bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrent and metastatic female adnexal tumor of probable Wolffian origin
Authors: Chen Qiuhe , Shen Yangmei , Xie Chuan 
Published: March 2021

Abstract

Rationale:
Female adnexal tumors of probable Wolffian origin (FATWOs) are rare gynecologic neoplasms arising from the mesonephric duct remnants. Less than 90 cases have been reported in the English literature. Although most cases of FATWO are considered benign, recurrence and metastasis may occur in very few cases during the course of the disease. Due to the small number of recurrent and metastatic FATWO cases, there are no clear recommendations regarding optimal treatment.

Patient concerns:
A 75-year-old postmenopausal woman, who underwent a mass excision of the right broad ligament three years ago, was found to have a right adnexal mass during a regular postoperative physical examination.

Diagnoses:
Vaginal ultrasound examination revealed a cystic and solid mass approximately 3.6 × 4.4 × 3.8 cm on the right side of the uterus. Three years ago, the mass of the right broad ligament was diagnosed with FATWO in the local hospital. Following extensive immunohistochemistry analysis and after reviewing the histology slides from the primary tumor, the final diagnosis of the mass on the right side of the uterus was recurrent and metastatic FATWO.

Interventions:
The patient underwent laparoscopic mass excision, hysterectomy and resection of the metastatic lesion in the small intestine, and then she received 6 cycles of docetaxel and carboplatin-based chemotherapy.

Outcomes:
The disease has recurred three years after the first surgery in the local hospital. After the second surgery followed by systemic chemotherapy, there is no evidence of recurrence with 24 months of follow-up till now.

Lessons:
FATWO is considered a benign entity. However, a few FATWOs have been shown to behave aggressively. Due to only a few reported cases, there are no comprehensive recommendations regarding the optimal clinical management of recurrent and metastatic FATWOs. Complete surgical resection followed by combination chemotherapy is considered to be the most effective therapy for recurrent and metastatic FATWOs. Chemotherapy with docetaxel plus carboplatin, which is most commonly used in malignant cases, may be effective in the treatment of recurrent and metastatic FATWOs.
Use of the Griffiths mental development scale-Chinese in the assessment of children with autism spectrum disorder and global developmental delay/intellectual disability
Authors: Wang Hui , Du Yu , Mao Zhenghuan , Che Yueping , Li Haifeng , Ding Li , Jin Huiying 
Published: March 2021

Abstract
The Griffiths Mental Development Scale-Chinese (GDS-C) is used in China to assess the development of children from birth to 8 years of age. Language disorders are a common symptom of autism spectrum disorder (ASD) and global developmental delay (GDD)/intellectual disability (ID). There is a need to identify distinct clinical characteristics in children suspected of having these 2 disorders, mainly presenting as language disorders. Here, we aimed to use the GDS-C to evaluate children presenting with language problems to identify characteristics that distinguish ASD and GDD/ID. Children with language problems were recruited between August 2018 and December 2019. A total of 150 children aged 25 to 95.2 months were enrolled (50 in the ASD group, 50 in the GDD/ID group, and 50 in the typical group). Each group was subdivided by age as follows: 24–36 months, >36–60 months, and >60–96 months. Developmental characteristics assessed using the GDS-C were analyzed and compared. Both, children with ASD and GDD/ID presented with a lower developmental level than typical children in all six subscales of the GDS-C. No significant differences were observed in the six subscale scores between the ASD and GDD/ID groups, except for the practical reasoning subscale score in the >36 to 60 months subgroups, which was significantly lower in the GDD/ID group than in the ASD group. The developmental imbalance of subscales within the ASD and GDD/ID groups identified troughs in the personal-social, language, and practical reasoning areas in children with ASD and in the language and practical reasoning areas in children with GDD/ID relative to typical children. The GDS-C is a useful, comprehensive tool for the assessment of the developmental state of children with ASD and GDD/ID. Characteristics of practical reasoning subscale help diagnose autism in >36 to 60 months old children.
Cerebral Small Vessel Disease Burden and Longitudinal Cognitive Decline from age 73 to 82: the Lothian Birth Cohort 1936
Authors: Hamilton OKL , Cox SR , Okely JA , Conte F , Ballerini L , Bastin ME , Corley J , Taylor AM , Page D , Gow AJ , Muñoz Maniega S , Redmond P , Valdés-Hernández M del C , Wardlaw JM , Deary IJ 
Published: March 2021

AbstractSlowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD), however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age:72.6□0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory, and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk, and childhood cognitive ability. In the fully-adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: -0.201; 95%CI: [-0.36, -0.04]; pFDR=0.022) and processing speed (−0.222; [-0.40, -0.04]; pFDR=0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [-0.39, -0.06]; p=0.008; pFDR=0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.
Prevalence of childhood cough in epidemiological studies: does it matter which question we use?
Authors: Mallet Maria Christina , Mozun Rebeca , Ardura-Garcia Cristina , Latzin Philipp , Moeller Alexander , Kuehni Claudia E. 
Published: March 2021

ABSTRACTWe assessed how prevalence estimates of cough in 6-17-year-olds vary depending on the question asked in the population-based Luftibus in the school (LUIS) study. 3427 parents answered three different questions on cough. The prevalence of parent-reported cough varied substantially depending on the question: 25% of parents reported cough without a cold, 11% dry night cough and 5% that their child coughs more than other children. There was only partial overlap with 3% answering yes to all questions. This suggests that the exact question used to assess cough strongly affects prevalence estimates and must be taken into account when comparing studies.
Shared and disease-specific host gene-microbiome interactions across human diseases
Authors: Priya Sambhawa , Burns Michael B. , Ward Tonya , Mars Ruben A. T. , Adamowicz Beth , Lock Eric F. , Kashyap Purna C. , Knights Dan , Blekhman Ran 
Published: March 2021

AbstractWhile the gut microbiome and host gene regulation separately contribute to gastrointestinal disorders, it is unclear how the two may interact to influence host pathophysiology. Here, we developed a machine learning-based framework to jointly analyze host transcriptomic and microbiome profiles from 416 colonic mucosal samples of patients with colorectal cancer, inflammatory bowel disease, and irritable bowel syndrome. We identified potential interactions between gut microbes and host genes that are disease-specific, as well as interactions that are shared across the three diseases, involving host genes and gut microbes previously implicated in gastrointestinal inflammation, gut barrier protection, energy metabolism, and tumorigenesis. In addition, we found that mucosal gut microbes that have been associated with all three diseases, such asStreptococcus, interact with different host pathways in each disease, suggesting that similar microbes can affect host pathophysiology in a disease-specific manner through regulation of different host genes.
Arf GTPase-Activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
Authors: Watanabe Asano , Hataida Hikari , Inoue Naoya , Kamon Kosuke , Baba Keigo , Sasaki Kuniaki , Kimura Rika , Sasaki Honoka , Eura Yuka , Ni Wei-Fen , Shibasaki Yuji , Waguri Satoshi , Kokame Koichi , Shiba Yoko 
Published: March 2021

AbstractArf GTPase-Activating proteins (ArfGAPs) mediate the hydrolysis of GTP bound to ADP-ribosylation factors, which are important for intracellular transport. ArfGAPs have been shown to be critical for cargo sorting in the Golgi-to-ER and post-Golgi traffic. However, their roles in the sorting of secretory proteins remains unclear. Weibel-Palade bodies (WPBs) are cigar-shaped secretory granules in endothelial cells that contain von Willebrand factor (vWF) as their main cargo. WPBs are formed at thetrans-Golgi Network, and this process is thought to be coupled with the sorting of vWF. WPB biogenesis was reported to be regulated by ADP-ribosylation factors and their regulators, but the role of ArfGAPs has been unknown. In this study, we performed siRNA screening of ArfGAPs to investigate the biogenesis of WPBs. We found two ArfGAPs, SMAP1 and AGFG2, to be involved in WPB size and vWF exocytosis, respectively. SMAP1 depletion resulted in small-sized WPBs, and the lysosomal inhibitor leupeptin recovered the size of WPBs. These results indicate that SMAP1 functions in preventing the degradation of cigar-shaped WPBs. However, AGFG2 downregulation resulted in the inhibition of vWF secretion upon Phorbol 12-myristate 13-acetate (PMA)-stimulation, suggesting that AGFG2 plays a role in vWF exocytosis. Our study revealed unexpected processes regulated by ArfGAPs for vWF transport.Summary StatementThe ArfGAP proteins SMAP1 and AGFG2 were identified as regulating WPB size and vWF exocytosis.
Healthcare workers’ perceptions and attitudes towards the UK’s COVID-19 vaccination programme
Authors: Manby Louisa , Dowrick Anna , Karia Amelia , Maio Laura , Buck Caroline , Singleton Georgina , Lewis-Jackson Sasha , Uddin Inayah , Vanderslott Samantha , Martin Sam , Vindrola-Padros Cecilia 
Published: March 2021

