bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac proteomics reveals the potential mechanism of microtubule associated protein 4 phosphorylation-induced mitochondrial dysfunction
Authors: Li Lingfei , Zhang Junhui , Zhang Qiong , Huang Yuesheng , Hu Jiongyu 
Published: March 2019

Abstract

Background
Our previous work suggested that microtubule associated protein 4 (MAP4) phosphorylation led to mitochondrial dysfunction in MAP4 phosphorylation mutant mice with cardiomyopathy, but the detailed mechanism was still unknown. Thus, the aim of this study was to investigate the potential mechanism involved in mitochondrial dysfunction responsible for cardiomyopathy.

Methods
The present study was conducted to explore the potential mechanism underlying the mitochondrial dysfunction driven by MAP4 phosphorylation. Strain of mouse that mimicked constant MAP4 phosphorylation (S737 and S760) was generated. The isobaric tag for relative and absolute quantitation (iTRAQ) analysis was applied to the heart tissue. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) were all analyzed on the basis of differential expressed proteins (DEPs).

Results
Among the 72 cardiac DEPs detected between the two genotypes of mice, 12 were upregulated and 60 were downregulated. GO analysis showed the biological process, molecular function, and cellular component of DEPs, and KEGG enrichment analysis linked DEPs to 96 different biochemical pathways. In addition, the PPI network was also extended on the basis of DEPs as the seed proteins. Three proteins, including mitochondrial ubiquitin ligase activator of NF-κB 1, reduced form of nicotinamide adenine dinucleotide (NADH)-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial and growth arrest, and DNA-damage-inducible proteins-interacting protein 1, which play an important role in the regulation of mitochondrial function, may correlate with MAP4 phosphorylation-induced mitochondrial dysfunction. Western blot was used to validate the expression of the three proteins, which was consistent with iTRAQ experiments.

Conclusions
These findings revealed that the DEPs caused by MAP4 phosphorylation in heart tissue using iTRAQ technique and may provide clues to uncover the potential mechanism of MAP4 phosphorylation-induced mitochondrial dysfunction.
DICER1 Mutations in the Era of Expanding Integrative Clinical Sequencing in Pediatric Oncology
Authors: Bailey Kelly M. , Jacobs Michelle F. , Anderson Bailey , Rabah Raja , Wu Yi-Mi , Else Tobias , Mody Rajen J. 
Published: March 2019

PURPOSE DICER1 syndrome is a recently described inherited cancer predisposition syndrome caused by pathogenic variants in DICER1. With the recent increase in integrative clinical sequencing for pediatric patients with cancer, our understanding of the DICER1 syndrome continues to evolve, as new and rare pathogenic variants are reported. As the frequency of integrative clinical sequencing increases, discussions regarding challenges encountered in the interpretation of sequencing results are essential to continue to advance the field of cancer predisposition. The purpose of this work was to identify patients with somatic and/or germline DICER1 variants in our patient population and to discuss sequencing interpretation and the clinical recommendations that result from the integrative clinical sequencing results. METHODS Patients were enrolled in the PEDS-MIONCOSEQ study. This integrative clinical sequencing study includes paired tumor/normal whole-exome sequencing and tumor transcriptome sequencing. Patients identified as having DICER1 variants were included. RESULTS We report a DICER1 variant of unknown clinical significance in a patient with a highly unusual response to therapy. Two patients had diagnoses clarified once the integrative clinical sequencing revealing a DICER1 variant was available. We also discovered a patient with low-level DICER1 mosaicism and the challenges encountered in the sequencing interpretation for this patient. In addition to the sequencing data and result interpretation, this work also highlights testing and screening recommendations made to patients with DICER1 variants and their families on the basis of these results. CONCLUSION This work serves to extend the DICER1 phenotype and advance the utility of clinical integrative sequencing in the fields of pediatric oncology and cancer genetic predisposition.
Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History
Authors: Dwyer Andrew A , Chavan Niraj R , Lewkowitz-Shpuntoff Hilana , Plummer Lacey , Hayes Frances J , Seminara Stephanie B , Crowley William F , Pitteloud Nelly , Balasubramanian Ravikumar 
Published: March 2019

