bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reticulate evolution in nuclear Middle America causes discordance in the phylogeny of palm‐pitvipers (Viperidae: Bothriechis)
Authors: Mason Andrew J. , Grazziotin Felipe G. , Zaher Hussam , Lemmon Alan R. , Moriarty Lemmon Emily , Parkinson Christopher L. 
Published: March 2019

AbstractAimA number of processes can lead to weak or conflicting phylogenetic signals, especially in geographically dynamic regions where unstable landscapes and climates promote complex evolutionary histories. The Middle American pitviper genus Bothriechis has a complex biogeographic distribution and previous phylogenetic analyses have recovered conflicting topologies based on the data type used. Here, we tested whether historic conflicts in the phylogeny were the result of reticulate evolution and whether the inferred biogeographic history of the group would enable contact among reticulate lineages.LocationMiddle America.TaxonPalm‐pitvipers (genus Bothriechis).MethodsWe generated a phylogenomic dataset using an anchored phylogenomics approach and inferred a genomics‐based species tree and mitochondrial tree to assess incongruence among datasets. We then generated a dated phylogeny and conducted ancestral area reconstruction to examine the biogeographic history surrounding the diversification of these species. We additionally tested whether the discordance among trees is better explained by lineage sorting or reticulate evolution by testing models of reticulate evolution inferred through multiple methods.ResultsWe found strong support for discordance in the phylogeny of Bothriechis and corresponding evidence for reticulate evolution among lineages with incongruent placement. Ancestral area reconstruction placed these taxa in adjacent regions during the time period when reticulation was projected to take place and suggested a biogeographic history heavily influenced by vicariant processes.Main conclusionsReticulation among geographically proximate lineages has driven apparent genomic discordance in Bothriechis and is responsible for historical incongruence in the phylogeny. Inference of the order of events suggests that reticulation among nuclear Middle American taxa occurred during a time of geologic upheaval, promoting lineage divergence and secondary contact. Reticulate evolution and similar processes can have substantial impacts on the evolutionary trajectory of taxa and are important to explicitly test for in biogeographically complex regions.
PMEPA1 induces EMT via a non‐canonical TGF‐β signalling in colorectal cancer
Authors: Zhang Lei , Wang Xue , Lai Chong , Zhang Honghe , Lai Maode 
Published: March 2019

AbstractProstate transmembrane protein androgen induced 1 (PMEPA1) has been reported to promote cancer progression. Metastasis is the main factor leading to cancer progression and poor prognosis, and at the beginning of metastasis, epithelial‐to‐mesenchymal transition (EMT) is a crucial activation. However, the relationship between PMEPA1 and EMT in colorectal cancer metastasis is still poorly understood. In this study, we first testified that PMEPA1 expresses higher in tumour than normal tissue in Gene Expression Omnibus database, in the Cancer Genome Atlas (TCGA) as well as in the clinical data we collected. Moreover, the higher expression was associated with poor prognosis. We furthermore demonstrated PMEPA1 promotes colorectal cancer metastasis and EMT in vivo and in vitro. We found that PMEPA1 activates the bone morphogenetic proteins (BMP) signalling of TGF‐β signalling resulting in promoting EMT and accelerating the proliferation and metastasis of colorectal cancer.
Conditioned media from dental pulp stem cells improved diabetic polyneuropathy through anti‐inflammatory, neuroprotective and angiogenic actions: Cell‐free regenerative medicine for diabetic polyneuropathy
Authors: Makino Eriko , Nakamura Nobuhisa , Miyabe Megumi , Ito Mizuho , Kanada Saki , Hata Masaki , Saiki Tomokazu , Sango Kazunori , Kamiya Hideki , Nakamura Jiro , Miyazawa Ken , Goto Shigemi , Matsubara Tatsuaki , Naruse Keiko 
Published: March 2019

