bluuebunny/crossref_metadata_2025_split huggingface dataset:
NGTS clusters survey – II. White-light flares from the youngest stars in Orion
Authors: Jackman James A G , Wheatley Peter J , Acton Jack S , Anderson David R , Belardi Claudia , Burleigh Matthew R , Casewell Sarah L , Eigmüller Philipp , Gill Samuel , Gillen Edward , Goad Michael R , Grange Andrew , Hodgkin Simon T , Jenkins James S , McCormac James , Moyano Maximiliano , Queloz Didier , Raynard Liam , Tilbrook Rosanna H , Watson Christopher A , West Richard G 
Published: July 2020

ABSTRACT
We present the detection of high-energy white-light flares from pre-main-sequence stars associated with the Orion Complex, observed as part of the Next Generation Transit Survey (NGTS). With energies up to 5.2 × 1035 erg these flares are some of the most energetic white-light flare events seen to date. We have used the NGTS observations of flaring and non-flaring stars to measure the average flare occurrence rate for 4 Myr M0–M3 stars. We have also combined our results with those from previous studies to predict average rates for flares above 1 × 1035 erg for early M stars in nearby young associations.
Periodic fast radio bursts from forcedly precessing neutron stars, anomalous torque, and internal magnetic field for FRB 180916.J0158+65 and FRB 121102
Authors: Sob’yanin (Денис Николаевич Собьянин) Denis Nikolaevich 
Published: July 2020

ABSTRACT
A recent discovery of the periodic activity of the repeating fast radio burst source FRB 180916.J0158+65 in the Canadian Hydrogen Intensity Mapping Experiment (CHIME) hints at possible origin of the FRB from a freely precessing neutron star with a magnetar magnetic field of about 1016 G. However, the absence of simultaneously detected high-energy emission in the Swift and AGILE observations imposes stringent constraints on the field magnitude and questions the possibility of such a progenitor. We show that consideration of forced precession of a neutron star does not encounter the difficulty. This kind of precession takes place even if the neutron star is not deformed and is brought about by the anomalous moment of electromagnetic forces induced by stellar rotation and determined by non-corotational currents. Contrary to what is expected for the currents of corotation, the anomalous torque calculated by the direct method appears to be non-zero. If the observed 16.35-d period corresponds to the period of stellar precession, the inferred internal magnetic field appears to be about 6 × 1014 G for rotational period 1 s. For another possibly periodic FRB 121102 with 157-d period, the magnetic field is even lower, 2 × 1014 G, thereby justifying earlier considerations and not ruling out the hypothesis of FRB origin from precessing neutron stars.
The chemical structure and phosphorothioate content of hydrophobically modified siRNAs impact extrahepatic distribution and efficacy
Authors: Biscans Annabelle , Caiazzi Jillian , Davis Sarah , McHugh Nicholas , Sousa Jacquelyn , Khvorova Anastasia 
Published: July 2020

AbstractSmall interfering RNAs (siRNAs) have revolutionized the treatment of liver diseases. However, robust siRNA delivery to other tissues represents a major technological need. Conjugating lipids (e.g. docosanoic acid, DCA) to siRNA supports extrahepatic delivery, but tissue accumulation and gene silencing efficacy are lower than that achieved in liver by clinical-stage compounds. The chemical structure of conjugated siRNA may significantly impact invivo efficacy, particularly in tissues with lower compound accumulation. Here, we report the first systematic evaluation of the impact of siRNA scaffold—i.e. structure, phosphorothioate (PS) content, linker composition—on DCA-conjugated siRNA delivery and efficacy in vivo. We found that structural asymmetry (e.g. 5- or 2-nt overhang) has no impact on accumulation, but is a principal factor for enhancing activity in extrahepatic tissues. Similarly, linker chemistry (cleavable versus stable) altered activity, but not accumulation. In contrast, increasing PS content enhanced accumulation of asymmetric compounds, but negatively impacted efficacy. Our findings suggest that siRNA tissue accumulation does not fully define efficacy, and that the impact of siRNA chemical structure on activity is driven by intracellular re-distribution and endosomal escape. Fine-tuning siRNA chemical structure for optimal extrahepatic efficacy is a critical next step for the progression of therapeutic RNAi applications beyond liver.
Healthcare Professionals’ Beliefs, Attitudes, Knowledge, and Behavior Around Vaping in Pregnancy and Postpartum: A Qualitative Study
Authors: Hunter Abby , Yargawa Judith , Notley Caitlin , Ussher Michael , Bobak Alex , Murray Rachael L , Nath Srabani , Cooper Sue 
Published: July 2020

