bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retained placenta: will medical treatment ever be possible?
Authors: Akol Achier D. , Weeks Andrew D. 
Published: January 2016

AbstractThe standard treatment for retained placenta is manual removal whatever its subtype (adherens, trapped or partial accreta). Although medical treatment should reduce the risk of anesthetic and surgical complications, they have not been found to be effective. This may be due to the contrasting uterotonic needs of the different underlying pathologies. In placenta adherens, oxytocics have been used to contract the retro‐placental myometrium. However, if injected locally through the umbilical vein, they bypass the myometrium and perfuse directly into the venous system. Intravenous injection is an alternative but exacerbates a trapped placenta. Conversely, for trapped placentas, a relaxant could help by resolving cervical constriction, but would worsen the situation for placenta adherens. This confusion over medical treatment will continue unless we can find a way to diagnose the underlying pathology. This will allow us to stop treating the retained placenta as a single entity and to deliver targeted treatments.
I148M variant of PNPLA3 increases the susceptibility to non‐alcoholic fatty liver disease caused by obesity and metabolic disorders
Authors: Xia M.‐F. , Ling Y. , Bian H. , Lin H.‐D. , Yan H.‐M. , Chang X.‐X. , Li X.‐M. , Ma H. , Wang D. , Zhang L.‐S. , Wang S.‐S. , Wu B.‐J. , He W.‐Y. , Zhao N.‐Q. , Gao X. 
Published: January 2016

SummaryBackgroundThe patatin‐like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non‐alcoholic fatty liver disease (NAFLD). However, the associations between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied.AimTo investigate the influence of the PNPLA3 gene polymorphism on the association of liver fat with serum metabolic factors and carotid atherosclerosis.MethodsLiver fat was measured by quantitative ultrasound in 4300 subjects in the Shanghai Changfeng community and analysed for its association with obesity and metabolic factors in individuals with the PNPLA3 CC, CG and GG genotypes.ResultsNon‐alcoholic fatty liver disease occurred in 37.9% and 28.8% of the subjects with the GG and CC genotypes respectively (P < 0.001). Liver fat was significantly associated with body mass index, waist circumference, serum triglycerides, high‐density lipoprotein cholesterol, fasting blood glucose and insulin in the PNPLA3 rs738409 G allele carriers (P < 0.001). Compared with the CC homozygotes, the GG homozygotes presented higher liver fat and liver fibrosis scores despite their better metabolic status (comparison of regression line slopes, P < 0.05). An increase in liver fat was accompanied by a significant increase in the average and maximum carotid intima‐media thickness in subjects with the PNPLA3 CC genotype but not in those with the GG genotype.ConclusionsPNPLA3 rs738409 G allele carriers were found to be more susceptible to the metabolic‐related hepatic steatosis, and developed NAFLD and liver fibrosis despite presenting relatively better metabolic statuses and lower risks for carotid atherosclerosis.
Quantifying Health Across Populations
Authors: Kershnar Stephen 
Published: January 2016

AbstractIn this article, I argue that as a theoretical matter, a population's health‐level is best quantified via averagism. Averagism asserts that the health of a population is the average of members’ health‐levels. This model is better because it does not fall prey to a number of objections, including the repugnant conclusion, and because it is not arbitrary. I also argue that as a practical matter, population health‐levels are best quantified via totalism. Totalism asserts that the health of a population is the sum of members’ health‐levels. Totalism is better here because it fits better with cost‐benefit analysis and such an analysis is the best practical way to value healthcare outcomes. The two results are compatible because the theoretical and practical need not always align, whether in general or in the context of population health.
Older (but not younger) preschoolers understand that knowledge differs between people and across time
Authors: Caza Julian S. , Atance Cristina M. , Bernstein Daniel M. 
Published: January 2016

