bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inherited and Sporadic Amyotrophic Lateral Sclerosis and Fronto-Temporal Lobar Degenerations arising from Pathological Condensates of Phase Separating Proteins
Authors: Fernandopulle Michael , Wang GuoZhen , Nixon-Abell Jonathon , Qamar Seema , Balaji Varun , Morihara Ryuta , St George-Hyslop Peter H 
Published: September 2019

AbstractRecent work on the biophysics of proteins with low complexity, intrinsically disordered domains that have the capacity to form biological condensates has profoundly altered the concepts about the pathogenesis of inherited and sporadic neurodegenerative disorders associated with pathological accumulation of these proteins. In the present review, we use the FUS, TDP-43 and A11 proteins as examples to illustrate how missense mutations and aberrant post-translational modifications of these proteins cause amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD).
The Fissured Worker: Personal Service Companies and Employment Rights
Authors: Ford Michael 
Published: September 2019

Abstract
A personal service company (PSC) is a form of intermediary with separate legal personality used as a vehicle to provide the labour of the individual who controls the PSC. The rapid growth of PSCs in recent years, and their potential to disguise employment status for tax purposes, have been the subject of much policy and legislation. But their detrimental effect on the employment rights, both individual and collective, has almost been ignored. Evidence shows that PSCs continue to increase at a faster rate than employment, are colonising sectors of the labour market characterised by dependent labour and are often imposed to avoid the duties owed to workers or employees. In this article, I analyse how the existing law might provide a means of protecting the labour rights of individuals who are engaged via PSCs, examining the statutory provisions specific to some legal rights and more general doctrines based on shams, labels and piercing the corporate veil. Although the law provides some protection in some circumstances, PSCs retain their allure as a means of avoiding employment rights. I discuss potential legislative solutions to this problem, which highlights the interaction of tax and employment law and the difficulties caused by relying on the bilateral contract as the keystone of labour rights.
Serum Mac-2-Binding Protein Glycosylation Isomer at Virological Remission Predicts Hepatocellular Carcinoma and Death in Chronic Hepatitis B-Related Cirrhosis
Authors: Su Tung-Hung , Peng Cheng-Yuan , Tseng Tai-Chung , Yang Hung-Chih , Liu Chun-Jen , Liu Chen-Hua , Chen Pei-Jer , Chen Ding-Shinn , Kao Jia-Horng 
Published: September 2019

AbstractBackgroundTo investigate serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels in predicting hepatocellular carcinoma (HCC) and mortality at virological remission (VR, HBV DNA <20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB) patients with cirrhosis.MethodsThis retrospective cohort study included patients with CHB-related Child-Pugh A cirrhosis undergoing long-term antiviral therapy. Serum M2BPGi levels were quantified and multivariable Cox proportional hazards regression models were used to identify risk predictors for HCC and death.ResultsA total of 126 and 145 patients were included in the derivation and validation cohorts, respectively. The mean age was 56, and the mean M2BPGi level was 1.86 cut-off index (COI) in the derivation cohort. After adjustment for confounders, a higher M2BPGi level at VR significantly predicted HCC (hazard ratio [HR]: 1.58, 95% confidence interval [CI]: 1.19-2.10, P=0.002) and death (HR: 2.17, 95% CI: 1.02-4.62, P=0.044). The M2BPGi ³3 COI significantly increased the risk of HCC and death in the derivation and validation cohorts. Serial M2BPGi levels declined significantly (P=0.0001) in non-HCC patients only, and remained significantly lower than those who developed HCC afterwards (P=0.039).ConclusionsSerum M2BPGi levels at antiviral therapy-induced VR predict HCC development and death in patients with CHB-related Child-Pugh A cirrhosis.
Formyl-Peptide Receptor Activation Enhances Phagocytosis of Community-Acquired Methicillin-Resistant Staphylococcus aureus
Authors: Weiß Elisabeth , Schlatterer Katja , Beck Christian , Peschel Andreas , Kretschmer Dorothee 
Published: September 2019

