bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the incidence and uptake of reproductive surgery versus in vitro fertilisation in Australia between 2001 and 2015: A population‐based study
Authors: Foster Leon , Robson Stephen J. , Yazdani Anusch , O'Shaughnessy Pauline Y. 
Published: November 2018

ObjectiveImprovements in success rates of assisted reproduction led to predictions that infertility surgery in both women and men would become extinct in developed countries. We sought to identify the changes in reproductive surgery that occurred between 2001 and 2015 to determine whether these predictions have been accurate.DesignThe Australian Institute of Health and Welfare (AIHW) national procedural dataset and the Australian Medicare Benefits Scheme (MBS) claims database were searched for procedure data for male and female reproductive surgery and assisted reproduction from January 2001 to December 2015. The denominators were based on annual point estimates of the total population aged 25–44 years (female) and 25–55 years (male) from the Australian Bureau of Statistics (ABS). This dataset provides procedures undertaken but not their indications.ResultsOver the study period the incidence of tubal surgery fell by 66%, vasectomy reversal by 33%, and surgical varicocoelectomy by 50%. In contrast, the rate of hysteroscopic myomectomy increased by 48%, hysteroscopic septoplasty by 125%, and laparoscopy for severe endometriosis increased by 84%. In vitro fertilisation oocyte retrievals increased by 90%. The rate of abdominal myomectomy was unchanged.ConclusionFertility surgery is not dead but has evolved.
Complete resection of colorectal cancer with ovarian metastases combined with chemotherapy is associated with improved survival
Authors: Al‐Busaidi Ibrahim S. , Bailey Teresa , Dobbs Bruce , Eglinton Tim W. , Wakeman Christopher J. , Frizelle Frank A. 
Published: November 2018

BackgroundOvarian metastases (OM) from colorectal cancer (CRC) are uncommon, and data about optimal management are lacking. The aim of this study was to examine the management and outcomes of patients with OM from CRC.MethodsA retrospective review of records of patients with a histopathological diagnosis of OM from CRC who were treated at Christchurch Hospital between 1 January 2000 and 31 December 2016. Data related to presentation, clinicopathological characteristics, treatment and outcomes were recorded. The primary outcomes were overall survival and disease‐free survival.ResultsThirty‐one patients were identified (median age 55 years, range 28–77), with a median follow‐up of 23 months (range 3–84 months). Abdominal pain was the most common presenting symptom (22 patients). Synchronous OM occurred in 22 patients, 14 patients had bilateral ovarian involvement. Twenty‐one patients received adjuvant chemotherapy. R0 resection was achieved in 14 patients. For all patients the 5‐year disease‐free and overall survival were 11% and 12%, respectively, while 5‐year overall survival for R0 resections was 30%. Improved median survival was associated with negative colon resection margins (26.7 months versus 7.8 months, P = 0.03), R0 resection (30.5 months versus 23.5 months, P = 0.04), and use of adjuvant chemotherapy (28.8 months versus 8.2 months, P < 0.0001); however, on multivariate analysis adjuvant chemotherapy was the only independent factor associated with improved prognosis (P = 0.01).ConclusionsOM from CRC are uncommon and carry a poor prognosis. Improved survival was associated with complete surgical resection of the primary tumour and metastatic disease in combination with systemic chemotherapy.
Severe vitamin D deficiency is a prognostic biomarker in autoimmune hepatitis
Authors: Ebadi Maryam , Bhanji Rahima A. , Mazurak Vera C. , Lytvyak Ellina , Mason Andrew , Czaja Albert J. , Montano‐Loza Aldo J. 
Published: November 2018