Abstract

Introduction
Finding effective ways to help pregnant women quit smoking and maintain long-term abstinence is a public health priority. Electronic cigarettes (ie, vaping) could be a suitable cessation tool in pregnancy for those who struggle to quit; however, healthcare professionals (HCP) must be informed about these devices to offer appropriate advice. This study used the Capability, Opportunity, Motivation, and Behavior (COM-B) model and Theoretical Domains Framework (TDF) to explore HCP attitudes towards vaping in pregnancy and postpartum; beliefs about the health risks of vaping; perceived barriers and facilitators of vaping in pregnancy; knowledge of current guidelines and policies; and training needs.

Methods
Interviews (n = 60) were conducted with midwives (n = 17), health visitors (n = 10), general practitioners (n = 15) and stop smoking specialists (n = 18) across the United Kingdom. Interview transcriptions were analyzed thematically using the framework approach and the COM-B.

Results
Discussing vaping as a tool for quitting smoking in pregnancy was prevented by a lack of capability (limited knowledge of vaping, lack of training in smoking cessation); lack of opportunity (restricted by organizational policies and guidelines, lack of time and financial issues impacting on training), and negative social influences (sensationalist media and stigma associated with vaping in pregnancy); and lack of motivation (fear of future litigation and comebacks should adverse effects from vaping arise).

Conclusions
Factors related to capability, opportunity, and motivation were identified that influence HCPs attitudes and behaviors towards vaping in pregnancy. Gaps in knowledge and training needs were identified, which could inform the development of targeted vaping training.

Implications
Vaping could be suitable in pregnancy for those struggling to quit smoking. However, HCPs must be informed about these devices to offer appropriate advice. These data extend our knowledge of factors influencing HCP attitudes and behaviors towards vaping in pregnancy. Generally, vaping was perceived as safer than cigarettes, but a perceived lack of evidence, health and safety risks, dependency, and regulation issues were concerning. Considering our findings, greater efforts are needed to ensure HCPs are sufficiently informed about vaping and guidelines available. More importance should be placed on training for all HCPs who have contact with pregnant women.
Diagnostic accuracy of interleukin-27 in tuberculous pleurisy: a systematic review and meta-analysis
Authors: Zhang Q , Ma Y , Zhang M , Wang Y , Wu W 
Published: July 2020

SummaryObjectiveThis study aimed to conduct a systematic review of the diagnostic value of interleukin-27 (IL-27) for tuberculous pleurisy (TP).MethodsLiterature on IL-27 diagnosis of TP was retrieved and screened from six databases (four English databases and two Chinese databases). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and summary receiver operating characteristic curve (SROC) were measured to assess accurately the comprehensive evaluation of IL-27 for TP.ResultsEleven studies with a total of 1454 patients were identified in the analysis. The combined diagnostic value of IL-27 for TP was as follows: sensitivity of 0.95 (95% confidence interval [CI]: 0.93–0.97), specificity of 0.91 (95% CI: 0.89–0.92), positive likelihood ratio of 13.99 (95% CI: 7.01–27.93), negative likelihood ratio of 0.07 (95% CI: 0.05–0.10), diagnostic odds ratio of 275.20 (95% CI: 112.83–671.23) and area under the SROC of 0.9830.ConclusionIL-27 has an excellent diagnostic value for TP and could be used as a diagnostic biomarker for TP.
Efficacy and serious adverse events profile of the adjuvanted recombinant zoster vaccine in adults with pre-existing potential immune-mediated diseases: a pooled post hoc analysis on two parallel randomized trials
Authors: Dagnew Alemnew F , Rausch Debora , Hervé Caroline , Zahaf Toufik , Levin Myron J , Schuind Anne ,   for the ZOE-50/70 study group
Published: July 2020

Abstract

Abstract Objective
In the ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials, the adjuvanted recombinant zoster vaccine (RZV) demonstrated ≥90% efficacy in preventing herpes zoster (HZ) in all age groups ≥50 years. Given the increased HZ risk associated with certain underlying autoimmune diseases or their treatment regimes, we conducted a post hoc analysis of RZV’s efficacy against HZ and safety profile [specifically, the occurrence of serious adverse events (SAEs)] in ZOE-50/70 participants who reported pre-existing potential immune-mediated diseases (pIMDs) at enrolment and were not on immunosuppressive therapies.