AbstractBackgroundFormyl-peptide receptors (FPRs) are important pattern recognition receptors that sense specific bacterial peptides. Formyl-peptide receptors are highly expressed on neutrophils and monocytes, and their activation promotes the migration of phagocytes to sites of infection. It is currently unknown whether FPRs may also influence subsequent processes such as bacterial phagocytosis and killing. Staphylococcus aureus, especially highly pathogenic community-acquired methicillin-resistant S aureus strains, release high amounts of FPR2 ligands, the phenol-soluble modulins.MethodsWe demonstrate that FPR activation leads to upregulation of complement receptors 1 and 3 as well as FCγ receptor I on neutrophils and, consequently, increased opsonic phagocytosis of S aureus and other pathogens.ResultsIncreased phagocytosis promotes killing of S aureus and interleukin-8 release by neutrophils.ConclusionsWe show here for the first time that FPRs govern opsonic phagocytosis. Manipulation of FPR2 activation could open new therapeutic opportunities against bacterial pathogens.
Nonoptimal Vaginal Microbiota After Azithromycin Treatment for Chlamydia trachomatis Infection
Authors: Tamarelle Jeanne , Ma Bing , Gajer Pawel , Humphrys Mike S , Terplan Mishka , Mark Katrina S , Thiébaut Anne C M , Forney Larry J , Brotman Rebecca M , Delarocque-Astagneau Elisabeth , Bavoil Patrik M , Ravel Jacques 
Published: September 2019

Abstract
We characterized the composition and structure of the vaginal microbiota in a cohort of 149 women with genital Chlamydia trachomatis infection at baseline who were followed quarterly for 9 months after antibiotic treatment. At time of diagnosis, the vaginal microbiota was dominated by Lactobacillus iners or a diverse array of bacterial vaginosis–associated bacteria including Gardnerella vaginalis. Interestingly, L. iners–dominated communities were most common after azithromycin treatment (1 g monodose), consistent with the observed relative resistance of L. iners to azithromycin. Lactobacillus iners–dominated communities have been associated with increased risk of C. trachomatis infection, suggesting that the impact of antibiotic treatment on the vaginal microbiota could favor reinfections. These results provide support for the dual need to account for the potential perturbing effect(s) of antibiotic treatment on the vaginal microbiota, and to develop strategies to protect and restore optimal vaginal microbiota.
Metacytofilin Is a Potent Therapeutic Drug Candidate for Toxoplasmosis
Authors: Leesombun Arpron , Iijima Masatomi , Umeda Kousuke , Kondoh Daisuke , Pagmadulam Baldorj , Abdou Ahmed M , Suzuki Yutaka , Ohba Shun-Ichi , Isshiki Kunio , Kimura Tomoyuki , Kubota Yumiko , Sawa Ryuichi , Nihei Coh-Ichi , Nishikawa Yoshifumi 
Published: September 2019

AbstractBackgroundToxoplasmosis, a parasitic disease caused by Toxoplasma gondii, is an important cause of miscarriage or adverse fetal effects, including neurological and ocular manifestations in humans. Current anti-Toxoplasma drugs have limited efficacy against toxoplasmosis and also have severe side effects. Therefore, novel efficacious drugs are urgently needed. Here, we identified metacytofilin (MCF) from a fungal Metarhizium species as a potential anti-Toxoplasma compound.MethodsAnti-Toxoplasma activities of MCF and its derivatives were evaluated in vitro and in vivo using nonpregnant and pregnant mice. To understand the mode of action of MCF, the RNA expression of host and parasite genes was investigated by RNAseq.ResultsIn vitro, MCF inhibited the viability of intracellular and extracellular T. gondii. Administering MCF intraperitoneally or orally to mice after infection with T. gondii tachyzoites increased mouse survival compared with the untreated animals. Remarkably, oral administration of MCF to pregnant mice prevented vertical transmission of the parasite. Interestingly, RNA sequencing of T. gondii–infected cells treated with MCF showed that MCF inhibited DNA replication and enhanced RNA degradation in the parasites.ConclusionsWith its potent anti–T. gondii activity, MCF is a strong candidate for future drug development against toxoplasmosis.
Colonoscopy Trainers Experience Greater Stress During Insertion than Withdrawal: Implications for Endoscopic Curricula
Authors: Lemke Madeline , Banwell Alison , Rubinger Natalie , Wiepjes Michelle , Ropeleski Mark , Vanner Stephen , Hookey Lawrence 
Published: September 2019

Abstract

Background
Optimal colonoscopy training curricula should minimize stress and cognitive load. This study aimed to determine whether withdrawal or insertion colonoscopy skills training is associated with less stress or cognitive load for trainees or trainers.