We examined 3‐ to 5‐year‐olds' understanding of general knowledge (e.g., knowing that clocks tell time) by investigating whether (1) they recognize that their own general knowledge has changed over time (i.e., they knew less as babies than they know now), and (2) such intraindividual knowledge differences are easier/harder to understand than interindividual differences (i.e., Do preschoolers understand that a baby knows less than they do?). Forty‐eight 3‐ to 5‐year‐olds answered questions about their current general knowledge (‘self‐now’), the general knowledge of a 6‐month‐old (‘baby‐now’), and their own general knowledge at 6 months (‘self‐past’). All age groups were significantly above chance on the self‐now questions, but only 5‐year‐olds were significantly above chance on the self‐past and baby‐now questions. Moreover, children's performance on the baby‐now and self‐past questions did not differ. Our findings suggest that younger preschoolers do not fully appreciate that their past knowledge differs from their current knowledge, and that others may have less knowledge than they do. We situate these findings within the research on knowledge understanding, more specifically, and cognitive development, more broadly.
Cord blood transplant for acute myeloid leukaemia
Authors: Ballen Karen K. , Lazarus Hillard 
Published: January 2016

SummaryUmbilical cord blood is a haematopoietic progenitor cell source for patients with acute myeloid leukaemia (AML), other haematological malignancies and metabolic diseases who can be cured by allogeneic haematopoietic cell transplantation, but who do not have a human leucocyte antigen compatible related or unrelated donor. Although the first cord blood transplants were done in children, there are currently more cord blood transplants performed in adults. In this review, we explore the history of umbilical cord blood transplantation, paediatric and adult outcome results, and novel trends to improve engraftment and reduce infection. Umbilical cord blood transplantation cures approximately 30–40% of adults and 60–70% of children with AML. Controversial issues, including the use of double versus single cord blood units for transplantation, optimal cord blood unit selection, infection prophylaxis, conditioning regimens and graft versus host disease prophylaxis, will be reviewed. Finally, comparison to other graft sources, cost, access to care, and the ideal graft source are discussed.
Intrinsic Astrocyte Heterogeneity Influences Tumor Growth in Glioma Mouse Models
Authors: Irvin David M. , McNeill Robert S. , Bash Ryan E. , Miller C. Ryan 
Published: January 2016

AbstractThe influence of cellular origin on glioma pathogenesis remains elusive. We previously showed that mutations inactivating Rb and Pten and activating Kras transform astrocytes and induce tumorigenesis throughout the adult mouse brain. However, it remained unclear whether astrocyte subpopulations were susceptible to these mutations. We therefore used genetic lineage tracing and fate mapping in adult conditional, inducible genetically engineered mice to monitor transformation of glial fibrillary acidic protein (GFAP) and glutamate aspartate transporter (GLAST) astrocytes and immunofluorescence to monitor cellular composition of the tumor microenvironment over time. Because considerable regional heterogeneity exists among astrocytes, we also examined the influence of brain region on tumor growth. GFAP astrocyte transformation induced uniformly rapid, regionally independent tumor growth, but transformation of GLAST astrocytes induced slowly growing tumors with significant regional bias. Transformed GLAST astrocytes had reduced proliferative response in culture and in vivo and malignant progression was delayed in these tumors. Recruited glial cells, including proliferating astrocytes, oligodendrocyte progenitors and microglia, were the majority of GLAST, but not GFAP astrocyte‐derived tumors and their abundance dynamically changed over time. These results suggest that intrinsic astrocyte heterogeneity, and perhaps regional brain microenvironment, significantly contributes to glioma pathogenesis.
Ranitidine‐induced anaphylaxis: clinical features, cross‐reactivity, and skin testing
Authors: Park K. H. , Pai J. , Song D.‐G. , Sim D. W. , Park H. J. , Lee J.‐H. , Jeong K. Y. , Pan C.‐H. , Shin I. , Park J.‐W. 
Published: January 2016