AbstractAims/IntroductionDental pulp stem cells (DPSCs) can be easily obtained from teeth for general orthodontic reasons. We have previously reported the therapeutic effects of DPSC transplantation for diabetic polyneuropathy. As abundant secretomes from DPSCs are considered to play a central role in the improvement of diabetic polyneuropathy, we investigated whether direct injection of DPSC‐conditioned media (DPSC‐CM) into hindlimb skeletal muscles ameliorates diabetic polyneuropathy in diabetic rats.Materials and MethodsDPSCs were isolated from the dental pulp of Sprague–Dawley rats. Eight weeks after the induction of diabetes, DPSC‐CM was injected into the unilateral hindlimb skeletal muscles in both normal and diabetic rats. The effects of DPSC‐CM on diabetic polyneuropathy were assessed 4 weeks after DPSC‐CM injection. To confirm the angiogenic effect of DPSC‐CM, the effect of DPSC‐CM on cultured human umbilical vascular endothelial cell proliferation was investigated.ResultsThe administration of DPSC‐CM into the hindlimb skeletal muscles significantly ameliorated sciatic motor/sensory nerve conduction velocity, sciatic nerve blood flow and intraepidermal nerve fiber density in the footpads of diabetic rats. We also showed that DPSC‐CM injection significantly increased the capillary density of the skeletal muscles, and suppressed pro‐inflammatory reactions in the sciatic nerves of diabetic rats. Furthermore, an in vitro study showed that DPSC‐CM significantly increased the proliferation of umbilical vascular endothelial cells.ConclusionsWe showed that DPSC‐CM injection into hindlimb skeletal muscles has a therapeutic effect on diabetic polyneuropathy through neuroprotective, angiogenic and anti‐inflammatory actions. DPSC‐CM could be a novel cell‐free regenerative medicine treatment for diabetic polyneuropathy.
Alopecia areata: a long‐term follow‐up study of 104 patients
Authors: Lyakhovitsky A. , Aronovich A. , Gilboa S. , Baum S. , Barzilai A. 
Published: March 2019

AbstractBackgroundAlopecia areata (AA) is a common autoimmune disease that considerably affects the quality of life. Although several studies have investigated the epidemiology, clinical characteristics and treatment of AA, limited recent data are available regarding its long‐term course.ObjectivesTo evaluate the long‐term course of AA in different age groups.MethodsA retrospective evaluation of patients who were newly diagnosed with AA from 2008 to 2011 and had at least 7 years of follow‐up. Data regarding the initial episode, treatment given, disease‐free interval and relapses were analysed.ResultsA total of 104 cases were analysed: 31 childhood‐onset, 63 adult‐onset and 10 late‐onset. At first episode, 88.5% of patients had mild, 3.8% moderate and 7.7% severe AA. Full or significant re‐growth was observed in 74%, 94% and 100% of childhood‐onset, adult‐onset and late‐onset AA patients, respectively. There was no re‐growth in 13%, 3% and 0% of childhood‐onset, adult‐onset and late‐onset patients, respectively. The duration of the initial episode and the disease‐free interval negatively correlated with age. Systemic steroids were the most effective treatment for the primary episode. The frequency of relapses was high overall (52%, 44% and 30% in childhood‐onset, adult‐onset and late‐onset, respectively), but significantly declined over time with a majority (79%) occurring within the first 4 years. The disease‐free interval and relapse rate were not correlated with gender, disease severity at onset or treatment given.ConclusionsThe prevalence of severe disease, duration of an initial episode and the rate of relapses decreased with an older age at onset. In addition, the outcome and the disease‐free interval improved with age at onset. The frequency of relapses declined over time and most appear early on. The current treatment modalities do not seem to influence the long‐term outcome.
Influence of Multimorbidity on Burden and Appropriateness of Implantable Cardioverter‐Defibrillator Therapies
Authors: Hajduk Alexandra M. , Gurwitz Jerry H. , Tabada Grace , Masoudi Frederick A. , Magid David J. , Greenlee Robert T. , Sung Sue Hee , Cassidy‐Bushrow Andrea E. , Liu Taylor I. , Reynolds Kristi , Smith David H. , Fiocchi Frances , Goldberg Robert , Gill Thomas M. , Gupta Nigel , Peterson Pamela N. , Schuger Claudio , Vidaillet Humberto , Hammill Stephen C. , Allore Heather , Go Alan S. ,   for the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators
Published: March 2019

