bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serious adverse effects occurring after chemotherapy: A general cancer registry‐based incidence survey
Authors: Ingrand Isabelle , Defossez Gautier , Lafay‐Chebassier Claire , Chavant François , Ferru Aurélie , Ingrand Pierre , Pérault‐Pochat Marie‐Christine 
Published: October 2019

AimsPharmaco‐epidemiological surveys enable the frequency of serious adverse effects—and also the determining factors of their occurrence and seriousness—to be quantified. Few studies systematically gathering post‐chemotherapy adverse effects data have been conducted. The objective was to assess the incidence of post‐chemotherapy serious adverse effects on the basis of cancer registry data.MethodsThe population was composed of new invasive cancer cases, with the exception of haematopoietic tumours and cutaneous carcinomas. These cancers were identified in 2012 among patients living at the time of diagnosis in a region covered by a general cancer registry and by a French regional pharmacovigilance centre, and treated with neo‐adjuvant and/or adjuvant first‐intention chemotherapy, followed or not by radiotherapy. The study was based on a sample of 1000 patients from the registry, followed by the collection of serious adverse effects and the required information to constitute a pharmacovigilance file.ResultsChemotherapy was associated with a particularly high incidence of serious adverse effects, affecting 44.5% (41.4–47.5%) of the patients. The highest incidence rates were observed when patients were exposed to topo‐isomerase II inhibitors such as etoposide and bleomycin (69.2%), vinca‐alkaloids (66.7%), topo‐isomerase I inhibitors (54.5%) and platinum derivatives (52.0%). The clinical context was also linked to incidence, especially in case of metastases (53.3%) and comorbidities (51.3%). Substantial differences were found according to localisation, with a particularly high incidence in bronchial–pulmonary cancers (59.0%).ConclusionThe high overall incidence rate of serious adverse effects should motivate a reinforcement of information about drug toxicities and improve knowledge by drawing on patient reporting.
Safety, tolerability and pharmacokinetics and pharmacodynamics of HL2351, a novel hybrid fc‐fused interleukin‐1 receptor antagonist, in healthy subjects: A first‐in‐human study
Authors: Oh Jaeseong , Huh Ki Young , Cho Young‐Gyu , Cha Ji‐Eun , Kim Se‐Jin , Yoon Seo Hyun , Park Sung Sup , Yoon Hyunyee , Lee Jieon , Lee Howard 
Published: October 2019

AimsWe performed a first‐in‐human study with HL2351, a novel hybrid Fc‐fused interleukin (IL)‐1 receptor antagonist, to evaluate its tolerability, pharmacokinetics and pharmacodynamics (PD) after a single subcutaneous (SC) administration in healthy subjects.MethodsA randomized, double‐blind, placebo‐ and active‐controlled, dose‐escalation study was conducted. Eligible subjects randomly received a single SC administration of HL2351 (1, 2, 4, 8 and 12 mg/kg) or placebo in a ratio of 8:2. Subjects in the active‐controlled group received a single SC administration of anakinra at 100 mg. Serial blood samples were collected for pharmacokinetics and PD analyses. An ex‐vivo activation test was performed to evaluate the PD using peripheral blood mononuclear cells treated with IL‐1β. Anti‐HL2351 antibodies were determined at baseline and 29 days postdose. Tolerability was assessed throughout the study.ResultsHL2351 was eliminated more slowly than anakinra (terminal half‐life: 27.21–45.28 vs 3.97 h). Serum concentrations of HL2351 were increased dose‐proportionally. The mean apparent clearance of HL2351 were 0.6, 0.66, 0.75, 0.51, 0.65 L/h at 1, 2, 4, 8 and 12 mg/kg, respectively. The percent inhibition of IL‐6 expression varied widely (range: 0–92.1%), showing no clear trend or discernible difference between HL2351, anakinra and placebo. HL2351 was well tolerated after a single SC administration.ConclusionHL2351 was well tolerated and showed linear pharmacokinetic characteristics after a single SC administration at doses up to 12 mg/kg in healthy subjects. HL2351 remained in the body 7‐11 times longer than anakinra. HL2351 can be developed as a potential therapeutic alternative to anakinra.
Intimate partner violence and severe acute maternal morbidity in the intensive care unit: A case‐control study in Peru
Authors: Ayala Quintanilla Beatriz Paulina , Pollock Wendy E. , McDonald Susan J. , Taft Angela J. 
Published: October 2019