AbstractContextAfter completion of puberty a subset of men experience functional hypogonadotropic hypogonadism (FHH) secondary to excessive exercise or weight loss. This phenomenon is akin to hypothalamic amenorrhea (HA) in women, yet little is known about FHH in men.ObjectiveTo investigate the neuroendocrine mechanisms, genetics, and natural history underlying FHH.DesignRetrospective study in an academic medical center.ParticipantsHealthy postpubertal men presenting with symptoms of hypogonadism in the setting of excessive exercise (>10 hours/week) or weight loss (>10% of body weight). Healthy age-matched men served as controls.InterventionsClinical assessment, biochemical and neuroendocrine profiling, body composition, semen analysis, and genetic evaluation of genes known to cause isolated GnRH deficiency.Main Outcome MeasuresReproductive hormone levels, endogenous GnRH-induced LH pulse patterns, and rare genetic variants.ResultsTen men with FHH were compared with 18 age-matched controls. Patients had significantly lower body mass index, testosterone, LH, and mean LH pulse amplitudes yet normal LH pulse frequency, serum FSH, and sperm counts. Some patients exhibited nocturnal, sleep-entrained LH pulses characteristic of early puberty, and one FHH subject showed a completely apulsatile LH secretion. After decreased exercise and weight gain, five men with men had normalized serum testosterone levels, and symptoms resolved. Rare missense variants in NSMF (n = 1) and CHD7 (n = 1) were identified in two men with FHH.ConclusionsFHH is a rare, reversible form of male GnRH deficiency. LH pulse patterns in male FHH are similar to those observed in women with HA. This study expands the spectrum of GnRH deficiency disorders in men.
Repúdio aos “súditos do eixo”: legalização dos campos de concentração na Era Vargas
Authors: Covolan Fernanda Cristina , Almeida Melissa Pinheiro 
Published: March 2019

Esta pesquisa dedicou-se ao estudo dos campos de concentração brasileiros na Era Vargas e do sistema legal que o amparou, para compreender de que maneira tais institutos se organizaram e encontraram legitimação no país. Inicialmente, buscou-se compreender o contexto histórico e os primeiros campos brasileiros, organizados para conter a migração em uma época de seca, para serem incrementados a partir da mudança de postura do governo Vargas diante dos imigrantes, que deveriam, então, ser nacionalizados. Na sequência, viu-se que o confi namento de italianos, alemães e japoneses, ou seus descendentes, nos campos de concentração, atendia não apenas às pretensões varguistas para o Estado nacional, mas também agradava aos parceiros internacionais na guerra, em especial os Estados Unidos. Por fim, esta pesquisa demonstrou como a ditadura iniciada em 1937 com o Estado Novo, em especial com a Constituição outorgada de 1937, deu subsídios jurídicos para a centralização de poder nas mãos do presidente, que governaria por meio de decretos até sua deposição. Uma vez que o país entrou em guerra ao lado dos Aliados, ocorreu a decretação do estado de guerra que derrubou direitos constitucionais antes garantidos aos estrangeiros e permitiu que estes fossem perseguidos e internados em campos de concentração.
Responsabilização na Lei Anticorrupção: natureza e amplitude subjetiva
Authors: Silva Cristiana Maria Fortini Pinto e , Dadalto Lucas Dutra 
Published: March 2019

O presente artigo busca abordar a questão da responsabilização na Lei nº 12.846/2013, também chamada de Lei Anticorrupção, a partir da defi nição de sua natureza jurídica e da delimitação de sua amplitude subjetiva. Antes disso, far-se-á rápida digressão para explanar o tema da Corrupção a partir de suas raízes históricas, demonstrando sua presença, desde os primórdios da colonização brasileira até os dias atuais. Destaca-se, assim, o liame temporal que acabou por desembocar na edição da Lei Anticorrupção como uma forma de completar o sistema legal pátrio de defesa da moralidade. No núcleo do artigo, questiona-se se a amplitude da referida lei também abarcaria a responsabilização das pessoas físicas responsáveis pelos atos lesivos defi nidos neste diploma ou se esta lei se restringiria apenas à responsabilização das pessoas jurídicas. Procura-se delimitar de forma mais objetiva os sujeitos ativos e passivos abarcados pela Lei Anticorrupção e como as sanções previstas se amoldam às especificidades de cada caso. Tudo isso visa a favorecer sua aplicação racional, sempre em homenagem ao princípio da segurança jurídica.
Typology, technical efficiency and scale economy of dibiteries in Dakar, Senegal
Authors: Orou Seko Malik , Ossebi Walter , Traoré Gnamien Sylvain , Ndour Andrée Prisca Ndjoug , Saric Jasmina , Fokou Gilbert , Dao Daouda , Bonfoh Bassirou 
Published: March 2019

