bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood Glaucoma: Long-Term Outcomes of Glaucoma Drainage Device Implantation Within the First 2 Years of Life
Authors: Daniel Moritz C. , Mohamed-Noriega Jibran , Petchyim Sakaorat , Brookes John 
Published: July 2019

Précis:
Glaucoma drainage device (GDD) implantation within the first 2 years of life yields an overall success rate of 59.0% at 5 years. It is safe and requires a relatively low number of postoperative interventions.

Purpose:
The purpose of this study was to evaluate the long-term outcomes of the treatment of childhood glaucoma with GDDs within the first 2 years of life.

Methods:
A total of 43 children (60 eyes) having undergone GDD implantation within the first 2 years of life at Moorfields Eye Hospital between July 2005 and November 2014 were included in this retrospective case series. Kaplan-Meier survival curves were created for the evaluation of surgical success. Log-rank analysis was performed for the detection of risk factors for failure. Main outcome measures: Overall success rates at 1, 5, and 7 years after surgery. Surgical success: intraocular pressure ≥5/≤21 mm Hg, no further glaucoma surgery required, nonoccurrence of loss of perception of light or devastating complications.

Results:
The results are listed as follows: Median duration of follow-up was 48.0 months. Median age at surgery was 11.5 months. Seventy-three percentage of children were white. Most common types of glaucoma were primary congenital glaucoma [(PCG); 67%], glaucoma following cataract surgery (18%), and anterior segment dysgenesis (10%). Overall success rates were 93%, 59%, and 59%, respectively. There were no differences in the survival rates as a function of PCG/non-PCG, sex, and removal of intraluminal stent suture. Mean number of general anesthesia administrations during the first postoperative year was 1.8.

Conclusions:
GDD implantation within the first 2 years of life is effective and safe. The low number of general anesthesia administrations required during the first postoperative year could help to reduce the burden placed on children and carers. Further research is required to directly compare the efficiency of GDD implantation with other surgical options.
Examining the Relationship Between Patient Fatigue-Related Symptom Clusters and Carer Depressive Symptoms in Advanced Cancer Dyads
Authors: Buck Harleah G. , Benitez Bryan , Fradley Michael G. , Donovan Kristine A. , McMillan Susan C. , Reich Richard R. , Wang Hsiao-Lan 
Published: July 2019

Background
Most symptom management takes place in the community, conducted by patient and/or informal carer dyads with guidance from clinicians. Given the prevalence of cancer, there is a critical need for examination of the impact of managing multiple symptoms, particularly those that cluster with fatigue, on informal carers.

Objectives
To (1) examine clustering of patient fatigue-related symptom severity and distress in individuals with cancer and (2) test the hypothesis that patient fatigue-related symptom clusters (severity, distress) will be positively associated with carer depressive symptoms.

Methods
Secondary analysis of 689 hospice patient/informal carer dyads using exploratory factor analysis and structural equation modeling. Patient symptoms were measured by the Memorial Symptom Assessment Scale, and carer depressive symptoms were measured by the Center for Epidemiological Study–Depression Scale.

Results
Patients were 73 (SD, 12) years old, and 43% were female. Carers were 65 years (SD, 14) years old, and 74% were female. For symptom severity, dyspnea, dry mouth, lack of appetite, drowsiness, cough, dizziness, and difficulty swallowing clustered with fatigue. For symptom distress, dyspnea, cough, and dry mouth clustered with fatigue. Structural equation modeling results indicated that the patient fatigue severity cluster was positively related to carer depressive symptoms (b = 0.12, P < .05), but distress was not.

Conclusion
Managing multiple symptoms that cluster with fatigue negatively impacts informal carers.

