therapy was used in 12 patients, of whom seven maintained GI continuity. Patients with late presentation PVF (60 months or longer postsurgery) and those with clinical features of Crohn’s disease appeared to benefit from anti‐TNF treatment.ConclusionPVF remains a challenging problem with overall healing rates and GI continuity rates of just over 50%. Anti‐TNF therapy may have a role in patients with late presentation PVF and those with features suggestive of Crohn’s disease.
The value of flexible bronchoscopy in pulmonary infections of immunosuppressed children
Authors: Eroglu‐Ertugrul Nesibe Gevher , Yalcin Ebru , Oguz Berna , Ocal Turgay , Kuskonmaz Baris , Emiralioglu Nagehan , Dogru‐Ersoz Deniz , Ozcelik Ugur , Tezcan Ilhan , Kiper Nural 
Published: November 2019

AbstractObjectivesTo demonstrate the value of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) when determining causes of lung infection in immunocompromised children; to investigate differences in causes and radiological features of lung infections following bone marrow transplantation (BMT) compared to other immunosuppressive conditions; to evaluate the reliability of radiological findings when predicting the pathogen.MethodsWe retrospectively evaluated 132 immunosuppressed children who underwent FB and BAL because pulmonary complications between January 1999 and May 2014 at the Hacettepe University Hospital Pediatric Pulmonology Unit. Two groups, Group I (n = 106) and Group II (n = 26), consisted of patients who had primary or secondary immunodeficiency and those who were immunosuppressed because BMT, respectively. Radiological findings before FB and macroscopic and microscopic findings of the procedure were evaluated.ResultsFB and BAL were diagnostic in 86/132 patients (65.1%) and the antimicrobial treatment changed for 75/132 patients (56.8%). The most common pathogen was bacteria (Streptococcus pneumoniae was the leading one). Bacteria were more frequent in Group I than Group II (P = .008). No significant difference in radiological findings between Groups I and II was found. Considering all patients, a significant association was detected between viral pathogens and radiologically interstitial infiltration and a ground‐glass appearance (P = .003). However, no significant association was detected between bacterial and fungal pathogens and the radiological findings.ConclusionIn immunosuppressed patients, FB and BAL should be evaluated early for clarifying the causative agents. Then, appropriate treatments can be utilised and the side effects and high cost of unnecessary treatment may be mitigated.
The presence of two reduced function variants in CYP2C9 influences the acute response to glipizide
Authors: Chen L. , Li J. H. , Kaur V. , Muhammad A. , Fernandez M. , Hudson M. S. , Goldfine A. B. , Florez J. C. 
Published: November 2019

AbstractAimsTo examine whether the presence of two common missense variants in the CYP2C9 gene (rs1799853, encoding Arg144Cys and denoted as *2, and rs1057910, encoding Ile359Leu and denoted as *3) influences the acute physiological response to a single glipizide dose in individuals naïve to diabetes medications.MethodsIn the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR‐MGH), 786 individuals genotyped for rs1799853/rs41291560 (*2) and rs1057910/rs9332214 (*3) were treated with 5 mg glipizide in the fasting state. Glucose and insulin levels were measured at baseline, 30, 60, 90, 120, 180 and 240 min for calculation of phenotypic endpoints of glipizide response. The challenge was aborted as a result of hypoglycaemia, defined as glucose <2.8 mmol/l or hypoglycaemia‐related symptoms.ResultsCarriers with two reduced function alleles had a 50% larger insulin area under the curve than carriers with zero or one copy (P=0.037), although this finding was primarily driven by an individual with a robust insulin response. In adjusted analyses, the risk of aborting the glipizide challenge was doubled in two‐copy carriers (P=0.034). No significant findings were observed in glucose‐based endpoints.ConclusionsCarriers of two reduced function alleles in CYP2C9 may experience an increased insulin response to glipizide and be predisposed to a higher risk of hypoglycaemia, although no effect of genotype was seen in glucose‐based measurements. Further studies are needed to clarify the utility of CYP2C9 genotyping to guide sulfonylurea treatment.
Increased proportion of time in hybrid closed‐loop “Auto Mode” is associated with improved glycaemic control for adolescent and young patients with adult type 1 diabetes using the MiniMed 670G insulin pump
Authors: Duffus Sara H. , Ta'ani Zain Al , Slaughter James C. , Niswender Kevin D. , Gregory Justin M 
Published: November 2019