Background: In recent years, a profound transformation has been observed in the eating habits of the populations of African cities, induced by accelerated socioeconomic and demographic growth. In Senegal, these changes have manifested in the proliferation of collective informal catering enterprises, such as the ‘dibiteries’, where the roasted meat of sheep is prepared and sold. The rise of the average household income has contributed substantially to increasing levels of meat consumption, leading to the expansion of the dibiteries. The purpose of the current work was to evaluate the managerial performance of these establishments in Dakar, Senegal. Methods: To achieve this, a cross-sectional study was conducted among 163 dibiteries using a questionnaire. Efficiency scores were determined via the data envelopment analysis method. The pure technical scores thereby obtained were subsequently used as dependent variables in a Tobit model to identify the socioeconomic determinants of dibiterie efficiency. Results: The resulting average score of the dibiteries suggests that the majority are operating inefficiently (79.6%). Moreover, it was demonstrated that this inefficiency seems to be related to scale rather than technical issues. However, few of the dibiteries assessed (20.4%) were nevertheless in a situation of constant scale economy. Among the socioeconomic variables tested, experience, leadership (family or individual-run), the ownership status of the restaurant building (own or lease) and the type of workforce (family, recruited, mixed or without) had a significant impact on the efficiency of the establishments. Conclusions: The scale economy and waste reduction in food production can result in economic gains that can in turn be used in the safety of finished products. Indeed, by following best practices, dibiteries can make gains which could be used to invest in good hygiene practices on handwashing, cleaning and disinfecting grilling tools, optimizing work space and training staff.
EpiLog: A software for the logical modelling of epithelial dynamics
Authors: Varela Pedro L. , Ramos Camila V. , Monteiro Pedro T. , Chaouiya Claudine 
Published: March 2019

Cellular responses are governed by regulatory networks subject to external signals from surrounding cells and to other micro-environmental cues. The logical (Boolean or multi-valued) framework proved well suited to study such processes at the cellular level, by specifying qualitative models of involved signalling pathways and gene regulatory networks. Here, we describe and illustrate the main features of EpiLog, a computational tool that implements an extension of the logical framework to the tissue level. EpiLog defines a collection of hexagonal cells over a 2D grid, which embodies a mono-layer epithelium. Basically, it defines a cellular automaton in which cell behaviours are driven by associated logical models subject to external signals. EpiLog is freely available on the web at http://epilog-tool.org. It is implemented in Java (version ≥1.7 required) and the source code is provided at https://github.com/epilog-tool/epilog under a GNU General Public License v3.0.
The nocebo effect as a source of bias in the assessment of treatment effects
Authors: Wartolowska Karolina 
Published: March 2019

The term nocebo effect refers to the harmful outcomes that result from people’s negative beliefs, anticipations, or experiences related to the treatment rather than the pharmacological properties of the treatment. These outcomes may include a worsening of symptoms, a lack of expected improvement, or adverse events, and they may occur after the active treatment and the placebo that is supposed to imitate it. The nocebo effect is always unwanted and may distort estimates of treatment effectiveness and safety; moreover, it may cause discontinuation of therapy or withdrawal from a trial. The nocebo effect may be unintentionally evoked by the explanations given by healthcare professionals during a clinical consultation or consent procedures, or by information from other patients, the media, or the Internet. Moreover, it may be a consequence of previous bad experiences with the treatment, through learning and conditioning, and the conditioning may happen without patients’ conscious awareness. In trial settings, a study design, for example lack of blinding, may introduce bias from the nocebo effect. Unlike the placebo effect, which is usually taken into consideration while interpreting treatment outcomes and controlled for in clinical trials, the nocebo effect is under-recognised by clinical researchers and clinicians. This is worrying, because the nocebo phenomenon is common and may have potentially negative consequences for the results of clinical treatment and trials. It is therefore important that doctors and medical researchers consider any potential nocebo effect while assessing the treatment effect and try to minimise it through careful choice and phrasing of treatment-related information given to patients.
Causes of death among homeless people: a population-based cross-sectional study of linked hospitalisation and mortality data in England.
Authors: Aldridge Robert W , Menezes Dee , Lewer Dan , Cornes Michelle , Evans Hannah , Blackburn Ruth M , Byng Richard , Clark Michael , Denaxas Spiros , Fuller James , Hewett Nigel , Kilmister Alan , Luchenski Serena , Manthorpe Jill , McKee Martin , Neale Joanne , Story Alistair , Tinelli Michela , Whiteford Martin , Wurie Fatima , Hayward Andrew 
Published: March 2019