AbstractBackgroundIntimate partner violence is a prevalent public health issue associated with all‐cause maternal mortality. This study investigated the relationship between intimate partner violence, severe acute maternal morbidity in the intensive care unit (ICU), and neonatal outcomes.MethodsThis was a prospective case‐control study in a hospital in Lima, Peru, with 109 cases (maternal ICU admissions) and 109 controls (obstetric patients not admitted to the ICU). Data were collected through face‐to‐face interviews and medical record review. Partner violence was assessed using the World Health Organization instrument. Multivariate logistic regression was used to model the association between intimate partner violence and severe acute maternal morbidity.ResultsThere was a significantly higher rate of intimate partner violence both before and during pregnancy among cases (58.7%) than controls (27.5%). In multivariate analysis, intimate partner violence both before and during pregnancy (aOR 3.83 (95% CI: 1.99‐7.37)), being married (3.86 (1.27‐11.73)), having <8 antenatal care visits (2.78 (1.14‐6.80)), and having previous abortions (miscarriage, therapeutic, or unsafe) (1.69 (1.13‐2.51)) were significantly associated with severe acute maternal morbidity. The ICU admission rate was 18.8 (per 1000 live births), and ICU maternal mortality was 1.7%. The perinatal mortality rate was higher in cases (9.3%) than in controls (1.8%).ConclusionsIntimate partner violence was associated with an increased risk of severe acute maternal morbidity. This suggests a more severe impact of intimate partner violence on pregnancy than has been previously identified. Inquiring about intimate partner violence during prenatal visits may prevent further harm to the mother‐baby dyad.
Rosiglitazone alleviates intrahepatic cholestasis induced by α‐naphthylisothiocyanate in mice: The role of circulating 15‐deoxy‐Δ12,14‐PGJ2 and Nogo
Authors: Zhang Shuang , Yu Miao , Guo Fangling , Yang Xiaoxiao , Chen Yuanli , Ma Chuanrui , Li Qi , Wei Zhuo , Li Xiaoju , Wang Hua , Hu Huaqing , Zhang Yujue , Kong Derun , Miao Qing Robert , Hu Wenquan , Hajjar David P. , Zhu Yan , Han Jihong , Duan Yajun 
Published: October 2019

Background and PurposeIntrahepatic cholestasis is mainly caused by dysfunction of bile secretion and has limited effective treatment. Rosiglitazone is a synthetic agonist of PPARγ, whose endogenous agonist is 15‐deoxy‐Δ12,14‐PGJ2 (15d‐PGJ2). Reticulon 4B (Nogo‐B) is the detectable Nogo protein family member in the liver and secreted into circulation. Here, we determined if rosiglitazone can alleviate intrahepatic cholestasis in mice.Experimental ApproachWild‐type, hepatocyte‐specific PPARγ or Nogo‐B knockout mice received intragastric administration of α‐naphthylisothiocyanate (ANIT) and/or rosiglitazone, followed by determination of intrahepatic cholestasis and the involved mechanisms. Serum samples from primary biliary cholangitis (PBC) patients and non‐PBC controls were analysed for cholestasis‐related parameters.Key ResultsRosiglitazone prevented wild type, but not hepatocyte‐specific PPARγ deficient mice from developing ANIT‐induced intrahepatic cholestasis by increasing expression of bile homeostatic proteins, reducing hepatic necrosis, and correcting abnormal serum parameters and enterohepatic circulation of bile. Nogo‐B knockout provided protection similar to that of rosiglitazone treatment. ANIT‐induced intrahepatic cholestasis decreased 15d‐PGJ2 but increased Nogo‐B in serum, and both were corrected by rosiglitazone. Nogo‐B deficiency in the liver increased 15d‐PGJ2 production, thereby activating expression of PPARγ and bile homeostatic proteins. Rosiglitazone and Nogo‐B deficiency also alleviated cholestasis‐associated dyslipidemia. In addition, rosiglitazone reduced symptoms of established intrahepatic cholestasis in mice. In serum from PBC patients, the decreased 15d‐PGJ2 and increased Nogo‐B levels were significantly correlated with classical cholestatic markers.Conclusions and ImplicationsLevels of 15d‐PGJ2 and Nogo are important biomarkers for intrahepatic cholestasis. Synthetic agonists of PPARγ could be used for treatment of intrahepatic cholestasis and cholestasis‐associated dyslipidemia.
Icariside II, a phosphodiesterase 5 inhibitor, attenuates cerebral ischaemia/reperfusion injury by inhibiting glycogen synthase kinase‐3β‐mediated activation of autophagy
Authors: Gao Jianmei , Long Long , Xu Fan , Feng Linying , Liu Yuangui , Shi Jingshan , Gong Qihai 
Published: October 2019

