bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoplasmic reticulum stress pathway PERK‐eIF2α confers radioresistance in oropharyngeal carcinoma by activating NF‐κB
Authors: Qiao Qiao , Sun Chaonan , Han Chuyang , Han Ning , Zhang Miao , Li Guang
Published: April 2017

Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis and development of malignant tumors, as well as in the regulation of radiochemoresistance and chemoresistance in many malignancies. ERS signaling pathway protein kinase RNA‐like endoplasmic reticulum kinase (PERK)‐eukaryotic initiation factor‐2 (eIF2α) may induce aberrant activation of nuclear factor‐κB (NF‐κB). Our previous study showed that NF‐κB conferred radioresistance in lymphoma cells. However, whether PERK‐eIF2α regulates radioresistance in oropharyngeal carcinoma through NF‐κB activation is unknown. Herein, we showed that PERK overexpression correlated with a poor prognosis for patients with oropharyngeal carcinoma (P < 0.01). Meanwhile, the percentage of the high expression level of PERK in oropharyngeal carcinoma patients resistant to radiation was higher than in patients sensitive to radiation (77.7 and 33.3%, respectively; P < 0.05). Silencing PERK and eIF2α increased the radiosensitivity in oropharyngeal carcinoma cells and increased radiation‐induced apoptosis and G2/M phase arrest. PERK‐eIF2α silencing also inhibited radiation‐induced NF‐κB phosphorylation and increased the DNA double strand break‐related proteins ATM phosphorylation. NF‐κB activator TNF‐α and the ATM inhibitor Ku55933 offset the regulatory effect of eIF2α on the expression of radiation‐induced cell apoptosis‐related proteins and the G2/M phase arrest‐related proteins. These data indicate that PERK regulates radioresistance in oropharyngeal carcinoma through NF‐kB activation‐mediated phosphorylation of eIF2α, enhancing X‐ray‐induced activation of DNA DSB repair, cell apoptosis inhibition and G2/M cell cycle arrest.
Serum monomeric laminin‐γ2 as a novel biomarker for hepatocellular carcinoma
Authors: Kiyokawa Hirofumi , Yasuda Hiroshi , Oikawa Ritsuko , Okuse Chiaki , Matsumoto Nobuyuki , Ikeda Hiroki , Watanabe Tsunamasa , Yamamoto Hiroyuki , Itoh Fumio , Otsubo Takehito , Yoshimura Toru , Yoshida Eisaku , Nakagawa Masatoshi , Koshikawa Naohiko , Seiki Motoharu
Published: April 2017

The diagnosis of hepatocellular carcinoma (HCC) in the early stages is important for successful clinical management. Laminin (Ln)‐γ2 expression has been reported in various types of malignant carcinomas. We recently developed a highly sensitive method to measure serum monomeric Ln‐γ2 levels using a fully automated chemiluminescent immunoassay (CLIA). Using our CLIA, we evaluated its diagnostic value in sera from patients with chronic liver disease (CLD) and patients with hepatocellular carcinoma (HCC). Serum alpha‐fetoprotein (AFP) and des‐gamma‐carboxy prothrombin (DCP) were also examined in these subjects. Median levels of Ln‐γ2 were significantly higher in patients with HCC (173.2 pg/mL; range: 39.5–986 pg/mL) compared with patients with CLD (76.7 pg/mL; range: 38.7–215.9 pg/mL) and with healthy volunteers (41.1 pg/mL; range: 10.9–79.0 pg/mL). The optimal cutoff value for Ln‐γ2 that allowed us to distinguish between HCC and nonmalignant CLD was 116.6 pg/mL. Elevated Ln‐γ2 levels were observed in 0% of healthy volunteers, 17% of patients with CLD, and 63% of patients with HCC. The positivity rate in patients with HCC for the combination of Ln‐γ2 and DCP was 89.5%, which was better than that for either of the two markers alone (63% and 68%, respectively). Among patients with early‐stage HCC (T1 or T2), the positivity rates for monomeric Ln‐γ2, AFP and DCP were 61%, 39% and 57%, respectively. Serum Ln‐γ2 may be a potential biomarker for HCC surveillance. The combination of Ln‐γ2 and DCP may be more sensitive for laboratory diagnosis of HCC than the combination of AFP and DCP.
Puquitinib, a novel orally available PI3Kδ inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia
Authors: Xie Chengying , He Ye , Zhen Mingyue , Wang Yulan , Xu Yongping , Lou Liguang
Published: April 2017

