bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sperm nuclear protamines: A checkpoint to control sperm chromatin quality
Authors: Steger Klaus , Balhorn Rod 
Published: May 2018

AbstractProtamines are nuclear proteins which are specifically expressed in haploid male germ cells. Their replacement of histones and binding to DNA is followed by chromatin hypercondensation that protects DNA from negative influences by environmental factors. Mammalian sperm contain two types of protamines: PRM1 and PRM2. While the proportion of the two protamines is highly variable between different species, abnormal ratios within a species are known to be associated with male subfertility. Therefore, it is more than likely that correct protamine expression represents a kind of chromatin checkpoint during sperm development rendering protamines as suitable biomarkers for the estimation of sperm quality. This review presents an overview of our current knowledge on protamines comparing gene and protein structures between different mammalian species with particular consideration given to man, mouse and stallion. At last, recent insights into the possible role of inherited sperm histones for early embryo development are provided.
Easy‐to‐use algorithm would provide faster diagnoses for mucopolysaccharidosis type I and enable patients to receive earlier treatment
Authors: Tylki‐Szymańska Anna , De Meirleir Linda , Di Rocco Maja , Fathalla Waseem M. , Guffon Nathalie , Lampe Christina , Lund Allan M. , Parini Rossella , Wijburg Frits A. , Zeman Jiri , Scarpa Maurizio 
Published: May 2018

AbstractAimThe aim of this study was to develop an algorithm to prompt early clinical suspicion of mucopolysaccharidosis type I (MPS I).MethodsAn international working group was established in 2016 that comprised 11 experts in paediatrics, rare diseases and inherited metabolic diseases. They reviewed real‐world clinical cases, selected key signs or symptoms based on their prevalence and specificity and reached consensus about the algorithm. The algorithm was retrospectively tested.ResultsAn algorithm was developed. In patients under two years of age, kyphosis or gibbus deformity were the key symptoms that raised clinical suspicion of MPS I and in those over two years they were kyphosis or gibbus deformity, or joint stiffness or contractures without inflammation. The algorithm was tested on 35 cases, comprising 16 Hurler, 10 Hurler–Scheie, and nine Scheie patients. Of these 35 cases, 32 (91%) – 16 Hurler, nine Hurler–Scheie and seven Scheie patients – would have been referred earlier if the algorithm had been used.ConclusionThe expert panel developed and tested an algorithm that helps raise clinical suspicion of MPS I and would lead to a more prompt final diagnosis and allow earlier treatment.
Transcriptomic rationale for synthetic lethality‐targeting ERCC1 and CDKN1A in chronic myelomonocytic leukaemia
Authors: Hurtado Ana M. , Luengo‐Gil Gines , Chen‐Liang Tzu H. , Amaral Fabio , Batta Kiran , Palomo Laura , Lumbreras Eva , Przychodzen Bartlomiej , Caparros Eva , Amigo Marıa L. , Dıez‐Campelo Maria , Zamora Lurdes , Salido Fierrez Eduardo J. , Maciejewski Jaroslaw P. , Ortuño Francisco J. , Vicente Vicente , del Canizo Marıa , Sole Francesc , Ferrer‐Marin Francisca , Wiseman Daniel H. , Jerez Andres 
Published: May 2018

SummaryDespite the absence of mutations in the DNA repair machinery in myeloid malignancies, the advent of high‐throughput sequencing and discovery of splicing and epigenetics defects in chronic myelomonocytic leukaemia (CMML) prompted us to revisit a pathogenic role for genes involved in DNA damage response. We screened for misregulated DNA repair genes by enhanced RNA‐sequencing on bone marrow from a discovery cohort of 27 CMML patients and 9 controls. We validated 4 differentially expressed candidates in CMML CD34+ bone marrow selected cells and in an independent cohort of 74 CMML patients, mutationally contextualized by targeted sequencing, and assessed their transcriptional behavior in 70 myelodysplastic syndrome, 66 acute myeloid leukaemia and 25 chronic myeloid leukaemia cases. We found BAP1 and PARP1 down‐regulation to be specific to CMML compared with other related disorders. Chromatin‐regulator mutated cases showed decreased BAP1 dosage. We validated a significant over‐expression of the double strand break‐fidelity genes CDKN1A and ERCC1, independent of promoter methylation and associated with chemorefractoriness. In addition, patients bearing mutations in the splicing component SRSF2 displayed numerous aberrant splicing events in DNA repair genes, with a quantitative predominance in the single strand break pathway. Our results highlight potential targets in this disease, which currently has few therapeutic options.
Breaking bad news to people with learning disabilities: A literature review
Authors: Brownrigg Sophie 
Published: May 2018