SummaryBackgroundVitamin D deficiency has been implicated in the outcome of chronic liver disease.AimTo determine the frequency of severe vitamin D deficiency in autoimmune hepatitis (AIH), assess its association with treatment non‐response, and evaluate the relationship between vitamin D status and liver‐related mortality and need for transplantation.MethodsTwo hundred and nine patients were evaluated by liver tissue examination at presentation. Serum vitamin D levels were determined, and serum levels <25 nmol/L (10 ng/mL) were considered severely deficient. Treatment non‐response was defined as non‐normalised aspartate aminotransferase/alanine aminotransferase and immunoglobulin G levels during conventional immunosuppressive therapy. Univariate and multivariate analyses were performed using binary logistic regression and Cox proportional hazards model.ResultsThe mean vitamin D level was 60 ± 38 nmol/L (range, 3‐263 nmol/L), and 42 patients (20%) had severe vitamin D deficiency. Treatment non‐response was more common in patients with severe vitamin D deficiency than in patients without (59% vs 41%, P = 0.04). Severe vitamin D deficiency was also independently associated with a higher risk of developing cirrhosis (HR 3.40; 95% CI 1.30‐8.87, P = 0.01) and liver‐related mortality or requirement for liver transplantation (LT; HR 5.26, 95% CI, 1.54‐18.0, P = 0.008). Patients with persistent severe deficiency following vitamin D supplementation continued to have poor outcomes.ConclusionsSevere vitamin D deficiency is associated with treatment non‐response, progression to cirrhosis, and liver‐related death or need for LT. Severe vitamin D deficiency is a prognostic biomarker in AIH.
Review article: emulsifiers in the food supply and implications for gastrointestinal disease
Authors: Halmos Emma P. , Mack Alexandra , Gibson Peter R. 
Published: November 2018

SummaryBackgroundDietary emulsifiers are the latest food additives to be associated with intestinal, cardiovascular and metabolic health. Most recently, there are postulations around certain emulsifiers playing a role in the development of Crohn's disease.AimTo review the use of food‐based emulsifiers, their content in the food supply and mechanisms by which they might exert potentially detrimental biological effects.MethodsInformation on emulsifiers and thickeners relevant to human health was critically examined.ResultsThe term, “emulsifier,” has been used loosely and has included thickeners as well as agents that truly promote emulsions. These comprise proteins, phospholipids and carbohydrates, alone or in combination, and play roles in optimising food appearance, texture and mouthfeel, delivering or disguising flavours and achieving palatable low‐fat foods. Their presence in the food supply is common, but not “ubiquitous” as frequently stated. Strict regulations limit the amount added to foods, but the lack of established methodologies to measure the actual food content of these diverse compounds limits our knowledge of consumption. Emulsifiers and thickeners have effects on the gut microbiota, mucosal barrier and inflammatory pathways, and can induce disease in experimental models. However, differentiating pharmacological from physiological effects and translating findings in experimental animals to humans raise uncertainties about the relevance of such effects.ConclusionsThere is limited evidence to directly link emulsifiers and thickeners to human disease, but multiple potential pathogenic mechanisms. Knowledge of actual dietary intake and high‐quality interventional studies is needed to enable the risks associated with their intake to be understood.
Hepatitis B virus relapse rates in chronic hepatitis B patients who discontinue either entecavir or tenofovir
Authors: Kuo Ming‐Te , Hu Tsung‐Hui , Hung Chao‐Hung , Wang Jing‐Houng , Lu Sheng‐Nan , Tsai Kai‐Lung , Chen Chien‐Hung 
Published: November 2018

SummaryBackgroundEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first‐line long‐term monotherapy for treatment of chronic hepatitis B (CHB) infection. High virological relapse rates are found after cessation of either ETV or TDF in CHB patients.AimTo compare hepatitis B virus (HBV) relapse rates in CHB patients without cirrhosis who discontinued ETV or TDF.MethodsA retrospective‐prospective study was conducted in 342 CHB patients (108 hepatitis B e antigen (HBeAg)‐positive and 234 HBeAg‐negative) who received ETV and 165 (46 HBeAg‐positive, 119 HBeAg‐negative) who received TDF were recruited. All patients had post‐treatment follow‐up for at least 6 months. All fulfilled the stopping criteria of the Asia‐Pacific Association for the Study of the Liver of 2012.ResultsPatients who discontinued TDF had significantly higher rates and earlier times of virological and clinical relapse than those who discontinued ETV. This was also seen in propensity score (PS)‐matched HBeAg‐positive and HBeAg‐negative patients. Multivariate analysis showed that being in the TDF group was an independent factor for virological and clinical relapse in all patients and PS‐matched HBeAg‐positive and HBeAg‐negative patients. The rate of off‐therapy HBsAg loss was comparable between the ETV and TDF groups after 2‐3 years follow‐up. Clinical relapse tended to be more severe in the TDF group compared with the ETV group.ConclusionHBV relapse occurs sooner and is more severe after cessation of TDF than after cessation of ETV.
Vaccination for influenza and pneumococcus in patients with gastrointestinal cancer or inflammatory bowel disease: A prospective cohort study of methods for improving coverage
Authors: Sitte Julien , Frentiu Emilia , Baumann Cédric , Rousseau Hélène , May Thierry , Bronowicki Jean‐Pierre , Peyrin‐Biroulet Laurent , Lopez Anthony 
Published: November 2018

SummaryBackgroundAlthough influenza and pneumococcal vaccinations for high‐risk populations are recommended by current guidelines, vaccination coverage is low in patients with gastrointestinal cancer (GC) or inflammatory bowel disease (IBD).AimTo evaluate the impact of a specialised infectious disease consultation on vaccination coverage rates in these patients.MethodsBetween December 2016 and April 2017, all patients with GC or IBD followed in the outpatient clinic of the Gastroenterology department at the Nancy University Hospital enrolled in a 3‐phase vaccination programme. Phase 1: Initial questionnaire (vaccination status, knowledge about vaccines and possible barriers to vaccination); Phase 2: Infectious disease consultation; Phase 3: Subsequent questionnaire (evolution of patients’ knowledge about vaccination).ResultsA total of 366 patients were included (GC = 99, IBD = 267). Vaccination rate was 34.7% for influenza and 14.5% for pneumococcus. About 43% of the patients feared side effects of vaccines. After the initial questionnaire, 49.3% of the interested patients participated in a specialised vaccination consultation (n = 102). 87.3% (n = 89) received new vaccination, 41.2% changed their mind about vaccination, and 92.2% would recommend this programme to other patients. Among vaccinated patients, 97.8% (n = 87) received pneumococcal vaccine, 40.4% received tetanus‐diphtheria‐polio vaccine, and 7.9% received influenza vaccine. In GC patients, anti‐pneumococcal vaccination rate was 87.5% after the specialised consultation compared with 10.1% before. In IBD patients, corresponding rates were 85.7% and 16.1%.ConclusionsA specialised infectious disease consultation can improve GC and IBD patients’ knowledge about vaccination and vaccination coverage. This approach could be applied to all high‐risk populations.
Differences in cardiovascular safety with non‐steroidal anti‐inflammatory drug therapy—A nationwide study in patients with osteoarthritis
Authors: Barcella Carlo Alberto , Lamberts Morten , McGettigan Patricia , Fosbøl Emil Loldrup , Lindhardsen Jesper , Torp‐Pedersen Christian , Gislason Gunnar Hilmar , Olsen Anne‐Marie Schjerning 
Published: November 2018