The PI3Kδ isoform (PIK3CD), also known as P110δ, is predominately expressed in leukocytes and has been implicated as a potential target in the treatment of hematological malignancies. In this report, we detailed the pharmacologic properties of puquitinib, a novel, orally available PI3Kδ inhibitor. Puquitinib, which binds to the ATP‐binding pocket of PI3Kδ, was highly selective and potent for PI3Kδ relative to other PI3K isoforms and a panel of protein kinases, exhibiting low‐nanomolar biochemical and cellular inhibitory potencies. Additional cellular profiling demonstrated that puquitinib inhibited proliferation, induced G1‐phase cell‐cycle arrest and apoptosis in acute myeloid leukemia (AML) cell lines, through downregulation of PI3K signaling. In in vivo AML xenografts, puquitinib alone showed stronger efficacy than the well‐known p110δ inhibitor, CAL‐101, in association with a reduction in AKT and ERK phosphorylation in tumor tissues, without causing noticeable toxicity. Furthermore, the combination of puquitinib with cytotoxic drugs, especially daunorubicin, yielded significantly stronger antitumor efficacy compared with each agent alone. Thus, puquitinib is a promising agent with pharmacologic properties that are favorable for the treatment of AML.
Do maternal depression and anxiety influence children's oral health‐related quality of life?
Authors: Costa Francine dos Santos , Azevedo Marina Sousa , Ardenghi Thiago Machado , Pinheiro Ricardo Tavares , Demarco Flávio Fernando , Goettems Marília Leão
Published: April 2017

Objective

This study aimed to investigate the influence of depressive and anxiety symptoms in young mothers on their perception in relation to their children's oral health‐related quality of life (COHRQoL).

Methods

This cross‐sectional study was carried out in Pelotas, Southern Brazil, and it was nested in a cohort of adolescent mothers having their prenatal care in public health service, starting in 2008. When the children were aged 24‐36 months, they and their mothers were interviewed and submitted to clinical examination by a trained team. Socioeconomic, educational, behavioural and psychological assessments were collected in the interview and oral examination investigated caries and gingival bleeding (in mothers) and caries and dental trauma (in children). Maternal perception of impact on COHRQoL was evaluated by Early Childhood Oral Health Impact Scale (ECOHIS). The outcome in the present study was the occurrence of impact on COHRQoL (ECOHIS≥2), that is the presence of at least one ECOHIS item reported as occasionally (score 2), often (score 3) or very often (score 4). Analysis was conducted using Poisson regression with robust variance and obtained prevalence ratios (PR) and respective 95% confidence intervals (CI).

Results

This study comprised 537 mother‐child dyads. After adjustment, higher scores of COHRQoL remained significantly associated with depressive symptoms (PR=1.80, 95% CI: 1.36‐2.38) and maternal anxiety symptoms (PR=2.28, 95% CI: 1.72‐3.00). Mothers with anxiety symptoms or depressive symptoms had a prevalence of impact 91% higher when compared with mothers without any symptoms (PR=1.91; CI 95% 1.35‐2.68), and mothers with both symptoms had almost 2.5 times higher risk of perception of negative impact on COHRQoL (PR=2.48; CI 95% 1.78‐3.45).

Conclusion

Poorer COHRQoL was associated with maternal depression and anxiety symptoms.
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

Alzheimer'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

Aim

There 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.

Method

This 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.

Results

The 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.