Background and PurposeCerebral ischaemia/reperfusion causes exacerbated neuronal damage involving excessive autophagy and neuronal loss. The present study was designed to investigate the effect of icariside II, one of main active ingredients of Herba Epimedii on this loss and whether this is related to its PDE 5 inhibitory action.Experimental ApproachFocal cerebral ischaemia was induced in the rat by transient middle cerebral artery occlusion over 2 hr, followed by reperfusion with icariside II, 3‐methylamphetamine or rapamycin. The effect of icariside II was determined measuring behaviour changes and the size of the infarction. The expressions of PDE 5, autophagy‐related proteins and the level of phosphorylation of glycogen synthase kinase‐3β (GSK‐3β) were determined. Cultured primary cortical neurons were subjected to oxygen and glucose deprivation followed by reoxygenation in the presence and absence of icariside II. A surface plasmon resonance assay and molecular docking were used to explore the interactions of icariside II with PDE 5 or GSK‐3β.Key ResultsIcariside II not only protected against induced ischaemic reperfusion injury in rats but also attenuated such injury in primary cortical neurons. The neuroprotective effects of icariside II on such injury were attributed to interfering with the PKG/GSK‐3β/autophagy axis by directly bounding to PDE 5 and GSK‐3β.Conclusions and ImplicationsThese findings indicate that icariside II attenuates cerebral I/R‐induced injury via interfering with PKG/GSK‐3β/autophagy axis. This study raises the possibility that icariside II and other PDE 5 inhibitors maybe effective in the treatment ischaemia stroke.
An experimental test of mate choice for red carotenoid coloration in the marine copepod Tigriopus californicus
Authors: Powers Matthew J. , Hill Geoffrey E. , Weaver Ryan J. 
Published: October 2019

AbstractColorful ornaments are hypothesized to have evolved in response to sexual selection for honest signals of individual quality that provide information about potential mates. Red carotenoid coloration is common in diverse groups, and in some vertebrate taxa, red coloration is a sexually selected trait whereby mates with the reddest ornaments are preferred. Despite being widespread among invertebrates, whether red carotenoid coloration is assessed during mate choice in these taxa is unclear. The marine copepod Tigriopus californicus displays red coloration from the accumulation of the carotenoid astaxanthin. Previous research on copepods has shown that astaxanthin provides protection from UV radiation and xenobiotic exposure and that carotenoid production is sensitive to external stressors. Because of the condition dependency of the red coloration, we hypothesized that Tigriopus would use it as a criterion during mate choice. To test this hypothesis, we conducted trials in which males chose between females that were wild‐type red (carotenoid‐rich algae diet) or white (carotenoid‐deficient yeast diet). To control for dietary differences and to isolate the effect of carotenoid coloration, we also presented males with restored‐red females fed a carotenoid‐supplemented yeast diet. We found that wild‐type red females were weakly preferred over white females. After controlling for diet, however, we found that restored‐red females were avoided. Our observations do not support the hypothesis that male copepods prefer the carotenoid coloration of females during mate choice. We hypothesize that algal‐derived compounds other than carotenoids play a role in mate choice. Red coloration in copepods appears to be a condition‐dependent trait that is not assessed during mating.
The diverse nature of island isolation and its effect on land bridge insular faunas
Authors: Itescu Yuval , Foufopoulos Johannes , Pafilis Panayiotis , Meiri Shai 
Published: October 2019