AbstractOsteoarthritis (OA) and the non‐steroidal anti‐inflammatory drugs (NSAIDs) used to relieve OA‐associated pain have been linked independently to increased cardiovascular risk. We examined the risk of cardiovascular events associated with NSAID use in patients with OA. We employed linked nationwide administrative registers to examine NSAID use between 1996 and 2015 by Danish patients with OA aged ≥18 years. Using adjusted Cox proportional hazard analyses, we calculated the risk of the composite outcome of cardiovascular death, non‐fatal myocardial infarction and non‐fatal ischaemic stroke/TIA, and of each outcome separately, up to 5 years after OA diagnosis. Of 533 502 patients included, 64.3% received NSAIDs and 38 226 (7.2%) experienced a cardiovascular event during follow‐up. Compared with non‐use, all NSAIDs were associated with increased risk of the composite outcome: hazard ratio (HR) for rofecoxib, 1.90 (95% confidence interval, 1.74‐2.08); celecoxib, 1.47 (1.34‐1.62); diclofenac, 1.44 (1.36‐1.54); ibuprofen, 1.20 (1.15‐1.25); and naproxen, 1.20 (1.04‐1.39). Similar results were seen for each outcome separately. When celecoxib was used as reference, ibuprofen (HRs: 0.81 [CI: 0.74‐0.90]) and naproxen (HRs: 0.81 [0.68‐0.97]) exhibited a lower cardiovascular risk, even when low doses were compared. Low‐dose naproxen and ibuprofen were associated with the lowest risks of the composite outcome compared to no NSAID use: HRs: 1.12 (1.07‐1.19) and 1.16 (0.92‐1.42), respectively. In patients with OA, we found significant differences in cardiovascular risk among NSAIDs. Naproxen and ibuprofen appeared to be safer compared to celecoxib, also when we examined equivalent low doses. In terms of cardiovascular safety, naproxen and ibuprofen, at the lowest effective doses, may be the preferred first choices among patients with OA needing pain relief.
Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves’ disease
Authors: Nalla Preethi , Young Stuart , Sanders Jane , Carter Joanne , Adlan Mohamed A. , Kabelis Katarzyna , Chen Shu , Furmaniak Jadwiga , Rees Smith Bernard , Premawardhana Lakdasa D. K. E. 
Published: November 2018

SummaryObjectiveTSH receptor antibodies (TRAb) are responsible for autoimmune hyperthyroid disease (Graves’ disease; GD) with TRAb levels tending to decrease following treatment. Measurement of TRAb activity during follow‐up could prove valuable to better understand treatment effectiveness.Study designTRAb concentration and stimulating (TSAb) and blocking (TSBAb) activity of patient serum were assessed following different treatment modalities and follow‐up length.MethodsSixty‐six subjects were recruited following treatment with carbimazole (n = 26), radioiodine (n = 27) or surgery (n = 13). TRAb, TPOAb, TgAb and GADAb were measured at a follow‐up visit as well as bioassays of TSAb and TSBAb activity.ResultsForty‐five per cent of all patients remained TRAb‐positive for more than one year and 23% for more than 5 years after diagnosis, irrespective of treatment method. Overall, TRAb concentration fell from a median (IQR) of 6.25 (3.9‐12.7) to 0.65 (0.38‐3.2) U/L. Surgery conferred the largest fall in TRAb concentration from 11.4 (6.7‐29) to 0.58 (0.4‐1.4) U/L. Seventy per cent of TRAb‐positive patients were positive for TSAb, and one patient (3%) was positive for TSBAb. TRAb and TSAb correlated well (r = 0.83). In addition, 38/66 patients were TgAb‐positive, 47/66 were TPOAb‐positive and 6/66 were GADAb‐positive at follow‐up.ConclusionsTRAb levels generally decreased after treatment but persisted for over 5 years in some patients. TRAb activity was predominantly stimulatory, with only one patient demonstrating TSBAb. A large proportion of patients were TgAb/TPOAb‐positive at follow‐up. All treatment modalities reduced TRAb concentrations; however, surgery was most effective.
Effects of intravitreal bevacizumab in Gram‐positive and Gram‐negative models of ocular inflammation
Authors: Lafreniere J. Daniel , Toguri James T. , Gupta Rishi R. , Samad Arif , O'Brien Dan M. , Dickinson John , Cruess Alan , Kelly Melanie E. M. , Seamone Mark E. 
Published: November 2018