AbstractObjectivesTo explore healthcare workers’ (HCWs) perceptions and attitudes towards the COVID-19 vaccination programme in the UK, including their expectations, concerns and views on whether to promote vaccination to others. To understand the key factors shaping HCWs’ attitudes towards COVID-19 vaccination in the UK.DesignThis study was designed as a rapid qualitative appraisal integrating data from a review of UK policies and guidance on COVID-19 vaccination with data from in-depth semi-structured telephone interviews with frontline HCWs in the UK. Data were analysed using framework analysis.ParticipantsInterviews were carried out with a purposive sample of HCWs from two large London-based hospital Trusts (n=24) and 24 government policies and guidelines on the vaccination programme were reviewed.ResultsThe level of uncertainty about the vaccines’ long-term safety and efficacy against mutant strains made it difficult for HCWs to balance the benefits against the risks of vaccination. HCWs felt that government decisions on vaccine rollout had not been supported by evidence-based science and this impacted their level of trust and confidence in the programme. The spread of misinformation online also impacted HCWs’ attitudes towards vaccination, particularly among junior level and Black, Asian and Minority Ethnic (BAME) HCWs. Most HCWs felt encouraged to promote vaccination to their patients and the majority said they would advocate vaccination or engage in conversations about vaccination with others when relevant.ConclusionIn order to improve HCWs’ trust and confidence in the UK’s COVID-19 vaccination programme, there needs to be clarity about what is known and not known about the vaccines and transparency around the evidence-base supporting government decisions on vaccine rollout. Effort is also needed to dispel the spread of vaccine-related misinformation online and to address specific concerns, particularly among BAME and junior level HCWs.Strengths and limitations of this studyThis is the first qualitative study to understand the factors influencing healthcare workers’ (HCWs) attitudes towards COVID-19 vaccination in the UKThis study integrated interview and policy data and captured HCWs’ perceptions and attitudes in real-time as the vaccination programme was being rolled out in the UKOur interview study sample was limited in its representation of junior level HCWs and areas of the UKThis research may have been impacted by selection bias as those with stronger views on vaccination may have been more likely to participate in the study
COVID-19 vaccine impact on rates of SARS-CoV-2 cases and post vaccination strain sequences among healthcare workers at an urban academic medical center: a prospective cohort study
Authors: Bouton Tara C. , Lodi Sara , Turcinovic Jacquelyn , Weber Sarah E. , Quinn Emily , Korn Cathy , Steiner Jacqueline , Schechter-Perkins Elissa M. , Duffy Elizabeth , Ragan Elizabeth J. , Taylor Bradford P. , Schaeffer Beau , Miller Nancy , Davidoff Ravin , Hanage William P. , Connor John , Pierre Cassandra , Jacobson Karen R. 
Published: March 2021

