bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcitonin gene‐related peptide (CGRP): A novel target for Alzheimer's disease
Authors: Singh Yogendra , Gupta Gaurav , Shrivastava Birendra , Dahiya Rajiv , Tiwari Juhi , Ashwathanarayana Madhu , Sharma Rakesh Kumar , Agrawal Mohit , Mishra Anurag , Dua Kamal 
Published: April 2017

SummaryAlzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid‐β (Aβ) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene‐related peptide (CGRP) is a thirty‐seven‐amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor‐stimulating peptide. It is a proof for a CGRP receptor within nucleus accumbens of brain that is different from either the CGRP1 or CGRP2 receptor in which it demonstrates similar high‐affinity binding for salmon calcitonin, CGRP, and amylin, a possession which is not shared by any extra CGRP receptors. Binding of CGRP to its receptor increases activated cAMP‐dependent pkA and PI3 kinase, resulting in N‐terminal fragments that are shown to exert complex inhibitory as well facilitator actions on nAChRs. Fragments such as CGRP1‐4, CGRP1‐5, and CGRP1‐6 rapidly as well as reversibly improve agonist sensitivity of nAChRs without straight stimulating those receptors and produce the Ca2+‐induced intracellular Ca2+ mobilization. Renin–angiotensin–aldosterone system (RAAS)‐activated angiotensin‐type (AT4) receptor is also beneficial in AD. It has been suggested that exogenous administration of CGRP inhibits infiltration of macrophages and expression of various inflammatory mediators such as NFkB, IL‐1b, TNF‐α, iNOS, matrix metalloproteinase (MMP)‐9, and cell adhesion molecules like intercellular adhesion molecule (ICAM)‐1 which attenuates consequence of inflammation in AD. Donepezil, a ChEI, inhibits acetylcholinesterase and produces angiogenesis and neurogenesis, in the dentate gyrus of the hippocampus of WT mice after donepezil administration. However, none of the results discovered in CGRP‐knockout mice and WT mice exposed to practical denervation. Therefore, selective agonists of CGRP receptors may become the potential candidates for treatment of AD.
Use of the Harmonic scalpel for Delorme's procedure
Authors: Parés D. , Drami I. , Adams K. , Grossi U. , Suliman I. , Knowles C. H. 
Published: April 2017

AbstractAimThere are many surgical techniques that deal with external rectal prolapse but perineal procedures have the advantage of reduced invasiveness. Therefore, despite concerns regarding high recurrence rates, the technique is still used by many surgeons.MethodThis manuscript and video describe our early clinical experience using the Harmonic scalpel in 11 consecutive patients who underwent a Delorme's procedure for external rectal prolapse.ResultsThe median age of patients was 76 (range: 30–94) years. There were no intra‐operative complications, and the median operative time was 78 min. Intra‐operative blood loss was minimal (mean 45 ml; range 20–70 ml). Median length of stay was 2 (range: 0–8) days. Overall morbidity and recurrence were both 18%, with a median follow‐up of 15 (range: 1–23) months. Nine patients were operated on by a senior trainee with consultant supervision.ConclusionThe advantages of this device are mainly those of ease of mucosal dissection, minimal blood loss and shorter operative time in comparison with published series.
Preverbal Infants Infer Third‐Party Social Relationships Based on Language
Authors: Liberman Zoe , Woodward Amanda L. , Kinzler Katherine D. 
Published: April 2017

AbstractLanguage provides rich social information about its speakers. For instance, adults and children make inferences about a speaker's social identity, geographic origins, and group membership based on her language and accent. Although infants prefer speakers of familiar languages (Kinzler, Dupoux, & Spelke, 2007), little is known about the developmental origins of humans’ sensitivity to language as marker of social identity. We investigated whether 9‐month‐olds use the language a person speaks as an indicator of that person's likely social relationships. Infants were familiarized with videos of two people who spoke the same or different languages, and then viewed test videos of those two individuals affiliating or disengaging. Results suggest that infants expected two people who spoke the same language to be more likely to affiliate than two people who spoke different languages. Thus, infants view language as a meaningful social marker and use language to make inferences about third‐party social relationships.
Deconstructed cat communities: Quantifying the threat to felids from prey defaunation
Authors: Sandom C. J. , Williams J. , Burnham D. , Dickman A. J. , Hinks A. E. , Macdonald E. A. , Macdonald D. W. 
Published: April 2017