AbstractBackgroundExogenous endophthalmitis is a potential complication of intraocular surgery and frequently results in visual impairment. Current treatment involves administration of intravitreal (IVT) antibiotics with or without vitrectomy surgery. Evidence for the use of adjunctive anti‐inflammatory agents is conflicting. We set out to determine if bevacizumab, a humanized monoclonal IgG1 antibody targeted against vascular endothelial growth factor (VEGF), has anti‐inflammatory properties in experimental models of Gram‐positive and Gram‐negative inflammation.MethodsBALB/c mice were subjected to lipopolysaccharide‐ (LPS) or peptidoglycan‐ (PGN) induced ocular inflammation and treated with IVT bevacizumab. Iris microvasculature was imaged 6 hours following irritant/treatment using intravital microscopy (IVM) before the mice were euthanized and the eyes were enucleated immediately post‐mortem. Following enucleation, levels of VEGF and 23 cytokines and chemokines (IL‐1α, IL‐1β, IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12 (p40), IL‐12 (p70), IL‐13, IL‐17, TNF, KC, G‐CSF, GM‐CSF, Eotaxin, INF‐γ, MCP‐1, MIP‐1α, MIP‐1β, RANTES) were quantified using a multiplex assay.ResultsLevels of VEGF were significantly increased during the inflammatory response, triggered by either PGN or LPS. Both the adherence of leukocytes to the iris vascular endothelium and the levels of pro‐inflammatory cytokines and chemokines were significantly increased following administration of either irritant. Treatment with bevacizumab decreased levels of leukocyte adherence in LPS‐treated eyes, however, not in PGN‐treated eyes. Conversely, bevacizumab treatment decreased levels of cytokines and chemokines (TNF, IL‐6, MCP‐1, MIP‐1α, MIP‐1β, RANTES, KC) in PGN‐treated eyes, however, not in LPS‐treated eyes.ConclusionsWithin a 6‐hour window bevacizumab had anti‐inflammatory actions that were distinct in both Gram‐positive (PIU) and Gram‐negative (EIU) models, respectively. Given our findings, this would suggest that bevacizumab may have utility as an adjunctive therapy to IVT antibiotics and vitrectomy in the management of exogenous endophthalmitis.
CSE1L participates in regulating cell mitosis in human seminoma
Authors: Liu Chunyan , Wei Jiajing , Xu Kang , Sun Xiaosong , Zhang Huiping , Xiong Chengliang 
Published: November 2018

AbstractObjectivesCSE1L has been reported to be highly expressed in various tumours. Testicular germ cell tumours are common among young males, and seminoma is the major type. However, whether CSE1L has functions in the seminoma is unclear.Materials and methodsThe expression of CSE1L was detected by immunohistochemistry in seminoma tissues and non‐tumour normal testis tissues from patients. CSE1L distribution during cell mitosis was determined by immunofluorescent staining with CSE1L, α‐tubulin and γ‐tubulin antibodies. The effects of Cse1L knockdown on cell proliferation and cell cycle progression were determined by Cell Counting Kit‐8 assay, flow cytometry, PH3 staining and bromodeoxyuridine incorporation assay.ResultsCSE1L was significantly enriched in the seminoma tissue compared with the non‐tumour normal testis tissue. CSE1L also co‐localized with α‐tubulin in the cells with a potential to divide. In the seminoma cell line TCam‐2, CSE1L was associated with the spindles and the centrosomes during cell division. The knockdown of CSE1L in TCam‐2 cells attenuated the cells’ proliferative capacity. Cell cycle assay revealed that the CSE1L‐deficient cells were mainly arrested in the G0/G1 phase and moderately delayed in the G2/M phase. The proportion of cells with multipolar spindle and abnormal spindle geometry was obviously increased by CSE1L expression silencing in the TCam‐2 cells.ConclusionsOverall, these findings showed that CSE1L plays a pivotal role in maintaining cell proliferation and cell division in seminomas.
MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression
Authors: Wang Rong , Xu Jiali , Xu Jing , Zhu Wei , Qiu Tianzhu , Li Jun , Zhang Meiling , Wang Qianqian , Xu Tongpeng , Guo Renhua , Lu Kaihua , Yin Yongmei , Gu Yanhong , Zhu Lingjun , Huang Puwen , Liu Ping , Liu Lianke , De Wei , Shu Yongqian 
Published: November 2018