Methods
In Phase I, participants were randomized to train on either insertion or withdrawal in a simulated environment. In Phase II, participants were randomized to begin with either insertion or withdrawal in patient encounters. Salivary cortisol levels, heart rate, and State-Trait Anxiety Inventory (STAI) surveys were used to assess stress in trainees and trainers. NASA Task Load Index (TLX) survey was used to assess cognitive workload in trainees.

Results
In Phase I, trainee stress increased during the simulation training during both withdrawal and insertion compared to baseline, while trainer stress changed minimally. Cognitive load was higher for trainees during withdrawal (P = 0.005). In Phase II, trainers’ STAI scores were greater during insertion training (P = 0.013). Trainees’ stress was highest prior to beginning patient training and decreased during training, while trainer’s stress increased during training. Trainees reported insertion training being of greater value (70.0%), while trainers reported withdrawal was preferred (77.8%).

Conclusion
Trainees and trainers exhibit important differences in stress during colonoscopy skills training. Trainees reported more stress during simulation training and greatest cognitive load during simulation withdrawal, whereas trainers reported greatest stress during patient encounters, particularly training of insertion techniques. Attention to the effect of stress on trainees and trainers and the drivers of stress is warranted and could be incorporated in competency based medical education.
“If He Has it, We Know What to Do”: Parent Perspectives on Familial Risk for Autism Spectrum Disorder
Authors: MacDuffie Katherine E , Turner-Brown Lauren , Estes Annette M , Wilfond Benjamin S , Dager Stephen R , Pandey Juhi , Zwaigenbaum Lonnie , Botteron Kelly N , Pruett John R , Piven Joseph , Peay Holly L ,   The IBIS Network, Piven J , Hazlett H C , Chappell C , Dager S , Estes A , Shaw D , Botteron K , McKinstry R , Constantino J , Pruett J , Schultz R , Pandey J , Paterson S , Zwaigenbaum L , Ellison J , Wolff J , Evans A C , Collins D L , Pike G B , Fonov V , Kostopoulos P , Das S , MacIntyre L , Gerig G , Styner M , Gu H 
Published: September 2019

AbstractObjectivePredictive testing for familial disorders can guide healthcare and reproductive decisions. Familial disorders with onset in childhood (e.g., autism spectrum disorder [ASD]) are promising targets for presymptomatic prediction; however, little is known about parent perceptions of risk to their children in the presymptomatic period. The current study examined risk perceptions in parents of infants at high familial risk for ASD enrolled in a longitudinal study of brain and behavior development.MethodsSemistructured interviews were conducted with 37 parents of high-risk infants during the presymptomatic window (3–15 months) that precedes an ASD diagnosis. Infants were identified as high familial risk due to having an older sibling with ASD. Parent interview responses were coded and interpreted to distill emerging themes.ResultsThe majority of parents were aware of the increased risk of ASD for their infants, and risk perceptions were influenced by comparisons to their older child with ASD. Parents reported a variety of negative emotions in response to perceived risk, including worry, fear, and sadness, and described impacts of perceived risk on their behavior: increased vigilance to emerging symptoms, altered reproductive and healthcare decisions, and seeking ongoing assessment through research.ConclusionsParents of children at high familial risk for childhood-onset disorders like ASD face a period of challenging uncertainty during early development. In anticipation of a future in which presymptomatic testing for ASD is made available, it is important to understand how parents react to and cope with the elevated—but still highly uncertain—risk conveyed by family history.
Higher Rates of Sleep Disturbance Among Offspring of Parents With Recurrent Depression Compared to Offspring of Nondepressed Parents
Authors: Hamilton Jessica L , Ladouceur Cecile D , Silk Jennifer S , Franzen Peter L , Bylsma Lauren M 
Published: September 2019

Abstract

Objective
Youth who have a parent with recurrent depression are at high risk for mental health problems. There is a need to identify transdiagnostic and clinically actionable mechanisms that explain higher rates of psychopathology among high-risk youth. The present study sought to examine whether offspring of depressed parents exhibit greater parent- and self-reported sleep disturbance, shorter sleep duration, and later sleep midpoint compared to youth without any parental psychopathology.