AbstractAimDefaunation, the emptying of ecosystems of fauna, has been highlighted as a likely threat to the conservation of carnivores, but the magnitude of this threat has yet to be quantified. We quantify the potential threat defaunation presents to wild felids.LocationGlobal.MethodsFor the 32 wild felids that feed primarily on mammals, we used 5,330 prey records from 237 published sources to compile a new diet dataset, FelidDIET. This dataset was used to determine the relative importance of mammalian species as prey for each felid. These data were used to quantify the relationship between felid and prey species‐richness, and to estimate the potential threat to wild felids from the loss of their prey.ResultsOur analyses reveal that models that include adjusted prey species‐richness as a predictor of felid‐richness outperform those with less precise measures of prey‐richness (potential prey‐richness and total mammal‐richness). This is true both when examined collectively and when split into those felids that prey upon large‐bodied prey and those that prey upon small‐bodied prey. For seven felid species, including six large felids (over 15 kg), 33% or more of their primary prey‐species are threatened. Of most concern is the Sunda clouded leopard Neofelis diardi, for which 66.0% of its primary prey‐species are threatened. In total, 57.6% of large felids’ primary prey‐species are threatened or declining, compared with 26.5% for small felids. Large felids are particularly vulnerable to primary prey decline in Indo‐Malaya and East and Central Africa.Main conclusionsOur findings indicate that imminent prey loss is likely to have substantial negative effects on large felids, many of which are already highly threatened. Considering the trophic cascades associated with large predators, the threat to large felids through the loss of prey diversity presents an ecosystem‐scale threat.
Rates of hypoglycaemia are lower in patients treated with insulin degludec/liraglutide (IDegLira) than with IDeg or insulin glargine, regardless of the hypoglycaemia definition used
Authors: Norwood Paul , Chen Roger , Jaeckel Elmar , Lingvay Ildiko , Jarlov Henrik , Lehmann Lucine , Heller Simon 
Published: April 2017

AimsTo re‐analyse, using a series of alternative hypoglycaemia definitions, the data from 2 trials, DUAL I and V, in which the once‐daily, fixed ratio combination of insulin degludec/liraglutide (IDegLira) was compared with basal insulin therapy.Material and Methods
Post hoc analyses of the DUAL I (patients uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on insulin glargine (IGlar) U100) trials were carried out using different definitions of hypoglycaemia and according to whether treatments were administered in the morning or afternoon. Rates of hypoglycaemia for the definitions of confirmed and American Diabetes Association (ADA)‐documented symptomatic hypoglycaemia were compared according to age, gender and body mass index (BMI).ResultsAlthough hypoglycaemia rates differed according to the alternative hypoglycaemia definitions, rates were consistently lower with IDegLira vs insulin degludec (IDeg) and IGlar U100. Despite glycated haemoglobin concentrations being lower with IDegLira at end of treatment, confirmed and nocturnal‐confirmed hypoglycaemia rates were lower for IDegLira vs IDeg and IGlar U100, irrespective of dosing time. The definitions of confirmed and ADA‐documented symptomatic hypoglycaemia did not have a significant effect on the treatment difference between IDegLira and IDeg, liraglutide or IGlar U100 when further assessed by baseline age, gender and BMI.ConclusionsTreatment with IDegLira, vs IDeg and IGlar U100, resulted in lower rates of hypoglycaemia regardless of dosing time and definition of hypoglycaemia used. The choice of hypoglycaemia definition did not influence the results of analyses when stratified by age, sex and BMI.
Availability of unfertilised eggs increases the fitness of nymphal crickets (Gryllidae)
Authors: ZENG YANG , ZHOU FENG‐HAO , KANG WEI‐NAN , ZHU DAO‐HONG 
Published: April 2017