AbstractObjectivesTo investigate the function and regulatory mechanism of Krüppel‐like factor 3 (KLF3) in lung cancer.Materials and MethodsKLF3 expression was analysed by qRT‐PCR and Western blot assays. The proliferation, migration, invasion, cycle and apoptosis were measured by CCK‐8 and EdU, wound‐healing and Transwell, and flow cytometry assays. The tumour growth was detected by nude mouse tumorigenesis assay. In addition, the interaction between KLF3 and Sp1 was accessed by luciferase reporter, EMSA and ChIP assay. JAK2, STAT3, PI3K and p‐AKT levels were evaluated by Western blot and IHC assays.ResultsThe results indicated that KLF3 expression was elevated in lung cancer tissues. Knockdown of KLF3 inhibited lung cancer cell proliferation, migration and invasion, and induced cell cycle arrest and apoptosis. In addition, the downregulation of KLF3 suppressed tumour growth in vivo. KLF3 was transcriptionally activated by Sp1. miR‐326 could bind to 3′UTR of Sp1 but not KLF3 and decreased the accumulation of Sp1, which further indirectly reduced KLF3 expression and inactivated JAK2/STAT3 and PI3K/AKT signaling pathways in vitro and in vivo.ConclusionsOur data demonstrate that miR‐326/Sp1/KLF3 regulatory axis is involved in the development of lung cancer, which hints the potential target for the further therapeutic strategy against lung cancer.
FOXM1c promotes oesophageal cancer metastasis by transcriptionally regulating IRF1 expression
Authors: Zhou Yuzhen , Wang Qi , Chu Li , Dai Weixing , Zhang Xiaozhou , Chen Jianfeng , Zhang Long , Ding Peipei , Zhang Xin , Gu Hongyu , Zhang Pingzhao , Li Ling , Zhang Wei , Li Luying , Lv Xinyue , Zhou Danlei , Cai Guoxiang , Chen Liang , Zhao Kuaile , Hu Weiguo 
Published: November 2018

ObjectivesWe aimed to elucidate the role and molecular mechanisms of FOXM1 in regulating metastasis in oesophageal squamous cell carcinoma (ESCC) as well as its clinical implications.Materials and methodsThe expression levels of four isoforms of FOXM1 were analysed by real‐time PCR. Next, genetically modification using overexpression and RNAi systems and transwell were employed to examine FOXM1c function in invasion and migration. Dual luciferase and ChIP assays were performed to decipher the underlying mechanism for transcriptional regulation. The expression levels of FOXM1 and IRF1 were determined by immunohistochemistry staining in ESCC specimens.ResultsThe FOXM1c was predominantly overexpressed in ESCC cell lines compared to the other FOXM1 isoforms. Ectopic expression of FOXM1c promoted invasion and migration of ESCC cells lines, whereas downregulation of FOXM1c inhibited these processes. Moreover, FOXM1c expression was positively correlated with IRF1 expression in ESCC cell lines and tumour specimens. IRF1 is, at least in part, responsible for FOXM1c‐mediated invasion and migration. Mechanistically, we identified IRF1 as a transcriptional target of FOXM1c and found a FOXM1c‐binding site in the IRF1 promoter region. Furthermore, high expression levels of both FOXM1c and IRF1 were positively associated with low survival rate and predicted a poor prognosis of oesophageal cancer patients.ConclusionFOXM1c promotes the metastasis by transcriptionally targeting IRF1 and may serve as a potential prognostic predictor for oesophageal cancer.