Conclusion

The 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

Language 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

Aim

Defaunation, 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.

Location

Global.

Methods

For 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.

Results

Our 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 conclusions

Our 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

Aims

To 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).

Results

Although 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.

Conclusions

Treatment 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

In 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

The 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

Objectives

Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials.

Methods

Using 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.

Results

Of 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.

Conclusions

We 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

The 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

Low‐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

Mammalian 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

The 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

Sexual 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

Tree 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.
The phenology of leaf quality and its within‐canopy variation is essential for accurate modeling of photosynthesis in tropical evergreen forests
Authors: Wu Jin , Serbin Shawn P. , Xu Xiangtao , Albert Loren P. , Chen Min , Meng Ran , Saleska Scott R. , Rogers Alistair
Published: April 2017

Leaf quantity (i.e., canopy leaf area index, LAI), quality (i.e., per‐area photosynthetic capacity), and longevity all influence the photosynthetic seasonality of tropical evergreen forests. However, these components of tropical leaf phenology are poorly represented in most terrestrial biosphere models (TBMs). Here, we explored alternative options for the representation of leaf phenology effects in TBMs that employ the Farquahar, von Caemmerer & Berry (FvCB) representation of CO2 assimilation. We developed a two‐fraction leaf (sun and shade), two‐layer canopy (upper and lower) photosynthesis model to evaluate different modeling approaches and assessed three components of phenological variations (i.e., leaf quantity, quality, and within‐canopy variation in leaf longevity). Our model was driven by the prescribed seasonality of leaf quantity and quality derived from ground‐based measurements within an Amazonian evergreen forest. Modeled photosynthetic seasonality was not sensitive to leaf quantity, but was highly sensitive to leaf quality and its vertical distribution within the canopy, with markedly more sensitivity to upper canopy leaf quality. This is because light absorption in tropical canopies is near maximal for the entire year, implying that seasonal changes in LAI have little impact on total canopy light absorption; and because leaf quality has a greater effect on photosynthesis of sunlit leaves than light limited, shade leaves and sunlit foliage are more abundant in the upper canopy. Our two‐fraction leaf, two‐layer canopy model, which accounted for all three phenological components, was able to simulate photosynthetic seasonality, explaining ~90% of the average seasonal variation in eddy covariance‐derived CO2 assimilation. This work identifies a parsimonious approach for representing tropical evergreen forest photosynthetic seasonality in TBMs that utilize the FvCB model of CO2 assimilation and highlights the importance of incorporating more realistic phenological mechanisms in models that seek to improve the projection of future carbon dynamics in tropical evergreen forests.
Climate‐ and successional‐related changes in functional composition of European forests are strongly driven by tree mortality
Authors: Ruiz‐Benito Paloma , Ratcliffe Sophia , Zavala Miguel A. , Martínez‐Vilalta Jordi , Vilà‐Cabrera Albert , Lloret Francisco , Madrigal‐González Jaime , Wirth Christian , Greenwood Sarah , Kändler Gerald , Lehtonen Aleksi , Kattge Jens , Dahlgren Jonas , Jump Alistair S.
Published: April 2017