Methods
Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomized to receive two doses of RZV or placebo 2 months apart. In this subgroup analysis of participants with at least one pIMD at enrolment, the efficacy was calculated for two-dose recipients who did not develop confirmed HZ before 30 days post-dose 2. SAE occurrence was evaluated for all participants who received at least one dose.

Results
Of the 14 645 RZV and 14 660 placebo recipients from the ZOE-50/70 studies, 983 and 960, respectively, reported at least one pre-existing pIMD at enrolment and were included in these analyses. The most frequent pre-existing conditions were psoriasis, spondyloarthropathy and RA. Efficacy against HZ was 90.5% (95% CI: 73.5, 97.5%) overall with the lowest being 84.4% (95% CI: 30.8, 98.3%) in the 70–79-year-old age group. SAEs and fatal SAEs were similar between RZV and placebo recipients.

Conclusion
In ZOE-50/70 participants with pre-existing pIMDs, RZV was highly efficacious against HZ and SAE incidence was similar between RZV and placebo recipients.

Trial registration
ClinicalTrials.gov, https://clinicaltrials.gov, NCT01165177 (ZOE-50), NCT01165229 (ZOE-70).
Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion
Authors: Zen Margherita , Loredo Martinez Marta , Benvenuti Francesco , Gatto Mariele , Saccon Francesca , Larosa Maddalena , Iaccarino Luca , Doria Andrea 
Published: July 2020

Abstract

Objective
The withdrawal of oral anticoagulation (OAC) in patients with SLE and secondary aPL syndrome (SAPS) who become seronegative has not been clearly investigated to date. Our aim was to evaluate the prevalence of aPL seroconversion and the prognosis of SLE patients with SAPS who withdrew OAC after aPL negativization.

Methods
We retrospectively analysed data of all SLE patients (ACR criteria) with SAPS (Sydney criteria) prospectively followed-up in our clinic. aPL seroconversion was defined as negativization of lupus anticoagulant, aCL, and anti-β2glycoprotein-1 antibodies on two or more consecutive measurements, at least 12 weeks apart. OAC discontinuation was defined as the definitive withdrawal of all anticoagulants.

Results
Fifty-five out of 513 (10.7%) SLE patients had vascular SAPS. Sixteen patients (29.1%) became aPL seronegative during follow-up. Immunosuppressive therapy predicted aPL negativization (odds ratio 5.211, 95%CI 1.341, 20.243), whereas APS diagnosis prior to that of SLE (odds ratio 0.078, 95%CI 0.008, 0.799) and triple-positive profile (odds ratio 0.264, 95%CI 0.115, 0.609) were negative predictors of aPL negativization. OAC was discontinued in 13/55 patients (23.6%), after a median follow-up of 45 months (range 1–276) from aPL seroconversion. SLE-related modifiable risk factors for thrombosis were observed in 10/13 patients (77%) at the time of the thrombotic event. No thrombotic recurrences were observed during a mean follow-up time of 44 (19) months from OAC discontinuation.

Conclusions
Our results suggest that OAC can be safely discontinued in SLE patients who became persistently seronegative for aPL, at least when aPL-related thrombotic events occurred in presence of other thrombotic risk factors.
Dopamine Functioning and Child Externalizing Behavior: A Longitudinal Analysis of Polygenic Susceptibility to Parenting
Authors: Fischer Karen , van den Akker Alithe L. , Larsen Helle , Jorgensen Terrence D. , Overbeek Geertjan 
Published: July 2020

ABSTRACT:

Objective:
This study investigated how genetic susceptibility may affect children's sensitivity to parenting practices in their development of externalizing behavior. We created a continuous polygenic index composed of 5 dopamine polymorphisms to investigate the moderating role of dopamine-related genes in shaping parent-child gene-by-environment (Gc×E) interactions. Accumulating research supports that differences in children's dopamine neurotransmission make certain children more susceptible to both negative and positive parenting practices, a “for-better and for-worse” effect.