Implications for Practice
When patients complain of severe fatigue, clinicians need to explore all causes and ask about other symptoms while exploring whether the informal carer is feeling burdened or depressed.
“I Am Sure That They Use My PROM Data for Something Important.” A Qualitative Study About Patients’ Experiences From a Hematologic Outpatient Clinic
Authors: Thestrup Hansen Stine , Kjerholt Mette , Friis Christensen Sarah , Brodersen John , Hølge-Hazelton Bibi 
Published: July 2019

Background
Patient-reported outcome measures (PROMs) in clinical practice have the potential to contribute to and support shared decision-making processes by giving voice to patient concerns during consultations. However, the perspectives of patients diagnosed with chronic hematologic cancer on the use of PROMs are unknown.

Objective
To describe how patients diagnosed with hematologic cancer experience participating in a randomized PROM intervention study, including initial invitation, completion of questionnaires, and outpatient clinic visits.

Methods
A qualitative conceptual framework guided the study, using Interpretive Description with a focused ethnographic approach to explore patient experiences with PROMs in applied practice. Analysis was inspired by Habermas’ social theory of communicative action.

Results
The analysis revealed 3 predominant themes of patient experiences: that PROMs were “In the service of a good cause,” “The questions are not really spot on,” and “PROMs are sometimes used for something,” that is, unknown to the patient.

Conclusions
The patients’ experiences were dominated by the perspective of the healthcare system and by gratitude and imbalanced power relations. During completion of questionnaires, patients struggled to identify with items, and the questionnaires were associated with low content validity. When visiting the outpatient clinic, patients reported that doctors and nurses rarely discussed patients’ PROMs.

Implications for Practice
This study contributes knowledge of patient experiences of the integration of PROMs in hematologic outpatient clinical practice. Findings can guide further research and improve future implementation of PROMs.
4-Phenylbutyrate Prevents Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Heatstroke in the Intestines of Mice
Authors: Cao Yan , Liu Zhifeng , Xiao Weiwei , Gu Zhengtao , Xiao Guizhen , Yuan Fangfang , Chen Fang , Pei Yanfang , Li Hui , Su Lei 
Published: July 2019

ABSTRACT

Objective:
Heatstroke can induce serious physiological dysfunction in the intestine. However, the underlying mechanisms of this condition are unknown, and therapeutic strategies are not available. In this study, we explored the role of endoplasmic reticulum (ER) stress signaling in this process and assessed whether pretreating mice with an inhibitor of ER stress could alleviate intestinal damage.

Methods:
A heatstroke model was established in male mice. Mice were pretreated with 4-phenylbutyrate (4-PBA) before exposure to heat stress. Intestinal morphological changes were observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy. The TUNEL assay was used to detect intestinal apoptosis. The expression of the ER stress-related proteins and apoptosis-related proteins was investigated by the Western blot assay.

Results:
Compared with control group, mice with heatstroke exhibited evidence of intestinal injury and epithelial apoptosis, accompanied by significantly increased expression of ER stress-related proteins in the intestines. The intestinal injury score and level of intestinal epithelial apoptosis were significantly reduced after administration of 4-PBA. Furthermore, the levels of the intestinal ER stress-related proteins GRP78, PERK, p-eIF2α, ATF4, and CHOP were decreased after 4-PBA treatment.

Conclusions:
Our results indicate that the ER stress-mediated apoptosis pathway is activated during heat stress-induced intestinal injury. 4-PBA can inhibit heatstroke-induced intestinal ER stress and attenuate intestinal injury. We provide evidence that the beneficial effect of 4-PBA is closely related to the inhibition of ER stress-mediated apoptosis. These findings suggest that ER stress may be a novel therapeutic target in patients with heatstroke.
Epidemiology of amyotrophic lateral sclerosis: an update of recent literature
Authors: Longinetti Elisa , Fang Fang 
Published: July 2019

Purpose of review
The cause of amyotrophic lateral sclerosis (ALS) remains unknown for most of the patients with the disease. Epidemiologic studies can help describe disease burden and examine its potential risk factors, providing thereby evidence base for future mechanistic studies. With this review, we aimed to provide a summary of epidemiologic studies published during the past 18 months, which studied the incidence and risk factors for ALS.