Intense droughts combined with increased temperatures are one of the major threats to forest persistence in the 21st century. Despite the direct impact of climate change on forest growth and shifts in species abundance, the effect of altered demography on changes in the composition of functional traits is not well known. We sought to (1) quantify the recent changes in functional composition of European forests; (2) identify the relative importance of climate change, mean climate and forest development for changes in functional composition; and (3) analyse the roles of tree mortality and growth underlying any functional changes in different forest types. We quantified changes in functional composition from the 1980s to the 2000s across Europe by two dimensions of functional trait variation: the first dimension was mainly related to changes in leaf mass per area and wood density (partially related to the trait differences between angiosperms and gymnosperms), and the second dimension was related to changes in maximum tree height. Our results indicate that climate change and mean climatic effects strongly interacted with forest development and it was not possible to completely disentangle their effects. Where recent climate change was not too extreme, the patterns of functional change generally followed the expected patterns under secondary succession (e.g. towards late‐successional short‐statured hardwoods in Mediterranean forests and taller gymnosperms in boreal forests) and latitudinal gradients (e.g. larger proportion of gymnosperm‐like strategies at low water availability in forests formerly dominated by broad‐leaved deciduous species). Recent climate change generally favoured the dominance of angiosperm‐like related traits under increased temperature and intense droughts. Our results show functional composition changes over relatively short time scales in European forests. These changes are largely determined by tree mortality, which should be further investigated and modelled to adequately predict the impacts of climate change on forest function.
Catheter‐related fungal endocarditis caused by Candida parapsilosis in a hemodialysis patient
Authors: Shu Ying , Yu Shaobin , Zha Ling , Fu Ping , Cui Tianlei
Published: April 2017

Fungal endocarditis (FE) is commonly regarded as a rare but fatal disease. The incidence of infective endocarditis (IE) in hemodialysis (HD) patients is thought to be obviously higher than that in the general population. Moreover, IE occurs more likely in HD patients with catheters. With the increase of HD population and extensive use of catheters in HD patients, FE, as a special form of IE, may increase and bring new challenges to clinicians. We reported a case of FE associated with catheter infection in a 44‐year‐old woman on HD. The risk factors and treatment strategies of FE in HD patients were discussed.
Molecular subtyping of mammary‐like adenocarcinoma of the vulva shows molecular similarity to breast carcinomas
Authors: Tessier‐Cloutier Basile , Asleh‐Aburaya Karama , Shah Varsha , McCluggage W Glenn , Tinker Anna , Gilks C Blake
Published: April 2017

Aims

Mammary‐like adenocarcinoma (MLA) of the vulva is thought to be derived from vulvar mammary‐like glands. The aim of this study was to characterize a series of MLAs by using an immunohistochemical algorithm that identifies the major molecular subtypes of breast cancer.

Methods and results

Seven cases of vulval MLA were stained for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, epidermal growth factor receptor (EGFR), cytokeratin (CK) 5, nestin, and inositol polyphosphate‐4‐phosphatase (INPP4b). Seventeen cases of vulval extramammary Paget disease (EMPD), seven with invasion, were studied for comparison. The median age of patients with MLA was 72 years. All tumours except one were early‐stage tumours. On the basis of an immunohistochemical panel, three of seven tumours were classified as luminal B, two of seven as HER2‐enriched, one of seven as luminal A, and one of seven as basal‐like. ER was expressed in four of seven tumours, PR in three of seven, HER2 in three of seven, EGFR in two of seven, and CK5 in one of seven, and the Ki67 index was >15% in six of seven cases. Nestin and INPP4b were, respectively, negative and positive in all cases. Of the seven cases of invasive EMPD, two showed a luminal A profile, three a luminal B profile (two of three with HER2 amplification), one a HER2‐enriched profile, and one a basal‐like profile. Three of seven were HER2‐amplified. Among the 10 cases of EMPD without invasion, seven showed a luminal A profile and three showed a luminal B profile (all HER2‐amplified); no HER2‐enriched or basal‐like subtypes were identified.

Conclusions

Breast cancer subtyping can be applied to vulvar MLAs. All four intrinsic molecular subtypes are seen, with frequencies similar to those in breast carcinoma. Our results support the potential use of breast cancer molecular profiling algorithms to guide treatment for these cancers.
Four cases of neoplasia in amphibians at two zoological institutions: Alpine newt Ichthyosaura alpestris, Red‐eyed tree frog Agalychnis callidryas, Common frog Rana temporaria and Puerto Rican crested toad Peltophryne lemur
Authors: O'Brien M. F. , Justice W. S. M. , Beckmann K. M. , Denk D. , Pocknell A. M. , Stidworthy M. F.
Published: April 2017