OBJECTIVETo determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies.DESIGNRetrospective cohort study.SETTINGSeven US healthcare delivery systems.PARTICIPANTSAdults with left ventricular systolic dysfunction receiving an implantable cardioverter‐defibrillator (ICD) for primary prevention.MEASUREMENTSData on 24 comorbid conditions were captured from electronic health records and categorized into quartiles of comorbidity burden (0‐3, 4‐5, 6‐7 and 8‐16). Incidence of ICD therapies (shock and antitachycardia pacing [ATP] therapies), including appropriateness, was collected for 3 years after implantation. Outcomes included time to first ICD therapy, total ICD therapy burden, and risk of inappropriate vs appropriate ICD therapy.RESULTSAmong 2235 patients (mean age = 69 ± 11 years, 75% men), the median number of comorbidities was 6 (interquartile range = 4‐8), with 98% having at least two comorbidities. During a mean 2.2 years of follow‐up, 18.3% of patients experienced at least one appropriate therapy and 9.9% experienced at least one inappropriate therapy. Higher comorbidity burden was associated with an increased risk of first inappropriate therapy (adjusted hazard ratio [HR] = 1.94 [95% confidence interval {CI} = 1.14‐3.31] for 4‐5 comorbidities; HR = 2.25 [95% CI = 1.25‐4.05] for 6‐7 comorbidities; and HR = 2.91 [95% CI = 1.54‐5.50] for 8‐16 comorbidities). Participants with 8‐16 comorbidities had a higher total burden of ICD therapy (adjusted relative risk [RR] = 2.12 [95% CI = 1.43‐3.16]), a higher burden of inappropriate therapy (RR = 3.39 [95% CI = 1.67‐6.86]), and a higher risk of receiving inappropriate vs appropriate therapy (RR = 1.74 [95% CI = 1.07‐2.82]). Comorbidity burden was not significantly associated with receipt of appropriate ICD therapies. Patterns were similar when separately examining shock or ATP therapies.CONCLUSIONSIn primary prevention ICD recipients, MCC burden was independently associated with an increased risk of inappropriate but not appropriate device therapies. Comorbidity burden should be considered when engaging patients in shared decision making about ICD implantation.
Traumatic Experiences and the Midwifery Profession: A Cross‐Sectional Study Among Dutch Midwives
Authors: Kerkman Tessa , Dijksman Lea M. , Baas Melanie A.M. , Evers Ruth , van Pampus Maria G. , Stramrood Claire A.I. 
Published: March 2019

IntroductionTraumatic events that occur in a clinical setting can have long‐lasting adverse effects on persons who are affected, including health care providers. This study investigated the prevalence of work‐related traumatic events, posttraumatic stress disorder (PTSD), anxiety, and depression among Dutch midwives. Additionally, differences between midwives working in primary care (independently assisting births at home and in birthing centers) and midwives working in secondary or tertiary care (hospital setting) were examined. Finally, this study investigated the support midwives would like to receive after experiencing a work‐related adverse event.MethodsA descriptive, cross‐sectional online survey of Dutch midwives was conducted. The respondents completed a questionnaire about demographic and work‐related events, as well as the Trauma Screening Questionnaire and the Hospital Anxiety and Depression Scale.ResultsThe estimated response rate was 23%, with 691 questionnaires eligible for analysis. Thirteen percent of respondents reported having experienced at least one work‐related traumatic event. Among these, 17% screened positive for PTSD, revealing an estimated PTSD prevalence of 2% among Dutch midwives. Clinically relevant anxiety symptoms were reported by 14% of the respondents, significantly more often among midwives working in primary care (P = .014). Depressive symptoms were reported by 7% of the respondents. The desired strategies to cope with an adverse event were peer support by direct colleagues (79%), professional support from a coach or psychologist (30%), multidisciplinary peer support (28%), and support from midwives who are not direct coworkers (17%).DiscussionDutch midwives are at risk of experiencing work‐related stressful or traumatic events that might lead to PTSD, anxiety, or depression. Midwives working in primary care reported higher levels of anxiety compared with their colleagues working in a clinical setting (secondary or tertiary care). Most midwives preferred peer support with direct colleagues after an adverse event, and some could have profited from easier access to seeking professional help. It could be speculated that midwives would benefit from increased awareness about work‐related traumatic events as well as implementation of standardized guidelines regarding support after a traumatic event.
Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT‐2 inhibitors and GLP‐1 receptor agonists
Authors: Bonaventura A. , Carbone S. , Dixon D. L. , Abbate A. , Montecucco F. 
Published: March 2019