SummaryBackgroundHistamine H2 receptor antagonists are commonly prescribed medications and are known to be well tolerated. However, 99 cases of ranitidine‐induced anaphylaxis occurred in Korea from 2007 to 2014.ObjectiveThe purpose of this study was to determine the incidence, clinical features, and diagnostic methods for ranitidine‐induced anaphylaxis.MethodsRanitidine‐related pharmacovigilance data from 2007 to 2014 were reviewed. Adverse drug reactions with causal relationships were selected, and clinical manifestations, outcomes, and drug‐related information were assessed. For further investigation, 8 years of pharmacovigilance data were collected at a single centre. Twenty‐three patients participated in in vivo and in vitro studies. Skin tests, oral provocation tests, and laboratory tests were performed, including tests using other kinds of histamine H2 receptor antagonists.ResultsOver 7 years, 584 patients suffered adverse reactions to ranitidine. The most common manifestation was cutaneous symptoms. Among them, 99 patients (17.0%) experienced anaphylaxis. In a single‐centre study, skin prick tests were positive in 91.7% of ranitidine‐induced anaphylaxis patients (11/12); the optimal concentration was 20 mg/mL. Detection of ranitidine‐specific immunoglobulin E failed. Cimetidine and proton pump inhibitors showed no cross‐reactivity with ranitidine based on the skin prick test, oral provocation test, or clinical determination. Surprisingly, 82.6% of patients reintroduced ranitidine and re‐experienced the same adverse reactions because ranitidine was not considered the culprit drug.Conclusions and Clinical RelevanceAlthough ranitidine is known as a safe drug, it can also cause diverse adverse reactions, including anaphylaxis. This study demonstrates the need to pay attention to adverse reactions to ranitidine and consider ranitidine as a cause of anaphylaxis.
IgA- and SIgA anti-PR3 antibodies in serumversusorgan involvement and disease activity in PR3-ANCA-associated vasculitis
Authors: Sandin C , Eriksson P , Segelmark M , Skogh T , Kastbom A 
Published: January 2016

SummaryCirculating immunoglobulin (Ig)A class anti-neutrophil cytoplasm antibodies (ANCA) directed against proteinase 3 (PR3) have been reported in ANCA-associated vasculitis (AAV) with mucosal involvement. However, secretory IgA (SIgA) PR3-ANCA has not been reported previously. In this study we compared serum levels of SIgA PR3-ANCA and IgA PR3-ANCA with IgG PR3-ANCA in relation to disease characteristics. Among 73 patients with AAV and PR3-ANCA at diagnosis, 84% tested positive for IgG PR3-ANCA, 47% for IgA-ANCA and 36% for SIgA PR3-ANCA at the time of sampling for the present study. IgA and IgG PR3-ANCA were represented similarly among patients with different organ manifestations, i.e. upper airway, lung or kidney at time of sampling. However, SIgA PR3-ANCA was significantly less represented among patients with upper airway involvement. During active disease, the proportions of IgA PR3-ANCA and SIgA PR3-ANCA-positive patients were significantly higher compared to inactive disease. Eight patients were sampled prospectively during 24 months from onset of active disease. In these patients, IgA PR3-ANCA and SIgA PR3-ANCA turned negative more often after remission induction compared to IgG PR3-ANCA. Our findings suggest that serum IgA PR3-ANCA and SIgA PR3-ANCA are related more closely to disease activity in AAV compared to IgG PR3-ANCA. Further studies are required to reveal if this has implications for disease activity monitoring. The mean number of PR3-ANCA isotypes increased along with disease activity, suggesting a global B cell activation during active disease.
Implant stability and bone remodeling up to 84 days of implantation with an initial static strain. An in vivo and theoretical investigation
Authors: Halldin Anders , Jinno Yohei , Galli Silvia , Ander Mats , Jacobsson Magnus , Jimbo Ryo 
Published: January 2016

AbstractObjectivesWhen implants are inserted, the initial implant stability is dependent on the mechanical stability. To increase the initial stability, it was hypothesized that bone condensation implants will enhance the mechanical stability initially and that the moderately rough surface will further contribute to the secondary stability by enhanced osseointegration. It was further hypothesized that as the healing progresses the difference in removal torque will diminish. In addition, a 3D model was developed to simulate the interfacial shear strength. This was converted to a theoretical removal torque that was compared to the removal torque obtained in vivo.Material and methodsCondensation implants, inducing bone strains of 0.015, were installed into the left tibia of 24 rabbits. Non‐condensation implants were installed into the right tibia. All implants had a moderately rough surface. The implants had an implantation time of 7, 28, or 84 days before the removal torque was measured. The interfacial shear strength at different healing time was estimated by the means of finite element method.ResultsAt 7 days of healing, the condensation implant had an increased removal torque compared to the non‐bone‐condensation implant. At 28 and 84 days of healing, there was no difference in removal torque. The simulated interfacial shear strength ratios of bone condensation implants at different implantation time were in line with the in vivo data.ConclusionsModerately rough implants that initially induce bone strain during installation have increased stability during the early healing period. In addition, the finite element method may be used to evaluate differences in interlocking capacity.
Biological sex and the risk of cerebral palsy in Victoria, Australia
Authors: Reid Susan M , Meehan Elaine , Gibson Catherine S , Scott Heather , Delacy Michael J ,   the Australian Cerebral Palsy Register Group
Published: January 2016