1. Female insects of many species lay both fertilised and unfertilised eggs, with the latter accounting for up to 50% of the total number laid. These unfertilised eggs do not hatch and so their relevance is unclear.2. In the present study, it was found that nymphs of the cricketVelarifictorus aspersusate unfertilised eggs regardless of whether there was other food available. This provision enabled nymphs to develop successfully when no other food was provided, and to gain additional body mass when other food was available under crowded conditions. These results suggest that unfertilised eggs have an important role in the survival and development of nymphs.3. Nymphs preferred to eat unfertilised rather than fertilised eggs, suggesting that they may have the ability to distinguish between these two types of eggs.4. Crowding promoted feeding on unfertilised eggs and accelerate nymphal development, suggesting that greater food consumption accounts for faster growth under grouped conditions.
Trends in morbidity: national statistics on sickness claims among the working population in Sweden, 1892–1954
Authors: Castenbrandt Helene 
Published: April 2017

AbstractIn this article national statistics from Swedish sickness funds are analysed from 1892 to 1954. The study is intended to provide better knowledge of changes in sickness claims, and to contribute to the discussion of morbidity trends. National statistics on sickness benefits are available from 1892, and are studied until the introduction of mandatory health insurance in 1955. Membership of Swedish sickness funds increased more than tenfold between 1900 and 1950. Just a small portion of members were women in 1900; however, women constituted the majority of members by 1941. There was a gender difference in morbidity, but this variation was not consistent over time. Before 1935 men had more but shorter sickness episodes; however, after 1935 women had significantly higher sickness rates. The law in 1931 meant that the recruitment of members was widened and compensation for longer periods of illness was made possible. The continuous increase in sick days can be partly explained by legislative changes; however, the increase in the period 1910–32 cannot. The study thereby highlights the importance of incorporating legislative changes into the interpretation. This increased understanding of trends in sick leave provides a sound basis for extending the study to the analysis of individual‐level data.
Education policy in Poland: The impact of PISA (and other international studies)
Authors: Białecki Ireneusz , Jakubowski Maciej , Wiśniewski Jerzy 
Published: April 2017

AbstractThe impact of the PISA study on Polish education policy has been significant, but probably different from any other country. Poland has not experienced the so‐called ‘PISA shock’, but its education system has been benefiting considerably from PISA. For experts and policy makers, it has been a useful and reliable instrument that has made it possible to measure the effects of consecutive reforms of the school education system. Moreover, PISA and other international studies have influenced the perception of education policy in Poland. The latter has shifted from an ideology‐driven, centralised policy to an evidence‐informed policy, developed with the involvement of multiple stakeholders, although this has mostly affected the thinking of experts and policy makers rather than the general public. The new government (in power from 2015), following public opinion polls, has reversed most of the previous education reforms, eliminating lower secondary schools introduced in 1999.
Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden
Authors: Kozlowski Piotr , Lennmyr Emma , Ahlberg Lucia , Bernell Per , Hulegårdh Erik , Karbach Holger , Karlsson Karin , Tomaszewska‐Toporska Beata , Åström Maria , Hallböök Heléne ,   the Swedish Adult Acute Lymphoblastic Leukemia Group (SVALL)
Published: April 2017