AbstractPatients with type 2 diabetes mellitus (T2D) present an increased risk for cardiovascular (CV) complications. In addition to improvement in glycaemic control, glucose‐lowering therapies, such as glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐dependent glucose cotransporter (SGLT)‐2 inhibitors, have been shown to significantly reduce CV events. In 2008, the US Food and Drug Administration mandated that all new glucose‐lowering drugs undergo CV outcomes trials (CVOTs) to determine their CV safety. These trials have largely demonstrated no major CV safety concerns. Most notably, the GLP‐1RAs and SGLT‐2 inhibitors have been found to be not only safe, but also cardioprotective compared to placebo. The SGLT‐2 inhibitors have opened a new perspective for clinicians treating patients with T2D and established CV disease in light of their ‘pleiotropic’ effects, specifically on heart failure, while GLP‐1RAs seem to present more favourable effects on atherosclerotic events. In this review, we discuss the role of GLP‐1RAs and SGLT‐2 inhibitors to reduce CV risk in T2D patients and suggest an individualized therapeutic approach in this population based on the presence of metabolic and CV comorbidities.
School Personnel's Bystander Action in Situations of Teen Relationship Abuse and Sexual Assault: Prevalence and Correlates
Authors: Edwards Katie M. , Sessarego Stephanie N. , Banyard Victoria L. , Rizzo Andrew J. , Mitchell Kimberly J. 
Published: March 2019

ABSTRACTBACKGROUNDRelationship abuse (RA) and sexual assault (SA) are major problems among high school students, and school personnel are an important part of preventing RA and SA among youth. Therefore, we examined the rates and correlates of bystander intentions among school personnel in situations of RA and SA.METHODSSchool personnel (N = 1150) from 25 high schools in New England completed surveys that assessed their RA and SA knowledge, perceptions of school climate specific to RA and SA, and RA and SA bystander efficacy and bystander intentions.RESULTSAcross each type of bystander behavior measured, the vast majority of school personnel reported intentions to intervene. In the multilevel regression analyses, both proactive and reactive bystander intentions were related to higher levels of RA and SA bystander efficacy and perceptions of a more positive school climate and lower levels of RA and SA barriers to intervene.CONCLUSIONSThese data support the utility of school‐based interventions that seek to improve school climate and teach school personnel skills that enhance bystander efficacy and reduce bystander barriers in student situations of RA and SA. Although they would need to be evaluated, such interventions could promote positive bystander action among school personnel and untimely contribute to reductions in RA and SA among high school youth.
Angiopoietin‐like 4 production upon treatment with hypoxia and L‐mimosine in periodontal fibroblasts
Authors: Janjić Klara , Schellner Alwina , Engenhart Alexander , Kernstock Kurt , Schädl Barbara , Moritz Andreas , Agis Hermann 
Published: March 2019

Background and objectiveA key factor in the modulation of angiogenesis as well as in bone resorption is angiopoietin‐like 4. However, the role of angiopoietin‐like 4 in periodontal tissue is unknown. Here, we hypothesized that hypoxia and the hypoxia mimetic agent L‐mimosine can induce the production of angiopoietin‐like 4 in periodontal fibroblasts.MethodsHuman periodontal ligament fibroblasts (PDLF) were cultured in monolayer and spheroid cultures. The cultures were incubated in the presence of hypoxia or L‐mimosine. Angiopoietin‐like 4 mRNA and protein levels were measured by qPCR and ELISA, respectively. Also, the impact of Lipopolysaccharides of E. coli and P. gingivalis, interleukin (IL)‐1β and tumor necrosis factor (TNF)α was evaluated. Furthermore, we tested dependency on hypoxia‐inducible factor (HIF)‐1 activity by Western blotting for HIF‐1 and inhibitor studies with echinomycin. Potential autocrine effects were assessed by exposure of PDLF to recombinant angiopoietin‐like 4 in full length, C‐terminal and N‐terminal fragments. The impact on viability, DNA synthesis, alkaline phosphatase, and matrix mineralization was evaluated.ResultsBoth hypoxia and L‐mimosine elevated angiopoietin‐like 4 mRNA and protein levels in monolayer cultures of PDLF. HIF‐1 was elevated after both hypoxia and L‐mimosine treatment. LPS, IL‐1β, and TNFα did not modulate angiopoietin‐like 4 levels significantly. Addition of echinomycin in the cultures inhibited the production of angiopoietin‐like 4. In spheroid cultures of PDLF, the increase did not reach the level of significance at mRNA and protein levels. Angiopoietin‐like 4 in full length, C‐terminal, and N‐terminal fragments did not modulate viability, DNA synthesis, alkaline phosphatase, and matrix mineralization.ConclusionOverall, we found that hypoxia and the hypoxia mimetic agent L‐mimosine can stimulate angiopoietin‐like 4 production in monolayer cultures of PDLF. This increase depends on HIF‐1 activity. Future studies will reveal how the modulation of angiopoietin‐like 4 in the periodontium contributes to periodontal disease and regeneration.
A comparison of the rates of postoperative complications between dogs undergoing laparoscopic and open ovariectomy
Authors: Charlesworth T. M. , Sanchez F. T. 
Published: March 2019