AimMales typically outnumber females in cerebral palsy (CP) cohorts. To better understand this ‘male disadvantage’ and provide insight into causal pathways to CP, this study used 1983 to 2009 Australian CP and population birth cohorts to identify associations and trends with respect to biological sex and CP.MethodWithin birth gestation groups, sex ratios were calculated to evaluate any male excess in the CP cohort compared with livebirths, neonatal deaths, neonatal mortality and survival rates, neonatal survivors, and CP rates in survivors. Sex‐ and gestation‐specific trends in neonatal mortality, CP rates, and CP sex ratios were assessed by plotting their annual frequencies and fitting quadratic curves.ResultsOver‐representation of males in preterm live births partly explained the male excess in the CP cohort after preterm birth, especially at 28 to 31 weeks. Higher CP rates in male neonatal survivors also contributed to the male excess in CP, particularly at <28 and 37+ weeks. Higher neonatal mortality rates in males at all gestations had little impact on the CP sex ratio. There was no clearly discernible change over time in the CP sex ratio.InterpretationGestation‐specific associations between sex and CP provide insight into causal pathways to CP and suggest sex‐specific differences in response to neuroprotective strategies.
Evolution of a pentameral body plan was not linked to translocation of anterior Hox genes: the echinoderm HOX cluster revisited
Authors: Byrne Maria , Martinez Pedro , Morris Valerie 
Published: January 2016

SUMMARYEchinodermata is a large phylum of marine invertebrates characterized by an adult, pentameral body plan. This morphology is clearly derived as all members of Deuterostomia (the superphylum to which they belong) have a bilateral body plan. The origin of the pentameral plan has been the subject of intense debate. It is clear that the ancestor of Echinodermata had a bilateral plan but how this ancestor transformed its body “architecture” in such a drastic manner is not clear. Data from the fossil record and ontogeny are sparse and, so far, not very informative. The sequencing of the sea urchin genome a decade ago opened the possibility that the pentameral body plan was a consequence of a broken Hox cluster and a series of papers dwelt on the putative relationship between Hox gene arrangements in the chromosomes and the origin of pentamery. This relationship, sound as it was, is challenged by the revelation that the sea star HOX cluster is, in fact, intact, thus falsifying the hypothesis of a direct relationship between HOX cluster arrangement and the origin of the pentameral body plan. Here, we explore the relationship between Hox gene arrangements and echinoderm body “architecture,” the expression of Hox genes in development and alternative scenarios for the origin of pentamery, with putative roles for signaling centers in generating multiple axes.
Health and economic benefits of public financing of epilepsy treatment in India: An agent‐based simulation model
Authors: Megiddo Itamar , Colson Abigail , Chisholm Dan , Dua Tarun , Nandi Arindam , Laxminarayan Ramanan 
Published: January 2016

SummaryObjectiveAn estimated 6–10 million people in India live with active epilepsy, and less than half are treated. We analyze the health and economic benefits of three scenarios of publicly financed national epilepsy programs that provide: (1) first‐line antiepilepsy drugs (AEDs), (2) first‐ and second‐line AEDs, and (3) first‐ and second‐line AEDs and surgery.MethodsWe model the prevalence and distribution of epilepsy in India using IndiaSim, an agent‐based, simulation model of the Indian population. Agents in the model are disease‐free or in one of three disease states: untreated with seizures, treated with seizures, and treated without seizures. Outcome measures include the proportion of the population that has epilepsy and is untreated, disability‐adjusted life years (DALYs) averted, and cost per DALY averted. Economic benefit measures estimated include out‐of‐pocket (OOP) expenditure averted and money‐metric value of insurance.ResultsAll three scenarios represent a cost‐effective use of resources and would avert 800,000–1 million DALYs per year in India relative to the current scenario. However, especially in poor regions and populations, scenario 1 (which publicly finances only first‐line therapy) does not decrease the OOP expenditure or provide financial risk protection if we include care‐seeking costs. The OOP expenditure averted increases from scenarios 1 through 3, and the money‐metric value of insurance follows a similar trend between scenarios and typically decreases with wealth. In the first 10 years of scenarios 2 and 3, households avert on average over US$80 million per year in medical expenditure.SignificanceExpanding and publicly financing epilepsy treatment in India averts substantial disease burden. A universal public finance policy that covers only first‐line AEDs may not provide significant financial risk protection. Covering costs for both first‐ and second‐line therapy and other medical costs alleviates the financial burden from epilepsy and is cost‐effective across wealth quintiles and in all Indian states.
The Importance of Toll‐like Receptors in NF‐κB Signaling Pathway Activation by Helicobacter pylori Infection and the Regulators of this Response
Authors: Hu Yi , Liu Jian‐Ping , Zhu Yin , Lu Nong‐Hua 
Published: January 2016