AbstractObjectivesOlder/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials.MethodsUsing Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age‐adapted protocol (introduced in 2009) in this population‐based study of patients aged 55‐85 years, diagnosed with ALL 2005‐2012.ResultsOf 174 patients, 82% had B‐phenotype, 11% Burkitt leukemia (excluded), and 7% T‐phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B‐ and T‐ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status ≥2 influenced the choice of palliation. Intensive, palliative, and both approaches resulted in complete remission rate 83/16/70% and 3‐year overall survival (OS) 32/3/26%. The age‐adapted protocol did not improve outcome. With intensive treatment, platelet count ≤35×109/L and age ≥75 years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55‐64 year age‐group.ConclusionsWe report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph‐negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age‐adapted treatment.
Loss of INK4a/Arf gene enhances ultraviolet radiation‐induced cutaneous tumor development
Authors: Ahmad Israr , Guroji Purushotham , DeBrot Amanda H. , Manapragada Padma P. , Katiyar Santosh K. , Elmets Craig A. , Yusuf Nabiha 
Published: April 2017

AbstractThe CDKN2A locus encodes for tumor suppressor genes p16INK4a and p14Arf which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation‐induced skin tumors. Panels of INK4a/Arf‐/− mice and wild‐type (WT) mice were treated with a single dose of UVB (200 mJ/cm2). For long‐term studies, these mice were irradiated with UVB (200 mJ/cm2) three times weekly for 30 weeks. At the end of the experiment, tissues were harvested from mice and assayed for inflammatory biomarkers and cytokines. A single dose of UVB resulted in a significant increase in reactive oxygen species (ROS) and 8‐dihydroxyguanosine (8‐oxo‐dG) lesions in INK4a/Arf−/− mice compared to WT mice. When subjected to chronic UVB, we found that 100% of INK4a/Arf−/‐ mice had tumors, whereas there were no tumors in WT controls after 24 weeks of UVB exposure. The increase in tumor development correlated with a significant increase in nuclear factor (NF)‐κB, cyclooxygenase‐2 (COX‐2), prostaglandin E2 (PGE2) and its receptors both in UVB‐exposed skin and in the tumors. A significant increase was seen in inflammatory cytokines in skin samples of INK4a/Arf‐/‐ mice following treatment with chronic UVB radiation. Furthermore, significantly more CD11b+Gr1+ myeloid cells were present in UVB‐exposed INK4a/Arf‐/‐ mice compared to WT mice. Our data indicate that by targeting UVB‐induced inflammation, it may be possible to prevent UVB‐induced skin tumors in individuals that carry CDKN2A mutation.
Expression of low‐density lipoprotein‐related receptors 5 and 6 (LRP5/6) in psoriasis skin
Authors: Duvetorp Albert , Olsen Renate Slind , Nyström Helena , Skarstedt Marita , Dienus Olaf , Mrowietz Ulrich , Söderman Jan , Seifert Oliver 
Published: April 2017

AbstractLow‐density lipoprotein‐related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signalling. Wnt ligands are thought to play an important role in innate immunity and psoriasis, and recent studies assigned LRP5/6 anti‐inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non‐lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV‐B radiation, LRP5/6 skin gene expression was analysed before and after narrowband UV‐B treatment. Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non‐lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV‐B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV‐B treatment suggest a possible role for LRP5/6 in psoriasis.
Ectopic expression of the transcription factor MafB in basal keratinocytes induces hyperproliferation and perturbs epidermal homeostasis
Authors: Miyai Masashi , Tsunekage Yukino , Saito Michiko , Kohno Kenji , Takahashi Kenzo , Kataoka Kohsuke 
Published: April 2017