Method
Participants included 82 youth, including 41 youth (ages 9–13; mean age = 11.07 years; 46% female) deemed to be at high-risk based on having a parent with a recurrent depression history, and 41 (mean age = 11.16 years; 49% female) at low-risk based on having parents without any history of psychopathology. Youth and their parents completed measures of youth sleep disturbance, and youth completed measures of sleep duration and midpoint using a daily sleep diary for 9 days.

Results
Offspring of parents with depression exhibited more sleep disturbance (e.g., problematic nighttime behaviors and daytime sleepiness) than low-risk youth as reported by both parents and youth. For parent-reported sleep disturbance, there were also sex differences. High-risk girls had more sleep disturbance than high-risk boys or low-risk girls. There were no group differences for daily sleep duration and midpoint.

Conclusion
Sleep disturbance may be an important area for assessment among offspring of parents with depression. Our findings highlight one potential transdiagnostic risk factor that may emerge among high-risk youth, and sex-specific differences in sleep disturbance, which have implications for prevention and intervention.
PROMIS® Pediatric Depressive Symptoms as a Harmonized Score Metric
Authors: Kaat Aaron J , Kallen Michael A , Nowinski Cindy J , Sterling Stacy A , Westbrook Sherrilyn R , Peters John T 
Published: September 2019

Abstract

Objective
To conduct an evidence-based review of adolescent self-report depression measures and to demonstrate how various measures can be rescored onto a harmonized metric.

Method
Six widely used person-reported outcome measures (PROMs) were reviewed. Psychometric properties were evaluated using previously published guidance for PROMs. Next, two secondary data sources (from an outpatient behavioral health clinic and from the general population) were evaluated to harmonize scores across three of the measures. Both item response theory and equipercentile linking methods were used and compared.

Results
All six PROMs demonstrated a high evidence base for widespread use depending on the purpose of the assessments. Adolescent involvement when developing the PROM for content validity and floor or ceiling effects were the least frequent available evidence. Three of the PROMs were linked to the PROMIS® Pediatric Depressive Symptoms v2.0 (PROMIS-PedDepSx) metric. The scales were highly correlated and essentially unidimensional when aggregated. All linking methods were broadly comparable. Group-level score conversions are recommended to minimize linking bias.

Conclusions
There are a number of strong, widely used PROMs for the evidence-based assessment (EBD) of adolescent depression. However, score comparability is a concern whenever there is a proliferation of measures. Harmonized score metrics support data aggregation and re-analysis. Using four PROMs, one of which served as the scoring metric, we demonstrated the possibility of harmonized depression scores. Future directions for EBD should evaluate whether harmonized PROMs for other pediatric health domains would be useful.
The Rudeness and Reverence of Geoffrey Hill’s Mariology
Authors: Russell Jesse 
Published: September 2019

Abstract
Due to his seemingly reactionary politics and theology, the recently deceased English lyricist Geoffrey Hill has courted controversy throughout his life. However, while Hill’s work is replete with qualified nostalgia for premodern British history, and he does treat a number of Christian themes in his work, the great British poet defies easy categorisation. Moreover, drawing from the theology of Simone Weil, Rowan Williams, and others, Hill’s work is saturated with a profound awareness of the fallen state of human nature. One of the most profound tropes Hill uses as a representative of what could be called Original Sin is the image of the Blessed Virgin Mary. As a tormented believer and a poet very aware of the fallenness of the world, Hill’s depiction of Mary reveals that Hill is a Christian poet who does not fall into ready categories.
DNMIVD: DNA methylation interactive visualization database
Authors: Ding Wubin , Chen Jiwei , Feng Guoshuang , Chen Geng , Wu Jun , Guo Yongli , Ni Xin , Shi Tieliu 
Published: September 2019