ObjectivesTo investigate whether dogs undergoing laparoscopic ovariectomy might have a lower overall and wound‐healing complication rate than those undergoing an open surgical approach.Materials and MethodsA retrospective study of dogs that underwent laparascopic or open surgical ovariectomy between January 1, 2013 and January 1, 2018 by the same team of similarly experienced surgeons using standard practice anaesthetic, theatre and perioperative protocols. General complications were described and graded using the Clavien‐Dindo system. Complication rates were compared between the two groups of dogs. Wound complications were further subdivided using the U.S. Centers for Disease Control guidelines.ResultsAccording to the Clavien‐Dindo system, 46 of 106 (44%) dogs undergoing open ovariectomy developed a complication. Thirty dogs (28.3%) had wound healing complications, the majority of which were minor and self‐limiting. Superficial site infections occurred in 50 (5%) cases and deep surgical site infections in one dog (1%). Incisional herniation occurred in four (4%) cases. Thirty‐one (20%) of 154 dogs undergoing laparoscopic ovariectomy developed a complication. Seventeen (11%) developed wound healing complications, most of which were minor; five (3%) developed superficial surgical site infections and none had deep surgical site infections. Incisional herniation occurred in none of the laparoscopic cases.Clinical SignificanceThe rates of overall and wound healing complications were lower for the laparascopic group than the open surgical group in this non‐randomised study. Laparoscopy might be considered preferable for ovariectomy in dogs but confirmation requires a randomised trial.
Sex allocation plasticity on a transcriptome scale: Socially sensitive gene expression in a simultaneous hermaphrodite
Authors: Ramm Steven A. , Lengerer Birgit , Arbore Roberto , Pjeta Robert , Wunderer Julia , Giannakara Athina , Berezikov Eugene , Ladurner Peter , Schärer Lukas 
Published: March 2019

AbstractPhenotypic plasticity can enable organisms to produce optimal phenotypes in multiple environments. A crucial life history trait that is often highly plastic is sex allocation, which in simultaneous hermaphrodites describes the relative investment into the male versus female sex functions. Theory predicts—and morphological evidence supports—that greater investment into the male function is favoured with increasing group size, due to the increasing importance of sperm competition for male reproductive success. Here, we performed a genome‐wide gene expression assay to test for such sex allocation plasticity in a model simultaneous hermaphrodite, the free‐living flatworm Macrostomum lignano. Based on RNA‐Seq data from 16 biological replicates spanning four different group size treatments, we demonstrate that at least 10% of the >75,000 investigated transcripts in M. lignano are differentially expressed according to the social environment, rising to >30% of putative gonad‐specific transcripts (spermatogenesis and oogenesis candidates) and tail‐specific transcripts (seminal fluid candidates). This transcriptional response closely corresponds to the expected shift away from female and towards male reproductive investment with increasing sperm competition level. Using whole‐mount in situ hybridization, we then confirm that many plastic transcripts exhibit the expected organ‐specific expression, and RNA interference of selected testis‐ and ovary‐specific candidates establishes that these indeed function in gametogenesis pathways. We conclude that a large proportion of sex‐specific transcripts in M. lignano are differentially expressed according to the prevailing ecological conditions and that these are functionally relevant to key reproductive phenotypes. Our study thus begins to bridge organismal and molecular perspectives on sex allocation plasticity.