AbstractHelicobacter pylori (H. pylori) is a common pathogenic bacterium in the stomach that infects almost half of the population worldwide and is closely related to gastric diseases and some extragastric diseases, including iron‐deficiency anemia and idiopathic thrombocytopenic purpura. Both the Maastricht IV/Florence consensus report and the Kyoto global consensus report have proposed the eradication of H. pylori to prevent gastric cancer as H.pylori has been shown to be a major cause of gastric carcinogenesis. The interactions between H. pylori and host receptors induce the release of the proinflammatory cytokines by activating proinflammatory signaling pathways such as nuclear factor kappa B (NF‐κB), which plays a central role in inflammation, immune response, and carcinogenesis. Among these receptors, Toll‐like receptors (TLRs) are classical pattern recognition receptors in the recognition of H. pylori and the mediation of the host inflammatory and immune responses to H. pylori. TLR polymorphisms also contribute to the clinical consequences of H. pylori infection. In this review, we focus on the functions of TLRs in the NF‐κB signaling pathway activated by H. pylori, the regulators modulating this response, and the functions of TLR polymorphisms in H.pylori‐related diseases.
Salian intellectual history in historiographical perspective
Authors: McCarthy T. J. H. 
Published: January 2016

AbstractThe Salian period (1024–1125) was one of momentous religious change and intellectual productivity in Germany. While on the one hand, it was dominated by the titanic struggle between empire and papacy known as the Investiture Contest, on the other, it saw the monasteries and cathedral schools of the kingdom produce a steady stream of important works in areas such as canon law, history, theology, rhetoric, poetry and music. Nevertheless, the period has not received the attention it deserves in English‐language scholarship. This article discusses the reasons for its comparative neglect, surveys the rich existing German historiography and suggests new avenues for future work.
Staphylococcus epidermidis and biofilm‐associated neutrophils in chronic rhinosinusitis. A pilot study
Authors: Marcinkiewicz Janusz , Stręk Paweł , Strus Magdalena , Głowacki Roman , Ciszek‐Lenda Marta , Zagórska‐Świeży Katarzyna , Gawda Anna , Tomusiak Anna 
Published: January 2016

SummaryA key role of bacterial biofilm in the pathogenesis of chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyps (CRSsNP) is commonly accepted. However, the impact of some bacterial species isolated from inflamed sinus mucosa on biofilm formation is unclear. In particular, the role of Staphylococcus epidermidis as aetiological agents of CRS is controversial. Moreover, the effect of biofilm formation on neutrophil infiltration and activity in CRSwNP calls for explanation. In this study, biofilms were found in three of 10 patients (mean age = 46 ± 14) with CRS undergoing endoscopic sinus surgery by means of scanning electron microscopy. Unexpectedly, S. epidermidis was the primary isolated bacteria and was also found to be present in all biofilm‐positive mucosa specimens, indicating its pivotal role in the pathogenesis of severe chronic infections associated with biofilm formation. We have also measured the activity of myeloperoxidase (MPO), the most abundant neutrophil enzyme, to demonstrate the presence of neutrophils in the samples tested. Our present results show that the level of MPO in CRS associated with biofilm is lower than that without biofilm. It may suggest either a low number of neutrophils or the presence of a type of neutrophils with compromised antimicrobial activity, described as biofilm‐associated neutrophils (BAN). Finally, we conclude that further studies with a large number of CRS cases should be performed to establish the association between S. epidermidis and other frequently isolated bacterial species from paranasal sinuses, with the severity of CRS, biofilm formation and the infiltration of BAN.