Background: Homelessness has increased by 165% since 2010 in England, with evidence from many settings that those affected experience high levels of mortality. In this paper we examine the contribution of different causes of death to overall mortality in homeless people recently admitted to hospitals in England with specialist integrated homeless health and care (SIHHC) schemes. Methods: We undertook an analysis of linked hospital admission records and mortality data for people attending any one of 17 SIHHC schemes between 1st November 2013 and 30th November 2016. Our primary outcome was death, which we analysed in subgroups of 10th version international classification of disease (ICD-10) specific deaths; and deaths from amenable causes. We compared our results to a sample of people living in areas of high social deprivation (IMD5 group).Results: We collected data on 3,882 individual homeless hospital admissions that were linked to 600 deaths. The median age of death was 51.6 years (interquartile range 42.7-60.2) for SIHHC and 71.5 for the IMD5 (60.67-79.0). The top three underlying causes of death by ICD-10 chapter in the SIHHC group were external causes of death (21.7%; 130/600), cancer (19.0%; 114/600) and digestive disease (19.0%; 114/600). The percentage of deaths due to an amenable cause after age and sex weighting was 30.2% in the homeless SIHHC group (181/600) compared to 23.0% in the IMD5 group (578/2,512).Conclusion: Nearly one in three homeless deaths were due to causes amenable to timely and effective health care. The high burden of amenable deaths highlights the extreme health harms of homelessness and the need for greater emphasis on prevention of homelessness and early healthcare interventions.
Is the laparoscopic approach a safe choice for the management of acute appendicitis in pregnant women? A meta-analysis of observational studies
Authors: Frountzas M , Nikolaou C , Stergios K , Kontzoglou K , Toutouzas K , Pergialiotis V 
Published: March 2019

Introduction Acute appendicitis is a common and serious situation during pregnancy, because of the increased risk of fetal loss and perforation in the third trimester, as well as a diagnostic difficulty. During recent years laparoscopic approach has been introduced to clinical practice with encouraging results. The purpose of this meta-analysis is to compare the surgical and obstetrical outcomes between laparoscopic and open appendectomy during pregnancy. Materials and methods MEDLINE, SCOPUS, Clinicaltrials.gov, CENTRAL and Google Scholar were searched for studies reporting on postoperative outcomes between laparoscopic and open appendectomy during pregnancy. The random effects model (DerSimonian–Laird) was used to calculate pooled effect estimates when high heterogeneity was encountered, otherwise the fixed-effects (Mantel–Haenszel) model was implemented. Results Twenty-one studies that enrolled 6276 pregnant women are included in the present meta-analysis. Of these women, 1963 underwent laparoscopic appendectomy and 4313 underwent an open appendectomy. Women who underwent laparoscopic appendectomy demonstrated an increase in fetal loss risk, while neonates of women that underwent open appendectomy presented decreased Apgar score at five minutes after birth. All the rest outcomes were similar between the two groups. The time that each study took place seemed to affect the comparison of birth weight and postoperative hospital stay between the two groups. Conclusion Laparoscopic appendectomy seems to be a relatively safe therapeutic option in pregnancy when it is indicated. Thus, it should be implemented in clinical practice, always considering the experience of the surgeon in such procedures. Nevertheless, the need of new studies to enhance this statement remains crucial.
Necrotising fasciitis in the North East of Scotland: a 10-year retrospective review
Authors: Neilly DW , Smith M , Woo A , Bateman V , Stevenson I 
Published: March 2019