AbstractBackgroundCOVID-19 vaccine trials and post-implementation data suggest vaccination decreases SARS-CoV-2 infections. We examine COVID-19 vaccination’s impact on SARS-CoV-2 case rates and viral diversity among healthcare workers (HCW) during a high community prevalence period.MethodsA prospective cohort study from Boston Medical Center (BMC)’s HCW vaccination program, where staff received two doses of BNT162b2 or mRNA-1273. We included PCR-confirmed SARS-CoV-2 cases among HCWs from December 09, 2020 to February 23, 2021. Weekly SARS-CoV-2 rates per 100,000 person-day overall and by time from first injection (1-14 and >14 days) were compared with surrounding community rates. Viral genomes were sequenced from SARS CoV-2 positive samples.ResultsSARS-CoV-2 cases occurred in 1.4% (96/7109) of HCWs given at least a first dose and 0.3% (17/5913) of HCWs given both vaccine doses. Adjusted SARS-CoV-2 infection rate ratios were 0.73 (95% CI 0.53-1.00) 1-14 days and 0.18 (0.10-0.32) >14 days from first dose. HCW SARS-CoV-2 cases >14 days from initial dose compared to within 14 days were more often older (46 versus 38 years, p=0.007), Latinx (10% versus 8%, p=0.03), and asymptomatic (48% versus 11%, p=0.0002). SARS-CoV-2 rates among HCWs fell below those of the surrounding community, with a 18% versus 11% weekly decrease respectively (p=0.14). Comparison of 48 SARS-CoV-2 genomes sequenced from post-first dose cases did not indicate selection pressure towards known spike-antibody escape mutations.ConclusionsOur results indicate a positive impact of COVID-19 vaccines on SARS-CoV-2 case rates. Post-vaccination isolates did not show unusual genetic diversity or selection for mutations of concern.Main PointCases of SARS-CoV-2 among health care workers dropped rapidly with COVID-19 vaccination. Sequencing 48 breakthrough infections (overwhelmingly in 14 days after 1st dose) showed no clear sign of any differences in spike protein compared with time-matched, unvaccinated control sequences.
Epigenome erosion drives neural crest-like phenotypic mimicry in triple-negative breast cancer and other SOX10+ malignancies
Authors: Saunus Jodi M. , De Luca Xavier M. , Northwood Korinne , Raghavendra Ashwini , Hasson Alexander , McCart Reed Amy E. , Lim Malcolm , Lal Samir , Vargas Ana Cristina , Kutasovic Jamie R. , Dalley Andrew J. , Miranda Mariska , Kalaw Emarene , Kalita-de Croft Priyakshi , Gresshoff Irma , Al-Ejeh Fares , Gee Julia M.W. , Ormandy Chris , Khanna Kum Kum , Beesley Jonathan , Chenevix-Trench Georgia , Green Andrew R. , Rakha Emad A. , Ellis Ian O. , Nicolau Dan V. , Simpson Peter T. , Lakhani Sunil R. 
Published: March 2021

AbstractBackgroundIntratumoural heterogeneity is a poor prognostic feature in triple-negative breast cancer (TNBC) and other high-grade malignancies. It is caused by genomic instability and phenotypic plasticity, but how these features co-evolve during tumour development remains unclear. SOX10 is a transcription factor, neural crest stem cell (NCSC) specifier and candidate mediator of cancer-associated phenotypic plasticity.MethodsUsing immunophenotyping, we investigated the expression of SOX10 in normal human breast tissue and breast cancer (n=21 cosmetic breast reduction and 1,860 tumour samples with clinical annotation). We then defined the context and evolution of its expression in TNBC compared to 21 other malignancies using systems-level transcriptomics.ResultsSOX10 was detected in nuclei of normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In breast cancer, nuclear SOX10 predicted poor outcome amongst cross-sectional (log-rank p=0.0015, hazard ratio 2.02, n=224) and metaplastic (log-rank p=0.04, n=66) TNBCs. Systems-level transcriptional network analysis identified a core module in SOX10’s normal mammary epithelial transcription program that is rewired to NCSC genes in TNBC. Reprogramming was proportional to DNA damage and genome-wide promoter hypomethylation, particularly at CpG island shores. Using a novel network analysis pipeline, we found that NCSC-like transcriptional reprogramming is also strongly associated with promoter hypomethylation in other SOX10+ malignancies: glioma and melanoma.ConclusionsWe propose that cancer-associated genome hypomethylation simulates the open chromatin landscape of more primitive cell states, and that on this relatively unrestricted background, SOX10 recreates its ancestral gene regulatory circuits by default. These findings provide new insights about the basis of intratumoural heterogeneity and resurrection of developmental phenotypes in cancer; and highlight the potential for therapeutics that limit chromatin remodelling.
Differential effects of environmental and endogenous 24h rhythms within a deep-coverage spatiotemporal proteome
Authors: Kay Holly , Grünewald Ellen , Feord Helen K. , Gil Sergio , Peak-Chew Sew Y. , Stangherlin Alessandra , O’Neill John S. , van Ooijen Gerben 
Published: March 2021