Recent findings
An increasing incidence and prevalence of ALS continue to be reported from different parts of the world. Several previously studied risk factors are confirmed as causally related to ALS by Mendelian randomization analysis. The previously known prognostic indicators for ALS appear to be the same across populations.

Summary
Provided with the increasing number of patients diagnosed with ALS and the improved societal awareness of the disease, more resources should be allocated to the research and care of ALS. Population-based studies, especially population-based disease registers, should be the priorities in ALS research, and more data from outside Europe are needed in gaining a better global perspective of the disease.
The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies
Authors: Vanhaesebrouck An E. , Beeson David 
Published: July 2019

Purpose of review
Congenital myasthenic syndromes (CMS) are a group of heterogeneous inherited disorders caused by mutations in genes encoding proteins whose function is essential for the integrity of neuromuscular transmission. This review updates the reader on the expanding phenotypic spectrum and suggested improved treatment strategies.

Recent findings
As next-generation sequencing is taken into the clinic, its use is both continuing to unearth new causative genes in which mutations underlie CMS and also broadening the phenotypic spectrum for known CMS genes. The number of genes in which mutations may cause neuromuscular transmission defects has now passed 30. The defective transmission may be part of an overall more complex phenotype in which there may be muscle, central nervous system or other involvement. Notably, mutations in series of genes encoding proteins located in the presynatic motor bouton have been identified. Rare cases of mutations in basal laminar proteins of the synaptic cleft are coming to light and additional mutations/phenotypic features have been located in some of the larger neuromuscular junction proteins such as AGRN and MUSK, where previously mutation screening by sanger sequencing was time consuming and costly. Finally, there are more reports of the beneficial effects of treatment with β2-adrenergic receptor agonists in patients, and the study of their action in disease models.

Summary
Recent studies of the CMS illustrate the increasing complexity of the genetics and pathophysiological mechanisms involved. With therapy tailored for the underlying disease mechanism treatment, although incomplete, is usually life-transforming. However, treatment for newly identified conditions in which myasthenia is only one component within complex multisystem disorder will prove challenging.
Anti-consensus: detecting trees that have an evolutionary signal that is lost in consensus
Authors: Huson Daniel H. , Albrecht Benjamin , Patz Sascha , Steel Mike 
Published: July 2019

AbstractIn phylogenetics, a set of gene trees is often summarized by a consensus tree, such as the majority consensus, which is based on the set of all splits that are present in more than 50% of the input trees. A “consensus network” is obtained by lowering the threshold and considering all splits that are contained in 10% of the trees, say, and then computing the corresponding splits network. By construction and in practice, a consensus network usually shows the majority tree, extended by a number of rectangles that represent local rearrangements around internal nodes of the consensus tree. This may lead to the false conclusion that the input trees do not differ in a significant way because “even a phylogenetic network” does not display any large discrepancies. To harness the full potential of a phylogenetic network, we introduce the new concept of an anti-consensus network that aims at representing the largest interesting discrepancies found in a set of gene trees. We provide an efficient algorithm for computing an anti-consensus and illustrate its application using a set of gene trees from species and strains in the genus Kosakonia.
A dynamic role for dopamine receptors in the control of mammalian spinal networks
Authors: Sharples Simon A. , Burma Nicole E. , Borowska-Fielding Joanna , Kwok Charlie H.T. , Eaton Shane E.A. , Baker Glen B. , Jean-Xavier Celine , Zhang Ying , Trang Tuan , Whelan Patrick J. 
Published: July 2019