Four cases of spontaneous neoplasia in different species of Amphibia at two zoological collections in the United Kingdom (2009–2016) are described: disseminated lymphosarcoma with leukaemia in an Alpine newt Ichthyosaura alpestris, nasal adenocarcinoma in a Red‐eyed tree frog Agalychnis callidryas, pulmonary carcinoma in a Common frog Rana temporaria and cutaneous mast‐cell tumour in a Puerto Rican crested toad Peltophryne lemur. History, and gross and histological findings are presented. In particular, mast‐cell tumours in Anura and respiratory tumours of amphibians have rarely been reported.
Commentary: On the importance of looking at nonlinearity and developmental effects – a reflection on Flom et al. (2017)
Authors: Rioux Charlie , Parent Sophie , Séguin Jean R.
Published: April 2017

By examining both linear and curvilinear associations between mental development and activity level, the study by Flom et al. (Journal of Child Psychology and Psychiatry, 2017) highlights the importance of going beyond linear associations in psychological fields of research. Results from Flom et al. (Journal of Child Psychology and Psychiatry, 2017) also raise interesting questions for future research. First, studies should look at variables that may explain the associations between activity level and mental development, such as self‐regulation and attention. Second, longitudinal changes in the strength of the association between activity level and mental development should be examined to determine when this association is at its strongest. Finally, longitudinal research looking at bidirectional effects is needed to confirm the direction of the associations between activity level and mental development. Answers to these questions will allow the identification of the best targets and developmental periods for interventions to take place.
Facts and values in psychotherapy—A critique of the empirical reduction of psychotherapy within evidence‐based practice
Authors: Berg Henrik , Slaattelid Rasmus
Published: April 2017

This paper addresses an implicit presupposition in research‐supported psychological treatments and evidence‐based practice in psychology. It argues that the notion of research‐supported psychological treatments is based on a reductive conceptualisation of psychotherapy. Research‐supported psychological treatments hinge upon an empirical reduction where psychotherapy schools become conceptualized as mere collections of empirical propositions. However, this paper argues that the different psychotherapy schools have distinct ethoses that are constituted by normative claims. Consequently, the evaluation of the different psychotherapy schools and the practice of psychotherapy should include the underlying normative claims of these ethoses.
Effect of an electronic medication administration record application on patient safety
Authors: Vicente Oliveros Noelia , Gramage Caro Teresa , Pérez Menendez‐Conde Covadonga , Álvarez‐Díaz Ana María , Martín‐Aragón Álvarez Sagrario , Bermejo Vicedo Teresa , Delgado Silveira Eva
Published: April 2017

Rationale, aims, and objectives

To evaluate the effect of an electronic medication administration record (eMAR) application on the rate of medication errors in medication administration recording (ME‐MAR).

Methods

A before‐and‐after, quasiexperimental study was conducted in a university hospital that implemented the eMAR application in March 2014. Data collection was conducted in April 2012 (pre‐) and June 2014 (post‐) by two pharmacists. The ME‐MARs were analysed by the staff involved to identify their cause. The two pharmacists independently classified the ME‐MARs. In the case of disagreement, a research team examined the ME‐MARs and categorized them by consensus. Three classifications were used: A classic medication error taxonomy and 2 technology‐induced error taxonomies.

Results

The pharmacists analysed 2835 (pre‐) and 2621 (post‐) medication administration records (MAR), respectively. Overall, the ME‐MAR rate decreased from 48.0% (pre‐) to 36.9% (post‐) (P < .05). The same types of ME‐MAR were observed in both phases except for “MAR with incomplete information,” which was not observed in the postimplementation phase. In both phases, the most frequent ME‐MAR was “MAR at the wrong time” (MAR before or after medication administration) (31.6% vs 30.2%). The main cause of ME‐MARs in both phases was the failure to follow work procedures. The potential future risk of ME‐MARs significantly decreased after the eMAR implementation (P < .05). All ME‐MARs were “use errors” because of human factors. New ME‐MARs (1.24%; n = 12) were observed in the postimplementation phase.