AbstractAimIsolation is a key factor in island biology. It is usually defined as the distance to the geographically nearest mainland, but many other definitions exist. We explored how testing different isolation indices affects the inference of impacts of isolation on faunal characteristics. We focused on land bridge islands and compared the relationships of many spatial and temporal (i.e., through time) isolation indices with community‐, population‐ and individual‐level characteristics (species richness, population density and body size, respectively).LocationAegean Sea islands, Greece.Time periodCurrent.TaxonMany animal taxa.MethodsWe estimated 21 isolation indices for 205 islands and recorded species richness data for 15 taxa (invertebrates and vertebrates). We obtained body size data for seven lizard species and population density data for three. We explored how well indices predict each characteristic, in each taxon, by conducting a series of ordinary least squares regressions (controlling for island area when needed) and a meta‐analysis.ResultsIsolation was significantly (and negatively) associated with species richness in 10 of 15 taxa. It was significantly (and positively) associated with body size in only one of seven species and was not associated with population density. The effect of isolation on species richness was much weaker than that of island area, regardless of the index tested. Spatial indices generally out‐performed temporal indices, and indices directly related to the mainland out‐performed those related mainly to neighbouring islands. No index was universally superior to others, including the distance to the geographically nearest mainland.Main conclusionsThe choice of index can alter our perception of the impacts of isolation on biological patterns. The nearly automatic, ubiquitous use of distance to the geographically nearest mainland misrepresents the complexity of the effects of isolation. We recommend the simultaneous testing of several indices that represent different aspects of isolation, in order to produce more constructive and thorough investigations and avoid imprecise inference.
Diagnosis of mild cognitive impairment using multiple neuroimaging modalities in addition to the Mini‐Mental State Examination
Authors: Kaneko Hiromi , Kimura Noriyuki , Nojima Saho , Abe Kanako , Aso Yasuhiro , Matsubara Etsuro 
Published: October 2019

AimThis prospective study investigated the additional utility of combining multiple imaging modalities with the Mini‐Mental State Examination (MMSE) in discriminating individuals with mild cognitive impairment (MCI) from cognitively normal individuals.MethodsA total of 103 individuals with amnestic MCI and normal cognitive function were recruited from outpatients; they underwent examination using the MMSE, magnetic resonance imaging, 18F‐fluorodeoxyglucose positron emission tomography and 11C‐Pittsburgh compound B positron emission tomography. Binary logistic regression with receiver operator characteristic analysis was used to assess the combination of the abovementioned single or multiple imaging modalities with the MMSE. Eight models were constructed, and their area under the curve values and misclassification rates in discriminating individuals with amnestic MCI from cognitively normal individuals were evaluated.ResultsThe addition of each of the imaging modalities improved the discrimination accuracy over that of the MMSE alone; the accuracy obtained with the addition of 18F‐fluorodeoxyglucose positron emission tomography was the highest. The best model with the highest accuracy included a combination of all the imaging modalities in addition to the MMSE (area under the curve value 0.902).ConclusionsThe combination of all the imaging modalities in addition to the MMSE could facilitate more accurate diagnosis of amnestic MCI. Of the individual imaging modalities, the highest accuracy resulted from the addition of 18F‐fluorodeoxyglucose positron emission tomography to the MMSE. Geriatr Gerontol Int 2019; 19: 1193–1197.
Severe obesity is associated with liver disease severity in pediatric non‐alcoholic fatty liver disease
Authors: Seth Aradhna , Orkin Sarah , Yodoshi Toshifumi , Liu Chunyan , Fei Lin , Hardy Jennifer , Trout Andrew T. , Arce Clachar Ana‐Catalina , Bramlage Kristin , Xanthakos Stavra , Mouzaki Marialena 
Published: October 2019