Methods:
Data from a 3-wave longitudinal study (4 months between waves) on 190 at-risk families with children aged 4 to 8 were used to investigate whether a heightened polygenic index score amplified the associations between negative and positive parenting and later children's externalizing behavior. Parenting practices and child externalizing behavior were assessed by parent-reported questionnaires.

Results:
Findings were not in line with the expectation that there was a stronger association between positive and negative parenting and later externalizing behavior for children with higher scores on the polygenic susceptibility index. Rather, children with a lower score on the polygenic susceptibility index showed more later externalizing behavior in response to positive parenting behavior, whereas for children with a higher score on the polygenic index, positive parenting was predictive of relatively lower levels of later child externalizing behavior.

Conclusion:
The results indicate that not only are children with higher but also lower scores on the polygenic index sensitive to parenting, they suggest that different phenotypical characteristics related to reward processing might underlie these genetic susceptibilities to parenting practices.
U-shaped relationship between pre-operative plasma fibrinogen levels and severe peri-operative bleeding in cardiac surgery
Authors: Mion Stefano , Duval Benoît , Besnard Thibaut , Darné Bernadette , Mouton Christine , Jecker Olivier , Labrousse Louis , Remy Alain , Zaouter Cédrick , Ouattara Alexandre 
Published: July 2020

BACKGROUND
An inverse linear relationship has been reported between pre-operative fibrinogen levels and postoperative blood loss in cardiac surgery. However, recently high pre-operative fibrinogen levels have also been reported to be associated with increased blood transfusion and re-operation.

OBJECTIVE
We tested the hypothesis that the relationship between pre-operative fibrinogen levels and severe peri-operative bleeding is not linear.

DESIGN
A large-scale (n = 3883) single-centre retrospective study.

SETTING
A tertiary care teaching hospital.

PATIENTS
We analysed data from our institutional database which includes all patients above 18 years who underwent on-pump cardiac surgery through a sternotomy between September 2010 and May 2014.

MAIN OUTCOME MEASURES
Peri-operative severe bleeding adapted from the Universal Definition of Peri-operative Bleeding, class 3 or 4. The relationship between pre-operative fibrinogen levels and peri-operative severe bleeding was analysed by binary logistic regression. A cubic B-spline transformation was used to estimate the relationship between pre-operative fibrinogen level associated with excessive peri-operative bleeding.

RESULTS
Severe peri-operative bleeding was observed in 957 (24.6%) patients. An L-shaped relationship was observed between pre-operative fibrinogen levels and 24-h postoperative blood loss. The relationship between pre-operative fibrinogen levels and severe peri-operative bleeding (i.e. Universal Definition of Peri-operative Bleeding class 3 or 4) was U-shaped: the risk of severe peri-operative bleeding bottomed at 3.3 g l−1 when the upward sloping curve started at 5.8 g l−1 with a steeper increase above 8.2 g l−1.

CONCLUSION
We reported a U-shaped relationship between severe peri-operative bleeding and pre-operative fibrinogen levels. While a low-level of fibrinogen appears to be associated with a high risk of bleeding, a high level does not necessarily protect the patient against such a risk and could even be a risk factor for peri-operative bleeding.
Novel antibody–drug conjugates: current and future roles in gynecologic oncology
Authors: Tymon-Rosario Joan , Zeybek Burak , Santin Alessandro D. 
Published: July 2020

Purpose of review
Antibody–drug conjugates (ADCs) represent a new class of drugs that combine a surface receptor-targeting antibody linked to a cytotoxic molecule. This review summarizes the current literature demonstrating their tremendous promise as therapeutic agents in the treatment of aggressive gynecologic malignancies.