Conclusion

Use of the eMAR application significantly reduces the rate of ME‐MAR and their potential risk. The main cause of ME‐MAR was the failure to follow work procedures.
Natural mortality and cause of death analysis of the captive chimpanzee (Pan troglodytes): A 35‐year review
Authors: Laurence Hannah , Kumar Shyamesh , Owston Michael A. , Lanford Robert E. , Hubbard Gene B. , Dick Edward J.
Published: April 2017

We present the spontaneous causes of mortality for 137 chimpanzees (Pan troglodytes) over a 35‐year period. A record review of the pathology database was performed and a primary cause of mortality was determined for each chimpanzee. The most common causes of mortality were as follows: cardiomyopathy (40% of all mortalities), stillbirth/abortion, acute myocardial necrosis, chimpanzee‐induced trauma, amyloidosis, and pneumonia. Five morphologic diagnoses accounted for 61% of mortalities: cardiomyopathy, hemorrhage, acute myocardial necrosis, amyloidosis, and pneumonia. The most common etiologies were degenerative, undetermined, bacterial, traumatic, and neoplastic. The cardiovascular system was most frequently involved, followed by the gastrointestinal, respiratory, and multisystemic diseases. Degenerative diseases were the primary etiological cause of mortality of the adult captive chimpanzee population. Chimpanzee‐induced trauma was the major etiological cause of mortality among the perinatal and infant population. This information should be a useful resource for veterinarians and researchers working with chimpanzees.
Sagittal crest formation in great apes and gibbons
Authors: Balolia Katharine L. , Soligo Christophe , Wood Bernard
Published: April 2017

The frequency of sagittal crest expression and patterns of sagittal crest growth and development have been documented in hominoids, including some extinct hominin taxa, and the more frequent expression of the sagittal crest in males has been traditionally linked with the need for larger‐bodied individuals to have enough attachment area for the temporalis muscle. In the present study, we investigate sagittal cresting in a dentally mature sample of four hominoid taxa (Pan troglodytes schweinfurthii, Gorilla gorilla gorilla, Pongo pygmaeus pygmaeus and Hylobates lar). We investigate whether sagittal crest size increases with age beyond dental maturity in males and females of G. g. gorilla and Po. pyg. pygmaeus, and whether these taxa show sex differences in the timing of sagittal crest development. We evaluate the hypothesis that the larger sagittal crest of males may not be solely due to the requirement for a larger surface area than the un‐crested cranial vault can provide for the attachment of the temporalis muscle, and present data on sex differences in temporalis muscle attachment area and sagittal crest size relative to cranial size. Gorilla g. gorilla and Po. pyg. pygmaeus males show significant relationships between tooth wear rank and sagittal crest size, and they show sagittal crest size differences between age groups that are not found in females. The sagittal crest emerges in early adulthood in the majority of G. g. gorilla males, whereas the percentage of G. g. gorilla females possessing a sagittal crest increases more gradually. Pongo pyg. pygmaeus males experience a three‐fold increase in the number of specimens exhibiting a sagittal crest in mid‐adulthood, consistent with a secondary growth spurt. Gorilla g. gorilla and Po. pyg. pygmaeus show significant sex differences in the size of the temporalis muscle attachment area, relative to cranial size, with males of both taxa showing positive allometry not shown in females. Gorilla g. gorilla males also show positive allometry for sagittal crest size relative to cranial size. Our results suggest that although patterns of sagittal crest expression have limited utility for taxonomy and phylogeny reconstruction, they could be useful for reconstructing aspects of social behaviour in some extinct hominin taxa. In particular, our results in G. g. gorilla and Po. pyg. pygmaeus, which suggest that the size of sagittal crests in males cannot be solely explained by the surface area required for attachment of the temporalis muscle, offer partial support for the hypothesis that large sagittal crests form in response to sexual selection and may play a role in social signalling.