AbstractDopamine is well known to regulate movement through the differential control of direct and indirect pathways in the striatum that express D1 and D2 receptors respectively. The spinal cord also expresses all dopamine receptors however; how the specific receptors regulate spinal network output in mammals is poorly understood. We explore the receptor-specific mechanisms that underlie dopaminergic control of spinal network output of neonatal mice during changes in spinal network excitability. During spontaneous activity, which is a characteristic of developing spinal networks operating in a low excitability state, we found that dopamine is primarily inhibitory. We uncover an excitatory D1-mediated effect of dopamine on motoneurons and network output that also involves co-activation with D2 receptors. Critically, these excitatory actions require higher concentrations of dopamine; however, analysis of dopamine concentrations of neonates indicates that endogenous levels of spinal dopamine are low. Because endogenous levels of spinal dopamine are low, this excitatory dopaminergic pathway is likely physiologically-silent at this stage in development. In contrast, the inhibitory effect of dopamine, at low physiological concentrations is mediated by parallel activation of D2, D3, D4 and α2 receptors which is reproduced when endogenous dopamine levels are increased by blocking dopamine reuptake and metabolism. We provide evidence in support of dedicated spinal network components that are controlled by excitatory D1 and inhibitory D2 receptors that is reminiscent of the classic dopaminergic indirect and direct pathway within the striatum. These results indicate that network state is an important factor that dictates receptor-specific and therefore dose-dependent control of neuromodulators on spinal network output and advances our understanding of how neuromodulators regulate neural networks under dynamically changing excitability.Significance statementMonoaminergic neuromodulation of neural networks is dependent not only on target receptors but also on network state. We studied the concentration-dependent control of spinal networks of the neonatal mouse, in vitro, during a low excitability state characterized by spontaneous network activity. Spontaneous activity is an essential element for the development of networks. Under these conditions, we defined converging receptor and cellular mechanisms that contribute to the diverse, concentration-dependent control of spinal motor networks by dopamine, in vitro. These experiments advance understanding of how monoamines modulate neuronal networks under dynamically changing excitability conditions and provide evidence of dedicated D1 and D2 regulated network components in the spinal cord that are consistent with those reported in the striatum.
Characterization of a Y-specific duplication/insertion of the anti-Mullerian hormone type II receptor gene based on a chromosome-scale genome assembly of yellow perch, Perca flavescens
Authors: Feron Romain , Zahm Margot , Cabau Cédric , Klopp Christophe , Roques Céline , Bouchez Olivier , Eché Camille , Valière Sophie , Donnadieu Cécile , Haffray Pierrick , Bestin Anastasia , Morvezen Romain , Acloque Hervé , Euclide Peter T. , Wen Ming , Jouano Elodie , Schartl Manfred , Postlethwait John H. , Schraidt Claire , Christie Mark R. , Larson Wes , Herpin Amaury , Guiguen Yann 
Published: July 2019

ABSTRACTBackgroundYellow perch, Perca flavescens, is an ecologically and commercially important species native to a large portion of the northern United States and southern Canada. It is also a promising candidate species for aquaculture. No yellow perch reference genome, however, has been available to facilitate improvements in both fisheries and aquaculture management practices.FindingsBy combining Oxford Nanopore Technologies long-reads, 10X genomics Illumina short linked reads and a chromosome contact map produced with Hi-C, we generated a high-continuity chromosome scale yellow perch genome assembly of 877.4 Mb. It contains, in agreement with the known diploid chromosome yellow perch count, 24 chromosome-size scaffolds covering 98.8% of the complete assembly (N50 = 37.4 Mb, L50 = 11). Genome annotation identified 41.7% (366 Mb) of repeated elements and 24,486 genes including 16,579 genes (76.3%) significantly matching with proteins in public databases. We also provide a first characterization of the yellow perch sex determination locus that contains a male-specific duplicate of the anti-Mullerian hormone type II receptor gene (amhr2by) inserted at the proximal end of the Y chromosome (chromosome 9). Using this sex-specific information, we developed a simple PCR genotyping test which accurately differentiates XY genetic males (amhr2by+) from XX genetic females (amhr2by−).ConclusionsOur high-quality genome assembly is an important genomic resource for future studies on yellow perch ecology, toxicology, fisheries, and aquaculture research. In addition, the characterization of the amhr2by gene as a candidate sex determining gene in yellow perch provides a new example of the recurrent implication of the transforming growth factor beta pathway in fish sex determination, and highlights gene duplication as an important genomic mechanism for the emergence of new master sex determination genes.
Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders
Authors: Barkhuizen Wikus , Pain Oliver , Dudbridge Frank , Ronald Angelica 
Published: July 2019