AbstractThe Medtronic MiniMed 670G system delivers insulin to patients with type 1 diabetes mellitus (T1DM) using either its hybrid closed‐loop (HCL) “Auto Mode” feature or an open‐loop mode. In this retrospective, cross‐sectional analysis, we quantified the association between time in Auto Mode and both haemoglobin A1c (HbA1c) and time in range (TIR, sensor glucose 70–180 mg/dL) among 96 paediatric and young adult patients with T1DM. The median percentage time in Auto Mode was 38.5% (interquartile range 0%–64%). The percentage time in Auto Mode significantly correlated with HbA1c after adjustment for covariables (β = −0.008, P = 0.014). Each daily 3.4‐h increase in Auto Mode time was associated with a 0.1% decrease in HbA1c. Auto Mode time was also correlated with TIR after adjustment for covariables (β = 0.14, P = 0.02): for each daily 8.6‐h increase in Auto Mode time, TIR increased by 5%. While Auto Mode use was low, increased time in Auto Mode was associated with a significantly lower HbA1c and increased TIR. These findings emphasize the importance of identifying strategies to improve the ease of use of HCL systems.
A food‐based, low‐energy, low‐carbohydrate diet for people with type 2 diabetes in primary care: A randomized controlled feasibility trial
Authors: Morris Elizabeth , Aveyard Paul , Dyson Pamela , Noreik Michaela , Bailey Clare , Fox Robin , Jerome Derek , Tan Garry D , Jebb Susan A 
Published: November 2019

AbstractAimTo examine the feasibility of a food‐based, low‐energy, low‐carbohydrate diet with behavioural support delivered by practice nurses for patients with type 2 diabetes.Materials and MethodsPeople with type 2 diabetes and a body mass index (BMI) of ≥30 kg/m2 were randomized 2:1 to intervention or control (usual care) and assessed at 12 weeks. The intervention comprised an 800–1000 kcal/day, food‐based, low‐carbohydrate (<26% energy) diet for 8 weeks, followed by a 4‐week weight maintenance period and four 15‐20‐minute appointments with a nurse. Primary outcomes were feasibility of recruitment, fidelity of intervention delivery and retention of participants at 12 weeks. Secondary outcomes included change in weight and HbA1c. Focus groups explored the intervention experience.ResultsForty‐eight people were screened, 33 enrolled and 32 followed‐up. Mean (±SD) weight loss in the intervention group was 9.5 kg (± 5.4 kg) compared with 2 kg (± 2.5 kg) in the control group (adjusted difference − 7.5 kg [−11.0 to −4.0, P < 0.001]). Mean reduction in HbA1c in the intervention group was 16.3 mmol/mol (± 13.3 mmol/mol) compared with 0.7 mmol/mol (±4.5 mmol/mol) in the control group (difference − 15.7 mmol/mol [−24.1 to −7.3, P < 0.001]).ConclusionsIt is feasible to recruit participants to a food‐based, low‐energy, low‐carbohydrate intervention, for practice nurses to deliver the programme in primary care, and to retain participants in both groups. There is evidence of clinically significant short‐term improvements in weight and glycaemic control.
Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis
Authors: Ferraro D. , Trovati A. , Bedin R. , Natali P. , Franciotta D. , Santangelo M. , Camera V. , Vitetta F. , Varani M. , Trenti T. , Gastaldi M. , De Biasi S. , Nasi M. , Pinti M. , Meletti S. , Sola P. 
Published: November 2019

Background and purposeCerebrospinal fluid (CSF) kappa free light chains (FLCs) may be a more sensitive marker of intrathecal immunoglobulin (Ig)G synthesis compared with oligoclonal bands (OCBs). Our aim was to retrospectively determine the additional value of the kappa and lambda index (CSF FLC/serum FLC)/(CSF albumin/serum albumin) in predicting a multiple sclerosis (MS) diagnosis in a group of OCB‐negative patients with suspected MS.MethodsThe CSF and serum kappa and lambda FLCs were tested using the Freelite kit (serum) and Freelite Mx (CSF) assay (The Binding Site Group, Bimingham, UK) in 391 OCB‐negative patients with suspected/possible MS and in 54 OCB‐positive patients with MS.ResultsThe CSF kappa FLC levels were below the detection limit (0.27 mg/L) in 61% of patients. Using quantitative data, we found the best kappa index cut‐off value for the prediction of MS to be 5.8. A kappa index ≥5.8 was present in 25% of OCB‐negative MS (23/92) and in 98% of OCB‐positive patients with MS. Using a qualitative approach and a kappa index cut‐off of 5.9, based on literature data, we likewise found that 24% of OCB‐negative patients with MS had a kappa index ≥5.9, compared with 5.4% of OCB‐negative patients without MS (P < 0.001). No reliable data could be obtained for the lambda index; lambda FLCs were below the detection limit (0.68 mg/L) in 90% of CSF samples.ConclusionsThe kappa index could contribute to the identification of OCB‐negative patients with a high probability of an MS diagnosis. Using more sensitive techniques might even improve the diagnostic performance of the kappa index and better define the role of the lambda index.
Fast and slow cancellations and trader behavior
Authors: McInish Thomas H. , Nikolsko‐Rzhevska Olena , Nikolsko‐Rzhevskyy Alex , Panovska Irina 
Published: November 2019