Accessible Summary

A literature review was undertaken to explore reasons why relatives, staff and healthcare professionals choose to tell or not tell people with learning disabilities bad news.

People with learning disabilities’ views on being told bad news are discussed.

The author looks at who should tell people with learning disabilities bad news.

The author found that relatives, staff and healthcare professionals have different reasons for telling and not telling people with learning disabilities bad news.

The author suggests talking about bad news is important.

AbstractBackgroundThis article provides a literature review exploring reasons for disclosure and nondisclosure of bad news to people with learning disabilities. Connections are made to current policy, law and ethics to highlight the complexity of this issue.MethodsThis review examines literature on disclosing bad news to people with learning disabilities from 2007 to 2017. A total of 13 articles were found with nine articles having a direct focus on breaking bad news.ResultsThe main themes identified from this review are maintaining rights and dignity, upholding duty of care, underestimating resilience, protection from harm and capacity to understand. Exploration of who should disclose is examined in reference to relatives, staff and healthcare professionals.ConclusionsTrends surrounding disclosure of diagnosis and prognosis to people with learning disabilities have not kept pace with the trend to disclose with the general population. People with learning disabilities are frequently not informed of their terminal diagnosis and often die without this knowledge. Equally, bad news concerning a friend or relative may also be withheld.
Spontaneous resting‐state gamma oscillations are not predictive of autistic traits in the general population
Authors: De Groot Kristel , Van Strien Jan W. 
Published: May 2018

AbstractThe autism spectrum hypothesis states that not only diagnosed individuals but also individuals from the general population exhibit a certain amount of autistic traits. While this idea is supported by neuroimaging studies, there have been few electrophysiological studies. In particular, there have been no spontaneous resting‐state studies yet. In order to examine the autism spectrum hypothesis, the present study tried to predict the level of autistic traits typically developing young adults (n = 93) exhibit from spontaneous resting‐state gamma power, a measure that has been linked to social functioning impairments seen in autism. The influence of age and gender was controlled for by employing regression. It was expected that enhanced gamma activity would be predictive of self‐reported autistic traits. The model with only age and gender included reached significance, with higher age within this student population being related to more autistic traits. However, no relationship between either low (30–50 Hz) or high (50–70 Hz) gamma power and autistic traits was found. Models with eyes closed low gamma asymmetry and eyes closed high gamma asymmetry included did reach significance, but these findings were not robust, and the gamma asymmetry explained very little additional variance above age and gender. In addition, exploratory correlation analyses showed no relationship between the other power spectra (delta, theta, alpha and beta) on the one hand and autistic traits on the other hand, suggesting that any relationship between spontaneous resting‐state brain electrophysiology and autistic traits might not be strong enough to be detected in the general population.
Challenging behaviours at early adulthood in autism spectrum disorders: topography, risk factors and evolution
Authors: Rattaz C. , Michelon C. , Munir K. , Baghdadli A. 
Published: May 2018