Abstract
Aberrant DNA methylation plays an important role in cancer progression. However, no resource has been available that comprehensively provides DNA methylation-based diagnostic and prognostic models, expression–methylation quantitative trait loci (emQTL), pathway activity-methylation quantitative trait loci (pathway-meQTL), differentially variable and differentially methylated CpGs, and survival analysis, as well as functional epigenetic modules for different cancers. These provide valuable information for researchers to explore DNA methylation profiles from different aspects in cancer. To this end, we constructed a user-friendly database named DNA Methylation Interactive Visualization Database (DNMIVD), which comprehensively provides the following important resources: (i) diagnostic and prognostic models based on DNA methylation for multiple cancer types of The Cancer Genome Atlas (TCGA); (ii) meQTL, emQTL and pathway-meQTL for diverse cancers; (iii) Functional Epigenetic Modules (FEM) constructed from Protein-Protein Interactions (PPI) and Co-Occurrence and Mutual Exclusive (COME) network by integrating DNA methylation and gene expression data of TCGA cancers; (iv) differentially variable and differentially methylated CpGs and differentially methylated genes as well as related enhancer information; (v) correlations between methylation of gene promoter and corresponding gene expression and (vi) patient survival-associated CpGs and genes with different endpoints. DNMIVD is freely available at http://www.unimd.org/dnmivd/. We believe that DNMIVD can facilitate research of diverse cancers.
New substituted quinoxalines inhibit triple-negative breast cancer by specifically downregulating the c-MYC transcription
Authors: Hu Ming-Hao , Wu Tian-Ying , Huang Qiong , Jin Guangyi 
Published: September 2019

Abstract
Conventional chemotherapy remains the primary treatment option for triple-negative breast cancer (TNBC). However, the current chemotherapeutic drugs have limited effects on TNBC, and often lead to serious side effects as well as drug resistance. Thus, more effective therapeutic options are sorely needed. As c-MYC oncogene is highly expressed during TNBC pathogenesis, inhibiting c-MYC expression would be an alternative anti-TNBC strategy. In this study, we designed and synthesized a serial of quinoxaline analogs that target c-MYC promoter G-quadruplex (G4), which is believed to be a repressor of c-MYC transcription. Among them, a difluoro-substituted quinoxaline QN-1 was identified as the most promising G4-stabilizing ligand with high selectivity to c-MYC G4 over other G4s, which is distinguished from many other reported ligands. Intracellular studies indicated that QN-1 induced cell cycle arrest and apoptosis, repressed metastasis and inhibited TNBC cell growth, primarily due to the downregulation of c-MYC transcription by a G4-dependent mechanism. Notably, inhibition by QN-1 was significantly greater for c-MYC than other G4-driven genes. Cancer cells with c-MYC overexpression were more sensitive to QN-1, relative to normal cells. Furthermore, QN-1 effectively suppressed tumor growth in a TNBC mouse model. Accordingly, this work provides an alternative strategy for treating TNBC.
The invasive proteome of glioblastoma revealed by laser-capture microdissection
Authors: Daubon Thomas , Guyon Joris , Raymond Anne-Aurélie , Dartigues Benjamin , Rudewicz Justine , Ezzoukhry Zakaria , Dupuy Jean-William , Herbert John M J , Saltel Frédéric , Bjerkvig Rolf , Nikolski Macha , Bikfalvi Andreas 
Published: September 2019

AbstractBackgroundGlioblastomas are heterogeneous tumors composed of a necrotic and tumor core and an invasive periphery.MethodsHere, we performed a proteomics analysis of laser-capture micro-dissected glioblastoma core and invasive areas of patient-derived xenografts.ResultsBioinformatics analysis identified enriched proteins in central and invasive tumor areas. Novel markers of invasion were identified, the genes proteolipid protein 1 (PLP1) and Dynamin-1 (DNM1), which were subsequently validated in tumors and by functional assays.ConclusionsIn summary, our results identify new networks and molecules that may play an important role in glioblastoma development and may constitute potential novel therapeutic targets.