SummaryBackgroundPaediatric non‐alcoholic fatty liver disease (NAFLD) is highly prevalent among children with obesity. The primary objective of this study was determining whether obesity severity is associated with NAFLD severity. By using paediatric classifications for severe obesity, clinicians may be able to better risk stratify patients, which in turn would guide more effective management and treatment.MethodsRetrospective cohort study including patients followed at Cincinnati Children's Medical Center for NAFLD. Patients were categorized as overweight or class I, II, III obese based on established body mass index (BMI) cut‐offs. Liver disease severity was determined using biochemical, imaging (magnetic resonance elastography [MRE]), and histologic evidence of liver injury.ResultsThree cohorts were studied individually based on the method used to assess disease severity (biochemical n = 767, imaging n = 366, and histology n = 249). Between the three cohorts, there were significant differences in age, proportion of patients with class II and class III obesity, and serum alanine transaminase (ALT) levels. In the biochemistry cohort, the odds of having ALT > 80 U/L were highest in patients with class III obesity (P = .026). In the imaging cohort, liver stiffness was significantly different between BMI groups of patients (P = .001). In the histology cohort, those with class III obesity had significantly higher odds of NAFLD activity score (NAS) ≥ 5 (P = .012).DiscussionObesity severity is associated with liver disease severity. Patients with more severe obesity are more likely to have more advanced liver disease, a finding that can assist in risk stratification, as well as monitoring and treatment approaches.
Intergenerational changes in adiposity and fat distribution from 1982 to 2011 in male children and adolescents from Kolkata (India)
Authors: Kryst Łukasz , Żegleń Magdalena , Das Sukanta , Dasgupta Parasmani , Saha Rana , Das Rituparna 
Published: October 2019

SummaryBackgroundIndia, as a developing country, is subjected to numerous socioeconomic changes. They can significantly influence human development and be mirrored by the secular trends regarding the adiposity and body fat distribution.ObjectivesThe aim of the study was to examine the intergenerational changes of adiposity and body fat distribution in Bengali boys, between 1982 and 2011.MethodsThe study group consisted of 2064 Bengali boys, aged 7–16, from the middle‐class families, examined in two cross‐sectional surveys in 1982–83 and 2005–2011. Triceps, biceps, subscapular and suprailiac skinfolds were measured. Their sum and the mean percentage of every skinfold were calculated. The percentage of body fat (%BF) was assessed using Slaughter's equations.ResultsPositive secular trend, significant for most of the age groups, was observed for %BF and sum of skinfolds. It was also present for suprailiac and subscapular skinfolds.ConclusionsAdiposity has significantly changed over the past three decades. The results confirm that the measurements of skinfold thickness are a great tool to relatively easily and accurately assess body adiposity in countries such as India. Moreover, further analysis of these trends can help to identify possible negative changes as well as establish their causes in a particular population.
A comparative study on the cellular viability and debridement efficiency of antimicrobial‐based wound dressings
Authors: Chen Rui , Salisbury Anne‐Marie , Percival Steven L. 
Published: October 2019

AbstractA concentrated surfactant gel containing polyhexamethylene biguanide (CSG‐PHMB) (CSG: Plurogel) was evaluated for in vitro cell cytotoxicity using the direct contact, extraction, and cell insert assays, along with its ability to breakdown artificial wound eschar and slough, compared with other clinically available wound gels: a wound gel loaded with 0.13% benzalkonium chloride (BXG) and a highly viscous gel loaded with 0.1% polyhexamethylene biguanide (PXG). Following treatment with CSG‐PHMB, BXG, and PXG at day 1, the viability of L929 and HDFa cells sharply decreased to lower than 20% of the culture media control in the direct contact assay; however, cell viability of L929 was 128.65 ± 1.41%, 99.90 ± 2.84%*, and 64.08 ± 5.99%* respectively; HDFa was 84.58 ± 10.41%, 19.54 ± 3.06%**, and 96.28 ± 33.67%, respectively, in the extraction assay. In the cell insert model, cell viability of L929 cells were 95.25 ± 0.96%, 47.49 ± 5.37%**, and 48.63 ± 7.00%**, respectively; HDFa cell viability were 92.80 ± 1.29%, 38.86 ± 4.28%**, and 49.90 ± 2.55%** (*: P < .01; **P < .001 compared with CSG‐PHMB; cell viability of culture medium without treatment at day 1 was 100%). The cell extraction model on day 1 indicated that CSG‐PHMB had higher viability of L929 cells compared with BXG. In addition, the cellular viability results indicated that CSG‐PHMB gel exhibited lower cytotoxicity when compared with BXG and PXG in the cell insert model assay. Within the in vitro debridement model, CSG‐PHMB exhibited an ability to potentially increase the loosening of the collagen matrix. The reason for this may be because of the concentrated surfactant found within the CSG‐PHMB, which has the ability to lower the surface tension, aiding in the movements of fragments and debris in the fluorescent artificial wound eschar model (fAWE).