AbstractBackgroundChallenging behaviours are highly prevalent in children and adolescents with autism spectrum disorders (ASD), but little is known about the prevalence and course of these behaviours during adulthood. The aims of this study were to describe the topography of challenging behaviours in a cohort of 106 young adults with ASD and to identify the risk factors for challenging behaviours. Our secondary objective was to study the changes in challenging behaviours from adolescence to early adult years.MethodThe present study uses data from the EpiTED prospective follow‐up study in France. The presence of challenging behaviours was assessed by the Aberrant Behaviour Checklist (ABC) completed by parent informants. Several dimensions of behaviour were studied: irritability, stereotypy, lethargy, hyperactivity and self‐injury. Clinical variables were collected on ASD symptom severity, cognitive and language levels, adaptive behaviours and comorbid medical disorders.ResultsThe presence of challenging behaviours at early adulthood was related to the young adult's cognitive and language level, ASD symptom severity and comorbid gastrointestinal and sleep disorders. The main risk factor for challenging behaviours was ASD symptom severity. The level of language impairment was a significant predictor of self‐injury. Gastrointestinal disorders were a significant predictor of stereotypy. The change in behaviour topography from adolescence to early adult years corresponded with decreased parent report of hyperactivity, but no significant decrease in parent reports of irritability, stereotypy, lethargy and self‐injurious behaviours.ConclusionsThe challenging behaviours in individuals with ASD persist in early adulthood and are related to core symptom severity, levels of cognitive and language impairments and medical comorbidity. The results emphasise the importance of early interventions for children with ASD to target cognitive and language abilities and to alleviate the severity of ASD symptoms. They also underscore the need to enhance opportunities for individuals with ASD to better communicate discomforts and pain in the context of medical illness.
Cross‐Border Auction Cycle Effects of Sovereign Bond Issuance in the Euro Area
Authors: BEETSMA ROEL , GIULIODORI MASSIMO , HANSON JESPER , DE JONG FRANK 
Published: May 2018

AbstractWe provide evidence for the euro area of spillovers from foreign public debt auctions into domestic secondary‐market auction cycles. We also confirm existing evidence of such spillovers from domestic issues into the domestic secondary market. Consistent with a theory of primary dealers’ limited risk‐bearing capacity, we find that auction cycles from domestic issues are stronger during the recent crisis period, whereas cross‐border effects are stronger in the precrisis period, but this evidence is not strong. This finding likely reflects the opposing effects of reduced sovereign bond market integration during the crisis and higher yield covariances caused by more market volatility.
The prevalence and morphological characteristics of the knee anterolateral ligament in a Chinese population
Authors: Zhang Hua , Qiu Man , Xu Zhongwei , Wang Weilin , Chen Shiyang , Zhang Jian , Zhou Aiguo , Lu Kaihui , Huo Michael , Jiang Dianming 
Published: May 2018

AbstractThe anterolateral ligament, a distinct structure connecting the lateral femoral epicondyle to the anterolateral proximal tibia, is gaining attention because of its possible function in ensuring internal rotational stability of the tibia. To study the prevalence and precise anatomical characteristics of the anterolateral ligament and its relationship to adjacent structures in a Chinese population, a total of 20 amputated knee specimens were collected. The anterolateral regions of the knees underwent detailed surgical dissection, followed by precise measurement of the anterolateral ligament and its adjacent structures. Histological analysis of the anterolateral ligament was performed using hematoxylin and eosin (H&E) staining. A thin soft tissue deep to the iliotibial band running obliquely across the lateral fibula ligament and connecting the lateral head of the gastrocnemius with the tibia, termed the ‘gastrocnemius‐tibial ligament’ or superficial layer of the anterolateral ligament, was observed in 18 of the 20 specimens, corresponding to a prevalence of 90%. Furthermore, a well‐defined anterolateral ligament deep to the gastrocnemius‐tibial ligament and distinct from the lateral fibula ligament was found in all 20 knees (prevalence, 100%). The independent gastrocnemius‐tibial ligament and anterolateral ligament had separate femoral originations at the lateral head of the gastrocnemius and the lateral femoral epicondyle, and the same osseous tibial insertion at the midpoint between Gerdy's tubercle and the most lateral aspect of the fibular head. H&E staining showed that both the anterolateral ligament and gastrocnemius‐tibial ligament were ligaments consisting of collagenous bundles. In the Chinese Han population, the gastrocnemius‐tibial ligament and anterolateral ligament may form a complex at the anterolateral aspect of the knee, which is likely involved in ensuring the internal rotational stability of the tibia.
Compassion satisfaction, burnout and secondary traumatic stress among termination of pregnancy providers in two South African provinces
Authors: Teffo Mantshi E. , Levin Jonathan , Rispel Laetitia C. 
Published: May 2018