Recent findings
Several antigens have proven to be differentially overexpressed in a variety of gynecologic tumors when compared with normal surrounding tissue and serve as novel targets for ADC therapy. In the last few years HER2/neu, folic acid-alpha (FRα) and Trop-2 overexpression have been exploited as excellent targets by novel ADCs such as Trastuzumab emtansine (T-DM1), SYD985, IMGN853 (Mirvetuximab soravtansine) and Sacituzumab govitecan (SG, IMMU-132) in multiple tumors including ovarian, endometrial and cervical cancers. Although the selectivity of ADCs with noncleavable linkers (i.e. T-DM1) has shown negligible effect on surrounding antigen negative cells, those ADCs with cleavable linkers (i.e. SYD985, IMGN853 and SG) may kill both antigen-positive target cells and surrounding antigen-negative cells via the bystander effect.

Summary
Preclinical data strongly supports these ADCs and ongoing clinical trials will shed further light into the potential of making these drugs part of current standard practice and providing our patients with a higher level of personalized cancer care.
Duration of Respiratory and Gastrointestinal Viral Shedding in Children With SARS-CoV-2: A Systematic Review and Synthesis of Data
Authors: Xu Cecilia L. H. , Raval Manjri , Schnall Jesse A. , Kwong Jason C. , Holmes Natasha E. 
Published: July 2020

Background:
Children with coronavirus disease 2019 (COVID-19) are more likely to have mild or no symptoms compared with adults and may represent important vectors for transmitting the virus. Little is known about the duration of respiratory and gastrointestinal viral shedding in children with COVID-19.

Objective:
To determine the average shedding times of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the respiratory and gastrointestinal tracts in children.

Methods:
We performed a systematic search of Ovid MEDLINE, Embase and Cochrane CENTRAL databases for studies reporting real-time reverse transcriptase polymerase chain reaction (rt-PCR) results in children with COVID-19, then extracted and synthesized data on duration of viral shedding from symptom onset in respiratory and gastrointestinal samples.

Results:
Based on data compiled from 69 pediatric cases, the duration of viral shedding through the respiratory tract is up to 24 days from symptom onset with a mean of 11.1 ± 5.8 days. Of the children who underwent testing with stool PCR, rectal swab or anal swab, 86% returned a positive result. The mean duration of viral shedding via the gastrointestinal tract was 23.6 ± 8.8 days from symptom onset. In 89% of cases, viral shedding via the gastrointestinal tract persisted after nasopharyngeal or throat swabs became negative, for as long as 4 weeks.

Conclusions:
To our knowledge, this is the first attempt to systematically review the duration of respiratory and gastrointestinal viral shedding of SARS-CoV-2 in pediatric patients. These findings may have important implications for infection control strategies during the COVID-19 pandemic.
Persistent Barriers to the Use of Long-Acting Injectable Antipsychotics for the Treatment of Schizophrenia
Authors: Lindenmayer Jean-Pierre , Glick Ira D. , Talreja Hiteshkumar , Underriner Michael 
Published: July 2020

Abstract

Purpose/Background
One of the major challenges in the treatment of schizophrenia is nonadherence, defined as the failure to take medications as prescribed. Nonadherence is a strong predictor of symptom relapse, hospital readmission, and poorer long-term outcome. Although long-acting injectable antipsychotics (LAIs) have been found to be superior to their oral analogs at reducing relapse in large-scale meta-analyses, their prevalence seldom exceeds 30% even in populations with a history of nonadherence. We review multiple barriers to the use of LAI utilization and suggest strategies to address them.

Methods/Procedures
We searched for the following terms: long-acting injectable/depot antipsychotics, schizophrenia, barriers, and attitude/perception in both the PubMed search index and Google scholar from 1995 to 2018. A total of 329 studies were selected, of which data from 13 were reviewed for this article. Only peer-reviewed studies, randomized controlled trials, systematic reviews, and meta-analyses that describe barriers to using LAIs were included.

Findings/Results
Several barriers to using LAIs were identified. These are organized into 3 overarching categories: those related to the clinician; those related to the patient; and systems barriers. Clinician factors include the perception of LAIs as coercive, fears of not being able to control the dose, as well as current practice patterns and guidelines. Patient factors include perception of the injection as painful or intrusive, general lack of knowledge, and a sense of coerciveness. For each identified barrier, we propose potential solutions.

Implications/Conclusions
We identified multiple barriers to using LAIs in patients with schizophrenia. Specific strategies are suggested for overcoming each of these barriers.