AbstractBackgroundThis study explores the degree to which genetic influences on psychotic experiences are stable across adolescence and adulthood, and their overlap with psychiatric disorders.MethodsGenome-wide association results were obtained for adolescent psychotic experiences and negative symptom traits (N = 6,297-10,098), schizotypy (N = 3,967-4,057) and positive psychotic experiences in adulthood (N = 116,787-117,794), schizophrenia (N = 150,064), bipolar disorder (N = 41,653) and depression (N = 173,005). Linkage disequilibrium score regression was used to estimate genetic correlations. Implicated genes from functional and gene-based analyses were compared. Mendelian Randomization was performed on trait pairs with significant genetic correlations.ResultsSubclinical auditory and visual hallucinations and believing in conspiracies during adulthood were significantly genetically correlated with schizophrenia (rg = .27-.67) and major depression (rg = .41-.96) after correction for multiple testing. Auditory and visual subclinical hallucinations were highly genetically correlated (rg = .95). Cross-age genetic correlations for psychotic experiences were not significant. Gene mapping and gene association analyses revealed 14 possible genes associated with psychotic experiences that overlapped across age for psychotic experiences or between psychotic experiences and psychiatric disorders. Mendelian Randomization indicated bidirectional associations between auditory and visual hallucinations in adults but did not support causal relationships between psychotic experiences and psychiatric disorders.ConclusionsPsychotic experiences in adulthood may be more linked genetically to schizophrenia and major depression than psychotic experiences in adolescence. Our study implicated specific genes that are associated with psychotic experiences across development as well as genes shared between psychotic experiences and psychiatric disorders.
The glycine locating at random coil of picornaviruses VP3 enhances viral pathogenicity by targeting p53 to promote apoptosis and autophagy
Authors: Mao Ruoqing , Yang Fan , Sun Dehui , Zhou Xiaoli , Zhu Zixiang , Guo Xuan , Liu Huanan , Tian Hong , Zhang Keshan , Dang Wen , Wu Qingfeng , Ma Xinwen , Liu Xiangtao , Zheng Haixue 
Published: July 2019

AbstractPicornaviruses, comprising important and widespread pathogens of humans and animals, have evolved to control apoptosis and autophagy for their replication and spread. However, the underlying mechanism of the association between apoptosis/autophage and viral pathogenicity remains unclear. In the present study, VP3 of picornaviruses was demonstrated to induce apoptosis and autophagy. Foot-and-mouth disease virus (FMDV), which served as a research model here, can strongly induce both apoptosis and autophagy in the skin lesions. By directly interacting with p53, FMDV-VP3 facilitates its phosphorylation and translocation, resulting in Bcl-2 family-mediated apoptosis and LC3-dependent autophagy. The single residue Gly129 of FMDV-VP3 plays a crucial role in apoptosis and autophagy induction and the interaction with p53. Consistently, the comparison of rescued FMDV with mutated Gly129 and parental virus showed that the Gly129 is indispensable for viral replication and pathogenicity. More importantly, the Gly129 locates at a bend region of random coil structure, the mutation of Gly to Ala remarkably shrunk the volume of viral cavity. Coincidentally, the Gly is conserved in the similarly location of other picornaviruses, including poliovirus (PV), enterovirus 71 (EV71), coxsackievirus (CV) and seneca valley virus (SVA). This study demonstrates that picornaviruses induce apoptosis and autophagy to facilitate its pathogenicity and the Gly is functional site, providing novel insights into picornavirus biology.