AbstractFocusing on compassion satisfaction, burnout and secondary traumatic stress (STS) among termination of pregnancy (TOP) providers, a cross ‐ sectional study was conducted among these providers in Gauteng and North West provinces of South Africa during 2014 and 2015. During 2014 and 2015, a cross‐sectional study was conducted among TOP service providers in Gauteng and North West provinces. Consented providers completed a self‐administered professional quality of life (PRoQOL) questionnaire, sociodemographic information and possible reasons for working as TOP providers. STATA 13 was used for data analysis. We recruited 105 TOP providers, obtaining 98% response rate. Participants mean age was 43.4 (standard deviation [SD] = 8.7), majority were nurses (70.9%), female (82%), married (47.6%) and 63% were working in hospitals. The overall mean score for compassion satisfaction was high at 42 (SD 5.5). Predictors of compassion satisfaction were finding work stimulating, belief in making a difference, enjoying relationships with other nurses and years of TOP service (P < 0.05). Province and gender were significant, with significant interaction. Burnout mean scores were average at 33 (SD = 4.0), with belief in helping women to make informed choices a marginally significant predictor of burnout. The overall STS mean score was average with a mean of 23 (SD = 6.8). Significant predictors of STS scores were finding work stimulating, belief in women's rights, belief in allowing informed choices, age and gender. Health policy makers and managers should endeavor to provide employee assistance programs that enhance compassion satisfaction and reduce burnout and STS among TOP providers.
Homonegativity in the Religious Dress History of the Marist Brothers, 1817–1840
Authors: Keenan William J.F. 
Published: May 2018

AbstractThis article presents a historical sociological case study of sexual oppression within the early nineteenth‐century foundation period of a French Roman Catholic male religious order, the Marist Brothers, founded in 1817. The different sexualities of two rival founder figures, the priests Jean‐Claude Courveille and Marcellin Champagnat, the former homosexual, the latter heterosexual, found expression in radically divergent conceptions of the religious habit. For Courveille, the costume design for the Brothers was ostentatious and stylish; for Champagnat, it was sober and clericalised. This archive‐based investigation shows how Courveille's sexual orientation led to his fall from grace within the Church and the suppression of his sartorial self‐expression. Champagnat, whose conventional dress rules prevailed, became a canonized saint. In the victory of the orthodox sacred dress code, the ideology of ‘clerical masculinism’ weaves its hegemonic power over the bodies of ‘men of the cloth’.
Serine/threonine protein phosphatase 5 is a potential therapeutic target in cholangiocarcinoma
Authors: Hu Ming‐Hung , Huang Tzu‐Ting , Chao Tzu‐I , Chen Li‐Ju , Chen Yen‐Lin , Tsai Ming‐Hsien , Liu Chun‐Yu , Kao Jia‐Horng , Chen Kuen‐Feng 
Published: May 2018

AbstractBackground & AimsFew molecules are currently verified to be actionable drug targets in cholangiocarcinoma (CCA). Serine/threonine protein phosphatase 5 (PP5) dysregulation is related to several malignancies. However, the role of PP5 in CCA is poorly defined.MethodsColony and tumorsphere formation assays were conducted to establish the role of PP5 in CCA tumorigenesis. Cantharidin (CTD) and norcantharidin (NCTD), both potent PP5 inhibitors, were used in in vitro and in vivo experiments to validate the potential therapeutic role of PP5.ResultsIncreased cell growth, colony formation and tumorsphere formation were observed in PP5‐overexpressing CCA cells, whereas PP5 knockdown by shRNA decreased cell growth and colony formation. Tumours from HuCCT1 xenograft‐bearing mice treated with PP5‐shRNA showed decreased growth and increased AMP‐activated protein kinase (AMPK) phosphorylation. Furthermore, CTD treatment decreased cell viability, reduced PP5 activity and enhanced AMPK phosphorylation in CCA cell lines. Overexpressing PP5 or enhancing PP5 activity suppressed AMPK phosphorylation and decreased CTD‐induced cell death. Suppressing p‐AMPK with siRNA or inhibitors also decreased CTD‐induced cell death, suggesting a pivotal role for PP5‐AMPK cascades in CCA. Immunoprecipitation revealed that PP5 interacted with AMPK. Importantly, treatment of HuCCT1 xenograft‐bearing mice with NCTD, a CTD analogue with a lower systemic toxicity in vivo, suppressed PP5 activity, increased p‐AMPK and reduced tumour volume.ConclusionsProtein phosphatase 5 negatively regulates AMPK phosphorylation and contributes to CCA aggressiveness; thus, PP5 may be a potential therapeutic target in CCA.
A combination of the on‐treatment FIB‐4 and alpha‐foetoprotein predicts clinical outcomes in cirrhotic patients receiving entecavir
Authors: Chiang Hung‐Hsien , Lee Chuan‐Mo , Hu Tsung‐Hui , Hung Chao‐Hung , Wang Jing‐Houng , Lu Sheng‐Nan , Lai Hsueh‐Chou , Su Wen‐Pang , Lin Chia‐Hsin , Peng Cheng‐Yuan , Chen Chien‐Hung 
Published: May 2018