AbstractWe investigate how short‐lived liquidity supply due to order cancellations affects the order‐placement behavior of slow traders. When order cancellations increase, slow traders submit fewer and less aggressive orders. Both short‐ and long‐lived liquidity supply have positive effects on the market overall, reducing spreads and increasing depth. We conclude that it is not necessary to require limit orders to have a minimum lifespan. We develop econometric and machine‐learning frameworks that allow traders to predict whether a quote is likely to have a short or long life, increasing the ability of slow traders to respond strategically to changing order flow.
Temporal β diversity—A macroecological perspective
Authors: Magurran Anne E. , Dornelas Maria , Moyes Faye , Henderson Peter A. 
Published: November 2019

AbstractIssueBiodiversity change, that is how the taxonomic identities and abundances of species in ecological systems are changing over time, has two facets: temporal α diversity and temporal β diversity. To date, temporal α diversity has received most attention even though compositional shifts in assemblages exceed expectations based on ecological theory. Growing concern about the state of the world’s biodiversity highlights the need for better understanding of the extent, and consequences, of compositional reorganization in ecological systems.ChallengesMost methods of measuring β diversity have been developed in a spatial context. We discuss the additional challenges involved in the assessment of temporal change, summarize existing methodological approaches, highlight the importance of establishing relevant baselines, and identify the need for appropriate null models of temporal β diversity. Given considerable potential for research on the macroecology of temporal β diversity we suggest future directions and challenges.ConclusionsAlthough data availability remains the main impediment to improved quantification of temporal β diversity at macroecological scales, there are substantial opportunities for improved methodology and theory. Taxonomic β diversity has received most attention, but other dimensions of diversity, including functional and phylogenetic, should be part of integrated assessments of biodiversity change. Future approaches need to be ecologically meaningful and interpretable as well as statistically robust.
Obscuring Corporate Violence: Corporate Manslaughter in Action
Authors: HÉBERT JASMINE , BITTLE STEVEN , TOMBS STEVE 
Published: November 2019

AbstractIn April 2008, the Corporate Manslaughter and Corporate Homicide Act 2007 (CMCHAct) came into force in the UK. Since then, the Act has failed to live up to expectations, resulting in only 26 convictions in the first decade of its existence, despite thousands of work‐related fatalities during this time. This article critically analyses these CMCHAct prosecutions in order to chronicle the problems of the law in action and to demonstrate how the Act serves to downplay the seriousness of corporate killing. In so doing, we approach law as an ‘active discourse’ that is mutually constitutive of the broader social formation, so that it both creates, but is also a product of, the capitalist social order. Thus we explore the extent to which the CMCHAct ultimately privileges dominant beliefs that corporate killing is not ‘true’ crime and that corporate capitalism is an inherent good that must be defended, not disrupted.
ZrSi2–MgO as novel additives for high thermal conductivity of β‐Si3N4 ceramics
Authors: Wang Weide , Yao Dongxu , Chen Huanbei , Xia Yongfeng , Zuo Kaihui , Yin Jinwei , Liang Hanqin , Zeng Yu‐Ping 
Published: November 2019

AbstractA novel ZrSi2–MgO system was used as sintering additive for fabricating high thermal conductivity silicon nitride ceramics by gas pressure sintering at 1900°C for 12 hours. By keeping the total amount of additives at 7 mol% and adjusting the amount of ZrSi2 in the range of 0‐7 mol%, the effect of ZrSi2 addition on sintering behaviors and thermal conductivity of silicon nitride were investigated. It was found that binary additives ZrSi2–MgO were effective for the densification of Si3N4 ceramics. XRD observations demonstrated that ZrSi2 reacted with native silica on the Si3N4 surface to generate ZrO2 and β‐Si3N4 grains. TEM and in situ dilatometry confirmed that the as formed ZrO2 collaborated with MgO and Si3N4 to form Si–Zr–Mg–O–N liquid phase promoting the densification of Si3N4. Abnormal grain growth was promoted by in situ generated β‐Si3N4 grains. Consequently, compared to ZrO2‐doped materials, the addition of ZrSi2 led to enlarged grains, extremely thin grain boundary film and high contiguity of Si3N4–Si3N4 grains. Ultimately, the thermal conductivity increased by 34.6% from 84.58 to 113.91 W·(m·K)−1 when ZrO2 was substituted by ZrSi2.