Introduction Necrotising fasciitis is a life-threatening rapidly progressing bacterial infection of the skin requiring prompt diagnosis and treatment. Optimum care warrants a combination of surgical debridement, antibiotics and intensive care support. All cases of necrotising fasciitis in 10 years in the North East of Scotland were reviewed to investigate and improve patient care. Methods Cases between August 2006 and February 2016 were reviewed using case notes and electronic hospital records. Data including mode of admission, clinical observations, investigations, operative interventions, microbiological and clinical outcomes was collected and reviewed. Analysis required multidisciplinary input including microbiology, infectious disease, trauma and orthopaedics, plastic surgery and intensive care teams. Results A total of 36 cases were identified. The mean laboratory risk indicator for necrotising fasciitis (LRINEC) score was 7 and 86% of patients fulfilled the criteria for necrotising fasciitis. Patients were commonly haemodynamically stable upon admission but deteriorated rapidly; 36% of patients had a temperature of over 37.5 degrees C on initial observations; 29/36 patients were discharged, 6 patients died acutely (acute mortality rate of 17%); 18/31 of cases were polymicrobial with Streptococcus pyogenes, the common organism. Six amputations or disarticulations were performed from a total of 82 operations in this group, with radical debridement the usual primary operation. The mean time to theatre was 3.54 hours. Highly elevated admission respiratory rate (50 breaths/minute) was associated with increased mortality. Conclusions Necrotising fasciitis presents subtly and carries significant morbidity and mortality. A high index of suspicion allows early diagnosis and intervention. We believe that a pan-specialty approach is the cornerstone for good outcomes.
Systematic review and meta-analysis on outcomes of salvage therapy in patients with tumour recurrence during ‘watch and wait’ in rectal cancer
Authors: On J , Shim J , Aly EH 
Published: March 2019

Introduction The ‘watch and wait’ approach has recently emerged as an alternative approach for managing patients with complete clinical response in rectal cancer. However, less is understood whether the intervention is associated with a favourable outcome among patients who require salvage therapy following local recurrence. Materials and methods A comprehensive systematic search was performed using EMBASE, PubMed, MEDLINE, Journals@Ovid as well as hand searches; published between 2004 and 2018, to identify studies where outcomes of patients undergoing watch and wait were compared with conventional surgery. Study quality was assessed using the Newcastle–Ottawa assessment scale. The main outcome was relative risks for overall and disease specific mortality in salvage therapy. Results Nine eligible studies were included in the meta-analysis. Of 248 patients who followed the watch and wait strategy, 10.5% had salvage therapy for recurrent disease. No statistical heterogeneity was found in the results. The relative risk of overall mortality in the salvage therapy group was 2.42 (95% confidence interval 0.96–6.13) compared with the group who had conventional surgery, but this was not statistically significant (P > 0.05). The relative risk of disease specific mortality in salvage therapy was 2.63 (95% confidence interval 0.81–8.53). Conclusion Our findings demonstrated that there was no significant difference in overall and disease specific mortality in patients who had salvage treatment following recurrence of disease in the watch and wait group compared with the standard treatment group. However, future research into the oncological safety of salvage treatment is needed.
Malakoplakia of the parotid gland: a case report and review of localised malakoplakia of the head and neck
Authors: Samian C , Ghaffar S , Nandapalan V , Santosh S 
Published: March 2019

Introduction Malakoplakia is a rare chronic inflammatory disorder, predominantly affecting the urinary tract. In the head and neck region, it is very rare and may confuse the clinicians during investigations, as features may mimic malignancy. Materials and methods We report a case of malakoplakia involving the parotid gland and review of the reported cases of malakoplakia in head and neck region. Results Histologically, this is the first classic case report of malakoplakia involving the parotid gland in the world literature. A total of 49 cases have been reported in the head and neck region; 38.7% of these are cutaneous. In soft tissue, the tongue is the most common site. Salivary gland involvement is very rare. Previously, submandibular salivary gland involvement has been reported. Conclusion A possibility of malakoplakia should be considered as a differential diagnosis in patients with enlarged head and neck masses. Histology is essential to diagnose this benign inflammatory disorder and to differentiate from a malignant process.