AbstractBackground & AimsThis study investigates the long‐term incidences and predictors of developing hepatocellular carcinoma (HCC), cirrhotic events and mortality in cirrhotic patients receiving entecavir (ETV) therapy.MethodsWe enrolled 481 nucleos(t)ide analogue‐naïve chronic hepatitis B (CHB) patients who had compensated cirrhosis upon entry and had received ETV monotherapy for >12 months.ResultsThe 8‐year cumulative incidences of developing HCC, cirrhotic events and liver‐related mortality were 26.5%, 8.62% and 10.03% respectively. Multivariate analysis revealed that diabetic mellitus (DM), higher fibrosis‐4 (FIB‐4) and alpha‐foetoprotein (AFP) levels at 12 months of treatment, and FIB‐4 increase from baseline to 12 months were independent factors of HCC. FIB‐4 and AFP levels at 12 months of treatment were also independent factors of cirrhotic events and mortality. FIB‐4 cut‐off values of 3, 3 and 5 as well as AFP cut‐offs of 5, 5, and 9 ng/mL at 12 months of treatment were optimal for predicting HCC, cirrhotic events and mortality during therapy respectively. The FIB‐4 and AFP levels at 12 months of treatment were assessed for the combined risk of developing clinical outcomes. The 8‐year incidences of HCC, cirrhotic events and liver‐related mortality in the subgroups with low FIB‐4 and AFP levels were only 5.95%, 1.03% and 2.43% respectively. DM was an independent predictor of HCC and mortality.ConclusionThe combination of FIB‐4 and AFP levels at 12 months of treatment is a useful marker for predicting the development of HCC, cirrhotic events and mortality in compensated cirrhotic patients with CHB who are receiving ETV therapy.
Differential insular cortex subregional vulnerability to α‐synuclein pathology in Parkinson's disease and dementia with Lewy bodies
Authors: Fathy Y. Y. , Jonker A. J. , Oudejans E. , de Jong F. J. J. , van Dam A.‐M. W. , Rozemuller A. J. M. , van de Berg W. D. J. 
Published: May 2018

AimThe insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), it reveals α‐synuclein pathology in advanced stages. The aim of this study is to assess the insular cortex cellular and subregional vulnerability to α‐synuclein pathology in well‐characterized PD and DLB subjects.MethodsWe analysed postmortem insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB and age‐matched controls. The load and distribution of α‐synuclein pathology and tyrosine hydroxylase (TH) cells were studied throughout the insular subregions. The selective involvement of von Economo neurons (VENs) in the anterior insula and astroglia was assessed in all groups.ResultsA decreasing gradient of α‐synuclein pathology load from the anterior periallocortical agranular towards the intermediate dysgranular and posterior isocortical granular insular subregions was found. Few VENs revealed α‐synuclein inclusions while astroglial synucleinopathy was a predominant feature in PDD and DLB. TH neurons were predominant in the agranular and dysgranular subregions but did not reveal α‐synuclein inclusions or significant reduction in density in patient groups.ConclusionsOur study highlights the vulnerability of the anterior agranular insula to α‐synuclein pathology in PD, PDD and DLB. Whereas VENs and astrocytes were affected in advanced disease stages, insular TH neurons were spared. Owing to the anterior insula's affective, cognitive and autonomic functions, its greater vulnerability to pathology indicates a potential contribution to nonmotor deficits in PD and DLB.