AbstractMammalian epidermis is composed of four morphologically and functionally distinct layers of keratinocytes. The innermost basal layer consists of proliferating self‐renewing keratinocytes, which also undergo asymmetric cell division to differentiate into postmitotic suprabasal cells throughout life. Control of the balance between growth and differentiation of basal cells is important for epidermal homeostasis to prevent skin disorders including malignancies; however, the underlying mechanism remains to be elucidated. Recently, MafB was identified as one of the transcription factors that regulate epidermal keratinocyte differentiation. MafB is expressed in postmitotic differentiating keratinocytes, and epidermal differentiation is partially impaired in MafB‐deficient mice. To further establish the roles of MafB in the epidermis in vivo, we generated mice transgenic for MafB under the control of the basal cell‐specific keratin (Krt) 14 promoter. In the epidermis of transgenic mice at embryonic day 18.5, the number of proliferating Krt14‐positive basal‐like cells was increased, and the granular and cornified layers were thickened. Furthermore, these MafB transgenic mice developed papillomas spontaneously with age. Therefore, MafB promotes differentiation in postmitotic keratinocytes and simultaneously has potential to promote growth when ectopically expressed in undifferentiated basal keratinocytes.
Methods for the isolation and 3D culture of dermal papilla cells from human hair follicles
Authors: Topouzi Helena , Logan Niall J. , Williams Greg , Higgins Claire A. 
Published: April 2017

AbstractThe dermal papilla is a cluster of mesenchymal cells located at the base of the hair follicle which have a number of important roles in the regulation of hair growth. As a consequence, in vitro models of these cells are widely used to study the molecular mechanisms which underlie hair follicle induction, growth and maintenance. While dermal papilla from rodent hair follicles can be digested prior to cell isolation, the unique extracellular matrix composition found in human dermal papilla renders enzymes such as trypsin and collagenase insufficient for digestion of the dermal papilla into a single cell suspension. As such, to grow human dermal papilla cells in vitro, the papilla has to first be isolated via a micro‐dissection approach from the follicle. In this article we describe the micro‐dissection and culture methods, which we use within our laboratory, for the study of human dermal papilla cells.
The Greek System: How Gender Inequality and Class Privilege Perpetuate Rape Culture
Authors: Jozkowski Kristen N. , Wiersma‐Mosley Jacquelyn D. 
Published: April 2017

AbstractSexual assault on college campuses is a pervasive public health issue. It is important to examine factors particular to universities that influence occurrences of sexual assault and people's perceptions of sexual assault. Using a lens of socialist feminism, we argue that institutional and sociocultural factors related to gender and class privilege on college campuses are due to patterns of power and control in university systems that contribute to the occurrence and facilitation of sexual assault. Our synthesis of the literature focuses on the male‐dominated party culture of the primarily White Greek system in American universities, which is reinforced by the university as an institution. We discuss how patterns of power and control dictate and influence contemporary campus norms in relation to gender and class, which then perpetuate sexual assault. We provide recommendations for policies and procedures regarding class and gender inequities in the scope of sexual violence on college campuses.
Climate variability drives recent tree mortality in Europe
Authors: Neumann Mathias , Mues Volker , Moreno Adam , Hasenauer Hubert , Seidl Rupert 
Published: April 2017

AbstractTree mortality is an important process in forest ecosystems, frequently hypothesized to be highly climate sensitive. Yet, tree death remains one of the least understood processes of forest dynamics. Recently, changes in tree mortality have been observed in forests around the globe, which could profoundly affect ecosystem functioning and services provisioning to society. We describe continental‐scale patterns of recent tree mortality from the only consistent pan‐European forest monitoring network, identifying recent mortality hotspots in southern and northern Europe. Analyzing 925,462 annual observations of 235,895 trees between 2000 and 2012, we determine the influence of climate variability and tree age on interannual variation in tree mortality using Cox proportional hazard models. Warm summers as well as high seasonal variability in precipitation increased the likelihood of tree death. However, our data also suggest that reduced cold‐induced mortality could compensate increased mortality related to peak temperatures in a warming climate. Besides climate variability, age was an important driver of tree mortality, with individual mortality probability decreasing with age over the first century of a trees life. A considerable portion of the observed variation in tree mortality could be explained by satellite‐derived net primary productivity, suggesting that widely available remote sensing products can be used as an early warning indicator of widespread tree mortality. Our findings advance the understanding of patterns of large‐scale tree mortality by demonstrating the influence of seasonal and diurnal climate variation, and highlight the potential of state‐of‐the‐art remote sensing to anticipate an increased likelihood of tree mortality in space and time.