AbstractThe cellular landscape of most eukaryotic cells changes dramatically over the course of a 24h day. Whilst the proteome responds directly to daily environmental cycles, it is also regulated by a cellular circadian clock that anticipates the differing demands of day and night. To quantify the relative contribution of diurnal versus circadian regulation, we mapped spatiotemporal proteome dynamics under 12h:12h light:dark cycles compared with constant light. UsingOstreococcus tauri, a prototypical eukaryotic cell, we achieved 85% coverage of the theoretical proteome which provided an unprecedented insight into the identity of proteins that drive and facilitate rhythmic cellular functions. Surprisingly, the overlap between diurnally- and circadian-regulated proteins was quite modest (11%). These proteins exhibited different phases of oscillation between the two conditions, consistent with an interaction between intrinsic and extrinsic regulatory factors. The relative amplitude of rhythmic protein abundance was much lower than would be expected from daily variations in transcript abundance. Transcript rhythmicity was poorly predictive of daily variation in abundance of the encoded protein. We observed coordination between the rhythmic regulation of organelle-encoded proteins with the nuclear-encoded proteins that are targeted to organelles. Rhythmic transmembrane proteins showed a remarkably different phase distribution compared with rhythmic soluble proteins, indicating the existence of a novel circadian regulatory process specific to the biogenesis and/or degradation of membrane proteins. Taken together, our observations argue that the daily spatiotemporal regulation of cellular proteome composition is not dictated solely by clock-regulated gene expression. Instead, it also involves extensive rhythmic post-transcriptional, translational, and post-translational regulation that is further modulated by environmental timing cues.
The nuclear receptor DHR3/Hr46 is required in the blood brain barrier of mature males for courtship
Authors: Lama Chamala , Love Cameron R. , Le Hoa Nhu , Lama Jyoti , Dauwalder Brigitte 
Published: March 2021

AbstractThe blood brain barrier (BBB) forms a stringent barrier that protects the brain from components in the circulation that could interfere with neuronal function. At the same time, the BBB enables selective transport of critical nutrients and other chemicals to the brain. Many of these processes are still poorly understood. Beyond these functions, another recently recognized function is even less characterized, specifically the role of the BBB in modulating behavior by affecting neuronal function in a sex dependent manner. Notably, signaling in the adultDrosophilaBBB is required for normal male courtship behavior. Courtship regulation also relies on male-specific molecules in the BBB. Our previous studies have demonstrated that adult feminization of these cells in males significantly lowered courtship. Here, we conducted microarray analysis of BBB cells isolated from males and females. Findings revealed that these cells contain male- and female-enriched transcripts, respectively. Among these transcripts, nuclear receptor DHR3/Hr46 was identified as a male-enriched BBB transcript. DHR3/Hr46 is best known for its essential roles in the ecdysone response during development and metamorphosis. In this study, we demonstrate that DR3/Hr46 is specifically required in the BBB cells of mature males for courtship behavior. The protein is localized in the nuclei of sub-perineurial glial cells (SPG), indicating that it might act as a transcriptional regulator. These data provide a catalogue of sexually dimorphic BBB transcripts and demonstrate a physiological adult role for the nuclear receptor DH3/Hr46 in the regulation of male courtship, a novel function that is independent of its developmental role.Author summaryThe blood brain barrier very tightly regulates which molecules can enter the brain. This is an important protection for the brain, however, it also complicates communication between molecules in the circulating fluid and the brain. In fly courtship, for example, circulating male-specific products are crucially required for normal courtship. But the neuronal circuits that ultimately control the behavior are inside the brain, separated from these molecules by the blood brain barrier. The mechanisms of this communication are not known. Here we show that the blood brain barrier itself contains sex-specific RNAs and we show that one of them, a nuclear receptor called DHR3, is required in adult males for normal courtship. These findings promise new insight into the communication between blood brain barrier and the brain.